NEW EDITION OF INTERVENTIONAL NEURORADIOLOGY

Neurointerventional
Management:
Diagnosis and
Treatment
Second Edition

Edited by
Robert W. Hurst
Robert H. Rosenwasser
Neurointerventional Management
Neurointerventional Management
Diagnosis and Treatment
Second Edition

Edited by

Robert W. Hurst, MD
Professor of Radiology, Neurosurgery, and Neurology, Department of Radiology-Neuroradiology,
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Robert H. Rosenwasser, MD
Jewell L. Osterholm Professor and Chairman of Neurological Surgery, Professor of Radiology,
Neurovascular Surgery, Interventional Neuroradiology, Thomas Jefferson University/Jefferson
Hospital for Neuroscience, Philadelphia, Pennsylvania, USA
This edition published in 2012 by Informa Healthcare, 119 Farringdon Road, London EC1R 3DA, UK.
Simultaneously published in the USA by Informa Healthcare, 52 Vanderbilt Avenue, 7th Floor, New York, NY 10017, USA.

First published in 2008 by Informa Healthcare USA as Interventional Neuroradiology

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Neurointerventional management : diagnosis and treatment / edited by Robert W. Hurst, Robert H. Rosenwasser. -- 2nd ed.
p. ; cm.
Rev. ed. of: Interventional neuroradiology / edited by Robert W. Hurst, Robert H. Rosenwasser.
Includes bibliographical references and index.
ISBN 978-1-84184-806-8 (hardback : alk. paper)
I. Hurst, Robert W. II. Rosenwasser, Robert H. III. Interventional neuroradiology.
[DNLM: 1. Cerebrovascular Disorders--diagnosis. 2. Cerebrovascular Disorders--surgery. 3. Cardiovascular System--anatomy &
histology. 4. Neuroradiography. 5. Radiography, Interventional. WL 355]
616.8'04757--dc23
2011035046

ISBN-10: 1-84184-806-9
ISBN: 978-1-84184-806-8
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Contents

Contributors vii
Preface xi

1. Vascular anatomy of the head, neck, and skull base 1

Michele H. Johnson, Hjalti M. Thorisson, and Michael L. DiLuna

2. Applied neurovascular anatomy of the brain and skull 21

Michael J Cirivello, Randy S. Bell, and Rocco A. Armonda

3. Vascular anatomy of the spine and spinal cord 40

Armin K. Thron

4. Intracranial collateral routes and anastomoses

in interventional neuroradiology 59
David S. Liebeskind

5. Management of cerebrovascular variants 88

Azam S. Ahmed and Felipe C. Albuquerque

6. CT imaging and physiologic techniques

in interventional neuroradiology 104
Bryan A. Pukenas and Ronald L. Wolf

7. MR angiography: Basic principles and applications in the CNS 132

Neerav R. Mehta and Elias R. Melhem

8. Ultrasonographic imaging and physiologic techniques

in interventional neuroradiology 157
Jaroslaw Krejza and Micha Arkuszewski

9. Non-shunting cerebrovascular anomalies: Cavernous, capillary,

and venous malformations 187
Mahua Dey and Issam A. Awad

10. Diagnosis and management of cerebral vasculitis 203

James S. McKinney and Brett L. Cucchiara

11. Techniques and devices in interventional neuroradiology 226

Walter Zink, Alejandro Santillan, Athos Patsalides, Y. Pierre Gobin,
and Howard A. Riina

12. Balloon occlusion, Wada, and pharmacological testing 254

Linda J. Bagley

13. Endovascular management of tumors and vascular malformations

of the head and neck 266
Johnny C. Pryor, Joshua A. Hirsch, and Robert W. Hurst

14. Dissections of the carotid and vertebral arteries 291

Igor Rybinnik, Scott E. Kasner, Qaisar A. Shah, and Robert W. Hurst

15. Direct carotid cavernous fistula 316

Uday Shankar Kanamalla and Charles A. Jungreis
VI CONTENTS

16. Endovascular management of intracranial aneurysms 327

Aaron S. Dumont, Pascal M. Jabbour, Stavropoula I. Tjoumakaris,
L. Fernando Gonzalez, Ciro G. Randazzo, Peter Kim Nelson,
and Robert H. Rosenwasser

17. Endovascular management of cerebral vasospasm

post-subarachnoid hemorrhage 367
George Ghobrial, Stavropoula I. Tjoumakaris, Aaron S. Dumont,
Pascal M. Jabbour Robert H. Rosenwasser, and L. Fernando Gonzalez

18. Endovascular management of brain arteriovenous malformations 374

John B. Weigele, Riyadh N. Alokaili, and Robert W. Hurst

19. Endovascular treatment of acute ischemic stroke 404

Stavropoula I. Tjoumakaris, Pascal M. Jabbour, Aaron S. Dumont,
L. Fernando Gonzalez, and Robert H. Rosenwasser

20. Endovascular treatment of extracranial carotid atherosclerotic disease 415

David Orion, Shady Jahshan, Sharon Webb, Adnan H. Siddiqui, Elad I. Levy,
and L. Nelson Hopkins

21. Stenting and angioplasty for intracranial atherosclerotic

occlusive disease 434
Gabriela Spilberg, Neil V. Patel, Anna Luisa Khn, Matthew J. Gounis,
and Ajay K. Wakhloo

22. Endovascular management of dural arteriovenous fistulas 450

J. Marc C. van Dijk and Robert A. Willinsky

23. Diagnosis and management of cerebral venous and

dural sinus thrombosis 469
John B. Weigele

24. Inferior petrosal sinus sampling in the diagnosis

of pituitary adenomas 485
Nicholas J. Patronas and Donald L. Miller

25. Diagnosis and management of pediatric cerebrovascular disease 495

Gregory G. Heuer and Robert W. Hurst

26. Diagnosis and management of uncommon and genetic

cerebrovascular diseases 508
Rebecca N. Ichord

27. Endovascular treatment of spinal vascular malformations 523

Mayumi Oka and Kieran Murphy

28. Neuroendovascular aspects of cerebrovascular disease in pregnancy 547

Bryan A. Pukenas and Robert W. Hurst

29. Percutaneous vertebral augmentation 558

Bryan A. Pukenas and Mary E. Jensen

30. Neurocritical care management of endovascular patients 586

Monisha A. Kumar and Joshua M. Levine

31. Anesthesia for interventional neuroradiology 601

Dimitry Baranov and W. Andrew Kofke

Index 621
Contributors

Azam S. Ahmed Barrow Neurological Institute, Phoenix, Arizona, USA

Felipe C. Albuquerque Barrow Neurological Institute, Phoenix, Arizona, USA

Riyadh N. Alokaili Department of Medical Imaging, King Abdul-Aziz Medical

City, Riyadh, Saudi Arabia

Micha Arkuszewski Department of Radiology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, USA, and Department of Neurology,
Medical University of Silesia, Central University Hospital, Katowice, Poland

Rocco A. Armonda Department of Neurosurgery, National Capital Consortium,

Walter Reed National Military Medical Center, Bethesda, Maryland, USA

Issam A. Awad Section of Neurosurgery, University of Chicago Hospitals,

Chicago, Illinois, USA

Linda J. Bagley Department of Radiology, Hospital of the University of Pennsyl-

vania, Philadelphia, Pennsylvania, USA

Dimitry Baranov Department of Anesthesiology and Critical Care, Hospital of

the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Randy S. Bell Departments of Neurosurgery and Radiology, National Naval

Medical Center, and Comprehensive Neurosciences Program, Uniformed Services
University of Health Sciences, Bethesda, Maryland, USA

Michael J. Cirivello Departments of Neurosurgery and Radiology, National

Naval Medical Center, and Comprehensive Neurosciences Program, Uniformed
Services University of Health Sciences, Bethesda, Maryland, USA

Brett L. Cucchiara Department of Neurology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, USA

Mahua Dey Section of Neurosurgery, University of Chicago Hospitals, Chicago,

Illinois, USA

Michael L. DiLuna Department of Neurosurgery, Yale University School of

Medicine, New Haven, Connecticut, USA

Aaron S. Dumont Department of Neurological Surgery, Thomas Jefferson

University, Philadelphia, Pennsylvania, USA

George Ghobrial Department of Neurological Surgery, Thomas Jefferson Univer-

sity Hospital, Philadelphia, Pennsylvania, USA

Y. Pierre Gobin Weill Cornell Medical College, New York Presbyterian Hospital,
New York, New York, USA

L. Fernando Gonzalez Department of Neurological Surgery, Thomas Jefferson

University, Philadelphia, Pennsylvania, USA
VIII CONTRIBUTORS

Matthew J. Gounis New England Center for Stroke Research, Department of

Radiology, University of Massachusetts Medical School, Worcester, Massachusetts,
USA

Gregory G. Heuer Department of Neurosurgery, University of Pennsylvania,

and, Division of Neurosurgery, Childrens Hospital of Philadelphia, Philadelphia,
Pennsylvania, USA

Joshua A. Hirsch Department of Interventional Neuroradiology and Endovascu-

lar Neurosurgery, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts, USA

L. Nelson Hopkins Department of Neurosurgery, University at Buffalo, The State

University of New York, and Department of Neurosurgery, Millard Fillmore Gates
Hospital, Kaleida Health, Buffalo, New York, USA

Robert W. Hurst Departments of Radiology, Neurology, and Neurosurgery,

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Rebecca N. Ichord Department of Neurology, Childrens Hospital of Philadel-

phia, Philadelphia, Pennsylvania, USA

Pascal M. Jabbour Department of Neurological Surgery, Jefferson Medical

College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Shady Jahshan Department of Neurosurgery, University at Buffalo, The State

University of New York, and Department of Neurosurgery, Millard Fillmore Gates
Hospital, Kaleida Health, Buffalo, New York, USA

Mary E. Jensen Departments of Radiology & Neurosurgery, University of Vir-

ginia Health Systems, Charlottesville, Virginia, USA

Michele H. Johnson Departments of Neurosurgery and Otolaryngology Surgery,

Yale University School of Medicine, New Haven, Connecticut, USA

Charles A. Jungreis Departments of Radiology and Neurological Surgery, Temple

University School of Medicine, Temple University Hospital, Philadelphia, Pennsyl-
vania, USA

Uday Shankar Kanamalla Department of Radiology, Temple University Hospital,

Temple University School of Medicine, Philadelphia, Pennsylvania, USA

Scott E. Kasner Department of Neurology, Hospital of the University of Pennsyl-

vania, Philadelphia, Pennsylvania, USA

W. Andrew Kofke Department of Neurointensive Care, Hospital of the Univer-

sity of Pennsylvania, Philadelphia, Pennsylvania, USA

Jaroslaw Krejza Department of Radiology, Hospital of the University of Pennsyl-

vania, Philadelphia, Pennsylvania, USA, IMAM University, Riyadh, Kingdom of
Saudi Arabia

Anna Luisa Khn New England Center for Stroke Research, Department of
Radiology, University of Massachusetts Medical School, Worcester, Massachusetts,
USA

Monisha A. Kumar Departments of Neurology, Neurosurgery and Anesthesiol-

ogy & Critical Care, Hospital of the University of Pennsylvania, Philadelphia,
Pennsylvania, USA

Joshua M. Levine Departments of Neurology, Neurosurgery and Anesthesiology

& Critical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsyl-
vania, USA
 CONTRIBUTORS ix

Elad I. Levy, Department of Neurosurgery, and Toshiba Stroke Research Center,

Millard Fillmore Gates Hospital, Kaleida Health, University at Buffalo, The State
University of New York, Buffalo, New York, New York, USA

David S. Liebeskind UCLA Stroke Center, University of California, Los Angeles,

California, USA

James S. McKinney Department of Neurology, University of Medicine and

Dentistry, New Jersey (UMDNJ), Robert Wood Johnson Medical School, and Robert
Wood Johnson University Hospital Comprehensive Stroke Center, New Brunswick,
New Jersey, USA

Neerav R. Mehta Department of Radiology, Hospital of the University of Penn-

sylvania, Philadelphia, Pennsylvania, USA

Elias R. Melhem Department of Radiology, Hospital of the University of Penn-

sylvania, Philadelphia, Pennsylvania, USA

Donald L. Miller Department of Radiology, Albert Einstein Medical Center,

Philadelphia, Pennsylvania, USA

Kieran Murphy Medical Imaging, Faculty of Medicine, University of Toronto,

Toronto, Ontario, Canada

Peter Kim Nelson Department of Radiology, New York University Medical

Center, Tisch Hospital, New York, New York, USA

Mayumi Oka Radiology Department, Methodist Hospital, Merrillville, Indiana,

USA

David Orion Department of Neurosurgery, University at Buffalo, The State

University of New York, and Department of Neurosurgery, Millard Fillmore Gates
Hospital, Kaleida Health, Buffalo, New York, USA

Neil V. Patel Russell H. Morgan Department of Radiology and Radiological

Sciences, The Johns Hopkins Hospital, Baltimore, Maryland, USA

Nicholas J. Patronas Department of Radiology, National Institutes of Health,

Bethesda, Maryland, USA

Athos Patsalides Weill Cornell Medical College, New York Presbyterian Hospital,
New York, New York, USA

Johnny C. Pryor Department of Interventional Neuroradiology and Endovascu-

lar Neurosurgery, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts, USA

Bryan A. Pukenas Department of Radiology, Hospital of the University of

Pennsylvania, Philadelphia, Pennsylvania, USA

Ciro G. Randazzo Department of Neurological Surgery, Thomas Jefferson

University, Philadelphia, Pennsylvania, USA, and Departments of Neurology,
Neurosurgery, and Radiology, New York University Medical Center, New York,
New York, USA

Howard A. Riina Departments of Neurological Surgery and Radiology, Weill

Cornell Medical College, New York Presbyterian Hospital, New York, New York, US

Robert H. Rosenwasser Department of Neurological Surgery, Thomas Jefferson

University, Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, USA

Igor Rybinnik Department of Neurology, University of Pennsylvania, Philadel-

phia, Pennsylvania, USA
X CONTRIBUTORS

Alejandro Santillan Weill Cornell Medical College, New York Presbyterian

Hospital, New York, New York, USA

Qaisar A. Shah Neurointerventional and Neurocritical Care Services, Neurosci-

ences Institute, Abington Memorial Hospital, Abington, Pennsylvania, USA

Adnan H. Siddiqui Departments of Neurosurgery & Radiology, and Neuroendo-

vascular Critical Care, University at Buffalo, The State University of New York,
Buffalo, New York, New York, USA

Gabriela Spilberg New England Center for Stroke Research (NECStR), Depart-
ment of Radiology, University of Massachusetts Medical School, Worcester, Massa-
chusetts, USA

Hjalti M. Thorisson LandspitaliUniversity Hospital of Iceland, Reykajavik,

Iceland, and Department of Diagnostic Radiology, Yale University School of
Medicine, New Haven, Connecticut, USA

Armin K. Thron Department of Neuroradiology, University Hospital, RWTH

Aachen University, Aachen, Germany

Stavropoula I. Tjoumakaris Departments of Neurological Surgery and Endovas-

cular Neurosurgery, Jefferson Medical College, Thomas Jefferson University,
Philadelphia, Pennsylvania, USA

J. Marc C. van Dijk Department of Neurosurgery, University Medical Center

Groningen, Groningen, the Netherlands

Ajay K. Wakhloo Department of Radiology, University of Massachusetts Medical

School, Worcester, Massachusetts, USA

Sharon Webb Department of Neurosurgery, University at Buffalo, The State

University of New York, and Department of Neurosurgery, Millard Fillmore Gates
Hospital, Kaleida Health, Buffalo New York, USA

John B. Weigele Department of Radiology, Hospital of the University of Pennsyl-

vania, Philadelphia, Pennsylvania, USA

Robert A. Willinsky Department of Medical Imaging, The Toronto Western

Hospital, Toronto, Ontario, Canada

Ronald L. Wolf Department of Radiology, Hospital of the University of Pennsyl-

vania, Philadelphia, Pennsylvania, USA

Walter Zink South Texas Radiology Group, Methodist Hospital, San Antonio,
Texas, USA
Preface

The second edition of Interventional Neuroradiology has been re-titled Neurointerven-

tional Management. The new title highlights only one facet of the revolutionary
changes, that of terminology, that characterize this rapidly advancing field. The book
is intended to provide the clinical practitioner with background information and spe-
cific descriptions of the anatomy, techniques, disorders, procedures, and decisions
most commonly encountered in neurointerventional management. Throughout the
past decade, neuroendovascular techniques have revolutionized therapy of disorders
of the head, neck, and central nervous system. These procedures have now become
standard treatment for many of the most common neurovascular disorders and make
possible treatment of many patients who only a short time ago would have had no
reasonable therapeutic options.
With progress, however, comes the requirement for increased knowledge
and technical skill in order to deliver these treatments safely and effectively. Areas
of fundamental knowledge in neurointerventional management cross the bound-
aries of classically delineated medical and surgical specialties including neurosur-
gery, neuroradiology, and neurology. Required knowledge includes familiarity
with neuroradiologic imaging of vascular disease, knowledge of vascular anat-
omy, and thorough understanding of cerebrovascular disorders and their endo-
vascular treatments. Most importantly, skill in basic neurointerventional
techniques must be coupled with good clinical judgment in patient management
and decision-making.
Ongoing rapid advances in neuroimaging require neurointerventional practi-
tioners to have excellent diagnostic skills with noninvasive neuroimaging modalities
to identify the presence of cerebrovascular disease, evaluate its effects, identify
potential candidates for neurointerventional procedures, and document the results
of treatment. Separate chapters on CT, MR and ultrasonographic evaluation of cere-
brovascular disease emphasize the current noninvasive evaluation of disorders of
importance to neurointerventionalists. In addition, the authors have made every
effort throughout the text to illustrate the integration of current neuroimaging into
the performance and decision-making associated with interventional neuroradio-
logic procedures.
As in all radiologic or surgical based specialties, thorough understanding of
pertinent anatomy is essential. For the neurointerventionalist, cerebrovascular anat-
omy is the workplace. Anatomic knowledge underlies the understanding of many, if
not all, cerebrovascular disorders, provides routes of endovascular access, and
defines the scope of treatment options. Chapters covering pertinent vascular anat-
omy of special importance to neurointerventional procedures have been included
and updated from the previous edition. These chapters are directed at key anatomic
concepts as well as specific anatomic features of the head, neck, brain, and spine
vasculature.
It is through basic neurointerventional techniques that treatment is delivered
to the individual patient. No amount of theoretical understanding can overcome
poor technique in an environment as unforgiving as the cerebrovascular system.
Discussion of basic techniques with appropriate illustrations should prove useful for
those of all levels of experience from students entering the field to experienced prac-
titioners who may benefit from review or additional technical options.
Coupled with anatomic and technical knowledge is the requirement for under-
standing the epidemiology, pathophysiology, and clinical features of the increasing
numbers of cerebrovascular disorders that are now amenable to endovascular treat-
ment. Clinically oriented discussions of the most common conditions of interest to
neurointerventional practitioners have been authored by recognized experts in the
field. Treatment discussions are illustrated with current images to emphasize perti-
nent technical and anatomic details. Extensive and current references are included to
serve as a basis for further research.
Perhaps most essential to successful neurointerventional practice is the require-
ment for correlating the appropriate application of knowledge and technical skills to
XII PREFACE

the care of patients. The clinical emphasis on topics throughout the book is designed
to illustrate the importance of integrating clinical information, knowledge of disease
processes, and technical skill through the use of good clinical judgment to formulate
and perform effective neurointerventional procedures.

Robert W. Hurst
Robert H. Rosenwasser
 1
Vascular anatomy of the head, neck, and skull base
Michele H. Johnson, Hjalti M. Thorisson, and Michael L. DiLuna
INTRODUCTION
The emphasis of this chapter is on the anatomy and
anatomic variations of the vasculature of the head and
neck beginning in the thorax at the level of the aortic
arch and extending superiorly to the level of the skull
base (vascular entrance through the dura). Selective
catheterization is predicated on familiarity with these
anatomic features. Cross-sectional (vascular) imaging,
including CTA and MRA, has supplanted catheter
studies for the purposes of pure anatomic diagnosis.
Identification of the common and uncommon varia-
tions and their adjacent soft tissue relationships is
important to the neurointerventionalist when assess-
ing the cross-sectional imaging prior to therapeutic
intervention. The anatomy of this region will be
explored using a combination of CTA, MRA, and con-
ventional angiographic images and case examples to
demonstrate features important to the neurointerven-
tionalist (1).
EMBRYOLOGY
The embryology of the aortic arch development is
complex and beyond the scope of this chapter; how-
ever, a few relevant embryologic considerations pro-
vide a basis for understanding important normal
variants that may have an impact on catheterization
and image interpretation (26). The convexity of the
aortic arch forms from the left fourth primitive aortic
arch. The innominate or brachiocephalic artery (BCA),
the left common carotid artery (LCCA), and the left
subclavian artery (LSUB) arise sequentially from the
aortic arch (from proximal to distal) (Fig. 1.1A). In the
majority of cases, the LCCA arises distinctly separate
from the BCA; however, in approximately 20% of
patients, the LCCA may arise in conjunction with the
BCA in a bovine configuration (Fig. 1.1B) (7,8). In 5%
of patients, the left vertebral artery may arise as a
branch of the aortic arch (Fig. 1.1C) (9). Even more
rarely, the right vertebral artery may arise directly
from the aortic arch (Fig. 1.1D,E) (9).
In rare cases, the arch is derived from the right
primitive arch and the brachiocephalic vessels arise as
a mirror image of the normal arrangement (Fig. 1.1F).
More commonly, an aberrant right subclavian artery
(RSUB) is present that is characterized by the right
common carotid as the first branch from the aortic
arch, followed by the LCCA, the LSUB, and finally
the RSUB, which arises distally and proceeds toward
the right behind the esophagus to give rise to the right
vertebral artery and remaining subclavian artery
branches (Fig. 1.1G). A focal dilatation of the aorta
adjacent to the origin of the aberrant right subclavian
is referred to as Kommerells diverticulum and may
occasionally become aneurysmal and require surgical
repair (Fig. 1.1H) (10,11).
AORTIC ARCH AND BRANCHES
The aorta arises from the heart and emerges from the
pericardium in the superior mediastinum, where it
forms the ascending aortic arch (AOA) anterior to the
trachea at the level of the sternal manubrium. From
this ascending arch arise three major branches: the
BCA, the LCCA, and the LSUB (Fig. 1.1A). The BCA
crosses obliquely cephalad into the right anterior to
the trachea before bifurcating into the right common
carotid artery (RCCA) and RSUB behind the sternocla-
vicular joint. Fluoroscopic recognition of the head of
the clavicle as the location of the bifurcation of the
BCA can be a useful adjunct to selective catheteriza-
tion of the RCCA and RSUB (Fig. 1.2). The anterior
location of the RCCA in relationship to the RSUB can
be exploited in the selective catheterization of the sub-
clavian artery by turning the patients head toward
the left and extending the arm to accentuate the sepa-
ration between these two vessels. The right vertebral
artery arises from the RSUB just opposite the origin
of the internal mammary (INM) artery. Additional
subclavian branches include the ascending cervical
artery, the thyrocervical trunk, and the costocervical
trunk (Fig. 1.3AC). These branches are important to
identify in the analysis of pathologic processes of the
lower neck as well as vascular malformations and
other pathologic lesions involving the cervical and/or
upper thoracic vertebral bodies and spinal cord.
VERTEBRAL ARTERIES
The vertebral arteries ascend posterior to the common
carotid between the longus colli and scalenus anterior
muscles, entering the transverse foramen at C6. They
traverse the transverse foramen of the cervical verte-
bral body between C6 and C2. After exiting the trans-
verse foramen at C2, the vertebral artery proceeds
posterolaterally through the transverse foramen of C2
and posteromedially between C1 and the occiput,
before entering the foramen magnum (1,4,5). The cer-
vical vertebral artery provides small branches to
2 NEUROINTERVENTIONAL MANAGEMENT

supply the vertebral bodies and the adjacent cervical when the transverse foramen is enlarged (Fig. 1.5). It
musculature (Fig. 1.4A,B). The cervical course is usu- is also important to recognize the potential for luminal
ally straight, although tortuosity may limit distal narrowing and/or flow alteration within the vertebral
microcatheterization and/or may lead to confusion artery as a consequence of normal head turning. This

RVT

VRT

L
Common
origin

Right VRT

(A) (B) (C) (D) (E)

RT SUB
Aneurysm L2
LCCA

FL
Common
origin
Aberrant Extravasation
RT SUB

Aneurysm
Aneurysm

Common
origin

(F) (G) (H) (I) (J)

Figure 1.1 (A) Normal LAO arch configuration. Note the typical configuration of the great vessels and the marked vertebral artery
asymmetry (right > left). (B) Bovine arch. Note the common origin of the BCA and the LCCA. The left vertebral artery is larger than the
right. (C) LAO arch injection demonstrates the origin of the left vertebral artery from the aortic arch between the origins of the LCCA
and the left SUB. Note the absence of vertebral originating from the left SUB. (D,E) Right vertebral artery arising from the arch demon-
strated on posterior view of 3D CTA. (F) Spontaneous aortic dissection in a patient with aberrant right subclavian and a bovine arch
configuration. The patient presented with chest and right arm pain. Note the false lumen (FL) and the dissection flap (arrows). (G)
EhlersDanlos with aberrant right subclavian, bovine origin, and multiple aneurysms (arrows). (H) Right aortic arch with aberrant left
subclavian and tracheal ring. Note the diverticulum of Komerell (arrows). (I) Massive oral bleeding. Aortic arch arteriogram demon-
strates a normal arch configuration; however, there is an increased distance between the BCA and RCCA and the LCCA (arrows) sec-
ondary to mediastinal hematoma. (J) Massive oral bleeding is associated with extravasation of contrast from this left common carotid
blow-out. Abbreviations: BCA, brachiocephalic artery; LCCA, left common carotid artery; SUB, subclavian artery; RCCA, right com-
mon carotid artery; LAO, left anterior oblique.

VRT
CCA

CCA

SUB
Innominate
INN V roadmap
C

SUB
(A) (B)

Figure 1.2 (A, B) 3D CTA demonstrates the normal relationships of the BCA as it bifurcates into the subclavian and carotid arteries on
the right bifurcation. The BCA road-map image demonstrates the clavicle as a landmark for the bifurcation in the AP view. Abbrevia-
tion: BCA, brachiocephalic artery.
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 3

Muscular
collaterals
VRT
VRT
Tumor
vessels

Thyrocervical
Tumor trunk
branches
Ascending
cervical

Ascending
Thyrocervical cervical
branch Ascending
trunk cervical

(A) (B) (C) (D)

Figure 1.3 Proximal subclavian branches (AC) SUB injection demonstrates proximal branches supplying T2 vertebral tumor. (D) The
ascending cervical artery is a potential collateral source to the vertebral artery. Abbreviation: SUB, subclavian artery.

(A) (B)

Figure 1.4 Vertebral artery cervical branches. AP view (A) and lateral view (B) of the cervical vertebral artery demonstrate small mus-
cular and vertebral body branches (arrows).

45:47 AM

(A) (B) (C) (D)

Figure 1.5 Vertebral artery variations mimicking dissection. Vertebral artery tortuosity versus dissection on CTA (A). Note the tortuosity without
dissection flap on the AP angiogram (B). Vertebral dissection vs fenestration on CTA (C). 3-D volume rendering confirms fenestration (D).
4 NEUROINTERVENTIONAL MANAGEMENT

normal phenomenon may be accentuated by the pres-
ence of osteophytes encroaching on the artery within
the transverse foramen (12). Provocative maneuvers
during angiography or, alternatively, during non-
invasive vascular imaging may demonstrate these
findings, which may correlate with clinical hypoperfu-
sion symptoms such as lightheadedness or vertigo
(Fig. 1.6A,B) (13,14).
(A) (B) (C)
Figure 1.6 Syncope on head turning. (A) Left vertebral artery:
neutral position. Note the compression of the cervical vertebral
artery by uncovertebral joint degenerative osteophytes accentu-
ated on moderate (B) and maximal (C) head turning.
The left vertebral artery is dominant (larger and
responsible for the majority of the posterior fossa
flow) almost half of the time, while the right vertebral
artery is dominant 25% of the time (12,1517). No size
or flow dominance is present in the remaining cases
(12,1517). Anastomoses exist at multiple levels with
the external carotid artery (ECA), the thyrocervical
trunk, and the costocervical trunk.
The vertebral arteries proceed through the dura
at the level of the foramen magnum and join to form
a common basilar artery. The posterior inferior cere-
bellar artery (PICA) is the largest, though frequently
variable, branch of the vertebral artery and usually
arises proximal to origin of the basilar artery. It can
arise as a single trunk or in duplicate, and occasion-
ally the vertebral artery can terminate as the PICA
(18,19). There is a balance between distal branches of
the PICA and hemispheric branches of the anterior
inferior cerebellar artery (AICA) such that an AICA-
PICA variant may be an absent PICA, with the PICA
territory supplied by distal branches of the AICA, or
vice versa (1820) (Fig. 1.7A,B).
The posterior spinal artery often arises from
the vertebral artery at the level of the medulla
oblongata or may arise from the PICA, coursing pos-
teriorly and dividing into anterior and posterior
branches to anastomose with small perforators from
the vertebral artery. The ascending cervical artery,
posterior intercostal arteries, and lumbar arteries
may each contribute collateral supply to the poste-
rior spinal arteries at their respective levels. The
anterior spinal artery arises from the distal end of
the vertebral artery and descends anterior to the

PICA
PICA

VRT
VRT

(A) (B) (C) (D) (E)

Foramen Foramen
magnum magnum
ASA ASA

VRT
PICA
AVM VRT Foramen Foramen
AVM magnum magnum

VRT PICA

(F) (G) (H) (I) (J)

Figure 1.7 Distal vertebral artery variations. (A) AP and (B) lateral vertebral ends in PICA. Vertebral artery fenestrations. Note the nor-
mal appearance and position of the PICA on 1.7D. (CE); T1-weighted sagittal MRI (F) and AP (G) and lateral (H) vertebral angio-
grams demonstrate an AVM fed by the ASA; AP (I) and lateral (J) views demonstrate the origin of PICA below the foramen
magnum. Abbreviations: AVM, arteriovenous malformation; ASA, anterior spinal artery; PICA, posterior inferior cerebellar artery.
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE
medulla oblongata, joining with its contralateral
branch to descend as a single vessel, forming multi-
ple anastomoses with similar segmental perforators
(as the posterior spinal artery), to supply the ante-
rior spinal cord to the filum terminale. The posterior
meningeal artery arises from the cervical vertebral
artery to supply the bone and dura of the posterior
fossa (12). Multiple small spinal branches enter the
vertebral canal through the intervertebral foramina
to supply the spinal cord. Muscular branches at the
level of the lateral mass of C1 supply the deep cervi-
cal musculature (Fig. 1.4).
COMMON CAROTID ARTERIES
The common carotid arteries proceed cephalad within
the fibrous carotid sheath along with the internal jug-
ular vein, the vagus nerve, and the ansa cervicalis.
The common carotid arteries have no normal branches
before the carotid bifurcation, although rare variations
may occur (Fig. 1.8C-F) (20). The hypoglossal artery
variant is the most common of the primitive anasto-
moses arising within the neck. Intracranially, the trige-
minal artery is most common. The terminal common
carotid artery dilates to form the carotid bulb and
bifurcates into the ICA and ECA. The bifurcation is
typically located between the level of thyroid cartilage
and the greater horn of the hyoid bone, although caro-
tid bifurcations may lie either above or below this
level (reported at the C1C2 to the C6C7 levels)
(21,22). The anatomic level of the carotid bifurcation is
more important when surgical rather than endovascu-
lar correction of carotid atherosclerotic disease is
planned. The bifurcation is located between C3 and
C5 in approximately 80% of patients, with the next
common location at the C5C6 level (13%) (22,23). The
internal carotid artery (ICA) courses posterolateral to
the ECA and then proceeds medially to enter the caro-
tid canal at the skull base (Fig. 1.8C,D).
External Carotid Artery
The ECA arises at the bifurcation of the common caro-
tid artery in the neck and supplies the face, scalp, and
dura primarily, with potential collateral contributions
to the brain parenchyma and orbital contents (23). The
ECA branches have many variations (Fig. 1.9). Supply
to the face and deep soft tissue structures is often bal-
anced between adjacent branches, such as the facial
and internal maxillary arteries. However, true ECA
anomalies are rare, the most common being a so-
called nonbifurcated common carotid artery, where
the ECA branches arise separately from the common
carotid trunk (24,25). Anomalous origin of the ECA
from the aortic arch is also rarely encountered (26).
The ECA courses anterolaterally from its initial posi-
tion along the lateral pharyngeal wall as it passes
beneath the posterior belly of the digastric and stylo-
hyoid muscles and pierces the parotid fascia. The
deep lobe of the parotid gland separates the ECA
from the ICA (1,4,5).
Two schemes for categorizing the ECA branches
according to cranial caudal or anterior and posterior
locations have been proposed to predict the vascular
source of neovascularity or bleeding on the basis of
5
cross-sectional imaging prior to intervention. In one
scheme, the ECA branches are conceptually divided
into three segments: (i) the lower cervical segment,
(ii) the middle segment (at the mandibular angle),
and (iii) the upper segment (in the area of the paro-
tid gland). An alternative organizational method is to
consider the ECA branches as anterior and posterior
branches. The anterior branches, listed in proximal to
distal order, are the superior thyroid, lingual, and
facial arteries. The posterior branches in proximal to
distal order are the ascending pharyngeal artery
(APA), occipital, and posterior auricular arteries. The
branch order corresponds to the associated soft tis-
sue structures, after which the vessels are named.
The ECA terminates by bifurcating into the internal
maxillary and superficial temporal arteries (Fig.
1.10A,B) (23).
Superior Thyroid Artery
The superior thyroid artery is usually the most proxi-
mal and anterior ECA branch and can be readily iden-
tified by the prominent thyroid blush after contrast
injection. This artery may also arise from the carotid
bifurcation or, occasionally, directly from the cervical
common carotid artery (Fig. 1.11) (23,27). The superior
thyroid artery arises from the anterior surface of the
ECA and courses directly inferiorly alongside the
gland to supply the superior pole of the thyroid gland
and larynx. There is extensive collateralization with
the contralateral superior thyroid artery and the infe-
rior thyroid artery, which originates from the thyro-
cervical trunk. Rarely, injury to the artery may occur
at the time of tracheostomy or laryngeal surgery,
resulting in bleeding and/or pseudoaneurysm forma-
tion (Fig. 1.12A,B).
Ascending Pharyngeal Artery
The APA is the first posterior ECA branch (23). Ante-
riorly directed APA branches supply the pharynx and
eustachian tube. Posteriorly directed branches supply
the tympanic cavity and prevertebral muscles (Fig.
1.13A,B). The main trunk of the APA parallels the
course of the ICA and can be occasionally mistaken
for the ICA on ultrasound in the setting of internal
carotid occlusion (a source of false-negative ultra-
sound screening examinations) (Fig. 1.14A,B) (28). The
APA, in its location adjacent to the pharyngeal
mucosal space, can be eroded by tumor and become
the source of intractable bleeding (Fig. 1.15A,B). A
small but clinically important branch vessel is the neu-
romeningeal branch, which supplies both the dura
and lower cranial nerves. There are extensive anasto-
moses between the APA and the intracranial vascula-
ture. These include rami anastomosing with the
middle meningeal and accessory meningeal arteries of
the external carotid circulation (23,29). There are also
anastomoses with the internal carotid system via the
inferior tympanic artery, which anastomoses with the
caroticotympanic artery of the petrous internal carotid.
Other variable anastomoses may also exist between
the APA and the vidian artery and inferolateral trunk.
The APA may also anastomose with cervical branches
of the vertebral artery via the artery of the odontoid
6 NEUROINTERVENTIONAL MANAGEMENT

IMA BA

A MMA

Microcatheter

Hypoglossal
IMA artery

ICA
ECA APA ICA Stump

CCA
ICA
CCA

(A) (B) (C) (D)

FMD
ICA

HGA FMD

HGA

ICA

(E) (F) (G)

Figure 1.8 Cervical carotid variations. (A) Normal bifurcation, (B) cervical loop, and (C) ascending pharyngeal artery arising from the
ICA. (D) Hypoglossal artery with ICA occlusion. (E) Hypoglossal artery CT. (F) Hypoglossal artery angiogram. (G) Fibromuscular dys-
plasia (FMD). Abbreviations: ICA, internal carotid artery.

IMA

IMA
IMA
Collateral

IMA
FAC
FAC collaterals
FAC
FAC branches catheter
FAC

(A) (B) (C) (D)

Figure 1.9 (A) Lateral CCA injection reveals a large facial artery (FAC) compared with the smaller IMA contribution to the face and
nasal arcade. Note the prominent nasal blush in this patient with epistaxis (arrows). (B) Lateral CCA injection reveals a large IMA and
smaller FAC in another patient. Rapid visualization of collateral circulation (C) from IMA to facial territory following FAC embolization
and (D) from FAC to IMA territory demonstrated in two different patients during embolization therapy for epistaxis. Abbreviations:
CCA, common carotid artery; IMA, internal maxillary artery.

arch (Fig. 1.16). These potential pathways of collateral- Lingual Artery

ization are extremely important to keep in mind dur-
ing therapeutic embolization of the APA territory
(23,29). Careful angiographic evaluation of the APA
branching pattern is imperative before therapeutic
embolization is performed.
The lingual artery arises from the anterior surface of
the ECA, loops upward, and proceeds anteriorly
along the hyoid and deep into the hypoglossal
muscle, to supply the ipsilateral tongue, sublingual
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 7

AMA

STA MMA

IMA
SUT

Figure 1.10 Terminal ECA branching. Lateral view demonstrates
the terminal branches of the ECA, the IMA, and the STA. Note
the normal origins of the MMA and AMA from the IMA. Abbrevi-
ations: ECA, external carotid artery; IMA, internal maxillary artery;
STA, superficial temporal artery; MMA, middle meningeal artery;
AMA, accessory meningeal artery; IMA, internal maxillary artery.
Figure 1.11 Superior thyroid artery (SUT). The normal SUT
(arrow) is the first branch of the ECA and provides a dense arterial
blush (*) to the richly vascular thyroid gland. Note the presence of
multiple branches and the incidental anterior communicating artery
aneurysm. Abbreviation: ECA, external carotid artery.

STA

RCCA RCCA

(A) (B) (C)

Figure 1.12 Superior thyroid artery (SUT) pseudoaneurysm: peritracheal bleeding nine days after radical neck surgery, laryngectomy,
and tracheostomy. Oblique RCCA injection demonstrates faint blush from the distal SUT (A) better seen on microcatheter injection (B).
It was successfully embolized with acrylic (C). Abbreviation: RCCA, right common carotid artery. Sources: Endovascular Today (39)
and Neurosurgical Clinics (32).
8 NEUROINTERVENTIONAL MANAGEMENT

APA
Anterior
division
APA
Anterior
APA division
Posterior
division APA
APA Anterior
Posterior division
division
APA

APA

(A) (B) (C)

Figure 1.13 Ascending pharyngeal artery. AP (A) and lateral (B) angiograms of the normal APA that divides into an anterior (pharyng-
eal) and posterior division. Collaterals exist between the posterior division and the vertebral and between the anterior division and the
internal carotid artery. (C) Note the extensive neovascular supply (arrows) from the anterior division of the APA to this JNA. Abbrevia-
tions: APA, ascending pharyngeal artery; JNA, juvenile nasal angiofibroma.

(A) (B) (C)

APA
ICA

(D) (E)

Figure 1.14 Ultrasound pitfalls. (AC) High-grade carotid stenosis misdiagnosed as ICA occlusion by ultrasound. An 80-year-old female
had known bilateral carotid stenoses, which had previously been estimated at 90% on the right by ultrasound 5 months ago. Pulsed Doppler
of right ICA (A) shows increased peak systolic velocity and prominent diastolic flow. The more distal ICA could not be visualized, and the
study reported RICA occlusion. By comparison, pulsed Doppler of the left ICA (B) shows a symmetric appearance of the diastolic flow on the
left as compared with the right. A true occlusion of the RICA would demonstrate no diastolic flow in the ICA proximal to the occlusion. (C) A
CTA 3D volume-rendered image with curved reformation confirms that the right ICA is severely narrowed, but patent. (D, E) APA mistaken
for the ICA by ultrasound. Pulsed Doppler ultrasound (D) image of a patient with congenital absence of the left ICA (same patient as shown
in Fig. 1.32CE) demonstrates an artery in the expected location of the ICA, which has low resistance flow. This vessel was mistaken for the
ICA on initial ultrasound interpretation. A CTA 3D volume-rendered image shows the absent ICA (E). The APA lies parallel to the carotid
sheath, and the presence of APA to ICA anastomoses lead to internalization of the waveform pattern, thus potentially causing confusion on
ultrasound. Abbreviations: ICA, internal carotid artery; APA: ascending pharyngeal artery; RICA, right internal carotid artery.
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 9

APA

APA Extrav Extrav

APA
APA
Acrylic
cast
SUT FAC Coils FAC Coils
Collaterals
(A) (B) (C)

Figure 1.15 APA extravasation (EXTRAV). (A) Lateral CCA injection demonstrates faint extravascular contrast in the region of the
APA. (B) Microcatheter injection reveals frank extravasation. (C) Acrylic injection (CAST) resulted in cessation of bleeding. Abbrevia-
tions: APA, ascending pharyngeal artery; CCA, common carotid artery. Source: Endovascular Today (39).

VRT

APA

Figure 1.16 Artery of the odontoid arch. (A) Selective

APA injection before embolization of skull base giant cell
VRT
tumor (arrows) demonstrates a midline vessel filling the
ART of vertebral artery from the APA. (B) Note the vessel filling
odontoid on the selective vertebral artery injection. Safe emboliza-
arch tion requires the catheter to be positioned distal to the
collateral branch. Abbreviation: APA, ascending phar-
(A) (B) yngeal artery.

gland, pharynx, and hyoid musculature (1,23). It may
occasionally arise from a common trunk with the
facial artery (Fig. 1.17). The lingual artery has a char-
acteristic U-shape on AP and lateral views. Lingual
artery injury, erosion, or laceration may result in
pseudoaneurysm formation and massive bleeding
(Fig. 1.18A,B).
Facial Artery
The facial artery is the third anteriorly oriented ECA
branch. It ascends along the superior constrictor
muscle, passes deep into the stylohyoid and digastric
muscles, and loops over the submandibular gland. It
crosses the anterior aspect of the mandible and
branches into the submental artery inferiorly, to supply
the floor of mouth and submandibular gland. The
facial artery and its superior branches course in an
oblique fashion from the inferolateral aspect of the
face, supplying the lips, face, palate, pharynx, and floor
of the nasal cavity before terminating as the angular
artery near the medial canthus of the eye (Fig. 1.9 and
1.19) (1,23).
Occipital Artery
The occipital artery is the second posteriorly oriented
ECA branch, arising opposite the facial artery. It
passes beneath the posterior belly of the digastric
and sternocleidomastoid muscles providing muscular
10 NEUROINTERVENTIONAL MANAGEMENT

LIN
LIN
LIN
(A) (B) (C)

Figure 1.17 Lingual artery normal. (A) AP and (B, C) lateral early- and late-phase images.

(A) (B)

Figure 1.18 (A) Massive oral bleeding. Axial CTA dem-

onstrates radiation seeds in the tongue/floor of mouth on
the left. A rounded collection of contrast is identified in
the tongue consistent with a lingual pseudoaneurysm
(arrow). (B) CTA coronal reconstruction demonstrates
the pseudoaneurysm (arrow) and correlates with the (C)
AP external carotid arteriogram, where the pseudoaneur-
FAC ysm is identified as arising from the LIN. (D) Lateral ECA
arteriogram demonstrates the markedly irregular lingual
LIN
artery and the contrast extending into the pseudoaneur-
ysm (arrow) arising from the irregular segment. Abbre-
LIN
viations: ECA, external carotid artery; LIN, lingual artery;
(C) (D) FAC, facial artery.

penetrating branches. It courses within the subcuta- Posterior Auricular Artery

neous tissues of the posterior scalp and supplies the
posterior skin, muscle, and meninges of the posterior
fossa (1,24,30). Prominent muscular branches provide
anastomoses between the occipital and vertebral
arteries, particularly in the setting of proximal steno-
sis or occlusion (Fig. 1.20A,B). It is important to
recognize that meningeal branches pass intracranially
through the hypoglossal and mastoid canals as well
as through the jugular foramen. These branches can
become enlarged in the setting of dural arteriove-
nous malformation (Fig. 1.21).
The posterior auricular artery arises from the posterior
aspect of the ECA just above the level of the occipital
artery (23). It may occasionally arise from or as a com-
bined trunk with the occipital artery (30). The stylo-
mastoid branch of the posterior auricular artery enters
the stylomastoid foramen and sends branches to the
chorda tympani within the tympanic cavity, the mas-
toid, and the semicircular canals. The auricular branch
supplies the scalp, the pinna, and the external audi-
tory canal. A prominent but normal vascular blush is
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 11

PSA IMA

Nasal
Collateral
blush

FAC

FAC
Catheter
FAC

(A) (B) (C)

Figure 1.19 Facial artery nasal supply. (A) AP and (B) lateral views of a FAC injection demonstrates marked vascular blush to the
nasal arcade and a focal PSA in this patient with epistaxis. Abbreviations: FAC, facial artery; PSA, pseudoaneurysm.

VRT

Collaterals

OCC TO VRT
OCC Retrograde
ICA VRT flow
catheter Collaterals
Collaterals

OCC OCC

Retrograde
VRT flow

(A) (B) (C) (D) (E)

Figure 1.20 Occipital artery. (A) Lateral selective occipital artery injection demonstrates scalp branches and distal meningeal branches
supplying a hypervascular meningioma (arrows). (B) Lateral common carotid injection demonstrates prompt filling of the vertebral artery
from muscular collaterals of the occipital artery. The anterior circulation fills via the posterior communicating artery in this patient with
occlusive disease of the internal carotid artery. (CE) OCC to vertebral muscular collaterals are demonstrated in this patient with left
subclavian origin occlusion. (C) Reconstitution of the intracranial vertebral artery, while later phase lateral (D) and AP (E) views demon-
strate reconstitution of the cervical vertebral artery and distal subclavian. Abbreviation: OCC, occipital.

noted in the pinna after injection of the posterior
auricular artery (Fig. 1.22). The stylomastoid artery
anastomoses with petrosal branches from the middle
meningeal artery.
Superficial Temporal Artery
The ECA terminates within the parotid gland in the
superficial temporal artery (STA) and the internal
maxillary artery. From its origin within the parotid
gland, the STA proceeds cephalad over the arch of
the zygoma and divides into frontal and parietal
branches. The STA is primarily a cutaneous artery
supplying the anterior two-thirds of the scalp, the
underlying cranium and musculature, and portions of
the parotid gland, ear, and temporomandibular joint
(1,23). Small local branches anastomose with the max-
illary and facial artery branches of the upper portion
of the face. The STA typically supply arteriovenous
malformations involving the scalp (Fig. 1.23). The
superficial course of the STA renders it vulnerable to
direct injury with resultant pseudoaneurysm forma-
tion. The pseudoaneurysms commonly present as
pulsatile lumps on the forehead or scalp following
remote trauma (Fig. 1.24).
Internal Maxillary Artery
The internal maxillary artery courses deep to the
neck of the mandible and enters the infratemporal
fossa. It commonly passes horizontally between the
heads of the medial and lateral pterygoid muscles
and through the pterygomaxillary fissure into the
pterygopalatine fossa (1,4,5,23). Three segmental
divisions of the internal maxillary artery are defined
by the position of the artery relative to the pterygoid
muscle. The first segment gives rise to the inferior
alveolar artery, which extends inferiorly along with
the mandibular nerve to the mandibular foramen
(Fig. 1.25). The middle and accessory meningeal
12 NEUROINTERVENTIONAL MANAGEMENT
LECA
MMA
to
STA MMV
MMA
OCC
Figure 1.21 Enlarged dural branches with dural arteriovenous
malformation. Lateral ECA arteriogram demonstrates an
enlarged middle meningeal artery with shunting into the trans-
verse sinus and middle meningeal vein. In addition, there are
enlarged dural branches of the occipital artery shunting into the
abnormal, distally occluded transverse sinus. The STA is normal
in size and does not provide AVM supply. Note the X markers
from the Gamma Knife frame. Abbreviation: ECA, external car-
otid artery, STA superficial temporal artery.
arteries pass through the foramen spinosum and
ovale, respectively. The middle meningeal artery has
a characteristic curve as it exits the foramen spino-
sum that parallels the floor of the sella on lateral
angiogram. The meningeal branches can be differen-
tiated from the scalp branches by their straight
rather than tortuous course. Remembering that you
can wrinkle your forehead, but you cannot wrinkle
your dura is a helpful key to differentiating these
branches (Fig. 1.26). The middle meningeal artery
may vary in size and may occasionally give rise to,
or arise from, the ophthalmic artery (31). The deep
auricular artery that supplies the external auditory
canal and the anterior tympanic artery that supplies
the tympanic membrane both arise from the first
segment of the internal maxillary artery. The ptery-
goid segment (middle) is located in the high, deep
masticator space and gives rise to masseteric, buccal,
and deep temporal arteries. These supply the ptery-
goid and temporalis muscles and the lingual and
buccal nerves. The third or sphenopalatine segment
of the internal maxillary artery lies within the ptery-
gopalatine fossa and sends branches along with each
nerve to the pterygopalatine ganglion (Fig. 1.27). It
terminates in multiple branches to the nasal cavity
supplying both nasal wall and septum. The posterior
superior alveolar artery supplies the palate and
posterior wall of the maxilla. The infraorbital artery
passes through the infraorbital fissure along the
orbital floor.
External Carotid Anastomotic Network
The importance of external carotid to internal carotid
collaterals and potential anastomotic pathways cannot
be overemphasized in the setting of disease and neu-
rointervention (23,29,30,32). These interconnections are
dynamic and may change in appearance and flow rate
during the interventional procedure, becoming most
dangerous near the end of the procedure. The IMA
has numerous extensive anastomoses with other ECA
branches in the face. It is clinically relevant to appreci-
ate the extensive collateral network between the lin-
gual, facial, and internal maxillary artery branches. A
complex hemodynamic balance exists between these
pedicles. If a hypoplastic facial artery is present, large
buccal and masseteric branches will be present from
the internal maxillary artery, and vice versa
(Fig. 1.9, 1.19). During embolization therapy for epis-
taxis, it is not uncommon to appreciate anastomotic
branches restoring proximal flow to an embolized ter-
ritory (Fig. 1.28).
External carotid to internal carotid anastomoses
exist, and flow may proceed in either direction
depending on the location and nature of the diseased
vasculature. The distal ethmoidal branches of the IMA
anastomose with distal ethmoidal branches of the
ophthalmic artery. Thus the IMA, via these ethmoidal
collaterals, may provide a supply route to the supra-
clinoid ICA via reversal of flow through the ophthal-
mic artery. The vidian artery anastomoses with the
petrous ICA. The artery of the foramen rotundum and
the inferolateral trunk anastomose with the cavernous
ICA. These ECA-ICA anastomoses vary to a signifi-
cant degree among patients and offer a clinically sig-
nificant collateral pathway between the ECA and the
ICA systems, seen most prominently in the setting of
occlusive vascular disease (Fig. 1.29A,B) (23,29). With
occlusion of the ECA, ICA branches may collaterally
restore external carotid flow (Fig. 1.30) (23,29).
Internal Carotid Artery
The ICA enters the skull base through the carotid
canal ascending anterior to the jugular bulb and poste-
rior to the eustachian tube (1,4,5,33). The ICA petrous
segment courses anteromedially to the tympanic cav-
ity, giving rise to the caroticotympanic artery (to the
tympanic cavity), the vidian artery, and small perios-
teal branches (34). The ICA courses superiorly, extend-
ing above the foramen lacerum to pierce the dura and
enter the posterior aspect of the cavernous sinus
(Fig. 1.31). The ICA is occasionally congenitally absent
and can be differentiated from acquired occlusion by
the absence of the carotid canal at the skull base
(Fig. 1.32A,B) (35).
Nomenclature varies, but the four-part division
of the internal carotid, designated as C1C4 and
described in the radiology and surgical literature, is
useful. The cervical segment (C1) begins proximally at
the origin of the ICA with the CCA and extends ceph-
alad to the external orifice of the carotid canal. The
petrous segment (C2) traverses the carotid canal and
enters the cavernous sinus (dura), where the caver-
nous segment (C3) begins. The cavernous segment
ends where the ICA pierces the dural roof of the
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 13

MMA

Nasal
arcade
OCC PAA

IMA

(A) (B)

AVM
fistula

AVM

AVM venous
drainage

PAA PAA

IMA
OCC OCC

EJV
(C) (D)

Figure 1.22 PAA supplying AVM of the left Pinna. (A) MRA 3D TOF axial source image demonstrates enlargement of the left pinna
and increased signal intensity consistent with hypervascularity. Digital AP (B) and early- and late-phase lateral (C, D) views of a selec-
tive OCC artery injection demonstrate the PAA arising from the OCC (a normal variant) and a prominent blush with early venous drain-
age into the external jugular system secondary to a high-flow AVM of the pinna. Abbreviations: AVM, arteriovenous malformation;
OCC, occipital; PAA, posterior auricular artery; TOF, time of flight.

VEIN

STA

STA
STA

(A) (B)

Figure 1.23 Scalp AVM. (A, B) AP and lateral selective STA angiograms demonstrate the enlarged feeders from the anterior division
of the STA to an AVM of the scalp. Note the normal size of the STA posterior division and the early draining vein. Abbreviations:
STA, superficial temporal artery; AVM, arteriovenous malformation.
14 NEUROINTERVENTIONAL MANAGEMENT

STA

STA MMA MMA

AMA
STA
Figure 1.24 STA pseudoaneurysm. (A, B) Two patients
with typical STA aneurysms (arrows) following direct
trauma. Note the typical hairpin turn of the STA as it
courses over the zygoma. Abbreviations: STA, superficial
(A) (B) temporal artery; MMA, middle meningeal artery.

LT
INT STA ACM
MMA
MAXILLARY

MMA
STA
2ND

3RD
3RD
2ND

1ST 1ST Figure 1.25 Internal maxillary artery. (A, B) AP and

lateral selective IMA injections demonstrate the three
segments and the important branches. Abbreviations:
IMA, internal maxillary artery; MMA, middle meningeal
artery; ACM, accessory meningeal artery; STA, super-
(A) (B) ficial temporal artery.

OPH
STA

MMA*

Figure 1.26 Middle meningeal artery variations. The

STA ophthalmic artery arises from the MMA in this patient.
The reverse can also occur, posing potential problems
IMA for embolization. Note the curve of the MMA at the skull
MMA base is similar to the curve of the sella(*). Abbrevia-
tions: MMA, middle meningeal artery.
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 15

MMA
Distal IMA
STA

Figure 1.27 IMA nasal arcade (A) AP DSA injection into

the distal ECA demonstrates the branches of the internal
maxillary artery and the nasal arcade (arrows). Note the
STA and MMA arteries. (B) Magnified superselective AP
view better demonstrates the nasal arcade and promi-
nent mucosal blush in this patient with epistaxis. Abbre-
viations: IMA, internal maxillary artery; DSA, digital
IMA subtraction angiography; ECA, external carotid artery;
STA, superficial temporal artery; MMA, middle meningeal
(A) (B) artery.

Nasal supply

OPH

T-meet: OPH
2.13
ICA Image:

(A) (B)

Nasal supply

Nasal
supply

Choroidal
OPH blush Choroidal blush
(C) (D)

Figure 1.28 Epistaxis: the importance of ophthalmic collaterals. (A) ICA injection at the time of initial epistaxis embolization demon-
strates normal terminal ophthalmic artery branches. (BD) One month later, the patient presents with recurrent epistaxis, and sequen-
tial ICA images demonstrate reconstitution of the nasal arcade by ophthalmic collaterals. Abbreviation: ICA, internal carotid artery.

cavernous sinus. The supraclinoid segment (C4)
begins where the ICA exits the dural ring and enters
the subarachnoid space, and it ends at the internal
carotid bifurcation into anterior and middle cerebral
artery branches (34,36). The supraclinoid segment
passes medially to the anterior clinoid and below the
optic nerve. Together, the C3 and C4 segments form
the characteristic S shape seen on lateral and obli-
que angiographic views of the skull base. C1 does not
normally provide any branches. C2 gives rise to three
potential branches: the caroticotympanic branch sup-
plying the middle and inner ear; the vidian artery, or
the artery of the pterygoid canal, which goes through
the foramen lacerum; and the artery of the foramen
16 NEUROINTERVENTIONAL MANAGEMENT

ETH
STA
ETH ICA ICA
Ethmoidals
OPH
OPH

IMA MMA VRT Figure 1.29 Extensive collaterals to the petrous, caver-
Vidian
MMA nous, and supraclinoid ICA from the branches of the
internal maxillary artery. (A) IMA to OPH to ICA ethmoi-
dal collaterals. (B) Vidian artery and inferolateral trunk
OCC to the petrous ICA. Note the occipital to vertebral artery
muscular collaterals. Abbreviations: ICA, internal caro-
tid artery; AMA, accessory meningeal; MMA, middle
(A) (B) meningeal artery; OPH, ophthalmic artery.

PICA

OCC
ASP
VRT
COL Figure 1.30 Restoration of ECA flow. (A) Lateral CCA
OCC arteriogram demonstrates extravasation of contrast
from the proximal ECA at the origin from the carotid
COL
Extrav bulb. Note the radiation seeds and the small occipital
artery identified before embolization. (B) Following par-
tial embolization of the ECA and occlusion of the right
CCA. Control arteriogram demonstrates filling of the
Extravasation ipsilateral vertebral artery with filling of a large muscular
collateral with reconstitution of the occipital artery and
VRT retrograde filling of the ECA with continued extravasa-
CCA tion into the pharynx. Control of bleeding required par-
ticulate embolization for occlusion and disconnection of
the muscular collateral to the occipital artery. Abbrevi-
CCA
ations: ECA, external carotid artery; CCA, common car-
(A) (B) otid artery.

rotundum (35,36). C3 gives rise to three trunks. The
posterior trunk, or the meningohypophyseal trunk,
branches into the tentorial artery (of Bernasconi and
Casinari) supplying the tentorium, the inferior hypo-
physeal artery supplying the posterior pituitary cap-
sule, and the dorsal meningeal artery supplying the
abducens nerve and the clivus (35,36). The lateral
trunk, or inferior cavernous sinus artery, supplies the
inferolateral cavernous sinus wall and region of the
foramen ovale and spinosum. The medial trunk, or
McConnels capsular artery, supplies the anterior and
inferior pituitary capsules and is present in only 28%
of the population (33,34,36). A pituitary blush is com-
monly identified on lateral internal carotid arterio-
grams. These small branches become important in the
analysis of skull base tumors and provide potential
anastomoses with external carotid branches in the set-
ting of disease (Figs. 1.32 and 1.33) (33,34,36).
VEINS OF THE HEAD, NECK, AND SKULL BASE
The venous drainage of the face is predominantly
superficial and empties into the external jugular
drainage pathways (1,4,5). The supraorbital and
supratrochlear veins of the face join to become the
angular vein and proceeds as the facial vein over
the angle of the mandible (1,4,5). The pterygopalatine
venous plexus is located around and within the
lateral pterygoid muscle. It may be recognized on CT
as a focal area of irregular enhancement adjacent
to the muscle. It is often identified as a variation in
the cerebral venous drainage pattern on cerebral
angiography, receiving flow from the greater middle
cerebral (sylvian) vein (Fig. 1.34A,C). The pterygopa-
latine venous plexus drains into a pair of maxillary
veins, which lie deep in the neck of the mandible
and join with the temporalis vein draining the
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE 17

Tuberculum

AChA
PCoA A P
Dural ring

(A) (B)

BAS
Clinoid

Trigeminal ICA
artery
Trigeminal artery
(C) (D)

Figure 1.31 The dural ring. The ICA enters the cavernous sinus dura, traverses the sinus and exits at the dural ring. This patient pre-
sented with SAH and demonstrates and ICA posterior wall aneurysm. The arrow marks the location of the dural ring on the conven-
tional angiogram (A) and on 3D CTA (B). The trigeminal artery is a primitive communication between the cavernous carotid segment
and the distal one-third of the basilar artery identified on conventional angiogram (C) and on 3D CTA (D). Abbreviations: ICA, internal
carotid artery; SAH, subarachnoid hemorrhage.

LICA

Ovale

CC

(A) (B) (C)

Normal
ICA
Normal
ICA

(D) (E)

Figure 1.32 ICA anomalies. (A) CT and (B) AP angiogram demonstrate the aberrant ICA with the characteristic lateral position of the
ICA (arrow) projecting into the middle ear cavity behind the tympanic membrane. The carotid canal is incomplete and the carotid is usu-
ally narrowed just distal to the middle ear segment. (C) CT and (D, E) CTA in agenesis of the ICA demonstrate absence (*) of the caro-
tid canal in addition to the absence of the ICA. Abbreviation: ICA, internal carotid artery.
18 NEUROINTERVENTIONAL MANAGEMENT

IPS

IJV Facial
vein

IJV IJV Facial

EJV
veins
EJV EJV

(A) (B) (C)

SOV

Facial
vein

Facial
nasal
branch
Nasal
blush

(D) (E)

Figure 1.33 Cervical and facial veins. (A) The proximal internal and external jugular veins are demonstrated as approached from the
femoral route. (B, C) Facial veins drain into the EJV. (D, E) Nasal and facial structures may drain superiorly into the superior and or
inferior ophthalmic veins. Abbreviations: EJV, external jugular vein; SOV, superior ophthalmic veins.

Sylvian
vein

PVP

(A) (B) (C)

Figure 1.34 Prominent PVP. (A) Axial CTA image demonstrates asymmetry of the PVP, prominent on the left (arrows)possible nor-
mal variant versus AVM. Digital subtraction images of the venous phase after ICA injection in AP (B) and lateral (C) projections demon-
strate a prominent sylvian (greater middle cerebral) vein (arrows) draining into an unusually large PVP (arrow), which subsequently
drains into the external jugular vein. This arrangement is a normal anatomic variant. Abbreviations: PVP, pterygopalatine venous
plexus; AVM, arteriovenous malformation; ICA, internal carotid artery.
 VASCULAR ANATOMY OF THE HEAD, NECK, AND SKULL BASE
IPS
SIG
Cervical IJV
veins
(A) (B)
Figure 1.35 Veins at the skull base. (A) Late venous-phase DSA image in AP projection after arterial injection shows the normal
course of the skull base venous sinuses. (B, C) DSA images in AP and lateral projections demonstrate the course of the IPS, which is
oriented medially and anteriorly. (D) DSA image in AP projection from another patient after right IJV injection demonstrates venous
communication with contrast filling the right IPS and refluxing into the left IPS. Note the cavernous sinus filling. Abbreviations: DSA,
digital subtraction angiography; IPS, inferior petrosal sinus; SIG, sigmoid sinus; IJV, internal jugular vein.
temporal region of the face and scalp to form the
retromandibular vein. The inferior ophthalmic vein
travels with the infraorbital artery and drains into
the cavernous sinus intracranially and the pterygopa-
latine venous plexus extracranially.
Occasionally, the facial veins will drain superi-
orly into the ophthalmic veins and into the cavernous
sinus as a normal variation in the absence of shunting
(37). The retromandibular vein passes through the
parotid gland and divides into anterior and posterior
branches that drain into the internal and external jug-
ular veins, respectively. The deep facial vein repre-
sents the anastomosis between the pterygopalatine
venous plexus and the facial vein. The anterior jugular
veins lie in the submental region extending inferiorly
to the suprasternal notch, where they communicate
with the external jugular vein deep to the sternoclei-
domastoid muscle. The external jugular also receives
the posterior auricular vein. The external jugular vein
empties into the subclavian vein near the midpoint of
the clavicle. The internal jugular vein originates from
the jugular bulb receiving blood from the sigmoid
sinus and its first extracranial tributary, the inferior
petrosal sinus (Fig. 1.35AC) (37,38). It descends
behind the ICA directly adjacent to the arch of C1,
where it joins the subclavian vein to become the bra-
chiocephalic vein. The left brachiocephalic vein joins
at the right of the second costal cartilage to become
the superior vena cava.
SUMMARY
Knowledge of the normal and variant anatomy of the
head, neck, and skull base is critical to the under-
standing of its vascular pathology and to the safe per-
formance of diagnostic and therapeutic angiographies.
Correlation with cross-sectional imaging is useful in
the anticipation of vascular supply and dangerous
anastomoses.
19
IPS SIG Intercavernous
IPS ICA
IPS
Cervical Cervical
veins IJV veins
(C) (D)
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 2
Applied neurovascular anatomy of the brain and skull
Michael J. Cirivello, Randy S. Bell, and Rocco A. Armonda
INTRODUCTION
Endovascular methods have expanded the way we
evaluate, follow, and ultimately treat vascular pathol-
ogy. Whether in conjunction with open surgical proce-
dures or in isolation, neurointerventional tools have
enabled previously untreatable conditions to be
tackled within acceptable margins of safety. Advances
continue to expand the array of pathologies treatable
through less invasive approaches. The benefit to the
patient manifested by increased success rates, shorter
hospital stays, and reduced morbidity and mortality
cannot be overstated. However, the utility of even the
most advanced biplanar machine with 3D rotational
capabilities is limited without a thorough understand-
ing of the craniocerebral angiographic anatomy. This
must include the significant arterial anastomoses and
collateral circulatory patterns that should be consid-
ered during any intervention. It is collateral circula-
tion that may prevent significant neurologic deficit
should parent artery occlusion be required. Con-
versely, circulatory anastomoses can result in unex-
pected patterns of infarct distal to the areas of
embolization or parent artery occlusion if not appro-
priately anticipated. The purpose of this chapter is to
provide an in-depth review of the normal cerebrovas-
cular angiographic anatomy as well as the significant
internal, external, and vertebrobasilar anastomoses to
be considered during treatment. The importance of
the contribution of individual anatomy in the formula-
tion of any treatment plan is paramount. Because
thorough reviews of anatomic variants have been pro-
vided elsewhere (15), only brief descriptions will be
highlighted here where considered relevant.
INTERNAL CAROTID ARTERY
The internal carotid artery (ICA) originates from the
common carotid artery in the neck at the approximate
level of the fourth cervical vertebrae. Though several
segmental naming schemes exist, this chapter will
refer to that provided by Bouthillier that follows a log-
ical numerical classification with anatomic correlations
in the direction of blood flow (6). The cervical seg-
ment (C1) ascends to the base of the skull without
producing any branches (Fig. 2.1). It enters the skull
through the carotid canal to become the horizontal
petrous portion (C2). This segment is seen as the first
medial turn on a standard AP projection, and the first
anterior turn on a lateral projection (Figs. 2.1 and 2.2).
The vidian and caroticotympanic branches originate
from this segment. The artery then exits the petrous
bone and for a short distance becomes the lacerum
segment (C3) before crossing under the petrolingual
ligament toward the cavernous sinus. Angiographi-
cally, this is represented by a 90 degree superior curve
from the horizontal petrous portion. The lacerum seg-
ment gives off no branches; however, the foramen
does receive the recurrent artery of the foramen lac-
erum from the inferolateral trunk (C4). Just distal to
this curve begins the cavernous portion (C4). The seg-
ment is manifested as a double arterial density on a
standard AP projection and an anteriorly projecting
hairpin turn on a lateral projection. Branches within
this segment include the meningohypophyseal trunk,
the inferolateral trunk, and McConnells capsular
arteries. The meningohypophyseal trunk gives rise to
the marginal and basal tentorial arteries, the dorsal
meningeal (lateral clival) branch, and the inferior
hypophyseal artery. The medial tentorial artery is also
known as the artery of Bernasconi and Cassinari
(important during embolization of tentorial meningio-
mas or tentorial AVMs (Figs. 2.3 and 2.5)). The infero-
lateral trunk, a vestige of the embryonic dorsal
ophthalmic artery, includes a branch to the superior
orbital fissure, the artery of the foramen rotundum,
the artery of the foramen ovale, the recurrent artery of
the foramen lacerum, and a posteriorly directed
branch along the course of the IVth cranial nerve to
supply the tentorium. A collateralized vascular net-
work in the paracavernous dura exists to connect the
internal carotid artery, the middle meningeal and
accessory meningeal artery, the ophthalmic artery, the
meningohypophyseal- and inferolateral trunks, and
the ascending pharyngeal artery (4). The cavernous
segment then progresses caudally and laterally as it
exits the cavernous sinus and enters through the prox-
imal dural ring to become the clinoid segment (C5).
This short, extradural segment is wedge shaped and
is comprised of the space between the proximal and
distal dural rings. After exiting the distal ring into the
subarachnoid space, the ophthalmic segment (C6)
begins, marked consistently on the lateral angiogram
by the ophthalmic artery. The superior hypophyseal
artery is present in this segment, often not visualized
on angiogram until aneurysmal dilatation occurs.
When present, this aneurysm often projects medially
on an AP projection, distinguishing it from other
branch origins. The posterior communicating artery
22 NEUROINTERVENTIONAL MANAGEMENT

indicates the beginning of the communicating segment
that continues until the bifurcation of the anterior cer-
ebral (ACA) and middle cerebral arteries (MCA).
Included in this segment is the anterior choroidal
artery, the final branch of the ICA that may arise from
the posterior communicating artery, or may appear as
a more proximal branch.
OPHTHALMIC ARTERY
The ophthalmic artery arises from the anterior wall of
the internal carotid artery as its first intradural branch.
It then travels in an anterior direction and enters the
orbit through the optic canal along with the optic
C1
nerve. On the lateral angiogram, the ophthalmic has a
characteristic bayonet-like course and a sharp upturn
as it courses over the dorsal aspect of the optic nerve
(Fig. 2.4). In 8% of cases, the artery may arise from
within the cavernous sinus with entry via the superior
orbital fissure (2). As a result of the variable outcomes
of the fetal hyoid-stapedial artery, the middle menin-
geal artery may incorporate the ophthalmic territory
or, conversely, a recurrent meningeal branch may
intermittently arise from the orbital portion of the
ophthalmic traveling back through the superior orbital
fissure to supply the meninges in that area.
The ophthalmic artery continues forward and
gives rise to the anterior and posterior ethmoidal
arteries that can occasionally have a pathological cor-
relation with anterior fossa meningiomas and vascular
malformations. The remaining terminal branches of
the ophthalmic artery are the central retinal, lacrimal,
long and short ciliary, supraorbital, medial palpebral,
infratrochlear, supratrochlear, and dorsal nasal arteries
(2). Significant collateral circulation exists between the
ophthalmic artery and the internal maxillary (long
sphenopalatine communication via the ethmoidal
arteries), the middle meningeal (via the ethmoidal
arteries), and the superficial temporal artery (via the
lacrimal and zygomatic-orbital arteries) (1,3). Anticipa-
tion of these anastomotic pathways becomes critical
when performing external carotid embolizations. The
central retinal artery has essentially no collateral path-
ways and inadvertent occlusion can result in
blindness.

POSTERIOR COMMUNICATING ARTERY

Figure 2.1 Lateral view of a right common carotid angiogram at
the level of the bifurcation into the ICA and ECA. The C1 extrac-
ranial segment is demonstrated beginning at the proximal ICA
and ending at the petrous canal.
The posterior communicating artery arises from the
postero-medial aspect of the internal carotid artery
(Fig. 2.5). It terminates at the posterior cerebral artery
and is the boundary between the P1 and P2 segments
of that artery. Anatomically, it courses below the edge
of the tentorium just superior to the third cranial
nerve. As a result of this proximity, aneurysms arising
in this location may present with an oculomotor palsy
with loss of pupillary reflex from direct compression.
In approximately 2030% of cases, the posterior
communicating artery is larger than the PCA or fails
to fuse with the PCA and becomes the dominant

C7 C6 Figure 2.2 AP (A) and lateral (B) projections of

C6 C7 a right ICA showing the segmental scheme
of Bouthillier. C2 spans the entrance and exit of
C5 C4
C5 the petrous bone shown by the solid black lines.
C4 The short C3 segment ends at the petroclival
C3
ligament represented by the white double lines.
C2 C3 C2 The C4 represents the cavernous segment end-
ing at the proximal dural ring. The segregation
C1 of the C5 clinoid segment, C6 ophthalmic seg-
C1
ment, and C7 communicating segment are rep-
(A) (B) resented by the dashed lines.
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL
Figure 2.3 Lateral ICA injection reveals a dilated marginal tento-
rial artery (arrows), commonly referred to as the artery of Ber-
nasconi and Cassinari, feeding a choroidal AVM with dual dural
and pial supply. The branches of the intercavernous MHT (white
arrow) include the marginal tentorial artery, the basal tentorial
artery, the inferior hypophyseal artery, and the clival branches.
Abbreviations: MHT, meningohypophyseal trunk; AVM, arteriove-
nous malformation.
LA
AeA
PeA
CrA
Figure 2.4 Ophthalmic artery with the appearance on the lateral
angiogram similar to an upturned saber. Observe the superior
turn of the artery as it courses over the optic nerve (arrow). Sig-
nificant terminal branches are noted. Abbreviations: LA, lacri-
mal artery; CrA, central retinal artery; PeA, posterior ethmoidal
artery; AeA, anterior ethmoidal artery.
23
circulation to the PCA territory (Fig. 2.6) (1,2,5). The
fetal-type PCA may course more laterally relative to
the third nerve compared with the normal course.
There are multiple, small perforating arteries
that arise from the posterior communicating artery.
The largest of these arteries is called the premamillary
artery (Fig. 2.5) (1,2). The thalamoperforating arteries
are divided into anterior and posterior perforating
arteries. The anterior perforators typically arise from
the posterior communicating artery to supply neuro-
logic tissue within the posterior limb of the internal
capsule, the anterior thalamus, the posterior hypothal-
amus, and the anterior one third of the optic tract.
Posterior perforators penetrate the rostral midbrain
and supply the subthalamic nucleus (1).
ANTERIOR CHOROIDAL ARTERY
The anterior choroidal artery is the last named branch
arising from the ICA prior to its bifurcation (Figs. 2.5
and 2.7). The anterior choroidal artery generally arises
from the posterior ICA distal to the posterior commu-
nicating artery but has been found in some studies to
occasionally arise directly from the posterior commu-
nicating artery (7). It travels in a posterolateral direc-
tion coursing through the carotid, crural, and ambient
cisterns toward the choroidal fissure and the choroid
plexus of the temporal horn of the lateral ventricle.
Like all choroidal arteries, it is divided into two seg-
ments: the cisternal (within the basal cisterns) and
plexal (intraventricular). Important perforating vessels
arise from the cisternal segment to supply the optic
tract, the internal capsule, the mesial temporal lobe,
Figure 2.5 Posterior communicating artery (white arrow) con-
necting the tip of the basilar (open arrow) and the PCA (curved
arrow) is demonstrated. The premamillary artery (double arrows)
can be seen arising off the middle of the posterior communicat-
ing artery. The anterior choroidal (black arrow) is also seen in
this view. Abbreviations: ICA, internal carotid artery; PCoA,
posterior communicating artery.
24 NEUROINTERVENTIONAL MANAGEMENT
Figure 2.6 Lateral ICA angiogram demonstrating a fetal-type
PCA (arrow). When the PCoA is larger than the ipsilateral P1
segment, it is classified as fetal-type circulation. When non-
opacification of a PCA occurs during a vertebral artery injection,
occlusion must be ruled out. This can be performed by an injec-
tion of the ipsilateral carotid and confirming fetal-type circula-
tion. Abbreviations: PCA, posterior cerebral artery; PCoA,
posterior communicating artery.
Figure 2.7 Contributions to another choroidal AVM including the
posterior communicating artery (white arrow), anterior choroidal
artery (black arrow), and the marginal tentorial artery (open
arrow). The choroidal point is clearly represented in this image
(dashed arrow). Abbreviations: DAVF, dural arteriovenous fis-
tula; MHT, meningohypophyseal trunk.
the geniculocalcarine fibers and the lateral geniculate
body. Once passing through the choroidal point and
entering the lateral ventricle there is a relative paucity
of perforators and the terminal vessels to the choroid
plexus receive abundant collaterals from posterior
choroidal anastomoses.
Clinical Considerations
Occlusion of the anterior choroidal artery produces a
classic clinical syndrome of hemiparesis, hemihypes-
thesia, and hemianopsia first described by Foix in
1925 (8). The anterior choroidal arterys small vessel
caliber and the lack of collateral circulation to its cis-
ternal end distribution predispose this territory to
ischemia from occlusion, whether temporary or per-
manent. This is unfortunate given that vascular mal-
formations and aneurysmal dilatation of this artery
are not altogether infrequent occurrences (Fig.2.8). The
degree to which a patient suffers from the aforemen-
tioned syndrome will vary according to both individ-
ual anatomy and the location of the arterial occlusion.
Early data from clip exclusion of aneurysms of the
anterior choroidal artery reveal a high percentage of
post-operative deficits (9). Endovascular therapies have
proven more successful in comparison and several case
series report excellent outcomes with both coiling and
stent/coiling of anterior choroidal aneurysms (10). A
more problematic area of interventional treatment exists
within embolization of the anterior choroidal artery for
arteriovenous malformations. The commonly accepted
belief is that distal to the plexal point, the intervention-
alist is safe to deliver embolic material and perform a
vessel sacrifice, as this is distal to the cisternal perfora-
tors as previously mentioned. In many cases, this may
be achieved with satisfaction; however, case reports and
anecdotal accounts of complications arising from embo-
lizations in this safe zone certainly encourage caution
in this undertaking (11).
PERSISTENT CAROTICOBASILAR
ANASTOMOSES
Persistent fetal circulatory patterns are the remnants of
transient segmental connections between primitive fore-
brain and hindbrain systems. The failure of involution
leads to a permanent anastomosis between the carotid
and basilar arteries. With the exception of the pro-
atlantal arteries, the vessels are named after the cranial
nerve they parallel and include the persistent trigemi-
nal, otic, and hypoglossal arteries (Fig. 2.9) The trige-
minal artery is the most common, occurring in 0.2
0.3% of the general population (Figs. 2.10 and 2.11)
(1,35). This artery arises from the pre-cavernous caro-
tid and anastomoses with the basilar artery. These
structures have also been associated with other vascu-
lar malformations (Fig. 2.11B) (1215). The elusive otic
artery is extremely rare and its existence continues to
be a matter of dispute among angiographers (15,16).
Its origin arises from the petrous portion of the caro-
tid artery and traverses through the IAC to terminate
at the mid-basilar artery. The persistent hypoglossal
artery is the second most common fetal anastomosis
and arises from the extracranial internal carotid artery,
passes through the anterior condyloid foramen, and
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL
(A)
Figure 2.8 Pre- and post-embolization of a sylvian fissure AVM occurring past the choroidal point (arrow) but resulting in a homony-
mous hemianopsia. Abbreviations: AVM, arteriovenous malformation.
terminates at the proximal basilar artery. The persistent
pro-atlantal artery is a primitive anastomosis between
the ICA or ECA and the cervical vertebral artery.
Clinical Considerations
The presence of persistent fetal circulations should be
ruled in or out before certain procedures. Wada test-
ing is employed to localize language and memory
dominance prior to partial or complete amygdalohip-
pocampectomy. During this test, Sodium amobarbital
is injected into the internal carotid artery on one side
to effectively anesthetize the ipsilateral hemisphere.
Should a persistent fetal circulation exist, the target of
the amobarbital would be the brainstem, potentially
resulting in respiratory arrest, stroke, or death (3). In
this case, it would be necessary to select the artery
distal to the persistent fetal circulation to avoid this
complication. The same principle applies to test bal-
loon occlusions (17).
Combined anterior and posterior circulation
strokes in the setting of persistent caroticobasilar con-
nections and concomitant carotid artery disease can
confuse the clinician by mimicking the presentation of
cardioembolic disease. Among the list of complica-
tions for carotid endarterectomy in the setting of a
persistent hypoglossal or trigeminal artery is the pos-
sibility of brainstem infarct from a fractured embolus
after the balloon dilatation (18,19). In this setting,
placement of the distal embolic umbrella proximal to
the fetal anastomosis could minimize the risk of such
a complication.
ANTERIOR CEREBRAL ARTERY
The anterior cerebral artery can be broken down into
five anatomical segments based on its location with
25
(B)
respect to the underlying corpus callosum (Fig. 2.12).
The A1 segment, or the pre-communicating segment,
extends from the ICA bifurcation to the anterior com-
municating artery. There are small perforating
branches that feed the optic chiasm, hypothalamus,
and lamina terminalis. The recurrent artery of Heub-
ner may occasionally arise from this segment, though
it primarily originates from A2 and contributes to sup-
ply of the head of the caudate, anterior limb of the
internal capsule, the paraterminal gyrus, and anterior
third of the putamen. The remaining post-communi-
cating segments include the infracallosal (A2), the pre-
callosal (A3), the supracallosal (A4), and the
postcallosal/splenial (A5). The A2 segment begins at
the anterior communicating artery and extends to the
bifurcation of the pericallosal and callosomarginal
arteries. The frontopolar and orbitofrontal arteries
arise from this segment (Fig. 2.13). Subserved neuro-
logic tissue includes the hypothalamus, septum pellu-
cidum, anterior commissure, columns of the fornix,
and portions of the basal ganglia. The A3 segment
includes the callosomarginal and the pericallosal
arteries. The A4-5 segments involve the terminal
branches of the ACA including those arteries that pro-
vide collateral flow to certain areas within the MCA
and PCA distributions.
Clinical Considerations
The anterior cerebral artery and its branches supply
the cortex within the medial frontal lobes and antero-
medial parietal lobes. This area includes the cingulate
cortex and the paracentral lobule with damage mani-
fested as lower extremity paresis or memory impair-
ment (2022). Surgical approaches to vascular
pathology in this area are technically challenging
owing to possible disruption of the superior sagittal
26 NEUROINTERVENTIONAL MANAGEMENT
e C1
ICA
Vert
C2
Figure 2.9 Lateral angiographic graphic representation of the
types of persistent fetal circulation. A fetal posterior cerebral
artery (A) is shown, though common enough to be considered a
normal variant. The persistent trigeminal artery (B) originates
from the cavernous segment of the internal carotid artery and
terminates at the basilar artery. The persistent otic artery (C)
originates from the petrous portion of the ICA and terminates at
the proximal basilar artery. Both the persistent hypoglossal (D)
and persistent pro-atlantal (E) arteries arise from the extra-
cranial internal carotid artery and terminate at the vertebral
artery. C1 and C2 indicate the location of the first and second
cervical vertebrae.
sinus, neurologic consequences of frontal lobe retrac-
tion, and variable anatomy (22,23).
Endovascular treatments of distal ACA pathol-
ogy can also be technically demanding due to vessel
tortuosity and reduced distal vessel caliber. However,
the possible neuropsychiatric consequences of open
surgery can be avoided with endovascular treatment.
Use of platinum coils in narrow necked, distal ACA
saccular aneurysms is a reasonable approach because
the anterograde flow through the preserved parent
artery may be possible. In more difficult cases, it may
be necessary to sacrifice the parent artery when bal-
loon remodeling or stent-assisted coiling of a wide
necked or fusiform aneurysm is not feasible. Parent
artery occlusion proximal to the pericallosal-calloso-
marginal artery bifurcation (A2-3) may result in some
or all of the neurologic consequences previously out-
lined. Occlusion distal to this vessel segment may be
clinically silent secondary to the extensive collateral
circulation between the anterior and posterior cerebral
circulation through the posterior pericallosal and sple-
nial arteries. Kim et al. (24) describe an elegant com-
bined open surgical and endovascular approach to an
A2 aneurysm where the distal artery arose from the
Figure 2.10 Lateral ICA unsubtracted angiogram demonstrating
a large persistent trigeminal artery leaving the cavernous carotid
(C4) and entering the basilar artery. Note the filling of both the
PCA and SCA distributions and the absence of the basilar artery
filling proximal to the anastamosis. Abbreviations: ICA, internal
carotid artery; PCA, posterior cerebral artery; SCA, superior cer-
ebellar artery.
aneurysm dome. In this case, a side-to-side perical-
losal-pericallosal anastomosis was performed prior to
unilateral endovascular parent artery occlusion of the
A2 segment. This resulted in preservation of distal
flow to both hemispheres and obliteration of the com-
plex aneurysm.
Anomalies at the anterior communicating com-
plex tend to be the norm rather than the exception
(1,3,4,25). Variability in this area causes abnormal flow
dynamics that commonly gives rise to aneurysmal
dilatation, particularly in the setting of a hypoplastic
A1 segment. The corresponding pressure created from
the dominant A1 segment against the anterior wall of
the anterior communicating artery is thought to give
rise to the large number of anteriorly projecting aneur-
ysms in this location. Other anomalies, such as a sin-
gle azygos ACA (Fig. 2.14), are also risk factors for
developing aneurysms because of similar circumstan-
ces (25).
A thorough understanding of what constitutes
normal vessel location, caliber, and contour can pre-
vent unrecognized patterns of shift, spasm, and occlu-
sion. Although the identification of intracranial
masses and midline shift on angiography is often rele-
gated to a historical discussion given the far better
localization on CT and MRI, the interventionalist must
be careful not to miss immediate signs of hydrocepha-
lus or hematoma secondary to an intraprocedural rup-
ture. Given the mobility of the proximal ACA vessels
in relationship to the falx and its inherent midline and
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL 27

(A) (B)

Figure 2.11 Digital 3D reconstruction of two different patients with PTAs (white arrows). In (B), the four arrows identify a cavernous
aneurysm. The incidence of vascular abnormalities associated with PTA approaches a quarter of cases, and aneurysms are found in
nearly 14% of all cases (5).

PIFA

CmA PceA
MIFA
A5
A4

A3
M3
AIFA

A2 Pericallosal artery

M2

A1 M1
FpA
RecA Acom AchA
PcomA

Figure 2.12 An oblique view identifying the anterior communicat-
ing complex (Acom) and a view of the recurrent artery of Heub-
ner (RecA). The classification schemes of the anterior cerebral
artery and middle cerebral artery used by Rhoton (2) are
demonstrated.
symmetrical position on the AP view, it is often easy
to assess shift by the vessels violation of the midline.
Terms such as round and square shift are used to
describe the pericallosal arterys deviation across the
midline in its relationship to the falx. Round shift
would occur more anteriorly given the large mobility
of the pericallosal artery, whereas square shift indi-
cated a more posterior focus of mass effect due to the
step-like appearance of pericallosal displacement from
OphA
Figure 2.13 3D reconstruction of a ICA angiogram demonstrat-
ing the branches of the anterior cerebral artery. The hyperdensity
near the distal pericallosal artery is a penetrating projectile.
Abbreviations: OphA, ophthalmic artery; PcomA, posterior com-
municating artery; FpA, frontopolar artery; AIFA, anterior internal
frontal artery; MIFA, middle interior frontal artery; PIFA, posterior
interior frontal artery; CmA, callosomarginal artery; PceA, pre-
central artery.
falcine constraint (4). On the lateral view, hydrocepha-
lus may appear as a taut and upward bowing of the
pericallosal artery. Subdural or epidural collections
can appear as displacement of the natural course of
28 NEUROINTERVENTIONAL MANAGEMENT
the pericallosal-callosomarginal branches and associ-
ated venous structures (Fig. 2.15).
MIDDLE CEREBRAL ARTERY
The middle cerebral artery originates from the internal
carotid and travels in a course parallel to the floor of
the middle cranial fossa. The artery partitions into
Figure 2.14 AP left ICA angiogram identifying an azygos ACA
(black arrow) with associated aneurysm (white arrow). Azygos
ACAs may be associated with the holoprosencephaly, neuronal
migration anomalies, and an increase risk of aneurysm forma-
tion. Abbreviations: ICA, internal carotid artery; ACA, anterior
cerebral artery.
(A)
Figure 2.15 An interesting case of bilateral subdural hematomas in conjunction with a partially thrombosed superior sagittal sinus.
Notice the abnormal contour of both the arterial and venous systems (black arrows). The callosomarginal branch is particularly
deformed (white arrow). Robust filling from the cortical surface can be seen draining into the vein of Labbe (open arrow) inferiorly.
four anatomic segments, and like the other cerebral
arteries organized in this fashion, the segments are
based on surrounding cerebral anatomy rather than
arterial branch points (Fig. 2.16). The M1 segment
extends from the internal carotid artery to the 90
degree turn the artery takes at the limen insula. The
MCA bifurcation may occur prior to or after this
point. Multiple, small perforating arteries that feed the
lentiform nuclei and the anterior limb of the internal
capsule characterize the M1 segment. These lenticulos-
triate arteries (also known as the candelabra given
their appearance on the AP angiogram) are divided
into medial, intermediate, and lateral groups, and
originate from the dorsal aspect of the M1 segment.
They are typically diametrically opposed to the ante-
rior temporal artery when identified in cadaveric dis-
section or surgery (2). The lateral lenticulostriates are
the most consistently visualized given their relatively
larger diameter and longer course (Fig. 2.17). With a
short pre-bifurcation M1 segment, these perforators
may arise from the superior division. The lenticulostri-
ates travel through the anterior perforated substance
to supply the deep hemispheric nuclei. The M2 seg-
ment extends from the limen insula to the second turn
of the artery at the circular sulcus. Though M2
branches are distinguishable on a lateral angiogram,
they appear as a group of double densities on an AP
view. The M3 segment specifically refers to the course
of the vessels over the frontal, parietal, and temporal
opercula. The M4 segment refers to the terminal corti-
cal branches that are classified by their areas of sup-
ply (Fig. 2.18).
Anomalies of the middle cerebral artery can
include an early bifurcation leading to a short M1
segment (considered a normal variant), accessory
MCAs, and duplicated MCAs (Fig. 2.19). Several
classification schemes exist to characterize whether a
vessel is a duplicated MCA versus accessory. The
(B)
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL
most commonly used classification systems are Teal
and Manelfe systems. Teal proposed a true duplicated
MCA arising at the main intracranial bifurcation, with
accessory MCAs arising from either the proximal A1 or
distal A1. Manelfe proposed all variants as accessory
MCAs, type 1 arising before the ICA bifurcation (Teal
duplicate), type 2 arising from proximal A1, and type 3
arising from the distal A1. Komiyama et al. (26) elected
to classify the accessory versus duplicate by its termi-
nal distribution, calling the duplicated MCA an anoma-
lous branch supplying the anterior temporal lobe and
the accessory MCA as supplying the anterior frontal
lobe. All such anomalies are thought to be associated
with an increase risk for further vascular and aneur-
ysm formation (27).
Clinical Considerations
The middle cerebral artery supplies hemispheric struc-
tures including the lentiform nuclei, the lateral aspect
of the frontal, parietal, and temporal cortices, and the
insular cortex. Clinical sequelae from arterial occlusion
are largely based on which segment of which MCA
M4
M3
M2
M1
R ICA
Figure 2.16 Right ICA injection AP view outlining the segmental
anatomy of the MCA, the lenticulostriates (open arrow), and the
anterior temporal artery (arrow). M1 extends from the intracranial
ICA bifurcation to the limen insula, M2 continues until the sharp
turn at the circular sulcus, the M3 travels over the operculum
and becomes the M4 cortical branches upon arriving to the corti-
cal surface. Abbreviations: ICA, internal cerebral artery; MCA,
middle cerebral artery.
29
(right or left) is occluded, with symptoms ranging
from contralateral hemiparesis or hemianesthesia to
aphasia and calculation difficulties. It is important to
remember that some of the distal MCA vessels feed
non-eloquent cortex (i.e., the temporopolar artery), but
vessels feeding the central area bilaterally (primary
motor cortex) and the angular area on the left could
result in significant neurologic deficit should occlusion
occur. Specifically, sacrifice of the superior trunk of
the MCA on the left may result in a Gerstmanns syn-
drome (right left dissociation, acalculia, agraphia with-
out alexia, finger agnosia), while sacrifice of the same
artery on the right might result in asomatagnosia
(neglect).
As was the case for the ACA, it is important to
consider patterns of displacement and derangements
in contour when considering pathology during MCA
evaluations. Temporal lobe hematomas can cause a
narrowing of the MCA branching pattern on the AP
view (Fig. 2.20). Diminished arterial caliber can indi-
cate vasospasm in the appropriate clinical scenario
with concomitant loss of distal filling. Evaluation of
the cortical blush in the late arterial phase will also
serve to identify any small branch occlusions during
the procedure.
MCA bifurcation aneurysms are difficult to treat
endovascularly because of the tendency toward wide-
neck morphologies or because of incorporation of
superior and inferior divisions within the aneurysm
neck and fundus. Fusiform aneurysms or giant MCA
bifurcation aneurysms may require parent artery occlu-
sion in combination with open surgical clipping and
bypass (28). Weill et al. describe two cases of giant MCA
trifurcation aneurysms that were successfully treated
Lateral lenticulostriates
Figure 2.17 3D reconstruction showing the lateral lenticulostriate
arteries arising from the distal M1 segment. These vessels
course around the lentiform nucleus as they ascend through the
internal capsule turning medial to traverse the basal ganglia and
supply the caudate nucleus.
30 NEUROINTERVENTIONAL MANAGEMENT

PPar
APar
Ang
Cen

Occ temp Pre cen

Figure 2.18 Late arterial phase injection, lateral view, of the

Post temp Pre fr internal carotid artery. The distal MCA vessels are shown
with approximate named locations. The dense tangle of ves-
sels approximates the location of the insula (black triangle);
Mid temp Ofr the most posterior and superior corner of which represents
the sylvian point (white circle). Abbreviations: Ofr, orbito-
Ant frontal artery; Pre fr, prefrontal artery; Pre Cen, pre-central
temp TP artery; Cen, Central artery; APar, anterior parietal artery;
PPar, posterior parietal artery; Ang, angular artery; Occ
temp, temporooccipital artery; Post temp, posterior temporal
artery; Mid Temp, middle temporal artery; Ant temp, anterior
temporal artery; TP, temporopolar artery.

(A) (B)

Figure 2.19 Two different MCA duplications shown on AP angiogram (A) and 3D reconstruction (B). The ACA (single arrow), superior
trunk of M1 (arrowhead), and inferior trunk of M1 (double arrows) are demonstrated as is a superior hypophyseal region aneurysm (B).

with EC-IC bypass and subsequent parent artery occlu-
sion. In these cases, the M1 segment was coil occluded
in a patient with an intact circle of Willis, while the
supraclinoid internal carotid was coiled in the patient
with an absent anterior communicating artery (29).
EXTERNAL CAROTID ARTERY
The external carotid artery originates from the com-
mon carotid artery in the neck. The named branches
in order of origin are the superior thyroid, lingual,
facial, ascending pharyngeal, occipital, posterior
auricular, superficial temporal and internal maxillary
artery (Fig. 2.21A). The ascending pharyngeal further
bifurcates into pharyngeal and neuromeningeal
trunks. The internal maxillary artery terminates in
the middle meningeal, accessory meningeal, and
sphenopalatine artery (Fig. 2.21B). Further terminal
branch description occur elsewhere in this text where
applicable.
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL 31

Right

(A) (B)

Figure 2.20 Temporal lobe hematoma identified on non-contrast head CT (A) which was demonstrated as mass effect (circle) and
deformation of the expected MCA branching pattern (arrows) on the AP angiogram (B). No vascular abnormality was identified.

STA
dSTA
MMA PA
dOcc

IMax
Occ

AscP
ICA
MMA
F
ECA

ST

(A) (B)

Figure 2.21 Lateral common carotid artery injection (A) and selective, late arterial phase injection of the external carotid artery (B).
The branches of the external carotid artery are identified. Note the tortuous course of the distal arteries (B) characteristic of external
carotid vessels. The black arrow indicates the sharp turn the middle meningeal artery makes just after passing through the foramen spi-
nosum. Abbreviations: ST, superior thyroid; L, lingual artery; F, facial artery; ECA, external carotid artery; ICA, internal carotid artery;
AscP, ascending pharyngeal artery; Imax, internal maxillary artery; MMA, middle meningeal artery; Occ, occipital artery; STA, superfi-
cial temporal artery; d, distal.
32 NEUROINTERVENTIONAL MANAGEMENT

dICA
c d
b e

NmT
IMAX
a PhB
f

PhB g
h Vert
NmT
ECA AscP

AscP Direct
CCA anast Vert

ECA branches

(A) (B)

Figure 2.22 Graphical angiographic representation of the ascending pharyngeal artery and its anastomoses (A). Middle pharyngeal
artery to internal maxillary artery via the descending palatine artery (a). Pterygovaginal artery (terminal branch of the superior pharyng-
eal artery) to internal maxillary artery via the accessory meningeal artery (b). Superior pharyngeal artery to the internal carotid artery
via the recurrent artery of the foramen rotundum and the inferolateral trunk (c). Clival branches (terminal branches of the neuromenin-
geal trunk) to the internal carotid artery via the meningohypophyseal trunk (d). Inferior tympanic artery to internal carotid artery via the
caroticotympanic branch (e). Hypoglossal artery to the vertebral artery via the odontoid arch system (f). Neuromeningeal trunk to the
vertebral artery via the odontoid arch system (g). Neuromeningeal trunk to the odontoid arch system. The odontoid arch then connects,
at times, to the occipital artery (h). Selective vertebral artery injection (B). A direct anastomosis of from the vertebral artery to the exter-
nal carotid artery via the ascending pharyngeal artery is shown. Abbreviations: AscP, ascending pharyngeal artery; NmT, neuromenin-
geal trunk; PhB, pharyngeal branch; CCA, common carotid artery; ECA, external carotid artery; Vert, vertebral artery; IMAX, internal
maxillary artery; dICA, distal internal carotid artery.

Clinical Considerations: Ascending Pharyngeal
Artery
In the extracranial circulation, all branches can form
pathologic intracranial anastomoses. Of these, the
ascending pharyngeal artery (APA) is one of particu-
lar significance since its anastomotic connections are
present normally. It provides anastomotic channels to
the internal carotid, the vertebral artery, and other
branches within the external carotid circulation (Fig.
2.22A) (30,31). It typically arises from the external car-
otid artery, but it can occasionally arise from the prox-
imal ICA or an aberrant PICA (3234). The APA starts
as a common trunk then bifurcates into a pharyngeal
and neuromeningeal trunk. The pharyngeal trunk ter-
minates as the superior, middle, and inferior pharyng-
eal branch, providing rich anastomotic connections
to the internal maxillary artery (middle pharyn-
geal via the descending palatine artery and pterygova-
ginal artery via the accessory meningeal artery) and
the internal carotid artery (superior pharyngeal via
the infero-lateral trunk and the recurrent artery of the
foramen lacerum) (Fig. 2.23). As the name implies,
this portion of the artery supplies the tissue of the
oropharynx. Though the artery is often difficult to see
on an external carotid angiogram, its clinical impor-
tance exceeds its size in certain circumstances. Specifi-
cally, the anastomotic channels previously described
can cloud the results of test balloon occlusion of the
internal carotid artery by providing collateral circula-
tory routes. These channels also become important
during the embolization of glomus jugulare, vagale, or
tympanicum tumors supplied predominantly by this
artery.
The neuromeningeal trunk courses in a postero-
superior direction toward the foramen magnum. Its
branches include the inferior tympanic, musculospi-
nal, hypoglossal, and jugular arteries with additional
terminal branches to the internal auditory canal, the
clivus, and the odontoid arch. As a result of these con-
nections, embolizations in this area can result in a
number of cranial nerve deficits. Clinically relevant
anastomoses occur between the hypoglossal and mus-
culospinal arteries to the vertebral artery, the inferior
tympanic branch to the internal carotid artery through
the caroticotympanic artery, lateral clival branches
directly to the internal carotid artery, and ECA to
ECA connections from the odontoid arch system to
the occipital artery (1,5,30). An example of a direct
anastomosis between the ascending pharyngeal and
vertebral artery is shown (Fig. 2.22B).
VERTEBROBASILAR SYSTEM
The vertebral arteries typically arise from the subcla-
vians bilaterally (V1). They proceed superiorly and
dorsally to enter the foramen transversarium at the
level of C6. The arteries subsequently travel to the
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL
Figure 2.23 Exquisite image of an external carotid angiogram
showing the pharyngeal branch (arrow) and neuromeningeal
trunk (white arrow) of the ascending pharyngeal artery giving off
anastomoses to the ICA through recurrent artery of the foramen
lacerum (open arrow). The inferolateral trunk receives the recur-
rent branch and opacifies the meningohyphopyseal trunk through
adjacent collaterals. The marginal tentorial artery emerges poste-
riorly (double arrows) to feed a choroidal AVM (curved arrow).
arch of C1, giving off a variable number of small spi-
nal muscular and segmental arteries (V2). Two charac-
teristic right angle turns are noted on both AP and
lateral angiographic projections at C1 and C2 (V2)
(Fig. 2.24). This has been described as a box on the AP
projection. The artery then progresses dorsally to the
atlanto-occipital joint and travels in an antero-superior
direction to enter the dura (V4). Prior to the basilar
anastomosis, the artery gives off the anterior spinal
(ASA) and posterior inferior cerebellar arteries (PICA).
The ASA supplies the anterior spinal cord, and the
PICA supplies the lower brainstem, cerebellar tonsils,
and the inferior aspect of the cerebellar hemispheres.
The basilar artery then travels anterior to the brain-
stem, giving off the anterior inferior cerebellar artery
(AICA), multiple small ponto-mesencephalic perfora-
tors, and the superior cerebellar artery (SCA). There
are multiple areas of collateral circulation between the
SCA, AICA, and the PICA, and distal parent artery
sacrifice in this area may be clinically silent (Fig. 2.25).
The AICA and PICA may at times arise from a com-
mon trunk. The basilar artery subsequently bifurcates
within the crural cistern into the posterior cerebral
arteries (PCA).
Clinical Considerations
Fenestrations within the posterior fossa are common-
place and represent the variability of the coalescence
of the longitudinal neural plexus in the fetal hindbrain
circulation (4). Fenestrations of the vertebral artery
(Fig. 2.26A) are found in 0.20.6% of angiographic ser-
ies and 6% on autopsy (35), the large discrepancy
33
P1
SCA
AICA
PICA
C1
C2
Figure 2.24 AP view of a dominant RVA injection showing the
posterior fossa circulation. Flow into the PCoA (arrowhead) is
seen projecting inferiorly off the P1 segment of the right PCA.
Approximate levels of C1 and C2 vertebrae are shown as well
as the box-like representation of the vertebral arteries at this
level. Abbreviations: RVA, right vertebral artery; PCoA, poste-
rior communicating artery; PCA, posterior cerebral artery; SCA,
superior cerebellar artery; AICA, anterior inferior cerebral artery;
PICA, posterior inferior cerebellar artery.
owing to the difficulty in identifying a small fenestra-
tion on angiography. Aneurysms in proximal and
mid-basilar region are strongly associated with fenes-
trations with a 3040% incidence (Fig. 2.26B) (36).
Open surgical treatment of these aneurysms is chal-
lenging, mainly from a standpoint of exposure.
Although available through complex skull base
approaches, the area nonetheless provides quite a for-
midable obstacle for the surgeon given the many per-
forators supplying the brainstem in this region. As a
result of these factors, endovascular treatment with
detachable coils has become the mainstay of treat-
ment. In addition to coils, techniques such as balloon
remodeling in combination with stent/coiling and
PAO of a unilateral vertebral artery have been utilized
for more complex lesions (37).
POSTERIOR CEREBRAL ARTERY
The PCAs, like the MCA and ACA, are segmentally
organized based on the relevant surrounding anatomy
(Fig. 2.27). The P1 segment starts at the basilar bifurca-
tion and extends to the insertion of the posterior com-
municating artery. The P2 segment is divided into the
anterior (P2a) and posterior (P2p) based on its cisternal
location. The P2a starts at the posterior communicating
artery and travels around the anterolateral aspect of
the mesencephalon in the crural cistern. The P2p con-
tinues posteriorly within the paramesencephalic and
ambient wing cisterns and ends at the quadrigeminal
34 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 2.25 Example of an AICA-PICA complex feeding a posterior fossa AVM with an associated aneurysm (arrow head) (A). The
post-procedural angiogram (B) showing the vessel sacrifice and Onyx cast. The patient awoke without deficit, showing that large ves-
sels may be sacrificed when providing solely fistula circulation. Abbreviations: AICA, anterior inferior cerebellar artery; PICA, posterior
inferior cerebellar artery; AVM, arteriovenous malformation.

(A) (B)

Figure 2.26 Incidental finding of a double fenestration of the vertebrobasilar junction (A). A 3D reconstruction on a second patient with
an aneursym occurring within a fenestration. Such fenestrations are normal variants that can occur anywhere along the posterior circu-
lation secondary to the coalescence of the fetal longitudinal neural arteries. Pathology in such fenestrations can also be present secon-
dary to alterations in flow dynamics.

plate cistern. Small, perforating arteries not well visual-
ized on an angiogram arise from this segment and sup-
ply the cerebral peduncles, brainstem, optic tracts,
thalamus, and choroids plexus, and hippocampus (Fig.
2.28). The posterior temporal artery also emerges in
this region. The P3 segment starts at the quadrigeminal
cistern (tectal plate) and continues to the origin of the
parieto-occipital and calcarine arteries (P4) which tran-
sition to terminal cortical vessels.
Clinical Considerations
Distal vascular anomalies in the posterior cerebral cir-
culation are difficult entities to treat. The surgical
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL
P4
PtA
P3
AtA
P2
P1
Figure 2.27 PCA branches displayed with a foramen magnum
projection or Townes view. The segmental anatomy of the PCA
is displayed as are the temporal arteries. P1 starts at the basilar
artery and ends at the PCoA. P2 is divided into a P2a segment
within the crural cistern and a P2p segment within the ambient
wing cistern. The P3 begins at the quadrigeminal plate cistern
and ends at the origin of the calcarine and parietooccipital artery.
The P4 segment includes the terminal cortical branches. Abbre-
viations: PCA, posterior cerebral artery; PCoA, posterior commu-
nicating artery.
approaches to the crural, paramesencephalic, ambient
wing, and quadrigeminal plate cisterns are elegant,
but the associated morbidity may lend itself to a treat-
ment strategy that achieves a less invasive approach
(3840). Upon presentation the findings can include
hemiparesis (from brainstem perforators or compres-
sion), homonymous hemianopsia (from compression
of optic tract or infarction of calcarine cortex), and
occasionally fourth nerve compression (39,41).
It is the eloquent nature of the neural tissue fed
by the PCA system that complicates the open surgical
or endovascular repair of vascular abnormalities in
this region. Surgical bypass followed by parent artery
occlusion is one successful approach to complicated
PCA pathology. Endovascular treatment without open
surgery can reduce morbidity, but the often-necessary
parent artery occlusion (PAO) can result in additional
deficit. There are diverging published opinions con-
cerning where along the PCA circulation PAO is safe
(38,42). Ciceri et al. treated 21 aneurysms in 20
patients with endovascular coil occlusion. The parent
artery was preserved in 14 patients, and PAO was
performed without preoperative test balloon occlu-
sion. Though relatively successful with proximal PAO,
the general recommendation posited by the authors
was that occlusion distal to P2 could be tolerated
35
secondary to adequate distal collateral circulation pro-
vided by the posterior temporal, the lateral posterior
choroidal, the medial posterior choroidal, and the
splenial arteries. Conversely, proximal PCA occlu-
sion could be associated with brainstem infarct.
However, Hallacq et al. occluded the parent artery
in 10 patients with P2 segment aneurysms without
post-occlusion deficit, concluding that P2 occlusion
was in fact safe (42). The safety of such a maneuver
often needs to take into account the posterior water-
shed and the contributions of the MCA to its supply.
The PCA and MCA often share a reciprocal relation-
ship in the region of the occipital cortex, with either
one or the other showing a pattern of dominance (1).
In the case of a dominant MCA, a P2 occlusion may
very well be a safe undertaking.
CEREBRAL VEINS
It is convenient to think of the venous anatomy as a
construct of intradural channels (sinuses) and cerebral
veins organized into a deep and superficial system.
The left and right sinuses tend to favor a dominant
pattern of drainage from the deep and superficial sys-
tems respectively (3). The sinuses receive the bulk of
venous outflow from the brain, and terminate in
the internal jugular veins. The following will review
the deep and superficial venous anatomy seen on
normal angiographic studies and venous malforma-
tions whose mainstay treatments involve endovascular
methods.
Superficial Venous System
The superior sagittal sinus is the large, midline vein
easily visualized on both AP and lateral angiographic
projections (Fig. 2.29). It receives direct inflow from
the hemispheres via the superficial frontal, parietal,
and occipital cortical veins as well as extra-axial
inflow from the diploic and meningeal veins. The two
dominant superficial cortical veins overlying the corti-
ces are the superior anastomotic vein of Trolard
(Fig. 2.30) and the inferior anastomotic vein of Labbe
(Fig. 2.15B). The superficial middle cerebral vein (syl-
vian vein) can often be seen draining toward the cav-
ernous sinus and basal plexi on the lateral angiogram
(4,5). The superior sagittal sinus terminates at the tor-
cula herophili at the confluence of the sinuses. Here
the straight sinus and the superior sagittal sinus
become the paired transverse sinuses. The straight
sinus receives venous inflow from the inferior sagittal
sinus, the vein of Galen, and meningeal veins from
the tentorium. The vein of Galen receives the internal
cerebral veins and the basal vein of Rosenthal. The
transverse sinuses make a 90 degree turn under the
asterion of the skull to become the sigmoid sinuses.
The base of the brain contains multiple venous
sinuses that are clinically relevant. The cavernous
sinus is a paired structure composed of multiple
venous sinusoidal channels that anatomically encircle
the sella turcica (Fig. 2.30). This structure is not
overtly obvious on a normal angiogram, but becomes
prominent in the setting of direct carotid cavernous
fistulae (Fig. 2.29). Just posterior and inferior to this
structure is the midline basal sinus. This sinus
36 NEUROINTERVENTIONAL MANAGEMENT

receives inflow from the superficial sylvian vein via
the sphenoparietal sinus, and sends outflow to the
superior petrosal sinus and eventually the jugular
bulb. In the pediatric population, an occipital sinus is
often present draining from the torcula in the inferior
midline and continuing to the foramen magnum and
an encircling marginal sinus. This marginal sinus con-
nects the jugular bulb, the basal sinuses (the superior
petrosal, inferior petrosal, and sphenobasalis), and the
anterior clival plexus. This may continue into adult-
hood as a vestigial remnant.
Deep Venous System
The deep venous structures are typically visible on a
lateral angiogram. The basal veins of Rosenthal
become visible within the crural cistern. They receive
flow from the deep middle cerebral veins and the

Lateral posterior choroidal arteries

Splenial branches

Medial posterior choroidal arteries

Thalamo-perforators

Figure 2.28 Late phase arterial injection, lateral view of the

PCAs and their perforators. The medial posterior choroidal
arteries arise typically from the P2 segment proximal to the
lateral posterior choroidal arteries. They travel around the
brainstem and then course forward into the velum interposi-
tum in the roof of the third ventricle. The entrance to the
velum is lower than the choroid plexus in the lateral ventricle
and therefore appears inferior to the lateral posterior choroi-
dal artery on the lateral angiogram. Abbreviations: PCA,
posterior cerebral artery.

SSS SSS
PrecV VoT ApV
PfV
IcV VoG
MfV
PpV
TsV SS
BVoR
VoL
AfV SPS TS

TS

SigS

IJ

(A) (B)

Figure 2.29 Lateral (A) and AP (B) projection, venous phase. Normal venous anatomy is shown. Abbreviations: IJ, internal jugular
vein; SigS, sigmoid sinus; TS, transverse sinus; SPS, superior petrosal sinus; SS, straight sinus; SSS, superior sagittal sinus; VoL, infe-
rior anastomotic vein of Labbe; BVoR, basal vein of Rosenthal; TsV, thalamostriate vein; VoG, vein of Galen; IcV, internal cerebral
vein; AfV, anterior frontal vein; MfV, middle frontal vein; PfV, posterior frontal vein; PrecV, precentral vein; VoT, superior anastomotic
vein of Trolard; ApV, anterior parietal vein; PpV, posterior parietal vein.
 APPLIED NEUROVASCULAR ANATOMY OF THE BRAIN AND SKULL 37

anterior cerebral veins. They subsequently course
within the paramesencephalic and ambient wing cis-
terns with the posterior cerebral arteries to finally end
at the vein of Galen. The vein of Galen also receives
venous drainage from the internal cerebral veins. This
paired venous outflow receives predominant feeders
from the thalamostriate veins, the anterior caudate
veins, and the anterior septal veins lining the lateral
ventricles. A helpful landmark for the foramen of
Monroe on the lateral angiogram is the venous angle,
defined by the point where the thalamostriate vein
meets the anterior septal vein. The internal cerebral
veins then course posteriorly within the velum inter-
positum adjacent to the medial posterior choroidal
arteries and terminate at the vein of Galen. The vein
of Galen is a short U-shaped segment that empties
directly into the straight sinus.

R ICA
Figure 2.30 Right internal carotid angiogram, venous phase
showing an atretic one third of the superior sagittal sinus. This
areas drainage is now served by enlargement of a prominent
frontal vein (white arrow). Also present is an unusually large
superior anastomotic Vein of Trolard (black arrow).
Clinical Considerations
In several instances, venous drainage can become
deranged when abnormal or fistulous circulation
dominates normal outflow. In childhood the most
common example of this is in Vein of Galen malfor-
mations (VOGMs) (Fig. 2.31). Two distinct clinical
entities exist: Vein of Galen aneurysmal malformations
(VGAM), which is a true fistulous connection between
choroidal or mural feeders into the prosencephalic
vein and the Vein of Galen aneurysmal dilatation
(VGAD), in which a subpial arteriovenous malforma-
tion of the brain adjacent to the velum interpositum
causes massive distention of the internal cerebral
veins or Vein of Galen secondary to the nearby, high-
flow shunt (5). Through the increasing improvements
in liquid embolic materials, endovascular treatment of
these lesions continues to improve.
The carotid-cavernous fistula (CCF) (Fig. 2.32)
is a unique pathology that has a classic clinical
presentation defined by an ocular bruit, chemosis, and

VOGM
SS

TS
PP
SigS

(A) (B)

Figure 2.31 Lateral internal carotid angiogram, mid-arterial phase (A) with a VOGM showing arterial branches from an enlarged ante-
rior choroidal artery as well as the pericallosal artery draining early in the enlarged, deep fistula. The normal cortical vessels are redir-
ected anteriorly to drain through cavernous sinus and pterygoid plexus (B). The cortical vessels will usually maintain their normal
caliber unless outflow obstruction of the sinuses has occurred. Abbreviations: VOGM, Vein of Galen Malformation; SS, straight sinus;
TS, transverse sinus; PP, pterygoid plexus.
38 NEUROINTERVENTIONAL MANAGEMENT
CS
IPS SOV
IJ
Figure 2.32 Lateral internal carotid angiogram, mid-arterial phase
showing a cavernous carotid fistula and dilated superior ophthal-
mic vein. Posterior drainage occurs through the inferior petrosal
sinus to the jugular bulb. Abbreviations: CS, cavernous sinus;
SOV, superior ophthalmic vein; IPS, inferior petrosal sinus; IJ,
internal jugular.
exophthalmos with occasional ophthalmoplegia. The
classic demographic is in young males with antecedent
head trauma. This aberrant connection can be a result
of two very different processes: the first is classified as
indirect and describes a dural arteriovenous fistula, the
second a direct connection of the ICA with the caver-
nous sinus either through trauma or as a result of rup-
ture of a cavernous (C4) aneurysm. Treatment may
require emergent action if vision becomes threatened
by venous hypertension, retinal hemorrhages, or
stretching of the optic nerve. The goal is to occlude the
cavernous sinus with preservation of the ipsilateral
carotid (if possible). A PAO after balloon occlusion
may need to be performed if the initial approach fails.
The indirect CCF is essentially a true dural arteriove-
nous malformation and is discussed below.
Dural arteriovenous malformations (considered
fistulas by some) can have extremely aggressive natu-
ral histories when coupled with certain angiographic
morphologies. Three classifications exist, the Djindjian,
Borden, and Cognard systems, with Cognard now
being the most widely utilized. The critical character-
istic indicative of aggressive behavior in all of the
classifications is the presence or absence of cortical
venous reflux. Of these with cortical reflux >75% have
an aggressive clinical course with hemorrhage
reported as the most significant complication (43). An
even greater percentage (66%) goes on to hemorrhage
if venous ectasia is present (44). Malformations in the
posterior fossa can begin draining directly into the
spinal perimedullary veins with subsequent myelop-
athy in addition to the risks of hemorrhage. Treatment
of these lesions by endovascular therapy alone (partic-
ularly with the new liquidembolic Onyx) or in con-
junction with surgery or stereotactic radiosurgery has
proven very successful (45).
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 3
Vascular anatomy of the spine and spinal cord
Armin K. Thron
INTRODUCTION
Due to progress in microneurosurgery and in interven-
tional neuroradiology even intramedullary spinal vascu-
lar lesions have become more and more accessible and
treatable. Unfortunately, a lack of knowledge about spi-
nal vascular anatomy is evident in many conferences
with neurologists and sometimes even with neurosur-
geons and neuroradiologists. This might be a reason for
unsatisfactory clinical results in the treatment of spinal
vascular diseases by invasive therapeutic techniques.
Furthermore, magnetic resonance imaging (MRI) and
magnetic resonance angiography (MRA) of blood vessels
in and around the spinal cord have substantially
improved. In order to provide a correct anatomical inter-
pretation of the demonstrated blood vessels, knowledge
of the anatomy of spinal cord blood vessels is the first
prerequisite. The most precise and detailed anatomical
description of these blood vessels was given by Kadyi (1)
at the end of the nineteenth century. His work was pub-
lished in 1889, seven years after the first extensive and
comprehensive study performed by Adamkiewicz (2).
This chapter deals with the essentials of spine and
spinal cord blood vessel anatomy (3), outlines the possi-
bilities to identify these vessels on tomographic images,
and illustrates main problems and pitfalls in the ana-
tomical evaluation of spinal vascular malformations.
ARTERIAL BLOOD SUPPLY
Sources of Arterial Blood Supply to the Spine
and Spinal Cord
The blood supply to vertebral body, paraspinal
muscles, dura, nerve root, and spinal cord is derived
from segmental arteries (Fig. 3.1). These vessels per-
sist as intercostal and lumbar arteries in the majority
of the thoracolumbar region. Several segments in the
upper thoracic region have a common feeder which is
the supreme intercostal artery.
Following intrauterine vascular rearrangements,
longitudinal arteries are established in the cervical
region. On each side, three vessels are potential sour-
ces of spinal blood supply in this region, namely the
vertebral artery, the deep cervical artery, and the
ascending cervical artery.
In the sacral and lower lumbar region, sacral
arteries and the iliolumbar artery (supplying the
L5 level) derived from the internal iliac arteries are
the most important supply to the caudal spine.
Generally, the segmental arteries supply all the
tissues on one side of a given metamere, with the
exception of the medulla. A spinal branch of the poste-
rior intercostal artery enters the vertebral canal
through the intervertebral foramen and regularly
divides into three branches: an anterior and posterior
artery of the vertebral canal for the spinal column, and a
radicular artery which supplies the dura and nerve
root at every segmental level.
The hemivertebral blush, resulting from injection
of a segmental artery may help in identifying the
artery. At the thoracic level, the artery is named
according to the number of the rib under which it
courses. The segmental arteries are connected across
the midline and between levels above and below,
through highly effective anastomoses (Figs. 3.2,3.7).
At certain segmental levels, this radicular artery
has persisted as a radiculomedullar artery which means
that it follows the anterior and/or posterior nerve
roots to form and supply the superficial spinal cord
arteries (Fig. 3.1).The number of these radiculomedul-
lar arteries is reduced during an embryonic transfor-
mation process. Two to fourteen, on average six
anterior radiculomedullar arteries persist as the result
of this ontogenic reduction of feeding vessels. The
posterior radiculomedullar arteries are reduced less
drastically to 1116 vessels. Figure 3.3 demonstrates
schematically the typical potential sources of arterial
supply to the anterior axis of the spinal cord.
Extra and Intraspinal Extradural Anastomoses
1. An extraspinal system connects the neighboring seg-
mental arteries longitudinally. The vessels course
on the lateral aspect of the vertebra or transverse
process (Figs. 3.1,3.2,3.7). This system is highly
developed in the cervical region, where the verte-
bral artery and the deep cervical and ascending cer-
vical arteries form the most effective longitudinal
anastomoses (Figs. 3.3,3.6). The system also is
present throughout the thoracic and lumbar levels
where extraspinal anastomoses often provide effec-
tive collaterals to adjacent levels (Fig. 3.3).
2. The intraspinal extradural system is mainly a trans-
verse anastomosis but also has longitudinal inter-
connections. The retrocorporeal and prelaminar
arteries are the relevant vessels for the supply of
bone and dura (Figs. 3.1,3.2,3.8). These anastomo-
ses provide an excellent collateral circulation, and
it is for this reason that numerous segmental

arteries can be visualized by injection of one seg-
mental artery (Fig. 3.2).
The extra- and intraspinal anastomoses protect
the spinal cord against ischemia when pathologies,
such as arteriosclerotic disease of the aorta, cause focal
vessel occlusion.
Radicular Supply and Superficial Spinal Cord
Arteries
Several nomenclatures and classifications have been
used to describe spinal cord arteries. This is an
ongoing cause of misunderstanding. A recent classifi-
cation proposed by Lasjaunias and Berenstein (4) dif-
ferentiates three types of spinal radicular arteries:
radicular, radiculopial, and radiculomedullary.
The first type of spinal radicular artery is a small
branch, present at every segmental level, which is
restricted to the supply of the nerve root. The second
type supplies the nerve root and superficial pial
plexus (e.g., posterior radicular artery). The third type
supplies the nerve root, pial plexus, and medulla (e.g.,
anterior radicular artery).
This classification may offer some advantages for
the interventional neuroradiologist when compared to
classical differentiations because it stresses the impor-
tance of the anterior supply for the gray matter of the
spinal cord parenchyma. From an anatomical point of
view, it is however not a clear cut differentiation
because on the one hand the anterior spinal artery ful-
Posterior Posterolateral
radiculomedullary spinal artery
artery
Dorsal branch
Ventral branch
Post. intercostal
artery
Anterolateral
anastomotic artery
Figure 3.1 Blood supply of the spinal column and spinal cord.
VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 41
fils the criteria of all three types of spinal radicular
arteries. On the other hand the posterior radicular
arteries do contribute to the supply of the central gray
matter, especially of the posterior horn.
We therefore suggest only a slight modification
of the older anatomical classification with the follow-
ing differentiation of spinal radicular arteries:
l Radicular arteries supplying only nerve root and
dura mater, but not spinal cord.
l Anterior radiculomedullary arteries in which the per-
sistent medullary branch is running with the ante-
rior nerve root to join the longitudinal trunk,
which has been called the anterior spinal artery
(Figs. 3.1,3.4).
l Posterior radiculomedullary arteries in which the per-
sistent medullary branch accompanies the poste-
rior nerve root and joins the longitudinal systems
of posterolateral and/or posterior spinal arteries.
The first one is lying laterally, the second one
medially of the posterior root entry zone. These
longitudinally oriented vessels are not continuous
and may replace each other (Figs. 3.1,3.11,3.12).
As has already been mentioned, the anterior
radiculomedullary supply is reduced to an average
of 6 radiculomedullary arteries (Fig. 3.4), whereas
1116 posterior radiculomedullary arteries persist
after embryonic life.
The thoracolumbar enlargement is the region
where the dominant anterior radiculomedullary artery
Dorsal muscular
branch
Posterior vertebral
canal artery
Anterior
radiculomedullary
artery
Anterior vertebral
canal artery
Anterior
spinal artery
Aorta
Source: Courtesy of Walter Korr, RWTH Aachen University.
42 NEUROINTERVENTIONAL MANAGEMENT
(A. radicularis magna Adamkiewicz) arises. But in this
region several posterior radiculomedullary arteries
may also be large-sized vessels which furnish blood
supply to this area. They are connected to the anterior
spinal artery through two anastomotic semicircles,
called the arcade of the cone (Figs. 3.4,3.9).
The superficial distribution of blood to the spinal
cord is achieved by the above mentioned anterior and
posterior longitudinal vessels which have been named
anterior spinal artery and posterior/posterolateral spinal
arteries. Both systems supply a superficial network of
smaller pial arteries that covers the spinal cord termed
the vasocorona (Figs. 3.11,3.12). The anterior spinal
artery may be small or absent as a continuous tract in
the upper thoracic and upper cervical region of the
spinal cord (Figs. 3.4,3.5).
The main source of arterial supply to the cord is
the anterior spinal artery (ventral axis) with a
Figure 3.2 Extra- and intraspinal extradural anastomoses. Selec-
tive injection in the first lumbar artery on the left opacifies homolat-
eral arteries as well as contralateral vessels. The typical
hexagonal configurations of the retrocorporeal intraspinal anasto-
mosis (small arrows) as well as the extraspinal pretransverse and
anterolateral anastomoses (large arrows) are demonstrated. The
injected artery gives rise to an anterior radiculomedullary artery
(arrowheads), probably the Adamkiewicz artery. Note the hemiver-
tebral blush corresponding to the injected artery.
multisegmental distribution of blood and a distinct ter-
ritory of supply. It gives rise to the hemodynamically
important central (centrifugal) system, which supplies
the major part of the gray matter. Additionally, there
are branches to the pial system on the anterior and
lateral surface, supplying the ventral two-third of the
vasocorona (Figs. 3.11,3.12).
The posterior and posterolateral spinal arteries
distribute blood to the dorsal one-third of the vasocor-
ona, and in this way share with central artery
branches in the supply of the posterior horn and mar-
ginal parts of the central gray matter (Figs. 3.11,3.12).
The posterior/posterolateral arteries do not have
such a distinct territory of supply like the anterior spi-
nal artery which means that they predominantly rein-
force the rope ladder-like network of posterior pial
arteries.
Differences in Arterial Supply of the Spinal Cord
Depending on Regions
Cervical Region
The cephalic origin of the anterior spinal artery typi-
cally arises from the intradural vertebral artery as
high as the vertebrobasilar junction (Fig. 3.6). One of
the ventral radicular feeders between C5 and C8 is
often distinctly larger (400600 mm) than the others
and was termed the artery of the cervical enlargement
by Lazorthes (5,6). It is more often derived from the
deep and ascending cervical arteries than from the
vertebral artery (Figs. 3.7,3.8). Therefore these vessels,
which originate from the thyrocervical and costocervi-
cal trunks respectively, must be demonstrated on
T11
T12
L1
Figure 3.3 Extraspinal collaterals. Injection of right T12 intercos-
tal artery (arrowcatheter tip) fills T11 and L1 levels (labeled)
via extraspinal anastomoses (arrowheads).
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 43

angiography for diagnostic and interventional proce-
dures. The average number of anterior radicular
feeders to the cervical medulla is 23.
The ventral feeders to the upper cervical cord,
originating from the intracranial section of the verte-
bral artery, may be very small. Their demonstration
on angiography is often impossible. If there are two
descending branches from both vertebral arteries, the
smaller or rudimentary vessel does not join the main
midline trunk but ends separately as a large central
artery (Figs. 3.4,3.5).
Duplication of the anterior spinal artery over
some distance is frequent in this region, pseudo-island
formation and even a net-like plexiform pattern of
arteries may be observed. Continuity of an anterior
spinal artery may not exist. All these variations have
to be regarded as a state more closely related to the
embryonic (or ontogenetic) condition (Fig. 3.5).
The posterior system of the upper cervical region
is constituted by a descending branch from the verte-
bral artery or PICA. The vessel may have a large cali-
ber and originates in a lateral position (lateral cervical
artery (7)).
The number of central arteries in the cervical
enlargement is about five per cm. They take a hori-
zontal course.
Thoracic Region
Occasionally, one segmental artery branches and sup-
plies two intercostal spaces. In this case, the dorsal
and spinal branch of one of the two segments may

Anterior spinal artery

Costocervical trunk
(deep cervical artery) Vertebral artery

Thyreocervical trunk
(ascending
cervical artery)

Subclavian artery

Carotid artery

Aorta

Intercostal
arteries

Great anterior radiculo-

medullary artery
(adamkiewicz artery)
Low intercostal
or upper lumbar artery

Figure 3.4 Sources of supply to the anterior spinal

artery. Source: Courtesy of Walter Korr, RWTH Aachen
University.
44 NEUROINTERVENTIONAL MANAGEMENT
not be seen. Therefore, a small posterior intercostal
artery, from which the spinal branch of this metamere
arises, must be looked for. This may be crucial, for
example when searching for the site of a dural arterio-
venous fistula.
C5
(A) (B)
Figure 3.5 Anterior spinal artery in the cervical spinal cord. The
pattern of supplying vessels varies considerably, especially in the
upper spinal cord. (A) Photograph of an injected specimen.
Plexiform pattern of arterial supply in the upper cervical levels,
without formation of a midline anterior spinal artery. (B) X-ray
film in AP view. The anterior spinal artery is formed by a large
unilateral descending branch from the left vertebral artery (arrow)
and is reinforced by a large anterior radiculomedullary artery at
the C5 level on the right. The small descending branch coming
from the right vertebral artery (arrowhead) ends in this network
of small tortuous superficial arteries. Source: From Ref. 13.
The upper and midthoracic regions are mostly
supplied by small radicular arteries (200400mm), mak-
ing angiographical demonstration difficult (Fig. 3.4).
In addition, the ventral anastomotic tract (anterior
spinal artery) may be discontinuous throughout these
regions.
The pial system plays an important role in this
spinal cord region where there is relatively less gray
matter and more white matter tracts (Figs. 3.10,3.11).
On the posterior surface of the cord, the longitudinal
tracts may run in posterior or posterolateral positions,
thus indicating the functional identity of these vessels
(Figs. 3.10,3.11).
The number of central arteries is only 23 per
cm for this region. This explains the prevalence of
steeply ascending and descending central artery
branches (Fig. 3.10A). As pointed out earlier, the
impression of an intrinsic longitudinal anastomosis on
sagittal images was not confirmed on coronal images
of our microangiographic studies.
Thoracolumbar Region and Cauda Equina
One of the ventral feeders between T9 and L1 (excep-
tionally at L2 or L3) is always dominant (80100mm)
and is therefore called the "artery of the lumbar enlarge-
ment" (Lazorthes) or the "great radicular artery"
(Adamkiewicz) (Figs. 3.4,3.9). Below its level of entrance,
additional significant ventral feeders are unusual.
Supply to the posterior system in this region often
includes two equally large dorsal feeders (400500mm),
which enter the spine above or below the great radicular
artery (Fig. 3.9).
The ventral and dorsal systems are connected to
each other around the conus (arcade of the cone, rami
anastomotici arcuati (1)). This pattern may constitute a
significant anastomosis, comparable to the circle of
Willis.
The densest concentration of central arteries
is found in the thoracolumbar enlargement where
68 vessels per cm can be counted on microangio-
grams (Fig. 3.11).
Intrinsic Spinal Cord Arteries
The arteries directly supplying the spinal cord are:
l central (or sulcal) arteries originating from the ante-
rior spinal artery and
l perforating branches arising from the pial network,
covering the spinal cord.
The first type of perforating arteries constitutes a
centrifugal system. Each central artery (inner vessel
diameter 100250mm) penetrates the parenchyma to
the depth of the anterior fissure, courses to one side
of the cord, and branches mainly within the gray mat-
ter. The second type of perforating artery arises from
the pial covering of the cord (vasocorona) and pene-
trates white matter tracts from the periphery (centripe-
tal system). These vessels are numerous with a
diameter of up to 50mm. Both types of intrinsic artery
and their region of supply can be appreciated on the
axial section of the microangiograms demonstrated in
Figures 3.11,3.12, and 3.13.
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 45

Superficial and Intrinsic Arterio-Arterial
Anastomoses
Arterio-arterial anastomotic interconnections are fre-
quent in the spinal cord.
The anterior spinal artery may be regarded as the
largest and most constant longitudinal anastomosis
(Figs. 3.4,3.9).
The posterior systems are not constantly devel-
oped or continuous. They include longitudinal and
transverse components and serve as anastomotic
pathways and distribution channels, at least over
some segments (Figs. 3.9,3.11).
The arcade of the cone has an anastomotic func-
tion, comparable to that of the circle of Willis.
Superficial interconnections between two or several
central arteries exist predominantly in the thoracic
region. They run immediately deep and parallel to the
anterior spinal artery at the entrance of the anterior
fissure within the pial system (Fig. 3.13A).
Additionally, there are horizontal anastomoses
between central artery branches and the superficial

(A)

(B) (C)

(E)

(D)

Figure 3.6 Vertebrobasilar junction origin of anterior spinal artery. (A) AP view of right vertebral artery injection demonstrates origin of
anterior spinal artery (arrowheads) from the region of vertebrobasilar junction. Note fenestration (arrow) at vertebrobasilar junction.
(B) 3D reconstruction without bone and (C) PA view with bone. (D) Lateral view without and with (E) bone confirm the anterior location
of the vessel (arrowheads) with respect to the cord.
46 NEUROINTERVENTIONAL MANAGEMENT
systems, especially in a centro-anterolateral or centro-
posterolateral direction. However, they do not seem to
play an important role in the plasticity of blood sup-
ply to the spinal cord.
But the most important message to note is that we
could not demonstrate an intrinsic longitudinal anasto-
mosis between the ascending and descending branches
of the central arteries within the spinal cord parenchyma
as was assumed by Adamkiewicz (2) and others (8).
VENOUS DRAINAGE
The pattern of venous drainage deviates substantially
from that of the arteries. Their arrangement will be
described in the direction of venous drainage from the
spinal cord parenchyma to the epidural plexus.
Figure 3.7 Demonstration of an anterior radiculomedullary
feeder to the cervical spinal cord by injecting the costocervical
trunk on the left. The ascending and descending branches
(arrowheads) are forming the anterior spinal artery at this level.
Intrinsic Veins
The blood of the spinal cord parenchyma is drained
by radial veins. They show a horizontal, radial, and
symmetrical course in most parts of the spinal cord
(Fig. 3.7A). Only in the lower thoracic cord, from the
lower lumbar enlargement to the conus medullaris,
are the sulcal veins (100250mm) larger than the
numerous radial veins.
Superficial Veins
At the level of the spinal pia mater, blood is accumu-
lated in essentially two longitudinal collectors: the ante-
rior and posterior median spinal vein (Figs. 3.12,3.13,
3.14,3.15). The anterior midline vein is located under
the anterior spinal artery (Fig. 3.12C). It has its largest
caliber lumbosacrally. In about 80% of cases it runs
together with the filum terminale as a sometimes very
large terminal vein to the end of the dural sac. The
venous longitudinal system on the anterior and poste-
rior surface of the cord is more variable in course,
size, and localization than the anterior spinal artery
(Fig. 3.13). The longitudinal midline veins are not
always continuous tracts and may be replaced by sec-
ondary systems of smaller caliber. The posterior
median spinal vein takes a course independent from
the posterolaterally located arteries and is especially
large above the thoracolumbar enlargement. Varicose
convolutions are frequent (Figs. 3.12,3.14B). The poste-
rior veins of the thoracolumbar enlargement are
undoubtedly the medullary vessels of largest caliber
(up to 1.5mm diameter) and are rarely matched by
superficial cervical veins. These are the vessels most
likely to be seen on MR images (Figs. 3.16A,3.17A). The
vessels are part of a pial vascular network which has
been called the venous plexus of the pia mater (9), the
coronal pial plexus (10,11), or the venous pial plexus (12).
Intraparenchymal Venous Anastomoses
They are quite common. However, they are not dis-
tributed uniformly over the length of a spinal cord.
There are two types of anastomoses.
Anastomoses of the first type are complex anas-
tomoses connecting central and peripheral branches
(sulcal and radial veins of 100200mm in diameter).
They are very frequent, and drain to smaller veins of
the superficial pial plexus.
More important are anastomoses of the second
type which are transmedullary midline-anastomoses of
300700mm in diameter, connecting the median veins
on both sides of the cord. They do not receive tributa-
ries from the intrinsic vessels. Due to their size, they
are not only seen on microangiograms (Fig. 3.16B), but
may also be seen on angiography or MRI (Fig. 3.16A).
Through these large anastomoses, blood can easily be
directed from one side of the cord to the other (13).
Differences in the Venous Drainage Depending
on Spinal Cord Region
Cervical Region
Radial symmetry of intrinsic veins is very pro-
nounced in the cervical spinal cord. Transmedullary
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 47

midline-anastomoses are also very frequent, but they
are of smaller caliber in the upper cervical region than
those in the lower cervical and upper thoracic regions.
The anterior median vein was frequently larger than
the posterior median vein in our material. Both veins
connect to the brainstem veins and basal sinuses
around the foramen magnum. Additionally and pre-
dominantly radicular outflow to the epidural plexus
occurs at many levels (Fig. 3.14A).
Thoracic Region
plexus). The anterior median spinal vein reaches its
maximum caliber in this region and it is important to
note, that the vein of the filum terminale is the contin-
uation of this anterior median vein (Fig. 3.17). Alterna-
tively, the anterior vein can follow a sacral nerve root
to reach the sacral epidural space (Fig. 3.14B). The
midline veins of the thoracolumbar enlargement are
the largest blood vessels of the spinal cord (Figs.
3.16,3.17). When demonstrated on contrast-enhanced
MRI studies, or CT myelography, they should not be
mistaken for spinal cord arteries.

The greatest concentration of large transmedullary
anastomotic veins is found in the cervicothoracic
region (12 per centimeter) followed by the mid- and
lower thoracic levels (Fig. 3.17), where they are more
widely separated. Anterior and posterior median
veins are mostly of equal size.
Lumbar Region
In this region, sulcal veins may be considerably larger
than radial veins (Fig. 3.12B). The posterior median
spinal vein is particularly large above the thoracolum-
bar enlargement (Fig. 3.17B), frequently forming vari-
cose convolutions (the so-called posterior venous
Radiculomedullary Veins and the Transdural
course
The superficial venous blood collectors drain into
the epidural venous plexus through radicular veins
(Fig. 3.14). The transition of the midline vessel to the
radicular vein forms a hairpin-course, similar to the
arterial configuration (Fig. 3.14). Therefore, on angio-
graphic images, the vein might be mistaken for an
artery (Fig. 3.15), particularly when an arteriovenous
malformation (AVM) with early venous filling is
present. For the same reason, it may be impossible to
distinguish anterior spinal artery from anterior spinal
vein on magnetic resonance images as long as no

Figure 3.8 Cervical anterior spinal artery supply. (A) AP view of right subclavian injection. Radiculomedullary artery originates from
deep cervical branch and enters the C6 foramen (arrow) before dividing into ascending and descending limbs (arrowheads). (B) Left
vertebral artery injection demonstrates radiculomedullary artery (arrow) originating from vertebral artery and giving rise to anterior spinal
artery supplying the cervical enlargement by ascending and descending limbs (arrowheads). Vertebral artery dissection is also present
(white arrowhead).
48 NEUROINTERVENTIONAL MANAGEMENT
sufficient time-resolved MR-angiography is available.
From an anatomical point of view, the number of
venous outlets is high. In some studies an average
number of 25 radicular veins were counted on the
(A) (B)
Figure 3.9 X-ray film (AP view) of a contrast-injected human
spinal cord specimen with arterial filling. (A) Lumbar and (B)
thoracic regions. Note the different calibers of the anterior (large
arrowheads) and posterior radiculomedullary feeders (small
arrowheads) and of the anterior spinal artery (small arrows) at
different spinal cord levels. The important supply coming from
the artery of the lumbar enlargement is obvious as well as its
connection with the posterior arteries around the cone (arcade
of the cone) (black arrow). The system of posterior/posterolat-
eral arteries is discontinuous; the largest posterior radiculome-
dullary feeder enters below and contralateral to the artery of
Adamkiewicz in this specimen (oblique arrowhead). Source:
From Ref. 13.
anterior and posterior surfaces of the cord (14,15).
However, purely radicular veins might have been
included in this number. If smaller veins (<250mm
diameter) are excluded, the number of radiculomedul-
lary veins draining the spinal cord is 611 for the
anterior and 510 for the posterior systems (1,16).
These latter studies are in agreement with our own
study (17). In addition, fibrotic radicular veins were
described by Moes and Maillot (18) at thoracic levels.
These may contribute to the vulnerability of the spi-
nal venous system such as in the chronic impairment
of venous drainage in Foix and Alajouanine disease
(19) as a late complication of dural AVF (20).
The transdural course of radicular veins exhibits
special features (3). The presence of venous valves
described by Oswald (21) could not be confirmed in
later studies. Instead, an oblique and zig-zag course
with considerable narrowing of the lumen was first
described by Tadie et al. (22). They concluded that
this configuration might act as an anti-backflow sys-
tem, protecting the spinal cord against high pressure
in the extraspinal veins. Our own studies are in
agreement with their findings, although reflux from
the epidural plexus to the superficial spinal cord
veins was not always prevented by this arrangement
when injecting contrast medium in post-mortem
specimen (23).
Extradural Venous Spaces and the Extraspinal
Venous System
The extradural plexus, well demonstrated by spinal
contrast venography, extends as a continuous system
from the sacrum to the skull base. It drains the spinal
cord and surrounding structures.
Drainage of blood from the spine (including spi-
nal cord) occurs through the internal and external
venous vertebral plexus and also extends as a continu-
ous system from the sacrum to the base of the skull.
They are identifiable as anterior and posterior sys-
tems; the anterior internal vertebral plexus is larger
than the posterior internal system. The external sys-
tems run anterior to the body of the vertebrae (ante-
rior external plexus) whilst posteriorly, the posterior
external plexus lies posterolateral to the vertebral
bodies.
This valveless system is connected with the
azygos- and hemiazygos venous systems by intercos-
tal or segmental veins and in the cervical region with
the vertebral and deep cervical veins. The segmental
veins in the lumbar region are connected by the
ascending lumbar vein, joining the azygos (right side)
and hemiazygos vein (left side) (3).
ANATOMICAL EVALUATION OF AVMS AND
VASCULAR NEOPLASMS
Some important problems and pitfalls in the clinical
application of blood vessel anatomy concerning spinal
AVMs and vascular neoplasms should be mentioned
and explained. They are illustrated in Figures
3.18,3.19,3.20,3.21,3.22,3.23 and 3.24.
1. Prior to a therapeutic intervention, it is essential
to identify the feeders of a spinal AVM or vascu-
lar neoplasm from intradural and extradural
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 49

(A) (B)

(C) (D)

Figure 3.10 Angiographical demonstration and identification of spinal cord arteries. (A, B) Selective injection of the 11th intercostal
artery with normal findings. (A) Frontal view. Typical hairpin configuration and midline position of the anterior radiculomedullary and ante-
rior spinal arteries [small ascending and larger descending branch at this level (arrowheads)]. Note the extra- and intraspinal longitudinal
and transverse anatomoses (arrows) and the hemivertebral blush. (B) Lateral view. Anterior location of the artery demonstrated in (A)
(arrowhead). The lateral projection is very helpful to differentiate the anterior or posterior position of the artery with certainty, which may
be difficult in cases of scoliosis, and especially AVMs. (C, D) Injection of the ninth intercostal artery in case of an intraspinal tumor.
(C) Frontal view. The segmental artery gives rise to an anterior (arrowhead) and posterior (arrow) spinal cord supplying artery. Note the
different positions of the hairpin curve and of the descending branches. (Displacement of the anterior and posterior spinal arteries
below the level of the injection and the equal size of both vessels are due to an intraspinal neurinoma.) (D) Lateral view. The anterior
(arrowhead) and posterior positions (arrow) of the anterior and posterior spinal artery can be distinguished. Abbreviation: AVM, arterio-
venous malformation.
50 NEUROINTERVENTIONAL MANAGEMENT

Anterior coronal Middle coronal Posterior coronal

(A) (B) (C)

Figure 3.11 Anterior spinal artery, intrinsic arteries, and pial plexus demonstrated on microangiograms of the lumbar spinal cord. The
spinal cord has been cut into three coronal sections, each 2--3mm thick. (A) Anterior coronal section. Numerous transverse and oblique
branches from the anterior spinal artery (arrow) supply the anterior part of the superficial pial plexus called vasocorona. (B) Middle
coronal section. The central arteries, derived from the anterior spinal artery, course to one side of the cord and branch mainly within
the gray matter. From the surface of the spinal cord, perforating branches of the vasocorona penetrate and supply the outer rim of fiber
tracts and parts of the posterior horn. (C) Posterior coronal section. The larger posterolateral (arrows) and smaller posterior spinal
arteries (arrowheads) form a rope ladder-like network, supplying the posterior part of the vasocorona. The position of the posterolateral
arteries is lateral of the posterior root and medial of the posterior arteries. Source: From Ref. 13.

sources as well as from both the anterior and pos-
terior circulation. Figures 3.18 and 3.19 illustrate
the different configuration of the hairpin-curve in
anterior and posterior radiculomedullary arteries.
Figure 3.20 demonstrates differentiation of extra-
dural supply to a dural-based lesion from spinal
artery supply to intramedullary lesions. Neverthe-
less it is often essential to have a lateral projection
or 3D angiogram for a definite identification.
2. Spinal dural AV-fistulae (SDAVF) may look very
similar to AVMs (Fig. 3.21). But as long as no typi-
cal radiculomedullary artery is involved, the AV-
shunt is much more likely situated at the level of
the dura mater.
3. Discrimination between a perimedullary fistula
(fistulous type of an AVM) and a SDAVF may
be difficult if the arterialized vein looks like an
anterior radiculomedullary feeder with a hair-
pin-curve (Fig. 3.22). This is not rare in SDAVF
at lower lumbar levels when the arterialized
vein is one of the large lumbar veins shown in
the post-mortem specimen of Figure 3.14B. To
avoid misinterpretation, careful analysis of the
vessel anatomy in the region of the interverte-
bral foramen is important, as well as a look at
the further course of the vessel on the spinal
cord surface on later images (Fig. 3.22C). If you
are unable to identify an arteriovenous shunt
(fistula) on or within the spinal cord, ask your-
self if the intradural blood vessels as a whole
could not be veins (Fig. 3.21).
4. Spinal cord supplying arteries and arterialized
veins (in case of a SDAVF) may be observed at
the same level and same side as demonstrated in
Figure 3.23. They are better discriminated on lat-
eral views.
5. If an anterior or posterior spinal artery seems to
be too large for the region to be supplied or if it
extends below the level of the cone, it should be
followed caudally. This is the only way not
to miss small AVMs of the filum terminale
(Fig. 3.24).
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 51

Arterial Venous

Cervical
Figure 3.12 Comparison between intrinsic spinal cord
arteries and veins demonstrated on microangiograms of
axial sections of 2-mm thickness. (A) Arteries at different
levels of the spinal cord (anterior spinal artery, arrow; pos-
terior/posterolateral spinal arteries at both sides of the pos-
terior root entry zone, small arrowheads). The central
Thoracic arteries (large arrowhead) are the predominant intrinsic
feeders at the level of the cervical and lumbar enlarge-
ments. They run within the anterior fissure and continue
either to the right or left side of the hemicord as a centrifu-
gal system. The perforating branches are the predominant
feeders of the thoracic spinal cord. They originate from the
superficial vasocorona as a centripetal system, and their
territory of supply can very well be differentiated from the
system of central Q10 arteries. (B) Veins at different levels
of the spinal cord. Radial and central veins are of almost
equal size and drain to the pial covering of the spinal cord
Lumbar (anterior and posterior median spinal veins, arrows).
(A) (B) Source: From Ref. 13.

Figure 3.13 Comparison between intrinsic spinal cord arteries

and veins demonstrated on microangiograms of sagittal sections
through the midline of the spinal cord (thickness, 2mm). (A)
Arteries at a lower thoracic level. Anterior spinal artery (large
arrow) with loss of contrast filling in small sections. The ascending
course of the central arteries with more vertical than horizontal
arborization within the gray matter is demonstrated. The impres-
sion of an intrinsic longitudinal anastomosis is not supported by
coronal images. Compare the small perforating arteries of the pos-
terior columns, originating from the pial network of the vasocorona.
(B) Veins at a lower thoracic level. Anterior median vein (arrow)
and posterior median vein (double arrow) with loss of contrast fill-
ing in sections. The sulcal veins are less numerous but larger than
the posterior veins. Several of them join to form a common stem
(arrowhead). The different pattern of intrinsic arterial supply and
venous drainage at approximately the same spinal cord level is
(A) (B) well demonstrated in this comparison. Source: From Ref. 13.
52 NEUROINTERVENTIONAL MANAGEMENT

Figure 3.14 Superficial spinal cord veins. (A)

Photograph of the dorsal aspect of a spinal cord
specimen following ink injection into the veins at
cervical and thoracic levels. The posterior
RV
median vein has a variable size at different lev-
els. Three large radiculomedullary veins (arrows)
and some smaller ones can be seen. (B) X-ray
film (AP view) of a contrast-injected thoracolum-
bar spinal cord specimen. There is much tortuos-
AMV ity mainly of the posterior spinal cord veins
(posterior venous plexus). Three large radiculo-
medullary veins accompany lumbar or sacral
nerve roots to reach the epidural space (arrows).
(C) Photograph of an injected spinal cord speci-
men with filling of the ventral veins at the thora-
cic level. Note the hairpin configuration of the
AMV, where it continues as RV. This configura-
tion is very similar to the arterial one. The non-
filled anterior spinal artery is running beside or
over the vein (arrow). Abbreviations: AMV,
(A) (B) (C) anterior median vein; RV, radicular vein.

Figure 3.15 DSA of an artery of Adamkiewicz with arterial and

venous phase. (A) Typical hairpin course between the anterior
radiculomedullary artery and the descending branch of the ante-
rior spinal artery. (B) Venous phase showing the radiculomedul-
lary vein coincidentally at the same level. The configuration
between midline and radiculomedullary veins is the same. This
configuration is important to know for the interpretation of angio-
grams in case of an AVM with early venous filling or of spinal
MRAs with insufficient time resolution. Abbreviations: DSA,
digital subtraction angiography; AVM, arteriovenous malforma-
(A) (B) tion. Source: Courtesy of Prof. G. Schroth, Berne, Switzerland.
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 53

U
HR

Figure 3.16 Venous midline anastomoses. (A) T1-

weighted sagittal MRI following injection of the contrast
medium. Demonstration of a large intramedullary mid-Q11
line anastomosis between the anterior and posterior mid-
line veins in a normal subject (arrow). Source: Courtesy
of Prof. D. Petersen, Lu beck, Germany. (B) Transparen-
chymal anastomosis near the medullary cone with a cali-
ber of 0.7mm (arrows). Microangiogram of a midsagittal
cut with venous filling (same specimen as in Fig. 3.10B).
Note the larger caliber of the anterior vein at the level of
the cone compared with the posterior vein. Source: From
(A) (B) Ref. 13.

HR

Figure 3.17 Superficial spinal cord veins in the lumbar spi-

nal cord and cauda equina. (A) MRI of T1-subtraction
image. The anterior median vein is running together with the
filum terminale to the end of the caudal sac (arrowheads),
which can be an abnormal arterialized Q12 vein or a normal
variant as is shown in (B, C). (B) X-ray film of an injected
specimen in lateral projection. Tortuous posterior venous
plexus at the level of the lumbar enlargement (small
arrows). The anterior median vein (arrowhead) continues as
a terminal vein (vein of the filum terminale). Several trans-
SP 6 medullary anastomoses can be assumed in this projection
radiography (small arrowheads). (C) Microangiogram of the
cone with a large terminal vein (arrowhead). Source: (B)
(A) (B) (C) and (C) From Ref. 13.
54 NEUROINTERVENTIONAL MANAGEMENT

Posterolateral right

T12

L1

(A) (B) (C)

Posterolateral left
Anterior
T11

T11

T12

Posterolateral left
during embolization
(D) (E) (F)

Figure 3.18 AVM at the level of the cone, supplied by two posterolateral feeders and the anterior spinal artery. (A) MRA showing
the malformation as a whole and the main drainage into a considerably enlarged terminal vein (arrow). (B) Unsubtracted angio-
gram. Typical midline position of the anterior spinal artery. Supply from this vessel is mostly running through the arcade of the
cone (arrowheads) to the posterior surface. (CE) DSA. Note the somewhat different hairpin configurations of anterior and post-
erolateral feeders in AP view (arrowheads). The largest part of the nidus is lying posteriorly (arrows). (F) Horizontal interconnec-
tions (black arrows) between the posterolateral tracts (arrowheads) are visualized with increasing peripheral resistance during
embolization.
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 55

(A) (B) (C)

Figure 3.19 Anterior and posterior spinal arteries. (A) Unsubtracted and Subtracted (B) AP view of left T8 injection of patient with spi-
nal AVM at T11-L1. Note the midline hairpin turn of anterior spinal artery (arrowheads) compared to off-midline position of posterolat-
eral spinal artery (arrows). Also note the different hairpin configurations of anterior and posterolateral feeders in AP view. (C) AP
injection at left L1 also demonstrates midline anterior spinal artery (arrowhead) and off-midline posterior spinal artery (arrow).

(C)

(A) (B)

(D) (E)
(F)

Figure 3.20 Spinal artery and radicular arterial supply to dural-based and intramedullary hemangioblastomas. An enhanced CT of
patient with Von Hippel--Lindau syndrome demonstrates spinal hemangioblastomas located in both extramedullary (A) and intramedullary
(B) locations (arrowheads). Angiogram shows dural supply (arrow) to extramedullary lesion (arrowheads) [AP subtracted view (C), and
3D reconstructions (D, E)]. Intramedullary lesions (arrowheads) receive supply from posterolateral spinal artery (arrow) (F). *Associated
renal cell carcinoma.
56 NEUROINTERVENTIONAL MANAGEMENT

T5

Figure 3.21 SDAVF T5 level. The AV shunt is at the level of the

dura mater (arrow) and is directed at two veins coming from
upward and downward. The mass of dilated veins resembles an
AVM, but no spinal cord artery is involved. Abbreviations: DSA,
digital subtraction angiography; SDAVF, spinal dural arteriove-
nous fistula; AVM, arteriovenous malformation.

Figure 3.22 DSA of a SDAVF at the L3 level

(arrowhead). (A) The blood vessel that is opacified
first resembles a radiculomedullary artery. It runs
L3 L3 upward to the cone and lumbar enlargement and
exhibits a narrow curve. (B) Anterior position of the
blood vessel in the lateral view. (C) Filling of typical
veins on the later image in the AP view. The config-
uration of a radiculomedullary vein can be very sim-
ilar to that of an artery (compare Figs. 3.11 and
3.12). Abbreviations: DSA, digital subtraction
angiography; SDAVF, spinal dural arteriovenous
(A) (B) (C) fistula.
 VASCULAR ANATOMY OF THE SPINE AND SPINAL CORD 57

(A) (B) (C)

Figure 3.23 DSA of a SDAVF with an anterior radiculomedullary artery entering at the same foramen. (A) AP view. The artery (arrow-
heads) is partially superimposed by the enlarged veins (arrow). (B) The lateral view demonstrates the anterior position of the artery
(arrowheads) and the posterior position of the mass of veins (arrow). (C) Spinal dural arteriovenous fistula with spinal artery at the
same level. In another patient with SDAVF, the dural shunt (arrow) drains into pial veins. An uninvolved anterior spinal artery (arrow-
heads) originates at the same level and enters through the same foramen. Abbreviations: DSA, digital subtraction angiography;
SDAVF, spinal dural arteriovenous fistula.

L2

L1

Figure 3.24 AVM of the filum terminale (DSA, AP

L4 views). (A) The anterior spinal artery (black arrows) is
not unusually enlarged, but it continues without a
change in caliber below the level of a cone in normal
position. (B) At the L4 level, a second blood vessel is
opacified that is a little bit larger than the artery and
runs in upward direction (artery, black arrow; arterial-
L3 ized terminal vein, arrowheads). The clinical signifi-
cance of this small AV shunt (white arrow) was
considerable. Abbreviations: AVM, arteriovenous
(A) (B) malformation; DSA, digital subtraction angiography.
58 NEUROINTERVENTIONAL MANAGEMENT
REFERENCES
1. Kadyi H. Uber die Blutgefae des menschlichen Rucken-
markes. Lemberg: Grubnowicz u Schmidt, 1889.
2. Adamkiewicz A. Die Blutgefae des menschlichen
Ruckenmarkes. II.Teil: Die Gefae der Ruckenmarkoberfl-
ache. Sitzungsberichte der Akademie der Wissenschaften
Wien. Mathematisch-Naturwissenschaftliche Klasse (Abt.III)
1882; 85: 10130.
3. Thron A. Vascular Anatomy of the Spine. In: Byrne J, ed.
Interventional Neuroradiology. Oxford: Copyright Oxford
University Press, 2002.
4. Lasjaunias P, Berenstein A, ter Brugge K. Surgical Neuro-
angiography. Vol. 1: Clinical Vascular Anatomy and Varia-
tions. 2nd edn. New York: Springer, 2002.
5. Lazorthes G, Poulhes J, Bastide G, Roulean J, Chancolle
AR. La vascularisation arterielle de la moelle. Recherches
anatomiques et applications a la pathologie medullaire et a
la pathologie aortique. Neurochirurgie 1958; 4: 319.
6. Lazorthes G, Gonaze A, Djindjian R. Vascularisation et cir-
culation de la moelle epiniere. Paris: Masson, 1973.
7. Lasjaunias P, Vallee B, Person H, TerBrugge K, Chin M.
The lateral spinal artery of the upper cervical spinal cord. J
Neurosurg 1985; 63: 23541.
8. Fazio C, Agnoli A. The vascularization of the spinal cord.
Anatomical and pathophysiological aspects. Vasc Surg
1970; 4: 24557.
9. Tveten L. Spinal cord vascularity. The venous drainage of
the spinal cord in the rat. Acta Radiol 1976; 17: 65362.
10. Gillilan LA. Veins of the spinal cord. Neurology 1970; 20:
8608.
11. Turnbull JM, Breig A, Hassler O. Blood supply of cervical
spinal cord in man; a microangiographic cadaver study.
J Neurosurg 1966; 24: 95165.
12. Crock HV, Yoshizawa H. The blood supply of the vertebral col-
umn and spinal cord in man. Wien, New York: Springer, 1977.
13. Thron AK. Vascular anatomy of the spinal cord. Wien,
New York: Springer, 1988.
14. Jellinger K. Zur Orthologie und Pathologie der Rucken-
markdurchblutung. Wien, New York: Springer, 1966.
15. von Quast H. Die Venen der Ruckenmarkoberflache.
Gegenbaurs Morphol Jahrb 1961; 102: 3364.
16. Suh TH, Alexander L. Vascular system of the human spinal
cord. Arch Neurol Psychiatr 1939; 41: 65977.
17. Jacobs T. Venae radiculares. Anatomische Untersuchungen
zur venosen Drainage des menschlichen Ruckenmarkes.
Thesis. Medizinische Fakultat der Rheinisch-Westfalischen
Technischen Hochschule Aachen, 1996.
18. Moes P, Maillot C. Les veines superficielles de la moelle
epiniere chez lhomme. Essai de systematisation. Archives
DAnatomie DHistologie DEmbryologie normales et
experimentales. Extrait du tome 64. Paris, Colmar: Edition
Alsatia, 1981: 5110.
19. Foix Ch, Alajouanine Th. La myelite necrotique subaigue.
Rev Neurol 1926; 33: 142.
20. Thron A, Koenig E, Pfeiffer P, et al. Dural vascular
anomalies of the spine- an important cause of progressive
myelopathy. In: Cervos-Navarro J, Ferszt R, eds. Stroke
and microcirculation. New York: Raven Press, 1987.
21. Oswald K. Untersuchungen Uber das Vorkommen von
Sperrmechanismen in den Venae radiculares des Men-
schen. Thesis. Berlin, 1961
22. Tadie M, Hemet J, Aaron C, et al. Le dispositif protecteur
anti-reflux des veines de la moelle. Neurochirurgie 1979;
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23. Otto J. Morphologie des Sperrmechanismus am Duradurch-
tritt der Venae radiculares des Menschen. Neuroradiologische
und histologische Befunde. Thesis. Medizinische Fakultat der
Rheinisch-Westfalischen Technischen Hochschule Aachen,
1990.
 4
Intracranial collateral routes and anastomoses in
interventional neuroradiology
David S. Liebeskind
INTRODUCTION
Collateral circulation in the brain compensates for
obstruction to arterial inflow or venous drainage (1,2).
Descriptions of collateral vessels date back to the
founding of neurology. Centuries after Sir Thomas
Willis described arterial collaterals and their potential
significance in disease, angiography illustrated the
influential role of these routes. Hemodynamic studies
later emphasized the critical impact of collaterals, yet
subsequent imaging advances diverted attention away
from angiography seeking neuroprotection and target-
ing tissue ischemia. In the routine clinical practice of
interventional neuroradiology, arterial and venous
intracranial collaterals are influential factors in the
diagnosis, treatment, and prognosis of various cerebro-
vascular disorders.
Knowledge of collateral anatomy and patho-
physiology may expand our understanding of numer-
ous disorders. Correlative studies of imaging features
and angiography may facilitate diagnosis and broaden
perspectives on novel treatment strategies. This chap-
ter reviews current knowledge of arterial and venous
collaterals, emphasizing the specific implications of
collaterals in various disorders.
ANATOMY
The anatomy of intracranial collaterals greatly impacts
the capacity of these channels to provide alternative
blood flow routes across different regions, with collat-
eral capacity primarily determined by luminal caliber.
A description of arterial collateral anatomy may be
subdivided between common routes including Willi-
sian collaterals at the circle of Willis or leptomeningeal
anastomoses, and atypical circuits that may develop
in response to particular lesions. Similarly, venous col-
lateral anatomy may be described by the typical anas-
tomotic routes and the atypical, a category where the
diversity and complexity of routes is innumerable.
Some connections such as the posterior communicat-
ing artery (PCoA) represent embryonic remnants.
Other routes form only in response to disease. There
are also numerous collateral extracranial-intracranial
(EC-IC) routes, not discussed herein, for both arterial
and venous flow diversion. Much of the knowledge
regarding anatomy of intracranial collaterals stems
from historical descriptions over the last few hundred
years. Only recently, with the advent of angiography
and modern imaging techniques, have the functional
correlates of these blood flow routes been established.
Prior reports have classified collateral routes as pri-
mary or secondary functional routes based on anatom-
ical location, yet this may be an oversimplification as
great variability exists. Knowledge of intracranial col-
lateral anatomy in humans is particularly important
with respect to understanding of ischemic stroke and
other clinical cerebrovascular disorders, as there are
considerable differences in anatomy that may pre-
clude successful translation of therapeutic approaches
studied in animals (3). Species differences in the con-
figuration of collaterals may also be compounded by
differences in collateral anatomy amongst various
individuals or populations.
The circle of Willis provides numerous potential
routes for blood flow diversion (Fig. 4.1). All of the
Willisian segments, including the anterior communi-
cating artery (ACoA), the proximal anterior cerebral
artery (ACA), PCoA, and the proximal posterior cere-
bral artery (PCA), may facilitate flow diversion in
either direction depending on intraluminal pressure
gradients. All of these segments may also be atretic or
hypoplastic, yet retain the ability to develop signifi-
cant blood flow capacity and luminal expansion (4,5).
These arterial segments are relatively closely matched
in size and vessel wall characteristics with respect to
their parent arteries. This configuration allows for
interhemispheric collateral flow or compensation for
gradients that may develop between the anterior and
posterior circulations. Much emphasis has been placed
on the anatomy of the PCoA (6,7). Various terms,
including persistent or fetal PCoA anatomy, have
been used to differentiate the status of this segment
based on diameter measurements at autopsy or on
imaging studies such as magnetic resonance angiogra-
phy (MRA), where the status of this vessel or domi-
nance is described in relationship to the proximal
PCA. Descriptive terms of the opposite situation,
where there has been involution of the embryonic ori-
gin of the PCoA from the internal carotid artery (ICA)
resulting in a hypoplastic PCoA, have questionable
validity as even small diameter remnants may once
again provide blood flow if the need arises. Arterial
patterns at the circle of Willis have been categorized
citing the prevalence of certain configurations, but
such descriptive data are also questionable as
60 NEUROINTERVENTIONAL MANAGEMENT

b
a d
c

DSL

(A) (B)

Figure 4.1 Schematic illustration of the circle of Willis and potential Willisian collaterals, including ACoA (A), proximal ACA (B), PCoA
(C), and proximal PCA (D).

including end-to-end anstomoses, end-to-side connec-

a
b
DSL
Figure 4.2 Schematic illustration of principal supratentorial lepto-
meningeal anastomoses in the brain, including ACA-MCA (A)
and PCA-MCA (B) routes.
anatomy may change with disease, age, or vary
amongst populations.
The leptomeningeal anastomoses bridging dis-
tal reaches of the major cerebral arteries are small
(~50400mm) arteriolar connections that allow for ret-
rograde perfusion of adjacent territories (Fig. 4.2) (8,9).
Such connections display variable configurations,
tions, and azygos variants (9,10). These arteriolar anas-
tomoses adjoin the middle cerebral artery (MCA) with
both the ACA and PCA. Anastomoses from the ACA
potentially feed the superior or anterior divisions of the
MCA, with most posterior or inferior division MCA
collateral flow arising from the PCA. Such connections
are relatively sparse between the ACA and PCA. The
seminal work of Vander Eecken and Adams on 20
human cadavers delineated the principal characteristics
of leptomeningeal anastomoses, illustrating consider-
able variability in the size, number, and location of
these collaterals (9). Such great variability likely influ-
ences the results of any particular anatomical study
and likely accounts for much controversy in correlative
studies of collateral function with age. Anastomoses
also converge over the cerebellar convexities where the
distal branches of the posterior inferior cerebellar
arteries (PICAs), anterior inferior cerebellar arteries,
and superior cerebellar arteries (SCAs) meet (Fig. 4.3).
The posterior meningeal artery may also provide collat-
eral flow in PICA occlusion (11). Due to the symmetric
anatomy of posterior fossa structures, such anastomo-
ses may allow for collateral flow between cerebellar
hemispheres and from proximal to distal aspects of the
basilar distribution.
In cases where flow demands and pressure gra-
dients exceed the capacity of primary arterial routes
and Willisian or leptomeningeal collaterals, atypical
routes of collateral flow may develop. Some collateral
routes may utilize the paths of normal variants such
as azygos connections between the ACAs. The ante-
rior and posterior choroidal arteries may distribute
blood flow in either direction between the anterior
and posterior circulations. In cases of moyamoya, this
choroidal network is commonly recruited. Other
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
a system, including the cortical veins and superior sagit-
b tal sinus, typically empties the majority of outflow
c toward the right transverse and sigmoid sinuses and
DSL
Figure 4.3 Schematic illustration of cerebellar anastomoses,
demonstrating potential collateral flow between SCA (A), AICA
(B), and PICA (C).
a tial anastomoses to relieve focal venous hypertension,
c
b
d The epidemiology of intracranial collaterals has occa-
e f
DSL
Figure 4.4 Schematic illustration of intracranial venous anatomy
and typical collateral routes, including vein of Trolard (A), vein of
Labbe (B), deep middle cerebral vein (C), superior petrosal sinus
(D), pterygoid plexus (E), inferior petrosal sinus and basilar
plexus (F).
moyamoya arterioles pervade subcortical structures,
meandering around occluded MCAs. Anastomoses
may shunt flow between the PCA and SCA at the
61
tentorial edge. More unusual arterial collateral routes
may also arise, commonly in association with promi-
nent EC-IC collaterals. Atypical collaterals can be
demonstrated in almost any configuration, limited to
an extent solely by physical barriers such as the falx
or tentorium.
Venous collateral anatomy is best understood in
light of typical venous flow patterns (Fig. 4.4) (12,13).
Venous drainage is balanced by superficial and deep
systems, with the transcerebral veins allowing for
potential shunting in either direction. The superficial
into the jugular. When jugular occlusion is present,
the majority of flow is diverted to the vertebral
venous drainage pathways (14). The anastomotic veins
of Trolard and Labbe shunt flow across the cerebral
hemisphere to drainage pathways with lower pres-
sures. Similarly, cortical veins share connections
allowing for diversion of flow. The deep system
includes the choroid plexuses and draining veins of
the thalami, striatum, periventricular white matter,
limbic regions, and rostral brainstem. Larger emissa-
ries of this system include the basal veins, vein of
Galen, and straight sinus. The deep system may drain
via the straight sinus and into the left transverse sys-
tem, or alternatively, send flow anteriorly toward the
basal veins. Numerous anastomoses abound toward
the inferior surface of the brain allowing for drainage
of the deep system. The deep middle cerebral vein,
inferior and superior petrosal sinuses, and the basilar
plexus may shuttle flow across these regions. Due to
the variability in venous outflow patterns and poten-
minimal attention has been placed on systematic char-
acterization of venous collateral anatomy.
EPIDEMIOLOGY
sionally been broached in the literature, citing varia-
tions in Willisian anatomy or unfounded theories
related to collateral development in different cohorts
such as the elderly. Most of these studies have utilized
anatomical data based on autopsy series. Unfortu-
nately, this approach of using anatomical postmortem
data to describe potential collateral function does not
make sense when one considers the dynamic changes
in collateral flow that take place during life. Studies of
Willisian configuration in normal individuals are also
limited as collaterals are irrelevant in the absence of
disease. Functional assays such as angiographic dem-
onstration of collateral flow during particular clinical
scenarios, such as acute ischemic stroke, provide fur-
ther information (Fig. 4.5), yet serial changes or a reflec-
tion of collateral development may still go unresolved.
Other reports in the literature have extrapolated find-
ings on coronary or peripheral arterial collaterals to the
cerebral circulation without validation. Much specula-
tion has addressed the influence of age with respect to
collateral flow, yet considerable variability with intra-
cranial collaterals likely occurs with increasing age (15).
The epidemiologic data on arterial collateral flow, via
Willisian or leptomeningeal routes, even within a
62 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 4.5 Right ICA injection at angiography demonstrating Willisian and leptomeningeal collateral flow in acute stroke due to left ICA
occlusion.
specific disease state remain scant. The epidemiology
of venous collaterals is unknown.
PATHOPHYSIOLOGY
The pathophysiology of collateral circulation in the
brain has largely been unexplored. Much of the
knowledge regarding arterial collaterals has been
extrapolated from studies of collateral circulation in
other vascular beds or in animal models where vast
differences exist with respect to collateral anatomy.
Venous collateral pathophysiology remains virtually
completely unknown. Most of the very few studies of
collateral flow in humans relate to anatomical patterns
and resultant blood flow, yet very little is known
about collateral recruitment. Recent animal studies
have shown that the extent or anatomy of collaterals
does not necessarily reflect the potential functional
role in collateralization (16). The process of arteriogen-
esis, or the recruitment and development of pre-exist-
ing arterioles to accommodate significant flow
changes, must be distinguished from angiogenesis, the
de novo growth of vessels (17). Features of both may
be simultaneously involved with various cerebrovas-
cular disorders, yet the role of these processes is quite
distinct. Furthermore, although arterial collaterals may
be emphasized in acute ischemic stroke, there are
likely implications or changes that take place in the
venous system as well. Similarly, failure of venous
collateralization in cerebral venous thrombosis (CVT)
may ultimately affect arterial inflow, leading to ische-
mia. As a result, the arterial and venous components
must be considered in concert. Venogenesis, the
venous counterpart of arteriogenesis, is assumed to be
similar to the pathophysiologic events that accompany
the arterial process. Time is also a critical variable, as
the capacity for collaterals to adapt to blood flow
derangements changes with time. The particular role
or influence of collaterals in specific disorders is con-
sidered in subsequent sections of this chapter. With
all of these entities, however, it remains important to
distinguish the presence of collaterals at a specific
DSL
(C)
timepoint versus the development or collateralization
process itself.
The presence or extent of collaterals defined at
angiography or imaging reflects the end result of an
adaptive process responding to significant blood flow
alterations. The process of collateralization may be
best studied in cases where collaterals are suboptimal
or in cases with progressive ischemia or congestion,
allowing for investigation over a prolonged time-
course. In cases of acute stroke with exuberant collater-
als, the process may be obviated or fully realized. The
pathophysiology of arteriogenesis has been established
in the peripheral and coronary circulations (18,19).
Arteriogenesis is principally mediated by increased
fluid shear stress due to mechanical forces that
accompany pressure gradients across anastomotic
vessel segments. Inflammation plays a key role,
incited by cytokine upregulation and macrophage
infiltration due to mechanical events at the anastomo-
ses (20). Vascular remodeling allows for potential
expansion of the anastomotic vessel radius, thereby
increasing flow and alleviating fluid shear stress. This
process has considerable differences with respect to
angiogenesis (Fig. 4.6). Arteriogenesis may rapidly
culminate in dramatic increases in blood flow,
whereas angiogenesis is a local phenomenon increas-
ing permeability and relatively fragile capillary
growth without the capacity for significant increases
in blood flow. Angiogenesis in the brain occurs in
perilesional areas around arteriovenous malforma-
tions, tumors, and stroke (21). Recently, the potential
for angiogenesis and concomitant neurogenesis has
been the focus of investigation in studies of stroke
recovery or restorative neurology. The potentially
beneficial role of inflammation in cerebral arteriogen-
esis has yet to be established. In other arterial beds,
inflammation simultaneously promotes atherosclero-
sis and corresponding arteriogenesis. Very recently,
genetic upregulation of the actin-binding Rho activat-
ing protein triggered by mechanical factors at anasto-
motic sites has been discovered (22). Although the
basic vascular pathophysiology of arteriogenesis and
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
Angiogenesis
Definition Formation of new capillaries
Vessel source Pre-existing capillaries
Location Periphery of ischemic lesion
Stimulus ischemia
Oxygen status Hypoxia
Inflammatory events Parenchymal ischemic damage
Potential blood flow increase ~ 1.5-fold
Compensation for arterial occlusion Unable
Figure 4.6 Table summary of the critical differences between arteriogenesis and angiogenesis and implications in acute cerebral
ischemia.
b
c constricting adjacent daughter arteries. The resulting
a
d occluded arterial segment. Intravascular deoxygenation
DSL
Figure 4.7 Diagram of retrograde leptomeningeal flow in the set-
ting of MCA occlusion (A), illustrating anastomotic inflow via iso-
lated distal segments (B, C) and predominant flow toward the
trunk of the occluded parent artery (D).
collateralization are likely to be similar, the anatomy
of intracranial collaterals and resultant pathophysiol-
ogy may be quite distinct (23).
Willisian collaterals allow for prompt flow diver-
sion across relatively small distances between arterial
territories. Pressure differentials allow for potential
circuits to open, allowing flow to course toward the
ischemic vessel or territory. The diameter of these con-
nections may be quite variable across individuals,
likely reflecting developmental variation and subse-
quent evolving changes during life. Willisian collater-
alization and the appearance of the circle of Willis is
therefore a dynamic process (24).
Leptomeningeal anastomoses may also evolve in
response to environmental stressors, yet the nature of
leptomeningeal collateral perfusion is quite complex.
The elongated pathways bridging arterial territories
provide blood flow via a limited number of distal
anastomoses that perfuse the ischemic territory in
63
Arteriogenesis
Growth of arterial collaterals
Pre-existing arterioles
Anastomoses from adjacent territories
Fluid shear stress
Normoxia
Cytokine and macrophage-mediated vascular remodeling of anastomoses
> 10-fold
Able
retrograde fashion. Such reverse arterial flow via selec-
tive daughter branches is extremely unusual (Fig. 4.7),
unlike other blood flow routes in the systemic circula-
tion. This pattern of blood flow violates the major
hemodynamic principal of Murrays Law, where flow
is configured in a manner that is energy efficient (25).
It remains unknown whether the distal arterial tree
adapts to conform to this ideal mode of blood flow by
slow flow is largely diverted toward the parent
likely occurs due to slow flow past ischemic endothe-
lium and neighboring ischemic brain parenchyma (26).
In response to ischemia, the microcirculation
adapts through loss of flow heterogeneity to accommo-
date maximal oxygen extraction (27). Low perfusion
hyperemia, the expansion of cerebral blood volume
(CBV) despite diminished blood flow due to arterial
occlusion, relies heavily on the venous system (15). The
mechanisms underlying venous engorgement remain
unclear, but progressive expansion of the venous bed
downstream from the ischemic arterial territory has
been well documented (15). A critical and potentially
influential question addresses what leads to the demise
of this compensatory mechanism. Cerebral venous
steal, reduction of the critical pressure gradient to
maintain collateral arterial inflow, and the veno-arterial
reflex have been postulated as potential factors (28).
These factors may also be important in the process of
arterialization of the venous system that accompanies
other cerebrovascular disorders.
Paradoxically, much of the vascular pathophysi-
ology relating to cerebral hemodynamics and intracra-
nial collateral flow was uncovered more than 25 years
ago. Angiography was pivotal in these investigations,
yet subsequently replaced by more noninvasive imag-
ing modalities. The unrealized hopes of neuroprotec-
tion and isolated focus on the ischemic cascade
without consideration of blood flow diverted attention
away from hemodynamics and vascular pathophysiol-
ogy often observed by interventional neuroradiologists
in the angiography suite.
CLINICAL CORRELATES
The clinical features associated with collateral circula-
tion are often manifest as a dramatic minimization of
symptoms despite severe obstruction to normal blood
flow. Examples of this phenomenon include asympto-
matic acute occlusion of the MCA, clinically silent ICA
64 NEUROINTERVENTIONAL MANAGEMENT
Figure 4.8 CTV demonstrating transverse and sigmoid sinus
thromboses (arrows) with isolated headache.
Figure 4.9 CTA source images depicting contrast opacification
of leptomeningeal vessels (arrows) in the setting of acute left
MCA occlusion.
occlusion, or even occlusion of all proximal arteries
without stroke (29). Similar events may occur even
more frequently with venous collateralization. For
instance, CVT involving the principal dural sinuses
may go undetected (Fig. 4.8). Such examples of collat-
eral ability to ameliorate or minimize clinical symptoms
are often only recognized when dynamic changes cause
transient loss of this ability. In such situations, wide
fluctuations in symptoms or neurological deficits may
be apparent. These fluctuations are most commonly
observed during the very early stages of acute ische-
mia, during the first minutes and hours after presenta-
tion. In cases of MCA ischemia triaged in the
prehospital setting as soon as 15 minutes after symp-
tom onset, deficits are often quite minimal, followed by
considerable changes, and often devastating conse-
quences at later timepoints. Certain clinical features
may also be described with specific disorders. Collat-
eral failure may occur during subacute stroke, despite
previously sustained perfusion and no apparent blood
pressure or hemodynamic changes. In similar fashion,
the limb-shaking transient ischemic attacks (TIAs) of
moyamoya may represent only transient collateral fail-
ure. Referred auditory phenomena or bruits may indi-
cate venous collateralization. Many of these clinical
features are often suspected to be mediated by collater-
als, yet imaging or angiography is often required to
substantiate these claims.
IMAGING
Unlike the principal arterial and venous routes in the
brain, imaging of collaterals evades most current tech-
niques (30). In part, this is due to the fact that when
disease alters the normal pathways for blood flow,
collaterals will develop via numerous trajectories. Fur-
thermore, collateral anastomoses tend to be diminu-
tive as they are recruited only as they are needed. As
a result, the goal of imaging collaterals often follows
an indirect path where much is inferred based on vas-
cular distributions and the oxymoronic objective of
attempting to see what cannot be seen. There is no
ideal imaging modality for demonstration of collater-
als (31). Although conventional angiography has been
extremely influential in characterization of collaterals
and angiographic correlation is often used to substan-
tiate noninvasive markers of collateral flow, there
remain qualitative aspects of collateral perfusion that
evade angiography. As a result, imaging characteriza-
tion of intracranial collaterals is founded upon inte-
gration of findings from various studies. Each
modality brings a specific advantage or limitation. For
instance, MRA may fail to demonstrate flow in a func-
tional ACoA if a specific threshold is not met. In con-
trast, CT angiography (CTA) may demonstrate fairly
extensive leptomeningeal collaterals yet the flow in
these segments may be quite minimal (Fig. 4.9). Dif-
ferences inherent to each modality may accentuate
flow or anatomical patency to varying degrees. For
most of the clinical disorders encountered in interven-
tional neuroradiology that are described in this chap-
ter, angiography remains paramount for definitive
characterization of collateral flow. Whereas Willisian
routes are more easily depicted with various imaging
modalities, leptomeningeal collaterals are more diffi-
cult to delineate. Many of the noninvasive imaging
correlates beyond definition of collaterals on conven-
tional angiography have been described and based on
findings in acute ischemic stroke. Extrapolation from
acute ischemia to other variants such as near occlu-
sion or recurrent ischemia bordering on critical perfu-
sion thresholds has provided insight on other clinical
scenarios where arterial collaterals are pivotal (30).
Paradoxically, the acute ischemic stroke imaging
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
Figure 4.10 CT in acute right MCA stroke with isolated hypoden-
sity of the insular region (arrows).
Figure 4.11 MRI evidence of flow voids (arrows) associated with
a previously undiagnosed CAVM.
65
findings of collateral perfusion may even have valua-
ble information related to venous collateral system as
well. For instance, imaging of congested venous drain-
age in low perfusion hyperemia may be similar to the
findings noted in CVT. Imaging of collaterals is best
described by distributions, direct visualization of the
anatomical structures themselves, and functional
aspects including perfusion. The advent and increas-
ingly routine clinical application of multimodal CT
and MRI, incorporating parenchymal images, some
extent of angiographic depiction of proximal lesions
and corresponding collateral circulation, as well as
perfusion may be gleaned.
The vascular distributions of arterial or venous col-
laterals mirror normal patterns of arterial supply or
venous drainage. For instance, the borderzones of the
MCA territory are based on the normal pattern for the
periphery of blood flow in this artery. Unfortunately,
these boundaries shift based on variations in normal
anatomy and with disease. In general, regions deep
within the expected primary vascular distribution are
collateral poor, whereas collaterals abound at the periph-
ery. The extreme variability of venous collateral anat-
omy makes it quite difficult to infer such distributions.
CT or MRI parenchymal sequences may demonstrate
patterns suggestive of collateral recruitment. Insular vul-
nerability in MCA occlusion suggests collateral salvage
of more peripheral cortical regions (Fig. 4.10). Similarly,
borderzone infarcts may suggest collateral hemody-
namic insufficiency.
Direct visualization or imaging of Willisian
routes may be feasible with most diagnostic modal-
ities. The short segmental collaterals at the circle of
Willis may be demonstrable with transcranial color-
coded Doppler ultrasonography, CTA, MRA, and con-
ventional angiography. In the setting of acute ischemic
stroke, Willisian flow patterns reflect changes that
took place shortly after arterial occlusion. Once flow is
restored with proximal recanalization, such diversion
of flow and the pattern of Willisian collaterals may
change abruptly. Changes in Willisian flow with appa-
rent arterial diameter expansion may also be evident
in serial imaging of cases with chronic hypoperfusion
or ischemia (24). Leptomeningeal collaterals may be
evident with conventional angiography and CTA, and
only in rare circumstances with MRA. The slow flow
in leptomeningeal collateral routes precludes adequate
visualization of these segments with MRA. CTA
source images may provide an indication of the extent
of leptomeningeal collaterals when viewed in axial
format. The ability to depict venous collaterals is anal-
ogous to demonstration of leptomeningeal arterial col-
lateralsconventional angiography and CTA may
illustrate these channels, yet MRA or magnetic reso-
nance venography (MRV) is limited. On review of
parenchymal sequences, venous collaterals may be
seen as engorged or dilated structures with prominent
flow voids. Such an appearance may indicate the pres-
ence of a peripherally situated arteriovenous malfor-
mation (Fig. 4.11). Conventional angiography may
easily demonstrate the presence of arterial or venous
collateral routes, with some information regarding
functional capacity evident by the temporal appear-
ance of delayed opacification or washout. Such images
provide a link between the anatomical information of
66 NEUROINTERVENTIONAL MANAGEMENT
Figure 4.12 Slow, retrograde leptomeningeal collateral filling of
the left MCA demonstrating FVH (arrows).
Figure 4.13 GRE prominence of the draining basal vein (arrow)
suggesting deoxygenation in the setting of acute stroke.
vessel appearance and functional aspects of resultant
perfusion.
Aside from demonstrating the presence of collat-
eral routes, imaging may also provide some insight on
the functional aspects or capacity of collaterals as well.
Various modalities may characterize features of collat-
eral blood flow and nutrient or oxygen exchange. The
amount of flow in various Willisian collaterals may be
estimated from transcranial Doppler (TCD); however,
velocity measures alone may be deceiving as diameter
changes may accompany collateral recruitment. In con-
trast to the previous discussion regarding direct visual-
ization of collaterals, MRA or MRV may have an
advantage over CTA or computed tomographic venog-
raphy (CTV) by accentuating flow characteristics rather
than anatomy. Therefore, standard time-of-flight (TOF)
MRA may provide very useful information regarding
capacity of specific collateral routes. Conventional MRI
sequences may provide some subtle, yet very useful
findings related to collateral flow. Fluid-attenuated
inversion-recovery (FLAIR) MRI vascular hyperinten-
sity (FVH) may be evident in distal aspects of an
occluded artery due to slow, retrograde leptomeningeal
collateral filling of the artery (Fig. 4.12) (3234). Deoxy-
genation in such distal arterial segments may be evi-
dent with gradient-recalled echo (GRE) sequences (26).
Such signal loss on GRE associated with deoxygenation
may also be observed in draining veins from the ische-
mic territory in stroke or in engorged venous collaterals
due to thrombosis (Fig. 4.13). Recent developments in
MRI have capitalized on the ability to encode spatial or
directional information with phase-contrast (PC) MRA
techniques, or selective labeling of specific arterial
inflow routes with selective arterial spin-labeled
(SASL) perfusion (35,36). Arterial spin labeled perfu-
sion MRI may reveal delayed arterial transit effects due
to slow, leptomeningeal flow supplying the periphery
of an ischemic lesion (3739). ASL may also reveal col-
lateral flow patterns that offset hemorrhagic transfor-
mation (40). Commonly used contrast-bolus perfusion
techniques with CT or MRI also provide important
information regarding collateral flow. Both modalities
demonstrate delay and dispersion of contrast passage
that is characteristic of collateral flow (Fig. 4.14). CBV is
often elevated and microcirculatory changes may be
evident if one analyzes the tissue concentration curves
in detail. When considering perfusion imaging techni-
ques, it is important to remember that specific patterns
may change rapidly with time and that certain perfu-
sion findings may have different implications in acute
versus chronic settings. During chronic phases, specific
perfusion abnormalities may be better tolerated.
DISORDERS
Arterial and venous disorders affecting the brain invar-
iably involve some element of collateral circulation.
Collaterals may serve a compensatory role to sustain
oxygen and nutrient delivery scaled to metabolic
demand or these alternative blood flow routes may
maintain homeostasis through relief of venous conges-
tion. These beneficial roles are complemented by poten-
tially detrimental aspects as well. For instance,
collateral arterial feeders and venous routes may hin-
der treatment of arteriovenous malformations as these
channels proliferate due to humoral and mechanical
influences. Although current clinical decision-making
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
c (t)
c (t)
(A) t (B)
Figure 4.14 Schematic illustration of the normal tissue concentration curve (A) and the delay and dispersion associated with collateral
flow (B) in the setting of acute stroke.
(A) (B)
Figure 4.15 Diffusion-weighted imaging (A), time-to-peak PWI map (B), and angiogram (C) in acute left MCA occlusion.
may only be marginally influenced by the extent of col-
laterals, the goals of revascularization procedures or
treatments are often synonymous with collateralization.
Similarities exist in the anatomy of collateral routes and
related pathophysiology, yet the role of collaterals is
best understood within the context and following dis-
cussion of specific cerebrovascular disorders.
ISCHEMIC STROKE
Collaterals play a crucial role in acute ischemic stroke
(2,30,41,42). Although not all strokes are associated
with thromboembolic occlusion of an intracranial
artery or arteriole, ischemia in an arterial territory or
bed is universal. Progressive stenosis of a proximal
artery may also incite ischemia and elicit collateral
recruitment. The degree or extent of collateral compen-
sation varies, as distal cortical branch occlusions or
lacunar strokes have limited collateral routes to balance
diminished antegrade flow. The vast majority of
knowledge regarding intracranial arterial collateral
pathophysiology has been garnered from clinical
67
t
(C)
observations and imaging correlates during acute or
subacute cerebral ischemia. During these dynamic
early stages of collateral adaptation to ischemia,
patients often undergo various imaging studies,
including angiography. At later stages, a more stable
balance between residual antegrade flow and collater-
als develops. As a result, some of the observations
regarding collaterals in acute ischemic stroke may be
relatively unique, precluding translation of these obser-
vations to other clinical settings. The critical role of col-
laterals is accentuated by the impressive impact of
collateral perfusion on recanalization and the fallacy of
neuroprotection without blood flow to the penumbra
beyond the occluded vessel segment (3). Great empha-
sis has duly been placed on proximal recanalization,
yet such approaches are often futile and sustenance of
the penumbra via collaterals may be the only viable
therapeutic option. In order to capitalize on potential
collateral therapeutic interventions, attention must be
focused on integration of the wealth of clinical, imag-
ing, and angiographic data that are often collected dur-
ing early stages after symptom onset (Fig. 4.15).
68 NEUROINTERVENTIONAL MANAGEMENT
Collateral pathophysiology in acute stroke may
be ideally described in the setting of MCA occlusion.
As soon as distal intraluminal arterial pressure
beyond the clot plummets due to failure of antegrade
flow, collaterals are recruited. Ischemia associated
with a large pressure gradient, and not hypoxia, is the
principal driving force that encourages blood flow to
traverse the leptomeningeal anastomoses between the
distal reaches of the ACA and PCA into the MCA
field. Augmented flow in these small anastomoses
causes a dramatic rise of fluid shear stress and resul-
tant vascular remodeling due to arteriogenesis. Upre-
gulation of various cytokines and macrophage
invasion leads to permeability derangements in these
areas at the far periphery of the ischemic field. Even-
tually, this process leads to an increase in the radii of
these small collateral routes. Release of angiotensin II
and neuropeptide Y may cause systemic hypertension,
yet ironically, the relatively intact vasoconstrictive
capacity of these distal arterioles may offset attempted
hypertension-mediated flow increases. Retrograde
MCA flow is highly energy inefficient and even slight
reductions in the driving pressure gradient may cause
collateral failure. CBV elevations principally due to
venous engorgement and loss of flow heterogeneity in
the microcirculation allow for optimal oxygen and
nutrient extraction. Eventually, however, a series of
detrimental events may ensue where CBV drops and
collateral failure is manifest. The triggers for failure of
such beneficial early stages of CBV elevation that has
been termed low perfusion hyperemia remain unclear.
Unless correlative imaging or angiographic stud-
ies are acquired, the dynamic clinical fluctuations due
to collateral flow during acute ischemic stroke may go
unfounded. Rapid changes in head positioning and
dramatic increases in volume due to fluid boluses
may produce profound changes and even normaliza-
tion of the neurological examination, despite persis-
tent arterial occlusion. Unfortunately, such changes
may be transient, as sudden deterioration due to col-
lateral failure may also occur. This paradigm is most
worrisome when early hemodynamic improvement
deters the clinician from intravenous thrombolysis
within 3 hours and subsequent deterioration occurs
well beyond this limited therapeutic window.
Case 1
A 92-year-old woman presented with acute onset of
right hemiparesis and aphasia. Emergent MRI was
acquired, revealing occlusion of the left MCA without
diffusion-weighted imaging evidence of tissue injury
(Fig. 4.16). FVH illustrated slow, retrograde collateral
filling of the left MCA (Fig. 4.17). After 20 minutes in
supine position during the MRI, her neurological defi-
cits completely resolved. On return to the ER, she sat
upright and her prior deficits of aphasia and hemipa-
resis recrudesced. Robust leptomeningeal collaterals
were evident on angiography (Fig. 4.18) and following
complete recanalization with mechanical thrombec-
tomy her exam normalized again. The decision to pro-
ceed with thrombectomy was prompted by her
transient collateral failure associated with changes in
head positioning. This case demonstrates that collater-
als may avert tissue injury despite abrupt cessation of
arterial flow and that vigorous collaterals may be evi-
denced even with advanced age.
Almost every imaging modality provides some
information regarding collateral flow in acute ischemic
stroke. Transcranial Doppler ultrasonography may
exhibit flow diversion at the circle of Willis during
acute MCA occlusion; increased velocities in other
arterial segments may signify collateral flow. Trans-
cranial color-coded ultrasonography may also provide
direct visualization of such Willisian correlates. Often,
the most demonstrable indirect evidence of collateral
flow is loss of the insular ribbon on noncontrast CT.
This finding suggests collateral preservation of the
remainder of the MCA field. Infarct growth in the
setting of persistent occlusion is also partially a reflec-
tion of collateral failure. MRI offers several further
facets of collateral flow in acute stroke (43). FVH in
distal segments of the MCA or occluded vessel is
due to slow, retrograde leptomeningeal collateral
flow (33,34). As the days from symptom onset lapse,
this finding subsides due to stabilization or equilibra-
tion of collateral flow with infarct growth. Correlation
with conventional angiography proves that FVH is
not due to thrombosis itself. GRE MRI sequences may
depict deoxygenation in distal leptomeningeal collat-
erals, draining veins, and in the ischemic tissue as
well. Permeability derangements at the borderzones
associated with collateral recruitment may also be
depicted as subarachnoid hyperintensity on FLAIR
(Fig. 4.19) or with dedicated permeability imaging
techniques. Collateral perfusion is most readily identi-
fied on perfusion CT or MRI techniques. The foot-
prints of collateral perfusion are evident as
prolongation in time-to-peak contrast bolus, elevated
mean transit times, augmented CBV, and microcircu-
latory measures demonstrating loss of flow heteroge-
neity. These individual parameter maps may be
generated with either CT or MRI perfusion techni-
ques. Other imaging techniques such as single-photon
emission computed tomography (SPECT) or positron
emission tomography (PET) may provide additional
hemodynamic or even metabolic information related
to collateral perfusion, yet such approaches are often
cumbersome or impractical in the setting of acute
ischemic stroke. The utility of such perfusion imaging
studies to depict regions dependent on collateral flow
gave rise to the development of mismatch as an imag-
ing surrogate of salvageable penumbra. Various defi-
nitions or iterations of mismatch have been developed
in order to ideally select candidates for therapeutic
intervention whilst minimizing risk. Although much
emphasis in the literature has been placed on imaging
identification of mismatch, incredibly few have sub-
stantiated the basis of this approach addressing the
actual source of collateral perfusion. Furthermore, it is
often forgotten that such imaging techniques provide
only a snapshot in time of an extremely dynamic
process that may radically differ within minutes.
Others have attempted to utilize noninvasive angio-
graphic depictions of collateral flow. CTA source
images (CTA-SI) may provide some indication for the
extent of collateral perfusion, yet the prolonged imag-
ing acquisition obliterates temporal information
related to flow in order to achieve more anatomical
images. CTA-SI of potential collaterals over the
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
(A)
(B)
Figure 4.16 Acute left MCA occlusion on MRA (A) with unrevealing diffusion-weighted imaging (B) despite extensive time-to-peak
abnormalities on perfusion-weighted imaging (C).
hemispheric convexity may accurately predict good
functional outcome in acute stroke (44,45). MRA may
fail to demonstrate leptomeningeal collaterals, yet ipsi-
lateral changes in the PCA may be indicative of PCA
to MCA collateral flow in acute stroke (Fig. 4.20).
Such changes may include prolongation or extension
of the apparent PCA course on MRA reconstructions,
or increases in the apparent PCA diameter (46). Ulti-
mately, definitive proof of collateral supply depends
on conventional angiography (47). Correlation of
angiographic findings, however, with the often subtle
noninvasive imaging findings noted above provides
important information in other cases when angiogra-
phy is not available or for ongoing imaging research
related to collateral circulation. Angiography may
reveal flow diversion via Willisian routes and lepto-
meningeal sources of perfusion during the arterial
phase. Adjacent arteries such as the ACA or PCA are
initially visualized, followed by a momentary delay
69
(C)
during transit through anastomoses beyond the reso-
lution of conventional angiography, culminating with
retrograde filling of the MCA. Similarly, PICA to SCA
anastomoses over the cerebellar convexities may
bypass severe stenoses or occlusions of the basilar.
The extent, but also the temporal features, of such fill-
ing patterns are important for adequate characteriza-
tion of collateral flow. Several scales have been
developed to capture such information, incorporating
the delay of collateral perfusion that may be pro-
longed well beyond the normal capillary filling and
into the late venous phases (48,49). Such prolongation
of venous perfusion may also provide important infor-
mation regarding the venous congestion associated
with elevated CBV and the low perfusion hyperemia
of acute stroke. As most of the limited number of
angiographic scales that capture information on collat-
eral flow emphasize arterial filling, angiographic cor-
relation with perfusion mismatch may be somewhat
70 NEUROINTERVENTIONAL MANAGEMENT

Figure 4.17 FVH in the distal left MCA (arrow) reflecting pre-
dominantly PCA to MCA collateral flow.
Figure 4.19 Subarachnoid hyperintensity on FLAIR due to
increased permeability and contrast leakage at the leptomenin-
geal borderzones.

LT CCA

Figure 4.18 Retrograde leptomeningeal collateral filling of the

left MCA territory demonstrated with angiography on a left com-
mon carotid artery injection.

inaccurate. Following effective reperfusion due to

recanalization and cessation of collateral dependence,
all of these imaging or angiographic markers of collat-
eral flow disappear. In fact, persistence of such
markers of collateral flow may be indicative of incom-
plete reperfusion. Many of these imaging markers of
collateral flow may be seen with other cerebrovascular
disorders, but multimodal correlation is often best Figure 4.20 Ipsilateral prominence of the PCA (arrows) on MRA
with the contemporaneous imaging approach unique in the setting of acute right MCA occlusion.
to acute ischemic stroke.
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY 71

The reliance on angiography for validation of col-

Figure 4.21 Frontal projection of a left ICA injection on angiogra-
phy demonstrating retrograde filling of the MCA.
lateral supply largely limits observations on collateral
flow in acute stroke to cases where endovascular ther-
apy is entertained or in the decreasing number of cases
where diagnostic conventional angiography is pursued.
Collateral flow has been demonstrated as a strong pre-
dictor of favorable clinical outcome in intra-arterial
thrombolysis and mechanical thrombectomy (50,51).
Collateral flow does not appear to influence the success
of proximal recanalization, yet ischemic injury may be
lessened in tissue supplied by collaterals beyond the
occlusion or such regions may be sustained until even
partial restoration of antegrade flow is established. Col-
lateral flow may also thereby decrease the risk of hem-
orrhagic transformation. The pattern of collateral
filling, such as Willisian diversion and configuration of
potential ACA collateral flow in ICA occlusion, may
have a substantial effect on outcome. The unusual fill-
ing pattern of retrograde arterial flow in the ischemic
field may also determine the quality or effects of collat-
eral perfusion (Fig. 4.21). Willisian collaterals have
recently been used for delivery of endovascular ther-
apy (52). The first endovascular device utilizing collat-
erals, NeuroFlo, has also recently been studied in
clinical trials (53). The device employs augmentation of
cerebral blood flow that accompanies titration of con-
comitant supra- and infra-renal artery aortic balloon
inflation during acute stroke (Fig. 4.22). The mechanism
of this approach remains to be elucidated, however.
Once proximal recanalization or antegrade flow is
restored, angiographic collaterals dissipate. In clinical
practice, the appearance of robust collaterals at angiog-
raphy may be deceiving in decision-making. One may
be compelled to forego relatively risky interventions to
establish antegrade flow when collaterals are excellent.

(A) (B)

Figure 4.22 Aortagram during placement and titration of balloons on the NeuroFlo device for potential collateral augmentation in
acute stroke.
72 NEUROINTERVENTIONAL MANAGEMENT
LT ICA
Figure 4.23 Frontal projection of an angiogram showing retrograde
collateral flow in severe atherosclerotic stenosis of the left MCA.
Unfortunately, when left untreated, many of these cases
may be prone to collateral failure (54). Alternatively,
the degree of collaterals may lessen stroke severity or
clinical outcome even after failed recanalization. A
recent series on emergent EC-IC bypass in acute stroke
demonstrated a potential beneficial role in select cases
(55). Despite these ostensibly critical implications of
collateral flow in acute stroke, collaterals are often
regarded as only a curious finding on angiography in
acute stroke. Most multicenter trials of endovascular
therapy to date have considered collaterals only in post
hoc analyses.
Ongoing investigations of collateral circulation in
acute cerebral ischemia may elucidate important clini-
cal features, imaging correlates, and undisclosed path-
ophysiology of collateral perfusion. Such studies may
also provide relevant information for translation to
the management of other cerebrovascular disorders.
These findings may cease the unshakable failure of
neuroprotection related to ongoing disregard for col-
lateral perfusion and facilitate the development of col-
lateral therapeutics (3,42,56). Endovascular therapy for
proximal recanalization may be refined, allowing for
collateral augmentation after failed recanalization and
prolonged windows of opportunity. The calculations
of time is brain assuming a linear function may also
be clarified through consideration of collaterals and
the ability to maintain tissue for prolonged periods of
time. Revision of this concept may recognize that time
is brain because collaterals may fail with time.
INTRACRANIAL ATHEROSCLEROSIS
Although the intracranial arterial collateral circulation
has been well described in acute ischemic stroke and in
chronic extracranial occlusive disease, knowledge of
collaterals in chronic intracranial occlusive disorders is
largely limited to moyamoya. In chronic intracranial
atherosclerotic disease, arterial stenosis may be isolated
to a specific arterial segment, invoking a particular pat-
tern of collateral development. Recent work suggests
that moyamoya collateral vessels develop when lepto-
meningeal collaterals are insufficient (57). Furthermore,
antegrade flow in that territory may not be viable via
shorter segmental bypasses provided by the lenticulos-
triate collaterals of moyamoya. In contrast with acute
ischemic stroke where complete or subtotal occlusion is
common, a wide range in the degree of stenosis may be
present with intracranial atherosclerosis. The influence
of time or temporal features may be quite distinct as
the pace of intracranial atherosclerosis may allow for
more considerable collateral compensation (Fig. 4.23).
Collateral flow should theoretically be inconsequential
or nonexistent if the stenosis is not hemodynamically
significant, exceeding luminal stenoses beyond 6070%.
Nevertheless, anecdotal descriptions relate collateral
findings with even mild to moderate stenoses. The
question remains as to whether such stenoses are
actually hemodynamically significant because of factors
beyond luminal stenosis. Collaterals with intracranial
occlusive disease may be far more complex than in
extracranial disease, as leptomeningeal and not only
Willisian routes are commonly utilized. If one segre-
gates focal intracranial lesions by potential collateral
routes, a different balance may exist between leptome-
ningeal and Willisian collateral influences. For instance,
leptomeningeal collaterals may be pivotal in MCA
stenosis, whereas Willisian routes may provide retro-
grade flow distal to a basilar stenosis. These differences
underscore the unique aspects of intracranial collaterals
in atherosclerotic disease.
Despite these potentially important aspects of
collateral flow with intracranial atherosclerosis, the
subject remains unexplored except for sporadic case
series or isolated reports that skirt the topic. Several
reasons for this lapse may exist. Intracranial athero-
sclerosis has only recently been studied in systematic
fashion in the Warfarin Aspirin Symptomatic Intracra-
nial Disease (WASID) trial (58). The study was
stopped prematurely based on the futility to detect a
significant difference in treatment between warfarin
and aspirin. A parallel investigation of noninvasive
imaging correlates, the Stroke Outcomes and Neuroi-
maging of Intracranial Atherosclerosis (SONIA) study,
demonstrated the relatively marginal performance of
MRA and TCD for detection of angiographic stenoses
in a multicenter setting (59). Willisian collaterals may
be readily detected with such noninvasive techniques,
yet leptomeningeal collaterals may require conven-
tional angiography (Fig. 4.24). As a result, many clini-
cians have deliberated the role of imaging versus
angiography and potential treatments for intracranial
atherosclerosis. Only very recently has the potential
impact of intracranial angioplasty and stenting
revived the consideration of conventional angiography
and concomitant characterization of collaterals. Future
studies will likely need to heed the impact of collater-
als on stroke risk and stenting for a given stenosis.
Such analyses of collaterals may reveal differences in
the role of intracranial collaterals at various stages of
disease. Specific collateral patterns, such as distal flow
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
(A)
Figure 4.24 Frontal projection of a left ICA injection at angiography of concomitant ACA and distal MCA stenoses (arrows).
Figure 4.25 Angiography demonstrating retrograde leptomenin-
geal filling of the MCA beyond a proximal stenosis.
reversal in the basilar or leptomeningeal recruitment
with MCA stenosis (Fig. 4.25), may be predicted based
upon luminal stenosis or provide critical clinical infor-
mation related to stroke risk. Similarly, the presence
of beneficial collateral flow may also be used in the
future to decide when stenting is not indicated despite
severe stenoses.
MOYAMOYA
Moyamoya is the quintessential model of collateral cir-
culation in the brain. The term has been used to describe
a severe, multifocal steno-occlusive intracranial arterial
73
(B)
disease that most frequently affects young women of
Asian descent. Moyamoya syndrome refers to a similar
pattern of predominantly proximal anterior circulation
occlusive lesions and exuberant collateral formation that
occurs in other cohorts or settings (Fig. 4.26) (60,61).
Although much debate has focused on distinguishing
this syndrome from the disease, the late stage patho-
physiology relating to collateral flow is identical (61).
The demographic and clinical features of moyamoya
cases in the United States may be strikingly different
than classic Asian descriptions (62). As an example, a
moyamoya pattern may be seen in older patients with
severe atherosclerotic disease due to numerous vascular
risk factors. Imaging definitions have been used to
describe a moyamoya pattern. Specific MRI criteria have
arisen from conventional angiographic stages, delineat-
ing patterns that correlate with disease progression.
Unfortunately, many aspects continue to fuel debate.
When unilateral or subtle findings are noted, many
question the diagnosis of moyamoya. Others resist usage
of the term when the pathognomonic fine network of
lenticulostriate collaterals is inapparent. Irrespective of
the diverse range of conditions that has been reported in
association with moyamoya, particular features are
universal including initial diversion of flow through
Willisian collateral routes and crucial recruitment of lep-
tomeningeal collaterals to supply the vascular territory
distal to the steno-occlusive lesions. Abnormal hemody-
namics or particular flow patterns may predispose to the
development of stenotic lesions and at later stages, fur-
ther flow disturbances may lead to aneurysm formation
(63). It has been suggested that areas of lower fluid shear
stress predispose to moyamoya stenoses in the distal
carotid arteries (64). Moyamoya patterns have been
described with various concomitant neurovascular
lesions, including atypical aneurysms, vascular anoma-
lies, and arteriovenous malformations (65,66).
The clinical features of moyamoya syndrome
have remained obscure as these patients often
present with diverse demographic backgrounds, vari-
ous co-morbidities, and often have minimal clinical
74 NEUROINTERVENTIONAL MANAGEMENT
Figure 4.26 TOF MRA illustrating multifocal anterior circulation
occlusions in moyamoya syndrome.
Figure 4.27 FLAIR depiction of the ivy sign in moyamoya, dem-
onstrating subtle hyperintensities of the subarachnoid space
(arrows).
symptoms due to well-developed leptomeningeal col-
laterals. Patients may present with migrainous head-
aches due to leptomeningeal dilatation, seizures, or
TIAs. Sensory TIAs may be ascribed to migrainous
events, yet these brief ischemic episodes may result
from transient failure of parietal collaterals. After
recovering from such brief symptoms, there is often
little impetus to pursue further diagnostic studies.
Devastating strokes, including hemorrhages, may
occur however. Imaging features, such as the ivy
sign (Fig. 4.27), may be subtle and vascular disease
may go unsuspected unless a dedicated angiographic
(noninvasive or conventional) study is acquired (67).
Due to such poor recognition of this disorder and
the reliance on conventional angiography, these
patients are probably most frequently encountered
by angiographers such as interventional neuroradiol-
ogists. Although angiographic descriptions have
often focused on the steno-occlusive lesions, angiog-
raphy of collateral patterns is often dramatic and
may be helpful in characterization of the disorder.
Aside from the fine, lenticulostriate collaterals that
bypass segmental occlusions of the MCA or ACA,
the PCA is often markedly enlarged or prominent
with vigorous leptomeningeal collaterals that supply
the cerebral convexities. Progressive enlargement of
the PCoA followed by proximal PCA stenosis fol-
lows obliteration of normal antegrade blood flow
routes in the anterior circulation (24). Deep trans-
cerebral collaterals may be evident as medullary
streaks on MRI (68,69). At later stages of the disor-
der, enlargement of collaterals between the anterior
and posterior choroidal arteries may herald intracere-
bral hemorrhage (70).
The lack of prospective studies of moyamoya,
especially within the United States, has lead to a clini-
cal quagmire where little knowledge has been garnered
regarding treatment of patients with moyamoya. In
general, once an imaging study or conventional angiog-
raphy confirms the diagnosis, most patients are
referred to select vascular neurosurgeons for potential
bypass or synangiosis (71). Medical treatment of moya-
moya remains uncharted. The specific extent of collat-
eral formation or perfusion derangements on
noninvasive studies is rarely used to select candidates
for intervention (72). Delineation of an exhausted oxy-
gen extraction fraction on PET may be useful in guid-
ing future standardized approaches (73). Intracranial
angioplasty and stent placement has only rarely been
described, perhaps due to the fear of dissection or per-
foration of the stenotic artery with presumed inflam-
matory infiltrates. The decision to proceed with EC-IC
bypass or synangiosis may be influenced by angio-
graphic features. It is imperative that collaterals are
carefully preserved during bypass to avoid complica-
tions (74). Following revascularization of such cases,
these patients may have limited clinical follow-up by
neurologists but they may be serially monitored by
neuroradiologists with multimodal CT, MRI, or con-
ventional angiography. Following revascularization,
clinical symptoms of this progressive disorder may
abate due to adequate collateral augmentation (75,76).
Interestingly, focal revascularization also appears to
improve global perfusion due to easing of demand on
various collateral channels (77). Future studies may
focus on moyamoya to model collateral flow in acute
stroke or to further characterize the pathophysiology of
collateral failure.
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
(A)
Figure 4.28 Willisian collateralization (A, B) of the PCoA chronicled with TOF MRA.
EXTRACRANIAL ARTERIAL STENOSIS OR
OCCLUSION
Prominent pressure differentials exerted at the circle of
Willis and resultant shifts in blood flow may occur
with stenosis or occlusion of the extracranial carotid or
vertebral arteries. Although alternative EC-IC routes of
blood flow diversion are frequently noted, these
changes are accompanied by shifts in blood flow in var-
ious Willisian segments. Unilateral carotid occlusion or
even vertebral occlusion with a contralateral hypoplas-
tic vertebral artery may elicit such changes. Willisian
segments are able to rapidly shunt flow to the poten-
tially ischemic region or hemisphere. Stenoses must
exceed 6070% before hemodynamic implications are
evident, yet severe stenoses or occlusions are necessary
to cause flow redistribution at the circle of Willis. Mod-
erate stenoses of the extracranial ICA for instance, may
not be hemodynamically significant but embolic risk
may be high. As Willisian collaterals respond only dur-
ing considerable intraluminal pressure shifts, even
severe, ulcerated carotid plaques may not elicit Willi-
sian changes unless hemodynamically significant.
Patency of only one collateral segment has been shown
to be sufficient to avert hypoperfusion during carotid
revascularization (78). Rapid downstream pressure
changes due to plaque rupture and sudden carotid
occlusion may not be adequately predicted based on
Willisian flow patterns unless the culprit lesion is
hemodynamically significant at baseline. More subtle
changes may be evident with progressive stenoses,
allowing Willisian segments such as the PCoA to grow
with time (Fig. 4.28). The end-diastolic velocity of the
75
(B)
CCA on duplex ultrasonography of carotid stenoses
may be able to determine the hemodynamic signifi-
cance of such lesions as correlated with Willisian collat-
eral patterns (79,80). Once flow is restored, these
changes may be readily reversed. For instance, rapid
changes in collateral flow and cerebral blood flow dis-
tribution may occur after endovascular or surgical
revascularization of extracranial stenoses (81,82). Caro-
tid revascularization of stenosis contralateral to an
occluded carotid may also improve ACoA flow to the
contralateral hemisphere (83).
A multitude of reports have described extensive
extracranial occlusive disease with good clinical out-
comes. Alternatively, in cases with rapid ICA occlusion
due to thromboembolic disease, failure of Willisian
segments to compensate for reduced blood flow may
lead to devastating strokes. Time appears to be a crit-
ical factorif stenoses or occlusions develop over a
long period of time, almost any degree of occlusive dis-
ease may be tolerated (84). Even bilateral common car-
otid occlusion may be sustained with a good clinical
course (66). The configuration of Willisian segments
and metabolic demand of downstream territories may
determine the size, severity, and pattern of cerebral
infarction (Fig. 4.29) (85,86). Presence of ophthalmic
flow reversal and leptomeningeal recruitment may sig-
nify relative insufficiency of Willisian segments (87).
The specific Willisian segments may also differentially
affect the pattern of cerebral ischemia. ACoA flow may
determine the size and occurrence of borderzone
infarction, whereas PCoA flow may be inconsequential
(86,88). Almost every diagnostic modality employed
in prior reports has demonstrated that collateral
76 NEUROINTERVENTIONAL MANAGEMENT
Figure 4.29 FLAIR demonstration of a relatively small infarct in
left ICA occlusion due to dissection and adequate collateral
capacity.
compensation and downstream blood flow require-
ments may play a critical role in delineating asympto-
matic and symptomatic carotid occlusions (89).
Prediction of recurrent stroke risk with sympto-
matic carotid occlusion has yielded conflicting results.
Some have reported that high residual flow rates in
other arterial segments and suggested that prominent
collateralization via PCoA flow may identify patients at
high risk for recurrent ischemia (90). Improved oxygen
extraction has been associated with increased collateral
flow after carotid occlusion (91). After symptomatic
carotid occlusion, recurrent stroke may not be offset by
improved collateral flow alone, however (92). The need
for collateral blood flow via the circle of Willis is likely
influenced by the size of the baseline lesion and subse-
quent demand. Differences in technique and patient
characteristics have likely influenced the results of
numerous studies attempting to conclusively delineate
the nature of this relationship (83,91,93). Angiographic
definition of collateral flow patterns, including Willi-
sian diversion, pial supply, and delayed venous opaci-
fication, may provide important information regarding
ischemic risk after symptomatic carotid occlusion. Brief
angiographic evaluation of Willisian segments alone
may not accurately predict misery perfusion on PET
(93). As much controversy persists regarding the role
of EC-IC bypass surgery, detailed evaluation of angio-
graphic, hemodynamic, and metabolic status with PET
(Fig. 4.30) was recently used to identify candidates for
revascularization in the Carotid Occlusion Surgery
Study (COSS) (94,95).
It has also been suggested that the etiology of
proximal ICA occlusion may influence outcome. ICA
occlusion due to dissection may produce larger
infarcts compared with progressive atherosclerotic
disease due to the relative insufficiency of collaterals
with rapid occlusion following dissection (96). The
extent of Willisian collaterals after an occlusion due
to dissection may also influence the likelihood for
spontaneous recanalization, as robust collaterals may
hinder reestablishment of patency in the proximal
dissected segment.
Various imaging techniques and provocative
maneuvers have been used to assess not just stroke
risk, but the need for shunting or other periprocedural
interventions for carotid revascularization (36,97,98).
The absence of ACoA or PCoA flow on angiography
has been used to predict the need for shunting during
carotid revascularization (99). Phase-contrast MRA,
because of its ability to reflect not just the presence of
flow, but direction may be useful to predict changes
that may occur with temporary carotid occlusion (100).
Prediction of ischemia and need for shunting may
ideally be defined based on noninvasive studies prior
to revascularization.
CEREBRAL VENOUS THROMBOSIS
CVT is relatively uncommon, yet it is often considered
as the prototypical venous disorder. The cerebral
venules and draining sinuses account for more than
6080% of CBV, yet much of the complex physiology
in the cerebral venous system, however, remains
unexplored. The diverse nature of CVT-associated pre-
disposing conditions or prothrombotic states has
attracted much attention. In fact, most of the literature
on CVT focuses on the thrombotic aspects without
consideration of venous flow patterns (Fig. 4.31). Sev-
eral neurovascular lesions such as arteriovenous mal-
formations or fistulae may have complex
angioarchitecture that promote venous thrombosis,
but venous collaterals are otherwise rarely considered.
The remarkable distensibility and ability to compen-
sate for pressure differentials within the cerebral
venous system has implications for every aspect of
CVT from diagnosis to treatment.
Thrombosis of a venous sinus or draining vein is
offset by diversion of flow into neighboring channels.
Unless considerable stasis ensues, the thrombus will
remain isolated to the occluded segment until endoge-
nous thrombolytic mechanisms allow for recanaliza-
tion. Venous pressure may rise in adjacent areas, but
this is generally well tolerated. Areas of the brain
with relative venous insufficiency may be prone to
venous hypertension, with subsequent vasogenic
edema, hemorrhage, and ultimately, ischemia. Venous
hypertensive hemorrhage is more common in areas
with relatively poor venous collaterals even with
small amounts of clot, whereas extensive thrombosis
of several major dural sinuses may be inconsequential.
Due to extreme variability in venous collateral net-
works, venous hemorrhage may be difficult to recog-
nize based on location alone, as the principal venous
territories are often vague (13,101). Hemorrhage con-
fined to the deep territory of the vein of Labbe (Fig.
4.32) may be one of the few exceptions. The relative
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY 77

Oxygen15 water blood flow image (cs17009) Max

L R 0
Oxygen15 oxygen metobolism image (cs17009)
Max

L R 0
Countbosed oxygen extroction image (cs17009) 1.0

L R 0

Z = 34 Z = 28 Z = 24 Z = 12 Z = 10 Z=2

Figure 4.30 Oxygen--15 PET data showing increased oxygen extraction fraction in the right hemisphere of a patient with carotid occlusion.

dominance of right- versus left-sided drainage of the

Figure 4.31 MRV illustration of prominent collateralization in
extensive CVT.
superficial and deep venous territories influences
venous hypertension and lesion location (13,101,102).
The medullary or transcerebral veins may also divert
flow in either direction between the superficial and
deep systems.
The clinical presentation and subsequent course
of CVT is completely determined by collaterals (103).
In fact, many CVT cases have been estimated to go
undiagnosed likely because of considerable compensa-
tion by venous collaterals. Even though isolated corti-
cal vein thrombosis may cause neurological deficits in
some individuals, the pursuit of this diagnosis is often
tempered as it is generally considered a benign disor-
der due to collateral outflow. When patients present
with CVT, headache, seizures, and focal neurologic
deficits may be noted. Sensory complaints, transient in
many cases, may occur due to venous congestion of
parietal regions with transverse or sigmoid sinus
involvement. Some patients may describe ear fullness,
bruits, or other auditory complaints associated with
shunting of venous flow (Fig. 4.33). Dependent head
positioning may elicit dramatic increases in symptoms
or jugular venous distention. On occasion, a patient
may present with an intracerebral hemorrhage of
unclear etiology until venous thrombosis or prominent
venous collateralization is noted.
This broad spectrum of clinical manifestations
and imaging presentation with hemorrhage has
78 NEUROINTERVENTIONAL MANAGEMENT
Figure 4.32 Intracerebral hemorrhage due to occlusion of the
left vein of Labbe.
Figure 4.33 Prominent venous collaterals on CTV causing audi-
tory phenomena in CVT.
caused much confusion. Imaging correlates are
extremely variable, best defined with MRI. Any
Figure 4.34 Mastoid fluid collection on MRI in the setting of
CVT.
angiographic technique (CTV, MRV, or conventional
angiography) can illustrate thrombotic occlusion and
some degree of venous collateralization. MRI offers
particular advantages including demonstration of iso-
lated cortical vein thromboses, prominence or disten-
tion of medullary veins, and silent edema or dramatic
parenchymal lesions including hemorrhage that may
easily resolve over time (85,104,105). MRI may also
show mastoid fluid collection due to venous conges-
tion and attempted outflow via collaterals (Fig. 4.34).
Angiography has assumed a minimal role in diagnosis
of CVT and is increasingly reserved for rescue treat-
ment when patients deteriorate.
Angiography may depict extensive venous collat-
erals in cases of dural sinus thrombosis. Following
thrombolysis or thrombectomy, such venous collater-
als may resolve but the timecourse may be protracted
if thrombus is retained or stasis continues.
Such residual venous collaterals may persist
indefinitely, causing other clinical symptoms. Residual
symptoms such as tinnitus or nystagmus may be par-
tially due to collaterals. These seemingly detrimental
manifestations of distended venous collaterals offset
the potentially high mortality rate of an otherwise rel-
atively benign disorder.
DURAL ARTERIOVENOUS SHUNTS
The development of dural arteriovenous shunts or fis-
tulae (DAVF) has not been elucidated, although angio-
genic factors are thought to promote vascular conduits
between superficial arteries and veins. Such shunts
may be expected to produce arterial steal syndromes,
but symptoms typically result from venous outflow
disturbances (Fig. 4.35). Cortical venous reflux and
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
LT CCA LT CCA
Figure 4.35 Lateral projection of a left common carotid injection demonstrating a left transverse sinus DAVF with numerous extracra-
nial carotid artery feeders and prominent venous cortical reflux.
RT. ICA
Figure 4.36 Angiographic demonstration of a complex CAVM
with multiple feeders and venous drainage pathways.
diversion of flow via venous collaterals may produce
focal neurological symptoms, tinnitus, or bruits. More
diffuse venous drainage patterns involving the sinuses
may promote thrombosis or engender cognitive defi-
cits, including a rapidly progressive dementia (106).
Abnormal flow in DAVFs may also be associated with
the development of concomitant aneurysms or cerebral
arteriovenous malformations. Due to the substantial
complexity and variable drainage patterns of these
lesions, DAVF classification standardly defines cases
based on specific venous outflow patterns. These spe-
cific drainage patterns are also used to guide emboliza-
tion or surgical resection. Venous drainage of DAVFs
through collateral channels may present a far more dif-
ficult therapeutic challenge than management of
venous congestion in CVT, as the presence and
79
LT CCA
development of a shunt increases the complexity of
hemodynamic factors (107).
CEREBRAL ARTERIOVENOUS
MALFORMATIONS
The complex arterial and venous angioarchitecture of
cerebral arteriovenous malformations (CAVMs) is akin
to the diverse anatomy and blood flow derangements
that accompany DAVFs. Unlike DAVFs, however, the
contribution of pial collaterals and influence on more
proximal intracranial arterial patterns is greater with
CAVMs. CAVMs represent a subset of vascular mal-
formations in the brain. These lesions incorporate arte-
rial and venous segments, typically centered about a
nidus where blood flow changes may induce angio-
genesis (Fig. 4.36). Concomitant arteriogenesis, or
development of pre-existent arterioles may also be
accompanied by venous recruitment, or venogenesis.
Such angioectatic elements are important correlates of
collateral circulation that continuously adapt to the
evolving hemodynamic disturbances within and
around a CAVM.
Collateralization is one component of a reactive
process within CAVMs in response to hemodynamic
disturbances that may diminish tissue perfusion or
exacerbate venous congestion. The presence of coexis-
tent angiogenesis within the nidus and more peripher-
ally situated arteriogenesis and venogenesis of
respective feeders and drainage routes offers an ideal
model for the study of collateralization in the brain.
Unfortunately, the complexity of these related but dis-
tinct processes and the diverse anatomy of each par-
ticular lesion limit standardized assessment of these
important pathophysiologic events. As a result, only
basic accounts regarding collateral circulation can be
described with respect to CAVMs.
High flow states with rapid shunting and dimin-
ished tissue perfusion adjacent to a CAVM may result
in capillary proliferation around the nidus due to
angiogenesis (108). Hypoxia triggers angiogenesis and
the formation of new capillaries. Mechanical influen-
ces, such as shear stress, drive arteriogenesis or veno-
genesis in the larger vessels supplying and draining
the CAVM. Marked hemodynamic changes due to
diversion of arterial flow may result in shifts or
80 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 4.37 Extensive posterior fossa CAVM on angiography before (A) and after (B) embolization with a small residual nidus.
transfers of the normal watershed or borderzone
regions. Leptomeningeal anastomoses from adjacent
arterial territories may contribute to such dramatic
shifts in perfusion. When a CAVM resides predomi-
nantly within a specific arterial territory such changes
may be less apparent, with only slight variations in
leptomeningeal circulation noted distal to such
lesions. As with other cerebrovascular lesions, CAVMs
may be associated with persistent embryonic variants
(e.g., trigeminal, hypoglossal arteries) (109). Variations
in the configuration of the circle of Willis are also fre-
quently noted with CAVMs, particularly when these
lesions are situated near borderzone regions. Arterial
stenoses that develop proximal to a CAVM may rarely
culminate in a moyamoya pattern or vasculopathy
(65). A combination of arteriogenic and angiogenic
factors likely leads to the proliferation of finer collat-
eral vessels in such cases. Complete occlusion of feed-
ing arteries to CAVMs has also been reported, with all
such patients developing exuberant pial collateral sup-
ply (110). The venous outflow of CAVMs may be
exceedingly complex, with variations of normal drain-
age patterns in up to one-third of cases (111). Detailed
angiographic evaluation of the venous phase may
delineate or distinguish abnormal outflow tracts with
respect to normal venous drainage. The venous collat-
erals associated with a CAVM may continuously
evolve in response to local changes in the CAVM and
remote or diffuse vascular events with age.
Clinical manifestations may also depend greatly
on the nature of the contributing vessels and resultant
perfusion patterns around a CAVM. Considerable lep-
tomeningeal supply may be associated with headaches
or seizures. Focal neurological deficits typically result
from venous congestion. Cortical venous reflux may
result in congestion and compromised perfusion, lead-
ing to symptoms. CAVMs situated in closer proximity
to the draining venous sinus are less likely to be
symptomatic. Although arterial and venous collaterals
(B)
are an important component of CAVM pathophysiol-
ogy, numerous other mechanisms are also influential.
Case 2
A 49-year-old man underwent embolization of an
extensive CAVM of the posterior fossa. Shortly after
the procedure, he began experiencing severe retro-
orbital headaches exacerbated when he placed his
head in dependent position. He also noted that when
he would rest his head with his hand on the right
side of his neck, these symptoms would also become
quite severe. Serial angiography revealed marked
reduction of the nidus (Fig. 4.37), yet MRV showed
enlarged venous collaterals abutting the right aspect
of the tentorium (Fig. 4.38). His referred trigeminal
pain syndrome due to engorgement of venous collat-
erals was likely exacerbated by compression of the
right internal jugular vein and abated within weeks
due to initiation of gabapentin.
Following an acute change of the hemodynamic
milieu within a CAVM, collaterals may rapidly
adapt in response to pressure changes (112,113).
Such changes may occur following rupture, emboli-
zation, surgery, or radiation of the CAVM (114). Pre-
dicting such changes in flow patterns may be quite
difficult (115). For this reason, care must be individ-
ualized to the specific case based on the anatomy,
flow physiology, clinical manifestations, and techni-
cal factors associated with any planned multidiscipli-
nary intervention. Intra-operative angiography may
be used to guide surgical management (116). Various
approaches, including combinations or staged proce-
dures, are utilized in clinical practice (117). After
embolization of a CAVM, serial angiography over a
period of months or 12 years may be necessary to
demonstrate adequate obliteration of the nidus.
Incomplete obstruction of the nidal-venous junction
may allow for angiogenesis and persistence or
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
(A)
Figure 4.38 Gadolinium-enhanced MRV demonstrating prominent venous collateral drainage along the right tentorial surface.
regrowth of the vascular lesion. In general, the
potential collateral supply to a given region influen-
ces the likely success of therapeutic embolization of
a CAVM (118). Intranidal deposition of embolic
material may be necessary to avoid collateral recruit-
ment and regrowth of the CAVM.
ANEURYSMS
The relatively proximal location of most intracranial
aneurysms influences the role of collaterals with such
lesions. Aneurysms are some of the few abnormal-
ities that directly involve several of the potential
collateral segments at the circle of Willis. ACoA
aneurysms constitute 3035% of all intracranial
aneurysms, whereas disease of this segment is other-
wise uncommon. PCoA aneurysms often involve
only the origin of this segment, yet other pathology
of this vessel is unusual (119). The embryonic devel-
opment of these anastomotic segments and blood
flow changes that may occur at these sites may pre-
dispose to aneurysm formation. Abrupt hemody-
namic changes may cause rapid shifts in these
communicating arterial segments due to pressure dif-
ferentials, but progressive ischemia may also impose
significant flow demands at these junctures. Flow
redistribution following occlusion of a proximal ves-
sel may also impart complex hemodynamic changes
leading to aneurysm formation that extends beyond
these short diversion segments at the circle of Willis
(120). Size and location are important variables not
only in aneurysm management, but also as they
relate to collateral circulation. Most small intracranial
aneurysms do not invoke or affect collateral flow;
however, collaterals play an important role in the
context of giant cerebral aneurysms (121). More distal
81
(B)
aneurysms may spare proximal Willisian routes for
blood flow diversion, yet these distal lesions may
also be more difficult to treat because of variability
in leptomeningeal collateral capacity (122,123). As
most current approaches for aneurysm treatment
involve surgical clipping or endovascular coil embo-
lization with attempted parent vessel preservation,
collateral flow may not be relevant. When endovas-
cular or surgical parent vessel sacrifice is entertained,
however, testing of collateral supply is mandatory
and EC-IC bypass surgery may even be indicated
prior to definitive aneurysm treatment (124).
Evaluation of collateral circulation with func-
tional studies is essential to properly gauge the risk of
parent vessel sacrifice with giant aneurysms (Fig. 4.39).
Sources of actual and potential collateral flow must be
carefully documented, including extracranial routes,
leptomeningeal anastomoses, and Willisian segments.
Various protocols have been utilized in the past
including clinical, imaging, and specific angiographic
measures. Provocative maneuvers, including induced
hypotension, have also been employed. Temporary
balloon test occlusion of the parent artery is rapidly
stopped if the patient becomes symptomatic. Other
aneurysms, when present, should be treated before tol-
erance testing for parent artery sacrifice. Angiographic
measures of adequate collateral circulation may
involve stump pressure measurements and preserved
perfusion throughout all phases of the injection of the
contralateral carotid and/or vertebral arteries during
balloon inflation (125,126). In order to assure adequate
tolerance testing, balloon placement may need to be
moved distally in cases where angiography demon-
strates potential collateral channels at the skull base
(127). In general, tolerance to parent artery occlusion is
greater in the pediatric population, whereas variability
82 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 4.39 After initial diagnosis of a large left cavernous carotid aneurysm (A) with adequate PCoA (B) and ACoA (C) collateral sup-
ply, parent vessel sacrifice was performed (D).
in collateral circulation with increasing age makes tol-
erance testing imperative in adults.
Unruptured aneurysms may grow with subse-
quent thrombosis and occlusion of the parent artery.
Mass effect from these lesions may also precipitate
flow diversion via collateral routes. These events may
culminate in strokes, yet adequate collateral routes may
compensate for distal hemodynamic insufficiency. In
the setting of occluded or thrombosed giant cerebral
aneurysms, collateral circulation typically involves peri-
callosal anastomoses between the ACA and PCA, or
lateral geniculate anastomoses between the anterior
choroidal artery (AchA) and PCA. At more distal sites,
the aneurysmal vessel and associated collateral blood
flow routes may greatly impact the risk of stroke. For
instance, giant or fusiform thrombosed aneurysms of
the PCA may be offset by efficient collateral anastomo-
ses through the geniculate network or via retrograde
leptomeningeal supply (125,128). Interestingly, giant or
fusiform thrombosed aneurysms of the MCA rarely
recruit adequate leptomeningeal collaterals.
Following rupture of an intracranial aneurysm,
vasospasm may ensue. Aneurysmal subarachnoid hem-
orrhage may seem radically dissimilar with respect to
ischemic stroke, yet the role of leptomeningeal collater-
als in vasospasm may be closely related to such influ-
ential blood flow routes in the setting of acute cerebral
ischemia. Although complete occlusion of a proximal
artery is commonly encountered in acute ischemic
stroke, vasospasm only partially diminishes antegrade
flow. Despite these differences in the degree of patency
of the proximal arteries, retrograde leptomeningeal col-
laterals are influential in both disorders. Recent studies
of vasospasm suggest that various medical therapies
and even investigational devices, such as NeuroFlo,
may be used to augment collateral flow and improve
clinical outcome (129132). The disproportionately
greater opportunity for studying the angiographic
aspects of leptomeningeal collateral circulation in vaso-
spasm may provide further insight regarding the influ-
ence and therapeutic manipulation of leptomeningeal
collaterals in ischemic stroke.
(C) (D)
TUMORS
The inherent vascular correlates in cancer or neoplasia
provide insight on the role of collaterals and arterio-
genesis in vascular disease. Much of the current
knowledge regarding arteriogenesis has emerged from
ongoing investigations of tumor angiogenesis, the
growth of new vessels feeding cancerous lesions (133).
In oncology, the therapeutic goal is anti-angiogenesis
or cessation of new vessel growth. This mechanism
may be important in the treatment of arteriovenous
malformations, yet the principal objective in most cer-
ebrovascular disorders is to grow or recruit additional
compensatory blood flow routes. Most molecular
studies capitalizing on insight from vascular correlates
in tumor pathophysiology remain at very early stages
in pre-clinical development, yet imaging of brain
tumors has already fostered translation of dedicated
imaging techniques to the vascular realm. Perfusion
CT or MRI techniques focusing on CBV and perme-
ability of the bloodbrain barrier in tumors provide
the ability to investigate arteriogenesis and collateral
recruitment in acute stroke or chronic ischemia.
Intracranial tumors may obliterate primary blood
flow routes causing diversion of flow through collater-
als, or such lesions may also utilize collaterals to sus-
tain ongoing tumor growth. This latter mechanism
may be used to treat tumors with intra-arterial deliv-
ery of chemotherapeutic agents or for embolization of
nutrient vessels. As tumors generally do not respect
vascular distributions, the anatomy of collateral ves-
sels may be quite complex or even unique in a partic-
ular case. Angiography is therefore critical for
diagnostic and therapeutic purposes (134).
Occlusion of arterial inflow due to invasion or
compression of a proximal vessel and diversion of
blood through collateral channels is most common
with rapidly growing lesions or vascular tumors such
as meningiomas (Fig. 4.40). Unlike the abrupt arterial
occlusion that commonly occurs in acute ischemic
stroke, tumor encroachment on a proximal artery typi-
cally follows a prolonged course that allows adequate
 INTRACRANIAL COLLATERAL ROUTES AND ANASTOMOSES IN INTERVENTIONAL NEURORADIOLOGY
Figure 4.40 Progressive encroachment and compression of the
torcula and proximal transverse sinuses due to a large meningi-
oma seen on MRI.
collaterals to develop. Carotid occlusion due to com-
pression from a meningioma may therefore be accom-
panied by adequate diversion of flow through the
circle of Willis. Mass effect and tumor compression
may be silent or more obscure on the venous side of
the circulation. Due to marked venous distensibility
and often complex patterns of venous collateralization,
tumor compression may be clinically inapparent. In
isolated cases, diversion of blood flow through venous
collaterals may elicit headaches, bruits, or tinnitus.
During surgical resection of intracranial or even
extracranial tumors, knowledge of collateral drainage
patterns may be important to avert post-operative
complications (103,135,136). Most recently, MRI tech-
niques have been developed to delineate cortical
venous drainage patterns prior to resection (137).
Collateral routes may be utilized for intra-arterial
chemotherapy or embolization. Effective treatment
may be dependent on such collateral feeders that may
allow continued tumor growth. Prior to therapeutic
embolization, assessment of the collateral circulation
is mandatory in order to avoid resultant ischemia.
Test occlusions with demonstration of collateral com-
pensation, including angiographic flow diversion,
stump pressure measurements, and various imaging
techniques may be used for this purpose (126).
OTHER CONSIDERATIONS
A description of collateral anatomy and pathophysiol-
ogy in the most common disorders encountered
within interventional neuroradiology may be outlined
based on the primary neurovascular lesion although
83
systemic aspects remain quite complex. Clinical
encounters typically center around restoration or oblit-
eration of blood flow to a focal region but such lesions
may engender manifestations or reflect diffuse patho-
physiology within the systemic circulation. Cerebral
ischemia due to atherosclerotic disease or moyamoya
may cause systemic upregulation of various inflam-
matory cytokines associated with arteriogenesis. Simi-
larly, cerebral aneurysms or arteriovenous
malformations may be associated with remote vascu-
lar lesions due to common underlying pathophysiol-
ogy. Such examples emphasize the important role of
endogenous homeostatic mechanisms and common
vascular pathophysiology despite our focus on the
cerebral circulation. Even within the cerebrovascula-
ture, concomitant lesions may be intertwined, such as
aneurysms in the setting of moyamoya or the associa-
tion of venous thrombosis with arteriovenous malfor-
mations. Our current knowledge of cerebrovascular
anatomy and flow physiology requires further investi-
gation with respect to the molecular and genetic deter-
minants associated with collateral recruitment.
CONCLUSIONS
The essential role of collateral circulation in cerebro-
vascular disorders has been recognized for centuries,
yet detailed characterization of these blood flow
routes remains an elusive goal. Collaterals develop in
concert with underlying vascular lesions or disorders,
compensating for potential blood flow derangements
but also serving as a marker of disease with manifes-
tations that may be also detrimental. Angiography
persists as the principal modality for defining the
anatomy and associated blood flow routes of collater-
als in the cerebral arterial and venous systems.
Advanced noninvasive imaging modalities provide
additional information regarding collateral patho-
physiology, yet correlation with conventional angiog-
raphy is often needed. The unique features of
collateral circulation in humans limit translation of
animal research to the clinical realm, thereby reinforc-
ing the need to learn from correlative studies in our
patients. Diagnostic, therapeutic, and prognostic
implications of intracranial collaterals underscore the
importance of these blood flow routes in interven-
tional neuroradiology. Ongoing refinement of current
therapeutic approaches for cerebrovascular disorders
will undoubtedly depend on further knowledge of
collateral perfusion.
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 5
Management of cerebrovascular variants
Azam S. Ahmed and Felipe C. Albuquerque
INTRODUCTION
Normal anatomic variants encountered in the course
of treatment are often identified as incidental findings.
However, depending on the pathology, these variants
may portend an increased treatment risk or, at worst,
may lead to disastrous consequences. These variants
are ubiquitous and can occur at any location in the
vascular system. Furthermore, although not variants
in the anatomical sense, the changes associated with
aging can often make it challenging to access and treat
cerebrovascular pathology. Detailed analysis of preop-
erative vascular imaging with either computerized
tomographic angiography or magnetic resonance
angiography is crucial to the identification of these
variants and formulation of a successful management
strategy. This chapter is therefore organized by vascu-
lar segments, from proximal to distal, and briefly
describes the pertinent normal anatomy, true anatomi-
cal variants, and acquired variants (i.e., effects of
aging and vascular disease). Recognition of these var-
iants is the most important first step in their manage-
ment. Where applicable, management techniques for
these variants conclude each section.
AORTIC ARCH
The aorta arises from the base of the left lateral ven-
tricle as the aortic root. From its origin, the ascending
aorta extends rostrally, anteriorly, and toward the
right between the superior vena cava and pulmonary
artery. At the junction of the ascending aorta and the
aortic arch is a short dilated segment, the aortic bulb.
The aortic arch or transverse aorta begins at the right
second sternocostal articulation, extends posteriorly
and to the right, ending on the left of the fourth thora-
cic vertebral body. The aortic knob is the projection of
the aortic arch on an anteroposterior projection radio-
graph. The aortic arch gives rise to the great vessels.
In the most common configuration, these vessels are,
from proximal to distal, the innominate (i.e., brachio-
cephalic trunk), left common carotid, and left subcla-
vian arteries (74%). The most common variant is a
bovine arch in which there is a common origin of the
innominate and the left common carotid artery (CCA;
2027%) (14). In a similar variant, the left CCA may
arise from the innominate artery (7% of cases) (1).
Other less common variants include the origin of the
right subclavian artery as the last of the great vessels
with the right CCA originating independently from
the aorta as its first branch (Fig. 5.1) and a common
origin of the carotid arteries (Fig. 5.2).
The aortic arch characteristically elongates with a
migration of the origin of the great vessels toward the
right or ascending aorta. The severity of elongation
has been classified according to the relationship of the
origin of these vessels to the greater and lesser (or
outer and inner) aortic curvatures. In the class I arch,
the great vessels originate above the greater aortic cur-
vature. When at least one of the aortic branches origi-
nates between the greater and lesser curvature, it is
classified as a type II arch. In the most severe form,
class III, some of the aortic branches originate below
the lesser curvature. The class dictates the difficulty in
accessing each vessel and the likelihood of throm-
boembolic complications. The difficulty in accessing
these vessels is not only related to the level of the ori-
gin of these vessels, but also to the angle at which
they originate with each successive class resulting in
increasingly acute angulation.
Success in traversing tortuous anatomy is
improved as distal wire purchase is increased. Aortic
arch elongation may be negotiated using stiff exchange
guidewires to straighten the anatomy. Coaxial systems
may improve the stability of the platform as well as
decrease the discrepancy between the caliber of the
wire and the catheter, thereby decreasing the likelihood
of vascular injury and dissection. Pathologic conse-
quences of infarction may occur when atheromatous
material is dislodged from the aortic arch. This risk
increases with the aggressiveness of manipulations nec-
essary to traverse tortuous anatomy. Alternative points
of access, such as the radial or brachial arteries, may be
exploited if the tortuosity or angulation involves the
aorta, subclavian, or innominate arteries. Furthermore,
this strategy is helpful if the trajectory favors the angle
of origin of the pathologic supraaortic vessel.
ANTERIOR CIRCULATION
Common Carotid Artery
The right CCA normally originates as one of the two
branches of the innominate artery. The left CCA usu-
ally arises as the second branch of the aortic arch
between the innominate and left subclavian arteries.
Occasionally, the left CCA may arise as a branch of
the innominate artery (7%), usually as the most proxi-
mal branch. The course of the left and right CCAs is

2011 BNI
(A) (B)
Figure 5.1 (A) Aortic arch variant with the origin of the right subclavian artery from the left of the aortic arch as the final great vessel.
The right CCA originates independently from the aorta in the normal position of the brachiocephalic trunk. (B) Coronal and (C) axial CT
angiograms (another patient) demonstrate origin of aberrant right subclavian artery (arrows) from aorta passing posterior to trachea
and esophagus (arrowheads). Source: (A) From Barrow Neurological Institute.
19172 F [17]
2011, BNI
Compressed 32:1
Figure 5.2 Aortic arch variant with the CCAs originating from a
common trunk as the first branch from the aorta and the right
subclavian artery originating as the second branch of the aorta.
The left subclavian artery origin is in the normal position and
configuration. Source: From Barrow Neurological Institute.
similar; however, usually only the left has a significant
thoracic component due to its relatively inferior origin
from the aortic arch. The CCAs course superiorly and
slightly laterally to bifurcate into the internal carotid
artery (ICA) and external carotid artery (ECA) at the
level of the fourth cervical vertebral body. In general,
the level of the bifurcation is located at the level of
the thyroid cartilage. The level of the bifurcation may
be as high as C2 and as low as T2 and is often higher
on the left. The level of the bifurcation on the right is
C2 (10%), C3 (5055%), C4 (3540%), and C5 (10%).
MANAGEMENT OF CEREBROVASCULAR VARIANTS 89
10.00mm/d
[P]
(C)
The level of the bifurcation on the left is C2 (10%),
C3 (60%), and C4 (40%) (5).
As a result of aging and precipitated by vascular
risk factors such as hypertension, atherosclerosis, and
calcification, vessels may become distorted. Such dis-
tortion may result in kinking, coiling, and tortuosity
of these vessels, which may become symptomatic if
severe (68). Navigating these turns may be difficult
or even impossible as is often the case for kinks in the
vessel. Accessing these lesions is often exceedingly
difficult because the anatomical constraints limit the
purchase of the distal wire. Straightening the vessel or
at least decreasing the severity of curvature is a pre-
requisite to advancing a catheter successfully. The
degree to which it can be accomplished is limited by
tools, skill, and the tolerance of the vessel to such
deformation. Straightening tortuous anatomy may
result in injury to the vessel and result in vasospasm,
dissection, occlusion, or even rupture. Therefore, each
access strategy must be individualized and considered
in the context of the risk of the pathology and the
goals of therapy. The effects of distortion are often
manifested in the sensation of increased friction or dif-
ficulty in advancing catheters over stiff wires.
Carotid Bifurcation
The carotid bifurcation constitutes the portion of the
carotid circulation where the CCA bifurcates into the
ICA and ECA. The ECA originates anteromedial to
the ICA and courses posterolaterally as it ascends.
When viewed from below in relationship to the ICA,
there is a 90-degree counterclockwise and clockwise
rotation of the right and left ECAs, respectively. The
relationship of the ICA and ECA may be reversed at
the bifurcation with the latter in an anterolateral posi-
tion (9). In a nonbifurcating variant, the branches of
the ECA arise directly from the CCA without forming
a bifurcation (10,11). The relative diameters of these
vessels demonstrate differences in relative size accord-
ing to ethnicity (12).
90 NEUROINTERVENTIONAL MANAGEMENT
External Carotid Artery Branches
The ECA supplies the tissues of the face, neck, scalp,
dura, and cranial nerves. It also contributes to the vas-
cular supply of the orbit. Importantly, it also has many
important anastomoses with branches of the ICA and
vertebral arteries. Under pathologic conditions, these
anastomoses may enlarge resulting in direct supply
from the ECA to the intracranial circulation.
In the most common configuration, the ECA has
eight branches. The branching pattern of the ECA has
been organized. The most popular and classical
method is to describe them in order of their origin,
from proximal to distal: (i) superior thyroid, (ii) ascend-
ing pharyngeal, (iii) lingual, (iv) facial, (v) occipital,
(vi) posterior auricular, and (vii) internal maxillary.
This organization, however, is limited because the ori-
gins of these vessels vary with respect to the order at
which they originate from the ECA. Many branches
can arise at the same rostral-caudal level.
A more constant finding is the position in which
these branches originate from the ECA: ventral/anterior
or dorsal/posterior. The anterior branches include the
superior thyroid, lingual, facial, and internal maxillary
arteries. The posterior branches include the ascending
pharyngeal, occipital, posterior auricular, and superfi-
cial temporal arteries (STAs). The caliber of these ves-
sels also varies, reflecting the reciprocal relationship
between the branches of the ECA. Finally, two adja-
cent branches often originate from a common trunk.
For example, a linguofacial trunk, or a common trunk
giving rise to both the lingual and facial arteries, is
found in 20% of cases (13).
The ECA branches have a reciprocal relationship
with respect to the scalp, face, and neck. The scalp is
supplied by the STA, posterior auricular, and occipital
arteries. The face is supplied by the lingual, facial,
posterior auricular arteries, and STA. The musculature
of the neck is supplied by the superior thyroid,
ascending pharyngeal, facial, occipital, and posterior
auricular arteries.
A rich anastomotic network exists between the
ECA and ICA and between the ECA and vertebral
artery (VA). Often, these connections are not evident
on normal angiograms; however, in the setting of
pathology, these channels may enlarge and become
significant. Recognition of these anastomoses is crucial
during embolization procedures to avoid inadvertent
reflux of embolic material into the normal cerebral
vasculature. Often, these channels may not become
evident until embolization commences with the embo-
lisate traversing from noneloquent ECA branches into
ICA or VA branches.
Superior Thyroid Artery
The superior thyroid artery originates from the ante-
rior surface of the ECA (25%), bifurcation (40%), or
CCA (35%) (14). It ascends briefly before coursing
inferiorly to terminate in the thyroid gland. It may
arise from a common trunk with the lingual artery as
the thyrolingual trunk (2.5%) or the lingual and facial
arteries as the thyrolingual-facial trunk (2.5%) (13). It
also may arise from a common trunk with the ascend-
ing pharyngeal artery (APA) (15).
Along its course, the superior thyroid artery pro-
vides branches to the musculature of the anterior neck
and to the thyroid gland. It anastomoses with its
counterpart from the contralateral superior thyroid
artery as well as with the inferior thyroid arteries
from the thyrocervical trunks. This artery terminates
to supply the superior pole of the thyroid gland and
the upper parathyroid gland.
Ascending Pharyngeal Artery
The APA usually arises from the posterior or medial
aspect of the ECA (80%) rostral to the origin of the occi-
pital artery. Variants include an origin directly from the
CCA bifurcation (5%), proximal occipital artery (OA)
(5%), or ICA (5%); as a common trunk with the lingual
and facial arteries (5%); or from the ascending cervical
artery (16,17). It can be the first (15%), second (15%), or
third (40%) branch of the ECA (16). It ascends as a long
straight vessel between the ICA and pharynx. The APA
usually bifurcates into an anterior pharyngeal trunk
and a posterior, neuromeningeal trunk.
The pharyngeal branches include the superior,
middle, and inferior pharyngeal arteries, which arise
from the APA in 65%, 40%, and 30% (as a common
trunk with the Eustachian tube branch) of the cases,
respectively. The neuromeningeal trunk originates from
the APA in 85% and the occipital artery (OA) in 10%
of cases. There is a constant branch to the jugular fora-
men and commonly a branch to the hypoglossal canal
(40%). The jugular branch supplies cranial nerves IX, X,
and XI. This branch also supplies the meninges of the
internal auditory canal, inferior petrosal sinus, and sig-
moid sinus. There also may be a supply to the vasa
nervorum of the portion of cranial nerve VI that is
proximal to Dorellos canal.
An inferior tympanic branch, carotid ramus, and
Eustachian tube branch are identified in 85%, 85%,
and 75% of cases, respectively. The inferior tympanic
branch usually arises as a proximal branch of the neu-
romeningeal trunk, but it can arise between the two
main trunks (17).
The APA has a rich anastomotic network with all
neighboring major arteries. The inferior tympanic
branch anastomoses with the caroticotympanic artery,
which is a branch of the petrous ICA. The APA also can
anastomose with the petrous ICA via a vidian artery,
lateral clival branch of the jugular artery, or recurrent
artery of the foramen lacerum. Indirect anastomosis
occurs between the superior pharyngeal branch and the
inferolateral trunk of the cavernous segment of the ICA
through the foramen lacerum. Clival branches of the
hypoglossal branch can reconstitute the ICA through
the meningohypophyseal trunk. A jugular branch from
the APA also can supply the ICA through Dorellos
canal associated with the abducens nerve. The APA can
anastomose with the VA through musculospinal
branches as well as through the hypoglossal branch via
the odontoid arterial arch.
Anastomosis between the APA and the occipital
artery can occur via a common trunk or through the
odontoid arch. The descending palatine artery, a branch
of the internal maxillary artery, can anastamose with the
APA via a middle pharyngeal branch or the pterygova-
ginal artery to the accessory meningeal artery (17).

Lingual Artery
The lingual artery usually originates as the third
branch of the ECA from the anterior aspect of the ves-
sel. This vessel courses inferiorly, hooks around the
hyoid bone, and then ascends to terminate in a dense
radiating pattern to supply the tongue. The lingual
artery may originate as a common trunk with the
facial artery (18,19).
Facial Artery
The facial artery arises from the ventral aspect of the
ECA as its fourth branch. This artery undulates anteri-
orly, courses around the mandible, and travels super-
omedially to terminate as the angular artery at the
medial canthus. The facial artery has a rich anasto-
motic network with many branches of the ECA. The
terminal branch of the facial artery, the angular artery,
anastomoses with the ophthalmic artery via its dorsal
nasal branch. This is an important anastomotic chan-
nel in cases of ophthalmic artery or ICA occlusions.
Superior nasal branches in the nasal septum can also
anastomose with the ethmoidal branches of the oph-
thalmic artery.
Occipital Artery
The occipital artery arises posteriorly from the ECA
and ascends posteromedially, terminating as a tortuous
vessel in the scalp. The occipital artery may rarely arise
directly from the ICA or VA (20,21). It gives rise to
numerous branches supplying the scalp and soft tissues
of the posterior neck. Approximately 20% of the time, a
stylomastoid branch originates from the occipital artery
(see posterior auricular). It may rarely give rise to the
posterior meningeal artery (22). The occipital artery can
anastomose with the VA via several muscular branches
at C1 and C2. A transmastoid branch through the mas-
toid foramen can also anastomose with the subarcuate
artery, which is also supplied by the anterior inferior
cerebellar artery (AICA) (23).
Posterior Auricular Artery
A minor branch of the ECA is the posterior auricular
artery. An important feature of the posterior auricular
artery is that in 70% of cases, it gives rise to the artery
of the stylomastoid canal, also known as the stylomas-
toid artery. This artery supplies the facial nerve and
middle ear and may anastomose with the petrosal
branches of the middle meningeal artery and ICA (24).
Superficial Temporal Artery
The STA, one of the terminal branches of the ECA,
ascends anterior to the tragus and then divides into ante-
rior and posterior branches. The course of these
branches becomes increasingly tortuous with age and is
therefore easily differentiated from the straight menin-
geal vessels on angiography. A zygomatico-orbital
artery exits from the STA, as do lacrimal and palpebral
branches that can anastomose with the ophthalmic
artery. A fronto-orbital branch of the STA can anasto-
mose with the supraorbital branch of the ophthalmic
artery via the supraorbital notch. Transosseous branches
MANAGEMENT OF CEREBROVASCULAR VARIANTS 91
of the STA also can anastomose with the anterior falcine
artery that arises from the ophthalmic artery (25).
Internal Maxillary Artery
The internal maxillary artery (IMAX) arises as the
larger of the two terminal branches of the ECA. The
vessels it gives rise to are divided into three groups:
mandibular, pterygoid, and pterygopalatine portions.
Important branches of the mandibular group include
the anterior tympanic and middle meningeal arteries
(MMAs). The anterior tympanic artery anastomoses
with the stylomastoid artery and anterior tympanic
branch of the petrous ICA (via the vidian artery or
artery of the pterygoid canal).
The MMA is one of the larger branches of the
IMAX and is often recognized by the acute turn in the
vessel as it traverses the foramen spinosum. The oph-
thalmic artery may arise from the MMA as the
meningo-ophthalmic artery (26). Conversely, the
MMA may arise from the ophthalmic artery (27).
A persistent stapedial artery arising from the cervical
portion of the ICA occasionally gives rise to the
MMA. In these cases, the foramen spinosum can be
quite small, and the MMA can still anastomose with
other branches of the ICA further distally (28).
The MMA gives rise to many important branches
and anastomoses. Among the most frequently encoun-
tered is the anastomosis between the MMA and the
ophthalmic artery. This anastomosis is referred to as
the meningolacrimal trunk because, in these instances,
the recurrent meningeal branch of the MMA typically
joins the ophthalmic artery via its lacrimal or ethmoi-
dal branches through the superior orbital fissure. The
MMA also can anastomose with the ophthalmic artery
through the anterior falcine artery further distally at
the level of the superior sagittal sinus. These are all
important anastomoses to rule out during the emboli-
zation of meningiomas situated in the anterior and
middle cranial fossae or in cases of dural arteriove-
nous fistulas supplied by the MMA.
The MMA occasionally supplies the basilar
artery through a persistent trigeminal branch. In these
cases, embolization of a vascular lesion supplied by
the MMA could be devastating if embolisate enters
the posterior circulation through the anastomosis.
Important branches of the pterygoid or second portion
of IMAX include the anterior and middle deep tempo-
ral branches of the IMAX, which may anastomose
with the ophthalmic artery via the inferior orbital fis-
sure (29).
The third portion of the IMAX, the pterygopala-
tine segment, gives rise to the infraorbital, sphenopa-
latine, vidian (pterygoid canal), and pterygovaginal
arteries as well as to the arteries of the foramina
rotundum and ovale. Various anastomoses exist
between these branches of the IMAX and the inferolat-
eral trunk located at the cavernous segment of the
ICA. These anastomoses can be supplied by the MMA
as well as by the accessory meningeal artery through
the foramen ovale or sphenoidal emissary foramen
(foramen of Vesalius), and the artery of the foramen
rotundum. The sphenopalatine occasionally anastomo-
ses with the ophthalmic artery through its ethmoidal
branches. The greater palatine artery may anastomose
92 NEUROINTERVENTIONAL MANAGEMENT
with the ethmoidal arteries (30). The sphenopalatine
artery does not have important anastomoses and is
therefore often embolized for the treatment of epis-
taxis or tumors.
Internal Carotid Artery
The ICA originates at the CCA bifurcation and termi-
nates after bifurcating into the M1 segment of the
middle cerebral artery (MCA) and the A1 segment of
the anterior cerebral artery (ACA). The many number-
ing schemes employed to describe the segments of the
ICA have led to confusion (31,32). Instead of a num-
bering system, a descriptive term for the segment of
the ICA avoids potential confusion. Descriptive seg-
ments of the ICA based on Bouthilliers segments
include the following: (33) (i) cervical, (ii) petrous,
(iii) lacerum, (iv) cavernous, (v) clinoidal, (vi) ophthal-
mic, and (vii) communicating. This system separates
the vessel into similar distinct segments.
Cervical Segment
This first segment of the ICA begins at the CCA
bifurcation and terminates immediately caudal to the
entry of this vessel into the carotid canal. The first
portion of the cervical segment encompasses the caro-
tid bulb, a focal dilation of the origin of the ICA. It is
approximately 5% larger than the CCA and approxi-
mately one-third larger than the distal ascending
segment (34,35).
Anomalies of the caliber of the cervical ICA may
be congenital or acquired, partial or complete, asymp-
tomatic or symptomatic (36). These anomalies have a
high incidence of coinciding with other intracranial
abnormalities, especially aneurysms. Congenital agen-
esis of the ICA is differentiated from aplasia based on
the presence of the carotid canal. Absence of a carotid
canal is consistent with agenesis (Fig. 5.3). ICA hypo-
plasia may result distal to severe stenosis at the origin
of the ICA due to decreased blood flow. In these
(A) (B)
Figure 5.3 Agenesis of the internal carotid artery. (A, B) Axial CT scans demonstrate normal carotid canal on the left (arrow) but
absence of carotid canal on the right. (C) AP Angiogram shows cross filling to supply hemisphere on the side of the agenetic ICA.
cases, stenosis may be a result of severe atherosclero-
sis, dissection, fibromuscular dysplasia, arteritis, or
external pathologic compression. The cervical segment
of the ICA usually has no branches; however, variants
include the origin of the superior thyroid artery, APA,
occipital artery, posterior meningeal artery, persistent
stapedial artery, and vidian artery (37).
Similar to elongation of the aortic arch, elonga-
tion of the ICA is often due to vascular risk factors
and may result in tortuosity, looping, kinking, and
increased angulation of the origin of this vessel (38)
Alternatively, patients with connective tissue disor-
ders may be at risk for developing elongation of the
ICA. Changes due to increased tortuosity may, in
turn, be a risk factor for atherosclerosis and may
become symptomatic due to hypoperfusion or cerebral
embolism (39,40).
Petrous Segment
The petrous segment begins as the ICA enters the car-
otid canal and terminates at the posterior aspect of the
foramen lacerum. This short segment includes a genu
in which the vertical ICA assumes a horizontal posi-
tion as it ascends. This segment may enter into the
middle ear cavity, often causing pulsatile tinnitus and
presenting as a pulsatile mass. This course may be
congenital, due to a normal ICA taking an aberrant
course or more commonly, acquired in which tortuos-
ity or aneurysmal dilation of this vessel erodes the
medial wall of the middle ear.
Inconstant branches of the petrous segment
include a periosteal branch, caroticotympanic artery,
and vidian artery. The second branch, the carotico-
tympanic branch, if present, arises at the level of the
genu and supplies the contents of the middle ear. The
vidian artery (artery of the pterygoid canal) originates
in the horizontal potion of this segment and extends
through the vidian canal to the pterygopalatine fossa.
Occasionally, a persistent stapedial artery origi-
nates from the vertical segment, passing through the
(C)

middle ear and terminating in the MMA. If present,
this anastomosis is important to recognize during
embolization procedures of the MMA. A persistent
otic artery also serves as a communication between
the petrous ICA and the basilar artery (see carotid
vertebrobasilar anastomoses below).
Lacerum Segment
The short lacerum segment extends along the course
of the foramen lacerum from its posterior to its ante-
rior edge marked by the petrolingual ligament. No
branches originate from this segment.
Cavernous Segment
The cavernous segment begins at the petrolingual
ligament and extends to the proximal dural ring. This
segment encompasses a posterior and anterior genu in
between which lies a horizontal portion. The course of
this artery may deviate such that one or more com-
monly both carotid arteries are displaced medially in
the sphenoid bone, sinus, or intrasellar (41). At worst,
the ICAs may contact one another (i.e., kissing) (42).
The three classically described branches of this
segment are named for the aspect of the ICA from
which they originate (relative frequency): the meningo-
hypophyseal (i.e., posterior) trunk (100%), inferolateral
(i.e., lateral) trunk (84%), and McConnells capsular
artery (28%). The meningohypophyseal trunk branches
into the marginal tentorial artery (of Bernasconi and
Cassinari), inferior hypophyseal artery, and the dorsal
meningeal artery. In 6% of cases, the latter may origi-
nate directly from the ICA. The inferolateral trunk has
a variable number of branches that anastomose with
branches of the ophthalmic artery and ECA. Rarely, the
2011, BNI
Figure 5.4 Dorsal ophthalmic artery in which the ophthalmic
artery originates from the usual location of the inferolateral trunk.
Notice the infundibulum of this variant vessel. Source: From
Barrow Neurological Institute.
MANAGEMENT OF CEREBROVASCULAR VARIANTS 93
ophthalmic artery (8%) arises directly from the caver-
nous segment of the ICA (43,44).
Clinoidal Segment
The clinoidal segment is the shortest segment of the
ICA and spans the transition from the extradural cav-
ernous sinus to the intradural subarachnoid space.
The exact location of this transition is crucial to iden-
tify, particularly as it relates to the risk of aneurysmal
rupture. This segment is bounded by two dural rings.
The proximal ring defines the roof of the cavernous
sinus. The distal dural ring is firmly adherent laterally
but redundant medially. The space between the
redundant dura and the ICA is termed the carotid
cave, and it may be located in the subarachnoid
space (45).
Ophthalmic Segment
The ophthalmic segment begins at the distal dural
ring and terminates immediately proximal to the ori-
gin of the posterior communicating artery (PCOM).
Branches of this segment include the ophthalmic
artery, superior hypophyseal artery, and a variable
number of perforating arteries arising directly from
the posterior and medial walls of the ICA (32). The
ophthalmic artery may originate from the cavernous
segment of the ICA or from the MMA. Rarely, the
ophthalmic artery may originate from the dorsal cav-
ernous ICA in the position of the inferolateral trunk
(Fig. 5.4). More common than a true origin of the oph-
thalmic artery from the MMA is enlargement of the
anastomotic connection between the orbital branch of
the MMA and the recurrent meningeal branch of the
ophthalmic artery.
There are three intraorbital segments of the oph-
thalmic artery (46,47). The first segment begins as the
artery enters the orbit and ends as the artery begins to
curve over or under the optic nerve. The second seg-
ment encompasses the portion of the ophthalmic
artery that courses over or under the optic nerve. The
third segment begins when the artery curves anteri-
orly after coursing over or under the nerve. Branches
of the first segment include the recurrent meningeal
and posterior ethmoidal arteries. The second segment,
while the shortest, is also the most important giving
rise to the central retinal artery and the ciliary arteries.
The ciliary arteries are responsible for the choroidal
blush visible on lateral angiograms. Barring reflux,
embolization beyond the second segment of the oph-
thalmic artery is considered safe. The third segment
gives rise to the lacrimal artery. A recurrent menin-
geal branch of the lacrimal artery anastomoses with
the MMA. It is important to identify this anastomosis
when performing embolization procedures through
the MMA to avoid inadvertent compromise of the
vascular supply to the central retinal artery, which
could lead to blindness.
The superior hypophyseal artery anastomoses
with its counterpart from the contralateral ICA and
branches from the PCOM to form a hypophyseal por-
tal system of the anterior pituitary. This rich vascular
network results in a blush, which is often visible on
lateral angiograms.
94 NEUROINTERVENTIONAL MANAGEMENT
2011, BNI
(A) (B)
Figure 5.5 (A) Lateral angiogram demonstrating opacification of the basilar artery upon injection of the ICA due to a persistent trige-
minal artery (arrow). (B) Lateral and AP (C) angiogram in another patient shows persistent trigeminal artery filling basilar artery
(arrows). Note hypoplasia of proximal basilar artery (arrowhead). Source: (A) From Barrow Neurological Institute.
Communicating Segment
The communicating segment begins immediately
proximal to the PCOM and ends immediately proxi-
mal to the origin of the anterior choroidal artery.
Other than the PCOM, this vessel gives rise to a varia-
ble number of perforating vessels.
The PCOM originates from the posterolateral
wall of the ICA and courses posteromedially to join
the posterior cerebral artery (PCA) at the junction
of the P1 and P2 segments. The only branches originat-
ing from the PCOM are the anterior thalamoperforating
vessels, the largest of which is the premammillary
artery.
The PCOM is usually much smaller than the P1
segment. However, in the fetal configuration, its diam-
eter is the same as that of the P2 segment. The P1 seg-
ment is usually hypoplastic. In this scenario, a branch
of the ICA irrigates the entire cerebral hemisphere.
Conversely, the PCOM may be hypoplastic or even
absent. The size of the PCOM is assessed through an
Alcocks maneuver during which the carotid artery is
compressed while contrast is injected into either VA.
When the PCOM is large, it may serve as an alternate
access route to vascular disease of the posterior
circulation.
The PCOM is the most common location for
infundibula. An infundibulum is symmetric, conical,
less than 3 mm, and has the PCOM originating from
its apex. One should not be confused with a PCOM
aneurysm. The PCOM gives rise to 412 perforating
branches (48). For this reason even a hypoplastic
PCOM must be sacrificed with caution in terms of
preserving the perforating arteries (49).
Choroidal Segment
The choroidal artery begins immediately proximal to
the anterior choroidal artery and terminates at the
ICA bifurcation into the first segments of the MCA
and ACA. The anterior choroidal artery originates
from the posterolateral aspect of the ICA and courses
posterosuperiorly in the cisternal segment. An acute
kink in the vessel, the plexal point, is evident on a lat-
eral angiogram and represents a change in the direc-
tion of this vessel as it turns medially to enter the
(C)
choroidal fissure. The intraventricular segment of this
vessel extends posteriorly to end in the choroid plexus
where it anastomoses with the lateral and medial pos-
terior choroidal arteries. It is important to identify this
vessel due to the breadth of critical structures it irri-
gates, including the retrolenticular internal capsule,
cerebral peduncle, optic tract and radiations, thala-
mus, lateral geniculate body, and globus pallidus
internus. The extent to which it supplies these struc-
tures is variable and is in reciprocal relationship with
other perforating vessels.
The anterior choroidal artery may have variant
origins such as an exit proximal to the PCOM or an
origin from the MCA or PCA (50).
Carotid Vertebrobasilar Anastomoses
Communication between the anterior and posterior
circulations arises at various points during develop-
ment and may fail to regress. This failure leads to per-
sistent connections between the carotid and
vertebrobasilar circulation. Such anastomoses include,
from rostral to caudal, the persistent trigeminal, per-
sistent otic, persistent hypoglossal, and proatlanto-
intersegmental arteries. The persistent trigeminal is
the most common and extends from the cavernous
segment of the ICA to the basilar artery (Fig. 5.5). The
artery takes a variable course through the suprasellar
or sellar space or alternatively through the clivus. A
persistent otic artery originates in the petrous segment
of the ICA and courses through the internal auditory
canal to anastomose with the basilar artery. A persis-
tent hypoglossal artery arises from the cervical ICA
and connects with the basilar artery by coursing
through the hypoglossal canal. A proatlanto-interseg-
mental artery connects the cervical ICA or ECA with
the VA through the condyloid foramen. These rare cir-
culatory patterns can cause posterior circulation
symptoms from anterior circulation pathology and
vice versa.
Circle of Willis
The circle of Willis includes the internal carotid arteries
between the A1 segments of the anterior cerebral artery
and the posterior communicating arteries, bilateral A1,

2011, BNI
Figure 5.6 Lateral angiogram demonstrating a complete circle
of Willis. Notice opacification of the bilateral PCOMs resulting in
opacification of the posterior circulation. Source: From Barrow
Neurological Institute.
2011, BNI
Figure 5.7 Lateral angiogram demonstrating triplication of the
A2 with three A2 segments of the ACA originating from A1.
Source: From Barrow Neurological Institute.
anterior communicating artery, bilateral posterior com-
municating arteries, P1 segments of the posterior cere-
bral artery and the top of the basilar. A complete circle
of Willis is found in only approximately 4050% of
patients depending on the modality used for imaging
(Fig. 5.6) (1,51,52).
MANAGEMENT OF CEREBROVASCULAR VARIANTS 95
2011, BNI
Figure 5.8 Variant demonstrating fetal PCOM and absence of
the right A1 segment of the ACA. Source: From Barrow Neuro-
logical Institute.
Anterior Cerebral Artery and Anterior
Communicating Artery
The ACA begins as the A1 segment at the bifurcation
of the choroidal segment of the ICA. The anterior
communicating artery (ACOM) marks the transition
from the A1 to A2 segment. The A2 segment branches
into the pericallosal and callosomarginal arteries (A3
segments). A normal ACA-ACOM complex is one
in which the bilateral A1 segments and ACOM are of
a configuration and caliber to allow unimpeded blood
flow between the two ICAs (53). Variants of the A1
segment include duplication and differences in caliber
that range from mild asymmetry to hypoplasia (712%)
or even absence with most or all blood flow to the
ACA territory originating in the contralateral A1 seg-
ment (Figs. 5.7,5.8) (53,54). Indeed, hypoplasia of the
A1 segment is highly associated with aneurysms
(85%) (55).
The ACOM serves as the connection between the
ACAs. Although its presence is a constant finding, its
configuration is highly variable (56). The diameter of
the ACOM increases as the discrepancy between the
two A1 segments increases (5), and it can be hypo-
plastic (6%) (54). The ACOM can be fenestrated, short,
or even nonexistent with an X configuration at the A1
and A2 junction. One, two, and three ACOMs have
been present in 60%, 30%, and 10% of cases, respec-
tively. Variants of the A2 segment of the ACA can be
triplicate or, alternatively, single with one vessel sup-
plying both ACA distributions. The latter may be rep-
resented as an azygos or bihemispheric ACA. In the
case of the former, a single unpaired vessel arises
96 NEUROINTERVENTIONAL MANAGEMENT
from the union of the bilateral A1 without an inter-
vening ACOM. Alternatively, in a bihemispheric
ACA, one A2 is hypoplastic and the remaining A2
supplies the bilateral ACA territories. Triplication of
the A2 may represent persistence of the median artery
of the corpus callosum (1).
Branches of the A2 include the recurrent artery
of Heubner, the frontopolar, and orbitofrontal arteries.
The important recurrent artery of Heubner usually
arises from the A2 segment (78%), but it can also arise
from A1 (14%) or the ACOM (8%). Its course is
unique in that it courses adjacent to the ipsilateral A1
and M1 before it enters the anterior perforated sub-
stance (53).
The A2 branches into the pericallosal and calloso-
marginal arteries (A3). These vessels branch into A4
and A5 segments. The terminal branches of the ACA
anastamose with their counterparts from the MCA and
PCA. A variable but balanced supply of contributions
from the ACA, MCA, and PCA irrigates the cerebral
hemisphere.
Variants of the ACA and ACOM are more com-
monly associated with aneurysms, and the microvas-
cular architecture must be understood prior to
embarking on therapy. Furthermore, the differences in
this anatomy, particularly as it pertains to the ACA-
ACOM complex, must be evaluated when alternative
approaches are considered for navigating aneurysms
with unfavorable morphologies or difficult access.
Middle Cerebral Artery
The MCA originates as the M1 segment at the ICA
bifurcation (or terminus). Strictly speaking, it does not
contribute to the arterial circle. The definition of the
MCA varies among anatomists and clinicians. Anato-
mists divide the segments based on the course of the
vessel and its relationship to the surrounding brain,
while clinicians rely on branch points as in the ACA
and PCA. M1 variants include origin from the ACA
as the accessory MCA from the ACA, fenestration, or
duplication (Fig. 5.9) (5759). Fenestration, the division
2011, BNI
(A) (B)
Figure 5.9 (A) Left ICA injection demonstrating duplication of the left M1 segment of the MCA. (B) Fenestration involving the origin of
the left MCA on angiogram and 3D (C) reconstruction (arrowfenestration; arrowheadearly temporopolar branch origin. Source:
(A) From Barrow Neurological Institute.
of an arterial lumen into two distinct parallel chan-
nels, has been reported to involve the MCA in 0.17%
of angiograms. The consistent origin of an early tem-
poropolar artery branch from the fenestrated segment
has been hypothesized to interfere with normal devel-
opment of the MCA and participate in the formation
of MCA fenestration (60). The M1 gives rise to a varia-
ble number (usually numerous) of lateral lenticulostri-
ate perforators. Alternatively, the M1 segment may
give rise to a few or even single perforating artery or
arteries that rapidly branch into multiple smaller ves-
sels. The M1 segment also may give rise to an early
temporal branch supplying the anterior temporal or
frontal lobes. The M1 branches into a bifurcation (78%)
or trifurcation (12%) or may yield multiple vessels
(10%) (61). The M2 branches are vertically oriented
and branch into the horizontally oriented M3 branches
at the circular sulcus.
Posterior Cerebral Artery
The PCA is unique among the major cerebral arteries
in that it may derive its circulation from either the
carotid or vertebrobasilar systems or, often, both. The
P1 (precommunicating, mesencephalic, or circular)
segments begin at the basilar artery bifurcation and
become the P2 segments after being joined by the
PCOM. The P2 (ambient) segment ends at the poste-
rior aspect of the midbrain. The P3 (quadrigeminal)
segment extends to the calcarine fissure beyond which
is the P4 segment. A fetal PCA, by definition, is a
PCOM of the same caliber as the P2 segment of the
PCA and is present in 2240% of cases (62,63). In the
case of a fetal PCA, the ipsilateral P1 is usually hypo-
plastic or absent (Fig. 5.8). Therefore, asymmetry of
the PCAs, on injection of the carotid or vertebral
arteries, is common. Rarely, the PCA is supplied by a
persistent trigeminal artery.
Branches of the P1 segment include numerous per-
forating arteries including the posterior thalamoperforat-
ing arteries. Rarely, a single large perforator (artery of
Percheron) may give rise to thalamoperforating branches
(C)

irrigating the bilateral thalami and midbrain (64).
A meningeal branch (artery of Davidoff and Schechter)
supplying the tentorium is rarely seen other than in
pathologic states (65).
Branches of the P2 segment include multiple perfo-
rators including the thalamogeniculate arteries. The
medial posterior choroidal artery usually arises as a sin-
gle branch and from the P2 segment, but it occasionally
arises from the P1 segment. The characteristic undulat-
ing appearance of this vessel as it conforms to the tectal
plate is visible routinely on lateral angiography. The
lateral posterior choroidal artery usually arises from the
P2 segment, but it may also arise from the P3 or P4 seg-
ments. It is more likely to comprise multiple arteries
(66). The posterior choroidal arteries exist in reciprocal
relation with the anterior choroidal artery. The inferior
temporal arteries originate from the P2 segment with a
highly variable configuration and irrigate the inferome-
dial aspect of the temporal and occipital lobes (63). Nota-
ble variations include a common temporal artery giving
rise to all inferior temporal arteries (16%). The hippo-
campal artery, if present, is the first cortical branch and
arises as a branch of the P2 segment (63).
The P3 segment branches into the calcarine and
parieto-occipital arteries. An important angiographic
landmark is the collicular point where the PCA trunk
or calcarine arteries are nearest one another.
The P4 segment includes the continuation of the
calcarine artery. The splenial (posterior pericallosal)
artery most commonly arises from the P4 segment,
although it may arise from the P2, P3, cortical
branches, or posterior choroidal arteries (Fig. 5.10).
The splenial artery anastomoses with the pericallosal
artery.
2011, BNI
Figure 5.10 Lateral VA angiogram demonstrating the posterior
pericallosal (splenial) artery (arrow). This vessel is likely well
visualized due to decreased flow from the anterior circulation as
a result of moyamoya disease. Source: From Barrow Neurolog-
ical Institute.
MANAGEMENT OF CEREBROVASCULAR VARIANTS 97
POSTERIOR CIRCULATION
Vertebral Artery
The VA is usually the first branch of the subclavian
artery and arises from the first segment on either side.
The left VA is dominant in 75% of cases (67). Variants
are more common on the left and include origin of
the left VA from the proximal subclavian trunk
instead of the superior portion or directly from the
aortic arch as a separate branch. The right VA may
arise rarely from the aortic arch, right CCA or ICA, or
as the last branch from the subclavian artery.
The first (extraosseous) segment of the VA extends
from its origin to its entry into the foramen transversa-
rium at C6. While it typically enters at the C6 level (90%),
it also may enter at C5 (7%) or C7 (3%). The V2 (fora-
minal) segment encompasses the portion of the VA
while it travels through the foramina transversaria, end-
ing at C2. Branches of the V2 segment include multiple
radiculomedullary arteries entering through the inter-
vertebral foramen to anastamose with the anterior spinal
artery (ASA). The largest, the artery of the cervical
enlargement, arises between C4 and C6. Although it can
originate from the VA, it is usually a branch of the costo-
cervical trunk (68). A variable number of muscular
branches originate along the course of the second seg-
ment and often anastomose with branches of the thyro-
cervical and costocervical trunk. The anterior meningeal
artery, a branch of V2, anastomoses with branches from
the APA (17). The V3 (extraspinal) segment begins as
the VA exits the bony foramen at C2, curves around the
lateral mass of C1, and enters the dura. This segment
usually contains no branches; however, in 520% of
cases, the posterior inferior cerebellar artery (PICA) may
originate from the extradural VA (22). The V4 segment
encompasses the intradural course of this vessel until it
joins with its contralateral counterpart to form the basi-
lar artery. Hypertension, smoking, and other vascular
disease can cause dolichoectasia of this segment, result-
ing in a circuitous course that often complicates treat-
ment of vascular pathology.
There are many important branches of the V4
segment. Angiographically, the most recognizable
branches are the PICA and the ASA. Angiographically
occult branches include a variable number of perforat-
ing branches, the lateral spinal artery, and meningeal
branches. The blood supply to the entire central aspect
of the spinal cord to the level of C4 originates from
the V4 segment. The posterior meningeal artery is
usually a branch of the V4 segment, but it also may
originate from the V3 segment and supplies the dura
of the posterior fossa. The ASAs can originate from a
single VA or from an anastomotic vessel connecting
the VAs (6.3%) immediately caudal to the vertebroba-
silar junction (VBJ). Alternatively, the ASAs can arise
from a common trunk (12.5%) or be duplicated
(15.6%) (69).
Vertebrobasilar Junction
The VBJ can occur at the level of the bulbopontine sul-
cus (20%), below the sulcus (67%), or above the sulcus
(12%) (69). The most common variant at the VBJ, fen-
estration, is associated with an increased rate of
98 NEUROINTERVENTIONAL MANAGEMENT

formation of aneurysms (Fig. 5.11) (70). Aneurysms
are rare at this location; therefore, fenestration should
be considered whenever an aneurysm, especially one
with a dumbbell morphology, is encountered. It may
be difficult to demonstrate the fenestration due to the
flow of unopacified blood from the contralateral VA.
Three-dimensional digital subtraction angiography is
often helpful in delineating this complex anatomy.
However, obtaining an optimal working projection
defining the fenestration may still be difficult.
of the basilar artery not only increases the difficulty of
navigation but also may cause symptoms and is asso-
ciated with a higher risk of stroke (71).
The basilar artery gives rise to the paired AICAs
and superior cerebellar arteries (SCAs). The basilar
artery also gives off numerous perforating arteries
that supply the ventral aspect of the brainstem.
Tortuosity and dolichoectasia are common in the
vertebral and basilar arteries and may be related to
VA dominance (72).

Basilar Artery Cerebellar Arteries

The basilar artery extends from the pontomedullary The distribution of the cerebellar arteries is in a recip-
junction to the pontomesencephalic junction where it rocal relationship with each artery supplying about
branches into the P1 segments of the PCAs. Tortuosity one-third of the cerebellar cortex, a portion of the

LVA

2011, BNI

(A) (B) (C)

(D) (E) (F)

Figure 5.11 (A) Postcoiling angiography of a basilar apex aneurysm demonstrating a basilar fenestration at the vertebrobasilar junc-
tion. (B) AP and lateral (C) right vertebral artery angiogram of another patient with VB junction aneurysm (arrow) (arrowheadleft intra-
dural vertebral artery). (D) Anterior and inferior (E) view of 3D reconstructions demonstrate bilobed aneurysm extending dorsal and
ventral to fenestration of the vertebrobasilar junction (arrowslimbs of fenestration). (F) 3D reconstruction of post stent-assisted coil
embolization of aneurysm (arrow), stent (arrowheads) extends through one limb of the fenestration. Source: (A) From Barrow Neuro-
logical Institute.

brainstem, a cerebellar peduncle, and a portion of the
vermis (73). The SCA supplies the tentorial surface,
while the PICA supplies the inferior and posterior
surfaces. The PICA is usually the largest of the cere-
bellar arteries and the AICA is most often the
smallest.
Posterior Inferior Cerebellar Artery
The PICA usually originates from the V4 segment of
the VA. There are four segments of the PICA: anterior
medullary, lateral medullary, tonsillomedullary, telo-
velotonsillar, and cortical. Perforating vessels supply-
ing the brainstem originate from the first three
segments of PICA. The tonsillomedullary and telove-
lotonsillar segments give rise to branches supplying
the choroid plexus of the fourth ventricle.
Variants of the PICA origin include an extradural
origin from the V3 segment in 520% of cases (22).
Alternatively, a hybrid AICA-PICA may originate at
the normal location of the exit of the AICA from the
midportion of the basilar artery (1). Rarely, the VA
may terminate in PICA without continuing on to join
the contralateral VA.
Anterior Inferior Cerebellar Artery
The AICA originates from the midbasilar artery and
gives rise to a number of perforators as it courses
around the brainstem. The AICA gives rise to the lab-
yrinthine (internal auditory) artery which supplies the
middle ear. The AICA and PICA often have a com-
mon origin (1).
2011, BNI
Figure 5.12 Variant configuration of the top of the basilar artery
with the P1 segment of the PCA and the SCAs originating from
a common trunk. Source: From Barrow Neurological Institute.
MANAGEMENT OF CEREBROVASCULAR VARIANTS 99
Superior Cerebellar Artery
The SCA originates from the region of the basilar
apex immediately proximal to the basilar bifurcation.
Rarely, the SCAs may originate from the P1 segment
of the PCA (Fig. 5.12). The four segments of the SCA
are the anterior pontomesencephalic, lateral pontome-
sencephalic, cerebellomesencephalic, and cortical seg-
ments. The SCA bifurcates a variable distance from its
origin into a rostral and caudal trunk. The SCA before
the bifurcation as well as its rostral and caudal trunks
gives rise to a variable number of perforating
branches that supply the brainstem. Cortical branches
of the SCA are subdivided into hemispheric and ver-
mian branches. The vermian branches originate from
the rostral trunk. The important precerebellar arteries
originate from cortical branches and supply the deep
cerebellar nuclei.
The rostral and caudal trunks may originate
directly from the basilar artery in 1428% of cases
(74,75). Rarely, the SCA may arise from the P1 seg-
ment of the PCA.
Upper Basilar Artery
The region of the upper basilar artery encompasses
the origins of the bilateral P1 segments of the
PCA, the origins of the bilateral SCA, and the seg-
ment of the basilar artery encompassing the origin
of these vessels. This segment of the basilar artery is
remarkable in that it contains a high density of brain-
stem perforators. Furthermore, while the diameter of
the basilar artery is relatively constant along its
length, in the region of the upper basilar artery, it
widens in 16% of cases giving it a cobra-like appear-
ance (Fig. 5.13) (48).
VENOUS SYSTEM
The cerebral venous circulation demonstrates a greater
degree of variability than its arterial counterpart.
Despite its variability, the principle of balance persists
such that the brain is efficiently drained of blood as
rapidly as the arterial blood arrives with each cardiac
cycle. Indeed, the rich anastomotic channels allow
alternate methods of venous drainage. Therefore, mul-
tiple veins must usually be affected before symptoms
occur. Endovascular interventions are often limited to
the thick-walled dural venous sinuses.
Dural Venous Sinuses
Dural venous sinuses are formed by separation of
either the meningeal or periosteal layers of the dura.
The dural venous sinuses are the most constant com-
ponent of the cerebral venous vasculature in terms of
location, course, and portions of the brain drained.
The dural venous sinuses accommodate cortical veins
draining brain as well as a limited number of emis-
sary and diploic veins draining the scalp and skull.
They also house the arachnoid granulations, which
drain cerebrospinal fluid into the venous system.
Occasionally, these granulations may become enlarged
and appear as a bubble angiographic defect mimick-
ing a thrombus.
100 NEUROINTERVENTIONAL MANAGEMENT
2011, BNI
Figure 5.13 Cobra-like appearance of the basilar apex with
the right P1 segment of the PCA and right SCA originating from
a common trunk as well as widening of the basilar trunk between
the left P1 segment of the PCA and left SCA. Source: From
Barrow Neurological Institute.
Superior Sagittal Sinus
The superior sagittal sinus (SSS) begins at the crista
galli and courses along the superficial midline to ter-
minate at the torcula. The SSS drains the majority of
the cerebral hemisphere by accommodating venous
drainage from frontal, parietal, and occipital cortical
veins as well as the diploic veins. It therefore enlarges
in an anterior-to-posterior direction. The SSS is often
divided into thirds with the anterior third being
deemed safe to sacrifice although this may not
always be the case. Venous infarction becomes more
likely as the SSS is occluded further posteriorly. The
middle third accommodates the most dense connec-
tions to cortical veins, while the posterior third con-
tains the least. The superior anastomotic vein of
Trolard also drains into the SSS.
Inferior Sagittal Sinus
The inferior sagittal sinus (ISS) extends along the infe-
rior border of the falx cerebri in a course paralleling
the SSS. The ISS joins the vein of Galen at the falcoten-
torial junction to form the straight sinus. Anastomotic
channels within the falx connect to the SSS and ISS.
Cortical veins draining the medial cerebral hemi-
spheres also drain into the ISS.
Transverse Sinus
The paired transverse sinuses (TS) begin lateral to the
torcula and extend along the posterolateral tentorial
margin to the sigmoid sinus. The TS receives blood
from the inferior anastomotic vein of Labbe as well as
from the superior petrosal sinus (SPS), extending from
the cavernous sinus. The right transverse sinus is usu-
ally larger than the left (76).
Sigmoid Sinus
The sigmoid sinus usually begins after the SPS drains
into the sinus and ends at the jugular bulb, a dilated por-
tion of the jugular vein at the skull base. The sigmoid
sinus receives blood from the inferior petrosal sinus.
Occipital Sinus
The inconstant occipital sinus extends inferiorly from
the torcula in the midline as the infratentorial analog
of the SSS. The occipital sinus is present in 64.5% of
cases (77). Most commonly, a single sinus is found in
the midline (35%). In 22.5% of cases, the occipital
sinus is split into two channels straddling the midline
occipital keel. Less commonly, a left-sided (4%) and
right-sided (3%) sinus are found.
Straight Sinus
The straight sinus begins at the falcotentorial junction
from the union of the ISS and the vein of Galen and
drains into the torcular.
Torcular Herophili
At the junction of the superficial and deep venous
systems is the torcular Herophili. In the most common
configuration, inflow to the torcula is through the SSS,
occipital sinus, and straight sinus, while the outflow is
to the bilateral transverse sinuses. Numerous varia-
tions in the torcula anatomy have been described.
A common variation of torcular anatomy is drainage of
the SSS directly into the left or right TS with the sig-
moid sinus draining into the contralateral TS. While the
aforementioned variation would be obvious on preop-
erative imaging, others may be occult, becoming evi-
dent only when unexpected wire or catheter deflections
occur. These variations include partitions (pads, septae,
or webs) that may extend through the torcular in vari-
ous directions.
Anastomotic Veins
Superior Anastomotic Vein of Trolard
The superior anastomotic vein connects the superficial
middle cerebral vein (SMCV) to the superior sagittal
sinus. The precentral, central, and postcentral veins
interconnect the SMCV and SSS. However, one of
these veins is usually dominant and is therefore
named the superior anastomotic vein. This vein is
most commonly found in the postcentral sulcus (75%).
Occasionally, there may be two such veins which are
equal in size (78).
Superficial Middle Cerebral Vein (Superficial Sylvian
Vein)
The configuration of the SMCV, also known as the
superficial Sylvian or simply as the Sylvian vein, is

highly variable. Anteriorly, it may join the sphenopar-
ietal sinus, cavernous sinus, superior petrosal sinus,
lateral tentorial sinus, or transverse sinus. Posteriorly,
it joins the anastomotic veins. The Sylvian vein may
be duplicated or absent. In the latter case, veins adja-
cent to the fissure are larger and drain superiorly to
the SSS or inferiorly to the temporal veins (78).
Inferior Anastomotic vein of Labbe
The vein of Labbe usually courses from the Sylvian
vein to the transverse sinus. However, it can instead
drain into the sinus, dural veins, or superior petrosal
sinus (79). While the inferior anastomotic vein may
originate from the Sylvian vein anywhere along its
course, it usually does so near the middle of the
vein (78).
Cavernous Sinus
The paired cavernous sinuses are unique among the
dural venous sinuses in that cranial nerves as well as the
ICA travel within it. The cavernous sinuses are situated
on either side of the sella and extend anteriorly to the
superior orbital fissure. The sinus receives veins anteri-
orly, draining the orbit via the superior and inferior oph-
thalmic veins, and draining posteriorly via the SPS and
inferior petrosal sinus (IPS). The intercavernous sinus
serves to interconnect the two cavernous sinuses. The
extent of this interconnection is highly variable and may
be absent. A circular sinus refers to the presence of ante-
rior and posterior interconnections (77).
The superior and inferior petrosal sinuses inter-
connects the cavernous sinus to the transverse sinus
by coursing along the petrous ridge. The superior pet-
rosal vein (Dandys vein) and other infratentorial
veins commonly drain into the SPS (80). Rarely, the
superficial Sylvian vein may drain into the sphenopar-
ietal sinus, which drains into the SPS.
The IPS interconnects the cavernous sinus to the
jugular bulb. There are four major variants (81). The
blood in the IPS may be sampled to determine laterality
of pituitary microadenomas. There is often an asymme-
try, which is important to identify because it can yield
false-negative results during IPS sampling (82).
Deep Venous System
The deep cerebral venous system drains the portions
of the brain surrounding the lateral ventricles, third
ventricle, and basal cisterns (83).
Internal Cerebral Vein
The internal cerebral vein forms at the confluence of
the septal vein and thalamostriate vein immediately
posterior to the foramen of Monro. The internal cere-
bral veins course posteriorly in the roof of the third
ventricle accommodating a number of ventricular and
cortical veins, including the thalamocaudate and atrial
veins. The thalamostriate and thalamocaudate veins
have an inverse relationship. In 10% of cases where
the former is absent, the latter drains the same area.
The internal cerebral veins join to form the great cere-
bral vein (of Galen).
MANAGEMENT OF CEREBROVASCULAR VARIANTS 101
Basal Vein of Rosenthal
The basal vein of Rosenthal begins at the junction of
the anterior cerebral and deep middle cerebral veins
and courses around the brainstem, inferior to the sple-
nium, to terminate in either the internal cerebral veins
or vein of Galen. Alternatively, the middle segment of
the basal vein may drain into a sinus in the tentorial
incisura. The angle at which the basal vein joins the
vein of Galen can vary substantially, from flat to
sharply angulated, depending on the position of the
falcotentorial apex in relation to the splenium (84).
Vein of Galen
The vein of Galen (great vein) begins at the confluence
of the internal cerebral veins and may receive the
basal veins before it terminates at the falcotentorial
junction in the straight sinus.
Veins of the Posterior Fossa
The veins of the posterior fossa are divided into a
Galenic, tentorial, and petrosal draining groups based
on which venous structure they drain into. The
Galenic group drains the superior aspect of the
cerebellum and brainstem and includes the midline
precentral cerebellar vein. The petrosal group drains
the anterior aspect of the cerebellum and brainstem.
These veins coalesce into the superior and inferior
petrosal veins draining into the analogously named
sinuses. The tentorial group drains the suboccipital sur-
face of the cerebellum and drains into the straight
sinus, torcula, and transverse sinuses. Tributaries of the
tentorial group may travel for variable distances
through the tentorium prior to draining into the sinuses
(8587).
WADA TESTING
The presence of communicating arteries (ACOM and
PCOM) has implications for WADA testing. In the
presence of a large ACOM or PCOM, the bolus of
sodium amytal and its rate of administration must be
measured so that there is no significant reflux to the
contralateral ACA or basilar artery, respectively. This
goal can be accomplished with a number of test injec-
tions to determine the optimal infusion rate. If reflux
occurs across the ACOM, false results can be achieved
due to contamination from the amytal effect from the
contralateral hemisphere. If reflux occurs into the basi-
lar artery, respiratory centers can be affected and
apnea can ensue.
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 6
CT imaging and physiologic techniques in interventional
neuroradiology
Bryan A. Pukenas and Ronald L. Wolf
BACKGROUND
The first clinical CT scans of the brain were obtained
in 1972 on a prototype CT scanner developed by
Hounsfield. The first clinical scanner, the EMI Mark I
scanner, was introduced in 1973. The Nobel prize in
medicine was awarded to Sir Godfrey Hounsfield
and Alan Cormack in 1979 for the development of
computer-assisted tomography, underscoring the
impact of this achievement on clinical medicine.
Improvements in design led to slip ring technology
and thus helical or spiral scanning, first introduced in
1975 at Varian and then reintroduced with a more
practical design in 1985 and 1987 by Toshiba and
Siemens, respectively. Where the EMI Mark I scanner
required approximately 5 minutes for the acquisition
of one imaging section, spiral scanners could cover
several centimeters in less than 60 seconds, obtaining
nearly isotropic resolution over a small field of view
but at the expense of tube heating (1).
Multidetector CT (MDCT) was actually first
implemented on the first generation EMI Mark I scan-
ner, which acquired two sections at a time. Elscint
introduced the first helical scanner with dual detectors
in 1992, followed by detector configurations of four
channels or more starting around 1998. Current config-
urations have up to 320 channels so that the entire head
(16cm) can now be covered in a single gantry rotation,
obtaining nearly isotropic resolution (1) as well as 4D
(the fourth dimension being time) imaging (2). With
MDCT configurations, thin and thick sections are effec-
tively acquired simultaneously while covering a large
distance along the z-axis. Data for thin sections can
thus be acquired and combined to reconstruct thicker
sections for reading while retaining advantages of thin-
section scanning such as minimization of partial vol-
ume artifact and resultant streaking. As long as raw
data are retained, additional thin-section reconstruc-
tions can be obtained retrospectively for multiplanar,
3D and 4D reformatting (3).
CT TECHNIQUES
Conventional CT and CT Myelography/
Cisternography
CT of the brain can be performed using sequential
single slice, helical multislice, or multidetector
multislice techniques. American College of Radiology
guidelines suggest section thicknesses in the supraten-
torial compartment of 10mm or less in adults (5mm
or less in children under age 10), and 5mm or less in
the posterior fossa in adults or children. For the skull
base, sections of 3mm or less are preferred. If multi-
planar reformats are required (e.g., facial and skull
base fractures in setting of trauma) or if 3D rendering
is to be performed, sections of 2mm or less should be
obtained. With multidetector scanners, multiple data-
sets (e.g., for standard CT brain, face, skull base, and/
or temporal bones) can be acquired prospectively and
simultaneously by selecting detector spacing on the
order of 1mm or less, combining thin sections for
evaluation of brain and soft tissues and reconstructing
thin sections with overlap for reformatting or render-
ing retrospectively as needed for face, skull base, and
temporal bones (Fig. 6.1). The same is true for CT
spine post myelogram or CT head and face post cis-
ternogram. Coronal sections can be directly acquired
by angling the gantry and positioning the patient with
neck extended. High quality reformatted images from
axial data are now obtainable with newer MDCT sys-
tems, but direct coronal acquisitions are still needed if
reformats do not provide sufficient detail for clinical
decision making. Also, if the patient moves during the
axial acquisition, the reformats will of course be
degraded.
CT is the primary imaging modality for emer-
gent indications such as trauma and acute changes
in neurologic status, including ischemia and intracra-
nial hemorrhage. For most applications concerning
structural imaging of the brain, skull base, cranial
vault, and spine, nonenhanced CT (NECT) is most
often adequate. The primary indications for use of
IV contrast in this setting include infection and neo-
plasm; but in practice the use of IV contrast is rela-
tively uncommon because central nervous system
(CNS) infection and neoplasm will almost always
prompt an MRI, obviating the need for enhanced
CT. IV contrast is however preferred for routine CT
of the soft tissues of the neck, and required for CT
angiography. In the setting of penetrating trauma,
NECT neck can be useful for assessing trajectory of
injury and proximity to vascular structures as well
as evaluating for foreign material like bullets and
fragments. Intrathecal contrast is of course required
for myelography or cisternography.
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
(A)
Figure 6.1 Simultaneous acquisition of standard NECT and high-resolution CT of skull base with MDCT. (A) NECT (3mm section)
shows pneumocephalus and temporal bone fracture (arrowhead). (B) 1mm bone reconstructions from the same raw data also reveal
fracture line through the right carotid canal (arrow), nearly invisible on standard NECT.
CT Angiography
CT angiography (CTA) has become an attractive alter-
native to digital subtraction angiography (DSA) for
rapid evaluation of the cervical and cerebral vascula-
ture. A complete evaluation of the brain with NECT,
CTA of the head and/or neck, and if indicated CT per-
fusion and contrast-enhanced CT (CECT) head can be
obtained in less than 1015 minutes. CTA is well toler-
ated, and in many cases preferred by patients as com-
pared with MR imaging and MR angiography (4).
Source images are available immediately and provide
most of the diagnostic information necessary for deci-
sion making. Data for head and neck can be obtained in
one acquisition, and smaller field of view reconstruc-
tions at more closely spaced intervals (i.e., on the order
of 0.5mm) reconstructed for the circle of Willis using
the initial dataset. Creation of volume rendered, multi-
planar reformatted and/or maximum intensity projec-
tion (MIP) images can be performed relatively quickly
at the scan console or on a separate workstation.
Typically, consecutive thin axial sections (~12
mm) are obtained during IV contrast administration
of 75100 cc iodinated contrast at 34 cc/sec followed
by a saline chasing bolus. Reconstructing with an
overlap of about 50% improves the appearance of vol-
ume rendered and reformatted images. Timing the
bolus based on contrast opacification in the aortic arch
or left ventricle allows optimal arterial opacification
and minimization of venous interference. Timing strat-
egies include automatic triggering using specialized
software, or using a fraction of the bolus administered
during a cine acquisition to obtain an enhancement
profile. Alternatively, at least for the circle of Willis, a
standard delay of about 25 seconds nearly always
105
(B)
gives good arterial opacification, with adjustments
made for patients with poor cardiac output. A CT veno-
gram (CTV) can be obtained by simply adding several
seconds (about 68 seconds) to the delay. Protocols
vary for different vendors and for different detector
configurations, and should be optimized for each site.
There are many options for postprocessing (5),
with the most commonly used techniques including
volume rendering (VR), MIP, and oblique/orthogonal
or curved reformatting. MIP, a ray-tracing algorithm
where the brightest pixel along a ray passed through
the volume is displayed in a projection image, is prob-
ably the most useful. VR is generated by assigning
colors and opacities to ranges of attenuation so that
vessels appear distinct from bone and soft tissues. It is
most helpful for intracranial applications where 3D
visualization is needed, especially aneurysms. VR is
less helpful in the neck where overlapping structures
like veins and the spine make postprocessing more
difficult, but it can be helpful in certain situations
such as visualizing the relationship of a high carotid
bifurcation relative to the mandible prior to endarter-
ectomy. Shaded surface display (SSD) methods are of
limited utility (6), often underestimating degree of
stenosis and now superseded by other rendering tech-
niques. Other useful postprocessing techniques
include automated vessel analysis techniques for cal-
culation of stenosis severity and for vessel extraction,
software for separating arteries and veins, and fly-
through techniques. The use of subtraction or mask-
ing algorithms for bone and metal exist allow for
improved visualization of aneurysms near the skull
base, of particular use in detection and aneurysm
treatment planning (7,8). Overlap between attenuation
of contrast in a vessel and adjacent bone or calcium is
often present, limiting threshold-based segmentation
106 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
(D) (E)
Figure 6.2 Stent evaluation. (A) Source and (B) curved reformatted CTA images show restenosis in a SMART
Stent (nitinol, Cordis),
poorly demonstrated on (C) contrast-enhanced MRA (open arrow). (D) CTA and (E) time-of-flight MRA show patent WALLSTENT

(stainless steel, Boston Scientific). Ends of stent are better shown with CTA (arrows). (F) Neuroform
stent (nitinol, Boston Scientific)
on CTA (arrowhead).
approaches. Dual energy bone subtraction techniques
can also be used (9,10). Associated artifacts like beam
hardening and streaking can limit diagnostic accuracy
with or without subtraction, an obvious problem with
routinely used aneurysm clips, metallic coils in aneur-
ysms or vessels, and stents. In general, CTA is pref-
erable for evaluation of stents (Fig. 6.2), while coils
are better evaluated using MRI techniques (Fig. 6.3).
CTA will often be more successful than MRA in prox-
imity to clips (Fig. 6.4) (11), with some clip materials
evaluated more successfully, e.g., titanium versus
cobalt alloy (12).
CT Perfusion
There are essentially two imaging approaches for the
measurement of cerebral blood flow (CBF) in clinical
practice: (i) intravascular or nondiffusible tracer
(bolus-contrast) techniques, and (ii) diffusible tracer
(the tracer can diffuse out of the vessels into sur-
rounding tissue) techniques. Most routine clinical CT
and MR perfusion-weighted imaging studies use an
intravascular contrast agent, rapidly injecting a bolus
(C)
(F)
and analyzing the first-pass. Diffusible tracer methods
include stable xenon CT perfusion, H215O positron
emission tomography (PET), and arterial spin labeled
perfusion MRI. Excellent discussions of different per-
fusion methodologies are available in papers by Win-
termark, et al. (13) and Latchaw et al. (14).
Bolus Contrast CT Perfusion
Bolus contrast CT perfusion (CTP) is based on the lin-
ear relationship of attenuation to concentration of
iodine in the brain. It is performed by scanning in
cine mode at between 1 and 4 imaging locations,
repeatedly imaging these locations over 4050 seconds
at a rate of about one image set every 12 seconds
before, during and after a bolus of iodinated contrast.
A volume of 4050 cc is infected at 58 cc/sec through
a large bore IV. Analysis of the time series of CT
images results in a timeattenuation curve (TAC).
Motion can significantly degrade the perfusion analy-
sis, and although software is available that allows
realignment of motion-degraded data to an extent,
care should be taken to prepare the patient
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 107

(A) (B) (C)

(D) (E) (F)

Figure 6.3 Intracranial embolization coils. Scout topogram and axial image from NECT (A, B) demonstrate large coil mass in basilar
tip aneurysm with extensive artifact (B) limiting CTA. Conventional (C, E) and contrast-enhanced MRA (D, F) show aneurysm remnant
(arrowheads) on source (C, D) and MIP (E, F) images with minimal artifact from coils (arrows). Thrombus was seen in coiled aneurysm
inferiorly (E, block arrow).

appropriately to minimize motion, including sedation
if necessary.
Hemodynamic parameters typically generated
include measures of the time-to-peak (TTP, time
from arrival of bolus in intracerebral arteries to peak
concentration in tissue, units of seconds), cerebral
blood volume (CBV, integral under the TAC normal-
ized to intravascular attenuation in large vessel such
as sagittal sinus, units of cc/100g), mean transit time
(MTT, average time for contrast to pass from arterial
to venous side, units of seconds), and cerebral blood
flow (CBF, blood flow in volume of tissue, units of
cc/100g/min). For parameters TTP and CBV, calcula-
tions are straightforward and relatively easy to
obtain. For MTT or CBF, calculations require more
sophisticated analysis, measuring and incorporating
the arterial input function (deconvolution techniques)
or evaluating the shape of the TAC (nondeconvolu-
tion techniques). Deconvolution techniques correct
for the imperfect bolus (in theory it should be an
instantaneous bolus, but in reality it is spread out),
deconvolving or removing the effect of the imperfect
arterial input function from the TAC to obtain the
residue function, from which the CBF and MTT can
be generated (Fig. 6.5). The central volume principle
describes the relationship between parameters as
CBF = CBV/MTT (15,16).
Nondeconvolution methods use the slope of the
tissue TAC to measure the change in concentration of
iodine over time, which is proportional to CBF and
the difference between iodine concentration in artery
and vein (16,17). A high injection rate of 68 cc/sec is
required, while deconvolution methods tolerate lower
rates of injection on the order of 5 cc/sec. Absolute
CBF quantitation is possible with deconvolution meth-
ods, but there are difficulties in assuring accuracy; for
example, large vessels in the analyzed volume can
lead to overestimation of CBF. Nondeconvolution
methods tend to underestimate CBF. In practice, rela-
tive values for perfusion parameters are often used for
interpretation, using normal-appearing and/or con-
tralateral brain as an internal reference. Another
approach which does not rely on deconvolution or
analysis of the bolus itself generates maps of percent
perfused blood volume (PBV) based on a subtraction
of registered unenhanced baseline CT images from
108 NEUROINTERVENTIONAL MANAGEMENT
[R]
[P]
(A)
(C)
Figure 6.4 Aneurysm clips. (A, C) Axial source and (B, D) MIP images show that CTA (top) shows the A1 segment and AcoA complex
near the clip (open arrow, B). On MRA (top), susceptibility artifact leads to extensive signal loss (arrows, C and D).
CTA source images (18), with change in parenchymal
attenuation linearly proportional to tissue concentra-
tion of iodine.
Stable Xenon Perfusion CT
Stable xenon can be used to measure absolute CBF.
Xenon is lipid soluble and thus diffusible and leads to
changes in attenuation which can be measured on CT
images. Xenon CT (XeCT) perfusion has been applied
in several clinical settings such as cerebrovascular dis-
orders, traumatic brain injury, balloon test occlusion,
and subarachnoid hemorrhage and vasopasm. How-
ever, it is not currently FDA-approved, primarily due
to reported adverse events such as apneic episodes or
increased intracranial pressure (19). These events tend
to be transient and the technique well tolerated, par-
ticularly with the lower inspired xenon concentration
of 28% now used (previously it was 33%).
The study is performed by obtaining two baseline
scans at 28 imaging locations without xenon, followed
by six additional scans at these locations during xenon
(B)
(D)
inhalation. To determine the change in attenuation
from xenon, the baseline scans are averaged for each
location and subtracted from that location for each of
the subsequent time points. Xenon is delivered mixed
with oxygen at a concentration of 28%. End-tidal xenon
concentration is measured, and end-tidal CO2 moni-
tored as well as any apneic episodes. Calculation of
CBF is based on the Fick principle; that is, the amount
of an indicator in a sample of tissue is proportional to
the difference between the amount supplied in arterial
blood and the amount carried away in venous blood.
Modified KetySchmidt equations are used describe
the relationship of xenon concentration in the brain and
in the arteries to the blood/brain partition coefficient
and CBF (20). The xenon concentration in the brain is
obtained from the CT measurements at baseline and
during inhalation of xenon, and the time-dependent
arterial concentration is obtained by measuring the
end-tidal xenon concentration which is proportional to
the time-dependent arterial concentration in patients
without severe lung disease leading to significant dead
space. The total time of acquisition is on the order of
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 109

300

280

260

240
220

200
180
160

140
120

100
80
60

40

20
8
1 4 8 12 16 20 24 28 32 36 40

(A) (B) (C)

Vein Vein
Vein

(D) (E) (F)

Figure 6.5 Bolus contrast CT perfusion. NECT (A) shows SAH in left basal cisterns and minimal hydrocephalus. Regions of interest
(ROIs) for artery (arrowhead) and vein (arrow) are chosen (B) to generate time attenuation curves (C), from which parametric maps
are generated such as (D) CBF, (E) CBV, and (F) MTT).

56 minutes, and studies take about 20 minutes from Aneurysm

start to finish, including data processing and creation
of CBF maps. Repeat studies can be obtained 20 minutes
after the end of a previous scan, allowing for washout
of xenon.
CLINICAL APPLICATIONS
Nontraumatic Hemorrhage
Common causes of nontraumatic intracranial hemor-
rhage include ruptured aneurysm, arteriovenous mal-
formation (AVM), hypertension, and prematurity of
the newborn. Other etiologies include reperfusion
injury, amyloid angiopathy, coagulopathy, drug
abuse, and intracranial neoplasms. Less common are
entities like venous hypertension or occlusion, eclamp-
sia, vasculitis, and infection (21). This section focuses
on common clinical entities most relevant to interven-
tional neuroradiology: aneurysm, AVM, and venous
hypertension/occlusion.
An aneurysm is a circumscribed dilatation of an
artery involving all three layers (intima, media, and
adventitia). There are different types and/or etiologies
of aneurysms, but the most common is the berry, or
saccular aneurysm. Other types include mycotic, fusi-
form, and traumatic aneurysms. A pseudoaneurysm is
a dilatation of the vessel typically caused by disrup-
tion of one or more layers of the arterial wall which
may form a contained wall hematoma and are often
caused by dissections. Aneurysms can be associated
with abnormal vasculature in neoplasms. Venous
aneurysms also occur, and both arterial and venous
aneurysms can be seen with AVMs. The most com-
mon locations of berry aneurysms (rupture or unrup-
tured) are proximal in the circle of Willis. About
8595% involve the anterior circulation, and 515%
involve the posterior circulation. The most likely loca-
tions are anterior communicating artery (AcoA, 30%),
internal carotid artery (including periophthalmic and
110 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 6.6 Aneurysm rupture and CTA. (A) NECT at presentation shows SAH in the sylvian fissure (white arrowhead) and a parenchy-
mal hematoma (black arrowheads). This pattern is suspicious for MCA aneurysm rupture, confirmed on (C) MIP images from CTA
(white arrow). A second unruptured MCA aneurysm is present (open arrow).
posterior communicating artery or PcoA, 25%), middle
cerebral artery (MCA, 20%), basilar artery (BA, 10%),
and posterior inferior cerebellar artery (PICA, 5%).
There are multiple aneurysms in about 20% of aneur-
ysm patients (22).
CT techniques play a prominent role in evaluating
of unruptured or ruptured aneurysms. For unruptured
aneurysms, MR angiography or MRA is more com-
monly used as a screening modality, where CTA is
more often used to verify suspicion of an aneurysm
(e.g., one suggested but not certain on MRA), to better
characterize an aneurysm detected on MRA or DSA
(e.g., giant or cavernous aneurysms), and when patients
cannot undergo MRI/MRA. Multiple studies have com-
pared CTA with MRA, DSA and/or rotational angiogra-
phy. Sensitivity for detection of aneurysms is at least as
good as MRA, but like MRA, drops off below 3mm (23).
CTA is also used to follow patients with known aneur-
ysms. Although aneurysm clips currently placed are
largely MR compatible, they create substantial artifact
which often renders MRA useless. Clips can also limit
CTA, but diagnostic information is still often obtainable,
even for previously clipped aneurysms. Previously
coiled aneurysms are better evaluated with MRA.
Subarachnoid Hemorrhage and Saccular Aneurysmal
Rupture
The most common cause of nontraumatic subarach-
noid hemorrhage (SAH) is ruptured aneurysm
(7585% of cases) (24), with significant associated mor-
bidity and mortality. Other less common causes
include perimesencephalic hemorrhage, AV malforma-
tion or fistula (intracranial or spinal, and possibly with
associated aneurysm), intracranial dissection, drugs
such as amphetamines or cocaine, coagulation disor-
ders, vasculopathies such as sickle cell disease and
(B)
moyamoya, and others (25,26). NECT is almost always
the first imaging study obtained, allowing for rapid
evaluation of SAH as well as immediate complications
such as hydrocephalus, is available around the clock,
and provides easy access to unstable patients. Acute
blood appears dense on CT, depending on hematocrit
and hemoglobin values (approximately 56 HU with
hematocrit of 45% compared to gray matter attenuation
of just under 40 HU or cerebrospinal fluid (CSF) at
around 05 HU) (27). Coagulopathies can lead to diffi-
culty in visualizing acute blood; for example, with a
low hemoglobin value of less than 10 g/dL acute hem-
orrhage may be isodense to CSF. The sensitivity for
NECT in detecting SAH is approximately 95% in the
first 12 days, but decreases over time to 50% after
1 week and almost 0% after 3 weeks. Negative NECT
should be followed by lumbar puncture to increase
sensitivity for SAH detection, assessing for blood and/
or xanthochromia (depending on time after initial
bleed).
The pattern of SAH on NECT may suggest the
most likely location of the ruptured aneurysm, at least
for AcoA and MCA aneurysms (28). The presence of
parenchymal hematoma with SAH increases accuracy
(28,29). When multiple aneurysms are present, the
pattern of hemorrhage and especially location of
parenchymal hematoma may provide useful informa-
tion in deciding which aneurysm was likely to have
bled, complementary to other indicators such as
aneurysm size and morphology (Fig. 6.6). However,
the amount and distribution of blood is very often not
predictive of site of aneurysm rupture (29,30).
Patterns associated with rupture of an AcoA
aneurysm include symmetric SAH, blood in the ante-
rior interhemispheric fissure, anterior pericallosal cis-
tern and/or cisterna lamina terminalis, anterior
interhemispheric clot, or inferior frontal parenchymal
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 111

(A) (B)

Figure 6.7 Ruptured AcoA aneurysm pattern. (A) Axial NECT image shows nearly symmetric SAH and a small interhemispheric or
midline parenchymal hematoma (white arrow). (B) DSA confirms AcoA aneurysm (black arrow), suspected for rupture. Small MCA and
ICA aneurysms were also detected (black arrowheads).

(A) (B)

Figure 6.8 Ruptured MCA aneurysm. (A, B) Axial NECT images at two locations show asymmetric SAH and focal hematoma expand-
ing left sylvian fissure (Fig. 6.9).

hematoma (Fig. 6.7). Intraventricular hemorrhage may
also be associated secondary to rupture through the
lamina terminalis. Other internal carotid artery (ICA)
aneurysms including PcoA aneurysms are more diffi-
cult to localize, often without lateralizing signs on CT.
MCA aneurysms may demonstrate asymmetric den-
sity in the sylvian fissure. More specific localizing pre-
sentations include parenchymal hematomas or
expansile clot in the sylvian fissure (Fig. 6.8). PICA
aneurysms may show disproportionate blood in the
posterior fossa and fourth ventricle, and basilar tip
aneurysms might show SAH primarily in the interpe-
duncular and prepontine cisterns (Fig. 6.9). van der
Jagt et al. (29) reported that validity of SAH distribu-
tion on CT was inconsistent or low for ruptured
aneurysm arising from MCA, ICA, or posterior circula-
tion aneurysms, unless a parenchymal hematoma was in
proximity. Blood distribution was a better predictor for
anterior cerebral artery (ACA) and AcoA aneurysms. An
atypical presentation of ruptured aneurysm is subdural
hematoma (SDH), often with some SAH but rarely with-
out any evidence of SAH. It has been described in ICA
112 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 6.9 Ruptured posterior circulation aneurysms. (A) NECT shows asymmetric blood in right cerebellopontine angle, suggesting
right PICA aneurysm. (B) NECT from a different patient with ruptured basilar tip aneurysm shows focal blood near basilar tip.
and anterior communicating artery (ACOM) aneurysms
(31), also with pericallosal aneurysms (Fig. 6.10). Perical-
losal aneurysms might also show parenchymal hema-
toma or large focal SAH above the corpus callosum.
While the most common causes of SAH are
trauma followed by intracranial aneurysm, this distinc-
tion cannot always be made clinically. Examples include
unwitnessed falls, patients found down without overt
evidence of trauma, or motor vehicle collision or a fall
where a ruptured aneurysm may have preceded the
traumatic event. Findings on NECT favoring trauma are
associated calvarial or skull base fractures, SDH, contu-
sions, and relative lack of blood in basal cisterns. On fol-
low-up imaging, confidence is increased when evolving
contusions or foci of diffuse axonal injury are clearly
demonstrated. Findings favoring aneurysm include
SAH in basal cisterns, excessive amount of SAH, and
lack of obvious traumatic findings. Occasionally, the
aneurysm itself can be clearly visualized on NECT
(Fig. 6.11). In some cases, it is impossible on cross-
sectional imaging to accurately assess whether the
source of SAH is aneurysmal versus traumatic, and con-
ventional angiography may be necessary.
Conventional angiography or digital subtraction
angiography is still considered the gold standard for
detection of aneurysms. However, CTA may be pre-
ferred in some instances, e.g., catastrophic SAH (32)
(Fig. 6.6). In a systematic review of noninvasive imag-
ing studies for aneurysm, White et al. (33) found that
CTA was not as sensitive as DSA for small aneur-
ysms, with accuracy of 96% for aneurysms larger than
3mm, but only 61% for aneurysms 3mm or less (over-
all accuracy of 89%). However, only studies up to
1998 were reviewed, and higher quality multidetector
scanners have become more widely available starting
in around 1998. More recently, Chappell et al. (34)
reviewed 21 studies in a meta-analysis comparing
CTA and DSA (the most recent in 2002). Overall
(B)
sensitivity and specificity weighted for numbers of
patients per study were 92.7% and 77.2%, respectively.
The specificity will likely be inaccurate since the rate
of true-negative cases is difficult to assess in most of
these studies, since most studies focus on cases where
an aneurysm was suspected clinically or radiographi-
cally (34). There is increasing evidence that missing a
symptomatic aneurysm on CTA would be quite rare
(23,3537). Indeed, there are reported cases where
aneurysms are detected on CTA and not DSA, and at
minimum CTA is a valuable adjunct study (38,39). For
example, the 3D anatomy of complicated or giant
aneurysms including those with significant intralumi-
nal thrombus, aneurysm relationship to bony struc-
tures (e.g., paraclinoid aneurysms), and calcifications
which might interfere with clipping may be demon-
strated more clearly (Fig. 6.12). Although there are
still questions regarding sensitivity for detection of
very small aneurysms (< 3mm) and false positives are
also of concern (23), some centers currently use CTA
only for routine aneurysmal SAH workup and have
found it safe and reliable (40,41).
SAH from Aneurysmal Rupture in the Subacute and
Chronic Setting
While MRI is more sensitive and specific for evalua-
tion of ischemia, it is not always a viable option in a
sick ICU patient. CT techniques are preferred for fol-
lowing subarachnoid hemorrhage patients after pre-
sentation and treatment, evaluating for complications
such as rebleeding, hydrocephalus, vasospasm, and
ischemia or infarct. CTA with or without perfusion
may be helpful in vasospasm cases (Fig. 6.13) (42,43).
The addition of CTP (13,43,44) or XeCT perfusion
studies (13,20) may also be helpful. Effectiveness of
treatment can be tested by obtaining perfusion data
before and after changes in therapy. Attention to
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
(A) (B)
(C) (D)
cumulative radiation dose is warranted with
repeated studies, and benefits of repeated imaging
weighed against potential long-term risks (45). Other
methodologies have also been applied to this prob-
lem, including PET, SPECT, and transcranial Doppler
(TCD) (44), but none have been established as a
definitive test (14). Imaging follow-up for the original
and any additional aneurysms depends on prior
intervention. Immediate (or intraoperative) conven-
tional angiography is often performed to verify clip
placement, but CTA can be used for follow-up in the
subacute or chronic setting (46,47). There are some
limitations related to artifacts from the clips (48),
some of which can be minimized with technique
(Fig. 6.14). Coils most often cannot be effectively
evaluated with CTA (Fig. 6.3).
Nonaneurysmal Subarachnoid Hemorrhage
Perimesencephalic hemorrhage as an etiology of SAH
occurs in about 10% of cases, and accounts for about
113
Figure 6.10 Atypical pattern of hemorrhage.
(AC) Axial NECT images at three locations show
subdural hemorrhage (arrows, A and C), and rela-
tively little SAH (B, arrowhead). (D) Volume ren-
dered image from CTA demonstrates a pericallosal
artery aneurysm.
70% of SAH cases which have normal DSA (24). The
typical pattern of hemorrhage is localized in cisterns
around the midbrain, without extension into sylvian
fissures, interhemispheric fissure, or parenchyma.
Intraventricular hemorrhage is also not typically
present. Since aneurysms may be missed initially due
to spasm, compression by hematoma, or perhaps sub-
optimal number or choice of views, DSA-negative
SAH should be followed in about 1 week with
another exam. CTA may provide the means to forego
follow-up (or initial) DSA. Other etiologies of nona-
neurysmal SAH (about 5% of cases) include intracra-
nial dissection especially of vertebral artery, AVM/
AVF, coagulopathy, drug use (e.g., amphetamines or
cocaine), and vasculopathies like sickle cell disease
and moyamoya (25,26).
Arteriovenous Malformation
CTA has been applied to diagnostic evaluation of
AVM, but cannot replace DSA at this time (49,50).
114 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 6.11 Demonstration of aneurysm on NECT. Axial NECT images from patients with (A) ruptured and (B) unruptured ICA aneur-
ysms. In each case, the aneurysm is clearly seen without IV contrast (arrows). Hydrocephalus is also noted in (A).

(A) (B) (C)

Figure 6.12 Giant aneurysm. (A) Sagittal T1-weighted MR image shows flow void/jet (arrowhead) and thrombus (arrow) in partially
thrombosed giant aneurysm. (B) MIP image from MRA fails to distinguish thrombus from patent aneurysm. (C) CTA MIP image distin-
guishes patent (black asterisk) from thrombosed (white plus sign) aneurysm.

CTA can be used as a complementary examination,
primarily for depiction of 3D morphology and for
stereotactic planning, but rotational angiography can
also provide this information. Recently, 4D CTA
techniques have shown promising results in the eval-
uation of arteriovenous shunting (51). AVMs and
AVFs can be detected using CTA, and it can be used
for following lesions after treatment; however, MRI
and MRA are probably better in this regard due to
superior evaluation of parenchyma and improving
temporal resolution of MR DSA methods. In the set-
ting of acute intracranial hemorrhage, nearly all
patients will initially undergo NECT, and in some
cases a presumptive diagnosis of AVM can be made
on NECT even without hemorrhage (Fig. 6.15). Cav-
ernomas and venous angiomas are commonly
encountered, and must be recognized to avoid
unnecessary testing. CTA provides a fast evaluation
of intracranial vasculature for emergent intervention
(Fig. 6.16), and the temporal resolution of CTA is
improving to the point where AV shunting and
delineating arterial or venous aneurysms, arterial
feeders and draining veins are becoming a practical
reality (51).
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 115

(A) (B) (C)

Figure 6.13 CTA and vasospasm. (A) Axial slab MIP from CTA demonstrates segmental narrowing of M2 segment of right MCA indi-
cating vasospasm (white arrow). (B) DSA confirmed vasospasm, and nicardipine was subsequently infused. SAH in this case resulted
from an ACA pseudoaneurysm, previously embolized (black arrowhead). (C) Axial slab MIP from follow-up CTA demonstrates resolu-
tion of the narrowing.

[R]

W
120 KV
ST: 1.0mm
Oblique 8
512x512

(A) (B) (C)

Figure 6.14 Aneurysm follow-up after clipping. (A) Source image from CTA demonstrates aneurysm remnant (arrowhead) despite arti-
fact from clip (block arrows). Slab MIP (B) and VR images (C) demonstrate topography of remnant (arrowheads).

Venous Occlusive Disorders Other Etiologies of Intracranial Hemorrhage

Venous occlusive disease may be suspected on ini-
tial NECT by demonstration of high-attenuation clot
in one or more venous sinuses or cerebral veins. As
opposed to arterial ischemia, venous ischemia or
infarction more often presents with hemorrhage or
with patterns of edema atypical for arterial ische-
mia. Examples include bilateral thalamic hypoden-
sities with deep venous occlusive disease (although
this could be mimicked by top of the basilar syn-
drome) and posterior temporal lobe hemorrhage
suggestive of vein of Labbe or transverse sinus
thrombosis. High-resolution imaging of the cerebral
venous system can be obtained with CT venography
(Fig. 6.17) (52).
There are multiple other etiologies of nontraumatic
intracranial hemorrhage, including hypertensive hem-
orrhage, amyloid angiopathy, coagulopathy, drug
abuse, and intracranial neoplasms. Additional less com-
mon etiologies are reperfusion injury, eclampsia, vascu-
litis, and infection. Some of these will be discussed in
the next section since they may also present as strokes
or stroke-like syndromes, but a complete discussion
is beyond the scope of this chapter.
Ischemia
Stroke represents the third largest cause of mortality
and leading cause of morbidity in the United States.
116 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 6.15 Vascular malformations on NECT. (A) Cavernous malformation (open arrow). (B) Developmental venous anomaly (white
arrow). (C) AVM (arrowheads).
The vast majority of strokes are ischemic in origin
(8085%), and the minority are hemorrhagic events.
Most ischemic infarcts are thromboembolic and
the prognosis, risk of recurrence, and management
options are influenced by infarct subtype (Trial of
ORG 10172 in Acute Stroke Treatment or TOAST
criteria) (53). Subtypes include cardioembolic, large
vessel, small vessel, other (determined) cause, and
cryptogenic.
Hyperacute and Acute Setting
Nonenhanced CT
Acute imaging addresses the following questions: (i) is
there hemorrhage or other explanation for symptoms;
(ii) what is the etiology of the infarct and status of the
vessel involved, if any; and (iii) what is the location
and extent, and is there tissue still at risk (54)? The first
study performed is usually NECT. In the acute setting
(first 36 hours for anterior circulation, longer for pos-
terior circulation), this is often the only imaging test
necessary for the stroke neurologist to decide to treat
with tissue plasminogen activator (tPA). MRI with dif-
fusion weighted imaging (DWI) is more sensitive and
specific for detection of acute ischemia. MRI is also
sensitive to hemorrhage (5456), though most practi-
tioners still prefer CT.
CT may show findings of ischemia within the
first 6 hours, often subtle initially but becoming
obvious within 12 to 24 hours. Early signs of infarct
include the dense artery or dot sign, loss of the insular
ribbon, blurring of basal ganglia, sulcal effacement,
and loss of gray white matter differentiation at cortical
margin (Fig. 6.18). The pattern may provide clues to
etiology. Infarcts corresponding to one or more arte-
rial territories with gray matter involvement are more
likely embolic, while infarcts falling between vascular
(C)
territories (borderzone or watershed distributions)
tend to reflect a more proximal lesion such as large
vessel stenosis or occlusion. Overlap in pathophysiolo-
gies and patterns occurs; for example, a high grade
carotid stenosis or occlusion may appear identical to
an ICA terminus embolus, and large vessel stenosis
might present with associated in situ thrombosis.
Small vessel ischemic events will most often be invisi-
ble early, appearing in subacute and chronic stages as
lacunar infarcts and subcortical white matter lesions.
Global injuries such as those seen with cardio-
pulmonary arrests may be ischemic, hypoxic, or
anoxic. Patterns include deep gray matter injury, corti-
cal laminar necrosis, diffuse white matter injury, or a
combination. Borderzone injuries may be precipitated
by arrest when a preexisting large vessel stenosis or
occlusion is present. Hypoxic-ischemic injury or peri-
natal asphyxic injury in the newborn, as well as pre-
mature injuries like PVL are also examples, but
beyond the scope of this chapter (57).
CT Angiography
Noninvasive imaging methods such as CTA play an
important role in the work up of cerebral ischemia, in
acute as well as subacute or chronic settings. Multiple
studies have shown good agreement with conven-
tional DSA (ranging from 86% to 100%) and other
imaging modalities (Fig. 6.18) (5862). CTA findings
are confirmed by follow-up studies (DSA, MRA, and
brain imaging) in approximately 80% of cases (63).
Potential for greatest benefit from thrombolysis has
been demonstrated in a subgroup of patients with
moderate or severe persisting deficit for less than 3 to
6 hours, MCA occlusion (as opposed to other sites
such as ICA terminus), lack of extended infarct signs,
and efficient collateral circulation (62). Also important
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 117

(A) (B)

(C) (D)

Figure 6.16 AVM with catastrophic presentation. (A) NECT showed fourth ventricular hemorrhage (block arrow), parenchymal hemor-
rhage (open arrow), SAH, and hydrocephalus. CTA obtained en route to surgery (B) showed left cerebellar AVM with focal aneurysms
(MIP, black arrow, arrowhead). On postoperative DSA, early (C) and delayed (D) phases from selective superior cerebellar artery injec-
tion confirmed findings.

is the ability to detect autolyzed thrombi and sponta-
neous recanalization.
Perfusion Imaging and Comprehensive Stroke
Evaluation
Perfusion changes are immediate in the setting of
acute ischemia (i.e., evident prior to parenchymal
abnormalities, including those identified on DWI),
and information is also provided regarding tissue at
risk. Some advocate a comprehensive exam consist-
ing of unenhanced CT, CTA, and CT perfusion (64,65)
(Figs. 6.18,6.19), attractive because of more widespread
availability of CT, better access to sick patients, patient
tolerance, and speed. While there is good evidence
that CTA contributes to evaluation in this setting, the
utility of CTP in this setting remains less well estab-
lished {AHA Scientific Statement Latchaw, stroke
2009; 40:3646}, and radiation dose is a consideration.
For these and other reasons, a comprehensive stroke
MR protocol has some advantages. In practice, combi-
nations are often used; for example, NECT brain and
CTA of the head and neck can be performed, followed
by MRI with DWI, PWI (perfusion-weighted imaging)
and gradient echo (susceptibility-weighted) imaging
sequences, especially for subacute and chronic ische-
mia workup (54). Most of the diagnostic imaging
information can thus be rapidly obtained in the hyper-
acute or acute setting, with DWI improving detection
and delineation of extent of infarcted tissue and sus-
ceptibility-weighted imaging providing a sensitive
evaluation for subtle hemorrhage.
The goal of intervention in the acute setting is to
rapidly reestablish blood flow, without causing harm.
Since use of tPA and mechanical thrombolysis cur-
rently relies on clinical history and early presentation
118 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 6.17 Transverse sinus thrombosis. (A) NECT shows increased density in right transverse sinus indicating thrombus. (B) Poste-
rior oblique MIP projection confirmed absent contrast opacification of right transverse sinus (arrowhead) on CTV.
of the patient (i.e., within 3 hours for intravenous tPA,
within 6 hours for intraarterial tPA and 8 hours for
mechanical thrombolysis for anterior circulation, longer
for posterior circulation), it is hoped that techniques
like perfusion imaging will help establish surrogate
markers for clinical decision making and endpoints in
clinical trials. If extent of existing infarct and perhaps
age can be established, and perfusion imaging can help
assess for tissue at risk, the window of opportunity for
treatment can be extended. Normal brain perfusion
suggests that thrombolysis or other methods for aug-
menting CBF are not immediately necessary. Patients
with penumbral tissue may benefit from thromboly-
sis, but reperfusion can lead to life-threatening hemor-
rhage in severely ischemic or infarcted tissue. MR
perfusion (66,67), CTP (65,6870) and XeCT perfusion
(71,72) have been applied in this setting. More thor-
ough reviews and guidelines for imaging in acute cere-
bral ischemia can be found in (73,74).
Subacute and Chronic Setting
When thrombolysis is no longer an option, many of the
same questions remain. Workup of subacute and
chronic cerebrovascular disease may involve multiple
diagnostic imaging modalities, including combinations
of NECT, CTA, CTP, Doppler ultrasound (DUS), MRI/
MRA and PWI, DSA, and/or XeCT perfusion. CT tech-
niques are typically better first-line imaging strategies,
while MRI/MRA and DUS are better in the subacute
and chronic settings. MRI is the most sensitive and spe-
cific for evaluation of the brain parenchyma. After ini-
tial workup of ischemic stroke, NECT can be used for
routine follow-up in the subacute setting, assessing for
2003
(B)
infarct evolution, hemorrhagic transformation, hydroce-
phalus, cerebral edema, or mass effect. Combinations of
DUS, MRA, and/or CTA are typically used for cerebro-
vascular imaging. In the neck, DUS is often the first or
screening exam. Reasonable accuracy as far as agree-
ment with DSA can be obtained by adding a second
noninvasive test, and adding a third if the first two are
discordant (4,75,76).
Cerebrovascular CTA
Atherosclerosis and Stenotic-Occlusive Disease CTA
has been shown to be useful in evaluating carotid
stenosis (7578). In general, CT tends to underestimate
degree of stenosis compared to DSA, while MRA
tends to overestimate. However, for severe carotid
stenosis (7099%, NASCET criteria), CTA has been
shown to be fairly accurate. In a meta-analysis of CTA
studies prior to 1998 (almost all single-detector CT
acquisitions), Hollingworth et al. (79) reported a
pooled sensitivity and specificity of 95% and 98%,
respectively. CTA remained sensitive (95%) when
stenoses > 30% were included, although specificity
decreased to 92%. Another systematic review of CTA
studies between 1990 and 2003 (80) (all single-detector
CT scanners) reported pooled sensitivity and specific-
ity for 7099% stenosis of 85% and 93%, respectively,
and for occlusions they reported sensitivity and spe-
cificity of 97% and 99%. Accuracy for carotid stenosis
(75,77) and for occlusion (81) will likely improve with
increasing use of MDCT. In general, MDCT angiogra-
phy (MDCTA) and contrast-enhanced MRA are rea-
sonable for accurate evaluation of 7099% stenosis or
occlusion, but accuracy under 70% is less clear (82).
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 119

(A) (C) (E)

Angio

(B) (D) (F)

Figure 6.18 Acute ischemic infarct. (A, B) NECT images show dense MCA sign (A, arrow) and blurred gray-white matter borders
(A and B, arrowheads). (C, D) CTA shows relative decrease in vascularity on source image (C, arrowheads) and occlusion versus high
grade stenosis (D, arrow) with distal filling MCA branches. (E, F) Follow-up NECT more clearly shows infarct, as well as hemorrhagic
transformation (F, block arrow).

Accuracy in detection of vascular wall pathology like
ulceration is unclear (Fig. 6.20), but neither is DSA
considered perfectly accurate in detection of ulcerated
plaques.
For intracranial occlusive disease, CTA perform-
ance is in general similar to that of MRA, except for
demonstration of very slow flow and collaterals,
where CTA is superior (Fig. 6.21) (62,83). Comparing
to MRA and DSA in a retrospective study, Bash et al.
(84) found higher sensitivity of CTA for intracranial
stenosis, higher positive predictive value for stenosis
and occlusion, and higher interobserver reliability.
They also found cases where a false positive occlusion
on DSA may have been present which appeared sten-
otic but patent on CTA. As for extracranial disease,
CTA performs reasonably well for normal and severe
stenotic-occlusive disease, but performs less well for
mild or moderate disease with negative predictive
value (NPV) about 84% for excluding 5099% stenosis
(85,86). A more recent study reported sensitivity/spe-
cificity of 97.1/99.5% for 50% stenosis or greater intra-
cranially (87). Combining noninvasive imaging
modalities likely increases confidence (88).
False positive occlusions in the cervical carotid
also occur (77). It is often not possible to be certain of
this, since time tends to separate the studies and inter-
val occlusion or recanalization could occur between
studies. DSA is considered the gold standard, but is a
projectional technique and limited projections are
obtained. CTA has essentially infinite projections in
any orientation, and thus is more likely to find the pro-
jection with the most narrowed lumen. Rotational
angiography would be a better comparison test in this
regard (77). Very slow flow in a small caliber artery
may be easier to detect with CTA (84). In the case of
hypoplastic or atretic carotid arteries, CTA is comple-
mentary and in some ways superior to DSA, detection
of a hypoplastic petrous carotid canal establishing the
120 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 6.19 Acute ischemic infarct and CTP

(same patient in Fig. 6.18). One time point (A)
from single section CTP is shown. Very low
CBF (B) and CBV (C) with prolonged MTT
(D) confirm right temporal lobe infarct. Less
severe decreased CBF, symmetric CBV, and
prolonged MTT in right occipital lobe (arrows)
(C) (D) indicate minimal penumbra.

(A) (B) (C)

Figure 6.20 Ulcerations. (A) DSA shows web-like focal stenosis in proximal ICA (arrow) with probable ulceration(s) more proximally
(arrowhead). (B) MIP image from CTA also shows the focal stenosis fairly accurately, but the ulceration is not as clearly depicted.
Ulceration can be seen on CTA source image (C), however (arrowheads).
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 121

(A) (B) (C)

Figure 6.21 Intracranial stenotic-occlusive disease and CTA. (A) Oblique axial MIP image from CTA shows high grade left M1 stenosis
(arrowhead) with collateral filling in MCA branches (arrow). (B) Coronal MIP projection from MRA shows the abnormal M1 segment
(arrowhead) but no convincing collaterals due to slow flow. (C) Oblique DSA projection shows the M1 stenosis (black arrowhead) and
delayed MCA filling.

(A) (B) (C)

Figure 6.22 ICA agenesis and atresia. CTA source images show hypoplastic right petrous carotid canal (A, black arrow), absent intra-
cranial ICA (B, white arrow), and trans-sellar collateral (C, arrowhead) from left to right anterior circulation.

diagnosis (Fig. 6.22). Problem areas for CTA in head or
neck include overlapping venous structures and ves-
sels in or around bony structures and heavy vascular
calcifications (75,77). CT can be used for direct evalua-
tion of atherosclerotic plaque and vessel wall as well as
lumen. Extent of calcification and other components
relevant to vulnerable plaque like ulceration and hem-
orrhage can be evaluated. MRI is likely superior in dis-
criminating plaque architecture, however (89).
Arterial Dissection Dissections can be categorized as
traumatic (discussed below) or atraumatic. Atraumatic
dissections may be spontaneous or associated with a
precipitating cause such as minor or trivial trauma
(e.g., a movement or position not related to an exter-
nal traumatic force). Genetic factors perhaps combined
with environmental factors have been implicated in
predisposition to spontaneous dissection (90). Inher-
ited disorders predisposing to dissection include fibro-
muscular dysplasia, Marfan syndrome, EhlerDanlos,
homocysteinuria, and others. Hypertension and smok-
ing may also predispose to dissection.
Dissection of the extracranial ICA is the most
common form of cerebrovascular dissection (90). Where
atherosclerotic disease typically involves carotid
bifurcation and bulb/ICA origin, spontaneous dis-
section often originates at least 1cm beyond the
bifurcation and involves more distal ICA. It typically
does not extend into the petrous carotid artery, but
this does occur on occasion and thrombus can also
propagate distally (Fig. 6.23). Acute ischemic infarct
in a younger patient should prompt a search for this
122 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 6.23 Distal cervical carotid dissection and CTA. (A) Narrowing of cervical ICA lumen (arrow) with dilatation of vessel overall
(arrowheads). (B) Intimal flap (open arrow) with true and false lumen apparent. (C) Occlusion or high grade stenosis ICA, possibly from
propagating thrombus (black arrowhead), with distal petrous ICA filling.
entity, occurring more commonly in the age range
3550. Vertebral artery dissections more commonly
involve the distal portions, where atherosclerotic dis-
ease is often found more proximally. Symptoms and
findings of extracranial dissection include neck pain,
headache, Horners syndrome, cranial nerve defects,
pulsatile tinnitus and bruit, and of course transient
or permanent ischemia. Compared to extracranial
dissection, intracranial dissection is less common,
more often traumatic, and has higher morbidity and
mortality. Patients are even younger than those with
extracranial dissection, and the ICA is involved more
frequently than VA (91). Intracranial dissection more
often presents with sudden early infarcts or subar-
achnoid hemorrhage, which affects treatment deci-
sions regarding anticoagulation (Fig. 6.24). Mass
effect from pseudoaneurysms will be more problem-
atic in the closed intracranial space. The supraclinoid
ICA is the most commonly affected segment, fol-
lowed by intradural and suboccipital VA (near intra-
dural transition).
Dissection represents a disruption of one or
more layers of the arterial wall. Intracranial arteries
lack a vasa vasorum, so an intimal tear is more
likely in intracranial dissections. If blood dissects
between intima and media, narrowing and potential
occlusion of the lumen results, whereas collection of
blood between media and adventitia may result in
expansion of artery diameter or pseudoaneurysm.
Combinations of arterial dilation and luminal narrow-
ing may occur. Imaging findings include narrowing
of the lumen, especially smooth or slightly irregular
tapered narrowing, intimal flaps with or without dou-
ble lumens, eccentric or crescentic wall hematoma,
and pseudoaneurysm formation (Figs. 6.23,6.24) (92).
Intimal flaps are specific for dissection but are seen
in a minority of cases. It is often difficult to distin-
guish intracranial dissection from other pathologies
such as atherosclerosis or embolism causing partial
or complete occlusion. Vasospasm can also mimic
(C)
dissection. Noninvasive evaluation of nontraumatic
dissection has been described more extensively with
MRI and MRA, but CTA has also been applied
(9396).
Perfusion Imaging and Evaluating Long-Term Risk of
Ischemic Event
The significance of cervicocranial stenotic-occlusive
disease is modified by collaterals, type of plaque
(i.e., vulnerable plaque), autoregulation and cere-
brovascular reserve, oxygen extraction fraction, car-
diac status, etc. This is one motivation for cerebral
perfusion imaging, but interpretation is more com-
plicated in the subacute and chronic setting as
opposed to hyperacute and acute settings. Symp-
toms may be intermittent with embolic and/or per-
fusional etiologies. Because of the modifying factors
noted above, a single baseline perfusion test may
not completely address the significance of a par-
ticular lesion (14,97). Baseline perfusion may be
normal or show only prolonged TTP or MTT, but a
delay is expected with high-grade stenosis and diffi-
cult to translate to stroke risk. Qualitative analysis
(i.e., comparing abnormal to contralateral side for
relative measures) may be misleading when both
sides are abnormal. Perfusion studies with a chal-
lenge can help identify patients who may benefit
from revascularization.
Hemorrhagic and Stroke-Like Conditions
Hemorrhagic stroke or stroke-like entities include
reperfusion or hyperperfusion syndromes, vasculitis/
vasculopathy, and posterior reversible encephalopathy
syndromes (PRES). Other causes for hemorrhagic
stroke include hypertensive hemorrhage, amyloid
angiopathy, coagulopathy, drug abuse, and intracra-
nial neoplasms. Venous hypertension and occlusion
were discussed briefly above.
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 123

(A) (B)

(C) (D)

Figure 6.24 Intracranial dissection presenting with SAH. (A) NECT shows SAH anterior to pontomesencephalic junction. (B) Oblique
coronal MIP image from CTA shows fusiform dilatation of intradural left vertebral artery (arrowhead), confirmed on AP (C) and lateral
(D) DSA projections. The appearance suggests dissecting aneurysm.

Reperfusion and Hyperperfusion risk of hemorrhage, edema and herniation with or

Attempts to establish reperfusion via medical or
catheter-based thrombolysis are aimed at rescuing tis-
sue at risk around an irreversibly injured core, but
early reperfusion can lead to edema and hemorrhage,
as well as neuronal injury in the penumbra (14,98).
Potential indicators for hemorrhagic transformation
include extent of parenchymal hypoattenuation on
baseline CT, older age, and administration of aspirin
prior to thrombolysis (99) although Ibrahim et al.
found no difference in the rate of symptomatic intra-
cranial hemorrhage in patients on antiplatelet therapy
and the use of IV tPA (100). Other indicators might
include those based on perfusion studies. One retro-
spective study using XeCT perfusion reported that
CBF values below 10 and perhaps even less than 15
cc/100g/min in aggressively managed acute MCA
infarct patients could be associated with increased
without reperfusion (101). CTP-derived measures of
permeability may also be helpful in predicting hemor-
rhagic transformation of acute infarcts (102,103); for
example, Aviv et al. (102) evaluated admission CTP
obtained in acute ischemic infarct patients presenting
within 3 hours and found that permeability-surface
(PS) area product values were significantly elevated in
regions ultimately progressing to HT compared to
those not showing HT. Dual energy CT techniques
may be helpful in distinguishing hemorrhage post-
lysis from contrast staining (104).
Hyperperfusion syndrome occurs when brain tis-
sue in a vascular territory experiencing low cerebral
perfusion pressure (CPP) due to a flow limiting vascu-
lar lesion is suddenly subjected to a normal CPP after
revascularization (105). Autoregulation is impaired or
overwhelmed leading to development of symptoms
such as headache, seizures, and hypertension minutes
124 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
(C) (D)
to hours after the procedure, in some cases appearing
identical to infarct. Imaging may demonstrate break-
down of the blood brain barrier with or without hem-
orrhage. CT, CTA, and perhaps perfusion studies
could be of use in this setting (105).
Vasculitis and Vasculopathy
Vasculitides and vasculopathies encountered in the
head and neck include fibromuscular dysplasia
(FMD), giant cell arteritis, Takayasu arteritis, granu-
lomatous angiitis of the CNS, systemic lupus erythe-
matosus (SLE), moyamoya disease, sickle cell disease,
infectious diseases such as syphilis and herpes virus,
and many others including PRES such as eclampsia
and hypertensive encephalopathy. Imaging findings
include segmental narrowing or beaded appearance,
multivessel or repeated dissections or pseudoaneur-
ysms (nontraumatic or minor trauma), occlusions, and
moyamoya pattern (Fig. 6.25). In some cases (e.g.,
PRES), the diagnosis can be made more effectively on
parenchymal imaging of the brain since the vascular
findings on imaging may be nonspecific, subtle, or
absent. In addition to the ability to image the brain,
CT and MRI allow direct visualization of the vessel
wall, which may be helpful in making the diagnosis
of vasculitis (Fig. 6.26).
Figure 6.25 Vasculitis/vasculopathy. CTA
MIP images demonstrating (A) neurosyphilis,
with nonspecific segmental arterial narrowing;
(B) FMD, with beaded appearance in both
ICAs; and (C, D) AIDS vasculopathy, with fusi-
form arterial dilations.
Trauma
The mechanisms of extracranial and intracranial trau-
matic neurovascular injury are primarily penetrating
and blunt, but all involve some form of disruption of
the vessel wall. This can be subtle, as with slight sepa-
ration of intima and media with small intramural
hematoma. More severe injuries are intimal disruption
with formation of flap and false lumen, pseudoaneur-
ysm, occlusion or transection, and arteriovenous fis-
tula (AVF). Morbidity and mortality increase with
severity, primarily due to secondary CNS injury and
typically due to thromboembolic disease, drop in cere-
bral perfusion pressure, and/or exsanguination.
NECT of the head is often the first exam for evaluat-
ing intracranial injury. NECT of the face and neck is
also used in trauma, but usually for detection of cra-
niofacial and spinal fractures as opposed to soft tissue
evaluation. NECT is suboptimal for direct visualiza-
tion of vascular injury, relying on indirect signs like
fractures predisposing to vascular injury, trajectory of
penetrating injury, proximity of penetrating injuries
and/or bullet fragments, hematoma, or soft tissue
swelling (Fig. 6.27).
The gold standard for neurovascular injury is
still conventional DSA. It is also considered the defin-
itive study, and can be combined with endovascular
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 125

(A) (B)

Figure 6.26 Cross-sectional imaging in giant cell arteritis. CTA source images show circumferential smooth thickening from great ves-
sel origins through (arrows) common carotid arteries (A), not seen distal to carotid bifurcation in the ICA (B, arrowheads).

(A) (B)

Figure 6.27 Indirect evidence of penetrating arterial injury on NECT. (A) Bullet trajectory passed through mandible transverse process
of C1 on right. Fracture includes transverse foramen (arrow), indicating potential vertebral artery injury. DSA confirmed occlusion.
(B) Bullet and fragment trajectories (arrow) are concerning for MCA injury, in this case directly confirmed by demonstration of right
MCA infarct (arrowheads).

intervention. There are some advantages to using
noninvasive imaging; for example, CTA is fast, pro-
vides information regarding nonvascular structures,
and directly images vessel wall and lumen. CTA is a
3D technique, so unlimited projections are available,
as opposed to primarily 2D projections obtained with
conventional DSA unless rotational angiography is
used. A disadvantage of CTA is low temporal resolu-
tion, making evaluation for AVF inadequate although
improving 4D CTA may resolve this problem (51).
Artifacts from bone, heavy calcifications, and metallic
objects like bullets can limit accuracy and render por-
tions of the CTA nondiagnostic. Poor arterial contrast
opacification can lead to uncertainty, and venous opa-
cification can limit evaluation of arterial structures.
Small distal arteries like external carotid branches are
suboptimally evaluated. CTA interpretation begins
with source images, evaluating for caliber change,
nonanatomic cross-sections, intimal flap, vessel wall
abnormalities such as hematoma, and of course
extravasation (Fig. 6.28). Normal arterial cross-sections
away from bifurcations, kinked vessels, and dra-
matic turns or loops are round or oval. Most diagnos-
tic information is available from source data, but
some pathology is seen best on rendered or reformat-
ted images (Fig. 6.29).
Penetrating Injury
There is increasing evidence supporting the use of
CTA in this setting; for example, a recent prospective
study of 175 patients with suspected arterial injury
from penetrating trauma using single-detector CTA
(106) reported a sensitivity and specificity of 100%
and 98.6% and positive and negative predictive values
of 92.8% and 100%, respectively. Accuracy should
126 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 6.28 Blunt carotid vertebral injury

(BCVI). CTA source images show abnormal
contour of bilateral ICAs (A and B, arrow-
heads). (C) Left ICA caliber change on MIP
image suggests dissection/pseudoaneurysm,
(C) (D) improved on 12-month follow-up (D).

(A) (B)

Figure 6.29 Blunt neck trauma. (A) Filling defect in the carotid artery proximal to flow divider is noted on CTA source image, but better
demonstrated on MIP (B).

improve with MDCT. A large study of CTA for intra- injury in penetrating or blunt trauma (Fig. 6.30). Pseu-
cranial penetrating trauma is not yet available, and doaneurysms occur in about one-third of penetrating
DSA may still be required (107). Partial or complete injuries to the ICA. Arterial extravasation or transec-
occlusions are the most commonly identified carotid tion is less commonly seen with noninvasive imaging
 CT IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 127

(A) (B) (C)

Figure 6.30 Penetrating vascular injury. (A) Source and (B) oblique MIP images from CTA show filling defects in left ICA lumen sug-
gesting thrombi (arrows), poorly visualized on (C) DSA. Caliber change suggesting dissection is visible on both studies.

(A) (B) (C)

Figure 6.31 Arterial transection or extravasation from penetrating injury. CTA source images demonstrate distorted true lumen of ICA
proximally (A, arrow) and faint filling of pseudoaneurysm or hematoma (B and C, arrowheads). Distal ICA was not visualized.

since these patients likely require a more aggressive
workup with DSA or surgery (Fig. 6.31). AVFs are
less commonly seen acutely, but may become evident
later on.
Blunt Injury
Blunt carotid vertebral injury (BCVI) is less common
than penetrating injury (Figs. 6.28,6.29). Aggressive
screening has been recommended based on the
impression that the rate of BCVI is higher than previ-
ously recognized, that patients are often asymptomatic
for hours to days before an injury becomes evident, and
that BCVI is treatable. Lesions for blunt carotid injury
(BCI) are typically graded on a five point scale (108):
Grade I, lumen irregularity/dissection (< 25% nar-
rowed); Grade II, dissection/intimal flap or intramu-
ral/intraluminal thrombus ( 25% narrowed); Grade
III, pseudoaneurysm; Grade IV, occlusion; and Grade
V, transection/extravasation (Fig. 6.32). Early reports
128 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 6.32 Blunt trauma with carotid pseudoaneurysm formation. (A) Source image from CTA demonstrates intimal flap (arrowhead, A)
with increased caliber overall. (B) Oblique MIP image better demonstrates pseudoaneurysm (arrow).
with single detector CT technology reported subopti-
mal accuracy of CTA, but accuracy will likely improve
with MDCT technology. One recent study (109)
reported an incidence of 0.60% for BCVI for all blunt
trauma admissions, incidence of BCVI of 3.7% in
screened high risk patients, and sensitivity and specific-
ity of CTA for BCVI of 100% and 94%, respectively.
Traumatic Intracranial Aneurysms
Traumatic intracranial aneurysms may be caused by
blunt trauma, penetrating injuries and/or fractures.
Though the term pseudoaneurysm is often used to
describe incomplete disruption of all layers of the ves-
sel wall (including this chapter), a true pseudoaneur-
ysm or false aneurysm is really complete disruption
of all vessel wall layers with blood contained by peri-
vascular clot. It is difficult to distinguish different
forms of traumatic aneurysm on imaging, and it is
unclear whether noninvasive imaging is adequate for
excluding traumatic intracranial aneurysms. These
aneurysms can form in the cavernous ICA in the set-
ting of skull base fractures or penetrating (or iatro-
genic) injuries. Peripheral vessels can be involved as
well, including MCA, ACA and middle meningeal
arteries and less commonly smaller branches. For
example, pericallosal aneurysms can form from shear-
ing or compressive injuries against the falx. They may
have a delayed presentation.
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 7
MR angiography: Basic principles and applications
in the CNS
Neerav R. Mehta and Elias R. Melhem
INTRODUCTION
It is of little doubt that noninvasive imaging in the
late 20th century and now the early 21st century has
been revolutionized by magnetic resonance imaging.
In particular, imaging of the vascular tree has become
possible with MRI technology, with continual refine-
ments and improvements driving it into the future.
Magnetic resonance angiography (MRA) has roots
that date back to the early 1950s, where in the Depart-
ment of Physics at the Indian Institute of Sciences,
G. Suryan, utilizing a U-tube and coils of wire, discov-
ered inflow effects. Singer in the late 1950s applied
Suryans discovery of inflow effects in vivo, utilizing a
mouse and a tourniquet. From these humble begin-
nings, MRI and MRA technology has progressed to its
current level of sophistication, with both neurological
and non-neurological applications (1,2).
TIME-OF-FLIGHT TECHNIQUE
The vast majority of neurovascular MRA performed
today is via time-of-flight (TOF) techniques. It is
widely employed due to its ready availability as well
as the ease of acquisition of diagnostic studies. Essen-
tially, these techniques make use of blood inflow
effects to produce high intravascular signal while sig-
nal from background, stationary tissues, are mini-
mized (36).
Lets begin with a look at a TOF sequence. If a
patient is placed within the bore of a magnet, all of
his or her protons get aligned either with the main
magnetic field, or against the main magnetic field.
There is a slight majority of spins aligned along the
positive Z-axis, leading to a net positive alignment.
For simplicity, it is easier to consider all spins as
aligned along the bore of the magnet in the positive
Z-axis. The spins are all precessing at the same Lar-
mor frequency (Fig. 7.1).
A slice select gradient is applied and spins within
a specific slice are tipped into the XY-plane via a
90 degree radiofrequency (Rf) pulse. If no other Rf
pulses are applied, then the spins will relax back toward
the positive Z-axis, realigning with the main magnetic
field. At time T1, approximately 63% of the magnetiza-
tion has recovered to the positive Z-axis (Fig. 7.2).
In TOF MRA, however, before the tissues can
relax back to the positive Z-axis, additional Rf pulses
are applied. These pulses are applied at time, TR,
such that TR is less than T1 of the tissues. Taking a
closer look at this, the first Rf pulse tips the spins
into the XY-plane. The XY-component of the signal
dephases quickly and the Z-component begins to
grow, as per the tissues T1 at the given magnet
strength. Before the Z-component has recovered, a
second Rf pulse is applied, and the partially recov-
ered Z-component is tipped into the XY-plane. This
results in a smaller XY-component, which subse-
quently dephases and results in a smaller recovering
Z-component. A third, fourth, and fifth Rf pulse are
applied in a similar manner, each resulting in smaller
and smaller Z-components and XY-components.
Eventually, this reaches a steady state and the spins
are saturated. The shorter the TR, the shorter the time
between subsequent Rf pulses, and the greater the
degree of saturation (Fig. 7.3).
The more saturated the spins become, the less sig-
nal that can be measured from those spins (as the XY-
components get smaller per Rf pulse until steady state
is reached). Recall that both Z-components and XY-
components of the saturated spins are small. If fresh
spins enter a slice with full Z-axis magnetization vec-
tor, then the moment they are tipped into the XY-plane,
they will produce a large amount of signal relative to
the saturated spins. Hence, a blood vessel bringing in
fresh spins will have high intravascular signal as the
fresh spins traverse a slice of saturated stationary
spins. This is the heart of TOF MRA (Fig. 7.4).
If the flow of blood is slow, and a volume of
blood lingers in a slice too long, then the repetitive Rf
pulses that saturate the stationary tissues also begin to
saturate the blood. As mentioned above, shorter TR
leads to greater background tissue saturation. This also
applies to blood, and a shorter TR will cause greater
blood saturation once it has entered into the slice.
When blood initially enters into the slice, it has its
greatest magnetization in the Z-axis. This is called entry
slice phenomenon. As blood traverses a volume that is
continuously receiving Rf pulses, the blood itself gets
saturated and the signal diminishes the further it trav-
els into the volume of interest. In practice, a longer TR
can be chosen in order to preserve intravascular signal
over a large volume. However, this is done at the cost
of decreased background tissue saturation.
In TOF MRA, 90 degree Rf pulses are not typi-
cally used, instead pulses of varying flip angles are
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
employed. The greater the flip angle, the greater the
background saturation of stationary tissues. This can
be better understood by comparing the scenario of the
90 degree pulse with a scenario where the flip angle is
1 degree. The 1 degree flip angle would lead to negli-
gible saturation of stationary tissues. A large Z-axis
component would exist even after multiple Rf pulses.
The signal obtained from in-flowing blood would be
poorly differentiated from stationary tissues. As the
flip angle increases, the saturation of stationary tissues
also increases. As in the case of shorter TR times, with
larger flip angles and greater background stationary
tissue saturation, there is also greater saturation of
blood as it traverses a volume. Hence, the same caveat
that applies to shorter TR times also applies to larger
flip angles, and flip angles can be varied to preserve
intravascular signal at the cost of decreased back-
ground tissue saturation. However, 90 degree flip
angles are typically not used in clinical practice. Blood
flowing within the carotid and cerebral arteries
+Z
+X
+Y
Figure 7.1
+Z
+X
+Y
After 90 degree Rf pulse
Figure 7.2
133
usually has laminar flow, where blood along the cen-
ter of the vessel moves at a faster velocity than blood
along the periphery of the vessel. The blood along the
periphery moves so slowly that the large 90 degree
flip angles quickly cause blood saturation. This is not
the case for the faster moving blood along the central
aspect of the lumen. The net result is signal arising
from the central portions of the vessel, and lack of sig-
nal from the periphery, ultimately causing a perceived
decrease in the caliber of the vessel. This should be
noted on most MRA sequences, particularly when
slow flow is involved in scans performed with larger
flip angles.
In Figure 7.5 (A through D), flip angles and TR
were varied on the same subject to produce MRA
images that are presented using collapsed maximum
intensity projection (MIP) algorithm in the axial pro-
jection. Figure 7.5A serves as the reference 3D TOF
MRA performed with a typical flip angle of 25 degrees,
TR of 42msec. Now, compare Figure 7.5A to Figure
7.5B, where the flip angle was decreased to 10 degrees
(TR remains 42 msec). The signal within the large ves-
sels is decreased; however, less blood saturation
results in better visualization of the small peripheral
arteries. Compare Figure 7.5B, flip angle of 10 degrees,
to Figure 7.5C, where the flip angle is increased to 50
degrees (TR remains 42 msec). Note that there is
increased signal within the large vessels; however,
blood saturation has resulted in poor visualization of
the small peripheral arteries. Compare Figure 7.5A to
Figure 7.5D, where the flip angle is kept at 25 degrees,
but the TR has been increased to 84msec. The
increased TR leads to less blood saturation, and hence
improved visualization of small peripheral arteries.
However, the stationary tissues are also less saturated,
resulting in less contrast between the arteries and sur-
rounding tissues. Figure 7.5E demonstrates 3D TOF
MRA performed on a 3 Tesla magnet. The TR and
echo (TE) time are 24 and 3 msec, respectively. The
higher field magnet theoretically doubles the signal to
noise ratio (SNR) as well as increases vessel contrast
with respect to surrounding tissues. Shorter TE times
+Z
+X
+Y
Relaxation back to Z-axis
134 NEUROINTERVENTIONAL MANAGEMENT
allow for less phase dispersion and hence higher
intravascular signal within more peripheral vessels
(see below for effect of TE times on time-of-flight
MRA). Compare Figure 7.5E to Figure 7.5A, which are
both performed on the same subject, and one can get
a taste of what can be expected as routine MR imag-
ing migrates from 1.5 Tesla to 3 Tesla.
2D TOF
2D TOF involves a sequential acquisition, slice by
slice. A thin slice is selected, and the spins within the
slice are saturated. Blood flowing perpendicularly into
the slice is bright, with high intravascular signal.
Blood flowing into the slice at an oblique angle would
have less intravascular signal, as it would have to tra-
verse a greater distance within the slice than the per-
pendicularly oriented vessel. As a volume of blood
traverses a greater distance within a slice, it experien-
ces a greater degree of blood saturation (Fig. 7.6).
+Z
+X
+Y +Y
Z magnetization before 1st Rf pulse
Figure 7.3
+Z
+X
+Y +Y
Saturated stationary tissue
Figure 7.4
If MRA images were to be acquired at this point,
inflowing blood from both above and below the slice
would provide intravascular signal. In the case of
neck MRA, if a slice of the mid-neck were to be
acquired, intravascular signal from carotid and verte-
bral arteries, as well as the jugular veins would be
acquired. If a parallel saturation band is placed above
the slice of interest, then the spins within the jugular
veins would get saturated before they entered the slice
of interest (Fig. 7.7). The resultant image would only
have intravascular signal from the carotid and verte-
bral arteries. If a parallel saturation band is placed
below the slice of interest, then the spins within the
carotid and vertebral arteries would get saturated
before they entered the slice of interest. The resulting
image would only have intravascular signal from the
jugular veins (7).
After multiple slices are acquired, the resultant
data set is usually stacked and displayed using MIP
algorithm. Post-processing of MRA data is required
in order to display projection images reminiscent of
+Z +Z
+X +X
+Y
Z magnetization before 2nd Rf pulse Z magnetization before 3rd Rf pulse
+Z +Z
+X +X
+Y
Intravascular fresh spins Flipped into XY plane for readout
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS 135

(A) (B) (C)

(D) (E)

Figure 7.5 Comparison of the differences between the reference MRA data set performed at 1.5 Tesla and those with varying flip
angles and TR times. Figure 7.5A Reference (TR 42, TE 3, flip angle 25). Figures 7.5B and 7.5C Flip angles of 10 degrees and
50 degrees, respectively (TR 42, TE 3). Notice that the 10 degree flip angle (B) preserves signal for the distal vessels at the cost of
the proximal vessels, while the 50 degree flip angle (C) provides higher signal for proximal vessels at the cost of the distal vessels.
Figure 7.5D Same TE and flip angle as the reference, but with a TR of 84. Figure 7.5E MRA of the same subject performed at
3 Tesla.

Length 1
Length 2

Length 2 > length 1 Figure 7.6

136 NEUROINTERVENTIONAL MANAGEMENT
Parallel saturation band
Slice of interest
Figure 7.7
Stacked slices
Individual slices
Figure 7.8
traditional angiography. Simply stacking the data and
then viewing the summation from the side does not
work, as there is too much background tissue that
overlaps and obscures the vasculature. MIPs transgress
this limitation by only displaying the maximum pixel
value for a given projection line. Multiple projection
images can be calculated from the stacked data set to
provide images at different angles (Fig. 7.8). By scroll-
ing through a data set of MIPs, a three-dimensional
appreciation of vasculature can be obtained (8).
Currently, 2D TOF is primarily used for imaging
carotid and vertebral arteries in the neck. These ves-
sels have an optimal orientation to acquire 2D slices
as they enter each slice with an almost perpendicular
orientation, lacking significant tortuosity.
3D TOF
This is the same concept as 2D TOF, except that a slab
or volume (38cm) instead of a thin slice (1.5mm) is
obtained. There is no slice selection; instead, the
Z-axis is partitioned into 3264 slices with multiple
phase encoding steps. This results in very thin slices,
usually 1mm or less in thickness. However, since
blood is flowing through a large 3D volume during
Unsaturated arterial blood Saturated venous blood
Maximum intensity projection
View at multiple angles
the acquisition, in contrast to the thin slices of 2D
acquisitions, blood can be saturated as it courses
through the slab. This does somewhat limit the evalu-
ation of slower flow. Modifications of the technique
include making slabs thinner and performing multiple
sequential acquisitions of these thinner slabs. This
technique has been termed multiple overlapping thin
slab acquisition (MOTSA). One of the major advantages
to employing MOTSA technique is in the reduction of
saturation effects. Flip angles are also adjusted accord-
ingly, with 3D acquisition flip angles smaller than
those of 2D acquisitions. With a smaller flip angle,
blood saturation can get minimized in the 3D TOF
sequence. Flip angles for 3D TOF range from
15 degrees to 35 degrees, whereas for 2D TOF the flip
angle ranges from 40 degrees to 90 degrees. Other
methods to reduce saturation effects within the vessels
and to enhance the visualization of the small periph-
eral intracranial arteries have been developed. These
include tilted optimized nonsaturating excitation (TONE)
or ramped Rf, and magnetization transfer imaging (MTI).
TONE, also known as ramped Rf, is based on varying
the flip angles across a volumetric slab. A voxel of
blood can enter a slab and experience a smaller flip
angle, and as it traverses the slab it experiences
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
gradually increasing flip angles. This can help mini-
mize saturation of blood as it traverses the volumetric
slab while maintaining appropriate background satu-
ration and intravascular signal. MTI is based on addi-
tional saturation of brain tissue surrounding the small
intracranial arteries. With magnetization transfer,
bound water within brain tissue is saturated with an
Rf pulse targeting bound water proton precession
rates (which is lower than that of free water). In MRI,
only free water is imaged, bound water, water mole-
cules bound to macromolecules, is not. The saturated
bound water then interacts with local free water to
exchange a saturated proton for an unsaturated pro-
ton. The previously free unsaturated water molecule
becomes bound, and the previous bound satu- ation, third-order accounts for change in acceleration,
rated water molecule becomes free. The net result is
of free water in tissues to become saturated, and
hence suppressed. MTI can assist in background sup-
pression without having to resort to increasing flip
angles or decreasing TR (911).
One of the major advantages of 3D acquisition
over 2D acquisition is in the characterization of flow
in tortuous vessels. This is because 2D acquisitions are
much more dependent upon angle of vessel entry into
a given slice (see above). In 3D acquisitions, blood can
flow in any direction and produce signal, as long as
blood saturation does not occur. Given the tortuosity
of the intracranial internal carotid artery, 3D TOF is
much more widely employed for intracranial vascula-
ture evaluation.
Limitations
Characteristics that limit TOF MRA include nonlami-
nar blood flow, slow flow, and tortuous vasculature.
Nonlaminar flow of blood leads to mixing of
blood of differing phases. If blood of two different
phases mixes within a voxel, the resulting voxel will
have lower signal intensity. This takes on particular
clinical importance in the assessment of vascular sten-
oses. The flow distal to a carotid stenosis is usually
nonlaminar flow, and this will subsequently result in
phase dispersion. The image produced will then over-
estimate the degree and length of stenosis. Techniques
to decrease the degree of phase dispersion include
minimizing TE, acquiring thinner slices, and using
flow compensation techniques (see below).
Slow flow is yet another source of error in MRA
sequences. Slow flow within a TOF acquisition results
in blood saturation, and hence signal loss. This can
somewhat be compensated for by increasing TR or
decreasing flip angles; however, it is at the cost of
background suppression and vessel signal. In general,
slow flow is more of a problem for 3D techniques
than for 2D techniques. The major reason for this is
greater blood saturation within a thick slab during the
3D acquisition compared to a thinner slice on a 2D
acquisition. If a smaller, slow-flow, vessel needs to be
imaged by increasing TR or decreasing flip angles,
then magnetization transfer imaging can be used as a
tool to assist in background suppression.
Tortuous vasculature is an intrinsic concern
when evaluating the intracranial circulation, particu-
larly at the level of the cavernous carotid artery.
A tortuous vessel may lie parallel within an imaging
137
slice and become subject to saturation effects. Tortuos-
ity can also result in vessels entering the slice both
from above and below the slice of interest, resulting
in signal loss in patent vasculature secondary to paral-
lel saturation bands.
Flow Compensation
Flow compensation, also known as gradient moment nul-
ling, is a necessity for high-quality MRA images. Flow
compensation addresses the issue of phase dispersion
as blood within a vessel moves at a constant velocity.
Accounting for velocity is a first-order flow compensa-
tion. Second-order compensation accounts for acceler-
and so on.
During an MR acquisition, blood will flow
through a given volume of interest. As the readout gra-
dient is applied across a slice, the flowing blood experi-
ences multiple different magnetic fields and changes
phase accordingly. Assume a voxel of blood traverses a
volume that is experiencing a magnetic field gradient.
As the voxel travels along, it experiences different
magnetic field strengths, and hence accumulates phase
as it travels through ever increasing local magnetic
fields. The signal from the flowing blood can either be
in-phase with the surrounding tissues or out-of-phase.
It so happens, through a quadratic relationship of
phase gain with time, that during odd echoes there is
dephasing, while during even echoes there is rephas-
ing. Hence, increased intravascular signal is seen dur-
ing even echoes. Flow compensation techniques
essentially change the shape of the magnetic field gra-
dient in order to reproduce the even echo rephasing
effect during the very first echo, resulting in increased
intravascular signal. This is used primarily in first-
order flow compensation. The gradient shape can be
changed to account for second-order and third-order
flow compensation; however, with each additional
order of compensation there is increased time of appli-
cation of the gradient. The increased time of applica-
tion leads to increased echo times. In general, the
shorter the echo times, the less the effects of signal loss
from nonlaminar flow. Thus, a balance must be struck
between how complex and long a shaped gradient can
be applied and the TE times. It so happens that first-
order flow compensation is optimal, with second- and
third-order flow compensation not worth the cost of
the increased TE times (12).
Echo Time
The effect of TE on MRA is also crucial to the under-
standing and production of adequate MRA images.
This is especially important in the case of nonlaminar
blood flow. Nonlaminar flow causes a loss of signal
secondary to phase dispersion. Between the Rf pulse
and the time for readout of signal, i.e., TE, nonlaminar
flow allows regions of blood within a vessel of differ-
ing phases to mix. This leads to loss of intravascular
signal. By decreasing the TE, there is less time for
these regions of blood with differing phases to mix,
and hence less loss of intravascular signal.
TE should also be chosen to suppress signal
from adjacent fat. Recall that fat and water precess at
138 NEUROINTERVENTIONAL MANAGEMENT

Figure 7.9 Comparison of out-of-phase (A)

and in-phase (B) MRA acquisitions. Note the
prominence of the orbital fat in the in-phase
(A) (B) sequence.

[H]

Aneurysm

Early phase

Delayed phase
[H]

Figure 7.10 Top image is the arterial phase of gadoli-

nium. The bottom image is delayed with both arterial and
venous signal. The top image demonstrates a left poste-
rior communicating artery aneurysm (confirmed on CT
angiography). Venous opacification on delayed image
Obscured aneurysm obscures the aneurysm. The timing on contrast-
enhanced MRA is critical, particularly in intracranial MRA,
to avoid missing pathology.

slightly different frequencies. At 1.5 Tesla, water pre- CONTRAST-ENHANCED MR ANGIOGRAPHY

cesses 220 Hz faster than fat. This difference in
precessional frequency allows for spins of water and
fat molecules to be either in-phase or out-of-phase
with each other. As both molecules exist within adi-
pose tissue, fat can be suppressed by choosing a TE
where the spins are out-of-phase, and hence have
decreased signal (Fig. 7.9, 7.9A is out-of-phase, 7.9B
is in-phase).
The administration of contrast at first appears to be a
natural evolution of MRA technique. The gadolinium
molecule itself is paramagnetic, and effectively serves
to shorten the T1 of blood around it. The shortened
T1 of blood has the potential to provide MRA images
with high contrast to noise ratios, high signal to noise
ratios, as well as potentially shortening acquisition
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
Figure 7.11 Bolus timed too early on the left, and bolus timed too late on the right.
Central k-space
times secondary to shorter TR and TE times. Gadoli-
nium administration also reduces the saturation
effects of slow flowing blood. The major limitation to
administering contrast is in the venous contamination.
The bolus of gadolinium must be administered and
timed accordingly to minimize both parenchymal and
venous phases. In essence, speed of imaging is one of
the core issues with contrast-enhanced MRA. Unfortu-
nately, for intracranial circulation, venous contamina-
tion in the cavernous sinuses and basal veins severely
limits evaluation of the circle of Willis (Fig. 7.10). For
this reason, contrast-enhanced MRA has yet to be
widely implemented for studies targeted to the circle
of Willis (with the exception of coiled aneurysms, as
discussed below). This is not an issue, however, in the
neck where gadolinium-enhanced MRA is now com-
monly used in the evaluation of carotid stenosis. In
performing contrast-enhanced MRA, typically 20cc of
gadolinium is administered at a rate of 2 to 3ml/sec
using a power injector. Timing the bolus of contrast is
critical and can be performed by a number of different
methods. Currently, these include best guess meth-
ods, automated timing bolus, and manual timing
bolus methods. Manual methods involve the adminis-
tration of a small bolus of gadolinium, typically 2cc,
followed by a 20cc saline flush. The volume of interest
is imaged with fast 2D gradient echo (GRE) sequence,
usually at a rate less than 1 frame per second. Once
maximal contrast appears in the target vessel, the
delay can be calculated accordingly. Automatic timing
bolus methods involve the beginning of the imaging
once contrast is detected in the vessel of interest.
139
Peripheral
Figure 7.12 Central k-space provides contrast. Periph-
eral k-space defines lines and borders.
Imaging is subsequently performed using 3D SPGR
(spoiled gradient recalled acquisition) technique. Early
or late bolus timing can lead to significant artifacts
and venous contamination, respectively (Fig. 7.11). As
a general rule, the acquisition of data to fill the center
of k-space has to occur at the time when the maximum
concentration of contrast material is in the vessel of
interest, as this region of k-space is where contrast to
noise is maximized. The periphery of k-space is used
to increase definition of edges and borders (Fig. 7.12).
Contrast-enhanced MRA has become very valua-
ble in neck MRA for the evaluation of carotid artery
stenosis. The faster acquisition times can result in 3D
slab acquisition times less than 20 seconds, as com-
pared to 2D TOF methods that can last longer than
12 minutes for the same coverage. During respiration,
there is motion of the neck vasculature, which subse-
quently causes artifacts on the 2D TOF sequence.
With the 3D gadolinium sequence, the entire acquisi-
tion can be performed in one breath-hold. In addi-
tion, the TE times of contrast-enhanced 3D MRA are
usually three to four times shorter than those of 2D
TOF MRA. With shorter TE, effects of intravoxel
phase dispersio get minimized. This is crucial for the
accurate assessment of the degree of a carotid stenosis.
Contrast-enhanced MRA has now widely supplanted
2D TOF sequences in the neck. 2D TOF data are com-
monly used to supplement interpretation and serve
as a backup in case the bolus of gadolinium is
poorly timed. Typical TR/TE times for 3D gadolinium-
enhanced MRA are 4.4msec/1.6msec with a 25 to 30
degree flip angle.
140 NEUROINTERVENTIONAL MANAGEMENT
Folded
sense
Figure 7.13 Reduced FOV acquisition is unfolded to produce the final image.
DYNAMIC MRA
Dynamic MR angiography, also known as time-
resolved MRA, has become feasible and is slowly
becoming a viable alternative to DSA in the diagnosis
of intracranial vascular abnormalities. The technique
essentially involves obtaining multiple fast T1-
weighted acquisitions during the administration of
gadolinium. The initial, pre-contrast, image is used as
a mask, which is then subtracted from the contrast-
enhanced sequences. 3D acquisitions occur every
second during contrast administration, providing the
dynamic flow. The two key developments allowing
for dynamic MRA are (1) parallel imaging and (2) cen-
tral k-space sampling (e.g., maximize the bolus of con-
trast with the acquisition of central k-space to
maximize contrast resolution while acquiring spatial
resolution data at the periphery of k-space before or
after the bolus).
Parallel imaging with image-domain reconstruc-
tion (e.g., SENSE) or frequency-domain reconstruction
(e.g., SMASH, GRAPPA) offers the ability to reduce
scan times and improve temporal resolution. Image-
domain reconstruction is more intuitive to under-
stand; however, please note that frequency-domain
reconstruction follows similar principles in k-space
itself. SENSE, sensitivity encoding, uses multiple coils
in combination with a reduced field of view to reduce
image acquisition times. If a reduced field of view
were used with traditional 2D or 3D Fourier transform
techniques, wrap-around artifact would result. How-
ever, SENSE uses multiple coils, each with different
sensitivity weightings determined by their orientation
around the volume to be imaged. This configuration
allows a reduced field of view image to be acquired.
The reduced field of view images are extrapolated to
a full field of view, which appears folded by the
wrap-around artifact. The different sensitivity weight-
ings from each coil are then used to unfold the
Unfolded
Abbreviation: FOV, field of view.
image (Fig. 7.13). With time-savings offered by SENSE,
contrast bolus can potentially be tracked into the arte-
rial, capillary, and venous phase (1318). As the num-
ber of receiver coils around a patient increases, so does
the potential acceleration factor, with decreased time
of imaging. This clearly plays a major role in the tem-
poral resolution of the study, and as coil technology
progresses, speed will increase. Acceleration factors of
0, 2, and 3 can result in temporal resolutions of slab
acquisition in 4.7, 1.7, and 1.3 seconds, respectively.
The drawback to higher acceleration factor is decreased
SNR. In general, the SNR decreases with the square
root of the acceleration factor. Currently, this decrease
in SNR makes an acceleration factor of 3 unacceptable,
while acceleration factor of 2 provides an optimal com-
promise between SNR and temporal resolution (19).
Additional application of central k-space sampling
with techniques such as time-resolved imaging of con-
trast kinetics (TRICKS) has further helped reduce tem-
poral resolution to 0.9 seconds, leading to improved
identification of feeding arteries in draining veins in
vascular malformations (20).
PHASE-CONTRAST MR ANGIOGRAPHY
Phase-contrast angiography (PCA) is yet another
technique that has been developed for MR. Unlike
time-of-flight angiography, which uses primarily
magnitude data from the MR acquisition, PCA uti-
lizes the phase data. One of the major advantages
that PCA has over TOF imaging is in the assessment
of flow direction and velocity. Imaging of the intra-
cranial arterial vasculature with PCA will only dem-
onstrate moving blood, as opposed to TOF MRA
(Fig. 7.14). A second advantage of PCA is in the
delineation of slow flow. TOF, however, is a faster
technique that requires only one acquisition, whereas
PCA requires four separate acquisitions to create one
data set.
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
[A]
[L]
C167
Time of flight MRA
Figure 7.14 (Left): TOF image. (Right): Phase-contrast angiogram. The TOF image demonstrates a saccular structure adjacent to the
left posterior cerebral artery with similar signal characteristics of the surrounding vasculature; findings were suspicious for aneurysm.
The phase-contrast angiogram shows no signal in the suspected aneurysm and no flow. The subsequent digital subtraction angiogram
demonstrates no aneursym. Abbreviation: TOF, time-of-flight.
Essentially, in PCA, contrast is achieved in blood
vessels by tagging moving blood with phase changes.
Moving objects develop a phase change as opposed to
stationary objects during the acquisition. Moreover,
the velocity and direction of the motion can be deter-
mined from the data set. The concept of phase con-
trast can be understood by taking the case of a blood
vessel within a slice of interest and following the
effects of the varying gradients on a voxel of blood
traveling within that vessel. The particular gradient
that makes phase contrast possible is the bipolar gra-
dient (2123).
Take a slice of certain thickness with a blood
vessel oriented within it such that the vessel is parallel
to the x-axis and perpendicular to the y-axis. In prac-
tice, such a vessel could represent the M1 segment of
the middle cerebral artery as a patient has been placed
supine within a magnet bore, with the cranial direc-
tion corresponding to the positive Z-axis. Initially,
prior to any radiofrequency pulse application, all
spins are initially oriented such that their net magnet-
ization points in the positive Z-direction, along the
bore of the main magnetic field of the magnet. Spins
of stationary tissue as well as spins within the blood
vessel are all initially oriented in the same direction
of the positive Z-axis. A 90 degree radiofrequency
pulse gets applied. The spins that were pointing in
the positive Z-axis now get flipped into the XY-plane
(Fig. 7.15). Both stationary tissue spins as well as spins
within the blood vessel get flipped.
A gradient is applied along the x-dimension
(Fig. 7.16). The gradient is such that spins on the left
side of the slice experience a larger field than the
spins on the right side of the slice. There is a larger
141
Phase contrast MRA
magnetic field on the left side, tapering down to a
smaller magnetic field on the right side. The spins on
the left side of the slice hence precess faster than the
spins on the right side. The gradient is turned off, and
this causes the spins throughout the slice to once again
precess at the same frequency. However, there has
been a change in the phase of the spins. The spins on
the left side of the slice have a different phase from the
spins on the right side; they have gained phase.
A second gradient is now applied along the
x-dimension. This second gradient is in the opposite
direction, reversed polarity, but equal in magnitude to
the first gradient (Fig. 7.17). This second gradient is
such that the spins on the left side of the slice experi-
ence a smaller magnetic field than the spins on the
right side of the slice. The spins on the left, hence,
precess slower than the spins on the right. The second
gradient is turned off, and the spins once again pre-
cess at the same rate. During the gradient, the spins
on the right gained phase, canceling the phase gain
that the spins on the left experienced during the first
gradient. For tissues that were stationary during the
time of application of the two gradients, no net
change in phase was induced.
Take the case of a blood vessel with a given vol-
ume of blood within it such that a volume of blood is
initially located on the left side of the slice, and even-
tually ends up located on the right side of the slice.
During the first gradient, the volume of blood experi-
ences a larger magnetic field compared to spins on
the right side of the slice. This induces a larger change
in phase for that volume of blood. During the applica-
tion of the first and second gradients, the volume of
blood moves from the left side of the slice (where the
142 NEUROINTERVENTIONAL MANAGEMENT
Y
Z
Spins are tipped into the XY-plane
X
Artery
Figure 7.15
y y y
X X
Strong magnetic field Weak magnetic field
larger magnetic field was experienced, and a large
phase change occurred) to the right side of the slice.
The second gradient is applied, and the volume of
blood experiences a larger magnetic field, as it is now
located on the right side of the slice. So its phase
never returns back to its original phase. The volume
of blood has gained phase relative to all the stationary
spins. Blood that travels in the opposite direction
would encounter a negative phase change. The dis-
tance the volume of blood traveled in the time the
two gradients are applied determines the degree of
phase change. If the blood had moved slowly, and
traveled a short distance, then the phase change
would be small. If the blood moved fast, from the
very edge of the slice on the left to the very edge of
the slice on the right, then the phase change would be
X
Figure 7.16
maximized. Hence, the change in phase is propor-
tional to the velocity (Fig. 7.18).
The initial gradient that was applied is referred to
as the first lobe of the bipolar gradient, while the sec-
ond gradient applied is aptly referred to as the second
lobe of the bipolar gradient. So a single application of a
bipolar gradient, both lobes, results in a data set dem-
onstrating phase change in tissues with motion, and no
phase change in stationary tissues. In phase-contrast
angiography, two acquisitions are performed with two
different bipolar gradients. The first acquisition is as
described above. The second acquisition is with a
reversed bipolar gradient (Fig. 7.19). Once both sets of
data are acquired, a subtracted data set is calculated.
The method of subtraction is either via a complex dif-
ference technique or a phase difference technique.
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS 143

y y y

X X X

Weak magnetic field Strong magnetic field Figure 7.17

+Y

+Z
Moving blood
Stationary tissue results in no net
+ Phase angle change in phase, whereas moving
+X blood undergoes a phase change.
Stationary
tissue

Figure 7.18

First lobe Second lobe

Initial acquisition Second acquisition

Time

Second lobe First lobe

Figure 7.19

To further clarify the purpose of the second
acquisition with reversed gradients and the subtrac-
tion technique, take the initial case of the first acquisi-
tion as described above. The initial bipolar gradient,
performed during the first acquisition, results in zero
phase change for stationary tissues. For moving blood
within our hypothetical blood vessel, blood that
traverses the slice from the left side to the right side,
assume the first gradient induces a positive phase
change. A second acquisition is subsequently per-
formed, identical to the first acquisition, but with the
two lobes of the bipolar gradient reversed. This rever-
sal of the gradient again results in zero net change in
phase for stationary tissues. However, for moving
144 NEUROINTERVENTIONAL MANAGEMENT
+Y
+Z
Moving blood
M sin + Phase angle
+
+X
Stationary
M sin
tissue
Figure 7.20
blood, the phase change is reversed compared to the
initial acquisition; the phase change is negative. If the
phase data from the second acquisition are then sub-
tracted from the phase data of the first acquisition,
the phase of the stationary spins cancels out. The
phase of the moving spins, on the other hand, being
in opposite directions, results in a phase value. As
can be seen from Figure 7.20, the x-components of
the phase cancel, while the y-components are addi-
tive. Notice that the result of the final calculated
phase change demonstrates a y-component magni-
tude that is maximized only in certain conditions. If
the phase shift of the moving protons after each bipo-
lar gradient is 90 degrees, the shift has the greatest
magnitude after subtraction, and hence the greatest
signal intensity. This particular phase shift correlates
with a given velocity, a parameter encoded by the
MR technologist, termed VENC. Velocities less than
this optimal encoded velocity, VENC, have phase
shifts less than 90 degrees (and greater than 0 degree)
for the first acquisition and phase shifts between
0 degrees and --90 degrees for the second acquisition.
These lower velocities have correspondingly lower
signal intensity. Velocities greater than the VENC
have phase shifts greater than 90 degrees and less
than 180 degrees, and also have less signal intensity.
Any less, or any greater, than the 90 degree phase
shift results in less signal, which is why the proper
velocity encoding is critical in phase-contrast angiog-
raphy. For spins moving in the opposite direction,
phase shifts with the velocity corresponding to
--90 degrees has the greatest negative signal. Typical
velocity encoding for arterial flow is around 60cm/sec,
and for venous flow around 20cm/sec.
The PCA acquisition therefore requires that
phase be utilized. In the vast majority of MR studies,
magnitude images are primarily used. So how does
one go about measuring phase? With quadrature coils,
signal is measured in both the positive x-axis and pos-
itive y-axis. The signal in the positive x-axis is the
real (also known as in-phase or I) component,
while the signal in the positive y-axis is the imagi-
nary (also known as the in quadrature or Q)
component. With both components, one can calculate
either a magnitude image or a phase image. The mag-
nitude data are what are commonly used in majority
+Y +Y
Moving blood
+Z +Z
2 M sin
Stationary
tissue
+X +X
Phase angle
Moving blood
of imaging sequences, including the TOF sequences.
The phase data are what are used in phase-contrast
angiography.
With the acquisition of phase data encoded with
a positive bipolar gradient along the x-dimension sub-
tracted from a second set phase data encoded with a
negative bipolar gradient along the x-dimension, sta-
tionary spins with the same phase get subtracted out,
and moving spins with phase changes are what is dis-
played in the resulting image. When phase-contrast
angiography was initially introduced, two sequences
were performed along each axis, for a total of six
acquisitions. Positive and negative bipolar gradients
were applied along each of the three dimensions
(x-axis, y-axis, z-axis). This would result in a full
phase-contrast angiogram with phase-contrast data in
the x, y, and z dimensions including data from the
stationary tissue (Fig. 7.21). This has been decreased
to four acquisitions using the Hadamard multiplex
flow encoding approach to yield the same data set.
Given the additional time for the application of
the bipolar gradients, TE times can be slightly longer
than for TOF sequences. As in TOF, shorter echo
times are desired to minimize artifacts from phase dis-
persion. Subtraction of two data sets allows for
increased vessel conspicuity. Hence, even though
blood saturation can occur with phase-contrast
angiography, the increased conspicuity allows for a
shorter TR (24msec for PCA versus 48msec for TOF).
In general, maximizing TOF effects will also help
maximize phase contrast, as phase contrast is depend-
ent on both inflow effects and phase effects.
ULTRA HIGH FIELD MRA
Technology is progressing toward higher field mag-
nets, and in the future 3 Tesla magnets might get
dwarfed by 7 Tesla magnets and beyond. The temp-
tation toward higher field strength is driven by a
theoretical increase in the signal to noise ratio
achieved. The signal is proportional to the square of
the magnetic field, while the noise is linearly pro-
portional to the field strength. Hence, SNR is line-
arly related to field strength, and a doubling of
the magnetic field strength theoretically doubles
the SNR.
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
(A)
Figure 7.21 Phase-contrast data at the level of the A1 and M1 segments (Fig. 7.20A) and the P1 segments (Fig. 7.20B). Note the
bright signal in the vessels flowing toward the subjects left and the dark signal in the vessels flowing toward the subjects right, corre-
sponding to the direction of flow.
As field strength increases, the T1 of tissues also
increases. This will lead to improved background sat-
uration on MRA and increased vessel conspicuity.
These improvements come at the cost of the specific
absorption rate (SAR). SAR is proportional to the
square of the field strength, and thus increases consid-
erably in higher field magnets. Finally, susceptibility
artifact increases as magnetic field strength increases.
Seven Tesla MRA has been shown to provide
improved visualization of distal arterial branches (24).
Recent studies have shown a decrease in the number
of arterial stems and branches arising from the lentic-
ulostriates in hypertensive individuals (25).
CLINICAL APPLICATIONS
Intracranial Aneurysms
An estimated 10 to 15 million people in the United
States have intracranial aneurysms (26). Aneurysms
that have come to the attention of physicians have pri-
marily presented themselves in the form of a subar-
achnoid hemorrhage. These aneurysms tend not to be
imaged by MRA, as the presentation is acute and con-
ventional angiography is performed expeditiously. At
most institutions, patients have subarachnoid hemor-
rhage detected by either unenhanced CT scan of the
head or a positive lumbar puncture. Typically,
patients continue onto CT angiography and finally
conventional angiography. Assessment of the aneur-
ysm at the time of conventional angiography is what
then determines whether treatment will proceed with
coiling or clipping. As can be seen, MRA has little
role in these patients upon presentation. It is, how-
ever, within the purview of MRA to play a role in the
follow-up of patients who have had aneurysm
coiling. Typically, patients who have had aneurysm
145
(B)
coiling return for follow-up conventional digital sub-
traction angiography (DSA) to assess for coil compac-
tion, residual neck, and parent vessel patency.
Approximately 14% of patients who have had coiling
will re-bleed; in addition, about 20% of coiled aneur-
ysms have recanalization, with currently about half of
these get re-treated.
The platinum alloys in coils are what help
increase visibility during aneurysm coiling proce-
dures. However, it is this increased visibility on DSA
which leads to extensive beam hardening and streak
artifact on CT. This exquisitely limits CTA in the
follow-up of coiled aneurysms. On the other hand, the
very same alloys cause very little magnetic field dis-
tortion on MR, although there is a small degree of
susceptibility artifact. MRA has emerged as the
method of choice in noninvasive follow-up of coiled
aneurysms.
With the varied flavors of MRA, there has been
much debate and investigation on the differences and
advantages over 3 Tesla MRA versus 1.5 Tesla MRA
as well as that of time-of-flight MRA versus contrast-
enhanced MRA. Accurate noninvasive imaging is nec-
essary to properly identify aneurysm recanalization
and diminish the need for diagnostic angiography.
In general, 3 Tesla MRA that provides higher SNR
however suffers from an increase in susceptibility
artifact. Contrast-enhanced techniques may or may
not provide significant advantages over TOF, and also
suffer from timing bolus and venous contamination
difficulties.
Initially, 3D TOF MRA performed at 1.5 Tesla were
reported to have sensitivities of 7592% in the detec-
tion of residual aneurysm neck (Figs. 7.22--7.24). Also,
addition of gadolinium had been reported to increase
sensitivity to 100%, with 96% specificity at 12 months
post-coiling (2729). When 3T TOF MRA was compared
146 NEUROINTERVENTIONAL MANAGEMENT

Se:3 [A]
Im:79

Recanalization

[R] [L]

C246
[P] W467

Figure 7.22 Coiled anterior communicating artery aneurysm with recanalizationdiscovered on MRA and confirmed on DSA. Abbre-
viation: DSA, digital subtraction angiography. Source: DSA courtesy of Dr. Mikolaj Pawlak, Department of Neuroradiology, University
of Pennsylvania, Pennsylvania, USA.

Se:2 [A] Se:2 [A]

Im:67 Im:66

Recanalization of
coiled aneurysm

[R] [L] [R] [L]

Intracranial stent

C401 C347
[P] W803 [P] W694

Figure 7.23 Coiled right supraclinoid ICA aneurysm with recanalization on 3D TOF MRA. Note the right carotid intracranial stent.
Abbreviations: ICA, internal carotid artery; TOF, time-of-flight.

to 3T CE MRA, of 32 equally detected aneurysm
recanalizations seen on both techniques, the CE
MRA demonstrated improved visualization of the
recanalization in 10 cases (30). Recent data regar-
ding the use of CE MRA versus TOF MRA have
suggested that CE MRA leads to improved visual-
ization of larger recanalizations compared to TOF
MRA secondary to the presence of flow-related
artifact in TOF (31).
More current research has begun to show an
advantage to MRA over even DSA at 3 Tesla. A recent
study comparing 3T TOF MRA to DSA, with 50 coiled
aneurysms, showed that DSA differed from MRA in
only three cases, where all three were suspected to be
recanalized on MRA and completely occluded on
DSA. Surprisingly, all the areas of suspected recanali-
zation on MRA were obscured by the coils on DSA,
suggesting that 3T MRA might be superior to DSA in
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS 147

Recanalization

Figure 7.24 Recanalization in a coiled giant aneurysm.

assessment of subtle recanalization (32). A comparison

of 1.5T TOF MRA to 3T TOF MRA showed a slightly
improved detection rate of aneurysm recanalization
on 3T versus 1.5T, with 3T demonstrating 16 (out of
60 aneurysms) recanalizations versus 14 with 1.5T.
Both modalities outperformed DSA, which showed 10
recanalizations (33).
Many centers use both TOF MRA and CE MRA for
coiled aneurysm follow-up. It is important to note that
during the TOF MRA sequence, care must be taken to
keep TE very short (less than 5msec), as susceptibility
artifact needs to be minimized. TE times over 5msec can
lead to a 12mm region of susceptibility artifact around
coils (34). If available, 3T should be used over 1.5T.
Finally, in the era of cost-containment, cost effectiveness
analysis using Markov modeling shows that potential
consequences of misdiagnosis by MRA will be offset by
the direct risk of complications associated with DSA,
and MRA will reduce costs considerably (35). Periophthalmic aneurysm
The second arena where MRA has a particularly
important role to play is in the detection of unrup-
tured aneurysms. Unruptured aneurysms (Figs.
7.25--7.27) can initially be brought to attention from
screening MRA. There is controversy pertaining to
the screening of asymptomatic individuals with a
first-degree relative with a ruptured intracranial Figure 7.25
aneurysm (36,37). Screening is also considered for
patients with a pre-existing condition (e.g., adult pol-
ycystic kidney disease, fibromuscular dysplasia,
collagen-vascular disease) that predisposes to aneur- the characterization of the aneurysm neck. Multi-
ysm formation. This is an area where noninvasive planar reconstructions are generated by reformatting
MRA can play an important role without the need for the source data in any desirable plane. This, of
invasive conventional angiography. In the detection course, then allows for the evaluation of the data set
of aneurysms, studies have shown sensitivities for in coronal, sagittal, and oblique planes, in addition to
MRA ranging from 55% to 75% in comparison with the traditional axial acquisition. In addition to post-
conventional DSA. The sensitivity of the MR study processed data, source data must also be meticulously
can vary depending upon reader experience, type of reviewed. Aneurysms whose size is less than 5mm
post-processing algorithm applied, as well as the size tend to be difficult to detect on MRA. One study
of the aneurysm. Post-processing algorithms typically found the sensitivity for detection to be 55% for
include MIPs; however, multi-planar reconstructions aneurysms 25mm, whereas for aneurysms greater
(MPR) have been shown to be useful, particularly in than 5mm, sensitivity has been reported to be 88%.
148 NEUROINTERVENTIONAL MANAGEMENT
Figure 7.26 Pseudoaneurysm secondary to dissection of PICA. Digital subtraction angiogram on the left, MRA on the right. Abbreviation:
PICA, posterior inferior cerebellar artery.
Three Tesla systems have now come into clinical
practice with the FDA clearance in 1999, promising
increased signal to noise and contrast to noise ratios.
Improved image quality has been reported with
improved aneurysm characterization (3843). Prospec-
tively, for aneurysms smaller than 3 mm, MRA sensi-
tivity was shown to be 67% versus 58% for CTA (gold
standard of DSA, with all aneurysms visible on retro-
spective review) (44).
Carotid Stenosis
Carotid stenosis is a common indication for MRA of
the neck vasculature. Traditionally, the gold standard
for depicting carotid stenosis has been digital subtrac-
tion angiography. Benefit was shown in the NASCET
(North American Symptomatic Carotid Endarterec-
tomy Trial) trial for treatment of symptomatic carotid
stenosis greater than 70%. Clearly, depicting degree of
stenosis is critical in the proper management of these
patients.
2D and 3D TOF techniques have been commonly
used for imaging neck vasculature. In carotid stenosis,
blood that flows distal to the stenotic segment tends
to be turbulent. Typically, the greater the degree of
stenosis, the greater the turbulence. This, in turn,
leads to signal loss on TOF imaging secondary to
intravoxel dephasing. In fact, the presence of a flow
void on 2D TOF MRA of the carotids has been dem-
onstrated to have a positive predictive value of 84%
for high grade stenosis (greater than 70% stenosis).
Unfortunately, the turbulence factor does lead to over-
estimation of degree of stenosis. This is rather critical
in the case of patients who have intermediate stenosis,
but whose MRA overestimated it to greater than 70%.
Hence, 2D TOF MRA has made its role in screening
for stenosis rather than becoming a substitute for DSA.
The addition of gadolinium to the imaging algorithm
Pseudoaneurysm
has held additional promise in the characterization of
stenosis. There is increased intravascular signal,
shorter acquisition times and echo times, as well as a
high contrast to noise ratio compared to TOF MRA.
With the increased intravascular signal from gadoli-
nium, which can be substituted for decrease in image
voxel size, the effects of turbulence, and hence intra-
voxel dephasing, are minimized. Increased speed of
scanning also helps with the minimization of motion
artifacts. As in TOF MRA, gadolinium-enhanced MRA
of the carotid vessels has a high sensitivity for the
detection of high grade stenosis (9397%). However,
this is similar to the sensitivities of 3D TOF MRA
without gadolinium. In moderate stenoses, the gadoli-
nium has not been particularly helpful, with sensitiv-
ities ranging between 14% and 68% (4551) (Fig. 7.28).
Carotid Plaque
Carotid plaque imaging, while not truly in the scope
of MR angiography, is a concept worth exploring as
this direction is highly likely to help differentiate
patients between intervention and medical manage-
ment, particularly in populations where there is mod-
erate (5069%) stenosis. NASCET trial demonstrated a
5-year rate of ipsilateral stroke of 15.7% in sympto-
matic patients with moderate stenosis who underwent
carotid endarterectomy compared to 22.2% for those
who were medically managed. Currently, recommen-
dations indicate that patients with moderate stenosis
may benefit from intervention given reasonable surgi-
cal and anesthetic risk factors (52). The presence of
vulnerable plaque may provide a further push toward
intervention in this large subgroup of patients.
MRI can provide excellent imaging of carotid
plaque to help identify vulnerable plaque. The Ameri-
can Heart Association has classified carotid plaque
based on eight histologic subtypes, Types I through
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS 149

Right MCA aneurysm

Figure 7.27

[H]

Carotid stenosis

[F]
2D TOF 3D Gadolinium enhanced DSA

Figure 7.28 Source: DSA courtesy of Dr. Mikolaj Pawlak, Department of Neuroradiology, University of Pennsylvania, Pennsylvania,
USA.

VIII. Of interest are the Type IV through Type VI sub-
types, which are the plaques thought to be prone to
rupture, thromboembolism, and subsequent cerebro-
vascular event. Types IV and V plaque have lipid
cores and fibrous caps, while Type VI plaque has
additional complexity of intraplaque hemorrhage and
ulceration (53).
MRI has the capability of identifying and character-
izing carotid plaque with high-resolution imaging and
ECG gating. T1, T2, proton density, and post-contrast
150 NEUROINTERVENTIONAL MANAGEMENT

scans are all helpful for full characterization of the

plaque in addition to MRA. All sequences need to be
combined with fat saturation for optimal imaging.
The three components of the plaque that need to
be assessed are (1) the fibrous cap (either with or
without a surface defect), (2) lipid core (presence or
absence), and (3) intraplaque hemorrhage or thrombus
(presence or absence). The fibrous cap is identifiable
on T2 and proton density sequences. The cap remains
relatively stable in signal intensity between a short TE
(proton density-weighted) image and a longer TE
(T2-weighted) sequence. This helps differentiate the
fibrous cap from the lipid core. The lipid core may be
bright or dark (or anywhere in-between) on T2
sequences. This is due to the theory that the lipid core
can be either in liquid state or solid state at body tem-
perature, leading to either T2 bright or dark signals,
respectively. As the TE shortens, and as proton den-
sity dominates, the lipid core will be brighter. There-
fore, comparison of proton density and T2-weighted
images will show a fibrous plaque that remains stable
in signal intensity and a lipid core that decreases in
signal intensity as TE lengthens from proton density
to T2 weightings (54) (Fig. 7.29).
T1-weighted images in combination with post-
contrast images also allow for the identification of an
enhancing fibrous cap compared to a nonenhancing
lipid core. The difficulty with use of T1-weighted
images alone is potential overestimation of the lipid
core, especially in cases where there is the presence of
intraplaque hemorrhage. Contrast-enhanced T1 fat
saturated sequences seem to provide a more accurate
assessment of fibrous plaque to lipid core. Presence of
recent intraplaque hemorrhage shows both T1 and T2
hyperintense signals.
For all pulse sequences, black-blood technique of
either dual inversion recovery (DIR) or inflow/outflow
saturation bands (IOSB) must be used. DIR involves
the application of a nonselective 180 degree pulse,
whereby all protons are flipped from positive Z-axis to
the negative Z-axis. This is followed by a slice (or slab)
selective 90 degree pulse at the null point of blood, and
subsequent image acquisition. IOSB involve the appli-
cation of saturation bands above and below the slice
(or slab) of interest (54,55). Typically, T1-weighted
sequences can be acquired with a gradient echo techni-
que, such as 3D SPGR (spoiled gradient recalled
acquisition), while T2 and proton density sequences
can be acquired with fast spin echo techniques. In gen-
eral, 3 Tesla imaging provides higher SNR and CNR
for all pulse sequences than 1.5 Tesla, giving superior
carotid wall imaging (56).
Intraplaque hemorrhage alone has been pro-
posed as an emerging marker for plaque instability.
Patients with intraplaque hemorrhage identified on
T1-weighted images alone have been shown to have
higher risk of developing subsequent stroke within
24 months (57). In addition, patients with type VI car-
otid plaque have been shown to have an odds ratio of
11.66 to have an ipsilateral event of TIA or stroke (58).
Dissection
Arterial dissections in the carotid and vertebral
arteries can either arise spontaneously or occur after a
Residual ICA
lumen
Calcification
Calcification
Hemorrhage within plaque
Figure 7.29 Hemorrhagic atherosclerotic plaque on TOF axial
image. Between the hyperintense lumen of the internal carotid
artery and hyperintense hemorrhage within the plaque, a thin
dark fibrous cap can be seen. Source: Courtesy of Dr. Ronald
Wolf, Department of Neuroradiology, University of Pennsylvania,
Pennsylvania, USA.
traumatic event. In both situations, MRA has sup-
planted conventional angiography in the initial diag-
nosis. The major findings to identify on MRA are
double lumen with an intimal flap or intramural hem-
atoma within the vessel wall. The hematoma is imme-
diately isointense to slightly hyperintense to muscle
during the first few days of a dissection (Fig. 7.30).
Gradually, this becomes hyperintense with time and
can remain for months after the dissection. A fat-
saturated T1-weighted sequence is also helpful for
identifying the hyperintense signal of the intramural
hematoma and subtract out the T1 hyperintense fat
surrounding the artery. One can also see complica-
tions of dissection such as pseudoaneurysm formation
(Fig. 7.31) (59).
Intracranial Vascular Malformations
Intracranial arteriovenous malformations (AVM) are
high-flow vascular lesions characterized by dysregu-
lated angiogenesis. The lesions tend to form during
development, with the vast majority sporadic in
occurrence, and only 2% being part of a syndrome.
Pathologically, these lesions demonstrate three major
components: feeding arteries, nidus, and draining
veins. The feeding arteries are mature vessels that
may or may not be enlarged. The arteries supply the
AVM nidus, which is composed of numerous dysplas-
tic, thin-walled vessels. These vessels are direct arte-
riovenous shunts, without intervening capillary
network. Also of note is that no brain parenchyma is
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS 151

Right carotid dissection

Figure 7.30 Right carotid dissection. Fat-saturated T1-weighted image on the right, 3D TOF MRA in the middle, and MIP on the right.
Note the T1 bright intramural hematoma in the fat-saturated sequence. There is high signal in the lumen and in the hematoma on the
TOF sequence (and MIP). Abbreviations: TOF, time-of-flight; MIP, maximum intensity projection.

visualization of draining veins as well as feeding

Dissection with
pseudoaneurysm
Figure 7.31
located within the nidus. The nidus subsequently
empties into enlarged draining veins. Occasionally,
there are associated pre-nidal, nidal, and post-nidal
aneurysms.
Imaging of these lesions has traditionally been
the domain of conventional DSA. Conventional MRI
demonstrates AVMs as multiple flow voids, with vari-
able amounts of associated hemorrhage. MRA has
been utilized to characterize morphology of the AVM.
Traditional 3D TOF MRA can demonstrate high flow
feeding vessels; however, the technique is not very
sensitive to slow-flowing draining veins (Fig. 7.32).
Utilization of contrast-enhanced MRA with very short
acquisition times (TR/TE 5/2msec) does improve the
arteries (60).
Recent application of dynamic MRA in the eval-
uation of residual AVM after radiosurgery demon-
strated sensitivity of 81% and specificity of 100% in
the identification of nidus or draining vein, as com-
pared with DSA (61).
As opposed to intracranial AVMs, dural arterio-
venous fistulas (AVF) are thought to be acquired later
in life, not occurring during development. Although
not completely understood, theories suggest that
venous sinus thrombosis forms and triggers angiogen-
esis for recanalization. The angiogenesis then results
in one of three types of dural AVFs. The three classifi-
cations are based on venous drainage patterns, with
type 1 draining anterograde into the venous sinus itself,
type 2 draining anterograde into the venous sinus and
retrograde into subarachnoid/leptomeningeal veins,
and type 3 draining solely retrograde into the subar-
achnoid/leptomeningeal veins (62). Detection of dural
AVF by MRI is challenging, with one study finding
that a majority of dural AVFs were characterized by
flow void clusters around a dural sinus (63). Type 2
and 3 lesions also tend to demonstrate dilated lepto-
meningeal and/or medullary veins. 3D TOF MRA has
a 45% sensitivity for directly demonstrating the fistu-
las, and a 91% sensitivity for detecting flow-related
enhancement in draining veins (Fig. 7.33). A recent
study comparing DSA with dynamic MRA found
100% sensitivity and specificity in diagnosis of 42 cases
of dural AV fistulas. Classification was also correct in
all but three cases (64). Dynamic MRA has successfully
been used for the follow-up of treated dural AV fistu-
las; however, only small groups of patients have thus
far been evaluated (65).
Spinal Vascular Malformations
Spinal vascular malformations are lesions that typi-
cally require an exhaustive angiographic search with
catheterization of multiple radicular arteries to help
localize the malformations. There are four types of
spinal vascular malformations, the most common
152 NEUROINTERVENTIONAL MANAGEMENT

Se:22 [A] [A] [A]

Im:1 Study Stu
Study Til Study
MRN: MRN: Study Time:8

[R] [L] [R] [L]

C376 C242
[P] W831 [P] W534 [P]

Figure 7.32 AVM on 3T TOF MRA. The image on the left is a MIP collapse, the central image is a source MRA slice, and the image
on the right is FLAIR weighted showing flow voids. Abbreviations: AVM, arteriovenous malformation; MIP, maximum intensity projec-
tion; FLAIR, fluid-attenuated inversion-recovery.

Figure 7.33 DAVF on dynamic gadolinium-enhanced MRA. From left to right: pre-contrast, arterial phase, delayed phase. The filling
of leptomeningeal veins and transverse sinus is immediately evident. Abbreviation: DAVF, dural arteriovenous fistula.

(80%) being Type 1 dural arteriovenous fistulas. These
are direct arterial to venous connections located
peripherally within the dura of a nerve root sleeve.
The lesions receive supply from a dural branch of the
radicular artery with drainage into the cord pial veins.
These type 1 lesions are best thought of as extrame-
dullary, intradural, peripheral AV fistulas. Type 2
lesions are true arteriovenous malformations located
within the cord itself. These intramedullary lesions are
supplied by branches of the anterior or posterior spi-
nal artery and typically have a compact nidus, with-
out intervening parenchyma. Type 3 lesions are more
complex than type 2 lesions, have both intramedullary
and extramedullary components. The nidus of the
type 3 lesion has intervening neural parenchyma.
Type 4 lesions are extramedullary arteriovenous fistu-
las, like type 1 lesions; however, they are centrally
located within the perimedullary meninges. Their sup-
ply is from either anterior or posterior spinal artery,
and there is no nidus, with direct drainage into spinal
veins.
When patients present with a suspected spinal
vascular malformation (e.g., progressive myelopathy),
they initially undergo MRI evaluation of the spine.
Conventional MR imaging shows T2 hyperintensity
within the cord with multiple flow voids from
engorged venous structures. Unfortunately, the site of
T2 hyperintensity in the cord, representing cord
 MR ANGIOGRAPHY: BASIC PRINCIPLES AND APPLICATIONS IN THE CNS
AVF
Figure 7.34 Spinal DAVF demonstrated at the T11 level by 3D contrast-enhanced MRA with an elliptic centric filling of k-space. The
level of the arterial feeder was subsequently confirmed on DSA and embolized. Abbreviations: DAVF, dural arteriovenous fistula;
DSA, digital subtraction angiography.
edema from venous hypertension and resultant cord
ischemia, does not correspond to the level of a malfor-
mation. Venous flow voids may or may not be seen. As
the majority of spinal vascular malformations are Type 1,
intramedullary flow voids are not reliable. Conven-
tional angiography is then used to painstakingly evalu-
ate multiple spinal levels in hope of discovering the
vascular lesion. Spinal MRA is showing great promise
in reducing this painstaking search, and assisting in
the targeting of these lesions. There has been a
reported improvement in true positive detection rate of
these lesions with 3D contrast-enhanced MRA, with
true positives improving from 15% with MRI data
alone to 50% with combined MRI and MRA data (66).
Recently, 3D contrast-enhanced MRA with an elliptic
centric filling of k-space was reported to have correctly
localized spinal vascular malformations in eight out of
nine patients (67). The elliptic centric algorithm fills the
central portion of k-space in the first one-tenth of the
total scan time. Central k-space determines contrast
resolution, while peripheral k-space determines spatial
resolution; hence, arterial contrast is maximized with
elliptic centric filling (Fig. 7.34).
Ischemic Stroke
Ischemic stroke is one of the most common causes of
morbidity and mortality. A 5-year mortality rate for
carotid territory infarction is 40% (68). Imaging has
taken on an ever increasing role in the diagnosis of
ischemic stroke. Perhaps more enticing is the prospect
of using imaging to help triage patients to proper ther-
apy. Intense research efforts are attempting to better
define ischemic penumbra and stratification for throm-
bolytic therapies. The pathophysiology of ischemic stroke
essentially boils down to decreased cerebral blood flow
(CBF). When CBF decreases to below 1015ml/100
grams of brain parenchyma/minute, neuronal death
ensues.
Conventional MRI sequences initially demonstrate
loss of flow void in the occluded vessel and T2 hyper-
intense signal in regions corresponding to ischemic
tissue. These findings are analogous to CT findings of
hyperdense arterial attenuation from thrombus and
associated hypodensity in affected brain parenchyma.
153
However, the true revolution in MRI of stroke came
with the advent of diffusion-weighted imaging (DWI)
sequences. DWI sequences essentially measure the free-
dom of water. If a water molecule is within an environ-
ment where it can move freely in all three dimensions
(e.g., outside of a cell), then it has quite a bit of free-
dom, and hence increased diffusivity. With the use of
diffusion gradients, MRI can measure the diffusivity of
water, creating maps of the apparent diffusion coeffi-
cient (ADC). Areas of the brain, which have restricted
diffusivity, are those areas where water is primarily
intracellular, not extracellular. Hypoxic neurons have
failure of their sodium/potassium ATP ion pumps,
leading to an influx of water into the cell, leading to
restricted diffusion. DWI, in animal models, has the
capability of imaging infarction as early as 5 minutes
upon the onset of ischemia. In humans, DWI abnormal-
ities have been detected as soon as 39 minutes after the
onset of stroke (69). Restricted diffusion then typically
returns to normal by day 7.
While DWI has served to image metabolic changes
occurring with stroke, recent efforts have focused on
perfusion. One of the observations made with DWI is
that the area of restricted diffusion can grow. The growth
of this hypoxic region of tissue means that there is
at-risk tissue not initially identified by DWI. Perfusion-
weighted imaging (PWI) sequences came into the
picture to help identify this at-risk tissue, also known as
the ischemic penumbra (70). PWI sequences are typically
performed by administering a bolus of gadolinium, fol-
lowed by sequential, rapid, images acquired as the bolus
traverses the cerebral circulation from artery to vein. As
gadolinium is paramagnetic, the T2* is shortened, and
this is used to track the bolus and assess its associated
signal changes in the vasculature and parenchyma. PWI
sequences result in maps of cerebral blood flow (CBF),
cerebral blood volume (CBV), and mean transit time
(MTT). These three variables are related by the central
volume principle, where CBF = CBV/MTT. Ischemic tis-
sue has decreased CBF, decreased, normal or elevated
CBV depending on the degree of vascular reserve, and
elevated MTT. Infarcted tissue has decreased CBF,
decreased CBV, and elevated MTT. It is thought that
elevated MTT may be the most sensitive indicator of
brain tissue at risk for infarction (Fig. 7.35). Another MR
154 NEUROINTERVENTIONAL MANAGEMENT
T2 D-WI
rCBV rCBF
Figure 7.35 Top-right image is T2 weighted, top central and top left are DWI and ADC, and bottom row is perfusion data. Note how
perfusion abnormalities encompass a large portion of the right MCA territory compared with the DWI images, which only show focal
abnormalities in the right external capsule and right parietal lobe. The difference between perfusion and diffusion data is the ischemic
penumbra. Abbreviations: DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient.
perfusion parameter, time to peak (TTP), which is
delayed in ischemic tissue, can be used to identify the
ischemic penumbra. On the assumption that the tissue
with restricted diffusion is infarcted, one can then sub-
tract DWI data from the MTT map. The final image is
that of the ischemic penumbra, the tissue that is presum-
ably ischemic but not yet infarcted. This is the tissue that
is targeted for salvage with thrombolytics. There is still
controversy as to whether all the tissue with decreased
CBF will proceed toward infarction or not (71). There is
also controversy as to whether or not the tissue identi-
fied on DWI represents infarcted tissue, as observations
have been made that thrombolytic therapy can decrease
the volume of DWI abnormality. Hence, current meas-
urements of ischemic penumbra can be thought of as an
overestimate of tissue that will proceed to nonsalvage-
able infarction without intervention. Also, the current
measurements of DWI abnormality can be considered
as an overestimate of nonsalvageable infarcted tissue.
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 8
Ultrasonographic imaging and physiologic techniques in
interventional neuroradiology
Jaroslaw Krejza and Michal Arkuszewski
INTRODUCTION
Since the introduction of echoencephalography in the
early 1950s, ultrasonic techniques have evolved dra-
matically. Ultrasound (US) imaging is now considered
an integral part of the evaluation of patients with cer-
ebrovascular disease (CVD), because it is noninvasive,
relatively inexpensive, accurate, and readily accessible.
This chapter provides the basics of US and summa-
rizes diagnostic and therapeutic applications of US in
interventional neuroradiology.
TECHNICAL ASPECTS OF US IMAGING
Basics of US
In US imaging, pulsed waves emitted by a transducer
pass into the body and reflect off the boundaries
between different tissue types. These reflections, or
echoes from the reflected waves, are then assembled
into a picture on a video monitor. The frequency, den-
sity, focus, and aperture of the US beam can vary.
Higher frequencies produce more clarity but penetrate
less deeply into the body. Lower frequencies penetrate
more deeply but produce lower resolution, or clarity.
US entering tissue may be transmitted, absorbed,
reflected, and/or scattered (1). The transmission prop-
erties of a tissue depend on its density and elasticity.
Density and speed of propagation determine a tissues
acoustic impedance. In homogeneous tissues, US
waves propagate until all their energy is dissipated as
heat. In nonhomogeneous tissues, reflection, scatter-
ing, transmission, or a combination of these processes
occurs when waves encounter a layer with different
acoustic impedance. The larger the difference in
acoustic impedance, the more the waves reflected
(1,2). Reflection further depends on the angle of inso-
nation, and stronger echoes are received when the
angle of insonation is zero (2). Strongly reflective
hyperechoic interfaces, such as bone or air, prevent
imaging of weaker echoes from deeper tissue and cast
an acoustic shadow. Hypoechoic or poorly reflective
tissues, including fluids, are called sonolucent.
Bioeffects and Safety of US
Diagnostic US can produce heat that may be hazard-
ous to sensitive organs (3). Nonthermal effects, such
as pressure changes and mechanical disturbances, in
tissue have not been demonstrated in humans (4). US
used in therapy, however, can cause both substantial
temperature increase and mechanical damage in the
tissue (46).
Thermal Effects
Generally, denser tissue absorbs more heat from US.
Therefore, the fluid does not heat very much, soft tis-
sues heat somewhat more, and bone heats the most.
The heating rate in the bone surface can be up to 50
times faster than in soft tissues. This heating effect is
of interest, particularly in regard to the transcranial
Doppler (TCD) ultrasonography and its therapeutic
applications. Diagnostic US systems now display
numbers that provide crude measures of a risk to
patients from the heat and/or mechanical effects. The
thermal index (TI) is an estimate of risk from heat.
When the TI is above 1, it is recommended that the
risks of US be weighed against the benefits (4). The
consensus is to minimize exposure, particularly in
pulsed Doppler applications, as a significant tempera-
ture increase can occur at the bonesoft tissue inter-
face. Nevertheless, short-term continuous TCD
monitoring did not increase temperature at the tempo-
ral window in vivo (7).
Nonthermal Effects
US can also produce various mechanical effects such
as cavitation, pressure amplitude, force, torque, and
acoustic streaming (3). Cavitation occurs when US
passes through an area that contains a cavity, such as
a gas bubble. US can cause the bubble to expand and
contract rhythmically. When bubbles pulsate, they
send secondary US waves in all directions. These sec-
ondary waves can actually improve US imaging. If the
bubbles contract toward the point of collapsing, they
can build up very high temperatures and pressures
for a few tens of nanoseconds. These high tempera-
tures and pressures can potentially produce free radi-
cals and other toxic compounds that, although
considered unlikely, could theoretically cause genetic
damage (8). The rapid contraction of bubbles can also
cause microjets of liquid that can damage cells. The
safety guidelines for diagnostic US are designed to
prevent cavitations to occur (3,4).
158 NEUROINTERVENTIONAL MANAGEMENT
Apart from cavitation, US produces changes in
pressure, force, torque, and streaming. These changes,
in turn, can cause audible sounds, electrical changes
in cell membranes that make them more permeable to
large molecules, movement and redistribution of cells
in liquid, and cell damage (9). In liquids, US causes a
type of stirring action called acoustic streaming. As
the acoustic pressure of US increases, the flow of
liquid speeds up. When the streaming liquid comes
near a solid object, shearing may occur, which can
damage platelets and lead to abnormal blood clotting.
Effects of US Contrast Agents
These agents usually take the form of stable gas-filled
microbubbles (MBs), which can potentially produce
cavitations and/or microstreaming, the risk of which
increases with the mechanical index (MI) value.
Diagnostic US Techniques
Grayscale Imaging
B-mode, or brightness mode, displays structures pro-
portional to the intensity of returning echoes. The US
beam is swept quickly through the field of view, and
the image is continuously renewed, allowing a real-
time visualization of the underlying tissue anatomy.
In M-mode imaging, used to evaluate the motion of
well-defined surfaces such as blood vessel walls, a
vertical time-base trace driven from left to right across
the display is simultaneously generated. The echoes
are displayed vertically as the depth of US penetration
increases.
Doppler Display Modes and Blood Velocity
Measurements
The difference in frequency between emitted and
reflected ultrasonic echoes is the Doppler frequency
shift. The magnitude of the shift depends on the US
transmission velocity in the tissue (C), the relative
velocity of blood (V), and the US emitted frequency
(Fo). The observed frequency shift (DF) is expressed as
DF = 2VFo/C.
The shift is measured only for the component of
motion along the axis of the US beam. Therefore,
absolute velocity measurements require that a correc-
tion be made for the angle (Q) between the vessel and
the beam as follows: V = DFC/(2Fo cos Q). Doppler
modes are used to measure flow velocity. The fre-
quency shift is proportional to the velocity of moving
blood. The simplest Doppler US instrument has two
identical piezoelectric crystal transducers. One crystal
continuously emits toward the region of interest, and
the other continuously receives reflected echoes. Flow
toward the transducer produces an increase in the
received frequency, whereas flow away from the
transducer causes a drop. Continuous Doppler sys-
tems can measure a wide range of velocities but pro-
vide no information about the depth of the reflecting
tissue, because any moving object in the beams path-
way reflects echoes. The depth or position insensitiv-
ity of continuous-wave Doppler is overcome to a large
extent by using pulsed-wave Doppler. In this techni-
que, a single transducer generates US pulses and
detects returning echoes. Assuming that the speed of
transmission of US in tissues is constant, the time
delay between the emitted pulse and the reflected
echo enables the sampled structures depth to be
determined. However, anatomy is not displayed, and
the pulse duration and repetition frequency impose
limits on the maximum velocity that can be measured.
This technique is used for conventional TCD. Anat-
omy is displayed in duplex imaging, which combines
pulsed-wave Doppler with two-dimensional real-time
grayscale imaging. The grayscale image of a selected
vessel is displayed, allowing precise placement of the
Doppler sample volume in the vessel to measure flow
velocity throughout the cardiac cycle. Optimal angle
correction for velocity calculations can be performed
as the course of the vessel in relation to the US beam
is visually depicted. Color duplex is the most com-
monly used technology today for extracranial carotid
imaging. It is also used for transcranial color-coded
duplex sonography (TCCS). Color is superimposed on
a conventional grayscale image to enhance the image
of the Doppler frequency shift. Red indicates flow
toward the transducer, whereas blue represents flow
away from the transducer. High flow velocities are
depicted with increasing brightness. As a result, the
presence of flow, its direction, and hemodynamic dis-
turbances can be quickly assessed. The color map in
color Doppler US can be displayed as the integrated
power of the Doppler signal, which is related to the
number of red blood cells that produce the Doppler
shift. Advantages of this power mode include inde-
pendence from the angle of insonation, absence of ali-
asing, and the ability to detect very low flows.
Piezoelectric crystals are arranged into an array
inside a transducer. Linear transducers (7.516 MHz)
for carotid imaging produce rectangular fields of
view, while phased-array transducers (13.5 MHz)
used in TCCS produce wedge-shaped fields of view.
DIAGNOSTIC US IMAGING IN INTERVENTIONAL
NEURORADIOLOGY
TCD
Since the early 1980s, TCD imaging has permitted
insonation of the basal brain arteries. TCD technology
substantially evolved during the mid- to late 1990s,
and TCCS is increasingly used today. Both TCD and
TCCS have specific advantages. TCD is based on
pulsed-wave Doppler measurements of blood flow
velocity. Its 2-MHz, relatively small, transducers are
easy to use, particularly when prolonged monitoring
is performed. Experience with this technology is
extensive, but the angle of insonation cannot be
assessed and exact placement of a sample volume in
the insonated artery cannot be controlled, leading to
an error in both velocity measurement and vessel
identification. TCCS combines two-dimensional real-
time grayscale imaging with pulsed-wave Doppler
and color-coded display of velocity information (10).
It is performed with phased-array, 1.6- to 3.5-MHz
transducers that are slightly larger and less easy to
manipulate than their TCD counterparts. In contrast
to TCD, however, TCCS enables the sonographer to
outline intracranial parenchymal structures, to acquire
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
a Doppler sample at a specific site of an insonated
artery, and to image segments of the basal cerebral
arteries in color (Fig. 8.1). These advantages permit
more rapid studies, provide more information, and
improve the sonographers confidence as well as the
tests accuracy (11). Both TCD and TCCS are noninva-
sive and enable bedside testing. Measurements are
also highly reproducible. Inadequate ultrasonic win-
dows, present in 1020% of patients (12), and limited
accuracy constitute the major disadvantages.
Reference Values
Reference values have been established for both TCD
and TCCS (13,14). Because of differences in correction
of insonation angles and depth of insonation, TCD
reference values cannot be used for TCCS measure-
ments. Normal reference data for TCD and TCCS
velocities have been published elsewhere, and are pre-
sented in Table 8.1 for TCCS (13,14). Velocities are
highest during the first decade of life and drop during
the fifth and sixth decades. Women tend to have higher
velocity values up to the age of 60. This tendency may
be partially explained by the effect of the hormonal fluc-
tuations that affect the reactivity and tone of the cerebral
vasculature (15,16). Other factors that affect flow veloc-
ities include intracranial pressure, Hct, fibrinogen,
cardiac rhythm disorders, and medications (17,18).
Referring of blood flow velocities obtained from a
patient to the age and sex increases accuracy of the
TCCS in detecting flow abnormalities (19).
Detection of Intracranial Arterial Occlusion
For current acute ischemic stroke therapy to be effec-
tive, it must be initiated in the first few hours after
stroke (20,21). The only current proven therapy for
acute ischemic stroke is thrombolysis with tissue
plasminogen activator (tPA) within three hours of
stroke (21,22). While this treatment appears to be effec-
tive in all major ischemic stroke subtypes, recent trials
have suggested that some therapies may offer a benefit
for one mechanism but not for others (23,24). If the
stroke mechanism could be determined in the first few
hours after stroke, then patients with specific subtypes
could be selected for specific potential therapies in clin-
ical trials and ultimately in clinical practice. The clinical
diagnosis of stroke subtype during the first 24 hours is
frequently inaccurate, since clinicians often rely only on
the history, physical examination, noncontrast CT, and
ECG. Thus, for mechanism-directed therapy to be
implemented, additional diagnostic information is
required (Fig. 8.2).
In the setting of acute stroke, rapid TCD testing
can be an attractive approach to early stroke subtype
diagnosis that subsequently influences patient manage-
ment (25). Early diagnosis of an acute large intracranial
artery occlusion with TCCS is made on the basis of
the absence of Doppler signal in the artery (26). The
suitability of the acoustic window, however, must be
proven by the visualization of at least one ipsilateral
cerebral artery (26,27). Flow disturbances in other
intracranial arteries can further increase the diagnostic
accuracy of TCCS. Occlusion of the M1 MCA, for
example, is frequently associated with increased
159
velocities in the ipsilateral ACA due to the increased
flow through leptomeningeal collaterals (28,29). Caro-
tid occlusion leads to the development of collateral
flow through the ophthalmic artery and the anterior
(ACoA) and posterior (PCoA) communicating arteries,
while basilar artery (BA) occlusion increases the flow
through PCoA (29,30). Intracranial occlusion of the
vertebral artery (VA), located proximal to the origin
of the posterior inferior cerebellar artery, may lead to
reverse flow in the ipsilateral distal VA. Occlusions of
the intracranial ICA, VA, and BA reduce upstream
velocities, except in the BA, if adequate collateral
flow through cerebellar arteries is present.
If the results of the TCCS study are inconclusive,
MR angiography (MRA) or CT angiography (CTA)
can be used for making the diagnosis of intracranial
occlusion.
Perfect sensitivity, specificity, PPV, and NPV of
TCCS in diagnosis of M1 MCA occlusion using prede-
fined criteria were found in a study of 30 patients with
ischemic stroke of less than 24 hours duration (31).
Another study has shown that MCA occlusions
located in the main stem or branches in 20 of 23
patients with acute ischemic stroke of less than five
hours duration can be rapidly (57 minutes) detected
using contrast-enhanced TCCS (32). Other authors, on
the basis of small series, also suggest high reliability of
contrast-enhanced TCCS in the detection of M1 MCA
occlusion (33,34). Moreover, high sensitivity (94%) and
specificity (93%) of contrast-enhanced TCCS were
reported in 30 patients with ischemic stroke within
12 hours after symptom onset (35). The accuracy of
TCCS/TCD in the detection of occlusion of M2 MCA
has not yet been studied. A TCD study, however, has
shown that occlusion of more than three MCA
branches is associated with decreased velocities in M1
MCA (36). Another TCD study has investigated the
diagnostic accuracy of intracranial occlusion assess-
ment using predefined criteria (37). The corresponding
sensitivities were 93% for M1 MCA, 56% for the VA,
and 60% for the BA, with specificities of 9698%.
In summary, TCD/TCCS can detect angiographic
MCA occlusions with high (> 90%) accuracy, and ICA
siphon, VA, and BA occlusions with fair to good
(7090%) accuracy. Furthermore, TCD-detected occlu-
sions are associated with poor neurological recovery,
disability, or death after 90 days (38,39), whereas nor-
mal results predict early improvement (40,41). In
patients with acute ICA territory stroke, TCD findings,
stroke severity at 24 hours, and CT lesion size were
independent predictors of outcome after 30 days (38).
When combined with carotid duplex sonography, the
presence and total number of arteries with suspected
steno-occlusive lesions (especially intracranial) by
TCD in patients with transit ischemic attack (TIA) or
ischemic stroke were associated with an increased risk
of further vascular events and death within six
months (42). TCD-detected M1 MCA occlusions
within six hours of stroke onset may be an independ-
ent predictor of spontaneous hemorrhagic transforma-
tion, with a positive predictive value of 72% (43).
Occluded intracranial arteries recanalize in most cases,
and TCD/TCCS provides a means to monitor the
process. Recanalization additionally confirms the diag-
nosis of a previous occlusion (44). A multicenter
160 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

A1CA M1CA Probe Temporal

window

(E) (F)

Figure 8.1 (A) Typical color image of the M1 segment of the right MCA superimposed on a sector-shaped conventional grayscale
image. The sample volume is precisely placed on a green color spot related to an aliasing artifact, which indicates the site of highest
flow acceleration in the segment, and the angle between the course of the vessel in relation to the US beam is measured by an elec-
tronic cursor. This approach allows us to obtain the angle-corrected flow velocity measurements from the waveform displayed below
the grayscale image. In this 57-year-old patient, the follow-up TCCS study, a year after clipping of MCA aneurysm, shows blood flow
velocities in the right M1 MCA (A), M2 MCA (B), A1 ACA (C), and P1 PCA (D) within normal reference range of 110cm/sec,
48cm/sec, 71cm/sec, and 58cm/sec, respectively. Angiographic study (E) performed at the same day showed normal caliber of the
vessel. (F) Shows complex spatial relationship between US beam, courses of M1 MCA and A1 ACA, and the site of temporal window.
Abbreviations: MCA, middle cerebral artery; US, ultrasound; TCCS, transcranial color-coded duplex sonography; ACA, anterior cerebral
artery; PCA, posterior cerebral artery.
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 161

Table 8.1 Mean and Normal Reference Limits of Vps, Vmean, and Ved Blood Flow Velocities in MCA, ACA, and PCA Cerebral Arteries
Arteries
Velocities (cm/sec) N MCA ACA PCA
All subjects VPS 304 105 (52--166) 76 (34--121) 69 (37--103)
VMEAN 68 (32--112) 50 (18--82) 46 (21--72)
VED 45 (17--77) 33 (10--57) 30 (11--51)
Women VPS 193 107 (48--168) 77 (39--124) 70 (40--107)
VMEAN 71 (31--115) 51 (23--83) 47 (24--74)
VED 47 (17--75) 33 (11--57) 31 (12--51)
VPS 100 (54--158) 74 (32--123) 67 (35--104)
Men VMEAN 111 64 (31--102) 48 (16--82) 45 (20--73)
VED 43 (17--72) 32 (8--57) 30 (12--53)
Abbreviations: Vps, peak-systolic velocity; Vmean, mean velocity; Ved, end-diastolic velocity; MCA, middle cerebral artery; ACA, anterior
cerebral artery; PCA, posterior cerebral artery.

(A) (B)

(C) (D)

Figure 8.2 Identification of arteries of the circle of Willis with TCCS enables for an operator to detect an isolated occlusion. (A) Angiog-
raphy shows not patent A1 ACA on the right side. Also TCCS shows no flow in the A1, while flow is clearly seen in the MCA (B), ICA (C),
and PCA (D). In contrast, the A1 ACA was erroneously identified in three sequential conventional TCD studies in this patient.
Abbreviations: TCCS, transcranial color-coded duplex sonography; ACA, anterior cerebral artery; MCA, middle cerebral artery; ICA,
internal carotid artery; PCA, posterior cerebral artery; TCD, transcranial Doppler ultrasonography.

TCCS study assessed M1 MCA occlusion and recanali-
zation in patients with acute ischemic anterior circula-
tion stroke who were treated with intravenous tPA or
aspirin or heparin (45). MCA recanalization rates were
50% and 78% two hours after therapy and 24 hours
after the onset of stroke in 10 cases treated with IV
tPA, and 0% and 8% in 12 conservatively treated
patients. A recent study showed that delayed (>6 hours)
spontaneous recanalization was independently asso-
ciated with hemorrhagic transformation (46).
The use of contrast enhancement improves the
quality of imaging and markedly increases the
162 NEUROINTERVENTIONAL MANAGEMENT
diagnostic confidence of TCCS, in particular in poste-
rior circulation (47,48). TCD/TCCS is probably useful
for the evaluation of patients with suspected occlu-
sion, particularly in the ICA siphon and the MCA.
The relative value of TCD/TCCS compared with
MRA or CTA remains to be determined; however, if
the results of the TCD/TCCS study are inconclusive,
MRA can be used for diagnosis.
Perfusion harmonic imaging (PHI) can detect
ischemic lesions earlier than CT and distinguish the
stroke subtype and severity of cerebral ischemia (49,50).
There is growing interest in PHI for diagnosis, predict-
ing recovery, differentiating stroke pathogenesis, and
monitoring therapy. PHI is based on the nonlinear emis-
sion of harmonics by resonant MBs pulsating in an
US field. The emission at twice the driving frequency,
termed the second harmonic, can be detected and sepa-
rated from the fundamental US frequency. The advant-
age of the harmonic over the fundamental frequency is
that MBs resonate with harmonic frequencies, whereas
adjacent tissue does so very little (51). In this way, PHI
may enhance the signal-to-noise ratio and the ability of
grayscale scanners to differentiate MBs in the tissue vas-
cular space from the echogenic surrounding avascular
tissue. PHI is able to identify abnormal contrast enhance-
ment in most patients with stroke. In one study, 84%
(21) of stroke patients were correctly classified on the
basis of PHI (75% sensitivity and 100% specificity in
predicting size and localization of the infarction). Par-
ticularly large ischemic areas affecting both the area of
the lentiform nucleus supplied by the lenticulostriate
arteries and the convex surface of the brain supplied
by the superficial MCA can be identified and differen-
tiated from isolated perforator ischemia or infarctions
that exclusively affect the areas supplied by the super-
ficial branches of the MCA. Cortical infarctions in
the territory of the superficial MCA can be identified
if the adjacent white matter was affected as well. By
contrast, lacunar infarctions could not be depicted.
PHI provides a bedside tool to locate acute cere-
bral ischemia, in particular a large space occupying
and striatocapsular MCA infarctions. A normal study
may imply a minor or lacunar stroke with minimal
tissue damage. The widespread availability of TCCS
makes this technique a practical alternative to MRI,
SPECT, and PET. Larger trials are required to estab-
lish value of PHI with respect to the extent, severity,
and short-term outcome of hemispheric stroke. Major
limitations of PHI are as follows: time-consuming
analysis of data, problems with adequate and sym-
metric transparency of temporal bone windows, lim-
ited sector-shaped view of brain parenchyma, and
restricted access to cortical areas of the brain. By con-
trast, the white matter is easily and reliably depicted
because of the favorable insonation depth, the median
localization in the US sector, and the marked increase
in optic intensity after echo contrast application.
Intracranial Atherosclerotic Stenosis
Ischemia related to intracranial artery stenosis is
believed to account for 610% of strokes in Whites
and up to 29% in African-Americans and Asians
(52). The most common mechanisms for ischemic
stroke from intracranial stenosis are hemodynamic
compromise of collateral blood flow and throm-
boembolism (53). The high rate of recurrent ischemia
in patients managed medically suggests that angio-
plasty and stenting can be effective when imple-
mented in a timely fashion (54,55). Thus, early
detection of the stenosis has important implications
for stroke prevention.
TCD has been studied more often than TCCS,
and available data suggest that when compared with
contrast angiography, TCD is approximately 8090%
sensitive and over 95% specific in detecting stenotic
lesions of the ICA siphon and M1 MCA (5659). In
expert hands, both the sensitivity and specificity of
TCCS for the same arterial segments are more than
98% (60,61). Both techniques are less accurate when
evaluating lesions of the PCA, VA V4 segment, and
proximal BA, with the respective sensitivity and spe-
cificity of 70% and 85% for TCD (56,62) and 70% and
98% for TCCS (60). For these lesions, CT or MRA may
be more useful, particularly in patients with acute dis-
tal BA occlusion.
There is no consensus in the literature today
regarding specific criteria for the severity of stenosis.
The investigators of the Stroke Outcomes and Neuroi-
maging of Intracranial Atherosclerosis (SONIA) study,
an NIH-funded investigation assessing the accuracy of
TCD and MRA in patients with symptomatic intracra-
nial stenosis, opted for a mean velocity of 100cm/sec
for the 50% narrowing of MCA, 90 cm/sec for the car-
otid siphon and supraclinoid segment, and 80cm/sec
for the distal VA and proximal BA as the minimal cut-
off points for enrollment in the study (56). Higher
peak-systolic cutoff velocities for 50% narrowing,
ranging from 180 to 220cm/sec, have been proposed
for TCCS (60,61). The major diagnostic problem, how-
ever, remains in patients with insufficient temporal
windows (12). The use of sonographic contrast agent
may further improve TCCS detectability of intracra-
nial stenosis in these patients.
Substantial efforts have been concentrated on
establishing a particular threshold of flow velocity,
which can be considered as diagnostic for a specific
degree of vessel narrowing. However, flow velocity in
an artery is affected by many factors, which limit the
diagnostic reliability of any isolated threshold of blood
flow velocity. Factors decreasing the flow velocity, such
as (i) increased intracranial pressure, (ii) decreased
cardiac output, (iii) advanced age of a patient, and
(iv) thromboembolic occlusion of peripheral vessels,
may lead to false-negative results. False-positive results
may arise from (i) increasing velocity in cerebral
arteries supplying collateral channels in the presence of
severe narrowing or occlusion of other cerebral arteries,
or supplying arteriovenous malformations (AVMs),
(ii) dilation of the cerebral resistance vessels and dis-
turbed autoregulation in the case of stroke, or brain
trauma, and (iii) systemic diseases such as anemia
(sickle-cell anemia) and hyperthyreosis, which may
raise the cerebral blood flow (CBF) and flow velocity in
all cerebral arteries (63).
The accuracy of transcranial sonography can be
improved if several Doppler parameters are taken into
account in defining the status of a vessel (64). The use
of an interhemispheric index might be helpful in
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
detecting the narrowing of a vessel (65). This index,
however, is not useful when dealing with multiple
lesions. High-grade MCA stenoses may also be sus-
pected because of the presence of increased velocities
in the ipsilateral ACA, which result from leptomenin-
geal collaterals (66). Intracranial arterial stenotic lesions
in the internal carotid distribution, however, are
dynamic and can evolve over time, with increasing or
decreasing flow velocities and appearance of new col-
lateral patterns, the latter suggesting further hemody-
namic compromise distal to the stenotic lesion (67,68).
In two recent studies in small, highly selected popula-
tions using peak-systolic or mean flow velocities and
variable noninvasive criteria for change in degree of
stenosis, progression of MCA stenosis was associated
with new ipsilateral stroke or TIA or major vascular
events (67,69).
In summary, TCS/TCCS can be the first-line
modality in the detection of MCA/ICA stenosis in
patients with sufficient temporal windows, though
data are insufficient to establish reliable criteria for
greater than 50% stenosis or for progression of steno-
sis in intracranial arteries. The use of sonographic con-
trast agents can increase TCCS detectability of the
artery in patients with an insufficient temporal win-
dow. MRA or CTA should be used instead of TCCS
in patients without the windows. Also, MRA or CTA
can be used to verify the results of TCD/TCCS before
referral of a patient to intra-arterial treatment. Cathe-
ter angiography, however, remains a first-line diag-
nostic modality in patients who cannot be
conclusively studied with TCCS, CTA, or MRA.
Diagnosis and Monitoring of Cerebral Vasospasm
Symptomatic vasospasm (VSP) contributes signifi-
cantly to the morbidity and mortality of patients after
subarachnoid hemorrhage (SAH), and evidence indi-
cates that early treatment can positively influence out-
come (see Chapter 14). Proper timing for intervention
is often uncertain, because the diagnosis and monitor-
ing of VSP are difficult when based solely on neuro-
logical examination, because other complications
common in this patient population, such as recurrent
hemorrhage, hydrocephalus, metabolic disorders, and
seizures, can also produce similar neurological
symptoms.
Digital subtraction angiography (DSA) remains
the standard criterion for defining the anatomy of
intracranial arteries to diagnose VSP, but is impracti-
cal in screening and monitoring of VSP because it
requires significant time, requires moving the patient
to the angiographic suite, is invasive, and carries a
small but definite risk of stroke, renal injury, and
other complications. Alternative vascular tests, such as
MRA and CTA, are less expensive and safer, but they
are substantially less accurate, cannot be performed at
the bedside, and have often limited accessibility. Fur-
thermore, the risk associated with transport from
intensive care unit and placement of the patient in an
environment where monitoring is difficult at best
should not be underestimated.
TCD is employed extensively for diagnosis and
monitoring of cerebral VSP, but recent systematic
meta-analysis of published reports revealed that
163
specificity of TCD in the diagnosis of MCA spasm is
high, at the expense of low sensitivity (70,71). For the
ACA, PCA, ICA, BA, and VA, the accuracy of TCD
has either not been estimated or is known to be low.
Opinions are that some published data are of low
methodological quality, and thus bias cannot be ruled
out. It has been suggested that mean velocities less
than 120cm/sec or greater than 200cm/sec, a rapid
rise in flow velocities, or a higher Lindegaard ratio
(VMCA/VICA) (6 0.3) can reliably predict the absence
or presence of clinically significant angiographic MCA
VSP, although prediction of neurological deterioration
is problematic (7173). Unfortunately, almost 60% of
patients have velocities that fall between these thresh-
olds. Consequently, the accuracy of conventional TCD
in diagnosis of VSP remains questionable. A variety of
factors, such as technical issues (the specific insona-
tion site and the angle between the artery and the US
beam cannot be determined in TCD), vessel anatomy,
age, increased ICP, mean arterial pressure, Hct, arte-
rial CO2 content, collateral flow patterns, and response
to therapeutic interventions, influence flow velocities
and must be taken into account when interpreting
TCD results. The other problems in the diagnosis of
VSP are related to the common presence of impaired
autoregulation and diffuse VSP. Although correspond-
ing data concerning the accuracy of TCCS in the diag-
nosis of VSP are scarce, published reports strongly
suggest that the accuracy of the color technique in
the detection of the condition is high (Fig. 8.3)
(19,70,74).
TCCS is most reliable in detecting angiographic
VSP of M1 MCA. The best predictive Doppler param-
eter is peak-systolic velocity, and an average threshold
of 182cm/sec corresponds to maximal efficiency of
discrimination between states of spasm and nonspasm
(efficiency, sensitivity, specificity, PPV, and NPV were
92%, 86%, 93%, 73%, and 97%, respectively) (70). In
the presence of VSP, the use of the VMCA/VICA ratio
[Lindegaard index (75)] might be able to identify
patients with hyperemia, especially on triple-H ther-
apy, whereas corresponding TCCS data (74) showed
that the overall accuracy of the VMCA/VICA ratio in
the diagnosis of mild and moderate-to-severe MCA
narrowing is better than the respective accuracy of
velocity measurements alone. Value 3.6 of the ratio is
the most efficient threshold in the diagnosis of mild
(up to 25% narrowing) M1 MCA spasm, while the
threshold of 4.4 is the most efficient in the diagnosis
of moderate-to-severe spasm (more than 25% artery
narrowing) (74). The thresholds are higher than the
upper normal reference limits of the VMCA/VICA ratio,
calculated on the basis of the mean velocity (76). This
ratio varies in healthy subjects from 0.86 to 3.14, for
VACA/VICA from 0.54 to 2.55, and for VPCA/VVA from
0.76 to 2.90 (76). Standardization of flow velocities
with respect to age and sex further increases the per-
formance of TCCS (19). Neural networks also can be
employed to improve the performance of TCCS, and
it has been shown that classification accuracy
amounted to 92% in moderate-to-severe spasm detec-
tion, and to 87% in the assessment of VSPs of other
grades (77). Thus, it could be recommended that
patients with suspicion of MCA VSP should be inves-
tigated first with TCD, especially with TCCS.
164 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

(E) (F)

Figure 8.3 Fifty-six-year old women six days after SAH. Angiography shows vasospasm in M2 MCA and A1 ACA (A) on the right side
and in the distal segment of M1 MCA of the left side (B). Based on increased mean velocities in these spastic segments 217cm/sec in
the M2 (C) and 393cm/sec in the M1 MCA (D), and referencing these velocities to velocities in carotid arteries in the neck (E, F) (flow
velocity ratios: 8.0 on the right side and 9.3 on the left side), imaging TCD study diagnosed severe VSP. Note that the aliasing artifact
(blue spot) enabled proper placement of a sample volume to measure the highest velocity in the M1 segment. The proper identification
of the artery and the site of highest velocity acceleration is important, because in this patient conventional nonimaging TCD study, per-
formed on the same day, detected only slight velocity increase (90cm/sec) in these arteries. Abbreviations: SAH, subarachnoid hem-
orrhage; VSP, vasospasm; MCA, middle cerebral artery; ACA, anterior cerebral artery; TCD, transcranial Doppler ultrasonography.
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
DSA should be reserved for patients who cannot be
conclusively investigated with TCCS.
TCCS diagnosis of ACA VSP using a mean
velocity threshold of 75cm/sec resulted in the sensi-
tivity and specificity values of 71% and 85%, respec-
tively (78). Visualization of the normal and
particularly the narrowed ACA is more difficult than
that of the MCA (10). False-negative results for ACA
may be explained by collateral flow through the
ACoA and by problems with angiographic differentia-
tion of frequently occurring ACA hypoplasia from
vessel narrowing. The VACA/VICA ratio can be helpful
in the differentiation of ACA spasm from the normal
status of the artery. In practice, however, diagnosis of
unilateral spasm of the ACA is not obligatory, because
its hemodynamic consequences for the downstream
flow are generally not a cause of concern. On the con-
trary, bilateral ACA spasm may reduce flow to the
postcommunicating ACA segments, and TCCS can
detect increases in velocity involving at least one
artery. Very few data have been provided on TCD
diagnosis of spasm of the PCA and BA (79). A recent
study evaluating the reliability of TCD assessment of
BA VSP found a 100% sensitivity and a 95% specific-
ity by using a ratio of peak mean velocity in BA to
the velocity in extracranial VA over 2 as diagnostic
criterion (80). Normal reference ranges of the velocity
ratio VPCA/VVA (0.762.90) can also be helpful in
interpreting abnormal velocity results (76).
TCD is not useful for the detection of VSP directly
affecting the convexity or vertically oriented branches
of the intracranial arteries distal to the basal cisterns
(82,83), although the presence of VSP at these sites may
be inferred in some cases by indirect Doppler wave-
form observations (e.g., decreased diastolic flow,
increased pulsatility, side-to-side differences in pulsa-
tility indexes). Data on TCCS in this context are lacking.
TCD/TCCS is useful in monitoring the temporal
course of angiographic VSP after SAH. Although no
adequate study has been conducted, TCD is thought
to be valuable in the day-to-day evaluation of SAH
patients in VSP and to assess the effect and durability
of neuroradiological interventions (84,85). TCD has
been used to detect angiographic VSP following pro-
phylactic transluminal balloon angioplasty in SAH
patients at a high risk of developing VSP (86), as a
noninvasive surrogate endpoint, or to demonstrate
biological effects of treatments for vasoconstriction or
VSP in uncontrolled trials of pharmacological thera-
pies for eclampsia and SAH (8789). Data are insuffi-
cient to make a recommendation regarding the use
and method(s) of autoregulation testing to predict the
risk of delayed cerebral ischemia.
The follow-up TCD/TCCS studies to assess VSP
dynamics should begin at admission, when the proba-
bility of VSP is still relatively low, in order to determine
reference velocities for further comparison. In many
patients, the rate of velocity increases and the maximal
velocity can identify patients at greatest risk of sympto-
matic VSP. Such patients should receive daily TCD/
TCCS studies, while those with normal velocities and
no substantial velocity rise can be monitored every two
to three days throughout the period of the high risk of
VSP. In interpreting Doppler results, the global and
local ICP increase and disturbed autoregulation should
165
be taken into account. In every patient, the velocity
ratios (VMCA/VICA, VACA/VICA, and VPCA/VICA)
should also be calculated. Increased impedance indexes
may suggest the presence of localized or generalized
increased ICP or hydrocephalus, necessitating appro-
priate diagnostic evaluation and treatment. A patient
whose neurological condition is deteriorating and who
has a normal or nondiagnostic TCD/TCCS study
should undergo angiography to detect TCD/TCCS
occult VSP if another cause for deterioration is not
identified. In addition, patients with VSP whose condi-
tion does not improve or continues to deteriorate in
spite of aggressive conservative management should be
considered for urgent endovascular treatment. TCD/
TCCS can demonstrate the effectiveness of the treat-
ment by showing a decrease in flow velocities and
velocity ratios.
TCD/TCCS can be helpful in proper timing for
aneurysm clipping or coiling, and postoperative man-
agement. If flow velocities are very high (mean veloc-
ity in MCA above 150cm/sec) or there is evidence of
altered autoregulation and low CBF in the first or
second week after SAH, operative results may be
poor, in particular if the patient develops hypotension
during the procedure. After the procedure, transfer
from the intensive care unit or mobilization of postop-
erative patients is inadvisable in the presence of high
velocities and should be postponed until flow velocity
in the affected vessel begins to decline.
Surveillance of Coiled Intracranial Aneurysms
Endovascular detachable coil treatment is being
increasingly used as an alternative to craniotomy and
clipping for many ruptured intracranial aneurysms.
Since the long-term risk of reopening and possibly for
rebleeding after endovascular coiling is somewhat
higher than after surgical treatment, the persistence of
aneurysm occlusion after coil embolization is of con-
cern. A significant problem of endovascular therapy is
the known instability of initial coil packing, and com-
plete occlusion of the aneurysm is not always possible
without running a high risk of inadvertent vessel
occlusion or coil migration. Consequently, an initially
occluded aneurysm can recanalize, which may be
associated with higher risks of regrowth and rebleed-
ing. DSA is currently used as the primary imaging
technique for the immediate and long-term evaluation
of endovascular therapy of intracranial aneurysms.
Diagnostic DSA is performed at least three times: at
the end of coiling procedure and at 6 and 18 months
after the procedure. If reopening resulting in moderate-
to-extensive residual flow is seen in subsequent DSA
studies, then re-embolization therapy is usually under-
taken. DSA, however, is a costly and invasive proce-
dure. Furthermore, the estimation of aneurysm
occlusion can sometimes be difficult because of X-ray
attenuation of metal coils and artifacts caused by the
densely packed coils (Fig. 8.4).
TCCS may be more cost effective in the surveil-
lance of coiled intracranial aneurysms. TCCS can identify
large- and medium-sized intracranial aneurysms located
in the proximal segments of the circle of Willis (9092).
Typically, an aneurysm is imaged as a pulsatile colored
structure adjacent to the large parent artery.
166 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 8.4 TCCS can identify large- and medium-sized intracranial aneurysms in the proximal segments of the circle of Willis. Angiog-
raphy (A) shows large ICA aneurysm, which is depicted with power TCCS as red pulsatile color structure (B). Abbreviations: TCCS,
transcranial color-coded duplex sonography; ICA, internal carotid artery.
Aneurysms can display various flow patterns. The
most typical color-coded feature is the presence of two
areas with inversely directed flow: half of the aneurysm
is coded blue and the other half is coded red. The colors
correspond to the direction of inflowing and outflow-
ing blood. Between these two areas, a black separation
zone with undetectable blood flow can be recognized.
Flow velocities are usually low, without turbulence and
spontaneous velocity fluctuations. Aneurysms located
in the basal arterial trunks can be recognized more
easily than those situated in the periphery. The use of
sonographic contrast material can improve the reliabil-
ity of TCCS in the detection of aneurysms.
Preliminary reports suggest that TCCS with con-
trast enhancement is highly specific and sensitive in
the detection of clinically relevant residual flow within
an aneurysm after endovascular coiling. Schuknecht
et al. (93) reported that TCCS, performed immediately
after embolization, reliably confirmed complete occlu-
sion of 42 out of 43 aneurysms. In four other aneur-
ysms, a slight residual flow was recognized with TCCS.
Furthermore, in 3 (ophthalmic and basilar tip and cav-
ernous carotid aneurysm) of 26 aneurysms reexamined
6 to 20 months after treatment, reappearance of color
flow signal adjacent to the coils was detected, which
was in agreement with DSA. The persistent occlusion
in the other 23 cases was demonstrated by TCCS, which
was either confirmed by angiography in 13, or by MRA
in 10. Turner et al. (94) reported that TCCS confirmed
complete occlusion in 19 of 20 aneurysms, while minor
residual flow was detected with TCCS in 4 of 10 aneur-
ysms. In the detection of clinically relevant residual
flow, the results of standard TCCS were less consistent.
While moderate residual flow was detected in eight of
nine aneurysms (sensitivity 89%, specificity 97%), more
extensive residual flow was detected only in three of
seven aneurysms (sensitivity 43%, specificity 100%).
The use of contrast slightly improves the sensitivity of
TCCS in the detection of moderate (100%) residual
flow, but substantially improves sensitivity in aneur-
ysms with extensive residual flow (86%) (94,95). These
Left ICA terminal
(B)
studies suggest that TCCS could be used to selectively
monitor intracranial aneurysms, which would reduce
the requirement for long-term invasive monitoring. The
detection of neck refilling is improved with contrast
enhancement. In our study (unpublished data), which
is based on 107 patients with coiled aneurysms, we
found that standard TCCS can be very specific in
detecting moderate-to-severe residual blood flow in rel-
atively large (over 10-mm-diameter) aneurysms located
at the basilar tip, at the ICA bifurcation, and at the
AcoA area. Thus, TCCS has great potential to replace
DSA in the surveillance of coiled intracranial aneur-
ysms in selected locations (Fig. 8.5).
Vascular Malformations
TCCS studies of AVMs show a focal accumulation of
vascular convolutions as a color mosaic with abnor-
mal Doppler waveforms (96,97). TCCS and TCD can
also detect the hemodynamic abnormalities in feeding
and draining vessels. Typically, flow velocities in
feeding vessels are high, ranging from 140 to 200cm/
sec, and impedance indexes are low, indicating a drop
in distal resistance (98,99). Draining veins are
enlarged, channeling pulsatile arterialized blood away
from the AVM nidus (Fig. 8.6).
The diagnostic accuracy of TCD and TCCS in
detecting AVMs is not known. Large (>4cm) and
medium-sized (24cm) radiologically proven AVMs
are regularly detected (100). Because more than one-
third of small (<2cm) AVMs can be missed, TCD is
not considered a reliable diagnostic tool in this setting.
Nevertheless, both TCD and TCCS are useful in moni-
toring the effects of therapeutic procedures (101,102).
The Intracerebral Venous System: A Neurosonological
Study with TCCS
The straight sinus, basal cerebral veins, cavernous
sinus, and superior and inferior sagittal sinuses can be
insonated with TCCS. Normal peak-systolic velocities
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 167

(A) (B)

(C) (D)

Figure 8.5 TCCS can detect clinically relevant residual flow within an aneurysm after endovascular coiling. In a patient with ICA bifur-
cation aneurysm (A), TCCS shows coils as hyperechoic structure (BD), while TCCS in power mode identifies residual flow in the neck
and body of the aneurysm. Abbreviations: TCCS, transcranial color-coded duplex sonography; ICA, internal carotid artery.

usually range from 5 to 35cm/sec, varying from one
sinus to the other (103). In sinus thrombosis, flow
velocities may decrease, or they may markedly
increase to above 100cm/sec, most likely indicating
increased collateral circulation (104,105). Follow-up
studies show gradual normalization after a period of
months (105). Venous flow velocities are also affected
by ICP changes (106). Experience with cerebral vein
insonation, however, remains limited.
Current View on Microemboli Detection
The physical and technical aspects of ultrasonic detec-
tion of microembolic signals (MES) by TCD have
recently been reviewed (56,107,108). Particulate (solid,
fat) and gaseous materials in flowing blood have dif-
ferent acoustic impedance properties than surround-
ing red blood cells. The Doppler US beam is both
reflected and scattered at the interface between the
embolus and blood, resulting in an increased intensity
of the received Doppler signal. MES are usually
observed within the spectral envelope, while artifacts,
which can resemble MES, extend outside the envelope
and are bidirectional. The hierarchy of backscatter of
the US, in descending order, is gaseous emboli, solid
emboli, and normal-flowing blood (including transient
red blood cell aggregates). In clinical practice, how-
ever, it is difficult to determine whether a given MES
corresponds to a large platelet embolus or to a small
atheroma due to a considerable overlap between MES
characteristics. Several techniques have been proposed
to resolve these issues (Fig. 8.7) (109).
Technical limitations present considerable diffi-
culties. For example, using a higher-decibel threshold
improves reproducibility, but it can decrease sensitiv-
ity (110). In an attempt to establish a general consen-
sus among investigators, a committee of experts has
defined MES characteristics (107). Manual saving of
suspicious signals by the recording operator and sub-
sequent offline analysis is the standard practice today,
but it is cumbersome and time consuming. Automated
systems for embolus detection have been developed
(111,112). Their accuracy remains limited. Although
the optimal duration of insonation needed to achieve
maximum sensitivity is unknown, most centers moni-
tor for 30 minutes to 1hour (113). Longer periods of
insonation, or repeat studies, may be needed in some
instances.
MES have been detected in patients with asymp-
tomatic and symptomatic high-grade ICA stenosis,
prosthetic cardiac valves, myocardial infarction, atrial
fibrillation, aortic arch atheroma, fat embolization
168 NEUROINTERVENTIONAL MANAGEMENT
(A)
(C)
Figure 8.6 TCCS shows an AVM in the base of the skull as an area of color mosaic with abnormal low-resistance Doppler waveforms
(A, B). TCCS in power mode (C) shows the arterial convolution of AVM in red color, which can help identifying the feeder and drainer
vessels. Angiography shows that the AVM is supplied from right (D) and left side (E). Abbreviations: AVM, arteriovenous malforma-
tion; TCCS, transcranial color-coded duplex sonography.
syndrome, and retinal or general cerebral vascular
disease. In addition, these signals occur in coronary
catheterization, coronary angioplasty, direct current car-
dioversion, cerebral angiography, carotid endarterec-
tomy (CEA), carotid angioplasty, and cardiopulmonary
bypass. TCD can be used to localize the embolic source
or monitor the effects of antithrombotic treatment in
patients with atherosclerotic CVD (114). In patients
with high-grade carotid stenosis, sources of asympto-
matic MES may include ulcerated plaques (115) and
microscopic platelet aggregates and fibrin clots (116).
Asymptomatic cerebral microembolization was associ-
ated with an increased risk of further cerebral ischemia
in this setting (115).
Comparison between studies on MES detection
is difficult, however, because of differences in (1)
diagnostic criteria, (2) detection threshold, (3) instru-
ments and instrument settings, (4) nature and severity
of disease, (5) time between last symptom and detec-
tion of MES, and (6) incidence of MES (56,107). Never-
theless, TCD is probably useful to detect cerebral MES
in a wide variety of cardiovascular or cerebrovascular
disorders. However, current data do not support the
use of TCD for diagnosis or for monitoring response
to antithrombotic therapy in ischemic CVD.
(B)
(D) (E)
Furthermore, data have not shown that detection of
MES leads to improved patient outcomes.
US Monitoring of Neurointerventional Procedures
Carotid Angioplasty and Stenting
MES have been associated with a higher neurological
complication rate and are a potential cause of peripro-
cedural stroke after CEA. MES have also been
observed during carotid angioplasty and stenting
(CAS). The high frequency of MES, however, is not
associated with a chronic cognitive impairment as
shown by TCD monitoring, although CAS is accom-
plished with increased dislocation of microemboli
compared with the surgical approach (117). Conse-
quently, cerebral protection devices are increasingly
used. TCD monitoring can help assess the efficacy of
cerebral protection devices deployed during stenting
(118), though a recent study showed that the fre-
quency of procedure-related silent cerebral lesions
appeared to be independent of the number of MES
during the procedure (119). Also, a systematic micro-
scopic analysis of debris captured by the filter device
has no predictive value for potential cerebral ischemia
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 169

cm/s

100
]<=

80

cm/s

100
]<=

80

Figure 8.7 TCD can detect MES in major intracranial arteries. The upper image shows MES during carotid angioplasty and stenting,
performed without a protective device. The MES are also present at clam release during CEA (lower image). Also note that flow veloc-
ities rebound substantially after the clamp release. Abbreviations: TCD, transcranial Doppler ultrasonography; MES, microembolic sig-
nals; CEA, carotid endarterectomy.

after carotid artery stent placement (120). In CAS,
TCD monitoring provides insight into the pathogene-
sis of procedure-related cerebral events. Microemboli
during poststent dilation, particulate macroembolism,
massive air embolism, and angioplasty-induced asys-
tole are associated with adverse outcome, as are male
gender and prior cerebral ischemia (121). TCD moni-
toring can also predict early cerebral outcome after
carotid bifurcation CAS (122). In CAS, in addition to
such obviously adverse events as particulate macro-
embolism and massive air embolism, multiple MES
(> 5 showers) at postdilation after stent deployment
and angioplasty-induced asystole and hypotension
with a significant reduction in MCA blood flow veloc-
ities are associated with periprocedural cerebral defi-
cits. In combination with the presence of preprocedural
cerebral symptoms, these four TCD-monitoring varia-
bles reasonably differentiate between patients with and
without adverse cerebral outcome (122). Additionally,
color-coded duplex sonography of carotid arteries can
demonstrate hemodynamic improvement after ICA
stenting (123). A study suggests that asymptomatic
MES correlate with clinical risk (124). However, out-
come studies are required to determine whether MES
detection may allow prediction of stroke risk and moni-
toring of the effectiveness of therapy.
170 NEUROINTERVENTIONAL MANAGEMENT
Percutaneous Angioplasty in Posterior Arteries
TCD monitoring is also useful to detect MES during
and after percutaneous transluminal angioplasty
(PTA) in the posterior circulation (125). In the patients
with subclinical microemboli released from the dilated
vessels for three days after vertebral and subclavian
PTA, anticoagulant or antiplatelet therapies may pre-
vent embolic complications after the procedure.
Monitoring of Endovascular Treatment of Intracranial
Aneurysms
Selective occlusion of intracranial aneurysms with
detachable coils has an overall estimated procedure-
related permanent complication rate of 3.7% to 6.8%.
Thromboembolic events with partially or completely
persisting neurological deficits are reported in 2.4% to
5.2% of endovascular-treated patients (126). Intraproce-
dural systemic administration of heparin is widely
used in several institutes to reduce the risk of throm-
boembolism. Acute clotting at the thrombogenic inter-
ventional materials is considered the most important
source of thromboembolism during endovascular
embolization of cerebral aneurysms. Potential clinical
complications can be avoided by early recognition of
thrombus at the coilparent artery interface and by
administering appropriate medical therapy (127). TCD
monitoring during and immediately after coiling can
help identify patients at high risk of thromboembolic
complications. Those with high risk can be selected for
a therapy. A relatively low-dose intra-arterial abcixi-
mab infusion can immediately dissolve an acute throm-
bus that forms during intracranial aneurysm coil
placement (128). An inhibition of the platelet function
by acetylsalicylic acid might be yet another effective
strategy to minimize the rate of thromboembolism (129).
However, even if the anticoagulation strategy is
the most important factor to decrease the rate of
embolic events during aneurysm treatment, the strat-
egy has to balance the risks of thromboembolism and
bleeding (129).
Duplex Sonography of Carotid and Vertebral
Arteries
Sonographic Assessment of Vascular Pathology
The earliest atherosclerotic changes include intimal
thickening secondary to lipid deposits and lipid-laden
macrophage infiltration of the arterial wall (130). As
the process advances, atheromatous plaques begin to
protrude into the arterial lumen. Initially, these pla-
ques are covered with a fibrous cap that gives them
mechanical stability. Fibrous plaques are rarely associ-
ated with neurological symptoms. On US, they appear
smooth, isoechoic, and homogenous. During subse-
quent stages, increasing amounts of extracellular lip-
ids and cholesterol esters are deposited, calcification
occurs, and intraplaque hemorrhages develop, giving
the plaque a heterogeneous appearance on US exami-
nation (108). When the mechanical support of the pla-
que surface erodes, embolization of plaque contents
may occur. In addition, plaque surface ulcers may
develop and serve as foci for thrombus formation.
These plaques appear heterogeneous with variable
echodensities, calcific shadows, and surface irregular-
ities. Morphological and physiological features readily
assessed with US and associated with an increased
risk of cerebral infarction include intraplaque echolu-
cency, surface ulceration, and most importantly
degree of stenosis (Fig. 8.8).
Degree of Stenosis
The North-American Symptomatic Carotid Endarter-
ectomy Trial (NASCET), the European Carotid Sur-
gery Trial (ECST), and the Asymptomatic Carotid
Artery Surgery (ACAS) trial demonstrated the benefit
of endarterectomy in symptomatic and asymptomatic
patients with moderate and severe carotid stenosis
(131133). In NASCET, however, endarterectomy was
only marginally beneficial when the degree of
stenosis was between 50% and 70%, underscoring the
importance of accurately measuring the severity of
stenosis. Ultrasonography must therefore be able to
distinguish between a carotid stenosis of 50% and of
70% in symptomatic patients and to identify 60%
diameter stenosis in asymptomatic patients.
Noninvasive evaluation of the extracranial ICA
with color duplex US and MRA is increasingly
regarded a replacement of DSA, but the role of ultra-
sonic quantification of narrowing is not undisputed
(134). In a recent study comparing duplex US to DSA,
duplex ultrasonography misclassified 28% of patients
considered candidates for CEA (135). Other studies
suggest that this classification can be performed more
accurately if high standards of ultrasonography are
maintained (136138).
Various diagnostic criteria have been proposed
for determining the percentage of stenosis (see reviews
of the criteria and tables) (108,138,139). These include
peak-systolic velocity, end-diastolic velocity, and the
ratio of peak-systolic velocities in the ICA to the mid-
CCA (ICA/CCA ratio). The peak-systolic velocity has
traditionally been felt to provide the closest angio-
graphic correlation and is easily obtained; however,
many laboratories rely also on the end-diastolic velocity
or the VICA/VCCA ratio to obtain improved diagnostic
accuracy and to correct for factors that may alter the
carotid blood flow. Such factors include low cardiac
output, valvular disease, acute elevations in blood pres-
sure, anemia, and abnormal collateral flow. Any of
these conditions may lead to flow alterations across a
carotid plaque and to either over- or underestimation
of the true degree of stenosis. In these instances, the
VICA/VCCA ratio often helps in correcting for hemody-
namic disturbances, but it has limitations (108). The
diagnostic impression is further confirmed by B-mode
and color flow imaging, which allow visual inspection
of the degree of stenosis caused by the plaque. A quan-
titative cross-sectional analysis of plaque stenosis
derived from color flow images was recently proposed,
which further increases diagnostic accuracy (140).
Reference Values
A wide range of criteria have been proposed to identify
the clinically relevant degrees of ICA stenosis. They are
summarized in Tables 8.2,8.3,8.4. The diagnostic accu-
racy of duplex US ranges between 85% and 95% and
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 171

(A) (B)

(C) (D)

Figure 8.8 Atherosclerotic plaques on US images. (A) Homogenous, soft, and fibrous plaque at the ICA origin without velocity
increase. In another patient, (B) the soft plaque in the ICA is irregular with hypoechoic area within the plaque as a potential source of
thromboembolism. In the third patient, (C, D) plaques are more complex with calcification. In the left, ICA (C) plaques cause over 70%
stenosis with subsequent peak-systolic velocity increase to 270cm/sec, while on the left side irregular plaques cause less than 50%
ICA narrowing. Abbreviations: US, ultrasound; ICA, internal carotid artery.

varies among laboratories. A survey of diagnostic crite-
ria showed that at least nine different diagnostic
parameters are currently used to measure the severity
of stenosis (141). These differences among laboratories
illustrate the fact that US testing is equipment and
operator dependent, and they emphasize the necessity
for each laboratory to develop its own diagnostic crite-
ria on the basis of DSA correlations (142,143).
Clinical Utility of Carotid Duplex
Characterization of plaque morphology and determi-
nation of degree of vessel stenosis are the most com-
mon clinical applications of carotid US and were
reviewed in many publications (108). In interventional
neuroradiology, carotid US is also used in the follow-
ing areas.
Monitoring After Revascularization Procedures
While the practice of serial follow-up examinations
after endarterectomy is intuitively appealing, the
value of routine postoperative surveillance is uncer-
tain. The incidence of restenosis (defined as a reduc-
tion in diameter of more than 50%) varies between
2% and 20% at one to three years after surgery (156), but
the incidence of recurrent symptoms is low (157,158).
Restenosis within two years of surgery is usually sec-
ondary to intimal hyperplasia and carries a benign
prognosis, since the risk of distal embolism is low and
lesions often regress (158,159). Late restenosis is most
likely secondary to recurrent atherosclerosis, and the
associated risk of ipsilateral hemispheric or retinal
symptoms may not be different than that of the origi-
nal primary lesion (159). In a small percentage of
cases, postoperative testing shows evidence of throm-
bus formation at the endarterectomy site, intimal flaps,
and occlusion.
Intracarotid and intravertebral stent placement is
being performed with increasing frequency. Repeat
testing after stent placement usually reveals an
improvement of the intraluminal hemodynamic pat-
tern. It is unclear, though, whether the diagnostic cri-
teria presented in Tables 8.2,8.3,8.4 are applicable in
the detection and monitoring of in-stent stenosis.
Arterial Dissection
The US features of dissection are less specific than
those observed with angiography and usually reflect
172 NEUROINTERVENTIONAL MANAGEMENT

Table 8.2 Diagnostic Parameters for Internal Carotid Artery Stenosis of 70% or More
Reference Diagnostic criteria Sensitivity (%) Specificity (%) Accuracy (%)
139 VPS > 230 80 90 NR
144 VPS > 325 83 100 88
ICA/CCA VPS ratio > 4 91 87 88
145 VED > 100 77 85 80
VPS > 210 89 94 93
VPS > 130 and VED > 100 81 98 95
146 VPS > 270 96 86 88
VED > 110 91 93 93
VPS > 270 and VED > 110 96 91 93
147 VED > 70 92 60 77
ICA/CCA VED ratio > 3.3 100 65 79
VPS > 210 94 77 83
ICA/CCA VPS ratio > 3 91 78 83
148 VPS > 130 and VED > 100 87 97 95
149 VPS > 230 86 90 89
VED > 70 82 89 87
ICA/CCA VPS ratio > 3.2 87 90 89
All velocities in cm/sec.
Abbreviations: NR, not reported; Vps and Ved, peak-systolic and end-diastolic velocities, respectively; CCA and ICA, common and inter-
nal carotid arteries, respectively.

Table 8.3 Diagnostic Parameters for Internal Carotid Artery Stenosis of 60% or More
Reference Diagnostic criteria Sensitivity (%) Specificity (%) Accuracy (%)
150 VPS > 260 and VED > 70 84 94 90
151 ICA/CCA VPS ratio > 2 97 73 76
VED >40 97 52 86
ICA/CCA VED ratio > 2.4 100 80 88
VPS > 170 98 87 92
152 VPS > 245 and VED > 65 89 92 NR
All velocities in cm/sec.
Abbreviations: NR, not reported; Vps and Ved, peak-systolic and end-diastolic velocities, respectively; CCA and ICA, common and inter-
nal carotid arteries, respectively.

Table 8.4 Diagnostic Parameters for Internal Carotid Artery Stenosis of 50% or More
Reference Diagnostic criteria Sensitivity (%) Specificity (%) Accuracy (%)
153 VPS > 120 79 84 82
145 VPS > 130 97 97 97
154 ICA/CCA VPS ratio > 1.6 95 92 93
155 EDV > 50 91 86 89
VPS > 150 98 84 92
ICA/CCA VPS ratio > 2 96 89 93
149 ICA/CCA VPS ratio > 1.6 93 83 88
VPS > 130 92 90 91
All velocities in cm/sec.
Abbreviations: Vps and Ved, peak-systolic and end-diastolic velocities, respectively; CCA and ICA, common and internal carotid arteries,
respectively.

flow abnormalities seen in high-grade stenosis secon- Pitfalls of Carotid Ultrasonography

dary to any etiology: high flow velocities, high resist-
ance flow patterns, or complete absence of flow
(108,160). Despite the advantage of US in displaying
luminal irregularities, an intimal flap is infrequently
seen, possibly because the size of the flap lies beyond
the resolution of US (Fig. 8.9) (161).
US is helpful in monitoring the course of natural
repair. Vertebral dissections follow a similar course.
VA flow disturbances are nonspecific and show the
same patterns as any stenotic lesion associated with
intraluminal hemodynamic change. Such patterns
include absence of a flow signal, bidirectional or
dampened flow, and elevated flow velocities with
associated turbulence (162,163).
Carotid Occlusion
US diagnosis of a carotid occlusion remains unreliable,
as a minimally patent arterial lumen with a trickle of
flow can be missed. In the case of symptomatic athero-
sclerotic disease, such a differentiation is vital because
CEA or CAS is clearly indicated in a patent vessel, but
is generally not possible in the case of occlusion. Early
reports suggested a diagnostic accuracy of 85% for ICA
occlusion, but in more recent studies, which were based
on color duplex imaging, the accuracy was shown to
exceed 96% (164,165). Difficulties arise from the pres-
ence of calcific plaque formation and the low flow
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 173

(A) (B)

(C) (D)

Figure 8.9 Carotid US of common carotid artery dissection. Grayscale image (A) shows luminal irregularities and an intimal flap. Color
image (B) confirms absence of flow beneath the flap. In the ipsilateral internal carotid artery (C), the flow pattern is abnormal with dis-
appearance of flow during diastole (high-resistance flow pattern). Note, compensatory high-velocity flow pattern in the VA (D). Abbre-
viations: US, ultrasound; VA, vertebral artery.

volume in near occlusions. In addition, arterial tortuos-
ity may cause angle artifacts, further compromising
sensitivity. Diagnostic confusion may also arise when
an external carotid artery branch overlies the ICA
occlusion and is incorrectly identified as a patent resid-
ual lumen. In some patients with ICA occlusion, the
external carotid artery assumes a low-resistance pattern
as it provides collateral flow to the brain. Tapping the
fingers over the temporalis muscle and the identifica-
tion of vascular branches may help differentiate the
external from the internal carotid artery. The ICA
occlusion and high-grade stenosis also lead to diagnos-
tic difficulties in determining the degree of stenosis on
the contralateral side. Increased contralateral flow
velocities may be secondary to collateral flow and lead
the sonographer to overestimate the degree of true
stenosis. In such cases, the use of peak-systolic velocity
alone is insufficient and misleading. The overestimation
is proportional to the degree of contralateral stenosis.
Increasing the number of diagnostic criteria in the set-
ting of contralateral stenosis improves the diagnostic
accuracy. The VICA/VCCA ratio may accurately reflect
the degree of stenosis in this setting.
velocities can then only be measured proximal and
distal to the lesion, and elevated flow velocities at the
level of the stenotic plaque can be missed (108). If the
width of the acoustic shadow does not exceed 1cm, it
may be inferred from normal distal flow velocities
that a high-grade lesion is not present.
Tortuosity
With the aging process, the ICA can become elongated
and develop loops or kinks, which may cause
increases in flow velocity, suggesting a focal area of
stenosis. Color duplex examinations are particularly
helpful in these cases.
High Bifurcation
In patients with high CCA bifurcation, the mandible
interferes with the US evaluation. A posterior
approach in these instances often allows a better eval-
uation of the artery.
Extracranial VA

Calcification Atherosclerotic plaques of the extracranial VA are usu-

ally localized at the arterys origin from the subclavian
Heavily calcified plaques often cast an acoustic artery, and they also tend to involve the vertebrobasilar
shadow that prevents duplex examination. Doppler junction. In addition, the VA is also susceptible to
174 NEUROINTERVENTIONAL MANAGEMENT
dissection at the V1 and V3 segments. Intraluminal
flow characteristics can be readily assessed with extrac-
ranial US. However, velocities are usually measured
only in the V2 intravertebral segment. Interrogation at
this point allows determination of flow direction and
pattern, but it gives only indirect evidence about proxi-
mal or distal stenotic lesions. Insonation of the VA
origin is technically difficult because of its deep intra-
thoracic location, which does not always allow for opti-
mal angle correction. Normal values range between
19 and 98cm/sec for peak-systolic velocity, and 6 and
30cm/sec for end-diastolic velocity (108,166). For the
normal VA origin, a peak-systolic velocity of 69cm/sec
and end-diastolic velocity of 16cm/sec have recently
been reported (167). Compared with the ICA and
MCA, flow is slower in the vertebrobasilar trunk.
There are no established US criteria for VA
stenosis. Hemodynamically significant VA disease can
be inferred when a focal flow velocity increase of 50%
or more is detected. The presence of a high-resistance
pattern suggests high-grade distal stenosis (168). How-
ever, because the resistance pattern is highly variable,
it is an unreliable finding, which is further con-
founded by the frequent presence of congenital var-
iants in the vertebrobasilar circulation, including
intradural VA hypoplasia (169). Flow in a hypoplastic
vessel may be dampened, mimicking a high-resistance
pattern with almost absent diastolic flow. This charac-
teristic confuses the interpreter and affects the tests
accuracy. Experience with extracranial VA US remains
limited, and the technique is not used as often as for
ICA disease. The subclavian steal syndrome is usually
a result of high-grade stenosis or occlusion of the
proximal subclavian artery. As perfusion pressure and
blood flow in the arm drop, the ipsilateral VA acts as
a collateral vessel, channeling blood distal to the
obstruction. Flow direction in the VA is reversed. The
syndrome can be diagnosed with US with high sensi-
tivity (Fig. 8.10) (170,171).
THERAPEUTIC USE OF US
Physical influence of US on body tissues, described at
the beginning of this chapter as direct heating, cavita-
tion, radiation pressure and acoustic streaming, may be
used in the controlled environment for treatment pur-
poses. Nondestructive mechanical heating of tissue to
stimulate or accelerate the normal physiological
response to injury was used initially for the treatment
of inflammatory conditions in the first half of 20th cen-
tury. Present research and clinical applications of US
use in the field of neurology embrace US-accelerated
thrombolysis in acute stroke, localized ablation, selec-
tive destruction of brain tissues with focused ultra-
sound (FUS), bloodbrain barrier (BBB) disruption for
targeted drug delivery or gene therapy, coagulation
and antitumor immunization.
US-Enhanced Thrombolysis in Acute Stroke
The current treatment of acute ischemic stroke
requires intravenous delivery of a large dose of a ser-
ine protease, such as tPA, urokinase, or streptokinase,
within three hours of symptom onset. Proteases work
by converting plasminogen to the natural thrombolytic
agent, plasmin (20,21,172). Plasmin lyses thrombotic
vascular occlusions by degrading fibrinogen and fibrin
contained in a blood clot. If therapeutic recanalization
of the occluded artery is prompt, a favorable outcome
is anticipated in about 60% of those with an ischemic
stroke compared with spontaneous thrombolysis,
which occurs in up to 20% of patients with variable
clinical recovery. With tPA treatment, a faster recanal-
ization results in moderate clinical improvement.
Small increments of delay in treatment decrease chan-
ces for timely return of flow and favorable outcome,
supporting the concept Time is brain.
If a thrombolytic agent is delivered three hours
after onset of symptoms, the risk of hemorrhagic
transformation increases substantially; however, by
using catheter-directed arterial delivery of the throm-
bolytic drug, the treatment window can be extended
to six hours with relatively low risk of hemorrhage
(22,173,174). This procedure involves a much smaller
dose of the trombolytic agent and is directly delivered
to the thrombus in the clotted artery. After six hours,
there is no effective pharmacological thrombolytic
treatment, because if late reperfusion occurs, the area
of ischemic stroke may convert into the much more
severe hemorrhagic stroke with worsened outcomes.
However, thrombolytic agents alone, even if
given in the desired time windows, have limited suc-
cess in recanalyzing thrombotically occluded arteries
(175,176). Major reasons for incomplete recovery
include a severe initial ischemic insult and slow and
incomplete thrombolysis (177,178). Successful throm-
bolysis depends on the delivery of tPA to the throm-
bus through residual blood flow around the arterial
obstruction (179,180). As such, there is a strong need
to enhance the effectiveness of thrombolytic agents by
shortening the time to reperfusion. Experimental and
limited clinical studies suggested sufficient penetra-
tion and thrombolytic effects of either low-frequency
(181,182) or diagnostic (183) US through the skull in
vitro and, hence, encouraged empiric assessments of
US for thrombolysis even with standard US equip-
ment (184).
Mechanism of US-Accelerated Thrombolysis
The mechanisms for US-accelerated thrombolysis in
externally applied exposures are unclear. Early studies
demonstrated that the effect was primarily nonther-
mal and did not involve mechanical fragmentation
(185). Enhancement has been shown to decrease with
increasing frequency and increase as a function of
time as the duty cycle is varied (186). US increases
the uptake of tPA into a clot, suggesting that enzyme
transport is important (179). It also increases the binding
of tPA to fibrin by maximizing access of the enzyme to
potential binding sites on the fibrin matrix (187). Fur-
thermore, it can reversibly increase fluid permeation
through fibrin (188), a finding shown to depend on
reversible increases in the number of fibers per unit
area and concomitant decreases in fiber diameter dur-
ing US exposure. Degassing reduces the effect of US
on flow through fibrin and associated structure
changes. These and other clues implicate gas concen-
tration as an important factor and suggest that acoustic
cavitation (see the section Technical Aspects of US
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 175

Figure 8.10 Subclavian steal syndrome as a result of high-grade stenosis of the proximal subclavian artery. The ipsilateral VA acts as
a collateral vessel, channeling blood distal to the obstruction. Flow direction in the VA is reversed, which is shown in red color com-
pared with the flow direction in the common carotid artery shown in blue color (upper image). Duplex US shows abnormal waveform
pattern (lower image). Abbreviation: US, ultrasound.

Imaging) may be a dominant mechanism. In stable
cavitation, the stiffness of the gas in the MBs controls
the radial pulsations of MBs driven by the US field. If
a bubble is induced to grow by US to a diameter
larger than the pore size of the fibrin lattice surround-
ing it, stretching of clot fibers may occur. Micro-
streaming around the MBs may cause damage to
nearby cells or fibers, or act to stir fresh fibrinolytic
enzyme into otherwise inaccessible regions in a clot.
In inertial cavitation, the radial motion of a bubble is
controlled by the inertia of the rapidly moving liquid
surrounding it. For symmetrical collapse, hot spots can
form that can produce hydroxyl free radicals capable
of attacking nearby fibers (8). For asymmetrical col-
lapse, microjets may form that can damage nearby
fibers in the manner of pitting on a ships propeller. If
MBs collapse sufficiently violently to produce broad-
band acoustic emissions, additional inertial cavitation
may produce localized stresses, hot spots, or microjets
that may further alter the structure of clot fibers.
176 NEUROINTERVENTIONAL MANAGEMENT
In all cases, US-driven MBs might exteriorize new
binding sites along fibers to allow fibrinolytic enzymes
increased access [see editorial by Polak (189)].
Besides cavitation, other effects, which depend
on the level of US energy applied, may play an impor-
tant role in vitro when the diagnostic range of US is
used. At very low energies, US promotes micro-
streaming of blood close to the occluding thrombus
and enhances the mixing of tPA, effectively increasing
the concentration of the agent that is in contact with
the thrombus. The pressure waves that are generated
may also increase the permeation of tPA into the inte-
rior of the fibrin network. At slightly higher US ener-
gies, the binding of tPA to the cross-linked fibrin and
fibrin elements within a matrix is enhanced, in vitro
(190), and the fibrin cross-links are weakened, further
increasing the binding of tPA. It is also possible that
the heat generated by US is additionally responsible
for accelerating thrombolysis (191). Experiments have
confirmed that the temperature elevation generated by
US of sufficient power can increase the dissolution
rate of thrombi. A major limitation of TCD, however,
is attenuation of US by the bones of the cranium;
consequently, diagnostic imaging and the therapeutic
use of US may not be possible in 10% to 15% of
patients (12). The US beam becomes attenuated, and
90% of energy is deposited in the bonesoft tissue
interface. Consequently, only 10% of the maximum
output intensity hits the thrombus, which comes to an
effective energy of about 0.07 W/cm2. Solid data con-
cerning comparatively low levels of energy and their
effects on thrombolysis are lacking. In summary, the
mechanism responsible for the effect of US on throm-
bus dissolution is not completely known.
The excessive heat deposition at the bonesoft
tissue interface is a major limitation in applying
higher US power through the temporal window, in
particular at higher-frequency US. To overcome this
problem, several strategies were developed: first, to
use endovascular wires and transducers to deliver
US locally; second, to use lower-frequency and sub-
sequently higher-power US for transcutaneous
US-enhanced thrombolysis; third, to use US contrast
to induce and increase the number of cavitations at
the site where the US beam of a high MI is targeted.
Endovascular US Thrombolysis
Intravascular devices such as vibrating wires at fre-
quencies of 20 to 25 kHz delivering very high power
levels of US of up to 20 W locally have been shown to
disrupt the clots in vitro (192194). This approach has
been used to fragment, mechanically, thrombi into
small particles, resulting in reperfusion in patients
with obstructed peripheral arteries (195197). These
arteries require great angiographic skill besides disad-
vantages such as unknown effects of distal emboliza-
tion of fragments, damage or perforation of the vessel
wall, heating, and ultrasonic wire breakage.
Miniaturized transducers also have been
attached to catheters for direct endovascular use,
offering the potential of localized US thrombolysis
while avoiding attenuation of intensity through the
skull and reducing insonation of the surrounding tis-
sue. Tachibana and Tachibana demonstrated enhanced
clot lysis in vitro using a microtransducer operating at
225 kHz. Similar in vitro results were demonstrated
for combined application of US (170 kHz, 0.5 W/cm2)
and thrombolytic infusion (198). The specialized US
thrombolytic infusion catheter (EKOS Corporation,
Bothell, Washington, U.S.) combines the use of a mini-
ature US transducer on the tip of the catheter with
infusion of a thrombolytic agent through the catheter.
After a bolus of tPA is injected, an infusion of tPA is
started with simultaneous US given for up to one
hour. Human trials showed great promise. Only large
vessels can be effectively treated with US, but tPA
may lyse peripheral fragments in the area. The delays
involved with angiography and demands for very
skilled operators, which apply to all mechanical devi-
ces, limit the potential of endovascular use of micro-
catheters for acute stroke treatment to specialized
centers; thus, a broader applicability seems unrealistic.
Transcutaneous US-Enhanced Thrombolysis
Noninvasive external application of US has greater
potential for wider therapeutic application because it
requires neither angiography nor selective catheteriza-
tion, eliminates the risk of vessel damage by the cathe-
ter, and can be used for vessels too small or
inaccessible for catheterization. Frequencies used
include 20 kHz (199), 40 kHz (200), 170 kHz (201,202),
300 kHz (182), 1 MHz (185,186,195,202,203), and
2 MHz (204), at intensities from 0.25 to 10 W/cm2.
In vitro studies have shown various levels of
moderate thrombolytic improvements averaging 30%
to 40% and required one to three hours of insonation to
get the effect (205). Several studies confirmed lytic
activity during transtemporal delivery of US using a
transducer similar to a regular TCD transducer. Lower
frequencies penetrate the skull more efficiently than
higher frequencies. Standard physical therapy devices
used a 1-MHz frequency for delivery, while TCD devi-
ces used a 2-MHz frequency to measure flow velocity.
In human clinical trials, recovery rates higher
than expected with simple tPA treatment have been
described (184,204,206,207). Better rates of recanaliza-
tion have been seen with those treated with continu-
ous US as well as tPA. Several reports showed the
bleeding rate with this technique to be similar to that
with simple tPA therapy.
The largest of these studies, the CLOTBUST
phase II study (204), used a standard TCD aimed by a
skilled sonographer at MCA thrombus in 126 random-
ized acute ischemic stroke patients. The flow in the
artery was observed, and intravenous tPA was given.
Continuous full-power TCD was used for two hours,
and flow was assessed intermittently. The US beam is
quite narrow; thus, it requires a highly skilled sonog-
rapher to target the occluded segment and keep the
beam on target using specially designed head frame.
The study showed that the technique is safe and that
TCD enhances recanalization.
Using lower frequencies (20 kHz to 1 MHz) than
those used for diagnostic purposes, tPA-mediated clot
degradation was shown to be as much as 50% more
efficient when US was applied transcranially (181,183).
As mentioned above, the CLOTBUST study using
2-MHz transcranial probes suggested enhancement of
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY
tPA activity with acceleration of arterial reperfusion, but
so far did not demonstrate clinical improvement.
Although encouraging, these data lack confirmation of
vascular and brain tissue effects through criterion stand-
ard imaging procedures and are in contrast to experi-
mental studies using diagnostic US plus tPA (208).
Consequently, Transcranial Low-Frequency US-
Mediated Thrombolysis in Brain Ischemia (TRUMBI)
trial (205), a phase II, prospective, nonrandomized study
at six German university stroke centers, was scheduled
to test safety and practicability of thrombolytic therapy
in acute stroke patients with combined application of
tPA plus low-frequency US. A secondary objective was
to compare clinical recovery and rates of recanalization,
reperfusion, and infarct size as evidenced by serial MRI.
Patients were alternately allocated a standard 0.9-mg/kg
tPA treatment and a combination of tPA treatment with
transcranial insonation of low-frequency pulse-wave
mode US (NeuroFlowTM, Walnut Technologies, And-
over, Massachusetts, U.S.) for 60 to 90 minutes.
The study was prematurely stopped because 5 of
12 patients from the tPA-only group, but 13 of
14 patients treated with the tPA plus US, showed
signs of bleeding in MRI. Within three days of treat-
ment, five symptomatic hemorrhages occurred within
the tPA plus US group (r-tPA) thrombolysis in
humans using low-frequency US (6).
Two reasons were considered to be responsible
for the increased risk of hemorrhage, the thermal
effect and disruption of the BBB.
A study by Fatar et al. (209) showed that brain
temperature increases within two to five minutes of
insonation. The brain temperature increase and cool-
ing time, however, were in proportion to power level,
and even with the highest intensity of 7 W/cm2 for
30 minutes, the maximum elevation of mean brain
temperature was 0.98C, with the highest cooling time
of 40 minutes. However, no deleterious side effects of
this treatment were found in histological examination.
Another study by Reinhard et al. (210) showed
abnormal permeability of the BBB after insonation
with low-frequency US generated by the NeuroFlow.
It indicates that the observed excessive bleeding rate
with low-frequency sonothrombolysis also involving
atypical locations (such as the intraventricular or sub-
arachnoid space) might in fact be attributable to pri-
mary disruption of the BBB. In comparison with
routine 2-MHz Doppler devices, as used in the CLOT-
BUST study without hemorrhagic side effects, the
applied device had a wider sonification field but com-
parable power. Transient disruption of the BBB by
focused US has been described recently in animals
when it is applied in the presence of preformed gas
bubbles (9). Ultrastructural animal studies have,
among other mechanisms, proposed endothelial injury
with high power, but partial opening of tight junctions
already with low-power insonation (211).
A clue to the mechanism of BBB disruption is
that it occurs distant to the target volume: Standing
waves near the bone at the borderzone of the large
insonation field may have occurred during continuous
insonation and lead to local heating or mechanical
effects disrupting the BBB. Therefore, small-field inso-
nation should likely be preferred for sonothrombolysis
in acute ischemic stroke.
177
MB-Augmented US Thrombolysis
MBs are small air- or gas-filled microspheres with
specific acoustic properties that make them useful as
US contrast agents for sonographic examinations. Two
agents (Definity, Bristol-Meyers-Squibb Medical Imag-
ing, Inc., Princeton, New Jersey, U.S., and Optison,
Amersham Health, Princeton, New Jersey, U.S.) are
commercially available with FDA approval for use in
clarifying the outlines of the ventricles in cardiac US
imaging. In diagnostic US, MBs create an acoustic
impedance mismatch between fluids and body tissues,
increasing the reflection of sound. Experimental stud-
ies have shown that US-accelerated thrombolysis may
be further enhanced by administration of MBs
(201,212,213). Low-frequency US with high power has
been demonstrated to produce cavitation and fluid
motion into the thrombus (213,214). MBs, by acting as
cavitation nuclei, lower the amount of energy needed
for cavitation. Application of high-acoustic-pressure
US has been shown to induce nonlinear oscillations of
MBs, leading to a continuous absorption of energy
until the bubbles explode, releasing the absorbed
energy (215). Thus, US-mediated MBs destruction may
further accelerate the clot-dissolving effect of US.
The synergistic effect of US and MBs on sono-
thrombolysis has been demonstrated in clinical studies
in patients with arteriovenous dialysis graft thrombo-
sis (216). Molina et al. investigated the effects of
galactose-based MBs on the beginning, degree, and
time to maximum completeness of MCA recanaliza-
tion after application of tPA intravenously plus 2-hour
continuous 2-MHz TCD monitoring plus three boluses
of 400mg/dL of the galactose-based MBs (Levovist),
given at 2, 20, and 40 minutes after tPA administra-
tion (217). They showed that administration of MBs
further enhances US-augmented systemic thromboly-
sis in acute ischemic stroke, leading to a more com-
plete arterial recanalization and to a trend toward
better short- and long-term outcome.
Further research is required to evaluate possible
combinations of thrombolytic drugs, MBs, and various
modes of US delivery. Once these combinations can
be assessed, some new techniques should be ready for
application in humans. Currently, human CLOTBUST
studies are progressing rapidly and involve not only
thrombolytic drugs but the addition of MBs and of
dedicated machines to make US delivery easier and
more reliable.
Focused US surgery
Heating of the live tissues above the threshold of
denaturation of proteins (5760C) for a short period
of time causes coagulation necrosis. Tissue destruction
may also occur at lower temperatures; however, the
exposure should be longer. Thermal heating caused
by absorption of ultrasonic energy by the tissues is
dependent on the intensity of the US energy and the
acoustic (US) absorption coefficient of the tissue. It is
assumed that almost all of the energy from the pri-
mary US beam results in tissue heating (218). In FUS
surgery, where the US beam is focused by acoustic
lens, the ultrasonic intensity at the beam focus is
much higher than that outside of the focus (219).
178 NEUROINTERVENTIONAL MANAGEMENT

Focusing of the beam allows to quickly elevate temper-
ature in tens of degrees of Celsius causing tissue coagu-
lation and denaturing tissues within seconds (220), and
only very limited volume is destroyed.
Intracranial pathologies seemed to be ideal for
treatment with US. Initial clinical experience included
various neurological disorders such as Parkinsons
disease (221), dementia paralytica, torticollis (222),
pain, psychoneuroses, anxiety, depression, and epi-
lepsy. The high-intensity US was found to be safe for
the destruction of brain tumors (223225). Most of
these treatments were performed after a craniectomy,
through the skin, where transducers were placed over
the US window, because of distortions of US field
caused by skull bones. Also absorption of the energy
that resulted in local heating of the cranium required
the craniectomy for the procedure. The solution for
that was focusing of the US beam, and dynamically
steering the focal point using positioning systems or
phased-array transducers. Greater control over the
acoustic field can be achieved by transducers that con-
sist of multiple elements with individual driving
signals (Fig. 8.11). Using full hemispheric phased
arrays around the head, the focus can be restored by
adjusting the driving phase of each phased-array ele-
ment according to the thickness of the underlying bone
(226229). Hemispheric arrays may be useful to target
different locations, to increase the focal volume per
sonication and to simultaneously create multiple focal
points. The aberration corrections are achieved using
acoustic models based on X-ray computed tomography
(CT) scans of the skull (Figs. 8.12, Fig. 8.13).
A noninvasive FUS procedure requires addi-
tional imaging for anatomical targeting and therapy
control. MR imaging has excellent sensitivity for soft
tissue tumors, for targeting tumor margins and for
quantification of tumor volumes. Additionally, MRI
allows to measure tissue temperature changes with
sensitivity better than 2C. Tissue temperature is
accepted as a surrogate measure of tissue viability.
Combination of MRI with FUS as a magnetic reso-
nance imaging-guided high-intensity focused ultra-
sound (MRgFUS) permits for image guidance for each
step of the procedure, thermal imaging to verify the

RF Emitting Skull Focal

Signals elements bone spot
010528c

2
z (mm)

4
4
2 4
0 2
0
2
y (mm) 2
4 4 x (mm)
(A)

RF Emitting Skull Focal

Signals elements bone spot
010528a

2
z (mm)

4
4
2 4
0 2
0
2
y (mm) 2
4 4 x (mm)
(B)

Figure 8.11 Schematic shows phased arrays in transcranial focal US. (A) No phase correction. (B) Phase correction to compensate
for skull thickness. Source: Courtesy Jolesz F, National Center for Image Guided Therapy, Boston, MA.
 ULTRASONOGRAPHIC IMAGING AND PHYSIOLOGIC TECHNIQUES IN INTERVENTIONAL NEURORADIOLOGY 179

focal coordinate before ablation, to monitor the tem- BBB Disruption

perature elevation to ensure a sufficient thermal dose
is delivered only to the focal zone and post-treatment
verification of the ablation. With real-time feedback on
tissue viability with MRgFUS, the treatment is person-
alized, and overtreatment may be avoided. Addition-
ally, it is not cumulative and can be repeated as many
times as necessary. MRgFUS is also more precise and
can cause less damage to adjacent structures than
radiosurgery.
Clinical applications at present are limited,
because of lack of sufficient scientific evidence and
limited access to very sophisticated equipment. FUS
in glioma treatment, similarly to conventional surgery,
is not able to destroy the entire tumor, because most
glioma is infiltrative and, in most cases, tumor coex-
ists with normal functioning brain tissue. Ablative
treatment with FUS may be of higher importance in
treatment of well-defined metastasis or benign brain
tumors. Real-time control of temperature provides a
precise step-by-step coagulation that can be done
close to nerves, cortical and subcortical grey matter,
and other critical structures (230). FUS can be ideal
for benign tumors that are inoperable because of inac-
cessible location (e.g., brainstem) or because of close-
ness to cranial nerves. McDannold et al., evaluated
clinical feasibility of MRgFUS in three patients with
glioblastoma, where they were able to focus US beam
through intact cranium in the desired target and to
monitor local temperature changes with MRI; how-
ever, they did not achieve thermal coagulation due to
low power of the device (231). In the future, FUS abla-
tive surgery may be useful for functional neurosurgi-
cal applications such as movement disorders,
epilepsy, or pain (232). Localized acoustic energy
delivery can block nerve conduction; thus, local
acoustic anesthesia can be used for pain control and
the treatment of spasticity (233).
Acoustic cavitation occurs in the presence of the gas
containing MBs generated by acoustic pressure waves
in the fluids and in tissues, or administered intrave-
nously as US imaging contrast agents. MBs may grow
in the focal area and interactively oscillate with US.
At low energy levels, cavitation may cause reversible
increase in permeability of vascular walls or cellular
membranes (234,235). This mechanism may be used
for targeted delivery of macromolecules. BBB is a con-
tinuous obstacle for therapeutic macromolecules deliv-
ery to central nervous system. Drugs or genes,
encapsulated in gas-containing MBs or liposomes,
administered systemically, using FUS may be released
in the focal spot to the blood stream or through BBB
(236,9). Experimental results showed ability to locally
deliver through BBB large molecules as antibiotics,
chemotherapeutics and antibodies (237240).
Coagulation
In animal experiments, FUS have been shown to pro-
vide an effective method of acute hemorrhage control,
with stimulation of recovery of the adventitia and tun-
ica media within 28 days (241). The studies were per-
formed on peripheral vessels in rabbits; however, the
hemostatic response to FUS in the case of intracranial
hemorrhage is yet to be determined.
Immunization
Destruction of tumor cells with FUS creates wide
range of tumor antigens which have the potential to
stimulate an antitumor immune response (242). After
FUS treatment, an increase in CD3+ and CD4+ subsets
and in the CD4+/CD8+ ratio in peripheral blood of
cancer patients has been observed. Residual tumor

(A) (B) (C)

Figure 8.12 Image shows the use of commercial system for MRgFUS treatment of brain tumors (Exablate 4000, Insightec, Haifa,
Israel). (A) MR thermometry image shows uniform temperature distribution around the skull and the focal heating during a clinical
MRgFUS brain tumor treatment (arrow). (B) T2-weighted MR image in axial plane during the MRgFUS procedure. Exablate 4000 uses
a hemispherical 1000-element phased-array transducer to sonicate through the intact skull, providing a completely noninvasive ablation
method. The region between the scalp and the transducer is filled with chilled, degassed water to provide acoustic coupling and cool-
ing. (C) Postprocedural T1-weighted MR image shows well-delineated region of coagulation necrosis within the center of the tumor.
Source: Courtesy Jolesz F, National Center for Image Guided Therapy, Boston, MA.
180 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 8.13 Screenshots from transcranial magnetic resonance imaging-guided focused ultrasound surgery (TcMRgFUS) treatment
planning workstation. (A) Coronal T2-weighted images of the patient in the TcMRgFUS device. The target of the current sonication is
indicated by the blue rectangle. The water filling the space between the patients shaved head and the transducer can be seen. (B) Pre-
treatment computed tomography (CT) scan data of the cranium is registered the intratreatment magnetic resonance imaging (MRI)
scans. The cranium is automatically segmented from the CT scan and displayed on top of the magnetic resonance images used for
treatment planning as a green region. Any registration errors can be seen on these images and corrected by the user by using a graphi-
cal tool. Magnetic resonance tracking coils integrated into the transducer are used to register the TcMRgFUS system coordinates with
the imaging coordinates. Acoustic models taking into account the patient-specific cranium geometry and density are used to correct for
aberrations to the US beam. (C) The beam paths for each phased-array element are superimposed on the images, allowing the user to
verify that no beams pass through undesired structures. (D, E) Pretreatment contrast-enhanced T1-weighted images, which can be use-
ful to define tumor margins, acquired the day before treatment can also be registered to the intratreatment images. Axial and sagittal
images are also acquired, allowing for treatment planning in three dimensions. (F) Sagittal T2-weighted image. Source: From Ref. (231).

cells in the site of primary treatment, and also remote
metastases, may be suppressed with this strong
immune antitumor response.
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 9
Non-shunting cerebrovascular anomalies: Cavernous,
capillary and venous malformations
Mahua Dey and Issam A. Awad
INTRODUCTION AND LESION DEFINITION
Cerebral cavernous malformation (CCM) also known
as cavernoma, cavernous angioma, and cavernous
hemangioma is a vascular lesion found primarily in
the central nervous system, and less frequently else-
where in the body. The lesions, which may affect
any brain region or the spinal cord, consist of clus-
ters of dilated vascular sinusoids of varying size,
filled with blood or thrombus at different stages
of organization, giving it the gross appearance of a
mulberry (Figs. 9.1,9.2). They grow by a process of
vascular cavern proliferation in the setting of repeti-
tive intralesional hemorrhages (1). Lesions typically
exhibit hallmarks of previous perilesional hemorrhage,
including gliosis and hemosiderin deposit (1). Patients
harboring CCMs are predisposed to a lifetime risk of
focal neurologic deficits related to hemorrhage or
lesion proliferation and epilepsy (2). Hemorrhage
from CCM lesion is less likely apoplectic than with
higher flow arteriovenous anomalies (35); however,
at times it can be life threatening (6). The CCM may
present as solitary pathology, or often in association
with other vascular lesions.
Capillary Malformations and CCMs
Capillary vascular malformations, also known as
capillary telangiectases are vascular malformations
that consist of a collection of dilated capillaries with
normal intervening brain parenchyma (7). Most com-
monly described in the pons, they are typically an
incidental finding at autopsy, although in some
cases, symptomatic capillary malformations have
been revealed on MR images as indistinct patches of
punctuate contrast enhancement (Fig. 9.3) (810).
Capillary malformations may also be found in asso-
ciation with more clinically overt lesions, such as
CCMs or venous malformations. Microscopically, the
vessel walls of capillary malformations appear simi-
lar to those of normal capillaries, lined with a single
layer of vascular endothelium. While both capillary
telangiectases and CCMs represent dilated capilla-
ries, the presence of hemorrhage (identifiable on MR
imaging or histopathological examination) has been
the cardinal difference traditionally distinguishing
CCMs from capillary malformations in the clinical
setting.
The association of CCMs and capillary malfor-
mations in the same patient has been recognized for
many years, with WyburnMason having noted as
early as 1943 that cavernous angioma develops from
telangiectases and both may occur in the same case
hence it seems that there is no justification for divid-
ing cavernous angiomata from telangiectases (11).
This was confirmed in more recent studies (12), but
the exact prevalence of this association remains
uncertain, in view of diagnostic insensitivity of clas-
sic imaging modalities for non-hemorrhagic capillary
ectasia. More recently, however, transgenic animal
models of CCM disease have demonstrated non-
hemorrhagic capillary ectasia, as the apparent early
stage of CCM development (13). And recent imaging
advances in man, with susceptibility-weighted (SW)
MR sequences, are revealing a greater lesion burden
in familial cases of CCM disease than was noted
with conventional and gradient-echo MR sequences
(Fig. 9.4), with many of the tinier lesions possibly
representing capillary ectasia, precursors of more
mature CCM lesions (14,15).
Capillary telangiectasiae (capillary malforma-
tions) should not be confused with micro-arteriovenous
malformations of hereditary hemorrhagic telangiectasia
(OslerWeberRendu disease), the latter affecting brain,
skin, mucosa, and lungs in association of gene loci
unrelated to CCM disease and lesions of different his-
tology than CCM (16).
Cerebral Venous Malformations and CCMs
The most common cerebrovascular malformation is the
venous malformation, also known as venous angioma
or developmental venous anomaly (DVA). This lesion
rarely bleeds, except in association with a CCM (17,18).
The DVA is composed of abnormally enlarged venous
channels separated by normal neural parenchyma. The
anomaly reflects regional venous dysmorphism,
arranged in a radial pattern extending from a dilated
central venous trunk, and there is paucity of other nor-
mal venous drainage in the region of the anomaly (19).
Sporadic non-familial CCMs are often associated with a
DVA, detected on contrast-enhanced T1-weighted MR
sequences (Fig. 9.4), while multifocal CCMs associated
with autosomal dominant inheritance and the three
gene loci of CCM disease are not typically associated
with DVA (Fig. 9.5) (17,20).
188 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 9.1 (A) Artists illustration of cavernous malformation, with cavern proliferation and hemorrhage. (B) Histologic appearance of
CCM, with blood-filled thin walled caverns of various sizes, lined by endothelium (immunopositivity for von Willebrand factor shown).
Intercavernous matrix comprises an amorphous structure devoid of smooth muscle, elastic lamella or mature blood vessel wall
angioarchitecture.

Figure 9.3 T1 MRI appearance of pontine capillary malforma-

tion (telangiectasia), with punctate contrast enhancement shown.
There is no signal of bleeding, and no blooming effect on gra-
dient-echo sequences (not shown).

Mixed Lesions and the Spectrum of Angiographi-

Figure 9.2 Left temporal lobe CCM shown by T1-weighted
MRI. Note popcorn like appearance, representing multiple cav-
erns, surrounded by a thin ring of hypointensity, representing
hemosiderin stain. Patient presented with partial complex seiz-
ures. In view of eloquent lesion location, lesionectomy was per-
formed without additional resection of adjacent tissue. The
patient has been lesion free, but continues anticonvulsant
medications.
cally Occult Vascular Malformations
Despite the apparently distinct clinical, imaging, and
pathological profiles of the various cerebral vascular
malformations, some CCM lesions exhibit mixed or
transitional features, implying related pathobiological
mechanisms (10,2124). Portions of CCMs may, like
arteriovenous or venous malformations, exhibit partial
or complete mature vessel wall elements, and many
 NON-SHUNTING CEREBROVASCULAR ANOMALIES: CAVERNOUS, CAPILLARY AND VENOUS MALFORMATIONS 189

T2 T2*/GRE SWI

Figure 9.4 MRI appearance of multifocal CCM (familial type). (Left): T2-weighted MR showing typical lesions with popcorn-like
appearance surrounded by hemosiderin. (Middle): T2*/gradient-echo images reveal blooming effect of the same lesions, exaggerating
the signal of associated hemosiderin. (Right) SW images revealing additional lesions not seen on conventional images, revealing lesion
burden with greater sensitivity.

T2 T1-Gad T2*/GRE

Figure 9.5 MRI appearance of developmental venous anomaly (DVA) associated with a cluster of CCMs. The patient presented with
subtle memory problems and headaches. He has been followed expectantly, without progression of imaging or clinical features during
several years. Excision of such cluster of CCMs could be associated with significant morbidity, and potential sacrifice of DVA, with
resulting venous infarct or edema.

CCMs appear to arise in close proximity to DVAs or EPIDEMIOLOGY

capillary malformations as noted above. Various cere-
brovascular malformations may be associated with skin
lesions in rare syndromatic settings, as with hereditary
hemorrhagic telangiectasia (OslerWeberRendu dis-
ease noted above) and encephalofacial angioma
(SturgeWeber disease). The skin lesions that occur
infrequently in association with familial CCMs have
been characterized as hyperkeratotic angioma (25), but
their precise prevalence and clinical significance have
not been well studied.
CCMs are a common vascular anomaly affecting more
than 0.5% of the population (5) and account for 5% to
13% of all vascular malformations (26,27). In 60 to
80 percent of cases, CCMs are sporadic solitary lesions
(Figs. 9.2,9.69.8). On rare occasion they occur as focal
clusters of lesions near a DVA (Fig. 9.5) or lesions in
previously irradiated brain region. The remaining
cases manifest an autosomal dominant inheritance
pattern and variable clinical expression, and typically
190 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 9.6 (A) T1-weighted MRI of pontine lesion presenting with progressive symptoms. This was resected via a transvermian corridor
through the floor of the fourth ventricle, with multimodality evoked potential and facial nerve monitoring. (B) Postoperative scan showing
lesion excision and surgical corridor. The patient achieved excellent functional recovery, including independent gait and binocular vision.
Figure 9.7 Right frontal CCM presented with new onset seiz-
ures in a young patient. Lesion was resected with a generous
margin including hemosiderin-stained brain (lesionectomy plus),
achieving seizure-free state despite tapering off anticonvulsant
medications. Mapping of perilesional tissue is performed in such
cases, with option of resection of cortical tissue with epileptiform
activity, in non-eloquent location.
(B)
involve multifocal lesions scattered throughout the
brain in a volume distribution (5) some of which may
only be revealed by gradient-echo MR, or other special-
ized imaging techniques (Fig. 9.4). Three distinct gene
foci on chromosomes 7q, 7p, and 3q have each been
linked to familial CCM (28). The identified proteins
encoded by CCM genes interact with the endothelial
cytoskeleton during angiogenesis, and are expressed in
neural tissue, potentially explaining the occurrence of
these lesions in the central nervous system (28,29). The
prevalence of multifocal CCM lesions approaches 100%
in adults with genotyped familial case, imaged with
gradient-echo or SW MR sequences (26,3036). His-
panic Americans of Mexican descent have a higher
predilection for familial CCMs (33,34,37), related to a
founder mutation (38), also affecting a large reservoir
of patients in the Southwestern United States (20).
Another unique founder mutation has recently been
described as a cause of CCM in patients of Ashkenazi
Jewish heritage (39). In familial clusterings of CCMs,
successive generations seem to manifest symptoms at
earlier ages (31,33,35,40,41).
The majority of studies and all recent large MRI-
based analyses demonstrate an equal prevalence of
male and female patients with CCMs (4,5,27,4244).
There is a predominance of male patients presenting at
<30 years of age, a preponderance of female patients
aged 30 to 60 years, and a more equal ratio thereafter
(5,45). There is predilection of female patients with
middle fossa (extradural) CCMs, a particular variant,
and male patients may manifest symptoms at an ear-
lier age than do female patients (5,45).
CCMs have been reported at both extremes of
age, but a majority of patients present between the
second and fourth decades of life (4,26,36,42,43,4652).
CCMs are less common in pediatric population (48,49)
and account for approximately one-fourth of the
 NON-SHUNTING CEREBROVASCULAR ANOMALIES: CAVERNOUS, CAPILLARY AND VENOUS MALFORMATIONS 191

(A)

(B) (C)

(D) (E)

Figure 9.8 (A) T1-weighted MRI scan of middle-aged female presenting with left hemiparesis and disabling left arm dystonia reveals
a large CCM lesion involving the lentiform nucleus and anterior limb of the internal capsule. Arrow reveals prominent venous anomaly
at the medial aspect of the CCM. Other images (not shown) confirming a large associated DVA. (B) Lesion was exposed via transsyl-
vian approach, with adjunct image guidance and evoked potential monitoring. (C) CCM lesion was resected with significant effort at
carefully preserving several lenticulostriate arteries coursing nearby, and also the large DVA. (D) Postresection MRI scan showing the
resection cavity and surgical corridor. (E) MRI scan reveals the preserved venous anomaly with its caput medusae-like branches adja-
cent to the lesion resection. The patient experienced immediate relief of disabling dystonia. Her left hemiparesis, which worsened tran-
siently postoperatively, resolved completely within 2 weeks of surgery.
192 NEUROINTERVENTIONAL MANAGEMENT
patients in published series (43,50,53). Among pedia-
tric patients, there is a bimodal peak of symptomatic
presentation at about 3 and 11 years of age. Patients
<40-years-old are likely to present with seizures,
whereas older patients more likely manifest focal neu-
rological deficits (5,54). There is a greater preponder-
ance of hemorrhage and acute neurological deficits
as presenting symptoms in children in contrast to that
in adult series, accounting for 43% to 78% of symp-
tomatic patients (48,49). Younger children display
more active lesion growth compared with the older
age group. It has been suggested that pediatric patients
have a greater propensity for overt hemorrhage
(31,43,46,48,53,55). Data from virtually all clinical ser-
ies demonstrate that symptomatic lesions are rare in
the elderly population.
The CCMs have been reported to range in size
from <0.1 to 9cm (4,26,27,43,50,56). A majority of
intracranial CCMs, 64% to 84% of reported CCMs, are
supratentorial with lobar preponderance (4,5,26,27,
32,42,56). The pons and the cerebellum are the most
common infratentorial sites (5,45,56). Other less com-
mon intracranial locations include the cerebellopon-
tine angle, pineal gland, middle fossa, cavernous
sinus, optic nerve and chiasm, and dura. CCMs are
more likely to be part of a mixed lesion than are other
vascular malformations, with most frequent associa-
tion with a venous malformation (12,45). Although
majority of lesions occur in the supratentorial com-
partment, substantially greater neurological sequelae
occur with CCMs in the infratentorial compartment
(5,54,56,57). This correlation remains significant even
after controlling for lesion size. Angiographically
occult brain stem vascular lesions have a high rate of
recurrent hemorrhage, up to 69%, and a significant
cumulative morbidity (5,54,56,58). They exhibit a char-
acteristic pattern of exacerbations and remission of
symptoms (56,57). When a CM is found in conjunction
with a venous malformation, the latter is readily
angiographically identifiable by its characteristic caput
medusae pattern of abnormal venous drainage,
whereas the CCM component of the lesion is angio-
graphically occult. Both components of such lesions
are generally identifiable on MRI (Fig. 9.5). When
lesions exhibit mixed histological features of CCM
and arteriovenous malformation (AVM) or capillary
telangiectasia, they are clinically and radiographically
indistinguishable from CCMs (12,59). Intracranial
CCMs are rarely associated with intraspinal extracere-
bral soft tissue and visceral hamartomas (60,61) and
other central nervous system tumors, such as meningi-
omas and astrocytomas (44,45,6062).
HISTOPATHOLOGY AND PATHOBIOLOGY
Histologic features of CCM include blood-filled sinus-
oidal spaces (the caverns) of various sizes, lined by
a single layer of endothelium and separated by a col-
lagenous stroma devoid of elastin, smooth muscle, or
other mature vascular wall elements (Fig. 9.1). The
endothelial cell layer borders an amorphous collage-
nous matrix devoid of smooth muscle cells (63). The
lesion is not always compact and may include race-
mose or satellite-like projections into the adjacent
brain (64). There are rare reports of disorganized,
scattered elastic fibers in lesions that have morpho-
logical features consistent with CMs (50). The sur-
rounding parenchyma consistently exhibits evidence
of prior microhemorrhage, hemosiderin discoloration,
and hemosiderin-filled macrophages. Within the
lesion, hyalinization, thrombosis with varying degrees
of organization, recanalization, calcification, cysts,
and cholesterol crystals are common (32,34,43,50,
6568). A gliomatous reaction of the surrounding
parenchyma is characteristic and may form a capsule
around the lesion. Hemosiderinladen macrophages
are nearly always present in perilesional tissue and
within the lesions themselves, and a robust infiltra-
tion of inflammatory cells has been recently charac-
terized in CCM lesions (69). The preponderant B cells
and plasma cells infiltrating lesions produce a mono-
clonal antibody, likely triggered by an antigen in the
lesional milieu, unrelated to recent overt bleeding or
lesion proliferation (70). Ultrastructural analysis of
CCM lesions reveals a partially compromised blood
brain barrier at the site of CCMs, which facilitates
erythrocyte diapedesis and the eventual deposition of
hemosiderin in perilesional tissue (71,72).
The CCMs are dynamic lesions with demon-
strated neuroimaging changes in lesion size and signal
characteristics in up to 38% of patients as well as in
the appearance of new lesions over time (33,36,42,
49,50,53,7377). In a recent study of familial CCMs,
with an average follow-up of 2.2 years, 29% of the
patients developed new lesions, with an average rate
of 0.4 new lesions per patient per year (36). In a patient
with multiple lesions, the excision of one previously
active lesion does not deter the growth, dynamics, or
development of symptoms of novel or previously qui-
escent lesions. These changes are thought to be attrib-
utable to intralesional hemorrhage, thrombosis,
organization, calcification, cyst formation, and involu-
tion of the caverns (36,55,56,74,75). Less commonly, a
lesion may expand after gross hemorrhage and then
involute as the hematoma organizes and is resorbed.
A review of the literature demonstrates several fea-
tures, some intrinsic to the lesion like microhemor-
rhages that may promote hemorrhagic angiogenic
proliferation and others to the patient, that seem to
influence the dynamics of CCMs. Patients with fami-
lial CCMs have been shown to develop new lesions
during prospective follow-up with serial MRI (36).
Other new lesions consistent with de novo CCM gen-
esis have been reported after radiation therapy (62)
and along the path of a stereotactic biopsy (78). New
CCMs have developed in association with pre-existing
venous malformations (47). The possibility of evolu-
tion of the new CCMs from smaller lesions or other
precursors not visible on earlier imaging studies,
rather than total de novo lesion genesis, cannot be
totally excluded. In particular, capillary telangiectases
have been associated with CCMs (12,79), and it is
possible that CCMs evolve from hemorrhagic coales-
cence of pre-existing telangiectases.
There is a marked difference in clinical presenta-
tion and neurological disability in patients with CCMs
based on gender. Female patients are more likely to
manifest gross hemorrhage, multiple lesions, and neu-
rological deficits, whereas male patients are more
likely to present with epilepsy (42,45,50,76,8082).
 NON-SHUNTING CEREBROVASCULAR ANOMALIES: CAVERNOUS, CAPILLARY AND VENOUS MALFORMATIONS
Furthermore, female patients with CCMs display a
significantly greater degree of neurological disability
compared with male patients (5,54). This trend is also
demonstrable in pediatric patients (75). There is also a
preponderance among female patients of mixed vas-
cular malformations (75). Several preliminary studies
have suggested that the reproductive cycle may have
an impact on the rate of growth and the hemorrhagic
risk of CCMs with documented aggressive clinical
course during pregnancy (53,58,83).
Among patients with multiple lesions, the larger
lesion is usually symptomatic (36,84). It has been
observed that certain morphological criteria (the pres-
ence of dense calcifications, ossifications, a thick glial
capsule, and a greater degree of intralesional organi-
zation) are associated with a less aggressive clinical
course (44,50,8587). Calcifications may be associated
with greater epileptogenicity (50). The only correlation
between the MRI characteristics and the clinical
behavior of CCMs was the observation that as long as
gross hemorrhage occurred within the hypodense
perilesional hemosiderin ring, the patient would likely
remain asymptomatic. However, if the bleed ruptured
through this margin, the patient would be likely to
manifest acute symptoms (88).
There is an increased risk of recurrent hemor-
rhage and progressive neurological decline after an ini-
tial bleed from a CM (54,56,57). It is not known
whether hemorrhage per se causes the lesion to behave
more aggressively or whether patient or extrinsic fac-
tors are responsible for repetitive hemorrhagic tenden-
cies. A series examining certain pathological features at
surgery and autopsy with a retrospective analysis of
clinical and biological behavior of the lesion found that
lesions with calcifications, evidence of chronic intrale-
sional hemorrhage with thrombus organization, and
thicker glial pseudocapsules were more likely to appear
with seizures than with gross hemorrhage (87). It is
possible that thrombus organization and the conse-
quent glial reaction may protect patients from gross
hemorrhage while predisposing them to seizures.
An evidence-based definition of significant hemorrhage
in CCM has recently been proposed, to allow more
consistent reporting in clinical series and therapeutic
trials (2).
PATHOGENESIS OF CCM LESIONS
There is growing evidence that the cellular pathology
in CCM lies in dysregulation of vascular development
and endothelial permeability. Familial form of CCM is
associated with three separate genes: CCM1/KRIT1,
CCM2/MGC4607, and CCM3/PDCD10. Each exhibits
a Mendelian autosomal dominant inheritance due to a
heterozygos loss-of-function mutation at 1 of 3 distinct
loci. The respective encoded proteins appear to inter-
act with cytoskeletal and interendothelial cell junction
proteins. CCMs are caused by germline mutations in
CCM1 and are involved in 40% of familial CCMs, and
nearly half of those patients will have neurological
symptoms before 25 years of age. With familial CCM
disease, roughly 100 distinct mutations in this gene
have been identified to date. CCM1 is located on chro-
mosome locus 7q11q22 and produces Krev interac-
tion trapped 1 or KRIT1 protein, a cytoplasmic
193
ankyrin repeat containing protein that interacts with
RAP-1A (Krev-1), a member of the Ras family of
GTPases involved in interendothelial junction integ-
rity, and integrin cytoplasmic domain-associated
protein-1a (ICAP-1), a nuclear protein that shuttles
between nucleus and cytoplasm and involved in b1-
integrin mediated signal transduction. KRIT1 is local-
ized, in part, to interendothelial cell junctions and that
its loss results in disruption of junctional stability that
leads to increased permeability in vitro and in vivo.
Loss of endothelial cell junctions readily explains the
leakage of blood in CCMs and their associated hemo-
siderosis and can account for the observed inflamma-
tory response in CCM lesions (89). CCM2 mutations
are involved in up to 40% of familial CCMs. Patients
with CCM2-associated disease have a lower number
of gradient-echo sequence lesions than those with
CCM1 or CCM3 disease, and the number of lesions
increases less rapidly with age than in patients with
CCM1 disease. CCM2, localized at chromosome
7p1513, produces malcavernin protein, shows similar
temporal expression patterns as KRIT1. CCM2 binds
to KRIT1 via a phosphotyrosine-binding domain, in a
manner similar to ICAP-1, and is able to sequester
KRIT-1 in the cytoplasm. The KRIT1CCM2 interac-
tion also stabilizes endothelial cell junctions by sup-
pressing a protein called RhoA and its effector protein
ROCK that are involved in actin stress fiber formation
and endothelial monolayer permeability. Loss of either
KRIT1 or CCM2 disinhibits RhoA and ROCK activity
leading to interendothelial barrier instability and vas-
cular leaking. Increased ROCK activity is noticed in
the endothelial cells lining sporadic and familial CCM
lesions. This suggests that a final common signaling
aberration involving ROCK activation takes place in
both sporadic and inherited lesions (90). Inhibition of
ROCK activation has emerged as a potential therapeu-
tic approach to prevent lesion genesis, or possibly
to alter lesional permeability (91). Third and most
recently discovered gene is CCM3, localized at
3q25.2q27, encodes programmed cell death protein
10 (PDCD10). CCM3 mutation carriers are less com-
mon than CCM1 or CCM2 carriers, but they are more
likely to present with hemorrhage and to have symp-
tom onset before 15 years of age (92). The temporal
expression of CCM3 mRNA correlates with that of
CCM2 in meningeal and parenchymal cerebral vessels.
Aberrant apoptosis, in the endothelium or neural cells,
may play a role in the pathogenesis of CCMs. CCM3
protein precipitates and co-localizes with CCM2.
Thus, all three CCM proteins interact to form a com-
plex that then interacts with other proteins such as
b1-integrin and ICAP-1 (91).
DIAGNOSTIC IMAGING
CCMs have very sluggish blood flow, or stasis and
thrombus at different stages of organization within of
the caverns; thus, they are not visible during conven-
tional angiogram. The inability of angiography to
adequately detect CCMs, capillary telangiectases, and
thrombosed AVMs led to the grouping of these
lesions as angiographically occult vascular malforma-
tions. A review of the literature shows that angio-
graphic results are normal in the majority of patients
194 NEUROINTERVENTIONAL MANAGEMENT
with CCMs (26,34,43,50,64,77,93,94). Occasional abnor-
malities shown on angiography may include an avas-
cular mass, minimal vascular abnormalities (including
early, late, or widened draining veins), a capillary
blush or stain, and evidence of neovascularity
(27,42,44,50,53,56,68,81,9396).
Plain computed tomographic (CT) scanning has a
sensitivity of 70% to 100% for CCMs in published ser-
ies (51,56,97). However, despite excellent sensitivity at
detecting the presence of a lesion, the specificity of CT
scanning for accurate diagnosis of a CM is quite poor
in most series (34,51,68). Because of isodense appear-
ance related to subacute hemorrhage or microcalcifica-
tions, CCMs are commonly missed or misdiagnosed
on CT scans of the brain. The CT scan of a CCM typi-
cally exhibits a conspicuous, well-circumscribed, nod-
ular lesion of uniform or variegated mixed density
reflecting the juxtaposition of calcifications, hemor-
rhage, and cystic components that is known to com-
prise these lesions. In patients who have recently
experienced hemorrhage, the homogeneous hyperden-
sity of a hematoma may overlie and obscure the lesion
(27,50,52,56,73,93). The addition of contrast may elicit
faint enhancement. The CT scan documents a hema-
toma or calcification but frequently does not delineate
an underlying lesion or differentiate the lesion type.
MRI is the most sensitive and specific diagnostic
tool for the evaluation of CCMs (98). The appearance
of CCMs on MRI scans is sufficiently characteristic to
allow confident preoperative evaluation of sympto-
matic lesions, identification, screening, and follow-up
of incidental lesions, and depiction of lesion behavior
including expansion, hemorrhage, and thrombosis
(34,68,73,88,99). They are characterized by a mixed sig-
nal within the lesion itself on T1- and T2-weighted
sequences, surrounded by a ring of T2 hypointensity
from hemosiderin, reflecting blood leakage. Smaller
CCM lesions may only be revealed by gradient-echo
MR images, in which they can be identified because of
the lesions hemorrhagic signal. Lesions confirmed by
pathological findings correlate with this MRI scan
appearance in 80% to 100% of patients (68). The mixed
signal intensities reflect the spectrum of lesion behav-
ior of CCMs. Repeated subclinical intralesional and
perilesional hemorrhages lead to ferritin deposition
secondary to erythrocyte breakdown and account for
the typical ring of low T2 signal around CCMs. The
reticulated low T2 signal within the lesions also reflects
speckled intralesional calcification (27,42,68,73). Areas
of hyperintensity correspond to acute and subacute
hemorrhages and different stages of thrombus organi-
zation. Associated cysts most likely represent residua
of previously expanded hemorrhagic caverns that have
since involuted with thrombus organization and reso-
lution (50,64,65,67,100104). A classification system
based on imaging and pathological features has been
reported to stratify these heterogeneous lesions (15).
l Type I lesions are characterized by hyperintensity
on both T1- and T2-weighted images (depending
on the state of methemoglobin), which is consis-
tent with subacute hemorrhage.
l Type II malformations, loculated regions of
hemorrhage are surrounded by gliosis and hemosi-
derin-stained brain parenchyma. These CCMs
exhibit a mixedsignal intensity core on both T1-
and T2-weighted images, with a well-circumscribed
hypointense rim on T2-weighted images; these
lesions are the classic CCMs, with a popcorn
appearance and a predilection to produce recurrent
symptoms.
l Type III lesions demonstrate a core that is iso- or
hypointense on T1-weighted sequences and hypo-
intense on T2-weighted sequences as well as a rim
that is hypointense on T2-weighted sequences,
compatible with chronic resolved hemorrhage or
hemosiderin within and surrounding the lesion.
l Type IV malformations are minute lesions often
seen as punctate hypointense foci on GRE MR
images. Pathologically, Type 4 lesions may repre-
sent capillary telangiectasias or early-stage CCMs
seen frequently in the familial form.
SW imaging provides a new mode that is partic-
ularly suited for imaging vascular malformations as it
is very sensitive to deoxyhemoglobin and iron con-
tent. SW imaging increases the sensitivity of lesion
detection in familial multifocal CCM lesions (14). It
does not per se reveal lesion multiplicity that had
not been already demonstrated by T2*GRE. The SW
images are highly sensitive to delineation of associ-
ated venous anomalies, and possibly telangiectasias,
without the need for contrast enhancement, and may
be a more sensitive imaging biomarker of lesion bur-
den in tracking disease progression in future thera-
peutic trials (15).
CLINICAL PRESENTATION
CCMs manifest a full clinical spectrum, from the asy-
mptomatic lesion, discovered incidentally at autopsy or
on neuroimaging, to the rare reported case of fatal
intracranial hemorrhage. The clinical course is highly
variable. Patients may present with acute or chronic
neurological deficits, periods of remission and exacer-
bation, or progressive, insidious deterioration. Patients
with asymptomatic lesions have traditionally included
those presenting with mild headaches and nonspecific
symptoms. Earlier autopsy series demonstrated asymp-
tomatic lesions in up to 95% of patients (43,84). Solitary
and multiple CMs of all sizes and locations may be clin-
ically silent. Asymptomatic patients with MRI-docu-
mented lesions account for 11% to 44% of patients in
clinical series (5,42,45,79). Headache may be the sole
clinical manifestation in more than one-fourth of
patients (26). In one study, 40% of patients with initially
clinically silent lesions became symptomatic within an
interval of 6 months to 2 years (5).
Because a majority of CCM lesions are supraten-
torial with a lobar predilection, it is not altogether sur-
prising that in 38% to 100% of patients with CCM,
seizure is the presenting symptom (Figs. 9.2,9.7)
(26,43,50,52,53,56,93,94,105). All seizure types have
been observed, including simple seizures in 27% to
31% of patients, complex partial seizures in 6% to
45%, and generalized seizures in 27% to 63%
(27,44,50). In patients with intractable seizures, one
series reported a predominance of complex partial
seizures. CCMs are almost twice as likely to be associ-
ated with seizures when compared with other lesions,
 NON-SHUNTING CEREBROVASCULAR ANOMALIES: CAVERNOUS, CAPILLARY AND VENOUS MALFORMATIONS
such as AVMs and tumors with similar volume distri-
butions and in virtually identical locations. CCMs
located in the temporal lobes are more commonly asso-
ciated with medically refractory epilepsy. In one series,
which included 27 vascular malformations associated
with intractable epilepsy, 74.7% of the malformations
were CCMs and only 14.8% were AVMs. The patho-
physiology of seizures in CCMs is postulated to be
related to irritation and compression secondary to
mass effect and multiple local hemorrhages with the
exposure of the surrounding brain to blood breakdown
products, particularly iron, and the subsequent local
gliomatous reaction (34,44,68,87,106). Adequately local-
izing the epileptogenic zone before ascribing a CCM as
the cause of seizures is important, particularly in cases
with multiple lesions. Unfortunately, in the majority of
patients, it is not possible to localize or even lateralize
the seizure focus by scalp electroencephalography
because the results of the study may be normal or of
indeterminate localizing value.
Another common clinical presentation of patients
with CCMs is with acute or progressive focal neurolog-
ical deficit. This is usually associated with intralesional
or perilesional hemorrhage that can be documented by
MRI. The frequency in clinical series ranges from 15.4%
to 46.6% (4,5,26,27,34,36,42,45,50,51,53,54,56,57,76,81,82,
88,107). The precise syndrome depends on the lesion
location and size (Figs. 9.6,9.8,9.9). The deficit may be
transient, progressive, recurrent, or fixed. Recurrent
hemorrhagic episodes result in cumulative disability,
often with severe fixed impairments (4,5,26,34,42,52,54,
56,57,76,107,108).
CCM AND INTRACRANIAL HEMORRHAGE
A distinction must be made between apoplectic or
gross hemorrhage and ongoing microhemorrhages
and intralesional hemorrhagic expansion in CCMs.
Al Shahi et al. (2) systematically reviewed the pub-
lished literature and suggested evidence-based criteria
for defining CCM-related hemorrhage as follows:
A clinical event involving both:
l Acute or subacute onset symptoms (any of head-
ache, epileptic seizure, impaired consciousness,
new/worsened focal neurological deficit referable
to the anatomic location of the CM).
l Radiological, pathological, surgical, or rarely only
cerebrospinal fluid evidence of recent extra- or
intralesional hemorrhage.
The mere existence of a hemosiderin halo, or
solely an increase in CM diameter without other evi-
dence of recent hemorrhage, is not considered a clini-
cally significant hemorrhage. Evidence of occult
bleeding is a defining feature that is present in every
lesion, regardless of clinical history. Overt hemor-
rhage, however, is a less common but clinically more
significant event and has been reported in 8% to 37%
of lesions in clinical studies (4,5,26,27,33,34,36,42,
5154,74,105,108). A higher association has been
reported in children, with a range of 36% to 60%
(43,48, 49,109). The annual clinically significant hem-
orrhagic risk has been estimated at 0.7% to 1.1% per
lesion per year (4,5,36). A majority of hemorrhages
are intraparenchymal within the region of the CCM.
195
Rarely they are subarachnoid (frequently seen with
optic nerve or chiasmal CMs) or intraventricular
(53,110,111). In mixed lesions comprised of a CCM and
a venous malformation, the hemorrhage is invariably
secondary to the CCM (12). In contrast to a bleeding
episode from an AVM, hemorrhage from a CCM is
rarely life threatening. There are rare documented
cases of patient death and few cases of rapid neurolog-
ical deterioration from an acute apoplectic episode
(50,81). More recent large series have also reported
rare mortality attributable to a first hemorrhage from a
CCM (5,50,110). The precise clinical presenting syn-
drome depends upon the location of the lesion. Typi-
cally, there is an acute onset of headache, which may
be accompanied by a neurological deficit and a change
in the level of consciousness (108). In the posterior
fossa, hemorrhages cause neurological sequelae with
greater frequency because of the concentration of
vital tracts and nuclei and the possibility of obstruc-
tion of cerebrospinal fluid pathways. In the cerebel-
lum, hemorrhages cause patients to present with
headache, emesis, ataxia, vertigo, and nystagmus,
whereas in the brain stem, typical signs of hemor-
rhage include diplopia, hemiparesis, sensory deficits,
and change in mental status (5,82,97,107, 112116). In
general, however, initial bleeds are self-limited and
patients generally achieve a good or fair neurological
recovery (5). In contrast, recurrent clinically overt
hemorrhages are associated with progressive neuro-
logical decline and severe residual deficits. When
hemorrhage occurs in the brain stem, periods of
exacerbation and then remission may occur, mimick-
ing demyelinating disease. Regardless of how
patients present, data from several studies suggest
that the risk of recurrent hemorrhage increases after
an initial bleed (5,26,45,50,51,5658,76,81,82,107,108).
Several studies have suggested that female patients
may have a higher risk of hemorrhage, particularly
during pregnancy (5,42,54).
MANAGEMENT STRATEGY
There are not sufficient firm scientific data to guide all
relevant clinical decisions regarding the optimal man-
agement of CCMs. However, the existing information
does provide a fundamental framework for rational
clinical decisions. Patients with CCMs may be consid-
ered in clinical categories with distinct risk of hemor-
rhage and neurological disability. Patients may have
only headache or nonspecific symptoms or may
present with neurological deficits (either fixed, fluctu-
ating, or progressive) or seizures. Each clinical sce-
nario requires the proposal of a distinct management
approach aimed at weighing the treatment risk against
the best estimate of the cumulative natural risk.
Expectant Management
Asymptomatic patients with single or multiple lesions
and only vague complaints, such as headache or diz-
ziness in the absence of focal neurological deficits,
present a low annualized risk of a first debilitating
hemorrhage. There are no current data to support an
aggressive approach in this group or in patients with
purely incidental lesions, in either sporadic or familial
196 NEUROINTERVENTIONAL MANAGEMENT
CCMs. Yet, surgical intervention for accessible solitary
lesions carries a very small risk and virtually elimi-
nates all subsequent serious risk from the lesions.
Follow-up of these patients clinically and with
sequential MRI seems reasonable. Alternatively, elec-
tive excision of readily accessible lesions may be con-
sidered in younger patients whose cumulative risk
over time may not be negligible. Young patients with
mild or non-disabling symptoms and solitary, accessi-
ble (usually supratentorial or cerebellar) lesions should
be followed up closely, and lesion excision should be
considered at the first manifestation of lesion growth
or exacerbation of symptoms. We have more recently
favored surgical excision of solitary, accessible lesions,
even when minimally symptomatic, because follow-up
of numerous such patients has shown that the psycho-
logical burden of living with the lesion, the costs,
the stress and inconvenience of repeated imaging, and
the outlook toward childbearing among young female
patients has not been negligible. Patients with less
accessible lesions and those associated with dominant
venous anomalies require a correspondingly higher
threshold for lesion excision (Fig. 9.5).
Medical Management
The major role of medical management in CMs is to
control epilepsy. The epileptogenicity may often be
localized to a single lesion. The clinical spectrum
ranges from those patients who respond well to anti-
convulsant medication to those patients with medi-
cally intractable and functionally debilitating seizures.
Several studies have shown that the symptoms of
patients with severe epilepsy who received anticon-
vulsant treatment persisted unabated with significant
clinical and social disability from seizures (5,44).
Other medical recommendations include the avoid-
ance of blood thinners for questionable indications,
and a higher threshold and closer monitoring if anti-
coagulation is otherwise recommended. No specific
lifestyle restrictions are imposed except those related
to epileptogenicity, and the avoidance of extreme
strenuous activities beyond normal fitness.
Surgical Resection
It is currently agreed that accessible symptomatic CMs
should be considered for resection. The current firmly
established indications for surgical management are
overt hemorrhage, focal neurological symptoms, and/
or medically intractable epilepsy. As previously noted,
patients presenting with initial hemorrhage are at
greater risk for recurrent hemorrhage. The resection
of accessible symptomatic supratentorial lesions has
been accompanied by a very low rate of morbidity
(5,43,44,4850,82,94,117). Deep supratentorial lesions
require a higher threshold for surgical intervention,
reserving surgery for lesions causing disabling or
recurrent hemorrhages (Fig. 9.8) (118). Favorable
results have also been reported in the resection of
brain stem lesions that appear at a pial or ventricular
surface (Fig. 9.6) (4,49,107,119). There is no consensus
as to whether the excision of these lesions should be
performed after a first bleed or should await symptom
recurrence or progression (120). Lesion accessibility
reflects on surgical risk (4,43,44,49,51,76,93,107,108,114,
117,121). The mortality risk in surgery for brain stem
CMs has ranged from 0% to 20%, with transient neu-
rological worsening in 20% to 40% of patients and
permanent worsening in <20% (76,82,114,119,121). In
one series of patients with brain stem lesions who pre-
sented with neurological deficits and did not undergo
surgery, 70% of patients had unremitting or fatal out-
comes (50). In patients with multiple lesions, only the
offending lesion should be resected, and the patients
should receive expectant follow-up for the remaining
lesions, as do patients with asymptomatic lesions.
Recurrences have been reported with subtotal removal
of lesions and are found more commonly in less acces-
sible and infratentorial locations.
Special Considerations in Patients with CCM and
Epilepsy
Patients with CCMs in cortical locations, especially in
temporal, frontal, and perilimbic locations, are subject
to a prospective lifetime risk of new seizures. Lesio-
nectomy with resection of adjacent hemosiderin-
stained brain tissue in less-eloquent brain locations
(Fig. 9.7) is associated with excellent postoperative
seizure control in many patients. The likelihood of
postoperative seizure control following simple lesion
excision is greater, approximately 6595%, in patients
with less intractable preoperative epilepsy and also in
patients with extratemporal lesions (122,123). Several
studies have shown that complete lesion excision is
necessary for seizure control in the majority of
patients who harbor a CCM that has been shown to
be responsible for their seizures (123). It also is well
documented that lesion excision alone may not always
be sufficient for seizure control, especially in patients
with truly intractable epilepsy. Thus, another strategy
of epilepsy control involves resection of the lesion and
a tailored resection of the epileptogenic cortex to
avoid the eloquent cortex. In patients with temporal
lobe lesions and intractable epilepsy, lesionectomy
without resection of mesiotemoral lobe structures has
documented relatively low seizure control rates, rang-
ing from only 20% to 45% (122,124,125). However,
some of these patients became seizure-free after addi-
tional resection of epileptogenic brain tissue in the
same region. When epileptogenic brain tissue is
resected in addition to the lesion during a first opera-
tion, it may provide the patient with seizure control
and spare him or her a second surgical intervention.
But the potential functional impact of resection of
additional brain tissue must be considered, especially
when contemplating resection of mesial structures in
the presence of high or normal material-specific mem-
ory function, or resection involving other eloquent
areas (such as the dominant temporal neocortex).
Intraoperative electrocorticography is sometimes per-
formed to further delineate the extent of the cortical
epileptogenic zone. This technique may provide prog-
nostic information by indicating the areas of residual
electric discharges after the resection of the vascular
malformation or what was thought to be the seizure
focus (126,127). It is important to remember, however,
that residual spikes in adjacent brain areas do not
reliably predict residual epileptogenicity, nor does
 NON-SHUNTING CEREBROVASCULAR ANOMALIES: CAVERNOUS, CAPILLARY AND VENOUS MALFORMATIONS 197

their absence guarantee postoperative seizure control
(126,127).
Often lesionectomy is performed as a first proce-
dure, especially with CCM in more eloquent locations
(Fig. 9.2), and only those patients with persistent
uncontrolled seizures are subjected to epilepsy surgery
evaluation and a second respective procedure if this
becomes necessary. Several studies (123,124,128,129)
have compared lesionectomy with the combination of
lesionectomy and corticectomy with controversial
results. A meta-analysis evaluating seizure outcome
following either lesionectomy or the combination of
lesionectomy and corticectomy concluded that at 2-
year follow-up, the prevalence of persistent seizures
following lesionectomy ranged from 1.4 to 4 times the
prevalence following the more extensive respective
procedures. In contrast, patients with fewer seizures
before presentation, shorter preoperative seizure his-
tories, or seizures that responded to antiepileptic
medications were more likely to be seizure-free fol-
lowing lesionectomy alone (130136).
Most patients in whom seizures are fully con-
trolled postoperatively will still require long-term
anticonvulsant therapy, although often with fewer
agents and at lower dosages than they required pre-
operatively. When the decision is made to reduce or
discontinue anticonvulsant therapy, it is important to
taper the dosage cautiously to avoid precipitating new
or recurrent seizures. Of patients who harbor a single
CCM, undergo lesionectomy for treatment of recent-
onset, localization-related seizures, and are seizure-
free postoperatively, up to half may be successfully
tapered off all anticonvulsant medications (Fig. 9.2)
(106,137139). This promising outcome, and its associ-
ated positive impact on quality of life, may play a role
in the decision to excise a solitary accessible cortical
CCM, even when seizures are not truly intractable to
medical therapy.

Figure 9.9 Stereotactic radiosurgery, using linear accelerator and micromultileaf collimator (13 Gy to 90% isodose line at lesion
periphery) targeting posterior capsular CCM lesion. The patient had suffered from repeated symptomatic hemorrhages with partial hem-
isensory residual deficit during the two years preceding treatment. Patient had no further hemorrhagic episodes or symptom exacerba-
tions in four years of follow-up after radiosurgery.
198 NEUROINTERVENTIONAL MANAGEMENT
Surgical Adjuncts in CCM Resection
CCMs of eloquent locations pose a special challenge
since in these cases benefits of improving the patients
clinical condition must be weighed against surgical
risks of the procedure. With the advancement of
image guidance technique and intraoperative monitor-
ing now, it is becoming possible to tackle these lesions
with minimal untoward consequences (140). A study
comparing clinical and surgical data of patients with
cavernoma treated surgically with and without intrao-
perative navigation showed that use of neuronaviga-
tion was associated with a more effective and safer
surgery of smaller and more deeper-seated caverno-
mas (141). In an attempt to evaluate tools that can
improve surgical precision and minimize surgical
trauma for removal of cavernomas in the paracentral
area, Zhou et al. defined four key factors that influ-
ence successful excision of these lesions (142):
l first, the precise location of the lesion;
l second, the precise evaluation of the functional area;
l third, the choice of a minimal invasive surgical
approach; and
l fourth, the entire removal of cavernoma and care-
ful removal of hemosiderin-stained tissue.
In this study by Zhou et al. of 17 patients with
paracentral cavernoma, by combining preoperative
fMRI and intraoperative neurophysiological monitor-
ing, including SEP, MEP, and cortical mapping, and
with the aid of ultrasonography-assisted neuronaviga-
tion, the damage to the primary motor area was suc-
cessfully avoided while achieving complete resection
via transsulcal microsurgical approach without neuro-
logical deficits (142). Another retrospective study
looking at the results of 26 patients operated for
supratentorial deep-seated or near eloquent brain area
cavernomas concluded that intraoperative visualiza-
tion of eloquent cortex areas by integration of func-
tional data for identification and exemption of
eloquent brain areas combined with neuronavigation
and intraoperative MR-guided resection allows safe
and complete resection of supratentorial cavernomas
in critical brain areas with low morbidity (143).
Surgical Considerations in CCM Associated
with DVA
Surgery may be indicated for resection of symptomatic
CCMs, even when associated with DVA (Fig. 9.8). In
such cases, the surgical approach and strategy should
aim to separate the CCM component of the lesion and
excise it, while avoiding injury to associated DVA.
While some reports have reported uneventful resection
of small supratentorial DVA associated with CCM (23),
many reports have described catastrophic complica-
tions of injury or resection of a DVA, resulting in seri-
ous and life-threatening edema, hemorrhage and/or
venous infarcts (144146). Other cases of clustering of
smaller CCMs with large predominant DVA should
not ideally be treated surgically (Fig. 9.5).
Radiosurgical Treatment of CCMs
Radiosurgery has been established as an effective alter-
native treatment option for small AVMs in eloquent and
inaccessible areas (77,117,147,148). With standard doses
as used for AVMs, CCMs exhibit a poor clinical
response and a high rate of complications (26,149). In
one series of 16 patients (13 with CCM alone and 3
with CCM associated with a venous malformation),
there was no radiographic change in 80% but 37.4%
eventually developed radiation-induced changes, 1 out
of 16 (6.25%) experienced a second hemorrhage, and
12.5% had persistent neurological deficits (150). When
lower margin doses are used, the results may be more
promising (Fig. 9.9) (149,151,152). One such report used
doses of 12 to 16 Gy for 39 deep-seated CMs, with an
average follow-up of 23 months. The authors reported
temporary neurological sequelae with MRI changes sec-
ondary to radiation in 10 patients (25.4%). There were
four deaths, two reportedly unrelated to radiosurgery
and two after delayed microneurosurgery. After 15
months, there were no patients with delayed hemor-
rhage (149,151,152). These data correlate with published
data on angiographically occult vascular malformations
in general (149). The use of radiosurgery needs further
investigation. In particular, issues of patient selection,
follow-up, long-term risks, and safe dose levels must be
addressed (153). End points of therapeutic success or
failure have been difficult to establish in view of the
variability of the natural behavior of the lesions. The
results of the treatment of CCMs must be judged
against the known natural history of the disease.
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 10
Diagnosis and management of cerebral vasculitis
James S. McKinney and Brett L. Cucchiara
INTRODUCTION
Cerebral vasculitis is a frequent consideration in
patients with recurrent or diffuse cerebrovascular dis-
ease of an otherwise occult etiology. Vasculitis is
defined by inflammatory cell infiltration of arteries,
capillaries, or veins and may affect the brain, spinal
cord, or peripheral nervous system (1). The terms
angiitis or arteritis may be used interchangeably with
vasculitis. Vasculitis may be isolated to the central
nervous system (CNS), as in the case of primary angii-
tis of the CNS (PACNS), or occur as a consequence of
a more diffuse process such as a systemic autoim-
mune disease, infection, or malignancy (1,2). Diagno-
sis of cerebral vasculitis can be extremely challenging
for a number of reasons. First, there can be significant
heterogeneity in the clinical presentations of patients
with various types of vasculitis. Second, a number of
noninflammatory vasculopathies, such as reversible
segmental vasoconstriction syndromes, or even athero-
sclerosis, may appear indistinguishable from vasculitis
on angiography. Third, the gold standard for diagno-
sis, pathologically proven inflammatory cell infiltra-
tion of blood vessel walls, depends on an invasive
procedure which due to sampling error may have lim-
ited sensitivity to confirm the diagnosis.
A rational approach to the patient with possible
vasculitis focuses on those clinical, anatomic, radio-
graphic, and laboratory features which are useful in
separating out the various potential diagnoses. This
includes an analysis of the following:
1. the size of affected vessels, distinguishing between
involvement of large proximal vessels or small
distal branch vessels;
2. the location of affected vessels, distinguishing
between intracranial, extracranial, or combined
intra- and extracranial involvement;
3. the presence of systemic disease, such as pulmo-
nary or renal dysfunction, which might suggest
vasculitis or vasculopathy affecting other organ
systems outside the CNS;
4. the presence of risk factors for/or clinical signs of
infection;
5. examination of the cerebrospinal fluid (CSF) for
evidence of inflammation;
6. serologic evidence of a systemic autoimmune
disease;
7. the temporal course of the clinical symptoms (i.e.,
rapid vs. slowly progressive); and
8. the type of brain imaging findings, such as ische-
mic stroke, intracerebral hemorrhage (ICH), subar-
achnoid hemorrhage (SCH), or some combination
of these.
This chapter will review the major types of vas-
culitis that can affect the CNS, as well as one of the
more common vasculitis mimics, the reversible seg-
mental vasoconstriction syndromes.
PRIMARY ANGIITIS OF THE CNS
Primary angiitis of the central nervous system (PACNS)
is a rare form of vasculitis that is isolated to the brain
and spinal cord (25). PACNS affects small-to-medium
sized arteries of the brain, leptomeninges, and/or spinal
cord causing neurological dysfunction. By definition,
PACNS is isolated to the CNS and does not affect any
other organ system. Several other names are used in the
literature to describe PACNS, including isolated CNS
vasculitis, primary CNS vasculitis, isolated angiitis of
the CNS, and granulomatous angiitis of the CNS (69).
These multiple synonyms and the lack of standardized
diagnostic criteria have created a lack of clarity sur-
rounding the diagnosis and treatment of PACNS.
PACNS occurs twice as often in men as women,
and the median age of onset is 50 years (5,7). Patients
with PACNS typically present with a subacute or
chronic course of progressive encephalopathy and head-
ache due to diffuse cerebral dysfunction. The median
time from symptom onset to diagnosis is over 40 days in
most cases (10). Rarely, symptoms may be more rapidly
progressive (10). Headaches occur in the majority of
patients and are typically insidious in onset, chronic,
and unrelenting (5). Stroke and transient ischemic
attack (TIA) occur relatively late in the course of the dis-
ease (2). Seizures may occur in up to a quarter of cases.
Constitutional symptoms, such as fever, night sweats,
arthralgias, myalgias, and/or rash, are uncommon in
PACNS and suggest a systemic process (5). The differen-
tial diagnosis of PACNS is presented in Table 10.1.
Aside from biopsy, there are no specific labora-
tory tests associated with PACNS. Acute phase reac-
tants and serum markers of inflammation, such as
hemoglobin level, leukocyte count, platelet count, and
the erythrocyte sedimentation rate (ESR) are usually
within normal limits (5). Markers of autoimmune and
connective tissue disorders are almost always negative
or within normal limits (5).
204 NEUROINTERVENTIONAL MANAGEMENT

Table 10.1 Differential Diagnosis of Cerebral Vasculitis Cerebral spinal fluid analysis is critical in differ-
entiating PACNS from other disorders with similar
Primary Angiitis of the CNS (PACNS) angiographic features. CSF abnormalities are present
Amyloid angiitis in 80% to 90% of patients with pathologically proven
Secondary CNS vasculitis PACNS (2,5). CSF abnormalities in PACNS typically
Infectious
include modest elevations in total protein levels and
 Bacterial
 Fungal
white blood cell (WBC) counts, with a lymphocytic
 Viral pleocytosis (5,11). Importantly, CSF analysis should
CNS involvement of a systemic vasculitis exclude malignancies as well as bacterial, fungal, or
 Large-vessel vasculitis viral infections which may mimic PACNS. Very high
& Giant cell arteritis (GCA) WBC counts (>250 cells/mm3) suggest infection rather
& Takayasu arteritis than PACNS (8,12). Appropriate cultures, fungal
 Medium-vessel vasculitis stains, viral polymerase chain reaction (PCR) testing,
& Polyarteritis nodosa (PAN)
and flow cytometry studies should be performed.
 Small-vessel vasculitis While computed tomography (CT) may detect
& Churg-Strauss syndrome (CSS)
& Wegeners granulomatosis (WG)
changes in the majority of patients with PACNS, these
& Microscopic polyangiitis (MPA)
changes are relatively nonspecific, with only 50% of
 Connective tissue disease vasculitis studies showing evidence of cerebral infarction (5).
& systemic lupus erythematosis (SLE) Magnetic resonance imaging (MRI) of the brain is the
& Sjogrens syndrome modality of choice for imaging the brain parenchyma
& rheumatoid arthritis in patients with suspected cerebral vasculitis. Although
& scleroderma the MRI changes associated with PACNS are not spe-
 Behcets disease cific, studies are abnormal in 90% to 100% of cases (2).
 Sarcoidosis The combination of a normal brain MRI and negative
 Malignancy-related angiitis CSF analysis makes a diagnosis of PACNS highly
& primary CNS lymphoma
& lymphomatoid granulomatosis
unlikely (13). The most frequently observed MRI abnor-
& angiotropic and intravascular lymphoproliferative disorders
malities are lesions in the subcortical white matter,
& carcinomatous meningitis cortical gray matter, deep gray matter, deep white mat-
Noninflammatory Vasculopathies ter, and cerebellum, with most patients having multiple
Reversible Cerebral Vasoconstriction Syndromes (RCVS) bilateral lesions (14). In contrast to adults with PACNS,
Atherosclerosis children are more likely to have multifocal unilateral
Fibromuscular dysplasia (FMD) lesions on MRI (15). Cerebral infarctions are the most
Cerebral autosomal dominant arteriopathy with subcortical common type of lesion present, occurring in half of
infarcts and leukoencephalopathy (CADASIL) cases (5). Infarctions may be in the distribution of large
Moya-moya syndrome vessels, branch arteries, or small penetrating vessels.
Radiation vasculopathy
ICH or SAH may be present in 10% of cases (2,5).
Approximately 30% of patients will have gadolinium-
enhancing lesions and 1015% will have leptomenin-
geal enhancement on contrast studies (Fig. 10.1) (2,5).

(A) (B) (C)

Figure 10.1 Primary CNS angiitis. Patient was an 81-year-old woman with progressive cognitive decline and difficulty with vision over
2 months. Biopsy confirmed PACNS. (A) Multiple areas of Fluid Attenuated Inversion Recovery (FLAIR) signal abnormality on MRI con-
sistent with infarction and/or edema. Also, increased FLAIR signal in the sulcal spaces likely reflecting proteinaceous fluid (CSF protein
192mg/dl). (B) T1 contrast-enhanced MRI showing diffuse leptomeningeal enhancement. (C) On follow-up imaging, areas of abnormal
signal on FLAIR MRI have progressed.
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 205

Mass lesions, suggesting a neoplastic process, may be
present in up to 15% of cases (2).
Magnetic resonance angiography (MRA) has
been suggested to show changes typical of vasculitis
in up to two-thirds of cases of suspected vasculitis in
adults and children (5,15). However, PACNS typi-
cally affects small-to-medium sized arteries below
the resolution of MRA, and its utility in the diagnosis
of PACNS is questionable (16). CT angiography
(CTA) may have improved spatial resolution over
MRA when imaging distal branch vessels, and may
more accurately assess vessels with severe stenosis or
sluggish arterial flow; however, its utility in the diag-
nosis of PACNS is also limited. A major pitfall in
use of both MRA and CTA is that the appearance of
vessel irregularity on these studies is very often
artifactual.
Catheter angiography plays an important role in
the diagnostic evaluation of patients suspected of hav-
ing cerebral vasculitis; however, there are no angio-
graphic features pathognomonic for PACNS (Fig. 10.2).
Angiographic changes typically seen with cerebral
vasculitis include vascular ectasia with alternating
areas of stenosis and dilatation or luminal irregularities
and stenosis (16). The presence of microaneurysms in
PACNS is rare and suggests either a systemic vasculitis
or infectious process (16). The typical features of cer-
ebral vasculitis may also be seen in other disorders,
including noninflammatory, infectious, and neoplastic
processes. The specificity of cerebral angiography for
the diagnosis of PACNS may be as low as 30% (17).
One case series reported that of 14 patients with typical
angiographic findings of CNS vasculitis, none had
PACNS at brain biopsy and 6 had an alternate diagno-
sis made by histopathology (18). Another study review-
ing cases of pathologically confirmed PACNS found
abnormal angiography in 56% of cases, but those
changes were suggestive of vasculitis in only 27% of
cases (19). Based on these data, it is apparent that a
diagnosis of PACNS should not be made on the basis
of angiographic changes alone.
A definitive diagnosis of PACNS can only be
made by biopsy or autopsy. Obtaining a histopatholog-
ical specimen by biopsy should be strongly considered

Stu

(A) (B)

(C) (D)

Figure 10.2 Primary angiitis of the CNS: (A) Axial FLAIR MRI image demonstrates deep and cortical infarcts of various ages B and C.
Lateral (B) and anteroposterior (AP) (C) views of left carotid catheter angiogram show irregular regions of focal narrowing involving
intracranial branches (arrowheads). Similar findings involve the right carotid intracranial branches in lateral (D) view.
206 NEUROINTERVENTIONAL MANAGEMENT
in all patients for whom PACNS is a diagnostic consid-
eration. Both leptomeninges and underlying cortex
should be biopsied to maximize yield. Cortical and
leptomeningeal biopsy is a relatively safe procedure
with less than 2% morbidity (12,20). The sensitivity of
biopsy for the diagnosis of PACNS may be as low as
5060% (2,5,6). In one series of pathologically proven
PACNS, half of patients with an initial negative biopsy
had the diagnosis confirmed at autopsy (6). This lack
of sensitivity is due, at least in part, to nondiagnostic
histopathological studies from segmental involvement
of vessels with skip lesions causing sampling error.
Despite this limited sensitivity, a major rationale for
proceeding with biopsy is that an alternative diagnosis
may be demonstrated in a substantial number of cases
on histopathological examination. In a series of 61
cases of suspected PACNS that underwent biopsy, a
diagnosis of PACNS was established in 22 (36%), an
alternative diagnosis was made in 24 (39%), and a non-
diagnostic study was reported in 15 (25%) (21). In this
series, 8 patients had malignant neoplasms at biopsy,
including 6 cases of primary CNS lymphoma and lym-
phomatoid granulomatosis (LYG) causing angiocentric
inflammation (21). Noninflammatory vasculopathies,
infectious causes, and other etiologies may be identi-
fied on biopsy with an important impact on treatment
plans (22).
The histopathological pattern of PACNS is most
commonly a granulomatous vasculitis (Fig. 10.3) (5,6).
Other patterns described in atypical PACNS include
lymphocytic infiltration, acute fibrinoid necrosis, vas-
cular thromboses without inflammation, bland neoin-
timal proliferation, and a healing pattern of resolving
vasculitis inflammation (2).
The natural history of PACNS without treatment is pro-
gressive neurologic deterioration. (9). Immunosuppressive
Figure 10.3 Primary angiitis of the CNS. Biopsy specimen with
hematoxylin and eosin stain showing granulomatous inflammation
of a leptomeningeal vessel. Image courtesy of Dr. Roy Rhodes,
UMDNJ Robert Wood Johnson Medical School, Department of
Pathology.
therapies may alter this course. An initial favorable
response to treatment was reported to occur in
approximately 80% of cases treated with either cortico-
steroids and/or cyclophosphamide (5). The median
length of treatment was 10 months with both thera-
pies, and a relapse leading to a change in treatment
occurred in 26% of cases (5). The initial benefit from
steroids may be a transient one, and other studies
suggest that the addition of cyclophosphamide is
needed (23,24).
The appropriate doses and length of therapy is
unclear and treatment guidelines are derived from
case series and expert opinion. Induction therapy
with high-dose glucocorticoids with oral prednisone
(1mg/kg/day) or intravenous pulse methylpredniso-
lone (1000mg/day for 3 days) followed by oral pre-
dnisone is required for disease control (16). Steroids
should be tapered slowly over 312 months. Cyclo-
phosphamide (12mg/kg/day or monthly pulses
750mg/m2 of body surface area) therapy usually lasts
for 3 to 6 months depending on treatment response
(5,16). Response to treatment may be made by serial
neurological examination, CSF evaluation, or MRI.
Repeat catheter angiography is not usually needed.
After remission of disease has been established, cyclo-
phosphamide should be switched to an immunosup-
pressive agent with less potential for long-term
adverse consequences, such as azathioprine or myco-
phenolate (16).
CEREBRAL AMYLOID ANGIITIS
Cerebral amyloid angiopathy (CAA) is generally
thought of as a noninflammatory small-vessel vas-
culopathy causing recurrent cortical hemorrhages
in the elderly. While sometimes considered a form
of atypical PACNS, vascular inflammation asso-
ciated with CAA has also been described and
appears to represent a specific immune response to
vascular deposits of beta-amyloid (25,26). Radio-
graphic features on MRI suggesting this diagnosis are
large, confluent, or patchy asymmetric regions of T2
hyperintensity affecting predominantly the subcortical
white matter, and prominent microhemorrhages on
gradient-echo sequences (GRE) (Fig. 10.4) (26). Find-
ings on angiography have not been well described;
however, given that the affected vessels are small
branch arteries, angiography is likely to be unre-
markable. Histopathological findings include inflam-
mation with giant cells surrounding amyloid affected
vessels (25). Inflammatory CAA appears to be
strongly correlated with the APOE e4/e4 genotype
(26). There is variable response to immunosuppressive
therapy.
SECONDARY CNS VASCULITIS
Inflammatory vasculitis of the cerebral vessels may
also be secondary to an underlying systemic illness
(Table 10.1). Systemic vasculitides, infectious proc-
esses, and malignancies may all cause inflammatory
changes in the blood vessels of the brain and spinal
cord. Depending on the underlying condition, large,
medium, or small vessels may be preferentially
affected.
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS
Systemic Vasculitides
Giant Cell Arteritis
Giant cell arteritis (GCA), or temporal arteritis, causes
segmental granulomatous inflammation along the inter-
nal elastic lamina of arteries and most commonly affects
the superficial temporal, ophthalmic, posterior ciliary,
and vertebral arteries (27). The carotid, vertebral, and
subclavian arteries are affected in up to 15% of cases
(28). Intracranial arteritis from GCA is exquisitely rare
and limited to case reports (29). Prior autopsy studies
have only demonstrated inflammatory changes a few
millimeters distal to the dural entry point of the verte-
bral arteries (30). Although not widely appreciated, the
aorta and its branches may be involved, even without
temporal artery changes (12,28). GCA is most prevalent
in the elderly, occurring in the eighth and ninth decades
of life. Typical symptoms of GCA include headache,
jaw claudication, scalp tenderness, and visual loss. Non-
specific symptoms including general malaise, weight
loss, fever, and night sweats are common. In the eld-
erly, 16% of fevers of unknown origin are caused by
GCA (31). GCA is also frequently associated with poly-
myalgia rheumatica. Involvement of the cervical vessels
may cause cerebral ischemia with corresponding focal
neurologic symptoms. The majority of cerebrovascular
events are due to thrombosis or occlusion of the extrac-
ranial vertebral and carotid arteries (29). On physical
examination, patients may have thickened nodular tem-
poral arteries or evidence of anterior ischemic optic
neuropathy on fundoscopic evaluation.
An elevated ESR is present in 9095% of patients
with temporal arteritis but is not ubiquitous (32). A
definitive diagnosis of GCA is made by temporal
artery biopsy. Diagnostic histopathological changes of
GCA persist for at least 2 weeks after initiation of ste-
roid therapy (33). A negative bilateral temporal artery
biopsy has a negative predictive value of 91% for
GCA (34). In those patients with cerebral ischemia
suspected due to GCA, the prominent large-vessel
involvement with this vasculitis supports noninvasive
vascular imaging with MRA or CTA. Catheter
(A) (B)
207
angiography is generally reserved for those being
evaluated for revascularization procedures (35).
Patients with GCA are treated with oral steroids,
and most patients have a rapid clinical response to
this treatment. Prednisone (4060mg/day) is most
often prescribed to achieve remission. In patients sus-
pected of having GCA, treatment should be initiated
as soon as possible and not delayed until a biopsy is
done. A study comparing 3 days of pulse intravenous
methylprednisolone (15mg/kg/day) followed by oral
steroids to standard therapy with oral prednisone
(40mg/day), found that initial intravenous pulse ther-
apy led to a more stable remission, allowed for more
rapid tapering of oral steroids, and resulted in a lower
total dose of glucocorticoids (36). The initial dose of
prednisone is usually maintained until remission of
symptoms and normalization of laboratory values has
been achieved, after which a slow taper is recom-
mended. Many patients remain steroid dependent
with only half able to discontinue treatment within
2 years (37,38). Antiplatelet therapy has been shown
to reduce the incidence of ischemic events in patients
with GCA in two small observational studies (39,40).
There is little data in the literature regarding the
safety and efficacy of revascularization procedures for
GCA. A case series of 29 patients with arm claudica-
tion from subclavian and axillary steno-occlusive dis-
ease from GCA reported a primary patency rate of
65% in patients treated by angioplasty despite excel-
lent technical success (41). A single case report of
angioplasty with stent placement for intracranial GCA
exists, which reports good technical success (42).
Takayasus Arteritis
Takayasus arteritis, or pulseless disease, is caused by
a panarteritic inflammatory infiltration of the aorta
and its large elastic arterial branches leading to throm-
bosis and vessel occlusion or aneurysm formation (27).
The syndrome generally affects adolescent or young
females of Asian or Mexican descent. Symptoms of
Takayasus arteritis may vary from asymptomatic
Figure 10.4 Cerebral amyloid angiopathy-related
inflammation. Right frontal biopsy showed necrotiz-
ing amyloid angiitis. (A) FLAIR sequence showing
confluent asymmetric subcortical hyperintensities.
(B) GRE sequence showing multiple diffuse
microhemorrhages.
208 NEUROINTERVENTIONAL MANAGEMENT
disease with asymmetric or impalpable pulses to heart
failure or severe neurological dysfunction (43). Most
patients complain of constitutional symptoms with
fever, generalized malaise, anorexia, carotidynia,
arthralgias, and/or myalgias (44). Some patients may
complain of thoracic back pain (12). Vertebral and car-
otid artery involvement occurs in up to 60% of
patients and may lead to cerebral or retinal ischemia
(Figs. 10.5, 10.6, 10.7) (12). Dilatation of the aortic root
and myocardium may cause aortic regurgitation and
congestive heart failure. Renal artery involvement may
lead to profound hypertension.
Acute phase reactants are abnormal in Takayasus
arteritis prior to initiation of treatment. Patients are often
anemic with elevated platelet count, ESR, and C-reactive
protein (CRP). Arterial imaging (MRA, CTA, or conven-
tional angiography) will show arterial narrowing, occlu-
sion, or aneurysmal dilatation of the great vessels. MRA
or CTA may provide additional or complimentary infor-
mation to that obtained by conventional angiography by
demonstrating perivascular or vascular wall abnormal-
ities (45,46). Catheter angiography allows for direct
aortic blood pressure measurements, which may appear
falsely normal by peripheral arterial recordings, and
may thus play a role even in patients in whom the diag-
nosis is established by noninvasive imaging (12). The
pathological findings in Takayasus arteritis are similar
to those found in GCA (44).
Patients with Takayasus arteritis are typically
treated with a combination of immunosuppressive
therapy with oral steroids and antiplatelets (43,44,47).
The 5-year survival is excellent but may depend
on the degree of cardiac, pulmonary, and neurolo-
gical impairment at diagnosis (44). Patients freque-
ntly require revascularization procedures and surgical
aneurysm repair. Despite good technical success, most
case series report relatively low rates of long-term
(A) (B)
Figure 10.5 Takayasus arteritis. (A) Marked concentric wall thickening of the aortic arch (arrowhead). (B) Wall thickening extends into
the supra-aortic branches including the common carotid arteries bilaterally (arrows). (C) Mild associated luminal narrowing of aortic
arch and proximal descending aorta with return to normal caliber (arrow).
patency following angioplasty with or without stent-
ing for arterial stenoses in Takayasus (47,48). Surgical
case series suggest that up to half of patients have
ongoing arteritis with vascular damage despite
improvement in symptoms and acute phase reactants
on medical therapy (49,50). In patients with recurrent
cerebrovascular symptoms, carotid bypass grafts may
be considered. The aorta, rather than the subclavian
or innominate artery, should serve as the proximal
site of anastomosis (12).
Polyarteritis Nodosa
Polyarteritis nodosa (PAN) is the prototypical
medium-vessel systemic vasculitis caused by focal
pan-mural necrotizing inflammatory infiltration of
affected arteries (51). PAN generally affects men more
than women and is most frequent in the fifth and
sixth decade of life (51). 10% of cases are associated
with hepatitis B viral infections (52). PAN most often
affects the skin, kidney, peripheral nervous system,
and gastrointestinal tract but there may be CNS
involvement in up to half of PAN patients (51). CNS
dysfunction usually occurs as the result of cerebral
infarction or hemorrhage or as a diffuse encephalop-
athy with alterations in level of consciousness and
seizures (1). PAN patients may also experience
monocular visual loss due to anterior ischemic optic
neuropathy (51).
A diagnosis of PAN may be made by a combina-
tion of clinical, angiographic, and histopathological
findings. Patients frequently have constitutional symp-
toms including fever, weight loss, chills, and general-
ized malaise. Acute phase reactants are often elevated.
The majority of patients will have positive antineutro-
phil cytoplasmic antibodies (ANCA) directed against
myeloperoxidase or perinuclear ANCA (p-ANCA) (1).
(C)
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 209

Neuroimaging may demonstrate infarction or hemor-
rhage involving both cortical and subcortical struc-
tures. The most common radiographic finding is
that of small cortical infarctions in territories supplied
by medium-sized arteries (53). Angiography may
demonstrate nonspecific luminal irregularities with
alternating areas of vessel narrowing and fusiform
dilatation, vascular cutoffs, or multiple saccular
aneurysms (Fig. 10.8) (12,51).
Patients with PAN are treated by a combination of
corticosteroids and cytotoxic agents, such as cyclophos-
phamide, azathioprine, rituximab or mycophenolate.

(A) (B)

(C) (D)

Figure 10.6 Takayasus arteritis. (A) CTA demonstrates wall thickening of the aortic arch and proximal great vessels (arrowhead) with
proximal narrowing of brachiocephalic artery (arrow). (B) Axial CT shows segmental dilation of the left common carotid artery (arrow)
(normal right common carotid arteryarrowhead) measuring 11.5mm in diameter, with wall thickening. (C) Sagittal reconstruction and
volume rendered. (D) Dilation of the left common carotid artery (arrows).
210 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E)

Figure 10.7 Takayasus arteritis. (A) MIP views from CTA shows tapered narrowing of proximal subclavian arteries bilaterally (arrows)
as well as areas of focal narrowing of (B) right common (arrowhead) and (C) left common carotid arteries (arrowhead). (D) Aortic arch
injection confirms involvement of proximal subclavian arteries on left and right (arrows). (E) Brachiocephalic injection better demon-
strates narrowing of right subclavian and right common carotid arteries (arrows).
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 211

(A) (B) (C) (D)

(E) (F) (G)

Figure 10.8 Polyarteritis nodosa. Patient 1 with known PAN presented with left arm weakness. (A) Axial FLAIR MR shows abnormal
signal in right frontal lobe consistent with infarction (arrow). (B) Catheter angiogram with right (B) and left (C) carotid injections as well
as left vertebral injection (D) demonstrates diffuse narrowing of intracranial vessels (arrows). Patient 2 with biopsy confirmed PAN. (E)
Catheter angiogram with AP (E) and lateral (F) views of right carotid shows diffuse irregular narrowing of intracranial vessels (arrows).
(G) Lateral view of left carotid shows small unruptured anterior cerebral artery (ACA) aneurysm (arrowhead) as well as diffuse irregular
narrowing of intracranial branches (arrows).

Alternative therapies may also include plasma exchange
or intravenous immune globulin (IVIG). Endovascular
therapies, including angioplasty and embolization, have
been employed for the treatment of systemic complica-
tions of PAN (5456).
ChurgStrauss Syndrome
ChurgStrauss Syndrome (CSS) is a rare systemic
necrotizing vasculitis marked by eosinophilic granu-
lomatous inflammation within small-to-medium size
blood vessels. CSS is relatively more common in
women and individuals with asthma. Clinically, it
manifest as severe asthma, sinusitis, and pulmonary
infiltrates (57,58). Nervous system involvement occurs
in up to 62% of patients but usually manifests as
peripheral nerve, cranial nerve, and ocular involve-
ment (59). CNS manifestations may include cerebral
infarction, ICH, SAH, and seizure (58,6062). SAH
may be spontaneous or due to arterial dissection with
pseudoaneurysm rupture (63,64). A case of primary
intraventricular hemorrhage from vasculitic involve-
ment of the choroid plexus has been described (65).
Diagnosis is based on clinical and laboratory fea-
tures of the disease. Virtually all patients have a strik-
ing eosinophilia, and 66% will have a positive
p-ANCA (58). Biopsy of an involved organ should be
performed to confirm the diagnosis. Histopathological
findings include eosinophilic tissue and blood vessel
infiltration and inflammation and necrosis (58).
Similar to other vasculitides, treatment of CSS is
usually a combination of corticosteroids and cyclo-
phosphamide (61). Alternative therapeutic regimens
may include azathioprine, mycophenolate, cyclospor-
ine, or IVIG (58).
Wegeners Granulomatosis
Wegeners granulomatosis (WG) is a fulminant necrot-
izing vasculitis that affects small-to-medium sized ves-
sels. WG is more common in men than women, and
the peak incidence is in the fourth and fifth decades
of life (51,52). WG usually affects the upper and lower
respiratory tract, causing chronic sinusitis, rhinitis,
epistaxis, hemoptysis, and dyspnea, as well as the kid-
ney, leading to a necrotizing glomerulonephritis. Con-
stitutional symptoms are common and fulminant WG
may be rapidly fatal. Up to 50% of patients develop
neurological complications (51). Ocular and peripheral
nervous system dysfunction is common. Strokes may
occur as a result of arterial or venous thrombosis
(66,67). Although typically a disease affecting
212 NEUROINTERVENTIONAL MANAGEMENT
small-to-medium sized vessels, arterial stroke has been
reported to occur as a result of large-vessel occlusion
from vertebrobasilar thrombosis and cardioembolism
from noninfective thrombotic endocarditis (66,68).
Spontaneous ICH has been reported and is associated
with a poor prognosis (69,70). Both aneurysmal and
nonaneurysmal SAH have also been described (71,72).
The diagnosis of WG is made by a combination
of clinical symptoms and abnormal laboratory tests
showing elevated acute phase reactants, eosinophilia,
and the presence of circulating classical-ANCA
(c-ANCA) antibodies. Histopathological samples dem-
onstrate a necrotizing vasculitis. Neuroimaging may
reveal dural thickening and enhancement, cerebral
infarction, and/or subcortical and brainstem white
matter changes (73). Cerebral angiography may show
vasculitic changes of small-to-medium sized vessels
(74). Large-vessel thrombosis has been described in the
basilar artery (66,75).
Treatment of WG is initially with corticosteroids
and cyclophosphamide. Initial remission may be
achieved in the majority of patients, but between
10% and 50% of patients relapse (76). Other cytotoxic
agents are alternative therapies.
Microscopic Polyangiitis
Microscopic polyangiitis (MPA) is a diffuse necrotiz-
ing vasculitis affecting small vessels including arterio-
les, capillaries, and venules. MPA is more common in
men than women and usually presents in the fifth or
sixth decade of life (51). Clinically, MPA usually man-
ifest with kidney failure caused by a rapidly progres-
sive focal segmental necrotizing glomerulonephritis
(51). This may be proceeded by the insidious onset of
skin, joint, or pulmonary involvement that usually
has a relatively indolent course (77). Neurological
complications are relatively uncommon; however,
peripheral nervous system involvement or small-
vessel strokes may occur. Diagnostic evaluations may
reveal renal dysfunction with hematuria, proteinuria,
and a positive p-ANCA. Unlike PAN, infection with
hepatitis B virus is uncommon (51). Untreated MPA
has a poor prognosis. Treatment with corticosteroids
and cyclophosphamide is generally recommended
(51,78).
Behcets Disease
Behcets disease is a multisystem vascular inflamma-
tory condition of unknown etiology. Behcets classi-
cally causes painful oral and genital ulceration,
uveitis, arthritis, retinal or cutaneous vasculitis, and
thrombophlebitis (1). Neurological involvement may
occur in up to 20% of cases, but is clinically apparent
in only 5% (79,80). Neuro-Behcets generally manifests
as acute inflammatory lesions of the brain paren-
chyma. Cerebral vasculitis is uncommon but can lead
to arterial and venous thrombosis (12,81,82). Neuro-
Behcets vasculitis has a predilection for the brainstem
and diencephalons (82,83). Behcets disease may be
diagnosed clinically by an appropriate constellation of
clinical features. Neurological involvement is usually
accompanied by inflammatory CSF. Corticosteroids
are the mainstay of treatment.
Sarcoidosis
Sarcoidosis is a multisystem granulomatous inflamma-
tory condition of unknown etiology that is more com-
mon in people of African descent. Neurological
involvement may occur in a minority of patients (84).
The diagnosis of neurosarcoidosis may be presump-
tively made on the basis of appropriate clinical and
radiographic features in a patient with sarcoid granulo-
mas demonstrated on tissue biopsy. Neurosarcoidosis
usually causes granulomatous inflammation of the lep-
tomeninges or brain parenchyma (84,85). MRI findings
may vary but most patients have evidence of leptome-
ningeal enhancement on contrast-enhanced studies;
abnormalities have also been described in the hypothal-
amus, pituitary gland, periventricular white matter,
ependyma, and optic chiasm (86). Leptomeningeal
involvement may lead to secondary perivascular
inflammatory changes in penetrating cortical and spi-
nal vessels causing cerebral or spinal cord ischemia
(8789). A diffuse large-vessel intracranial vasculop-
athy has also been reported (90). ICH and SAH appear
relatively rare in neurosarcoidosis, and their descrip-
tion is limited to case reports (91,92). Treatment with
steroids or other immunosuppressant drugs is usual.
Angioplasty and stenting of hemodynamically signifi-
cant large-vessel stenosis has been suggested in
patients who fail traditional medical therapies (90).
Cryoglobulinemia
Cryoglobulins are soluble serum proteins that are usu-
ally composed of immunoglobulins (IgG, IgM, or
mixed) (51). Monoclonal cryoglobulinemias are usually
associated with lymphoproliferative disorders, while
mixed cryoglobulinemias may result from connective
tissue diseases, systemic vasculitides, and chronic
infections (hepatitis C virus) (51). Mixed cryoglobuline-
mia typically presents with purpura from a cutaneous
vasculitis and progressive renal failure due to glomeru-
lonephritis (51). Peripheral neuropathies may occur,
but CNS involvement is unusual and may vary in pre-
sentation and severity. Reports of cases of progressive
encephalopathy, seizures, and coma exist (9395). Some
patients experience focal neurological dysfunction from
cerebral ischemia (93,95). Petechial hemorrhage of
white matter tracts, termed cerebral purpura was
previously described at autopsy (96). Angiography in
cases of mixed cryoglobulinemia has suggested a large-
vessel vasculopathy affecting the circle of Willis with
multiple areas of luminal narrowing (95). Acute treat-
ment with plasma exchange is recommended for emer-
gency treatment while immunosuppressive agents are
used for maintenance therapy (97). Patients with associ-
ated chronic hepatitis C infection should be considered
for interferon therapy (97).
Connective Tissue Disease Vasculitides
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a multisystem
disorder that affects skin, mucous membranes, kid-
ney, joints, heart, and lung. Neurological involvement
is common and usually manifest with diffuse cerebral
dysfunction causing neuropsychiatric disturbances (98).
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS
Headache, pseudotumor cerebri, transverse myeli-
tis, and optic neuropathy may also occur (51). Stroke
and ICH may occur; however, this is usually due to
causes other than cerebral vasculitis (98100). While
up to 1015% of SLE patients have a systemic vasculi-
tis, intracranial vessel involvement is exceedingly
rare (51). Cerebral vascular changes in SLE may take
the form of a necrotizing vasculitis affecting small
arteries, arterioles, and capillaries, or as a noninflam-
matory vasculopathy caused by circulating antiphos-
pholipid antibodies (APLA) leading to arterial and
venous thrombosis (51). Diagnosis is made by an
appropriate constellation of clinical symptoms and
signs and supported by laboratory studies. SLE
patients have antinuclear antibodies, and may have
an elevated ESR and low complement levels. Patients
are usually treated with steroids and immunosup-
pressive agents. APLA positive patients with a history
of arterial or venous thrombosis are usually treated
with anticoagulants.
Sjogrens Syndrome
Sjogrens (sicca) syndrome is characterized by dry
mouth and dry eyes and caused by lymphoid inva-
sion of exocrine tissues (51). Sjogrens syndrome is
commonly associated with other autoimmune condi-
tions. Stroke may be a presenting feature of Sjogrens
syndrome due to a vasculitis of small-to-medium
sized arteries (101). Sjogrens is typically associated
with extractable RNA proteins Ro (SS-A) or intranu-
clear RNA-associated antigen La (SS-B) (1). Antineuro-
nal antibodies (anti-TA/MA2), more commonly
associated with paraneoplastic syndromes, have also
been implicated in Sjogrens cerebral vasculitis (102).
Immunosuppressive drugs are used for treatment.
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a multisystem inflamma-
tory disease that most often affects the joint space. RA
also frequently affects the peripheral nervous system.
Mononeuritis multiplex results from a systemic small-
to-medium vessel vasculitis affecting the vasa nervo-
rum. Rheumatic pachymeningitis is caused by lym-
phocytic infiltration and fibrinoid necrosis of the
meninges leading to headache, seizure, encephalop-
athy, and subarachnoid and/or ICH (1). Involvement
of the cervical spine with pannus formation or sublux-
ation of the atlantooccipital junction may cause verte-
bral artery compression and stroke (1,103). Symptoms
may fluctuate with head turning causing varying
degrees of arterial obstruction or occlusion (104). Cere-
bral vasculitis due to RA is rare but may resemble
that of PAN with necrosis of medium-sized arteries
(105). Most patients will have a positive rheumatoid
factor (RF), and the treatment is with steroids and
immunosuppressant drugs.
Scleroderma
Scleroderma (systemic sclerosis) and the CREST (calci-
nosis, Raynaud phenomenon, esophageal dysfunction,
sclerodactyly, and telangectasia) syndrome are idio-
pathic diseases characterized by progressive fibrosis of
213
the skin and internal organs. The underlying etiology
is believed to be autoimmune and may lead to a vas-
culopathy from blood vessel fibrosis (106,107). ANCA-
associated vasculitis (AAV) may also occur in up to 7%
of patients with scleroderma causing a necrotizing
small-vessel vasculitis similar to that found in WG,
MPA, and CSS. Scleroderma with AAV may affect the
skin, heart, kidneys, lungs, and nervous system (107).
Neuropathological findings in scleroderma with CNS
involvement include vascular calcification with necrosis
in small caliber arteries and arterioles primarily affect-
ing subcortical structures (108,109). Scleroderma
patients with AAV may be treated with steroids and
cyclophosphamide; however, the prognosis is poor.
Despite treatment up to a third of patients die (107).
Infectious Vasculitides
Cerebral vasculitis may be caused by a number of
viral, fungal, and bacterial organisms. Infectious vas-
culitides may cause either ischemic or hemorrhagic
stroke. The presence of fever, signs of meningeal irri-
tation, or other systemic symptoms and signs of infec-
tion should prompt a thorough infectious work-up.
Cerebral spinal fluid analysis is paramount and may
show elevated protein levels, increased WBC count,
which may be lymphocytic predominant in the case of
viral infections or polymorphonuclear predominant in
bacterial infections. Decreased glucose levels suggest
bacterial or mycobacterial infections. CSF gram stain,
cultures, serological studies, or PCR may provide a
definitive diagnosis; however, the sensitivity for detec-
tion of many infections is suboptimal.
Bacterial Infections
Bacterial infections may cause vasculitic changes of the
cerebral vessels by several mechanisms (Fig. 10.9). Ton-
sillitis, paratonsillar, and retropharyngeal infections
may cause a secondary arteritis of the neighboring
internal carotid artery (110). Basilar meningitis causes a
secondary cerebral vasculitis as purulent material
causes an inflammatory infiltration of arteries within
the subarachnoid space (1). Direct vessel invasion may
also occur with a corresponding inflammatory reaction.
A study of vascular changes in bacterial meningitis
reported angiographic changes, including large-vessel
narrowing and dilatation, branch vessel occlusion, and
venous sinus thrombosis, in approximately half of
patients (111). Infective endocarditis may lead to septic
embolization with cerebral infarction and hemorrhage
or mycotic aneurysm formation and SAH.
The primary treatment in cases of bacterial infec-
tion affecting the cerebral vasculature is appropriate
antibiotic therapy with good CSF penetration. Adjunc-
tive dexamethasone may also play a role in the treat-
ment of bacterial meningitis in developed countries,
especially in cases of S. pneumonia meningitis (112).
Mycobacterium Tuberculosis
Chronic basilar meningitis caused by Mycobacterium
tuberculosis may be complicated by a secondary vas-
culitis (113). Patients usually have signs of meningitis
including fever, headache, meningismus, cranial
214 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 10.9 Bacterial meningitis associated with intracranial vessel narrowing. (A) AP views of right and left (B) carotid injections dem-
onstrate intracranial ICA, proximal middle cerebral artery (MCA), and proximal ACA narrowing due to bacterial meningitis.
neuropathies, and may have other focal neurological
deficits. Tuberculous endarteritis may be complicated
by either ischemic or hemorrhagic infarction usually
in subcortical structures supplied by the penetrating
arteries at the base of the brain (114). The diagnosis
should be considered in areas where tuberculosis is
endemic or in the immunocompromised patient. The
diagnosis is confirmed with demonstration of the
organism in the CSF by culture or positive staining
for acid-fast bacilli staining. The CSF will typically
have a markedly elevated WBC count and protein,
and very low glucose. The treatment of tuberculosis is
generally a multidrug approach using isoniazid,
rifampin, ethambutol, and pyrazinamide (115).
Meningovascular Syphilis
Syphilis is caused by infection with Treponema pallidum.
Meningovascular syphilis, or Heubners arteritis, is the
most common neurological manifestation of syphilis
and occurs in up to 61% of cases of neurosyphilis (116).
Vasculitic infiltration of medium-to-large arteries leads
to arterial stenosis and occlusion (117). Arterial involve-
ment may be purely intracranial preferentially affecting
the middle cerebral artery (Table 10.2), or it may affect
intracranial and extracranial vessels including the aorta
and its branches (Fig. 10.10, 10.11).
Neurological involvement from meningovascular
syphilis may occur within weeks to years of the pri-
mary infection (118).
Screening of stroke patients in high-risk popula-
tions by measuring nontreponemal serologic test, such
(B)
Table 10.2 Site of Thrombosis in Cerebrovascular Syphilis from
the Original Boston City Hospital Study (172)
Artery involved Number of cases
Internal carotid 1
Anterior cerebral 3
Middle cerebral 26
Anterior choroidal 1
Posterior cerebral 3
Basilar of its branches 5
Posterior inferior cerebellar 3
Analysis of 42 cases, 5/42 cases with thrombosis at multiple sites.
as the serum rapid plasma regain (RPR) or venereal
disease research laboratory (VDRL) assay, may be
warranted. The sensitivity of the RPR and VDRL in
patients with neurosyphilis is only 6075% and may
be even lower in immunocompromised patients lead-
ing some to recommend treponemal tests to screen
this population (119). A positive RPR or VDRL test
may be confirmed using treponemal-specific tests,
such as the fluorescent treponemal antibody (FTA).
When neurosyphilis is a diagnostic consideration, a
lumbar puncture should be performed. The CSF in
meningovascular syphilis should have a lymphocytic
pleocytosis, elevated protein, reactive CSF-VDRL, or
positive T Pallidum PCR. Penicillin is the treatment of
choice for neurosyphilis and may reverse the associ-
ated vascular changes (117,118). Antiplatelet agents
may also be used in those with symptoms of cerebral
ischemia.
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 215

(A) (B) (C)

Figure 10.10 Neurosyphilis with large-vessel involvement. (A) Injection of left carotid artery shows tapered narrowing of M1-2 (arrow).
(B) Catheter angiogram with AP (B) and lateral (C) views of right vertebral artery injection show proximal basilar occlusion (arrow).

(A) (B) (C)

(D) (E) (F)

Figure 10.11 Neurosyphilis with both proximal and distal involvement. (A) Axial CTA demonstrates irregularity of intracranial branches
(arrowheads). (B) Coronal view of irregularity of basilar artery (arrow). (C) Right vertebral artery injection shows irregularity of basilar
artery (arrow) as well as involvement of distal left vertebral artery and PCA branches bilaterally (arrowheads). (D) Left internal carotid
artery injection shows middle cerebral artery (arrow) and cortical branch involvement (arrowhead). Lateral views of left (E) and right
(F) carotid injections show irregularity of cortical branches (arrowheads).

Angioinvasive Aspergillosis typically from pulmonary infections, can lead to neuro-

logical involvement through infection of the cerebral ves-
Aspergillosis is a fungal infection that typically occurs in sels. Direct extension of aspergillosis from orbital and
immunocompromised patients. Hematogenous spread, paranasal sinus infection may lead to septic thrombosis of
216 NEUROINTERVENTIONAL MANAGEMENT
(A)
[R]
C1
[P] W
(C)
Figure 10.12 Aspergillus fungal sinusitis with vascular involvement. (A) Axial and (B) Coronal CT scans show soft tissue in sphenoid
sinus with destruction of carotid canal (arrow). (C) Axial time of flight MR shows narrowing of right internal carotid artery (arrow). (D)
Angiography confirms narrowing of right internal carotid artery (arrow). Patient underwent endovascular carotid occlusion followed by
endoscopic removal of debris from sphenoid sinus.
arteries and veins (Fig. 10.12) (120). Angioinvasive asper-
gillosis is an infectious vasculopathy that may cause cere-
bral infarction, ICH or SAH, cerebritis, or abscess
formation (121). Aspergillosis preferentially affects the
lenticulostriate and thalamoperforating arteries leading to
infarction of the basal ganglia, corpus callosum, and tha-
lami (121). Lesions typically have unusual enhancement
patterns, may grow rapidly, and cause reactive edema as
fungal brain invasion occurs. The diagnosis should be
considered in any immunocompromised person with or
without a history of pulmonary aspergillosis presenting
with the above pattern of infarction or hemorrhage.
Infarction of the corpus callosum by involvement of the
medial lenticulostriates and penetrating branch vessels of
the pericallosal arteries is relatively uncommon in other
conditions and should suggest aspergillosis (121). The
diagnosis may be confirmed by biopsy demonstrating the
organism (Fig. 10.13). CNS aspergillosis generally has a
very poor prognosis, but may be effectively treated if
diagnosed early and treated with appropriate antifungal
drugs (122,123).
(B)
[L]
(D)
Mucormycosis
Mucormycosis is a fungus that usually infects the par-
anasal sinuses in poorly controlled diabetics and other
immunocompromised hosts. Direct extension of the
infection to the brain, cavernous sinus, or orbit causes
a necrotizing vasculitis with thrombosis of adjacent
vessels (1,124). Cerebral angiography may show vessel
wall abnormalities with terminal carotid artery steno-
sis and distal branch occlusion (1). The prognosis is
generally poor, but initial treatment with intravenous
amphoteracin B or newer second generation triazoles
may be effective (125). Surgical debridement and sinus
reconstruction may be necessary.
Varicella Zoster Virus
Varicella zoster virus (VZV) commonly causes chicken-
pox in children and reactivation causes shingles in
adults. Rarely VZV infects the cerebral arteries leading
to a necrotizing vasculitis of the media of affected blood
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 217

vessels causing ischemic and hemorrhagic stroke (1,126).

Figure 10.13 Aspergillus vasculitis. Biopsy specimen with
Gomori methenamine silver stain showing aspergillus invading a
cortical vein. Image courtesy of Dr. Roy Rhodes, UMDNJ-Robert
Wood Johnson Medical School, Department of Pathology.
VZV vasculopathy may affect large or small arteries
and usually occurs in one of two patterns. Single large-
vessel involvement typically occurs in the elderly after
ophthalmic-distribution zoster due to involvement of
the carotid, anterior cerebral, or middle cerebral arteries
(127,128). A diffuse vasculopathy affecting small arteries
and branch vessels of larger arteries generally occurs in
the immunocompromised patient leading to multiple
bilateral infarcts (Fig. 10.14) (127,128).
The majority (63%) of adult cases of VZV vascul-
opathy are preceded by a rash (127). On average,
there is a 4-month interval between the occurrence of
a rash and neurological involvement (127). Strokes
may be preceded by TIAs or perfusional symptoms
due to flow limiting large-vessel stenoses. CSF analy-
sis should be performed in patients suspected of hav-
ing VZV vasculopathy. CSF abnormalities may
include a lymphocytic pleocytosis, positive anti-VZV
IgG antibodies (93%), elevated anti-VZV IgG CSF to
serum synthesis rate (93%), or identification of VZV
DNA (30%) by PCR (127). Angiography is abnormal
in the majority of cases. Acute treatment with oral or
intravenous antiviral therapy with or without concom-
itant steroid therapy may be used. Chronic

R]

(A) (B) (C)

(D) (E)

Figure 10.14 Varicella zoster vasculitis. Patient presented with left hemiparesis and a left visual field deficit. (A) Axial-enhanced T1-
weighted MRI demonstrates enhancing infarct involving right occipital cortex. Higher cuts (not shown) showed additional areas of watershed
infarction. MPR (B) and volume rendered (C) reconstructions from CT angiogram demonstrate smooth narrowing of right supraclinoid ICA
(arrows). (D) AP view of right internal carotid artery injection shows abrupt smooth narrowing of the supraclinoid ICA, proximal MCA and
ACA (arrow). (E) AP view of left vertebral artery injection shows tapered occlusion of the PCA (arrow) distal to the inferior temporal branch.
218 NEUROINTERVENTIONAL MANAGEMENT
suppressive therapy with oral antivirals may be used
to prevent recurrence.
Human Immunodeficiency Virus
Stroke may occur in patients with human immunode-
ficiency virus (HIV)/acquired immune deficiency syn-
drome (AIDS) by a multitude of mechanisms,
including secondary or opportunistic infectious organ-
isms causing meningitis and/or vasculitis, disorders
of coagulation, cardioembolism, altered cholesterol
metabolism leading to advanced atherosclerosis, or
primary HIV vasculopathy (129,130). Cerebral infarc-
tion is more common than ICH (130).
Two forms of HIV-associated vasculitis have
been reported. The first reported pattern is identical to
PACNS without evidence of direct viral or opportun-
istic infection (1,120). The second pattern reported
shows evidence of a perivascular necrotizing inflam-
matory response to HIV infection (1). However, stroke
and vasculopathy in HIV-infected patients are more
commonly associated with other causes than vasculi-
tis, and a search to exclude opportunistic infections
should be performed. The treatment of HIV-associated
vasculopathies revolves around treatment of HIV with
antiretroviral drugs and appropriate therapy for any
underlying secondary infection.
Other Infectious Agents Associated with Vasculitis
Other fungal, bacterial, and viral infections have been
associated with an infectious vasculitis. Leptospirosis
is a spirochetal infection, found primarily in China
and Southeast Asia, that may lead to meningitis or
cerebral arteritis. Leptospiral arteritis causes a moya-
moya syndrome leading to recurrent ischemic events,
ICH and SAH (131). Angiographic findings include
stenosis or occlusion of the extracranial internal caro-
tid (C1-C2 segment), proximal middle cerebral, and/
or proximal anterior cerebral arteries with moyamoya
collateral vessels (131). Cryptococcal meningitis is a
fungal infection that may occur in either normal or
immunocompromised individuals and typically
results in a chronic meningitis with granuloma and
abscess formation. However, cases of vascular
involvement with stroke and pseudoaneurysm forma-
tion have been described (132). Coccidioidomycosis is
a fungal infection endemic in the Southwest U.S. that
usually causes a self-limited pulmonary infection in
immunocompetent hosts. However, in the immune
suppressed coccidioidomycosis may infect the CNS
causing a chronic meningitis, encephalomyelitis,
parenchymal abscess formation, and endarteritis oblit-
erans (133). Chronic hepatitis C viral infections may
lead to mixed cryoglobulinemia and an associated
small-vessel vasculitis which was previously dis-
cussed. Hepatitis B infections may be associated with
PAN and a medium-vessel vasculitis.
REVERSIBLE CEREBRAL VASOCONSTRICTION
SYNDROMES
The reversible cerebral vasoconstriction syndromes
(RCVS) are a group of pathophysiologically related disor-
ders, in which abnormalities in cerebrovascular tone lead
to diffuse constriction and dilatation of medium-to-large
cerebral arteries (134). The spectrum of RCVS includes
primary RCVS (also called CallFleming syndrome or
benign angiopathy of the CNS), post-partum angiopathy
(PPA), migrainous vasospasm, drug-induced arteritis,
hypertensive encephalopathy, and reversible posterior
leukoencephalopathy syndrome (also called posterior
reversible encephalopathy syndrome) (16).
Several vasoactive substances, including many
commonly prescribed medications, have been associated
with developing RCVS and are presented in Table 10.3
(135143). PPA is a well-described RCVS that may fol-
low pregnancy, especially when complicated by pre-
eclampsia/eclampsia (136,137,144). Pheochromocytoma,
carcinoid tumors, hypercalcemia, porphyria, as well as
some vascular and neurosurgical procedures have also
been associated with RCVS (134).
RCVS is more common in younger females with
a mean age of onset at 45 (2,134,145). Headache is a
prominent feature, and patients often present acutely
with severe thunderclap headaches, similar to those
described in aneurysmal SAH (134). Although some-
times termed benign, patients may present with
seizures, TIAs, cerebral ischemia, or intracranial bleed-
ing (134,146). Unlike that associated with aneurysm
rupture, SAH associated with RCVS is typically
located superficially over the convexities of the cere-
bral hemispheres. Approximately, one-third of RCVS
patients will have intracranial bleeding (145). Between
25% and 30% develop SAH, and an additional 12%
and 2% have ICH and SDH, respectively (145,146).
Cerebral infarction occurs in about 5% of cases as a
result of flow-limiting vasoconstriction or as a conse-
quence of arterial dissection (144,147). The clinical fea-
tures and differences between RCVS and cerebral
vasculitis are presented in Table 10.4.
There are no specific diagnostic laboratory tests
for RCVS. CSF analysis may be useful in selected
patients for differentiating RCVS from cerebral vascu-
litis. Assuming SAH is not present, the CSF in RCVS
should be normal or near-normal (CSF protein < 80
mg/dL, CSF WBC < 10mm3, and normal CSF glucose)
Table 10.3 Substances Associated with Reversible Cerebral
Vasoconstriction Syndromes
Sympathomimetic drugs
Phenylpropanolamine
Pseudoephedrine
Amphetamine and derivatives
Cocaine
Ephedra
Isometheptene
Serotonergic drugs
SSRIs
Triptans
Ergotamine and ergot derivatives
Dopaminergic drugs
Bromocriptine
Lisuride
Immunosuppressant drugs
Tacrolimus
Cyclophosphamide
Others
Erythropoietin
Intravenous Immunoglobulin
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 219

Table 10.4 Clinical Features of Primary Angiitis of the CNS and Reversible Cerebral Vasoconstriction Syndromes

Characteristics PACNS RCVS

Sex Male > Female Female > Male
Age (median, years) 40 60 20 40
Symptoms
Headache >60%, Chronic and progressive Acute and severe
Encephalopathy Common, insidious and progressive Possible, acute
Stroke/ TIA 40%, usually late feature May occur at onset
Seizures <25% Yes
Prodromal symptoms (fever, nightsweats) <20%, more common with systemic vasculitis No
CSF findings Lymphocytic pleocytosis, elevated protein Normal

(A) (B)

(C) (D)

Figure 10.15 Reversible cerebral vasoconstriction syndrome (RCVS). Patient was a 26-year-old woman with thunderclap headache.
(A) CT demonstrates subtle cortical SAH in right frontal region (arrow). (B) MRI FLAIR and GRE (C) images show signal abnormality
in sulci compatible with SAH (arrow). (D) Lateral view of right carotid catheter angiogram shows cortical vessel narrowing in same
region (arrows). Narrowing resolved on follow-up angiogram at 3 months (not shown).
220 NEUROINTERVENTIONAL MANAGEMENT

(134). In contrast, cerebral vasculitis will often be asso-
ciated with inflammatory CSF.
CT and MRI in RCVS may show evidence of cere-
bral infarction, intracranial bleeding, or cerebral edema
(Fig. 10.15). However, the sensitivity of CT imaging to
detect changes of RCVS is low, with approximately 12%
showing abnormalities, mostly cortical SAH (147). MRI
may show evidence of cortical SAH, ICH, acute infa-
rction, or parenchymal edema in one third of cases
(146,147). White matter changes consistent with vaso-
genic edema are seen in 9% of cases (147).
The presence of transient segmental narrowing and
dilatation on cerebrovascular imaging defines RCVS.
Conventional catheter angiography or noninvasive imag-
ing with MRA or CTA shows the characteristic changes
in the medium-to-large vessels surrounding the circle of
Willis (Fig. 10.16). Catheter angiography is much more
sensitive and specific for identifying these changes than
noninvasive imaging. Follow-up vascular imaging should
show resolution of these changes by 3 months from onset.
It may be useful to correlate an initial noninvasive vascu-
lar imaging study with initial catheter angiography so
that follow-up to assess for resolution of the vascular
changes can be performed without repeating catheter
angiography. Transcranial Doppler ultrasound may be
useful for this purpose if elevated flow velocities are

(A) (B) (C)

Figure 10.16 Reversible cerebral vasoconstriction. Patient experienced thunderclap headache (arrows). (A) Unenhanced CT shows
cortical SAH over right frontal lobe. (B) Right and (C) left carotid angiography shows multiple areas of focal narrowing (arrows).

(A) (B) (C)

Figure 10.17 Extracranial fibromuscular dysplasia in a patient with a transient visual disturbance. (A) Injection of right CCA demonstrates
characteristic stack of coins configuration of FMD involving cervical internal carotid artery (arrow). (B) Right vertebral artery injection (AP
view) shows additional involvement with FMD (arrow). (C) AP view of right intracranial ICA shows ophthalmic artery aneurysm (arrow).
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VASCULITIS 221

documented initially to serve as a baseline. Alternatively,
CTA or MRA may be used if the vascular abnormalities
are clearly visible with these imaging modalities.
The optimal treatment of RCVS is unclear given
the lack of controlled clinical trials and is based on
anecdotal evidence and expert opinion. In most cases,
RCVS is a self-limited illness and may resolve without
treatment (11,136,142). There may be some benefit
from treatment with calcium-channels blockers, such
as nimodipine or verapamil (11,148150). Nimodipine
may reduce headache severity, but has not been
shown to prevent or limit recurrent stroke or intracra-
nial hemorrhage (145). In patients with prominent
fluctuating focal neurological symptoms or evidence
of cerebral infarction, caution should be exercised to
avoid decreasing cerebral perfusion pressure when
using these antihypertensive medications. Magnesium
sulfate infusions are often used to treat PPA given the
frequent association with pre-eclampsia/eclampsia
(151). Short courses of high-dose corticosteroids have
also been suggested as a possible treatment option (11).
Withdrawal of potential precipitating medications is
essential (Table 10.3).
OTHER IMPORTANT VASCULITIS MIMICS
A number of other vasculopathies may mimic the
angiographic appearance of CNS vasculitis. Fibromus-
cular dysplasia (FMD) is a noninflammatory
vasculopathy that classically affects the renal arteries
but may affect both extracranial and intracranial ves-
sels and cause multifocal vascular irregularity with a
stack of coins appearance (Fig. 10.17, 10.18). The
carotid circulation is involved in between 25% and
30% of cases, and intracranial aneurysms are reported
to occur in up to half of patients (152). FMD may lead
to ischemic stroke through arterial dissection, local
atherosclerosis, or in-situ thrombosis (152155). Anti-
platelet therapies are generally recommended for sec-
ondary stroke prevention; however, a short course of
anticoagulation may be considered in patients with
arterial dissection. Percutaneous angioplasty may be
appropriate in some cases of symptomatic cerebrovas-
cular FMD (152).
Several malignancy-related disorders, including pri-
mary CNS lymphoma, cerebral LYG, angiocentric lym-
phoproliferative disorders, and carcinomatous meningitis
may all mimic cerebral vasculitis. LYG is a rare angiocen-
tric lymphoreticular disease associated with EpsteinBarr
infection and B-cell lymphoma that may affect the CNS
(156,157). Blood vessel wall infiltration leads to areas of
focal constriction and aneurysmal dilatation (158).
Moyamoya disease is an idiopathic progressive
large-vessel vasculopathy relatively more common in
Asians. The disease causes progressive obliteration of the
terminal internal carotid arteries and their proximal
branches (159). A network of small collateral vessels
forms at the skull base to compensate for the progressive

(A) (B) (C) (D)

(E) (F) (G) (H)

Figure 10.18 Multifocal fibromuscular dysplasia. Patient 1 had aortic and bilateral renal artery stenosis treated with bypass at age 8, and
at age 14 had a left hemispheric TIA. (A) Aortic stenosis (black arrow) treated by bypass (arrowheads) and bilateral renal bypass (white
arrows) (B) MRA shows no filling of left MCA branches. (C) Left ICA injection demonstrates supra-ophthalmic occlusion of intracranial ICA
(arrow). (D) Right ICA injection shows smooth focal narrowing of proximal right A1 (arrow). (E) Vertebral artery injection shows collaterals
to left anterior circulation. Patient 2 presented with acute left hemiparesis at X age. (F) Axial FLAIR MRI shows right hemisphere water-
shed infarction. (G) Injection of right common carotid artery shows characteristic extracranial FMD involving cervical internal carotid artery
(arrows). (H) Intracranial view shows narrowing of intracranial ICA and tapered focal narrowing of right A1 (arrows).
222 NEUROINTERVENTIONAL MANAGEMENT
loss of carotid circulation. Leptomeningeal collaterals
may also form to supply the cortical surface from the
extracranial carotid circulation. A similar angiographic
pattern (moyamoya syndrome) may occur in other condi-
tions, such as atherosclerosis, sickle cell disease, hyper-
coagulable disorders, radiation-induced vasculopathy,
head trauma, neurofibromatosis, Downs syndrome, and
other inflammatory or infectious diseases (159,160).
Radiation therapy for treatment of head and
neck cancers may cause an noninflammatory vasculop-
athy due to endothelial damage, vessel fibrosis, and/or
accelerated atherosclerosis (161164). Radiation-induced
vasculopathy may affect both extracranial and intracra-
nial large vessels as well as the microvasculature circula-
tion. Large-vessel steno-occlusive disease may be treated
with endarterectomy or percutaneous angioplasty with
or without stent placement (165167). Endovascular
treatment may be preferred in patients with cervical car-
otid disease as soft-tissue scarring and fibrosis may
make an open surgical approach more difficult.
Cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy (CADA-
SIL) is an inherited condition causing headache,
stroke, and progressive dementia (168). CADASIL is
caused by a mutation in the NOTCH 3 gene and causes a
small-vessel arteriopathy. MRI changes include
subcortical white matter changes with prominent involve-
ment of the external capsules and anterior temporal lobes
(168). The diagnosis may be confirmed by skin biopsy
and gene mutation analysis (168,169). Angiography may
sometimes reveal large-vessel involvement, but is not
routinely used for diagnosis and may be associated with
an increased rate of complications (170,171).
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 11
Techniques and devices in interventional neuroradiology
Walter Zink, Alejandro Santillan, Athos Patsalides, Y. Pierre Gobin, and Howard A. Riina
INTRODUCTION
In this chapter, we discuss basic techniques used in
the neurointerventional suite and review many
devices available to the interventional neuroradiolo-
gist. Unfortunately, the sizes of these devices are
described in many different units of measurement.
Catheters are described in French (Fr), wires are
described in inches (), needles are described in
gauge (G), and vessel diameter commonly is meas-
ured in millimeters (mm). When determining which
instruments to use for an intervention, it is essential
to keep in mind that 3-Fr = 1mm = 0.039, where
larger values are used to describe a larger instru-
ment. Gauge describes the outer diameter (O.D.) of a
needle, while the inner diameter (I.D.) varies among
manufacturers. Unlike the other three units just
described, larger caliber needles are described with
increasingly lower gauge number (e.g., a 19-G needle
has a larger O.D. than a 21-G needle).
PREOPERATIVE EVALUATION
Whether in the emergent or elective setting, the
approach to the patient begins with a review of
the patients past medical, surgical, and anesthesia his-
tory, which can affect whether the intervention should
be performed at all, the technical approach, and device
selection. Relevant history includes recent surgery, prior
neurovascular or neurologic disease, coronary artery dis-
ease with or without prior placement of coronary stents,
and renal function requiring or not requiring dialysis.
Current medications should be reviewed with particular
attention to antiplatelet and anticoagulant drugs. Aller-
gies should be reviewed and if the patient is being
assessed for a possible neurovascular procedure, pre-
vious iodinated contrast administration should be deter-
mined. If the patient has had an adverse reaction
following contrast injection (e.g., hives, rash, stridor, lar-
yngedema, hemodynamic instability), oral prednisone
and diphenhydramine usually are administered as
standard premedication protocol for preventing subse-
quent allergic reaction to iodinated contrast (1--3),
although recent evidence suggests diphenhydramine has
no significant effect in prophylaxis for contrast reaction
(46). At our institution, we dose adults with 50mg oral
prednisone 24-, 12- and 1-hour prior and 50-mg diphen-
hydramine 1-hour prior to contrast administration.
Next, a physical examination should be per-
formed and relevant recent laboratory and imaging
studies reviewed. The physical exam should include
an assessment of vital signs, pulmonary and cardiac
status, complete neurological examination with docu-
mentation of any preprocedural deficit, peripheral
pulse evaluation, including bilateral dorsalis pedis
and posterior tibial pulses for transfemoral approaches
and an Allens test prior to procedures requiring
radial artery access. Laboratory evaluation of the
patients platelet and coagulation pathway function
should include platelet count (PLT), prothrombin time
(PT), partial thromboplastin time (PTT), and interna-
tional normalized ratio (INR). For patients who have
diminished absolute platelet value, are taking antipla-
telet therapy or have prolonged coagulation times, we
commonly use a 21-G micropuncture set to access the
common femoral artery (CFA) rather than a standard
19-G base plate needle. Laboratory evaluation of the
patients renal function should include blood urea
nitrogen (BUN) and creatinine (CRT). We define renal
insufficiency as CRT > 1.5mg/dL and for patients, the
most important consideration is to use only the mini-
mum volume of contrast necessary to conduct the pro-
cedure safely. Prehydration with sodium bicarbonate
(130 mEq/L IV solution at 3.5mL/kg bolus over
1 hour, then 1.2mL/kg/hr during the procedure and
for 6 hours after the procedure) and administration of
N-acetylcysteine (600mg orally at 24 and 12 hours
before and after the procedure) has been recom-
mended (7,8), although more recent literature suggests
these pretreatments offer no added renal protection
compared with the intravenous normal saline (9). At
our institution, we administer sodium bicarbonate
150mEq/1150mL in 5% dextrose in water at a dose of
3mL/kg for 1 hour prior and 6 hours after contrast
administration. Before cerebral angiography, in addi-
tion to reviewing relevant axial imaging, a prior
contrast-enhanced chest CT, often performed for other
reasons, can provide useful information about the
anatomy of the aortic arch. Similarly, prior femoral
ultrasound or pelvic MR or CT angiogram can pro-
vide anatomic information that is useful in prepara-
tion for transfemoral access.
Of paramount importance in the preoperative
patient visit is a succinct but comprehensive discus-
sion of the intended procedure, as well as the risks,
benefits, and alternatives of the suggested therapy.
Many patients may require education about the
intended procedure, after which, informed written
consent should be obtained from the patient or
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
his/her representative (health care proxy or closest
relative) if the patient is incapacitated. In the latter
circumstance, the discussion should be documented
in the patients medical record. In extenuating situa-
tions, emergency consent by two physicians allows
the rapid institution of lifesaving therapy (e.g., for
acute stroke). Particular requirements for consent vary
between regions and institutions and must be learned
and strictly followed during the consenting process.
Depending on the patients age, clinical status,
and anesthesia requirements, further investigation and
testing may be required, including electro- and echo-
cardiography, chest X-ray, pulmonary function tests,
and one or more referrals to specialists in internal
medicine, cardiology and/or pulmonology may be
required for presurgical clearance. The use of general
endotracheal anesthesia versus monitored sedation
during endovascular procedures depends on several
factors related to the patient (e.g., age, anxiety level),
the procedure and operator preference. At our institu-
tion, we prefer to perform aneurysm or arteriovenous
malformation (AVM) embolization, stent placement,
intracranial angioplasty, and intracranial chemother-
apy administration under general anesthesia. We usu-
ally perform carotid artery stenting (CAS) and tumor
embolization using monitored conscious sedation.
In the case of intracranial arterial and venous throm-
bectomies, the method of anesthesia depends on the
accessibility of an anesthesiology team, the patients
level of consciousness and the ability of the patient to
remain still for the procedure. Some procedures, such
as kyphoplasty and vertebroplasty, can be performed
safely using either method (10).
VASCULAR ACCESS
Patient Monitoring
Before the patient is brought to the angiography suite
and placed in the supine position, an 18- or 20-G
peripheral intravenous catheter (i.v.) is placed, usually
by the anesthesiologist. Continuous electrocardiogra-
phy, pulse oximetry, and an intermittent automated
blood pressure cuff are connected to the patient dur-
ing all endovascular procedures. In general, no seda-
tive should be administered without these forms of
patient monitoring. An arterial line is inserted for pro-
cedures requiring continuous blood pressure monitor-
ing and control, including post-subarachnoid
hemorrhage (SAH) vasospasm therapy, aneurysm
embolizations and revascularization of critically ste-
nosed or occluded extra- or intracranial vessels. Intra-
cranial pressure monitoring is typically utilized in
patients with higher-grade SAH during aneurysm
embolization or vasospasm therapy.
Vascular Access Sites and Techniques
Common Femoral Artery
The choice of arterial access site depends mostly on
operator preference, experience, and patient anatomy.
The right common femoral artery (CFA) is more com-
monly punctured, since most interventionalists are
right handed but aside from operator comfort, the
227
right CFA offers no advantage to the left. Both groins
are prepared and draped in case right CFA access is
unsuccessful or bilateral arterial access is required.
The latter is sometimes necessary when simultaneous
catheterization of two vessels is required, most com-
monly during vascular malformation embolization.
Self-limited, superficial groin hematoma is by far
the most common complication of the transfemoral
approach, occurring in 310% of angiography patients
(11,12). In the population of patients taking antiplate-
let therapy and to a lesser degree anticoagulation ther-
apy, the incidence of groin hematoma exceeds 10%.
Uncommon complications following femoral puncture
which occur in <1% of patients include pseudoaneur-
ysm, arterial dissection, arteriovenous fistula (AVF),
thromboembolism to the distal lower extremity, in
situ thrombosis and femoral nerve injury. CFA throm-
bosis can occur more easily in small children owing to
the small caliber of these vessels and an increased
propensity for arterial spasm. In patients who have
had prior angiography, care should be taken not to
puncture through a site that has been closed with an
intravascular closure device, as, doing so predisposes
to pseudoaneurysm formation.
The most desirable level for arterial puncture is
the segment of CFA that crosses the medial aspect of
the femoral head at a point approximately 12cm
below the midpoint of the inguinal ligament. Using
fluoroscopy and/or manual palpation, identification
of the location of the femoral head and inguinal liga-
ment prior to femoral puncture is essential. Using flu-
oroscopy, a radioopaque marker such as the tip of a
hemostat is placed over the patient and adjusted
under fluoroscopy to localize the medial convexity of
the femoral head, often described as the middle-third
of the femoral head in the rostral-caudal. The pulse
palpated at this level represents a safe CFA puncture
site and allows for ready arterial compression of the
artery against the femoral head after the procedure.
Using surface landmarks, the first step to identifying a
safe CFA puncture site is to palpate the anterior supe-
rior iliac spine (ASIS) and symphysis pubis to define the
course of the inguinal ligament. An arterial pulse pal-
pated two finger widths inferior to the midpoint of this
line represents the CFA at or appropriately near the
medial convexity of the femoral head. Deep palpation at
this level identifies the femoral head. In most slender
patients and children, the groin skin fold also passes
over the CFA at the mid-femoral head, so it may be
enticing to puncture the artery at the level of the fold as
common practice. However, the skin fold becomes dis-
placed inferiorly in overweight and obese patients and
so regular use of this surface landmark predisposes to
low punctures involving the superficial or profunda
femoral arteries, confers increased risk of injury to these
smaller arteries and can obviate the use of a closure
device (13). More dangerous, a high arterial puncture
involving the external iliac artery (cephalad to the ingui-
nal ligament, by definition) can bleed into the peritoneal
and/or retroperitoneal spaces rather than the subcutane-
ous compartment of the groin if not closed appropri-
ately. Hemorrhage from a high arterial puncture site
often is not detected until the patient complains of flank
or abdominal pain or becomes hemodynamically
unstable. In these circumstances, a significant volume of
228 NEUROINTERVENTIONAL MANAGEMENT
blood usually has extravasated by the time the hemor-
rhage is recognized. High arterial punctures also are dif-
ficult to close with manual pressure and are more likely
to require surgical repair. A hematoma from a puncture
of the CFA (below the inguinal ligament, by definition)
is more readily detected and more easily compressed
against the femur as a primary or secondary method of
arterial closure.
Once the artery is palpated, the overlying skin is
anesthetized by injecting a 1-cm wheal of 1 % lido-
caine at the skin surface using a long 21-G needle.
The needle is then advanced through the wheal and
310mL of lidocaine infused subcutaneously on either
side of the artery and along a track to the artery. The
lidocaine syringe should be aspirated slightly before
each injection to ensure extravascular infiltration. For
single-wall punctures, a 19-G single-wall base plate
needle (Fig. 11.1) is commonly used at a 45 angle to
the skin with the artery fixed in position by placing
the left third, fourth, and fifth fingers above the punc-
ture site and the index finger just below. With the
bevel up, the needle is held in the right hand and
advanced toward the artery. A transmitted pulse com-
monly can be felt against the right thumb positioned
over the needle hub. A pulsatile efflux of bright red
blood is an indication of successful needle insertion in
the artery lumen. Only when pulsatile efflux is seen
should the guidewire be inserted (commonly a 0.035
wire with a 3-mm J tip; Fig. 11.1). A small skin inci-
sion can be made just prior to needle insertion or,
after the guidewire has been placed, through the nee-
dle lumen, along the side of the needle. However, we
prefer to incise the skin only when resistance to
sheath introduction is encountered. The needle then is
removed over the guidewire with firm pressure main-
tained over the puncture site to prevent bleeding. The
introducer sheath and a coaxial dilator are advanced
over the guidewire into the arterial lumen using the
Seldinger technique.
Alternatively, double-wall arterial puncture can
be performed using a 19-G styletted needle (e.g.,
Pulse-Vu Needle; AngioDynamics, Inc.). If guidewire
insertion meets resistance, fluoroscopically guided
guidewire advancement should be performed to avoid
(A) (B)
(C)
(D)
subintimal insertion and vessel dissection. Contrast
injection into the needle against pulsatile return or
into the sheath can verify intra-arterial (IA) catheter-
ization. In patients with multiple past transfemoral
catheterizations, groin fibrosis may significantly
increase resistance to sheath insertion. In these cases,
the skin tract and arteriotomy can be progressively
enlarged by advancing dilators of increasing diameter
(58 Fr; Cook, Inc., Bloomington, Indiana, U.S.) over a
stiff introducer wire (e.g., 0.035 Terumo Glidewire;
Boston Scientific, Fremont, California). Once a dilator
is used, the operator is committed to using a sheath of
the same or larger size, since a smaller sheath will not
be hemostatic during the procedure nor allow for
introduction of a properly sized closure device at the
end of the procedure. It is important to remember that
the French system describes the I.D. of a sheath. For
example, a standard 5-Fr sheath has an O.D. equiva-
lent to 7-Fr. Once the sheath is in place it may be
secured with Tegaderm (3M Health Care, St. Paul,
Minnesota, U.S.) or suture and connected to continu-
ous pressurized heparin saline flush (5 IU per cc of
normal saline).
Radial Artery
Radial artery access offers several potential advan-
tages over CFA access. The transradial approach
obviates the requirement for prolonged bed rest and
eliminates the risk of occult hematoma, making it
safer in patients taking antiplatelet or anticoagulation
therapy (14). The transradial approach is particularly
useful in the 210% of patients in whom transfemoral
access is technically limited due to tortuous aortic
arch vessels, aortic occlusion, peripheral vascular dis-
ease, or morbid obesity (15,16). The right radial artery
can be used to access the right vertebral or carotid
arteries, and the left radial artery can be used to
access the left vertebral artery. Successful and safe
utilization of the transradial approach requires the
performance of Allens collateral circulation to the
hand from the ulnar artery and a cocktail of injec-
tions administered through the micropuncture intro-
ducer, including verapamil (2.5mg), cardiac lidocaine
Figure 11.1 Photograph of standard arterial sheath intro-
ducer set. (A) 6-Fr introducer sheath. (B) 19-G single-wall
needle. (C) Dilator. (D) 0.035 J-wire with tip straightener.
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
(2%, 1mL), and nitroglycerin (0.1mg) to prevent vaso-
spasm, as well as intravenous heparin (5070 IU/kg).
Factors that cause many interventionalists not to use
the transradial approach include potential median
nerve injury, brachial artery thrombus, and operator
comfort level.
Left Common Carotid Artery
When the transfemoral approach to the left anterior cir-
culation has failed, the left common carotid artery
(CCA) can be accesssed by direct puncture with a 21-G
micropuncture needle found in a micropuncture set
(AngioDynamics, Inc., Queensbury, New York, U.S.).
The right carotid arteries usually are more safely
accessed through a right transradial approach. The
CCA bifurcation usually is found caudal to the supe-
rior border of the thyroid cartilage and so direct left
CCA puncture, if performed, should be performed
below this landmark but not too low to obviate man-
ual compression of the puncture site at the end of
the procedure. The neck should be examined using
fluoroscopy to determine whether there are visible
course calcifications that might suggest the exact
level of the CCA bifurcation. Generally, an appropri-
ate site can be found two or three finger widths
below the superior border of the thyroid cartilage
and two finger widths above the clavicle. Following
left CCA puncture, the arteriotomy can be dilated to
5-Fr or 6-Fr with exchanges performed under real-
time fluoroscopy with care taken not to advance a
0.035 wire distal to the skull base. If there are
coarse carotid bulb calcifications, the sheath should
not be advanced beyond the calcific plaque. When
introduced, the sheath is not advanced to the hub
but instead sutured to the skin with approximately 4
cm of the sheath exposed between the skin and the
sheath hub.
External Carotid Artery
Direct puncture of the external carotid artery (ECA) or
its branches can be performed in patients with facial
AVMs previously treated with surgical ECA ligation
(16) or for embolization of bleeding ECA branches in
head and neck cancer patients with occlusion of the
CCA or main ECA trunk. In these situations, anterog-
rade injection of the contralateral ECA may provide
enough cross filling to opacify abnormal branches on
the side of the hemorrhage for localization.
Direct Percutaneous Puncture of a Vascular Lesion
For some superficial lesions of the head and neck,
including lymphangiomas and capillary and venous
angiomas and for some juvenile nasopharyngiomas
(JNA) and AVMs of the face and neck, the lesion can
be accessed by direct puncture using a 20-G butterfly
needle, long 20-G angiocatheter (i.v.) or 20-G spinal
needle. For JNAs, we prefer to advance a 20- or 22-G
spinal needle through the nostril and into the lesion
under real-time fluoroscopy with the stylet in place.
When the needle is placed within the lesion, the stylet
is removed. In the absence of spontaneous blood
return to confirm intravascular placement, gentle aspi-
ration can provide return. Contrast then is injected
229
through the needle to verify placement prior to injection
of liquid embolization material. For smaller lesions, such
as AVMs or venous angiomas of the lip, we prefer to
puncture the lesion under direct visualization and after
obtaining blood return, inject a sclerosing agent such as
sotradecol. For some smaller superficial lesions, ultra-
sound guidance or direct visualization without fluoro-
scopy can be sufficient.
Surgical Exposure for Intracranial Venipuncture
There are several reports describing craniotomy, with
exposure of a dural sinus or less commonly diploic
vein. In cases of dural sinus puncture, a micropunc-
ture needle is used for access and exchanged over a
wire for a 4-Fr introducer sheath, allowing for the
introduction of a microcatheter into the punctured
sinus or neighboring venous structures. Using this
approach, platinum coils (17) or liquid embolization
material (18) can be deployed via the microcatheter.
Alternatively, the same micropuncture needle can be
placed for administration of liquid embolic material
directly through the puncture needle (19).
MicroPuncture Technique
For transradial and transbrachial approaches, patients
on anticoagulation, and children and infants, a micro-
puncture set (AngioDynamics, Inc.; Fig. 11.2) is recom-
mended. The system most commonly used for trans-
femoral puncture includes a 21-G needle and a 0.018
guidewire and comes with a 4-Fr or 5-Fr dilator
sheath. Following the puncture, and the 0.018 wire is
then exchanged through the dilator sheath lumen for
a 0.035 guidewire. Micropuncture sets from other ven-
dors also are available, all of which include a 21-G
needle for puncture.
Introducer Sheaths
Standard short femoral sheaths (Fig. 11.1) are 11-cm
long and range in size from 4 Fr to 9 Fr. On the bench
top, an introducer is placed within the sheath lumen.
The hub of the introducer extends out of the hub of
the sheath and the distal tip of the introducer extends
beyond the distal tip of the sheath. The sheath and
introducer are advanced together over a wire, with
the wire passing through the introducer lumen. When
the sheath is positioned appropriately, the introducer
and guidewire are removed together and the sheath
is connected to continuous heparin saline flush, mak-
ing sure to allow for backflow of blood into the
sheath to prevent IA infusion of air. It is important to
note that the Fr designation of sheaths describes the
caliber of the inner (luminal) diameter of the sheath,
as opposed to the Fr designation of catheters, which
describes the O.D. of the catheter. This convention
ensures that a 6-Fr catheter fits through a 6-Fr sheath,
for example.
For pediatric diagnostic angiography, a short
4-Fr sheath is commonly placed to permit passage of
a 4-Fr diagnostic catheter, while adult diagnostic
angiograms usually begin with placement of a short
5-Fr sheath. Short 6-Fr or 7-Fr groin sheaths are rou-
tinely placed at the beginning of most embolization
230 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
(C)
and revascularizations procedures. A 7-Fr sheath is
placed when use of two devices is anticipated (e.g.,
during balloon-assisted coil embolization). A short
femoral 8-Fr or 9-Fr sheath is required for mechanical
embolectomy using the mechanical embolus removal
in cerebral ischemia (MERCI) retriever (Concentric
Medical, Inc., Mountain View, California, U.S.).
When more catheter support is needed, as in car-
otid artery angioplasty and stenting (CAS) procedures,
a standard short femoral sheath can be exchanged over
a guidewire for a long (90-cm) sheath that extends
from the femoral puncture site into the CCA. Like
short femoral sheaths, the 90-cm sheaths are introduced
over a stiff coaxial introducer. The Shuttle Select
TuohyBorst and Vista Brite Tip (Cordis Corp., Miami
Lakes, Florida, U.S.) 90-cm sheaths (68 Fr) provide
excellent support. Of these, the Shuttle Select Tuohy
Borst can be purchased with three different tip curves
that can be useful when navigating tortuous vessel
anatomy. It is important to note that while a long 6-Fr
sheath extending from the groin to the carotid system
provides ample lumen for passage of two instruments,
the 6-Fr sheath actually has a larger outer lumen than
a 7-Fr guide catheter. In rare instances where support
is imperative and exchanges are considered undesir-
able, a long (90-cm) 6-Fr sheath can be introduced
through a short 8-Fr femoral sheath.
Anticoagulation
Systemic heparinization during endovascular proce-
dures should be initiated following sheath insertion.
A loading dose of 5070 IU/kg is given to target an
activated clotting time (ACT) of two to three times
baseline. At our institution, we recheck the ACT
hourly and redose heparin in boluses. All sheaths and
guide catheters are connected to pressurized heparin
saline flush bags (5000 IU/L for adults and 1000 IU/L
for pediatrics). At the end of the procedure, protamine
Figure 11.2 Photograph of 5-Fr Micro Access Kit (Angiody-
namics Inc.). (A) 21-G echo tip needle. (B) 10-cm micro
access dilator assembly. (C) 0.018 stainless steel guidewire
with platinum tip (inset).
sulfate can be administered slowly to avoid systemic
hypotension and anaphylaxis, at a dose of 0.5 to
1mg/100 units of heparin remaining in the patient,
with a maximum of 50mg given over 10 minutes. Fast
correction post procedure, however, is rarely indicated
and in most circumstances we allow the patients anti-
coagulation to correct spontaneously.
CATHETERS
We will distinguish three main types of catheters:
diagnostic catheters, guide catheters, and microcath-
eters (balloon catheters are discussed later in the sec-
tion on balloons). Safe catheter use requires that
(i) the catheter be advanced over a guidewire, espe-
cially in atherosclerotic patients; (ii) the guidewire be
withdrawn to just within the catheter tip when turn-
ing the catheter to exclude blood from the catheter tip;
(iii) the catheter and guidewire tips never be out of
fluoroscopic visualization during navigation; (iv) the
cause of resistance, if encountered, be investigated
and the catheter not forced; and (v) the guide catheter
is continuously flushed with heparinized saline to
avoid thrombosis at the catheter tip and in advertent
embolic complications. Regarding the last of these pre-
cautions, some operators prefer to affix a continuous
flush system to diagnostic catheters as well. If a diag-
nostic catheter is not continuously flushed, the wire
should not be left in the catheter for more than 60 sec-
onds at a time, after which the wire should be with-
drawn and the catheter double flushed.
Diagnostic Catheters
A wide variety of catheters are available from differ-
ent companies and, in general, catheter selection is
based on personal experience and preference. Most
standard diagnostic catheters for adult head and neck
angiography are 90-cm or 100-cm long and are 4 Fr or
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
(A) (B) (C)
5 Fr in outer diameter (O.D.). 5-Fr, 65-cm diagnostic
catheters generally are used for spine angiography.
Diagnostic catheters are divided into simple-
curve and complex-curve devices based on the shape
of the catheter tip. Simple-curve devices have only a
primary (distal) curve and are used for diagnostic
angiography of uncomplicated aortic arches. Exam-
ples of simple-curve catheters include the Tempo
Vert (Cordis Corp.), Torcon Vert (Cook Medical,
Bloomington, IN) and the Terumo Glidecath Angled
taper (Scimed/Boston Scientific, Fremont, California,
U.S.) catheters. Tortuous great vessels and a common
origin of the innominate and left CCA (so-called
bovine arch) can be challenging to access. When cath-
eterizing with simple-curve catheters, maneuvers
including having the patient cough while advancing
the catheter, turning the patients head away from
the target vessel, and breath holding in deep inspira-
tion to unbend a tortuous vessel can enable catheter
advancement. The use of digital roadmap technique
and the transradial approach can also be helpful in
these instances.
Complex-curve devices have both primary and
secondary curves that necessitate reforming of the dis-
tal curve once the catheter is positioned in an appro-
priate aortic arch vessel (typically, the left subclavian
artery). Complex-curve catheters are used for catheter-
izations that cannot be achieved with simple-curve
catheters using standard technique. The Simmons II
catheter (Terumo Glidecath; Boston Scientific, Fre-
mont, California, U.S., and SIM 2; Merit Medical Sys-
tems, Inc.) (Fig. 11.3) is a complex-curve catheter that
facilitates entry into the proximal segment of a tortu-
ous vessel. However, its secondary curve may inhibit
distal catheterization. In this circumstance, an
exchange length guidewire (0.035 or 0.038, 260cm) tip reassumes the horseshoe shape previously seen on
may be used to exchange for a simple-curve
guidewire.
For spinal angiography, complex-curve catheters
such as the Cobra 1 and 2 (Terumo Glidecath; Boston
Scientific, Fremont, CA) or VS-2 (Cook Medical,
231
Figure 11.3 Photograph of several diagnostic cathe-
ters (Terumo Glidecath; Boston Scientific, Fremont,
California, U.S.). (A, B) Complex-curve Simmons
1 and 2 diagnostic catheters, respectively. (C) Simple-
curve Cobra 2 diagnostic catheter.
Bloomington, Indiana, U.S.) can be used because their
shape enables access of posterior intercostal and lum-
bar arteries with relative ease. For lower lumbar
arteries, a Simmons 1 catheter (Fig. 11.3) or Mikaels-
son catheter (Angiodynamics, Latham, NY) also can
be helpful. Once placed, these complex catheters pro-
vide stability for microcatheter introduction into seg-
mental arteries for spinal embolization procedures.
Most guide catheters used for spine procedures do
not have large enough lumina to allow for angiogra-
phy or roadmapping around most microcatheters.
This is not usually an issue, though, since angiogra-
phy and roadmapping for spine procedures usually is
performed by injecting the microcatheter.
Multiholed flush catheters are high flow diagnos-
tic catheters used for aortography. The most common
flush catheter is the 5-Fr pigtail (Merit Medical Sys-
tems, Inc.) (Fig. 11.4). On the bench top, a 0.035
guidewire is introduced through the hub and beyond
the catheter tip until the distal pigtail loop straightens
into a horseshoe shape. The torque device then is
cinched up the wire to abut the catheter hub. The
wire is then retracted, allowing the distal pigtail loop
to reform, and the catheter tip is introduced into the
short femoral sheath using a short plastic introducer.
Once the catheter tip is inside the sheath (but not out
of the sheath tip!), the guidewire is advanced until the
torque device again abuts the catheter hub. The pigtail
catheter then can be advanced into the aortic root
using standard technique. Prior to aortography, the
wire is removed allowing the pigtail tip to reform.
After double-flushing, the catheter hub can be
attached to a flush line and an automated power injec-
tor using a three-way stopcock. Following aortogra-
phy, the guidewire is re-advanced until the catheter
the bench top, with the guidewire extending inferi-
orly. The catheter then is retracted so that the wire
extends into the common iliac artery contralateral to
the groin sheath. The pigtail catheter then can be
retracted safely into the sheath and out of the patient.
232 NEUROINTERVENTIONAL MANAGEMENT
Guide Catheters
A guide catheter is a large lumen catheter placed in a
cervical vessel to allow ready introduction of endovas-
cular instruments into the head and neck. Guide cath-
eters for adult patients usually are 90-cm or 110-cm
long, range from 5-Fr to 8-Fr O.D. and typically have
stiffer, thinner walls than diagnostic catheters. When
advancing a stiff guide catheter through tortuous
great vessels, certain techniques can ease navigation.
The guide catheter can be advanced coaxially over an
exchange length guidewire placed with its tip distal to
the targeted vessel. For example, a 5-Fr diagnostic
catheter placed in the CCA can be exchanged over a
0.038 exchange length Glidewire with its tip in the
ECA for a 6-Fr guide catheter. To help a guide cathe-
ter take turns into the aortic arch branch vessels, a
long (125-cm) 4- or 5-Fr diagnostic catheter placed
within the larger guide catheter can facilitate naviga-
tion or exchange. Coaxial placement of a long diag-
nostic catheter also reduces mismatch between the
O.D. of the wire and the I.D. of the guide catheter,
reducing risk of shearing off a subintimal plaque and
dissection. Catheters larger than 6-Fr should be
advanced coaxially over a long (120 cm) 5-Fr catheter
to reduce mismatch. As previously mentioned, a long
sheath advanced over its stiff introducer into aortic
arch branch vessels is an alternate method for gaining
added support.
In cases where a single device will be advanced
through the guide catheter, working at 6-Fr permits
instrument passage while still allowing for strong
injections around the device for roadmapping. If
strong injections are not considered essential, a 5-Fr
guide catheter with a minimum lumen of 0.038 can
suffice. When two devices are necessary, for instance
during balloon-assisted aneurysm embolization, a 7-Fr
guide catheter is usually necessary. All guide cathe-
ters, once placed, must be connected to a continuous
heparin saline flush to prevent thrombus formation at
the catheter tip.
Figure 11.4 Arch aortogram, anteroposterior view, in a
patient with Takayasus Arteritis demonstrating the angio-
graphic appearance (inset) and use of the pigtail diagnos-
tic catheter. Note the absence of the bilateral common
carotid arteries and left vertebral artery and the compen-
satory hypertrophied ascending and deep cervical arteries.
Distal Access Catheters
The distal access catheter (DAC) has gained increased
use in recent years, primarily during embolus aspira-
tion (Concentric Medical, Inc., Mountain View, Cali-
fornia, U.S.). DACs come in 3.9-, 4.3- and 5.2-Fr O.D.
with lengths ranging from 115cm to 136cm and are
intended to provide extra support during in patients
with tortuous vasculature. The DAC originally was
used only during mechanical thrombectomy but more
recently has demonstrated utility in other applications.
Indeed, we have found DACs quite useful during
tumor and vascular malformation embolizations with
Onyx embolization material (eV3), particularly when
removing an entrapped microcatheter. This latter
application will be discussed in the section on emboli-
zation materials and techniques. Like guide catheters,
the DAC must be connected to a continuous heparin
saline flush to prevent thrombosis.
Microcatheters
Microcatheter characteristic include visibility, I.D.,
O.D., stiffness, trackability (ability of a microcatheter to
glide smoothly across a microwire), responsiveness
(fidelity between the distance advanced or retracted at
the hub compared with the distance the tip moves
accordingly), tensile strength (stretch resistance), and
flexibility. Microcatheter I.D. is described in inches and
O.D. in French. However, the diameter descriptions
included in the microcatheter title can be misleading
since they usually refer to the wire over which the
microcatheter optimally performs rather than the true
I.D. For example, the Excelsior SL-10 (Boston Scientific,
Fremont, CA) and Prowler-10 microcatheters (Cordis,
Miami Lakes, FL) are designed for use over a 0.010
microwire. However, the true lumen sizes are 0.0165
and 0.0150, respectively and as such, both can accom-
modate a 0.014 wire, albeit with reduced trackability.
Microcatheters for intracranial applications typically
range in length from 135cm to 165cm.
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
(A) (B) (C)
Figure 11.5 Illustration of various microcatheter shapes. (A) Straight. (B) 458 curve. (C) 908 curve. (D) J-shaped curve. (E) S-shaped
curve. (F) C-shaped curve. Source: Courtesy of Boston Scientific, Fremont, California, U.S.
Historically, there has been a trade-off between
microcatheter stiffness and flexibility. Stiff microcath-
eters tend also to be pushable and stretch resistant,
characteristics that are desirable for the operator.
However, a microcatheter with poor flexibility predis-
poses to iatrogenic vascular injury and can be difficult
to navigate around acute branch points. Recent advan-
ces in microcatheter engineeringmost notably com-
posite shaft construction, variable shaft stiffness an
O.D. taperinghave afforded a suitable balance
between stiffness and flexibility. Advances in hydro-
philic coating have led to improved trackability pro-
vided the microcatheter lumen is adequately flushed
and the external coating of the microcatheter soaked
in heparin saline prior to use.
Like guide catheters, microcatheter selection is
based on experience and preference rather than sci-
ence. In general, microcatheters can be divided into
guidewire-directed and flow-guided categories, the
latter being more suitable for distal catheterizations.
Guidewire-Directed Microcatheters
There are multiple guidewire-directed microcatheters
with more being developed almost monthly. Most
recently developed guidewire-directed microcatheters
are tapered, with distal segments ranging from 1.7-Fr
to 2.8-Fr O.D. Most are radiolucent with small, radio-
paque marker bands placed at the microcatheter tip
and 3cm proximal to the tip. Many are manufactured
with preformed tip shapes, including 45 or 90 angles
or J-, S-, or C-shaped curves (Fig. 11.5). The same
microcatheters are available with straight tips, and all
microcatheters can be shaped or reshaped with steam.
The angle of origin of a targeted vessel or aneurysm
from its parent artery dictates which curve is selected.
In our experience, the preformed Excelsior SL-10 and
-1018 (Boston Scientific, Fremont, California, U.S.)
microcatheters work well for accessing aneurysms.
The Prowler 10, 14 and Plus (Cordis Corp.) microcath-
eters are well suited for polyvinyl alcohol (PVA) par-
ticle embolization of extracranial and dural lesions.
And the Echelon 10 and 14 (Micro Therapeutics, Inc.,
Irvine, California, U.S.) are not degraded by dimethyl
sulfoxide (DMSO), making them suitable for intra- or
extracranial embolizations using Onyx.
233
(D) (E) (F)
Flow-Guided Microcatheters
Flow-guided microcatheters are designed for catheter-
izing tiny vessels as may be encountered when gain-
ing distal access to a vascular malformation, when
canulation of a choroidal or lenticulostriate branch is
absolutely necessary or when distal access in a pedia-
tric patient is desired, such as in the case of intra-
ophthalmic chemotherapy delivery for retinoblastoma.
The Balt Magic (Balt/Boston Scientific, Fremont,
California, U.S.), the Spinnaker Elite (Boston Scientific,
Fremont, California, U.S.), and the Marathon (eV3
Neurovascular, Irvine, CA) microcatheters all have a
tapered design. All are 155- or 165-cm long, with a
100- or 120-cm, 2.73.0 Fr proximal shaft designed for
support and pushability, a supple 2530cm, 2.5-Fr
mid-shaft segment enabling navigation through tortu-
ous vessels and an extra supple 1030cm, 1.2-, 1.5- or
1.8-Fr shapeable distal segment that allows for flow-
guided vessel selection. In high flow lesions, any of
these microcatheters can be guided without a micro-
wire. However, in normal-flow situations or in distal
branches approaching a vascular malformation, the
Magic 1.2- and 1.5-Fr microcatheters have demon-
strated the most reliable ability to advance without a
microwire. Any of these microcatheters can be
advanced over a 0.008 microwire such as the Mirage
(eV3 Neurovascular, Irvine, CA), when necessary,
although the Magic 1.2 Fr will deform even a 0.008
microwire that is introduced and removed more
than once.
Stopcocks, Rotating Hemostatic Valves and
Continuous Flush Systems
A rotating hemostatic valve (RHV) and continuous
flush system must be affixed to the hub of all guide
catheters and DACs. The RHV has two ports: a rotat-
ing port for hemostatic introduction of endovascular
instruments and a threaded, angled port for applica-
tion of a flush system, with or without a three-way
stopcock. At our institution, the flush system consists
of a pressurized bag containing 5000 mm heparin in
1L normal saline, connected by pressure tubing to a
three-way stopcock that is affixed to the threaded
port, allowing the operator to flush the RHV and
234 NEUROINTERVENTIONAL MANAGEMENT
guide catheter continuously, then open a separate port
for contrast injection by turning the stopcock when
desired. The Guardian II hemostasis valve (Vascular
Solutions, Minneapolis, MN) is a useful, large-bore
RHV that allows for ready passage of two or even
three endovascular instruments (e.g., a microcatheter
and balloon) through the instrument port.
Guidewires
Guidewire navigation and rotation is aided by the use
of a torque device (Fig. 11.6) placed approximately
2 cm from the catheter hub. Guidewires used coaxially
with diagnostic and guide catheters are typically
0.035 or 0.038 in diameter and are available in
standard 150-cm or exchange 260-cm lengths with
angled or shapeable tips (e.g., Terumo Glidewire and
Glidewire LT; Scimed/Boston Scientific). In certain
situations, a stiffer wire, such as the Amplatz 0.038
145-cm Super Stiff wire (Scimed/Boston Scientific),
may be needed to facilitate catheter advancement into
complex vessels or to increase guide catheter/sheath
support in patients with severely tortuous great vessel
anatomy (the so-called buddy wire method).
Microwires
As with microcatheters, there is a myriad of microwires
available. Important microwire characteristics include
flexibility, coating, and torqueability. In general, stiffer
wires are more torqueable, are more likely to cause
arterial injury, and may be difficult to navigate around
branch points. Common 0.014 O.D. microwires used
in our practice include the Transend-14, EX-14, and
Synchro-2 soft (Boston Scientific). The Transend-10
(Boston Scientific) is our most common 0.010 micro-
wire. And the Mirage (Micro Therapeutics, Inc.) is the
only 0.008 O.D. wire we use. Exchange microwires
typically are 300-cm long and have an O.D. of 0.010
or 0.014.
Manually shaping the microguidewire tip
greatly aids catheterization of small or tortuous vas-
culature. For example, if a targeted branch vessel
arises at an obtuse angle, a 90 or J-shape usually is
helpful. And for making and acute turn, such as
encountered when accessing the ophthalmic artery,
an S-shaped curve may be appropriate. Even with
experience, trial and error with different wire shapes
and microcatheters may be needed to catheterize a
challenging target.
To maintain control when navigating a microcath-
eter over a microguidewire, it is important to look for
slack and tension buildup in the guide catheter and
microcatheter. These irregularities are anticipated when
the system becomes less responsive (i.e., the operators
movements are not being effectively translated at the
microcatheter/microguidewire tip). In addition, at the
conclusion of a maneuver, a slight contrary movement
may be helpful to maintain the device in a steady posi-
tion. For instance, when a microcatheter is advanced to
the correct position within an aneurysm dome, it is
necessary at the end of the motion to withdraw slightly
on the microcatheter to abolish the forward motion
that could inadvertently advance the device into the
aneurysm wall.
EMBOLIC PROTECTION DEVICES
During extracranial carotid angioplasty and stenting,
the rate of embolic debris may be as high as 80% to
90%. The advent of improved pharmacological pro-
phylaxis combined with placement of an embolic pro-
tection device (EPD) at the beginning of the procedure
is believed to lower the risk of stroke or death from
59% to 03% (20,21). There are currently two types of
cerebral protection strategies: distal protection in the
form of an occlusion balloon or filter, and proximal
protection in the form of flow interruption or reversal
devices.
Distal Embolic Protection Devices
The most commonly employed form of distal EPD is
comprised of a polyurethane filter mounted on a 0.014
microwire. At the beginning of the procedure, the col-
lapsed filter is advanced within a microcatheter beyond
the stenosis, with a floppy segment of microwire
Figure 11.6 Photograph of torquer device over
microguidewire (Concentric Medical, Inc.)
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
extending distal to the filter and out the tip of the
microcatheter. After the filter is placed into straight
vessel segment, the microcatheter is unsheathed,
deploying the filter. The deployed filter typically is
umbrella shaped. This system allows for flow distal to
the deployed device and captures thrombi as small as
100 mm. The guidewire remains within the target vessel
during the procedure and serves as access over which
monorail balloon and stent systems can be advanced
and deployed. At the conclusion of the procedure, the
filter is recaptured and retrieved by readvancing the
microcatheter over the filter to resheath it. At our insti-
tution, we commonly use the Rx Accunet (Fig. 11.7)
and Emboshield filter EPD systems (Abbott Laborato-
ries, Abbott Park, Illinois, U.S.). The second type of dis-
tal EPD is an occlusive balloon that is navigated
through the carotid stenosis and inflated distal to the
lesion prior to angioplasty and stenting. Like the filter,
the inflated balloon also captures debris liberated from
the lesion. However, unlike the filter EPD systems,
there is flow arrest within the treated vessel during the
procedure, reducing cerebral blood flow and obviating
intra-procedure angiography. Also, debris must be
aspirated from the vessel prior to balloon deflation at the
end of the procedure. The PercuSurge distal occlusion
balloon (Medtronic, Inc., Santa Rosa, California, U.S.) is
an example of this design.
(A) (B)
Figure 11.7 (A) Photograph of Accunet distal embolic protection
device. (B) Cervical angiogram, PA view, left common carotid artery
injection demonstrating the angiographic appearance of a deployed
Accunet device. Source: (A) Courtesy of Guidant Corp.
235
Proximal Embolic Protection Devices
The proximal EPDs consist of an aspiration balloon
guide catheter that is inflated in the CCA proximal to
the stenosis. Once the balloon catheter is occlusive, suc-
tion is applied to generate flow reversal distal to the
balloon. Aspirated blood is returned to the patient via
an extra corporeal catheter, then drains into a common
femoral vein. While the CCA balloon is inflated, a sec-
ond balloon is inflated in the ECA to prevent reflux of
debris into the carotid bifurcation through collateral
anastomoses. The Parodi AntiEmbolism System (Ante-
riA Medical Science, San Francisco, California, U.S.) is
an example of a flow-reversing proximal EPD.
BALLOON CATHETERS
The specifications of O.D. (mm) and length (mm) are
used in daily practice to describe the balloon component
of a balloon catheter. For example, a 4-mm O.D. balloon
that is 15 mm long is described as a 4  15 balloon. The
nominal pressure of a balloon describes the inflation pres-
sure at which it is expanded to its named diameter. For
example, a 4-mm O.D. balloon with a nominal pressure
of 8 atm has an O.D. of < 4mm when inflated to < 8 atm
(i.e., underinflated) and > 4mm when inflated to > 8 atm
(i.e., overinflated). A rated burst pressure (RBP) also is
provided for each balloon catheter, above which the bal-
loon may rupture. Careful sizing of the balloons diameter
is critical for minimizing the risk of artery dissection or
rupture. If the operator feels compelled to inflate a bal-
loon near or up to burst pressure to accomplish a task, the
balloon has been undersized, should be removed and
replaced with a larger balloon. Conversely, inflating
an oversized balloon to nominal pressure markedly
increases the risk of pseudoaneurysm or frank rupture.
INR balloons may be divided into high- or low-
pressure and there are four major applications for bal-
loon catheters in INR: extracranial or intracranial
angioplasty for atherosclerotic stenotic lesions, intra-
cranial angioplasty for vasospasm, balloon-assisted
aneurysm remodeling, and balloon test occlusion (BTO).
At our institution, intra- or extracranial angioplasty for
atherosclerosis is performed with a high-pressure bal-
loon. Intracranial angioplasty for vasospasm, aneurysm
remodeling, and test occlusions are performed with a
low-pressure balloon. All balloons used in interventional
neuroradiology (INR) have a hydrophilic coating.
All balloon catheters are prepared on the bench
top prior to patient introduction by flushing with con-
trast and purging air from the balloon lumen, then
training a low-pressure balloon by inflation or even
gentle overinflation with contrast solution. Following
preparation, a column of contrast should extend from
the deflated balloon back to the hub prior to endovas-
cular introduction. In general, concentrated contrast (e.
g., 80% omnipaque-320 in heparin saline) is used with
small balloons to ensure visualization when inflated.
More dilute contrast solution (e.g., 50% omnipaque-320
in heparin saline) is used with larger balloons to allow
for appropriate deflation.
Low-Pressure Balloons
Most low-pressure balloons usually are manufactured
with a single lumen design. HyperGlide and HyperForm
236 NEUROINTERVENTIONAL MANAGEMENT
balloon catheters (eV3) are examples of low-pressure,
single-lumen balloons designed for aneurysm remodel-
ing (Fig. 11.8). The design of the HyperGlide and Hyper-
Form balloons is the same. Proximal to the balloon, the
catheter I.D. is significantly larger than the O.D. of the
accompanying microwire, allowing ready contrast flow
around the microwire. Distal to the balloon, the soft tip
has an I.D. that matches the O.D. of the microwire so that
the balloon catheter and is hydrostatic when the tip of an
Expedion-10 or SilverSpeed-10 microwire is advanced a
few mm distal to the balloon catheter tip. The Hyper-
Glide balloons, intended for treating sidewall aneur-
ysms, are manufactured with 3-, 4-, and 5-mm O.D. and
with balloon lengths of 10, 15, 20, and 30mm. Hyper-
Glide balloons have a 4-mm soft tip distal to the balloon
that according to the manufacturer are supercompli-
ant. The HyperGlide balloons were intended for treat-
ing sidewall aneurysms. The HyperForm balloons are
manufactured with 4- and 7-mm O.D. and a standard
balloon length of 7mm. HyperForm balloons have a
2-mm soft tip distal to the balloon and are described as
compliant by the manufacturer. In addition to aneur-
ysm remodeling, we regularly use these balloons for
intracranial angioplasty secondary to vasospasm.
Bench preparation begins by attaching a RHV to
the single balloon catheter hub, then affixing two-way
stopcock to the angled port of the RHV. With the
rotating valve open, the balloon-catheter then is
flushed through the angled RHV port using a 3-mL
syringe affixed to a two-way stopcock. After tighten-
ing the rotating valve, the balloon catheter is flushed
until contrast flows out the distal tip. The balloon
should not inflate. Once flushed, an Expedion-10 or
Silverspeed-10 microwire is advanced through the
contrast-filled balloon catheter lumen. When the wire
tip extends a few mm distal to the balloon tip, a 1-mL
syringe is affixed to the angled RHV port and the bal-
loon is gently inflated and in some circumstances
even overinflated. The wire is then retracted proximal
to the balloon allowing deflation. Only after the bal-
loon deflates entirely, should the wire be readvanced
distal to the balloon tip. The 1-mL syringe is left
(A) (B)
affixed to the RHV-angled port, the wire tip is left
extended beyond the balloon catheter tip and the sys-
tem is immersed in a saline bath with the balloon
deflated. After shaping the wire tip, the single-lumen
balloon system is appropriately prepared.
To achieve nominal pressure in the 4-mm Hyper-
Form and HyperGlide balloons, 0.06mL of contrast
solution is required and in the 7-mm variety, injection
of 0.27mL will achieve full balloon diameter (see indi-
vidual device package insert for specific nominal and
maximal inflation volumes). In our experience, when
inflating the eV3 Hyper- balloons within an artery
having a normal segment diameter of 2.5mm, a
4-mm O.D. balloon can be used and inflated until the
sides of the balloon are flat and well approximated to
the vessel wall. For an artery with a normal segment
diameter 2.5mm, a 3-mm O.D. balloon generally is
preferred, although occasionally, a markedly underin-
flated 4-mm O.D. balloon is used.
In general, there are two ways to deflate a
single-lumen balloon. Gentle aspiration of the angled
RHV port with a 1mL and with the microwire tip
beyond the balloon catheter tip provides for slow,
controlled deflation. Alternatively, the balloon can be
deflated more rapidly by simply retracting the wire
into the catheter, proximal to the balloon. The disad-
vantage of the latter technique is that blood invariably
enters the catheter tip and after multiple deflations,
will fill the balloon, excluding contrast during subse-
quent inflations and making the inflated balloon more
difficult to visualize and predisposing to vessel
rupture.
Balloon-Assisted Aneurysm Remodeling
Balloon-assisted remodeling using a low-pressure bal-
loon is sometimes required during coil embolization
of wide-neck aneurysms and always required during
aneurysm embolization with Onyx-500 (eV3). In these
cases, the balloon is positioned across the neck of the
aneurysm, while a second microcatheter is positioned
into the dome of the aneurysm. The balloon typically
Figure 11.8 Illustration of (A) HyperGlide and (B) Hyper-
Form low-pressure balloons used during balloon aneurysm
remodeling. Source: Courtesy of Micro Therapeutics Inc.
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
is inflated during coil placement, although sometimes
a deflated balloon alone is useful enough to visualize
the lumen of a parent or branch vessel that cannot be
seen using roadmap technique alone. Observation of
coil loops near the aneurysm neck during gradual bal-
loon deflation can provide valuable information
regarding the relationship of the coil loops to the
aneurysm neck and parent vessel. If a coil mass does
not move during balloon deflation, there is no extru-
sion of coil into the parent vessel. However, signifi-
cant extension of the coil mass into the parent vessel
upon balloon deflation is an ominous sign, typically
necessitating readjustment or removal of an unde-
tached coil.
Placement of a balloon across the aneurysm neck
also can provide hemostasis in the event of intra-
procedure aneurysm rupture. In this event, the bal-
loon can be left inflated for 35 minutes, then
deflated. This maneuver alone sometimes can achieve
hemostasis. More often, though, addition embolization
of the aneurysm is required. This can be achieved
with placement of additional coils or even injection of
nBCA with the balloon inflated (Fig. 11.9).
Intracranial Angioplasty for Cerebral Vasospasm
When performing angioplasty for post-SAH vaso-
spasm that is refractory to IA vasodilator infusion, we
typically use a low-pressure balloon. Because long
segments of vessels usually are affected (unlike arte-
rial narrowing seen in cerebral vasculitis that typically
preferentially involves bifurcations), a HyperForm or
HyperGlide balloon is advanced into the distal most
aspect of an affected vessel segment, is inflated for
510 seconds and then deflated, retracted just over half
the length of the balloon, and re-inflated (Fig. 11.10).
Using this technique, selection of a longer balloon can
reduce the number of inflations necessary, slightly
reducing risk. Angioplasty of second order cerebral
branches in spasm can be performed. However, distal
angioplasty carries with it increased risk and should be
reserved only for necessary clinical scenarios.
Balloon Test Occlusion
Balloon test occlusion (BTO; Fig. 11.11) may be per-
formed to evaluate a patients ability to tolerate per-
manent artery occlusion, for example, during the
treatment of giant or fusiform aneurysms. BTO should
be performed following CT or MR angiogram or fol-
lowing digital subtraction angiogram to determine
where collateral flow to the occluded vessel may arise.
For example, following occlusion of the right internal
carotid artery (ICA), the right supraclinoid and peri-
ophthalmic segments may receive collateral flow via
the posterior circulation via PComm, from the con-
tralateral internal carotid circulation via AComm or
less likely, via the ipsilateral external carotid circula-
tion via retrograde flow in the ophthalmic artery.
While the balloon is inflated, the possible source of
collateral flow needs to be interrogated with angiogra-
phy using a diagnostic catheter introduced through a
second groin puncture.
At the beginning of the procedure, both femoral
arteries are punctured. A guide catheter is advanced
237
into the artery to be occluded and into the artery
where collateral flow may arise. (If flow to the intra-
cranial carotid is expected to arise via the ispilateral
ophthalmic, a single, larger guide catheter may be
placed into the CCA.) The balloon is navigated into
place, usually in the distal cervical ICA or the V2 seg-
ment of the vertebral artery at the level of C3-C4.
A neurologic examination is examined preinflation
and then repeated serially for 30 minutes during infla-
tion. For the first 15 minutes of inflation, the patient is
maintained normotensive. For the latter 15 minutes,
the patients systolic blood pressure typically is
reduced to 6070% of normal. Any neurological deficit
during balloon inflation represents a clinical failure of
BTO. In the case of a carotid BTO, when angiography
is performed to determine collateral flow, delayed
perfusion of the cerebral hemisphere ipsilateral to the
balloon represents angiographic failure, even in the
absence of observable neurologic deficit.
High-Pressure (Double-Lumen) Balloons
High-pressure balloons are most commonly used for
angioplasty of extra- or intracranial atherosclerotic
lesions. High-pressure balloons typically are manufac-
tured with a single-lumen design: one lumen for con-
trast injection and balloon inflation and a separate
lumen for wire passage. Unlike single-lumen low-
pressure balloon catheters, two-lumen high-pressure
balloon catheters rely on rapid exchange or mono-
rail systems. The proximal segment of the catheter
shaft usually is stiffer than a typical microcatheter
affording easier and more rapid advancement, while
the distal segment is softer, more akin to a typical
microcatheter. The microwire enters the wire lumen
port at the junction of the stiff and soft segments and
extends out the distal tip of the device. In preparation
on the bench, the wire lumen can be flushed retro-
grade from the tip to facilitate smoother tracking. The
contrast lumen is blind ended, terminating distally in
the balloon and must be prepared by vigorously aspi-
rating the lumen with a syringe containing contrast
solution to create a negative pressure column, then
releasing the negative pressure to allow anterograde
flushing of contrast. Deflation of a double-lumen bal-
loon catheter requires vigorous aspiration from the
external contrast port.
These balloons are prepped on the bench top by
aspirating approximately 5mL of 1:1 heparin saline:
contrast into a 60-mL syringe. The syringe is then
affixed to the angled balloon port at the hub of the
balloon catheter and with the syringe in the vertical
position, the plunger is vigorously retracted to create
negative tension within the balloon and its lumen.
The plunger is held in this position until air bubbles
stop entering the syringe from the angled balloon
port. The plunger is then slowly released, allowing
for contrast to fill the balloon lumen. After contrast
travels through the balloon lumen, up to but not into
the balloon, the 60-mL syringe is removed and
replaced by an insufflation device. The straight wire
port then is flushed with heparin saline, and a
hydrated 14-wire is advanced through the lumen.
After shaping the wire tip, the balloon system is
appropriately prepared.
238 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 11.9 (A) Unsubtracted left posterior oblique fluoroscopic projection demonstrates coil masses in aneurysms arising from the ophthal-
mic and supraclinoid segments of the right internal carotid artery (ICA) following embolization of the periophthalmic aneurysm and during
embolization of the smaller, more distal supraclinoid aneurysm. An Excelsior SL-10 microcatheter is situated within the distal aneurysm, and
an eV3 4mm  15mm HyperGlide balloon is positioned across the necks of both aneurysms. (B) Subtracted cerebral arteriography per-
formed following coil advancement into the distal aneurysm demonstrates new extravascular contrast extravasation. The balloon was imme-
diately inflated across the aneurysm neck to achieve temporary hemostasis and nBCA was injected through the microcatheter to achieve for
permanent occlusion. (C) Unsubtracted left posterior oblique projection shows the coil masses traversed by an Enterprise stent subsequently
deployed across the necks of both aneurysms to reinforce the coil masses. (D) Follow-up angiography three weeks later shows minimal
residual filling at the lateral aspect of the larger aneurysm. There is no filling of the smaller, distal aneurysm.

During extracranial or intracranial angioplasty for
atherosclerotic stenosis, balloon diameter is selected
to approximate 80% of the vessel diameter just distal
to the stenosis. The microguidewire is advanced past
the stenosis, and the balloon is tracked over a micro-
guidewire and positioned with the proximal and dis-
tal radiopaque markers straddling the stenosis. The
balloon is carefully inflated by turning an insufflator
device (Fig. 11.12) attached to the angled balloon
lumen. If two operators are performing carotid angio-
plasty with a high-pressure balloon, one watches the
insufflator pressure gauge, while the other watches
the balloon inflate under real-time fluoroscopy, and
then the balloon is deflated. Several inflations may be
necessary to achieve the desired lumen diameter, and
the balloon position may be readjusted proximally or
distally between inflations (once the balloon is fully
deflated). Angioplasty of an atherosclerotic plaque
creates microdissections in the nondiseased arterial
wall adjacent to the plaque (22). For concentric extrac-
ranial plaques and in-stent restenosis, a cutting bal-
loon (e.g., Ultra2 Monorail; Boston Scientific, Fremont,
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY 239

(A) (B)

Figure 11.10 (A) PA projection demonstrating moderate vasospasm of the right supraclinoid internal carotid artery (ICA) and severe
focal vasospasm of the distal right A1 segment. Balloon angioplasty of these segments was performed with a 3mm  10mm HyperGlide
balloon and postangioplasty images are shown (B).

(A) (B)

(C)

(D)

Figure 11.11 Cerebral angiogram during balloon test occlusion. (A) Unsubtracted PA projection demonstrates a HyperGlide balloon
(eV3) across the vertebrobasilar junction. * identifies the proximal and distal aspects of the balloon, situated in the distal right and left
V4 segments, respectively. This procedure was performed to assess tolerance of bilateral vertebral artery occlusion for treatment of a
large, complex aneurysm. (B) 3D rotational projection presented in a PA projection arising from the proximal aspect of a fenestrated
basilar artery. Selective right (C) and left (D) vertebral artery injections verify that there is no anterograde flow into the aneurysm or
basilar artery.
240 NEUROINTERVENTIONAL MANAGEMENT
Figure 11.12 Photograph of an insufflator device used to inflate
high-pressure angioplasty balloons. The device is filled with 10
to 20 cc of 50% contrast solution and purged of air bubbles
prior to use.
California, U.S./Scimed) may be more useful to create
controlled dissections within the lesion.
Extracranial Carotid Angioplasty of
Atherosclerotic Plaque
The Aviator (Cordis Corp.) and Viatrac 14 Plus (Gui-
dant Corp., Indianapolis, Indiana, U.S.) balloon cathe-
ters are examples of high-pressure balloons used for
extracranial angioplasty, usually performed following
placement of an EPD in the distal aspect of the cervi-
cal ICA and before placement of a self-expanding car-
otid artery stent.
Intracranial Angioplasty of Atherosclerotic
Plaque
When performing intracranial angioplasty to treat
atherosclerotic stenosis, we typically use the double-
lumen Gateway balloon (Boston Scientific) prior to
deployment of a Wingspan stent (Boston Scientific).
The Gateway is described as an intermediate pres-
sure balloon. The Gateway balloon catheter is 3.2-Fr
and the balloon is available in 1.5-, 2.0-, 2.25-, 2.75-,
3.0-, 3.25-, 3.5-, 3.75-, and 4.0-mm O.D. The nominal
pressure is 6 atm with an RBP of 12 atm. The balloon
is sized so that when inflated to nominal pressure, it
occupies approximately 80% of the normal vessel
diameter. For example, for angioplasty is a normal
segment vessel diameter of 2.5mm, a 2.0-mm Gateway
balloon would be chosen. If the vessel has different
diameters proximal and distal to the stenosis, the
diameter of the distal vessel is used for sizing. The
Gateway balloon catheter has a monorail design.
Prior to angioplasty, a standard-length 6-Fr guide
catheter is placed into the internal carotid or vertebral
artery and the atherosclerotic stenosis is crossed by
advancing a microcatheter over a standard-length 0.014
wire. The microcatheter is removed and replaced, leav-
ing the microwire for access. The Gateway balloon cath-
eter is flushed on the bench top using 50% contrast in
the balloon lumen and heparin saline in the wire lumen.
The Gateway balloon catheter then is introduced to the
guide catheter over the microwire, then across the steno-
sis using monorail technique. The balloon is inflated up
to or sometimes just beyond nominal pressure, left in
place for 510 seconds, then deflated and removed.
Other Balloon Applications
For IA infusion of small branch vessels, a HyperGlide or
HyperForm balloon can be inflated in the larger parent
artery, distal to the target branches, occluding distal
flow. A microcatheter placed at or near the ostia of the
target branch vessels then can be used for infusion.
When using this technique, we usually leave the balloon
inflated only for four minutes at a time, infusing behind
the balloon for the first three minutes. After deflating the
balloon, we wait 23 minutes before re-inflating and
resuming infusion. A detachable balloon can be used for
permanent artery occlusion (e.g., detachable silicone bal-
loon; Target Therapeutics/Boston Scientific, Fremont,
California, U.S.). On occasion, we have used an inflated
balloon to apply counter tension to a vessel while trying
to retrieve a microcatheter entrapped in Onyx (23).
However, with increasing experience, we have learned
that a DAC can be more effective for this purpose.
STENTS
Radial force, flexibility, and scaffolding are critical
properties of stents. Radial force refers to the energy
the stent exerts against the vessel wall. Flexibility
describes the ability of a stent to conform to the natu-
ral curves of a vessel. Scaffolding describes to the den-
sity of struts approximated to the vessel wall. In the
context of aneurysm stent-coiling the term coverage
is used to describe the density of struts across the
aneurysm neck.
Regarding methods of deployment, there are two
types of stents: self-expanding and balloon mounted.
A stent with significant radial force that is spring-
loaded into a microcatheter can be delivered by retract-
ing the microcatheter, allowing the unsheathed stent to
expand andif appropriately sizedapproximate the
vessel wall. Self-expanding stents have high radial
force and most are made of nitinol, a nickeltitanium
memory alloy. The Pipeline is an exception, as it is a
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY 241

self-expanding stent constructed of cobalt chromium.

Balloon-mounted stents are delivered coaxially over a
balloon catheter within and approximated to the vessel
wall by inflation of the balloon within the stent lumen.
Balloon-mounted stents have lower radial force and
are usually made only of stainless steel. The vast
majority of stents used in contemporary INR practice
are self-expanding.
There are three broad construction designs for
vascular stents: open-cell, closed-cell, and covered. An
open-cell design describes a stent in which there are a
few long, thin space-containing cells within the stent
wall. When expanded, open-cell struts usually assume
a complex helical conformation. In a closed-cell design,
there are more numerous, smaller polygonal-shaped
cells, separated from neighboring cells by struts much
like a honeycomb. Typically, the closed-cell design
affords greater scaffolding at the expense of flexibility,
while the converse is true of the open-cell design.
Stents are useful in varied circumstances, such
as the treatment of atherosclerotic stenosis, arterial
dissection, and wide-necked aneurysms. The utiliza-
tion of all stents require pre- and postmedication
with aspirin and clopidogrel. Our standard pretreat-
ment regimens are 5 days of Aspirin (325mg) and
clopidogrel (75mg). Alternate pretreatment regimens
include 3 or 4 days of Aspirin (325mg) and clopi-
dogrel (150mg), 2 days of Aspirin (325mg) and clo-
pidogrel (300mg) or for emergencies, a single dose
of Aspirin (325mg PO or 300mg PR) and clopidogrel
(600mg), the latter of which can be crushed and Figure 11.13 Photograph of Acculink 6 30mm to 8 30mm
administered by nasogastric tube, if necessary. Fol- tapered stent (Guidant Corp.). Inset shows the Acculink delivery
lowing stenting, clopidogrel is continued for 4 to 26 system.
weeks and aspirin often is continued for life.

Extracranial Carotid Artery Stenting

Most commonly, extracranial carotid stenting is
applied to symptomatic lesions with 50% luminal
stenosis and asymptomatic lesions with 70% luminal
stenosis. Stent sizing is a crucial component of the
procedure and so an accurate measurement of the ves-
sel proximal and distal to the stenosis is necessary.
Most angiography suites have the capacity to generate
accurate vessel diameter measurements using at least
the frontal projection. CT angiography also can be
applied for this purpose. Self-expanding extracranial
stents typically are oversized 0.51.5mm relative to
the largest lumen of the native vessel where the stent
will be positioned. Undersizing creates a dangerous
situation where the stent can migrate, fold, or kink,
predisposing to emboli, restenosis, or occlusion.
Extracranial CAS procedures begin with place-
ment of a long 6-Fr sheath into the CCA, followed by
placement of an EPD and mounted on a microwire into
the distal ICA. After removal of the EPD deployment
system, the microwire allows for rapid exchanges of
balloon, stent, and EPD recapture system. When treat-
ing flow-limiting, high-grade stenosis, prestenting
angioplasty is appropriate. Using monorail technique,
an appropriately sized high-pressure balloon can be
advanced across the lesion, inflated to or slightly above
nominal pressure, then deflated. This process can be
repeated and the balloons can be gradually upsized to
achieve a residual stenosis of <30%. Self-expanding
stents have radial force so that they widen to a preset
diameter on the bench top. However, the stents radial
force rarely is sufficient to expand the vessel lumen sig-
nificantly from its postangioplasty diameter. Further,
angioplasty within a stent can be performed but
increases the risk of the procedure owing to the
cheese-grater effect, in which atheroemboli can be
liberated through the pores of an open stent. So appro-
priate, effective prestenting angioplasty is crucial. The
Acculink Carotid Stent (Fig. 11.13) is an example of an
open-cell self-expanding stent for extracranial carotid
atherosclerotic lesions that is well suited for treatment
of high-grade flow limiting lesions. The Acculink Caro-
tid Stent is available in tapered (710mm and 68mm
diameter) and straight diameters (510mm) and range
in length from 20mm to 40mm. More moderate sten-
oses that are symptomatic but not flow limiting typi-
cally have one or more ulcerations that are a source of
distal atheroemboli. These lesions need not be angio-
plastied and usually can be treated effectively with a
closed-cell stent such as the Wallstent (Boston Scien-
tific) (Fig. 11.14).
Intracranial Stenting for Atherosclerosis or
Dissection-Related Stenosis
Intracranial stenting is typically appropriate only for
patients with cerebral artery steosis who have failed con-
servative medical management. Intracranial stenting is
242 NEUROINTERVENTIONAL MANAGEMENT
Figure 11.14 Lateral projection fluoroscopic projection following
carotid angioplasty and stenting demonstrates a Wallstent placed
across the carotid bifurcation.
performed with the Wingspan stent, an open-cell, self-
expanding stent with high radial force. There are four
tines at its proximal and distal ends. The stent is avail-
able in 2.5-, 3.0-, 3.5-, 4.0-, and 4.5-mm O.D. and lengths
of 9, 15, and 20mm. The Wingspan system was designed
to treat atherosclerotic-related stenosis, usually follow-
ing angioplasty with the Gateway balloon. It also can be
used to treat intracranial dissection-related stenosis, usu-
ally without adjuvant angioplasty. Before introducing
the Wingspan system into a guide catheter, the lesion to
be stented must be crossed with a standard-length
0.014 microwire. Commonly, angioplasty is performed
first using the Gateway balloon, as described above.
Stent-Coiling of Intracranial Saccular Aneurysms
Stent-coiling of intracranial saccular aneurysms refers
to the deployment of a stent across an aneurysm neck
to prevent coil herniation into the parent vessel and to
provide a more regular surface for endothelialization
following treatment. The Neuroform (Boston Scien-
tific) and the Enterprise (Cordis, Johnson & Johnson)
stents are commonly used for this purpose. Both are
self-expanding nitinol stents that allow for flow into
perforating vessels arising near the aneurysm neck
that may be covered by the stent. Either may be
deployed (i) prior to coil placement with the micro-
catheter delivered through the stents struts; (ii) prior
to coil placement, with the microcatheter positioned
within the aneurysm dome and wedged between the
stent and the vessel wall, the so-called jail method; or
(iii) following coil occlusion performed with or with-
out balloon remodeling (Fig. 11.15). Although the
Neuroform and Enterprise stents were designed for
aneurysm stent-coiling, either can be used to treat
arterial dissection, as well, when the desired goal is to
tack an intimal flap against the vessel media.
The Neuroform has an open-cell design and so
can be easier to navigate into position. The Neuroform
has an open-cell design with struts spaced 0.026
0.032 apart, allowing for passage of a typical 0.014
I.D. microcatheter (0.0220.025 O.D.) when the stent
is deployed in an unfolded conformation (i.e., flush
against the parent vessel wall) (Fig. 11.16). The Enter-
prise has a closed-cell design and so offers greater cov-
erage of the aneurysm neck, up to 10%. When fully
expanded, it has a diameter of 4.5mm in its central seg-
ment, with struts spacing similar to that of the Neuro-
form. Both stents have four radiopaque tines that flare
slightly following deployment. Unlike the Neuroform,
the Enterprise can be resheathed and recaptured after
70% of the stent has been unsheathed.
Typical 0.014 I.D. microcatheters have O.D.s
of 1.71.9 Fr (0.022-0.025), allowing for navigation
through the struts of a previously placed stent. How-
ever, microcatheters with a 0.018 I.D. typically have
an O.D. of 0.0260.029 and can be difficult to navi-
gate through the Neuroform struts. For this reason,
0.018 coils are difficult to deploy after stent place-
ment, unless the operator is willing to force 0.018
coils through a 0.014 microcatheter.
Flow Diversion Treatment of Intracranial
Saccular Aneurysms
While the Neuroform and Enterprise self-expanding
stents have a great deal of space between their struts,
the Pipeline Embolization device (eV3) and Silk (Balt,
Montmorency, France) are stents with three- to five-
fold greater wall coverage at the aneurysm neck. As
such, it is described as a near-covered design that has
been suggested as a treatment option for broad-necked
and fusiform aneurysms and cavernous-carotid fistu-
las. Some have suggested that it eventually may pro-
vide risk reduction in the management of aneurysms
currently treated with coil embolization owing to a
decreased likelihood of aneurysm perforation.
The Pipeline device consists of 16 closed-cell
platinum struts and 16 strands of braided stainless
steel that are heat-treated in the expanded configura-
tion, mounted on a delivery microwire, then com-
pressed and loaded into an introducer sheath. The
Silk stent is composed of 4 large platinum struts and
44 strands of nitinol braided together that are pre-
treated and loaded much like the Pipeline. The
strands of the stent are able to slip on each other dur-
ing unsheathing so that coverage of a treated aneur-
ysm depends on the curvature of the parent vessel.
The proximal and distal ends of the stent flare
slightly to prevent migration. The packaged Pipeline
device can be loaded into a standard microcatheter
with a 0.027 I.D. and is delivered by unsheathing.
The Pipeline undergoes shortening by up to 50% dur-
ing deployment, depending on the diameter of the
parent vessel.
When placed across an aneurysm neck, these
flow exclusion devices are intended to reduce flow
into the aneurysm sufficiently to allow thrombosis
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY 243

(A) (B)

(C) (D)

Figure 11.15 Illustration of aneurysm coil embolization techniques. (A) Coils positioned through a microcatheter in a narrow-necked
aneurysm. (B, C) For wide-necked aneurysms, coil placement with balloon remodeling followed by stent deployment is preferred. (D)
Additional coils may be placed following stent deployment by positioning the microcatheter through the stent struts into the residual
aneurysm neck or dome. Source: Courtesy of Boston Scientific, Fremont, California, U.S.

2
1

34
2

(A) (B)

Figure 11.16 Cerebral angiogram, unsubtracted PA view. (A) The Neuroform stent has (1) four distal and (2) four proximal radiopaque
markers. (B) The Neuroform3 Microdelivery System has four radiopaque indicators representing (1) the microdelivery catheter tip, (2)
the compressed distal stent markers, (3) the compressed proximal stent markers, and (4) the stent stabilizer tip.
244 NEUROINTERVENTIONAL MANAGEMENT
within the blind-ended aneurysm sac. Promising pre-
liminary data describing the effectiveness of flow
diversion systems has been tempered by scattered
case reports describing infarction from occlusion of
small perforator vessels arising near the aneurysm
neck (24).
If possible, stent-coiling and flow diversion tech-
niques should be limited to the treatment of unrup-
tured aneurysms because the required anticoagulation
and antiplatelet therapy may carry an excessively high
hemorrhagic complication risk for recently ruptured
aneurysms (25). If complete occlusion of a ruptured
aneurysm following coil embolization necessitates stent
deployment, we prefer first to protect the majority of
the aneurysm sac, including irregularities at the aneur-
ysm dome, with incomplete aneurysm embolization,
then return to place a stent during a second procedure,
staged 2 to 10 weeks following discharge. As of this
writing, the Neuroform and Enterprise stents have not
yet gained approval from the United States Food and
Drug Administration.
DEVICES FOR MANAGEMENT OF ACUTE
EMBOLIC STROKE
Historically, IA thrombolytic administration or
mechanical thrombectomy has been reserved mainly
for acute anterior circulation stroke patients who pre-
senting within 3 hours of ictus but have a contraindi-
cation to i.v. tissue plasminogen activator (tPA) or
who present 36 hours from ictus. In addition to
time from ictus, we also consider the NIH stroke
scale, patient age and comorbidities, and advanced
CT imaging techniques to stratify patients into one of
four treatment arms: oral aspirin, i.v. tPA, endovas-
cular intervention, or combined i.v. tPA/endovascu-
lar intervention. Most patients suspected of having
an acute ischemic stroke get a non-contrast head CT,
a CT angiogram (CTA) and a CT perfusion (CTP)
scan upon arrival for which an 18-G intravenous
(i.v.) line is a necessary prerequisite. The CTA por-
tion of the examination consists of 0.625mm slices
acquired from the aortic arch to the cranial vertex
during a 90 cc bolus of Omnipaque-300 (General
Electric, Milwaukee, WI) timed using SmartPrep soft-
ware (General Electric). The CT perfusion scan con-
sists of dynamic imaging through four axial sections
usually at the level of the basal ganglia, insulae, and
Sylvian fissures during an untimed bolus injection of
30 cc Omnipaque-300. Using free-standing image
processing workstations (Vitrea, Vital Images, Minne-
tonka, MN; or General Electric), volume rendered
angiograms of the circle of Willis and its second
order branches and axial maps describing cerebral
blood volume (CBV), blood flow (CBF), and mean
transit time (MTT) maps are generated. In the appro-
priate clinical setting, the CTA localizes or excludes a
large vessel embolus and the CTP defines a core
infarction and an ischemic penumbra.
Technical questions to consider prior to beginning
an intracranial revascularization procedure include:
Can a device be advanced into the involved cervical
vessel via a standard transfemoral approach? Can an
appropriate guide catheter or long sheath be advanced
through the cervical vessels close enough to the skull
base to provide appropriate access? Are there robust
pial collaterals supplying the ischemic penumbra? If
prior axial imaging does not answer these questions,
then a complete three- or four-vessel diagnostic angio-
gram should be performed prior to intervention. When
the patient is on anticoagulation or tPA or when radial
or carotid puncture is performed, a micropuncture kit
is used to gain access. When the decision has been
made to perform intracranial revascularization for
acute embolic stroke, multiple devices are available.
Penumbra Reperfusion System
Penumbra Reperfusion Catheters (RC; Penumbra Inc.
Alameda, CA) are a set of four tapered microcatheters
named for their distal I.D. (0.054, 0.041, 0.032, and
0.026) and intended for intracranial embolus aspira-
tion. Following CT angiogram or diagnostic catheter
angiography, the location of the occlusion and caliber
of the occluded vessel help guide the operator to
select an appropriately sized RC. The 0.054 RC is
132-cm long, has a distal O.D. of 0.066 (1.67mm) and
typically is useful for anterior circulation emboli
located proximal to the anterior temporal artery ori-
gin. The 0.041 RC is 137-cm long, has a distal O.D. of
0.054 (1.37mm) and usually is not advanced beyond
the MCA bifurcation or the basilar terminus. The
0.032 and 0.026 RCs are 150-cm long and can be
used for retrieval of more distal emboli. An RC is pre-
pared by placing an RHV and three-way stopcock at
the proximal hub and flushing with saline. A micro-
catheter and microwire are then placed coaxially
within the RC prior to introduction.
After determining which RC will be most useful,
an appropriate sheath or guide catheter should be
selected. For anterior circulation emboli proximal to
the anterior temporal artery origin, we usually prefer
the 0.054 RC. For access, we advance a 6-Fr, 90-cm
sheath over a 5-Fr diagnostic catheter and 0.035 Gli-
dewire into or just proximal to the carotid bulb. In
practice, the RC does not extend a full 47cm beyond
the guide catheter, as the RHV used to flush the guide
catheter reduces the RC effective length. Alternatively,
an 8-Fr guide catheter such as the MERCI balloon
guide catheter can be used.
Unlike the 0.054 RC, the 0.041, 0.032, and
0.026 RCs can be introduced through a standard 6-Fr
guide catheter, such as the Neuron (90cm or 105cm;
Penumbra Inc.) or Envoy (90cm; Cordis, Miami Lakes,
FL). The Envoy guide catheter should not be advanced
beyond the skull base. The Neuron guide catheter
should not be advanced beyond the ophthalmic artery
origin. For a patient with a diminutive MCA or for a
distal MCA embolus, a 90-cm, 6-Fr guide catheter can
be advanced up to the skull base or if using a 105-cm,
6-Fr Neuron guide catheter, as far as the cavernous seg-
ment. When additional support is needed in a patient
with tortuous or aberrant arch or cervical anatomy or
when aspirating a posterior circulation thrombus from
a patient with a large caliber vertebral artery for access,
a 6-Fr, 105-cm Neuron guide catheter can be advanced
through a 90-cm, 6-Fr sheath. A 0.041 RC then can be
delivered coaxially over a microcatheter with 2.8 Fr
O.D., such as the Rebar 18 (EV3) or Prowler Select Plus
(Johnson & Johnson), to ease tracking around the
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
ophthalmic bend. Figure 11.17 depicts frontal angio-
grams performed before (A) and after (B) revasculariza-
tion of a left M1 segment using a 0.041 RC advanced
through a 6-Fr Neuron guide catheter and long (90-cm),
6-Fr sheath.
If a vertebral artery is judged large enough to
accept a 6-Fr guide catheter without occluding flow, a
long 6-Fr sheath can be advanced into the subclavian
artery, then a 6-Fr Neuron can be advanced as far
cephalad as the V2V3 junction. For emboli into a nor-
mal caliber basilar artery, a 0.041 RC usually is suit-
able, while a 0.032 RC can be advanced into normal
caliber P1 segments.
Once the Penumbra RC has been advanced up to
and even slightly into the intracranial embolus, some
operators prefer to advance the microcatheter over a
microwire distal to the embolus so that simultaneous
road maps can be performed through the microcath-
eter and guide catheter. The RC then is advanced into
the proximal aspect of the embolus and 500mm Hg
continuous negative pressure is applied using a suc-
tion pump affixed to the angled port of the RHV at
the external end of the RC. Absence of blood return
from the RC confirms that its tip is inside the embo-
lus. At this point, the microcatheter is then replaced
with a Penumbra Separator, consisting of a soft tipped
wire with a tear-dropped polymer bulb 6mm from the
distal end that is designed specifically to clean the dis-
tal RC lumen. The Separator is advanced approxi-
mately 4mm distal to the RC tip, then retracted
approximately 20mm into the RC. This process is
repeated many times to ensure RC patency. When
inside the RC lumen, the Separator bulb greatly
reduces negative pressure that is applied to the embo-
lus so when not in use, the Separator should be left
outside of the RC, ideally within the distal aspect of
(A)
Figure 11.17 Subtracted cerebral angiogram in the PA projection before (A) and after (B) embolus aspiration using the Penumbra sys-
tem. Abrupt truncation of the left M2 segment (A) represents an embolic occlusion. Robust pial collateral flow to the left MCA territory
supplied from the left anterior temporal and anterior cerebral arteries prevented immediate cerebral infarction in this patient who was
revascularized within four hours of symptom onset.
245
the embolus, no more than 56mm distal to the RC.
When blood return is seen, angiography is performed
through the guide catheter. If there is some embolus
remaining distally, the Separator can be removed and
the RC advanced over a microwire into the remaining
embolus. Although the Separator tip is soft, it is not
intended for use as a microguidewire.
MERCI Retriever
The Mechanical Embolus Removal in Cerebral Ische-
mia (MERCI; Concentric Medical, Mountain View,
CA) devices are corkscrew-shaped nitinol memory
wires with five helical loops at the distal tip named
for the diameter of the largest, proximal most loop
(3.0mm, 2.5mm, 2.0mm). Like Penumbra, MERCI can
be used in the anterior and posterior circulations, pro-
vided an appropriate guide catheter can be placed in
the neck. For anterior circulation emboli, an 8-Fr short
sheath is placed into the CFA, allowing for passage of
a balloon guide catheter into the ICA. The O.D. of the
MERCI guide catheter itself is only 6 Fr. However,
with the added diameter of the balloon, an 8-Fr sheath
is required. For posterior circulation emboli, when nei-
ther vertebral artery is large enough to accept the
MERCI balloon catheter, a standard 6-Fr guide cathe-
ter can be placed into the dominant or more easily
accessible vertebral artery.
Once the guide catheter has been placed, a distal
access catheter (DAC; described above) is advanced
intracranially, usually into a cavernous or V4 segment.
An 18L MERCI microcatheter (3-Fr O.D. proximally,
2.4-Fr O.D. distally) is advanced over a microwire
through and distal to the embolus. After the wire is
removed, simultaneous roadmaps can be performed
though the microcatheter and guide catheter. The
(B)
246 NEUROINTERVENTIONAL MANAGEMENT
(A)
(B)
(C)
Figure 11.18 Photograph of the MERCI mechanical embolec-
tomy system (Concentric Medical, Inc.). (A) Tapered loops of the
X6 Retriever. (B) 18 microcatheter. (C) Balloon guide catheter
with balloon inflated.
MERCI retriever then is advanced through the micro-
catheter until its tip is situated at the microcatheter
tip. The microcatheter then is retracted, exposing the
distal two loops. The retriever then is rotated counter-
clockwise two revolutions, and the retriever and
microcatheter then are retracted gently to ensure that
the distal loops of the retriever have purchase at
aspect of the embolus. The microcatheter alone then is
retracted to expose the retrievers proximal loops. The
retriever can be rotated counterclockwise to loosen the
proximal loops of the helix, while the distal loops
ideally remain engaged in the distal aspect of the
embolus. If a balloon catheter has been placed into the
ICA, the balloon is inflated at this time. Whatever
guide catheter is used, the next step is for the micro-
catheter and retriever to be retracted simultaneously
into the guide catheter while vigorous negative pres-
sure is applied to the angled port of the guide catheter
using a 60 cc syringe. After the retriever and micro-
catheter have been removed from the guide catheter,
the system is inspected for emboli and the guide cath-
eter is allowed to backflow by leaving the rotating
RHV port open. If no or slow blood return is seen
from the guide catheter, there is clot within the guide
and it should be removed and flushed on the bench
top. Figure 11.18 shows the working segments of the
MERCI system on the bench top.
EMBOLIC MATERIAL
Coils
In 1990, Guido Guglielmi introduced the first electro-
lytically detachable bare platinum microcoils
(Guglielmi Detachable Coils, GDC; Boston Scientific).
The first GDC coils were available only in a helical con-
formation. Contemporary coil shapes include standard
helical, 2D (two diameters) and complex (three-dimen-
sional and 360) (Fig. 11.19). Coils with a smaller first
loop and larger subsequent loops have two diameters
of loops and so are called two-diameter coils by most
manufacturers. Complex coils usually form a regular or
irregular spherical conformation, although non-spheri-
cal complex coils do exist. The diameter of a deployed
coil can range from 1.5mm to 24mm. Coil stiffness
availability includes ultrasoft, soft, standard, firm, and
extrafirm. Most contemporary coils are manufactured
with stretch-resistant technology.
Over two decades since the introduction of GDC
coils, advancements have led to the availability of a
plethora of coils of varying properties (Fig. 11.20). In
addition to bare platinum, coils coated in biologically
inert or active materials also are available, as are coils
constructed with interwoven microfilaments. As
examples, coils coated with polyglycolic-polylactic
acid (PGPL) (Matrix coil, Boston Scientific) have been
said to promote formation of granulation tissue within
the aneurysm sac in the weeks following deployment;
coils coated with hydrogel (HydroFrame, HydroSoft
coils; Microvention, Aliso Viejo, Calif) (Fig. 11.21) are
thought to expand within hours of deployment, lead-
ing to increased volume of the embolization mass;
and coils constructed with interwoven microfilaments
(Nexus, eV3) are said to provide increased compliance
within complex aneurysms. Most coil filaments are
manufactured in 0.010, 0.012, and 0.018 filament
diameter (to be distinguished from coil mass diame-
ter). However, more recently, 0.020 diameter coils
have become available (Penumbra).
Coil embolization of saccular aneurysms involves
careful placement of a framing coil (typically a stand-
ard 2D or 3D coil is most suitable) into the aneurysm
dome under fluoroscopic guidance using roadmap or
subtraction fluoroscopy technique (Fig. 11.22). Once
coil position within the aneurysm and without hernia-
tion into the parent vessel is confirmed by fluoro-
scopy, the coil is detached. The coil pusher wire is
then carefully withdrawn under fluoroscopic guidance
while ensuring that the coil was fully detached. If
residual aneurysm opacification is seen, then addi-
tional coils of various shapes and successively dimin-
ishing sizes are added to the coil mass until complete
occlusion (if possible) is obtained. The first coil is usu-
ally sized to match the smallest dimension of the
aneurysm. Subsequent coils are delivered in decreas-
ing sizes, to nest within previously deployed coils and
fill with aneurysm from the periphery to the center.
Appropriate choice and placement of the first coil is
fundamental and sometimes will alone determinate
the success of the procedure. The most hazardous
coils are the first (framing coil), which has the greatest
chance of causing aneurysm rupture and the last (fin-
ishing coil), placed at the neck and with the highest
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY 247

(A) (B) (C)

Figure 11.19 Illustration of coil shapes. (A) Standard helical coil. (B) 2D (2-diameter) coil. (C) 3D coil. Source: Courtesy of Boston Sci-
entific, Fremont, California, U.S.

(C)

(A) (B)

Figure 11.20 Illustration of coil coating. (A)

Bare platinum coil (GDC) and (B) PGLA-coated
coil (Matrix). (C) Magnified view showing the
PGLA coating over the platinum base of the
Matrix coil. Abbreviations: GDC, Guglielmi
detachable coils; PGLA, polyglycolic-polylactic
acid. Source: Courtesy of Boston Scientific,
Fremont, California, U.S.

likelihood of herniation into the parent vessel. For Onyx

embolization of ruptured aneurysms and in occasional
cases of unruptured aneurysm, a half-dose heparin
bolus (2535mm/kg) will be administered before
microcatheter introduction and a second half-dose
bolus administered after placement of one or two
framing coils.
Onyx (eV3) is a liquid embolic agent composed of eth-
ylene vinyl alcohol copolymer dissolved in DMSO
and opacified with tantalum powder. Onyx is avail-
able in three densities 18, 34, and 500 (high den-
sity, HD). The Onyx kit includes a 1.5-mL vial of
248 NEUROINTERVENTIONAL MANAGEMENT
(A)
(B)
Figure 11.21 (A) Photograph of a hydrated Hydrocoil and (B)
electronmicrograph of the dehydrated Intelligel coating of the
Hydrocoil. Source: Courtesy of MicroVention Inc.
Onyx, a 1.5-mL vial of DMSO and syringes for the
delivery of each. In our practice, Onyx is most com-
monly used for embolization of brain AVMs, dural
arteriovenous fistula (dAVFs), and tumors. Because
Onyx polymerizes by dessication, it does not solidify
easily while moving. Onyx also is not adhesive or
thrombogenic. Because of these properties, when look-
ing at an Onyx cast using fluoroscopy, it is not possi-
ble to tell if a vessel opacified with Onyx is in fact
occluded. Onyx may deposit along the endothelial
surface of a vessel so that the lumen appears entirely
opacified under fluoroscopy. However, in some
instances, only the periphery of a vessel lumen is
coated with Onyx, while one or more central channels
permit distal passage of blood or additional Onyx.
These properties allow for extended, interrupted injec-
tions of Onyx from a single arterial feeder, unlike
nBCA. Although the risks of excessive arterial reflux
of embolization material, microcatheter entrapment,
and venous outflow obstruction are reduced with
Onyx compared with nBCA (26,27), these risks remain
significant. At the beginning of a case where emboli-
zation with Onyx is anticipated, multiple Onyx vials
should be mechanically agitated to ensure homogene-
ous distribution of tantalum. If a vial of Onyx is left
on the bench top for more than a few minutes, it can
be reintroduced into its vial and re-agitated.
When treating intracranial vascular malforma-
tions, it is possible to achieve total cure of an AVM or
dAVF using Onyx (Fig. 11.23). However, the most
common scenario involves multiple, staged partial
embolizations followed by radiation therapy or
Figure 11.22 Right posterior oblique fluoroscopic projection
showing a GDC 10 standard 8mm  30mm, two-diameter (2D)
coil placed to frame an anterior communicating artery aneurysm.
A 3mm  10mm eV3 HyperGlide balloon has been advanced
into the right anterior cerebral artery and is positioned across the
aneurysm neck. The distal tip of an Excelsior SL-10 microcath-
eter with a J-shaped tip is poorly visualized owing to superimpo-
sition of the coil mass.
surgery. Any attempt to cure a vascular malformation
with Onyx necessarily entails creating a sturdy Onyx
plug in around the microcatheter tip and advancing
Onyx up to or into a draining vein. This approach car-
ries with it increased risk of reflux into arteries sup-
plying normal brain, microcatheter entrapment
following embolization, or venous outflow obstruction
compared with a more cautious and quicker preopera-
tive or preradiation embolization.
For access, we usually prefer to advance a (90-
cm, 6-Fr) Envoy guide catheter into a distal cervical
vessel, then advance a short (115-cm, 3.9- or 4.3-Fr)
DAC intracranially over a Marathon or Echelon (eV3)
microcatheter. Both are Onyx-compatible and DMSO
and Onyx should not be injected through Onyx-
incompatible microcatheters, since DMSO can degrade
many microcatheter polymers and deform or even
rupture the microcatheter in vivo. The Marathon or
Echelon then is advanced over a microwire into a
small branch vessel supplying only the lesion. Ideally,
selective contrast injection through a well-placed
microcatheter should opacify only a few mm of feed-
ing artery, followed immediately by the nidus, fistula,
or tumor to be embolized. Before injecting Onyx, it is
quite useful to find at least one projection depicting
the tip of the microcatheter separate from (i.e., not
projecting over) the lesion so that reflux around the
microcatheter tip can be readily identified. The major
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
Figure 11.23 Fluoroscopic PA projection demonstrates preoper-
ative embolization of a juvenile nasal angiofibroma supplied by
branches of the bilateral internal maxillary arteries (IMAs), right
greater than left. Onyx-18 was injected via direct puncture
through the right nostril and transarterially, from the bilateral
sphenopalatine arteries. Because supply from the right was par-
ticularly vigorous prior to embolization, two GDC coils were
placed into the distal right IMA.
draining veins also should be identified so venous
efflux can be rapidly identified and outflow obstruc-
tion avoided. At this time, the operator also should
predetermine how much arterial reflux around the
microcatheter can be tolerated safely.
After achieving appropriate microcatheter place-
ment and determining appropriate working projec-
tions, the microcatheter should be flushed with
0.20.3mL of saline, then 0.20.3mL DMSO. Once the
microcatheter lumen is filled with DMSO, 0.10.2mL
of Onyx can be injected into the microcatheter dead
space without fluoroscopy. Then, Onyx should be
gently injected into the feeding artery en route to the
lesion. All strategies for Onyx injection attempt to bal-
ance distal advancement of Onyx into the lesion
indeed into the draining vein in the case of dAVFs
and some parenchymal AVMswhile minimizing the
procedural risks stated above. One useful strategy
involves allowing just a drop of Onyx to escape the
microcatheter tip during first advancement to form a
kernel at the microcatheter tip. After waiting
2 minutes to allow the kernel to solidify, Onyx again
can be gently injected against the kernel, which pro-
vides a small amount of resistance and directs Onyx
retrograde around the microcatheter tip. In this way, a
plug is formed in a controlled fashion around the
distal few mm of the microcatheter. The plug should
be left for 5 minutes to solidify before continuing the
injection. Some operators prefer first to form a plug
with Onyx-34 before attempting to advance Onyx-18
249
anterograde into the lesion. Successive injections are
best performed using a blank roadmap to identify
additional Onyx reflux into the plug. It is desirable to
continue to inject Onyx retrograde into the plug to
increase the density of the plug without increasing its
length. During this process and throughout the remain-
ing embolization process, 23 minutes should be left
between Onyx injections to allow previously injected
Onyx time to polymerize. At some point following
plug formation, when the resistance to flow of the plug
exceeds that of the kernel and lesion, Onyx will begin
to advance anterograde. At this time, it is recom-
mended that Onyx injection continue until additional
reflux is identified or there is unwanted venous opacifi-
cation. In the absence of a detachable-tip microcatheter,
the decision about how long to continue injecting Onyx
can be difficult. If multiple arterial curves have been
traversed en route to the desired embolization position
and/or most of the catheterized length of vessel is
within a cistern rather than being anchored in brain
parenchyma, embolization times <30 minutes per feed-
ing artery are suggested. That said, for large and com-
plex lesions, many operators prefer to continue
embolizing beyond 30 minutes, even for hours. At the
end of the embolization, when resistance to microcath-
eter retraction is encountered (i.e., entrapped micro-
catheter, microcatheter glued in place), it is useful to
have a coaxial DAC, which can be advanced distally
sometimes all the way up to the Onyx mass. Gentle
counter tension applied with the DAC can stabilize the
cisternal segment of a vessel, allowing retraction of the
microcatheter with greater force. Although this techni-
que is effective, many operators prefer simply to leave
an entrapped microcatheter in place, severing it in the
subcutaneous tissues overlying the CFA. Some neuroin-
terventionalists regularly leave entrapped microcath-
eters in place and obtain written informed consent for
this circumstance prior to the procedure. Retained
microcatheters are known to have a low morbidity (28,)
can be thrombogenic, and some patients with retained
microcatheters are maintained on anticoagulation for
624 months, after which time the microcatheter frag-
ment becomes endothelialized. On other occasions, the
microcatheter can snap during retrieval, usually
between the tip of the DAC and the Onyx mass. On
these occasions, the retained fragment can be removed
during surgical resection of the lesion, if the emboliza-
tion is not curative.
Onyx-500 (High Density, HD) was deigned for
balloon-assisted liquid embolization of intracranial
saccular aneurysms (29). With a Marathon or Echelon
microcatheter placed within an aneurysmideally
near the domean eV3 HyperForm or HyperGlide
balloon is inflated across the aneurysm neck and
100% Omnipaque-320 is gently injected into the aneur-
ysm to ensure that the balloon prevents all efflux
from the aneurysm. After performing this seal test,
the balloon is deflated and the microcatheter flushed
with saline then DMSO, as described above. The bal-
loon then is reinflated and Onyx-500 is slowly injected
at 0.1mL/min using the Cadence Precision Injector
(Micro Therapeutics, Inc.) until the aneurysm is filled.
After gentle, gradual balloon deflation, DMSO will
diffuse out of the aneurysm over approximately
10 minutes and the Onyx will polymerize and solidify.
250 NEUROINTERVENTIONAL MANAGEMENT
The balloon then is reinflated and the microcatheter
gently removed (30). Minimal Onyx extravasation into
the parent vessel at the aneurysm neck is acceptable
and in some cases, even preferred as long as the
extravasated Onyx coats the parent vessel lumen only
within a mm of the neck and does not migrate.
Polyvinyl Alcohol Particles
Mechanical occlusion of arterioles can be achieved by
infusion of polyvinyl alcohol (PVA) particles. Arterial
occlusion with PVA may be temporary with recanaliza-
tion occurring over days to months as the periparticle
thrombus resorbs (31). Thus, PVA embolization is most
appropriate for achieving hemostasis in epistaxis cases
and for preoperative tumor embolization. PVA particles
are mixed in 80100% contrast solution and injected
selectively through a microcatheter under fluoroscopic
guidance. A single vial of PVA particles provided by the
manufacturer contains a range of particles, ranging from
very small (45 to 150mm) to large (1000 to 1180mm)
(Contour PVA particles; Boston Scientific, Fremont,
California, U.S.). PVA particles wedge into arterioles,
adhere to microvascular endothelium, and accumulate
within richly vascularized tissue beds.
During PVA preoperative tumor embolization,
the microcatheter is advanced distally into a feeding
branch until contrast injection through the microcath-
eter opacifies only tumor. Wedge flow is avoided to
prevent particle reflux and delivery of particles into
unpredictable territories. PVA then is infused in a pul-
satile fashion until particles accumulation at the
microcatheter tip and stagnant flow in the injected
vessel are noted. Some tumors have micro arteriove-
nous shunts that are too small to be visualized with
angiography. For this reason, we generally avoid very
small (45- to 150-mm) particles and instead embolize
with medium-sized (150- to 250-mm) particles. If rapid
arteriovenous shunting is seen, particle embolization
either is deferred or performed with larger (e.g., 350-
to 450-mm or 500- to 710mm) particles (Fig. 11.24), tak-
ing care to stop the embolization is flow reduction is
not encountered within a few minutes of particle
injection.
Figure 11.24 Photograph of 500-to 710-mm PVA particles.
The microcatheter should be flushed between
successive embolizations to avoid particle accumula-
tion in the microcatheter hub or shaft. A microcatheter
containing PVA may be flushed gently into the lesion
following embolization or outside the patient, away
from other devices and baths. Tumor necrosis may be
accompanied by significantly increased surrounding
edema, so for large tumors with mass effect, we give
a bolus dose of dexamethasone at the time of tumor
embolization.
Embosphere Microspheres
Embospheres (Biosphere Medical, Inc., Rockland, Mas-
sachusetts, U.S.) are an alternative particulate embolic
agent composed of trisacryl gelatin microspheres.
Unlike PVA particles, which have uneven surfaces
and variable sizes (Fig. 11.25), microspheres are spher-
ical particles of uniform size and shape. These charac-
teristics are ideal for improving distal penetration of
vascular lesions and tumor vascular beds. In a direct
comparison with PVA particles, preoperative meningi-
oma embolization with Embospheres resulted in sig-
nificantly less procedural blood loss (32). Following
tumor and vascular malformation embolization, the
microsphere, unlike PVA particles, do not aggregate;
therefore, a 100-mm Embosphere bead will reliably
occlude a 100-mm vessel, whereas a 100-mm PVA par-
ticle is less predictable and may bind to a 200-mm ves-
sel wall causing obstruction following aggregation
with other PVA particles. This absence of aggregation
Figure 11.25 Photograph of PVA particles in solution demonstrat-
ing the rough surface and aggregation tendency typical of PVA.
 TECHNIQUES AND DEVICES IN INTERVENTIONAL NEURORADIOLOGY
also enhances delivery because the microspheres do
not clump within the microcatheter.
Absolute Ethyl Alcohol, Sotradecol and
Bleomycin
Sclerosing agents sometimes are used in the treatment
of vascular malformations of the head and the neck not
amendable to surgical resection. Access is by selective
IA or transvenous approach or by direct percutaneous
puncture. Alcohol has low viscosity, facilitating deep
penetration of the nidus, and is extremely cytotoxic,
causing fibrinoid necrosis of the endothelium and ves-
sel thrombosis (33,34). Ethanol is carefully infused into
the lesion and requires 5 to 10 minutes for its throm-
botic effect. Complete occlusion typically requires a
staged embolization approach (33). General anesthesia
is required because ethanol embolization is painful.
The main risk of intravascular ethanol infusion is acute
pulmonary hypertension.
Sotradecol and Bleomycin are sclerosing agents
that do not cause tissue necrosis if extra vascular
injection occurs. Sotradecol is our preference for per-
cutaneous embolizations of the head and neck because
of its safety. However, sotradecol occasionally is less
effective than alcohol. Bleomycin has recently been
identified as a safe sclerosing agent with efficacy and
safety similar to that of sotradecol. In some hospitals,
bleomycin is more readily available than sotradecol.
ENDOVASCULAR INFUSIONS
Wada Testing
Developed in the late 1940s by Juhn Atsushi Wada, a
Canadian neurologist, this diagnostic study test entails
intracarotid infusion of amobarbital followed by neu-
rological and/or neuropsychological assessment for
the purpose of lateralizing eloquent cortex involved in
language, memory, and speech. During preoperative
evaluations for epilepsy surgery, the patient is con-
nected to continuous electroencephalographic moni-
toring, and 80 to 140mg of amobarbital (10mg/mL in
saline) is injected through the diagnostic catheter at
12mL/sec into the ICA with the patients arms ele-
vated to watch for intended contralateral hemiplegia.
The patient typically recovers complete neurological
function within 15 minutes to allow testing of the con-
tralateral hemisphere. During AVM embolization, a
feeding artery supplying the lesion is catheterized
with a microcatheter and 25 to 50mg of amobarbital
in a 1-mL aliquot is then injected. Neurological and/
or neuopsychological testing then is performed to pre-
dict dysfunction prior to permanent vessel occlusion
by endovascular or open surgical modalities (35).
Intra-Arterial Infusion of Chemotherapy
Management of refractory neoplasms with IA chemo-
therapy delivery has been performed for years with
varying degrees of success. Early trials for IA chemo-
therapy delivery for intracranial neoplasms were lim-
ited by catheter-related technical complications and
poor efficacy that did not justify the procedural risk
(36). However, improved catheter technology combined
251
with new or modified chemotherapy regimens holds
great promise for the expansion of this area of INR.
Intra-ophthalmic artery infusion of various combina-
tions of melphalan, topotecan, and carboplatin for
newly diagnosed retinoblastoma or in retinoblastoma
patients who have failed intravenous chemotherapy has
demonstrated efficacy in most patients, achieving total
cure or affording vision-sparing surgery instead of enu-
cleation (37). In separate work, there is growing evi-
dence suggesting that IA chemotherapy infusion is safe
and more effective than intravenous delivery in high-
grade glioma patients as well (38).
In our experience, we have found that chemo-
therapy regimens should be dosed based on the vol-
ume of territory to be infused rather than the weight
of the patient. Also, we believe that pulsatile infusion
achieves more even distribution of solution through-
out the territory of the injected vessel compared with
constant infusion. For infusion of small vessels, we
rarely advance the microcatheter into the target vessel
over a microwire because of the risk of dissection.
Instead, we advance the microcatheter over a micro-
wire past the target vessel ostium, then retract the
microcatheter back into the vessel origin. When the
microcatheter is precariously situated at the vessel ori-
gin, the operator should train himself/herself with
gentle injection of contrast under fluoroscopy, taking
note of the strength of infusion necessary to generate
reflux. For vessels that cannot be catheterized directly,
the balloon-assisted infusion technique (described
above in greater detail) can achieve selective chemo-
therapy infusion into branch vessels that cannot be
directly cannulated, such as the lenticulostriates, thala-
mic perforators, or even a diminutive ophthalmic
artery in a toddler (39).
Vasodilator Infusions
Both catheter-induced and post-SAH vasospasm can
be managed with IA verapamil. One to two milligrams
of verapamil infused through a guiding catheter is
usually sufficient to treat catheter-induced vasospasm,
and pretreatment with verapamil can provide effective
prophylaxis for vasospasm susceptible vessels (e.g.,
ECA). For management of post-SAH distal vasospasm
diffusely affecting a vascular territory, a diagnostic
catheter can be advanced into the appropriate verte-
bral or carotid artery for infusion of 510mg of verapa-
mil diluted in 1020mL heparin saline at a rate of 1
mL/min. For vasospasm affecting a specific vessel seg-
ment, selective catheterization with a microcatheter
can be performed for administration of the same dose
and concentration of verapamil (although higher doses
may be given if needed). Slow infusion limits cardiac
side effects of hypotension and bradycardia. The safety
and efficacy (though not durability) of chemical infu-
sion for post-SAH vasospasm has been demonstrated
in retrospective studies for both verapamil (40) and
nicardipine (41). A starting dose used for nicardipine
also is 510mg per injected vessel. IA infusion of papa-
verine will also dilate spastic vessels. However, the
effect is short-lived and there are numerous side
effects, including hypotension, intracranial hyperten-
sion (also occurs to a lesser extent with verapamil and
nicardipine), and seizures (41). The advantages of
252 NEUROINTERVENTIONAL MANAGEMENT
chemical infusion over angioplasty for vasospasm
therapy include decreased risk and the ability to treat
distal and small artery vasospasm not reachable by
balloon. However, balloon angioplasty is more
durable.
Intra-Arterial Thrombolysis
IA thrombolysis by direct thrombolytic infusion fol-
lowing superselective catheterization offers treatment
to acute ischemic stroke patients who have failed or
are ineligible for intravenous thrombolysis. Since the
landmark PRO-ACT II trial (42), recombinant tissue
plasminogen activator (r-tPA) has been increasingly
used for endovascular stroke therapy at many centers.
Prior to infusion, the microguidewire is passed several
times through the clot to increase the surface area for
thrombolysis. The use of IA glycoprotein (GP) IIb/IIIa
inhibitors to treat intracerebral artery occlusion refrac-
tory to IA thrombolysis also appears to be safe (43).
Our anecdotal experience with IA infusion of the GP
IIb/IIIa inhibitor abciximab, including for the treat-
ment of procedure-related thromboembolic complica-
tions, has been superb. However, it should be noted
that because abciximab needs to affect the entire circu-
lating platelet pool to be effective (44), there should be
no benefit of IA delivery of this drug over IV.
Transvenous Thrombolysis
Targeted transvenous thrombolytic therapy for medi-
cally refractory dural venous sinus thrombosis involves
direct thrombolytic infusion through a microcatheter
positioned in the thrombosed sinus. Sinus access is typ-
ically from the common femoral vein, though subcla-
vian venous access may be required if the transfemoral
route is obstructed (e.g., by femoral or inferior vena
caval clot). Complete sinus recanalization customarily
requires the microcatheter (e.g., Prowler Select 170-cm
microcatheter is needed to navigate from the common
femoral vein to the superior sagittal sinus; Cordis
Corp.) to be kept within the sinus for continuous infu-
sion (e.g., intrasinus r-tPA at a rate of 1 to 2mg/hr
over 24 to 48 hours, with or without a thrombolysis
may be done alone, but is usually performed in con-
junction with mechanical thrombectomy using the
microguidewire, balloon angioplasty, or rheolytic
thrombectomy device (Angiojet; Possis Medical, Inc.,
Minneapolis, Minnesota, U.S.; requires an 8-Fr guide
catheter).
ARTERIAL CLOSURE DEVICES
There are two major types of arterial closure devices:
intra- and extravascular. Intravascular closure devices
include the Angio-Seal (St. Jude Medical, St. Paul,
MN), Perclose (Abbott Vascular Inc. Redwood City,
CA), and Starclose (Abbott Vascular Inc.) devices. The
Mynx is an example of an extravascular closure
device. In our experience, the intravascular devices
offer greater reliability for patients with arteriotomies
7 Fr and on anticoagulation, while the extravascular
devices carry a lower risk of arterial dissection. When
an arterial closure device fails to achieve hemostasis
due to complicated anatomy or operator error, direct
manual pressure should be applied. If deployed
within rather than across an arteriotomy (i.e., too
superficial), an intravascular closure device can
actually maintain arteriotomy patency, necessitating
extended manual compression or even open surgical
repair. Extravascular closure devices do not carry this
risk. In general, for patients who are not on antiplate-
let or anticoagualation therapy (other than periproce-
dure IV heparin), we prefer to draw an activated
clotting time (ACT) immediately after femoral punc-
ture and conclusion of the procedure, and if the final
ACT value is 2.5x the baseline value, close with
manual pressure. When manual pressure fails, the
appropriate first response is invariably more manual
pressure.
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 12
Balloon occlusion, Wada, and pharmacological testing
Linda J. Bagley
INTRODUCTION
Technical advances in interventional neuroradiology
have rendered the majority of intracranial vascular
lesions treatable with coils and/or stents; yet, in some
cases parent vessel sacrifice remains the only viable
therapeutic option for complex intracranial lesions. As
such, there continues to be a role for occlusion testing
in the preprocedural management of certain aneur-
ysms and of neoplasms with associated vascular
encasement or potential vascular compromise.
Functional magnetic resonance imaging (fMRI),
magnetoencephalography (MEG), and diffusion-tensor
imaging-based MR tractography have been increas-
ingly utilized as noninvasive means of function and
tract localization. There, however, remain some limita-
tions of these modalities for memory localization and
when performed in the presence of tumors or vascular
malformations, which may be associated with dis-
torted brain architecture, altered venous drainage pat-
terns, and/or reorganization of function. As such,
selective and superselective pharmacological tests may
be employed in the preprocedural assessment of cer-
tain patients prior to arteriovenous malformation
(AVM) embolization, epilepsy surgery, and select
tumor resections.
This chapter discusses the indications, techni-
ques, and potential complications and limitations of
arterial and venous occlusion, Wada, and pharmaco-
logical testing. Illustrative case examples are also
provided.
ARTERIAL AND VENOUS OCCLUSION TESTING
Indications
Arterial and/or venous occlusion tests are appropri-
ate for patients scheduled for endovascular, neuro-
surgical, and/or otorhinolaryngological procedures
in which vascular occlusion is indicated as therapy
or in which there is a significant risk of intraproce-
dural vascular occlusion (112). Such patients may
include those with aneurysms not amenable to coil
embolization, stent placement, or microsurgical
repair (Fig. 12.1) (2,3), those with tumors encasing or
in intimate contact with the carotid or vertebral
arteries (Fig. 12.2) (4), and those with tumors involv-
ing a dural venous sinus or necessitating a surgical
approach that could result in sacrifice of a dural
venous sinus.
TechniqueVenous Occlusion Testing
A guiding catheter is typically placed within the inter-
nal jugular vein, and a nondetachable balloon micro-
catheter is advanced into the transverse or sigmoid
sinus. Arterial catheterization as well as angiography
is performed during balloon occlusion of the trans-
verse or sigmoid sinus that is at risk. The venous
phase of the angiogram is then assessed for drainage
of the affected hemisphere through collateral path-
ways. Larger balloon sizes (often up to 1.5cm) are
required than those employed in arterial testing. Ana-
tomic data are obtained, but functional data are not,
as symptoms of venous ischemia are more likely to be
insidious at the onset.
TechniquesArterial Occlusion Testing
A number of techniques have been described for tem-
porary arterial occlusion testing. In virtually all cases,
diagnostic angiograms are initially performed (1,5).
This technique allows assessment of the cervical vas-
culature for atherosclerotic disease and of the intracra-
nial circulation for integrity of the circle of Willis and
potential collateral flow. Following diagnostic angiog-
raphy and prior to nondetachable balloon inflation,
patients are routinely anticoagulated, typically with
5000 to 10,000 units of heparin with elevation of the
activated coagulation time (ACT) to two to three times
the baseline value. Heparinized saline flush is also
employed (1,5,8). Most cases are performed with con-
scious sedation. Both double-lumen balloon catheters
and nondetachable balloon microcatheters (with maxi-
mal balloon diameters of 58mm) have been used in
these procedures. In some institutions, a second cathe-
ter is utilized to perform diagnostic angiography dur-
ing the occlusion (confirming occlusion and assessing
adequacy of collateral circulation in the arterial,
parenchymal, and venous phases). Delays in cortical
venous drainage of the affected hemisphere of less
than 0.5 to 2 seconds compared to the contralateral
hemisphere have been suggested to imply adequate
collateral supply (911). During carotid occlusion test-
ing, larger balloon catheters are typically inflated in
the proximal internal carotid artery, while microcath-
eters may be advanced to the petrous segment.
Inflation times of 15 to 30 minutes have typically
been reported (1,5,8). Continuous clinical monitoring
of the neurological exam is performed, with any
changes in the exam prompting immediate deflation
 BALLOON OCCLUSION, WADA, AND PHARMACOLOGICAL TESTING
(A)
Figure 12.1 (A, B) AP and lateral views of digital subtraction angiogram obtained during right common carotid artery injection demon-
strate a lobulated, wide-necked approximately 2.5cm  2.0cm  2.0cm right internal carotid artery aneurysm, located predominately
within the cavernous segment with extension into the supraclinoid segment. There are multiple surgical aneurysm clips about the supra-
clinoid internal carotid artery.
of the balloon and termination of the procedure. Fol-
lowing deflation of the balloon, angiography is
repeated to evaluate the internal carotid artery for
injury/dissection and to exclude emboli in the intra-
cranial circulation. Almost all patients failing the bal-
loon occlusion test by clinical criteria will develop a
permanent neurological deficit if a revascularization
procedure is not performed prior to the intended vas-
cular occlusion (12). Of those who tolerate the test by
clinical criteria, between 5% and 20% have been
reported to incur a permanent neurological deficit fol-
lowing permanent vascular occlusion (7,13), generally
within hours to days of the permanent occlusion. Defi-
cits may result from perfusional ischemia and/or
stump emboli.
Numerous adjuvant techniques, including meas-
urement of stump pressures (14,15), induced hypoten-
sion (9,13,16), single-photon emission tomography
(SPECT) (8,1720), transcranial Doppler (TCD) exami-
nations (2123), xenon CT (1,15,21,24,25), cerebral
blood flow (CBF) measurements (26), perfusion imag-
ing (7,27,28), electroencephalography (EEG) (2935),
and monitoring of somatosensory-evoked potentials
(SSEP) (36,37) have been employed to improve the
predictive value of occlusion testing. Unfortunately,
for many of these techniques, conflicting results have
been reported in the literature.
Measurement of Stump Pressures
Arterial pressure can be monitored distal to the
occlusion by the use of a double-lumen catheter with
connection of the second lumen to a pressure trans-
ducer. The utility of this technique is controversial.
Some authors have reported that maintenance of a
255
(B)
stump pressure ratio (initial mean stump pressure/
preocclusion mean arterial pressure) of 60% or more
during test occlusion is a useful marker of adequate
collateral circulation (14). A number of studies have
found a significant correlation between stump pres-
sures and measures of cerebral perfusion, such as
SPECT (8), while others have failed to demonstrate
such a correlation (15).
Induced Hypotension
This technique is applied in patients who have toler-
ated 10 to 20 minutes of arterial occlusion while nor-
motensive (13,16). Following initial testing, systolic
blood pressure is pharmacologically lowered by
approximately 30% (typically with nitroprusside infu-
sion or intravenous labetalol), and neurological testing
is continued for additional 10 to 20 minutes. Standard
et al. (13) reported the identification of an additional
19% of patients in his series with limited cerebrovascular
reserve and a 5% false-negative rate for patients tolerat-
ing balloon occlusion testing with hypotensive challenge
(reduced compared with reported false-negative rates of
conventional occlusion testing of up to 20%). In con-
trast, Dare et al. (16) reported a 15% false-negative rate
for such patients. False negatives may in part be secon-
dary to vasodilatory effects of nitroprusside. Concerns
have also been raised that induced hypotension may
falsely elevate the sensitivity of this test and thus inap-
propriately subject these patients to revascularization
procedures. Wong et al. (9) reported no transient or
permanent neurological deficits in patients tolerating
test occlusions with induced hypotension and demon-
strating a less than 2 second delay in cortical venous
drainage of the affected hemisphere.
256 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)
Resample v

(C) (D)

Figure 12.2 (A, B) Axial gadolinium-enhanced T1-weighted images fat saturated and coronal fat saturated T2-weighted images
through the orbits demonstrate an enhancing extra-axial mass (metastatic pheochromocytoma) in the right cavernous sinus, encasing
the right internal carotid artery, extending to the sphenoid sinus and orbital apex. (C, D) AP and lateral projections of digital subtraction
angiogram obtained during common carotid artery injection reveal hypervascular tumor blush in the cavernous sinus and sinonasal cavity.
The mass abuts the right internal carotid artery but does not appear to narrow it.

SPECT
With this technique, Tc 99m hexamethylpropylene-
amine oxime (HMPAO) is injected immediately follow-
ing balloon inflation and vascular occlusion. SPECT
imaging is performed following balloon deflation and
removal of the catheter with measurement of activity
ipsilateral and contralateral to the occlusion. Activity
reflects CBF within a few minutes of the injection
(8,18). Hemispheric asymmetries and reductions in
tracer uptake (in comparison to preocclusion testing
when available) have been shown to correlate with the
development of clinical deficits.
MR Perfusion
MR perfusion imaging (7) may be performed with
dynamic gadolinium-enhanced imaging during balloon
occlusion when MR is available in the interventional
suite. Gadolinium is administered by bolus injection at
a dose of 0.1mmol/kg. Cerebral blood volume (CBV)
may be calculated on the basis of signal intensity
changes in brain with and without contrast agent.
Mean transit time (MTT) of contrast through the arte-
rial system may also be calculated, allowing determina-
tion of regional cerebral blood volume (rCBV) (28).
Authors have demonstrated greater perfusion delays in
 BALLOON OCCLUSION, WADA, AND PHARMACOLOGICAL TESTING
patients who have clinically failed the test. Authors
have also described alterations in contrast enhancement
and in brain parenchymal signal intensity in areas of
hypoperfusion (7).
CT Perfusion
Perfusion CT and acetezolamide challenge have also
been employed in patients who have clinically toler-
ated test occlusion again in attempts to improve sensi-
tivity. The technique described by Jain et al. (27)
requires transport of the patient with a catheter in the
internal carotid artery and re-inflation of the balloon
without fluoroscopic guidance, but on the basis of the
volume used to inflate the balloon initially. Multiple
perfusion CTs are performed with axial images
through the basal ganglia obtained during rapid
administration of intravenous contrast (4mL/sec) ini-
tially during balloon re-inflation and then following
balloon deflation. Additionally, perfusion CT is
repeated 20 minutes following administration of 1g of
acetezolamide with balloon re-inflation.
Xenon CT
This CT technique also attempts to measure CBF in
patients who have clinically tolerated test occlusion
(1,15,21,2426). Again, it requires transport of the
patient to the CT scanner with a catheter in the inter-
nal carotid artery and re-inflation of the balloon. The
patient inhales a gas mixture of 33% xenon and
67% oxygen. Baseline scans are obtained prior to bal-
loon inflation and are repeated during balloon infla-
tion. Xenon uptake in the middle cerebral artery
(MCA) distribution is used to estimate regional cere-
bral blood flow (rCBF). Regions with CBF of less than
30mL/100g/min are judged to be at risk.
Transcranial Doppler Ultrasound
Transcranial Doppler (TCD) interrogation of the MCA
may be performed during test occlusion. There is an
imperfect correlation between CBF and mean velocity
in the MCA, as velocity is also affected by vascular
caliber, hematocrit, viscosity, and insonation depth
and angle (21). However, reductions of mean blood
flow velocity and pulsatility index of less than 30%
have been shown to be predictive of clinical tolerance,
whereas reductions of more than 50% have been
shown to correlate with clinical symptoms (22). Fur-
thermore, with the use of TCD and its high temporal
resolution, Studevart et al. (23) reported ultraswift
(6090 second) internal carotid artery occlusion times.
Test occlusions were performed during contralateral
carotid and vertebral artery injections with assessment
of arterial collaterals and venous drainage. TCD inter-
rogations of MCA velocities were performed concur-
rently. In those patients undergoing permanent
internal carotid artery occlusion and maintaining
MCA velocities of >65% of baseline during test occlu-
sion, none incurred a neurological deficit. One patient
with reduction of MCA velocity to between 55% and
64% of baseline suffered a transient neurological fol-
lowing vessel occlusion, and the two patients who
underwent vessel sacrifice despite reductions in MCA
257
velocities to <55% of baseline suffered devastating
infarctions. Utilizing these techniques, the authors
were able to achieve low complication rates (0.7%
neurologic and 1.5% nonneurologic).
Neurophysiological Monitoring
Many studies have documented the utility of neuro-
physiological monitoring (NPM) (EEG, SSEP, and brain
stemevoked potentials) in patients undergoing cere-
brovascular surgery, most notably carotid endarterec-
tomy, performed under general anesthesia (2932).
EEG changes have been reported when rCBF is less
than 10mL/100g/min. An rCBF of 15mL/100g/min
appears to be a critical value below which cortical
SSEP amplitude is reduced, central conduction time is
prolonged, and cerebral infarction is likely to occur.
Liu et al. (37) also described the use of NPM in
patients undergoing endovascular procedures and
demonstrated NPM changes in 26% of the patients in
his series, with resultant alterations in management in
14% of the patients. Monitoring proved most benefi-
cial in patients who were unable to cooperate with
neurological testing. However, NPM changes were
also observed in cooperative patients without corre-
sponding abnormalities noted on physical neurologi-
cal exam (37).
COMPLICATIONS
Reported complications of balloon occlusion testing
include arterial dissections, embolic infarcts, and per-
fusional ischemia. Reported rates of complication
range from less than 1% to 15% (the majority between
1% and 7%), with higher rates being reported in ear-
lier studies. Complication rates have decreased with
improvements in catheter and balloon technology.
Adequate anticoagulation during balloon inflation has
reduced the number of embolic complications (1,5,6).
However, adjuvant techniques intended to increase
the sensitivity of the test (e.g., those requiring trans-
port of patients with indwelling catheters, blind
re-inflation of the balloon, and/or induction of hypo-
tension) have sometimes been associated with higher
complication rates (due to vascular injury and creation
of perfusional deficits) (1,13,2427).
ILLUSTRATIVE CASE
The patient is a 52-year-old woman with history of
hypertension who presented with a three-week history
of headache and right eye pain. Physical examination
was notable for a right sixth nerve palsy and mild pto-
sis. Imaging studies were notable for an approximately
2-cm aneurysm of the cavernous right internal carotid
artery (Fig. 12.3AC). Prior to definitive treatment and
following systemic anticoagulation, a 30-minute test
occlusion of the distal cervical right internal carotid
artery was performed. No changes in the patients
neurological exam were noted during the test occlu-
sion. Subsequently, treatment of the aneurysm with
Neuroform (Boston Scientific, Natick, Massachusetts,
U.S.) stent placement and coil embolization was
attempted, but resulted in compromise of the parent
vessel (Fig. 12.3D,E). Ultimately, permanent occlusion
258 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

(E) (F) (G)

Figure 12.3 (A) Axial CT scan demonstrates enlargement of the right cavernous sinus with a mildly hyperdense extra-axial mass.
(B, C) AP oblique and lateral views of digital subtraction angiogram obtained during right common carotid artery injection reveal an
approximately 2cm irregular aneurysm, without discernable neck and with possible intraluminal thrombus, of the cavernous right inter-
nal carotid artery. (D, E) AP and lateral digital subtraction angiograms obtained following stent placement and partial coil embolization
of the aneurysm are notable for markedly decreased flow within the internal carotid artery. (F) Lateral digital subtraction angiogram
demonstrates multiple embolization coils and complete occlusion of the right internal carotid artery. (G) AP angiogram obtained during
left common carotid artery injection demonstrates extensive flow across the anterior communicating artery with contrast opacification of
the right anterior and middle cerebral arteries, without opacification of the previously demonstrated aneurysm.

of the right internal carotid artery was performed therefore commonly undergo functional preoperative
without neurological complication (Fig. 12.3F,G). testing to minimize these risks.

WADA TEST
Epilepsy
Epilepsy, the condition of spontaneously recurring
seizures, is quite common, affecting approximately
0.5% to 1% of the population (38). It is a potentially
psychosocially devastating, life-altering, and even
life-threatening disorder (due to associated increased
incidences of sudden death, traumatic injuries, and
suicide). While many advances have been made in the
medical therapy of epilepsy, many cases, between 5%
and 20%, remain medically intractable (38,39). Surgical
therapies are appropriate for certain patients and
include lesional resections, temporal lobectomies, cal-
losotomies, hemispherectomies, and sub-pial transac-
tions (39,40). The most common cause of intractable
epilepsy is mesial temporal sclerosis. As such, tempo-
ral lobectomy is the most commonly performed surgi-
cal procedure for the treatment of epilepsy. Patients
undergoing temporal lobectomy are at risk of devel-
oping speech/language and/or memory deficits, and
Historical Background
Amobarbital is a lipid soluble substance that can cross
the bloodbrain barrier and temporarily block neuronal
function (41). Currently, the intracarotid amobarbital test
is performed in conjunction with neuropsychological
testing to determine lateralization of speech/language
and memory functions, most often in patients with med-
ically intractable epilepsy scheduled for surgical resec-
tion of epileptogenic tissue (4244). This test is also
sometimes employed in nonepileptic patients scheduled
for resection of unilateral temporal or frontotemporal
lesions.
Juhn A.Wada first performed the intracarotid
amobarbital procedure in the 1940s. Wada initially
injected sodium amobarbital into the left common caro-
tid artery of a patient with frequent status epilepticus
in an attempt to arrest the convulsions. In 1949, he first
described the use of this procedure to determine lan-
guage lateralization (42) in an attempt to improve the
safety and efficacy of electroconvulsive therapy in psy-
chiatric patients (by placement of the electrodes over
the nonspeech dominant hemisphere). In 1960, Wada
 BALLOON OCCLUSION, WADA, AND PHARMACOLOGICAL TESTING
collaborated with Rasmussen and reported the use of
the intracarotid amobarbital procedure for determi-
nation of hemispheric language dominance in epi-
lepsy surgical patients. In 1962, Milner, Branch, and
Rasmussen reported the use of this test for assess-
ment of memory function in the isolated hemisphere.
Subsequent studies have examined the correlation of
memory lateralization with location of the seizure
focus and prediction of surgical outcomes (4562).
Technique
The intracarotid amobarbital procedure is performed
without sedation, as sedation may confound neuro-
psychological test results. Diagnostic angiography is
initially performed with catheter placement in the
cervical internal carotid artery to assess for anatomic
variation in the anterior circulation, in particular to
exclude a carotid-basilar anastomosis, but also to
assess the likely distribution of amobarbital. The
internal carotid artery supplying the presumed abnor-
mal hemisphere is generally the one initially selected.
Following diagnostic angiography, approximately
80 to 140mg of sodium amobarbital are injected into
the internal carotid artery over approximately three to
five seconds, while the patient counts backward and
attempts to maintain his or her arms in an elevated
position. Efficacy of amobarbital administration may
be confirmed in several ways: concurrent unilateral
EEG slowing and/or development of a neurological
deficit (hemiparesis and/or aphasia). Testing of lan-
guage skills and of visuospatial and verbal memory is
then performed. Following a 30- to 45-minute delay (to
allow the effects of amobarbital to diminish), the con-
tralateral internal carotid artery is selected, and the
procedure is repeated. When a carotid-basilar anasto-
mosis is present, a microcatheter can be advanced
beyond it and the procedure continued. Similarly,
when there is significant cross-flow through the ante-
rior communicating artery, bifrontal impairment may
result, and the neuropsychological testing may be ren-
dered invalid secondary to impaired patient conscious-
ness and inability to cooperate. In such cases, selective
MCA and posterior cerebral artery (PCA) amobarbital
administration has often been described with some-
what reduced dosages of the agent (7580mg). Selec-
tive MCA amobarbital administration has been used
when language lateralization was of primary concern
and selective PCA administration has been employed
for memory assessment (54).
The intracarotid amobarbital test has also long
been used to determine language lateralization.
Multiple studies have also investigated its validity in the
prediction of postoperative memory deficits (45,46,53
55,58,62). Cohen-Gadol et al. (56) demonstrated statisti-
cally significant correlations between Wada test scores
and hippocampal volumetry, as well as a significant
inverse correlation between the disparity of the scores
and changes in verbal (though not visuospatial) mem-
ory following temporal lobectomy. Andelman et al. (53)
demonstrated a significant correlation between mem-
ory scores in the ipsilateral hemisphere and postsurgi-
cal memory changes. Multiple additional studies have
also demonstrated a correlation between Wada mem-
ory test results and seizure-free outcome, most notably
259
in patients with temporal lobe epilepsy. Correct lateral-
ization of the seizure focus (and hence, prediction of
outcome) has been reported in 75% to 85% of patients
using various criteria (4952).
Alternative Agents
There have been repeated global shortages of amobar-
bital, most recently in 2010. As such, alternative agents
have been investigated. Jones-Gotman et al. (63)
reported successful experience with etomidate, given
by bolus followed by infusion, which was continued
during sampling of speech measures and presenta-
tion of objects for memory testing. In the 30 hemi-
spheres tested, contralateral hemiplegia developed in
all patients, and slowing of EEG was observed in all
injected hemispheres. Aphasia followed dominant
hemisphere injections. All affects reversed over
approximately four minutes, following termination of
infusion. Methohexital (Brevital) has been employed,
but it is quite short acting, and reinjection is often
required. 3mg are typically initially injected followed
by a 2mg reinjection when grip strength has returned
to >2/5 (64). A third injection may be required if
object presentation has not been completed by the
time motor function has partially recovered. Propofol
(65,66), administered in doses of 10 to 20mg (typi-
cally less than 15mg), has also been employed, with
results comparable to those obtained with amobarbi-
tal. However, in Mikunis study (66), adverse reac-
tions (including eye pain, shivering, facial contortion,
confusion, involuntary movements, increased muscle
tone, rhythmic movements, and tonic posturing)
were noted in one-third of the patients, and in some
cases precluded completion of the testing. Adverse
reactions were observed more frequently in patients
over 55 years and when larger doses of propofol
were administered. The most severe reactions likely
result from hyperexcitic phenomena, which have
been shown to occur with sudden increases in cerebral
propofol concentrations. Recently, Mikuna et al. (67)
reported a reduction in such adverse reactions when
patients received intravenous infusions of 250500mg
of methylprednisolone prior to propofol administration.
Noninvasive Testing
Increasingly noninvasive tests have been used to
replace the Wada test in the presurgical evaluation of
patients with intractable epilepsy (6871). A review of
practices in European centers revealed a decrease in
performance of the Wada test in presurgical patients
from 56% in 2000 to 35% in 2005 (70). In one American
center, only 14.4% of patients scheduled for temporal
lobectomy in 2007 underwent Wada testing, as
opposed to 81% in 1997 (69). Most notably, fMRI has
been proposed as a replacement for the Wada test
(5962,6888); fMRI has the advantages of being less
time consuming (typically requiring 3060 minutes), of
posing minimal risk to the patient, and of being signif-
icantly less expensive (74). Numerous studies have
examined the validity of fMRI in language lateraliza-
tion (Fig. 12.4). Binder et al. (71) found 96% concord-
ance between fMRI and Wada test results for language
dominance. Yetkin et al. and Lehericy et al. have
260 NEUROINTERVENTIONAL MANAGEMENT
(A)
(C)
Figure 12.4 (A, B, C) Functional MRIs obtained in a left-handed patient with intractable epilepsy during sentence completion
(A), verb generation (B), and word generation (C) tasks confirm left language dominance.
reported similar results (83,84). However, the most
promising results have been achieved in patients with
left hemispheric language dominance (the majority of
patients studied) and temporal lobe epilepsy. False
categorization of language dominance by fMRI was
reported to be approximately 9% in Woermanns
series, ranging from 3% in left-sided temporal lobe
epilepsy to 25% in left-sided extratemporal epilepsy
(76,80). Sabbah et al. (80) reported 95% concordance of
the Wada test and fMRI in a group of epileptic patients
with suspected atypical language lateralization.
Additional studies have examined the ability of
fMRI to predict memory following temporal lobectomy
(5962) and to lateralize temporal lobe epilepsy [and
hence predict surgical outcome (60)]. Rabin et al. (59)
examined fMRI activation during complex visual
scene encoding (which is believed to engage both
visuospatial and verbal memory systems) and
reported a correlation between activation asymme-
tries in the mesial temporal regions on fMRI with
hemispheric memory dominance. Additionally, Rabin
et al. reported correlation of these activation asym-
metries with postsurgical memory as well as an
inverse correlation between absolute activation in the
hemisphere to be resected and postsurgical memory.
Jokeit et al. (60) reported 90% accuracy of lateraliza-
tion of seizure focus in patients with unilateral
(B)
temporal lobe epilepsy on the basis of memory-
induced mesial temporal lobe activation asymmetries
on fMRI. Recently, Dupont et al. (62) reported supe-
rior prognostic accuracy of fMRI for prediction of
post-operative memory deficits compared with Wada
testing and preoperative neuropsychological testing
when fMRI protocols included immediate recogni-
tion, encoding and 24hour delayed recognition tasks.
MEG
MEG has also been proposed as an alternative to the
Wada test (8994). MEG is based on the principle that
all electrical currents are associated with magnetic
fields. Cohen (94) developed a superconducting quan-
tum interference device to measure magnetic fields
generated by intracranial currents. Approximately
10,000 to 100,000 neurons must be simultaneously
generating current to produce a magnetic field strong
enough to be detected with present technology. Mag-
netic fields are minimally distorted by intervening tis-
sue, and hence MEG may provide precise localization
of the source of electrical current (e.g., seizure foci or
functional cortex). Data can then be co-registered with
conventional MRI. MEG has been used to localize
visual, auditory, and somatosensory cortex, and to
lateralize language (93). Papanicolaou et al. (89)
 BALLOON OCCLUSION, WADA, AND PHARMACOLOGICAL TESTING 261

(A) (B) (C)

(D) (E)

Figure 12.5 (A) Coronal T2-weighted image demonstrates atrophy and hyperintensity of the left hippocampus, indicative of mesial
temporal sclerosis. (B, C) AP and lateral angiograms obtained during left internal carotid artery injection reveal a persistent trigeminal
artery. (D, E) AP and lateral angiograms obtained with a microcatheter placed in the supraclinoid left internal carotid artery beyond the
origin of the trigeminal artery.

demonstrated a high degree of (though not absolute)
concordance (87%) between MEG and Wada data for
determination of hemispheric language dominance.
MEG tended to detect more activity in the nondomi-
nant hemisphere (similar to fMRI) than predicted by
the Wada test.
ILLUSTRATIVE CASE
The patient is a 41-year-old right-handed man with
history of fall at the age of 2 associated with brief
coma with subsequent development of medically
intractable partial complex and generalized tonic
clonic epilepsy in adulthood. EEG was suggestive of a
left temporal lobe seizure focus. MRI was notable for
left mesial temporal sclerosis (Fig. 12.5A) and positron
emission tomography (PET) was notable for mild left
temporal hypometabolism. A Wada test was per-
formed as part of the presurgical evaluation for sched-
uled left temporal lobectomy. Digital subtraction
angiography performed following selection of the left
internal carotid artery revealed a persistent left trige-
minal artery (Fig. 12.5B,C). A microcatheter was sub-
sequently advanced beyond the origin of the
trigeminal artery into the supraclinoid left internal
carotid (Fig. 12.5D,E), and 125mg of sodium amobar-
bital were instilled. The patient developed transient
right hemiparesis and aphasia. Neuropsychological
testing revealed left hemispheric language dominance
and right hemispheric memory dominance. The
patient subsequently underwent right temporal lobec-
tomy with histological confirmation of mesial tempo-
ral sclerosis.
PHARMACOLOGICAL TESTING
Indications
The development of permanent neurological deficits
following embolizations of cerebral and spinal AVMs
has been reported in 5% to 10% of the cases, largely
due to ischemic sequelae in eloquent tissue. Ischemic
262 NEUROINTERVENTIONAL MANAGEMENT
injury to the cranial nerves, to the eye, or to cerebral
cortex (via external to internal carotid artery or exter-
nal carotid artery to vertebral artery anastamoses)
may complicate external carotid artery embolizations.
As such, superselective angiography and provocative
pharmacological tests are often employed to predict
the safety of arterial embolization of cerebral and spi-
nal AVMs, dural AVMs, facial and oral vascular mal-
formations, and tumors (9598). Similar to Wada
testing, super-selective provocative pharmacological
testing may also be employed prior to planned surgi-
cal intervention.
Technique
Typically, provocative testing for arteries with extra-
axial destinations is performed with lidocaine, and
provocative testing for arteries with intraaxial destina-
tions is performed with barbiturates, such as amobar-
bital, though both agents have also been utilized in
both situations (95100). Patients undergoing such
procedures usually receive a small amount of intrave-
nous sedation. Neurological assessments are made
immediately before and after anesthetic injection and
completed within a few minutes. In some cases NPM
supplements the physical exam (particularly when the
territory involved is the brain stem or thalamus),
whereas in patients under general anesthesia it may
completely replace it. Amobarbital is generally admin-
istered in doses of 30 to 75mg, and lidocaine is typi-
cally administered in doses ranging from 10 to 40mg.
Some authors have reported the administration of
both agents (lidocaine and amobarbital) prior to
embolization, as these agents produce anesthetic
effects via different mechanisms, and concomitant
administration may thus improve the sensitivity of
provocative testing.
Amobarbital acts at the gamma aminobutyric
acid A (GABA-A) receptor through inhibition of post-
synaptic neurons in cortical and deep gray matter and
in the hippocampus. As cerebral white matter contains
a paucity of GABAergic synapses, it is largely unaf-
fected by the drug. Lidocaine blocks voltage-gated
sodium channels, which are present on all nerve cell
membranes and thus inactivates neurons in gray and
white matter (99). Fitzsimmons et al. reported detec-
tion of clinically significant deficits with superselective
lidocaine administration in four patients that did not
develop a deficit with super-selective amobarbital
testing (99). With high-flow lesions, such as AVMs,
hemodynamic factors may produce false-negative
and false-positive tests with amobarbital or lido-
caine. The anesthetic agent may bypass adjacent nor-
mal tissue, but liquid embolic agents will polymerize
and may initially occlude high-flow channels, lead-
ing to redistribution of the embolic agent (96). Devei-
kis et al. (100) advocated the use of amobarbital
injections in the external carotid circulation (to sup-
plement lidocaine test injections) to improve the sen-
sitivity for detection of external carotid to internal
carotid or vertebral artery anastomoses. When a defi-
cit is produced with pharmacological testing, thera-
peutic options include advancing the microcatheter
closer to the nidus and repeating the testing, protect-
ing the normal territory by placement of a coil or
similar agent and repeating the testing, utilizing a
different embolic agent (such as larger particles) or
abandonment of embolization of that particular
pedicle. Complications of provocative pharmacologi-
cal testing are uncommon. Injection of lidocaine into
the external circulation often produces some degree
of discomfort in the patient. While rare, injection of
lidocaine into the cerebral circulation has been
reported to be complicated by seizures and cardior-
espiratory depression (100).
Noninvasive Alternatives
While pharmacological testing provides specific infor-
mation about the function of tissue within a vascular
territory, fMRI (101) and tractography (102105) may
noninvasively localize eloquent tissue prior to planned
surgical intervention. As above, fMRI has been shown
to localize (though imperfectly) language and memory.
It has also been utilized to localize motor, sensory, and
visual cortex. Similarly, thin-section diffusion tensor
imaging has been employed to localize sensory, motor,
and visual cortex, and pathways (102105). As diffu-
sion of water perpendicular to the neural axis is lim-
ited by cell membranes and myelin sheaths, and
diffusion along the nerve axis is less limited, the pri-
mary direction of the principal eigenvector of the dif-
fusion tensor at each location can be determined and
corresponds to the trajectory of the corresponding
fiber. Thus, sensory and motor tracts may be mapped
in three dimensions and in relation to AVMs and their
draining veins (102). Additionally, tractography may
be fused with conventional MRI images and utilized
with neuronavigational systems (104). This technique
offers advantages over pharmacological testing as
drug distribution may be altered by arteriovenous
shunting and as such testing yields no information
about displacement of cortex and tracts or relationship
of draining veins to eloquent cortex and tracts. This
technique has also been attempted with tumors, but its
utility is decreased by the presence of vasogenic
edema. The presence of hemorrhage may also degrade
images due to susceptibility artifacts.
SUMMARY
Arterial and venous occlusion, Wada, and pharmaco-
logical tests provide vital information in the manage-
ment of complex aneurysms, neoplasms, AVMs, and
epilepsy. A variety of techniques have been employed
to improve the accuracy of these tests. Complications
are rare, but their incidence may be increased with
increasing complexity of the tests. A number of nonin-
vasive alternatives (predominantly employing MRI) to
these tests have been developed, have demonstrated
promising though imperfect results, and have been
employed with increased frequency. The neurointer-
ventionalist must remain knowledgeable of the indica-
tions, limitations, and potential complications of
provocative testing and its noninvasive alternatives.
ACKNOWLEDGEMENT
The author would like to acknowledge Dr. Ronald
Wolf for use of his fMRI images.
 BALLOON OCCLUSION, WADA, AND PHARMACOLOGICAL TESTING
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 13

Endovascular management of tumors and vascular

malformations of the head and neck
Johnny C. Pryor, Joshua A. Hirsch, and Robert W. Hurst

INTRODUCTION cavernous malformations, which occur in adults, are

Vascular lesions of the head and neck are a wide rang-
ing and often confusing constellation of lesions, and
diagnosis and treatment are ideally approached
through multidisciplinary cooperation. Mulliken and
his colleagues were the first to present a rational classi-
fication of hemangiomas and vascular malformations
(15). With modifications over time this classification
has evolved into a clinically useful system that helps us
understand the etiology and pathophysiology of these
lesions and gives us a context within which to under-
stand their behavior and plan a rational treatment strat-
egy (6,7). This context also helps establish proper
communications between physicians and patients. Pre-
viously, vascular lesions of the face and head were
often ubiquitously referred to as hemangiomas and this
mistake is often still repeated even in modern clinical
practice. Mulliken and his colleagues demonstrated
that craniofacial vascular lesions can be generally dif-
ferentiated into vascular tumors or malformations of
vascular structures. Craniofacial vascular malforma-
tions can involve any or all of the vascular components
including arteries, capillaries, veins, and lymphatic tis-
sue. These malformations may be simple or complex
and may represent angiodysplastic syndromes that are
congenital and possibly have a genetic basis. Therefore,
while most craniofacial vascular lesions present in
childhood, many of those that do not, have their origins
or predispositions determined in utero. Certain vascular
pathologies may arise as a result of exogenous causes
such as traumatic arteriovenous fistulae or erosion of a
nonvascular tumor into a significant vascular structure;
however, even these seemingly unrelated occurrences
may have an underlying genetic predisposition. Under-
standing the underlying pathophysiology allows us to
predict clinical behavior and propose rational treatment
strategies.
VASCULAR TUMORS
Vascular tumors are differentiated from vascular
malformations by their patterns of cellular growth.
Hemangiomas are a vascular neoplasm of endothe-
lial cell origin, and proliferation of those cells leads
to tumor growth. Two types of lesions often referred
to as hemangiomas can be differentiated clinically:
cavernous hemangiomas, more commonly known as
not associated with high arterial flow, and are asso-
ciated with thrombosis pathologically; and capillary
hemangiomas, which are found in children and have
a propensity to spontaneously involute.
CAPILLARY HEMANGIOMA
Capillary hemangiomas are five times more common
in girls and are usually detected in the first three
months of life. Though they are only identified at birth
in about a third of patients, hemangiomas typically
display a proliferative phase in the first six months of
life that is characterized by rapid growth of these
lesions. Gradual involution is usually detected by
about the childs first birthday, and is the hallmark of
capillary hemangiomas. Involution is typically com-
plete by age seven and will occur in over 95% of
patients presenting in infancy. The triggers and mecha-
nisms of this spontaneous involution remain incom-
pletely understood, though an apoptotic mechanism
seems important (8). Cavernous hemangiomas prolifer-
ate over a different time course and continue to prolif-
erate into and potentially throughout adulthood.
Since spontaneous involution can be expected in
approximately 90% of children presenting with capil-
lary hemangiomas, conservative treatment is warranted
in the vast majority cases. Nevertheless, no means is
currently available to differentiate those lesions fated to
progress from the vast majority, which will go on to
complete resolution. Propranolol has been recently
described as a treatment for cases associated with
growth in a critical location (6,9). Some patients may
require relatively urgent therapeutic intervention based
on the clinical scenario. Such situations include lesions
that impinge on or compromise anatomically critical
structures and those which cause functional impair-
ment or prevent normal development of critical func-
tions. Examples of complications related to capillary
hemangioma that may mandate urgent treatment
include congestive heart failure, which may develop as
a result of high intralesional flow with arteriovenous
shunting. In addition, compromise of airway, feeding,
or visual function are indications for immediate treat-
ment. Moreover, hemorrhage or coagulation abnormal-
ities such as consumptive coagulopathy, which in
association with rapid tumor growth and thrombocyto-
penia is known as Kasabach Merritt phenomenon, is
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK
well described with capillary hemangiomas (10). Kasa-
bach Merritt syndrome is also called the hemangioma
thrombocytopenia syndrome or thrombocytopenic
coagulopathy.
It should be emphasized that Kasabach Merritt
syndrome has rarely been associated with capillary
hemangiomas, but is most often associated with tumors
having lymphatic-like vessels such as either kaposiform
hemangioendothelioma or tufted angioma (11,12).
Treatment of Kasabach Merritt syndrome begins with
corticosteroid therapy with the possible addition of
dipyridamole (13). The efficacy of high dose steroids
is a matter of debate, especially considering the bal-
ance of positive response versus complications. More-
over, interferon, the second line of treatment if the
platelet count does not quickly rise, is not without
complications. For example, interferon therapy for
hemangiomas has been associated with spastic diple-
gia (14). Lastly, the course of interferon treatment is
prolonged and typically extends over a year. Should
the platelet count not respond to interferon, other
treatment options include chemotherapeutic agents
such as vinblastine or vincristine, radiation therapy,
or surgical resection. While radiation therapy has been
shown to be effective in selected patients, however,
worries about its potential long-term side effects such
as inhibition of regional growth, scarring, and malig-
nancy limit its application (15). Vincristine has also
been shown to be effective in treating patients with
respiratory compromise (16).
Because capillary hemangiomas often demon-
strate high arterial flow, endovascular embolization
can help stabilize the situation in selected patients and
may also be used to buy time for medical therapy to
work or as an adjunct to surgical resection (3,17,18).
Embolization may obliterate arteriovenous shunting
through the tumor vasculature and thereby reverse
high output heart failure. Embolization may also
markedly shrink capillary hemangiomas to relieve
mass effect on the airway or esophagus. Mass effect
on the eyelid, which impairs sight from one eye and
may permanently interfere with the development of
binocular vision in the neonate, represents an addi-
tional indication for endovascular treatment (3).
Embolization with absolute ethanol is also
reported to quickly reverse thrombocytopenia (19).
However, one should be aware of potential complica-
tions with absolute ethanol such as significant swel-
ling, necrosis of normal tissue, hemolysis, renal
failure, and pulmonary hypertension. In addition, it is
important to understand that the full effect of absolute
alcohol infusion is not immediately angiographically
apparent and additional closure of the malformation
may occur within a relatively short time.
JUVENILE ANGIOFIBROMA
Although a histologically benign neoplasm, juvenile
angiofibroma (JAF) often grows aggressively, spread-
ing by local invasion throughout the nasal fossa and
anterior skull base. Nearly all patients are male and
typically present between the ages of 14 to 17. Symp-
toms are determined by the tumor size and extent
with unilateral nasal obstruction being the most com-
mon initial symptom. Far more importantly, epistaxis,
267
often associated with major blood loss, is the symp-
tom that brings most patients to medical attention.
Tumor occlusion of the sinus ostia may obstruct
drainage and cause sinusitis.
JAFs originate from the posterolateral nasophar-
ynx in the region of the pterygopalatine fossa. Exten-
sion into adjacent spaces determines staging (2023).
At the time of diagnosis, JAF virtually always extends
through the sphenopalatine foramen, involving both
the pterygopalatine fossa and posterior nasal cavity.
Lateral extension into the infratemporal fossa through
the pterygomaxillary fissure is also characteristic.
Maxillary sinus involvement may occur through direct
destruction of the sinus walls. The tumor often
extends into the sphenoid sinus through the sinus
ostium from where destruction of the sinus wall may
afford access into the medial portion of the middle
fossa. Orbital extension via the inferior orbital fissure
occurs in approximately one-third of patients (24).
Intracranial involvement, present in less than 20%,
makes complete resection difficult (25,26).
Imaging studies are essential prior to angio-
graphic evaluation and embolization of JAF to make
the diagnosis, delineate the extent of tumor, and dif-
ferentiate tumor from retained sinus secretions (27).
On computed tomography (CT) scan, the tumor is
isodense to muscle prior to contrast administration
(Fig. 13.1). Avid homogeneous contrast enhancement
is characteristic. Remodeling and expansion of the
bony walls of the pterygopalatine fossa is most often
present. This results in anterior bowing of the poste-
rior wall of the maxillary antrum, a characteristic
finding on the lateral skull film. Expansion of the
sphenopalatine foramen indicates extension between
the pterygopalatine fossa and the nasopharynx. Gener-
ally 2 to 6cm in diameter at the time of diagnosis, JAF
also remodels and expands the nasal cavity.
Magnetic resonance (MR) findings include charac-
teristic salt-and-pepper appearance on most sequen-
ces, with punctate dark regions representing flow voids
from the tumors high vascularity. Intense enhancement
follows contrast administration (Fig. 13.2). MR imaging
is important to differentiate between enhancing tumor
and retained sinus secretions. Fat saturated enhanced
images are often best for delineating involvement of the
skull base foramina and extension into the cavernous
sinus, sphenoid sinus, orbit, or intracranial cavity.
Initially, arterial supply to JAF arises from the site
of origin, with the most common feeders from the ptery-
gopalatine portion of the internal maxillary artery,
including the sphenopalatine, infraorbital, and descend-
ing palatine branches (Fig. 13.3). Recruitment of adjacent
vessels including the accessory meningeal, ascending
pharyngeal, and ascending palatine arteries is often seen
with larger tumors. Sphenoid sinus extension results in
development of blood supply from extradural branches
of the internal carotid artery (ICA) (Fig. 13.4). Supply
from pial branches of the ICA although uncommon
should be sought since it reflects intracranial extension
into the anterior and middle fossa (28). Bilateral supply
is frequent, particularly with large tumors, and should
be sought in each case to avoid excessive hemorrhage at
the time of resection (29).
Early, dense, persistent contrast staining character-
izes JAF angiographically. Unlike many other vascular
268 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 13.1 Juvenile angiofibroma. Eighteen-year-old

male with epistaxis. Axial CT scan. (A, B) Small posterior
nasal mass (arrowhead) extends into expanded pterygo-
palatine fossa (*) widening the sphenopalatine foramen.
(C, D) Higher cuts show extension anteriorly toward
infraorbital foramen and posteriorly toward vidian canal
(C) (D) and foramen rotundum.

(A) (B) (C)

(D) (E) (F)

Figure 13.2 Juvenile angiofibroma (same patient as Fig. 13.1). (A, B, C) Axial T2-weighted MR images demonstrate soft tissue signal
intensity with salt-and-pepper pattern involving nasal fossa (arrowhead) as well as pterygopalatine fossa. (D, E, F) Axial fat saturated
enhanced T1-weighted MR images demonstrate homogeneous, avid enhancement.
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK
(A) (B)
(C) (D)
neoplasms including paragangliomas (see below), signif-
icant enlargement of feeding arteries and arteriovenous
shunting are uncommon.
Complete surgical removal is the therapy of choice.
Preoperative embolization of JAF has been shown to
reduce both perioperative blood loss and the duration of
surgical resection even for very large tumors (26,3032).
Recent experience with endoscopic resection has
improved surgical outcomes and reinforces the value of
preoperative embolization in JAF (3335).
The location of and typical routes of extension of
JAF mandate particular attention to the possibility of
orbital or intracranial anastomoses from vessels that
also supply tumor. Supply to cranial nerves is also of
concern as in all cases of embolization involving the
skull base. Presurgical embolization is usually accom-
plished using polyvinyl alcohol (PVA) particles of
150350 microns in diameter (3638).
PARAGANGLIOMAS
Paragangliomas, also known as glomus tumors, are
highly vascular neoplasms which arise from chemore-
ceptor cells of the paraganglia or glomus bodies (39).
In the head and neck, the carotid body location is most
common. Temporal bone paragangliomas are next in
frequency and represent the most common neoplasms
affecting the temporal bone, comprising nearly 80% of
temporal bone tumors in some series (40). These
include glomus tympanicum tumors that involve the
269
Figure 13.3 Juvenile angiofibroma (same patient as
Fig. 13.1). (A) Lateral view of ECA injection demon-
strates intense tumor blush in the posterior nasal
region. (B) Microcatheter injection illustrates nonen-
larged feeding arteries, tumor blush, and lack of arterio-
venous shunting. (C) Post-embolization microcatheter
injection of internal maxillary arteryno residual tumor
filling. (D) Post-embolization CCA injection demon-
strates no residual tumor supply.
middle ear and glomus jugulare tumors involving the
jugular fossa. Jugulotympanic paragangliomas involve
both temporal bone locations. Paragangliomas associ-
ated with the vagus nerve (glomus vagale) and those
involving the larynx are less common (41).
The usual age of onset is in the fourth to fifth
decade but a wide age distribution is reported with
earlier onset in familial cases. A female predominance
of nearly 3:1 is present in most head and neck loca-
tions, except for carotid body tumors.
As many as 50% of all paragangliomas have been
found to be hereditary and may be associated with
familial paraganglioma, neurofibromatosis Type 1, von
HippelLindau disease, the Carney triad, and, rarely,
with multiple endocrine neoplasia Type 2 (42). Multi-
plicity is common in hereditary forms, affecting up to
one-third of patients. Although less common in non-
familial cases, multiple tumors may occur in up to
10%, usually with vagal or carotid body locations. The
high frequency of heritability and multiple lesions
requires imaging evaluation to detect undiagnosed
lesions in any patient with a paraganglioma involving
the head and neck. Genetic counseling should be
offered to all patients with a family history of paragan-
glioma while patients positive for paternal paragan-
glioma locus gene should undergo regular radiological
screening with MRI (43).
The typically slow, locally invasive growth of par-
agangliomas causes bony destruction and infiltration of
adjacent structures. Lymph node involvement and
270 NEUROINTERVENTIONAL MANAGEMENT

S
S
*
*

(A) (B) (C)

(D) (E) (F)

Figure 13.4 Juvenile angiofibroma. Seventeen-year-old male with severe epistaxis and nasal obstruction. (A) Coronal CT and MR (B)
demonstrate avidly enhancing JAF expanding the posterior right nasal cavity with extension through the right sphenopalatine foramen
into the pterygopalatine fossa (*normal left pterygopalatine fossa). Tumor has eroded the nasal septum to cross the midline. Sphe-
noid sinus extension is present on the right. (C) Antero-posterior (AP) view of angiogram demonstrates vascular tumor blush involving
the same region with supply from the pterygopalatine branches of the internal maxillary artery. (D) Lateral view of angiogram demon-
strates vascular tumor blush and internal maxillary supply (internal maxillary arteryarrow). (E) Lateral view shows microcatheter route
through the internal maxillary artery (arrow) into the pterygopalatine location from which embolization was performed. (F) Post-
embolization, CCA injection shows delayed ECA filling with residual tumor supply from ascending pharyngeal artery (arrowhead) and
cavernous branch of the ICA (arrow). The latter supply angiographically indicates the sphenoid sinus extension seen on CT and MR.

metastases are rare, reported in less than 5% (44). Clini-
cal manifestations related to mass effect depend on the
tumor location.
Carotid body tumors typically present as slow-
growing painless neck masses at the bifurcation of the
common carotid artery (CCA). The lesions are often
pulsatile to palpation. Mean age of presentation is in
the fourth decade. Hoarseness, tongue atrophy, or dys-
phagia may reflect cranial nerve involvement. Resec-
tion of carotid body tumors is recommended at the
time of diagnosis after careful analysis of the tumor
extent and involvement of adjacent vessels, particu-
larly the ICA, which may require sacrifice for complete
resection (45).
Symptoms associated with paragangliomas of
the temporal bone reflect the extent of tumor spread.
The Fisch classification evaluates tumors on a scale of
A through D, with A representing localized tympanic
tumor, B mastoid extension, C erosion of the carotid
canal (with subtypes), and D indicating intracranial
extension (46,47). Typical symptoms include hearing
loss, pulsatile tinnitus, and cranial nerve palsy. The
latter most often involves the lower cranial nerves or
CN VII within the temporal bone.
While the vast majority of paragangliomas give
histological evidence of catecholamines, clinical hyper-
secretion occurs in less than 5% of cases and causes
signs and symptoms identical to hyperfunctioning
adrenal pheochromocytoma: episodic hypertension,
headache, nausea, excessive perspiration, and nausea.
When a catecholamine-secreting tumor is suspected
because of paroxysmal symptoms, biochemical docu-
mentation of catecholamine and fractionated meta-
nephrine hypersecretion should precede imaging
evaluation (42). Laboratory or clinical evidence of
hypersecretion suggests an increased risk of blood
pressure alterations during angiography, emboliza-
tion, or surgical resection.
Noninvasive imaging must detect and character-
ize the lesion, as well as determine multiplicity. CT
scanning can show demineralization, erosion, and
destruction of the temporal bone structures in jugulo-
tympanic paragangliomas. Features include destruc-
tion of the jugular plate, indicating involvement of
middle ear structures as well as the jugular fossa.
Encasement or displacement of the facial nerve should
also be evaluated. Anterior extension with destruction
of the vertical segment of the petrous carotid canal
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK
may indicate ICA encasement, involvement, and vas-
cular supply.
MR is the mainstay of noninvasive imaging. Both
T1- and T2-weighted sequences typically demonstrate
the characteristic salt-and-pepper appearance of high
velocity flow voids within the tumor. Following gadoli-
nium administration, intense enhancement is present,
frequently with residual flow voids. The extent of the
tumor should be evaluated including intraluminal jug-
ular vein growth, ICA encasement, dural enhancement,
and invasion of posterior fossa structures. Magnetic
resonance angiography (MRA) using 3D Time of Flight
(TOF) or contrast-enhanced sequences may be useful to
initially delineate arterial supply.
Angiography may also provide diagnostic infor-
mation when the diagnosis is in doubt (48). Preopera-
tive angiographic evaluation, guided by MRI, is
however necessary for all but very small tumors con-
fined to the middle ear or involving the carotid body.
Angiographic features of paraganglioma reflect the
high vascularity with enlarged feeding arteries, rapid
appearance of dense vascular tumor blush, and early
venous drainage. Paragangliomas often consist of mul-
tiple compartments, each receiving separate arterial
supply. Multiple superselective catheterizations may
therefore be necessary to opacify or embolize the entire
tumor. Evaluation of the normal intracranial venous
outflow is also necessary, should jugular vein or sig-
moid sinus sacrifice be required. The angiographic dif-
ferential diagnosis for vascular lesions of the temporal
bone includes other highly vascular neoplasms includ-
ing metastases from thyroid, or renal cell carcinoma,
endolymphatic sac tumors (ELST), and hemangioperi-
cytoma (HPC). In addition, nonneoplastic lesions
including dural arteriovenous fistulas, AVMs and pet-
rous or cavernous ICA aneurysms, should be differenti-
ated from neoplastic lesions (38,49).
Complete surgical resection, usually with preoper-
ative embolization of major external carotid artery (ECA)
feeding pedicles, is the mainstay of therapy. In very large
or unresectable tumors radiotherapy, conventional or
stereotactic is a viable therapeutic option (5053).
Preoperative embolization of the ECA supply
usually gives the most favorable riskbenefit ratio for
the vast majority of paragangliomas of the head and
neck (54). Vogel et al. recently reviewed the impact of
carotid reconstruction combined with preoperative
embolization for surgery of carotid body tumors. They
concluded that embolization was beneficial in signifi-
cantly lowering both complications and blood product
utilization (55).
Occlusion testing of the ICA may also be neces-
sary when carotid encasement is present or carotid
sacrifice is anticipated. Superselective angiography is
necessary to delineate cranial nerve supply or danger-
ous anastomoses with the ICA or vertebral artery. Pre-
operative embolization is usually performed using
particles of PVA from 150 to 350 microns in diameter.
This agent has been shown to be both safe and effec-
tive in reducing intraoperative blood loss in paragan-
gliomas (56,57).
Safe and effective embolization requires knowl-
edge of vascular anatomy specific to the particular
tumor location. Jugulotympanic paragangliomas virtu-
ally always receive major supply from ascending
271
pharyngeal artery branches to the most common areas
of origin (58). The middle ear receives supply from the
inferior tympanic branch while the neuromeningeal
branch supplies both the jugular fossa and hypoglossal
canal (Fig. 13.5). Additional ECA supply including the
stylomastoid branch of the occipital artery is also
extremely common in jugulotympanic paragangliomas.
In addition, supply from the temporal branch of the
middle meningeal artery (MMA) may also develop in
tumors with anterior extension. Extradural ICA supply
from caroticotympanic or cavernous branches may also
occur, particularly with anterior extension of temporal
bone paragangliomas. The acquisition of pial supply
from branches of either the internal carotid or vertebro-
basilar system indicates transdural invasion and usu-
ally a worse prognosis (Fig. 13.6).
Carotid body tumors characteristically widen the
CCA bifurcation, splaying apart the proximal ICA and
ECA. Early dense tumor blush between the two ves-
sels reflects tumor vascularity, usually originating
from the proximal ECA. Ascending pharyngeal artery
supply may also be present, typically to the superior
aspect of the tumor. Multiple short feeders originating
in close proximity to the CCA bifurcation mandate
meticulous fluoroscopic monitoring during emboliza-
tion to prevent emboli from entering the ICA.
Anterior displacement of the cervical ICA is often
seen in cases of glomus vagale tumors, which in rare
cases may occur synchronously with carotid body
tumors (59). Treatment implications differ significantly
between carotid body tumors and glomus vagale
tumors because of increased morbidity due to injury to
the carotid artery, jugular vein, and cranial nerves asso-
ciated with the latter. The musculospinal branch of the
ascending pharyngeal artery typically supplies vagal
paragangliomas inferior to the skull base (Fig. 13.7).
Supply from deep and anterior cervical arteries may
also be present.
MENINGIOMAS
Meningiomas, the most common nonglial primary
intracranial tumor, account for approximately 15% of
primary intracranial tumors in the general population.
Believed to arise from arachnoid granulation cells,
meningiomas most often present between 20 to 60
years of age. A female predominance of nearly 3:1 is
present with meningiomas comprising more than 50%
of primary intracranial tumors in women (60).
Meningiomas most often arise over the cerebral
convexities particularly in the parasagittal area
(Fig. 13.8). Other common locations include the sphe-
noid wing, parasellar region, olfactory groove, and ten-
torium. Approximately 10% of meningiomas involve
the posterior fossa (61,62). Multiple meningiomas may
occur up to 10% of cases and may rarely appear in
children, in which cases initiating factors, such as prior
radiation or underlying genetic abnormalities such as
Neurofibromatosis Type 2, must be considered (6366).
Because meningiomas arise from the dura,
meningeal arterial branches, usually originating from
the ECA, are the initial source of blood supply to the
majority of the tumors. Nevertheless, meningiomas
often recruit blood supply from adjacent meningeal
arteries or invade the dura, receiving supply from pial
272 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 13.5 Glomus jugulare. (A) Axial CT scan demon-

strates enlargement and bony erosive changes involving
right jugular fossa (arrowheads). (B) Right CCA angio-
gram demonstrates highly vascular glomus jugulare tumor
(arrow). (C) Lateral view of microcatheter injection of
ascending pharyngeal artery demonstrates major tumor
supply. (D) Post-embolization angiogram demonstrates no
(C) (D) residual vascularity.

[R] [R] [R]

(A) (B) (C) (D)

(E) (F) (G)

Figure 13.6 Glomus jugulotympanicum with intradural extension into posterior fossa. (A, B, C) Axial enhanced T1-weighted images
show tumor involvement of jugular fossa (white arrow in A), extension into middle ear (white arrow in B), through dura (black arrow-
heads) and large component in posterior fossa (white arrowheads). (D) Coronal enhanced T1-weighted image shows extension from
jugular fossa into posterior fossa (white arrowheads). (E) Lateral view of common carotid injection shows extensive tumor vascularity
originating from ECA (arrowheads) with early venous drainage (arrow). (F) Vertebral artery injection shows vascularity to posterior
fossa component originating from anterior and posterior inferior cerebellar arteries (arrowheads).
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 273

* *

(A) (B)
Figure 13.7 Carotid body and glomus vagale.
(A) Sagittal enhanced fat-saturated T1-weighted MR dem-
onstrates left-sided carotid body tumor and glomus vagale
tumor (asterisk). (B) Left CCA angiogram demonstrates
intense tumor blush with characteristic splaying of carotid
bifurcation due to carotid body tumor and anterior dis-
placement of the cervical ICA due to glomus vagale tumor
(asterisk). (C) Microcatheter angiogram during emboliza-
tion demonstrates dangerous anastomosis with the verte-
bral artery (arrow). No embolization was performed from
this site (arrowheadmicrocatheter tip). (D) Post-emboli-
zation left CCA angiogram demonstrates decreased tumor
(C) (D) blush characteristic displacements of the ICA remain.

(A) (B)

(C) (D)

Figure 13.8 Meningioma. (A) Sagittal T1-weighted enhanced MR demonstrates parasagittal meningioma with considerable mass
effect. (B) Lateral left CCA injection demonstrates meningioma supply originating from MMA and ACA. (C) Microcatheter injection of
left MMA shows tumor supply with early venous drainage (arrowcatheter tip). No orbital communication is present. (D) Post-embolization
angiogram demonstrates decrease in tumor supply.
274 NEUROINTERVENTIONAL MANAGEMENT

vessels. The arterial supply to the tumors meningeal
site of origin remains, however, and aids prediction of
primary blood supply based on tumor location.
The MMA, which supplies dura of the sphenoid
wing, cerebral convexities, and much of the anterior
fossa, is the vessel most often providing arterial supply
to meningiomas. MMA supply is often bilateral in men-
ingiomas of the parasagittal region or those crossing
the midline. Meningiomas of the olfactory groove most
often receive supply from dural branches of the ICA
including ethmoidal artery supply from the ophthalmic
artery. Tumors originating from the tentorium and cli-
vus may receive supply from cavernous ICA branches
in addition to the MMA (Fig. 13.9) (67). Embolization of
these ICA dural branches is often associated with
increased risk and is not commonly performed.
Postero-medially located posterior fossa meningio-
mas often receive supply from meningeal branches of
the vertebral artery. Those more laterally located in the
posterior fossa commonly receive transmastoid branches
of the occipital artery as well as contributions from the
ascending pharyngeal artery. Similar to the case with
ICA dural branches, preoperative embolization of
meningeal arteries originating directly from the verte-
bral artery or of pial branches may not provide as favor-
able a riskbenefit ratio as for embolization of supply
that originates from branches of the ECA (68,69).
Angiographic evaluation of meningiomas is
guided by noninvasive imaging but provides additional
information currently impossible to obtain noninva-
sively. The angiogram should be designed to acquire
particular information to aid the safest and most com-
plete resection possible. Vascular supply to the tumor,
including dural supply, pial supply, and any evidence
of trans-osseous supply must be identified. Anatomic
variants, particularly those involving the MMA and the

(A) (B)

(C) (D)

Figure 13.9 Meningioma. (A) Sagittal T1-weighted enhanced MR demonstrates extra axial mass on the superior surface of the tento-
rium. (B) Lateral view of CCA angiogram shows dense contrast blush involving the mass. (C) Superselective injection of MMA demon-
strates enlargement of tentorial branch supplying the meningioma. Note spokewheel appearance of tumor vasculature (arrowhead
microcatheter tip). (D) Post-embolization angiogram demonstrates no residual tumor filling.
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 275

ophthalmic artery may impact the ability to safely embo-
lize and must be identified (Figs. 13.10, 13.11). It is also
important to understand that the filling of dangerous
anastomoses may change during the embolization pro-
cedure (Fig. 13.12). Examination of the venous phase is
also exceedingly important. In particular, depiction of
large cortical and deep draining veins often impacts the
surgical approach. In addition, patency of dural venous
sinuses adjacent to or involved by the tumor, particu-
larly the sigmoid, transverse, and superior sagittal
sinuses, must be evaluated.
The angiographic appearance of meningioma
typically demonstrates a spokewheel pattern of
intratumoral arteries centered on the primary menin-
geal feeding vessel. A contrast stain or blush outlining
the tumor may be present depending on the tumor
vascularity. Some tumors show little vascularity while
others are highly vascular and manifest rapid promi-
nent venous drainage.
Preoperative embolization of feeding arteries to
meningiomas is usually confined to larger tumors or
those manifesting high vascularity. Designed to
decrease blood loss and engender tumor necrosis,
quantitative measurement of the success of emboliza-
tion has proved difficult. Nevertheless evidence of
reduction in perioperative transfusion associated with
embolization has been presented (70,71).
The skull base origin of the meningeal arteries
most commonly involved in meningioma supply means
that close inspection of the selective microcatheter angio-
gram for dangerous anastomotic connections assumes
paramount importance. Testing with intra-arterial
sodium amytal or lidocaine may aid in the clinical detec-
tion of anastomoses or cranial nerve supply which might

(A) (B)

Figure 13.10 Meningioma. (A) Axial FLAIR and coronal enhanced T1 (B) weighted images demonstrate an enhancing dural-based lesion
crossing the falx near the vertex. Several areas of punctuate flow void are present within the lesion. An enhancing dural tail is present (arrow).

(A) (B) (C)

Figure 13.11 (Same patient as Fig. 13.10.) (A) AP and lateral (B) views of the right CCA angiogram demonstrate an enlarged parietal
branch of the MMA (arrows) supplying the meningioma. In addition, a frontal dural branch (open arrowheads), normally a branch of the
MMA, originates from the ophthalmic artery. (C) Lateral view of the right ECA angiogram also demonstrates the enlarged parietal
branch (arrows) of the MMA with tumor blush. Embolization of this branch was accomplished prior to surgical resection.
276 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 13.12 Meningioma with filling of MMA-ophthalmic artery anastomosis. (A) Pre-embolization injection of external carotid shows
enlarged MMA supplying meningioma (black arrowheads). Small communication with the orbit (black arrow) is identified but no filling of
ophthalmic artery is present. (B) Post-embolization injection demonstrates orbital communication (black arrow) filling ophthalmic artery
(black arrowheads) with retrograde ophthalmic flow (white arrow) into ICA (C) (white arrowhead).
be as risk (see Chapter 10). Preoperative embolization of
meningiomas has been associated with an increased inci-
dence of gross-total resection, particularly in large
tumors. Embolization of both ECA and ICA feeders may
be beneficial in preoperative devascularization (72).
Embolization may be performed using particles of PVA,
although the use of liquid embolic agents including
Onyx has been increasingly reported (Fig. 13.13) (73).
Complications associated with the procedure have been
found to be low; however, the use of small particles (45
150 microns) may be associated with an increased rate of
complications (71,74).
HEMANGIOPERICYTOMA
First described in 1942, HPCs are rare tumors which
comprise from 3% to 5% of soft tissue sarcomas and
approximately 1% of all soft tissue tumors. The cell of
origin is believed to be the pericyte of Zimmerman, a
modified smooth muscle cell that is found in the
capillary wall. Although they may occur throughout
the body, up to 25% of HPCs involve the head and
neck, where the sinonasal region is the most common
location (Fig. 13.14) (75,76). A number of reports also
highlight intracranial involvement and HPC should be
considered in the differential diagnosis of tumors
involving the dura.
Typically presenting in the fifth or sixth decade of
life, the tumor has been found in nearly all age groups
and affects both sexes equally. The most common ini-
tial manifestation is a painless slow growing mass.
Intracranial lesions may present with focal neurological
deficits or evidence of increased intracranial pressure
(77). Despite an apparently benign initial presentation,
a propensity for local aggressiveness and metastases
frequently characterizes HPC, leading to significant
mortality rates (78). Recurrence, often with aggressive
(C)
extension, may appear even after macroscopic total
resection and metastases have been reported over 20
years after initial surgical therapy (79,80).
Diagnosis relies on pathologic examination charac-
terized by features of high cellularity and a relatively
nonspecific staghorn pattern of thick-walled vascular
branching. Various histologic criteria of malignancy have
been reported including increased cellularity, a mitotic
index of >4 mitoses per 10 HPF, and a lack of alternating
sclerotic hypocellular areas; however, correlation with
subsequent clinical behavior is often poor (81,82).
The lesions are typically highly vascular, a fea-
ture which impacts their imaging diagnosis and has
implications for management. CT may demonstrate an
expansile bony pattern; however, erosive or destruc-
tive features are often present. Typically there is
intense often homogeneous enhancement. Smooth
margination is more common than an infiltrative pat-
tern on imaging and may falsely suggest a lesion with
a benign clinical course. Intracranial HPCs are fre-
quently dural based and may demonstrate imaging
features identical to meningioma or other dural-based
tumors. Intratumoral or adjacent parenchymal hemor-
rhage may be present. They are most often supraten-
torial although posterior fossa locations have also
been reported (Figs. 13.15, 13.16) (83). Bony erosion
may allow differentiation from the more characteristic
hyperostosis seen with meningiomas. Calcification is
rarely, if ever, encountered. MR characteristics
include isointensity on T1-weighted images, while
T2-weighted images have been reported to vary from
isointense to hyperintense. Flow voids may occur, com-
mensurate with high tumor vascularity. Enhancement
after administration of gadolinium is the rule and a
dural tail may be present in intracranial lesions (77).
Angiography often demonstrates high vascular-
ity and should be considered when HPC is a
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 277

(A) (B)

(C) (D)

(E) (F)

Figure 13.13 Meningioma embolization with Onyx. (A) Sagittal T1-weighted MR shows large extra axial tumor (arrowheads) originating
from falx. (B) Lateral common carotid angiogram demonstrates enlarged MMA (arrows) supplying tumor. (C) Unsubtracted and sub-
tracted (D) angiogram through microcatheter in MMA shows tumor supply (arrowmicrocatheter tip, arrowheadstumor vasculature).
(E) Post-embolization unsubtracted and subtracted (F) images with Onyx cast (arrows) and absent tumor supply.

differential consideration. In such cases, including
intracranial HPC, preoperative embolization has been
recommended to aid in achieving the most complete
resection (Fig. 13.17) (75,84,85).
Treatment includes wide excision with the goal
of complete resection, often in combination with adju-
vant radiation. Rutkowski et al. in a review of out-
come predictors for 563 reported intracranial HPC
concluded that gross-total resection provides the
greatest survival advantage with a median survival of
13 years compared with 9.75 years for subtotal resec-
tion and recommended gross-total resection as an ini-
tial therapy. They also found, however, that the
addition of postoperative adjuvant radiation did not
seem to confer a survival benefit and raised the issue
of relative radio-resistance of some HPCs (78). Never-
theless, the role of adjuvant radiation in conjunction
with excision has been supported by others including
278 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 13.14 Sinonasal HPC. (A) Coronal and axial (B) unenhanced CT demonstrates expansile destructive lesion (arrowheads) of
the nasal cavity and left maxillary sinus. (C) Common carotid angiography illustrates blood supply originating from both the ophthalmic
artery (arrowhead) as well as the internal maxillary branch of the ECA (arrow). (D) External carotid injection illustrates internal maxillary
supply to the inferior component of the tumor (arrows) which was embolized preoperatively (E) (arrowmicrocatheter tip). (F) Post-
embolization injection shows residual supply from ophthalmic artery.

Schiariti et al. who recently found that its use
conveyed the highest probability of an increased
recurrence-free interval and overall survival (86,87).
Recent data have also suggested a role for gamma
knife in management of recurrences (88). The high
frequency of late recurrences and metastases makes
careful long-term follow-up mandatory in all cases.
ENDOLYMPHATIC SAC TUMORS
Endolymphatic sac tumors (ELST), first described in
1989 by Heffner et al., are rare lesions, making up
approximately 4% of cases in large series of tumors of
the temporal bone (40,89).
Females are affected more frequently than males
with a mean age of symptom onset in the fourth dec-
ade. Nevertheless the age range in which the tumor
has been described is wide, ranging from 15 to 71 years
of age. ELST most often occur sporadically; neverthe-
less, they have also been described as a component of
von Hippel Lindau Syndrome (VHL). In 1997, Manski
et al. identified ELST in 10% to 15% of patients other-
wise diagnosed with VHL. In up to 30% of ELST asso-
ciated with VHL, the tumors may occur bilaterally (90).
Although histologically benign, the lesions are
locally invasive, often demonstrating destructive exten-
sion into the temporal bone and surrounding structures.
A more aggressive clinical course has been associated
with sporadic occurrence, occurrence in young patients,
and for tumors with larger size at presentation (91).
The tumors arise from the endolymphatic sac, a
complex structure composed of interconnecting
tubules and cisterns which is located in the bony ves-
tibular aqueduct. The endolymphatic sac communi-
cates with the endolymphatic duct which in turn joins
the utricular and saccular ducts. Believed to be
involved in regulation of endolymphatic fluid volume,
the endolymphatic apparatus likely plays a role in
various disorders including labyrinthine hydrops and
Meniers disease (92).
In a series of patients with ELST and VHL,
Butman et al. reported that presenting symptoms
typically include ipsilateral hearing loss which is
usually acute, but occasionally may progress over
months to years. Most hearing loss occurs early in the
course of symptoms and is not reversible. Tinnitus is
also an early manifestation in up to 90% of patients,
while approximately two-third complain of vertigo.
Less common symptoms include aural fullness and ear
pain. Facial paresis is uncommon and has been
described in approximately 8% of cases (91).
Butman et al. also noted that in 60% of VHL
patients complaining of vestibulocochlear symptoms,
evaluation demonstrated no imaging evidence of ELST.
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 279

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 13.15 Intracranial HPC. (A, B, C) Axial unenhanced CT shows hyperdense tumor (arrow) involving the right transverse sinus with
adjacent intraparenchymal hemorrhage (arrowheads). (D, E, F) Axial unenhanced FLAIR images. (G, H, I) Enhanced T1-weighted images.

They raised the question as to whether these symptoms
were due to small ELST below the resolution of imag-
ing, to hyperplasia or other dysfunction of the endo-
lymphatic sac in these patients with VHL (90,91).
CT findings in ELST include an expansile, erosive
soft tissue mass initially involving and destroying the
temporal bone adjacent to the vestibular aqueduct,
between the sigmoid sinus and internal auditory canal.
Spiculated or rim calcification may be present. Exten-
sion may occur laterally, into the middle and external
ear, and or medially through the dura to the cerebello-
pontine angle and the jugular foramen (Fig. 13.18) (93).
MRI typically demonstrates a soft tissue mass
which is frequently heterogeneous in signal intensity. The
signal heterogeneity results from components of hemor-
rhage, cyst, residual bone, and cholesterol granuloma.
Flow voids may be present suggesting high vascular
flow. Heterogeneous enhancement is typically present
after the administration of gadolinium. Intralabyrinthine
hemorrhage, characterized by T1 hyperintensity of the
vestibule, cochlea, and semicircular canals, separate from
the tumor, has also been reported (40,91,94).
Angiography typically shows a high degree of vas-
cularity in ELST. As expected from the site of origin, the
ascending pharyngeal, middle meningeal, and occipital
branches of the ECA typically provide arterial supply.
As the lesions enlarge, they may acquire supply from
branches of the ICA or vertebral artery. The vascular
nature of the neoplasms has led to recommendations
for preoperative embolization to aid in surgical resec-
tion (93,95).
VASCULAR MALFORMATIONS
In contrast to neoplasms such as hemangiomas, vascu-
lar malformations are nonproliferative in nature and
enlarge by recruiting flow rather than increasing the
number of cells (4,6,7). Vascular malformations may
280 NEUROINTERVENTIONAL MANAGEMENT
(A)
(C)
Figure 13.16 Intracranial HPC (same patient as Fig. 13.15). (A) Lateral view of right common carotid injection early and late (B)
phases illustrates highly vascular tumor (arrows). (C) Unsubtracted post-embolization view shows Onyx cast. (D) Subtracted post-
embolization angiogram, no residual tumor vascularity.
be comprised of any or all vessel types singly or in
combination, including arterial, capillary, venous, and
lymphatic malformations. Vascular malformations are
typically present at birth and often grow proportion-
ally with the patient. They do not spontaneously
regress and are usually apparent throughout life.
A spectrum of flow characterizes the lesions.
Venous, capillary, and lymphatic vascular malforma-
tions, are low-flow lesions, while arteriovenous mal-
formations (AVM) or fistulae demonstrate very high
flow. Venous malformations, composed of saccular
venous channels, are the most common vascular mal-
formation of the head and neck requiring treatment.
They represent up to 50% of patients seen at centers
treating such lesions (96). Capillary malformations
such as port-wine stains involve pathological capillary
and venular-sized vessels in the dermis and may be
the most common cutaneous vascular anomaly in the
general population. Though they are often confused
with the harmless vascular birthmarks that usually
occur in the neck, eyelids, glabella, or lips of up to
40% of newborns, stork bites typically disappear
spontaneously within a year leaving no trace and are
not considered to be dermatopathologic lesions.
(B)
(D)
Arteriovenous malformations are characterized
by a short-circuit or nidus between the feeding
arteries and draining veins with no intervening capil-
laries, and their presentation may vary from conges-
tive heart failure at birth to presentation with mass or
hemorrhage in early adulthood.
Lymphatic malformations are composed of clusters
of channels derived from defective lymphatic vessels
within the cutaneous and subcutaneous compartments.
They are found most commonly in the cervicofacial area
and are usually microcystic in that location. Combined
malformations involving arterial, capillary, venous, and
lymphatic components also exist and are more often
found unilaterally, especially on the limbs.
Differentiation between high- and low-flow
lesions has important imaging and treatment impli-
cations (6). High-flow lesions (AVMs) are usually
well demonstrated on angiography and are fre-
quently amenable to treatment via transarterial
catheter-based embolization techniques. Low-flow
lesions are not readily demonstrable angiographically
although occasionally angiography may be used to
exclude rapid flow indicative of an AVM and con-
firm the diagnosis. Low flow lesions are usually
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 281

(A) (B) (C)

(D) (E) (F)

Figure 13.17 Posterior cervical HPC. Presentation as painless cervical mass. (A, B) Axial unenhanced T1-weighted images show isoin-
tense mass with internal flow voids (arrows). (C) Sagittal T1-weighted image with flow void (arrow). (D) Early and late (E) phase angio-
gram demonstrates supply to vascular mass (arrowheads) originating from occipital branch of the ECA (arrow). (F) Post-embolization
injection of the ECA shows no residual supply.

(A) (B) (C) (D)

(E) (F) (G)

Figure 13.18 Endolymphatic sac tumor. Patient with left-sided hearing loss and pain. Biopsy complicated by excessive hemorrhage.
(A) CT of temporal bone shows destructive lesion centered in region of the vestibular aqueduct (arrow). (B) Sagittal unenhanced T1,
enhanced coronal T1 (C), and unenhanced FLAIR (D) show heterogeneous signal with enhancement. (E) Lateral view of common caro-
tid angiogram reveals tumor vascularity (arrows). (F) Early and (G) late phase post-embolization angiography following embolization of
stylomastoid, ascending pharyngeal, and middle meningeal branches of ECA, show obliteration of tumor vasculature.
282 NEUROINTERVENTIONAL MANAGEMENT
imaged noninvasively and treated via percutaneous
injections and sclerotherapy (97).
Arteriovenous Malformations
Arteriovenous malformations (AVM) of the head and
neck are far less common than low-flow vascular
anomalies. Nevertheless, these lesions deserve atten-
tion because of their frequent presentation with cos-
metic defects or life-threatening hemorrhage (6).
Kohout et al. reported an extensive retrospective
analysis of 81 patients with AVM of the head and neck
evaluated over a period of 20 years (98). The age of pre-
sentation varied widely, from 2 to 66 years with a male
to female ratio of 1:1.15. A vascular anomaly was appa-
rent at birth in 59 percent of patients (82 percent in
men, 44 percent in women). Ten percent of patients
noted onset in childhood, 10 percent in adolescence,
and 21 percent in adulthood. Eight patients first noted
the malformation at puberty, and six others experi-
enced exacerbation during puberty. Fifteen AVMs
appeared or expanded during pregnancy.
Clinical presentation was categorized according to
the authors modification of Schobinger clinical staging:
27 percent in stage I (quiescence), 38 percent in stage II
(expansion), and 38 percent in stage III (tissue destruc-
tion). There was a single patient with stage IV malforma-
tion (cardiac decompensation). Stage I lesions remained
stable for long periods. Expansion (stage II) was usually
followed by pain, bleeding, and ulceration (stage III).
Once present, these symptoms and signs inevitably pro-
gressed until the malformation was resected.
Sites of occurrence could be categorized in ana-
tomic patterns. Sixty-nine percent occurred in the
midface, 14 percent in the upper third of the face,
and 17 percent in the lower third. The most common
sites were cheek (31 percent), ear (16 percent), nose
(11 percent), and forehead (10 percent) (98).
Angiographically, high-flow malformations such
as AVMs or fistulae are characterized by enlarged
arteries and veins with early filling of the draining
veins (Fig. 13.19). Depending on the complexity of the
lesion, the relationship of the feeding arteries and
draining veins to the nidus may be difficult to define.
Superselective angiography is often necessary to best
define the anatomy, particularly in complex lesions.
Angiographic evaluation of head and neck AVMs
must include all vessels likely to provide arterial supply.
Persky et al. found the inferior alveolar artery character-
istically supplied AVMs of the mandible (Fig. 13.20).
Supply to regions of soft tissue extension depended on
additional sites involved (e.g., labial and submental
arteries to the lower lip and floor of mouth, occipital
artery to the ear lobe, and the masseteric branch of the
internal maxillary artery to the masseter muscle). AVMs
isolated to the mandible often had contralateral supply
from branches of the lingual, facial, and inferior alveolar
arteries (99). They found that supply to maxillary AVMs
consisted of distal branches of the internal maxillary
artery. Maxillary arterial vascular malformations with
soft tissue extension were supplied by their correspond-
ing arterial systems, and the ophthalmic artery was most
commonly recruited. Both the internal maxillary and
facial artery systems supplied combined maxillary/
mandibular arterial vascular malformations.
MR typically demonstrates enlarged, serpiginous
vessels with flow voids and phase shifts. Use of fat
saturation technique with T2 and gadolinium
enhanced T1 images are often beneficial in providing
enhanced detail (100). MR is often superior because
CT image quality can be compromised by dentition
and metal artifacts such as dental appliances or fil-
lings. Although the lesion may appear compact on
cross-sectional imaging or angiography, the appear-
ance may be deceptive because the surrounding tissue
is often predisposed to develop shunting. This may
lead to recurrence or recanalization via collaterals
through the adjacent tissue.
AVM involvement of bony structures of the face
may be documented on CT, MR and plain or Panorex
films. CT findings include radiolucencies, often having
the appearance of a honeycomb or soap bubbles, with
small rounded and irregular lacunae. Root resorption has
been observed, creating an appearance of teeth floating in
the adjacent alveolar osseous erosion. The lesion is often
well demarcated and may mimic the appearance of odon-
togenic cysts (101). Recognition of bony involvement, par-
ticularly the roots of the teeth, is important because
catastrophic bleeding may occur when teeth become
loose, are pulled, or are lost in an uncontrolled fashion.
Kohout et al. found bony involvement in 22
patients: 11 in the nasomaxillary region and 8 the
mandible. In 7 patients, the bone was the primary site;
in 15 other patients, the bone was involved seconda-
rily. Nasomaxillary AVMs invariably encompassed
the overlying soft tissues, whereas mandibular AVMs
were confined to bone in 50 percent of cases. In both
sites, AVM extensively permeated and expanded the
bone, crossing the midline in many patients. Persky
et al. retrospectively reviewed 26 patients with AVM
involving the mandible and/or maxilla (99). They also
found that soft tissue involvement was near universal
with maxillary lesions, while that associated with
mandibular lesions was more limited.
MR imaging of low flow lesions such as venous
vascular malformations are characterized by significant
enhancement, intermediate T1 signal, heterogeneous
high T2 signal and may demonstrate venous lakes and/
or phleboliths, which appear as foci of low signal (102).
These lesions may also demonstrate septations or be
associated with satellite nodules (103).
Treatment options for venous and other slow flow
malformations include surgical resection, laser treatment
of skin or mucous membranes, or percutaneous sclero-
therapy with a variety of agents including ethanol,
sodium tetradecyl sulfate, OK-432, bleomycin as well as
others (104). In performing percutaneous sclerotherapy,
one must be careful to have free flow of sclerotic agent
within the vascular channels. Extravasation of these
agents into the soft-tissue may produce significant dam-
age to skin or mucous membranes manifested by blister-
ing or deep ulceration. In addition, severe damage to
adjacent structures such as the cranial nerves or the
orbital contents may result, especially with ethanol.
Hematuria is a frequent sequel and local swelling is
often pronounced. Swelling can be controlled by elevat-
ing the head of the bed and early ambulation along with
ice packs. Powdered contrast agents such as Amipaque
are no longer commercially available to mix with etha-
nol and thereby allow visualization, making precise
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 283

(A) (B)

(C) (D)

Figure 13.19 Facial AVM. (A) Axial T1-weighted MR demonstrates left facial swelling with flow voids (arrowheads). (B) Lateral left
ECA injection demonstrates AVM supplied by left facial artery (arrowheadearly venous drainage). (C) Microcatheter injection of left
facial artery demonstrating AVM supply and early venous drainage (arrowhead). (D) Post-embolization angiogram demonstrates no
residual filling, patient underwent surgical resection.

delivery impossible. In our practice, we mix sodium tet-
radecyl sulfate (Sotradecol 3%; Bioniche Pharma U.S.A.
Inc., Bogart, GA 30622) 2:1 with iopamidol 76% (Isovue-
370; Bracco Diagnostics, Inc., Princeton, NJ 08543) to
make a 1% injection. This can be foamed by passing
between syringes so the material is more stable at the site
of injection. Ethanol (Dehydrated Alcohol; American
Regent, Inc., Shirley, NY 11967) is ~98% pure without
bacteriostatic agents and is injected without alteration.
We typically use small (22 or 24 gauge) intravenous cath-
eters (JELCO; Medex, Inc., Carlsbad, CA 92008) and
approach the lesion through adjacent normal skin. Ultra-
sound guidance may be useful. When free flow of blood
is demonstrated, one may image the lesion and identify
routes of venous outflow by gently injecting contrast.
A piece of connecting tubing can be connected to prevent
inadvertent loss of position of the angiocatheter due to
hand movement or torquing. Bleeding from the puncture
site may be controlled by injecting a very thin slurry of
collagen (Avitene; Davol, Inc., Cranston, RI 02920)
through the angiocatheter as it is being withdrawn. One
must take into consideration that thrombosis and inflam-
mation will continue to occur for some period of time
after the injection of material has ceased that may lead to
unwanted tissue damage, particularly with ethanol. We
believe it prudent to conclude injections while the lesion
still demonstrates filling to decrease the risk of complica-
tions, although patients should be warned that further
embolization sessions may be needed. Lymphatic malfor-
mations also respond well to sclerotherapy, with macro-
cystic lesions responding particularly well to OK-432,
which modulates the immune response (105). Surgery
and/or laser therapy may also play a role in the treat-
ment of lymphatic malformations. Capillary vascular
malformations have shown good results when treated
with laser therapy although other treatment options may
be considered in special cases (106).
Treatment of high flow lesions such as AVM can
include surgery, laser, embolization, sclerotherapy, or
a combination of options. A multidisciplinary team
approach is required for the assessment and treatment
of these lesions, which typically involves preoperative
284 NEUROINTERVENTIONAL MANAGEMENT
(A)
(C)
Figure 13.20 Mandibular AVM. (A) Lateral CCA injection demonstrates intra-osseous mandibular AVM supplied by inferior alveolar
artery. (B) Microcatheter injection of the inferior alveolar artery demonstrates AVM with intra-osseous venous drainage. (C) Post-NBCA
embolization, glue cast of arterial supply, AVM nidus, and proximal venous drainage (arrowheads). (D) Post-embolization angiogram
demonstrates minimal residual AVM.
angiography with superselective embolization, fol-
lowed by resection of the lesion (107).
Embolization options include particles, coils, n-
Butyl Cyanoacrylate (TruFill Liquid Embolic System;
Cordis Neurovascular, Inc., Miami Lakes, FL 33102),
Onyx (Onyx Liquid Embolic System; Micro Therapeu-
tics, Inc., Irvine, CA 92618), or other materials. Scleros-
ing agents can be injected intra-arterially or via direct
percutaneous puncture using an intravenous angio-
catheter and include primarily ethanol and Sotradecol.
Important considerations in selection of appropriate
interventional methods include: briskness of flow;
relationship to nerves; proximity to the surface of the
skin or mucous membranes; relation to the vermillion
border of the lips, the ear or hair bearing areas; and
pigmentation of skin. Platinum coils may be placed to
slow flow in extremely high flow lesions or to treat
fistulae that are difficult to define angiographically or
are in particularly dangerous areas, such as in close
relation to the spinal cord. While coils are useful,
Kohout and others have emphasized that proximal
ligation of arterial feeding vessels by any technique
frequently resulted in rapid clinical progression and
(B)
(D)
acquisition of diffuse collateral arterial supply and is
to be avoided if possible (98,108).
Until very recently, our preferred agents of choice
have been ethanol and n-Butyl Cyanoacrylate; however,
our recent experience has led us to rely on Onyx for
embolization of AVM that are not near the surface of
the skin. One should be aware that Onyx is opacified
with microparticulate tantalum in suspension and will
cause permanent visible staining of the skin if injected
near the surface. However, the performance characteris-
tics of Onyx allow excellent penetration and prolonged
injections producing essentially anatomic injections of
deep malformations. Practitioners need to be aware,
however, of proximity to important anatomical struc-
tures such as blood supply to cranial nerves and the
eyes, as well as dangerous anastamoses to vessels com-
municating with the internal carotid, vertebral or other
critical arteries. We have found that penetration of
embolic material into malformations, especially large,
complicated ones, seems to be significantly improved
with Onyx compared to n-Butyl Cyanoacrylate. Our
recent experience also suggests the decrease in flow fol-
lowing embolization with Onyx is much more consistent
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK
and predictable than with sclerosing agents such as
ethanol. We feel this may be because ethanol does not
remain in contact with the vessel wall for a sufficient
period of time to damage the endothelium and promote
complete thrombosis and scarring. This issue can be cor-
rected at least partially by manually occluding the
venous outflow, if the venous drainage is accessible.
This maneuver is also helpful to prevent ethanol pene-
trating and damaging sensitive structures, such as the
orbital veins. Direct percutaneous attack can be used
when microcatheters cannot be navigated distal enough
in very tortuous, normal anatomy to allow safe deposi-
tion of material. Ultrasound may be useful in directing
percutaneous catheter placement. Superficial bleeding
can usually be controlled by direct pressure or via percu-
taneous injection of Avitene slurry through an intrave-
nous angiocatheter, though at times these techniques
need to be augmented or supplemented with open other
endovascular or surgical procedures.
Local control of bleeding at the time of emboliza-
tion may rarely be necessary but is especially difficult,
particularly in bony lesions, because pressure is diffi-
cult to apply within the tooth socket without the pres-
ence of the tooth. Urgent control of bleeding from AVM
with mandibular involvement by local pressure may be
facilitated by retaining the tooth. Using a tea bag to
tamponade bleeding may help, presumably due to the
vasoconstricting properties of tannic acid. Avitene or
materials that promote clotting may also be useful.
EPISTAXIS
While a common clinical problem, the vast majority of
epistaxis is minor in magnitude, originates from the
anterior nasal septum, and is self-limited or ceases with
a short period of nasal compression (109). Epistaxis
originating posteriorly in the nasal cavity, however, is
inaccessible to direct pressure or cauterization and may
be life threatening. In many cases, permanent hemosta-
sis is achieved by the use of nasal packing to provide
tamponade within the nasal cavity. When nasal pack-
ing fails, surgical ligation of the distal branches of the
internal maxillary artery supplying the nasal fossa has
been advocated. Both prolonged nasal packing and
internal maxillary ligation have been associated with
patient discomfort, complications, and recurrence
(110,111). In such cases, endovascular techniques, spe-
cifically arterial embolization, may rapidly relieve most
cases of epistaxis and permit removal of packing with-
out surgical intervention. Recent literature emphasizes
early consideration of endovascular techniques in the
management of difficult to control epistaxis (112).
A relatively broad differential diagnosis must be
considered in patients presenting with severe epistaxis.
The vast majority of cases, considered idiopathic, arise
from the effects of longstanding hypertension and arte-
riosclerosis on the vessels of the nasal mucosa. Often
exacerbated by low humidity, patients often present in
the fall, when home heating systems lacking humidifiers
are turned on. Nevertheless, in any case of severe epis-
taxis, it is imperative that a specific etiology be identified
if present, so that the most effective treatment can be
directed to the underlying cause of the bleeding.
Conditions that should be considered in the dif-
ferential diagnosis for severe epistaxis include:
285
Idiopathic epistaxis: often occurs in elderly patients
with hypertension or evidence of generalized
atherosclerosis.
Tumor: Juvenile angiofibroma, nasal polyps, malig-
nant nasal or sinus tumors.
Coagulopathy: including medications (particularly
antiplatelet or anticoagulation therapy)/uremia/
hepatic failure.
Hereditary Hemorrhagic Telangiectasia
Trauma: with damage to ECA or ICA, particularly in
the cavernous or petrous segments (including aneur-
ysms or pseudoaneurysms) (Fig. 13.21).
Pre-embolization evaluation should exclude spe-
cific etiologies including neoplasm and traumatic
lesions. A careful medication history should be taken
with particular attention to newly added medications
such as antiplatelet agents.
Hereditary hemorrhagic telangiectasia (HHT or
RenduOslerWeber syndrome) should be given par-
ticular consideration in patients with multiple epi-
sodes of epistaxis or a family history. A number of
features of the physical examination, history, and
angiogram suggest the diagnosis (Fig. 13.22).
HHT is an autosomal dominant disorder with
very high penetrance that affects 1:10,000 of the gen-
eral population. The disease may involve multiple
organ systems, the manifestations of which arise from
inherited abnormalities of vascular structure (113,114).
These genetically determined abnormalities result in
the development of arteriovenous communications of
varying sizes. The nasal mucosa, skin, lung, gastroin-
testinal tract, and central nervous system are most fre-
quently affected. In the nasal mucosa and skin, the
usually tiny lesions are referred to as telangiectasias.
In the central nervous system, both AVM and direct
arteriovenous fistulas involving both brain and spinal
cord have been described. Cerebrovascular malforma-
tions may be multiple in up to 50% of HHT patients,
a significant increase over the 1% to 3% multiplicity seen
in the general population (115118). In the lung most
lesions are direct arteriovenous fistulas (Fig. 13.23). Gas-
trointestinal tract lesions include telangiectasias, AVMs,
as well as angiodysplasias.
The four major diagnostic criteria for HHT include:
1. Epistaxis: spontaneous, recurrent nose bleeds.
2. Telangiectases which are usually multiple, and
occur at characteristic sites including the lips, oral
cavity, fingers, and nose.
3. Visceral lesions including: gastrointestinal telangiec-
tasia (with or without bleeding), pulmonary AVM,
hepatic AVM, cerebral AVM, and spinal AVM.
4. Family history of a first degree relative with HHT
according to these criteria.
The diagnosis of HHT is considered definite if
three of the above criteria are present, possible if
two criteria are present and unlikely if only one is
present (119,120).
Nasal telangiectasias are responsible for the most
common manifestation of HHT, epistaxis. This occurs
in over 90% of affected patients, usually beginning
before the third decade. Severity, while variable, tends
to increase with age, often leading to chronic anemia
286 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E)

Figure 13.21 Nasal aneurysm. Patient developed intractable epistaxis following functional endosinus surgical procedure. (A) Lateral
ECA injection shows small aneurysm originating from nasal branch of internal maxillary artery (arrow). (B) Unsubtracted and subtracted
(C) images from microcatheter (arrowheads) injection into distal internal maxillary artery fill aneurysm (arrow). (D) Unsubtracted and
subtracted (E) images post-embolization show no filling of aneurysm (arrowcoil).

(A) (B) (C) (D)

(E) (F) (G)

Figure 13.22 Hereditary hemorrhagic telangiectasia. A 72-year-old man presented to the emergency room with severe epistaxis which had
occurred intermittently for over 24 hours. He reported a family history of epistaxis affecting his mother, brother, and several cousins. (A, B)
Physical examination revealed multiple red, slightly raised lesions on his lips, tongue, conjunctiva, fingertips, and nail beds. Unsubtracted (C)
and subtracted late arterial phase (D) Right internal carotid artery (RICA) angiographic examination demonstrates telangiectasias as multiple
intravascular contrast collections involving the mucosa of the lips, tongue, and nasal fossa (arrows). (E) Unsubtracted and subtracted (F) lat-
eral right internal maxillary injection demonstrates telangiectasia (arrow) with early venous drainage (arrowhead) indicating arteriovenous
shunting from these multiple lesions (asteriskmicrocatheter tip). (G) Lateral view of CCA injection after embolization of internal maxillary
arteries was performed bilaterally using PVA particles. Embolization was followed by removal of nasal packing with no recurrence of epistaxis.
 ENDOVASCULAR MANAGEMENT OF TUMORS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK 287

(A) (B) (C)

Figure 13.23 Vascular malformations in HHT. (A) Angiogram demonstrates multiple AVMs in a patient with HHT (arrows). (B) CT angiogram
identifies pulmonary arteriovenous fistula (arrow). (C) Pulmonary angiogram demonstrates multiple pulmonary arteriovenous fistulas (arrows).

(A) (B) (C)

Figure 13.24 Petrous carotid aneurysm. Patient presented with severe epistaxis. (A) Axial CT scan (bone windows) demonstrates
sharply marginated expansile skull base lesion (arrowheads) with extension into the middle ear (arrow) and sphenoid sinus. (B) Right
CCA angiogram identifies an aneurysm of the petrous ICA as source of epistaxis. (C) Right common carotid angiogram post coil embo-
lization of aneurysm with parent vessel occlusion (arrowscoil mass).

and requiring multiple episodes of treatment. The
lesions of the nasal fossa can be identified angiograph-
ically, suggesting the diagnosis. Embolization has
been shown to be a safe and effective treatment for
prolonged epistaxis and is a treatment that can be
repeated if necessary (121).
Pulmonary arteriovenous fistulas have been
identified in 1015% of HHT patients. Conversely, it is
estimated that over half of patients with pulmonary
AV fistulas have HHT. The direct right-to-left shunts
may initially manifest as neurological deficits caused
by cerebral emboli. Most often diagnosed by CT
angiography, these lesions are currently treated with
endovascular techniques.
Recent genetic studies have confirmed that HHT
is inherited as an autosomal dominant trait whose
penetrance and expressivity are variable. Mutations
involving either of two genes, endoglin or ALK-1, may
cause HHT. Two disease subtypes, HHT1 and HHT2,
result from mutations of endoglin or ALK-1 respec-
tively. The variability of disease severity in different
family members suggests, however, that other factors
in addition to the specific mutations modify the HHT
phenotype (122).
Normally most patients with epistaxis are given
a trial of nasal packing. If this is unsuccessful, endo-
vascular treatment with embolization should be con-
sidered in management of most cases. Embolization of
the arterial supply to the nasal fossa is most often suc-
cessful in idiopathic cases as well as in specific etiolo-
gies of epistaxis directly related to disease of the nasal
fossa vessels, including uncorrectable coagulopathy
and HHT. The procedure is associated with very low
complication rates (123).
In the angiographic evaluation of epistaxis, visu-
alization of both the ICA and ECA is necessary (124).
ICA evaluation excludes rare vascular lesions such as
petrous or cavernous aneurysms which might cause
epistaxis and whose presence would change therapy
(Fig. 13.24). Sources of collateral supply to the nasal
fossa should be identified including the facial arteries
and ethmoidal branches of the ophthalmic artery. In
288 NEUROINTERVENTIONAL MANAGEMENT
idiopathic epistaxis, no significant vascular abnormal-
ities are normally identified.
Most cases of idiopathic epistaxis respond to
bilateral embolization of the pterygopalatine branches
of the internal maxillary arteries, which give the
majority of supply to the nasal fossa. PVA particles
(150350 microns) is usually the preferred embolic
material. In most cases, proximal blockage of the
internal maxillary arteries using coils or other devices
is not necessary, is usually ineffective in preventing
collateral formation, and interferes with re-treatment.
Embolization of the distal facial artery may also be
necessary to block collateral vascularization, particu-
larly in patients who have undergone prior ligation of
the internal maxillary artery or its major branches.
Ethmoidal branches of the ophthalmic artery may also
provide collateral supply to the nasal fossa, particu-
larly in patients who have undergone prior surgery
for maxillary ligation. Embolization of these vessels is
not routinely performed because of the risk to vision.
Typically, patients undergo embolization with nasal
packing in place. Following initial embolization of the
internal maxillary branches, packing is removed in the
angiographic suite before removal of the femoral
sheath. If hemorrhage persists, additional emboliza-
tion of additional collaterals may then be performed.
CONCLUSION
Vascular lesions of the face and head are a complex
group of pathologies that are undergoing explosive
growth in understanding and treatment. Diagnosis
and treatment are best carried out by a multidiscipli-
nary team including specialists bringing unique inter-
ests, knowledge, and skills.
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 14
Dissections of the carotid and vertebral arteries
Igor Rybinnik, Scott E. Kasner, Qaisar A. Shah, and Robert W. Hurst
INTRODUCTION
Arterial dissection occurs when intraluminal blood
penetrates the vessel wall, usually through a tear in
the intima, and extends through and between the tis-
sue layers of which the wall is comprised. Dissections
occurring in the head and neck may involve either the
internal carotid or vertebral arteries (VAs), and may
affect either the extradural or intradural portions of
the vessels. Dissections involving the extradural por-
tions of the internal carotid artery (ICA) and vertebral
artery (VA) are more common than intradural dissec-
tions, with extradural ICA dissection occurring more
commonly than that of the VA. Conversely, among
intradural dissections, involvement of the VAs is con-
siderably more common than dissections of the ICA
or its intracranial branches.
EPIDEMIOLOGY
Cervicocerebral arterial dissection is an uncommon
cause of stroke in the general population but accounts
for 1520% for all strokes in patients under 55 years
of age (1). The true incidence of dissection is difficult
to ascertain because some patients may remain
asymptomatic or have minor symptoms and are never
diagnosed. One community-based study reported the
overall incidence of cervicocerebral dissection to be
2.6 per 100,000 per year (2). Other estimates place the
annual incidence of ICA dissection as high as 3.5 per
100,000 per year and that for VA dissection at 11.5
per 100,000 per year (3).
Dissections of the extradural ICA accounted for
7080% of overall cervical arterial dissections, exceed-
ing extradural VA dissection fourfold, according to a
prospective study of 200 patients (4). The mean age of
presentation for extradural ICA dissection is 44 years
and there is no sex predilection while extradural VA
dissection presents at a mean age of 39 years with a
female preponderance (5).
The vast majority of extradural ICA dissections
involve the cervical portion of the ICA with petrous
or cavernous involvement representing less than 5%.
Sixty-five percent of VA dissections involve the suboc-
cipital segment (V3) with nearly 15% extending into
the intradural segment (V4). The proximal VA seg-
ment (V1) is the second most common extradural VA
location involved. Bilateral VA dissections are also rel-
atively common and have also been reported with
coexistent ICA dissections (6,7).
Intradural arterial dissections are far less com-
mon than those involving the extradural portions
of the vessels. VA dissection makes up over 80% of
intradural dissections with intradural (V4) involve-
ment often representing distal extension of a dis-
section involving the V3 or suboccipital segment.
Intradural VA dissection may also occur in isola-
tion or uncommonly with extension into the basilar
artery. Two-thirds of patients with intradural VA
dissection are male and on average are 8 years
older than those with extradural VA dissections
and 9 years older than those with intradural ICA
dissection (51.8 years vs. 43.8 years) (8).
Dissection of the intradural ICA represents less
than 20% intradural dissections (9). Intradural dissection
of the anterior circulation may involve individual ves-
sels (ICA, MCA, or ACA) alone or involve the intra-
dural ICA with extension into the MCA or ACA (10).
Isolated middle cerebral artery (MCA) or anterior cere-
bral artery (ACA) dissection is rare and usually associ-
ated with direct arterial injury or head trauma.
PATHOGENESIS
Arterial dissections are often characterized as either
spontaneous or traumatic. Traumatic dissections occur
due to overt head and neck trauma. Major thoracic
injuries, traumatic brain injury, and facial and skull
base fractures increase the risk of carotid artery dis-
sections. The risk of VA dissections is increased with
cervical spine fractures (11).
Spontaneous dissections occur without obvious
traumatic injury, although in some cases, subclinical
trauma may be implicated. For example, dissection has
been attributed to seemingly trivial traumatic events
such as nose blowing, severe coughing, sudden neck
movements (12), head turning while backing an automo-
bile, swinging a golf club (13), chiropractic manipulation
of the neck (14,) or prolonged telephone conversations,
probably related to prolonged flexion of the neck (5).
Furthermore, an association between elongated styloid
process and cervical carotid artery dissection has been
reported hinting at direct bony mechanical injury as a
possible important cause of dissections (15).
The pathophysiology of arterial dissections
remains poorly understood. The arterial wall may be
inherently weakened and at increased susceptibility to
injury from otherwise subclinical trauma. The coexis-
tence of connective tissue disorders in some patients
with arterial dissections gives credence to this
292 NEUROINTERVENTIONAL MANAGEMENT
vasculopathic theory. Conditions associated with an
increased incidence of dissection include fibromuscu-
lar dysplasia (FMD), Marfans syndrome, Ehlers
Danlos syndrome (type IV), osteogenesis imperfecta,
cystic medial necrosis, and pseudoxanthoma elasticum
(16). Conditions other than connective tissue disorders
have also been associated with dissection including
recent infection, migraine, and hyperhomocysteinemia
(17,18). Redundancy and loops of the cervical ICA
have also been associated with an increased incidence
of ICA dissections (19). With the exception of FMD,
potentially predisposing conditions are identified in
only a minority of patients with dissection.
There is reasonable evidence suggesting that
genetic predisposition plays a role in the pathophysi-
ology of cervical arterial dissections. Familial cases of
cervical arterial dissections have been reported even
in the absence of known connective tissue disorders,
and family history is strongly associated with dissec-
tion recurrence (20,21).
While studies of genetic linkage failed to convinc-
ingly identify specific genetic mutations associated
with increased risk of cervical artery dissections,
association with 677TT genotype of the 5,10-methylene-
tetrahydrofolate reductase (MTHFR 677TT) gene has
been suggested (22). The international genome-wide
association Cervical Artery Dissections and Ischemic
Stroke Patients (CADISP)-genetics project is currently
underway to identify genetic variants associated with
an increased risk of cervical arterial dissections (23).
Dissection of the carotid or VAs sets in motion a
sequence of events the understanding of which is
essential for proper management. Arterial walls are
composed of three layers: an internal or endothelial
layer (tunica intima), a middle or muscular layer (tun-
ica media), and an external or connective-tissue layer
(tunica adventitia). Most commonly, a tear or disrup-
tion of the intima initiates the damage. Disruption of
the arterial intima exposes the subintimal components
of the wall, permits adherence of platelets at the site of
injury, and serves as a nidus for thrombus formation.
The extent of injury to the wall and the hemodynamic
features of the injury site determine the subsequent
effects of the initial injury. Penetration and extension of
blood into the vessel wall results in an intramural hem-
atoma. The hematoma extends between the layers of
the vessel wall and, particularly if located between the
intimal and medial layers, may constrict the residual
lumen with narrowing or complete occlusion. Flow
impairment may then result in ischemic symptoms as a
result of hypoperfusion of neural structures supplied
by the damaged vessel. Continued flow through the
injured lumen is also potentially detrimental since it
permits distal embolization of the in-situ thrombus
formed at the injury site. This embolization mechanism
is supported by observation of microemboli with trans-
cranial Doppler monitoring, occurrence of distal branch
occlusions, and the infarct lesion pattern on brain imag-
ing (24). Furthermore, artery-to-artery cerebral embo-
lism rather than hemodynamic compromise seems to
be the underlying mechanism in the vast majority of
ischemic lesions with extracranial internal carotid dis-
sections (25,26).
Intramural hematoma may also disrupt the struc-
tural integrity of the wall, resulting in aneurysmal
expansion of the vessel. Aneurysm formation is more
likely when the intramural hematoma extends
between the medial and adventitial layers of the ves-
sel wall. The term dissecting aneurysm is applied
when the walls of the dilated segment are comprised
of the incomplete remaining elements of the vessel
wall. Hara and Yamamoto note that the term dissect-
ing aneurysm was originally a pathological term
defined as a lesion produced by penetration of the
circulating blood into the substance of the wall of a
vessel, with subsequent extension of the effused blood
for varying distances between its layers. In contrast,
the term fusiform aneurysm refers to the morphol-
ogy of the aneurysm and makes no reference to its eti-
ology. Consequently, some dissecting aneurysms,
particularly those located intradurally, are often
referred to as fusiform aneurysms on the basis their
morphology as identified on imaging or angiographic
studies (27). Other dissecting aneurysms, particularly
those involving the extradural portions of the vessels,
do not have fusiform morphology and may be con-
nected to the true lumen through a relatively narrow
neck.
Complete disruption of the arterial wall permits
extravasation of blood into adjacent structures. If the
hemorrhage is into soft tissue, as is usually the case in
extradural locations, a pseudoaneurysm may form.
Unlike dissecting aneurysms, the walls of pseudoa-
neurysms are not comprised of layers of the vessel
wall.
In cases of aneurysmal dilation, the aneurysm
often retains communication with the flowing blood
within the lumen. The increased diameter of the
injured segment exposes the damaged and weakened
wall to increased wall tension compared with the
more normal vessel. These factors may permit delayed
growth of aneurysmally dilated portions of the dis-
sected vessel. In addition, the slowing of flow within
an aneurysmally dilated segment combined with the
absence of intimal lining creates an environment that
encourages intra-aneurysmal clot formation and sub-
sequent embolization.
The pathophysiology of dissection is similar
whether the damage occurs in either extracranial or
intracranial locations. It is the environment surround-
ing the vessel at the site of injury that is often the
major determinant of the subsequent course and even-
tual outcome. In their extracranial course, the ICA and
VAs are surrounded primarily by soft tissue, which
usually gives some physical support to the artery wall
and limits, although does not always prevent subse-
quent rupture.
Consequently, the most common symptoms asso-
ciated with extradural dissection are ischemic and
arise from hypoperfusion or emboli. Dissection of the
extradural vessels results in hemorrhage only rarely
and in specific locations, such as within the sphenoid
sinus, middle ear, or other cavities of the skull base
(28). Carotid artery disruption within the cavernous
sinus may also give rise to direct carotid cavernous
fistulas (see Chapter 12).
After entering the dura however, the vessels and
their branches course within the subarachnoid space,
surrounded only by cerebrospinal fluid. In the subar-
achnoid space, there is no external structural support
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES
for the vessel wall and no significant restriction or
confinement of hemorrhage should the wall be
breached completely. In addition, thinning of the
media and adventitia as well as a high incidence of
defects involving the internal elastic lamina has been
documented in the intradural segment of the VA (29).
These histological features also may impair the struc-
tural integrity of the vessel wall. Consequently, the
chance of aneurysmal enlargement of the weakened
vessel and subsequent rupture is significantly
increased compared to the situation where similar
damage involves an extradural location. In addition,
hemorrhage that occurs within the subarachnoid space
gives rise to the well-known sequence of events asso-
ciated with the very high morbidity and mortality of
aneurysmal subarachnoid hemorrhage (SAH).
Extradural cervical arteries are more prone to
dissection than the intradural segments because of
their greater mobility, lack of protection by the skull,
and their susceptibility to mechanical damage by
neighboring bony structures. Sites where a relatively
mobile segment of a vessel must traverse a fixed loca-
tion, such as skull base foramina, can also serve to
concentrate mechanical forces. These factors determine
the characteristic locations affected by dissection.
Extradural ICA dissections characteristically begin
several centimeters distal to the relatively fixed com-
mon carotid bifurcation where the ICA originates (17).
Therefore, dissection most often involves the relatively
mobile cervical portion of the ICA, and stops at the
skull base where the artery is secured by fibrous tissue
as it enters the carotid canal.
The VA is mobile at both its most proximal (V1)
and most distal (V3) extradural segments. The vessels
location is fixed at the origin, within the foraminal
segment (V2), and at the site of dural perforation.
Extradural VA dissections most often involve the V3
or suboccipital segment, the most mobile segment of
the vessel. Dissection may also involve the intradural
(V4) portion of the VA, often by extension from V3. In
contrast, the more proximally located foraminal or V2
portion of the vessel, because of its lack of mobility
and protection by the bony walls of the transverse for-
amina, is only rarely affected. The preforaminal or V1
segment is involved in approximately 10% of VA dis-
sections. Dissections often terminate as the relatively
mobile V1 segment enters the fixed structure of the
transverse vertebral foramen (17).
Intradural dissection, although much less com-
mon than dissection of the extracranial portions of the
vessels, is increasingly recognized because of better
diagnostic techniques and more clinical suspicion of
the disorder. The intradural ICA and its branches,
while better protected from mechanical stress than the
cervical ICA, are still prone to dissection although
much less commonly than the extradural ICA. Simi-
larly, the posterior inferior cerebellar artery (PICA) or
basilar artery is rarely dissected in isolation, but may
be involved when a vertebral dissection extends ceph-
alad to involve the vertebrobasilar junction.
CLINICAL MANIFESTATIONS
Clinical features of arterial dissections include head-
ache, neck pain, Horners syndrome, transient ischemic
293
attack (TIA), ischemic stroke, pulsatile tinnitus, or bruit.
Uncommon findings include cranial nerve palsies and
loss of taste. Intradural dissection most often presents
with either ischemic stroke or SAH.
Extradural ICA Dissection
Clinical manifestations of extradural ICA dissection
arise either from local effects at the site of injury or
from distal ischemia. Extradural internal carotid dis-
sections with high-grade stenosis and occlusions seem
more likely to be associated with ischemic events,
while non-occlusive dissections seem to have higher
prevalence of local symptoms, such as Horners syn-
drome and cranial nerve palsies (30).
Pain is the most common albeit nonspecific local
effect, with headache being reported in at least half of
patients. Silbert et al. reported headache, typically
anteriorly located and ipsilateral to the dissection, in
68% of patients with ICA dissection (31). Constant
pain of a sharp, aching, or pressing quality is more
frequent than pain of throbbing or pulsating character.
Headache typically precedes other signs or symptoms
of dissection with a median interval between the onset
of headache and other neurologic symptoms of
approximately 4 days. Ten percent of patients with
ICA dissections have eye, facial, or ear pain without
headache (32,33).
Ophthalmologic manifestations represent the sec-
ond most common group of findings associated with
extradural ICA dissection. Ipsilateral Horners syn-
drome occurs in over half of patients (34). Horners
syndrome in the setting of ICA dissection is often par-
tial, consisting of only meiosis and ptosis without
anhidrosis as sympathetic fibers to the facial sweat
glands travel through the external carotid artery
(ECA) and remain uninjured. Ocular ischemic syn-
dromes such as, amaurosis, ischemic optic neuropa-
thy, and central retinal artery occlusion have been less
frequently reported and may result from emboli or
extension of dissection into the petrous or cavernous
segments (35).
Cerebral ischemia associated with extradural
ICA dissection may occur from two potential mecha-
nisms: embolization from thrombus at the site of dis-
section, or hypoperfusion due to luminal compromise.
The former appears to be the more common with
extracranial ICA dissection. TIAs, hemispheric strokes,
or both are seen in about half of patients (4).
Other signs or symptoms, while less frequent,
should be assessed in patients with suspected ICA
dissection. Pulsatile tinnitus is noted in nearly 25% of
patients. Lower CN palsies (CN VII to XII) have been
reported in 10%, ocular motility disorders as a result
of CN III, IV, or VI dysfunction in 4%, and dysgeusia,
likely from involvement of the chorda tympani, in 2%
(30,36).
Several mechanisms may underlie cranial nerve
palsies, including compression or stretching of the
nerve by the expanded artery or associated hematoma,
particularly when mass effect occurs in the region of
the skull base. An alternative mechanism may involve
interruption of the nutrient vessels supplying the
nerve (vasa nervosum). A combination of ipsilateral
cranial nerve findings and hemispheric deficits may
294 NEUROINTERVENTIONAL MANAGEMENT
mimic a brain stem stroke and have been referred to
as false localizing signs (37,38).
Extradural Vertebral Artery Dissection
Headaches and/or neck pain are typically the first
clinical features of extradural VA dissection. Head-
aches are located posteriorly and ipsilateral to the dis-
section in 83% of patients, while 43% present with
associated neck pain (4,31). Similar to the case with
ICA dissection, neurological signs are often delayed
with a median time of development of 14.5 hours after
the onset of headache (31). The most common neuro-
logical symptoms of VA dissection include dizziness,
vertigo, double vision, ataxia, and dysarthria. As with
ICA dissection, cerebral ischemia may occur either
from thromboembolism or hypoperfusion.
Stroke arising from extradural VA dissection is
most commonly the lateral medullary syndrome
although cerebellar, basilar tip, or posterior cerebral
artery strokes may also occur. Occasionally, anterior
spinal infarcts may occur. TIAs are reportedly seen
less commonly than in extradural ICA dissections (4).
Aneurysmal dilatation of the extracranial VA adjacent
to the cervical nerve roots may cause radicular motor,
sensory, and reflex abnormalities, most commonly at
the C5-6 level.
Extradural VA dissection has also been found to
be frequently associated with cervical spine fractures,
particularly those with a rotational component. While
a high index of suspicion should be maintained in
patients with this type of injury, there is disagreement
as to the clinical significance of vertebral dissection in
this setting and consequently, the need for treatment
(39,40).
Intradural ICA Dissection
Sequelae of intradural ICA dissections differ consider-
ably from those of the extradural ICA with ischemia
being more frequent than with extradural ICA dissec-
tions. In most series ischemia predominates as the
major symptom although SAH may also result from
intradural ICA dissection. In part, the differing pre-
sentations may reflect the proportion of spontaneous
dissections (4143). In a series reported by Ohkuma et
al. including 49 patients with intradural ICA dissec-
tion, 63% presented with ischemic symptoms and 36%
with SAH (9). In a series reported by Chaves et al.
describing spontaneous intradural ICA dissections,
ischemia developed in 90% while SAH was present in
only 10% (44). A few series also suggest that ischemia
may be a more common presentation than SAH in iso-
lated dissections of the MCA or ACA, although num-
bers are small and presentation may vary between
neurosurgical and neurological series (4547).
Severe unilateral headache almost always heralds
the onset of intradural ICA dissection and is followed
by symptoms of ischemia or SAH within minutes to
hours. The appearance of ischemic symptoms is there-
fore not only more frequent but also more rapid than
is the case in extradural dissections (41,45,47).
Migraine-type headaches have also been associated
with intradural dissection, but the etiology is unknown,
and the possibility of SAH must be thoroughly
investigated before a diagnosis of migraine can be
accepted in the setting of intradural dissection (44).
Cerebral ischemia due to intradural ICA dissec-
tion may be due to either hypoperfusion and/or distal
emboli, although hypoperfusion due to arterial narrow-
ing has been suggested to be a more prominent mecha-
nism than is the case in extracranial dissection (44).
Intradural VA Dissection
Four times more common than intradural ICA dissec-
tion, intradural VA dissection often represents exten-
sion from the more proximal V3 segment of the VA.
Dissection can remain confined to the VA or extend
into the PICA or basilar artery. Rarely, the dissection
primarily involves the basilar artery, PICA, or posterior
cerebral arteries. Intradural VA dissection is associated
with headache in approximately 55% of patients. Other
neurological symptoms include vertigo, tinnitus, nau-
sea, and vomiting. Cerebrovascular events include
ischemia of the cerebellum and brain stem, or SAH. As
is the case with extradural VA dissections, lateral
medullary or Wallenberg syndrome is the most fre-
quent ischemic stroke syndrome, occurring in 2643%
of patients who develop infarcts (48).
However, unlike intradural ICA dissections,
most series report that the majority of intradural VA
dissections are associated with SAH (49). A nation-
wide study in Japan evaluated features of 357 patients
with intracranial dissection without reported trauma.
Over 90% involved the VA. The major clinical presen-
tation was found to be SAH due to rupture, the pre-
senting feature of 60% of patients. The remaining
patients presented with ischemia or infarction due to
stenosis, occlusion or emboli from the dissection site.
In addition, the study found that recurrence was more
frequent in patients with SAH (14%) than in patients
with no hemorrhage (4.2%) (8). Other series have
reported SAH recurrence rates of over 70%, associated
with mortality exceeding 50% in the absence of effec-
tive treatment of the dissection (50).
In keeping with the high rate of SAH, aneurysmal
dilatation has been demonstrated in 4576% of intra-
dural VA dissections, a much larger proportion than is
the case with intradural ICA dissections (51,52).
DIAGNOSIS
Dissection may be diagnosed noninvasively using
ultrasonography, computed tomography angiography
(CTA), magnetic resonance imaging (MRI), and mag-
netic resonance angiography (MRA). Each of these has
been proposed as a reliable method to identify arterial
dissection, but each has its limitations. In most cases
however, digital subtraction angiography remains the
gold standard diagnostic test for the definitive diag-
nosis of both extradural and intradural dissections.
Digital Subtraction Angiography
Extradural Dissection
Digital subtraction angiography retains a major role in
diagnosing dissection, depending on the type and
location. In most cases of extradural ICA dissection,
MRI can provide the pertinent information necessary
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES
for diagnosis and medical management. Suspected
extradural VA dissection is less completely evaluated
by MRI than that involving the extradural ICA and
more often requires angiographic evaluation (see
below). Similarly, MRI can suggest the diagnosis of
intradural dissection. However, digital subtraction
angiography remains necessary to conclusively evalu-
ate virtually all suspected intradural dissections,
regardless of the artery involved. Angiography is also
indicated when endovascular treatment of dissection
or its sequelae is necessary.
Angiographic evaluation of suspected ICA dis-
section usually begins with injection of the common
carotid artery (CCA) on the suspected side of involve-
ment. Imaging of the CCA bifurcation depicts the
most proximal extent of ICA dissection since the CCA
bifurcation is usually spared in ICA dissection (53).
Evaluation should include the intracranial circulation
to demonstrate intracranial collateral routes if present.
Filming should be extended into the venous phase in
order to demonstrate slow flow or stagnation of con-
trast within damaged portions of the vessel, including
aneurysms.
Angiographic examination of suspected extra-
dural VA dissection often begins with contrast injec-
tion into the proximal subclavian artery with filming
of the extradural and intradural VA. A tourniquet is
placed on the ipsilateral arm to enhance reflux of con-
trast into the VA. This permits exclusion of proximal
VA abnormality prior to selective catheterization of
the vessel. After excluding proximal damage, selective
catheterization of the VA is performed to further eval-
uate the vessel.
Angiographic evaluation of the intracranial circu-
lation is essential in all cases of suspected dissection
to evaluate potential intradural extension of an extra-
dural dissection as well as to exclude related intracra-
nial abnormalities such as emboli.
Contralateral angiographic evaluation is impor-
tant to exclude bilateral dissection, which has been
reported to occur in from 12% to 25% of cases. Bilat-
eral VA dissection is more common than that involv-
ing the ICA (54).
Table 14.1 Angiographic Features in Extracranial ICA and VA Dissection (%)
Feature
Author/Artery/N
(arteries) Normal Stenosis Aneurysm
Mokri 76% 40%
(147)/Spont.
ICA/65
Dziewas 5% 41%
(54)/ICA/78
Dziewas 7% 37%
(54)/VA/46
Baumgartner 17% 17% 9%
(36)/ICA/200
Pelkonen 47% 22%
(55)/ICA/76
Bin Saeed 54%
(58)/VA/ 26
Classification of features varies between reports.
295
The most common angiographic findings in
extradural carotid dissection are luminal stenosis and
occlusion (Table 14.1). The irregular stenosis seen in
dissection differs in both location and configuration
from that caused by atherosclerotic disease. Dissection
characteristically spares the carotid bulb, concentri-
cally and irregularly narrows the vessel beginning
approximately 46 cm distal to the ICA origin, and
stops at the skull base. Reconstitution of the arterial
lumen characteristically occurs as the vessel enters the
petrous bone. Similarly, dissection resulting in occlu-
sion usually spares the proximal 46 cm of the ICA,
and has a tapered distal extent in the acute phase
(Fig. 14.1). Other angiographic findings which may be
identified in carotid dissection include intimal flap;
double lumen; intraluminal filling defects; and dissect-
ing aneurysms (55). Cerebral infarction was found in
76% of cases of vascular occlusion, but in only 40% of
cases with irregular luminal stenosis and 12% of other
non-occlusive angiographic findings (56).
Angiographic features of conditions that poten-
tially predispose to dissection should also be sought.
This most often includes FMD, a condition reported in
up to 20% of ICA dissections, a higher prevalence
than is found in either the general population or in
patients with VA dissection (54) (Fig. 14.2).
The most common angiographic feature of extra-
dural VA dissection is also irregular stenosis, either
with or without occlusion. Involvement most often
centers at the C12 level with intradural extension in
up to 15% of cases (57,58). Dissecting aneurysms are
less commonly found associated with extradural VA
dissection than is the case with either extradural ICA
dissection or intradural VA dissection.
Intradural dissections involve the VA far more
commonly than the ICA and its branches. Angio-
graphic findings of intradural VA dissection include
segmental narrowing, referred to as the string sign or
the pearl and string sign if narrowed areas are associ-
ated with adjacent segments of vessel dilatation. Addi-
tional angiographic findings include aneurysms, either
fusiform or saccular, double lumen, and tapered nar-
rowing with occlusion of the vessel. An angiographic
Slow Branch
Intimal flap Occlusion ICA-MCA flow occlusion FMD
29% 17% 24% 11%
41% 18%
56% 7%
72% 23%
(occlusion or
stenosis >
80%)
1% 29%
42%
296 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 14.1 Angiographic findings in extradural dissections. (A) Lateral CCA angiogram of the neck demonstrates characteristic flame-
shaped occlusion from dissection beginning several cm above the CCA bifurcation. (B) Lateral view of the head (patient A) shows ECA
collaterals reconstituting the intracranial ICA via the ophthalmic artery. (C) Lateral and (D) AP view shows characteristic narrowing of
ICA lumen beginning above the CCA bifurcation and returning to normal as the vessel enters the petrous bone. (E) Dissection with nar-
rowing and tell tale pouch representing mild aneurysmal dilation. (F) AP and lateral (G) view of ICA dissection with dissecting aneur-
ysm (arrow shows narrowing of residual lumen). (H) Surgical specimen from a different case with identical angiographic findings as (F)
and (G) demonstrates resected dissecting aneurysm. (I) Extradural VA dissection affecting the V3 portion.
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES 297

(A) (B) (C)

(D) (E) (F)

Figure 14.2 Angiographic findings in intradural VA dissection: (A) AP and lateral (B) views of left intradural VA dissection with intradural
dissecting aneurysm. Angiographic findings in a patient with bilateral intradural VA dissection: (C) AP and lateral (D) views of right VA
injection with string of pearls configuration. (E) AP view of left intradural dissecting aneurysm. (F) CTA demonstrates bilateral dissection.

pattern of isolated stenosis tends to be associated with
an ischemic presentation while those demonstrating
aneurysmal dilation, including the pearl and string
sign are more frequently associated with SAH at pre-
sentation (51) (Fig. 14.3).
Suspicion for intradural VA dissection, even
without a history of trauma, must remain high when
SAH, particularly involving the posterior fossa, is
found without identification of an aneurysm. In such
cases, both intradural VAs must be visualized angio-
graphically in order to exclude dissection as a cause
of the SAH.
A number of authors have reviewed the type and
frequency of angiographic findings in intradural VA dis-
section (Table 14.2). Terminology varies however, and
firm conclusions are difficult because of the small num-
bers reported. While aneurysmal dilation including the
pearl and string sign is commonly identified in intra-
dural VA dissections, stenosis is more common with
intradural ICA dissection. Although rare, dissections
involving the ICA branches may demonstrate either
stenosis or aneurysmal dilation (59).
Ultrasonography
Ultrasonographic techniques are commonly used in
the evaluation of both extracranial and intracranial
vessels. Duplex ultrasonography has two components:
it evaluates the alteration in the flow velocity by Dop-
pler spectrum analysis and the morphologic appear-
ance of the vessel wall with the help of B-mode
scanning. Color duplex ultrasonography combines
duplex ultrasonography with the addition of color-
coded blood flow.
Ultrasonography is more reliable in detection of
ICA dissection than VA dissection. However, as many
ICA dissections occur above the field of optimal insona-
tion, ultrasound techniques have significant limitations
298 NEUROINTERVENTIONAL MANAGEMENT
in this vessel as well. Duplex ultrasonography can
detect the following flow patterns in ICA dissection:
absence of flow, high resistance obstructive flow with
severely diminished systolic and absent or low diastolic
flow (staccato flow), diminished peak systolic velocity
with at least 50% reduction compared to the contrala-
teral side, and increased ICA velocity. B-mode scanning
can potentially demonstrate a tapered lumen, mem-
brane crossing the vessel lumen, double lumen, and
floating intimal flap (60). Sensitivity for ICA dissections
ranges from 68% in routine clinical practice to 95% in
highly experienced centers, particularly when severe
stenosis or occlusion is present. However, sensitivity
decreases to 20% in low grade stenosis (48,61). Interest-
ingly, with a reported negative predictive value esti-
mated at 97%, normal ultrasound findings essentially
excluded the possibility of extracranial ICA dissection
in acutely symptomatic patients (62). Arning et al.
Figure 14.3 Lateral common carotid angiogram in patient with
dissection (arrowhead) associated with characteristic changes of
FMD (arrow).
Table 14.2 Angiographic Features in Intracranial VA Dissection (%)
Feature
Author/N (arteries) String sign Pearl and string sign
Yoshimoto (148)/14 21% 14%
Shin (51)/24 58% (or occlusion)
Hosoya (76)/41 68%
Naito (149)/21 5% 38%
Classification of features varies between reports.
found that morphological criteria alone allowed detec-
tion of a dissection in 47.8 % of patients. By the com-
bined use of morphological and hemodynamic criteria
they identified ICA dissections at the time of admission
in 73.9%. An increase in sensitivity, to over 90%, was
reported by follow-up ultrasonography (63).
Ultrasonography is limited in excluding ICA dis-
sections involving relatively distal sites (64). Ultraso-
nography may however be helpful in follow-up
evaluation of treatment in confirmed dissection. The
study most often demonstrates normalization of the
Doppler spectrum within weeks to months.
Ultrasound is much less useful in the evaluation
of VA dissection. Obstruction by surrounding bone
from the V2 through V4 segments makes evaluation
of the majority of the vessels course difficult and
unreliable (64,65). In the V1 segment, stenosis can
sometimes be visualized as well as alteration in the
normal flow pattern, but the sensitivity of this finding
is unknown.
Magnetic Resonance Imaging/Magnetic Resonance
Angiography
The types of MRA used in clinical practice for the
detection of dissection include phase contrast, two-
dimensional (2D) and three-dimensional (3D) time of
flight (TOF), and contrast-enhanced MRA (CE-MRA).
TOF images depend on the movement of flow and the
flowing blood appears bright. TOF can demonstrate
intramural hematoma in which the vessel wall can
appear widened with increased signal secondary to
methemoglobin in the hematoma. TOF sequences per-
mit scanning long segments of the vessel within a
short period of time. TOF sequences are however,
prone to signal loss from turbulent blood flow and
can falsely give the appearance of stenosis. 3D TOF
has better spatial resolution and is less susceptible to
signal loss than 2D TOF. Phase contrast techniques
depend on the velocity and the direction of the flow.
Phase contrast sequences are time consuming and
therefore often degraded by artifact in ill or restless
patients.
CE-MRA has proven to be helpful in evaluation
of dissection and also has the added potential advant-
age of differentiating residual flow from mural hema-
toma (66). It can also demonstrate an intimal flap as
linear enhancement in the vessel wall. The sensitivity
of MR techniques is highest within the first 2 days
after the dissection occurs. MRI/MRA can be used for
follow up monitoring of dissections and can show
improvement within few weeks to months (67). MR
studies have limitations, however, as they may fail to
identify pseudoaneurysms, mild stenosis, and associ-
ated conditions such as FMD.
Aneurysm Double lumen Occlusion
7% 29% 21%
42%
32%
14% 5% 33%
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES 299

MRI has assumed a primary role in the evalua-
tion of extradural ICA dissection. Intramural hema-
toma, best seen on axial T1-weighted fat saturated
images as a hyperintense crescent-shaped signal, has
been noted to be a relatively specific finding (68)
(Fig. 14.4). Combined with narrowing or disappear-
ance of the central flow void, the finding has been
identified 70100% of dissected vessels. In addition,
MRA can identify luminal stenosis and occlusion
whose characteristic location can suggest dissection
even in the absence of hyperintense wall hematoma
(69). The sensitivity and specificity for MRI in detect-
ing cervical ICA dissection has been reported as 84%
and 99% respectively and for MRA, 95% and 99%
respectively. Recent data suggest that contrast-
enhanced MRA may also contribute significantly to
the noninvasive evaluation of extracranial carotid dis-
section (70).

(A) (B)

(C) (D)

Figure 14.4 Thirty-nine-year-old female presented with left hemiparesis 2 days following motor vehicle accident. (A) T2 axial image
shows deep watershed infarct on the right. (B, C) Axial T1-weighted MRI shows hyperintense mural hemorrhage involving the right ICA
(arrow). (D) AP right CCA angiogram shows irregular cervical ICA narrowing characteristic of dissection.
300 NEUROINTERVENTIONAL MANAGEMENT
An MRI study of confirmed extradural VA dis-
section showed ischemic lesions of the brain in 18 of
19 patients (95%). In the acute and subacute stage,
MRA detected signal abnormalities within the dis-
sected VA in 94% (16/17) but MRI was specific for
dissection in only 29% (71). The relatively low specif-
icity of MR for detecting VA dissection likely arises
from two possible confounding features. First, fat sur-
rounding the VA in the transverse foramina is com-
mon and may mimic high intensity thrombus in the
vessel wall. Fat suppressed images may be useful in
these circumstances. Second, slow flow in the venous
plexus surrounding the VA can also mimic clot,
though its typically bilateral presence may help to
identify venous flow (72). MRA can however, be help-
ful in the identification of luminal stenosis and occlu-
sion whose characteristic location may suggest
dissection even in the absence of hyperintense wall
hematoma or more specific features.
Computed Tomography Angiography
Computed tomography angiography (CTA) has
evolved into an accepted technique for detecting dis-
section. There are several advantages to this imaging
technique. Improvements in technology have allowed
for rapid data acquisition and interpretation. Multide-
tector CTA has enabled thinner sections allowing for
volume reconstructions. CTA is more widely available
than MRA, especially on emergent basis, though post-
imaging processing on a dedicated workstation is
often required. However, limitations secondary to
motion and bone artifact exist, as well as the minimal
risk of intravenous contrast administration. Also,
given the relatively young population of patients with
dissection and the frequent need for follow-up imag-
ing, the use of ionizing radiation is concerning.
CTA may demonstrate a narrowed eccentric
lumen, mural thickening, and thin annular contrast
enhancement. Calcification of dissection, particularly in
cases of dissecting aneurysm may also be demonstrated
on unenhanced images (Fig. 14.5). In a study of 16
patients with cervical ICA dissection, Leclerc et al. dem-
onstrated narrowing with maximal stenosis in the distal
portion of the dissected vessel, in contrast to maximal
stenosis in the proximal portion in atherosclerotic ICA
disease (73). CTA has been reported to have sensitivity
and specificity of 100% for the cervical ICA, with eccen-
tric luminal narrowing in the distal cervical ICA as the
most robust finding. For extracranial VA dissection,
CTA has reportedly shown sensitivity of 100% and spe-
cificity of 98% (73,74). In retrospective comparative ser-
ies of multidetector CTA and MRI study comprised of
DWI, fat-suppressed sequences and CE-MRA, CTA was
able to identify more imaging features associated with
dissection, especially in VAs, and thus was the preferred
study in the majority of cases (75).
Intradural Dissection
The use of ultrasonography, MRI/MRA, and CTA
has been reported in the literature for intracranial
arterial dissection, but the sensitivity and specificity of
these tests are unknown. Using MRI and MRA as a
screening test, Hosoya et al. demonstrated intramural
hematoma on T1-weighted images in 32% of cases
with intracranial dissection (76). A double lumen was
seen on 3D spoiled gradient-recalled acquisition
(SPGR) in 87% of cases and thus has been considered
as a more sensitive test then T1 images alone.
There are three different patterns that can be seen
with MRA in association with intradural dissection:
focal aneurysmal dilatation, intimal flap, and occlu-
sion/stenosis. In a case series by Shin et al., MRA find-
ings of aneurysmal dilatation and intimal flap were
found to correlate well with conventional angiogram
findings. However, the accuracy of an MRA finding of
luminal stenosis was difficult to assess. This MRA find-
ing was difficult to differentiate from hypoplasia, vaso-
spasm, or dysplasia without dissection (51).
TREATMENT
Some dissections are believed to occur without pro-
ducing any symptoms and therefore may remain com-
pletely unrecognized. Therefore, it is possible that
some dissections have a benign prognosis and do not
require therapy. Unfortunately, at present there is no
reliable method to identify these low risk patients and
observation without therapy cannot be recommended.
In the vast majority of cases, medical treatment repre-
sents the first line of therapy.
Medical Treatment of Extradural Dissection
Patients with arterial dissection who present with acute
ischemic stroke within 4.5 hours of symptom onset
may be candidates for thrombolysis with intravenous
tissue plasminogen activator (IV-tPA), provided they
meet the appropriate inclusion criteria without having
medical contraindications (77,78). Patients who develop
dissection secondary to severe trauma are usually
excluded from receiving intravenous tPA, but many
patients with dissection have trivial or no trauma, thus
intravenous tPA is not contraindicated. Theoretically
IV-tPA increases the chance of potential bleeding into
the injured vessel wall causing progression to complete
vessel occlusion, but there has been no report support-
ing this concern. In a prospective cohort of 1062 acute
stroke patients treated with IV-tPA, outcomes and com-
plications of treatment were compared in patients with
extracranial artery dissections (n = 55) to those with
strokes due to other etiologies. IV-tPA treated patients
with extracranial cervical dissections had lower chan-
ces of excellent recovery with 90-day modified Rankin
score 1 (36.4% vs. 44.4% in non-dissection related
strokes), and that difference persisted despite adjust-
ment for age, gender, and stroke severity. However,
this result was not driven by a difference in intracranial
bleeding or recurrent stroke rates between the two
groups (79). Thus IV-tPA seems to be safe, albeit less
efficacious in treatment of acute stroke attributed to
cervical arterial dissections.
Between 3 and 6 hours after symptom onset, intra-
arterial (IA) tPA has also been advocated, with adminis-
tration of the lytic agent distal to the dissected arterial
segment (80). There have been several case series of dis-
section successfully treated with IA-tPA (24,8183)
(Fig. 14.6). Some authors have recommended IA-tPA
even within 3 hours to avoid the aforementioned
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES 301

(A) (B) (C)

(D) (E) (F)

Figure 14.5 Axial unenhanced CT demonstrates peripheral calcification involving the right (A) and left (B) ICA (arrows). Left common
carotid angiogram (C) and 3D (D) views show irregular dissection beginning approximately 12 cm distal to the origin of the ICA,
expanding into aneurysm and resuming normal caliber at the skull base. Right common carotid angiogram (E) and 3D angiogram (F)
illustrate dissection on the right.
302 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F) (G)

[H]

(H) (I) (J) (K)

Figure 14.6 Post motor vehicle accident, patient presents with right amaurosis and left hemiparesis. CTA (A, B) demonstrates bilateral
narrowing (arrows) but patent ICAs compatible with dissection. Intracranial image (C) shows filling defect (arrow) in proximal right
MCA. Angiogram of left CCA (D) demonstrates continuous filling of dissected LICA. Angiogram of right CCA (E) early and later (F)
demonstrates delayed but continuous filling of RICA with intraluminal clot in cervical and intracranial ICA. Post tPA microcatheter injec-
tion of right supraclinoid ICA (G) demonstrates reopening of supraclinoid ICA and MCA. Post treatment right CCA injection (H) shows
residual intraluminal clot, and no stenting was performed. Left VA injection shows filling of both posterior circulation and right MCA (I).
Patient was treated with acute anticoagulation followed by antiplatelet therapy with resolution of left hemiparesis and no additional neu-
rological symptoms. Follow-up at 3 months demonstrates normal configuration of right (J) and left (K) ICA.
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES
theoretical risk, though others recommend intravenous
IV-tPA in this context (see below) (84).
After the hyperacute period, antithrombotic
therapy is usually recommended, though there has
been no clear agreement on the optimal medical man-
agement. In the first few days, there appears to be a
relatively high risk of ischemic symptoms, thus anti-
coagulation therapy has commonly been recom-
mended (85,86). There are however no controlled
trials supporting the use of anticoagulation. The risk
of anticoagulation is both cerebral and systemic hem-
orrhage, and early anticoagulation in most stroke
patients yields no net benefit (87,88). A large system-
atic review of 49 observational studies comprising 683
patients suggested no significant benefit for anticoa-
gulation over antiplatelet therapy with regard to the
outcome of death or disability from the initial stroke
and stroke recurrence (89). Another systematic review
of 34 case series including 762 patients with either
carotid or VA dissections echoed the abovementioned
findings (90).
Recently, three large cohorts examined the risk
of vascular events with extracranial dissection. Touze
et al. showed an annual stroke incidence to be only
0.3% in a historical cohort of 459 patients with carotid
and vertebral dissections (91). On the other hand, in a
prospective cohort of 250 patients presenting with a
clinical vascular event, Weimar et al. found the risk to
be as high at 5.2% during hospitalization and 10.7%
within the first year (92). The most robust data to date
come from a prospective cohort of 298 patients
reported by Georgiadis et al. that found a very a low
overall risk of stroke (0.3% within 3 months) with
extracranial carotid dissections regardless of treatment
with aspirin or anticoagulation. However, recurrent
TIAs and retinal ischemic events may have been less
frequent in patients treated with anticoagulation com-
pared to those treated with aspirin. Recurrent ische-
mic events of all types were more common in patients
who presented with initial ischemic symptoms com-
pared to those who only had local symptoms. A
potential limitation of this study was the initial exclu-
sion of eight patients who received early revasculari-
zation therapies (93).
The optimal antithrombotic treatment of acute
extracranial dissections is currently unclear, and the
data remain difficult to interpret. The growing body
of evidence hinders the recommendation of antico-
agulation as the mainstay of early treatment. The
American Heart Association and American Stroke
Association guidelines note that early anticoagulation
does not lower the risk of early recurrent stroke or
early neurologic worsening, and that the efficacy of
urgent anticoagulation is not established for treatment
of patients with arterial dissections (94). For most
patients with extracranial dissection, antiplatelet ther-
apy is recommended (150). However, it may be rea-
sonable to judiciously use anticoagulation in the acute
period and for about 3 months thereafter in certain
cases, such as those with multiple recurrent ischemic
events in the distribution of dissected artery, micro-
emboli detected with transcranial Doppler, which
have been associated with a seven-fold greater rate of
new vascular events (24), or those with evident intra-
luminal thrombus. Even in these circumstances,
303
antiplatelet agents are preferred, and anticoagulation
should likely be avoided when the risk of bleeding is
high, particularly when intracranial dissection is present
due to the high risk of SAH (56), or in the setting of a
large infarction due to the increased rate of sympto-
matic hemorrhagic transformation (87,88).
Follow-up imaging studies are recommended in
approximately 3-month intervals until recanalization
is established. If repeat studies show residual stenosis
and irregularity, anticoagulation treatment may be
continued in select cases (95,96). If a dissection recan-
alizes, it is appropriate to change anticoagulation ther-
apy to antiplatelet therapy for secondary stroke
prevention, or discontinue antiplatelet therapy in
patients with isolated local symptoms lacking an indi-
cation for primary stroke prevention. The complete
recanalization rates of dissection-attributed cervical
artery occlusive disease are estimated to be 16% at 1
month, 28% at 3 months, 45% at 6 months, and up to
60% at 12 months. The majority of complete recanali-
zations seems to occur within 6 months, but this proc-
ess may take as long as 18 months in 0.9% of cases.
Isolated local symptoms and signs at presentation are
the strongest predictors of complete recanalization. On
the other hand, cervical artery dissection presenting
with ischemic stroke, aortic root dilation, and C677T
MTHFR polymorphism appears to be independent
negative predictors of recanalization (21,97). Thus, the
use of anticoagulation therapy beyond 6 to 12 months
is not recommended even if there is persistent irregu-
larity or stenosis of the lumen, as there is low risk of
stroke beyond this mark (67,84,98).
The feasibility phase of the prospective multicen-
ter randomized-controlled trial in acute extracranial
carotid and VA dissection is currently underway. The
Cervical Artery Dissection in Stroke Study (CADISS)
aims to clarify the optimal medical therapy as it com-
pares single and dual antiplatelet therapy with 3
months of anticoagulation with respect to recurrent
vascular events, death, and serious adverse events of
therapies (94).
Surgical Treatment of Extradural Dissections
Surgical options for treatment of extradural dissection
have included carotid ligation, aneurysmal resection
with carotid reconstruction, and extracranial to intra-
dural ICA bypass (supraclinoid or petrous ICA) (99).
However, surgical morbidity may be high. Periopera-
tive stroke rates may approach 10%, peripheral cranial
nerve injury occurs in more than half, and mortality is
2%. Asymptomatic extradural dissecting aneurysms
generally do not warrant surgical intervention as they
tend to resolve spontaneously or at least remain sta-
ble. However, symptomatic dissecting aneurysms may
be resected with reconstruction of the ICA with saphe-
nous vein graft or primary reanastomosis (100102).
Increasing experience and evidence support the
conclusion that in many cases where medical treat-
ment is not appropriate or unsuccessful, endovascular
procedures may be preferable to a surgical approach
for treatment of dissection-related injury. Neverthe-
less, additional study continues to more rigorously
document the indications and optimal management of
these patients.
304 NEUROINTERVENTIONAL MANAGEMENT
Endovascular Treatment of Extradural
Dissections
While medical therapy is currently the mainstay and
initial management in most cases of extradural carotid
or VA dissections, recognition of the role of endovas-
cular treatment and its timely application has become
increasingly important. As in all neuroendovascular
techniques, recognition of proper indications for inter-
vention is just as essential as meticulous technique to
insure patient benefit (103).
In the acute period following extradural dissec-
tion, symptoms arise most often from intracranial
emboli and may require emergent thrombolysis of
either the carotid or vertebral circulations. In cases
where intravenous thrombolytic treatment is ineffec-
tive or contraindicated, IA-thrombolysis plays a role.
Less frequently, acute symptomatic arterial stenosis or
occlusion may require revascularization of the dis-
sected artery using angioplasty and stenting.
The need for endovascular treatment most often
occurs with symptomatic extradural ICA dissections
(Fig. 14.7). Nevertheless, extradural vertebral dissec-
tions with stenosis or occlusion may also require
emergent treatment in cases with significant VA
asymmetry or intracranial emboli. A number of inves-
tigators have confirmed not only the dismal outcome
of untreated acute vertebrobasilar embolic occlusion
but also the potential for significant benefit if throm-
bolysis and reopening is accomplished prior to irre-
versible infarction (104,105).
In general, indications for endovascular treat-
ment of extradural dissections include the following:
1. patients in whom intravenous thrombolysis for
ischemia is contraindicated because of systemic
hemorrhage, recent surgery, or trauma;
2. patients with contralateral stenosis or occlusion;
3. patients in whom there is a need for elective occlu-
sion of the contralateral internal carotid or VA for
other pathology;
4. patients in whom there is a need to avoid flow
increase through the anterior communicating
artery because of an associated aneurysm; and
5. when intradural extension of dissection occurs
with consequent risk of SAH (106),(107).
IA-thrombolysis may be needed acutely when dis-
sections result in symptomatic intracranial emboli or
arterial narrowing with superimposed clot causing
impairment of flow. In such cases, thorough investiga-
tion as to the etiology of cerebral ischemia is necessary
to identify dissection if present. Identification of salvage-
able tissue on neuroimaging studies is becoming more
widely available and can assist in the selection of the
most appropriate patients for acute treatment. IA-throm-
bolysis is performed using the techniques for acute
stroke (see Chapter 16). Particular attention must how-
ever be directed to determining the presence and extent
of dissection-related injury and consideration given to
specific treatment of the dissected vessel if necessary.
As noted, small series and case reports support the
use of IA-thrombolysis in dissection, particularly outside
the conventional time constraints of intravenous throm-
bolysis, or in specific cases where intravenous thrombol-
ysis is contraindicated (24,8084).
In cases of symptomatic stenosis as a result of
dissection, angioplasty using a stent can be used to
exclude a false lumen, relieve hemodynamically sig-
nificant stenosis, and restore the true lumen to more
normal size, thereby increasing flow (108,109). In a
small cohort of 26 patients undergoing carotid angio-
plasty and stenting for cervical carotid artery dissec-
tion, endovascular interventions were found to be
effective in reducing stenosis and had low rates of
ischemic complications (110). The technique has also
been found to be successful when the dissected ves-
sel is completely occluded. In cases of complete
occlusion however, the potential for distal emboliza-
tion on reopening the vessel may be substantial
depending on the clot burden within the occluded
segment of the vessel. Careful consideration must be
given to relative risks and benefits of reopening an
occluded vessel.
The technique of stent angioplasty begins with
angiographic confirmation of the location and extent of
stenosis resulting from dissection. A microcatheter and
microguidewire (0.36 to 0.45 mm) are then maneuvered
through the true arterial lumen using roadmapping
angiography. Multiple projections may be required and
care is taken to insure that the true lumen is selected
and catheterized. The microcatheter is advanced to a
position distal to the damaged segment.
An exchange length (260300 cm) microguide-
wire is used to exchange the microcatheter for the
stent catheter. The stent is then deployed within the
stenotic segment of the vessel. Because of the rela-
tively low levels of radial force needed for restoration
of lumen diameter in dissected vessels, primary angio-
plasty is not normally necessary and may place exces-
sive stress on the already damaged arterial wall. The
stent maintains sufficient radial force on the damaged
segment of the artery wall, placing the layers sepa-
rated by the intramural hematoma in contact with one
another. The result is obliteration of the false lumen,
restoration of the normal luminal diameter, and reso-
lution of the stenosis (Fig. 14.8).
The stent length should be chosen to cross the
entire damaged segment of the vessel when possible.
In some cases of long segment dissection, multiple
overlapping stents may be required. In such cases, the
initial stent is usually placed at the proximal margin
of the dissection to eliminate the inflow zone of the
false lumen. Following initial stent placement, addi-
tional angiography is done to confirm the need for
additional stents. Both self-expanding and balloon-
mounted stents have been found to be suitable for
this application (107). Following stent placement,
patients are maintained on an appropriate antiplatelet
regimen to prevent stent thrombosis.
In cases of dissection-associated aneurysm, stent
placement has also been found useful, both alone as
well as to provide a scaffold to permit coil emboliza-
tion (see below).
The dynamic nature of carotid and VA dissec-
tions and their ability to change over very short peri-
ods of time has been emphasized (17). Consequently,
the need for endovascular treatment of extradural
internal carotid or vertebral dissections may also
develop after the acute phase of the injury (111).
Because medical treatment of extradural dissections
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES 305

Acute carotid artery dissection

Medial defect

True lumen

Inflow zone

Medial defect

True lumen False lumen

Inflow zone

1. Spontaneous 2. Formation of 3. Residual 4. Pseudoaneurysm

healing false lumen stenosis formation

GDC
electrolyticaly
detachable
coils

Stent acts Stent acts

to decrease hemodynamically as a scaffold to
significant stenosis buttress coils
or to occlude false lumen

Figure 14.7 Simplified schematic illustration of the pathophysiologic process of carotid artery dissection proceeding from the acute
stage to either spontaneous healing (1), formation of false lumen (2), residual stenosis of varying degree or complete occlusion (3),
and formation of a pseudoaneurysm (4). A stent is used in cases that have not responded to medical therapy either to relieve a hemo-
dynamically significant stenosis, to occlude a false lumen, or to serve as a scaffold to enable coil embolization of a wide-necked pseu-
doaneurysm. Source: From Ref. (107).

is usually quite effective, situations which merit
delayed intervention, while uncommon, usually repre-
sent failure of medical therapy (112). They are usually
manifested by new onset, fluctuating, or recurrent
neurological dysfunction referable to the vascular
distribution of the damaged artery (91). As is the case
in the acute phase, delayed ischemic symptoms usu-
ally result either from recurrent emboli or develop-
ment of symptomatic stenosis with poor collateral
circulation (Fig. 14.9).
306 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 14.8 Forty-five-year-old female with 1 week of right frontal headache and neck pain following a motor vehicle accident. Exam
remarkable for right Horners syndrome, no other neurological deficits. Unenhanced CT on admission demonstrated subacute right
hemispheric watershed infarct (A, B, C). CT angiography shows narrowing of RICA compatible with dissection in axial (D) (arrow) as
well as lateral (E) and AP (F) images. Patient was initially anticoagulated but 24 hours later experienced transient left-sided weakness.
AP view (G) from angiogram confirms right ICA dissection. Stent placement within RICA (H). Post stent angiogram (I).
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES 307

(A) (B) (C)

(D) (E) (F)

Figure 14.9 Twenty-four-year-old male status post gunshot wound to left neck. (A) Initial lateral and AP (B) angiogram demonstrates
irregularity (arrow) consistent with LICA dissection. Six months later, while on anticoagulation therapy, patient presented with aphasia last-
ing 4 hours followed by complete resolution. CT scan (C, D) shows hyperdensity within left MCA branches (arrow) representing emboli.
(E) Angiogram demonstrated interval growth of dissecting aneurysm. (F) Patient underwent carotid occlusion (lateral angiogram).

In either situation, persistent abnormality within Endovascular Treatment of Extradural

the damaged segment of the artery is usually identi-
fied. Specific features include failure of the dissected
segment to heal effectively with the development of
luminal stenosis, or persistent arterial damage with a
nidus of clot formation sufficient to overwhelm the
effects of medical treatment. In either case, angiographic
evaluation or treatment of the persistent damage is often
required. Evaluation must determine whether intracra-
nial emboli are present, the status of the dissected vessel,
and collateral routes to the affected vascular distribution.
Any areas of damage not present or recognized at the
time of the initial evaluation must also be sought and
identified.
When intracranial embolic occlusion occurs after
the acute phase of dissection, thrombolysis, either
intravenous or intra-arterial, may be necessary as an
initial step. Should symptoms have occurred in a set-
ting of appropriate medical therapy, additional endo-
vascular treatment such as stent angioplasty may be
required to minimize the chance of recurrence.
Dissection-Associated Aneurysms
As noted above, some controversy often surrounds
the terminology applied to aneurysms associated with
arterial dissection. While the underlying pathology is
similar regardless of the morphology, the morphologi-
cal features of a dissecting aneurysm have major
implications for endovascular techniques that may be
useful for its treatment.
Extradural aneurysms associated with dissection
represent a radiologic finding that often engenders
considerable concern and uncertainty as to manage-
ment. While extradural ICA aneurysms may arise
from other causes including atherosclerosis and infec-
tion, a significant percentage is the result of prior
dissection. Older series have recommended nearly
universal treatment of extradural carotid artery aneur-
ysms to prevent neurological deterioration (113). Sev-
eral recent studies, however, have found that
extradural dissecting aneurysms of either the internal
308 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 14.10 Acute neck-pain following motor vehicle accident. Initial MRI (not shown) demonstrated wall hematoma. Two months
post accident, left Horners syndrome noted after transient right arm weakness. (A) Lateral and (B) AP view of LICA dissecting aneur-
ysm. (C) Unsubtracted view of stent in place. (D) Six-month follow-up with resolution of aneurysm. No symptom recurrence.

carotid or VAs, although common, rarely enlarge over
time. These studies have also concluded that the vast
majority of such aneurysms remain asymptomatic in
the face of appropriate medical management, and in
most cases require no additional treatment (114,115).
Nevertheless, documented examples confirm that
dissection-associated aneurysms can, under some
circumstances, cause neurological deterioration as a
result of embolization or expansion with compression
of cranial nerves (116119). In addition, when located
within or adjacent to the skull base, these aneurysms
may pose a significant risk of potentially fatal bleed-
ing (28). Consequently, despite uncertainties regarding
its specific role, stenting should remain a considera-
tion for symptomatic patients with nonocclusive caro-
tid dissection and pseudoaneurysm (120). Small
studies support good safety and effectiveness in both
the acute phase and in multi-year follow-up (121).
Analogous to the role of cavernous carotid
artery injury and aneurysm rupture in the genesis
of direct carotid cavernous fistulas, extracranial VA
dissection with disruption of the artery wall may
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES
engender vertebrovenous fistula formation either
with or without an identifiable aneurysm. While
most often associated with penetrating trauma, blunt
trauma with VA dissection may also result in vertebro-
venous fistula formation. Extracranial VA dissection-
associated aneurysm also been rarely reported to be
associated with spinal SAH. This exceedingly uncom-
mon occurrence is believed to result from extension of
VA dissection and aneurysm to involve an adjacent
radiculomedullary artery (122).
Consequently, dissection-associated extradural
aneurysms should be seriously considered for treat-
ment when they are found to be enlarging or caus-
ing symptoms related to mass effect, or symptoms
occur which are attributable to emboli from an extra-
dural aneurysm in a patient on appropriate medical
management.
Therapy for dissecting extradural aneurysms is
usually feasible using endovascular techniques. Often
the simplest, safest, and most effective option may be
permanent occlusion of the involved carotid or VA.
Feasibility of vessel sacrifice is of course dependent
on collateral flow from adjacent circulations. Prior to
sacrifice of the vessel, an occlusion test is usually per-
formed as outlined elsewhere (Chapter 9).
A number of techniques have been described to
treat extradural aneurysms with preservation of the
involved vessel. The morphology of the aneurysm is a
primary feature that dictates the endovascular technique
that may be successful in treating the lesion. In cases of
extradural aneurysms with relatively narrow necks,
treatment has been accomplished using coil embolization
alone. More recently stent-assisted coiling has been rec-
ommended (123). Similar to the treatment of wide-
necked or fusiform intracranial aneurysms, a stent is
placed across the dissected segment and neck of the
aneurysm. The stent provides support to the dissected
vessel wall and also prevents herniation of coils into the
parent vessel.
A significant percentage of dissection-related
aneurysms will resolve after endovascular stent place-
ment without the necessity for additional coil emboli-
zation (124126).
The presence of the stent across the aneurysm
neck likely results in impaired inflow and promotes
intra-aneurysmal clot formation with subsequent
thrombosis and closure of the aneurysm (Fig. 14.10).
Placement of covered stent grafts has been
reported in small numbers of cases to be successful in
obliterating dissection-associated aneurysms (127129).
The technique has shown promise at moderately long-
term follow-up, and may be especially useful in cases
of patients symptomatic from mass effect (130).
Despite the frequent success of endovascular
treatment, a role for surgical treatment remains for
some cases of extradural aneurysms of the ICA. This
is ideally accomplished for lesions located relatively
proximally in the neck and arises most often as a
result of difficulty with placement of endovascular
devices across the lesion. Difficulty in crossing the
lesion may be due to associated arterial disease such
as FMD or excessive tortuosity of the vessel. The latter
feature is encountered with some frequency and has
in fact been noted as a potentially predisposing factor
to carotid dissection (19). The use of more flexible
309
stents has, however, been reported to make even rela-
tively tortuous vessels amenable to endovascular treat-
ment (131).
Lastly, aggressive evaluation and consideration
of endovascular or surgical treatment should be enter-
tained in situations where intradural extension of
extradural dissection is suspected. This situation most
often affects the region of dural penetration of the
VAs (57). As discussed below, intradural dissection,
whether primary or by extension from an extradural
injury, may represent a significant risk of morbidity
and mortality as a result of either ischemia or SAH.
Medical Treatment of Intradural Dissection
Treatment of intradural dissection is dictated by the
initial clinical event. Patients who present with ische-
mic stroke are usually treated with antiplatelet or
anticoagulant therapy with the reasoning and cav-
eats described above for extradural dissections.
Nevertheless, because systemic medical therapy may
present excessive bleeding risks with intradural dis-
sections, careful diagnosis prior to medical treatment
is necessary. As with extracranial dissections, surgi-
cal or endovascular approaches may be considered
in patients whose symptoms recur despite medical
therapy.
Patients with intradural dissection who present
with SAH often require aggressive treatment with
either surgical or endovascular repair, since conserva-
tive medical management alone may result in poor
outcome (50,132).
SURGICAL TREATMENT OF INTRADURAL
DISSECTION
Surgical procedures have included proximal occlusion
of the parent artery, trapping of the lesion, vascular
reconstruction, surgical wrapping, or clipping of the
aneurysm. Because the vast majority of intradural dis-
secting aneurysms are fusiform, the role of clipping,
the standard surgical technique for addressing saccu-
lar aneurysms, is limited (132).
ENDOVASCULAR TREATMENT OF INTRADURAL
DISSECTIONS
Because of the propensity for vessel rupture and
recurrent hemorrhage, intradural dissections require
anatomic correction at a higher rate than with extra-
dural dissections. Nevertheless, indications for treat-
ment as well as alternatives remain controversial. In
cases without aneurysm or evidence of hemorrhage
who present with ischemia, conservative treatment or
medical therapy has most often been advocated.
In patients presenting with SAH, poor outcome
with conservative management has been emphasized
and a number of surgical and endovascular alterna-
tives have been reported (50,132).
Endovascular treatment has assumed a major role
in the management of intradural dissecting aneurysms.
A number of endovascular treatments have been advo-
cated in the management of intracranial dissections.
Permanent endovascular occlusion has been
shown to be a useful therapeutic endovascular
310 NEUROINTERVENTIONAL MANAGEMENT

technique for the treatment of fusiform and acute
intradural dissecting aneurysms of the vertebrobasilar
system (133135). Techniques vary, utilizing combina-
tions of detachable balloons and coils and are often
preceded by test occlusion of the involved vessel if
this can be safely accomplished. Leibowitz et al.
reported long-term outcomes suggesting that patients
with aneurysms involving only one VA, where com-
plete thrombosis can be achieved by permanent occlu-
sion, have better clinical outcomes than those with
aneurysms involving the basilar artery or both VAs,
where complete thrombosis cannot achieved by using
permanent vessel occlusion (136). The authors also
reviewed prior series supporting the usefulness of
this relatively simple endovascular occlusion techni-
que. Other investigators have emphasized the techni-
que of trapping the diseased segment proximally and
distally to insure closure of the dissection site by the
coil mass thereby preventing regrowth or rehemor-
rhage (137) (Fig. 14.11). Endovascular occlusion of the
intradural VA has also been found useful in cases
where dissection involves isolated vertebrobasilar

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 14.11 Thirty-six-year-old female with acute onset headache, no SAH. (A) AP view of left VA angiogram at presentation demon-
strates mild irregular fusiform dissection of intradural VA (arrow). (B, C, D) MRI at time of presentation shows minimal enlargement of
intradural left VA (arrow). (E, F, G) CT scan 10 years after initial presentation, when patient developed progressive left hemiparesis,
shows hyperdense mass in region of previous abnormality. (H) Angiography of right VA (J, K) demonstrates growth of thrombus filled
fusiform aneurysm. (I) AP plain film following coil embolization with packing of aneurysmal segment and left VA occlusion.
 DISSECTIONS OF THE CAROTID AND VERTEBRAL ARTERIES
branches or extends more distally into the basilar
artery (138) (Fig. 14.12). Nevertheless, obvious limita-
tions of the technique exist in more extensive dissec-
tions where vessel preservation is necessary (139).
The appearance of newer endovascular techni-
ques with the potential to preserve vessel patency has
not excluded permanent vessel occlusion from the
endovascular therapeutic armamentarium. Reports of
reformation of aneurysms following stent supported
embolization treatment designed to preserve arterial
patency have led to suggestions that parent vessel
occlusion remain the first option for treatment in
patients who will tolerate sacrifice of the parent vessel
along its diseased segment (140).
Nevertheless, techniques that promise to treat
intradural dissections while preserving vessel patency
are of increasing clinical importance and interest.
Advantages include maintaining maximum intracra-
nial flow, a particular advantage in older patients who
might have coexisting vascular disease, but also
potentially beneficial in younger patients who would
be expected to live longer with the results of treat-
ment. In addition, vessel-preserving treatment extends
the advantages of endovascular therapy to patients
who will not tolerate vessel occlusion including those
with more extensive lesions.
The usually fusiform morphology and structur-
ally incompetent wall of intradural dissecting aneur-
ysms eliminates any major role for selective aneurysm
embolization using coils alone. The use of stents,
either alone or more often followed by coil placement
through the interstices of the stent, has emerged as a
significant advance in managing intradural dissections
while preserving the affected vessel (141). The techni-
que is identical to that utilized in stent supported coil
embolization of saccular aneurysms. It has shown
high rates of success in the limited numbers of
reported cases with low incidence of delayed vessel
occlusion or ischemic stroke (123) (Fig. 14.13).
Stent treatment of dissecting aneurysms extends
endovascular options to portions of vessels where sacri-
fice of a dissected segment is not possible without neu-
rological deficit. This is particularly true when
intradural vertebral dissections extend to involve the
(A) (B)
Figure 14.12 A. Lateral right VA angiogram showing dissection of right PICA (arrow) in patient who presented with SAH. (B) Unsub-
tracted and subtracted (C) images following coil occlusion of right PICA.
311
basilar artery (142). The usefulness of stenting has been
demonstrated in both aneurysmal and occlusive basilar
dissection (143). In addition, increasing numbers of
reports document the effectiveness of the technique in
intradural dissections of the anterior circulation (144).
Recent reports indicate that intradural fusiform
aneurysm treatment may also be accomplished using
covered stent grafts (130,145). Long-term outcome and
specific indications for this technique await additional
experience.
PROGNOSIS AND OUTCOME
The majority of patients with stroke due to ICA or
VA dissection have relatively mild deficits with ulti-
mate resolution of their symptoms, though a signifi-
cant minority (510%) suffer disabling stroke. The
annual recurrence rate of thromboembolic episodes
post cervical carotid dissection is reported to be 0.3
10.7%, with prospective studies supporting the lower
end of that range and retrospective and inherently
more biased studies suggesting higher risk. Higher
rates are also typically reported in patients present-
ing with stroke while lower rates occur in those pre-
senting with only local or no symptoms. The greatest
risk of recurrence seems to occur during the first
few days in patients with ischemic events at presen-
tation (91,92,112). There may be a tendency for VA
dissections to cause more severe strokes than ICA
dissections. Traumatic dissections appear to have a
worse prognosis than spontaneous dissections
in terms of persistent neurologic symptoms (146).
Patients with intradural dissection have worse out-
comes compared to those with extracranial dissec-
tion. Intradural dissection associated with dissecting
aneurysm and associated SAH carries high risk of
morbidity and mortality, 2050%, and thus requires
urgent medical, endovascular, or surgical interven-
tion as discussed above (135).
In general, the rate of recurrent arterial dissection
is low. Recurrence rate in previously unaffected vessels
within 3 to 12 months of admission was reported to be
less than 3%. The majority of recurrent dissections was
asymptomatic or presented with isolated local signs
(C)
312 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 14.13 Enlarging intradural VA dissecting aneurysm in a patient who had already undergone left VA occlusion for an enlarging
intradural VA aneurysm (*coil mass within occluded left VA dissecting aneurysm). (A) Subtracted AP view after placement of two
overlapping stents across the aneurysm neck (arrowheadsmarkers at the ends of the overlapping stents). (B) Microcatheter (arrows)
crosses the interstices of the stent to deploy coils within the aneurysm. (C) Aneurysm coiled, follow-up confirmed aneurysm occlusion
with normal flow through parent vessel.
and symptoms (21). Recurrence in the same vessel is
rare, though may possibly occur due to a vascular
defect created by scar tissue formation. The recurrence
rate may also be higher in patients with a family his-
tory of arterial dissection (20).
Patients who have had cervicocerebral arterial dis-
sections should be advised to avoid activities that may
cause sudden rotation or extension of the neck. How-
ever, no substantial data exist to define the limits of
activity for these patients. There is no apparent reason to
manage physical therapy differently during rehabilita-
tion following stroke resulting from dissection.
Dissection of the carotid and VAs represents a
significant etiology of stroke in young patients. The
understanding, recognition, and diagnosis of this dis-
order has rapidly advanced in recent years and the
development of endovascular techniques made a
major contribution to those patients for whom medical
treatment is not suitable.
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145. Chiaradio JC, et al. Intravascular graft stent treatment of a
ruptured fusiform dissecting aneurysm of the intracranial
vertebral artery: technical case report. Neurosurgery 2002;
50: 21316; discussion 216--17.
146. Ast G, et al. Spontaneous dissection of the internal carotid
artery in 68 patients. Eur J Med 1993; 2: 46672.
147. Mokri B. Dissections of cervical and cephalic arteries. In:
Meyer FB, ed. Sundts Occlusive Cerebrovascular Disease.
Philadelphia: W. B. Saunders Co, 1994.
148. Yoshimoto Y, Wakai S. Unruptured intracranial vertebral
artery dissection. Clinical course and serial radiographic
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149. Naito I, Iwai T, Sasaki T. Management of intracranial verte-
bral artery dissections initially presenting without subarach-
noid hemorrhage. Neurosurgery 2002; 51: 9307; discussion
937--8.
150. Furie LK, Kasner SE, Adams RJ, et al. Guidelines for the
prevention of stroke in patients with stroke or transient
ischemic attack: a guideline for healthcare professionals
from the American Heart Association/American Stroke
Association. Stroke 2011; 42: 227276.
 15
Direct carotid cavernous fistula
Uday Shankar Kanamalla and Charles A. Jungreis
INTRODUCTION
Carotid cavernous fistula (CCF) is an abnormal com-
munication between the internal carotid artery (ICA)
and the cavernous sinus. Direct CCF represents one
specific form of CCF with high-pressure arterial blood
entering the low-pressure venous cavernous sinus,
most commonly via a single hole in the cavernous seg-
ment of the ICA (Fig. 15.1). In contrast, the other variety
of CCF has been coined an indirect CCF and is char-
acterized by a nidus of dural arterioles (13). Indirect
CCF is described more fully in another chapter.
ETIOLOGY
While most indirect CCFs are of spontaneous origin
and uncertain etiology, direct CCFs most often occur as
the result of closed head injury associated with a basal
skull fracture (13). The ICA is fixed between the fora-
men lacerum and the anterior clinoid process by dural
attachments. Shearing forces from head trauma, some-
times with accompanying penetrating injury from bony
spicules, can cause the ICA to be torn between its
points of dural attachment. In most cases, the laceration
is single and unilateral. Sometimes the holes in the ICA
are multiple, and sometimes bilateral CCFs occur.
Direct CCF can also result from penetrating trauma,
including iatrogenic trauma, such as transsphenoidal
surgery (4). Collagen deficiency diseases, such as
EhlersDanlos syndrome, ruptured cavernous aneur-
ysms, dissections, osteogenesis imperfecta, and fibro-
muscular dysplasia, have also been associated with the
development of a CCF (5,6). The etiology of spontane-
ous direct CCF remains speculative and has most com-
monly been attributed to rupture of a preexisting
cavernous aneurysm (2,3) (Fig. 15.2). Direct CCF is
more common in the younger population as opposed to
indirect CCF, which tends to occur in the older popula-
tion. However, trauma at any age remains the most
common etiology of direct CCF.
CLINICAL FEATURES
The onset of symptoms and signs of a direct CCF is
usually acute and most commonly occurs within a
few days of the instigating trauma. A day or two
delay is typical, a curious feature of the pathological
process. The length of time between the onset of the
first symptoms, however, and the radiographic diag-
nosis of a CCF has been reported to be variable and
has ranged up to 18 months (1,7). The severity and
acuity of clinical features do not directly correlate to
the size of the fistula, but are affected by the venous
drainage.
The most common symptoms and signs are orbi-
tal (Table 15.1) and include pulsatile tinnitus with a
periorbital bruit, proptosis, chemosis, and injection (1
3,8,9). Less common presentations include intracranial
hemorrhage (10). Cerebral ischemia, related to vascu-
lar steal, appears to be an exceedingly rare phenom-
enon, though it may occur in patients with an
incomplete circle of Willis. The orbital symptoms and
signs appear to relate not only to the degree of shunt
but also to the pattern of venous drainage. The symp-
toms of CCF may be present in the contralateral eye
secondary to drainage of the fistula through the inter-
cavernous veins to the opposite side.
Improvement or resolution of orbital symptoms
following successful occlusion of the fistula tends to
occur in about 80% of patients (11). The symptoms
typically tend to resolve significantly in hours or days,
though total resolution could take weeks or months, if
it occurs at all. Duration of symptoms is also an
important prognostic factor, with prolonged symp-
toms resolving more slowly. A relatively common,
though dangerous, clinical scenario occurs in the set-
ting of major trauma. Several days or a week after the
trauma, an acute onset of severe proptosis, chemosis,
injection, and pain associated with a pulsatile bruit
over the orbit develops. Intraocular pressures elevate
dramatically, and the patient becomes ophthalmople-
gic in the affected eye. Despite the severe signs and
symptoms, intervention within the next day or two
typically results in rapid improvement (Fig. 15.3).
ANATOMY AND PATHOPHYSIOLOGY
The cavernous sinus has been regarded as a contigu-
ous network of anatomically separated sinusoids
rather than actual veins (12). A rent in the wall of the
intracavernous carotid artery, or rupture of one of its
branches that traverses and is surrounded on all sides
by the cavernous sinus cavity, produces an arteriove-
nous fistula without concomitant venous injury in
contradistinction to fistulas elsewhere in the body.
The superior and inferior ophthalmic veins pro-
vide normal venous drainage from the orbit to the
cavernous sinus. The superficial middle cerebral veins
drain the brain through the sphenoparietal sinus to
the cavernous sinus. The cavernous sinus, in turn,
normally drains through the superior and inferior
 DIRECT CAROTID CAVERNOUS FISTULA 317

(A) (B) (C)

(D) (E)

Figure 15.1 Direct CCF embolized with detachable coils. (A) Axial MR shows large varices especially in relation to the left cavernous
sinus. (B) Axial MR shows dilated superior ophthalmic veins bilaterally. (C) Lateral angiographic view during a selective ICA injection
shows rapid flow into the varices. The posterior venous drainage is poor, and most of the flow is anterior into the superior ophthalmic
vein. (D) Postembolization with detachable coils shows a minimal remnant. No arteriovenous shunting persists and the ICA is pre-
served. (E) Unsubtracted angiographic view showing coil nest postembolization. Abbreviations: CCF, carotid cavernous fistula; MR,
magnetic resonance; ICA, internal carotid artery.

1
4
(A) (B)

Figure 15.2 Direct CCF secondary to rupture of a cavernous ICA aneurysm embolized with a detachable balloon. (A) Lateral angio-
graphic view during a selective ICA injection shows rapid flow into the varices. The venous drainage is mainly posterior into the IPS.
(B) Postembolization. The cavernous aneurysm is now apparent. The fistula is closed. Abbreviations: CCF, carotid cavernous fistula;
ICA, internal carotid artery; IPS, inferior petrosal sinus.

petrosal sinuses (IPSs) to the sigmoid sinus and jugu-
lar bulb and via emissary veins to the pterygoid
venous plexus.
When the fistula develops between the ICA and
the cavernous sinus, the high flow and pressure
within the venous drainage pathways increase and
there is reversal of flow within the normal tributaries
to the cavernous sinus. Furthermore, the venous
drainage pathways dilate to accommodate the
increased flow. It is this abnormal venous diversion of
flow that results in the characteristic signs and symp-
toms associated with direct CCF.
The reversed and increased flow into the supe-
rior and inferior ophthalmic veins causes orbital
venous hypertension. Visual deterioration results from
a combination of reduced arterial perfusion and
venous hypertension with accompanying glaucoma.
Retinal perfusion suffers. Intraocular pressures rise
as a result of venous hypertension. Rubeosis iridis,
a neovascularity of the iris induced by prolonged
318 NEUROINTERVENTIONAL MANAGEMENT
Table 15.1 Symptoms and Signs Associated with Direct CCF (1)
Symptoms
Diplopia
Eye redness
Proptosis
Headache
Bruit
Diminished vision
Facial numbness
Ocular pain
Signs
Dilated episcleral veins
Diminished vision
Elevated intraocular pressure
Sixth nerve paresis
Chemosis
Third nerve paresis
Papilledema
Total number of cases
ischemia, may also contribute to overall ocular
necrosis (9). Obtrusive diplopia and ophthalmoplegia
occur as a result of cranial nerve compression secon-
dary to mass effect in the cavernous sinus from dis-
tended vessels. Edema of extraocular contents,
including the muscles, can also contribute to diplopia
and appears to be related to vascular engorgement
and enlargement of the extraocular muscles. The
symptoms and signs vary depending on which veins
drain the fistula and how distended they become. For
example, posterior drainage via the superior and infe-
rior petrosal sinuses can result in pulsatile tinnitus
without any cranial nerve palsies.
Intracranial hemorrhage is a dreaded complica-
tion. This is due to reversal of venous drainage into
the sphenoparietal sinus, with resultant cerebral corti-
cal venous hypertension.
Additionally, during treatment, one should
always remember the possibility that inadvertent redi-
rection of flow into dangerous venous channels may
occur from the treatment itself. This kind of acute
venous diversion into the remaining venous pathways
following selective occlusion of one venous channel can
result in aggravation of symptoms and increase the
morbidity and mortality associated with the disease.
For example, if the IPS is occluded during treatment,
diversion of flow into the superior ophthalmic vein
may increase proptosis and may also increase cortical
venous drainage with associated increased risk of intra-
cerebral or subarachnoid hemorrhage (10,13).
CLASSIFICATION
CCFs can be classified according to the following
three criteria:
(i) pathogenically into spontaneous or traumatic
fistulas, (ii) hemodynamically into high-flow or low-
flow fistulas, and (iii) angiographically into direct or
indirect (dural) fistulas. Some CCFs are hybrids of
the above. An angiographic classification provides an
objective and very helpful method for grouping CCF,
determining prognosis, and planning the therapeutic
management. All CCFs can be placed into one of four
angiographic categories based on whether the CCF is
direct and on the anatomical origin of the arteries
14
13
10
9
8
7
6
5
14
12
10
10 (A)
10
4
4
14
(B)
Figure 15.3 Sixty-four-year-old female before and after emboli-
zation of a CCF. (Top): Photograph before treatment. Note the
bilateral proptosis, chemosis, and injection. The pupils are dilated.
(Bottom): Photograph 10 days after treatment. It shows significant
resolution. Abbreviation: CCF, carotid cavernous fistula.
supplying the fistula (Fig. 15.1) (2,3). Type A fistulas are
direct shunts between the ICA and cavernous sinus.
Types B, C and D are indirect or dural shunts. Type B is
a fistula between meningeal branches of the ICA and the
cavernous sinus. Type C is a dural shunt between
meningeal branches of the external carotid artery (ECA)
and the cavernous sinus. Type D, the most common
type, is a dural shunt between meningeal branches of
both the ICA and ECA and the cavernous sinus. Bilateral
CCFs represent a special case of the above.
The angiographic criteria for differentiating a fis-
tula into high-flow or low-flow categories are quite
subjective. High-flow fistulas fill the cavernous sinus
and efferent veins within a fraction of a second, and
the intracranial branches of the ICA fill partially or
are not visualized at all during angiography. In con-
trast, an angiogram of a low-flow fistula will reveal
slower drainage into the venous system and filling of
the intracranial branches of the ICA. Note that the
terms high flow and low flow are relative to each
other. Both are high flow compared with normal.
INDICATIONS FOR TREATMENT
The indications for treatment are not absolute and
depend on the general physical condition of the
patient, the severity of the symptoms, and the anat-
omy of the fistula, which, in turn, determines the
treatment options. Type A direct fistulas will rarely
 DIRECT CAROTID CAVERNOUS FISTULA 319

(A) (B) (C)

(D) (E)

Figure 15.4 Direct right CCF embolized with a detachable balloon. (A) Axial CT showing dilated left superior ophthalmic vein. (B) PA
angiographic view during a right ICA injection shows arteriovenous shunting with cross-filling to the opposite side, including the left
cavernous sinus and left superior ophthalmic vein. (C) Lateral angiographic view during a right ICA injection again demonstrates rapid
arteriovenous shunting. (D) Lateral angiographic view with balloon in position closing the fistula with preservation of the ICA.
(E) Unsubtracted view showing balloon postembolization. Abbreviations: CCF, carotid cavernous fistula; CT, computed tomography;
PA, posteroanterior; ICA, internal carotid artery.

resolve spontaneously and almost always require
treatment. Progressive visual loss, uncontrollable ele-
vations of intraocular pressure, an intolerable bruit or
headache, or enlargement of traumatic aneurysms
beyond the cavernous sinus are all strong indications
for treatment. Additionally, treatment is also appropri-
ate because of corneal exposure, obtrusive diplopia, or
cosmetically offensive proptosis. Finally, the presence
of cortical venous drainage, where there is concern for
intracranial hemorrhage, constitutes an indication for
therapy (27,14).
Halbach et al. have identified certain high-risk
features that represent indications for urgent treat-
ment. These include development of intracranial hem-
orrhage, epistaxis, increased intraocular pressures,
decreased visual acuity, rapidly progressive proptosis,
and cerebral ischemia (10).
IMAGING STUDIES
Conventional catheter angiography is usually
required. It helps confirm the diagnosis, helps deter-
mine the type of fistula, and provides the therapeutic
capability.
CT or MRI can establish the diagnosis of CCF.
Their primary role, though, is to evaluate the brain
parenchyma for associated injuries in the setting of
trauma and to detect possible ischemic changes. Addi-
tionally, thin-section CT with coronal reconstructions
can help evaluate skull base fractures. The findings of
CCF on cross-sectional imaging include proptosis,
swelling of extraocular muscles, and dilation of the
superior ophthalmic vein with distention of the ipsi-
lateral cavernous sinus (Fig. 15.4). However, CT or
MRI will not typically help with differentiation of
direct from the indirect types.
Orbital ultrasound can demonstrate findings of
thickened extraocular muscles as well as dilated supe-
rior ophthalmic veins. In the right clinical setting, this
procedure can confirm the clinical diagnosis.
Other tests that are often performed include com-
plete ophthalmologic workups inclusive of visual acuity,
pupillary function, intraocular pressure measurement,
fundoscopy (direct and indirect), and gonioscopy.
For optimal angiography, high-resolution digital
subtraction is essential. The goals of the diagnostic
angiogram are to evaluate the location and size of the
fistula and the venous drainage pathways. Addition-
ally, associated traumatic vascular injuries, ICA pseu-
doaneurysms, and cavernous sinus varices need to be
excluded. To help differentiate a direct from an indi-
rect fistula, an angiographic search should be carried
out for an ECA supply to the fistula. The angiographic
evaluation of CCF should, therefore, include selective
catheterization and angiography of the ICAs and
ECAs bilaterally.
Because of very high flow, it may not be possible
to identify the morphology of the fistula in terms of
exact location or size on selective angiograms without
specific maneuvers to slow the flow across the fistula.
The maneuvers could consist of ipsilateral ICA com-
pression to slow the flow while injecting into the
artery. Alternatively, the contralateral ICA or vertebral
artery (so-called Allcock maneuver) can be injected
320 NEUROINTERVENTIONAL MANAGEMENT
while providing ipsilateral ICA compression (Dr. Allan
Fox, personal communication). Often, because of
the high flow, injection of the contralateral ICA or the
vertebral artery will opacify the CCF even without
compression.
The venous drainage from the cavernous sinus
of a direct CCF can extend anteriorly into the ophthal-
mic veins, inferiorly into the pterygoid venous plexus,
posteriorly into the petrosal sinuses, superiorly into
the cortical veins via the sphenoparietal sinus, and
finally, into the contralateral cavernous sinus. The pat-
tern of venous drainage dictates the predominant
symptom or sign seen in the patient. Most often a
combination of the above patterns of venous drainage
will be seen.
Other adjunctive diagnostic angiographic techni-
ques have been employed with varying degrees of
success. Rotational angiography can be obtained in
CCF and might provide additional useful information.
IVUS (intravascular ultrasound) monitoring has also
been shown to be useful during embolization of a
direct CCF with coils. IVUS accurately detected pro-
trusion of a coil into the parent ICA and consequently
an intervention ensued that enabled the parent artery
to be preserved. IVUS remains challenging and
requires a device with high trackability to overcome
the tortuous and long pathway to the target (1518).
TREATMENT OPTIONS AND CONSIDERATIONS
While there are reasons to intervene very early, in
general, the treatment of CCF is rarely an emergent
procedure, but it is often urgent. That is, treatment
can usually be undertaken semi-electively when the
patient is otherwise stable.
The treatment of CCF has evolved over the past
40 years. The earliest surgical treatments of proximal
occlusion of the ICA or trapping have largely been
abandoned because of the high risk of stroke and
blindness, often without obliteration of the fistula (9).
Today, the primary treatment modality is endovascu-
lar therapy. Approaches to occlude CCFs have been
described, with an increased focus on preserving ICA
flow. In the past, ICA occlusion was often unavoid-
able in order to completely seal the fistula. The ability
to maintain patency of the ICA after treatment, how-
ever, is increasing largely because of improvements in
the technology (better devices), but will probably
never reach 100% (3,1921).
The goal of treatment is to obliterate the fistula
which can be accomplished with a wide variety of
techniques and agents, each with advantages and dis-
advantages. The treatment of CCF takes into consider-
ation the speed of flow through the fistula, its arterial
supply, and the routes of venous drainage. Equally
important is to take into consideration the general
physical condition of the patient prior to formulating
a therapeutic plan. For example, in the setting of acute
CCF in a multitrauma patient, the more critical inju-
ries of the patient must be addressed first.
Medical Therapy
In the acute setting of vision loss and/or paralysis of cra-
nial nerves, glucocorticosteroids (e.g., dexamethasone)
may be used while waiting for definitive diagnostic
studies and treatments. Similarly, in patients with ele-
vated intraocular pressures, pharmacologic management
with topical b-adrenergic blockers and acetazolamide
(Diamox) is performed as adjunctive therapy, until
definitive therapy for the fistula is undertaken.
Surgical Therapy
Surgical therapy is presently considered only as a last
resort. The earliest treatments in the form of proximal
ICA occlusion or ICA trapping have largely been
abandoned. Surgical therapy is only considered in
cases where there has been a failure of endovascular
therapy or is used in conjunction with endovascular
therapy.
One form of surgical intervention has been to
expose the superior ophthalmic vein in the orbit in
order to provide endovascular access to the superior
ophthalmic vein. In patients without arterial or
venous access to the fistula, direct access to the supe-
rior ophthalmic vein following surgical exposure of
the vein in the orbit has been used successfully in
conjunction with transvenous embolization of the fis-
tula (22). Direct surgical exposure of the cavernous
sinus via craniotomy followed by direct puncture for
embolization and closure of the fistula remains an
alternative when all other routes are exhausted (23).
There are also reports in the literature of using a
superficial temporal artery to middle cerebral artery
bypass prior to sacrifice of the ipsilateral ICA in
patients who are unable to tolerate ICA occlusion (2).
Adjunctive surgical procedures in the form of a
lateral canthotomy have been performed as a tempo-
rizing measure for orbital symptoms such as severe
proptosis, markedly elevated intraocular pressures,
and rapidly declining visual acuity.
Endovascular Therapy
This therapy is performed transarterially and/or
transvenously. Large series have shown the effective-
ness of transarterial balloon embolization (3,1921). In
the United States, however, detachable silicone bal-
loons have been withdrawn from the market, which
has led to the use of various alternative embolization
agents including platinum microcoils and acrylic (N-
butyl cyanoacrylate, or NBCA) (2430). More recently,
closure of fistula via stent graft and stent/balloon
assist has been reported (3044). Currently, our initial
treatment attempt is with endovascular coils via the
transarterial approach.
Transarterial Approach
Conceptually, the ideal goal of treatment is to occlude
the fistula on the venous side, thereby preserving the
ICA. However, sometimes this treatment proves to be
impossible, and sacrifice of the ICA is required to
close the fistula. If the ICA requires sacrifice, then it
must be occluded both above and below the fistula or
flow to the fistula will persist (Fig. 15.5). This method-
ology of occluding the ICA is called trapping and
can be done surgically, endovascularly, or by a combi-
nation thereof. In treating 54 traumatic CCFs with

19. 11. 1957 10: 02 19. 11. 1957
Scene:
I: 15/30
W-U: M: 5/28
FL TR: 30% I: 13/28
W-L:
PLANE: B FL TR: 10%
LNDMK: 0%
PLANE: A
(A) (B)
Figure 15.5 Direct CCF secondary to a gunshot wound. The right ICA required sacrifice to close the fistula completely. Endovascular
coils were utilized to trap the fistula. (A) Lateral view after embolization. The detachable coils are in the right ICA and trap the fistula.
Detachable coils are both above and below the fistula. Note also that some larger free coils are in the proximal ICA to provide
additional stability to the coil nest. (B) Frontal angiographic view after right carotid sacrifice during left ICA angiogram showing excellent
cross-filling without flow into the fistula. (C) Lateral angiographic view after embolization during a vertebral artery angiogram. The distal
right ICA is filled via the posterior communicating artery, but the coils prevent retrograde flow to the fistula. Abbreviations: CCF,
carotid cavernous fistula; ICA, internal carotid artery.
detachable balloons, Debrun et al., had to sacrifice the
ICA to close to the fistula in 20 (37%) of their cases.
ICA occlusion at the level of the fistula can be per-
formed with detachable balloons or with platinum
coils. Interestingly, since the ICA flow above the level
of the fistula is usually reversed into the fistula, test
occlusion of the ICA is not usually required. However,
in a patient in whom some distal ICA flow above the
fistula remains antegrade, tolerance to ICA occlusion
using the balloon occlusion test prior to occlusion of
the ICA may be required. In the uncommon event
of failure to tolerate the occlusion, alternate methods
of therapy will need to be strongly considered.
Selective embolization of the fistula via the trans-
arterial approach with detachable balloons or coils is
presently considered the method of choice for the
treatment of most single-hole CCFs. When using bal-
loons, the procedure involves the detachment of single
or multiple balloons into the cavernous sinus (venous
side) close to the fistula to occlude the abnormal fistu-
lous communication. Thromboembolic complications
from the procedure, though rare, are well described in
the literature and could be the result of catheter or
balloon manipulation causing endothelial damage or
the result of inadvertent balloon detachment or bal-
loon migration. Transarterial balloon embolization
fails in at least 5% to 10% of cases (24,30,45). Failure
occurs because the fistula orifice may be too small to
allow entry of the balloon catheter, the venous com-
partment of the fistulous communication may be too
small to allow balloon inflation, or sharp margins of
the adjacent bony fragments or foreign bodies may
rupture the balloon during inflation (46). Also, in
some patients who have subtotal occlusion after initial
balloon embolization, navigation of additional bal-
loons into the fistula may be unsuccessful owing to
the presence of balloons partially blocking the fistula
orifice. Lastly, the ability to microcatheterize and hold
a position within the fistula may be limited depending
on the position of the fistula ostium. Typically, the fis-
tula orifice is more difficult to catheterize when it is
just beyond the posterior genu along the inferior wall
DIRECT CAROTID CAVERNOUS FISTULA 321
IU:
Scen: X: 0
0%
W- B: Y: -0
0%
W-C: B
X:
Y:
(C)
of the C4 segment of the cavernous carotid artery
because the angle of entry from the ICA is very acute.
The development of steerable microcatheters and
microguidewires has allowed successful use of other
embolic agents such as platinum coils or liquid embolic
material. It is technically easier to guide a microcatheter/
microguidewire combination through a small fistula
than it is to guide a detachable balloon, and the former
also allows for precise placement of embolic agents
within the cavernous sinus close to the fistula orifice.
Care must be taken to ensure that these embolic agents
are not deposited within the carotid artery. An intraca-
vernous venogram should always be obtained to verify
that the microcatheter is positioned properly on the
venous side and to delineate accurately the cavernous
sinus prior to deposition of coils. The occluding coils
should be placed as close to the fistula orifice as possible.
Also, fewer coils are needed if the fistula can be blocked
at its orifice. The use of standard non-detachable or
free platinum coils in the successful treatment of CCF
has been described (24). Since the development of
detachable platinum coils, though, embolization using
free coils by themselves is rarely performed. Technical
pitfalls associated with embolization using free plati-
num coils, including difficulty in retrieval, the relative
stiffness of the coils, the risk of perforation, and the
difficulty in packing them tightly, have encouraged
the use of the newer-generation detachable coils. With
detachable coils, if the microcatheter recoils during
placement of the coil, the coil can be repositioned. Non-
detachable balloon assistance during coil insertion can
also be helpful.
The development of detachable or retrievable
platinum coils has significantly reduced the risks asso-
ciated with standard free platinum coils (2430). The
advantage of using detachable platinum coils is the
ability to control their placement and to easily
retrieve, reposition, or exchange them if necessary.
Technical pitfalls are possible with detachable plati-
num coils also. The soft platinum coils exert little
force on the surrounding structures and might
be more easily displaced in a high-flow fistula.
322 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 15.6 Stent graft (courtesy of Robert Hurst). (A, B) Lateral and AP views of a selective left internal carotid artery angiogram
showing the CCF draining to the left superior ophthalmic vein.
Again, use of stent-or ballooned-assisted placement of
the detachable platinum coils may allow for tighter
packing and more complete closure of the fistula.
Liquid adhesives such as NBCA or IBCA have
also been used in conjunction with balloons or
coils (30). Initial placement of detachable balloons or
coils within the fistula helps significantly reduce the
flow allowing for a more controlled injection of a
liquid adhesive to complete the occlusion of fistula.
Flow control is paramount in importance when liquid
adhesives are used. Reflux into the carotid artery with
devastating strokes can occur. This risk increases
when closure of the fistula is nearly complete and the
pressure gradient between the carotid artery and cav-
ernous sinus is lowered. Real-time live subtraction
and careful slow injections of small volumes of
embolic material can mitigate against this potential
complication. Equally of concern with liquid agents is
that liquid agents can be sucked through a high flow
fistula with pulmonary complications. Newer liquids
agents such as Onyx (Onyx Liquid Embolic System;
Micro Therapeutics, Inc., Irvine, California, U.S.) hold
interesting promise but remain unproven (47).
In the last decade, covered stents have been used
within the aorta and peripheral, visceral, and coronary
arteries as an effective alternative to open surgical
repair. More recently, covered stents have been used
in the cerebral circulation for the treatment of aneur-
ysms, pseudoaneurysms, arterial dissections, and arte-
riovenous fistulas. Covered stents have also been
utilized to treat direct CCFs with successful short- to
midterm clinical results (611).
In younger patients and in those with a straighter
course of the vessel, it is possible to deliver covered
stents to bridge the site of a fistula and, thereby,
close the fistula with preservation of the ICA (37,38)
(Figs. 15.6,15.7). Delivery of stents to the small-caliber,
tortuous intracranial arteries requires low-profile, flexi-
ble stents with high elasticity as well as good push-
ability properties for the delivery catheter. Stent
designs are continually being improved in order to
(B)
overcome problems in delivery, deployment, and pre-
vention of stent thrombosis.
A device of appropriate diameter is placed over
a guidewire under roadmap guidance to the diseased
segment of the ICA. As usual, control angiograms are
obtained to confirm the correct position, and then the
stent is inflated to 810 atm. Although several vari-
eties of covered stents have been used by the neuro-
vascular community, only the Willis covered stent
(MicroPort, Shangai, China) reported by Li et al. (40)
is specifically designed for the intracranial vascula-
ture. More commonly, however, a Jostent GraftMaster
Coronary Stent Graft (JoMed International AB,
Helsingborg, Sweden) has been used. The Jostent
GraftMaster Coronary Stent Graft is constructed like
a sandwich with two bare stainless steel stents and a
thin layer of expandable polytetrafluoroethylene
(PTFE) in between. Due to this composition and con-
struction, the stent is relatively rigid, and it is some-
times difficult or impossible to be navigated within a
tortuous ICA. The use of a stiff guidewire and a dis-
tally advanced guiding catheter with firm backup are
essential. Possible complications that may result from
this rigidity are dissection and periprocedural spasm
of the cerebral arteries. Technical success can be
achieved, however. Patient selection, or more specifi-
cally, vessel selection, with less tortuous anatomy is
important during the procedure. Adjunctive tools
such as antispasmotics can be helpful. The other main
problem with covered stents is the development of an
endoleak following successful stent deployment. In
most cases, reinflation inside the stent with a larger
balloon tends to fix this problem. If this fails, how-
ever, then carotid sacrifice becomes the alternative.
Even after apparent successful deployment, stent
thrombosis constitutes an important potential compli-
cation, especially with covered stents. Adequate antico-
agulant and antiplatelet treatment before and after the
procedure are essential to prevent thromboembolic
complications, therapeutic requirements that might not
be desirable or possible in the multitrauma patient.
 DIRECT CAROTID CAVERNOUS FISTULA 323

(A) (B)

Figure 15.7 (A, B) Lateral views post insertion of a covered stent (JoStent). The CCF is closed and ICA flow is preserved. Arrows
stent.

(A) (B) (C)

Figure 15.8 Venous approach after carotid sacrifice (courtesy of Robert Hurst). After the initial trauma, a right ICA sacrifice with
detachable balloons had been performed. The symptoms abated temporarily, but the fistula had not been closed. Because the RICA
had been occluded, a venous approach to the fistula was subsequently undertaken. (A) AP view of a left ICA injection demonstrates
cross filling to the right ACA and MCA. Retrograde flow through the right supraclinoid ICA is present with opacification of a large right
cavernous aneurysm and a right-sided CCF. Markers on previously placed detachable balloons are within the proximal occluded right
ICA (arrows). (B, C) Early and late lateral views of a left vertebral artery angiogram demonstrate filling of the anterior circulation via the
posterior communicating artery. The cavernous aneurysm and CCF fill with venous drainage continuing through to the IPS (arrows
balloon markers within the occluded right ICA).

Transvenous Approach the sphenoparietal sinus. These alternate venous

When transarterial routes are unsuccessful, or if the
venous anatomy is opportune, transvenous emboliza-
tion can be performed (19,30,45,48). Access to the cav-
ernous sinus through the ipsilateral jugular vein
and IPS is the most common transvenous approach
(Figs. 15.8--15.10). Other venous routes that have been
used on occasion to access the cavernous sinus
include the contralateral IPS, pterygoid plexus of
veins, superior ophthalmic vein, and cortical veins via
routes were used because of nonvisualization of the
IPS or inability to adequately gain access to the caver-
nous sinus via the ipsilateral IPS. Following transve-
nous access to the cavernous sinus, detachable
balloons, detachable platinum coils, or liquid embolic
agents have been used successfully. In transvenous
cases, an arterial catheter (45 French) typically has to
be placed into the ipsilateral common carotid artery or
ICA for angiographic localization of the fistula site
and confirmation of fistula closure.
324 NEUROINTERVENTIONAL MANAGEMENT

16
(A) (B)

Figure 15.9 (Same patient as Fig. 15.8.) (A, B) Interventional procedure: the fistula was approached from the venous side of the cir-
culation. A guide catheter was placed in the right jugular vein through which a microcatheter was inserted. Contrast injection into the
left vertebral artery demonstrates the microcatheter (arrowheads) passing through the IPS and fistula to the aneurysm (arrowsballoon
markers within the occluded right ICA). Coils were packed into the aneurysm and brought back into the fistula.

(A) (B) (C)

Figure 15.10 (Same patient as Figs. 15.8 and 15.9.) (A, B, C) Post embolization. Lateral plain film (A) shows coils in position includ-
ing to the level of the fistula (arrows). Lateral left vertebral artery angiogram (B) and AP left CCA angiogram (C) show no residual filling
of the fistula.

While the transvenous approach may be effective,
it is not without risk. The most common complication
associated with the procedure is perforation of intracranial
veins during catheterization. Although arterialization
of venous structures can occur in long-standing shunts,
the draining veins and dural sinuses in CCFs are often
still thin-walled and can be perforated by a catheter or
guidewire. With the increased pressure and flow of the
arterialized blood in these structures, small perfora-
tions can result in rapidly fatal subarachnoid hemor-
rhage. Another potential complication from a venous
approach is venous thrombosis which may occur
following injury to the veins or venous occlusion with
embolic agents that are not at the fistula. This could be
significant if the venous drainage is altered but the
fistula remains open. For example, if the posterior
drainage (IPS) is occluded without closure of the fistula,
aggravation of ocular symptoms (superior ophthalmic vein)
or hemorrhage (cortical drainage) may occur. Similarly,
if the superior ophthalmic vein is occluded, fistula
flow may be diverted into cortical veins, increasing the
risk of hemorrhagic complications. In our experience,
closure of the distal superior ophthalmic vein is often
associated with severe aggravation of ocular symptoms
if persistent fistula remains. As a technical note, there-
fore, care must be taken not to occlude the access vein
before the other venous channels and fistula are closed.
If cortical venous drainage is noted, occlusion of the
cavernous sinus at the junction with the cortical vein or
alternatively, direct placement of coils into the spheno-
parietal sinus should be performed as a first step. Also,
if a vein is occluded, drainage of the pons and brain
stem may be impaired. Debrun et al. (19), in his report
of trans-femoral venous occlusion of CCF with detach-
able balloons, noted that the percentage of success was
low because partitions within the cavernous sinus

precluded placement of a balloon near the fistula ori-
fice. With the development of softer and smaller cathe-
ters and steerable guidewires, the risks of these
complications have been reduced.
Transorbital Approach
The transorbital approach entails direct cut-down
under ultrasound guidance into the superior ophthal-
mic vein with retrograde catheterization and emboli-
zation of the fistula. We found this approach more
difficult and cumbersome than the others and have
abandoned it.
FOLLOW-UP
Angiographic residual flow through the fistula is not
a definite indication for further treatment. Subtotal
occlusion of a fistula may not indicate failure. On the
contrary, the goals of treatment are to alleviate the
clinical symptoms, to control the intraocular pressures,
and to eliminate cortical venous drainage. We use a
follow-up angiogram at three to six months after treat-
ment for evaluation in conjunction with a thorough
ophthalmologic exam.
SUMMARY
Direct CCF results from a tear in the cavernous ICA.
Endovascular occlusion of the fistula is the preferred
method of treatment. With improvements in cathe-
ter techniques as well as embolic agents and stents,
the treatment of these complex lesions is generally
effective.
ACKNOWLEDGMENT
We wish to thank Cathy Wright for her great assis-
tance in preparation of the manuscript.
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 16
Endovascular management of intracranial aneurysms
Aaron S. Dumont, Pascal M. Jabbour, Stavropoula I. Tjoumakaris, L. Fernando Gonzalez, Ciro G.
Randazzo, Peter Kim Nelson, and Robert H. Rosenwasser
INTRODUCTION
Intracranial aneurysms are an important and common
clinical problem. Although the etiology of saccular
aneurysms remains incompletely defined, the patho-
genesis of aneurysm formation and rupture is likely
multifactorial. Environmental factors, such as cigarette
smoke, in combination with hemodynamic factors and
genetic or developmental aberrations are likely contrib-
utory (112). With the nearly ubiquitous availability of
noninvasive imaging studies, many endovascular
therapists are witnessing an increase in referrals for
patients with unruptured aneurysms (many of which
are entirely asymptomatic). Additionally, with the pub-
lished results of the International Subarachnoid Aneur-
ysm Trial (ISAT) (1315) demonstrating a significantly
improved outcome with coiling compared to clipping
in patients whose ruptured aneurysms were deemed
suitable for either method, the proportion of patients
harboring ruptured aneurysms treated with endovas-
cular techniques has increased (1619). The present
chapter discusses pertinent issues associated with the
endovascular management of intracranial aneurysms in
this era where endovascular techniques have become
adopted as an important therapeutic tool in the care of
patients harboring these lesions.
EPIDEMIOLOGY
The prevalence of unruptured aneurysms varies depend-
ing upon the methods used for detection (2027). The
overall incidence in an adult population without specific
risk factors may be estimated at 2.3% (95% CI (confidence
interval), 1.73.1%) (26),(27). Risk factors for cerebral
aneurysms include female gender, increasing age, smok-
ing, hypertension, autosomal dominant polycystic kidney
disease, excessive alcohol use, family history [one or
more affected relatives with subarachnoid hemorrhage
(SAH)], and a previous history of SAH (26,27).
Rupture of an intracranial aneurysm producing
SAH is the most dreaded complication of patients
with unruptured aneurysms. SAH accounts for
approximately 5% of all strokes and may affect up to
30,000 Americans annually (28,29). The age-adjusted
annual incidence of SAH varies widely between coun-
tries ranging from 2.0 cases per 100,000 population in
China to 22.5 per 100,000 in Finland (30). The inci-
dence may be even higher in Japan with adjusted
annual incidences of up to 32 per 100,000 (3133). The
annual incidence in the United States is approximately
11 per 100,000 (34). SAH is a particularly devastating
form of stroke with a case fatality rate of 3286% (35
39). Additionally, there is a 1020% long-term depend-
ence in survivors and a significant risk of neurocogni-
tive dysfunction (35,40).
HISTORICAL PERSPECTIVES
Early Beginnings
Remarkable progress has been made in the endovas-
cular treatment of intracranial aneurysms since its
inception. The contemporary state of endovascular
techniques is the result of numerous contributions
over the years; the earliest beginnings may date back
to the 1800s. The concept of an endovascular approach
to aneurysms was demonstrated by Velpeau (41)
where he presented his observations demonstrating
intravascular thrombosis using an endovascular nee-
dle insertion at the Academy of Science in Paris in
1832. Furthermore, he advocated for needles to be
used to treat arterial aneurysms. Contemporaneously
but independently, Benjamin Phillips (42) also pub-
lished similar work demonstrating potential utility for
needles (including with the addition of electric current
to the needles) for the treatment of an aneurismal
sac. These concepts were later applied to the treat-
ment of aortic aneurysms in humans by Ciniselle (43)
in 1846 (using needles and electric current), Moore
and Murchinson (44) in 1864 (using 78 feet of iron
wire), and by Corradi in 1879 (introducing a wire into
the aneurysm through an insulated needle and apply-
ing current to the wire to induce thrombosis) (45). The
use of wires for the treatment of aneurysms was intro-
duced to the United States by Ransohoff in 1886 (46),
with further refinements made by Finney (47) as well
as Blakemore and King (48). Werner, Blakemore, and
King (49) were the first to use the wire and electrocoa-
gulation technique for an intracranial aneurysm. They
treated a giant intracranial internal carotid artery
(ICA) aneurysm by introducing 30 feet of silver wire
into the aneurysm via a transorbital approach. They pro-
ceeded to heat the wire to 80 C for nearly a minute to
successfully treat the aneurysm.
This innovative work, however, appeared to be
ahead of its time. These methods were largely aban-
doned due to variability in results with poor outcomes,
limited resources, and evolution of surgical alternatives.
328 NEUROINTERVENTIONAL MANAGEMENT
Moreover, there were completely inadequate imaging
techniques.
Cerebral Angiography: Establishment of a
Critical Prerequisite for Endovascular
Aneurysm Treatment
The work of a Portugese neurologist, Egaz Moniz, pro-
vided a critical catalyst for the endovascular field by
introducing angiographyan imaging modality which
could not only magnificently outline the cerebral vascu-
lature but also provide a potential means for endovas-
cular access to intracranial vascular lesions including
aneurysms. Although Egaz Moniz was awarded the
Nobel Prize in Medicine and Physiology for his work
on prefrontal lobotomy (which subsequently fell out of
favor), his monumental contribution to medicine was
in the successful introduction of cerebral angiography
in humans (50,51). After initial trepidations, Moniz was
successful in performing cerebral angiography and was
able to outline human cerebral vascular anatomy on
June 28, 1927 (50). Interestingly, in 1931 an editorial
commentary in the Lancet (52) recognized possible
applications of cerebral angiography through a state-
ment, its possibilities as an avenue for therapeutics
should not be lost sight of in the future.
Intracranial Endovascular Navigation and
Embolization
With the basic tenets of cerebral angiography and
refinements in technique in place, the next step in the
evolution of endovascular therapy occurred with the
establishment of intracranial, endovascular navigation,
and embolization. In 1931, Brooks (53) used a piece of
muscle introduced into the ICA to embolize a carotid
cavernous fistula. Important contributions were made
by Luessenhop and Velasquez through publications
appearing in 1960 (54) and 1964 (55). The authors
attempted to embolize an arteriovenous malformation
(AVM) (54). They speculated that if an embolic agent
was introduced to the cerebral vascular system proxi-
mal to the AVM, it would be preferentially drawn to
the lower vascular resistance of the AVM via a sump
effect. They reported a case of emoblization of an
AVM using methylmethacrylate and termed the tech-
nique artificial embolization. In 1964, Luessenhop
and Velasquez (55) described a technique of using
flexible silastic tubing as a flow-guided catheter to
access the intracranial vasculature. The catheter was
introduced to the ICA through an external glass cathe-
terization chamber placed in the external carotid
artery. Furthermore, they used this technique to selec-
tively occlude the neck of a posterior communicating
artery with a silastic balloon that was temporarily
inflated resulting in aneurysm occlusion. This pro-
vided new impetus for further investigation of endo-
vascular techniques for intracranial aneurysms.
Based upon earlier work by Tillander (56,57)
demonstrating a potential role for a magnetically
guided catheter used for abdominal aortography, Frei
and colleagues (58) reported endovascular navigation
using a catheter called a paraoperational device (POD)
that could be navigated through blood vessels using
an external magnet in 1966. They designed a catheter
tip with an attached micromagnet. Through the appli-
cation of an external magnetic field, navigation of the
catheter could be achieved. Using a glass model, they
demonstrated that the POD catheter could be navi-
gated through the carotid siphon and into an aneur-
ysm. Yodh et al. (58) extended the work of Frei et al.
in 1967. They assembled an electromagnetic system
around a patients head to improve intravascular navi-
gation. They also introduced a system whereby a
magnet could be introduced into an aneurysm and
subsequently attract iron particles injected through
another catheter to promote intraneurysmal thrombo-
sis. Yasargil also believed that aneurysm thrombosis
could be achieved through directing iron particles into
an aneurysm magnetically (59). He discussed this
with Robert Rand (59). In turn, a pupil of Rand
named John Alksne conducted investigations incorpo-
rating intracranial catheterization with magnetically
directed embolization (6065). Aneurysm thrombosis
was achieved with both iron particles and a liquid
acrylic mixture suspension. In 1974, Hilal and associ-
ates (66) published their investigations into the use of
magnetically directed catheters and electrothrombosis
for the treatment of intracranial aneurysms.
The next step in the evolution arose as intracranial
neuronavgiation shifted away from magnetically
directed catheters. The magnetically directed catheters
represented a significant advance, however, suscepti-
bility of the image intensifier and fluoroscopic image to
the magnetic field was a significant limitation (46,67).
Erik Engelson, an engineer from Target Therapeutics,
developed a catheter for intracranial neuronavigation
directed over a wire with a shapeable tip (46,67). This
new catheter, called the Tracker, was first used by
Berenstein and Choi in 1986 at New York University
(46,67). This basic catheter and wire design has been
modified over the years, but is the basis for current
techniques for endovascular treatment of intracranial
aneurysms.
Electrothrombosis for the Treatment of
Intracranial Aneurysms
Electrothrombosis for the treatment of intracranial
aneurysms was pioneered by Sean Mullan and col-
leagues at the University of Chicago (6870). The team
performed the first intracranial aneurysm electro-
thrombosis by positioning platinum electrodes in con-
tact with a posterior communicating artery aneurysm
via a burr hole (69). After 6 hours, only partial
occlusion was achieved and this led the investigators
to conclude that an intraluminal electrode was neces-
sary to promote thrombosis. They refined their techni-
ques and presented their work. However, this
technique was not adopted in the long term as a result
of inadequate aneurysm treatment and complications
such as vasospasm and adjacent branch occlusion.
Balloons and Endovascular Treatment of
Intracranial Aneurysms
Rothenberg and associates at University of California,
Los Angeles (UCLA) reported their concept of angio-
tactic surgery in 1962 (71). Essentially, this system
used a carrier catheter and balloon to deliver and
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
deploy a polyester sleeve inside a blood vessel leaving
the sleeve within the blood vessel while the delivery
system was removed (71). They found that the sleeve
was often covered with endothelium in animal models
after deployment. They suggested that this could be
used for aneurysm treatment (71) although it was
never taken much further.
Another significant advance in the use of bal-
loons for the potential treatment of aneurysms
occurred with the development and introduction of
the Fogarty catheter by T. J. Fogarty and associates
(72). The catheter was designed for the removal of
arterial thromboemboli but the basic design laid the
foundation for effective balloon catheters (7375).
A major advance in this area occurred as a result
of the novel efforts of Fedor Serbinenko who was a neu-
rosurgeon at the Burdenko Neurological Institute in
Moscow. In fact, Serbinenko has been recognized as a
founder of endovascular neurosurgery (76) for his
work on the use of balloon catheterization and occlu-
sion of intracranial aneurysms. Serbinenko published
his seminal work on balloon catheterization and occlu-
sion of intracranial aneurysms in 1974 (77). Balloon
occlusion of intracranial aneurysms became a major
endovascular technique for the treatment of intracranial
aneurysms and other intracranial vascular pathology
including fistulas. Technical modifications were made
by endovascular surgeons throughout the world
including Debrun et al. (78,79), DiTullio and associates
(80,81), Laitinen and Servo (82), Romodanov and
Scheglov (83), Hieshima et al. (84), Higashida and col-
leagues (8588), Moret et al. (46), Taki et al. (8991) and
Goto et al. (92). Others, including Debrun (93) and
Berenstein (94) used detachable balloons to perform
endovascular parent vessel occlusions for the treatment
of giant intracranial aneurysms (rather than endosaccu-
lar occlusion with parent vessel preservation). Eventu-
ally, however, balloon embolization of intracranial
aneurysms fell out of favor due to suboptimal results
and the introduction of new technologies (95). Signifi-
cant shortcomings of balloon embolization included the
following. (i) Access to the aneurysm could be difficult
as guidewires could not be used to facilitate aneurysm
catheterization. (ii) The round or oval shape of the bal-
loon device did not adequately conform to many irreg-
ularly shaped aneurysms thereby resulting in an
inability to achieve initial complete occlusion or in the
promotion of recanalization or regrowth as a result of
the water-hammer effect where arterial blood pres-
sure is transmitted by a balloon (that did not ideally fill
the aneurysm) against the aneurysm wall (96). (iii) A
high rupture rate because of balloon non-compliance.
(iv) The absence of a healing response between the bal-
loon and aneurysm wall. (v) Possible balloon deflation
slowly over time depending on the substance used to
fill the balloon (45).
Introduction of Coils for Endosaccular
Aneurysm Treatment
The introduction and refinement of coils for the embo-
lization of intracranial aneurysms was the next major
advance in the endovascular therapy of aneurysms
that helped the field mature into its current state.
329
Although Bacelli and Montenovessi first intro-
duced coils for the treatment of aortic aneurysms in
1877 (46), further refinements in the use of coils for
transcatheter arterial occlusion were not made until
1975 by Gianturco and coworkers (97). In 1985, Braun
et al. (98) reported their experience using coils for
parent vessel occlusion where they used 5-mm coils to
occlude a parent carotid vessel after they had
exhausted their balloon supply in the management of
a giant cavernous ICA aneurysm. Subsequently, Hilal
and colleagues presented their results using coils to
treat aneurysms of lenticulostriate perforators in 1988
(46). Reports of early experiences with pushable
coils emerged (99102); however, coil delivery was
severely limited by a lack of control as the coils could
not be retrieved or repositioned.
A quantum leap in the endovascular manage-
ment of intracranial aneurysms occurred with the
development of the electrolytically detachable coil or
Guglielmi detachable coils (GDCs). Guido Guglielmi
is an innovative Italian neurosurgeon who began
experiments combining the concepts of Mullans work
on electrothrombosis with Serbinenkos concept of
endovascular delivery (46). In working with Ivan
Sepetka, an engineer from Target Therapeutics,
Guglielmi developed an electrolytic detachable coil
which truly revolutionized the field (103105). Subse-
quent modifications of this basic concept have
emerged over the years but virtually all are deriva-
tives of Guglielmis work. The field has enjoyed other
technical advances such as the introduction of balloon
remodeling, stent-assisted coil emoblization, liquid
embolic agents, and flow diversion. These recent
developments/modifications will be discussed below.
NATURAL HISTORY OF INTRACRANIAL
ANEURYSMS
The treatment for an individual patient with an intra-
cranial aneurysm must consider the natural history of
the patients aneurysm(s) [the risk of rupture or re-
rupture (for ruptured lesions) and the associated con-
sequences] against all risks associated with treatment.
Consequently, understanding the natural history of
unruptured as well as ruptured aneurysms is impor-
tant in formulating a treatment plan for patients har-
boring intracranial aneurysms.
Unruptured Intracranial Aneurysms
The most important study conducted to date concern-
ing the natural history of intracranial aneurysms was
the International Study of Unruptured Intracranial
Aneurysms (ISUIA) (36,106). The first report of the
ISUIA was published in 1998 (36). Two-thousand six-
hundred twenty-one patients at 53 centers in the
United States, Canada, and Europe were enrolled. The
study included a retrospective component in which
1449 patients with 1937 unruptured intracranial aneu-
rysms were enrolled. Seven-hundred twenty-seven
patients had no history of SAH from a different
aneurysm (Group I) and 722 had a history of SAH
from a different aneurysm that had been repaired
successfully (Group II). The prospective component
assessed treatment-related morbidity and mortality in
330 NEUROINTERVENTIONAL MANAGEMENT
1172 patients with newly diagnosed unruptured intra-
cranial aneurysms. The results of both components of
this study are summarized in Table 16.1 (modified
from Dumont et al. (37)). Taken together, the
authors concluded that the likelihood of rupture of
unruptured intracranial aneurysm <10 mm in diame-
ter was very low (<0.05% per year) among patients
in Group I, while the risk of rupture was substan-
tially higher among those patients in Group II
(approximately 11 times higher or 0.5% per year).
Furthermore, the risk of rupture of an intracaver-
nous (vs. intradural) aneurysm was exceedingly
low. The risks of morbidity and mortality associated
with surgery appeared to greatly exceed the 7.5-year
risk of rupture among patients in group 1 with
unruptured intracranial aneurysms less than 10 mm
in diameter. The results of the first report of the
ISUIA were met with some degree of criticism (107
111). Criticisms that remain today such as the unusu-
ally low risk of aneurysm rupture for small anterior
circulation aneurysms compared to other reports
(0.05% per year in the ISUIA (36) compared to a con-
temporaneous meta-analysis (27) illustrating a 0.7%
risk per year), the strong possibility of surgical selec-
tion bias (37) and the fact that many aneurysms that
rupture are small (>60% of ruptured aneurysms have
been reported to be <5mm (112)) and aneurysms do
not appear to shrink after rupture (113).
The above criticisms notwithstanding, the first
publication of the ISUIA was influential. Indeed, the
results of the ISUIA, at least in part, provided the
impetus for the Stroke Council of the American Heart
Association to issue a scientific statement outlining
recommendations for the management of patients
with unruptured intracranial aneurysms (114). The
report indicated that the existing literature supported
the following recommendations (options) (114):
1. Small incidental intracavernous ICA aneurysms
should generally not be treated. For large, sympto-
matic intracavernous aneurysms, treatment deci-
sions should be individualized on the basis of
patient age, severity and progression of symptoms,
Table 16.1 Results Reported from the First International Study of Unruptured Intracranial Aneurysms (ISUIA) Publication (36). (A)
Data Presented from the Retrospective Component. (B) Data Presented from the Prospective Component
A. ISUIA Retrospective Component
Group I
(n = 727) No history of subarachnoid
hemorrhage (SAH)
Rates of Rupture <10mm0.05%/year
>10mm~ 1%/year
25mm6% in 1st year
Predictors of Rupture 1. Increasing size
2. Location (basilar tip, posterior cerebral or
vertebrobasilar distribution, posterior communi-
cating region)
B. ISUIA Prospective Component
Group I
(n = 961) No history of SAH
Treatment Surgery n = 798, 83%
Endovascular in remainder
Overall morbidity and mortality At 1month17.5%
At 1year15.7%
Predictors of Poor Surgical Outcome Increasing age
and treatment options. The higher risk of treat-
ment and reduced life expectancy in older patients
must always be considered and favors observation
in older patients with asymptomatic aneurysms.
2. Symptomatic intradural aneurysms of all sizes
should be considered for treatment (urgently for
acutely symptomatic aneurysms). As symptomatic
large and giant aneurysms have higher associated
surgical risks, individualized patient and aneurys-
mal risks must be considered along with surgeon
and center expertise.
3. Coexisting or remaining aneurysms of all sizes in
patients with a history of SAH due to another
treated aneurysm are associated with a higher risk
for future rupture than are similarly sized aneur-
ysms in patients without a history of SAH and
warrant consideration for treatment.
4. Due to the low apparent risk of hemorrhage in
patients with small (<10mm) aneurysms without a
prior history of SAH, treatment rather than observa-
tion cannot be generally advocated. However, spe-
cial consideration for treatment should be exercised
for young patients. Additionally, small aneurysms
approaching the 10-mm diameter size, those with
daughter sac formation and other unique hemody-
namic features, and patients with a positive family
history for aneurysms or aneurysmal SAH warrant
special consideration. In those patients managed
with observation, periodic follow-up imaging eval-
uation should be considered and is necessary if a
specific symptom arises. If changes in aneurysm
size or morphology are seen, special consideration
should be given for treatment.
5. Asymptomatic aneurysms > 10mm in diameter
merit strong consideration for treatment, taking into
account patient age, existing medical and neurologi-
cal conditions as well as the relative risks of
treatment.
Other studies surfaced shortly after the initial
ISUIA report concerning the natural history of intra-
cranial aneurysms (38,39). Juvela et al. (38) followed
142 patients with 181 unruptured aneurysms. The
Group II
(n = 722) History of SAH from another aneur-
ysm repaired successfully
<10mm0.5%/year
>10mm~ 1%/year
25mminsufficient data (n=3)
1. Location (basilar tip)
2. Older age
Group II
(n = 211) History of SAH from another aneur-
ysm repaired successfully
Surgery n = 198, 94%
Endovascular in remainder
At 1month13.6%
At 1year13.1%
Increasing age
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
median follow-up was 19.7 years. During 2575 per-
son-years of follow-up, there were 33 first episodes of
hemorrhage from previously unruptured aneurysms
with an average annual incidence of 1.3%. In 17
patients, hemorrhage led to death. Cigarette smoking,
size of the unruptured aneurysm and age, inversely,
were important factors determining the risk for subse-
quent aneurysm rupture. The authors concluded that
such unruptured aneurysms should be surgically
treated regardless of their size and of a patients
smoking status, especially in young and middle-aged
adults, if this is technically possible and if the
patients concurrent diseases are not contraindications.
Tsutsumi and colleagues (39) followed 62 patients with
unruptured aneurysms for an average of 4.3 years.
Seven patients (11.3%) developed SAH, six of whom
died and one of whom recovered with a major defi-
cit. The 5- and 10-year cumulative risks of SAH were
7.5% and 22.1%, respectively, for total cases, 33.5%
and 55.9%, respectively, for large (> 10mm) aneur-
ysms, and 4.5% and 13.9%, respectively, for small
(<10mm) aneurysms. They advocated for preventive
surgical treatment of incidental aneurysms given the
higher than previously reported rupture risk and the
high fatality rate of SAH.
Phase 2 of the ISUIA was published in 2003 and
was a landmark contribution Table 16.2 (106). Partici-
pating centers from the United States, Canada, and
Europe enrolled 4060 patients. One-thousand six-hun-
dred ninety-two did not undergo aneurysm repair,
1917 had open surgery, and 451 underwent endovascu-
lar treatment. Five-year cumulative rupture rates for
patients who did not have a history of SAH with aneur-
ysms arising from the ICA, anterior communicating or
anterior cerebral artery, or middle cerebral artery
(MCA) were 0%, 2.6%, 14.5%, and 40% for aneurysms
less than 7mm, 712mm, 1324mm, and 25mm or
greater, respectively. Aneurysms of the posterior circu-
lation and posterior communicating artery carried a
cumulative 5-year rupture risk of 2.5%, 14.5%, 18.4%,
and 50% for the same size categories. The risks of
aneurysm repair reported were higher than previously
noted. The overall morbidity and mortality for patients
Table 16.2 Results Reported from the Second ISUIA Publication (106). (A) Data Presented Outlining the Risk of Rupture by Size and
Location. (B) Results of Surgical and Endovascular Treatment
ISUIAPhase 2
A.
Location ICA, AComm, ACA, MCA
Risk of Rupture <7mm0%
(5yr cumulative risk) 712mm2.6%
1324mm14.5%
25mm40%
B.
Treatment Surgical
Risk of morbidity and mortality Group I12.6%
at 1year Group II10.1%
Predictors of Poor Outcome 1. Increasing age (>50 years)
2. Increasing aneurysm size (>12mm)
3. Location (posterior circulation/PComm)
Group Ipatients with no prior history of SAH; Group IIpatients with a history of SAH from another aneurysm that was successfully
repaired. Abbreviation: ICA, internal carotid artery; AComm, anterior communicating artery; ACA, anterior cerebral artery; MCA, mid-
dle cerebral artery; PComm, posterior communicating artery.
331
with and without a prior history of SAH undergoing
open surgical repair was 12.6% and 10.1%, respectively
at 1year. The overall morbidity and mortality for
patients with and without a prior history of SAH
undergoing endovascular repair was 9.8% and 7.1%,
respectively at 1year. Increasing age (>50 years) was a
strong predictor of poor surgical outcome, while
increasing aneurysm size (>12mm) and posterior circu-
lation/posterior communicating artery location was a
strong predictor of both surgical and endovascular out-
comes. The authors concluded that many factors are
involved in the management of patients with unrup-
tured intracranial aneurysms. They asserted that site,
size, and group-specific risks of the natural history
should be analyzed in light of site, size, and age-spe-
cific risks of repair for a given patient.
Clearly this report from the ISUIA was the
most important contribution to date concerning
unruptured intracranial aneurysms. However, it was
also met with some criticism (115). Exclusion criteria
were wide and no account of the number of patients
excluded from the study was provided. Further-
more, data concerning recruitment rates were not
provided. Anterior cerebral/anterior communicating
artery aneurysms appear underrepresented with respect
to the population of patients with SAH. Additionally,
aneurysms under 2mm were arbitrarily excluded even
though these aneurysms can rupture. Family history
was also not clearly defined. Finally, separate results for
patients in groups 1 and 2 were not consistently
provided.
In summary, considerable data have emerged
concerning the natural history of unruptured intra-
cranial aneurysms. These data, although imperfect,
provide the clinician with important information to
be considered in the formulation of a treatment plan
for a given patient with an unruptured intracranial
aneurysm.
Ruptured Intracranial Aneurysms
The natural history of ruptured intracranial aneur-
ysms is well defined. The peak of rebleeding from a
Posterior circulation, PComm
<7mm2.5%
712mm14.5%
1324mm18.4%
25mm50%
Endovascular
Group I9.8%
Group II7.1%
1. Increasing aneurysm size (>12mm)
2. Location (posterior circulation/PComm)
332 NEUROINTERVENTIONAL MANAGEMENT
ruptured aneurysm occurs on the first day (4% on
day 1) (116). The risk is then 1.5% per day for
13 days. Fifteen to 20% of patients with ruptured
aneurysms will rebleed within 14 days and 50% will
rebleed within 6 months (116). Thereafter the risk is
~3% per year (116). The mortality associated with
rebleeding is extremely high (117119), approaching
80% in some series. In general, this dismal natural his-
tory warrants expeditious treatment of ruptured intra-
cranial aneurysms except perhaps in extreme
circumstances such as patients who are medically
unstable or in a devastated neurological condition
with no significant chance for recovery.
PATIENT SELECTION
Patient selection for the treatment of intracranial
aneurysms has changed as endovascular techniques
have evolved and data have arisen concerning the
safety and efficacy of endovascular aneurysm ther-
apy. It is critically important to note that endovascu-
lar therapy and open microsurgical aneurysm
treatment are complementary options for patients
harboring intracranial aneurysms that can be used in
isolation or in combination for a given patient. The
subspecialty concerned with the treatment of intra-
cranial aneurysms appears to be shifting from a pro-
cedure-specific focus (i.e., only craniotomy or only
coil embolization) to a disease-specific focus where
all options are available and considered for a given
patient (often by the same practitioner or in the set-
ting of a collaborative, multidisciplinary team). The
overall goal of treatment for a patient with an intra-
cranial aneurysm is to offer the most efficacious and
durable treatment that can be performed with accept-
ably low risk using whatever tools and skills are
necessary.
In the beginning, endovascular techniques for
intracranial aneurysms were reserved for patients
with intracranial aneurysms that were moribund from
their hemorrhage (poor neurological condition) or
who had significant medical problems preclud-
ing traditional open surgery. This eventually evolved
to include many patients with posterior
circulation aneurysms (especially at the basilar bifur-
cation location). At present, the indications for endo-
vascular aneurysm treatment have broadened with
endovascular therapy emerging as an important
option to be considered in nearly all patients.
Ruptured Intracranial Aneurysms
For ruptured intracranial aneurysms, the compelling
data emanating from the ISAT reports have had a res-
onating influence on treatment throughout the world
(120122). The initial results of ISAT appeared in
the Lancet in 2002 (13). The ISAT study enrolled
2143 patients with ruptured intracranial aneurysms
whose aneurysms were deemed suitable for treatment
with either endovascular treatment or microsurgery.
These patients were randomly assigned to neurosurgi-
cal clipping (n = 1070) or endovascular treatment
(n = 1073). The primary outcome measure was the
proportion of patients who were dead or dependent at
1year as defined by a modified Rankin scale score of
36. One-hundred ninety of 801 (23.7%) patients allo-
cated to endovascular treatment were dependent or
dead at 1year compared with 243 of 793 (30.6%) of
patients allocated to clipping which was highly signifi-
cant (p=0.0019). News of these significant results
spread throughout the media as well as the medical
community. A second report of ISAT was published
in the Lancet in 2005 (15). This report included more
complete follow-up and assessed the risk of epilepsy
in the two groups as a secondary outcome measure.
Two-hundred fifty of 1063 (23.5%) patients allocated
to endovascular treatment were dead or dependent
at 1 year, compared with 326 of 1055 (30.9%) patients
allocated to clipping with an absolute risk reduction
of 7.4% (95% CI 3.611.2, p = 0.0001). The apparent
early survival advantage was maintained for up to
7 years and was significant. Finally, the risk of epile-
psy was substantially lower in patients allocated
to endovascular treatment (relative risk 0.52, 95%
CI 0.370.74), although the risk of late rebleeding was
higher (7 of 1073 patients allocated to coiling rebled
after 1year compared to 2 of 1070 patients allocated to
clipping). The most recent follow-up from ISAT was
published in 2009 (14). Patients enrolled in ISAT were
followed annually for a minimum of 6 years and a
maximum of 14 years (mean follow-up 9 years).
Twenty-four rebleeds occurred more than 1year after
treatment. Of these, 13 were from the treated aneurysm
(10 in the coiling group and 3 in the clipping group,
p=0.06). At 5 years, 11% (112 of 1046) of the patients in
the endovascular group and 14% (144 of 1041) of the
patients in the neurosurgical group had died (p=0.03).
The risk of death at 5 years was significantly lower in
the coiling group than in the clipping group but the
proportion of survivors who were independent did not
differ between the groups (83% in the endovascular
group and 82% in the neurosurgical group). Finally,
the standardized mortality rate for patients treated for
ruptured aneurysms was increased compared to the
general population.
Criticisms of ISAT surfaced including exclusion
of almost 80% of screened patients, enrollment almost
exclusively from Europe (with five centers enrolling
over half of the patients), over-representation of good
grade patients [88% World Federation of Neurosurgical
Societies (WFNS) grade 1 or 2], under-representation
of MCA aneurysms, established minimum criteria for
endovascular therapists (30 aneurysms) but none for
neurosurgeons performing the clippings, and seem-
ingly poorer surgical results than prior studies with
no report of procedural complications (123131).
Despite the above shortcomings, this was a well-
conducted trial whose results apply to at least a spe-
cific population of patients whose aneurysms are
deemed suitable for treatment with microsurgery and
endovascular treatment. Clearly, the results have
changed practice patterns for the treatment of rup-
tured intracranial aneurysms with a strong shift
toward endovascular treatment (120122).
Subsequent analyses of the ISAT data have also
appeared. Late retreatment was not unexpectedly
higher in coiled patients (6.9 fold) (132). For elderly
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
patients (age >65 years), there was no overall differ-
ence in clinical outcome between clipped and coiled
patients but a higher incidence of epilepsy in the sur-
gical group (133). For patients <40-years old, Mitchell
and colleagues suggest that the advantage of coiling
cannot be assumed in this age group due to the poten-
tial risk of late rebleeding (134). At 1year, endovascu-
lar treatment appeared to be more costly but
associated with better outcomes (135). Finally, cogni-
tive outcome was found to be superior in coiled com-
pared to clipped patients at 1year (136).
The above data are taken into consideration
when formulating a treatment plan for an individual
patient with a ruptured aneurysm. In general, all
treatment options are presented to the patient and
their family. As neurological condition is a powerful
predictor of outcome in aneurysmal SAH (137), the
clinical grade of the patient factors into the treatment
decision-making process. Patients in HuntHess
Grades IIV (or WFNS grades IIV) are offered defini-
tive treatment of their aneurysm. The treatment of
Grade V patients remains controversial and has been
the subject of substantial investigation (138149).
These data demonstrate that the mortality of Grade V
SAH patients is high but a proportion of patients may
achieve a functional outcome. We advocate for place-
ment of an external ventricular drain and aggressive
critical care management in all Grade V patients. If
these patients improve, they are subsequently offered
aggressive treatment of their aneurysms. If no
improvement is seen, many patients may not be
offered treatment of their aneurysm although younger
patients receive stronger consideration for treatment.
However, any patient who presents in Grade V condi-
tion with a space occupying hematoma is considered
for emergent craniectomy, clot evacuation, and defini-
tive aneurysm treatment (usually with concomitant
clipping but occasionally aneurysm coiling and then
craniectomy/clot evacuation).
The selection of treatment modality for a rup-
tured aneurysm must take into consideration multiple
factors including aneurysm size, morphology, location,
the procedural risk (secondary to age, clinical condi-
tion, medical co-morbidities) as well as the potential
risk for recurrence and the impact of recurrence (par-
ticularly for young patients). Table 16.3 outlines cur-
rent selection criteria for endovascular treatment (both
for ruptured and unruptured aneurysms). However,
these are only guidelines that must be applied to an
individual patient. For example, Fig. 16.1 illustrates
the principles of therapy tailored to an individual
patient. In this patient with diffuse SAH and two pos-
terior circulation aneurysms with uncertain source of
hemorrhage, the basilar bifurcation aneurysm was
treated with coil embolization resulting in complete
occlusion, and the large PICA aneurysm was treated
with microsurgical clipping with complete occlusion
at the same setting based upon the factors discussed
above.
Stent-assisted coil embolization in the setting of
acute SAH warrants brief discussion due to the poten-
tial risks of hemorrhagic complications (secondary
to necessary dual antiplatelet therapy) in the acute
setting particularly when cerebrospinal fluid (CSF)
333
Table 16.3 Selection Criteria for Endovascular Treatment. (A)
Inclusion Criteria for Endovascular Treatment. (B) Exclusion
Criteria
Selection Criteria for Endovascular Treatment
A. Inclusion Factors
. Ruptured and unruptured aneurysms that appear favorable
for endovascular coiling
. Elderly patients
. Patients in poor neurological condition
. Patients with significant medical co-morbidities
. Posterior circulation aneurysms (especially basilar
bifurcation)
. Some paraclinoid aneurysms
. Previously clipped aneurysms (residual or recurrent)
. Previously coiled aneurysms
. Existence of concomitant vasospasm
B. Exclusion Factors (relative only)
. One or more branches incorporated into the neck/dome
. Wide-neck ruptured aneurysms that can be satisfactorily
clipped (if a stent is deemed likely)
. Space occupying hematoma requiring emergent surgical
evacuation
It is important to note that none of these criteria are absolute. For
example, for wide-neck ruptured aneurysms that are difficult or
dangerous to clip, stent-assisted coil embolization can be readily
performed. For aneurysms incorporating branches into the dome
or neck, endovascular treatment can still be performed with bal-
loon- or stent-assistance if other options are less suitable.
diversion procedures are necessary (150152). This
does not preclude the use of stent-assisted coil embo-
lization in the acute SAH setting if this is deemed to
be the best option, but does provide impetus to con-
sider alternatives such as balloon remodeling or
aneurysm clipping.
Unruptured Intracranial Aneurysms
Patient selection for treatment of their unruptured
aneurysm must weigh the risks of the proposed treat-
ment with the risks posed by the natural history of
the aneurysm over the patients projected life span.
The natural history of unruptured aneurysms was
discussed above. Factors that are likely important
include aneurysm size, location, prior history of
SAH, family history of SAH, and certain aneurysm
morphological factors (such as aspect ratio or irregu-
larities/teats). The patients physiological age and
medical co-morbidities must also be considered.
Finally, the results of the treating team must be fac-
tored in. In highly experienced hands, complication
rates are low. In a recent report by Benes and col-
leagues (153), they suggested that unruptured aneur-
ysms can be treated with coil embolization with low
rates of complication (6-month combined morbidity
and mortality of 1.5%) justifying offering treatment
to most patients with unruptured aneurysms. Along
similar lines, surgical treatment produced low rates
of morbidity and mortality in patients with unrup-
tured aneurysms in expert hands (154158). Tufflash
et al. (154) demonstrated no cognitive effects of cra-
niotomy for unruptured aneurysms. Furthermore, the
unparalleled team of Dr. Charles Drake and collea-
gues was able to clip unruptured basilar bifurcation
334 NEUROINTERVENTIONAL MANAGEMENT

H
LAO/RAO
CRAN/CAUD

(A) (B)

(C)

Figure 16.1 Coil embolization and clip ligation of posterior circulation aneurysms in a patient with SAH and unknown source of hemor-
rhage. (A) CT scan shows diffuse SAH with no definite localizing features. (B) 3D angiography demonstrates a relatively narrow-necked
basilar bifurcation aneurysm and a broad-necked left PICA - posterior inferior cerebellar artery aneurysm (arising from a large PICA -
posterior inferior cerebellar artery parent vessel). (C) Post-treatment angiogram at 6 months demonstrates complete occlusion of both
aneurysms (the coiled basilar bifurcation aneurysm and the clipped posterior inferior cerebellar artery (PICA) aneurysm).

aneurysms <12.5mm with a 3.6% risk of poor out-
come and no mortality (156). Later in their monu-
mental series, the combined risk of morbidity and
mortality was reduced below 3% (155). The same
basic considerations outlined for ruptured aneurysms
apply to the selection of treatment of a given
patients unruptured aneurysms with the exception
that stent-assisted coil embolization and flow-diver-
sion may be used more liberally as dual antiplatelet
therapy does not carry the same risk in the elective
setting (Table 16.3).
TECHNIQUES FOR ENDOVASCULAR
ANEURYSM TREATMENT
As mentioned, endovascular techniques have evolved
remarkably from their earliest beginnings and continue
to develop at a rapid pace. Endovascular aneurysm
treatment has emerged into a viable option for both
ruptured and unruptured intracranial aneurysms.
Endovascular techniques for aneurysm treatment can
be divided into two basic strategies. A deconstructive
endovascular approach involves sacrifice of the parent
vessel as a component of the aneurysm treatment.
A reconstructive endovascular approach involves
selective occlusion of the aneurysm with intentional
preservation of the parent vessel.
Deconstructive Approach for Endovascular
Aneurysm Treatment
Deconstructive approaches may be considered in spe-
cific circumstances including symptomatic cavernous
ICA aneurysms (or other aneurysms presenting with
mass effect not amenable to selective obliteration), dis-
secting aneurysms or pseudoaneurysms of the anterior
and posterior circulations, peripherally located aneur-
ysms or for recurrent aneurysms that cannot be
handled with reconstructive techniques (endovascular
or surgical).
Parent vessel occlusion was traditionally
achieved through a surgical approach. Early surgical
series reported high rates of morbidity and mortality
(159,160). However, with refinements in technique,
and perhaps more importantly with improved patient
selection, the safety and efficacy of surgical occlusion
has improved to acceptable figures (161163). There
has been a definite shift toward endovascular occlu-
sion for deconstructive aneurysm therapies using bal-
loons, coils, vascular plugs, liquid embolics, or
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
combinations thereof (77,86,87,93,94,164172). There
has been little comparison of surgical versus endovas-
cular techniques for parent vessel occlusion. A recent
study compared endovascular occlusion versus com-
mon carotid surgical ligation for carotid sacrifice as a
treatment for unclippable and uncoilable aneurysms
(161). They noted excellent results with both techni-
ques and low rates of complications in a series of
27 patients (15 treated with endovascular techniques
and 12 treated with CCA ligation). There are, how-
ever, theoretical advantages to an endovascular
approach. The endovascular approach is minimally
invasive with quicker recovery times. Parent vessel
occlusion may easily be performed on an awake patient.
A balloon occlusion test and parent vessel occlusion can
be performed at one setting with concomitant evalua-
tion of angiographic collaterals. Additionally, the poten-
tial for residual flow within the aneurysm can be
evaluated for each level of parent vessel occlusion
(which may be particularly important for aneurysms of
the paraclinoid/supraclinoid ICA segment and aneur-
ysms of the vertebrobasilar circulation). Aneurysms in
these locations may remain open by collaterals after
parent vessel occlusion depending upon the occlusion
strategy employed (Fig. 16.4B) (173).
Endovascular deconstructive therapies have
demonstrated overall excellent efficacy and safety for
intracranial aneurysm treatment (161,164,167,168,172,174).
Selection is critically important as with any type of
aneurysm therapy. Assessment of collateral circula-
tion/tolerance of parent vessel occlusion as well as
the potential for residual aneurysm flow must be eval-
uated. For patients with inadequate collateral flow,
parent vessel occlusion can still be performed after a
distal revascularization (bypass) strategy is employed.
Fig. 16.2 illustrates this concept where a surgical
bypass was constructed followed by endovascular
obliteration of a ruptured posterior inferior cerebellar
artery (PICA) aneurysm and large PICA vessel that
could not be easily obliterated with a reconstructive
strategy.
Assessment of collateral circulation and patient
tolerance of parent vessel occlusion is discussed in
detail elsewhere in this monograph. In brief, assess-
ment of collateral supply is undertaken angiographi-
cally. A rapid assessment of the Circle of Willis can
be undertaken during the diagnostic angiogram. Car-
otid cross-compression can be performed to assess
the anterior communicating artery (the ipsilateral
carotid artery is manually compressed while the con-
tralateral carotid artery is injected). An Allcock test
can be performed to assess the presence of posterior
communicating arteries (an individual carotid artery
is manually compressed while the dominant verte-
bral artery is injected to assess the posterior commu-
nicating artery on that side). A more detailed
assessment of collateral flow can be determined dur-
ing a balloon test occlusion. With the patient fully
anticoagulated (typically to an activated clotting time
23 times baseline), a balloon is inflated in the large
vessel of interest (most commonly the ICA). Colla-
teral supply to the vascular territory at risk with
parent vessel occlusion can be supplied via (1) the
Circle of Willis (via the anterior communicating
artery and/or posterior communicating artery), (2)
335
pial or leptomeningeal collaterals, (3) external-to-internal
carotid artery anastomoses arising at the ophthalmic,
cavernous and/or petrous ICA segments. These
potential collaterals can be assessed directly by inject-
ing other vessels with the balloon inflated in the large
vessel of interest.
As part of the assessment of collateral circula-
tion, it is also important to evaluate the extracranial
and intracranial vasculature outside of the territory
of interest for evidence of pathology. The presence of
other aneurysms, vascular stenoses, vessel dissections,
evidence of fibromuscular dysplasia, or other patholo-
gies should be carefully researched as this may factor
into the decision to proceed with permanent parent
vessel sacrifice.
Once the collateral circulation has been assessed,
clinical balloon test occlusion can then be performed
with the balloon inflated at or near the site of proposed
vessel occlusion. For balloon occlusion testing of the
ICA, we perform clinical assessment over a period of
30 minutes and induce hypotension. Adjunctive tests to
assess adequacy of cerebral blood flow (such as SPECT,
PET, and XeCT) may be added (167,175180). If the
patient passes the test, parent vessel occlusion can then
be performed. If the patient fails the test, an alternate
therapy should be employed or occlusion performed
after a bypass is constructed.
To present a balanced perspective, some groups
do not perform a clinical balloon test occlusion prior
to sacrifice of the ICA but rely solely on angiographic
data (181). Abud et al. (181) reported the use of
venous phase timing during balloon test occlusion as
a criterion for permanent ICA sacrifice in a series of
60 patients. They performed all test occlusions under
general anesthesia. They assessed symmetry of the
venous phases of each hemisphere. They conclude
that carotid sacrifice was possible when the delay
between the venous phase of the control and tested
hemisphere was <3 seconds. They reported no peri-
procedural complications and no neurological deficit
development using this criterion.
Our protocol for occlusion of distal vessels
(for example, for peripherally located aneurysms)
involves provocative testing using sodium amobarbi-
tal and lidocaine with the patient awake (for clinical
testing) or under general anesthesia with neurophy-
siological monitoring [using somatosensory evoked
potentials (SSEPs), motor evoked potentials (MEPs),
electroencephalography (EEG), and brainstem audi-
tory evoked responses (BAERs) depending upon
the vascular territory at risk]. If the patient passes
the test (clinically or with no change in neurological
monitoring) parent vessel occlusion can then be
performed.
With careful selection, satisfactory results can be
achieved with endovascular parent vessel occlusion.
For example, in a systematic review conducted by van
der Schaaf and colleagues (172), endovascular parent
vessel occlusion for treatment of aneurysms of the
cavernous sinus was accompanied with a 1.6% rate of
complications in the first 24 hours (4 of 247 patients)
and a 3.4% chance of late ischemic complications (5 of
148 patients). One-hundred fifty-three of 157 aneur-
ysms (97.5%) were completely thrombosed at most
recent follow-up.
336 NEUROINTERVENTIONAL MANAGEMENT

Technical Aspects of Deconstructive dissecting, ruptured vertebral artery aneurysm depicted

Endovascular Aneurysm Treatment
Parent vessel occlusion can be performed using vari-
ous endovascular tools including balloons, coils, vas-
cular plugs, liquid embolics, or combinations thereof
(77,86,87,93,94,164172,182). Balloons are now used
rarely and are not readily available. Coils are used
most frequently alone or in combination with liquid
embolic agents or vascular plugs.
Parent vessel occlusions are generally performed
under full anticoagulation. We prefer to perform vessel
occlusions under proximal flow arrest achieved using a
balloon guide catheter (placed in the proximal parent
vessel) or using a separate balloon catheter system such
as a Hyperform or Hyperglide (ev3, Irvine, California) or
Ascent (Micrus, San Jose, California) balloon delivered
simulataneously with a microcatheter through a stand-
ard guide catheter. Proximal flow arrest is thought to
prevent distal embolization while the parent vessel is
undergoing occlusion (without the balloon, flow would
occur through the coil mass until tight enough packing
was achieved). Second, proximal flow arrest may mini-
mize the chance of inadvertent distal coil migration to
occur until a stable coil mass is achieved (and will also
prevent uncontrolled distal migration of liquid embolic
agent if it is employed). In general, we attempt to trap
the aneurysm if at all possible. For example, the
in Fig. 16.3 was treated by trapping the aneurysm
(occluding the vertebral artery distal to the aneurysm but
proximal to its junction with the basilar artery) followed
by occluding the aneurysmal segment and the more
proximal vertebral artery under flow arrest using a prox-
imal Ascent balloon. Once it is thought that complete
vessel occlusion has been obtained, the proximal balloon
can be deflated to confirm complete vessel occlusion.
Liquid embolic agents such as Onyx (ev3, Irvine, Califor-
nia) or n-BCA can be used as an adjunct to achieve com-
plete vessel occlusion (usually after a framework of coils
has been deposited) (Fig. 16.4). Vascular plugs such as
the Amplatzer varieties can be used in large proximal
vessels (usually the extracranial carotid or vertebral
arteries) to achieve complete vessel occlusion. They are
inexpensive compared to coils, are easy to deploy
through standard guide catheters and achieve rapid ves-
sel occlusion (182).
Reconstructive Approach for Endovascular
Aneurysm Treatment
A reconstructive approach for endovascular aneurysm
treatment involves selective occlusion of the aneurysm
with preservation of the parent vessel. An endosa-
ccular reconstructive approach involves filling the

(A) (B)

(C) (D)

Figure 16.2 Complementary microsurgical and endovascular treatment for a complex ruptured, PICA aneurysm. (A) CT scans demon-
strate posterior fossa SAH and hydrocephalus. (B) CT angiogram demonstrates a complex PICA aneurysm. Although the aneurysm
arises from the left PICA vessel, it is located to the right of the midline which would make surgical obliteration more difficult. (C) Angio-
gram demonstrating a broad-necked left PICA aneurysm incorporating a large PICA branch into its base. (D) An occipital artery to
PICA bypass was constructed. Intraoperative photograph upon completion of the anastomosis. (Continued)
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 337

(E)

(F)

Figure 16.2 (Continued) (E) Due to potential difficulties with a surgical approach, the PICA aneurysm and PICA vessel were occluded
with coil embolization. (F) The patent occipital to PICA bypass is seen filling the entire PICA territory.
338 NEUROINTERVENTIONAL MANAGEMENT

(A)

RVERT
RVERT

(B)

(C) (D)

Figure 16.3 Deconstructive approach to a ruptured dissecting intracranial vertebral artery aneurysm. (A) Non-contrast head CT demon-
strates posterior fossa SAH and intraventricular hemorrhage. (B) Right vertebral injection demonstrates a ruptured dissecting vertebral artery
aneurysm (arrows). No right PICA is visualized. (C) The black arrow indicates the tip of the microcatheter that will be used to deposit coils to
trap the dissecting vertebral artery aneurysm. Coil deposition is begun distal to the aneurysm but proximal to the vertebrobasilar junction.
The proximal black arrow indicates the position of the balloon that will be inflated during the vertebral artery occlusion.(Continued)
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
(E)
Figure 16.3 (Continued) (E) Control angiograms from the right ICA demonstrate a large right posterior communicating artery filling the
distal basilar artery and basilar trunk (arrows).
aneurysm sac with embolic material (for example,
coils or liquid embolic agent such as Onyx HD 500).
An endoluminal reconstructive approach aims to
achieve aneurysm sac occlusion while restoring the
integrity of the vessel wall (such as with flow divert-
ing devices). At times, both strategies can be com-
bined to achieve aneurysm occlusion (183).
Coil technology has advanced remarkably since
the detachable coil was first released in 1991. Coils
have evolved from being available in limited sizes
and helical configurations to being available in many
diameters, lengths, and complex shapes (in addition
to standard helical shapes). Additionally, some coils
are manufactured with bioactive coatings [such as the
Micrus (San Jose, California), Presidio and Stryker
Neurovascular (Fremont, California) Matrix2 series
containing polyglycolic acid coating], or volume
expanding gels [Microvention (Tustin, California)
hydrocoil system with coils containing hydrogel] in an
attempt to promote stable aneurysm occlusion. Plati-
num coils generally employ 0.015-inch or 0.010-inch
thickness platinum wire although some companies uti-
lize different wire thickness dependent upon the diam-
eter of the coil loop [thicker wire for progressively
larger coil loop diameter such as in the ev3 (Irvine,
California) Axium coil line]. The majority of modern
coils are also designed to be stretch resistantthat
is, to resist stretching during manipulation or retrieval.
The platinum coil wire is delivered through a micro-
catheter using a delivery mandrel that is typically
175cm in length. The platinum coil is attached to the
delivery mandrel via an intermediate segment con-
taining the potential detachment zone. In currently
available coils, the detachment zone is located 3cm
distal to a radioopaque marker located on the deliv-
ery mandrel. Current microcatheters contain two
radioopaque markersthe distal marker is located at
the tip of the microcatheter and the proximal marker
339
is located 3cm proximal to the distal marker. When
the radioopaque marker on the delivery mandrel is
aligned with the proximal radioopaque marker on
the microcatheter, the detachment zone is then
located outside of the microcatheter allowing for
accurate detachment of the coil (Fig. 16.5). Detach-
ment of the coil from the delivery mandrel occurs
through a temperature-dependent dissolution of a
polymeric linkage, electrolysis, or by a hydraulic
mechanism. Detachment now is performed almost
exclusively through a handheld device.
Technical Aspects of Coil Embolization for
Intracranial Aneurysms
At the majority of centers, including our own, coil
embolization of intracranial aneurysms is performed
under general anesthesia. There have been some
reports of performing coil embolization in awake
patients (184) but we believe that general anesthesia
facilitates the acquisition of better quality images and
hemodynamic management. We perform all intracra-
nial coil embolization procedures under general anes-
thesia with continuous neurophysiological monitoring
including SSEP, EEG, and BAER monitoring for all
ruptured aneurysms and unruptured posterior com-
municating artery and posterior circulation aneurysms
and SSEP and EEG monitoring for all unruptured
anterior circulation aneurysms (16,17).
Intracranial pressure monitoring with a ventricu-
lostomy and hemodynamic monitoring with a Swan
Ganz catheter and radial arterial line are highly rec-
ommended in ruptured aneurysm patients with Hunt
and Hess grades of III and above. For patients with
unruptured aneurysms and patients with ruptured
aneurysms with Hunt and Hess grades I and II, blood
pressure is typically monitored through a sheath
(upsized from the guiding catheterusually a 7F
340 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B) (C)

(D)

Figure 16.4 ICA occlusion using coils and Onyx. Thirty-year female with a history of radiation therapy for a brain tumor. She had stent
and coiling of a fusiform, dysplastic right ICA but returned after noting progressive visual deficits. (A) Right ICA injections demonstrating
dysplastic supraclinoid ICA segment. (B) With the balloon inflated proximally in the ICA (black arrows), injection of the common carotid
artery demonstrates robust filling of the supraclinoid segment via external carotid collaterals to the ophthalmic artery (white arrow) and
retrograde filling of the supraclinoid ICA (blue arrow). (C) The Ascent balloon is inflated in the ICA (black arrows). Onyx 34 is injected
into the coil mass via the microcatheter nested within the coil mass (white arrow denotes the catheter tip). (D) Final control runs from
the right common carotid artery demonstrate no filling of the ICA or aneurysmal segment. The ophthalmic artery continues to fill via
external collaterals (white arrow) and the choroidal blush is noted (black arrow).
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 341

(A)

(B)

Figure 16.5 Microatheter placement and alignment of radiopaque coil marker with proximal microcatheter marker. (A) The microcath-
eter has been placed into the AComm aneurysm under roadmap guidance in the AP and lateral projections. The distal (black arrows)
and proximal (blue arrows) microcatheter markers can be seen. (B) The radioopaque marker on the coil delivery mandrel can be seen
aligned with the proximal marker on the microcatheter (black arrows). This ensures that the detachment zone is located at the tip of
the microcatheter (3cm from the proximal marker) and the coil will be detached outside of the microcatheter in the aneurysm.

sheath when a 6F guiding catheter is used). The
sheath also provides continuous access for drawing
blood specimens to measure the ACT.
Arterial access is normally obtained by inserting
the desired sheath through a common femoral artery
puncture. We typically use fluoroscopy and anatomi-
cal landmarks to ensure that the puncture site is
located at or below the femoral head. We usually
puncture the artery on the side opposite the pathology
of interest (or opposite the side used to gain access to
the pathology) or on the right side if the side of the
pathology is not known. The sheath is secured with a
stitch or Tegaderm and is connected to a heparinized
flush system.
342 NEUROINTERVENTIONAL MANAGEMENT
A guiding catheter connected to a continuous
heparinized flush system is advanced over a guide-
wire into the aortic arch. If the aneurysm location is
unknown, a six-vessel angiogram is typically per-
formed including bilateral ICAs, external carotid
arteries, and vertebral arteries. Digital subtraction
angiography is performed in the AP, lateral, and obli-
que projections as necessary. A three-dimensional
(3D) spin angiogram can also be performed and these
data can be processed on a separate workstation to
create 3D projections. The purpose of these views is to
identify the site of the aneurysm as well as optimal
working projections that will allow effective coil
embolization of the aneurysm and preservation of all
afferent and efferent vessels. Specific data to be
acquired include the following. (i) The size, shape and
projection of the aneurysm as well as the size of the
aneurysm neck in relation to the aneurysm dome and
parent vessel. (ii) Potential incorporation of branches
into the aneurysm dome or neck. (iii) The size and
morphology of the parent vessel (particularly if
adjunctive strategies are being considered such as bal-
loon- or stent-assistance). (iv) Potential collateral sup-
ply to the vascular territory involved with the
aneurysm (particularly for large, giant, or complex
lesions where parent vessel occlusion may be contem-
plated as a primary or bail-out strategy). (v) Pres-
ence of vasospasm or other pathology such as
dissection, fibromuscular dysplasia, vascular malfor-
mations, etc.
Once the optimal working projections are
obtained, a microcatheter is advanced over a micro-
guidewire into the aneurysm using roadmap guid-
ance. Some angiographic equipment includes a
fluoro fade function where a previous run can be
faded in to overlay the live screens. Sometimes the
working projections for coiling are suboptimal to
allow navigation of the more proximal vasculature
and two sets of roadmaps or overlays need to be uti-
lized (one for accessing the aneurysm and one for
coiling the aneurysm). The microcatheter may be
steam-shaped according to aneurysm geometry and
its relation to the parent vessel although pre-shaped
and unshaped microcatheters can be effectively uti-
lized depending on the operator.
For unruptured aneurysms, the patient is fully
anticoagulated prior to accessing the aneurysm with
an ACT 23 times baseline or ACT of 250300s. For
ruptured aneurysms, anticoagulation administration
varies based upon operator preference, aneurysm
characteristics, and patient-specific factors (such as the
presence of a large intracerebral hemorrhage). In gen-
eral, we prefer to heparinize as the first coil is being
deployed and we are confident that the aneurysm will
be coiled. If stent or balloon assistance will be utilized
(see later) in the setting of an acutely ruptured aneur-
ysm, we heparinize prior to use of these techniques
due to the heightened risk of thromboembolic
complications.
With the microcatheter in the aneurysm, the first
coil is selected and deployed. The first coil will gener-
ally be the largest coil utilized. We select coil diameter
based upon averaging the size of the aneurysm in
three planes (for example, an 8  10  12mm aneur-
ysm would likely be treated with an initial coil
diameter of 10mm). The first coil serves to frame the
aneurysm, ideally filling the confines of the aneurysm
and spanning the aneurysm neck. Subsequent coils
are selected of decreasing diameter to progressively
fill the aneurysm (like a Russian doll concept). If
the coil herniates out of the aneurysm neck or appears
to compartmentalize (fill only a portion of the aneur-
ysm), it can be withdrawn and repositioned until a
more desirable coil configuration is achieved. Prior to
detachment of the coil, a digital subtraction run is per-
formed to confirm accurate position of the coil within
the aneurysm, preservation of the associated branches,
and the absence of thrombus formation or emboliza-
tion. If the coil position is acceptable, the coil is then
detached from the delivery mandrel and the mandrel
is subsequently removed from the microcatheter. The
initial coil used is typically a complex-shaped coil,
and subsequent coils may be complex or helical
depending on operator preference and aneurysm char-
acteristics. With deposition of subsequent coils in the
aneurysm, it may become difficult to visualize where
the coil is being deposited and when it has been com-
pletely deposited. A blank roadmap can be used to
facilitate visualization of the coil being deposited and
the operator knows the coil is completely deposited in
the aneurysm after the radioopaque marker on the
delivery mandrel is aligned with the proximal marker
on the microcatheter (Fig. 16.5B). Coiling is continued
until the aneurysm is densely packed with no residual
filling seeing on angiography (while anticoagulated)
and/or until the microcatheter backs out of the aneur-
ysm with coil deployment. For ruptured aneurysm,
coiling is tenaciously pursued until the objectives of
the procedure are attained (usually no residual aneur-
ysm filling).
Follow-up After Coil Embolization
Patients who have undergone coil embolization
undergo prolonged follow-up. The majority of patients
undergo a follow-up catheter angiogram and magnetic
resonance (MR) angiogram at 6 months. If the results
are satisfactory, these patients undergo MR angiogra-
phy every 6 months for the next 18 months and then
every year until year 5. If there is recurrence found on
a follow-up MR angiography at any of these interval
follow-ups, a catheter angiogram is performed at
the time the recurrence is documented. Otherwise, the
patient undergoes a catheter angiogram at year 5.
Thereafter, the patient may be followed annually or
semi-annually with MR angiography.
Results of Coil Embolization for Intracranial
Aneurysms
We have previously reported the results from the
ISAT reports demonstrating an improved outcome
associated with coiling compared to clipping in
patients with ruptured intracranial aneurysms whose
aneurysms were deemed suitable for treatment with
either method (1315). The safety and efficacy of
endovascular treatment for unruptured aneurysms
has also recently been reviewed. Naggara et al. (185)
conducted a systematic review and meta-analysis
focused on the potential safety and efficacy of
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
endovascular treatment for unruptured aneurysms. In
this review, they examined 71 studies. Procedural
unfavorable outcome was seen in 4.8% of patients
(189 of 5044). Satisfactory immediate angiographic
occlusion of the treated aneurysm was seen in 86.1%
(2660 of 3089 aneurysms). Recurrence of the aneurysm
was seen in 321 (24.4%) of 1316 patients followed for
0.4 to 3.2 years. Retreated was performed in 9.1% of
patients (166 of 1699). The annual risk of hemorrhage
after therapy was 0.2%. Further support for endovas-
cular treatment of unruptured intracranial aneurysms
was provided by Benes et al. (153) as mentioned
above. This study included 131 patients with 151
unruptured intracranial aneurysms. Endovascular
treatment was successful in 145 aneurysms (96%). The
combined morbidity and mortality rate at 6 months
was 1.5% in their expert hands.
The experienced group from UCLA published an
11year experience with coil embolization of cerebral
aneurysms (186). They reported their results in treat-
ing 818 patients with 916 aneurysms. They divided
their experience into their initial 5 years experience
(230 patients with 251 aneurysms) (Group A) and
compared this with their subsequent 6 years experi-
ence (comprised of 588 patients harboring 665 aneur-
ysms) (Group B). They were able to achieve complete
angiographic obliteration in 55% of aneurysms and a
neck remnant in 35.4% of lesions. Incomplete emboli-
zation was encountered in 3.5% of aneurysms and coil
occlusion was unsuccessfully attempted in 5%. There
was a higher complete embolization rate in Group B
compared to Group A. The overall morbidity/mortal-
ity rate was 9.4%. Recanalization was seen in 26.1% of
aneurysms in Group A compared to 17.2% of those in
Group B. The overall recanalization rate 20.9% and
correlated with the size of the dome and neck of the
aneurysm.
Pandey et al. (187) recently published the Tho-
mas Jefferson University experience with the endovas-
cular treatment of posterior circulation aneurysms.
Two-hundred seventy-five patients were included and
mean clinical and angiographic follow-up was 31.8
and 31.3 months, respectively, for patients treated
before 2004. One-hundred six patients (38.5%) har-
bored unruptured aneurysms. The most common loca-
tion was the basilar apex or posterior cerebral artery
(PCA) which comprised 189 of the lesions (68.7%).
Two-hundred thirty-seven patients (87.8%) had suc-
cessful embolization (>95% occlusion). On angiographic
follow-up, 55 patients (24.5%) developed recanalization
of at least 5% and retreatment was required in
11 patients (4.9%, 0.01%/patient yr). Rehemorrhage
occurred in 3 patients (1.1%, 0.003%/patient yr).
Complications causing clinical morbidity occurred in
14 patients (5.1%).
Several other recent studies have examined the
utility of endovascular treatment for ruptured intra-
cranial aneurysms. The Cerebral Aneurysm Rerupture
after Treatment (CARAT) study was an ambidirec-
tional cohort study across nine institutions (188).
Among 1001 patients, who were either clipped or
coiled, during a mean follow-up of 4 years, there were
19 post-procedural re-ruptures. The median time to
rerupture was 3 days and 58% led to death. The
degree of aneurysm occlusion was strongly correlated
343
with risk of rerupture. The overall risk of rerupture
tended to be greater after coil embolization compared
with surgical clipping (3.4% vs. 1.3%, p = 0.092), but
the difference did not persist after adjustment. Investi-
gators from the CARAT study also examined the
potential for delayed rebleeding (189). Rerupture of
the index aneurysm after 1year occurred in 1 patient
treated with coil embolization during 904 person-years
of follow-up (annual rate 0.11%) and in no patients
treated with surgical clipping during 2666 person-
years (p = 0.110). Aneurysm retreatment after 1year
was more frequent in patients treated with coil embo-
lization (p < 0.0001), but major complications were
rare during retreatment.
Reports from the Clinical and Anatomical Results
in the Treatment of Ruptured Intracranial Aneurysms
(CLARITY) series have recently surfaced (190). This
was a prospective multicenter consecutive series
including patients treated with coiling for ruptured
aneurysms. A total of 773 patients were included. The
rate of immediate aneurysm occlusion as adjucated by
two independent reviewers was complete occlusion for
366 aneurysms (47%), neck remnant for 324 aneurysms
(42%), and aneurysm remnant for 83 aneurysms (11%).
Postoperative anatomic results were significantly linked
to age but not to technique of endovascular treatment
or aneurysm characteristics (location, size, dome-to-
neck ratio) (190). The authors also analyzed factors
affecting the rate and outcome of endovascular treat-
ment complications in this series (191). The authors
demonstrate that a higher rate of thromboembolic com-
plications was seen in patients with aneurysms larger
than 10mm, in smokers, and in patients with aneur-
ysms with a neck larger than 4mm. The frequency of
intraoperative rupture was higher in MCA aneurysms,
in patients younger than 65 years, and in patients with-
out hypertension.
Collective, these data demonstrate safety and
efficacy of coil embolization for the treatment of intra-
cranial aneurysms although recanalization rates are
not insignificant (discussed further under the compli-
cations section).
Adjunctive Techniques for Coil Embolization of
Intracranial Aneurysm
Aneurysms that were not previously thought to be
amenable to coil embolization are now being treated
with increasing frequency as a result of improvements
in intracranial balloon and stent technology. Balloon
remodeling, stent-assisted coil embolization and multi-
ple microcatheter technique are examples of adjunc-
tive techniques that have broadened the indications
and expanded feasibility for the endovascular treat-
ment of intracranial aneurysms.
Balloon Remodeling Technique
The balloon remodeling technique employs a balloon
occlusion microcatheter that is intermittently inflated
across the neck of an aneurysm providing a scaffold-
ing against which coils are deployed through a sepa-
rate microcatheter from within the aneurysm. The
barrier provided by the inflated balloon allows succes-
sive coils to achieve a more stable configuration
344 NEUROINTERVENTIONAL MANAGEMENT
within the aneurysm without herniating into the
parent vessel as they are deployed. Reperfusion
occurs after each balloon deflation.
The balloon remodeling technique was devel-
oped by Moret and associates and has been subse-
quently used by many other groups (192202). This
technique was introduced to allow the treatment of
broad-necked aneurysms and possibly to enhance
packing density within the aneurysm.
Shapiro and colleagues recently conducted an
extensive review of the safety and efficacy of adjunc-
tive balloon remodeling for the endovascular treatment
of intracranial aneurysms (198). They reviewed a total
of 83 potential studies (4973 patients). Twenty-three
studies reporting results for 867 unassisted coiled and
273 balloon-assisted coiled aneurysms were examined
for thromboembolic complications and 21 articles with
993 unassisted coiled and 170 balloon-assisted coiled
aneurysms were examined for iatrogenic perforation
rates. They also examined initial and follow-up aneur-
ysm occlusion rates. No significant difference was
found in the rates of thromboembolism or iatrogenic
perforation. Moreover, follow-up aneurysm occlusion
rates were higher in balloon-assisted cases.
There are numerous nuances that have been
incorporated into the balloon remodeling technique.
The balloon remodeling technique can be performed
using a 6 French or larger guide [such as the Micro-
vention Chaperone (Tustin, California) with a 0.071
inner diameter or the Codman Neurovascular Envoy
(Raynham, Massachusetts) with a 0.070 inner diame-
ter], a 6 French sheath (such as the Shuttle sheath;
Cook Inc., Bloomington, Indiana), or two guiding
catheters placed through separate groin sites (particu-
larly if more than one balloon is being contemplated).
If a single guide or sheath is being used, a Y
adapter is placed on the guide/sheath to allow intro-
duction of both the microcatheter and balloon while
maintaining continuous heparinized flush. We have
found the 6F Chaperone guide to be useful as its
larger lumen allows friction-free simultaneous naviga-
tion of the balloon catheter and microcatheter.
The microcatheter is advanced under roadmap
guidance into the vessel of interest. The balloon
microcatheter is then advanced cross the neck of the
aneurysm. We typically use a HyperGlide balloon
(ev3, Irvine, California) whose diameter (3, 4, or 5
mm) and length (1030mm) is matched to the anat-
omy of the aneurysm at hand. The microcatheter is
advanced into the aneurysm. One or two loops of the
initial coil are deployed before the balloon is inflated.
Prior to balloon inflation, the patient is generally hep-
arinized to minimize the risk of thromboembolism.
The balloon is then inflated across the neck of the
aneurysm. The minimal amount of balloon inflation is
performed to allow occlusion of the parent vessel
across the neck of the aneurysm. The coil is then
deployed within the aneurysm. The balloon prevents
herniation of the coil into the parent vessel as it
achieves a stable configuration within the aneurysm.
We generally deflate the balloon after the first coil is
deployed to evaluate stability of the coil mass within
the aneurysm (Fig. 16.6). If it appears stable, the coil
is detached. The balloon may be reinflated as subse-
quent coils are deployed. At times, it may be desirable
to place multiple coils before the balloon is ever
deflated. It is thought that as more coils are deployed,
a more stable configuration is achieved.
Once the final coil is placed and detached, the
microcatheter is removed with the balloon inflated to
avoid potentially dragging out any of the coil mass.
The balloon is then removed under continuous fluoro-
scopic guidance to ensure that the balloon and/or
microguidewire does not snare any of the existing coil
mass as it is removed. If at any time, the coil mass
does not appear stable or one or more loops herniate
out of the aneurysm neck, a stent can be deployed.
Stent-Assisted Coil Embolization
Stent-assisted coil embolization represents an important
advance in the endovascular treatment of intracranial
aneurysms. It allows the treatment of wide-necked
aneurysms that were not otherwise treatable with other
endovascular techniques. Stent-assisted coil emboliza-
tion can also be employed in instances where balloon-
remodeling fails.
As a technique under the category of a recon-
structive endovascular approach, stent-assisted coil
embolization is definitely used for endosaccular
aneurysm occlusion (by permitting coils to be placed
within the aneurysm). However, it may also be
thought of, at least in part, as an endoluminal strategy
for aneurysm occlusion as the stent may induce flow
diversion and helps to reconstruct the vessel wall
(16,203,204). The endoluminal strategy will be dis-
cussed in more detail later.
The feasibility of stent-assisted coil embolization
was established in a canine aneurysm model (205).
Subsequent clinical reports emerged establishing and
validating the technique in patients (206211). Initial
experience was with balloon-expandable coronary
stents but subsequent experiences have been with self-
expanding intracranial stents designed for stent-
assisted coil embolization. As discussed by Orbach et
al. (204), use of a stent in the treatment of wide-
necked intracranial aneurysms may provide more ben-
efit than simply providing a barrier to prevent coil
herniation into the parent vessel (i.e., has properties
that apply to an endoluminal reconstructive strategy).
(1) Stent placement may promote uncoupling of
momentum exchange between the parent artery and
aneurysm which may promote intra-aneurysmal con-
ditions (such as stasis) that may make recanalization
less likely. (2) Endothelialization of the stent (subinti-
mal incorporation of the stent into the vessel wall)
provides additional integrity to the vessel wall and
may potentially reduce the probability of recurrence.
(3) Placement of the stent provides a neck-bridging
barrier effect that may facilitate more dense packing,
particularly across the aneurysm neck which may sup-
port healing.
There are currently two major stents approved
for stent-assisted coil embolization of intracranial
aneurysms in the United States. The Neuroform stent
(Stryker Neurovascular, Fremont, California) was
the first stent approved for this indication. It has
undergone modifications over time and is currently
available in the Neuroform3 and Neuroform EZ plat-
forms. The Enterprise stent (Codman Neurovascular,
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 345

(A) (B) LVERT

OPLEX 18 14X51 COSMOS

(B)

Figure 16.6 Balloon remodeling for a ruptured broad-neck basilar bifurcation aneurysm where the working projection could not offset
aneurysm dome from the left PCA. (A) AP and lateral projections demonstrating the lobular nature of the basilar bifurcation aneurysm.
(B) The first coil has been placed with balloon-assistance. The balloon has been deflated and a control performed. The first coil has
been placed (the white arrow denotes alignment of the radioopaque marker on the delivery mandrel with the proximal microcatheter
marker) but not detached. The black arrows indicate the proximal and distal markers of the balloon catheter positioned in the left PCA/
basilar artery. (C) Control angiogram demonstrates dense packing of the aneurysm. On the lateral view, the white arrow demonstrates
the patent PCA and the channel within the coil mass corresponding to where the balloon was inflated in the PCA.

Raynham, Massachusetts) was more recently int-
roduced and is being used with increasing
frequency.
Experience with the Neuroform stent has been
the subject of numerous publications (207,212232).
Collectively, these reports document high success in
stent deployment and overall low rates of complica-
tions (particularly with the use of dual antiplatelet
therapy) (218221). Although the vast majority of the
studies lack a control group, the data also suggest that
the results with a stent are better than coiling alone
for wide-neck aneurysms (218221). There is also
some data to suggest that the Neuroform stent indu-
ces progressive occlusion of coiled intracranial aneur-
ysms (223) through its endoluminal reconstructive
properties.
The Neuroform stent may be deployed in several
different ways. In all cases, the patient is pretreated
with aspirin and Plavix dual antiplatelet therapy prior
to the procedure to minimize the risk of thromboem-
bolic complications. A microcatheter can be advanced
past the aneurysm and an exchange length wire
placed into the distal vascular territory. The micro-
catheter can then be exchanged for the Neuroform3
stent system. Alternatively, we have successfully navi-
gated the Neuroform3 stent system using a regular
length guidewire to deploy it in a single step if the
anatomy is not too tortuous. The Neuroform3 can also
be deployed using a stent transfer technique if the
anatomy is more challenging. With this technique, a
Neuro Renegade HI FLO catheter (Stryker Neurovas-
cular, Fremont, California) is navigated over a regular
346 NEUROINTERVENTIONAL MANAGEMENT
length wire distal to the aneurysm neck. The stent is
then transferred from the catheter it is packaged in,
into the new microcatheter already in position. The
stent is then advanced using the stabilizer (with an
0.014 wire within the stabilizer for support) and is
subsequently deployed. The stent transfer technique
may overcome difficulties associated with delivering
the stent in very tortuous anatomy. Finally, the Neu-
roform EZ stent is delivered in a similar fashion to the
stent transfer technique. The Neuro Renegade HI FLO
catheter is advanced into position. The Neuroform EZ
stent (which comes as a separate component similar to
the Enterprise stent) is then advanced into position. It
is important to note that the delivery catheter must be
navigated more distally than the aneurysm neck as
the Neuroform EZ has a leading wire that must be
advanced out of the catheter. We have found some
friction in delivery of the EZ stent through the Rene-
gade catheter if the system is tortuous and it has been
suggested that the EZ stent can be deployed through
a Marksman catheter (ev3, Irvine, California) which is
the same catheter used for deployment of the Pipeline
Embolization Device (ev3, Irvine, California). In gen-
eral, the stabilizer (for the Neuroform3) or delivery
wire (for the EZ system) is held in place, while the
microcatheter is moved proximally thereby unsheath-
ing the self-expanding stent across the neck of the
aneurysm. The position of the stent is identified by
the presence of proximal and distal radioopaque
markers.
The Enterprise stent is delivered using similar
principles and has also been shown to be safe and
effective for stent-assisted coil embolization (233235).
A Prowler Select Plus (Codman Neurovascular, Rayn-
ham, Massachusetts) microcatheter is advanced over a
guidewire of choice distal to the aneurysm neck. The
Enterprise stent is then delivered by stabilizing the
delivery wire and moving the microcatheter proxi-
mally thereby unsheathing the stent. We have found
that the Enterprise stent can be successfully deployed
in any case where the microcatheter can be navigated
to the desired location (including as distally as the
pericallosal-callosomarginal junction).
Stent-assisted coil embolization can be accom-
plished in separate sessions or in one session. For
elective aneurysm therapy, the stent can be deployed
during one session and the aneurysm can be coiled 4
to 6 weeks later. This approach allows the stent to
heal and may reduce the risk of stent migration or
deformation as well as possibly reduce the risk of in-
stent stenosis. The obvious disadvantage is that the
aneurysm is not obliterated until the second stage
with the continued possibility of rupture until it is
secured. The single session paradigm for stent-associ-
ated coil embolization involves placing the stent fol-
lowed immediately by coiling of the aneurysm. This
can be accomplished by deploying the stent and
bringing up a new microcatheter through the newly
placed stent into the aneurysm. Although this is usu-
ally straightforward, it can occasionally be difficult to
cross a freshly placed stent. Another strategy is to use
a Y shaped adapter on the guiding catheter. The
microcatheter for stent delivery is positioned along
with a microcatheter used to coil the aneurysm (which
is placed in the aneurysm itself). The stent is then
deployed and the microcatheter is jailed by the stent
in the aneurysm. The aneurysm is then coiled and the
microcatheter is removed. This avoids the potential
difficulty of crossing through the stent into the aneur-
ysm. The microcatheter, however, may not be as free
to move due to constraints imposed by the deployed
stent. The majority of us prefer to deploy the stent
and coil the aneurysm in the same session if possible;
although this is based upon operator preference and
experience.
For particularly challenging aneurysms, several
variations on stent placement can be employed to
achieve successful aneurysm obliteration. For wide-
neck bifurcation aneurysms, stents can be deployed out
each branch in a Y configuration to reconstruct
the bifurcation (230,231,234,236) (Fig. 16.7). Alterna-
tively, stents can be deployed across the Circle of Willis
if the anatomy is suitable (216,237). For example, for a
carotid bifurcation aneurysm, a stent can be navigated
across the AComm from a contralateral approach
and deployed from the MCA across the ACA if the
AComm is suitably large; alternatively, a stent can
be navigated from the ICA through the PComm and
deployed from PCA to PCA if the PComm is appropri-
ate for basilar bifurcation aneurysms (Fig. 16.8). Finally,
a stent can be placed in isolation as a waffle cone
where the distal stent is positioned at the aneurysm
neck or as a waffle cone in combination with another
stent out a branch involved with the aneurysm
(238242) (Fig. 16.9).
Multiple Microcatheter Technique
The multiple microcatheter technique can be used to
treat wide-neck intracranial aneurysms not amenable
to simple coil embolization using a single catheter
(Fig. 16.10). By using more than 1 catheter, at least
two coils can be deployed before one is detached. The
coils can interact with one another to achieve a stable
configuration. The technique was originally described
by Baxter et al. (243) in dealing with complex wide-
neck aneurysms but has been used by others success-
fully (244247). Alternatively, one of the microcath-
eters can be navigated out a branch incorporated into
the aneurysm sac for protection and another catheter
advanced into the aneurysm to coil the aneurysm
(248).
Liquid Embolic Agents for Aneurysm Treatment:
ONYX HD500
Onyx HD-500 is a viscous liquid embolic agent com-
prised of ethylene vinyl alcohol copolymer mixed
with tantalum that is dissolved in dimethylsulfoxide
(DMSO). It was designed as a liquid embolic agent to
treat intracranial side wall aneurysms. Mawad et al.
(249) first reported the use of this liquid embolic agent
in humans in 2002. Molyneux and associates (250)
reported the results of the Cerebral Aneurysm Multi-
center European Onyx (CAMEO) trial in 2004. Twenty
European centers enrolled 119 patients with 123 aneur-
ysms (although data were only available from
97 patients with 100 aneurysms). Complete angiogra-
phic occlusion was seen in 79% of aneurysms, subtotal
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 347

(A) (B)

Figure 16.7 Y-stent deployment and coiling of a basilar bifurcation aneurysm. (A) Broad-necked unruptured basilar bifurcation aneur-
ysm after placement of two stents in a Y configuration out each PCA. The white arrows denote the proximal and distal tines of the stent
placed out the right PCA and the black arrows outline the proximal and distal tines of the stent placed out the left PCA. (B) After coil
embolization, the stents have facilitated coiling of the aneurysm and preservation of both PCAs.

occlusion in 13%, and incomplete occlusion in 8%. Pro-
cedure- or device-related permanent neurologic morbid-
ity at final follow-up was present in 8 of 97 patients
and procedural deaths occurred in 2 patients. There
were delayed vessel occlusions in 9 patients (patients
were not routinely placed on dual antiplatelet therapy
at that time). They concluded that aneurysm occlusion
rates were superior to reported rates of coil occlusion
and treatment morbidity was comparable to that of
published prospective data on endovascular results in
similar subgroups of patients. Subsequent reports have
corroborated the safety and efficacy of Onyx HD-500
but with a lower rate of parent vessel occlusion with
routine implementation of dual antiplatelet therapy and
possibly with use of a stent when necessary to secure
unstable Onyx casts (251256).
We perform Onyx HD-500 embolization of intra-
cranial aneurysms under general anesthesia with neu-
rophysiological monitoring. The patient is pretreated
with aspirin and Plavix prior to the procedure and is
fully heparinized as for stent-assisted coil emboliza-
tion. A guiding catheter with a Y adapter is placed
into the vessel of interest. A 6F guide is sufficient if
an Echelon-10 microcatheter (ev3, Irvine, California) is
used for the Onyx injection but a 7F guiding catheter
is necessary if the Rebar catheter (ev3, Irvine, Califor-
nia) is used. The balloon catheter [usually the Hyper-
Glide (ev3, Irvine, California)] is placed across the
aneurysm neck. We tend to select a balloon that is
longer rather than shorter to easily occlude the aneur-
ysm neck in a stable fashion. The microcatheter is
then advanced into the aneurysm. The balloon is
inflated and contrast is injected through the micro-
catheter in the aneurysm to ensure that there is an
adequate seal and no leakage of contrast occurs into
the parent vessel (Fig. 16.11). The volume of inflation
to achieve the seal is noted (and used for subsequent
inflations of the balloon during the Onyx injection).
The contrast is then purged from the microcatheter in
the aneurysm with saline (to avoid confusion between
residual contrast and Onyx HD-500 which are both
radioopaque). The Onyx delivery syringe is then pre-
pared. The microcatheter is flushed with DMSO (fill-
ing the entire deadspace of the microcatheter). A
meniscus of DMSO is left in the microcatheter hub
which is held upright. The Onyx delivery syringe is
then connected to the microcatheter hub using the
appropriate interface device (SCIFA) [which is specific
to the microcatheter selected (i.e., Rebar vs. Echelon)].
With the balloon deflated, approximately 0.150.2mL
of Onyx is delivered into the microcatheter. The bal-
loon is then inflated to the predetermined volume and
Onyx is injected at a steady rate. The manufacturer
suggests a rate not to exceed 0.1mL/min for up to
2 minutes and to allow the balloon to stay inflated for
a total of 5 minutes to allow Onyx solidification. The
balloon is then deflated to allow distal perfusion and
then is reinflated and the cycle repeated. We have
modified the technique to some extent. We assess col-
laterals prior to the Onyx treatment and we perform
the procedure with continuous neurophysiological
monitoring. We leave the balloon inflated for longer
periods of time if the monitoring is stable and some-
times complete the entire embolization with a single
balloon inflation. Once control angiographic runs con-
firm obliteration of the aneurysm, the balloon is then
deflated for 10 minutes to allow complete Onyx solidi-
fication. The balloon is then reinflated and the micro-
catheter is removed. The balloon is then deflated and
removed.
348 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B)

(C) (D)

Figure 16.8 Stent placement across the Circle of Willis. (A) Broad-necked ruptured basilar bifurcation aneurysm associated with a
broad-neck where balloon-assistance failed. The white arrows outline the intended route for stent placement, via the right ICA, across
the PComm thereby placing the stent from left PCA to right PCA. (B) Selective microcatheter injection demonstrating navigation of the
microcatheter through the PComm into the right PCA. (C) Following stent placement. The white arrows outline the proximal and distal
tines of the stent. (D) Following coil embolization, the basilar bifurcation aneurysm is completely occluded.
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 349

(A) (B)

(C) (D)

Figure 16.9 Waffle cone technique for coiling of a wide-necked anterior communicating artery aneurysm. (A) A 3D view demonstrating
a wide-necked ACOM aneurysm with incorporation of both A2 origins. A white arrow indicates a small left supraclinoid ICA aneurysm
distal to the ophthalmic artery. (B) An unsubtracted view after stent placement demonstrating the proximal end of the stent was in the
left A1 segment (arrow) and the distal end was masked by the coil mass. (C) The aneurysm is completely occluded after the final coil
detachment. The bilateral A2 segments were widely patent. (D) Follow-up angiogram at 6 months demonstrating stable aneurysm
occlusion.

With the Onyx injection, we believe that it is
important to occlude the aneurysm neck completely
(often leaving a hat-like rim of Onyx at the neck
around the inflated balloon). Although the middle
phases of the Onyx injection can be rapidly com-
pleted, we perform the final phase of injection at the
neck very slowly to ensure controlled Onyx delivery.
Endoluminal Reconstructive Strategy for
Intracranial Aneurysms: Flow Diversion
Some of the advantages of stent placement across an
aneurysm neck have been discussed above (such as
preventing coil herniation in wide-neck aneurysms
and promoting dense packing but also uncoupling
momentum exchange between the parent vessel and
aneurysm and enhancing structural integrity of the
vessel wall once the stent has been incorporated into
the vessel). There has been a paradigm shift in think-
ing about the potential utility of stents for the treat-
ment of aneurysms; the shift has occurred from a
view of stents as simple neck-bridging devices to pre-
vent coil herniation into the parent vessel to a view of
stents as flow-diverting devices that provide endolu-
minal reconstruction of the diseased segment of the
parent artery from which the aneurysm arises. Such a
concept may provide a more physiological and dura-
ble therapy for aneurysms.
Endoluminal reconstruction and flow diversion
has been attempted with currently available stents
(such as the Neuroform or Enterprise stents) by placing
one or multiple stents to promote flow diversion
(257,258). Multiple stents, in particular, provide a
higher metal-surface-area coverage across the aneur-
ysm neck while still keeping vital perforator vessels
350 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B)

Figure 16.10 Dual microcatheter technique. (A) This road map view illustrates positioning of the microcatheters. The first microcatheter
is in the aneurysm (proximal and distal markers outlined by the black arrows) and the second microcatheter is in the process of being
positioned into the aneurysm (proximal and distal markers outlined by the white arrows). (B) Pre-embolization (left) and post-emboliza-
tion (right) angiograms demonstrating complete occlusion of the aneurysm using the two catheter technique and no balloon or stent.

open. Dramatic results have been seen using this tech-
nique (257) (Fig. 16.12). An extreme example of endolu-
minal reconstruction for a diseased aneurysm segment
involves the placement of a covered stent to immedi-
ately obliterate the aneurysm (259264). This, however,
has significant limitations due to the inflexibility of
most covered stents (and hence difficulty in delivery)
as well as the potential applicability to only a select
group of aneurysms (this could not be used with
confidence in any segment with perforating vessels or
branches where occlusion could produce significant
morbidity). The concept of partially covered stents (or
asymmetric vascular stents) is currently under investi-
gation where only the segment of the stent at the neck
of the aneurysm is covered (265269).
Two flow-diverting devices, the Silk stent (Balt,
Montmorency, France) and the Pipeline Embolization
Device (ev3, Irvine, California), for intracranial
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 351

RCCA
TEST

(A) (B)

(C) (D)

Figure 16.11 Onyx HD-500 treatment of right paraclinoid ICA aneurysm. (A) Right ICA injection demonstrates a broad-necked paracli-
noid aneurysm. (B) Leak test. (Left): Unsubtracted view demonstrates the tip of the microcatheter in the aneurysm (black arrow) and
the balloon inflated across the neck (white arrow). (Right): Inject of contrast through the microcatheter demonstrates stasis of contrast
within the aneurysm and no leakage of contrast into the parent vessel. (C) Injection of Onyx using a blank roadmap. The black arrows
outline the new Onyx being deposited in the aneurysm. The Onyx is filling back at the neck and further injection is continued slowly to
avoid poorly controlled reflux into the parent vessel. (D) Final control angiograms demonstrate complete obliteration of the aneurysm.

aneurysms have been the subject of recent clinical tri-
als. Several reports have emerged examining the use
of the Silk stent as a flow diverting device for aneur-
ysm treatment (270274). Lubicz et al. (273) recently
published a prospective study examining 29 patients
with 34 fusiform or wide-neck aneurysms that were
treated with the Silk flow-diverting device. Endovas-
cular treatment was successfully performed in 26
patients (90%), while in 3 patients the stent could not
be delivered. Mortality and morbidity rates were 4%
(1 of 26) and 15% (4 of 26), respectively. One patient
died from delayed aneurysm rupture related to stent
migration, 3 patients sustained a thromboembolic
event, and 1 patient developed a progressive visual
deficit related to increased mass effect. On angio-
graphic follow-up of 24 patients (29 aneurysms), there
were 20 complete occlusions (69%), 1 neck remnant
(3.5%), and 8 incomplete occlusions (27.5%). Signifi-
cant parent artery stenosis was seen in 8 cases (33%)
at 6 months. The authors concluded that the delayed
complication rate was quite high and suggested use of
this technique only in selective cases. Byrne et al.
(271) recently published the results of a multicenter
prospective study examining the use of the Silk flow
divertor. They enrolled 70 patients over a period of 8
months. The flow divertor alone was implanted in 57
(81%) or with coils in 10 (14%) aneurysms. Difficulties
in device deployment occurred in 15 (21%) and parent
artery thrombosis in 8 (11%) procedures. Procedural
complications included 1 stroke and serious extracra-
nial bleeding in 3 patients. Delayed worsening of
symptoms occurred in 5 patients (3 transient, 1 per-
manent neurological deficit, and 1 death) and fatal
aneurysm bleeding in 1 patient. Overall permanent
morbidity rates were 4% and mortality 8%. The
authors encouraged care in selecting patients for treat-
ment and future larger studies to be conducted.
The Pipeline Embolization Device has been the
subject of significant recent interest (Fig. 16.13)
(183,275279). Early reports emerged documenting the
potential efficacy of the Pipeline device (183,276). Sub-
sequent clinical series have been published. Lylyk and
352 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B)

(C)

Figure 16.12 Multiple overlapping stents for the treatment of a fusiform basilar aneurysm in a 2-year-old boy. (A) Left vertebral artery
injections outline the fusiform aneurysm and dysplastic basilar artery. (B) Left vertebral artery roadmap and injection during deployment
of one of the Enterprise stents. (C) Left vertebral artery injections immediately following placement of three Enterprise stents across the
aneurysm (without placement of coils). (Continued)
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
(D)
Figure 16.12 (Continued) (D) One-year follow-up angiogram demonstrates obliteration of the aneurysm with straightening of the verte-
brobasilar system.
colleagues (277) reported their experience using the
Pipeline embolization device in treating 53 patients
with 63 intracranial large and giant wide-necked, non-
saccular and/or recurrent aneurysms. Treatment was
achieved with a single device in 44 aneurysms, with
two overlapping devices in 17 aneurysms, and with
three overlapping devices in 3 aneurysms. Complete
angiographic occlusion was achieved in 56%, 93%,
and 95% of aneurysms at 3 (n = 42), 6 (n = 28), and
12 (n=18) months, respectively. The only aneurysm
that remained patent at 12 months had previously
been treated with stent-assisted coil embolization.
There were no recanalizations and no major complica-
tions (stroke or death). Szikora et al. (279) reported
similar efficacy in 18 patients with 19 wide-neck
aneurysms. Complete occlusion was achieved in 17 of
18 patients. There was one abrupt stent thrombosis
producing a transient deficit and one patient died due
to rupture of a coexisting aneurysm. Most recently,
Nelson et al. (278) reported the results of the Pipeline
Embolization Device for the Intracranial Treatment of
Aneurysms Trial. Thirty-one patients with unruptured
aneurysms that were wide-necked (>4mm), had
unfavorable dome/neck ratios (<1.5), or had failed
previous therapy were enrolled. Device placement
was successful in 30 of 31 patients (97%). Two patients
experienced major periprocedural stroke. Follow-up
angiography demonstrated complete aneurysm occlu-
sion in 28 (93%) of 30 patients who underwent follow-
up angiography. No significant in-stent stenosis was
seen at follow-up angiography. They concluded that
the Pipeline Embolization Device was technically fea-
sible with a similar safety profile to stent-assisted coil
embolization. The device resulted in a high oblitera-
tion rate at 6 months in the most anatomically chal-
lenging subtype of aneurysms.
The Pipeline Embolization Device is currently
under review by the Food and Drug Administration
353
(FDA) and the Silk device is being used in Europe.
Although the preliminary results are promising in
terms of safety and efficacy, there are some potential
concerns that await further clarification. There is report
of very late thrombosis of a device at ~ 23 months fol-
lowing implantation (275). There are also concerns of
delayed aneurysm rupture after flow-diversion treat-
ment (272,280); albeit uncommon, the cause(s) remain
unknown.
PROCEDURAL COMPLICATIONS AND
DELAYED SEQUELAE ASSOCIATED
WITH ENDOVASCULAR INTRACRANIAL
ANEURYSM TREATMENT
Complications can arise during different phases of
endovascular aneurysm therapy. Complication rates
vary depending upon operator and team experience,
patient-specific factors (such as vascular tortuosity,
atherosclerotic disease, and resistance to antiplatelet
therapy), and aneurysm-specific factors (such as size,
location, morphology, rupture status, incorporation of
branches, presence of thrombus, etc.). The main acute
complications of endovascular treatment include
thromboembolism, intraprocedural rupture, and access
complications. Delayed sequelae of treatment may
include aneurysm (re)bleeding, recanalization, and
other uncommon occurrences such as hydrocephalus.
Thromboembolism
Thromboembolic complications are among the most
frequently seen complications during endovascular
treatment of intracranial aneurysms. Thromboembo-
lism can arise from clot formation on catheters, clot for-
mation on the coil mass, or clot formation in a vessel in
the setting of vasospasm or prolapsed coils. van Rooij
et al. (281) recently conducted a careful analysis of
354 NEUROINTERVENTIONAL MANAGEMENT

RT ICA PRE-EMBO

RT ICA PRE-EMBO

(A) (B)

RT ICA POST-PED4
RT ICA POST-PED4

(C) (D)

RT CCA

RT CCA

(E) (F)

Figure 16.13 Endoluminal reconstruction using flow diversion devices for the treatment of a giant cavernous ICA aneurysm. (A) Frontal
and (B) Lateral arterial phase images demonstrating a giant cavernous segment aneurysm of the RICA in a patient with history of diplopia,
now presenting with R hemispheric (transient ischemic attack) TIA. Previous workup included a failed BTO. Frontal (C) and lateral (D)
angiographic images demonstrating the immediate post-treatment result. Note the markedly altered intra-aneurismal flow, with stagnant
contrast pooling in the dependent portion of the aneurysm fundus. Frontal (E) and lateral (F) angiographic images of the RICA at 6month
follow-up. (Continued)
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS
RT CCA
(G)
Figure 16.13 (Continued) Unsubtracted images (G, H) demonstrate the disposition of the endoluminal construct. Note the normaliza-
tion of the RICA lumen and resolution of mass effect.
procedural complications associated with coiling of
ruptured aneurysms. In a series of 681 consecutive
patients, they noted 32 thromboembolic complications
for a rate of 4.7%. They found that balloon assistance
was the only significant risk factor for complications.
van Rooij and Sluzewski (282) also analyzed procedural
complication rates for coil embolization of unruptured
aneurysms. In a series of 176 aneurysms in 149 patients,
a 2.8% incidence of thromboembolic complications was
noted. The incidence of reported thromboembolic com-
plications does vary widely depending upon criteria
for identification (clinical, versus angiographic, vs.
restricted diffusion abnormalities on MR imaging)
(16,283) and on the use of antiplatelet pretreatment
(284). Yamada (284) reviewed a series of 369 consecu-
tive patients undergoing elective coil embolization.
Symptomatic thromboembolic complications occurred
in 4 (16%) of 25 patients receiving no antiplatelet ther-
apy, in 2 (2.3%) of 86 when antiplatelet therapy was
administered after embolization and in 5 (1.9%) of
258 patients receiving antiplatelet therapy before and
after embolization. Extracerebral hemorrhagic compli-
cations occurred in no patients when no antiplatelet
therapy was prescribed and in 11 (3.2%) of 344 when it
was prescribed (not statistically significant). This is fur-
ther corroborated by Brooks and colleagues (283) who
examined 155 aneurysms treated in 132 patients. They
found small diffusion-weighted imaging abnormalities
in the treated vascular territory in 24% of cases
(37 lesions). Twenty-one (32%) of 66 lesions were found
in the coil-treated group, 6 (13%) of 45 in the stent-
assisted coil group, and 8 (24%) of 33 in the balloon
remodeling group had diffusion-weighted abnormal-
ities. Moreover, 25 (68%) of the 37 cases that had
restricted diffusion on MR imaging were ruptured
cases. Clinically evident stroke or TIAs were present in
10 (27%) of 37 cases. They concluded that adjunctive
devices (balloon or stents) do not appear to increase the
frequency of embolic or ischemic events. Lesions and
clinically evident stroke were actually less frequent
when adjunctive devices were used and in elective
355
RT CCA
(F)
cases which is most probably a result of perioperative
antiplatelet therapy.
Should a thromboembolic complication be noted
during the procedure, the operating team should ensure
that the patient is adequately heparinized as confirmed
by ACT measurements. If the patient is adequately hep-
arinized and a branch occlusion is seen (or clot is present
at the coilvessel interface) pharmacological or mechani-
cal thrombolysis can be performed. Pharmacological
thrombolysis can employ tissue plasminogen activator
(tPA) or potent intra-arterial antiplatelet agents (glyco-
protein IIb/IIIa receptor antagonists). Intra-arterial gly-
coprotein IIb/IIIa receptor antagonists such as
abciximab (Reopro) or eptifibatide (Integrilin) have been
used with safety and efficacy during coil embolization
procedures (285290). Prior to administration of any
thrombolytic in the setting of an acutely ruptured aneur-
ysm, the aneurysm should be well coiled to avoid the
calamity of aneurysm re-rupture. Mechanical thrombol-
ysis can be performed with currently available devices
such as the MERCI (Concentric Medical, Mountain
View, California) or Penumbra (Penumbra, Alameda,
California) system for significant branch occlusions if
necessary.
Intraprocedural Rupture
Intraprocedural aneurysm rupture has been reported
to occur in 15% of coil embolization procedures
(281,282,291297). At our institution, intraprocedural
rupture occurred in 1.4% of coil embolization proce-
dures (16). In our experience, intraprocedural rupture
occurs most commonly during the introduction of the
microcatheter or guidewire into the aneurysm or dur-
ing coil delivery. Risk factors for intraprocedural rup-
ture may include ruptured status of the treated
aneurysm, lower initial Hunt and Hess grade, opera-
tor experience, volume of treatment center, possibly
use of balloon remodeling, and small aneurysm size
(281,291293,295297). The report of Raymond and
Roy demonstrated the importance of operator
356 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B) (C)

(D)

Figure 16.14 Intraprocedural rupture during coil embolization of a small, ruptured anterior communicating artery aneurysm. (A) Head
CT demonstrates SAH with focal clot in the interhemispheric fissure. An EVD catheter tip is seen on the right image. (B) Left ICA injec-
tion outlining the small anterior communicating artery aneurysm. (C)During the placement of the first coil, contrast is seen extravasating
through a focal point in the aneurysm dome (black arrow). The white arrows outline the contrast extravasation into the subarachnoid
space. (D) Following balloon placement and coiling, the perforation was controlled without clinical sequelae. (Continued)
 ENDOVASCULAR MANAGEMENT OF INTRACRANIAL ANEURYSMS 357

(E)

Figure 16.14 (Continued) Intraprocedural rupture during coil embolization of a small, ruptured anterior communicating artery aneur-
ysm. (A) Head CT demonstrates SAH with focal clot in the interhemispheric fissure. An EVD catheter tip is seen on the right image.
(B) Left ICA injection outlining the small anterior communicating artery aneurysm. (C)During the placement of the first coil, contrast is
seen extravasating through a focal point in the aneurysm dome (black arrow). The white arrows outline the contrast extravasation into
the subarachnoid space. (D) Following balloon placement and coiling, the perforation was controlled without clinical sequelae. (E) Post-
procedure head CT demonstrates increased subarachnoid and interventricular hemorrhage with a small clot in the left gyrus rectus.

experience in coil embolization of intracranial aneur- Aneurysm Bleeding or Rebleeding

ysms. They reported a 20% rate of rupture in their
first 25 patients, a 4% rate in their next 25 patients
and a 0% rate in their subsequent 25 patients under-
going coil embolization of their ruptured intracranial
aneurysm (295). Traditionally, intraprocedural rupture
was associated with a combined risk of permanent
neurologic disability and death of 38% for acutely
ruptured aneurysms and 29% for unruptured aneur-
ysms (292). However, as demonstrated in the experi-
ence of Berenstein et al., in expert hands the risk of
intraprocedural rupture can be low (1%) and the
sequelae of rupture can be minimized (17% morbidity
and 0% mortality in 6 patients with intraprocedural
rupture among 600 patients undergoing coil emboliza-
tion) (291).
If an intraoperative rupture occurs, protamine
should be immediately available and administered if the
patient is heparinized. The specifics of dealing with the
rupture depend upon the site of rupture. If the aneur-
ysm is perforated at the dome, the aneurysm can be rap-
idly packed with coils (Fig. 16.14). A balloon can be
inflated for temporary parent vessel occlusion. For per-
forations at the neck or parent vessel other strategies
may be necessary such as parent vessel occlusion or a
salvage technique using a balloon and liquid embolic
agents. Intracranial pressure should be aggressively con-
trolled after securing the aneurysm with ventricular
drainage and medical management. An immediate com-
puted tomography (CT) scan should be obtained to rule
out a large parenchymal hemorrhage that may need
evacuation. Finally, if antiplatelet agents were adminis-
tered, the patient should receive platelet transfusions in
the appropriate context (particularly if ventriculostomy
insertion or further open surgery is necessary).
Aneurysm bleeding or rebleeding in well-treated
aneurysms appears to be an uncommon event
(17,187,298), but long-term data are just beginning to
emerge. A recent meta-analysis concerning the safety
and efficacy of endovascular treatment of unruptured
aneurysms concluded that the annual risk of hemor-
rhage after treatment was 0.2% per year but follow-up
was short (185). Murayama et al. (186) demonstrate in
a 5-year experience including 546 patients, 3 patients
sustained a delayed rupture (0.5%) over a follow-up
period of 3 months to 8 years. Pandey et al. (187)
demonstrate a very low rate of hemorrhage following
endovascular treatment in a population of patients
with both ruptured and unruptured aneurysms [3
patients (1.1%), 0.003% per patient-year]. In the ISAT
study, rebleeding within the first year following coil
embolization occurred in 28 of 1073 patients (2.6%)
versus 11 of 1070 patients (1.0%) in the clipped group
(15). After 1year, 24 rebleeds had occurred of which
13 were from the treated aneurysm (10 in the coiling
group and 3 in the clipping group) (14). The authors
concluded that there was an increased risk of recur-
rent bleeding from a coiled aneurysm compared with
a clipped aneurysm, but the risks were small (14). The
CARAT study was discussed earlier. Nineteen rerup-
tures over a period of 4 years occurred in 1001
patients whose ruptured aneurysms were either coiled
or clipped (188). The median time to rerupture was
3 days and there was a trend for a higher overall risk
of rerupture in coiled compared to clipped patients
(3.4% vs. 1.2%, p = 0.092). The risk of re-rupture was
strongly associated with the degree of aneurysm
occlusion. Rerupture of the index aneurysm after
358 NEUROINTERVENTIONAL MANAGEMENT
1 year occurred in 1 coiled patient during 904 person-
years of follow-up (annual rate 0.11%) (189).
Taken together, hemorrhage following endovas-
cular treatment of an intracranial aneurysm is low
providing that satisfactory aneurysm obliteration is
achieved upon completion of the procedure. Long-
term follow-up is still necessary, however, to defini-
tively establish durability in the protection against
rupture or re-rupture conferred by endovascular
aneurysm treatment.
Aneurysm Recurrence/Recanalization
Recanalization/recurrence is not a procedural complica-
tion per se, but remains a significant limitation of the
endovascular approach. Data have accrued highlighting
a risk of long-term aneurysm recurrence of 534% (299
304). The presumed factor involved with recurrence is
incomplete occlusion of the aneurysm (loose packing)
although coil compaction, regrowth secondary to vessel
wall weakness, thrombus organization, and fibrosis
may be contributory (299,300,304). Aneurysm location
may play a role with the posterior communicating
artery and basilar bifurcation artery locations having a
higher rate of recurrence (37% and 39%, respectively),
compared to the anterior communicating artery location
(25%) (303). Ruptured aneurysms and smoking status
may also impart a higher risk of recurrence in coiled
aneurysms (299,300,302,305). Morphological aneurysm
features predisposing to recurrence may include large
aneurysm volume, wide neck, medial dome orientation,
a symmetrical orientation of both A1 segments (for an
AComm aneurysm), a posteroinferior dome orientation
and a small size PComm (for PComm aneurysms), and
a cranial symmetrical fusion for basilar bifurcation
aneurysms (299,300,302,304).
As previously mentioned, stents may reduce the
risk of aneurysm recurrence (217,219,220,223) (at least
compared to historical controls), and liquid embolic
agents (251,252,254) also appear to be associated with
a lower risk of recurrence. The potential utility of bio-
active coils in reducing recurrence remains unproven,
although preliminary data from the Hydrocoil Endo-
vascular Aneurysm Occlusion and Packing Study
(HELPS) trial (306) suggest that hydrocoils (which
contain hydrogel that swells) may reduce recanaliza-
tion rates (P. White, personal communication, 7th
Annual Meeting of the Society of Neurointerventional
Surgery meeting, Carlsbad, California). We await
long-term data concerning the durability of flow-
diverting devices despite promising preliminary data.
Other
Other select complications associated with endovas-
cular aneurysm treatment may include access-related
complications (such as pseudoaneurysms or retroper-
itoneal hematomas), vessel dissection or injury,
delayed hydrocephalus, and neurological deficits
from increased mass effect (such as cranial neuropa-
thies). Access-related complications can include ves-
sel pseudoaneurysms, fistulas and hematomas (local
and retroperitoneal). Reporting of these complica-
tions is generally not emphasized, but extracerebral
hemorrhagic complications were reported in 3% of
369 patients undergoing elective intracranial aneur-
ysm coil embolization (284). Access complications
and vessel dissection/injury can be minimized with
meticulous attention to technique. Delayed hydroce-
phalus is an extremely rare complication that has
been reported following coil embolization with bioac-
tive coils as well as bare platinum coils (307309)it
is a communicating hydrocephalus of uncertain etiol-
ogy that tends to occur in large/giant aneurysms.
CONCLUSIONS
Endovascular treatment of intracranial aneurysms
appears to be a safe and efficacious treatment for both
ruptured and unruptured aneurysms. Significant
advances have emerged since the inception of this
treatment method and this area is currently under
rapid evolution due to continuous improvements in
materials, technology, and device development. It is
important to note that endovascular treatment is one
potential therapeutic tool available to patients harbor-
ing intracranial aneurysms. There is a movement
toward a disease specific rather than procedure
approach to patients with cerebral vascular disease
including aneurysms. Each patient afflicted with an
intracranial aneurysm should be evaluated by some-
one versed in all therapeutic options (medical man-
agement, endovascular therapy and microsurgery
including bypass techniques) or in the setting of a
multidisciplinary team where all such options are
available. A treatment plan should be formulated for
each patient taking into consideration all patient-spe-
cific, aneurysm-specific and treating team-specific
data such that the safest and most effective therapy
can be implemented. Future progress in the treatment
of intracranial aneurysms will be realized by enhanc-
ing our basic understanding of the biology and hemo-
dynamic properties of intracranial aneurysms. Such
knowledge can then be translated to improvements in
minimally or noninvasive therapies. Small refinements
in microsurgery may occur but not to a similar extent;
however, microsurgery will continue to have a role
and will complement other therapies as they evolve.
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 17
Endovascular management of cerebral vasospasm
post-subarachnoid hemorrhage
George Ghobrial, Stavropoula I. Tjoumakaris, Aaron S. Dumont, Pascal M. Jabbour, Robert H.
Rosenwasser, and L. Fernando Gonzalez
INTRODUCTION
Cerebral vasospasm affects approximately 60% to 70%
of patients after subarachnoid hemorrhage (SAH),
resulting in symptomatic ischemia in approximately
half of these patients (1). It reaches the peak of maximal
severity between 7 and 14 days after the ictus of SAH,
typically resolving spontaneously in the third or fourth
week. Vasospasm causes death or serious disability
from infarction in up to one-third of patients with
SAH. For this reason, vasospasm constitutes the most
serious threat to disability after aneurysm rupture sec-
ondary to delayed ischemic events. Although the
pathogenesis is not clearly known, the risk is related to
the amount of subarachnoid blood (13). Therefore,
vasospasm can occur in the absence of a ruptured
aneurysm (angiographic negative SAH) Fig. 17.1.
PATHOPHYSIOLOGY
The cause of cerebral vasospasm appears to be multi-
factorial, involving oxyhemoglobin, thromboxane,
serotonin, and calcium (4). Calcium activates calmo-
dulin, which activates the myosin light-chain kinase
and interacts with actin filaments causing muscle con-
tractions (5). Vessel tone is determined by a balance
between both endothelial-derived constricting factors
(EDCFs) and endothelial- derived relaxation factors
(EDRFs). Nitric oxide (NO), a product largely created
by endothelial-derived nitric oxide synthase, is the
most prominent EDRF. Studies have demonstrated
that vasospasm after SAH involves a dysfunction of
the vasodilator mechanisms. SAH leads to decreased
NO activity (6,7). Histological analysis has shown
morphological changes of the spastic vessel wall, with
necrosis and fibrosis of the intima and media. Genetic
studies have shown an association between patients
with single nucleotide polymorphisms resulting in
dysfunctional EDRFs and an increased risk of vaso-
spasm after SAH (8).
The diagnosis of cerebral vasospasm (also known
as delayed ischemic neurologic deficit, DIND) is
mainly clinical, but suspicion is raised with the help
of noninvasive techniques commonly employed at the
bedside in most intensive care units (ICUs). One such
technique is the transcranial Doppler (TCD) ultra-
sound, which is performed by insonating the circle of
Willis through bone windows such as the foramen
magnum, the orbit, and the thin temporal bone. This
noninvasive bedside procedure has a varied sensitiv-
ity, but a much higher specificity for vasospasm (9).
Technical expertise and experience is required for its
reliable use (9). The course of TCD-documented vaso-
spasm correlates closely with the course and clinical
sequelae of vasospasm detected on angiography, and
its severity closely correlates with the clinical sequelae
of brain ischemia. Computerized tomographic angiog-
raphy (CTA) may be used to confirm vasospasm in
equivocal clinical situations or when the clinical
decline is questionable. This is especially true in the
case of concomitant clinical situations such as the
presence of seizures, fever or poor baseline neurologi-
cal status. Digital subtraction angiography (DSA) is
indicated in cases where an intervention is planned if
the diagnosis is confirmed.
Numerous advances in neurosurgical critical care,
such as rheological manipulation of cerebral blood flow
(CBF) and the administration of calcium-channel block-
ers, have reduced the ischemic and neurological seque-
lae associated with this devastating complication.
Primarily, the treatment of vasospasm is preven-
tive, including the use of the calcium-channel blocker
nimodipine (10), which has shown improvement in
functional motor outcome. Additionally, measure-
ments commonly known as hyperdynamic therapy
include (when all four parameters employed, referred
to as 4-H therapy) hypervolemia (increasing the blood
volume), hemodilution (decreasing the hematocrit),
induced hypertension, and hyperdynamics (the maxi-
mization of cardiac performance) (812).
Understanding Poiseuilles law is the basis for
the treatment of vasospasm.
8mLQ
P =
pr 4
where DP is the pressure drop, L is the length of pipe,
m is the dynamic viscosity, Q is the volumetric flow
rate, r is the radius, and p is the mathematical constant.
This law directly relates the flow to the pressure
difference and to the diameter of the vessel and indi-
rectly to the bloods viscosity. This formula explains
the rational behind the use of hyperdynamic therapy.
Measures such as increasing the blood pressure, blood
volume (increasing cardiac preload), decreasing the
368 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 17.1 Patient with diffuse Subarachnoid hemorrhage (SAH), no aneurysms identified. Developed severe vasospasm on the basi-
lar artery that required balloon angioplasty. (A) antero-posterior (AP) projection showing the basilar artery spasm. (B) Increased diame-
ter of the basilar artery post balloon angioplasty. (C) Fluoroscopic visualization of the balloon inflated in the basilar artery on the AP
projection and on the lateral projection (D).

blood viscosity through increasing the blood volume
with fluid transfusions (thereby improving the CBF,
but without affecting the oxygen transport capacity of
the hemoglobin), all have a beneficial effect on
increasing CBF. Some patients do not tolerate this
enhancement therapy due to poor myocardium func-
tion or as a result of cardiac ischemia, secondary to
the effect of the SAH on the myocardium (from a
surge in catecholamines, called stunned myocardium,
or Takotsubo cardiomyopathy), that precludes or lim-
its the use of pressors limiting these patients with lim-
ited medical therapies. In this case, endovascular
techniques are particularly useful in the management
of cerebral vasospasm (913).
ENDOVASCULAR TREATMENT
In patients that present with clinical decline despite
4-H therapy or in those where these treatments are
exhausted or limited due to poor cardiac function,
endovascular treatment should be considered (14). It is
clear that not all cases where TCD elevations reflecting
spasm require endovascular intervention, since these
therapies introduce an added risk which must be con-
sidered and carefully weighed. Conversely, endovascu-
lar treatment of spasm should not be delayed until a
completed stroke has developed. It is generally felt that
in medically refractory vasospasm, with DIND, endo-
vascular treatment should be pursued without delay.
Systemic Endovascular Techniques
Intraaortic balloon pump counter pulsation becomes a
logical further step when myocardial reserve is
reached. The synchronized balloon inflation in diastole
and deflation, while in systole, decreases the after load
and increases the cardiac output. The balloon displaces
a volume of blood that equals its own volume increas-
ing the coronary and cerebral blood (15). With this
therapy, the CBF has been shown to increase by 18% in
 ENDOVASCULAR MANAGEMENT OF CEREBRAL VASOSPASM POST-SUBARACHNOID HEMORRHAGE
the canine model (16). However, this therapy has been
shown to exhibit the risk of decreasing renal perfusion
with the potential for aortic dissection and embolic
events. As a result, anticoagulation is usually under-
taken (17). The registry on the use of intraaortic balloon
pump (IABP) with close to 25,000 patients reported a
7.2 risk of major complication including in-hospital
mortality associated with the use of intraaortic balloon
counter pulsation (18). The necessity of anticoagulation
and potential for aortic dissections limits the use of this
balloon to selected cases, often with SAH and simulta-
neous left ventricular heart failure.
Under the same rational, another device, the Neu-
roflo (CoAxia Mapple Grove, Minnesota) inserted from
the femoral artery into the aorta has two balloons that
are coaxially assembled with the idea of placing one
above and below the origin of the renal arteries. The
proximal balloon is inflated to a volume that allows
perfusion of the kidneys while the inferior is occlusive,
limiting the blood flow into the lower extremities. This
device has Food and Drug Administration (FDA)
approval under the humanitarian device exemption
(HDE) for treatment of cerebral vasospasm and later
stroke application has derived. Scarce data are avail-
able and currently research is undergoing.
Angioplasty
The ultimate goal in the treatment of vasospasm is to
increase the diameter of the affected vessel therefore
augmenting the distal blood flow (1921). This can be
obtained using pharmacologic measures including
intraarterial infusion of vasodilators such as calcium-
channel blockers and vasodilators, or performing
angioplasty on the affected vessel.
Pharmacological Angioplasty
Papaverine, an alkaloid derived from the opium, pre-
vents smooth muscle contraction; is usually delivered
as a 300mg dose infused over a 3060-minute period.
A potent vasodilator, papaverine has shown using
Xenon computed tomography (Xe-CT) to have an
increase on the CBF, from 13 to 44cc per 100 grams of
brain tissue per minute (p < 0.005) (22). Papaverine
simultaneously causes dilatation of the venous system
causing concomitant elevations in the intracranial
pressure which makes it less than ideal in patients
with borderline Intracranial Pressure (ICP) (23).
Verapamil, a calcium-channel blocker is usually
administered in dosages between 2.5mg and 10mg
infused over a 510-minute period. Local infusion
into the target artery through a microcatheter has
shown more effective results allowing the use of
lower doses (24).
Nimodipine, a dihydropyridine calcium antago-
nist that reduces the influx of calcium in smooth-
muscle cells, is considered standard of care in the
treatment of SAH through oral route. Some authors
recommended its use intraarterially at doses of
0.1mg/min (25). Usually dosages do not exceed 5mg;
unfortunately, there is no nimodipine available for
routine intravascular delivery in the US (26).
Nicardipine, is another calcium-channel antago-
nist that reduces the influx of calcium in L-type
369
smooth-muscle cells, it has more selectivity for vascu-
lar cells than myocardium. It seems to be better toler-
ated intraarterially than after intravenous use,
although causes drop in the systemic blood pressure
and frequently requires the concomitant use of intra-
venous pressure agents to maintain the cerebral perfu-
sion pressure.
Intrathecal nitroprusside has been proven safe, but
its efficacy is still controversial (2729). The use of intra-
arterial calcium-channel blockers such as nicardipine,
verapamil, or nimodipine has been shown to signi-
ficantly reduce TCD velocities, providing a clinical
benefit in up to 72% of patients. Increased vessel cali-
bers have been demonstrated in up to 44% of studied
subjects (30,31). The application of nicardipine pro-
longed-release implants in the basal cistern of Fisher
Grade III SAH patients has shown promising results
(32). Future therapies for vasospasm will be aimed at
improved delivery systems and developing biological
agents that target the numerous cellular substrates
responsible for vasospasm. Many animal research stud-
ies are being carried out on intrathecal immunotherapy,
which is also a vast field to explore (3335).
Balloon Angioplasty
In 1984, the first reported use of angioplasty for the
treatment of cerebral vasospasm was published by
Zubkov et al. (3639). This opened up a new modality
of treatment for patients who were medically refrac-
tory to reversal of their ischemic neurological syn-
drome (14,38,39). Despite successful improvement in
the narrowing of the cerebral vessels with restored
normal circulation time (as demonstrated angiographi-
cally), there have been many reports of equivocal clin-
ical improvement (14,20,4042). The ideal scenario is
to treat these patients before irreversible neurological
deficits are present, similar to the penumbra on
patients with ischemic strokes. Endovascular treat-
ment of vasospasm traditionally has consisted of bal-
loon angioplasty, mostly for large vessel spasm, and/
or intraarterial pharmacological infusions for more
distal branch vasospasm. Angioplasty is associated
with greater risk of arterial rupture or dissection,
especially if applied to more distal vessels, but its
effect is more durable than intraarterial pharmacologic
infusions (4346). For patients with delayed SAH who
have severe vasospasm proximal to the aneurysm site,
a combined endovascular treatment with angioplasty
and endovascular aneurysm coiling is safer than sur-
gical clipping (Fig. 17.2) (47,48).
The clinical success rate of balloon angioplasty
(BA) is variable (36,41,42,49,50). The angiographic
improvement with TBA seems to vary between 80%
and 100% in most series. Clinical improvement ranges
from 30% to 80%. Early treatment seems to be associ-
ated with better results.
There is a lack of randomized, clinical studies that
assess the effect of TBA on outcome, nor is much
known of the long-term effects of TBA. The effect of
angioplasty in the setting of cerebral vasospasm has
been found to be lasting. Furthermore, the angioplas-
tied vessels normalize in luminal diameter over time
based on follow-up angiography. There are risks associ-
ated with this procedure including: vessel perforation,
370 NEUROINTERVENTIONAL MANAGEMENT

LICA-PA&LAT RICA-POST HYPERGLUIDE BALLOON

Compressed 6:1 Clipped/1.9x Compressed 6:1 Compressed 6:1

(A) (B) (C)
LICA-POST BALLOON #2 LICA-POST COIL #3

Compressed 7:1 Compressed 6:1

(D) (E)

Figure 17.2 Patient that came 1 week after having the worst headache of life. (A) Right internal carotid injection on Townes projection
demonstrates severe spasm on the supraclinoid internal carotid Artery (ICA), minimal visualization of anterior communicating artery
(Acom) aneurysm. (B) Left internal carotid injection showing diffuse spasm and ACom aneurysm. (C) Right internal carotid injection
post balloon angioplasty. (D) Left internal carotid artery injection post balloon angioplasty. (E) Left internal carotid artery injection post
balloon angioplasty and coil embolization.

unprotected aneurysm rerupture, branch occlusion,
hemorrhagic infarction, and arterial dissection.
Vessel rupture is reported in 4% of cases, usually with
catastrophic outcome, and rebleeding from unclipped
aneurysms is found in roughly 5% of cases (39,41,42,51).
Currently, the availability of highly compliant and very
conformal balloons allow us to perform angioplasties
with significantly less risk of vessel dissection and
rupture than with the use of coronaryless compliant
balloons (52).
Timing of the Angioplasty
Zwienenberg et al. (53) and Muizelaar JP et al. (54)
demonstrated in Randomized controlled trial (RCT)
that balloon angioplasty performed on the major intra-
cranial vessels prior to the onset of DIND that the out-
come is equivocal on routine follow-up where Glascow
Outcome Score (GOS) was measured. In a pilot study
and phase II trial, no significant difference in neurolog-
ical outcome (GOS) at 3 months was shown. A 5% inci-
dence of vessel perforation was reported, with a high
incidence of mortality resulting from rupture. Bejjani
et al. (55) found a tendency toward better outcome in
patients that had angioplasty earlier rather than after
symptoms develop.
Likewise, Rosenwasser et al. (36) studied the
endovascular treatment of vasospasm after the medical
therapy failed in patients that developed focal neuro-
logical deficits. All patients were treated with standard
triple-H therapy, noninvasive monitoring with TCD,
showing elevated velocities or a trend toward increased
luminal velocities with increasing Lindegaard ratios
(36,52,56). With the development of a new focal deficit
or a change in mental status, a computed tomographic
scan was performed to rule out hydrocephalus, stroke,
or rebleeding. Triple-H therapy would then be maxi-
mized to the point of elevating the mean arterial pres-
sure to 130 to 140mm Hg.
In a group of 466 patients, 93 (22%) underwent
endovascular management of medically refractory cer-
ebral vasospasm. Eighty-four of these patients were
available for a minimum of 6 months of follow-up.
There were 51 patients (61%) who underwent
 ENDOVASCULAR MANAGEMENT OF CEREBRAL VASOSPASM POST-SUBARACHNOID HEMORRHAGE
endovascular management within a 2-hour window
due to the inability to reverse the patients neurologi-
cal deficits with medical measures. In this group, 90%
of patients demonstrated improvement angiographi-
cally and 70% of patients sustained clinical improve-
ment, based on Glasgow Coma Scale parameters as
previously outlined (P < 0.01) ([chi]2 = 8.02). Thirty-
three patients (39%) failed to improve with the best
medical therapy available; they were treated in more
than a 2-hour window (range: 2--17 hours) and had
88% angiographic improvement, but only 40% sus-
tained clinical improvement. Clinical improvement
was noted as early as 60 minutes after the procedure
when gross motor movement was able to be eval-
uated; however, global improvement (Glasgow Coma
Scale) continued for up to 48 hours, and further recov-
ery continued during the hospital stay (36).
Balloon Angioplasty Technique
The procedure involves transfemoral angiography with
placement of a 7-French femoral sheath. All patients
have continuous monitoring of the arterial pressure
either through a separate arterial line or slaving using
the femoral access sheath. Full heparinization is obtained
to achieving an activated clotting time (ACT) of twice
baseline, to prevent thromboembolic complications, and
all of these patients received general anesthesia and had
neurophysiological monitoring while being treated.
A four-vessel angiography is performed begin-
ning with the vessel that is most suspected for the clin-
ical decline. After the angiogram is performed two
scenarios are encountered, proximal spasm of the circle
of Willis vessels or distal spasm of the cortical vessels.
In the event of proximal spasm, a highly compliant bal-
loon is utilized such as The Hyperglide (EV3, Irvine,
California). The inflation starts on the most distal
aspect of the compromised vessel, and progressive in a
retrograde fashion move backward with a sequence of
inflation/deflation. An angiogram is performed after
the inflation to verify the change; if no significant
change is obtained, the procedure is repeated.
Proximal or large vessel such as the supraclinoid
internal carotid artery, middle cerebral artery in its
first and second segments, the anterior cerebral artery
and the vertebrobasilar system are amenable for bal-
loon angioplasty. It is very important to evaluate
the initial angiographic study in order to identify the
presence of hypoplastic arteries that may preclude the
use of balloon angioplasty due to the risk of rupturing
the artery during the inflation.
In the event that distal spasm is found, a micro-
catheter is navigated into the affected vessel and after
performing a selective microangiography demonstrat-
ing flow within that vessel, an infusion of nicardipine
is started. An infusion pump can be utilized in order
to obtain continuous infusions of the vasodilatory
agent; or more commonly aliquots of the vasodilatory
agent are administered paying close attention to
changes in the arterial pressure.
CONCLUSION
Aggressive 4-H management in the ICU and con-
tinuous monitoring using TCD facilitates early
371
identification of patients that develop vasospasm.
Increasing hemodynamic patterns such as the blood
pressure, cardiac output, and decreasing the blood vis-
cosity have limits and are not well tolerated in all
patients especially those with a compromised cardiac
function. In patients who are refractory to medical ther-
apy; angioplasty in the affected territory may be of
benefit in improving not only the angiographic appear-
ance but also the ultimate outcome for the patient, if
performed in a timely fashion. Our experience indicates
that a 2-hour window may exist for the restoration of
blood flow, which is analogous to a patient who
presents with a vascular-related event from either an
embolic or thrombotic occlusion. At this point there is
no evidence that support the use of prophylactic angio-
plasty before symptoms, and not having the opportu-
nity to maximize the medical therapy.
In selective cases the intraaortic balloon can be
considered, weighing the risk of aortic dissection and
anticoagulation. At this point, the use of compliant
balloons to dilate selected arteries is very effective,
still with close to 5% risk of vessel rupture.
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 18
Endovascular management of brain arteriovenous
malformations
John B. Weigele, Riyadh N. Alokaili, and Robert W. Hurst
INTRODUCTION
Brain arteriovenous malformations (BAVMs) are rare
central nervous system disorders that are responsible
for significant long-term morbidity and mortality.
Their decisive treatment requires complete obliteration
of the BAVM nidus to prevent future hemorrhage. The
primary therapeutic options include microvascular neu-
rosurgery, stereotactic radiosurgery, and endovascular
embolization. Although curative in some cases, emboli-
zation usually is combined with surgery or radiosurgery
for definitive therapy. Embolization is associated with
significant risks that must be balanced against potential
benefits in each patient. When performed by experi-
enced operators in appropriately selected cases, emboli-
zation improves the overall safety and efficacy of BAVM
treatment.
CLASSIFICATION AND PATHOGENESIS OF
BAVMs
Five categories of intracranial vascular malformations
have been defined based on gross and microscopic
pathology: BAVM, capillary telangiectasia, cavernous
malformation, venous malformation, and mixed malfor-
mation (14). BAVMs are comprised of arterial feeders
that connect directly to the venous system without an
intervening capillary bed, resulting in high-flow arterio-
venous (AV) shunts. The direct AV connections form a
nidus (Latin for nest). The vessels within the nidus vary
in size and histology from relatively well-differentiated
arteries and veins to thick- and thin-walled, hyalinized,
malformed vessels. Gliotic brain parenchyma is present
within and surrounding the nidus (3).
Although most are sporadic, BAVMs occur in a
number of congenital or hereditary syndromes, inclu-
ding: RenduOslerWeber, KlippelTrenaunay, Parks
Weber, WyburnMason, and SturgeWeber syndromes
(5). Rare familial cases unassociated with syndromes
have been described (6). Although most BAVMs are con-
genital due to the failure of capillary formation during
early embryogenesis (7), rare BAVMs appear to form in
response to a postnatal stimulus of angiogenesis (5,811).
EPIDEMIOLOGY OF BAVMs
Several population-based studies of the incidence and/
or prevalence of BAVMs have been reported (12). The
Mayo Clinic identified a total of 48 intracranial vascular
malformations in the population of Olmstead County,
Minnesota over a 27-year period from 1965 to 1992. The
BAVM detection rate was 1.11 (95% confidence interval
[CI] 0.71.5) per 100,000 person-years (13). The inci-
dence of symptomatic BAVMs was 1.1 (95% CI 0.61.8)
per 100,000 patient-years in the Leeward Islands of
the Netherlands Antilles between 1980 and 1990 (14). A
prospective, population-based study in Scotland found
that the detection rate for BAVMs was 1.12 (95% CI
0.901.37) per 100,000 adults per year (15). An ongoing,
prospective population-based study of BAVMs in
Manhattan, Staten Island and Long Island reported a
BAVM detection rate of 1.34 (95% CI 1.181.49) per
100,000 person-years (16).
NATURAL HISTORY OF BAVMs
The risks of treating a BAVM must be weighed against
the natural history of the disease; in particular, the risk a
BAVM will hemorrhage or rehemorrhage. Unfortu-
nately, little unbiased natural history data are available
since BAVMs are relatively rare, quite heterogeneous,
and usually undergo treatment. No level I or level II nat-
ural history study has been published (17). Data are very
limited on specific predictors for the clinical course of a
BAVM. In many natural history studies, there is a selec-
tion bias toward untreatable BAVMs. In addition, natu-
ral history outcomes usually have not been correlated
with the type of presentation, analyses have differed,
and follow-up periods have been brief (12).
Despite these limitations, some general observa-
tions can be made about the natural history of BAVMs.
They can present at any age, with the mean age of
presentation in the fourth decade of life. There is an
essentially equal distribution between sexes (12).
Many BAVMs present with intracranial hemor-
rhage (17). In a retrospective population-based study,
65% of newly diagnosed BAVMs had intracranial
hemorrhage (18). The hemorrhage was intraparen-
chymal in 41%, subarachnoid in 24%, intraventricular
in 12%, and combined in 23%. The second most
common BAVM presentation is epilepsy. In several
studies, 19%, 18%, and 27% of newly discovered
BAVMs were diagnosed following seizures (1820).
Less commonly, BAVMs present with headache (1%
and 11% in two hospital-based series) (19,20), a focal
neurological deficit (7% and 5% in two hospital-based
series) (19,20) and as an incidental finding (15% in one
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS
population-based study, 0% and 3% in two hospital-
based series) (1820). Nonetheless, the growing
utilization of magnetic resonance imaging has dramat-
ically increased the detection of unruptured, inciden-
tal BAVMs; recent series suggest the majority of newly
detected BAVMs are unruptured (21).
Hospital-based series have been retrospectively
analyzed to identify risk factors for BAVM hemorrhage
(12). These findings have not been confirmed by pro-
spective population-based studies. The features most
consistently associated with an increased risk of hemor-
rhage include deep venous drainage, a single draining
vein, venous stenoses, and high feeder mean arterial
pressure (12). Less consistent risk factors for hemor-
rhage are a small nidus, associated aneurysms, and
deep or posterior fossa locations (12). Gender and preg-
nancy do not appear to affect the risk of hemorrhage
(22). Features possibly associated with a decreased risk
of hemorrhage include a large nidus (23), arterial sten-
oses and ectasias (24), dural arterial supply (25), venous
recruitment (26), and neoangiogenesis (24).
A recent prospective study of 622 consecutive
patients from the Columbia BAVM database found that
increasing age (hazard ratio [HR] 1.05, 95% CI 1.031.08),
initial presentation with hemorrhage (HR 5.38, 95% CI
2.6410.96), deep brain location (HR 3.25, 95% CI 1.30
8.16), and exclusive deep venous drainage (HR 3.25, 95%
CI 1.015.67) were independent predictors for hemor-
rhage; annual hemorrhage rates ranged from 0.9% for
patients without hemorrhagic presentation, deep brain
location, or exclusive deep venous drainage to 34.5% for
those with all three risk factors (27).
An annual 24% risk of first-ever BAVM hemor-
rhage is widely quoted from several hospital-based
series (19,2831). However, no prospective, population-
based study of the clinical course of unruptured
BAVMs has been published (12). After an initial bleed,
the risk for recurrent hemorrhage has been reported to
be 718% in the first year (20,32). This risk appears to
subsequently decrease to the baseline 24% annual risk
of hemorrhage over time (32).
Fatality rates from BAVM hemorrhage range
from 0% to 18% during the first year (1820,31,33).
The reported long-term annual fatality rates are 1% to
1.5% (19,31). In a prospective observation of 166
untreated symptomatic BAVMs over a mean follow-
up period of 23.7 years, there was a 4.0% annual rate
of hemorrhage and a 1.0% annual mortality rate (31).
The combined annual rate of mortality and major
morbidity was 2.7%. During the study, 23% of the
patients died from hemorrhage. The incidence of
bleeding and death did not correlate with the type of
initial presentation. In another study, 47% of patients
with a first-ever BAVM hemorrhage sustained no neu-
rological defect and 37% experienced no significant
disability despite symptoms (33). Parenchymal hemor-
rhage had a greater likelihood (52%) of producing a
neurological defect. The morbidity rate of recurrent
hemorrhage appears similar to the initial bleed (32).
CEREBRAL ANGIOGRAPHY OF BAVMs
BAVMs demonstrate AV shunting on angiography,
resulting in early opacification of the draining veins
and a decrease in the AV transit time (34). Shunting is
375
the result of a direct connection between the arterial
and venous sides of the cerebral circulation without an
intervening capillary bed. There are two categories of
AV connections: fistulous and plexiform (35). A fistu-
lous nidus contains direct large-caliber AV connections
(Fig. 18.1). A plexiform nidus consists of a conglomer-
ate of smaller and more numerous vascular channels
supplied by one or more arterial feeders (Fig. 18.2).
These are collected into one or more draining veins. A
plexiform nidus can contain one or more direct fistulas
(mixed plexiform-fistulous nidus) (Fig. 18.3) (35,36).
Complete angiographic evaluation of a BAVM
consists of: (i) selective digital subtraction angiogra-
phy (DSA) of the entire cerebral circulation using 4 or
5 French (Fr) diagnostic catheters and (ii) superselec-
tive DSA of the feeding arterial pedicles, the nidus,
and the venous drainage using microcatheters (34).
The goals of the selective DSA are listed in
Table 18.1 (34). This provides a global assessment of
the arterial supply to the BAVM, the general character-
istics of the nidus, the venous drainage of the BAVM,
and the rest of the intracranial circulation. However,
selective DSA has limitations. Rapid AV shunting often
obscures important features such as small feeders,
pedicle and nidal aneurysms, direct AV fistulae, and
small accessory draining veins (34).
The goals of superselective DSA are listed in
Table 18.2 (34). Information from superselective DSA
about the distal arterial feeders, the nidus, and the
proximal draining veins is critical for planning and
performing endovascular embolizations (34).
CLASSIFICATION OF BAVMs
BAVMs are categorized into superficial (cortical) and
deep types. Cortical BAVMs are subcategorized into
sulcal, gyral, and mixed (sulcogyral) types. Deep
BAVMs are subdivided into subarachnoid, deep
parenchymal, plexal, and mixed types (34).
A sulcal BAVM nidus occupies the subpial space
of the sulcus. The nidus may remain contained within
the sulcus or variably extend through the sulcus into
the cerebral cortex, the subcortical and deep white
matter to the ventricular wall. Sulcal BAVMs assume
a conical or pyramidal shape conforming to the sulcal
space. Primary arterial supply is from terminal pial
branches. The most superficial aspect is covered by
the meninges; meningeal arterial supply to the super-
ficial aspect is common (Fig. 18.4) (34).
Gyral BAVMs are covered by cortex and are typ-
ically spherical (Fig. 18.5). The gyrus usually is
enlarged and adjacent sulci are compressed. A large
gyral BAVM may extend into the subcortical white
matter toward the ventricular wall. The arterial sup-
ply is primarily from non-terminal pial branches;
meningeal supply typically is absent (34).
Mixed (sulcogyral) are large BAVMs that combine
both sulcal and gyral features; they typically involve
gyri and sulci and extend into the subcortical white
matter to the ventricular wall. Arterial supply includes
meningeal arteries and terminal pial branches from
the sulcal component, non-terminal pial branches from the
gyral component and basal perforating arteries (34).
Deep BAVMs are relatively rare. They can be
subdivided into subarachnoid, deep parenchymal,
376 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 18.1 Large, fistulous BAVM (A and B, large arrows). Note proximal arterial aneurysms (A, small arrows), venous ectasia
(B, arrowheads), and venous aneurysms (C and D, small arrows). Also note non-visualization of normal anterior and middle cerebral
arterial territories due to vascular steal. (A) AP angiogram-arterial phase. (B) Lateral angiogram-arterial phase. (C) AP angiogram-
venous phase. (D) Lateral angiogram-venous phase. Abbreviations: BAVM, brain arteriovenous malformation; AP, anteroposterior.

plexal, and mixed types. Subarachnoid BAVMs are
found in the basal cisterns and fissures, supplied by
the subarachnoid portions of the choroidal and perfo-
rating arteries. Deep parenchymal BAVMs are
located in deep gray and white matter (Fig. 18.6),
supplied by basal perforators, choroidal arteries,
basal circumferential arteries, and medullary pial
branches. Plexal BAVMs are intraventricular, sup-
plied by the choroidal arteries. Mixed deep BAVMs
are larger, combining subarachnoid, deep parenchymal,
and plexal features. Venous drainage is predominately
into the deep venous system; however, transmedullary
cortical venous drainage also is seen (34).
ANGIOARCHITECTURE OF BAVMs
Feeding Arteries
Classification of the BAVM arterial feeders by ana-
tomic, geometric, and hemodynamic criteria is essen-
tial to plan and perform embolizations. Pial supply
may be provided by extracortical (subpial), cortical,
medullary, and/or corticomedullary branches. Menin-
geal supply may be direct or through transdural pial
anastamoses (Fig. 18.7). Collateral supply can occur
through leptomeningeal and subependymal anastamo-
ses. Choroidal artery supply can arise from the extra-
ventricular (fissural, parenchymal) or intraventricular
portions (35,36).
Geometric classification of arterial feeders defines
three types: terminal, pseudoterminal, and indirect
(35,36). The terminal feeder ends within the nidus dis-
tal to branches supplying normal brain. Embolization is
relatively safe (35,36). The pseudoterminal feeder
appears to end in the nidus, but has a distal segment
supplying normal parenchyma that is not angiographi-
cally visible because of high flow (sump effect) into
the nidus. A wedged catheter position during superse-
lective angiography can contribute to nonvisualization
of the distal portion. Changing hemodynamic condi-
tions during embolization of a pseudoterminal feeder
can occlude the distal portion, resulting in an infarct
(35,36). The indirect feeder (feeder en passage) supplies
the nidus from an artery that passes in close proximity
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 377

(A) (B)

(C) (D)

Figure 18.2 Plexiform BAVM (arrowheads in A, B and C). (A) AP angiogram. (B) Lateral angiogram. (C) Superselective angiogram
(microcatheter tip, arrow). (D) Lateral post-embolization angiogram (residual nidus, arrow). Abbreviations: BAVM, brain arteriovenous
malformation; AP, anteroposterior.

while continuing on to supply normal brain (Fig. 18.8).
Indirect feeders are typically smaller and shorter, usu-
ally originating at an acute or right angle from the
parent vessel (35,36).
Feeding arteries may be characterized hemody-
namically into dominant or supplementary according to
the amount of flow. Dominant feeders supply more of
the nidus, are larger, and carry more flow than supple-
mentary feeders. Dominant and supplementary feeders
can arise from the same or different vascular territories.
Most BAVMs contain a combination of both types (34).
High-flow angiopathy causes feeding artery
stenoses in up to 20% of BAVMs. Diffuse stenoses
with a moyamoya appearance occasionally are seen
in younger patients (36). An arterial stenosis that
decreases distal perfusion pressure may shift the water-
shed zone toward the nidus (watershed transfer) in
up to 30% of superficial (cortical) BAVMs. Cortical
arteries and leptomeningeal collaterals are recruited to
supply more of the territory distal to the BAVM. With
watershed transfer, angiogenesis can occur in response
to chronic parenchymal ischemia; it has no AV shunt-
ing and is not a true component of the BAVM (36).
BAVM Nidus
The nidus is the region between very distal aspects of the
readily identifiable arterial feeders and the proximal
aspects of the draining veins. AV shunting occurs here
and represents the primary target of embolization (35,36).
Most BAVMs have a compact, well-defined nidus, dis-
crete feeding arteries, and draining veins. A minority
have diffuse and ill-defined margins. Angiogenesis asso-
ciated with watershed transfer may mimic a diffuse
nidus. Nidal sizes vary tremendously. Their shapes tend
to conform to their anatomic environments (34).
378 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 18.3 Mixed plexiform (A, arrowheads) and fistulous (B, arrow) nidus in an 11-month old. (A) Selective lateral angiogram.
(B) Superselective lateral angiogram.

Table 18.1 Goals of Selective Angiographic Evaluation of

BAVMs
Arterial territories supplying the BAVM
Feeding pedicles
High-flow arteriopathy (stenoses, ectasias, flow-related aneurysms)
Nidus (size, shape, location, flow, fistulae, ectasias, aneurysms)
Venous drainage (territories, deep, superficial)
Individual draining veins
High-flow venous angiopathy (dural sinuses, venous stenoses,
occlusions and varices)
Venous drainage of normal brain parenchyma
Table 18.2 Goals of Superselective Angiographic Evaluation of
BAVMs
Distal feeding pedicles (anatomy, aneurysms, geometry,
hemodynamics)
Arterio-nidal junction
Nidus (compartments, direct arteriovenous fistulae, plexiform
regions, intranidal ectasias, and aneurysms)
Veno-nidal junction
Proximal aspects of the draining veins

Abbreviation: BAVM, brain arteriovenous malformation. Abbreviation: BAVM, brain arteriovenous malformation.
Source: From Ref. 34. Source: From Ref. 34.

Figure 18.4 Sulcal BAVM. (A) Triangular

nidus (arrow) on lateral angiogram. (B) n-BCA
in nidus (arrow) on unenhanced axial CT
image. Abbreviations: BAVM, brain arterio-
venous malformation; n-BCA, n-butyl cyanoa-
(A) (B) crylate; CT, computed tomogram.
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 379

Figure 18.5 Gyral BAVM. (A) Axial T2-weighted

MRI and (B) lateral angiogram demonstrate a
small gyral BAVM (arrows). Abbreviations:
BAVM, brain arteriovenous malformation; MRI,
(A) (B) magnetic resonance imaging.

Figure 18.6 Deep BAVM (large arrow in

A and B) on (A) lateral angiogram and (B)
axial T2-weighted MRI. Note venous ectasia
(A, arrowhead) and venous aneurysm
(A, small arrow). Abbreviations: BAVM,
brain arteriovenous malformation; MRI, mag-
(A) (B) netic resonance imaging.

Figure 18.7 External carotid supply to

BAVM from middle meningeal (B, arrow) and
occipital (B, arrowheads) branches. (A) AP
angiogram. (B) Lateral angiogram. Abbrevi-
ations: BAVM, brain arteriovenous malforma-
(A) (B) tion; AP, anteroposterior.
380 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 18.8 En passage supply during embolization of a plexiform BAVM. (A) AP angiogram shows superficial (arrow) and deep
(arrowhead) venous drainage. (B) Lateral angiogram shows venous ectasia (arrowhead) and venous aneurysm (arrow). (C) Lateral
superselective angiogram following partial embolization shows en passage supply (arrowheads) to nidus (large arrow); microcatheter
tip (small arrow). (D) Lateral angiogram shows residual nidus after embolization (arrowheads). Abbreviations: BAVM, brain arteriove-
nous malformation; AP, anteroposterior.

A nidus may be composed of one or multiple
vascular compartments of varying sizes and flow pat-
terns. The AV connections within a given compart-
ment may be plexiform, fistulous, or mixed. These
compartments are often hemodynamically intercon-
nected; occlusion of the compartmental feeders with-
out occlusion of the AV shunting may allow the
compartment to continue to fill from neighboring
units. Compartmental vein occlusion can increase the
risk of nidal rupture. Hence, careful characterization
of the compartmental angioarchitecture is essential for
planning an embolization (34).
Nidal histology reveals a complex system of
coiling and intercommunicating vascular channels
emptying into tortuous thin-walled collecting veins.
Three intranidal zones have been described: arterial,
intermediate, and venous. The arterial zone consists of
a plexus of interconnecting thick-walled vessels. The
intermediate zone is very heterogeneous, containing
four types of coiled, interconnected channels ranging
from 0.151.0mm in diameter. The venous zone con-
sists of 13-mm thin-walled vessels converging into
the draining veins. AV shunting occurs between the
arterial and intermediate zones (37).
Draining Veins
Cortical BAVMs typically drain through cortical veins
into nearby dural sinuses. Those with subcortical or
ventricular extension often have both superficial (cort-
ical) and deep (subependymal) venous drainage. Cen-
tral BAVMs usually drain into the deep venous
system. Unexpected patterns, however, such as trans-
cerebral cortical venous drainage of a deep BAVM or
deep venous drainage of a cortical BAVM, may be
seen approximately 30% of the time. These probably
represent venous collaterals that developed after
occlusion of the original venous drainage system (36).
Important aspects of nidal venous drainage
include anatomic variations, collateral venous drainage,
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS
(A)
Figure 18.9 Large, high-flow BAVM with left transverse sinus occlusion (A, arrow) and right sigmoid sinus stenosis (B, arrow) causing
venous hypertension and cognitive impairment. (A) AP angiogram-venous phase. (B) Lateral angiogram-venous phase. Abbreviations:
BAVM, brain arteriovenous malformation; AP, anteroposterior.
and high-flow angiopathy (Fig. 18.9). Venous obstruc-
tion may be due to mechanical venous compression or
intrinsic venous stenoses/thromboses due to high-flow
angiopathy. Insufficiently developed collateral venous
drainage may result in venous hypertension, venous
aneurysms, and venous ectasia (varix) proximal to the
obstruction, especially in high-flow BAVMs (Fig. 18.1).
Direct compression of the brain or cranial nerves by
a varix can cause seizures, neurological deficits, or
hemorrhage (34,36).
BAVM-Associated Aneurysms
The association of aneurysms with BAVMs has been
reported for many years. However, little was known
about their frequency or clinical implications until
recent publications of relatively large series. Although
much remains to be understood, it is clear that signifi-
cant clinical and therapeutic implications may arise
from their relatively common association.
Classification
The Tew classification (Table 18.3) (38) divides
BAVM-associated aneurysms into four groups based
on their relationship to the feeding arteries and nidus.
This classification suggests potential mechanisms for
aneurysm formation based on location. In addition, it
has proven useful in attempts to relate aneurysm
types to clinical behavior (Fig. 18.10) (39).
Epidemiology
The reported prevalence of aneurysms associated with
BAVMs varies widely from 5.8% to 58% (Table 18.4)
(Figs. 18.11,18.12) (35,4051). This variability probably
arises from a number of factors, including: differing
definitions, data collection methodology, and inclusion
criteria.
The prevalence of BAVM-associated aneurysms
is similar in men and women; it increases with age,
381
(B)
Table 18.3 Tew Classification of BAVM-Associated Aneurysms
(38)
Type I Dysplastic or remote, not related
to BAVM supply
Type II Proximal, arising from the circle of Willis or origin
of a vessel supplying the BAVM
Type III Pedicular, arising from the midcourse
of a feeding pedicle
Type IV Intranidal, within the BAVM nidus
Abbreviation: BAVM, brain arteriovenous malformation.
increasing flow rate, and increasing size of the nidus.
Reported multiplicity of BAVM-associated aneurysms
is common but quite variable. Almost half of the
patients with BAVM associated-aneurysms will have
more than one aneurysm; a significant proportion will
have more than two (44,49,52).
Pathogenesis
Three major theories have addressed the association
of BAVMs and aneurysms: coincidental occurrence, an
underlying congenital vascular defect responsible for
both lesions, and the flow-related (hyperdynamic)
theory.
Early suggestions were made that the relationship
between BAVMs and aneurysms was simple chance
occurrence. For adults without specific risk factors, the
prevalence of intracranial aneurysms has been estimated
at approximately 2.3% (52). Most studies report a consid-
erably higher frequency of aneurysms occurring in asso-
ciation with BAVMs; therefore, this theory is currently
given little credence (Table 18.4) (35,4051).
To date, no underlying congenital defect has
been identified to explain an association between aneur-
ysms and BAVMs. While a number of genes have been
found to be differentially expressed in BAVM feeding
pedicles compared with normal cerebral arteries, this
382 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Nidal
aneurysm

(C) (D)

(E)

Figure 18.10 (A) Distal flow-related aneurysm. (B) Additional example of distal flow-related aneurysm. (C) Intranidal aneurysm.
(D) Proximal flow-related aneurysm. (E) Non-flow-related aneurysm. Source: From Ref. 39.

differential expression is likely a consequence of the development of aneurysms to the hyperdynamic

increased flow dynamics rather than an underlying
cause of the BAVM-associated aneurysm (53).
Flow phenomena provide a logical mechanism to
explain BAVM-associated aneurysms. This theory,
introduced by McKissock over 50 years ago, attributes
flow caused by AV shunting through the BAVM (54).
Hyperdynamic flow increases shear stress on the ves-
sel walls; this has been found to play a role in the for-
mation, growth, and rupture of all types of arterial
aneurysms (5557).
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 383

Table 18.4 Reports of BAVM-Associated Aneurysms

Multiple On feeding
Author Year AVMs Aneurysms (pts) aneurysms vessel Intranidal Unrelated
Perret (40) 1966 490 37 (7.6%) 15/34 (37%) NE 18/34 (43%)
Yasargil (35) 1987 414 45 (11%) 42/45 (93%) NE 3/45 (7%)
Brown (42) 1990 91 16 (17.6%) 25 NE
Cunha e Sa (47) 1992 400 39 (9.8%) 63/64 (98%) NE 1/ 64 (2%)
Turjman (43) 1994 100 58 (58%) 34/58 (58.6%)
Redekop (46) 1998 632 97/632 (15.3%) 71 pts (11.2%) 35 (5.5%) 5/632
had 123 flow (0.8%)
related aneurysms
Thompson (41) 1998 600 45 (7.5%) 51% 30/45 (66%) NE 15/45 (33%)
Meisel (44) 2000 662 (450 Rxd) 305 (46.1%) 205/305 (67.2%) 138/450 (30.7%) 181/450
(40%)
Westphal (48) 2000 222: 198 Total: 13/222 (5.8%); 1/222 (0.045%) All by definition NE 1/222
supra, 24 Supratent 3.5%; (0.045%)
infratent infratent 20.8%
Ezura (49) 2000 172 25 (14.5%) 18/25 (72%)
Piotin (50) 2001 270 30 (11%) 14/30 (47%) all NE
Stapf (51) 2002 463 117 (25.3%) 24/117 (20.5%) 77/463 (17%); 35/463 32/463
54/117 (46%) BAVMs (7%);
(8%); 18/117
(21/117 (15.3%)
(17.9%)
Halim (45) 2002 Total of 28 (34%) (UCSF)/74 16/82 (23%); 11/82 2/82 (4%);
336- 82/254 (29%)(CPMC) 35/254 (16%) (17%); 10/254 (5%)
23/254
(11%)
Total 4852 929/4852 (19.1%)
Abbreviations: BAVM, brain arteriovenous malformation; NE, not evaluated.

(A) (B)

Figure 18.11 Proximally located aneurysms. (A) M1-2 junction. (B) Basilar tip.

Support for a flow-related mechanism comes
from the observation that aneurysms arise far more
commonly on arterial feeders to the BAVM than on
unrelated vessels. There is also a tendency for aneur-
ysms to occur more often on arteries feeding larger,
high-flow BAVMs than on arteries supplying smaller,
low-flow BAVMs (46,47,58). Additionally, BAVM-
related aneurysms can decrease in size or disappear
following treatment of the BAVM and correction of
the high-flow state (46).
Controversy surrounds the etiology of intra-
nidal aneurysms. Many believe these represent
true aneurysms located in the most distal arterial
branches. Others have suggested that some of these
may represent early filling of dilated venous
pouches rather than true arterial aneurysms or
384 NEUROINTERVENTIONAL MANAGEMENT
represent pseudoaneurysms arising as residua of
prior hemorrhages (59).
Clinical Implications
The natural history of BAVMs with associated aneur-
ysms has been the subject of considerable controversy
and little firm agreement. In large part this uncer-
tainty is due to the heterogeneity of BAVM-associated
aneurysms as well as to the heterogeneity of BAVMs
themselves.
Some data suggest there are increased rates of
both initial and recurrent hemorrhage when aneurysms
are associated with BAVMs. In one series, patients with
an BAVM-associated aneurysm had an annual hemor-
rhage risk of 7% at 5 years following diagnosis, signifi-
cantly higher than the 1.7% annual hemorrhage rate for
BAVMs without coexisting aneurysms (42). In several
series studying BAVMs accompanied by aneurysms
Figure 18.12 Distal feeding artery aneurysm arising from the
anterior choroidal artery.
(A)
Figure 18.13 Distal feeding artery aneurysm (arrows) arising from the superior cerebellar artery (nidus, arrowheads). (A) AP and
(B) Lateral views. Abbreviation: AP, anteroposterior.
presenting with hemorrhage, the aneurysm was consid-
ered to be the source of the hemorrhage in 5080% of
the cases (47,50,60). Redekop et al. found intranidal
aneurysms were associated with a higher incidence of
initial hemorrhage as well as with multiple episodes of
recurrent bleeding (46).
In contrast, other studies did not find initial
BAVM hemorrhage to correlate with any type of aneur-
ysm (27,41,44). Halim et al. studied the association
between BAVM-associated aneurysms and presenta-
tion with intracranial hemorrhage in 336 patients from
two separate institutions. While aneurysm prevalence
was similar at both centers, they found that initial pre-
sentation with hemorrhage was associated with a coex-
isting aneurysm at only one institution, while the
opposite trend was found at the other institution (45).
Infratentorial BAVM-associated aneurysms may
behave in an especially aggressive fashion. A study of
222 BAVMs identified five aneurysms associated with
infratentorial BAVMs; four were located distally and
75% were responsible for intracranial hemorrhage
(Figs. 18.13,18.14) (48). Kaptain et al. evaluated 27 cer-
ebellar BAVMs, all of which were associated with
aneurysms; 89% had findings of aneurysm rupture
(61). Khaw et al. also reported a higher prevalence of
aneurysms associated with infratentorial BAVMs;
these were significantly more likely to present with
intracranial hemorrhage than BAVMs without associ-
ated aneurysms (62).
Treatment Approaches
Specific management recommendations for patients
having both aneurysm(s) and a BAVM are difficult to
formulate because of sparse and often conflicting data.
However, general guidelines have been suggested
(Table 18.5) (41,44,46,49). For cases presenting with
hemorrhage, the first step is to determine which lesion
caused the bleed. It is that lesion toward which the
initial treatment should be directed. As noted, higher
rates of hemorrhage may result from feeding artery
aneurysms associated with posterior fossa BAVMs
(B)
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 385

than from supratentorial BAVMs (Fig. 18.15). When
the source of hemorrhage cannot be determined, the
greater morbidity and higher chance of repeat hemor-
rhage from an aneurysm dictates that the aneurysm
be addressed as a first priority.
Initial treatment should target the BAVM when
it is identified as the source of hemorrhage. Differing
recommendations have been made regarding prophy-
lactic treatment of feeding artery aneurysms in this
setting. Some recommend occluding the aneurysm to
prevent rupture prior to definitive treatment of the
BAVM (41,49). Others argue that the decreased flow
after BAVM treatment frequently results in the spon-
taneous regression of extranidal aneurysms without
the need for direct treatment (44,46).
BAVM GRADING SYSTEMS
Because of the tremendous variability of BAVMs with
respect to their anatomy and biological behavior, a
number of studies have attempted to correlate specific
criteria of BAVM characteristics with therapeutic
outcomes to guide clinical decision making. Most of
these grading systems have focused on surgical man-
agement (6365).
The Spetzler-Martin grading system is the most
widely utilized. This system was designed to be sim-
ple and applicable to all BAVMs, providing a reason-
able estimate of operative morbidity and mortality.
The system employs three criteria: BAVM size, the
venous drainage pattern, and the eloquence of adja-
cent brain parenchyma. The BAVM size (largest diam-
eter) is divided into three categories: small (<3cm),
medium (36cm) and large (>6cm). The venous drain-
age is designated as superficial if all of the venous
drainage empties into the cortical venous system. If
any of the venous drainage egresses through deep
veins (internal cerebral, basal veins, precentral cerebel-
lar vein), it is categorized as deep. A BAVM is consid-
ered to be adjacent to eloquent brain parenchyma if it
is next to the sensorimotor cortex, language areas, vis-
ual cortex, hypothalamus, thalamus, internal capsule,
brainstem, cerebellar peduncles, or deep cerebellar
nuclei (65).

(A) (B)

(C) (D)

Figure 18.14 (A) Intranidal aneurysm responsible for cerebellar BAVM hemorrhage (arrow). (B) Unsubtracted and (C) subtracted
microcatheter injection of feeding pedicle (aneurysm, arrow; catheter tip, arrowhead). (D) Post-embolization, no filling of pedicle (arrow)
or aneurysm. Residual BAVM treated with radiosurgery. Abbreviation: BAVM, brain arteriovenous malformation.
386 NEUROINTERVENTIONAL MANAGEMENT

Table 18.5 Management of BAVM-Associated Aneurysm Patients with Hemorrhage

Aneurysm Location Rx
Aneurysm hemorrhage
BAVM Resectable Intranidal Aneurysm Both lesions simultaneously
Distal Pedicle Aneurysm Aneurysm first- consider BAVM resection at same time
Proximal Aneurysm Aneurysm first- consider BAVM resection at same time
Unrelated Aneurysm Aneurysm first
BAVM Unresectable Intranidal Aneurysm Embolization of Aneurysm and pedicle
Distal Pedicle Aneurysm Aneurysm
Proximal Aneurysm Aneurysm
Unrelated Aneurysm Aneurysm
BAVM hemorrhage
BAVM Resectable Any Rx BAVM first- consider distal pedicle aneurysm treatment if low risk
BAVM Unresectable Intranidal Aneurysm Embolization of intranidal aneurysm feeder first
Radiosurgery, consider embolization of intranidal feeder first
Distal Pedicle Aneurysm Consider aneurysm Rx first (controversial)
Proximal Aneurysm BAVM first
Unrelated Aneurysm BAVM first
Unknown hemorrhage source
BAVM Resectable Intranidal Aneurysm Rx BAVM and aneurysm
Distal Pedicle Aneurysm Rx BAVM and aneurysm
Proximal Aneurysm Rx Aneurysm first
Unrelated Aneurysm Rx Aneurysm first
BAVM Unresectable Intranidal Aneurysm Embolization of intranidal feeder first
Distal Pedicle Aneurysm Rx Aneurysm
Proximal Aneurysm Rx Aneurysm
Unrelated Aneurysm Rx Aneurysm
Abbreviations: BAVM, brain arteriovenous malformation; Rx, targeted treatment.

Points are assigned for each parameter and
added together; the total corresponds to the Spetzler-
Martin grade (I to V) (Table 18.6) (65). For example, a
2-cm anterior frontal lobe BAVM with cortical venous
drainage (1 point for size, 0 points for venous drain-
age, 0 points for eloquence) is a Spetzler-Martin grade
I BAVM; whereas, a 4-cm thalamic BAVM with deep
venous drainage (2 points for size, 1 point for venous
drainage, 1 point for eloquence) is a Spetzler-Martin
grade IV BAVM. BAVMs with no possibility of surgi-
cal resection (e.g., diffuse brainstem or holohemi-
spheric involvement) are grade VI (65).
Retrospective correlation of surgical experience
found a low incidence of minor deficits (0%, 5%) and
no major neurological deficits following resection of
Spetzler-Martin grade I and II BAVMs, whereas grade
IV and V BAVM resections were associated with sig-
nificant incidences of minor (20%, 19%) and major
(7%, 12%) deficits (65). A subsequent prospective eval-
uation confirmed the accuracy of the Spetzler-Martin
grading system for predicting both new-temporary
and new-permanent neurological deficits (66).
Although there was significant interobserver variabil-
ity between a neuroradiologist and a neurosurgeon
performing Spetzler-Martin grading in 27.7% of
patients, this variability did not diminish the predic-
tive value of the system (67).
EMBOLIZATION OF BAVMs
Historical Background
The first therapeutic embolization of a BAVM was
reported in 1960 (68). Silastic spheres were injected
directly into a surgically accessed cervical internal
carotid artery relying on high flow to carry the
spheres into the BAVM feeders. This flow-dependent
embolization was unreliable; there was a significant
risk of non-target embolization causing an infarct. In
addition, the relatively large spheres lodged in proxi-
mal feeders. The nidus remained unoccluded and
could recruit deep perforating arterial supply that was
much more difficult to control during surgery (6972).
Superselective catheterization and BAVM embo-
lization was first reported in 1974 with detachable bal-
loons attached to flexible, flow-directed catheters (73).
Similar to flow-directed silastic spheres, the detach-
able balloons occluded proximal arterial feeders; this
induced the nidus to recruit new blood supply that
was often more difficult to control during surgery.
In 1976, the use of a microcatheter with a
calibrated-leak balloon for superselective embolization
was reported; a liquid embolic agent (isobutyl-2-
cyanoacrylate ([IBCA]) was injected into the BAVM
nidus (74). However, calibrated-leak balloon micro-
catheters caused multiple complications, including
vascular injuries and becoming permanently glued
into the BAVM (75). In addition, the IBCA trans-
formed the BAVM into a hard, incompressible mass
that was difficult to surgically cut or coagulate (75,76).
IBCA also was reported to be carcinogenic and associ-
ated with toxic reactions (77,78).
These pioneering efforts provided the foundation
and stimulus for the development of the microcath-
eters, guidewires, and embolic agents currently used
for BAVM embolization. These early experiences also
established the concept of targeting the nidus for
embolic occlusion, and defined the risks of embolizing
too proximally (the arterial feeders) and too distally
(the venous outflow).
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 387

(A) (B)

(C) (D)

Figure 18.15 Embolization of an ectatic distal arterial feeder and aneurysm supplying a cerebellar BAVM presenting with hemorrhage.
(A) Selective and (B) superselective lateral vertebral angiograms show a cerebellar BAVM supplied by an ectatic distal feeder (arrow-
heads) containing an aneurysm (arrows). (C) Post-embolization with n-BCA demonstrates no filling of the pedicle or aneurysm.
(D) Unenhanced CT image shows an n-BCA -filled aneurysm (arrow) surrounded by subarachnoid hemorrhage (arrowheads). Abbre-
viations: BAVM, brain arteriovenous malformation; n-BCA, n-butyl cyanoacrylate; CT, computed tomogram.

Table 18.6 Spetzler-Martin grading system for BAVMs

Indications for BAVM Embolization
BAVM feature Points
Definitive treatment of a BAVM requires its complete
Size of nidus obliteration to prevent subsequent hemorrhage. Thera-
< 3cm (small) 1 peutic options include embolization, microvascular
36cm (medium) 2
surgery, stereotactic radiosurgery, and combined thera-
> 6cm (large) 3
Eloquence of adjacent brain
pies. No randomized, controlled study has compared
Non-eloquent 0 active treatment with conservative management; there-
Eloquent 1 fore, BAVM treatment remains controversial, especially
Venous drainage for unruptured BAVMs (16). A recent prospective, pop-
Superficial 0 ulation-based cohort study found worse short-term
Deep 1 (3year) outcomes for unruptured BAVMs that under-
The assigned grade equals the sum of the points for all three went active treatment (79). Conversely, a long-term
features. study (median follow-up = 11.9 years) in 623 consecu-
Abbreviation: BAVM, brain arteriovenous malformation. tive patients found that active treatment reduces excess
Source: From Ref. 65. mortality associated with BAVMs (80). A Randomized
388 NEUROINTERVENTIONAL MANAGEMENT
Multicenter Clinical Trial of Unruptured Brain AVMs
(the ARUBA study) is currently underway to compare
5 to 10-year outcomes for intervention (embolization,
surgery, radiosurgery, and combined modalities) with
conservative medical management (81,82).
The goal of combined therapy is to decrease the
morbidity and/or increase the efficacy of the overall
treatment. In many centers, BAVM embolization is
most commonly performed before microsurgical resec-
tion to decrease surgical morbidity and mortality.
When embolization is performed prior to radiosurgery,
the goal is to permanently occlude enough of the nidus
that stereotactic radiation can target the rest with a
higher dose and better chance for cure. Less frequently,
embolization is used as a stand-alone curative techni-
que, especially for small, surgically difficult lesions.
Occasionally, embolization is employed to palliate
symptoms from an otherwise untreatable BAVM.
Ideally, a multidisciplinary team collectively evaluates
and formulates an individualized plan for each patient.
Presurgical Embolization
BAVM embolization can improve surgical outcomes
through several mechanisms. Often, the most valuable
contribution is the elimination of deep or surgically
inaccessible feeders. Preoperative embolization of the
deep arterial supply can allow an otherwise inoperable
BAVM to be successfully resected (83). Additional
advantages of embolization include shorter surgical
times and less blood loss. Embolized vessels are easily
identified, providing a roadmap for the resection of the
arterial feeders and nidus while helping to preserve
en passage arteries to nearby eloquent parenchyma
(Fig. 18.8). In addition, the staged embolization of a
large, high-flow BAVM can decrease the incidence of
potentially catastrophic hemorrhage caused by rapidly
changing hemodynamics (e.g., normal perfusion pres-
sure breakthrough). Finally, preoperative embolization
of feeding vessel and nidal aneurysms can eliminate
those angioarchitectural risk factors for perioperative
hemorrhage (83,84).
Many superficial Spetzler-Martin grade I and II
BAVMs can be resected without preoperative emboliza-
tion with minimal morbidity and mortality. However,
there are exceptions such as a grade I or II BAVM with a
deep feeder that is difficult to surgically access (85,86).
Also, embolization of an intranidal aneurysm in a grade
I or II BAVM presenting with acute hemorrhage can
stabilize the nidus until surgery (86). Embolization is
used frequently for Spetzler-Martin grade III BAVMs,
particularly for those in central and eloquent locations
and those with deep feeders. Preoperative embolization
(often staged) also is commonly employed for those
Spetzler-Martin grades IV and V BAVMs considered for
resection.
Preradiosurgical Embolization
There is a wide variability in the use of combined
embolization and radiosurgery. Some centers fre-
quently use embolization to render large BAVMs ame-
nable to stereotactic radiosurgery. The rate of cure after
stereotactic radiosurgery decreases significantly as the
volume of BAVM being treated increases (8789). In
this setting, the goal for embolization is to reduce the
size of the BAVM, increasing the probability of a radio-
surgical cure (90). Embolization is also performed prior
to radiosurgery to occlude nidal aneurysms that repre-
sent a risk for hemorrhage until the radiosurgically
induced obliteration occurs and also to occlude high-
flow fistulae that may be refractory to radiosurgery
(90). Repeat embolization or surgery also can be used
to treat a residual nidus after radiosurgery (91,92).
Curative Embolization
At present, there are limited, well-proven roles for
curative embolization of BAVMs (Fig. 18.16). Although
embolization can successfully obliterate some small
BAVMs with few feeders, it rarely cures large, complex
BAVMs. However, recent experience suggests curative
embolization may be possible for more BAVMs using
Onyx, but significant questions remain concerning
safety and durability (9395). Most of the BAVMs that
have a relatively high probability of cure with emboli-
zation also are amenable to complete surgical removal
with negligible morbidity and mortality. Therefore, the
risks of an attempted curative embolization must be
justified (66,96,97). Small deep central BAVMs with
limited feeders are exceptions where curative emboliza-
tion can play an important role (98).
Palliative Embolization
Most non-curable BAVMs do not appear to benefit
from palliative embolization (99). However, there are
roles for palliative embolization in select circumstan-
ces, including: alleviation of symptoms due to vascu-
lar steal and mechanical compression, obliteration of
specific aneurysms responsible for repeated hemor-
rhages, and embolization of meningeal supply to
improve intractable headaches (100102).
Embolization Tools
Microcatheters and Guidewires
The flow-directed and guidewire-directed microcath-
eters used for embolization with liquid agents are
designed for safe and reliable navigation into the very
distal aspects of the intracranial circulation. They have
several segments of progressive softness. The proxi-
mal segments are relatively stiff and thick-walled for
efficient transmission of longitudinal motion and tor-
que. The transitional middle segments have thinner
walls and progressively increase in flexibility but
remain pushable. The distal segments of flow-
directed microcatheters are small (1.3 to 1.8 French
outer diameter), thin-walled, and extremely soft and
supple. They provide no intrinsic transmission of lon-
gitudinal force. The catheter tips are slightly bulbous
so blood flow will pull them forward. The microcath-
eters have hydrophilic surface coatings to decrease
thrombogenicity, facilitate movement through small
tortuous vessels, and prevent adhesion of embolic
agents. Guidewires designed for use in the cerebral
arteries (0.008 to 0.014 inch) have very flexible distal
segments and soft, shapeable platinum tips. They also
are covered with a hydrophilic coating to reduce fric-
tion between the catheter and guidewire. They remain
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 389

(A) (B)

(C) (D)

Figure 18.16 Curative BAVM embolization. (A) Lateral angiogram shows occipital BAVM nidus (arrow). (B) Superselective angiogram
(arrow, microcatheter tip). (C) AP and (D) lateral views of a post-embolization angiogram reveal complete obliteration of the nidus.
Abbreviations: BAVM, brain arteriovenous malformation; AP, anteroposterior.

torquable even after they have gone through several
curves. Only the smallest guidewires such as the 0.008
inch Mirage (ev3 Endovascular Inc., Plymouth, Minne-
sota, U.S.) will pass through the flow-directed and
small guidewire-directed microcatheters commonly
used with liquid embolic agents (103).
Embolic Agents
There are three general categories of embolic agents:
solid occlusive devices (coils, silk threads, balloons), par-
ticulates (polyvinyl alcohol [PVA] particles), and liquids
(cyanoacrylates, Onyx, ethanol) (104). Coils are used
to occlude large direct AV fistulae and some BAVM-
associated aneurysms. At most centers, PVA particles
have been replaced by liquid embolic agents for BAVM
embolization (105,106). Less frequently, ethanol and silk
threads have been used to embolize BAVMs (107,108).
PVA Particles
PVA particles were commonly used for BAVM embo-
lization prior to liquid agents. They are available in
various size ranges, from 50 to 1000m. The non-
radiopaque particles are mixed with iodinated con-
trast for delivery. PVA particles are often used in
combination with coils or silk threads to facilitate their
retention, especially in larger fistulae (109). Larger
(e.g., 3 Fr) over-the-wire microcatheters are required
to inject the bigger PVA particles (> 500mm), resulting
in more proximal embolizations, although more distal
PVA embolizations recently have been made possible
with hybrid flow-guided/over-the-wire catheters (86).
PVA particles have several disadvantages com-
pared to liquid embolic agents. The particles often
occlude small, flow-directed microcatheters. Also,
since the particles are radiolucent it is not possible to
observe where they deposit. Evidence suggests the
particles frequently aggregate and occlude the arterial
feeder rather than the nidus. The nidus can then
recruit collateral blood supply and regrow (109,110).
This lack of permanency is undesirable for an emboli-
zation performed for cure or as an adjunct for radio-
surgery (88,111). The lack of a durable occlusion,
however, may not be a significant disadvantage for
presurgical embolizations. A prospective, randomized,
390 NEUROINTERVENTIONAL MANAGEMENT
multicenter trial concluded PVA and n-butyl cyanoa-
crylate (n-BCA) were similar in safety and effective-
ness for preoperative BAVM embolization (86).
n-Butyl Cyanoacrylate
Cyanoacrylates have been used for BAVM emboli-
zation for more than two decades. Early problems
preventing widespread use have been solved with the
replacement of previous formulations with n-butyl
cyanoacrylate (n-BCA) and with advances in micro-
catheter and guidewire technology (105). The n-BCA
liquid monomer undergoes a rapid exothermic poly-
merization catalyzed by nucleophiles found in blood
and on the vascular endothelium to form an adhesive,
non-biodegradable solid.
n-BCA has a number of useful properties for
BAVM embolization. The liquid monomer can be
injected through small (1.5, 1.8 Fr) flow-directed micro-
catheters that can be reliably and safely positioned in
the distal arterial feeder or within the nidus. This distal
catheter positioning maximizes the likelihood of
adequate nidal penetration and minimizes the risk of
inadvertent embolization of normal branches (105).
The rate of n-BCA polymerization can be
adjusted to match an individual BAVMs angioarchi-
tecture and hemodynamics. The goal is to form a solid
n-BCA cast in the nidus, avoiding early polymeriza-
tion in the arterial feeder or late polymerization in the
venous outflow. Pure n-BCA polymerizes instantane-
ously at the catheter tip. Although this may be desir-
able to occlude a direct high-flow fistula, pure n-BCA
will not penetrate a plexiform nidus (105). Mixing
Ethiodol with the n-BCA monomer progressively
slows the polymerization rate as more Ethiodol is
added. The mixture is adjusted for optimal nidal pen-
etration. The use of a wedged catheter position (the
catheter occludes the lumen), where forward flow is
controlled by the rate of injection, facilitates slower,
more controlled injections; in this setting, more dilute
n-BCA/Ethiodol mixtures (e.g., 2533%) with longer
polymerization times are used (105). Glacial acetic
acid also can be added to slow the rate of polymeriza-
tion, without causing the increased viscosity of higher
Ethiodol concentrations. This may result in better
nidal penetration and more solid casting (112).
Portions of the BAVM nidus that are well cast
with n-BCA can be considered permanently obliter-
ated (105,113,114). However, BAVMs incompletely
embolized with n-BCA demonstrate histologic evi-
dence of capillary regrowth (115). The wedged cathe-
ter flow-control technique can improve nidal filling
(Fig. 18.17) (105). n-BCA provokes an inflammatory
response leading to vessel necrosis and fibrous
ingrowth. These histologic responses also may contrib-
ute to the permanency of n-BCA occlusions (115,104).
n-BCA embolization therefore has the potential to
transform inoperable BAVMs into surgically resectable
lesions, sufficiently reduce the BAVM nidal size to
make radiosurgery possible, and cure some small
BAVMs by embolization alone.
BAVMs embolized with n-BCA have favorable
properties for surgical resection. The vessels are easily
compressible and transected. The embolized feeders
can be readily identified and differentiated from
non-embolized en passage branches to normal brain
(Fig. 18.8). In addition, embolization provides a dist-
inct surgical plane between the BAVM and normal
brain (116).
Onyx
Onyx (ev3 Endovascular) is a premixed, liquid
embolic agent consisting of ethylene-vinyl alcohol
copolymer (EVOH) and tantalum powder (for radio-
pacity) dissolved in dimethyl sulfoxide (DMSO).
EVOH contains 48mol/L ethylene and 52mol/L vinyl
alcohol (106). The use of EVOH to embolize BAVMs
was first described in 1990 (117). Subsequent studies
led to a multicenter randomized trial that demon-
strated non-inferiority of Onyx compared to n-BCA in
achieving 50% volume reduction for presurgical
BAVM embolization, resulting in U.S. Food and Drug
Administration (FDA) approval of Onyx for presurgi-
cal BAVM embolization in 2005 (106,118120).
Onyx is a cohesive, non-adhesive liquid embolic
agent. The copolymer holds together (cohesive) as it is
injected, but it does not adhere to the endothelium or
to the microcatheter tip. When the mixture contacts an
aqueous solution the DMSO solvent diffuses away
rapidly, causing the copolymer to precipitate into a
soft, spongy solid. The precipitation progresses from
the outer surface inward, forming a skin with a liquid
core that continues to flow as the solidification contin-
ues. During the injection, the column of Onyx advan-
ces into the path of least resistance. The rate of
precipitation of the copolymer is proportional to the
concentration of EVOH in the solution. Two concen-
trations of EVOH are available for BAVM emboliza-
tion: Onyx 18 (6% EVOH) and Onyx 34 (8% EVOH).
Onyx 18 travels farther and penetrates more deeply
into the nidus because of its lower viscosity and
slower precipitation rate. Onyx 18 is used for distal
feeding pedicle injections into a plexiform nidus,
whereas Onyx 34 is recommended for embolizing
high-flow fistulas. Complete solidification of both for-
mulations occurs within 5 minutes.
DMSO was chosen as the solvent because it rap-
idly diffuses in aqueous solution and its physiological
properties in humans are well known (117). However,
DMSO is very angiotoxic with adverse effects on
blood vessels that include vasospasm, angionecrosis,
arterial thrombosis, and vascular rupture (121). These
undesirable consequences are related to the volume of
DMSO infused and the endothelial contact time (118).
Severe angiotoxic effects do not occur when the
DMSO infusion rate does not exceed 0.25mL/90 sec-
onds (106,118). Only specifically approved microcath-
eters (Ultraflow, Marathon, Echelon, Rebar; ev3
Endovascular) can be used with Onyx because DMSO
will dissolve incompatible catheters. These are some-
what stiffer than DMSO-incompatible flow-directed
microcatheters. Patients may notice a garlic-like taste
for several hours, and their skin and breath may have
a characteristic odor due to the DMSO for 12 days
after an embolization with Onyx.
Onyx has several advantages compared to n-BCA.
Because Onyx is non-adhesive, cohesive, and solidifies
more slowly than n-BCA, typical injections are per-
formed much more slowly (over minutes) and are easier
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 391

(A) (B)

(C) (D)

(E) (F)

Figure 18.17 Wedged catheter embolization of nidal pseudoaneurysm presenting with hemorrhage. (A) AP and (B) lateral angiogram
images show a plexiform cerebellar BAVM. (C) Superselective superior cerebellar angiogram shows large nidal pseudoaneurysm
(arrow) and small nidal aneurysm (arrowhead). (D) Wedged catheter injection visualizing pseudoaneurysm and superior nidus (micro-
catheter tip, arrow). (E) n-BCA cast in pseudoaneurysm (arrow) and superior nidus (arrowheads). (F) Lateral post-embolization angio-
gram. Abbreviations: AP, anteroposterior; BAVM, brain arteriovenous malformation; n-BCA, n-butyl cyanoacrylate.

to control. This results in a much more leisurely emboli-
zation, with the time to analyze the progress with inter-
val angiography if desired and with less risk of
refluxing the embolic agent too proximally in the arterial
feeders or extending too distally into the venous outflow
(Fig. 18.18). It is also possible that a more complete and
solid casting of the nidus may be obtained with Onyx
compared to n-BCA (Fig. 18.19). This may result in an
increased rate of curative embolization, but this remains
to be proven. In addition, the catheter also can be reposi-
tioned into a second pedicle and another embolization
can be performed, a maneuver that is not possible with
n-BCA. Finally, Onyx does not cause inadvertent gluing
of the catheter tip to the vessel; however, stuck catheters
have occurred (106,122).
Embolization Technique
Vessel Selection
BAVM embolization requires advancing a suitable
microcatheter into the very distal aspect of an arterial
392 NEUROINTERVENTIONAL MANAGEMENT
(A)
Figure 18.18 Angiogram obtained during BAVM embolization with Onyx. (A) Onyx cast (arrowheads) and microcatheter tip (arrow) on
lateral radiograph. (B) Lateral angiogram obtained through guide catheter during embolization. Abbreviation: BAVM, brain arteriove-
nous malformation.
feeder to the nidus. A microcatheter (e.g., 1.5 or 1.8 Fr
Spinnaker Elite, Boston Scientific, Natick, Massachu-
setts, U.S.; Marathon or Ultraflow, ev3 Endovascular),
optionally configured with a small steam-shaped distal
curve, is navigated through the cerebral arteries under
fluoroscopic (roadmap) imaging. There are two pri-
mary techniques for intracranial navigation: flow-
directed and guidewire-assisted. Flow-directed naviga-
tion uses arterial blood flow to drag the very flexible
distal catheter segment and slightly bulbous catheter
tip forward. The tip will tend to advance preferentially
into the vessel with the highest flow, which is usually
the desired feeder. Directional control can be facilitated
by gentle injections of contrast (puffing) to redirect the
curved tip into the desired branch. For guidewire-
assisted navigation, a 0.008 inch Mirage guidewire (ev3
Endovascular) is advanced into the distal segment of
the microcatheter to augment pushability and to
change shape of the catheter tip. Advancing and with-
drawing the guidewire in the distal segment also
changes its elasticity often prompting the catheter tip
to spring forward. When necessary, the Mirage guide-
wire can be extended beyond the microcatheter tip to
navigate difficult anatomy; however, this must be done
with extreme caution to avoid arterial perforation or
dissection. Current Onyx-compatible microcatheters are
somewhat stiffer, and usually require careful guide-
wire-assisted navigation. Blood pressure augmentation
with neosynephrine or vasodilatation with papaverine
or hypercapnea also can be used to facilitate distal
catheter advancements (103,123,124).
Provocative Testing (Superselective Wada Test)
Approximately 10% of BAVM embolizations result
in a permanent neurological deficit (125). Many of
these deficits are caused by embolization of branches
arising from a feeder that supply normal brain
(B)
parenchyma (126). Provocative testing (the superselec-
tive Wada test) is intended to prevent this complica-
tion by identifying any angiographically occult blood
supply to eloquent brain parenchyma from the feeder
targeted for embolization. A short-acting barbiturate
(amobarbital) is injected intraarterially through the
microcatheter positioned at the site of planned emboli-
zation, and appropriate neurological and/or neuro-
physiological testing is carried out. Although some
experts are strong proponents for the use of this pro-
vocative testing, others argue it is not necessary
(105,127131).
n-BCA Technique
A microcatheter is negotiated through the cerebral
vasculature using a combination of flow and guide-
wire guidance (see vessel selection) into the distal
aspect of the desired feeder in a nidal/perinidal posi-
tion. Operator preference and the nidal anatomy
determine whether a free or wedged catheter tip posi-
tion is used. Excess slack (redundant loops) in the
microcatheter is pulled out to facilitate the catheters
removal after the embolization. A superselective DSA
is performed with a 1 cc syringe and a gentle hand
injection. The angioarchitecture is analyzed. If no nor-
mal branches are visible, provocative testing can be
performed with amobarbital.
For a wedged injection (105), a relatively dilute
concentration of n-BCA (2533%) is made by mixing
1 cc of n-BCA with 2 or 3 cc of Ethiodol in a shot glass,
and tantalum powder is added to increase radiopacity
(Trufill; Codman Neurovascular, Raynham, Massachu-
setts, U.S.). The n-BCA/Ethiodol/tantalum mixture is
prepared using clean gloves on a separate sterile table
to prevent contamination with ionic catalysts. Relative
hypotension is induced (2030% decrease in mean
arterial pressure). Test injections are made with
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 393

(A) (B)

(C) (D)

(E) (F)

Figure 18.19 Onyx embolization of a left frontal lobe BAVM. (A) Lateral and (B) AP angiogram images show a large, plexiform left
frontal lobe BAVM. (C) Lateral and (D) AP angiogram images following multistage embolization with Onyx demonstrate almost com-
plete obliteration of the nidus. (E) Lateral and (F) AP images of the Onyx cast. Abbreviations: BAVM, brain arteriovenous malforma-
tion; AP, anteroposterior.

subtracted fluoroscopic imaging to confirm the cathe-
ter position and determine the optimal injection rate.
The microcatheter is irrigated with 5% dextrose to
flush the ionic catalysts from the lumen. The dilute
n-BCA solution is then injected slowly into the nidus
over 15 to 60 seconds during continuous subtracted
fluoroscopic observation. The injection rate is modi-
fied to obtain a solid nidal cast without causing
proximal reflux. If a drop of n-BCA enters a draining
vein, the injection is paused several seconds. The
injection is then restarted and continued if additional
nidal filling is observed. If another drop enters a vein,
394 NEUROINTERVENTIONAL MANAGEMENT
the injection is terminated. The injection is also termi-
nated if proximal reflux occurs. The microcatheter
is aspirated and briskly removed. The guide catheter is
aspirated and its tip is examined fluoroscopically.
A post-embolization angiogram is then obtained.
A non-wedged injection is performed in a similar
fashion; however, a more concentrated n-BCA solution
( 4080%) is used because of the more rapid flow and
short AV transit time through the nidus. The injection
rate is more brisk and the injection time is much shorter
(13 seconds). If a large, direct fistula is present, maxi-
mal induced hypotension and a very high n-BCA con-
centration ( 80%) are used. In this setting, coils can be
inserted first into the fistula to slow the flow rate.
We typically occlude a maximum of 33% of a
large nidus during one session to minimize the risk of
normal perfusion pressure breakthrough induced
hemorrhage (132). Embolization is also terminated if
venous outflow stagnation occurs, to minimize the
risk of post-procedural hemorrhage caused by venous
outflow compromise (133).
Onyx Technique
Embolization with Onyx can be painful; general anes-
thesia may minimize discomfort and motion. An Onyx-
compatible microcatheter is positioned in the distal
feeder. The Onyx solution is vigorously shaken for 20
minutes just prior to embolization to fully suspend the
micronized tantalum powder. Failure to do this may
result in inadequate radiopacity (106). The catheter is
flushed with saline and the dead space is loaded with
pure DMSO. The Onyx mixture is drawn into a DMSO-
compatible 1cc syringe, the syringe is connected to the
microcatheter and a slow, steady injection is begun at a
rate of 0.25mL/90sec to displace the DMSO from the
dead space. Subtracted fluoroscopy is begun just before
the dead space has been replaced. As Onyx begins
to exit the microcatheter, the injection is continued at
0.1mL/min. The injection rate is not allowed to exceed
0.25mL/90sec to prevent angiotoxicity.
Onyx embolizations are usually performed with a
plug-and-push technique; a plug of Onyx is allowed to
form around the catheter tip to prevent proximal reflux
and promote distal flow. As the initial injection begins, at
some point antegrade flow stops and proximal reflux
will begin. The Onyx is allowed to reflux a few mm prox-
imal to the microcatheter tip, and then the injection is
paused up to 2 minutes. This process is repeated with
additional injections causing additional reflux until the
microcatheter tip is surrounded by Onyx and a solid
plug has formed around the tip. Once the plug has
formed, subsequent injections typically will flow distally
into the nidus. Optionally, Onyx 34 can be used initially
to form the plug, and the subsequent injection can be
continued with Onyx 18. Proximal reflux around the
catheter tip during formation of the plug should be lim-
ited to 11.5cm to avoid causing difficulty with catheter
retrieval. If Onyx begins to fill a draining vein, a pause in
the injection will allow that material to solidify; when the
injection is restarted, the additional Onyx usually breaks
into and fills new areas of the nidus. The Onyx injection
should never be paused for more than 2 minutes to pre-
vent Onyx from precipitating in the catheter lumen. If
there is resistance to pushing the Onyx after a pause, the
injection should be discontinued to avoid rupturing the
catheter. Continuing to inject Onyx through a proximal
tear in the catheter could be catastrophic.
There are two catheter retrieval techniques. The
slow traction method uses incremental catheter with-
drawal (cm by cm) with moderate sustained tension on
the catheter. The quick wrist-snap technique is done
by withdrawing the catheter enough (35cm) to create
slight tension, then quickly snapping the wrist (not
the entire arm) 1020cm away. Pulling too far or too
hard runs the risk of causing a catheter separation.
Post-procedural Care
Patients are observed in neurointensive care for
24 hours and usually discharged to home on the sec-
ond post-embolization day. Mild hypotension (mean
arterial pressure ~ 90% of normal) may be induced
for 24 hours if a large, high-flow BAVM has been
embolized. Additional embolization sessions for large,
high-flow BAVMs are staged every 34 weeks.
Results
The literature on BAVM treatment outcomes consists
primarily of uncontrolled, single institution case ser-
ies. Many of these have demonstrated an important
role for BAVM embolization in selected cases. None-
theless, these studies have relatively small sample
sizes, and there is tremendous variability in selection
criteria, techniques, patient evaluation, and follow-up.
Randomized, controlled outcome trials such as the
ongoing ARUBA study are needed to form a scientific
basis for the selection of optimal therapeutic plans
(81,82). Since BAVM embolization is used most com-
monly as an adjunct to surgery or radiosurgery, these
study will need to compare the natural history of
untreated BAVMs with the overall results of individ-
ual and combined treatment strategies.
n-BCA versus Onyx
Many neurointerventionalists have switched from
n-BCA to Onyx for most BAVM embolizations, espe-
cially for the embolization of a compact, plexiform nidus
when an Onyx-compatible microcatheter can be placed
into a nidal or perinidal position. Some of the perceived
advantages of Onyx include the ability to occlude more
of the nidus (possibly with an increased rate of curative
embolization) and a much less stressful (and possibly
safer) procedure. However, the current data do not pro-
vide definitive support for these conclusions.
There has been only one randomized, controlled
trial comparing n-BCA to Onyx for BAVM emboliza-
tion; this trial was designed to prove non-inferiority of
Onyx to gain FDA approval (120). The primary end-
point was achieving 50% reduction of the BAVM vol-
ume. Onyx obliterated 50% of BAVM volume in 96%
cases versus 85% for n-BCA. This difference was not
statistically significant. Secondary endpoints (opera-
tive time and blood loss) were not significantly differ-
ent between the two materials. In addition, serious
adverse events were similar for both agents.
Several case series have been published recently
that suggest curative BAVM embolization is feasible in
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS 395

Table 18.7 Recent Large Case Series of BAVM Embolization with Onyx: Mortality, Permanent Morbidity, and Complete Nidal
Occlusion
Author Year No. of patients Mortality rate Permanent morbidity rate Total nidal occlusion rate
Mounayer (135) 2007 94 3.2% (3/94) 8.5% (8/94) 49% (26/53)
Van Rooji (136) 2007 44 2.3% (1/44) 4.6% (2/44) 16% (7/44)
Weber (122) 2007 93 0% (0/93) 9.7% (9/93) 20.4% (19/93)
Katsaridis (93) 2008 101 3% (3/101) 8% (8/101) 53.9% (28/52)
Panagiotopoulos (94) 2009 82 2.4% (2/82) 9.0% (7/78) 19.5% (16/82)
Pierot (134) 2009 50 4.0% (2/50) 8.0% (4/50) 8.3% (4/48)
Maimon (95) 2010 43 0% (0/43) 7.0% (3/43) 55% (16/29)
Abbreviation: BAVM, brain arteriovenous malformation.

a greater percentage of cases using Onyx rather than
n-BCA (Table 18.7) (9395,122,134136). A few series
have reported cure rates of approximately 50% with
Onyx (93,95,135). However, it has been suggested there
may be a concomitant increase in morbidity and mortal-
ity when curative embolization is attempted; no study
has directly compared outcomes for attempted curative
embolization with conventional combined therapy (97).
Complete obliteration was most successful in small
(<3.0cm) BAVMs with a compact, plexiform nidus and
superficial venous drainage; these are typically amenable
to surgical resection with minimal morbidity and mortal-
ity (94,122). In addition, late recanalization after emboli-
zation with Onyx has been documented in multiple
series (94,122,137). Another concern is a recent report
that six BAVMs that were completely obliterated on com-
pletion angiography after Onyx embolization were found
to have residual filling at surgery (138). A recent histolog-
ical study from resected human BAVM embolization
specimens found Onyx penetrated into smaller nidal ves-
sels than n-BCA (81.4 103.8 m vs. 170.5 244.4 m,
respectively). Of note, there was evidence for recanaliza-
tion in 4/22 (18.2%) Onyx embolizations, while there
was no evidence of recanalization after 10n-BCA emboli-
zations, raising a question about the long-term durability
of embolizations for cure using Onyx (139).
The use of a detachable-tip microcatheter (SONIC;
Balt, Montmorency, France) for BAVM embolization
with Onyx has been recently reported; a high rate of
complete BAVM obliteration (55%) was obtained with a
low complication rate (7.0%). The tip is soft and can be
flow-directed; the detachable tip permits formation of a
solid plug resulting in more robust nidal filling without
risk of vascular injury during catheter removal (95).
Not surprisingly, Onyx embolization has longer
procedure and fluoroscopy times compared to n-BCA,
likely increasing radiation exposure for the patient
and the operator (140).
Presurgical Embolization
A number of case series comparing groups under-
going surgical resection of BAVMs with and without
preoperative embolization have demonstrated that
selective preoperative embolization improves overall
outcomes (116,141). Combined embolization and
surgery is also cost-effective compared to surgery
without embolization, with cost per quality-adjusted
life-year savings as high as 34% (142).
Pasqualin et al. compared direct surgery (27
cases) and surgery following embolization (32 cases)
for large, high-flow BAVMs. Preoperative emboliza-
tion was associated with less intraoperative bleeding,
and fewer post-operative neurological deficits, seiz-
ures and deaths. The frequency of major deficits was
31% in the direct surgery group versus 5% in the
embolization and surgery group (143).
Demeritt et al. compared 30 patients who under-
went preoperative BAVM embolization with n-BCA
followed by surgery with 41 patients who had direct
surgery. The combined embolization and surgery
group had a higher average Spetzler-Martin score com-
pared to the direct surgery group (89% vs. 68% grade
IIIIV) and a larger average nidal maximal diameter
(4.2 +/ 1.5cm versus 3.4 +/ 1.8cm). Nonetheless,
2 week and long-term Glasgow Outcome Scale scores
were better in the combined embolization and surgery
group than the direct surgery group; 70% versus 41%
respectively had a 2 week Glasgow Outcome Scale
score of 5, 86% versus 66% respectively had a long-
term Glasgow Outcome Scale score of 5 (141).
Similar results have been reported for Onyx.
Natarajan et al. reported 28 BAVMs treated with Onyx
embolization followed by surgery; the average Spetzler-
Martin grade was 2.75, 27 were completely resected,
with 1 (3.6%) death and 1 (3.6%) disability (138).
Preradiosurgical Embolization
The concept of embolizing BAVMs to reduce nidal
size, in turn making radiosurgery more effective with
increased cure rates has not been definitively proven;
conflicting data have been published.
Gobin et al. reported the results in treatment of
125 patients with embolization and radiosurgery.
Approximately half of the BAVMs had diameters
greater than 4cm and most were Spetzler-Martin grade
III or greater. Embolization cured 11% and made 77%
suitable for radiosurgery. Greater than 50% of the
BAVMs with diameters greater than 6cm and more
than 10% with diameters between 4 and 6cm did not
have sufficient nidal size reduction for subsequent
radiosurgery. Overall cure rates were 7678% for
BAVMs less than 4cm in diameter, 59% for those 4 to
6cm and 7% for those over 6cm. Therefore, adjunctive
embolization was most effective for BAVMs 4 to 6cm
in diameter. There was no convincing advantage for
combined embolization and radiosurgery compared to
radiosurgery alone for BAVMs smaller than 4cm.
Embolization and radiosurgery did not result in a sig-
nificant cure rate for lesions larger than 6cm. Emboliza-
tion did not provide protection from hemorrhage
during the latent period before radiosurgical oblitera-
tion; there was approximately a 3% annual rate of hem-
orrhage during the 13year follow-up period, similar to
reported natural history BAVM hemorrhage rates (90).
396 NEUROINTERVENTIONAL MANAGEMENT
In contradistinction, Andrade-Souza et al. found
BAVM embolization before radiosurgery significantly
reduced the obliteration rate following radiosurgery
(144). Forty-seven patients who underwent BAVM
embolization followed by radiosurgery were compared
with 47 patients who underwent radiosurgery alone.
The groups were matched for BAVM volume, location,
and marginal dose. Complete obliteration of the nidus
at 3-year follow-up was 47% in the combined emboliza-
tion and radiosurgery cohort versus 70% in the radio-
surgery alone group (P = 0.036). Serious adverse events
were similar in the two groups. There was a non-
statistically significant trend for more excellent out-
comes in the radiosurgery only cohort. Similarly, Back
et al. found embolization prior to gamma knife surgery
may reduce the BAVM obliteration rate (145).
Embolization can also be used to treat BAVM
remnants that persist after radiosurgery. Marks et al.
reported six patients with residual nidus 24 to
55 months (mean 34 months) after radiosurgery.
Embolization resulted in one cure, facilitated surgical
resection in three, and caused sufficient volume
reduction in two patients to allow repeat radiosur-
gery; there were no complications (91). Also, residual
fistulae following stereotactic radiosurgery can be
effectively occluded (146).
Curative Embolization
Published embolization cure rates vary considerably
due to selection bias, differing therapeutic goals, and
techniques. Small BAVMs with few feeders have the
highest probability of endovascular cure. PreOnyx case
series performed without specific selection of those
BAVMs most likely to be cured by embolization alone
have reported an overall durable embolization cure in
540% of patients, but most are in the 10% range
(90,147149). Valavanis and Yasargil had a 74% rate of
curative embolization in a subgroup of patients with
favorable angiographic features such as one or few dom-
inant feeders, no perinidal angiogenesis and a fistulous
nidus, versus a 40% rate of curative embolization for
their entire series of 387 patients (148).
As noted above, recent case series suggest a
higher rate of curative embolization (approximately
50%) may be feasible using Onyx; however, complica-
tion rates may also be greater with attempted cure
(Table 18.7) (97). Some BAVMs that were completely
obliterated after Onyx embolization on completion
angiography have been found to have residual filling
at surgery, or recanalization on follow-up angiography
Table 18.8 PreOnyx BAVM Embolization: Mortality and Permanent Morbidity
Author Year
Frizzel (149) 1995
Debrun (105) 1997
Valavanis (148) 1998
Hartmann (153) 2002
Meisel (154) 2002
n-BCA Trial investigators (86) 2002
Taylor (155) 2004
Haw (156) 2006
Abbreviation: BAVM, brain arteriovenous malformation.
Source: From Ref. 156.
or histological examination (94,122,137139). In addi-
tion, there are no long-term data addressing the perma-
nence of occlusion with Onyx (138).
Palliative Embolization
Palliative embolization does not appear to improve on
conservative medical management and may even wor-
sen the subsequent clinical course (150). Kwon et al.
obtained long-term follow-up in a group of 27 patients
with inoperable BAVMs. Sixteen were treated medi-
cally and 11 were partially embolized. There was no
significant difference between the two groups in clini-
cal status at follow-up. In addition, 46% of the parti-
ally embolized group experienced hemorrhage in the
follow-up period versus 25% in the non-embolized
group (P = 0.27) (99).
Nonetheless, palliative embolization can be benefi-
cial in selected circumstances; progressive neurologic
deficits can be stabilized or improved in 90% of cases
(151). In one case, ischemic neurologic deficits caused by
vascular steal and venous hypertension in a high-flow,
inoperable BAVM were improved following partial
embolization (101). In another patient, hemifacial spasm
caused by a dilated lateral mesencephalic vein draining
an inoperable temporo-occipital BAVM was cured by
selective transvenous embolization (100). Embolization
of dural supply can alleviate intractable headaches. In
patients with repeated hemorrhages, targeted emboliza-
tion of angioarchitectural risk factors such as proximal
and nidal aneurysms can limit additional bleeds (102).
Complications
Incidence
The reported incidence of overall complications from
BAVM embolization prior to the introduction of Onyx
varied from 3% to 25% (85,126,143,147,152). The rates
of permanent morbidity and mortality in large case
series ranged from 3.8% to 14% and 1.0% to 3.7%,
respectively (Table 18.8) (86,105,148,149,153156). Most
complications were caused by hemorrhagic and ische-
mic events (102). The rates of permanent morbidity
and mortality in recent large Onyx case series range
from 4.6% to 9% and 0.0% to 3.0%, respectively
(Table 18.7). Since complications are related to a num-
ber of technical and hemodynamic factors, the wide
range in reported rates probably reflects at least in
part differences in case selection, embolization techni-
ques, and management strategies.
No. of patients Mortality rate Permanent morbidity rate
1246 1.0% 8.0%
54 3.7% 5.6%
387 1.3% 5.1%
233 1.0% 14.0%
450 1.1% 3.8%
54 1.9% 13.0%
201 2.0% 9.0%
306 2.6% 4.9%
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS
Post-embolization neurological defects increase
in frequency with the number of pedicles embolized
and with the grade of the BAVM. In a study of 153
patients who had 508 feeders embolized in 203 ses-
sions, the long-term rates of neurological deficits for
grade I to V BAVMs were 0%, 5%, 7%, 10%, and 18%,
respectively (157).
Specific Complications
Periprocedural Hemorrhage
There are a number of causes of periprocedural hemor-
rhage associated with BAVM embolizations. Technical
factors include catheter or guidewire-induced arterial
perforations and dissections, rupture of aneurysms, vas-
cular injuries during catheter retrieval, and accidental
embolization of venous outflow (105,156).
Physiological factors include venous outflow
thrombosis, hemodynamic changes in the setting of
impaired cerebrovascular reactivity, and hemodynamic
stresses on angioarchitectural weak sites such as feeder,
nidal, and venous aneurysms. Embolization can mark-
edly reduce flow through a fistulous nidus causing stag-
nation in the draining veins (Fig. 18.20). This can result in
venous outflow thrombosis, nidal congestion, and a delayed
hemorrhage or a venous ischemic infarct (133,156,158).
Normal perfusion pressure breakthrough is
another important physiological cause of hemorrhage
following treatment of a large, high-flow BAVM. The
sump effect of a large shunt causes low pressure in
the arterial feeders and nearby parenchymal branches.
High flow through the nidus elevates venous pres-
sures. The result is chronically low cerebral perfusion
pressure in the surrounding parenchyma that can
impair cerebrovascular autoregulation. If sudden,
therapeutic disruption of the shunt occurs, there is an
(A) (B)
Figure 18.20 Partially embolized BAVM nidus with venous stagnation (C, arrowheads). Note venous stenosis (B, large arrow) and
venous aneurysm (B, small arrow). (A) Lateral angiogram-arterial phase. (B) Lateral angiogram-venous phase. (C) Lateral angiogram-
late venous phase. Abbreviation: BAVM, brain arteriovenous malformation.
397
immediate increase in arterial pressure and a decrease
in venous pressure, resulting in a dramatic increase
in the cerebral perfusion pressure. If cerebrovascular
autoregulation is impaired, resulting parenchymal
hyperperfusion can cause cerebral edema or hemor-
rhage. This usually occurs in large, high-flow BAVMs
that demonstrate poor angiographic filling of normal
cerebral arteries and extensive collateral flow (steal)
(Fig. 18.1), external carotid supply, and progressive
or fluctuating neurological deficits (102,132). Attempts
to embolize too much of the nidus in a single stage
may increase the risk for hemorrhage (159). Step-wise
reduction in the degree of shunting in large, high-flow
BAVMs through multiple embolizations staged every
34 weeks may minimize this risk by facilitating the
gradual recovery of normal vascular reactivity (102).
Prompt surgical evacuation of an embolization-
related cerebral hematoma usually results in a good out-
come. Jafar and Rezai reported the emergent surgical
evacuation of acute intracerebral hematomas from
10 BAVM patients experiencing acute neurological dete-
rioration, including eight cases occurring after emboliza-
tion. They employed immediate intubation, hyperventilation,
osmotic diuresis, barbiturate anesthesia, and surgery.
The hematoma was evacuated and the BAVM was
totally resected if possible (8 out of 10). Post-operative
cerebral perfusion pressure was maintained above
55mm Hg with mannitol and barbiturates. Nine of the
10 patients had good to excellent outcomes (160).
Ischemic Stroke
Causes of ischemic stroke during embolization include
the showering of n-BCA droplets from the catheter tip
as it is removed, catheter or guidewire-related arterial
dissections and thromboemboli, the embolization of
en passage or pseudoterminal supply to normal
parenchyma distal to the nidal feeders, and the
(C)
398 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 18.21 Partially embolized BAVM with arterial stagnation (B, arrowheads). (A) Lateral angiogram-arterial phase. (B) Lateral
angiogram-venous phase. Abbreviation: BAVM, brain arteriovenous malformation.

inadvertent reflux of embolic material into normal

branches proximal to the catheter tip. Ischemic stroke
can result from retrograde thrombosis in stagnant
feeding arteries propagating into branches supplying
normal brain (Fig. 18.21) (161). Delayed venous
thrombosis can cause a venous infarct (158). Careful
attention to the angioarchitecture on superselective
angiography and to embolization technique can mini-
mize these events (156).

Other Complications
Embolization with cyanoacrylates can permanently
glue the microcatheter tip to the embolized vessel.
This incidence has decreased in recent years with the
use of n-BCA rather than IBCA, a wedged microcath- (A)
eter position to prevent proximal reflux, more dilute
n-BCA/Ethiodol mixtures with slower polymerization
rates, and more durable microcatheters with hydro-
philic coatings. Careful technique also is important.
Retained catheters usually can be transected and
buried in the femoral arteriotomy without adverse
sequelae; however, brain and lower extremity ische-
mic complications have been reported (156,162). Stuck
catheters have also been reported with Onyx; the use
of a new detachable tip catheter may limit this com-
plication (95).
Pulmonary emboli (PE) have occurred with both
particulate and liquid embolic agents (Fig. 18.22). Most
are asymptomatic, although respiratory distress and
death have occurred. The risk of pulmonary emboli is
increased with high-flow fistulas, the use of Ethiodol (B)
or glacial acetic acid to slow n-BCA polymerization
time and not using flow-arrest techniques (163,164). Figure 18.22 n-BCA pulmonary embolus on chest CT scan
Several additional rare complications have been causing pulmonary infarct. (A) n-BCA embolus (arrow). (B) Pul-
reported. Severe pulmonary edema following a monary infarct (arrow). Abbreviations: n-BCA, n-butyl cyanoa-
BAVM embolization with Onyx occurred in a patient, crylate; CT, computed tomogram.
possibly due to DMSO pulmonary toxicity (165). In
 ENDOVASCULAR MANAGEMENT OF BRAIN ARTERIOVENOUS MALFORMATIONS
another case, a brain abscess developed 4 years after
embolization of a BAVM with n-BCA (166). Multistage
angiography and embolization procedures result in
significant radiation doses. Temporary alopecia has
been reported; this typically occurs after a short-term
radiation dose of 36 Gy (167).
CONCLUSIONS
BAVMs are very heterogeneous, rare central nervous
system vascular malformations associated with signifi-
cant long-term morbidity and mortality. Embolization is
an important therapeutic option, usually in combination
with surgery or stereotactic radiosurgery. It is, however,
associated with significant risks that must be considered
in the context of the overall treatment plan. BAVMs are
optimally managed by a multispecialty team. Random-
ized controlled trials are needed to validate the safety
and efficacy of active BAVM treatments. One such trial,
the ARUBA study, is currently in progress.
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165. Murugesan C, Saravanan S, Rajkumar J, et al. Severe pul-
monary oedema following therapeutic embolization with
Onyx for cerebral arteriovenous malformation. Neuroradi-
ology 2008; 50: 43942.
166. Chagla AS, Balasubramaniam S. Cerebral N-butyl cyanoa-
crylate glue-induced abscess complicating embolization.
J Neurosurg 2008; 109: 347.
167. Wen CS, Lin SM, Chen Y, et al. Radiation-induced
temporary alopecia after embolization of cerebral arterio-
venous malformations. Clin Neurol Neurosurg 2003; 105:
21517.
 19
Endovascular treatment of acute ischemic stroke
Stavropoula I. Tjoumakaris, Pascal M. Jabbour, Aaron S. Dumont, L. Fernando Gonzalez, and
Robert H. Rosenwasser
Stroke is a major cause of serious, long-term disability
and the third leading cause of death, accounting for
one in every 18 deaths in the United States. Approxi-
mately 800,000 strokes occur in the United States each
year, leading to an estimated cost of 74 billion dollars
in 2010 (1). The majority of these events are ischemic
(87%), as opposed to intracerebral (10%) and subar-
achnoid hemorrhages (3%) (1). Management of acute
ischemic stroke was previously geared toward preven-
tion, supportive care, and rehabilitation. Over the past
few decades, however, the medical management of
stroke has progressed exponentially, beginning with
the US Food and Drug Administration (FDA) appro-
val of tissue plasminogen activator (r-tPA, alteplase)
in 1996. Intravenous administration of r-tPA within a
limited 3-hour window from symptom onset has
shown a significant improvement in patient outcome
at 3 months and at one year following an acute cere-
brovascular event (2).
The intra-arterial (IA) injection of therapeutic
agents was first published nearly 60 years ago, when
Sussman and Fitch described the IA treatment of acute
carotid occlusion with fibrinolysin injection in 1958 (3).
It was not until the late 1990s that the endovascular
management of acute stroke experienced exponential
progress and development. Recent advances in endo-
vascular techniques have increased the therapeutic
window of r-tPA administration and introduced new
agents such as reteplase and abciximab. Furthermore,
the use of IA devices for clot retrieval and vessel recan-
alization has revolutionized the neuroendovascular
management of acute ischemic stroke.
PATIENT SELECTION
The goal of endovascular management of acute
ischemic stroke is to enhance the survival of local
ischemic brain tissue (penumbra) and limit the extent
of infarcted brain parenchyma. An initial evaluation
with a non-contrast computerized tomography (CT)
head scan is necessary. In a retrospective review of
85 patients from the Penumbra Pivotal Stroke Trial,
Goyal and colleagues found that a baseline CT scan
by ASPECTS score>7 (Alberta Stroke Program Early
CT Scale) had a 50% chance of a favorable clinical out-
come with early recanalization (p = 0.0001). In addi-
tion, ASPECTS scores of less than four did not show
clinical improvement regardless of endovascular
recanalization (4). Patients with large territorial
infarcts on CT scan are at a higher risk for hemorrha-
gic conversion following treatment and are therefore
poor candidates for endovascular therapy (5). In addi-
tion, the presence of an intra-parenchymal hematoma
is a contraindication to endovascular recanalization.
Lastly, the presence of a hyperdense middle cerebral
artery (MCA) sign on the initial head CT does not
have a significant prognostic value in patient outcome
and vessel recanalization rates (68).
Over the past decade, the clinical application of
CT perfusion scans has facilitated the pre-treatment
evaluation of salvageable tissue. A scan consistent
with a mismatch between cerebral blood volume
(CBV; core cerebral lesion volume) and cerebral
blood flow or mean transient time (CBF or MTT;
penumbra lesion volume) is a favorable patient
selection criterion (9). In our institution, a favorable
CT perfusion scan may overcome the six-hour post-
symptom onset time restriction.
Although patient age and initial National
Institutes of Health Stroke Scale (NIHSS) score do not
show statistically significant correlation with post-
treatment intracranial hemorrhage (ICH), careful
attention should be paid to both (5). In a recent retro-
spective review of 156 patients, Zacharatos and col-
leagues found that thrombolytic therapy (chemical or
mechanical) showed a favorable clinical outcome ver-
sus supportive management in the 80 years and older
age group (10). However, patient co-morbidities are
evaluated prior to treatment. Specifically, the presence
of hyperglycemia, defined as blood sugar levels
greater than 200mg/dl within 24 hours from presenta-
tion, can significantly increase the likelihood of post-
thrombolysis hemorrhagic conversion (5).
Previous administration of intravenous tPA is
not a contraindication to IA intervention. However,
the hemorrhagic complications in these patients are
significantly higher, especially if urokinase was the
arterial agent (5). One must therefore clearly explain
the risks and benefits of the procedure to the family
and include them in the decision-making process.
Overall, endovascular intervention is an invaluable
tool in the management of acute ischemic stroke.
However, the duration of ischemia and the presence
of viable ischemic tissue in excess of irreversibly dam-
aged tissue are both critical factors in the successful
management of acute stroke.
 ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE
ANGIOGRAPHIC EVALUATION
Initial angiographic evaluation of the patients vascu-
lature is of paramount importance for the establish-
ment of the ischemic etiology and initiation of
treatment. Thus far, the use of general anesthesia is
preferred due to motion elimination contributing to
procedural safety and efficacy (11). However, newer
studies suggest that conscious sedation or local anes-
thesia may lead to more favorable radiographic and
clinical outcomes by decreasing time delay and cere-
bral ischemia from hypoperfusion (1113). Femoral
access is established in the symptomatic lower extrem-
ity, if no vascular contraindications exist. A thorough
examination of the cerebrovascular anatomy begins
with the aortic arch. The brachiocephalic vessels are
visualized and any proximal stenosis, irregularities, or
occlusion noted. Proximal vessel disease may require
immediate treatment with balloon angioplasty and/or
stenting to allow access to the intracranial pathology
or may itself be the cause of the acute ischemic event.
Based on the patient symptomatology and pre-
procedure imaging, selective catheterization of the car-
otid or vertebrobasilar circulation supplying the
affected territory is performed. Attention is paid to
the extracranial collateral circulation, the leptomenin-
geal anatomy, the circle of Willis, and overall global
cerebral perfusion. Recent data showed that the grade
of angiographic collaterals is a decisive factor for the
degree of reperfusion and clinical improvement fol-
lowing endovascular intervention in acute ischemic
stroke (14).
The modality of treatment (for example IA throm-
bolysis, balloon angioplasty, stenting, clot retrieval
mechanisms) is tailored to each individual case. At
times, advanced age or significant atherosclerotic dis-
ease may limit treatment options.
INTRA-ARTERIAL CHEMICAL THROMBOLYSIS
Over the past decade, several agents have been investi-
gated for IA thrombolysis with variable dosages and
administration routes. Overall, these drugs act by acti-
vating plasminogen to plasmin, which in turn degrades
fibrin and its associated derivatives. Although studies
targeting direct comparisons of the different agents have
not yet been published, fibrin-specific agents, such as
recombinant tissue plasminogen activator (r-tPA) and
recombinant pro-urokinase (rpro-UK) have been widely
studied and used most frequently (15).
First-generation agents, such as streptokinase and
urokinase, are non-fibrin selective and could therefore
have greater systemic complications (16). Streptokinase,
a protein derivative from group C beta-hemolytic strep-
tococci, has a half-life of 1690 minutes. It has an
increased association with intracranial and systemic
hemorrhages, and was therefore removed from the
chemical armamentarium for the management of acute
ischemic stroke (17). Urokinase, a serine protease, has a
half-life of 14 minutes and dosage range of 0.022 mil-
lion units (18).
Second-generation agents have a higher fibrin
specificity and are most commonly studied in IA stroke
management studies. Alteplase (r-tPA), also a serine
protease, has a half-life of 3.5 minutes and a dosage
405
range of 2060mg (18). The precursor of urokinase
(rpro-UK) has a half-life of 7 minutes and may be
favorable to r-tPA due to decreased side effects. Kaur
and colleagues published potential neurotoxic proper-
ties of alteplase, such as activation of NMDA receptor
in the neuronal cell-death pathway, amplification of
calcium conductance, and activation of extracellular
matrix metalloproteinases (19). These effects may facili-
tate exacerbation of cerebral edema, disturbance of the
blood brain barrier, and development of ICH.
Third-generation agents, such as reteplase and
tenecteplase, have longer half-lives (1518 minutes)
and theoretically favorable vessel recanalization and
local recurrence rates (16). Newer-generation agents
are genetically engineered, such as desmoteplase and
microplasmin (Thrombogenics, Heverlee, Belgium).
Besides their fibrinolytic properties, the aforemen-
tioned agents have prothrombotic effects by the pro-
duction of thrombin during thrombolysis, and
subsequent activation of platelets and fibrinogen (16).
As a result, concomitant use of systemic anticoagula-
tion during IA thrombolysis is recommended with cau-
tion to risk of ICH. The most widely used adjuvant
systemic agent is heparin. Newer generation agents
under the category of glycoprotein (GP) IIIb/IIa antag-
onist, such as Reopro (abciximab) and Integrilin (eptifi-
batide), are currently under investigation. Memon and
colleagues reviewed 35 cases of adjunctive use of eptifi-
batide in salvage reocclusion and thrombolysis of distal
thrombi with a single bolus of 180 mg/kg. They
reported a partial to complete recanalization of 77%.
However, incidence of post-operative hemorrhage was
37% and symptomatic in 14% of patients (20).
Anterior Circulation
Middle Cerebral Artery
Three major clinical trials evaluated the efficacy of
IA thrombolysis in MCA circulation, specifically the
PROACT I and II (Prolyse in Acute Cerebral Throm-
boembolism), and MELT trials (Middle Cerebral Artery
Local Fibrinolytic Intervention Trial). Although IA
thrombolysis shows a favorable outcome in the setting
of acute ischemic injury, FDA approval has thus far
been granted for its intravenous counterpart alone (21).
In 1998, del Zoppo and colleagues presented a
phase II clinical trial investigating the safety and effi-
cacy of IA delivery of recombinant pro-urokinase
(rpro-UK) in acute MCA stroke, PROACT I (22). Fol-
lowing the exclusion of ICH with a non-contrast head
CT, 40 patients were randomized for treatment of
acute ischemic stroke within 6 hours of symptom
onset. Cerebral angiography was performed, and M1
or M2 occlusions were treated with 6mg of rpro-UK
(n = 26) or placebo (n = 14). All patients received a
concomitant heparin bolus followed by a 4-hour infu-
sion. The final endpoints were recanalization efficacy
at the end of the infusion period and neurological
deterioration from ICH within 24 hours of treatment.
Rpro-UK treated patients had higher vessel recanaliza-
tion rates compared to placebo (57.7% versus 14.3%).
Furthermore, the incidence of ICH was higher in the
rpro-UK group (15.4% versus 7.1%). Overall, PROACT
I was the first organized trial proving the safety and
406 NEUROINTERVENTIONAL MANAGEMENT
efficacy of IA thrombolysis for the management of
acute ischemic stroke.
PROACT II was a subsequent phase III clinical
trial that studied the safety and efficacy of rpro-UK in
a larger patient population (n = 180) (23). This random-
ized, controlled clinical trial treated patients with MCA
occlusion within 6 hours of symptom onset with either
9mg of IA rpro-UK and heparin infusion (n = 121) or
heparin infusion alone (n = 59). The studys primary
endpoint was the 90-day patient neurological disability
based on the modified Rankin score scale. Secondary
outcomes included mortality, vessel recanalization, and
neurological deterioration from the development of
ICH. Patients who received IA rpro-UK had signifi-
cantly lower Rankin scores at the 90-day endpoint com-
pared to heparin only treated patients. Furthermore,
the MCA recanalization and mortality rates favored
the rpro-UK group as opposed to the control group
(66% versus 18%). Albeit a higher incidence of ICH in
the rpro-UK group (10% as opposed to 2% in the con-
trol group), the PROACT II multicenter trial demon-
strated that the use of IA chemical thrombolysis in
acute ischemia of the anterior circulation leads to radio-
graphic and clinical improvement.
Recently, the MELT Japanese study group inves-
tigated the IA administration of UK in the setting of
MCA stroke within 6 hours of onset (24). Although
the study showed favorable 90-day functional out-
come in the UK-treated patients with respect to con-
trols, results did not reach statistical significance.
Unfortunately, the investigation was aborted prema-
turely following the approval of intravenous r-tPA in
Japan for the treatment of acute ischemic stroke.
The optimal window for IA thrombolysis in the
anterior circulation has been investigated in multiple
clinical trials. Overall, results show that IA treatment of
acute MCA infarction outweighs potential hemorrhagic
risks when implemented within a 6-hour window from
symptom onset (15). Theron et al. investigated the effi-
cacy of IA thrombolysis in patients with acute internal
carotid artery (ICA) occlusion as it related to the timing
of treatment and angiographic location (25). Based on
his work, IA fibrinolysis of the MCA should be per-
formed within 6 hours from ischemia onset, when the
occlusion involves the horizontal segment of the MCA
extending into the lenticulostriate arteries. Treatment
complications, mainly hemorrhagic incidence, increase
significantly beyond this optimal time-frame. However,
if the occlusion does not involve the horizontal MCA
segment and the lenticulostriate arteries, then the treat-
ment window can be extended to 12 hours following
symptoms (15). The paucity of collateral circulation in
the lenticulostriate arteries, as well as their distal distri-
bution, both contribute to their sensitivity to ischemia
in the setting of acute stroke. When initiating endovas-
cular intra-arterial thrombolysis, the operator should
account for time required to perform the procedure.
Considering that the average intervention time varies
from 45 to 180 minutes, high-risk patients should be
treated within 45 hours from ischemia onset (2628).
Internal Carotid Artery
Occlusions of the proximal internal carotid artery
(ICA) (extra-cranial) generally have a better prognosis
than intracranial occlusions. The presence of external
internal carotid collateral flow and the anastomosis at
the circle of Willis account for this observation.
Patients with insufficient extracranialintracranial
anastomoses or an incomplete circle of Willis may be
predisposed to developing significant neurological
symptoms. These patients are potential candidates for
IA intervention. In these cases, mechanical thromboly-
sis, in addition to pharmacological thrombolysis, is
of paramount importance for recanalization. In a
25-patient series, Jovin and colleagues demonstrated
successful revascularization in 92 % of patients follow-
ing thrombolysis and ICA stenting (29).
Intracranial ICA acute occlusions have a dismal
natural history and overall prognosis. Negative prog-
nostic factors include distal ICA distribution involving
the M1 and A1 segments (T occlusion) and poor neu-
rological presentation. Furthermore, as observed by
Bhatia et al., recanalization following IV r-tPA in
patients with T occlusion is the lowest at 4.4% (30).
Arnold and colleagues presented a series of 24 patients
with distal ICA occlusions treated with IA urokinase.
Favorable 3-month functional outcome was present in
only 16% of patients, and the mortality rate was
approximately 42% (31). Adjuvant mechanical assis-
tance with devices for balloon angioplasty, clot
retrieval, and vessel stenting enhance the probability of
vessel recanalization (Fig. 19.1). Flint et al. published a
series of 80 patients with ICA occlusion who were
treated with combinations of the Merci retriever (Con-
centric Medical, Mountain View, California) with or
without adjunctive endovascular therapy. Recanaliza-
tion rates were higher in the combination group (63%)
as opposed to the Merci group (53%). At a 3-month fol-
low-up, 25% of patients had a good neurological out-
come, with their age being a positive predictive
indicator (32). Overall, these results are encouraging,
and IA intervention in select cases of acute ICA occlu-
sion should be considered.
Central Retinal Artery
Occlusion of the central retinal artery (CRA) is an
ophthalmologic emergency with a natural history that
leads to loss of vision. Conventional medical therapy
includes ocular massage, carbohydrate inhibitors,
inhalation of carbogen mixture, paracentesis, topical
beta-blockers, aspirin, and intravenous heparin (15).
However, the limited efficacy of all these therapies
made acute CRA occlusion a potential candidate for
endovascular management.
Several studies have documented successful ves-
sel recanalization with visual improvement compared
to controls. In most studies, IA alteplase is most com-
monly used within 46 hours from symptom onset.
The agent is infused via supraselective catheterization
of the ophthalmic artery. Padolecchia and colleagues
showed that intervention within 4.5 hours of ischemic
onset leads to visual improvement in all patients (33).
Studies performed by Arnold, Aldrich, Noble, and
their colleagues showed visual improvement in a sig-
nificant amount of patients treated with IA thromboly-
sis that ranged from 22% to 93% compared to much
lower conventionally treated controls (3436). The IA
agent was r-tPA or urokinase and the treatment time
 ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE 407

LICA LICA
PRE
PRE

(A) (B)

4X10 DIL
LICA

LICA

POST MERCI/4X10 HYPERGLIDE/760.OOOU UROKINASE

(C) (D)
POST MERCI/4X10 HYPERGLIDE/760.000U UROKINASE

LICA

(E)

Figure 19.1 (AE) Acute left internal carotid artery (ICA) occlusion. The patient presented 6 hours following onset of global aphasia
and right (R) hemiplegia. (A, B) Mid-arterial digital subtraction angiogram of left ICA artery showing complete occlusion of the distal
ICA (T occlusion), frontal and lateral views. (C) Frontal view of balloon angioplasty and recanalization of the distal left ICA. (D, E) Fron-
tal and lateral views of left ICA angiograms following mechanical and chemical recanalization with balloon angioplasty, Merci device,
and administration of Urokinase.
408 NEUROINTERVENTIONAL MANAGEMENT
varied from 6 to 15 hours from symptom onset. Ische-
mic and hemorrhagic complications were either not
present (Arnold, Aldrich) or occurred at significantly
low rates (Noble).
Posterior Circulation
Acute basilar artery (BA) occlusion is a life-threatening
event that poses a significant therapeutic challenge.
The natural progression of untreated BA occlusion
has mortality rates ranging from 86% to 100% (15).
The rare incidence of this disease, less than 10% of
acute ischemic strokes, could account for the lack of
significant randomized controlled studies in the
topic. Several meta-analyses of case reports and case
series reflect the severity of the disease. In a series of
nearly 300 patients, Furlan and Higashida reported
an IA recanalization rate of 60%, and mortality rates
of 31% in at least partially recanalized patients as
opposed to 90% in non-recanalized patients (37).
Lindsberg and Mattle compared BA occlusion treat-
ment with IV or IA thrombolysis. They found that
although recanalization rates were higher with IA
treatment (65% versus 53%), dependency or death
rates were equal between the two groups (7678%).
Overall, 22% of treated patients had good outcomes,
as opposed to only 2% of untreated individuals.
Therefore, emergent thrombolysis via either techni-
que is of paramount importance to the survival of
this patient population.
The timing of treatment initiation in relation to
symptom onset is a controversial topic. Theoretically,
the same treatment restrictions apply as in the anterior
circulation; however, in practice, the therapeutic win-
dow can be successfully extended beyond 6 hours. In
our institution, we have achieved favorable clinical out-
comes in patients treated up to 12 hours from symp-
tom onset. Between 12 and 18 hours, incidence of
hemorrhagic conversion is more significant, and treat-
ment is rarely extended beyond the 24-hour window.
In the Basilar Artery International Cooperation Study
(BASICS), 624 patients with radiographically confirmed
occlusion of the BA were enrolled in nearly 50 centers
over a 5-year period (38). All patients (n = 41) treated
with IA or IV thrombolytics beyond 9 hours from
symptom onset had a poor reported outcome.
Recent advances in mechanical and pharmaco-
logical approaches to endovascular therapies may
increase BA recanalization rates and improve patient
outcome (Fig. 19.2). In a meta-analysis of 164 patients
with BA occlusion over a 10-year period, Levy et al.
reported several predictive factors in treatment con-
sideration (39). Factors with a negative prognostic
value were coma at initial presentation, failure of ves-
sel recanalization, and proximal vessel occlusion. Dis-
tal BA occlusions are more commonly embolic in
nature and therefore have a better response to throm-
bolytic agents.
INTRA-ARTERIAL MECHANICAL
THROMBOLYSIS
The use of mechanical endovascular devices for
thrombolysis is emerging as a powerful adjuvant, or
even an alternative to chemical thrombolysis. In their
multi-center review, Gupta and colleagues have dem-
onstrated that multimodality approach with chemical
and mechanical thrombolysis leads to higher recanali-
zation rates (40). The mechanical disruption of the
arterial clot has several advantages to IA management
of acute stroke (16). First, it increases the working sur-
face area for thrombolytic agents thereby enhancing
their efficacy. Even partial removal of clot via retrieval
or thromboaspiration techniques lessens the concen-
tration of IA agent required to dissolve the remainder
pieces. As a result, the risk of ICH is further
decreased and the treatment window could be
extended beyond the 6-hour limit. Mechanical throm-
bolysis provides patients with contraindications to
anticoagulation with a reasonable alternative to endo-
vascular therapy.
The use of mechanical thrombolysis is associated
with several associated risks. The endovascular
trauma to the blood vessel could cause endothelial
damage, permanent vascular injury, and ultimately
vessel rupture, especially in old friable vessels. The
technical skills needed for the endovascular naviga-
tion of such devices, especially through severely
occluded segments, are substantial, and require rigor-
ous training. Finally, the dislodged clot material could
become an embolic source, exposing the already com-
promised distal circulation to additional ischemic
risks.
Overall, the multiple advantages of mechanical
endovascular devices have revolutionized current
therapies of acute ischemic stroke, and are safe adju-
vant and/or alternatives to chemical thrombolysis in
experienced hands. The conceptual basis of such devi-
ces can be broadly categorized into the following cate-
gories: thrombectomy, thromboaspiration, thrombus
disruption, augmented fibrinolysis, and thrombus
entrapment (16).
Endovascular Thrombectomy
Devices under this category apply a constant force to
the clot material at its proximal or distal end and
facilitate clot removal. Proximal end forces are applied
through grasp-like attachments, whereas distal end
forces are applied via basket-like devices. The advant-
age of these devices is their decreased association
with embolic material since there is no attempt for
mechanical clot disruption. Some of the most widely
used examples are the Merci retriever (Concentric
Medical, Mountain View, California), the Neuronet
device (Guidant, Santa Clara, California), the Phenox
clot retriever (Phenox, Bochum, Germany), the Catch
thrombectomy device (Balt Extrusion, Montmorency,
France), and the Alligator retrieval device (Chestnut
Medical Technologies, Menlo Park, California) (16).
The Merci device became FDA-approved in 2004 for
the endovascular clot retrieval in acute ischemic stroke
(41). It is a flexible nitinol wire with coil loops that
incorporates into the clot and facilitates retrieval.
Recent analysis of the Mechanical Embolus Removal
in Cerebral Ischemia (MERCI) and Multi-MERCI trials
showed that patients with M2 occlusions had higher
recanalization rates, decreased procedure duration,
and similar complication rates with M1 occlusion
patients (42). In a recent study that investigated the
 ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE 409

RVERT PRE
RVERT PRE

(A) (B)

(C) (D)

RVERT POST
RVERT POST 4X20 GATEWAY BALLOON
4X20 GATEWAY BALLOON 4.5X20 WINGSPAN STENT
4.5X20 WINGSPAN STENT

(E) (F)

Figure 19.2 (AF) Acute right vertebro-basilar occlusion. (A, B) Mid-arterial digital subtraction angiogram of the right vertebral artery
(dominant) showing complete occlusion with no distal filling of the BA, frontal and lateral views. (C) Frontal view of balloon angioplasty
of the right vertebro-basilar junction. (D) Road map during deployment of Wingspan stent at the vertebro-basilar level. (E, F) Frontal
and lateral views of right vertebral artery mid-arterial angiograms depicting vessel recanalization following mechanical thrombolysis.
410 NEUROINTERVENTIONAL MANAGEMENT
efficacy of current thrombectomy mechanisms, the
Merci, Phenox, and Catch devices presented equal
results with clot mobilization and retrieval (43).
Endovascular Thromboaspiration
The functioning mechanism in this category utilizes an
aspiration technique, which is suited for fresh non-
adhesive clots. These devices also have the advantage
of fewer embolic material and decreased vasospasm.
Some examples in this category are the Penumbra sys-
tem (Penumbra, Alameda, California) and the AngioJet
system (Possis Medical, Minneapolis, Minnesota) (16).
The Penumbra system includes a reperfusion catheter
that aspirates the clot and a ring-shaped retriever
(Fig. 19.3). The favorable results of a prospective multi-
center trial conducted in the United States and Europe
led to the approval of the device by the FDA for the
endovascular treatment of acute ischemic stroke in
2008 (44). The AngioJet system uses a high-pressure
saline jet for clot agitation and an aspiration catheter
for retrieval. Technical difficulties with endovascular
navigation resulting in vessel injury led to the prema-
ture discontinuation of its trial in acute ischemic stroke
patients (45).
Thrombus Disruption
In this category, mechanical disruption of the clot is
accomplished via a microguidewire or a snare. Some
devices utilizing this mechanism are the EPAR (Endo-
vasix, Belmont, California) and the LaTIS laser device
(LaTIS, Minneapolis, Minnesota) (16). The potential
endothelial damage with resultant vessel injury and
genesis of embolic material make these devices less
favorable in the setting of acute ischemic stroke.
Traditional balloon inflation techniques could
also cause central intra-arterial clot disruption and
vessel recanalization (Fig. 19.4). The balloon is posi-
tioned across the vascular filling defect and gently
inflated. Typically, a Hyperglide balloon (ev3 Neuro-
vascular, Toledo, California) is utilized for this techni-
que. The final revascularization result and residual
clot burden determine the possibility of additional
stenting across the lesion.
Augmented Fibrinolysis
These devices, such as the MicroLysUS infusion cathe-
ter (EKOS, Bothell, Washington), utilize a sonographic
micro-tip to facilitate thrombolysis through ultrasonic
vibration (16). As a result, clot removal is augmented
without any additional fragment embolization to the
distal circulation. Recent studies show a favorable out-
come with the use of such devices for the endovascu-
lar management of acute ischemic stroke (46,47).
Thrombus Entrapment
The underlying mechanism of these devices utilizes a
stent to recanalize the occluded vessel and therefore
trap the clot between the stent and vessel wall.
Besides their use at the site of occlusion, stents could
recanalize proximal vessels (such as the extracranial
ICA) to allow device navigation to the site of pathol-
ogy. Stents can be deployed via a balloon mechanism
or could be self-expandable. The latter are becoming
increasingly popular due to their flexibility and ease
of navigation. They include the Neuroform stent
(Boston Scientific, Natick, Massachusetts), the Enter-
prise stent (Cordis, Miami Lakes, Florida), the LEO
stent (Balt Extrusion, Montmorency, France), the Soli-
taire/Solo stent (ev3, Irvine, California), and the
Wingspan stent (Boston Scientific). The first four
stents are utilized in stent-assisted coiling of wide-
neck aneurysm, whereas the Wingspan is the only
stent approved for intracranial treatment of athero-
sclerotic disease (16). Their use in acute ischemic
events has been investigated in several trials (4850).
Kim and colleagues reported recanalization rates as
high as 71.4% in acute ischemic stroke with the use of
Neuroform stent in 14 patients (48). In two studies
investigating the Neuroform and Wingspan stents,
recanalization rates ranged from 67% to 89% and early
follow-up (mean of 8 months) showed small (5%) or
no restenosis rates (51,52).
ALTERNATIVE REPERFUSION STRATEGIES
Cerebral reperfusion during acute ischemic stroke can
be augmented via alternative strategies that utilize an
anterograde or retrograde route. Anterograde reperfu-
sion can be facilitated systemically with vasopressors
leading to global reperfusion by increasing the mean
arterial blood pressure. Retrograde reperfusion can be
facilitated with a transarterial or transvenous
approach. The transarterial approach involves the
endovascular deployment of the NeuroFlo device
(CoAxia, Maple Grove, Minnesota). This dual balloon
catheter allows for partial occlusion of the aorta above
and below the level of the renal arteries, therefore
diverting flow away from the systemic and toward
the cerebral circulation (53). Several clinical trials are
currently underway investigating the safety and effi-
cacy of NeuroFlo and similar devices.
Transvenous retrograde reperfusion is an experi-
mental technique with potential benefit in acute ische-
mic stroke. Animal studies suggest that diversion of
blood from the femoral artery into the transverse
venous sinuses via transvenous catheters could lower
infarction size and improve neurological outcome in
the setting of acute cerebrovascular ischemia (54). Fur-
ther investigational human trials are required prior to
introducing such a novel concept to current stroke
therapies.
FUTURE DIRECTIONS
Advances in knowledge about pharmacology, endo-
vascular biomechanics, and endothelial properties are
stimulating research on new diagnostic and therapeu-
tic tools in the management of acute ischemic stroke.
Currently there are several clinical trials targeting
neuroendovascular therapy (21). The Interventional
Management of Stroke Study III (IMS III) is a phase III
multicenter clinical trial that continues the investigation
of combined IA and IV therapies in the management of
acute stroke. The SYNTHESIS Expansion trial is a
phase III clinical study that compares the safety and
efficacy of IV thrombolysis to IA chemical and mechan-
ical thrombolysis. Future studies may include the
 ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE 411

PRE RICA

PRE RICA

(A) (B)

FINAL
RICA POST PENUMBRA 032
RICA

(C) (D)

FINAL
RICA POST PENUMBRA 032

(E)

Figure 19.3 (AE) Acute right middle cerebral artery (MCA) occlusion. The patient presented 4 hours after an acute event of MCA occlu-
sion. (A, B) Mid-arterial digital subtraction angiogram of right ICA shows complete MCA occlusion at the level of the bifurcation, frontal
and lateral views. (C) Mechanical thrombolysis with Penumbra device showing recanalization of the superior M2 division in a frontal
high magnification view. (D, E) Frontal and lateral views of right ICA angiograms following MCA mechanical recanalization.
412 NEUROINTERVENTIONAL MANAGEMENT

RCCA PRE
RCCA PRE

(A) (B)

HYPERGLIDE BALLOON
3X15

HYPERGLIDE BALLOON
3X15

(C) (D)

RICA POST

RICA POST

(E) (F)

Figure 19.4 (AF) Acute right ICA occlusion. The patient presented 5 hours after an acute event of left hemiplegia. (A, B) Mid-arterial
digital subtraction angiogram of right common carotid artery (CCA) shows complete ICA occlusion at the level of the ophthalmic artery,
frontal and lateral views. (C, D) Balloon angioplasty across the lesion with a Hyperglide 3  15mm balloon, frontal and lateral native
angiographic views. (E, F) Frontal and lateral views of right ICA angiograms following ICA mechanical recanalization.
 ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE
individual comparison of mechanical devices versus
intravenous thrombolytics (55).
Multiple studies are investigating the safety and
efficacy of new generation endovascular devices, such
as the Safety and Efficacy of NeuroFlo Technology in
Ischemic Stroke (SENTIS). The neurological outcomes
of optimal medical management versus IA thromboly-
sis are examined in clinical trials such as RETRIEVE
(Randomized Trial of Endovascular Treatment of
Acute Ischemic Stroke Versus Medical Management)
and PISTE (Pragmatic Ischemic Stroke Thrombectomy
Evaluation). Extending the timing of endovascular
intervention is being evaluated in conjunction with
new radiographic techniques. Examples include the
DWI and CTP Assessment in the Triage of Wake-Up
and Late Presenting Strokes Undergoing Neurointer-
vention Trial, and the MR Imaging and Recanalization
of Stroke Clots During Embolectomy Trial (21).
These and several other upcoming trials will
hopefully provide sufficient clinical data for the FDA
approval of IA agents, the introduction of new endo-
vascular devices, and other adjunctive therapies for
the management of the acute stroke patient.
CONCLUSION
The preponderance of data shows that endovascular
intervention has become a mainstay treatment in the
setting of acute ischemic stroke, and will continue to
evolve. Innovative techniques in both chemical and
mechanical intra-arterial thrombolysis increase the
safety and efficacy of endovascular management and
expand its indications in acute cerebral infarction.
Additional larger clinical trials are warranted for the
improvement of the endovascular care of stroke
patients resulting in faster and safer reperfusion
mechanisms. Continuous advancements in the field
mandate the establishment of performance and train-
ing standards as set by guidelines from multiple neu-
roscience societies (56).
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 20
Endovascular treatment of extracranial carotid
atherosclerotic disease
David Orion, Shady Jahshan, Sharon Webb, Adnan H. Siddiqui, Elad I. Levy, and
L. Nelson Hopkins
INTRODUCTION
Atherosclerosis from supra-aortic vessels and espe-
cially from the common carotid bifurcation accounts
for approximately 15% of all strokes (1,2). The benefit
of carotid endarterectomy (CEA) in reducing the risk
of stroke in symptomatic and asymptomatic patients
with carotid artery (CA) stenosis has been established
in randomized trials. In The North American Sympto-
matic Carotid Endarterectomy Trial (NASCET), the
risk of any ipsilateral stroke was reduced significantly
in patients with carotid stenosis of 7099% (absolute
risk reduction [ARR] SE: 17 3.5% in 2 years) and
with stenosis of 5069% (ARR of 6.5% in 5 years) (36).
This risk reduction did not extend to patients with
<50% stenosis (68). In the European Carotid Surgery
Trial (ECST), CEA led to a reduction in the 5-year risk
of any stroke by 5.7% [95% confidence interval (CI),
0 to 11.6] in patients with 50% to 69% stenosis and by
21.2% (95% CI, 12.9 to 29.4) in patients with 70% to
99% stenosis (911). In both the NASCET and the
ECST, randomization within 2 weeks of the last ische-
mic event contributed to an increase in the effectiveness
of surgery in the number needed to treat to prevent
one ipsilateral stroke (p = 0.009) (12). Randomized trials
in asymptomatic patients with stenosis >60% showed
an ARR for ipsilateral stroke at 5 years of 5.9% in the
Asymptomatic Carotid Atherosclerosis Study (ACAS)
and 5.4% in the Asymptomatic Carotid Surgery Trial
(ACST), with a net gain of 4.6% at 10 years according
to the results of ACST (1316).
Despite the benefits associated with CEA, however,
many patients cannot safely undergo this extensive oper-
ation because of technical or anatomical factors or under-
lying severe medical illnesses, such as coronary artery
disease and cardiac failure (1719). In an analysis of the
NASCET results, CEA was approximately 1.5 times
more likely to be associated with medical complications
in patients with a previous history of myocardial infarc-
tion (MI), angina, or hypertension (20). Moreover, the
benefits of carotid revascularization surgery shown by
NASCET (6,7), ACAS (14), ACST (15), and ECST (9,10)
are lost if the 30-day rate of perioperative stroke or death
exceeds 6% for patients with symptomatic carotid steno-
sis or 3% for those with asymptomatic carotid stenosis.
With the advent of embolic protection techni-
ques, standard surgical techniques for extracranial CA
stenosis in high-risk surgical patients were challenged
by catheter-based angioplasty and stenting. In August
of 2004, the U.S. Food and Drug Administration
(FDA) approved the first CA stenting system (Accu-
link stent and Accunet embolic protection device; Gui-
dant, Santa Clara, California, U.S.) for use in patients
with 50% symptomatic and 80% asymptomatic car-
otid stenosis who were viewed by the treating sur-
geon as high-risk for CEA because of anatomical risks
or medical comorbidities. The subsequent Centers for
Medicare & Medicaid Services coverage decision,
which allowed reimbursement for patients with 70%
symptomatic stenosis or who was enrolled in FDA-
sponsored clinical trials, gave CA stenting an entry to
the clinical arena as a legitimate alternative to CEA.
More recently, after the publication of the results of
the Carotid Revascularization Endarterectomy versus
Stenting Trial (CREST) (21), the Circulatory System
Devices Panel of the FDA voted in favor of expanding
the indication for CA stenting to patients at standard
risk for surgical complications, and several medical
societies collaborated to develop a practice guideline
with new recommendations that view stenting as a
viable alternative to surgery in many cases (22).
In this chapter, the indications for treatment of
cervical (extracranial) CA disease and patient selection
for CA revascularization are reviewed, trials compar-
ing CA stenting with CEA before and after the avail-
ability of embolic protection devices are reviewed,
endovascular technique for carotid revascularization is
described, and advantages of this approach are dis-
cussed. Procedure-related limitations and complica-
tions are also discussed.
SELECTION OF PATIENTS FOR CAROTID
ARTERY REVASCULARIZATION
The results of major trials have validated CEA and
have shown annual ARRs for stroke of approximately
1% for asymptomatic patients (1315,23) and 8% for
symptomatic patients (5,6,8). However, trials evaluat-
ing CEA have systematically excluded patients consid-
ered to be high-surgical-risk candidates (Table 20.1)
(6,7,1315,24). The conditions that have been shown to
predispose patients to a high perioperative risk of
stroke and death in various CEA reports (17,19) were
behind the rationale for developing CA stenting as a
416 NEUROINTERVENTIONAL MANAGEMENT
Table 20.1 Exclusion Criteria for CEA Trials
. Older than 79 years of age
. Heart, kidney, liver, or lung failure
. Cancer likely to cause death within 5yr
. Cardiac valvular lesion or rhythm disorder likely to be associ-
ated with cardioembolic stroke
. Previous ipsilateral CEA
. Contralateral CEA within 4 mo
. Angina or MI within the previous 6 mo
. Progressive neurological signs
. Major surgical procedure within 30 days
. Severe comorbidity due to other surgical or medical illness
. Cerebrovascular events in the distribution of the treated CA
with ongoing disabling symptoms
. Symptoms referable to the contralateral side within the pre-
vious 45 days
. More severe stenosis of an intracranial lesion than of the
treated lesion
less-invasive endovascular approach for carotid revas-
cularization. Moreover, the publication of results
obtained with coronary balloon angioplasty and stent-
assisted balloon angioplasty played a supporting role
in the performance of studies in which endovascular
and surgical approaches for the treatment of CA dis-
ease were initially compared.
Evidence in the literature documents a much
greater risk for CEA in clinical practice than is reflected
in major CEA trials in which the lowest risk patients
were operated on by experienced surgeons performing
a relatively high volume of procedures (2529). Never-
theless, although surgical experience may be an impor-
tant factor contributing to significant differences in
complication rates, careful patient selection has been
found to be the key determinant in maintaining a low
perioperative complication rate (17,18,20,30).
Factors Associated with High Periprocedural
Risk
The following conditions or characteristics have been
shown to predispose patients to a high perioperative
risk of stroke and death in various CEA reports
(17,18,20,30) with one or more of these risk factors gen-
erally excluded from enrollment in the early prospec-
tive CEA trials. Recent studies comparing standard-risk
to high-risk patients undergoing CEA or CAS contrib-
ute to better understanding and patient selection.
Age
In a comparative, population-based study, the inci-
dence of symptomatic, 50% CA stenosis ranged from
0.5 per 1000 for patients aged 6069 years and 1.5 per
1000 for patients aged >80 years or older (31). Octoge-
narians represent a group considered at higher risk
for CEA and were generally excluded from the land-
mark CEA randomized clinical trials, NASCET and
ACAS (7,13,14).
In a subgroup analysis of ECST and NASCET
studies, age was a significant determinant in benefit
from CEA with the number of patients needed to
undergo surgery to prevent one ipsilateral stroke in
5 years was five for age 75 years versus 18 for <65
years (12,17), without a clear benefit in asymptomatic
patients <75 years in the ACST (15). On the other
hand, octogenarians appear to have a higher rate of
postoperative stroke or death with CEA. Perioperative
mortality in 113,300 Medicare patients undergoing
CEA was three times higher in patients >85 years
than those <70 years (29). An increased risk of CA
stenting associated with advancing age has been
reported in several studies (3234), as well as the
Stent-Protected Angioplasty versus Carotid Endarter-
ectomy (SPACE) trial (35), the International Carotid
Stenting Study (ICSS) (36), and the Carotid Revascula-
rization Endarterectomy versus Stenting Trial
(CREST) (21). Excess tortuosity and calcification of the
CA are age-associated anatomic risks that may con-
tribute to excess morbidity and mortality (34).
Severe Coronary Artery Disease
The coexistence of severe CA disease and significant
coronary artery disease is not uncommon and repre-
sents a dilemma for the clinician (20). During coronary
angiography in patients undergoing elective CA stent-
ing, 61% of patients were found to have significant cor-
onary artery disease (37). The surgical repair of one
condition cannot be accomplished without significant
risk of complication from the other. In a NASCET sub-
group analysis, patients who had previous treatment of
coronary artery disease had a lower CEA complication
rate than those who had undiagnosed coronary artery
disease (38). In the New York Carotid Artery Surgery
study of 9,308 CEAs, the presence of underlying coro-
nary artery disease increased the 30-day risk of stroke
and death after CEA [odds ratio (OR), 1.5] (39).
The Stenting and Angioplasty with Protection in
Patients at High Risk for Endarterectomy (SAPPHIRE)
trial evaluated high-risk patients in whom coronary
artery disease was present in 85% of the stent group
and 75% of the CEA group (40). The cumulative inci-
dence of periprocedural death, MI, or stroke was lower
among those who were treated with stent placement.
Subsequent to this study, patients with moderate-
to-severe underlying coronary artery disease were
included in several high-risk CA stenting registries
demonstrating an acceptable threshold of stroke and
death rates (4145). In the CREST, the stenting group
had a lower periprocedural rate of MI (1.1% vs. 2.3%,
P = 0.03) (21). Carotid stenting, which is a minimally
invasive procedure without the need for general anes-
thesia, offers a lesser-risk treatment option for patient
at high risk for surgery because of pre-existing severe
coronary artery disease.
Adjunct to Coronary Bypass Operation
Patients with severe coexistent disease of the carotid
and coronary arteries represent a higher risk group. In
a multicenter study, the presence of coexistent disease
was significantly associated with adverse neurological
outcomes postcoronary artery bypass grafting (CABG)
in 6.1% of patients, of whom 3.1% had severe compli-
cations, including stroke and coma (46). In a series of
539 patients who underwent noninvasive testing for
the detection of CA disease before undergoing CABG,
carotid stenosis severity of >75% was found in 8.7%
and was an independent predictor of stroke risk
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
during the bypass operation in 14.3% (47). For
patients with severe coexistent disease of the carotid
and coronary arteries, debate exists whether revascu-
larization is appropriate for both conditions as well as
regarding the timing and sequence of the procedures
and whether to perform a simultaneous or a staged
procedure.
Combined CEA and CABG procedures report-
edly are associated with a risk of stroke or death
ranging from 7.4% to 9.4%, which is roughly 1.5 to
2.0 times the independent risk of each operation (20).
In a multicenter review, the composite risk of stroke
and death was higher in patients who had CEA per-
formed in conjunction with CABG (18.7%) than in
those who had CEA alone (2.1%) (18). Conversely,
patients who undergo CEA before CABG also have a
higher risk of perioperative complications (48,49).
A meta-analysis of 56 studies reported a composite
incidence of stroke, MI, and death of 16.4% for com-
bined carotid and coronary operations, 26.2% for
CEA proceeded by CABG, and 16.4% for CABG pro-
ceeded by CEA (50). A larger systematic review of
97 studies, including 9000 patients undergoing CEA
and CABG, found an incidence of 10% to 12% of
death, stroke, and MI after staged or synchronous pro-
cedures (51). These high complication rates would
clearly offset the long-term benefit from secondary
stroke prevention. In this high-risk subgroup, avoid-
ing a major operation or general anesthesia by per-
forming CA stenting may represent a valid alternative
to CEA (52,53). The SAPPHIRE trial showed superior-
ity of CA stenting over CEA with respect to cardiac
complications in high-risk patients (40).
Another important consideration is the timing
for performing a coronary revascularization procedure
after CA stenting. Close clinical and hemodynamic
monitoring to prevent systemic hypotension may be
critical after successful CA stenting to reduce the risk
of cardiac complications while the patient is waiting
to undergo CABG (54,55). In a review of six studies
with 277 patients who underwent CA stenting fol-
lowed by staged CABG (mean time to CABG was
32 days), there was a 4.7% incidence of stroke and
death associated with the stent procedure, and 2.2%
of the patients developed stroke associated with
CABG (54). The overall combined 30-day event rates
for CA stenting and CABG were as follows: minor
stroke, 2.9%; major stroke, 3.2%; mortality, 7.6%; and
combined death and any stroke, 12.3%.
For patients undergoing staged CA stenting and
CABG, antiplatelet treatment is also of relevance with
the current standard of care to prescribe dual antipla-
telet therapy with aspirin and clopidogrel for 4 weeks
after CA stenting, followed by a single antiplatelet
agent for life. There is no clear consensus on the opti-
mal management. Some groups perform CABG as
soon as needed, based on the clinical presentation of
the patient and irrespective of the use of dual antipla-
telet therapy; others perform the CABG on the same
day as the CA stenting using only aspirin and heparin
and start the clopidogrel immediately after CABG or
use short-acting glycoprotein IIb/IIIa inhibitors during
CA stenting and perform CABG 4 to 6 hours after
stenting; still others may wait approximately 30 days
between interventions (56).
417
A small study (consisting of 37 patients) showed
that sequential hybrid carotid and coronary artery
revascularization (consisting of CA stenting immedi-
ately followed by CABG) was a feasible and promising
therapeutic strategy, with a 30-day cumulative inci-
dence of disabling stroke, MI, or death of 8.1% (57).
The Study of Heart and Renal Protection evaluated
101 patients with an elevated cardiovascular surgical
risk who had a symptomatic CA stenosis of 50% or
asymptomatic CA stenosis of 80% and were treated
by the hybrid approach (58). Study patients received
aspirin before and heparin during the CA stenting
procedure; upon completion of the CA stenting proce-
dure, they were transferred directly to the operating
room for CABG. Clopidogrel was given as a loading
dose of 300mg 6 hours after the end of the CABG
operation and then as a daily dose of 75mg for
1month. The 30-day cumulative incidence of disabling
stroke, acute MI, or death was 4% (2% had a stroke
immediately after CA stenting, and 2% died of multi-
ple-organ failure approximately 30 days after CABG).
The potential advantage in this simultaneous hybrid
approach is the reduced risk of acute MI because the
interval between the two procedures is eliminated.
Congestive Heart Failure
Patients with congestive heart failure have a higher
rate of perioperative stroke or death with CEA than
suggested by the NASCET (7) and the ACAS (14), in
which patients were carefully selected. A multicenter
review of patients undergoing CEA found a perioper-
ative stroke or death rate of 8.6% in patients with con-
gestive heart failure, as opposed to 2.3% in patients
without this condition (17,18). Another review showed
that congestive heart failure had a negative impact on
long-term survival rates after CEA [hazard ratio (HR)
2.85] (59). The SAPPHIRE trial which included high-
risk patients (more than 17% with CHF) showed alto-
gether a lower rate of death, stroke, or MI at 30 days
in the CA stenting group (40). Since then, high-risk
CA stenting registries (4145) or trials (60,61) that
have included small proportions of patients with
severe CHF have demonstrated acceptable rates of
stroke and death.
High- or Low-Lying Lesions
Anatomical variations may increase the technical diffi-
culty of CEA and adversely influence the results. A
high carotid bifurcation near the skull base, extending
higher than the level of the second cervical vertebra,
especially in a patient with a short or thick neck, neck
immobility, or a long CA stenosis that extends to the
skull base, can be difficult to expose surgically, can be
very difficult and often extremely traumatic. Low
lesions that extend close to or below the clavicle can
also be technically difficult and should be avoided (2).
In these cases, an endovascular procedure may be
superior.
Tandem Lesions
The presence of tandem CA lesions in which the distal
lesion was more severe than the proximal lesion was
418 NEUROINTERVENTIONAL MANAGEMENT
a NASCET exclusion criterion (7). Tandem lesions are
frequently detected during cerebral angiography; in a
study of the angiograms of 672 patients with CA
stenosis, the incidence of tandem carotid stenosis was
13.5% at the siphon or intracranial internal CA and
4.3% at the proximal common CA (62). Among symp-
tomatic patients with ipsilateral carotid siphon steno-
sis, the risk of postoperative stroke or death
associated with CEA in a multicenter review of 1160
procedures was 13.9%, versus 7.9% in patients with-
out distal stenosis (17). In a systematic review of
36 studies, an increased risk for perioperative stroke
or death was associated with CEA in patients with
tandem stenosis of the ipsilateral carotid siphon (19).
The presence of a tandem carotid stenosis has been
thought by some to be a relative contraindication to
CEA and has been viewed as a source of thrombus
formation at the endarterectomy site because of persis-
tent slow flow through the stenotic segment (62).
Arch Type and Arch Disease
The main obstacles associated with negotiating the
aortic arch have to do with arch variation, arch config-
uration, and atherosclerotic plaques in the arch. Arch
configuration tends to change over time with age and
prolonged hypertension. As the arch elongates, it
becomes more tortuous (63). An analysis of the results
of the Endarterectomy versus Angioplasty in Patients
with Symptomatic Severe Carotid Stenosis (EVA-3S)
trial suggests that patients with increased internal
CAcommon CA angulation 60 degrees have a higher
risk of stroke or death not statistically significant
increase with Type III aortic arch, aortic arch calcifica-
tions (64). The authors consider preoperative aortic
arch imaging necessary as part of patient selection and
essential prior to CA stenting to understand the varia-
tions of the arch and the risk associated with soft aortic
plaques and to plan the endovascular approach safely.
Ipsilateral Intraluminal Thrombus
Intraluminal thrombus involving the internal CA is
uncommon, occurring in <2% of patients with carotid
stenosis (7), but carries a high risk for stroke. In a sub-
group analysis of 53 patients enrolled in the NASCET
who had intraluminal clot superimposed on athero-
sclerotic plaque, which was identified during angio-
graphic procedures, the 30-day risk of stroke was
10.7% in those randomly assigned to receive medical
treatment and 12% in those who underwent CEA (65).
In a multicenter review of 1160 endarterectomies, the
risk of postoperative stroke or death was found to be
17.9% in symptomatic patients with intraluminal
thrombus in the ipsilateral CA versus 8.1% in those
without thrombus (17). The high morbidity-mortality
rate in this subgroup is related to the presence of
fresh clot and the substantial risk of emboli dislodg-
ment during surgical dissection of the CA.
New endovascular techniques offer a reduced
risk of treating stenosis with intraluminal thrombus
via flow arrest via internal cross clamping and a
combination of distal embolic protection (DEP) and
proximal flow arrest techniques (66,67). A few small
series describe the feasibility and effectiveness of
carotid stenting for the treatment of stenosis with
intraluminal thrombus (6870).
Contralateral Carotid Occlusion
Patients with recent symptoms referable to severe CA
stenosis and coexistent contralateral CA occlusion have
a high risk of ipsilateral ischemic stroke. The risk of
ipsilateral stroke in medically treated patients with
severe stenosis of the symptomatic CA and occlusion of
the contralateral CA was 69.4% at 2 years in a NASCET
subgroup analysis (71). Although CEA led to a signifi-
cant reduction in the stroke risk in this group, the peri-
operative risk of stroke or death in the presence of
contralateral CA occlusion was a high 14.3%. This
increased risk may be related to ischemia during caro-
tid clamping and shunting during CEA. The presence
of contralateral occlusion is considered an indication
for CA stenting by expert-panel consensus groups that
included specialties from different disciplines (inter-
ventional radiology, vascular surgery, interventional
cardiology, and neurosurgery) (2,72).
Postendarterectomy Restenosis
Restenosis after CEA has been described in 8% to 19%
of patients, of whom 14% to 23% become symptomatic
(73,74). Technically, a repeat operation is more chal-
lenging than the initial procedure because of scarring
around the arteries, friability of the recurrent plaque,
and the necessity for complex anastomosis techniques.
Among 82 patients undergoing operations for recurrent
carotid stenosis at one institution, the composite rate of
major morbidity and mortality was 10.8%, a rate that
was five times the risk associated with primary CEA at
the same institution (74). Investigators at another insti-
tution found an increased risk of cerebral ischemic
events associated with CEA for recurrent stenosis (75).
The 30-day rates of perioperative stroke and transient
ischemic attack (TIA) were 4.8% and 4%, respectively,
in the reoperation group, as compared with 0.8% and
1%, respectively, in the primary endarterectomy group.
These investigators also found a high rate (17%) of cra-
nial nerve palsy with reoperation (75).
A multicenter review of data on CA stent proce-
dures performed in 338 patients with post CEA resteno-
sis reported a 30-day stroke and death rate of 3.7% (76).
Other studies have shown that CA stenting is safe and
technically feasible with a low complication rate in
symptomatic and asymptomatic patients (7783). The
European Society for Vascular Surgery recently recom-
mended CA stenting for cases of postendarterectomy
restenosis in their updated guidelines for the invasive
treatment of carotid disease (2).
Radiation-Induced Carotid Stenosis
Accelerated, radiation-induced carotid stenosis
presents an increased risk for perioperative complica-
tions, primarily because of the technical pitfalls associ-
ated with a surgical approach. The presence of a long
lesion, lack of well-defined dissection planes, and
scarring around the vessels make the surgery more
difficult (84,85), exposing these patients to a higher
risk of wound infections and cranial nerve palsies.
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
Additionally, restenosis occurs more frequently after
CEA in patients with radiation-induced atheromatous
disease (86,87).
Carotid stent placement may be superior to CEA
and provides an effective method for the treatment of
carotid stenosis associated with radiation therapy
(2,22,88,89). In a series of 210 carotid stenting patients, 28
patients received stents after neck radiation therapy (90).
Perioperative outcomes, including the composite 30-day
stroke/MI/mortality rate did not differ significantly
between the two groups (0% radiation group vs. 3.2%
non-radiation group, with no difference in 12-month
restenosis rates).
Recurrent Nerve Palsy
Recurrent laryngeal nerve palsy is a risk posed by sur-
gical dissection during CEA (91). For a patient who
already has a contralateral laryngeal nerve palsy,
bilateral palsy would result in the need for tracheos-
tomy. Additionally, those who rely significantly on
their voice (such as actors, speakers, and singers) are
better served by CA stenting considering the lower
risk of cranial nerve injury associated with the endo-
vascular procedure (2,21,92).
EARLY CA STENTING TRIALS
The Carotid and Vertebral Artery Transluminal Angio-
plasty Study (CAVATAS), the first randomized com-
parison of endovascular versus surgical treatment in
patients with carotid stenosis, was started in 1992 and
completed in 1997 (93). This study was designed to
compare balloon angioplasty, with or without stenting
(stents developed for the CA were not introduced until
1994 after the study had begun), to CEA. As in the
major CEA trials, patients considered unsuitable for
surgery because of medical or surgical risk factors
were excluded from enrollment. A total of 504 patients
from 24 centers in Europe, Australia, and Canada were
randomized, 253 to CEA and 251 to CA stenting.
Ninety percent of patients were symptomatic in the
preceding 6 months before their procedure, 7% had
been symptomatic but for more than 6 months before
the procedure, and only 3% of patients were asympto-
matic. The mean percentage of stenosis was 86.4%.
Endovascular treatment was technically successful
(balloon inflated across the stenosis at least once or
stent successfully used) in 213 of 240 treated patients.
Balloon angioplasty was performed in 158 of
213 patients (74%). Only 55 (26%) patients received a
stenteither the Wallstent (Boston Scientific, Natick,
Massachusetts, U.S.), Palmaz stent (Johnson & Johnson
Interventional Systems, Warren, New Jersey, U.S.), or
the Strecker stent (Meditech/Boston Scientific, Natick,
Massachusetts, U.S.). No embolic protection devices
were used. The results were essentially equivalent
between the stenting and endarterectomy groups at
30 days with respect to the postprocedure rate of dis-
abling stroke or death (6.4% vs. 5.9%, respectively). No
significant difference was found in the ipsilateral stroke
rate with survival analysis up to 3 years after random-
ization. The rate of severe (7099%) restenosis docu-
mented by ultrasound imaging at 1year after treatment
was 14% in the endovascular group and 4% in the
419
surgical group. Patients in the surgical group were
found to have a higher incidence of cranial nerve palsy
(8.7% vs. 0%) and major neck hematoma (6.7% vs. 1.2%).
The Wallstent trial was a multicenter equiva-
lency trial of CEA and CA stenting in which 209
symptomatic patients with 60% to 99% stenosis were
enrolled; 107 patients were assigned to CA stenting
and 112 to CEA (94,95). The 30-day periprocedural
complication rate (any stroke or death) occurred in
12.1% of the CA stenting group and 4.5% of the CEA
group. The primary endpoint of ipsilateral stroke,
procedure-related death, or vascular death at 1year
was reached by 12.1% of those randomized to stent-
ing and 3.6% of those randomized to endarterectomy.
The major stroke rates were 3.7% for stenting and
0.9% for endarterectomy. The study was terminated
before completion because of the inferiority of CA
stenting.
Another randomized clinical trial featuring the
Wallstent compared CA angioplasty and stenting with
CEA among patients with symptomatic severe (>70%)
internal CA stenosis (96). No embolic protection devi-
ces were used in the carotid stenting group. The main
outcome measures included death or stroke (disabling
or non-disabling) within 30 days. Twenty-three
patients were randomized to CEA with patch graft-
ing or CA angioplasty with stenting; however, only
17 patients underwent the treatment allocated before
the study was suspended because of an unacceptably
high morbidity rate in the stenting group. At 30 days
after treatment, none of the 10 patients who underwent
CEA had a periprocedural TIA or stroke, whereas 5 of
7 patients who underwent CA angioplasty with stent-
ing had a periprocedural TIA or non-disabling stroke
and 3 had disabling stroke. The Wallstent trials
showed that CA stenting without embolic protection
was not acceptable as an alternative to CEA for the
majority of patients with symptomatic CA disease.
EMBOLIC PROTECTION DEVICES
Cerebral embolization of friable atheromatous material
from the aortic arch and CA has been found to occur
during all stages of the CA stenting procedure and may
cause periprocedural neurological deficits (97100).
Three types of embolic protection devices have been
developed: those that arrest antegrade internal CA
flow, those that reverse internal CA flow, and filters
for DEP. Five filter-type devices have received FDA
approval for carotid use in the U.S.: these are the
Accunet (with the Acculink stent), the EmboShield
(with the Xact stent) (Abbott Vascular, Redwood City,
California, U.S.), the Spider (with the Protege stent)
(ev3, Plymouth, Minnesota, U.S.), the AngioGuard
(with the Precise stent) (Cordis, Warren, New Jersey,
U.S.), and the EZ filter wire (with the NexStent)
(Boston Scientific, Natick, Massachusetts, U.S.). Sev-
eral non-approved commercially made filters exist.
Flow-arrest devices include the PercuSurge Guardwire
(Medtronic, Minneapolis, Minnesota, U.S.) and TriAc-
tiv System (Kensey Nash, Exton, Pennsylvania, U.S.)
balloon occlusion catheters.
The flow-reversal and proximal occlusion
embolic protection devices include the GORE Flow
Reversal System (W.L. Gore & Associates, Flagstaff,
420 NEUROINTERVENTIONAL MANAGEMENT
Arizona) and the MO.MA System (Invatec, Brescia,
Italy), respectively. The Gore device received FDA
approval in 2009 after the completion of the Embolic
Protection with Reverse Flow (EMPiRE) clinical study,
the results of which were published in 2011 (101). In
the EMPiRE study, the safety and efficacy of the
GORE Flow Reversal System during CA stenting was
assessed in patients at high risk for CEA. The EMPiRE
study met the primary endpoint of major adverse
events of death, stroke, TIA, and MI. The 30-day
stroke, death, and MI rate was 3.7%, and the rate of
death or any stroke was 2.9%. The study also showed
a low death, stroke, and MI rate of 2.6% for octogenar-
ians and 3.8% for symptomatic patients.
The MO.MA device received FDA approval in
2009 after completion of the proximAl pRotection
with the MO.ma device dUring caRotid stenting
(ARMOUR) trial, the results of which were published
in 2010 (102). The ARMOUR trial evaluated the safety
and effectiveness of the MO.MA device in patients at
high-surgical risk for CEA undergoing CA stenting.
The results showed a low 30-day stroke rate of 2.3%
and a major adverse cardiac and cerebrovascular
events (MACCE; stroke, death, and MI) rate of 2.7%
in the primary endpoint 220-patient population set.
A clear indication for proximal versus distal pro-
tection has not been established. Logically, intralumi-
nal thrombus, soft plaque, severe symptomatic
stenosis, and poor distal landing zone (tortuous post-
stenotic vessel) would be indications for proximal pro-
tection. A study that evaluated the frequency of
periprocedural events with proximal protection
showed fewer microembolic signals on transcranial
Doppler ultrasonography and fewer hyperintense sig-
nals on diffusion-weighted magnetic resonance (MR)
imaging when compared with distal protection devi-
ces during carotid stenting (103). The implication is
that proximal protection allows for fewer periproce-
dural events. The results of the European Imaging in
Carotid Angioplasty and Risk of Stroke (ICAROS)
prospective registry showed that grayscale median
(GSM) scores of 25 or less (representing echogenic pla-
que) are associated with higher embolic potential (104).
Eleven of 155 (7.1%) patients with preprocedural
GSM scores of 25 had strokes after stenting versus
4 of 263 (1.5%) patients with GSM >25 (p=0.005). The
authors, therefore, then validated the use of DEP in
patients with GSM >25 (p = 0.01). However, for
patients with GSM of 25, stenting with proximal
embolic protection devices or CEA may prove safer.
TRIALS OF ANGIOPLASTY AND STENT
PLACEMENT WITH EMBOLIC PROTECTION
VERSUS CEA IN HIGH-RISK PATIENTS
SAPPHIRE
The aims of the SAPPHIRE randomized trial were to
compare CA stenting with CEA and to demonstrate
statistical non-inferiority of stenting to CEA (105). The
study population consisted of high-risk patients with
50% symptomatic stenosis and 80% asymptomatic
stenosis. There were 117 asymptomatic patients in the
stenting group and 120 in the CEA group, whereas
only 50 symptomatic patients underwent stenting and
46 underwent CEA. For the endovascular group, the
Smart or Precise stent (Cordis) and the AngioGuard or
AngioGuard XP (Cordis) DEP device were used. Pri-
mary endpoints included a composite of death/stroke/
MI within 30 days and death or ipsilateral stroke
between 31 days and 1 year. Secondary endpoints
included target-vessel revascularization at 1 year, cra-
nial nerve palsy, and complications at the surgical site
or the vascular access site. SAPPHIRE had a broad
endpoint by comparison with previous CA intervention
trials, in particular with NASCET (6,7) and ACAS (14)
in which MI and death after 30 days were not primary
endpoints. Similar to coronary intervention studies, MI
was included in the primary composite endpoint of
SAPPHIRE and the secondary endpoint of the Carotid
Revascularization using Endarterectomy or Stenting
Systems (CaRESS) study (60,61) and was a component
of the primary endpoint in CREST. Moreover, perioper-
ative non-Q wave MI after peripheral vascular opera-
tions has been associated with a 6-fold increase in
mortality and a 27-fold increase in recurrent MI during
the 6 months after the operation (106).
At 1 year in the SAPPHIRE trial, 12.2% of
patients undergoing CA stenting had reached the pri-
mary endpoint versus 20.1% of the CEA group
(p-value for superiority, 0.053; p-value for lack of infe-
riority, 0.004). Target vessel revascularization occurred
in 4.3% of the CEA group versus 0.6% of the CA
stenting group (p = 0.04). Considering secondary end-
points at 1 year, CA stenting was superior to CEA
with respect to MI (2.5% stenting vs. 8.1% CEA;
p = 0.03) and major ipsilateral stroke (0% stenting vs.
3.5% CEA; p = 0.02). Superiority was an unexpected
finding, and one that was not necessary for the trial to
succeed in its goal of providing data for regulatory
approval of CA stenting in high-risk patients. More-
over, an analysis of the trial outcome that excludes MI
confers non-inferiority of stenting compared with
CEA and does not change the results of this trial.
At 3 years, data were available for 260 patients
(77.8%), including 85.6% of the stenting group and
70.1% of the endarterectomy group (107). The secon-
dary end point of cumulative incidence of death,
stroke, or MI within 30 days after the procedure or
death or ipsilateral stroke between 31 days and 1 year
was met by 24.6% who underwent stenting and 26.9%
who underwent endarterectomy. At 3 years, the over-
all major adverse event rate (30.3% CEA, 25.5% stent-
ing; p = 0.20) and incidence of death (24.2% CEA,
20.0% stenting; p = 0.280), ipsilateral stroke (7.1% CEA
vs. 6.7% stenting; p = 0.945) and target lesion revascu-
larization (7.1% CEA vs. 3.0% stenting; p = 0.084) all
favored CA stenting over CEA but not to statistical sig-
nificance. There were 15 strokes in each treatment
group. The rates of stroke in patients with asympto-
matic disease at 3 years were 10.3% in the stenting
group and 9.2% in the endarterectomy group. The
overall rates of the composite end point for the asymp-
tomatic patients were 21.4% for the stenting group and
29.2% for the endarterectomy group. The rates of
stroke in the symptomatic patients were 6.0% in the
stenting group and 8.7% in the endarterectomy group.
For these symptomatic patients, rates of the composite
end point were 32% for the stenting group and 21.7%
for the endarterectomy group. At 3 years, the end
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
result is that among the high-risk patients studied and
with the endpoints chosen, CA stenting was not
inferior to CEA in MI, stroke, and target lesion
revascularization.
EVA-3S
EVA-3S was a French multicenter, non-inferiority
randomized trial that was designed to compare the
efficacy of CA angioplasty and stent placement with
or without embolic protection against CEA for secon-
dary prevention of ischemic stroke (108). Enrollment
in the study group in which CA angioplasty and
stent placement were performed without protection
devices was halted because unprotected treatment
was associated with an excess 30-day stroke or death
rate. Starting in January 2003, patients presenting
within 4 months of ischemic cerebral or retinal stroke
with ipsilateral carotid stenosis of 60% (according
to NASCET criteria (7)) were randomized into
either the protected CA angioplasty and stent place-
ment group or the CEA group (109). Primary end-
points included any death or recurrent stroke within
30 days and at 2 to 4 years. Secondary outcomes
included MI, TIA, cranial neuropathy, functional sta-
tus at the end of the study, and degree of restenosis
in treated vessels. The incidence of stroke or death at
30 days was 3.9% after CEA versus 9.6% after stent-
ing (relative risk [RR] 2.5); at 6 months, it was 6.1%
and 11.7%, respectively (92). The HR for stenting ver-
sus endarterectomy was 1.97 (95% CI 1.063.67). The
HRs were 1.77 (1.033.02), for any stroke or peripro-
cedural death, 2.00 (0.755.33) for any periprocedural
disabling stroke or death or any non-procedural fatal
or disabling ipsilateral stroke, and 1.68 (0.743.84) for
any fatal or disabling stroke or periprocedural death.
For disabling stroke or death, the rate was 1.5% after
CEA and 3.4% after CA stenting (RR 2.2). Cranial
nerve injury was more common after CEA than stent-
ing. There were more major local complications after
stenting and more systemic complications (mainly
pulmonary) after endarterectomy, but the differences
were not significant.
EVA-3S was designed to test non-inferiority of
CA stenting, but technical shortcomings limit the inter-
pretation of this study. Patients treated without DEP
had a 25% 30-day stroke or death rate versus 7.9% in
those treated with DEP. Comparing the 7.9% with the
rate in the CEA group (3.9%), the RR becomes 2.05
(95% CI, 0.97 to 4.36), which is not statistically signifi-
cant. Surgeons were fully trained and completed 25
endarterectomies in the year before enrollment. How-
ever, interventionists were certified after performing as
few as five carotid stent procedures (5 carotid stents
among at least 35 stent procedures of supra-aortic ves-
sels or 12 carotid stents) or were allowed to enroll
patients in the trial while they were receiving their
training in CA stenting. The 12.3% stroke or death rate
among endovascular physicians tutored in CA stenting
during the trial, the overall 9.6% associated with CA
stenting with or without DEP and the 7.9% with DEP
are higher rates than those of contemporary trials or
registries (35,40,41,44,61,110).
The 4-year estimated cumulative risks of peripro-
cedural stroke or death and non-procedural ipsilateral
421
stroke in EVA-3S were significantly higher after stent-
ing than after endarterectomy (111). This difference is
largely accounted for by the higher periprocedural
risk of stenting compared with CEA. The risk of ipsi-
lateral stroke beyond the periprocedural period was
low and similar in both groups. There was no differ-
ence in mortality between the two groups.
The 4-year risk of non-procedural ipsilateral
stroke was 1.26% in the stenting group and 1.97% in
patients treated with CEA (HR 0.75) (111). Non-proce-
dural stroke risk was 4.49% for stenting and 4.94% for
CEA (HR 1.02). The 4-year risk of non-procedural
death was 16% in the CEA group and 16.1% in the
stent group (HR 1.07). Four patients in the stent group
and one patient in the CEA group required an addi-
tional revascularization procedure.
The EVA-3S trialists further analyzed the relation-
ship between anatomic and technical factors and the
30-day risk of stroke or death after CA stenting (64).
The risk of stroke or death was higher in patients with
internal CAcommon CA angulation 60 degrees (RR
4.96) and lower in those treated with cerebral protec-
tion devices (RR 0.38). The risk of stroke or death was
higher in the systematic review in patients with left-
sided CA angioplasty and stenting (RR 1.29) and when
the target internal CA stenosis was >10mm (RR 2.36).
However, no significant increase in the risk of stroke or
death was noted in patients with type III aortic arches,
aortic arch calcification, or with ostial involvement, cal-
cification, ulceration, or degree of stenosis of the target
internal CA stenosis.
SPACE
To compare the safety and prophylactic efficacy of
CEA with CA angioplasty and stent placement against
stroke in patients with symptomatic CA stenosis, the
German Ministry of Science sponsored the SPACE trial,
a prospective, randomized multicenter study (112).
Eligibility for this study was extended to patients
with severe CA stenosis (70% by duplex ultrasonog-
raphy, 50% by NASCET criteria (7), or 70% by
ECST criteria (9)) who had experienced amaurosis
fugax, TIA, or mild stroke within 180 days of ran-
domization. A total of 1,200 patients were random-
ized, 605 to CA stenting and 595 to CEA. Primary
outcome measures included 30-day incidence of ipsi-
lateral cerebrovascular events or death. A total of
1183 patients were included in the 30-day results
analysis (35). The rate of death or ipsilateral ischemic
stroke from the time of randomization up to 30 days
after the procedure was 6.84% with CA stenting and
6.34% with CEA. SPACE failed to prove non-inferior-
ity of CA stenting compared with CEA for the peri-
procedural complication rate, even though there was
no statistical difference in the outcome event rates
between CEA and CA stenting. The failure of this
trial to show non-inferiority may have resulted from
an underpowered sample and higher than expected
event rates in both groups of patients evaluated.
A secondary analysis of data from the SPACE
trial showed that the rates of ipsilateral stroke or ipsi-
lateral stroke death within 30 days were 6.2% in patient
who underwent CA stenting without DEP and 8.3% in
those treated with CA stenting and DEP, showing no
422 NEUROINTERVENTIONAL MANAGEMENT
statistical difference in the two groups (113). However,
the choice of stent did affect the periprocedural compli-
cation rate, with the outcome event rate being signifi-
cantly lower in the closed-cell stent group (5.6%) than
in the open-cell stent group (11%).
The SPACE trial 2-year results looked at 1196
patients who were randomized (607 assigned to CA
stenting and 589 assigned to CEA) (114). The rates of
primary end point events (ipsilateral ischemic stroke/
ipsilateral disabling ischemic stroke/ipsilateral ischemic
stroke or vascular death/ischemic stroke after day 30/
all-cause mortality/incidence of recurrent carotid
stenosis) after 30 days in the intention-to-treat group
were 6.45% in the CEA group and 6.92% in the CA
stenting group (p = 0.09). Overall mortality in the CA
stenting group was 6.3% and 5.0% in the CEA group
intention-to-treat population (HR 1.11, 95% CI 0.67
1.85; p = 0.63). Mortality rates in the per-protocol
groups were 6.2% in the CA stenting group and 4.9%
in the CEA group (HR 1.14, CI 0.671.94; p = 0.63).
Ipsilateral ischemic strokes in the periprocedural period
(between day 31 and year 2) occurred in 12 patients
(2.2%) in the CA stenting group and in 10 patients
(1.9%) in the CEA group (HR 1.17, 95% CI 0.512.70 in
the intention-to-treat group and HR 1.8, CI 0.512.73 in
the per-protocol patients). Ipsilateral ischemic strokes
within 2 years plus any periprocedural strokes or
deaths were 9.5% in the CA stenting group and 8.8%
in the CEA group (HR 1.10, CI 0.751.61; p = 0.62 in
the intention-to-treat analysis). Ipsilateral ischemic
strokes within 2 years plus any periprocedural strokes
or deaths in the per-protocol population were 9.4%
after CA stenting and 7.8% after CEA (HR 1.23, CI
0.821.83; p = 0.31). Intention-to-treat life-table esti-
mates of recurrent stenosis of 70% or more of the caro-
tid lumen in the CA stenting group was 10.7% and
4.6% in the CEA group (p = 0.0009) versus 11.1% in
the CA stenting group and 4.6% in the CEA group
(p = 0.007) when looking at per-protocol life table esti-
mates. Patients who were younger than 68 years
showed a strong tendency toward a better outcome
after CA stenting with respect to ipsilateral ischemic
stroke plus any periprocedural strokes and deaths
[9.0% for CEA vs. 5.0% for CA stenting (HR 0.54, 95%
CI 0.281.03 in the intention-to-treat group); 8.0% ver-
sus 4.8% (HR 0.57, 95% CI 0.291.14 in per-protocol
population)]. Patients who were at least 68-years old
were more likely to have favorable outcomes (with
respect to number of ipsilateral ischemic strokes plus
any periprocedural strokes and deaths) when treated
with CEA (8.6%) than with CA stenting (13.7%) in the
intention-to-treat group (HR 1.8, 95% CI 0.963.4) as
well as the per-protocol group (CEA 7.6% vs. CA stent-
ing 13.8% [HR 2.00, 95% CI. 904.44]). However,
patients with severe contralateral carotid stenosis had
better results after CA stenting: 23.5% versus 9.1% with
CEA (HR 0.38, 85% CI 0.071.95) in the intention-to-
treat group and the per-protocol group [CA stenting
21.9% vs. 4.8% CEA (HR 0.20, 95% CI 0.021.84)].
ICSS (CAVATAS-2)
The International Carotid Stenting Study (ICSS) is a
multicenter, international, randomized controlled trial
of patients with recently symptomatic CA stenosis (36).
The patients were randomly assigned to receive CA
stenting or CEA. The primary outcome measure of the
trial will be the 3-year rate of fatal or disabling
stroke in any territory. The main outcome measure for
the interim safety analysis was the 120-day rate of
stroke, death, or procedural MI. A total of 1,713
patients were enrolled in the trial. Between randomiza-
tion and 120 days, there were 34 (4%) events of dis-
abling stroke or death in the stenting group compared
with 27 (3.2%) in the endarterectomy group. The inci-
dence of stroke, death, or periprocedural MI was 8.5%
in the stenting group, compared with 5.2% in the CEA
group. There were more cranial nerve palsies (45 vs. 1)
and hematomas (50 vs. 31) in the CEA group than in
the stenting group. The final outcome data will be
available once the study has been completed.
TRIALS OF ANGIOPLASTY AND STENT
PLACEMENT WITH EMBOLIC PROTECTION
VERSUS CEA IN LOWER-RISK PATIENTS
CaRESS
CaRESS was a multicenter, non-randomized, prospec-
tive study comparing CA stenting with DEP and CEA
in a relatively broad-risk population (60,61,115).
Importantly, the choice of the revascularization proce-
dure was left up to the treating physician. In this way,
the CaRESS study may represent a more real-world
perspective on carotid intervention. Symptomatic
patients with >50% stenosis and asymptomatic
patients with >75% stenosis were considered for treat-
ment. The primary end point was all-cause mortality
at 30 days and 1year.
Overall, in the real-world setting of the
CaRESS study, CA stenting exhibited a trend toward
lower morbidity and mortality than CEA but
appeared slightly less durable at 30 days and 1 year.
Importantly, morbidity and mortality approached the
range of ACAS (14) and NASCET (6,7). In reviewing
the demographics of the CaRESS study population,
the only statistically significant difference was the
inclusion of more patients who had undergone pre-
vious revascularization procedures (CEA and/or CA
stenting) in the stenting cohort. Of note, no statisti-
cally significant difference was found between
CaRESS cohorts with respect to many of the high-risk
criteria in other studies (including contralateral steno-
sis, coronary artery disease, and congestive heart
failure). The lack of statistical significance in the pri-
mary endpoint suggests that the treating physicians
were able to triage these high-risk groups successfully.
The 4-year outcome data showed no differences
in the primary outcome measures of all-cause mortal-
ity, any stroke, and MI (115). The incidences of any
stroke at 4 years were 9.6% for CEA and 8.6% for CA
stenting. When these were combined with death, the
composite rate of death/nonfatal stroke and MI at
4 years was 27% in the CEA group versus 21.7% in
the CA stenting group. The secondary endpoints of
restenosis and repeat angiography were higher in the
CAS arm (these patients had a two-fold higher reste-
nosis rate). The 4-year incidences of death/nonfatal
stroke and death/nonfatal stroke/MI were higher in
the CEA arm among patients <80 years of age.
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
The differences in the 4-year incidences of death/non-
fatal stroke and death/nonfatal stroke/MI between
CEA and CA stenting were not statistically significant
in the octogenarian subgroup (patients >80 years). No
differences in outcome were seen between sympto-
matic and asymptomatic patients.
CREST
The CREST is a multicenter, randomized North Ameri-
can trial that compared the efficacy of CEA with that
of CA stent placement performed with the aid of an
embolic protection device in the prevention of stroke,
MI, and death in symptomatic patients (TIA or ipsilat-
eral non-disabling stroke within the previous 180 days)
with >50% CA stenosis and asymptomatic patients
with >70% stenosis (21). The primary endpoints were
periprocedural stroke, MI, or death, or postprocedural
ipsilateral stroke up to 4 years in standard/average-
risk patients (21,116). A credentialing phase for inter-
ventionists was included that required previous carotid
stenting experience and monitoring of the performance
of up to 20 procedures using the Acculink stent and
Acculink embolic protection system (117). During this
lead-in phase, major adverse event rates were 5.7% for
symptomatic patients and 3.5% for asymptomatic
patients. The 30-day composite rate of stroke and death
was 6.1% for symptomatic patients and 3.8% for
asymptomatic patients. Similar periprocedural morbid-
ity was observed in women and men (118) and for
those treated with or without an embolic protection
device (119). For octogenarians (120,121), the 30-day
stroke and death rate was 11.9%, which was signifi-
cantly higher than for patients aged 79 years and
younger. On the basis of experience, training, and lead-
in results, the CREST International Management Com-
mittee selected 224 interventionists to participate in the
randomized phase of the trial. The credentialing and
training of the interventionists participating in CREST
have been the most rigorous reported to date for any
randomized trial evaluating endovascular treatments.
The CREST results included 2,502 patients, 1,262
assigned to CAS and 1,240 to CEA (21). No significant
differences in the estimated 4-year rates of the primary
endpoints of death, stroke, or MI at 30 days or ipsilat-
eral stroke within 60 days of the procedure were found
between CA stenting and CEA (7.2% vs. 6.8%). The
4-year rate of stroke or death was 6.4% in the stenting
group, as compared with 4.7% in the endarterectomy
group (HR 1.50, 95% CI 1.052.15; p = 0.03). The
respective rates were 8.0% and 6.4% among sympto-
matic patients (HR 1.37, 95% CI 0.902.09; p = 0.14)
and 4.5% and 2.7% among asymptomatic patients (HR
1.86, 95% CI 0.953.66; p = 0.07). The incidence of the
primary endpoint during the periprocedural period
was similar for symptomatic CA stenting and CEA
patients (6.7% vs. 5.4%; HR for stenting 1.26, 95%
CI 0.811.96) as well as asymptomatic patients (3.5%
vs. 3.6%; HR 1.02; 95% CI 0.551.86), but there were
differences in the endpoint components (stroke 4.1%
vs. 2.3%, p = 0.012; MI 1.1% versus 2.3%, p = 0.032;
and death 0.7% vs. 0.3%, p = 0.18). After the periproce-
dural period, the incidence of ipsilateral stroke was
similarly low with CA stenting and with CEA (2.0%
and 2.4%, respectively; p = 0.85). The risk of stroke or
423
death was significantly higher for CA stenting com-
pared with CEA in symptomatic patients (6.0% vs.
3.2%, HR 1.89) but not for asymptomatic patients (2.5%
vs. 1.4%, HR 1.88). Cranial nerve palsies were less fre-
quent for CA stenting (0.3% vs. 4.7%, HR 0.07, 95% CI
0.020.18). There was a lower incidence of MI immedi-
ately after CA stenting and a lower incidence of stroke
immediately after CEA. Neither symptomatic status
nor sex showed an effect on treatment difference.
Patients aged >70 years had a slightly better outcome
after CEA and patients aged <70 years had a slightly
better outcome after CA stenting (21). The periproce-
dural safety outcomes for CREST are the best reported
to date. These results likely reflect a validated and
effective surgeon credentialing process, the rigorous
training and credentialing of interventionists, and the
increasing assimilation of endovascular expertise.
TRIALS UNDER WAY
Three prospective, randomized trials in low-risk
patients are under way, the Asymptomatic Carotid
Stenosis Stenting versus Endarterectomy Trial (ACT I)
ACST-2, and the Transatlantic Asymptomatic Carotid
Interventional Trial (TACIT). ACT I is currently enroll-
ing low-surgical risk patients with asymptomatic CA
stenosis (a single internal CA lesion with 80% but
99% stenosis) at multiple centers in North America.
The devices used in this trial are the EmboShield DEP
device and the Xact stent (Abbott Vascular). The ran-
domization scheme is 3:1 for CA stenting to CEA. The
ACST-2 trial is also randomizing asymptomatic
patients with severe CA stenosis to CEA versus stent-
ing (122). The primary analysis will include clinical MI,
stroke, and death within 30 days of either treatment,
and chances of long-term (5 years) stroke-free survival.
The investigators will use Conformite Europeenne-
marked devices, usually with cerebral protection.
TACIT will study all-risk patients with asymptomatic
CA stenosis, assigning these patients to one of two
treatment groups (122,123). The first group will receive
optimal medical therapy alone, consisting of antiplate-
let, antilipidemic, and antihypertensive therapy, as well
as strict serum glucose control and tobacco-cessation
efforts. The second group will receive optimal medical
therapy plus CA stenting using embolic protection
(with commercially available devices). The aim of the
TACIT investigators is to enroll approximately 2,400
patients, equally divided between the two treatment
groups. The primary endpoint is a composite of 30-day
mortality, all strokes within the 5-year study period,
and a neurocognitive component (neurocognitive
decline, which is defined as vascular dementia or vas-
cular depression) measured using predominantly
depression scales. Secondary endpoints will include a
detailed quality-of-life and cost-effectiveness analysis as
well as plaque characterization (detailed core labora-
tory assessments of ultrasound plaque features).
EXTRACRANIAL CA DISEASE MANAGEMENT
GUIDELINE
Recently, several medical societies collaborated to
develop a practice guideline with new recommenda-
tions on the management of patients with extracranial
424 NEUROINTERVENTIONAL MANAGEMENT
CA disease (22). On the basis of the CREST results, this
guideline includes a recommendation for CA stenting
as an alternative to CEA for symptomatic patients at
average or low risk of complications with stenosis of
>50% documented by catheter angiography or >70%
documented by noninvasive imaging, in whom the
anticipated rate of periprocedural stroke or mortality is
<6% (Class I, Level of Evidence B). For asymptomatic
patients with low perioperative risk who have >70%
carotid artery stenosis, the Class IIa recommendations
are that it is reasonable to perform CEA (Level of Evi-
dence A) and that it is reasonable to choose CA stent-
ing over CEA in patients with neck anatomy that is
unfavorable for CEA (Level of Evidence B).
In January 2011, the FDAs Circulatory System
Devices Panel voted in favor of expanding the indica-
tion for RX Acculink Carotid Stent System (Abbott,
Abbott Park, Illinois) to patients at standard risk for
surgical complications stating that the benefits of caro-
tid stenting in these patients outweigh the risks of the
endovascular procedure. Based on the proposed indica-
tion, CA stenting would be an option in standard-risk
patients with angiographic stenosis of >50% in sympto-
matic patients and >60% in asymptomatic patients.
CA STENTING PROCEDURE
Training for Carotid Stenting
Successful management of the patient with CA stent-
ing requires not only a mastery of the procedure itself
but also knowledge of clinical neurology, neuroanat-
omy and physiology, and access to appropriate imag-
ing and clinical facilities (124). Patients are entitled to
know what experience the surgeon or clinician has
before giving consent. The complications of CA stent-
ing may be devastating and require a high level of
skills. Virtual-reality training is not yet sufficiently
advanced to help in achieving these skills. The CREST
credentialing committee recognized that surgeons had
performed well at CA stenting in the lead-in phase of
the trial because they had already acquired basic skills
in catheter and guidewire manipulation (34). Multi-
specialty consensus recommendations include the fol-
lowing: primary operator experience, CA stenting
training program, basic requirements of the facilities
in which to perform CA stenting safely, and continu-
ous monitoring of performance (2,125).
Patient Preparation and Procedure Overview
The CA stenting procedure is an evolving procedure
that has been modified according to operator experi-
ence and device development. The usual sequence of
a procedure performed in conjunction with the use of
a filter device for DEP is outlined below.
The processes of angioplasty and stenting create
intimal injury that promotes thrombosis (126). There-
fore, patient preparation with a dual antiplatelet regi-
men is essential in all patients undergoing CA stenting
(127). Patients receive a dual antiplatelet regimen con-
sisting of aspirin (325mg daily) and a thienopyridine
derivative (i.e., clopidogrel, 75mg daily; or ticlopidine,
250mg twice daily) for at least 3 days before stent treat-
ment, or a loading dose of clopidogrel (300 to 600mg)
is administered for a faster response. In a randomized
comparison of aspirin and heparin versus aspirin and
clopidogrel in patients undergoing CA stenting, a 25%
rate of adverse neurological outcomes was reported in
the heparin group, compared with 0% in the clopidog-
rel group, without an additional increase in bleeding
complications (128). Premedication with clopidogrel, in
contrast to aspirin, does not achieve adequate platelet
inhibition in about two-third of the patients (129).
Different studies report clopidogrel non-response
rates from approximately 5% to 30%, which is likely
related to individual differences in clopidogrel absorp-
tion and metabolization (130). Administering a loading
dose of clopidogrel on the day of the procedure may be
insufficient to achieve adequate platelet inhibition. In a
study of 50 neurologic patients undergoing supra-aortic
stent placement procedures who received a loading dose
of 300mg of clopidogrel at least 12 hours before the
intervention, 28% were found to be clopidogrel nonres-
ponders; adverse events occurred in 5 patients (10%), all
of whom were clopidogrel nonresponders, which is a
statistically significant correlation between adverse
events and clopidogrel nonresponse (130). Testing of
platelet inhibition before neurointerventional stent
placement is advisable to reduce the risk of thromboem-
bolic complications (130) and is performed in the
authors practice before the procedure (131). In patients
who are not responsive to clopidogrel, the administra-
tion of an additional dose of clopidogrel or changing to
ticlopidine is advisable.
The procedure is performed in an angiography
suite with biplane digital subtraction and fluoroscopic
imaging capabilities. The patient is sedated but arous-
able for neurological assessment. A Foley catheter and
two peripheral intravenous lines are inserted. Blood
pressure, oxygen saturation, and cardiac rhythm are
monitored during the procedure. The CA is generally
approached percutaneously from the common femoral
artery. The interventionist should also be familiar
with radial and brachial approaches in case femoral
artery access is not possible.
An aortic arch angiogram is initially performed,
if computed tomographic (CT) angiography of the
arch was not done, to define the atherosclerotic bur-
den as well as the anatomical configuration of the
great vessels, which allows the operator to predict the
feasibility of carotid cannulation and select the devices
needed for the procedure. Selective carotid angiogra-
phy is then performed, and the severity of the stenosis
is defined. The diameters of the common CA and
internal CA are measured with attention paid to
determining a landing zone for the protection device.
Intracranial angiography is also essential prior to
intervention because the presence of tandem lesions
should be considered in the management strategy.
An intravenous bolus dose of heparin (5060 U/kg)
is administered after obtaining femoral artery access,
for a goal activated coagulation time of 250 to 300 sec-
onds. In addition, the guide catheters are flushed fre-
quently with normal saline (0.9% NaCl) with 5000 units
of heparin in each pressure bag. The air should be
actively removed from each flush bag.
Bradycardia occurs occasionally during the
angioplasty portion of the procedure. Atropine or gly-
copyrrolate and vasopressors can be given before the
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
angioplasty or should be readily available should sig-
nificant bradycardia and hypotension develop. Contin-
uous intraprocedural monitoring of heart rate, blood
pressure, and neurological status is essential.
After completion of the diagnostic angiogram
and positioning of the catheter in the common CA,
roadmapping of the cervical CA is performed. A
super-stiff 0.035-inch or 0.038-inch exchange wire is
positioned in the external CA. The diagnostic catheter
is exchanged over the wire for a 6-French (Fr) guide
sheath which is advanced over the 0.038-inch guide-
wire into the common CA below the bifurcation. For
patients who have undergone complete diagnostic cer-
ebral angiography before the stenting procedure, a
combination of a 6-Fr, 90-cm shuttle over a 6.5-Fr
head-hunter 125-cm slip-catheter (Cook, Bloomington,
Indiana, U.S.) or a 5-Fr 125-cm Vitek Catheter (Cook)
can be used. In these cases, the shuttle is introduced
primarily in the femoral artery over a 0.38-inch wire
and is parked in the descending aorta. The inner obtu-
rator and wire are removed. The 125-cm catheter is
then advanced into the shuttle, and the target vessel is
catheterized. The shuttle is brought over the wire and
the catheter in the common CA. The size of the shuttle
is usually dictated by the embolic protection device
profile and compatibility with the stent system. An
optimal angiographic view that maximizes the opening
of the bifurcation and facilitates crossing of the stenosis
should be sought. The lesion is crossed with the filter
protection device. Predilation of the stenotic vessel seg-
ment is performed at the operators discretion. A 3- to
4-mm coaxial angioplasty balloon is advanced to the
lesion over the 0.014-inch wire holding the protection
device. On rare occasions, predilation needs to be per-
formed prior to the introduction of an embolic protec-
tion device. In such cases, the balloon system is then
exchanged for a stent system.
The diameter of the stent should be sized to the
caliber of the largest segment of the CA to be covered
(usually 1 to 2mm more than the normal caliber of
the common CA). Oversizing of the stent in the inter-
nal CA does not usually result in adverse events, but
a tapered stent can better conform to the vessel wall.
Particular attention should be paid to the selection of
a stent that is long enough to cover the entire lesion.
After removing the stent system, poststent dila-
tion should be performed using a balloon with a
diameter matching that of the internal CA distal to
the stent. A coaxial balloon is usually preferred for
this purpose. The embolic protection device is then
removed, using its retrieval catheter. (When a balloon
occlusion catheter is used for cerebral protection,
instead of a filter device, the embolic debris is aspi-
rated before deflation and retrieval of the balloon.)
The most common settings for difficulty in cap-
turing deployed filter protection devices are with an
open-celled stent on a significant vessel curve (in which
a stent strut may impinge on the vessel intima) and
when the device is parked in a tortuous distal vessel.
A systematic approach will generally lead to successful
recapture of the device. Advancing the guide catheter
into the stent will bias the wire away from the stent
wall, allowing the recaptured sheath to pass. Having
the patient inhale deeply or turn his or her head oppo-
site to the direction of the vessel curve can help
425
straighten the curve or elongate the artery enough for
passage of the sheath. More aggressively, pressing on
the stent in the patients neck will also change the bias
of the wire. If the sheath is impeded by a stent strut,
re-dilatation with a larger balloon or spinning the
sheath with forward pressure will help flatten the strut
or allow passage of the sheath. If other maneuvers fail,
a 4- or 5-Fr angled glide catheter can be passed over
the DEP wire and used to capture the filter.
Proximal occlusion with flow-reversal cerebral
protection devices is used in cases with intravascular
thrombus or mobile lesions to create an absolute seal.
The previously mentioned MO.MA and Gore devices
are two such devices. The MO.MA device comprises a
catheter system compatible with an 8- or 9-Fr intro-
ducer sheath with a working channel of 6-Fr, which is
compatible with stent placement. After the perform-
ance of the diagnostic angiogram, an exchange-length
super-stiff 0.035-inch or 0.038-inch exchange wire is
positioned in the external CA. The MO.MA catheter is
advanced under roadmap guidance and with position-
ing the markers of the two inflatable low-pressure
compliant balloons to allow independent occlusion of
both the common CA (maximum diameter 513mm)
and external CA (maximum diameter 36mm), which
allows antegrade and retrograde blockage of flow,
respectively. This device may be superior to distal
protection devices, because protection is obtained
prior to crossing the stenosis with the wire, theoreti-
cally decreasing the chance of microembolization and
is maintained throughout the procedure by the work-
ing channel, which allows particulate debris to be
removed by syringe aspiration prior to restoration of
blood flow (as is the case in surgical CEA) (132). In
particular, the MO.MA device may be superior to dis-
tal filter devices by preventing microembolization of
small particles that are smaller than the filter pores or
which can pass around the filter due to poor filter
apposition on the vessel wall and thus may embolize
to the brain (133). Another advantage of this device is
in patients with significant tortuosity of the distal
internal CA in which the landing zone of distal pro-
tective devices is not optimal. For these reasons, the
use of the MO.MA is thought to be most useful in
symptomatic, elderly patients, as they are the group
with the highest risk of microembolization during car-
otid stenting (having more tortuous, significant athe-
rosclerosis, and plaques on the vessel wall). With the
Gore device, a 9-Fr arterial sheath and a 6-Fr venous
sheath are needed. Flow reversal is achieved at the
treatment site by separate balloons for temporary
occlusion of both the common CA and the external CA.
By establishing a shunt between the CA and the femo-
ral vein, blood from the collateral vessels is redirected
to the lower-pressure venous return. Redirected blood
is filtered outside the body before being reintroduced
into the venous system.
In cases in which proximal occlusion is used, the
stent is advanced over a 0.014-inch wire to cross the
lesion. After deploying the stent and performing post-
stent angioplasty, blood is withdrawn to remove par-
ticles, and the balloons are deflated. Intracranial views
are obtained to identify any intravascular occlusion or
segmental delay in contrast opacification and any vaso-
spasm or dissection at the site of the wire placement. A
426 NEUROINTERVENTIONAL MANAGEMENT
brief neurological examination is performed to identify
any new deficits. The catheter is withdrawn.
For all CA stenting cases, the access site may be
closed by closure device (e.g., Starclose, Abbott Vascu-
lar; Perclose, Abbott Vascular; Angio-Seal, St. Jude
Medical, Minnetonka, Minnesota, U.S.; or Mynx,
AccessClosure, Inc., Mountain View, California) on
the basis of operator preference, patient anatomy, and
puncture site location.
Postintervention Follow-Up
Good hydration should be maintained after the proce-
dure. Hypotension and hypertension should be
avoided. Particular attention must be paid in cases of
severe stenosis and contralateral occlusion to prevent
reperfusion hemorrhage. If a closure device has not
been used, the arterial sheath should be removed
when the activated coagulation time is <150 seconds.
The patient is usually discharged the following morn-
ing. Patients require surveillance imaging to evaluate
vessel patency. Duplex sonography evaluation should
be obtained before discharge, at 6 months, at 1 year,
and then annually thereafter. The dual antiplatelet
regimen of aspirin and clopidogrel is maintained for
4 to 6 weeks postprocedure, after which patients
remain on aspirin therapy.
Markers of High-Risk CA Stenting
Unfavorable anatomic and lesion characteristics are
factors that may influence the risk of CA stenting.
Stenotic or occluded iliac arteries or abdominal aorta
are among the unfavorable access characteristics.
A difficult arch (type II or III, calcification, or bovine
configuration) can be challenging for a less-experi-
enced operator. Occlusion of the external CA or steno-
sis involving the common CA may increase the risk in
positioning the guiding catheter or shuttle. Tortuosity
of the internal CA, severity of the lesion, degree of
calcification, and presence of intraluminal thrombus
represent other adverse factors. Low plaque echolu-
cency (GSM) on carotid ultrasound imaging is also an
adverse prognosticator (104,134).
MR imaging with ultra-high-resolution contrast-
enhanced carotid MR angiography with dedicated
carotid surface coils on a 3-tesla MR imaging scanner
may depict luminal changes related to underlying
plaque pathology (135). A study in 50 patients with
mild or moderate stenosis demonstrated significant
associations between the presence of the following
plaque characteristics and symptoms: thin/ruptured
fibrous cap and lipid-rich necrotic core, with mar-
ginal association with hemorrhage (136), which cor-
relates with a previous histologic plaque study (137).
Improvements in MR imaging of carotid plaque in
patients with carotid stenosis may help fill this gap
in the knowledge of plaque histology and further the
development of a risk-stratification treatment
approach (136,138).
Durability of CA Stenting
Durability of carotid revascularization with CA stent-
ing is a concern frequently expressed by the surgical
community. In prospective multicenter studies of
patients undergoing CA stenting, 50% restenosis
was detected by follow-up Doppler imaging in 2.9%
to 22% of cases (76,93,139141). The rate of ipsilateral
stroke with restenosis within the same period was 0%
in these studies. The wide range of restenosis rates in
these studies could be related in part to the different
definitions for restenosis (50% vs. 70%). In the CAV-
ATAS, there was a 22% restenosis rate in the endo-
vascular treatment group; this high percentage was
due to the technical inferiority of the poststenting
angioplasty and the performance of angioplasty
alone (without stenting) in this group (93). In the
SAPPHIRE study, the rate of target-vessel revascula-
rization (defined as repeat percutaneous or surgical
treatment of the CA) at 3 years was 2.4%, which was
comparable to the rate for the endarterectomy group
(107). The SPACE trial showed a higher risk of 10.7%
for restenosis (>70%) within 2 years poststenting
(114). Significant (symptomatic or 80%) recurrent
stenosis was detected by follow-up Doppler imaging
in 6 (5%) of 112 patients in our CA stenting series,
which included a follow-up review of at least
6 months in duration; repeat revascularization was
performed in three patients due to stenosis of >80%
and another three patients due to symptoms (142).
The 3-year follow-up results from the EVA-3S study
showed that restenosis (defined as 50% or occlu-
sion) was 2.5 times more frequent in the CAS group
but occurred in both treatment groups (143). Reste-
nosis of 70% or occlusion was diagnosed in 2.8%
(5 patients including 1 occlusion) of 242 patients
treated with CA stenting and 3.3% (7 patients includ-
ing 2 occlusions) of 265 patients treated with CEA. A
total of 17 patients had a recurrent stroke (10 in the
CAS group and 7 in the CEA group) but only 6 had
an ipsilateral stroke (3 in each group). Recurrent
stroke occurred (after restenosis) in 1 (2.6%) of the
39 patients with restenosis compared to 16 (3.4%) of
the 468 patients without restenosis. A stroke or TIA
occurred in 4 (10.3%) of the patients with restenosis
and 25 (5.3%) of those without restenosis during the
same follow-up period.
COMPLICATION OCCURRENCE AND
AVOIDANCE
From puncture of the femoral artery to retrieval of the
protection device and performance of the final angio-
gram, potential exists for complications during CA
stenting that can be threatening to life, limb, kidneys,
or brain. Delayed neurological, cardiac, and peripheral
complications can also occur and may require imme-
diate intervention for meaningful salvage. Knowledge
of these complications is essential to ensure quick rec-
ognition and effective management. Patient selection
is the most important factor in minimizing complica-
tions associated with CA stenting. The experience of
the interventionist and staff are the second most
important factor. It is essential that all personnel are
familiar with all the equipment, devices, and pharma-
cological agents, critical care management, and the
disease process treated. Many risks associated with
CA stenting can be mitigated before and during the
procedure (Table 20.2).
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE
Table 20.2 High-risk Features for CA Stenting
. Access: stenotic or occluded iliac arteries or abdominal aorta
. Aortic arch: type II or III, bovine configuration
. Arch disease: calcifications and plaque
. Supra-aortic vessel origin disease: tortuous proximal target
vessel, occluded external carotid artery, stenosis at the bifur-
cation involving both the internal and external CAs
. Lesion: location at a curve, severe stenosis, circumferential
calcification, intraluminal thrombus
. Distal internal CA tortuosity
Access-Related Complications
The rate of access-related complications occurring dur-
ing diagnostic cerebral angiography can be as high as
5% (144). The most common access problems include
pseudoaneurysms, arteriovenous fistulas, hematomas
(local or retroperitoneal), deep vein thrombosis, and
local neurologic complications (involving the femoral
nerve or lateral cutaneous nerve). Femoral artery
occlusion and bleeding can also occur in an acute or
delayed fashion.
Pseudoaneurysms can occur in up to 7.5% of
femoral artery catheterizations and can cause distal
embolization, local neurovascular compression, or
hemorrhage; clinically, the patient complains of pain or
pulsatile groin mass (145). Arteriovenous fistulas occur
less often (incidence of approximately 1%); the clinician
should be suspicious in a patient with limb pain or a
new femoral hematoma or bruit following femoral
catheterization (146). Local hematomas manifest usually
as a swelling or growing mass around the puncture
site, associated with local pain. For the management of
this complication, local compression is preferred with
follow-up hemoglobin levels obtained. Retroperitoneal
hematoma should be ruled out in patients with hypo-
tension, lower abdominal or flank pain, or with acute
drop in hemoglobin. In the setting of acute femoral
artery occlusion, the patient may complain of limb par-
esthesia, a painful or cold limb; and the physical
examination may reveal a cold, pale limb with the
absence of peripheral pulses. Due to the proximity of
the femoral artery to the femoral nerve and the lateral
cutaneous nerve, symptoms like local hypesthesia, dys-
esthesias, or hypalgesia can be caused by direct injury,
local anesthesia injection, or local hematoma (147).
These symptoms can last for up to 6 months.
The external CA and its branches are used to
support a guidewire during the exchange of a diag-
nostic catheter for a guide sheath or catheter. Vessel
perforation in this setting has been described by our
group (148). To prevent this complication, large
branches of the external CA, preferably the internal
maxillary artery or occipital artery, should be used for
exchange maneuvers.
Neurological Complications
Stroke can occur at any point after femoral artery
access has been obtained. If a patient develops a sud-
den neurological change, the differential diagnosis
entertained should include hemorrhage and ischemia,
most often due to embolism. On the basis of findings
of the neurological examination, rapid access should
427
be gained to the vessel suspected of harboring the
problem. If the patients airway is compromised, intu-
bation should be performed. If no vessel cut-off or
slow flow is appreciated, hemorrhage must be ruled
out; and the patient should undergo a cranial CT
scan. On the basis of transcranial Doppler data in
which protected stenting with the PercuSurge device
was compared to unprotected stenting, the highest-
risk maneuvers for embolism in conjunction with
unprotected stenting, from lowest to highest risk,
were predilation angioplasty, stenting, and postdila-
tion angioplasty (97).
The intracranial complications of CA stenting
can be grouped into large vessel occlusion, shower of
emboli, and hemorrhage. If a clear large vessel cut-off
can be seen, an immediate attempt should be under-
taken to recanalize the occluded vessel. If the angio-
gram documents slow flow and the CT scan is
negative for hemorrhage, IIb/IIIa antiplatelet agents
can be administered. If a hemorrhage is identified,
heparin anticoagulation is reversed with protamine,
the blood pressure tightly controlled, and a repeat CT
scan is obtained within 6 to 12 hours. Life-threatening
intracranial hematomas in neurologically salvageable
patients can be evacuated.
Carotid dissection or spasm occurring during
the stenting procedure may lead to neurological com-
plications. For cases of small, asymptomatic and
non-flow-limiting dissections, clinical observation is
recommended. Stenting is warranted if the dissection
is symptomatic or flow-limiting. Spasm is frequently
encountered when the DEP device or the guide cathe-
ter straightens or moves a kink in the CA. This can
be ignored, as it will resolve with device retrieval and
often resolves after stenting and postdilatation
angioplasty.
Systemic Complications
Systemic complications may also occur following CA
stenting. These include seizures, MI, contrast-induced
nephropathy, cholesterol-embolization syndrome, and
contrast-induced allergy. The interventionist, treating
institution, and ancillary staff should be versed in the
management of all these conditions as most can be
readily treated.
Contrast-induced nephropathy may occur in
2% to 25% of patients (149). This complication may
not be recognized for 4872 hours because of the rela-
tively slow accumulation of creatinine (150).
Our aim is to minimize the risk of procedural
complications by prevention, which requires identifi-
cation of high-risk patients, elimination of predispos-
ing conditions, and, if needed, the application of
treatments that lower this risk.
ILLUSTRATIVE CASES
Case 1 (Tortuous Anatomy)
A 68-year-old woman with a remote history of two
left hemispheric strokes was found to have severe left
internal CA origin stenosis on noninvasive studies.
Her past medical history also included diabetes,
hypertension, morbid obesity, and inactive congestive
428 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

Figure 20.1 Case 1: (A) Anteroposterior (AP) and (B) lateral projections of left common CA injection demonstrating 80% stenosis of
the internal CA origin. Note the sharp turn in the internal CA just distal to the stenosis. Such tortuosity is a relative contraindication to
DEP devices. (C) AP view showing the establishment of flow reversal after occlusion in the external CA and distal common CA. An
arteriovenous conduit had been created between the left internal CA and the left common femoral vein prior to flow reversal. (D) AP
view shows good positioning of the stent. The stent does not involve the tortuous segment of the internal CA.

heart failure. She had a mild residual right hemipare-
sis and had no additional ischemic symptoms since
her strokes 3 years earlier. Angiography confirmed
80% stenosis of the left internal CA origin. Because
she had a short, immobile neck and a high carotid
bifurcation at the level of the C2 vertebral body, the
patient was selected for internal CA stenting. The tor-
tuosity of the internal CA prohibited safe advance-
ment of a DEP device (Fig. 20.1A, B). Carotid stenting
with angioplasty was performed successfully using
proximal protection with a flow-reversal system (Gore
Flow-Reversal System) (Fig. 20.1C). Care was taken
not to position the stent in the tortuous segment of
the internal CA (Fig. 20.1D). Occlusion time was
approximately 12 minutes, and the patient tolerated
the procedure well. She was discharged the next day
at her baseline neurological condition.
Case 2 (Difficult Access)
A 76-year-old man had an extensive vascular history
consisting of bilateral CEA, left common CA origin
stenting (Fig. 20.2A), pacemaker placement for sick-
sinus syndrome, CABG, and peripheral vascular dis-
ease. Surveillance Doppler imaging studies revealed
progressively elevated velocities in the left carotid bifur-
cation. A diagnostic angiogram confirmed 86% stenosis
of the left carotid bifurcation (Fig. 20.2B), with a patent
left common CA origin stent from the arch and a type
II arch (Fig. 20.2A). The patient had left CEA restenosis,
and CA origin stenting was planned for carotid
bifurcation stenosis treatment with consideration of the
difficult access, along with the need to cross the stent in
the left origin common CA without damaging that
stent. The patient received 3,500 units of heparin (acti-
vated coagulation time of 309 seconds). Using a Supra-
Core 0.035-inch wire (Abbott Vascular), an 8-Fr
Simmons II catheter was reconstituted in the left subcla-
vian artery and was engaged safely in the left common
CA (Fig. 20.2C). A 7.2-mm EmboShield NAV6 DEP
(Abbott Vascular) was deployed. With the aid of a road-
map, an 8mm  36mm Wallstent (Boston Scientific)
was deployed, covering the lesion. Poststenting angio-
plasty was performed with a 5mm  30mm Viatrac
balloon (Abbott Vascular) (Fig. 20.2D). The patient toler-
ated the procedure well and was discharged the next
day, neurologically intact.
CONCLUSIONS
In 2011, the CA angioplasty and stenting procedure
may be considered equivalent to CEA for the treat-
ment of standard- to high-risk patients. In real-world
patient selection, CA stenting and CEA are comple-
mentary procedures. The availability of both
approaches at a single center can certainly optimize
patient care (151). CA stenting studies in the average-
or lower-risk population showed that CA stenting can
be performed with acceptable risks and is indicated as
an alternative to CEA for symptomatic patients and
for selected patients with asymptomatic stenosis. In
2011, the FDA expanded the indication of CA stenting
 ENDOVASCULAR TREATMENT OF EXTRACRANIAL CAROTID ATHEROSCLEROTIC DISEASE 429

(A) (B)

(C) (D)

Figure 20.2 Case 2: (A) AP arch study shows a Type II aortic arch and a stent placed at the origin of the left common CA. (B) Lateral
projection of left CA, 86% stenosis. (C) AP view of the left common CA; an 8-Fr Simmons II catheter positioned in the common CA
through the stent. (D) Poststenting angiogram: AP view of the left CA.

to patients at standard risk. In terms of durability,
stenting is slightly inferior to endarterectomy (as
shown in studies mentioned in this chapter), and the
results of longer-term follow-up will be accumulated.
With future technological developments, including
improved embolic protection systems and refined
stents with smaller delivery platforms, with adequate
risk stratification, and careful selection of patients, CA
stenting may become the more common procedure for
carotid revascularization.
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 21
Stenting and angioplasty for intracranial atherosclerotic
occlusive disease
Gabriela Spilberg, Neil V. Patel, Anna Luisa Kuhn, Matthew J. Gounis, and Ajay K. Wakhloo
INTRODUCTION
Intracranial atherosclerotic disease (ICAD) is the major
cause of stroke worldwide and accounts for about 10%
of ischemic stroke in the United States. As technology
and our understanding of ICAD have evolved, treat-
ment has come to encompass a diversity of medical,
surgical, and endovascular approaches. In this chapter,
we will review relevant anatomy and pathophysiology,
describe the current state of the art in endovascular
ICAD treatment, and discuss developing trends that
will shape the future management of this disease.
HISTORY
The father of interventional radiology, Charles T.
Dotter, introduced the concept of percutaneous translu-
minal angioplasty (PTA) in 1964, at the University of
Oregon in Portland. Though the technique was initially
used for femoropopliteal vessels, Dotter recognized the
potential of this technique for use in the coronary,
renal, carotid and vertebral arteries. Presciently, he sug-
gested the need for a device with externally controlled
concentric expansion and the possibility of using intra-
vascular splints to keep arteries patent (1,2). In 1974, a
Zurich cardiologist, Andreas Gruntzig, addressed the
first of these suggestions by inventing a balloon cathe-
ter to dilate peripheral arteries. In 1978, he published
the first five cases of percutaneous transluminal coro-
nary angioplastya feat made possible by this new
device (3,4). This publication helped to fuel the devel-
opment of PTA as an endovascular approach to treat-
ing vascular occlusive disease of the peripheral, renal,
and coronary vascular systems.
In 1980, Klaus Mathias pioneered the application of
PTA to the carotid bifurcation (5,6). In the same year,
Sundt and colleagues published the first report of suc-
cessful intracranial angioplasty, done to treat atheroscler-
otic lesions in the basilar arteries of two patients (7).
More recently, the endovascular treatment of
ICAD has been aided by the development of stents and
delivery systems specifically designed to facilitate safer,
easier, and more effective navigation through the neu-
rovascular system. The advent of this new generation
of neurovascular devices has prompted consideration
of stent-assisted angioplasty as a primary approach to
treating intracranial arterial stenosis. This remains
an exciting, rapidly developing field, and our under-
standing of ICAD and the best treatment strategies,
including the role of stenting and angioplasty, contin-
ues to evolve (8).
BACKGROUND
Stroke is the third most common cause of death in the
United States and affects more than 790,000 people each
year. This disease is a leading cause of major disability
and a major public health problem, resulting in an esti-
mated direct and indirect cost of $73.7 billion in 2010 (9.)
ICAD is responsible for 810% of all ischemic strokes in
North America (10,11). Not surprisingly, the risk factors
for stroke mirror those for ICAD; these include smoking,
hypertension, diabetes mellitus, and hypercholesterole-
mia (12,13). Interestingly, there are racial differences in
the patterns of atherosclerotic disease. African-Americans
and Hispanics are more likely to develop intracranial
atherosclerosis, while Caucasians are more likely to
suffer from extracranial disease. Japanese and Chinese
have also been found to have a higher incidence and
more severe type of intracranial atherosclerosis when
compared to American Caucasians (1417). The reason
for the higher frequency of ICAD amongst African-
Americans, Chinese, Japanese, and Hispanic populations
is not known. There may be a genetic basis for these
trends; however, given the diversity of these populations,
any genetic predisposition is likely to be multi-factorial.
Four mechanisms have been proposed to cause
transient ischemic attacks (TIAs) and ischemic strokes
in patients with intracranial atherosclerosis: (i) hypo-
perfusion (18,19); (ii) thrombosis at the site of stenosis
due to plaque rupture, intra-plaque hemorrhage, or
occlusive plaque growth (20,21); (iii) thromboembolic
events distal to the site of stenosis (2224); or (iv)
direct occlusion of small penetrating arteries at the
site of the plaque (25,26). These proposed mechanisms
can occur in conjunction or separately (27,28).
Atherosclerosis is also closely dependent on local
hemodynamic factors, including the shear stress that
develops in the boundary between flowing blood and
the vascular endothelium. Abnormal shear forces pro-
mote the endothelial dysfunction and inflammation
that initiate atherosclerosis (29).
INTRACRANIAL ATHEROSCLEROTIC DISEASE
Baker and Iannone described the anatomical distribution
and severity of atherosclerosis in 173 consecutive
autopsies (30). The most common sites of involvement
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE
were the internal carotid artery (ICA) origin, the distal
basilar artery, and the proximal-to-mid basilar artery.
The middle cerebral artery (MCA) was the next most
frequently involved, followed by the vertebral artery and
the posterior cerebral artery (PCA). The vessels most
commonly spared were the posterior inferior cerebellar
artery (PICA), the superior cerebellar artery (SCA), and
the distal anterior cerebral artery (ACA) (12).
The prevalence and importance of asymptomatic
ICAD is unknown. In a recent study, autopsies were
done in 259 patients, mostly Caucasians, with patho-
logical evidence of brain infarction (31). The overall
prevalence of intracranial plaques in this population,
including stenotic and non-stenotic lesions, was 62.2%.
The study used a control group of patients with brain
hemorrhage and after controlling for age, gender, and
heart weight, this difference remained statistically sig-
nificant: intracranial plaques were 24 times more
common in patients with brain infarction than in
patients with brain hemorrhage.
INTRACRANIAL VESSEL STRUCTURE
Cerebral arteries have a different structure from sys-
temic muscular arteries, particularly when compared
to the coronaries. Cerebral arteries are smaller in
diameter than the proximal coronary arteries; the
outer diameter of the proximal MCA has been meas-
ured as 2.41 0.41mm (32), while the outer diameter
of the left anterior descending coronary artery ranges
from 4.5 0.3mm proximally to 2.5 0.37mm distally
(33,34). Cerebral arteries also have thinner walls and
lack a robust adventitia (35). The external elastic lamina
and vasa vasorum are nearly absent, the media is thin,
and there are multiple perforators originating from the
vessel segments supplying healthy brain tissue. In addi-
tion, the cerebrospinal fluid in which the pial vessels
run is a radically different microenvironment than the
soft tissues that surround the coronary arteries (36).
These environmental differences have important prac-
tical implications. For instance, the inflation pressures
during balloon angioplasty of the cerebral arteries are
lower than those achievable in the coronary arteries
(37,38). Also notably, the flow, flow velocity, and pulse
index in cerebral arteries are higher than the values
found in the coronary system.
DIAGNOSTIC STUDIES
Noninvasive Imaging
There is a variety of noninvasive tests available for
evaluating patients with suspected ICAD. Transcra-
nial duplex ultrasonography, including Doppler and
structural images, is a rapid, low-cost technique that
is often used for monitoring patients that have known
arterial stenosis. Single photon emission computed
tomography (SPECT, Fig. 21.1A-D) is most useful in
the evaluation of cerebral perfusion and cerebrovascu-
lar reserve (by using an acetazolamide challenge). A
SPECT study is typically performed using technetium-
based tracers (99mTc-HMPAO or 99m-Tc-ECD), but can
also be achieved using radiolabeled Xenon. Computed
tomography can provide angiographic information
(CTA) and perfusion information (CTP, Fig 21.1E-H),
435
though the spatial and temporal resolution are typically
much lower than achievable by conventional catheter-
based angiography. Magnetic resonance imaging (MRI)
and magnetic resonance angiography (MRA) are a
powerful set of techniques that can provide information
about the presence and composition of arterial stenosis
and about the sequelae of ischemic injury to the brain.
MRI, however, is typically hampered by limitations
in spatial resolution and is susceptible to substantial
artifacts. Owing to its high spatial and temporal reso-
lution, catheter-based digital subtraction angiography
(DSA) remains the most sensitive and specific test for
ICAD (28,39--42).
INDICATIONS FOR TREATMENT
In the United States, ICAD causes nearly 70,000 to 90,000
ischemic strokes per year (11). The estimated risk of
stroke in the setting of intracranial arterial stenosis varies
from approximately 7% to 40% per year with or without
medical treatment (43,44). Intracranial stenosis may
progress, regress, or remain unchanged (45,46). Little is
understood about the mechanisms of disease progres-
sion. What is known is that of patients who present with
a TIA, up to a quarter will die within a year (47).
The Warfarin versus Aspirin for Symptomatic
Intracranial Disease (WASID) study was a double-
blind randomized clinical trial that compared War-
farin (target international normalized ratio between 2
and 3) versus aspirin (1300mg/day) in preventing
stroke and vascular death in symptomatic patients
with stenosis of 5099% in a major intracranial artery.
The study was prematurely terminated because of
safety concerns with Warfarin. The drug was associ-
ated with significantly higher rates of death and major
hemorrhage, providing no significant benefit over
aspirin for preventing stroke in this subset of patients.
The risk of stroke was still significant in both the War-
farin and the aspirin arms during the mean follow-up
period of 1.8 years. Of the 280 patients treated with
aspirin, 15% suffered strokes in the territory of the
stenotic artery. Of the 289 patients receiving Warfarin,
12.1% had ischemic stroke in the same territory. The
study concluded that aspirin should be the preferred
medical therapy for patients with stroke or TIA due to
intracranial stenosis, but additional therapies were
necessary for secondary prevention (44,48).
WASID also contributed by delineating the sub-
group of patients with highest risk of stroke due to
intracranial stenosis. Risk of stroke in the territory of
the stenotic artery was highest with stenosis greater
than 70% (hazard ratio 2.03; 95% confidence interval
1.29 to 3.22; P = 0.0025). Risk of stroke for 1 and
2 years was 6% and 10%, respectively in patients with
5069% stenosis, but rose to 19 and 20% in patients
with 7099% stenosis. Patients enrolled early (17
days) after the event (hazard ratio 1.69; 95% confi-
dence interval 1.06 to 2.72; P = 0.028) also had higher
risk. Recent symptoms led to a stroke risk of 15% at
1 year compared with a stroke risk of 8% in those
with symptoms more than 17 days from enrollment.
Women were also at increased risk, even though this
was of borderline significance (hazard ratio 1.59; 95%
confidence interval 1.00 to 2.55; P = 0.051). The follow-
ing risk factors were not significantly associated with
436 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

(sec) (ml/100g/min)

(E) (F)

(sec) (ml/100g/min)
(G) (H)

Figure 21.1 Examples of imaging methods employed to study cerebral hemodynamics prior to and after endovascular treatment of
intracranial atherosclerosis. A 56-year-old female was diagnosed with symptomatic, tandem left internal carotid and left Middle cerebral
artery (MCA) stenoses (AD). 99mTechnetium-hexamethylpropyleneamine single photon emission computed tomography before stent-
ing (A, Btwo separate axial slices) shows mild degree of decreased cortical radiotracer uptake in the left frontal and temporal/parietal
lobes at baseline (A) and that with Diamox demonstrates a moderate to severe perfusion deficit (B). One-month after endovascular
treatment with intracranial angioplasty and stent placement, the baseline (C) and post Diamox administration (D) images depict a nor-
mal pattern of radiotracer distribution. A 73-year-old man presented with an acute ischemic stroke and was found to have a right MCA
stenosis. Computed-tomography perfusion imaging prior to stent placement revealed a large area of increased mean transit time (MTT)
(E) and somewhat deceased Cerebral blood flow (CF) (F) in the right MCA distribution. Two-days following endovascular treatment
with stent deployment there was resolution of MTT (G) and CBF (H) deficits of the right MCA distribution.
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE
an increased risk of stroke in the territory of the sten-
otic artery: age, race, location of stenosis, length of
stenosis, other vascular risk factors, co-morbidities
and treatment with antithrombotic agents at the time
of the qualifying event (49,50).
Recently, a retrospective analysis was carried out
in a single center trial from Taiwan, which evaluated
medical therapy alone versus medical therapy and
stenting for 114 symptomatic patients with angiograph-
ically proven 70% intracranial atherosclerotic stenosis.
The Mean follow-up period was 17.3 months. The total
ischemic event rate was similar in the two groups dur-
ing a 3-year follow-up; however, the stent group had a
more favorable functional outcome despite an
increased rate of minor periprocedural strokes (51).
A randomized double-blind, controlled, manufac-
turer-supported trial was conducted to study the role
of cilostazol secondary stroke prevention. This drug is
a phosphodiesterase3 inhibitor with antiplatelet, vaso-
dilatory, antiatherogenic, and antiproliferative actions.
One hundred and thirty-five patients were enrolled
and received cilostazol or placebo within 2 weeks after
an ischemic event. All patients also received aspirin.
ICAD was assessed by MRA and transcranial Doppler
at recruitment point and 6 months later. The group
treated with cilostazol had less progression of sympto-
matic ICAD than the group who received placebo
(6.7% vs. 28.8%). Also, ICAD regression was more fre-
quent in the cilostazol group (24.4% vs. 15.4%); how-
ever, the statistical significance of these findings is not
reported. Cilostazol might have an adjunctive role for
patients with symptomatic ICAD; however, further
studies are necessary to evaluate these effects (52).
At this time, there are no published data that
establishes equivalence or superiority of other available
antiplatelet agents over aspirin for secondary stroke
prevention in patients with intracranial stenosis (53).
SURGICAL TREATMENT
An international randomized trial, called The EC/IC
Bypass Study Group, was done to evaluate whether
bypass surgery would benefit patients with sympto-
matic atherosclerotic disease of the ICA. A total of
1377 patients with recent hemispheric strokes, retinal
infarction, or TIAs, who also had atherosclerotic dis-
ease of the ipsilateral internal carotid or MCA, were
randomized. Of those, 714 were assigned to the best
medical therapy, and the other 663 to the bypass sur-
gery, plus medical therapy. Average follow-up was
55.8 months. The results were published in 1985; non-
fatal and fatal stroke occurred both more frequently
and earlier in the surgical arm. Secondary survival
analyses comparing both groups for major strokes and
all deaths, for all strokes and all deaths, and for ipsi-
lateral ischemic strokes demonstrated lack of benefit
from surgery (54). Since bypass surgery failed as a
treatment option, the development of treatment has
increasingly focused upon endovascular techniques.
PERCUTANEOUS TRANSLUMINAL BALLOON
ANGIOPLASTY
Prior to the development of stents that could be safely
navigated into the intracranial circulation, PTA was
437
the only available endovascular approach to treating
ICAD. The major risks of intracranial balloon angio-
plasty are distal embolization, vessel dissection and
occlusion, vasospasm, vessel rupture, and arterial
thrombosis during or immediately after PTA. Another
major disadvantage of the procedure is the risk of
restenosis at follow-up, which can result from neointi-
mal hyperproliferation or from progression of the
underlying disease (54). The risks of dissection and
restenosis have formed the chief impetus for the cur-
rent move away from isolated PTA to the primary or
adjunctive use of intracranial stents.
In 1999, Connors et al. (55) published a retro-
spective analysis of elective intracranial angioplasties
for primary ICAD. Since 1994, the use of an under-
sized balloon was routine and since 1996 all patients
were treated with the antiplatelet agent abciximab
(ReoPro, Eli Lilly & Co., Indianapolis, Indiana, U.S.)
during the angiographic procedure. The authors
described the results of 50 elective PTAs performed
after 1994. Antiplatelet drug therapy was adminis-
tered in 43 of these cases. A good angiographic and
clinical outcome was achieved in 98% (49 cases). Com-
plications observed included a postprocedural suba-
cute infarction with hemorrhagic conversion (2%), a
vessel perforation with the occlusion wire causing a
delayed intracranial bleed and death of the patient
(2%), and two cases of periprocedural TIA events
(4%). Residual stenosis after angioplasty was seen in
16% (8 cases; >50% but <70%). Four cases of late reste-
nosis (8%) were diagnosed between 3 and 12 months
of angiographic follow-up.
A further retrospective study conducted by
Marks and colleges (56) published in 2005 evaluated
36 patients who were treated with primary balloon
angioplasty for symptomatic intracranial atheroscl-
erotic stenosis. All patients underwent angioplasty
alone. Improvement in the degree of the stenosis was
achieved in 35 patients (97.2%). One patient suffered a
MCA vessel rupture during treatment. Other clinical
complications (8.3%) within 30 days postprocedural
included one stroke (2.8%) and two deaths (5.5%).
Residual stenosis remained in 18 cases (50%) and
ranged between 50% and 90%. During follow-up, two
strokes on the appropriate site of angioplasty treat-
ment and three strokes outside of the angioplasty
territory occurred within a time period of 2 months to
9 years. The annualized stroke rate in the area of
angioplasty was 3.36% compared to 5.38% for strokes
in the contra-lateral territory of treatment. Three
deaths based on cardiac reasons were observed within
25 months and 10 years after treatment.
Wojak et al. (57) included 60 patients with 71
atherosclerotic lesions into their study. Although on
maximal adjunctive medical therapy, 40.8% of the
lesions remained recurrently or repeatedly sympto-
matic. Only 14% were asymptomatic. The authors
reported a complication-free outcome rate of 90.5%. A
total of 84 procedures were performed. Twenty-two of
these procedures (26.2%) required additional stent
placement due to insufficient re-opening of the sten-
otic vessel. In 62 cases (73.8%), angioplasty alone was
performed. One periprocedural death occurred
because of vessel rupture (1.2%). Seven non-fatal pro-
cedural complication events included three TIAs
438 NEUROINTERVENTIONAL MANAGEMENT

(A)

(B) (C)

Figure 21.2 Endovascular devices approved by the U.S. FDA for the endovascular treatment of intracranial atherosclerosis include
the Pharos Vitesse Neurovascular Stent System (A, unexpanded) which consists of cobaltchromium stent with gold plating to improve
radiopacity and coated with silicon carbide. This low-profile device is mounted on a balloon, that when inflated (B) plastically expands
the stent device. The Wingspan system consists of a balloon for pre-dilation angioplasty (C top panel: Gateway PTA Balloon Catheter)
and a self-expanding nickeltitanium stent with proximal and distal radiopaque markers (C bottom panel: Wingspan Stent System).
Images A and B provided courtesy of Codman Neurovascular and C provided courtesy of Stryker Neurovascular (formerly Boston
Scientific Neurovascular).

(43%), two contralateral strokes (28.6%), a cerebral
bleed due to hyperperfusion syndrome (14.2%), and
a wire perforation (14.2%). The overall complication
rate was 8.3% (7 out of 84 procedures) and the total
periprocedural stroke and death rate was 4.8%. In 10
cases, artery dissections were radiographically detected;
however, none of these had to be treated. Residual
stenosis (>50%) was seen in 13% of the cases but
remained asymptomatic. Restenosis was diagnosed
in 23 cases (27.4%). Only 5 of these were asymp-
tomatic. The annual stroke rate amounted to 1.8%
compared to the total annualized stroke and death
rate of 3.0%.
PRIMARY STENTING AND STENT-ASSISTED
ANGIOPLASTY
The term stent is derived from the name Charles
Stent (18451901), an English dentist who developed a
mold that was used to form an impression of the teeth
and oral cavity. Later, the term was used in asso-
ciation with a device that held a skin graft in position,
and for a support for tubular structures that were
being anastomosed. More recently, the term has been
used to describe an endovascular scaffolding used
relieve and prevent vascular obstructions (58).
The potential advantages of stenting over balloon
angioplasty alone were first hypothesized to be a
smaller risk of acute thrombosis from intimal dissec-
tion, and improved long-term patency from larger post-
procedural vessel diameters. The main problem for the
use of stents to treat intracranial lesions was the avail-
ability of devices that could be navigated within the
intracranial circulation. Most of the experience with
intracranial stenting had been with the off-label use of
balloon mounted coronary stents, but these were diffi-
cult to deliver. Another question that has been raised is
the patency of side branches when using stents across
segments that have perforating arteries (59).
The lack of specific neurovascular stents was
quickly addressed by the industry, developing new
technologies.
NEUROLINK SYSTEM
The Neurolink System (Guidant Corporation, San
Francisco, California, U.S.) was the first dedicated neuro-
vascular stent. The Stenting of Symptomatic Atheros-
clerotic Lesions in the Vertebral or Intracranial Arteries
(SSYLVIA) study was a prospective, multicenter, single-
arm trial that assessed the safety and procedural
feasibility of this device. It consisted of a balloon dilata-
tion catheter and a stent delivery system for treatment
of vertebral or intracranial artery stenosis. The stent
was successfully delivered in position in 95% of the
61 patients. The composite 1-year stroke rate was 13.1%
(8/61), and 35% (18/51) of the patients in the study
developed a stenosis of more than 50% at angiography
by 6 months. After this trial, the Neurolink received a
humanitarian device exemption (HDE) from the Food
and Drug Administration (FDA) for the treatment of
high stroke risk patients who had failed medical therapy
(60). This device is no longer commercially available.
WINGSPAN STENT
The second stent designed for the treatment of ICAD
was the Wingspan stent (Stryker Neurovascular,
Fremont, California, U.S.) (Fig. 21.2C). The treatment
concept was new: undersized pre-dilatation with a
Gateway balloon catheter at nominal pressure with
slow inflation, followed by deployment of a self-
expanding nitinol stent (case example Fig. 21.3 AC).
The Wingspan Multicenter European Study enrolled
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE 439

(A) (B) (C)

(D) (E) (F)

Figure 21.3 (Top panel): A 61-year-old female with history of hypertension and tobacco use presented to the emergency department
with aphasia. An MRI study showed multiple recent infarcts in the left Middle cerebral artery (MCA) territory. Digital subtraction angiog-
raphy (DSA). demonstrated a >80% stenosis of the left Middle cerebral artery (MCA) (Afrontal projection, white arrow). Angioplasty
and deployment of the Wingspan self-expanding stent was performed, and control angiography revealed partial resolution of the steno-
sis (Bfrontal projection, white arrow). Follow-up DSA performed 16-months after treatment reveals complete remodeling of the dis-
eased MCA with excellent distal perfusion (Cfrontal projection, white arrow). (Bottom panel): A 49-year-old man with history of
hypertension experienced left-sided weakness and slurred speech. An MRI study revealed multiple cortical infarcts in the right hemi-
sphere. Subsequent DSA revealed >70% stenotic lesion of the right cavernous carotid artery (Dlateral oblique projection, black
arrow). Endovascular treatment with the Pharos balloon-mounted stent showed complete revascularization (Elateral oblique projec-
tion, black arrow). Follow-up DSA performed 1-year after treatment shows a completely patent right Internal carotid artery (ICA) with no
signs of in-stent stenosis (Flateral projection, black arrow).

45 medically refractory patients from 12 European
sites with symptomatic intracranial stenosis, angio-
graphically demonstrated greater than 50%. Technical
success with angioplasty and stenting was achieved in
98% (44/45) of patients. The periprocedural 30-day
death or ipsilateral stroke rate was 4.5% (2/44), and
the 6-month death or ipsilateral stroke rate was 7.1%
(3/42), with an all-cause stroke rate of 9.5% (4/43). At
6 months, 3 of 40 patients (7.5%) evaluated angio-
graphically showed a restenosis of 50% or more, but
remained asymptomatic (8). Based on these data, the
U.S. FDA granted an HDE approval for the Wingspan
stent system in 2005 for treatment of symptomatic
intracranial stenosis greater than 50% and refractory
to maximal medical therapy. Approval for this stent
system was also obtained in Europe.
To study the value of Wingspan for ICAD in a
larger population, the National Institutes of Health
(NIH) funded the Multicenter Wingspan Intracranial
Stent Registry, with 16 medical centers involved.
A total of 129 patients with symptomatic 70% to
99% intracranial stenosis were enrolled. The techni-
cal success rate was 96.7%. The stented intracranial
arteries were the MCA in 33%, carotid 26%, verte-
bral artery 24%, and basilar artery 17%. The fre-
quency of any stroke, intracerebral hemorrhage, or
death within 30 days or ipsilateral stroke beyond
30 days was 14.0% at 6 months. Restenosis (>50%
luminal diameter) on follow-up angiography was
seen in 13 patients (25%). Compared to the previous
Wingspan study, this registry demonstrated higher
rates of a restenosis and stroke or death within
30 days of stenting. Technical success achieved was
similar. The authors concluded that the event rates
in high-risk patients in the Warfarin-Aspirin Symp-
tomatic Intracranial Disease (WASID) study versus
the results obtained in the NIH registry did not
answer the question whether treatment with the
Wingspan stent is beneficial in comparison to medical
therapy (61).
440 NEUROINTERVENTIONAL MANAGEMENT
Another US Trial was supported by Boston Scien-
tific (Natick, Massachusetts, U.S.), to better understand
the periprocedural complications of the Wingspan stent.
Seventy-eight, mostly symptomatic patients (stroke or
TIA), were enrolled with intracranial stenosis. Stenosis
70% was present in 54 patients. Fifty-nine patients
had failed medical therapy. Technical success for stent-
ing was achieved in 98.8% of all stenosis (81/82). Major
periprocedural morbidity and mortality was 6.1% (five
procedures). The complications were defined as device
related in two cases: 1 vessel rupture after angioplasty
and 1 microwire perforation during stent delivery. There
was one reperfusion hemorrhage after a technically suc-
cessful procedure; one patient had a contra-lateral hemi-
spheric stroke; and one patient was treated in an acute
basilar stroke setting, and postprocedure MRI dem-
onstrated extensive posterior circulation infarctions.
Of these, four patients expired. Minor complications
included a transient visual symptom that completely
resolved within 36 hours. Five extracranial parent
vessel dissections related to guide catheter placement
were diagnosed, two of which required stenting. One
intracranial dissection was observed after balloon
angioplasty, which resolved after Wingspan stent
placement, with no neurological deficits (62).
PHAROS
A recent study was conducted in 32 patients with the use
of a balloon-expandable stents (Pharos, Biotronik AG,
Bulach, Switzerland) (Fig. 21.2 A, B). The Pharos stent
is mounted on a rapid-exchange PTA catheter and is
specifically designed for intracranial endovascular appli-
cations (case example Fig. 21.3 DF). In this study, all
patients presented with a stenosis greater than 50%
angiographically, and 30 patients (93.7%) were sympto-
matic (TIA or stroke). Due to technical difficulties in
one case the stent could not be deployed. The 30-day
composite of morbidity and mortality was 15%. There
were three deaths in this small series. One patient
discontinued the medication on his own several days
after the procedure and presented 14 days later with a
severe stroke. The patient that failed the procedure had
a fatal stroke 3 days following the attempted treatment.
Another patient had a hypertensive episode with cardio-
respiratory failure one week following an uneventful
endovascular procedure. The restenosis rate with a mean
follow-up of 10.2 months was 13%; (restenosis <10%:
4.3%; restenosis >50%: 8.7%) (63). This study helped
to receive the CE Mark approval (European market)
of the Pharos stent for ICAD (Codman & Shurtleff,
Johnson & Johnson Medical, Raynham, Massachusetts,
U.S.) (64).
The initial Pharos experience in Europe was
reported by Kurre et al. in a series of 21 symptomatic
patients with intracranial stenosis >70%. In this study,
7 patients were treated in the setting of acute stroke.
The antiplatelet medication in this subset of patients
was tirofiban as an intravenous bolus or IV aspirin +
IV heparin. Clopidogrel loading dose was given as
soon as possible postprocedure. Treatment was suc-
cessful in 19 of 21 patients. Primary passage of the
stent delivery catheter without pre-dilatation was suc-
cessful in 12 out of 14 elective patients; 2 patients with
subtotal occlusion required pre-dilatation. Of these
14 elective patients, 2 had strokes in the first 30 days.
Two out of the 7 stroke patients died during the first
30 days. In this study, no systematic follow-up was
performed (64).
A systematic review of the stenting literature for
intracranial atherosclerosis was recently published and
included 31 studies with 1177 procedures. Technical
success rates varied from 71% to 100%, with a median
of 96.9%. Although a very high initial success rate is
reported, adverse events and complications, mainly
within the first weeks, vary widely depending on lesion
location and the experience of the operator (65).
Periprocedural minor or major stroke and death
occurred to a median of 7.7%. The periprocedural com-
plications did not differ between the treatment methods
but were significantly higher in the posterior circulation
(P = 0.01). Fifty-five (12.1%) stroke or death events
occurred in the posterior and 28 (6.6%) in the anterior
circulation. The overall complication rate within the
anterior circulation ranged from 0% to 30% (median
5.1%) and from 0% to 50% with a median of 8.3% with-
in the posterior circulation. Long-term follow-up data
showed 77 cases (14.4%) of restenosis (>50%) among
535 patients. These restenoses caused stroke, TIA, or
death in 32.7%. In general, restenoses were found to
develop more often after use of a balloon-mounted
stent than after treatment with a self-expanding stent
(P < 0.001) (65).
TRIALS IN PROGRESS
The Vitesse Intracranial Stent Study for Ischemic Ther-
apy (VISSIT) is an investigational device exemption
(IDE) study designed to compare clinical outcomes
between patients treated with the Pharos Vitesse
Balloon Expandable Stent and the current best medical
therapy. It is a multicenter randomized trial, spon-
sored by Micrus Endovascular Corporation Industry
(San Jose, California, U.S.), now part of Codman Shur-
tleff, Johnson & Johnson Medical (Raynham, Massa-
chusetts, U.S.). Primary endpoints are safety, benefit
and effectiveness of the stent to treat ICAD. Secondary
goal is to evaluate the cost-effectiveness of the treat-
ment, evaluating hospital length of stay, charges and
costs. Enrollment was halted by the sponsor in Janu-
ary of 2012, and no data is yet published.
The Stenting versus Aggressive Medical Manage-
ment for Preventing Recurrent stroke in Intracranial
Stenosis (SAMMPRIS) was a trial in the United States,
sponsored by the NIH/NINDS, evaluating the use of
aggressive medical therapy alone versus angioplasty
and stenting combined with intensive medical ther-
apy (66). Patients with symptomatic intracranial stenosis
of 70% to 99% and a TIA or stroke within 30 days
were enrolled. Patients in both treatment groups
received careful risk factor management (325mg
aspirin/day and 75mg clopidogrel/day for 90 days
postenrollment; systolic blood pressure <140 mmHg;
LDL<70mg/dl). The stent used was the Wingspan
Gateway system. On April 5th 2011, the trial was
stopped by the NIH due to a higher risk of stroke and
death in the stented group. Recruitment began in
November of 2008 and was finalized on April 2011
after 451 (59%) of the planned 764 patients had been
enrolled at 50 participating sites in the United States.
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE
Two hundred and twenty-four patients were assigned
to the stenting arm and 227 to medical therapy alone.
Despite decreasing the degree of stenosis in the stent-
ing arm, medical therapy alone was superior in pre-
venting recurrent stroke (67). The 30-day stroke or
death rate was 14.7% (non-fatal stroke: 12.5%; fatal
stroke: 2.2%) compared to 5.8% (non-fatal stroke 5.3%;
non-stroke related death: 0.4%; p = 0.002). These
results were unexpected. The SAMMPRIS investiga-
tors were surprised by such a high complication rate
in the Wingspan stent group as previously conducted
studies by Henkes et al. (68) and Bose et al. (8) stated
a complication rate of around 10%. Even in clinical
practice, the use of the Wingspan stent has presented
convincing results (69). Now the question arises, what
may have led to these unfortunate results.
The implantation of stents within the cerebrovas-
culature can be technically challenging due to the tor-
tuosity of the intracranial vessels and demands a high
level of experience of the operator (67). As for every
operative technique, there is a learning-curve effect
regarding the performance of the interventionalist, and
also the competence of the entire neurological and
intensive care unit team in handling the patients needs
and maintaining his or her well-being (70). This learn-
ing process may be a possible reason that has led to
this disappointing outcome since the interventionalist
had to provide experience of only three Wingspan
cases performed in order to be accepted as a center
within the trial. Another possible explanation for the
higher stroke rate in the stenting arm may be the fact
that all patients treated in the SAMMPRIS trial showed
recent symptoms which may be due to an inflamed
and thus, unstable plaque that is more likely to cause
embolism during the stent procedure. This has been
investigated and identified as a cause for increased
embolic events in stenting of extracranial carotid artery
disease (7173). Up to now, only the short-term follow-
up data are available. Less than half of the patients
enrolled in the SAMMPRIS trial received follow-up
examinations for more than 1 year. It will be important
to determine the long-term benefit in the aggressive
medical management arm versus stenting group to
show if medical therapy alone is sufficient to inhibit
the progression of stenosis, which may lead to hypo-
perfusion or embolic stroke and to which degree an in-
stent stenosis has developed that may also cause later
stroke events (70,73).
A very important point regarding the prospec-
tive approach of ICAD is to individually assign the
patients to the best treatment group, medical or endo-
vascular. Therefore, more fundamental understanding
of the disease is needed. Also, future data collection
should be homogenous including appropriate criteria
of patient selection, unified definitions of the patients
symptomatic status and TIA, standardized endovascu-
lar approach with perioperative and postoperative
antithrombotic therapy and universal risk factor modi-
fication (74).
TECHNICAL STENTING PROCEDURE
Patients are selected for intracranial angioplasty and
stenting according to institutional policies, ongoing
trials and patient/family involvement. Complete
441
neurological status must be assessed prior to the pro-
cedure. Imaging studies are done to evaluate preexist-
ing ischemic areas, rule out hemorrhage, and obtain
information on cerebrovascular anatomy. An informed
consent describing potential complications must be
obtained from all patients.
Procedures can be done under general or local
anesthesia (60,7579). General anesthesia has the
advantage of reducing motion artifacts and the possi-
bility of reducing surgical time. However, the major
disadvantage is the inability to monitoring neurological
status. Treatment of basilar artery lesions should be
done under general anesthesia due to the possibility of
loss of consciousness and apnea while creating flow
arrest to the brainstem during angioplasty (28).
Blood pressure control before, during, and after
the procedure is fundamental. Patients with poor cere-
bral perfusion tolerate very little periods of relative
hypotension, hypoxemia, hypocarbia, or hypercarbia,
so even small variations of these induced by anesthe-
sia can be harmful. An experienced anesthesiologist
and pre-procedural anesthesia evaluation are manda-
tory. Maximum dose of contrast should be controlled
as much as possible, even in patients with good renal
function; an amount of 6mg/kg total dose of non-
ionic iso-osmolar agent is suggested (28,35).
One of the femoral arteries is accessed with a 5-
French (Fr) or a 6-Fr sheath, and rarely a 7-Fr sheath if
a larger guide catheter is necessary for a tri-axial
approach. The guide catheter is then placed in the dis-
tal cervical ICA or the cervical vertebral artery. The
degree of vascular stenosis is studied with catheter
angiography. The percentage of stenosis is calculated
as the ratio of the smallest diameter to the diameter of
the normal-calibre vessel distal to lesion (NASCET
method). In cases of a poststenotic collapse, the diame-
ter of the vessel proximal to the stenosis is used. The
dimensions of the normal artery adjacent to the lesion,
the length of artery, and the smallest diameter of the
stenosis are measured to choose the appropriate bal-
loon and stent size. Another method to calculate the
percentage of the stenosis is the ECST method (Euro-
pean Carotid Surgery Trial). Here, the ratio of the diam-
eter of the stenosis to the diameter of the actual vessel
diameter at the stenotic site is calculated. Two newer
formulas to calculate the degree of stenosis exist. First,
the Common Carotid method (CC method) which is
based on a comparison of the residual lumen at the
stenotic site to the diameter of the common carotid
artery about 3 to 5 centimeters below the bifurcation
and secondly, the Carotid Stenosis Index (CSI) that is
based on the well-known relationship between the
proximal common carotid artery and the internal cere-
bral artery (1.2  CCA diameter = proximal ICA
diameter).
There is not a goal established to what degree
the stenosis should be treated in the procedure (28).
Calibration of the angiographer for precision and
accuracy is mandatory to ensure patient safety.
A microcatheter is navigated across the lesion
over a microguidewire with a soft tip (0.010 or
0.014), and placed distal to the lesion. An exchange
soft-tipped microguidewire is placed distal to the
lesion to provide support for the stent catheter. The
over-the-wire technique might help avoid vessel
442 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

Figure 21.4 Illustrative case: Intra-procedural left-anterior-oblique digital subtraction angiography (DSA) (A) acquired after primary
stenting of an acute ischemic stroke associated with an atherosclerotic lesion in a 43-year-old female shows a filling defect of the left
Middle cerebral artery (MCA) (arrowhead). Contrast enhanced Cone-beam CT in the same projection (B, 5.0mm MIP) and a cross-
sectional projection (C, 1.0mm MIP) demonstrate that the filling defect is most likely a clot (asterisk) on the stent surface (struts noted
by arrows) rather than a plaque material deforming the stent extrinsically. (Printed with permission from AJNR 2011 32:137--144.)

dissection. Angioplasty should be performed with an
undersized balloon, and preferably slowly, reaching
610 atm, over several minutes. Proper stent place-
ment should be confirmed by high-resolution Cone-
beam CT when available (Fig. 21.4). One potential
complication during placement of the stent and angio-
plasty is dislocation of plaque fragments with emboli-
zation of side branches, or acute in-stent thrombosis.
Intra-procedure unfractionated heparin should be
administered at 70 units/kg as an IV bolus to achieve
an activated clotting time (ACT) of 250 to 300 seconds.
Some specialists advocate the use of continuous glyco-
protein IIb/IIIa inhibitor; for these patients, the hepa-
rin dose should be reduced to 50 units/kg IV bolus.
Heparin should not be reversed postprocedure; it is
either maintained for another 24 hours or discontinued
immediately postprocedure. Patients require a neuro-
intensive or general critical care unit at least 24 hours
for close hemodynamic and neurologic monitoring.
Stented patients should be treated with anti-
platelet therapy. Currently, most institutions use dual
anti-aggregation, aspirin 81mg/day and clopidogrel
75mg/day, for at least 6 weeks. Aspirin is kept for a
longer period, usually 12 months to lifelong. The pre-
procedural protocols vary considerably depending on
the available drugs and acute versus non-acute treat-
ment. In an elective treatment, drugs (loading doses)
should be started at least 3 days before the procedure.
Prabhakaran et al. studied resistance to antiplate-
let therapy in patients undergoing neurovascular stent-
ing procedures (80). Aspirin resistance was found to be
relatively uncommon; however, clopidogrel resistance
(clinical non-responders) occurred in half of the studied
patients. The group suggested that platelet function
tests should be done in patients undergoing cerebro-
vascular stenting. Another group reported a case that
angiographic in-stent restenosis was due to platelet
aggregation in the luminal stent surface, despite opti-
mal medical therapy. In this patient aggregometry was
done, and a clinical non-response to clopidogrel was
reported (81). Two loading doses of 300mg clopidogrel
were administered, and the next day angiography dem-
onstrated normal stent patency. Clopidogrel dose was
increased to 150mg/day, and 18-months follow-up
demonstrated no lumen reduction. In practice, aggreg-
ometry is still not adopted as a routine in most
institutions.
REPERFUSION SYNDROME
Hyperperfusion is a rare but serious complication
following cerebrovascular angioplasty and stent place-
ment, reported in up to 5% of patients undergoing
endovascular revascularization procedures of the cranio-
cervical arteries (82). Successful revascularization leads
to sudden increase in arterial pressure and blood flow
to the ipsilateral cerebral hemisphere which is assumed
to have an impaired autoregulation. Presentations of this
entity include cerebral edema, hemorrhage, or increased
cerebral perfusion. Related symptoms are headaches,
nausea, vomiting, confusion, seizures, and systemic arte-
rial hypertension (83). Patients submitted to stenting
procedures should be carefully monitored for evid-
ence of hyperperfusion, especially regarding blood pres-
sure, heart rate, and anticoagulation. As anti-hypertensive
drugs, beta-blockers with alpha and beta-receptor block-
age are optimal due to reduction of pressure and
pulsatility (35).
RESTENOSIS AFTER STENTING
Restenosis rates reported vary and range from 7.5%
to 32.4% (60,8488). The effects of patient age and
lesion location for in-stent restenosis have been
studied (84). Patients younger than 55 years with
symptomatic intracranial stenosis tend to have ante-
rior circulation lesions, whereas patients older than
55 years tend to have an equal distribution of ante-
rior and posterior circulation lesions. Supraclinoid
ICA disease, particularly in younger patients, has a
higher risk to develop an in-stent stenosis that is
often symptomatic.
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE 443

ISR Pattern I: Focal type 1A ISR Pattern II: Intra-stent

ISR Pattern I: Focal type 1B ISR Pattern III: Proliferative

ISR Pattern I: Focal type 1C ISR Pattern IV: Total occlusion

Figure 21.5 Schematic depiction of the angiographic patterns of in-stent restenosis. Class I, focal group. Lesions involving less than half
of the length of the stented segment and involving the end of the stent (IA), the body of the stent (IB), or multiple foci (IC). Class II, diffuse
intra-stent group. Lesions involving more than half of the length of the stented segment but contained within the confines of the stented
segment. Class III, proliferative group. Lesions involving more than half of the length of the stented segment, extending beyond the con-
fines of the stented segment. Class IV, complete stent occlusion group. (Printed with permission from Neurosurgery 2008 63:23.)

A multicenter study analyzed the angiographic
patterns of in-stent stenosis for the Wingspan stent (85).
Their classification was a modification of the one used in
the cardiology literature, originally developed to charac-
terize in-stent restenosis after coronary percutaneous
angioplasty (89). The investigators studied the geo-
graphic distribution of intimal hyperplasia within the
stent. In this Wingspan study, restenosis was defined as
a lesion demonstrating more than 50% stenosis (within
or 5mm adjacent to the stent ends or more than 20%
absolute luminal loss at follow-up imaging). The most
common in-stent stenosis found was the focal type (25
out of 41 lesions; 61%), within the stent body and
remained mostly clinically asymptomatic. Fifteen out of
41 patients had symptomatic lesions (36.6%). Thirteen of
these symptomatic lesions were due to in-stent resteno-
sis (86.7%) and two due to stent occlusion (13.3%). Dif-
fuse stenosis was less common, representing 26.8% of
the total restenosis seen. Complete stent occlusion was
seen in 12.2% of both, asymptomatic and symptomatic
cases. Also, in more than half of the cases, restenosis
was angiographically more severe than the original
lesion treated, with respect to the severity of the stenosis,
length of the stenosis, or both.
A retrospective study of 29 patients with symp-
tomatic ICAD (>70%) who underwent angioplasty
and stenting for intracranial lesions showed a success
rate of 97% (characterized by >50% endoluminal
revascularization after stent placement). No periproce-
dural complications occurred. Of the 26 patients avail-
able for follow-up examination after 1.8 years, 3 had a
stroke (11.5%) and 2 a TIA (7.7%). Hypertension, dia-
betes and hyperlipidemia were not associated with
symptomatic patients. Past or current history of smok-
ing was the only modifiable risk factor that showed
statistical significant association with the symptomatic
group (P = 0.020). However, there was no association
of diabetes, hypertension, hyperlipidemia, or smoking
with the occurrence of in-stent restenosis (90).
MODIFIED MEHRAN SYSTEM (85) (Fig. 21.5)
Class I: Focal in-stent stenosis. Lesions involving
less than half of the length of the stented segment and
either involving the end of the stent (IA), the body of
the stent (IB), or multiple foci (IC).
Class II: Diffuse in-stent stenosis. Lesions invol-
ving more than half of the length of the stented seg-
ment but contained within the confines of the stented
segment.
Class III: Proliferative form of in-stent stenosis.
Lesions involving more than half of the length of the
stented segment, extending beyond the confines of the
stented segment.
Class IV: Complete stent occlusion.
Because of the significant restenosis rate, imag-
ing follow-up should be performed. MRA is useful as
a non-invasive technique (91); however, not all stenoses
can be detected with this modality, and the measure-
ments are not always accurate because time-of-flight
angiography is affected by metal susceptibility of the
stent struts and small vessels may be evaluated
444 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D) (E)

(F) (G) (H) (I)

Figure 21.6 Illustrative case: A 61-year-old female presented with visual field disturbances, ataxia, and worsening neurological status.
MRI (not shown) revealed focal areas of restricted diffusion throughout the vertebrobasilar distribution. Digital subtraction angiography
(DSA) demonstrated bilateral VA ulcerated plaque with extension into the basilar artery (ALVertebral artery (VA) injection frontal
projection, BLVA injection lateral projection, and CRVA injection frontal projection). After angioplasty of both vertebral and the basilar
arteries, bilateral Wingspan Stent Delivery Systems are positioned through each VA for stenting in a side-by-side, or kissing, fashion
(D). DSA post stent implantation showed improved arterial caliper and distal perfusion (E, Ffrontal and lateral projection, respectively,
with bilateral VA injection). Two months following the procedure, the patient presented to the emergency department with worsening
ataxia and memory loss. Areas of new focal ischemic lesions were found on MRI (not shown) in the right thalamus. DSA revealed tight
stenosis of the basilar artery, in-stent stenosis of the LVA and complete occlusion of the RVA (Gfrontal projection). Angioplasty of
the basilar artery and implantation of a balloon-expandable, drug-eluting stent in the LVA improved the distal perfusion (DSA in H, frontal
projection). Contrast-enhanced Cone-beam computed tomography depicts excellent apposition of the stents to the LVA and basilar artery (I).

incorrectly (92,93). CTA is limited by the beam-hard-
ening and streak artifacts. Although this can partially
be improved with better scanner technology and
imaging post processing (94,95), the resolution is still
inferior to Cone-beam CT (9699). Cone-beam CT with
intravenous application of contrast material might be
a good option as a non-invasive imaging method; fur-
ther studies are needed to validate this technique
(95,100). Currently, most authors recommend angio-
graphic follow-up, starting at 3 months postprocedure
(35,101,102) up to 2 years (Fig. 21.6).
Treatment of restenosis has been described, and
includes medical management only, especially for
asymptomatic lesions, angioplasty, or re-stenting. To
date, there is no consensus about the optimal
approach (103).
To reduce the incidence of in-stent stenosis,
drug-coated devices with antiproliferative agents have
been developed and are being considered for the neu-
rovascular system (104). Sirolimus (rapamycin), an
antifungal agent, and paclitaxel, a microtubule inhibi-
tor, have shown to prevent neointimal proliferation
and restenosis in the coronary arteries as compared
with bare metal stents (105). Experience in the coro-
nary system provided the impetus to study the effect
of antiproliferative agents for the intracranial system
(106,107). Levy et al. studied the effects of heparin-
coated and sirolimus-eluting stents compared to bare
metal stents, which were implanted in healthy canine
basilar arteries. Four heparin-coated and three bare-
metal stents implanted in six mongrel dogs were
available for follow-up examination in the study con-
ducted in 2003 (108) and eight sirolimus-eluting stents
could be compared to eight uncoated devices in the
year 2004 (107). The mean percentage of stenosis at
12 weeks after implantation was less in the group
treated with heparin-coated stents (12%) as compared
with the group treated with uncoated devices (22%;
P = 0.07). The reduction of neointimal proliferation
(0.18 mm2 in the heparin stent group vs. 0.42 mm2
in the bare metal stent group) reached statistical sig-
nificance (P = 0.04). Both, neointima/media ratio
(P = 0.05) and neointimal thickness (P = 0.04) were
increased in the uncoated stent group. Compared with
bare-metal stents, the sirolimus-coated devices did not
impair endothelialization and, furthermore, tended to
 STENTING AND ANGIOPLASTY FOR INTRACRANIAL ATHEROSCLEROTIC OCCLUSIVE DISEASE
reduce the proliferation of smooth muscle cells which
was found to be statistical significant (P = 0.003). In this
study both, bare metal and sirolimus-coated stents did
not show any evidence of restenosis (<50%). Histolo-
gical analysis of the sirolimus-eluting stents not only
showed an increased fibrin content of the intimal layer
(P < 0.0001) but also presented a tendency toward lower
inflammation scores (P = 0.34). Further research in this
area is necessary to evaluate the translation of these early
research results to clinical scenario.
NEW CONCEPTS AND FUTURE TRENDS
ICAD is diagnosed usually when symptomatic. New
MRI techniques, especially high-resolution plaque
imaging, will bring further understanding to the
asymptomatic stages of this pathology (109). Also,
understanding better the components of the plaques
such as lipid-rich necrotic core, intra-plaque hemor-
rhage and calcium can help assess which patients are
more likely to have a more aggressive form of the dis-
ease. Quantitative methods of evaluating intracranial
stenosis are likely to be replaced for more qualitative
methods. Case reports have described plaque charac-
terization with the use of intravascular ultrasound
(IVUS) (45,110). IVUS may be incorporated into neuro-
interventional procedures, provided more flexible and
low-profile devices are available.
Evaluation of collateral circulation, as suggested
in a recent analysis of the WASID trial, might help to
improve patient selection for treatment options (111).
Patients may vary in their tolerance to impaired cere-
bral perfusion. Imaging techniques targeted at estimat-
ing poor cerebrovascular perfusion may be helpful to
define the patient population that may be at high-risk
for stroke.
Currently, we compare stenting as a single modal-
ity, without addressing technical variability that may
generate significantly different results. Technical aspects
that may affect the outcome are considered to be use of
self-expanding stents versus balloon-expandable stents,
pre- or postdilatation of the stenosis, use of angioplasty
prior to stent placement, oversizing or undersizing stent
and PTA balloon, and operator experience.
THE ROLE OF INFLAMMATION
Endothelial dysfunction is considered to be the first
step in atherosclerosis. Vessel wall injury leads to
release of distinct chemical mediators and recruits cir-
culating blood cells, monocytes and T-lymphocytes, to
the injury site (112). The release of various cytokines
like monocytes chemotactic protein, interleukin 1 and
TNF-alpha results in further inflammatory cell recruit-
ment and in atherosclerotic plaque formation over the
longer term (113).
Arterial lesions are the main factors in multiple
processes, i.e., vessel thrombosis, plaque progression,
and rupture (114). Such vascular lesions may result
from PTA procedures or stent placement. The induced
inflammatory cascade as a response to the vessel wall
injury induces smooth-muscle cell stimulation and
migration resulting in neointimal growth (115).
The amount of in-stent stenosis has been consid-
ered to be correlated to the level of inflammation.
445
Experimental studies have shown that arterial injury
is associated with an increased expression of vascular
endothelial growth factor (VEGF) by macrophages and
smooth-muscle cells leading to vessel wall remodeling
and lumen narrowing at the worst (115,116). Moreno
et al. (117) investigated tissue obtained from atherot-
omy catheters at the time to develop angioplasty and
found a highly positive correlation between the
amount of macrophages in the examined tissue sam-
ples and the tendency to develop in-stent stenosis
(117). Better understanding of the correlation between
inflammatory reaction and neointimal proliferation in
the intracranial vasculature may be obtained by ana-
lyzing coronary stent studies. For instance, Farb et al.
(116) report a correlation between inflammatory cell
density and increased neointimal growth in stented
coronary arteries (P < 0.0001). The findings by Dibra
et al. (118) support this result. The study conducted in
2005 investigated 1800 consecutive patients who
underwent stenting in native coronary arteries. The
authors concluded that the higher the degree of
inflammation at the stented site, the higher the risk of
stent restenosis.
An experimental pig study conducted in 1998 by
Karnowski and collegues (119) showed a significant
correlation between the amount of inflammatory cells
at the stented site and neointimal formation in the
examined coronary arteries (neointimal thickness,
P < 0.01, neointimal area, P = 0.01, percent area stenosis,
P < 0.01). They also found a significant positive corre-
lation between the degree of arterial injury and the
resulting neointimal proliferation which may be exp-
lained by the assumption that the higher the degree of
arterial injury, the higher the extent of inflammatory
response.
Ongoing studies to predict neointimal prolifera-
tion based upon the degree of inflammation focus
on the inflammatory activity which can be measured,
for example, by the serum values of C-reactive pro-
tein (CRP), serum amyloid A (SAA), and fibrinogen
(120,121). These are specific, sensitive, and fast reacting
markers of acute phase reaction, but their predictive
value for assessment of intracranial arteriosclerotic lesions
has to be questioned. Bang et al. (122) compared CRP,
fibrinogen, and matrix metalloproteinase-9 (MMP-9)
serum blood values in a total of 272 patients with
either occlusive lesions of the carotid sinus (carotid-type,
n = 112) or occlusive lesions on the proximal vessel
portion of the MCA (MCA-type, n = 160). The degree of
arterial stenosis did not differ between the two groups.
Inflammation markers were found to be significantly
higher in patients with carotid sinus lesions than in
the MCA-type (P = 0.007 for CRP and P = 0.005 for
fibrinogen). MMP-9 values were obtained in a smaller
number of patients (n = 82; 30 carotid-type and 52
MCA-type patients), but still, there was an obvious
difference between the MMP-9 level (P = 0.287) and
activity (P = 0.004) in the two groups. Future studies
on the comparison between intracranial and extracranial
atherosclerosis regarding inflammatory markers will be
needed to confirm or reject these findings.
Current imaging techniques to visualize athero-
sclerotic plaques include IVUS, CT, MRI, and fluoro-
deoxyglucose positron emission tomography (FDG
PET). Unfortunately, CT imaging of molecular
446 NEUROINTERVENTIONAL MANAGEMENT
structures alone is limited by a significantly lower
sensitivity than PET. On the other hand in MRI imag-
ing, ultrasmall paramagnetic particles of iron oxide
(USIPO) have demonstrated to be good clinical
markers and were already successfully used to deter-
mine the success of statin therapy by showing
reduced inflammation activity in patients with severe
(70%) symptomatic intracranial atherosclerosis (51).
A limitation of this technique is, however, the time
delay of 36 hours between IV injection and scanning.
Also, it can be difficult to distinguish between the par-
ticle-induced signal loss on T2-weighted images and
signal loss due to artifacts.
Recent imaging studies using FDG PET either
combined with CT or MRI, because of limited spatial
resolution of PET alone, present encouraging findings
regarding the differentiation between stable and active
atherosclerotic lesions. Stable lesions are known to be
less inflamed and, thus, are expected to show less
FDG uptake than symptomatic plaques. The results
reveal that PET is capable to detect inflammatory hot-
spots in atherosclerotic lesions by reflecting the mac-
rophage density and activation within atherosclerotic
plaques (113,123125).
Although PET presents good results regarding
quantification of atherosclerotic inflammation, future
interest will likely be directed toward prediction of
plaque rupture and clinical event occurrences. Worse
outcomes may be predicted by a higher baseline
uptake of FDG, as a small pilot study in carotid artery
stenosis patients suggests (126).
Future studies anticipate showing that FDG
PET is able to further characterize the pathophy-
siological inflammatory processes in atherosclerotic
lesions and to monitor their response to medical
treatment (123125).
CONCLUSION
Endovascular treatment of symptomatic ICAD has
rapidly evolved and has adopted technology and
experience from the peripheral and coronary sys-
tems. The natural history of intracranial stenosis will
have to be better understood to determine acceptable
rates of risks for revascularization. Patient selection,
periprocedural management, use of appropriate endo-
vascular devices and intra-procedural imaging tech-
niques, as well as proper training play a pivotal role
for positive clinical results. Advances in coating tech-
nology, micro-fabrication of stents, delivery systems
and access catheters will allow a safe navigation of
the stent through the challenging intracranial arterial
circulation. Advances in technology and endovascu-
lar tools will ensure a low periprocedural morbidity
and mortality. New generations of coated intracra-
nial stents will further improve the long-term out-
come currently hampered by a high rate of in-stent
stenosis. Nevertheless, prevention which includes a
healthy lifestyle, control of genetic factors, cessation
of smoking, and adequate management of blood
pressure, use of statins, antiplatelet, and non-steroidal
anti-inflammatory drugs, will remain the long-term
pillars of combating ICAD.
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 22
Endovascular management of dural arteriovenous fistulas
J. Marc C. van Dijk and Robert A. Willinsky
INTRODUCTION
Excluding traumatic lesions and CC-fistulas, three basic
categories of dural arteriovenous shunts can be discrimi-
nated: the (pediatric) dural sinus malformation with
arteriovenous shunting, the infantile high-flow dural
arteriovenous fistula (DAVF), and the adult-type DAVF.
Since the dural lesions in the pediatric age group are
beyond the scope of this chapter, the focus will be on the
adult-type dural arteriovenous fistula.
The adult-type DAVF is a rare neurovascular
lesion. A recent population-based study mentions a
crude detection rate of 0.16 per 100.000 adults per
year and from angiographic studies it has been esti-
mated that dural lesions represent just 1015% of all
intracranial AV-shunts (1,2).
A DAVF consists of one or more true fistulas, i.e.,
direct arteriovenous connections without an intermedi-
ate capillary network or even a nidus. The fistula itself
is confined to the leaflets of the dura mater, which
unquestionably discerns a DAVF from an arteriove-
nous malformation (AVM) that has a (sub)pial locali-
zation within the brain or spinal cord. It is generally
acknowledged that DAVF are acquired (36), in con-
trast to the congenital nature of a vascular malforma-
tion (7), and thus the term dural arteriovenous fistula
is clearly favored over the term dural arteriovenous
malformation.
The anatomical setting of the fistula within the
dura mater explains that both cranial and spinal
Dural Arteriovenous Fistulas (DAVFs) are recognized.
Although their pathophysiological principle is the
same, their clinical presentation and behavior (and
therefore their classification) is quite distinct. Conse-
quently, cranial and spinal DAVFs will be discussed
in separate sections of this chapter.
PATHOPHYSIOLOGY
The cause of DAVFs is still a matter of debate, although
many postulations have been discussed in the literature.
The development of a DAVF has been described follow-
ing surgery (even in remote parts of the body), head
trauma, and in relation to sinus thrombosis, yet without
revealing a definite etiologic pathway.
Over the decades, two main hypotheses of
pathogenesis can be identified. The first hypothesis
states that DAVFs already exist within the dura mater
as dormant channels between the meningeal arterial
circulation and the venous system. Histological and
radiological studies have demonstrated that these
communications are indeed present in the dura of
normal individuals (8). According to the theory, these
channels should open due to the venous hypertension
associated with sinus thrombosis or sinus outflow
obstruction (9). Similarly, the existence of thin-walled
venous pouches close to small meningeal arteries has
been reported. Rupture of these fragile pouches should
be responsible for instant arteriovenous communica-
tions within the dura (10).
The second hypothesis claims that the development
of DAVFs is a direct consequence of neovascularization
processes within the dura mater, attributable to the
release of angiogenetic factors. These factors, e.g.,
Vascular Endothelial Growth Factor (VEGF) and Basic
Fibroblast Growth factor (bFGF), can be either directly
provoked by the organization of a venous sinus throm-
bosis, or indirectly induced by the increased intraluminal
venous pressure by way of a tissue hypoxia pathway.
Major support for the second hypothesis is brought by
the positive staining of excised dural fistulas for venous
thrombosis (11) and angiogenetic factors (12), and by the
demonstration that the development of DAVFs in a rat
model can be reproduced using a combination of venous
sinus thrombosis and venous hypertension (3,6).
Histopathologically it is proven that a DAVF is
located within the meningeal wall of a venous sinus,
although originally it has been described to reside within
the thrombosed lumen of a sinus. The location within
the wall clarifies the existence of the type of DAVF that
drains directly into the cortical venous network, without
venous drainage in the involved sinus (13). At a closer
look, the fistula consists of small venules with a diameter
of approximately 30 mm. These vessels have been named
crack-like vessels, since they resemble cracks in the
wall of the dural sinus after histological staining. Further
immunohistochemical assessment of the crack-like ves-
sels revealed a layer of endothelial and smooth muscle
cells and no internal elastic lamina, confirming their
venous origin (14).
In spinal DAVFs a small series of high-resolution
micro-angiography after en bloc resection of the fis-
tula has been reported. The ex vivo surgical removal
included the involved dural root sleeve, proximal
nerve root, and adjacent spinal dura. The subsequent
detailed imaging showed that in all of the lesions the
artery splits into daughter vessels that coalesced one
to three times to form a network of arterial loops in
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS
the dura that invariably emptied into a medullary
vein without an intervening capillary plexus. Several
collateral vessels arising from adjacent intercostal or
lumbar arteries were commonly present in the dura
and converged at the site of the fistulous point to join
a single medullary vein, providing an anatomical
explanation for the presence of a multiple segmental
arterial supply (15).
CRANIAL DURAL AV-FISTULAS
Early descriptions of cranial DAVFs date from the first
decades of the 20th century, however typically in the
form of case reports, e.g., by Tonnis in 1936 (16). The
first presentation of the concept of dural fistulas origi-
nates from 1951 in a publication by Fincher (17).
Despite the development of cerebral angiography in
the late 1920s (18), it took about 40 years before the
DAVF emerged as a distinct entity due to the advan-
ces in angiography, such as magnification, subtraction
techniques, and selective arterial catheterization. In
those days all DAVFs were regarded as benign in
comparison to the pial AVMs (19).
In the early 1970s pioneers including Aminoff,
Newton, and Djindjian expanded the anatomical and
clinical understanding of the dural fistulas. In 1972
the perception grew that the pattern of venous drain-
age was related to the clinical signs and symptoms;
nevertheless, it wasnt until 1975 before the risks of
cortical venous reflux (CVR) were recognized (20,21).
Djindjian and Merland proposed the first classification
based on this concept, emphasizing that DAVFs with
a free outflow into a sinus are relatively harmless,
while the presence of CVR is related to severe compli-
cations (22).
The 1980s were an important decade for the cra-
nial DAVFs, dominated by the publication of three
large reviews in the literature. In 1984, based on a ser-
ies of 223 cases, Malik concluded that venous outflow
was a key factor in the occurrence of hemorrhage or
neurological symptoms, stressing the importance of
location of the fistula within or outside a major venous
sinus (23). Lasjaunias performed a meta-analysis on
195 cases, concluding that focal neurological deficits
were dependent on the territory of draining veins and
that CVR was related to a high risk of intradural bleed-
ing (24). The third major review was done by Awad,
studying 377 cases. In this report the term aggressive
was introduced for DAVFs presenting with a hemor-
rhage or a focal neurological deficit. Awad did not
only emphasize the importance of CVR, but also
pointed out venous ectasias and galenic drainage as
additional risk factors (25).
Cranial Classification
A number of classification schemes have been pro-
posed based on different aspects of DAVFs. At first
the anatomical location of the fistula was considered
the key discriminating feature. In 1973 Aminoff rec-
ommended the arrangement in an anteroinferior
group and a posterosuperior group (26). Subsequently
other large studies have pointed out an association
between location and clinical presentation of a DAVF,
noticing that cavernous sinus and transverse sinus
451
lesions behave differently than tentorial or anterior
fossa fistulas. Over the years however it became evi-
dent that not location as such, but location-related
venous drainage pattern was crucial for the clinical
presentation. Cranial DAVFs in some locations have a
higher likelihood of developing CVR due to the local
venous anatomy, e.g., the absence of a venous sinus
in the direct vicinity. Although no location of a cranial
DAVF is immune from aggressive behavior, it was
recognized that certain regions raise the index of sus-
picion for the development of CVR.
Following the original format by Djindjian, based
on the venous drainage pattern, numerous classifica-
tion schemes for cranial DAVFs have been put for-
ward, of which the classifications of Borden and
Cognard are most frequently applied (Table 22.1)
(27,28). Both are used in everyday practice and have
their own advantages: the three-step classification of
Borden is very simple to apply and requires only little
knowledge of cerebral angiography; the Cognard clas-
sification is certainly theoretically superior, since it
incorporates the additional effect of the flow-direction
in the dural sinus, but its multiple steps require a
more advanced comprehension of DAVFs. The added
value of judging the flow-direction in the sinus is evi-
dent: retrograde flow can prohibit the cortical veins to
drain into the involved sinus and can subsequently
lead to venous congestion of the brain, without the
occurrence of CVR. Both classifications have been vali-
dated (29).
A new classification has been proposed based on
the venous drainage of the epidural spaces according to
the embryology of the structures surrounding the central
nervous system (30). The three venous epidural sub-
groups are ventral, dorsal, and lateral, and correspond
to the skull base, calvarium, and vertebra. The ventral
epidural shunts have a female predominance and typi-
cally have no CVR unless there is venous thrombosis of
the epidural venous drainage or the shunts are high-
flow. The dorsal epidural shunts are often seen in the
pediatric age group, are frequently multiple, and typi-
cally have no CVR unless there is extensive venous
thrombosis or the shunts are high-flow. The lateral
Table 22.1 Classification Schemes for DAVFs
Borden classification
1 Venous drainage directly into dural venous sinus or
meningeal vein
2 Venous drainage into dural venous sinus with CVR
3 Venous drainage directly into subarachnoid veins (CVR
only)
Cognard classification
I Venous drainage into dural venous sinus with antegrade
flow
IIa Venous drainage into dural venous sinus with retrograde
flow
IIb Venous drainage into dural venous sinus with antegrade
flow and CVR
IIa + b Venous drainage into dural venous sinus with retrograde
flow and CVR
III Venous drainage directly into subarachnoid veins (CVR
only)
IV Type III with venous ectasias of the draining subarach-
noid veins
V Venous drainage into the perimedullary plexus
452 NEUROINTERVENTIONAL MANAGEMENT
Table 22.2 Benign and aggressive clinical features of DAVFs
Benign features Aggressive features
Pulsatile bruit Intracranial hemorrhage
Orbital congestion Non-hemorrhagic focal neurological deficit
Cranial nerve palsy Dementia
Chronic headache Papilledema
(Asymptomatic) Death
epidural shunts have a male predominance, present at a
later age and always have CVR. Spinal DAVFs are part
of the lateral epidural group.
Cranial Clinical Features
The expressions benign and aggressive have been put
forward in the literature and used in this chapter in
relation to the typical clinical signs and symptoms of
cranial DAVFs. Features such as non-hemorrhagic
neurological deficits (NHND), hemorrhage, and death
are regarded aggressive, whereas complaints of
chronic headache, pulsatile bruit, and orbital symp-
toms, including cranial nerve deficits, e.g., due to cav-
ernous sinus fistulas, are considered benign, even
though these signs and symptoms might be deemed
intolerable by the patient (Table 22.2).
Benign DAVFs
There is a proven relationship between the so-called
benign symptoms and the absence of CVR in the
venous drainage pattern. Borden 1, Cognard I, and
Cognard IIa DAVFs are thus regarded as benign fistu-
las. Large series have acknowledged that the benign
DAVFs never present with grave pathology (25,31,32).
Most frequently benign fistulas involve the cavernous
sinus or the transverse-sigmoid sinus. Although
DAVFs can occur at any age, typically the patient is
over 50 years of age and complains of a disturbing
pulse-synchronous tinnitus. The bruit can be loud and
audible by the physician, indicative of a high turbu-
lent flow through a venous sinus in direct contact
with the petrous bone. Another characteristic com-
plaint is the red eye, indicative of a DAVF involving
the cavernous sinus with subsequent proptosis, con-
junctival injection, and chemosis of one or both eyes.
The orbital symptoms may be progressive and the
congestion can lead to raised intraocular pressure that
may result in decrease of visual acuity. However,
worsening of the visual function or diplopia may as
well be caused by (transient) cranial nerve dysfunc-
tion, e.g., leading to ophthalmoplegia, or orbital
edema with extraocular muscle swelling. Hence, in
cavernous sinus DAVFs, close interaction with the
ophthalmologist is essential to decide when clinical
symptoms are no longer to be considered benign and
palliative endovascular treatment is necessary.
Even more important than the clinical presenta-
tion is the subsequent natural disease course of benign
DAVFs. In a retrospective evaluation of 205 cases Cog-
nard reported the probable benign disease course of
111 fistulas without CVR (28), but significant follow-
up could only be obtained in 66% of the cases and it
is difficult to draw conclusions on clinical stability
from this article, since clinical events before and after
presentation are not well differentiated. Two years
later they mentioned seven patients in their experi-
ence that initially had a DAVF without CVR, but
showed a worsening in the venous drainage pattern
during a mean 7 years follow-up. Five patients were
embolized with particles, one patient had proximal
ligation of the occipital and middle meningeal artery,
and one patient had conservative management. In all
cases, the change in venous pattern was accompanied
by a worsening of the clinical symptoms (33). The first
large prospectively collected series of patients with a
benign DAVF was reported by Davies with a cohort
of 55 cases without CVR over a mean follow-up
period of 33 months. The vast majority of these
DAVFs without CVR behaved in a benign fashion,
with stability over time. One patient died after pallia-
tive endovascular treatment, without angiographic
conversion into a lesion with CVR. This unusual
course of a predicted benign disease was explained as
the result of venous hypertension due to functional
obstruction of the superior sagittal sinus (SSS) (32). In
2002 Satomi confirmed the benign disease course of
DAVFs without CVR in a prospective study of 117
cases. Observation resulted in a tolerable, stable dis-
ease in 67 out of 68 patients. One patient had a seiz-
ure during follow-up due to a hemorrhage after the
development of CVR. Treatment was performed in 44
patients, aimed at the palliation of unbearable symp-
toms or pressing ophthalmologic phenomena. In 15
patients, multiple treatment-sessions (up to four ses-
sions) were required to obtain a satisfactory result.
Treatment resulted in a tolerable disease in all but one
patient. Both in the observational and the palliatively
treated group approximately 66% of the patients were
cured after mean 28 months, demonstrating that a
benign DAVF is a self-limiting disease. The remaining
one-third of patients had symptoms that were well
tolerated. In conclusion observation or palliation
resulted in a stable, tolerable disease course in more
than 98% of the cases (34).
Benign DAVFs are a dynamic disease, and pro-
gression of venous thrombosis may result in rerouting
of the venous drainage. Two caveats must be made:
the possible significance of retrograde flow in the
sinus, and the small, but noteworthy risk of conver-
sion into an aggressive DAVF. The importance of ret-
rograde flow in the sinus without CVR is stressed in
the Cognard classification. Type IIa was related to
papilledema and raised intracranial pressure in 8 out
of 27 patients (30%). In the series by Davies and
Satomi however this phenomenon was seen in a much
smaller percentage (31,33). Theoretically, retrograde
flow can indeed prohibit the cortical veins from drain-
ing into the involved sinus leading to venous conges-
tion of the brain. Among other authors Hurst has
related this venous congestion of the brain to global
neurological deficits, such as dementia (35). The con-
gestion has been shown to project as T2-hyperintensity
on Magnetic Resonance Imaging (MRI) (Figs. 22.1
and 22.2) (36). Willinsky additionally pointed out the
presence of tortuous, engorged veins on the cerebral
angiography in cases of venous congestion and
labeled this the pseudophlebitic pattern (37). Benign
DAVFs may secondarily develop CVR. In the series
by Davies and Satomi this phenomena occurred in
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 453

(A) (B) (C)

Figure 22.1 Venous congestive encephalopathy secondary to a DAVF. A 58-year-old male presented with ataxia. The axial T2-
weighted MR (A) shows a central hyperintensity within the right cerebellar hemisphere surrounded by a diffuse hypointensity. Note the
prominent flow voids (arrows). The gadolinium-enhanced MR (B) shows a diffuse peripheral enhancement. A selective arteriogram
(C) of a dural artery (arrows) arising from the right vertebral artery shows a DAVF inferior to the straight sinus with marked reflux over
the cortical veins of the right cerebellar hemisphere.

approximately 2% of the cases. This finding mandates
close clinical follow-up and renewed radiological eval-
uation with any sudden or unexpected change in
symptoms. Kim updated the Toronto experience by
reporting on the spontaneous angiographic conversion
of cranial DAVFs in non-treated patients. Spontaneous
occlusion occurred in 12.5%, with transverse and cav-
ernous sinuses being the most common location.
However, one has to consider that this percentage is
most likely an underestimation, since many patients
did not undergo a cerebral angiography when symp-
toms gradually subsided. Angiographic conversion to
an aggressive lesion from a benign one was observed
in 4 of 99 patients (4%) after a sudden or unexpected
change in symptoms; all of these were found to have
an occlusion of the pre-existing venous drainage pat-
tern (38).
Aggressive DAVFs
Cranial DAVFs with the presence of CVR on angiogra-
phy are associated with grave pathology. In the classifi-
cation schemes Borden 2/3 and Cognard type IIb/IIa
+b/III/IV/V DAVFs are labeled as aggressive. Initially
the term aggressive was based on the frequent clinical
presentation with intracranial hemorrhage, NHND, or
even death. Nevertheless, presentation with pulsatile
tinnitus or orbital congestion, mimicking a benign
DAVF, is also possible (25,28). Hemorrhage may be sub-
dural, subarachnoid, or intracerebral, since the refluxing
cortical veins go through all these different compart-
ments. Location of the DAVF does not correlate with
hemorrhage; some locations however are more prone to
present with a hemorrhage because of local venous anat-
omy, e.g., anterior cranial fossa DAVFs. The NHND is
typically focal and directly related to regional venous
congestion (24), although more global neurological defi-
cits are also encountered analogous to the Cognard type
IIa fistulas with retrograde flow in the sinus. Cranial
DAVFs can be responsible for spinal neurologic
disorders, in case of perimedullary CVR from a Cognard
type V lesion (39,40).
The natural disease course of aggressive DAVFs
has been a debate for a long time. In the literature contra-
dictory reports were published, with post-presentation
annual hemorrhage rates varying from 1.8% in a series
by Brown (41) to almost 20% in a series by Davies (42).
Brown followed patients for mean 6.6 years, however
did not select for the presence of CVR, so it is very
likely that they underestimated the annual risk
because of a large portion of benign DAVFs. A series
by Duffau found a rebleeding percentage up to 35%
within two weeks after the presenting hemorrhage in
case of Cognard type III/IV fistulas (43). Davies calcu-
lated an annual mortality of 19.3%, with a 19.2%
annual rate of hemorrhage and a 10.9% annual rate of
NHND during the disease course of DAVFs with
persistent CVR. The study by Van Dijk recalculated
these rates based on a larger population and four times
the follow-up time. During a combined follow-up time
of 86.9 patient-years an annual mortality rate of
10.4% was yielded, with an annual hemorrhage rate of
8.1% and an annual NHND rate of 6.9% (44). This
result mandates a prompt and curative management
of the aggressive DAVFs. Soderman found a lower
annual risk of hemorrhage or NHND in patients with
DAVFs with CVR, reporting a 7.4% annual risk of re-
hemorrhage in patients presenting with hemorrhage
and a 1.5% risk if the presentation did not include
hemorrhage (45). In a letter to the editor Van Dijk poin-
ted out a number of flaws in the paper by Soderman
including a short mean follow-up time and exclusion
of a number of patients (46). Subsequently, the study
by Strom not only confirmed the Toronto experience of
a high event rate in the natural disease course of a
DAVF with CVR, but also found a significant differ-
ence between asymptomatic DAVFs and fistulas with
an initial aggressive presentation (47).
454 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 22.2 Resolution of T2 hyperintensity post treatment. A 58-year-old female presented with a progressive quadriplegia. Axial
T2-weighted MR (A) shows diffuse central hyperintensity within the medulla (arrow). AP view of the right vertebral arteriogram
(B) shows a DAVF at the foramen magnum with drainage into a large perimedullary vein (arrow). Selective arteriogram (C) of the dural
branch feeding the fistula better defines the fistula. Embolization was not done because we could not obtain a safe position to inject
liquid adhesives. Surgical disconnection was done with a single clip to close the intradural draining vein. The patients clinical condition
gradually improved and at 6 months the T2 hyperintensity on the MR had resolved (D).

Cranial Diagnostic Imaging
Computer Tomography (CT)
In the absence of CVR with congestion of the brain,
benign DAVFs are practically always occult on CT
imaging. In cases of an aggressive DAVF, unenhanced
CT may show hypodensities that represent areas of
edema or venous ischemia. Abnormally enlarged
pial veins can sometimes be visualized as increased
densities in comparison to the brain parenchyma.
Contrast-enhanced CT shows enhancement of the
refluxing cortical venous network, and CT angio-
graphy may show the fistula site with enlarged
feeding arteries and braining veins. A promising tech-
nique is the development of 4D-CT angiography, espe-
cially in emergency situations (48).
MRI/Magnetic Resonance Angiography
On MRI, it is difficult to detect a benign DAVF,
although suspicion might be raised in case of an
irregular or stenotic venous sinus. MR angiography
is more sensitive, but still has its limitations to depict
the fistula. Aggressive DAVFs are better visualized
by MRI, characterized by flow voids on the cortex
corresponding to dilated pial vessels. The brain
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 455

(A) (B)

Figure 22.3 Gadolinium-enhanced MRA detects a DAVF and its cortical venous drainage. A 58-year-old male presented with conjunc-
tival injection and chemosis in the right eye. The collapsed axial image from the gadolinium-enhanced MR angiogram (A) shows an
early draining cortical vein (short arrow) and drainage into the right superior ophthalmic vein (long arrow). The lateral view from the right
external carotid arteriogram (B) confirms that there is a cavernous sinus DAVF with CVR (arrow).

parenchyma can show T2 hyperintensity in the white
matter secondary to the venous congestion of the brain,
especially in the deep white matter. The differential
diagnosis for T2 hyperintensity includes sinus throm-
bosis (with venous infarction or venous congestion),
demyelinization, and neoplasm. However, T2 hyper-
intensity in the parenchymal in combination with a
surplus of pial vessels is highly suggestive of a vascu-
lar malformation (Fig. 22.1) (49). This T2 hyperintensity
resolves after treatment (Fig. 22.2). With real-time
Auto-Triggered Elliptic Centric-Ordered 3D gadolinium-
enhanced MR angiography (ATECO) it is possible to
diagnosis DAVFs without DSA (Fig. 22.3) (50). Time-
resolved MR angiography at 3 Tesla improved the
diagnostic acumen in DAVFs allowing us to detect
and classify these lesions (Fig. 22.4). This technique
is ideally suited to follow DAVFs that do not require
treatment, since the development of CVR will be evi-
dent in most patients (51). Gradient-echo (GRE) and
susceptibility weighted images have highlighted the
presence of diffuse hemosiderin deposition within
the brain secondary to venous congestive encephalo-
pathy (Fig. 22.4) (52).
long-standing venous hypertension. This finding has
been referred to as the pseudophlebitic pattern and
correlates with a greater risk of future hemorrhage or
NHND (35). Careful analysis of the venous phase of
the cerebral circulation is critical in planning treat-
ment. The main goal in the imaging of cranial DAVFs
is to detect the existence of CVR. Global non-selective
angiography should be avoided as subtle CVR might
be missed. Another important objective is to look for
venous sinus outflow obstruction, which can result in
extracranial drainage through collateral routes, includ-
ing the orbital system. Venous stenosis or obstruction
is a common finding in patients with retrograde flow
into the cortical and cerebellar veins. Careful analysis
of the venous phase of the angiogram may reveal dis-
tinct pathways that separately drain the fistula and
the brain. This compartmentalization of the involved
dural sinus may allow closure of the fistula and
preservation of that compartment of the fistula that
drains the brain (53). In diagnostic imaging the exis-
tence of multiple DAVFs within one patient should
be considered, since this is reported in a frequency
of 78% (54).

Digital Subtraction Angiography Cranial Therapeutic Considerations

Conventional angiography remains critical for treat-
ment planning. Selective contrast injections into the
divisions of the external carotid artery will show
rapid arteriovenous shunting through the fistula into
the cranial venous system. Contrast injection selec-
tively into the internal carotid or vertebral arteries
may reveal a delayed circulation time, compatible
with venous congestive encephalopathy (37). On the
venous phase of the internal carotid or vertebral
artery angiogram, tortuous dilated collateral veins
may be evident over the surface of the brain indicating
If treatment of a DAVF is indicated, the endovascular
approach should be the first choice. Surgery is used in
combination with the endovascular technique or if
endovascular therapy fails. Surgery can allow access
for an endovascular approach or is used to occlude
the diseased sinus or disconnect the CVR (55). The
endovascular treatment can be done from a transarte-
rial approach, a transvenous route, or a combination
of both. The transvenous approach is often preferred
due to its effectiveness in obliterating the fistula or
the CVR.
456 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 22.4 Time-resolved MRA shows Borden 3 DAVF, and GRE technique shows extensive hemosiderin deposition. An 87-year-
old male presented with a seizure, fluctuating right arm weakness and cognitive decline. Axial MIP CTA image of the brain (A) shows
extensive transmedullary collateral veins and prominent cortical veins. Axial T2-weighted MR (B) shows hyperintensity in the left motor
cortex with adjacent cortical hypointensity. GRE shows dilated transmedullary veins and patchy cortical hemosiderin deposition (C, D).
Time resoled gadolinium-enhanced MRA (E) shows venous shunting into the SSS with CVR. Lateral right internal carotid arteriogram
(F) shows no filling of the anterior SSS and a pseudophlebitic pattern of the transmedullary veins. Right external carotid arteriogram
(G) shows the fistula into the SSS. Lateral skull film (H) shows the results of the transvenous coil embolization of the involved sinus
using a tri-axial catheter system. Note the tip of the 6F shuttle in the internal jugular vein and the tip of the 0.70 inch Neuron beyond
the torcular to allow a stable guiding system for placement of the microcatheter in the involved sinus. Post embolization lateral external
carotid arteriogram (I) shows the fistula closed. The patients symptoms improved within days of treatment and he has been seizure
free with normal power.
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 457

Management of Benign DAVFs symptoms, but symptoms usually recur, often to a

In benign cranial DAVFs reports show that the vast
majority of patients have an excellent natural history,
indicating that in general observation with time-
resolved gadolinium-enhanced MRA re-evaluation is
the best available management. If there is any sudden
or unexpected change in the clinical status, either wor-
sening or improvement (even disappearance), prompt
follow-up with time-resolved MR angiography is
needed to look for the development of CVR or progres-
sive thrombosis with retrograde flow in the sinus (51).
In patients that either suffer an intolerable bruit
or have orbital symptoms which compromise vision,
palliative arterial endovascular embolization could be
considered to reduce symptoms. Arterial embolization
alone often reduces the symptoms but is frequently
not effective in obtaining a complete angiographic
obliteration of the fistula, although in some cases
arterial embolization with liquid adhesives can per-
manently close the fistula (Fig. 22.5). Particle embo-
lization often results in an early improvement of
lesser degree. Transvenous coil embolization of the
diseased venous sinus is an effective treatment for
symptoms, and as a rule results in total angiographic
obliteration of the DAVF (Fig. 22.6). However, sacri-
fice of a venous sinus should only be done when it
exclusively drains the fistula and does not participate
in the venous drainage of the brain. Targeted emboli-
zation of a compartment of the sinus may be effective
in obliterating the fistula with preservation of that
part of the venous sinus that is not participating in
the fistula (Fig. 22.7) (56).
In most patients, sacrifice of the venous sinus is
done using a transvenous approach. In exceptional
cases, catheterization of the venous sinus can be
reached using the transarterial approach. This can be
feasible in traumatic DAVFs due to the large connec-
tion between the dural artery and the adjacent vein
(Fig. 22.8) or in high-flow fistulas. In most spontane-
ous DAVFs the feeding arterial network is too tortu-
ous and serpiginous to allow catheterization of the
sinus from the arterial approach.

(A) (B)

(C) (D)

Figure 22.5 Embolization of a cavernous sinus DAVF with liquid adhesives. A 64-year-old male presented with chemosis, conjunctival
injection and raised intraocular pressure in the right eye. Lateral right external carotid arteriogram (A) shows a DAVF draining exclu-
sively into the superior ophthalmic vein (open arrow). The fistula is into a small compartment in the anterior aspect of the cavernous
sinus (long arrow). A selective injection (B) into a dural branch of the middle meningeal artery (small arrow) delineates the fistula site
(long arrow). The cast of the liquid adhesive (arrow in C) shows that there is good penetration through the fistula. The control right
external carotid arteriogram (D) confirms that the fistula is closed.
458 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

(E) (F) (G)

Figure 22.6 Transvenous facial approach to bilateral cavernous DAVFS. A 52-year-old female presented with diplopia, bilateral che-
mosis, and bilateral conjunctival injection. Lateral right (A) and left (B) external carotid arteriograms show bilateral cavernous sinus
DAVFs draining into both superior ophthalmic veins. Note the subtle CVR (arrow in A) on the right. Using a femoral venous approach a
left transfacial route (C) was used to reach the contralateral cavernous sinus. On the AP view note the selective catheter position in
the contralateral cavernous sinus (D). The right cavernous sinus venogram (E) during the coil embolization of the right cavernous sinus
shows the reflux into cortical veins (arrow in E). Coil embolization of both cavernous sinuses was done (F). The control AP external
right and left arteriograms (G) show that the DAVFs were closed. The patients orbital symptoms improved over time; however, her
ophthalmoplegia had not resolved at 6 months.

Management of Aggressive DAVFs with Direct CVR
(Borden 3)
Aggressive cranial DAVFs demonstrate severe compli-
cations in their natural disease course, as such man-
dating aggressive treatment. Treatment procedures
aimed at the selective disconnection of CVR have been
amply reported for DAVFs with direct CVR in the
absence of dural sinus drainage (Borden 3/Cognard
type III and IV). Pathophysiologically a DAVF is con-
sidered a venous disease, and thus a permanent cure
of a cranial DAVF with direct CVR can be obtained by
a selective intradural division of the venous outlet of
the fistula, analogous to the well-known treatment of a
spinal DAVF. Primarily this procedure has been
described as a neurosurgical technique; however, with
the advances in interventional neuroradiology the
same result has been demonstrated using endovascu-
lar means as well (5761). A transvenous approach is
the most likely endovascular technique to disconnect
the CVR (Fig. 22.9). In some patients, transarterial
embolization with liquid adhesives may obliterate the
fistula. This is done with a wedged catheter and a
liquid adhesive that has a long polymerization time.
Both NBCA (N-Butyl cyanoacrylate) with varying con-
centrations of lipiodol, and ONYX [ev3] have been
used. The advantages and disadvantages of each of
these liquid adhesives have been debated. Often the
choice of the liquid adhesive is dependent on the oper-
ators and their familiarity with the use of that agent.
The arterial catheter must be close to the fistula site to
allow the slow push of the liquid adhesive through
the fistula into the proximal venous outlet. A too prox-
imal embolization allows persistent arterial shunting
and recruitment of collateral flow, and a too distal
embolization may result in venous occlusion and
venous infarction. Transarterial particle embolization
may transiently reduce the flow through the fistula
and should only be used in high-flow, complex
DAVFs in combination with a transvenous approach
or with surgery.
Management of Aggressive DAVFs with Dural Sinus
Drainage and CVR (Borden 2)
In case of combined dural sinus drainage and CVR
(Borden grade 2; Cognard type IIb or IIa+b), the oblit-
eration of the whole fistula including excision or
endovascular packing of the involved dural sinus has
been advocated (6265). The drawback of permanent
occlusion of an involved sinus may be impairment of
the venous drainage of the normal brain, resulting in
(hemorrhagic) venous infarction and/or leading to
chronic complications of venous hypertension, e.g.,
dementia. Mironov reported the treatment of two Bor-
den 2 DAVFs, in which the CVR was endovascularly
disconnected without changing the venous drainage
of the dural sinus (66). In this way the fistula itself
was not obliterated, but instead converted into a
benign DAVF. This may be done by either a transarte-
rial approach with liquid adhesives (Fig. 22.10) or a
transvenous approach with coils (Figs. 22.11, 22.12).
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 459

(A) (B) (C)

(D) (E) (F)

Figure 22.7 Targeted transvenous embolization of a cavernous DAVF. A 54-year-old male presented with chemosis, conjunctival
injection, and proptosis in the left orbit. His raised intraocular pressure in the right eye could not be relieved with topical medication.
Lateral left internal (A) and external (B) carotid arteriograms showed shunting into the left cavernous sinus and drainage into the supe-
rior ophthalmic vein and inferior petrosal sinus (arrow). Transvenous catheterization (C) was done via the inferior petrosal sinus. The
site of the fistula was identified to be in the anterior lateral compartment of the cavernous sinus. Deposition of four Hydrocoils (Micro-
vention, California) was done to close the fistula site (arrow in D). Control left internal (E) and external (F) carotid arteriograms show
closure of the fistula. The patients signs and symptoms resolved completely within a few weeks.

The transvenous route is preferred, since it is more
likely to be successful compared to the injection of
liquid adhesives from the arterial feeders. This is clini-
cally important, as it has been demonstrated in the ser-
ies by Davies and Satomi that benign DAVFs follow a
disease course without any grave neurological events
and this is mostly a self-limiting disease (32,34).
If the endovascular treatment fails to eliminate
the CVR then there are a number of surgical options.
A burr hole can be placed over the diseased sinus to
allow packing of the sinus with a microcatheter placed
through a small sheath. The burr hole can be localized
using a roadmap technique from an arterial injection
or using neuronavigation equipment. Packing of the
sinus must be done under fluoroscopic guidance and
control angiography can be done from the arterial
side to determine when the fistula is closed or the
CVR is eliminated. Alternatively, direct packing of the
sinus can be done after surgical exposure of the entire
sinus. Surgical resection of a sinus is often associated
with high morbidity and mortality, even in experi-
enced hands (67). However, the surgical technique of
selective disconnection of the CVR, leaving the actual
fistula in the wall of the dural sinus untouched, is
relatively simple. Coagulation and division of the
refluxing cortical veins as they enter the subarachnoid
space is sufficient to convert an aggressive DAVF into
a benign one. In complex, high-flow DAVFs, pre-
operative embolization with liquid adhesives or
particles can be helpful to reduce blood loss during
surgery and may improve the results of a surgical dis-
connection or packing of the sinus. The permanent
application of aneurysm-clips has been increasingly
avoided during the past decade, because of local dis-
tortions of the magnetic field in MRI (55).
Transvenous Approaches to the Cavernous Sinus:
Special Considerations
There are a number of transvenous approaches to the
cavernous sinus. From the femoral venous route these
include: opacified ipsilateral or contralateral inferior
petrosal sinus, unopacified ipsilateral or contralateral
inferior petrosal sinus, superior petrosal sinus, ptery-
goid plexus, and facial vein. Using the contralateral
inferior petrosal sinus the operator needs to cross the
midline through the basal venous plexus or the intra-
cavernous venous sinus. Intracranial surgical exposure
460 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E)

Figure 22.8 Transarterial approach to venous packing of a traumatic DAVF. A 22-year-old male complained of a pulsatile tinnitus
after trauma. The left lateral external carotid arteriogram (A) shows an osseous fistula draining toward the pterygoid plexus. The selec-
tive middle meningeal arteriogram (B) shows a high flow fistula within the sphenoid bone draining into an extracranial venous pouch
(arrow). Selective catheterization (C) of the venous pouch allowed deposition of coils into the pouch (arrow in D). Liquid adhesives
were injected into the pouch from the fistula site after the coils had significantly reduced the flow (arrow in D). A control left external
carotid arteriogram (E) shows that the fistula is closed.

of the superficial middle cerebral vein allows access
to the cavernous sinus through the sphenoparietal
sinus. Also, surgical exposure of the superior oph-
thalmic vein allows transvenous navigation into the
cavernous sinus (63). In Meyers report of 117 dural
AVFs of the cavernous sinus transvenous access was
achieved through the inferior petrosal sinus or supe-
rior ophthalmic vein in 76% of cases (68). Based on
the venous drainage, Klisch divided the cavernous
DAVFs into four compartments: anterior, posterior,
lateral, and inferior. In their report, cavernous
DAVFs were treated transvenously in 60% of cases,
with complete obliteration of the fistula in 78% (69).
Recognition of the type of cavernous DAVF based on
the compartment can help plan the approach and the
treatment can be targeted to the involved compart-
ment (Fig. 22.6) (56).
Transvenous Embolization of Transverse Sinus
DAVFs: Special Considerations
If the affected sinus is isolated from the circulation
then sinus occlusion is effective to close the fistula
and eliminate the CVR. In such cases the risk of
venous infarction is low since the cortical veins do not
drain into the affected sinus. In some patients, the iso-
lated sinus can be reached transvenously through an
occluded segment. The ipsilateral approach is pre-
ferred to avoid inadvertent retrograde catheterization
of cortical veins during the contralateral approach.
Improved guiding catheterization stabilization can be
achieved using a tri-axial system (Fig. 22.4). Passage
through an occluded sinus may be facilitated with
quick back-and-forth rotations of a 0.35 inch Glidewire
[Terumo]. Once the open sinus has been reached with-
drawal of the Glidewire under a blank roadmap
will expedite the placement of a microcatheter/guide-
wire. If the transvenous route is unsuccessful, a burr
hole or direct surgical exposure can allow packing of
the isolated sinus. Irrespective of the applied technique,
the operator has to be aware that if the affected sinus
drains both the fistula and the cortical veins then occlu-
sion of the sinus carries a significant risk of venous
infarction. It has been shown that a number of trans-
verse/sigmoid DAVFs have a parallel venous channel
as the recipient compartment for the fistula that is dis-
tinct from the compartments that drain the cortical
veins. Superimposition of the arterial and venous
phases of the angiogram is important to illustrate these
distinct compartments. Recognition of this parallel
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 461

(A) (B)

(C) (D)

Figure 22.9 Transvenous disconnection of a Borden type 3. A 62-year-old male presented with a brainstem hemorrhage (A). The left
lateral internal carotid arteriogram (B) shows a DAVF fed by an inferior marginal tentorial artery (single arrow) draining into a cortical
vein (double arrows). Note the venous pouch that likely represented a pseudoaneurysm at the site of the previous bleed. Using a trans-
venous approach catheterization of the venous pouch was feasible (C). Coils were deposited within the cortical vein and the venous
pouch. A control internal carotid arteriogram (D) showed that the fistula was closed. A six-month control catheter angiogram confirmed
the stability of the embolization.

channel allows selective transvenous embolization of
that part of the sinus that participates in the CVR
(Fig. 22.12). Caragine recognized this parallel venous
channel in 10 patients and performed selective trans-
venous embolization with preservation of the transverse/
sigmoid sinus in all 10 cases (70). Piske highligh-
ted the concept of the parallel venous channel and
reported on the selective embolization of the affected
compartment in the SSS with preservation of the sinus
itself (53).
Role of Radiosurgery
Although case reports and small series persist in the
literature, there is a limited role for the radiosurgical
treatment of cranial DAVFs, with or without CVR
(7173). Benign cranial DAVFs do not require treat-
ment or may in case of intolerable symptoms benefit
from the instant effect of palliative embolization.
Aggressive cranial DAVFs have a poor natural history
with a high annual event rate, making the delayed
effects of radiosurgery to be unacceptable. Only after
failed endovascular and/or surgical treatment DAVFs
might be considered for radiosurgery (74).
SPINAL DURAL AV-FISTULAS
The first description of spinal AVMs dates back to 1888
by Gaupp as a cluster of hemorrhoids on the pia mater
of the spinal cord (75). Medical descriptions in those
days were based on postmortem dissection or surgical
exposure, and then related to the observed clinical
symptoms. Brasch, in 1900, reported a severe case of
myelopathy to a serpentine-like transformation of the
spinal cord vasculature (76). The first documented sur-
gical exploration of a spinal vascular disorder (with a
poor result) was performed in 1911 by Krause, fol-
lowed by the first curative surgical exposure by Elsberg
in 1916 (77,78). Following the introduction of angiogra-
phy techniques, radiological descriptions of spinal
pathology became available. Despite these primitive
circumstances, WyburnMason published a relatively
462 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

Figure 22.10 Conversion of a Borden type 2 DAVF to a type 1 by arterial embolization with liquid adhesives. A 72-year-old male pre-
sented with pulsatile tinnitus and a bruit 12 months after a motor vehicle accident. The lateral left external carotid arteriogram
(A) shows shunting into an irregular transverse sinus and reflux into the vein of Labbe (arrow). Selective catheterization of the posterior
branch of the left middle meningeal artery allowed deposition of the liquid adhesive (N-Butyl cyanoacrylate) (arrow in B) at the site of
the CVR. Control occipital (C) and external carotid (D) arteriograms at the time of the embolization show persistence of the shunting
into the transverse sinus with elimination of the CVR. A repeat catheter angiogram two years later showed no change from the immedi-
ate post embolization study.

(A) (B) (C)

st E
(D) (E) (F)

Figure 22.11 Conversion of a Borden type 2 cavernous DAVF to a type 1 by transvenous embolization with coils. A 77-year-old
female presented with bilateral conjunctival injection and chemosis. The left external carotid arteriogram (A) shows a DAVF of the cav-
ernous sinus draining into cortical veins (arrow) and the inferior petrosal sinus. Using a transvenous approach through the ipsilateral
inferior petrosal sinus (small arrows in B) we were able to catheterize the sphenoparietal sinus (arrow). We packed the sphenoparietal
sinus and the adjacent cavernous sinus with coils (C). A control left external arteriogram (D) shows that the CVR was eliminated and
there was less flow through the fistula. On the venous phase of the lateral internal carotid arteriograms before (E) and after (F) treat-
ment we see that the cortical veins over the temporal lobe (arrows) could drain the brain after the cortical venous disconnection. The
patients symptoms resolved and she has been stable for five years.
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 463

(A) (B) (C) (D)

(E) (F) (G) (H)

Figure 22.12 Conversion of a Borden type 2 transverse sinus cavernous DAVF to a type 1 by transvenous embolization of a parallel
channel. A 37-year-old female developed SSS thrombosis (arrow in A) one year after renal transplantation. Three years later the
patient developed a bruit and her MR showed prominent, tortuous flow voids (arrows) over the surface of the brain (B). Multiple intra-
cranial DAVFs were found on a cerebral angiogram. The lateral left external arteriogram (C) shows a DAVF of the transverse sinus
with CVR (arrows) and occlusion of the ipsilateral sigmoid sinus. A transvenous approach via the contralateral transverse sinus allowed
selective catheterization of a parallel channel that connected to the cortical veins that participated in the reflux. Venography in this par-
allel channel (D) shows the veins that were draining the fistula. This parallel channel was embolized (arrow in E) with a combination of
platinum coils and Hydrocoil (Microvention, California). A control left external arteriogram (F) shows that the CVR was eliminated
although the fistula persists. On the venous phase of the lateral internal carotid arteriograms before (G) and after (H) treatment we see
that these cortical veins can participate in the venous drainage of the brain after disconnection.

large series (110 patients) and classified them into
venous angiomas and arteriovenous angiomas (79).
Even after the introduction of the concept of venous
congestion of the spinal cord in the early seventies, spi-
nal DAVFs were categorized into the group of the spi-
nal AVMs (80). This led to the unfortunate assumption
that the congested perimedullary venous plexus was a
part of the nidus. It needs no explanation that the strip-
ping of the venous plexus as a part of the surgical ther-
apy therefore often gave rise to increased postoperative
neurological deficits (81).
In the late seventies, spinal DAVFs were
described as extramedullary fistula-type lesions drain-
ing into the perimedullary venous plexus distinguish-
ing them from true spinal AVMs (82,83). Oldfield and
Symon recognized that a single shunting vein to the
perimedullary venous plexus allowed simple surgical
occlusion of the shunting vein (84,85).
Spinal Classification
Spinal vascular arteriovenous shunts are a heterogene-
ous group of congenital malformations and acqui-
red fistulas. Therefore, several classification schemes
have been proposed that each tries to regroup these
separate lesions on different insights in pathology.
The most commonly used is the following scheme
with four subdivisions: type I, dural AVF; type II,
intramedullary glomus; type III, juvenile; type IV,
perimedullary (86). However, it doesnt take an expert
to realize that these categories are too static and that
classification is often difficult. In 2002, Rodesch intro-
duced a much more advanced classification of the
intradural AV-shunts based on the Bicetre experience,
in which they differentiate on quantity (single/multiple),
general aspect (nidus or fistula), associated metameric
disorders, and myelomere location. Notably, in this
arrangement the spinal DAVFs are excluded (87).
Spetzler introduced a classification with a wider scope
that subdivides the spinal vascular lesions in neoplas-
tic vascular lesions, spinal aneurysms, spinal AVMs,
and spinal AVFs. Within the spinal AVFs, three sub-
groups are identified: extradural AVFs, intradural
ventral AVFs, and intradural dorsal AVFs (the latter
group essentially DAVFs) (88).
Spinal DAVFs embody the vast majority of all
spinal vascular lesions in the adult population and are
virtually absent in the pediatric age group. The
acquired AV-fistula is typically located at the thoracic
or lumbar level (89). Remarkably, at the cervical level
DAVFs are rare. This has been explained by the exis-
tence of numerous venous outlets at the cervical level,
in contrast with the thoracolumbar level, and by the
influence of gravity facilitating the venous reflux to
the vena cava system. Presentation with subarachnoid
hemorrhage may be secondary to either cranial DAVFs
464 NEUROINTERVENTIONAL MANAGEMENT
or extradural AVFs draining into the perimedullary
venous plexus (90).
Spinal Clinical Features
The clinical features of a spinal DAVF are directly
related to the venous congestion of the spinal cord,
caused by a direct fistula of the radiculomeningeal
artery to the perimedullary venous plexus. This leads
to a clinical picture of chronic progressive myelopathy
of the lower thoracic cord and conus, irrespective of
the location of the shunt (91). Venous congestion lead-
ing to hypoxia and ischemia is accepted as the theory
of choice. This is supported by histopathological find-
ings from biopsies of the spinal cord (92).
Spinal DAVFs typically present in the fourth to
sixth decade, commonly in males. In a study combin-
ing the clinical findings in 172 patients from five ser-
ies in the literature, leg weakness was the initial
complaint in 40%; however, at the time of diagnosis it
was present in 88% of the cases. The same phenom-
enon is described in bladder and bowel dysfunction
(5% versus 85%). This discrepancy is explained by the
extensive delay between the initial presentation and
the actual diagnosis. In the report by Symon only one-
third of patients were diagnosed within one year of
the onset of symptoms and only two-thirds of patients
had their diagnosis within three years (93). Hemor-
rhage practically never occurs, although it is a major
presenting sign of the cranial DAVFs with reflux in
the leptomeningeal veins. This is likely explained by
the slow-flow characteristics of these lesions (94).
Intracranial DAVFs with perimedullary venous reflux
may present with a cervical myelopathy or with a cer-
vical intradural hemorrhage (95)
Van Dijk reviewed 49 patients with a spinal
DAVF. The mean age was 63.2 years, with an 80%
male predominance. The fistulas were located between
the nerve roots of C7 and S1, 94% situated below the
T5-root level, in majority on the left side (70%). It
hypothesized that the position of the heart is related to
these findings. Multiplicity was encountered in one
patient (2%). At the time of diagnosis, all but one
patient (who complained of radicular pain) had signs
and symptoms of myelopathy. The majority of the
patients (96%) suffered from spastic paraparesis or leg-
weakness and 90% had sensory disturbances. Bladder
and bowel malfunctions as well as pain (either back or
remote pain) were other significant complaints. The
time interval between the initial symptoms and diag-
nosis was median 10.5 months (96).
In the natural disease course of spinal DAVFs,
the thoracic myelopathy gradually progresses to a
state of paraplegia and incontinence. Eventually this
leads to the Foix-Alajouanine syndrome, originally
described in 1929, as a subacute necrotizing myelop-
athy (97). To classify the severity of the thoracic myel-
opathy frequently the classification scale for motor
and bladder function as used by Aminoff is applied
(Table 22.3) (98).
Spinal Diagnostic Imaging
The current mainstay of diagnosing a spinal DAVF is
MRI. Typically on T2 images there is a hyperintense
Table 22.3 Aminoff Score of Disability
Classification of Gait Disturbance
Grade 1 Leg weakness or abnormal gait; no restricted activity
Grade 2 Grade 1 with restricted activity
Grade 3 Requires one stick or similar support for walking
Grade 4 Requires two sticks or crutches for walking
Grade 5 Unable to stand, confined to bed or wheelchair
Classification of Micturition
Grade 1 Hesitance, urgency, or frequency
Grade 2 Occasional urinary incontinence or retention
Grade 3 Total urinary incontinence or retention
signal within a slightly swollen lower thoracic spinal
cord and medullary conus, outlined by a peripheral
hypointensity (99). Spin-echo techniques are supreme
to reveal the vascular nature of the congestive myelop-
athy. Contrast enhancement with Gadolinium can be
useful in differentiating from an intramedullary tumor,
although in severe congestive myelopathy patchy
enhancement is common. Enhancement of the convo-
luted perimedullary venous plexus supports the diag-
nosis of a spinal DAVF, but the abnormal flow voids
are nonspecific for the actual location of the fistula.
To point out the level of the fistula-enhanced
ATECO MRA has been effective (Fig. 22.13). This tech-
nique, published by Farb, proves useful in determin-
ing the level of the fistula and expediting the selective
catheter angiogram (100). The spinal angiography can
be limited to bilateral injections of the radicular
arteries at the level of the fistula and the immediate
adjacent levels above and below. The fistula is typi-
cally located at the level of a root sleeve; however,
it may be remote. In the latter cases, a bimetameric
arterial supply can be expected. The fistulous point is
recognized on the angiogram by a caliber change
between the artery and the dilated vein. The intradural
vein is unpredictable in its location and direction, but
typically it follows the course of the nerve root. For
treatment planning, visualization of the anterior spinal
artery (Adamkiewicz) is essential and warrants addi-
tional injections. The Adamkiewicz artery often arises
between T8 and T11, in 50% of the cases from the inter-
costal artery at T9 or T10 on the left (101). Injection of
the Adamkiewicz artery typically reveals a prolonged
circulation time within the spinal cord, indicative of
venous congestion (102).
If ATECO MRA does not reveal the fistula site,
but the MRI and the clinical picture are highly sugges-
tive of a spinal DAVF, a more extensive spinal angiog-
raphy is necessary, including selective injections of all
intercostal and lumbar arteries, as well as both inter-
nal iliac arteries. If still no spinal DAVF is determined,
subsequently the cervical cord and intracranial circu-
lation should be visualized. This includes selective
injections of both vertebral arteries as well as the cost-
ocervical and thyrocervical arteries. A study of the
intracranial circulation should include the vertebral,
internal, and external carotid arteries (95).
Spinal Therapeutic Considerations
All spinal DAVFs should be treated by occlusion or
division of the fistulous vein. Intradural surgical liga-
tion has proven very effective with durable results
 ENDOVASCULAR MANAGEMENT OF DURAL ARTERIOVENOUS FISTULAS 465

(A) (B) (C)

Figure 22.13 Gadolinium-enhanced MRA expedites treatment of spinal DAVF. A 63-year-old male presents with a thoracic myelop-
athy. The T2-weighted MR of the spine (A) shows a central T2 hyperintensity within the cord and prominent posterior perimedullary
veins (arrows). The gadolinium-enhanced MR angiogram (B) identifies the fistula site (arrow) of the spinal DAVF thereby facilitating the
catheter angiogram (C) that is done in order to embolize the fistula.

(84,103). Surgical interruption of the draining radicu-
lar vein is preferentially done using bipolar coagula-
tion. Excision of the whole fistula site is obsolete and
may cause unnecessary CSF-leakage and nerve root
sacrifice. In case of both intradural and extradural
venous drainage, surgical interruption of the intra-
dural vein will treat the congestive myelopathy; the
extradural drainage can be left alone (104). Endovas-
cular techniques using a diluted liquid adhesive
(NBCA) have proven effective with durable results
(105,106). Newer embolic agents such as ONYX pro-
vide significant promise for definitive initial manage-
ment of these lesions, yet require longer clinical
follow-up analysis (107). Particle embolization is not
recommended because the incidence of symptomatic
recurrence is high (108). It is essential that the embolic
material reaches the proximal part of the draining
vein, otherwise collateral dural branches may keep the
fistula open and recurrences occur despite what was
thought to be an adequate treatment (109). The collat-
eral flow may not be evident at the time of emboliza-
tion and therefore patients need close follow-up.
Patients may improve initially after the embolization,
but will experience delayed deterioration following
partial treatment.
Although it is generally accepted that surgery
and endovascular therapy are equally effective, a
recent meta-analysis suggests that a surgical approach
is preferable (110). The advantage of endovascular
embolization is that it is less invasive and there can be
immediate angiographic control of the treatment.
Using ATECO-MRI the diagnostic angiography can
even be combined with the treatment. Therefore, ini-
tial attempt at endovascular embolization with liquid
adhesive material can be justified, but should not be
undertaken if catheterization of the branch to the feed-
ing pedicle proves to be difficult on the diagnostic
angiogram or in case there is a common segmental
origin of the anterior spinal artery and the radiculo-
meningeal branch supplying the fistula (111). In case
of a partial result or abstention from endovascular
embolization, surgical therapy should be instituted
shortly after. It is mandatory to have a curative
treatment.
Using the Aminoff-score the meta-analysis by
Steinmetz reports that both following surgery and
embolization for gait disturbances there is a 55%
chance of improving and an 11% chance of being
worse. Therefore, patients have an 89% chance of
improving or stabilizing. The results for improvement
in bladder function were less favorable. Only 33% of
patients demonstrated an improvement in micturition,
whereas 11% worsened (110).
If aggravation of the symptoms occurs after
treatment and there is angiographic proof of a cure
and no multiplicity, then the clinical deterioration
466 NEUROINTERVENTIONAL MANAGEMENT
may be due to a venous thrombosis of the perimedul-
lary veins. Such deterioration usually occurs within
days of the treatment and may warrant anticoagula-
tion therapy. For this reason, some authors propose
heparin for 3 days following embolization for all
patients with a significantly compromised venous
drainage (109).
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 23
Diagnosis and management of cerebral venous and dural
sinus thrombosis
John B. Weigele
INTRODUCTION
Cerebral venous and dural sinus thrombosis (CVST) is
an uncommon cause of stroke; it can occur at any age,
presenting with varied and frequently nonspecific
symptoms and signs (1,2). Due to these issues, as well
as the diverse spectrum of CVST findings on neuroi-
maging exams, an accurate clinical diagnosis can be
difficult and is often delayed (3). The prognosis for
CVST is generally favorable after conventional medi-
cal treatment with systemic anticoagulation; however,
a significant minority of patients experience poor out-
comes (death or dependency) (1,2,4). Individuals at
high risk for unfavorable outcomes can potentially
benefit from more aggressive management, such as
endovascular recanalization of the dural sinuses or
decompressive hemicraniectomy. This chapter will
review the diagnosis and management of CVST, with
an emphasis on diagnostic neuroimaging exams and
therapeutic neurointerventional procedures.
EPIDEMIOLOGY
Although no large population-based studies have
been performed, CVST is estimated to cause <1% of
all strokes (3). The reported annual incidence is 34
cases per million in adults and 7 cases per million in
children (2). In adults, CVST presents most frequently
in the third decade; pediatric CVST occurs most com-
monly in neonates (2,3,5). In children and the elderly,
CVST occurs with equal frequency in both sexes. In
young adults, CVST is 24 times more common in
females due to gender-specific risk factors (2,4,5). On
average, a large tertiary care medical center may see
58 cases of CVST per year (6).
RISK FACTORS
More than 100 risk factors for CVST have been identi-
fied (7). Categories include acquired and inherited proth-
rombotic conditions, cancer, dehydration, drugs,
infections, hematologic disorders, infections, inflammatory/
autoimmune diseases, and traumatic/mechanical fac-
tors (Table 23.1) (2,8,9). A direct cause or risk factor
for CVST is identified in approximately 85% of
patients; 15% of cases are considered idiopathic (2).
Often, the pathogenesis of CVST is multifactorial; for
example, trauma or the use of oral contraceptives
might precipitate CVST in an individual with an
underlying prothrombotic genetic condition (2,10).
In young adults, most cases of CVST occur in
women due to gender-related hormonal risk factors. In
epidemiologic studies from North America and Western
Europe, the rates of CVST during pregnancy and the
post-partum period averaged from 10 to 20 per 100,000
deliveries, representing 520% of all cases of CVST. This
was much greater than the rates within the general
population (11,12). Even higher rates for pregnant and
post-partum women have been reported from other
countries (12). The use of exogenous female hormones
also significantly increases the risk for CVST (10,13). In
a case series from Italy, 68% of the women who pre-
sented with CVST were on oral contraceptives (14).
Non-hormonal acquired and genetic prothrombotic con-
ditions of the coagulation system, fibrinolytic system,
endothelial cells or platelets have been found in 33% of
adults and 3399% of children with CVST (15).
Cranial infections, especially otitis media and mas-
toiditis, were the leading causes of CVST prior to the
widespread availability of antibiotics. Although these
are now less frequent causes for CVST, an infectious eti-
ology recently was found in 510% in the International
Study on Cerebral Vein and Dural Sinus Thrombosis
(ISCVT), which was a multinational, multicenter, pro-
spective observational study of 624 consecutive adult
patients with CVST (4). Higher frequencies of infectious
causes have been reported in children.
PATHOPHYSIOLOGY
CVST commonly affects multiple dural sinuses simul-
taneously (16). Intracranial venous thrombosis usually
begins in the dural sinuses, and may subsequently
extend into the cortical veins. In the ISCVT, the
transverse/sigmoid sinuses were the most commonly
affected sites, involved in 86% of patients (Fig. 23.1) (4).
The superior sagittal sinus (SSS) was involved in
62%, often in combination with transverse sinus (TS)
thrombosis. The straight sinus (StrS) was involved in
18%, and the Vein of Galen (VOG) and internal cere-
bral veins (ICV) were each involved in 11%. Thrombo-
sis extended into one or both internal jugular veins (IJ)
in 12%. The cortical veins were involved in 17%. How-
ever, given the relative insensitivity of conventional
neuroimaging exams for cortical vein thrombosis per-
formed without T2*-weighted magnetic resonance
470 NEUROINTERVENTIONAL MANAGEMENT
Table 23.1 CVST: Risk Factors and Causes
Acquired Prothrombotic Conditions
Anticardiolipin antibodies
Antiphospholipid antibodies
Homocysteinemia
Lupus anticoagulant
Nephrotic syndrome
Pregnancy
Puerperium
Inherited Prothrombotic Conditions
Antithrombin deficiency
Factor V Leiden mutation
Protein C deficiency
Protein S deficiency
Prothrombin mutation 20210G/A
MTHFR mutation
Infectious Diseases
Acquired immunodeficiency syndrome
Otitis and mastoiditis
Sinusitis
Meningitis
Sepsis
Systemic infections
Inflammatory and Autoimmune Diseases
Behcets syndrome
Inflammatory bowel disease
Sarcoidosis
Systemic lupus erythematosus
Thromboangiitis obliterans
Temporal arteritis
Wegners granulomatosis
Abbreviations: CVST, cerebral venous and sinus thrombosis; MTHR, methylenetetrahydofolate reductase.
Source: From Refs. 2,69.
imaging (MRI), its true incidence is probably signifi-
cantly greater (17).
Cortical vein thrombosis and dural sinus throm-
bosis contribute to the pathophysiology of CVST
through two mechanisms; both likely coexist in many
patients (2). One mechanism is obstruction of venous
outflow by the cortical vein thrombosis resulting in
increased venous pressure, in turn producing elevated
capillary pressure in the regional brain parenchyma.
A consequent reduction in cerebral perfusion pressure
may cause cytotoxic edema and ischemia. In addition,
the increased capillary pressure can disrupt the blood
brain barrier causing vasogenic edema. Cytotoxic and
vasogenic edema often coexist; common sequelae
include: localized cerebral edema, mass effect, and
venous infarcts (18). These cases often present with
focal neurologic findings. Venous infarcts frequently
are hemorrhagic, and can evolve into frank parenchy-
mal hematomas. The severity of parenchymal damage
has been correlated with the degree of increase in
venous pressure (19).
The second mechanism is the interference with
cerebrospinal fluid (CSF) resorption through the arach-
noid granulations in the dural sinuses caused by
obstructing thrombus, resulting in increased intracra-
nial pressure. Approximately 2040% of CVST patients
present with an isolated intracranial hypertension (IIH)
syndrome (i.e., headache, papilledema, but no focal
neurologic deficit except for a possible sixth nerve
palsy) due to this mechanism (4,20).
Hematologic Conditions
Anemia
Heparin-induced thrombocytopenia
Leukemia
Polycythemia
Thrombocythemia
Thrombotic thrombocytopenic purpura
Mechanical/Traumatic Factors
Compression/encasement (tumor)
Head injury
Jugular vein catheterization, injury
Lumbar puncture
Neurosurgery
Medications
L-asparaginase
Illicit drugs
Intravenous immunoglobulin
Hormone replacement therapy
Lithium
Oral contraceptives
Steroids
Sumatriptan
Other
Cerebral infarcts and hemmorhages
Cerebral vascular malformations
Congenital heart disease
Dehydration
Malignancy
Radiation
Thyrotoxicosis
CLINICAL PRESENTATION
CVST presents with a wide variety of clinical mani-
festations that are frequently nonspecific (4,2123).
Headache is the most common presenting symptom,
occurring in approximately 90% of adult cases (4). It
usually has a gradual, subacute onset that can pre-
cede other symptoms and signs by days. However,
up to 10% of patients present with the sudden onset
of a thunderclap headache, often associated with nau-
sea and vomiting, that may mimic a subarachnoid
hemorrhage (24). Approximately 50% of patients
develop one or more neurologic deficits, including
focal motor or sensory loss, aphasia, and visual field
deficits. Papilledema has been reported in 3080%.
Focal or generalized seizures occur in 1063%; this far
exceeds the frequency associated with arterial ischemic
stroke. Changes in mental status or level of conscious-
ness (delirium, amnesia, mutism, confusion, stupor, or
coma) have been reported in 1020%; these are more
common with involvement of the deep venous system
(4,25). Coma is a relatively strong predictor for a poor
clinical outcome.
Several relatively distinct clinical syndromes have
been described for CVST, although none is pathogno-
monic for the disorder (21,26). The most common syn-
drome is IIH; this occurs in up to 40% of cases (20).
These patients have headaches and papilledema
due to intracranial hypertension caused by impaired
CSF resorption, but do not have other neurologic
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS 471

Cortical veins Superior

17% sagittal sinus
62%

Straight
sinus
18%

Vein of galen
and internal
cerebral veins
11%

Transverse
sinuses
86%

Jugular veins
12% Figure 23.1 Relative frequencies of thrombosis
in the cerebral veins and dural sinuses from
ISCVT data. Abbreviation: ISCVT, International
Study on Cerebral Vein and Dural Sinus Throm-
bosis. Source: From Ref. 2.

manifestations except for a possible isolated abducens
nerve palsy due to the increased intracranial pressure.
Untreated IIH may eventually cause optic atrophy
and visual loss (2). This syndrome can be confused
with pseudotumor cerebri; these diagnoses are often
difficult to distinguish solely by clinical criteria (27).
This is potentially detrimental to the patient, since the
therapeutic and prognostic implications are signifi-
cantly different for these conditions (20,28).
A second syndrome that occurs nearly as often
as IIH consists of headaches combined with focal
neurologic deficits and/or seizures (with or without
Todds paresis); this is commonly associated with
focal parenchymal lesions on neuroimaging and typi-
cally is diagnosed more rapidly than IIH. One pre-
sentation of this syndrome that is uncommon but
particularly suggestive of CVST is the development
of symptoms and signs initially referable to one cere-
bral hemisphere, followed by findings related to the
other hemisphere; this reflects the sequential devel-
opment of bilateral parenchymal lesions as the result
of extension of thrombosis from the SSS into cortical
veins draining both cerebral hemispheres (2,26).
Less frequently, an acute or subacute encephalo-
pathic syndrome occurs with changes in mental status
and a progressive decline in the level of conscious-
ness; this is often associated with headache, nausea,
and long tract signs. This presentation, reported in
1020%, frequently reflects thalamic and/or brainstem
involvement from deep venous thrombosis and may
portend a poor outcome (25,26).
Finally, cavernous sinus thrombosis is usually
associated with infection and typically presents with
fever and pain in the V1 distribution of the trigeminal
nerve associated with characteristic orbital findings,
including periorbital edema, proptosis, chemosis, and
painful ophthalmoplegia (4).
DIAGNOSIS
Although CVST is an uncommon cause of stroke, the
diverse and often nonspecific spectrum of its clinical
presentation and evolution necessitates consideration
of its diagnosis in many clinical scenarios, including
patients with symptoms and signs of intracranial hyp-
ertension, young and middle-aged individuals with
the recent onset of an atypical headache or stroke-like
symptoms and signs without the usual vascular risk
factors, pregnant and post-partum women with stroke-
like findings, patients with hemorrhagic infarcts, and
individuals with infarcts that are not clearly confined
to arterial vascular territories especially when they are
multiple (2).
472 NEUROINTERVENTIONAL MANAGEMENT
Delays in patient presentation and the frequently
prolonged, unpredictable time course of symptoms
and signs add to the diagnostic dilemma; only a
minority of patients (2533%) are seen in the first
24 hours following clinical onset, while 25% initially
are evaluated more than 2 weeks after onset (29,30).
The average time from clinical onset to the diagnosis
of CVST was 7 days in the ISCVT (4). A delay in diag-
nosis affects clinical outcomes; in the ISCVT a diag-
nostic delay was associated with an increased risk of
visual deficit, and an increased risk of death or
dependency in patients with IIH (31).
Diagnostic Neuroimaging
Computed Tomography
Because of the considerable challenges in the clinical
diagnosis of CVST, diagnostic imaging plays a pivotal
role. Given the very frequent presentation of CVST
with headache and a wide spectrum of other potential
clinical manifestations, non-contrast-enhanced com-
puted tomography (NC-CT) is often the first neuroi-
maging exam that is obtained. Unfortunately, specific
findings are relatively uncommon in cases of CVST on
NC-CT, and the scan may be completely normal in
more than 30% of cases (32).
Recent thrombosis of a cortical vein or dural
sinus may be visible on NC-CT as a hyperdense struc-
ture (the cord sign) (Fig. 23.2); this is a relatively
specific diagnostic finding but infrequently identified,
reported in 2056% of patients with CVST (33,34).
Artifactually hyperdense cortical veins and dural
sinuses due to a high hematocrit (dehydration, polycy-
themia) or low-attenuation brain parenchyma (non-
myelinated white matter in neonates) can be misdiag-
nosed as cord signs. Adjacent subdural or subarach-
noid hemorrhage can also be confused with thrombus
in the dural sinuses (32).
Indirect findings of CVST on NC-CT include
brain edema and infarcts, particularly hemorrhagic
infarcts and those that are not located in a typical
(A) (B)
arterial distribution. A hemorrhagic infarct in the pos-
terior temporal and parietal lobes is characteristic of
thrombosis of the TS and the inferior anastamotic vein
of Labbe (Fig. 23.3) (2).
On contrast-enhanced CT (CE-CT), dural sinus
thrombosis may be visualized as a low attenuation
filling defect surrounded by enhancing dural sinus
walls (the empty-delta sign); however, this is only
seen in 28.8% of cases (33,35). The same finding can
be identified on contrast-enhanced MRI (CE-MRI)
(Fig. 23.4). However, as subacute to chronic clot
organizes, it can enhance with an appearance very
similar to a patent sinus and may mimic a non-throm-
bosed lumen. Prominent transmedullary veins func-
tioning as collaterals can also be seen on CE-CT and
CE-MRI with CVST (33).
Magnetic Resonance Imaging
On non-enhanced magnetic resonance imaging (MRI),
the absence of normal flow voids combined with
abnormal signal within the involved dural sinuses is
suggestive of CVST; however, the abnormal signal
intensities due to CVST are time and flow dependent
and are easily mimicked by artifacts such as slow or
turbulent flow (32).
The signal intensity of dural sinus thrombosis
varies with time. In the acute stage (07 days) the
thrombus consists predominantly of intracellular
deoxyhemoglobin that is isointense on T1-weighted
images and hypointense on T2-weighted images.
This may be indistinguishable from normal slow
flow in a patent sinus on MRI. In the subacute phase
(715 days), the thrombus evolves from intracellular
methemoglobin (hyperintense on T1-weighted images
and hypointense on T2-weighted images) to extracel-
lular methemoglobin (hyperintense on both T1- and
T2-weighted images); this is the easiest stage to
detect a thrombosed sinus on MRI images. The
thrombosed sinus is hyperintense on T1-weighted
images (Fig. 23.5). Chronic thrombus is usually
T1-isointense and T2-isointense to hypointense;
Figure 23.2 Cord signs on axial NC-CT images.
(A) Cord sign (hyperdense thrombus) in a throm-
bosed left TS (arrow) and hemorrhagic cerebellar
venous infarcts. (B) Cord signs in a thrombosed
SSS (arrow) and StrS (arrowhead). Abbrevia-
tions: NC-CT, non-contrast computed tomogra-
phy; TS, transverse sinus; SSS, superior sagittal
sinus; StrS, straight sinus.
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS
although signal intensities vary, at this stage it may
again be impossible to distinguish thrombus from
slow flow (32).
Cortical vein thrombosis has proven to be diffi-
cult to diagnose. Recently, T2*-weighted gradient echo
(GE) imaging has been found useful because of its
sensitivity to local inhomogeneities in magnetic sus-
ceptibility. This approach takes advantage of the
microscopic heterogeneity in the magnetic susceptibility
Figure 23.3 Typical hemorrhagic venous infarct secondary to
TS/vein of Labbe thrombosis imaged on NC-CT. Right posterior
temporal/parietal subcortical lesion with peripheral low attenua-
tion, central high density (hemorrhage), and local mass effect.
Abbreviations: TS, transverse sinus; NC-CT, non-contrast com-
puted tomography.
(A) (B)
473
of an acute and/or subacute thrombus (due to deoxy-
hemoglobin and/or methemoglobin within intact red
blood cells), which causes a blooming loss of signal
in the thrombosed vein on T2*-weighted GE imaging
(Fig. 23.6). A blinded, controlled, multi-reader study
found T2*-weighted GE imaging was 97.4% sensitive
for cortical vein thrombosis compared to 70% for
T1-weighted imaging (17). Other MRI pulse sequences,
CT, magnetic resonance venography (MRV) and com-
puted tomographic venography (CTV) all had sen-
sitivities 50%. Nonetheless, all of the modalities
were accurate when positive, with specificities and
positive predictive values of 100% (36). Although
T2*-weighted GE MRI is useful for detecting cortical
vein thrombosis, it is insensitive for dural sinus
thrombosis (17).
MRI is more sensitive than CT for the indirect
signs of CVST; MRI detects focal brain abnormalities
in as many as 57% of patients. These include focal or
diffuse brain parenchymal swelling, vasogenic edema,
cytotoxic edema, and venous infarcts. Venous infarcts
are often hemorrhagic and are frequently not confined
to a typical arterial vascular territory (Fig. 23.7) (32).
Thrombosis of the deep venous system can produce a
characteristic pattern of vasogenic and/or cytotoxic
edema in the thalami, basal ganglia, and deep white
matter (Fig. 23.8).
Magnetic Resonance Venography
A complete neuroimaging evaluation for CVST should
include dedicated vascular imaging; magnetic reso-
nance venography (MRV) has proven to be an excellent
non-invasive alternative to conventional digital sub-
traction angiography (DSA). Current MRV techniques
that are commonly used to detect CVST include
2-dimensional (2D) time-of-flight (TOF) MRV, 2D
phase-contrast (PC) MRV, and 3-dimensional contrast-
enhanced short echo time GE MRV (3D CE-MRV). Each
method has its relative strengths and weaknesses.
2D TOF MRV detects the inflow of fully magne-
tized spins into the imaging field; the bright signal of
flow-related enhancement (FRE) is maximal when the
Figure 23.4 Empty delta sign on MRI. (A) Con-
trast-enhanced coronal T1-weighted MRI image
demonstrates an empty delta sign in the left TS
(arrow). (B) Coronal source image from a 2D PC
MRV confirms the absence of flow in the TS
(arrow). Abbreviations: MRI, magnetic resonance
imaging; TS, transverse sinus; 2D PC MRV,
2-dimensional phase contrast magnetic resonance
venogram.
474 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

Figure 23.5 Hyperintense dural sinus thrombus due to methemoglobin imaged on sagittal T1-weighted MRI. (A, B) Hyperintense
thrombus in the right TS (A, arrow) and SSS (B, arrows); normal FV in non-thrombosed, patent left TS (C, arrow). Abbreviations:
MRI, magnetic resonance imaging; TS, transverse sinus; SSS, superior sagittal sinus; FV, flow void.

Figure 23.6 Cortical vein thrombosis on T2*-

weighted MRI. (A, B) Axial T2*-weighted GE
images demonstrate hypointensity and blooming
(arrows) within a left frontal cortical vein consistent
with thrombus. Abbreviations: MRI, magnetic res-
(A) (B) onance imaging; GE, gradient echo.

direction of blood flow is perpendicular to the imag-
ing plane. In practice, coronal acquisitions usually are
obtained because the bulk of intracranial venous flow
is from front to back; 2D TOF MRV is a relatively
rapid technique that often provides high quality MRV
images (Fig. 23.9). It is essential to review the source
images and the corresponding MRI exam, in addition
to the angiographic projections images, since 2D TOF
MRV can exhibit a number of artifacts. FRE may be
lost (flow gap) in the posterior portion of the SSS
and also in the TS due to loss of magnetization when
the spins dwell for a longer time within the imaging
plane (in-plane flow). Turbulence, often seen in the TS
and sigmoid sinus (SS), can also cause loss of signal
due to intravoxel dephasing. FRE can also be lost due
to slow, diminished or absent flow in a hypoplastic or
atretic venous sinus. This is a common source of
confusion when examining the TS. One study that
imaged normal subjects with 2D coronal MRV identi-
fied flow gaps in 31% of the transverse sinuses (90%
non-dominant, 10% co-dominant) due to normal ana-
tomic variants (37). A recent report described a TS/SS
septation misdiagnosed as sinus thrombosis on TOF
MRV resulting in unnecessary long-term anticoagula-
tion (38). A careful comparison of the 2D TOF MRV
and MRI images is essential to avoid these pitfalls
(Fig. 23.10). Occasionally, an additional venographic
technique may be required to resolve uncertainty. In
addition, since 2D TOF MRV is a T1-weighted techni-
que, high-signal methemoglobin within subacute
thrombus can simulate the hyperintense FRE of a pat-
ent sinus; therefore, inspection of T1-weighted MRI
images for hyperintense clot is necessary when the 2D
TOF MRV appears normal (Fig. 23.5) (39).
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS 475

(A) (B)

(C) (D)

Figure 23.7 Typical hemorrhagic venous infarct imaged with MRI (same case as Fig. 23.11). (A) Axial T2-weighted FSE image demon-
strates heterogeneous high signal intensity and mass effect in the right frontal lobe. (B) T2*-weighted GE image shows markedly hypo-
intense regions consistent with hemorrhagic transformation. (C) Axial DWI image demonstrates hyperintensity and (D) axial ADC image
reveals low signal intensity consistent with restricted diffusion (cytotoxic edema). Abbreviations: MRI, magnetic resonance imaging;
FSE, fast spin echo; GE, gradient echo; DWI, diffusion weighted imaging; ADC, apparent diffusion coefficient.

2D PC MRV is an alternative technique that
detects the phase shifts of spins in flowing blood. Some
advantages compared to 2D TOF MRV include the lack
of sensitivity to signal loss from in-plane flow, as well
as insensitivity to the T1-shortening effect of methemo-
globin and the superior suppression of signal in the
background tissue. However, acquisition times are lon-
ger, resulting in poorer patient tolerance and greater
image degradation by motion artifact. In addition, the
peak velocity of blood flow must be accurately esti-
mated before the study, or the sensitivity to slow flow
may be compromised. This technique is used less fre-
quently than 2D TOF MRV (40).
Recently, 3D CE-MRV has been gaining in popu-
larity to evaluate CVST. Rather than relying on the
demonstration of the dural sinuses by measuring an
indirect effect of blood flow on the spins, this techni-
que directly images the presence of contrast within
the patent dural sinus lumen (similar to DSA or
CTV) by performing a rapid, timed acquisition of
high-resolution GE images after the intravenous bolus
of an MRI (gadolinium-based) contrast agent. A recent
retrospective, blinded study demonstrated that elliptic-
centric 3D CE-MRV had greater sensitivity and specif-
icity for detecting CVST (85.7%/97.2%) than 2D TOF
MRV (71.4%/55.6%) (Fig. 23.11) (41). One potential
disadvantage is the relative contraindication to using
gadolinium-containing agents in pregnant patients.
Computed Tomographic Venography
The development of multidetector-row helical CT
scanners with high spatial and temporal resolution
has led to the introduction of high-quality computed
tomographic venography (CTV) that is very useful to
evaluate CVST. Rapid scanning during peak cerebral
venous opacification is used to acquire data sets with
isotropic 1mm diameter voxels that are reformatted
into several display modes according to institutional
protocols, including source, maximum intensity
476 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

Figure 23.8 Deep venous thrombosis. (A) Axial T2-weighted MRI image demonstrates extensive hyperintensity (edema) in the thalami,
basal ganglia, and central white matter. (B) Axial NC-CT image reveals cord signs in the StrS (arrow) and the VOG (arrowhead).
(C) Sagittal MIP image from a 2D-PC MRV shows absent flow in the StrS and VOG. Abbreviations: NC-CT, non-contrast computed
tomography; StrS, straight sinus; VOG, vein of Galen; MIP, maximum intensity projection; 2D PC MRV, 2-dimensional phase contrast
magnetic resonance venogram.

Figure 23.9 Normal appearing coronal 2D TOF

MRV. (A) Sagittal view, (B) coronal view. Abbre-
viation: 2D TOF MRV, 2 dimensional time-of-flight
(A) (B) magnetic resonance venogram.

projection (MIP), sliding thin-section MIP, multiplanar
reformatted and integral algorithm images. It is essen-
tial to review several data sets, including the source
images, to optimize CTV interpretation (42). CTV has
been found to be as accurate as MRV to diagnose
CVST, and may be easier to interpret correctly
(39,42,43). CTV has the advantage that it can be
obtained in the emergency setting immediately after a
NC-CT. The intracranial arterial and venous systems
both can be rapidly evaluated during the same study
with a single contrast injection, useful when the clinical
presentation could represent arterial or venous ische-
mia (39). Some additional advantages include a quick
imaging time (less than one minute) that facilitates
exams in uncooperative patients and the ability to eval-
uate individuals with a contraindication to MRI/MRV.
Relative disadvantages include the risks of iodinated
contrast (allergic reaction, contrast nephropathy) and
the exposure to ionizing radiation (43).
Digital Subtraction Angiography
The development of robust MRV and CTV techniques
has replaced DSA as the gold standard for the diag-
nosis of CVST. Nonetheless, digital subtraction angiog-
raphy (DSA) may occasionally be necessary when
non-invasive imaging remains inconclusive. In addition,
DSA is often performed during neurointerventional
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS 477

(A) (B)

Figure 23.10 Normal variant. Hypoplastic right

TS on coronal 2D TOF MRV. (A) Coronal and
(B) base MIP images of a coronal 2D TOF MRV
demonstrate normal FRE in the left TS and mark-
edly diminished FRE in the right TS (arrows).
(C, D) Sagittal T1-weighted MRI images reveal a
diminutive FV in the right TS without evidence of
thrombosis, consistent with a markedly hypoplastic
sinus (C, arrow) and a normal FV in the left TS
(D, arrow). Abbreviations: TS, transverse sinus;
2D TOF MRV, 2 dimensional time-of-flight magnetic
resonance venogram; MIP, maximum intensity
projection; FRE, flow-related enhancement; MRI,
(C) (D) magnetic resonance imaging; FV, flow void.

Figure 23.11 Right frontal lobe hemorrhagic

venous infarct due to SSS thrombosis (same
case as Fig. 23.7). (A) Axial NC-CT image
reveals a right frontal lobe hemorrhagic venous
infarct. (B) Sagittal MIP image of a 3D CE-MRV
demonstrates occlusive thrombus in the anterior
half of the SSS (arrows) and partially occlusive
thrombus in the posterior half of the SSS (arrow-
heads). Abbreviations: SSS, superior sagittal
sinus; NC-CT, non-contrast computed tomogra-
phy; MIP, maximum intensity projection; 3D CE-
MRV, 3-dimensional contrast-enhanced magnetic
(A) (B) resonance venogram.

procedures to treat CVST, and occasionally unsuspected
CVST may be identified on a cerebral DSA performed
for other indications.
The optimal angiographic technique for imaging
CVST includes the use of long contrast injections to
obtain complete intracranial venous opacification and
the use of extended imaging acquisitions (at least
30 seconds) because the intracranial circulation time
(ICT) often is prolonged. It is essential to obtain
images in multiple projections. The mid-portion of the
SSS usually is visualized best on a lateral view,
whereas a slightly oblique posteroanterior image may
478 NEUROINTERVENTIONAL MANAGEMENT
optimally demonstrate the most anterior and posterior
components of the SSS. The Townes projection and
standard oblique views usually display the transverse
and sigmoid sinuses well.
Characteristic findings of CVST on the venous
phase of a cerebral DSA include: nonopacification of
the thrombosed sinuses, contrast outlining incom-
pletely occlusive thrombus within a sinus, prominent
collateral venous drainage channels, non-visualization
of the deep venous system, tortuous (corkscrew)
cortical veins proximal to the obstruction, and a pro-
longed ICT (Fig. 23.12, A, B) (44). The ICT is defined
as the time interval from the first appearance of con-
trast in the cerebral arteries to its complete washout
from the intracranial venous system; normal is less
than 9 seconds. In a study of 79 patients with CVST,
the mean ICT was higher in those with a fatal out-
come (mean ICT = 21.2 seconds) than survivors (mean
ICT = 13.3 seconds) (25). The ICV, VOG, and StrS are
normally readily visible on the cerebral DSA venous
phase; their absence indicates thrombosis of the deep
venous system. The normal ICV appear early and per-
sist late in the venous phase.
Angiographic artifacts and anatomic variants can
complicate the interpretation of a cerebral DSA. Poor fill-
ing of the SSS or TS may result from a suboptimal con-
trast injection combined with the inflow of unopacified
blood from the opposite cerebral hemisphere. Arachnoid
granulations can be mistaken for nonocclusive throm-
bus; however, these are typically very discreet and well
defined, with a rounded shape. The anterior segment of
the SSS may be absent or hypoplastic as a normal var-
iant; in this situation ascending frontal cortical veins
drain into the mid-segment of the SSS (45). Unilateral
hypoplasia or absence of a TS occurs in 8% to 15% of the
population. Careful correlation of the DSA with an
MRI/MRV is often useful in these cases.
OUTCOMES AND TREATMENT
Systemic Anticoagulation
The clinical outcomes for CVST are widely variable,
ranging from complete recovery to permanent dis-
ability and death (1,2,4,46,47). Although some contro-
versy still exists, therapeutic systemic anticoagulation
for CVST in adults with unfractionated intravenous
heparin or subcutaneous low molecular weight hepa-
rin (LMWH) is considered the standard medical ther-
apy; a hemorrhagic venous infarct is not considered
a contraindication to anticagulation (2). Anticoagulation
is thought to prevent extension of the thrombus while
intrinsic thrombolysis and sinus recanalization occur;
this may prevent clinical deterioration due to new
venous infarcts, worsening cerebral edema, and pulmo-
nary emboli. However, continuing concern is expressed
that the clinical benefit is unproven and that anticoagu-
lation may cause or increase intracranial hemorrhage,
particularly in the 3040% of patients with existing
intracranial hemorrhage at the time of presentation
(4850).
The evidence for the safety and effectiveness of
systemic anticoagulation for CVST was extensively
reviewed in 2002 (51), and has been periodically
re-examined (3,52). The only well documented,
randomized, controlled clinical trials are two relatively
small studies with a total enrollment of 79 patients
(23,53). In the combined data from those trials, anticoa-
gulation was associated with a 13% absolute reduction
in death; this effect trended toward but did not quite
reach clinical significance (P = 0.08). The 95% confi-
dence interval (CI) was 27% to 1%. The relative risk of
death for the pooled anticoagulation group was 0.33
(95% CI, 0.161.2) and the relative risk of death or
dependency was 0.46 (95% CI, 0.161.31) (51). No new
or increased intracranial hemorrhage occurred in the 40
patients treated with heparin, even though 18/40 (45%)
had some degree of intracranial hemorrhage at the
time of presentation. Conversely, in the control groups,
there were two new hemorrhagic infarcts and two
probable cases of pulmonary emboli, one fatal. The
data suggested that anticoagulation for CVST appeared
safe and a clinical benefit was reasonably likely (48).
A number of uncontrolled case series that have
also evaluated the treatment of CVST with anticoagu-
lation have corroborated the results from the con-
trolled trials, reporting safety and trends toward
improved outcomes. These studies also found individ-
uals with hemorrhagic venous infarcts could be
treated safely (1,4,21).
Based on the limited controlled data that are
available, the European Federation of Neurological
Societies (EFNS) 2010 guidelines on the treatment of
CVST in adult patients recommends the treatment of
adults without a contraindication to anticoagulation
with therapeutic body-weight adjusted subcutaneous
LMWH or with therapeutic dose-adjusted unfractio-
nated intravenous heparin (activated therapeutic
thromboplastin time 2.0); intracranial hemorrhage is
not a contraindication (level B evidence) (3). LMWH is
suggested for uncomplicated cases since serious bleed-
ing complications may occur less frequently, the route
of administration provides greater patient mobility,
and laboratory monitoring and dose adjustments are
not necessary. Intravenous heparin may be preferable
in complicated cases where rapid reversal of anticoa-
gulation may be required.
There are no randomized, controlled clinical
trials that evaluate anticoagulation for pediatric CVST,
and data from adult trials cannot be extrapolated to
infants and children. As a result, widely divergent
consensus-based guidelines have been suggested for
the treatment of pediatric CVST (54,55). Wide practice
variations exist; a recent multinational registry found
only 28% of neonates with CVST in the United States
were treated with antithrombotic medications,
whereas 69% were treated in non-U.S. centers; geo-
graphic location was the only significant variable (55).
This is an important issue since pediatric CVST
is being diagnosed more frequently, and adverse clini-
cal outcomes have been reported in approximately 50%
of infants and children (5,56). A recent prospective
study assessed the safety and outcomes of antico-
agulation for pediatric CVST at a single center (54).
Anticoagulation appeared safe in both neonates and
children, and was associated with significantly lower
incidences of thrombus propagation and new venous
infarcts. The results strongly support further investi-
gation of the treatment of pediatric CVST with antico-
agulation in randomized, controlled trials.
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS 479

(A) (B) (C)

(D) (E) (F)

Figure 23.12 Direct chemical thrombolysis of the intra-dural sinuses. (A) Lateral and (B) PA images from the late venous phase of a
cerebral DSA demonstrate complete thrombosis of the SSS (white arrowheads) and the TS. Frontal cortical veins demonstrate indirect
signs of downstream thrombosis, including corkscrewing (A, arrows) and collateral venous drainage through the right superficial mid-
dle cerebral vein into the basal venous plexuses (A and B, black arrowheads). (C) Lateral right IJ DSV demonstrates complete occlu-
sion of the right SS and reflux into an enlarged right inferior petrosal sinus (arrowheads), a major route of collateral venous drainage.
(D) Lateral right TS/SS DSV through a microcatheter (arrowhead) reveals occlusive thrombus. (E, F) Completion DSV in (E) lateral and
(F) PA projections after pulse-spray infusion of TPA throughout the SSS and both TS demonstrates marked recanalization, with mini-
mal residual non-occlusive thrombus (the left TS is hypoplastic). Abbreviations: PA, posteroanterior; DSA, digital subtraction angio-
gram; SSS, superior sagittal sinus; TS, transverse sinus; IJ, internal jugular; DSV, digital subtraction venogram; SS, sigmoid sinus;
TPA, tissue plasminogen activator.

Endovascular Intervention were left to the discretion of the attending physicians;

Indications
Clinical outcomes from CVST are varied and unpre-
dictable. A significant percentage of patients experience
poor outcomes despite therapeutic anticoagulation.
Reported mortality rates for CVST range from 530%
(1,4,57). In addition, 1225% of the individuals who
survive suffer significant neurological deficits (1), and
3544% experience long-term neurocognitive impair-
ments (58).
Several studies have analyzed outcomes for CVST
in efforts to identify high-risk subgroups for whom more
aggressive treatment (e.g., endovascular recanalization
techniques) could provide clinical benefit. The ISCVT
currently is the largest trial with outcomes data. In this
multicenter observational study therapeutic decisions
most of the cases (83%) were treated with systemic anti-
coagulation. Primary outcome was death or dependency
at the end of follow-up, defined by a modified Rankin
Scale score (mRSS)>2. At final follow-up (median = 16
months) of a total of 624 adult patients, 13.4% were dead
or dependent; 356 (57.1%) had no symptoms (mRSS = 0),
137 (22%) had no disabilities despite symptoms
(mRSS = 1), 47 (7.5%) had slight disabilities (mRSS = 2),
18 (2.9%) had moderate disabilities (mRSS = 3), 14 (2.2%)
had severe disabilities (mRSS = 4 or 5), and 52 (8.3%)
were dead (mRSS = 6). Multivariate predictors of poor
outcomes were: central nervous system infection [hazard
ratio (HR) = 3.3], deep cerebral venous thrombosis
(HR = 2.9), malignancy (HR = 2.9), coma (HR = 2.7),
age>37 years (HR = 2.0), mental status disorder (HR =
2.0), cerebral hemorrhage on admission (HR = 1.9), and
480 NEUROINTERVENTIONAL MANAGEMENT
male gender (HR = 1.6) (4). Approximately 30% of the
cases with one or more risk factors had poor outcomes
despite anticoagulation (59). Twelve of 31 (39%) comatose
patients were dead or dependent at final follow-up (4).
The Dutch-European Cerebral Sinus Thrombosis
Trial prospectively studied outcomes in 59 patients
with CVST. At 12 weeks, 10/59 (17%) had poor out-
comes (death or dependency). On multivariate analysis,
coma [odds ratio (OR) 8.2, 95% CI, 1.350.1] and cere-
bral hemorrhage (OR 20.7, 95% CI, 1.6264.3) were
independent predictors for poor outcomes; 5 of 9 (56%)
of patients in coma and 9 of 29 (31%) with intracerebral
hemorrhage had a mRSS>2 on follow-up (60).
In another study, 79 patients treated with intra-
venous heparin were retrospectively evaluated for
predictors of a fatal outcome. The overall mortality
rate for the series was 10% (8/79). There was a strong
association between level of consciousness and out-
comes; 53% (8/15) of the patients with stupor or
coma at the start of treatment died, whereas, all of
those (64) with a normal or mildly impaired level
of consciousness survived (25).
These data emphasize that there is a significant
subset of patients with CVST for whom conventional
medical management with systemic anticoagulation is
inadequate. Selected individuals may benefit from
rapid endovascular recanalization of the thrombosed
sinuses before irreversible cerebral damage occurs.
Although specific selection criteria are controversial
and will require analysis in controlled trials (61),
many experts agree that endovascular therapy cur-
rently should be considered for a patient with CVST
who presents with a significantly depressed level of
consciousness (stupor or coma), severe and rapidly
progressive neurologic deficits, or significant clinical
deterioration despite adequate anticoagulation (62).
Other causes for clinical deterioration need to be
excluded prior to endovascular treatment, including
worsening of the underlying medical condition,
uncontrolled seizures, pulmonary embolism, and
impending transtentorial herniation (63).
Technique
Dural sinus thrombolysis is typically performed under
general anesthesia. In many of the cases reported in the
literature, arterial DSA was performed to confirm the
diagnosis, to define the location and extent of CVST, to
characterize normal anatomic variants, and to determine
the optimal approach. With increasing experience, most
operators find this information can be gleaned from non-
invasive imaging; as a result arterial DSA currently is
performed less frequently during endovascular recanali-
zation of CVST. Thorough review, however, of the MRI/
MRV before the procedure is critical. Venous access is
usually obtained from a trans-femoral approach with a
6 or 7 French (Fr) introducer sheath; occasionally, a trans-
jugular approach is necessary. A 6 or 7 Fr guide catheter
[e.g., Envoy guide catheter (Cordis, Miami Lakes,
Florida, U.S.)] is advanced into the appropriate internal
jugular vein and the tip is placed in the jugular bulb.
A retrograde jugular venogram defines the extent
of distal thrombosis (Fig. 23.12, C). Subsequently, an
appropriate microcatheter [e.g., Prowler Plus (Cordis)]
and microguidewire [Synchro-14 (Boston Scientific,
Natick, Massachusetts, U.S.)] are negotiated through
the thrombosed sinus segments during fluoroscopic
manipulation. At intervals, a digital subtraction veno-
gram through the microcatheter is obtained to assess
the exact catheter position and the extent of thrombus
(Fig. 23.12, D). When the microcatheter is positioned in
the most proximal aspect of the CVST, the thrombolytic
agent, usually recombinant tissue plasminogen acti-
vator (Activase; Genentech, South San Francisco,
California, U.S.), is infused (Fig. 23.12, E, F). A number
of methods have been described, including continuous
infusions and pulse-spray techniques that report
widely varying doses and total infusion times (6469).
In order to accelerate thrombolysis and/or to
enhance the disruption of organized thrombus, the
combined use of a thrombolytic agent and the
mechanical disruption of the clot can be employed.
A variety of devices have been utilized, including
microguidewires, snares, and balloons (Fig. 23.13)
(59,65,70). These maneuvers likely accelerate throm-
bolysis by increasing the surface area of the clot and
improving dispersal of the thrombolytic agent within
the thrombus, as well as physically dislodging some
of the clot.
Mechanical extraction of the thrombus with a
low profile rheolytic catheter [Angiojet (Possis Medi-
cal, Minneapolis, Minnesota, U.S.)] has been described
in case reports and small series (Fig. 23.14) (62,7174).
Accumulating data suggest the Angiojet is effective
and safe, often removing the sinus clot more rapidly
and completely than chemical thrombolysis (62,75).
Rheolytic thrombectomy can be combined with the
intra-sinus infusion of a thrombolytic agent that may
potentially facilitate the recanalization of bridging
veins (62), or performed without thrombolysis to
avoid increasing the risk of intracranial hemorrhage
(Fig. 23.14) (74). Recent case reports describe mechani-
cal extractions of dural sinus thrombus with the
MERCI device (Concentric Medical Inc., Mountain
View, California, U.S.) (76) and the Penumbra throm-
bectomy system (Penumbra Inc., Alameda, California,
U.S.) (77,78).
Outcomes/Guidelines
No randomized controlled trial that evaluates the
safety and efficacy of treating CVST with endovascular
recanalization techniques has been performed (3). Only
uncontrolled case series have been published. In 2008,
Stam et al. reported a prospective case series of endo-
vascular thrombolysis in 20 patients with CVST (com-
bined with mechanical techniques in 15) and reviewed
the previous literature (59). Twelve individuals were
comatose and 14 had hemorrhagic infarcts prior to
treatment. Outcomes were good in 12 (mRSS 2) (60%),
poor in 2 (10%), and 6 (30%) died. Five of the 6 patients
who died had large infarcts and transtentorial hernia-
tion prior to treatment. After treatment, 5 (25%)
patients had increased cerebral hemorrhage (3 minor,
2 major); 4 of whom died.
The authors compared their results with the data
from a systemic review (Canhao et al.) of all of the
cases of CVST thrombolysis reported up to 2001 (75),
and also to a summary of the six largest published
case series (up to 20 subjects) (16,19,64,6668). In the
 DIAGNOSIS AND MANAGEMENT OF CEREBRAL VENOUS AND DURAL SINUS THROMBOSIS
(A)
Figure 23.13 Combined chemical and mechanical thrombolysis of the SSS. (A) Initial lateral DSV though a microcatheter demonstrates
complete thrombosis of the SSS and collateral frontal cortical venous flow. (B) Completion lateral DSV after pulse-spray infusion of TPA
followed by compliant balloon clot maceration and thrombectomy in the SSS demonstrates a widely patent result with excellent flow
through the SSS. Abbreviations: SSS, superior sagittal sinus; DSV, digital subtraction venogram; TPA, tissue plasminogen activator.
systematic review of all the cases reported up to 2001
(169 subjects), 32% presented in coma and 33% with
hemorrhagic infarcts. Following treatment, 17% had
new or progressive hemorrhage, 5% symptomatic. At
discharge, 7% were dependent and 9% had died. In
the summary of the 6 large case series (82 total sub-
jects), only 4% presented in coma and 18% with hem-
orrhagic infarcts. Following treatment, 7% had new or
increased hemorrhage and 5% had died. These data
underscore the difficulty in comparing uncontrolled
studies using heterogeneous selection criteria and dif-
ferent treatment protocols. It is not possible to com-
pare the safety and efficacy of anticoagulation for
CVST with thrombolysis because of these limitations.
The authors concluded that thrombolysis can be effec-
tive for severe CVST, but increased cerebral hemor-
rhage may cause deterioration. Patients with large
infarcts and impending transtentorial herniation did
not benefit. The major risk of intra-sinus thrombolysis
is new or increased intracranial hemorrhage; the mag-
nitude of the risk appears dependent on a number of
technical and clinical factors (59,75).
In 2008, Zhang et al. reported a retrospective case
series of 6 patients with CVST treated with rheolytic
thrombectomy (Angiojet) and summarized all of the
published cases of rheolytic thrombectomy (total, 24) for
CVST available at that time (62). Rheolytic thrombec-
tomy was safe; no intracranial complication occurred in
a total of 33 procedures in the 24 patients. Potential sys-
temic complications included intravascular hemolysis,
dilutional anemia, and aspiration anemia; however,
none was seen. Ninety three percent (75/81) of all
attempted sinus recanalizations were technically suc-
cessful. Fifteen of 24 patients (63%) had excellent out-
comes, 5/24 (21%) had good outcomes, 1/24 (4%) had a
poor outcome, and 3/24 (13%) died. Eight of 9 patients
(89%) who presented with parenchymal hemorrhages
experienced good to excellent clinical outcomes, 1/9
(11%) died. Five of 7 (71%) who presented in coma had
481
(B)
good to excellent outcomes, 2/7 (29%) died. Nineteen
of 24 (79%) met the criteria for having high risk for
poor outcomes; 16/19 (84%) experienced good to excel-
lent clinical outcomes (MRSS 2). The authors concluded
rheolytic thrombectomy was safe and the clinical out-
comes compared favorably with the reported outcomes
for high-risk patients treated with anticoagulation;
however, randomized controlled trials were needed.
The EFNS 2010 guidelines on the treatment of
CVST in adult patients conclude that there is insuffi-
cient evidence to support the use of thrombolysis
because of the lack of randomized, controlled data;
nonetheless, the guidelines suggest thrombolysis may
be a reasonable therapeutic option for patients at
high-risk for poor outcomes (e.g., comatose or deterio-
rating despite adequate anticoagulation, with other
etiologies excluded), particularly in those without a
large intracranial hemorrhage or impending transten-
torial herniation (good practice point) (3).
Management of Increased Intracranial Pressure
Transtentorial herniation is the most common cause of
early death in patients with CVST (59,79). In severe
cases due to a large unilateral hemorrhagic infarct,
decompressive hemicraniectomy may be lifesaving
(3,80,81). Local thrombolysis does not appear benefi-
cial in this circumstance (59,80). Patients with IIH and
threatened vision may require serial lumbar punctu-
res, acetazolamide, CSF-shunting procedures or optic
nerve sheath fenestrations (3).
CONCLUSIONS
CVST is a rare cause of stroke with nonspecific and
extremely variable clinical presentations. Timely diagno-
sis requires familiarity with the etiologies and risk fac-
tors for CVST, as well as a high index of suspicion in
appropriate clinical scenarios. Advances in neuroimag-
ing have facilitated the early and accurate diagnosis of
482 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 23.14 Mechanical thrombectomy (Angiojet) of left TS, SS and IJ thrombosis. (A) Axial NC-CT image reveals a left temporal
lobe hemorrhagic venous infarct characteristic of TS and vein of Labbe thrombosis. (B) Initial DSV (PA view) through a guide catheter
in the left IJ demonstrates left TS, SS, and IJ thrombosis (arrows). (C) PA radiograph demonstrates an Angiojet being advanced over a
microguidewire through the SS. (D) Completion PA DSV demonstrates marked improvement; some residual adherent non-occlusive
thrombus is visible. Abbreviations: TS, transverse sinus; SS, sigmoid sinus; IJ, internal jugular; NC-CT, non-contrast computed tomography;
DSV, digital subtraction venogram; PA, posteroanterior.

CVST. Therapeutic anticoagulation is the recommended
medical treatment for uncomplicated CVST in adults.
The prognosis for CVST is generally favorable; however,
death or disability are outcomes for a significant number
of patients. In patients at high-risk for poor clinical out-
comes, more aggressive interventions may be beneficial,
including endovascular recanalization of the throm-
bosed dural sinuses and decompressive hemicraniec-
tomy. Additional research ultimately will be necessary
to determine the appropriate roles for these techniques.
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 24
Inferior petrosal sinus sampling in the diagnosis of
pituitary adenomas
Nicholas J. Patronas and Donald L. Miller
INTRODUCTION
Inferior petrosal sinus sampling (IPSS) is used in the
differential diagnosis of Cushings disease and when
there is a strong clinical suspicion of a hyperfunctioning
pituitary adenoma and non-invasive methods have
failed to establish the diagnosis. These adenomas
may secrete prolactin, adrenocorticotropin (ACTH),
growth hormone (GH), or thyrotropin secreting hor-
mone (TSH). The initial application of IPSS was the
evaluation of patients with Cushings syndrome. This
remains the main indication for its use.
Cushings syndrome is a clinically recognizable
entity. It is characterized by a variety of symptoms, the
most important of which include: hypertension, diabe-
tes mellitus, weight gain with central obesity, moon
faces, purple abdominal striae, hirsutism, hyperpig-
mentation, and osteoporosis. The common denomina-
tor of Cushings syndrome is hypercortisolemia. The
causes of Cushing syndrome may be classified as
ACTH-dependent or ACTH-independent. Simply put,
patients with ACTH-dependent Cushings syndrome
have elevated levels of ACTH and cortisol, while
patients with ACTH-independent Cushings syndrome
have elevated levels of cortisol alone. Elevated is rel-
ative; patients with hypercortisolism should have low
or undetectable levels of ACTH, due to suppression of
both corticotrophin releasing hormone (CRH) and
ACTH production by the normal feedback loops in the
hypothalamic-pituitary-adrenal axis. Normal levels
of ACTH are abnormal in patients with Cushing syn-
drome, and indicate an ACTH-dependent cause.
Overproduction of cortisol alone is typically due
to an adrenal lesion. Approximately 5% of patients
with Cushings syndrome have an adrenal lesion that
demonstrates autonomous functionit does not
require stimulation by ACTH to produce cortisol. These
non-ACTH dependent lesions include hyperfunction-
ing adrenal adenomas, adrenocortical carcinomas, pri-
mary pigmented nodular adrenal disease (PPNAD),
and macronodular hyperplasia of the adrenals. ACTH-
independent Cushings syndrome can also occur as a
result of exogenous steroid administration. There is no
role for IPSS in patients with ACTH-independent Cush-
ings syndrome.
The remaining patients with Cushings syn-
drome have an ACTH-dependent cause. Approxi-
mately 80% of patients with Cushings syndrome have
an ACTH-secreting pituitary adenoma. This etiology
(and only this specific etiology) is referred to as Cush-
ings disease. An additional 15% of patients with
Cushings syndrome have an ACTH-secreting tumor
at a site other than the pituitary gland. Most of these
patients have an obvious primary malignancy with
ectopic hormone production, typically in the lung.
Some patients have a small, clinically occult tumor,
and present with what is termed the occult ectopic
ACTH syndrome. Most commonly, these small tumors
are found in the bronchial tree, but localization of
these lesions can be extremely difficult. Both depres-
sion and alcoholism can cause elevated CRH levels
and present as pseudoCushings syndrome. Very
rarely, CRH-secreting tumors are responsible for
ACTH-dependent Cushings syndrome.
The endocrinologist is responsible for determin-
ing whether the patient has the ACTH-dependent or
the ACTH-independent form of Cushings syndrome.
Patients with ACTH-independent disease require
adrenal imaging, but not pituitary imaging. Patients
with ACTH-dependent disease require further endo-
crinologic evaluation to determine whether the ACTH
is from a pituitary source (Cushings disease) or an
ectopic source of ACTH. A number of biochemical
tests have been developed to aid in this effort. These
include suppression tests with dexamethasone and
stimulation tests with CRH. The details of biochemi-
cal testing are outside the scope of this chapter.
Briefly, these tests rely on differences between pitui-
tary adenomas and ectopic tumors. In general, pitui-
tary tumors retain some capacity to demonstrate
suppression of ACTH in response to high levels of
exogenous steroids, and some ability to demonstrate
stimulation of ACTH in response to exogenous CRH,
while ectopic tumors do not respond. Unfortunately,
none of these biochemical tests is 100% sensitive and
100% specific.
Magnetic resonance imaging (MRI) of the pitui-
tary gland has become a routine test for evaluating
patients with ACTH-dependent Cushings syndrome.
MRI has proven useful not only for establishing the
presence of an adenoma but also for demonstrating its
location within the gland. This information is of para-
mount importance for surgical planning since preser-
vation of pituitary function after successful resection
of the adenoma is a cardinal objective of the opera-
tion. The sensitivity of MRI in detecting pituitary
486 NEUROINTERVENTIONAL MANAGEMENT
adenomas primarily depends upon tumor size. The
sensitivity to ACTH-secreting adenomas has been
reported to be as low as 45% in post-contrast scans. In
other type of adenomas the sensitivity is considerably
higher since they become clinically apparent when
larger in size.
One of the problems with pituitary MRI is the
absence of uniformity in the imaging protocols used
at various centers. One cause of false negative results
is the use of suboptimal imaging techniques. In the
past we routinely used the following imaging parame-
ters: field strength 1.5 T, repetition time/echo time
400/9msec; 192  256 matrix; two excitations; 12-cm
field of view in the coronal and 16cm in the sagittal
plane; and 3-mm thick sections without gap. More
recently we have used a gradient echo T1-weighted
technique before and after contrast material adminis-
tration [0.01 mmol/Kg gadopentetate dimeglumine
(Magnevist, Berlex Laboratories, Inc. Montville, New
Jersey)] with repetition time/echo time 9.6/2.3msec, a
20 flip angle, 160  256 matrix, 6 excitations and 1.5mm
slice thickness. With this technique we can exploit the
superior contrast resolution of the gradient echo techni-
que and acquire thinner tomographic sections.
Difficulties in demonstrating ACTH-secreting
pituitary adenomas have several other causes that are
less amenable to correction. First, these tumors are
usually very small when patients first present. The
spatial resolution limitations of current MRI scanners
may cause them to be obscured by averaging artifacts.
Second, pituitary adenomas often enhance in a fashion
similar to normal pituitary parenchyma. Finally,
detection of functioning pituitary adenomas is also
confounded by the fact that identical-appearing, small
focal space-occupying lesions can be encountered
within the pituitary parenchyma of normal subjects.
Autopsy studies and MR scans of normal volunteers
have demonstrated that there is a 6% to 10% incidence
of non-functioning adenomas (incidentalomas) in the
pituitary gland (1,2).
Neither biochemical tests nor imaging studies
can provide an accurate diagnosis in all patients with
Cushings syndrome, and an additional diagnostic
method is sometimes required. In these patients, pet-
rosal sinus sampling can be used to confirm or
exclude the presence of a functioning pituitary
adenoma. It is most useful when the results of bio-
chemical tests and MRI are discrepant. In addition,
when biochemical tests provide a firm indication of
Cushings disease, but no lesion is identified on pitui-
tary MRI, IPSS may provide lateralization of the pitui-
tary adenoma to one side of the pituitary gland. This
permits the surgeon to perform a hemihypophysec-
tomy and preserve pituitary function.
INDICATIONS FOR PETROSAL SINUS
SAMPLING
Patients with a confirmed endocrine diagnosis of
ACTH-dependent Cushings syndrome and one of the
following:
l Absence of a discrete pituitary lesion on MRI.
l Equivocal biochemical tests in the presence of a
discrete pituitary lesion on MRI.
l Persistent Cushings syndrome after transsphenoi-
dal surgery.
l Clinical need to resolve other discrepancies
between clinical, biochemical, and imaging tests.
Patients with a confirmed endocrine diagnosis of
an endocrine syndrome typically associated with a
hyperfunctioning pituitary adenoma (acromegaly, thy-
rotropin secreting hormone (TSH) overproduction) and:
l Surgical resection is contemplated and the results
of pituitary MRI are negative.
When petrosal sinus sampling is performed in
patients with Cushing syndrome for these indications,
the procedure has a sensitivity of 92% and a specific-
ity of 90%, and lateralization provided by IPSS is cor-
rect in 70% of patients (3).
Prior to sampling 15 lavender-top tubes [Vacu-
tainer, no. 6457, with ethylenediaminetetraacetic acid
(EDTA) (K3); Becton-Dickinson, Rutherford, New Jer-
sey] are labeled and placed in an ice-water bath. Bilat-
eral femoral vein puncture is performed under local
anesthesia with ultrasound guidance using a micro-
puncture system. A sheath is placed in each femoral
vein through which a 4-F catheter is introduced. The
sampling catheters are pre-shaped over steam to form
a 75 bend for the left side and a 95 for the right.
Alternatively, pre-shaped vertebral catheters may be
used. It is important that there be no side holes. At
least one of the femoral vein sheaths should be one
French size larger than the catheter used. This sheath
is used to draw the peripheral vein samples which are
obtained as part of the sampling procedure.
A coaxial technique using a microcatheter to cathe-
terize the inferior petrosal sinus (IPS) has become
increasingly popular (3,4). This includes a 5-F or 6-F
introducer catheter advanced into the internal jugular
vein and a Target-10 or a Tracker-18 or Tracker-25 micro-
catheter (Target Therapeutics, Freemont, California) and
a Seeker 10 or a Seeker 16 wire (Target Therapeutics,
Freemont, California) for the selective catheterization of
the IPS. Prior to introduction of any catheter into the pet-
rosal sinus a bolus of 3,0004,000 IU of heparin is admin-
istered intravenously. In addition 5,000 IU of heparin is
added to the flush solution which is used to irrigate the
petrosal sinus catheters and the femoral vein sheaths.
The use of sedation is not recommended, but during the
procedure intravenous midazolam and fentanyl may be
used as needed.
The right femoral vein introducer catheter is
advanced into the right internal jugular vein, usually
without difficulty, along a straight line through the
inferior vena cava, the right atrium, and the superior
vena cava. Advancement of the left femoral introducer
catheter into the left internal jugular vein is usually
more problematic since the catheter must first turn by
90 from the superior vena cava into the left innomi-
nate vein and then turn by another 90 into the left
internal jugular vein. In addition, there is a valve at
the base of the left internal jugular vein, located at its
junction with the innominate vein. The valve can usu-
ally be successfully negotiated by positioning the tip
of the catheter at the base of the internal jugular vein
and advancing a flexible guidewire into this vessel
during expiration or a reverse Valsalva maneuver.
 INFERIOR PETROSAL SINUS SAMPLING IN THE DIAGNOSIS OF PITUITARY ADENOMAS 487

(A) (B)

Figure 24.1 Inferior petrosal sinus (IPS) venogram in a patient with Cushings disease. (A) Injection in the right and (B) injection in the
left IPS. Note asymmetry of the IPS with the left being smaller than the right.

From the internal jugular vein selective catheter-

ization of the IPS is accomplished by rotating the intro-
ducer catheter medially and anteriorly as it is moved
from the dome of the jugular bulb downward. This is
done while injecting contrast to opacify the venous
channels draining into this vessel. It is not uncommon
to identify more than one such vessel. The tip of the
introducer catheter is then anchored at the orifice of
the most prominent venous channel (Fig. 24.1). Further
advancement of the catheter into this vessel should be
attempted only over a flexible guidewire coated with
hydrophilic material (Glidewire, 46-151; Medi-tech/
Boston Scientific). The guidewire should never be
advanced into the cavernous sinus and the catheter
never be advanced more than 11.5cm into the IPS.
Successful catheterization of the IPS is documented
fluoroscopically in the anteriorposterior projection
during gentle hand injection of contrast (Fig. 24.2).
Digital subtraction angiography should also be
obtained at this time and opacification of the ipsilat-
eral cavernous sinus as well as the opposite cavernous
and inferior petrosal sinuses documented; unless there Figure 24.2 Right IPS injection. There is good opacification of
is documentation of proper positioning of the catheter cavernous sinuses and retrograde flow into the left IPS. Arrow
into the IPS, the results of venous sampling become heads point to the tip the catheters on both sides.
questionable (Fig. 24.3).
If one IPS is difficult to identify, it is usually
advisable to abandon the attempt and switch to the and the internal jugular vein, just inferior to the jugular
other side, which may be easier to catheterize. The bulb. There is substantial variation in the diameter,
roadmap obtained from the contralateral catheteriza- number of channels and degree of symmetry of the
tion can then be used to assist catheterization of the IPS, and in the extent of drainage into the basilar
more difficult side (Figs. 24.4, 24.5). plexus and vertebral venous plexus (5) (Fig. 24.6). Shiu
Successful catheterization of the inferior petrosal et al. classified the spectrum of drainage patterns at
sinuses requires familiarity with the anatomical varia- the junction between the IPS and the internal jugular
tions that can be encountered at the junction of the IPS vein, ranging from exclusive drainage into the internal
488 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

(E)

Figure 24.3 Microcatheter technique of IPSS: (A) Subtracted AP view of injection into right IPS (white arrowheadintroducer catheter
tip at junction of right jugular vein and IPSS). (B) Injection of left IPS with cross filling into right IPS (arrowheadsintroducer catheter
tips in jugular veins). (C, D) Injection through right (C) and left (D) microcatheters in IPS (arrowsmicrocatheter tips in IPS). (E)
Unsubtracted view showing arrangement of introducer catheters and microcatheters in position for sampling.
 INFERIOR PETROSAL SINUS SAMPLING IN THE DIAGNOSIS OF PITUITARY ADENOMAS 489

(A) (B)

Figure 24.4 IPS venogram in a patient with Cushings disease. (A) Injection in the right and (B) injection in the left IPS. Note promi-
nent vertebral plexus. The right IPS is hypoplastic. The roadmap from the left IPS injection was used to achieve selective catheteriza-
tion of the hypoplastic right IPS.

(A) (B)

Figure 24.5 Contralateral injection to aid IPSS. (A) Unsubtracted and subtracted (B) AP views of introducer catheter tips (arrows) in
the jugular bulbs at the junction with the inferior petrosal sinuses. Jugular venogram in AP (B) and lateral (Continued)

jugular vein to exclusive drainage into the vertebral
venous plexus, into four different variations (6). This
classification was subsequently modified by Miller
et al. (7). In type I anatomy, the IPS drains directly
into the internal jugular vein as a single, large chan-
nel. There may be a small communication with the
vertebral venous plexus via the anterior condylar vein
or other anastomotic channel. In type II anatomy, the
IPS is a single channel. Drainage into the vertebral
venous plexus is via a relatively large channel, greater
than 1.7mm in diameter. In type III anatomy the IPS
drains into the internal jugular vein via multiple chan-
nels. In type IV anatomy there is no anastomosis
between the IPS and the internal jugular vein. Instead,
one or more veins (typically a plexus) originating
from the cavernous sinus drains into the vertebral
venous plexus. A variant of type II or III anatomy,
incomplete type IV, also occurs. In this variant, a very
490 NEUROINTERVENTIONAL MANAGEMENT

(C) (D)

(E) (F)

(G) (H)

Figure 24.5 (Continued) (C) views fills left IPS into the posterior left cavernous sinus (arrowhead, C). Left sigmoid sinus also fills
(black arrow, C). (D) Right jugular venogram: no filling of right IPS (arrowintroducer catheter tip). (E) Unsubtracted and (F) subtracted
AP views following microcatheter placement into the left IPS. Contrast injection through microcatheter (large arrowmicrocatheter tip)
fills left IPS (arrowheadimpression of left cavernous carotid artery) with cross-filling into right IPS, demonstrating junction with right
jugular vein (small arrows), thereby aiding microcatheterization of right IPS. (G, H) Unsubtracted AP view shows microcatheters in
place for IPSS.
 INFERIOR PETROSAL SINUS SAMPLING IN THE DIAGNOSIS OF PITUITARY ADENOMAS 491

(A) (B)

(C) (D)

Figure 24.6 Low junction of IPS with jugular vein: (A) AP and lateral (B) views of right jugular venogram show IPS junction with jugular
vein (arrow) several cm below skull base (arrowheadjugular bulb). (C) Lateral and AP (D) views after microcatheter placement into
right IPS, injection fills IPS bilaterally (*introducer catheter tip in left jugular vein; arrowintroducer catheter tip in right jugular vein;
arrowheadscourse of microcatheter in right IPS).

small connection is present between the IPS and the
internal jugular vein, but the vast majority of petrosal
venous drainage is into the vertebral venous plexus.
IPS anatomy is symmetrical about two-thirds of
the time; the other one-third of individuals have one
anatomic type present on the right and a different
anatomic type on the left. In a venographic study of
268 inferior petrosal sinuses, type I anatomy (the
easiest to catheterize), was encountered in 20% of
sinuses, type II anatomy was encountered in 46% of
sinuses, type III was encountered in 37% of sinuses,
and type IV was encountered in 0.4% of sinuses (7).
Incomplete type IV anatomy was encountered in 3%
of sinuses (classified above as type II or type III).
Catheterization of inferior petrosal sinuses with type
II and III anatomy may occasionally be difficult, since
the IPS is relatively small. The incomplete type IV
variant is particularly difficult to catheterize. True
type IV anatomy is fortunately rare, because this var-
iant makes catheterization via the internal jugular vein
impossible. In experienced hands, bilateral petrosal
sinus catheterization is possible in 93% to 99% of
patients with patent internal jugular veins bilaterally
(3,7,8).
Successful petrosal sinus sampling demands
meticulous attention to detail. Petrosal venous sam-
pling requires that simultaneous samples be obtained
from two catheters and a venous sheath, and that
these samples be placed immediately into correctly
numbered and labeled tubes. Multiple timed samples
are obtained from each catheter: a baseline set and
sets at 3, 5, and 10 minutes after the intravenous
administration of 1mcg/kg (maximum dose 100 mcg)
CRH. Prior to sampling 23ml of blood is withdrawn
492 NEUROINTERVENTIONAL MANAGEMENT

from each catheter into a waste syringe and discarded.

Each 10ml blood sample is drawn into a plastic 10ml
syringe over 2040 seconds. Each sample is then trans-
ferred into the appropriately numbered and labeled
tube using a 16 gauge needle. The tube is gently tilted
to mix the sample with the EDTA in the tube and is
GH pg/ml
returned to the ice-water bath. In between sampling,
Peripheral 19
the position of both catheters is checked fluoroscopi-
cally to confirm that neither catheter has slipped out
of the petrosal sinus. At the end of the procedure a
digital subtraction venogram of each petrosal sinus is
obtained separately by gentle hand injection of 5ml 100 19
non-ionic contrast material. This serves as a perma-
nent record of catheter position during sampling, in
the event that questions arise when the data are
interpreted.

INTERPRETATION OF SAMPLING DATA

The physiologic basis for interpretation of sampling
data is straightforward: the inferior petrosal sinuses
drain pituitary venous blood. If the patient has a func-
tioning pituitary adenoma, ACTH will be present at
higher concentration in petrosal sinus samples than in
peripheral vein samples. If ACTH is coming from an
ectopic source, ACTH concentrations in petrosal sinus
samples will be similar to those in peripheral venous
blood. In cases of Cushings disease, petrosal sam-
pling can provide unequivocal evidence of ACTH
secreting adenoma by demonstrating elevated values
of ACTH in the blood samples from the petrosal
sinuses as compared to those of the peripheral blood.
Since ACTH concentrations in left and right petrosal
sinus blood samples are usually not identical, it is
essential to sample both sinuses. The side with the
higher ACTH concentration in each sample set is used
as the IPS value for the data analysis.
In baseline samples (obtained prior to CRH
administration) an inferior petrosal sinus to peripheral
(IPS:P) ACTH ratio greater than 2 is indicative of
Cushings disease. An IPS:P ACTH ratio greater than 3
in any sample set obtained after CRH stimulation is
also diagnostic. When the results of the method were
first reported by Oldfield et al., the sensitivity and spe-
cificity for detection of a pituitary source of ACTH
secretion was found to be 95% and 100%, respectively,
in the baseline samples (9). After intravenous adminis-
tration of CRH both sensitivity and specificity were
100%. Subsequent investigators have found that both
false negative and, rarely, false positive results can be
encountered (3,1012). The sensitivity and specificity
after CRH stimulation range from 90% to 97% and
from 67% to 100%, respectively (3,11,12).
A negative result from petrosal sinus sampling is
not conclusive proof that the patient has an ectopic
ACTH source. The cause of these false negative results
is not always clear. Displacement of the catheter dur-
ing sampling, or incorrect catheter placement may be
responsible in some cases. IPS anatomyparticularly
the presence of a hypoplastic IPSand changes in
venous drainage after surgical intervention have also
been implicated (13).
IPSS has also a role in lateralizing the pituitary
adenoma to one side of the pituitary. This is particu-
larly important in patients with microadenomas.
Figure 24.7 IPS venogram in a patient with GH secreting pitui-
tary adenoma. The measured values of GH in pg per ml are
recorded. A GH secreting adenoma was found at surgery in the
right half of the pituitary.
Successful lateralization permits the surgeon to per-
form a hemihypophysectomy and preserve pituitary
function. A ratio of 1.4 or more between the ACTH
concentrations of the two petrosal sinus samples
from any sample set indicates that the adenoma is
located on the side of greater ACTH concentration
(Fig. 24.7). The reported sensitivity of IPSS for lateral-
ization of pituitary adenomas in adults ranges from
57% to 90% (3,4,12,1416). Occasionally, samples
obtained before CRH administration and samples
obtained after CRH administration provide discord-
ant lateralization. In this situation, neither lateraliza-
tion can be relied upon (17).
There are several reasons for this relatively low
yield. Often times the adenoma is located in the center
of the pituitary and it drains into both cavernous
sinuses. The same drainage pattern also occurs in
larger adenomas. Anomalies in petrosal venous anat-
omy such as hypoplasia of one sinus can result in false
lateralization to the opposite side, as can asymmetry in
petrosal sinus anatomy or previous transsphenoidal
surgery (4,17). In a recent study, the sensitivity of later-
alization in a series of 141 pediatric patients was found
to be only 54%, which is more than conventional MR
imaging, and no better than chance (18). In a different
study, smaller series of 11 patients, however, lateraliza-
tion was correct in 91% (19). The reasons for this dis-
agreement are unclear.
COMPLICATIONS OF INFERIOR PETROSAL
SINUS SAMPLING
Neurologic and other complications have been
encountered by various investigators during IPSS
(2024). The incidence of such complications is low,
 INFERIOR PETROSAL SINUS SAMPLING IN THE DIAGNOSIS OF PITUITARY ADENOMAS
and ranges from 0.2% to 1.1%. Miller et al. reported a
case of hematoma in the pons associated with hemor-
rhage in the fourth ventricle. This resulted in right
hemiplegia with partial recovery and left facial para-
lysis. An ischemic infarction in the medulla was also
reported by the same authors, in a patient who
underwent IPSS by other operators at a different
institution. Subarachnoid hemorrhage, Raymonds
syndrome (sixth nerve palsy and hemiparesis), and
brainstem infarction have been reported by other
investigators (21,23,24).
A variety of other less severe or transient neuro-
logic events have also been reported, including
slurred speech, paresthesias, visual disturbances, tran-
sient sixth nerve palsy, vertigo, nausea, vomiting, and
transient muscle weakness. These complications may
not have a common cause. While the etiology is not
known, it appears that most serious complications
occur as a result of rupture or thrombosis of a venule
in the brain stem or a bridging vein within the subar-
achnoid space. These complications may be due to the
highly variable venous anatomy in this region. When
test injections of contrast material are made to identify
the orifice of the IPS, special attention should be paid
to the size of the veins and to ensure that the catheter
tip is not a small vein. Catheterization of an extremely
small vein or forceful hand injection of contrast mate-
rial in a catheter wedged in such a vein can easily
lead to either elevated venous pressure or rupture of
that vein. However, the presence of adequate-sized
venous channels and proper position of the catheter
tip do not guarantee that a serious complication will
not occur, since these complications have occurred
despite seemingly unremarkable petrosal sinus anat-
omy (20). Additionally, catheterization of extremely
small petrosal sinuses has been performed without
incident (7).
A neurologic event may be heralded by minor
and seemingly insignificant symptoms. Arterial hyper-
tension, slurred speech, difficulty swallowing, a sensa-
tion of an enlarged tongue, a woozy feeling, and
hemifacial paresthesias have all been encountered as
initial manifestations of a brain stem insult. These
may be subtle, and the patient may not mention them
unless asked. If present, they should not be inter-
preted as evidence of anxiety, oversedation, or a reac-
tion to contrast material. Brainstem injury may be
preventable if the catheter is withdrawn at the earliest sign
of even a minor, insignificant problem. Subtle symptoms
and signs that may not appear to be neurologic may herald
a clinical catastrophe if not heeded.
Patients with Cushings syndrome are also prone
to venous thrombosis, and both deep venous throm-
bosis and pulmonary embolus have been reported as
complications of petrosal sinus sampling (25).
ALTERNATIVES TO INFERIOR PETROSAL
SINUS SAMPLING
Catheterization of, and sampling from, the cavernous
sinus has been suggested as an alternative to petrosal
sinus sampling, on the grounds that it is both safer and
more accurate (14,26,27) Other studies indicate that
sampling from the cavernous sinus is no more accurate
than petrosal sinus sampling for distinguishing
493
between Cushings disease and an ectopic ACTH
source, and is less accurate for lateralization of an
adenoma within the pituitary gland (4,28). In Lefour-
nier et al.s series of 14 cavernous sinus sampling pro-
cedures, transient sixth nerve palsies occurred in two
patients (4).
Sampling of the internal jugular veins has been
advocated by Doppman et al. because of the technical
difficulties that can be encountered in selective cathe-
terization of the IPS, the long learning curve for pet-
rosal sinus sampling, and the need to abandon the
procedure in patients who develop suspicious symp-
toms, systemic hypertension, or neurologic events
during the procedure (29). In this simpler procedure,
catheters are placed in both internal jugular veins at
the level of the mandible. In the initial description of
the procedures, the catheters were inserted through
bilateral femoral vein punctures, but in a subsequent
series catheters were placed via the internal jugular
vein (30). In our own practice, we routinely use ultra-
sound guidance and a micropuncture set to access the
internal jugular vein as inferiorly as possible in the
neck, and advance the inner 3-F dilator of the micro-
puncture set retrogradely, so that its tip lies at the
level of the mandible. The outer dilator is not used.
No skin nick is necessary, and the procedure is per-
formed with local anesthetic alone. Samples are
obtained before and after CRH administration in the
same fashion as for petrosal sinus sampling.
In a series of 79 patients, the NIH group found a
sensitivity of 83% for jugular venous sampling, using
arbitrary thresholds (jugular vein: peripheral vein
ACTH ratio > 1.7 before CRH administration or > 2.0
after CRH administration) to set specificity at 100%. In
the same patients, IPSS had a sensitivity of 94% when
specificity was set at 100% (30). Erickson et al. demon-
strated similar results in a series of 35 patients. They
suggest that the sensitivity of internal jugular vein
sampling can be improved by placing the catheter
near the medial rather than the lateral wall of the
internal jugular vein during sampling and by using a
jugular vein: peripheral vein ACTH ratio > 2.5 for the
diagnosis of Cushings disease (31).
Although internal jugular vein sampling is less
sensitive than petrosal sinus sampling, it is simpler
and avoids the risk of neurologic complications inher-
ent in petrosal sinus sampling. It is reasonable to per-
form jugular venous sampling first, and to reserve
petrosal sinus sampling for those patients in whom
jugular venous sampling does not confirm Cushings
disease. These patients may be referred to centers
where extensive experience in performing petrosal
sinus sampling is available.
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pituitary lesions in 1,000 unselected autopsy specimens.
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2. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield
EH. Pituitary magnetic resonance imaging in normal
human volunteers: Occult adenomas in the general popula-
tion. Ann Intern Med 1994; 120: 81720.
3. Bonelli FS, Huston J III, Carpenter PC, et al. Adrenocorti-
cotropic hormone-dependent Cushings syndrome:
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Sensitivity and specificity of inferior petrosal sinus sam-
pling. AJNR 2000; 21: 6906.
4. Lefournier V, Martinie M, Vasdev A, et al. Accuracy of bilat-
eral inferior petrosal or cavernous sinuses sampling in pre-
dicting the lateralization of Cushings disease pituitary
microadenoma: Influence of catheter position and anatomy of
venous drainage. J Clin Endocrinol Metab 2003; 88: 196203.
5. Gebarski SS, Gebarski KS. Inferior petrosal sinus: Imaging-
anatomic correlation. Radiology 1995; 194: 23947.
6. Shiu PC, Hanafee WN, Wilson GC, Rand RW. Cavernous
sinus venography. AJR Am J Roentgenol 1968; 104: 5762.
7. Miller DL, Doppman JL, Chang R. Anatomy of the junction
of the inferior petrosal sinus and the internal jugular vein.
AJNR 1993; 14: 107583.
8. Miller DL, Doppman JL. Petrosal sinus sampling: Techni-
que and rationale. Radiology 1991; 178: 3747.
9. Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal
sinus sampling with and without corticotropin-releasing
hormone for the differential diagnosis of Cushings syn-
drome. N Engl J Med 1991; 325: 897905.
10. Yamamoto Y, Davis DH, Nippoldt TB, et al. False-positive
inferior petrosal sinus sampling in the diagnosis of Cushings
disease. Report of two cases. J Neurosurg 1995; 83: 108791.
11. Swearingen B, Katznelson L, Miller K, et al. Diagnostic
errors after inferior petrosal sinus sampling. J Clin Endocri-
nol Metab 2004; 89: 375263.
12. Kaltsas GA, Giannulis MG, Newell-Price JDC, et al. A crit-
ical analysis of the value of simultaneous inferior petrosal
sinus sampling in Cushings disease and the occult ectopic
adrenocorticotropin syndrome. J Clin Endocrinol Metab
1999; 84: 48792.
13. Doppman JL, Chang R, Oldfield EH, et al. The hypoplastic
inferior petrosal sinus: a potential source of false-negative
results in petrosal sampling for Cushings disease. J Clin
Endocrinol Metab 1999; 84: 53340.
14. Graham KE, Samuels MH, Nesbit GM, et al. Cavernous
Sinus Sampling Is Highly Accurate in Distinguishing
Cushings Disease from the Ectopic Adrenocorticotropin
Syndrome and in Predicting Intrapituitary Tumor Location.
J Clin Endocrinol Metab 1999; 84: 160210.
15. Booth GL, Redelmeier DA, Grosman H, et al. Improved
diagnostic accuracy of inferior petrosal sinus sampling over
imaging for localizing pituitary pathology in patients with
Cushings disease. J Clin Endocrinol Metab 1998; 83: 22915.
16. Oldfield EH, Chrousos GP, Schulte HM, et al. Preopera-
tive lateralization of ACTH-secreting pituitary microadeno-
mas by bilateral and simultaneous inferior petrosal venous
sinus sampling. N Engl J Med 1985; 312: 1003.
17. Miller DL, Doppman JL, Nieman LK, et al. Petrosal sinus
sampling: discordant lateralization of ACTH- secreting pitui-
tary microadenomas before and after stimulation with corti-
cotropin-releasing hormone. Radiology 1990; 176: 42931.
18. Batista D, Gennari M, Riar J, et al. An assessment of
petrosal sinus sampling for localization of pituitary
microadenomas in children with Cushing disease. J Clin
Endocrinol Metab 2006; 91: 2214.
19. Lienhardt A, Grossman AB, Dacie JE, et al. Relative contri-
butions of inferior petrosal sinus sampling and pituitary
imaging in the investigation of children and adolescents
with ACTH-dependent Cushings syndrome. J Clin Endo-
crinol Metab 2001; 86: 571114.
20. Miller DL, Doppman JL, Peterman SB, et al. Neurologic
complications of petrosal sinus sampling. Radiology 1992;
185: 1437.
21. Bonelli FS, Huston J III, Meyer FB, Carpenter PC. Venous sub-
archnoid hemorrhage after inferior petrosal sinus sampling
for adrenocorticotropic hormone. AJNR 1999; 20: 3067.
22. Lefournier V, Gatta B, Martinie M, et al. One transient
neurological complication (sixth nerve palsy) in 166 consec-
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diagnosis of Cushings syndrome [letter]. J Clin Endocrinol
Metab 1999; 84: 34012.
23. Seyer H, Honegger J, Schott W, et al. Raymonds syn-
drome following petrosal sinus sampling. Acta Neurochir
(Wien) 1994; 131: 1579.
24. Sturrock ND, Jeffcoate WJ. A neurological complication of
inferior petrosal sinus sampling during investigation for
Cushings disease: a case report. J Neurol Neurosurg Psy-
chiatry 1997; 62: 5278.
25. Obuobie K, Davies JS, Ogunko A, Scanlon MF. Venous
thrombo-embolism following inferior petrosal sinus sam-
pling in Cushings disease. J Endocrinol Invest 2000; 23:
5424.
26. Teramoto A, Nemoto S, Takakura K, Sasaki Y, Machida T.
Selective venous sampling directly from cavernous sinus in
Cushings syndrome. J Clin Endocrinol Metab 1993; 76:
63741.
27. Vandorpe RA, Fox AJ, Pelz DM, Lee DH. Direct sampling
of the cavernous sinus in Cushings disease. Can Assoc
Radiol J 1994; 45: 2347.
28. Doppman JL, Nieman LK, Chang R, et al. Selective venous
sampling from the cavernous sinuses is not a more reliable
technique than sampling from the inferior petrosal sinuses
in Cushings syndrome. J Clin Endocrinol Metab 1995; 80:
24859.
29. Doppman JL, Oldfield EH, Nieman LK. Bilateral sampling
of the internal jugular vein to distinguish between mecha-
nisms of adrenocorticotropic hormone-dependent Cushing
syndrome. Ann Intern Med 1998; 128: 336.
30. Ilias I, Chang R, Pacak K, et al. Jugular venous sampling:
An alternative to petrosal sinus sampling for the diagnostic
evaluation of adrenocorticotropic hormone-dependent
Cushings syndrome. J Clin Endocrinol Metab 2004; 89:
3795800.
31. Erickson D, Huston J III, Young WF Jr, et al. Internal jugular
vein sampling in adrenocorticotrophic hormone-dependent
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sinus sampling. Clin Endocrinol 2004; 60: 41319.
 25
Diagnosis and management of pediatric cerebrovascular
disease
Gregory G. Heuer and Robert W. Hurst
Cerebrovascular lesions are rare but significant lesions
in the pediatric population. Some of these lesions
present almost exclusively in the pediatric patient and
while some can present in adult patients, the pediatric
condition often needs to be approached differently,
either due to the physiology of the pediatric patient
or due to differences in presentation in the younger
patient.
Lasjaunias classified vascular lesions in pedia-
tric patients into three subtypes: (1) proliferative dis-
eases such as Moyamoya disease and hemangiomas;
(2) venous malformations such as cavernomas; and
(3) arteriovenous (AV) shunts (Table 25.1) (1). The
focus of this chapter will be the on the last subgroup,
those lesions that present as a result of AV shunts
including Vein of Galen aneurysmal malformations
(VGAMs), AV fistulas, arteriovenous malformations
(AVMs). In addition, pediatric aneurysms will be dis-
cussed. Those lesions that present more commonly
in adults are adequately discussed in the previous
chapters.
VEIN OF GALEN ANEURYSMAL
MALFORMATION
Description
Vein of Galen aneurysmal malformations (VGAMs)
are rare lesions, making up only about 1% of all intra-
cranial vascular lesions (24). However, these congeni-
tal lesions are disproportionately represented in
pediatric patients where they constitute up to 30% of
intracranial vascular abnormalities in the neonatal
population. Despite the name, these lesions are not
aneurysmal dilations but rather represent a dilated
ectatic venous structure. Also, although they are
found in the normal location of the Vein of Galen,
true VGAMs do not involve this vessel (5). Structur-
ally, VGAMs result from direct AV connections (fistu-
las) between a persistent embryonic precursor, the
median vein of the prosencephalon (Vein of Markow-
ski), and arteries that embryologically supply the cho-
roid plexus. This connection normally regresses before
birth, at the 50mm stage (6). The persistent median
vein of the prosencephalon does not drain normal
brain tissue. As a result the AV shunts of VGAMs are
located in the subarachnoid space (Table 25.1). This
differentiates VGAMs from AVMs, PAVFs, and
DAVFs. True AVMs in this location that drain normal
brain are referred to as Vein of Galen aneurysmal
dilations (VGADs) (5). Unlike VGAMs, VGADs pos-
sess a distinct nidus that drains into the normal Vein
of Galen. As a result, although they may appear simi-
lar on some imaging modalities, VGADs behave and
are treated similarly to AVMs and not VGAMs.
In the modern era, patients with VGAMs are com-
monly diagnosed in utero, either by fetal ultrasound (7,8)
or by fetal magnetic resonance (MR) imaging (MRI) (912).
After birth, MRI and MR angiography (MRA) are cur-
rently the main imaging modalities used to evaluate
these lesions (13,14). The detailed structure of the VGAMs
can be seen from these sequences (Fig. 25.1A). A good
quality MRI delays the need to perform technically diffi-
cult diagnostic neuroangiography on very young patients
(Fig. 25.1B). Also, additional information can be obtained
from the MRI such as the presence of thrombosis, areas of
parenchymal damage, problems with Cerebrospinal Fluid
(CSF) flow, information that is important to guide and
monitor treatment.
VGAMs are divided into two broad subcate-
gories based on their angioarchitecture, mural and
choroidal types (5). The subcategories differ anato-
mically in the number and location of the shunts.
The architecture of choroidal lesions is characte-
rized by numerous bilateral choroidal artery feeders
(Fig. 25.1C). These numerous feeders result in an
extremely high flow. In contrast, the architecture in
mural VGAMs consists of a single or at most a few
feeders that converge into the venous sac and present
more often in infants and older children. Because of
the differences in the flow between the two sub-
categories, mural and choroidal VGAMs have different
effects on the patient. Choroidal VGAMs often present
soon after birth (15,16). Due to the high flow, neonatal
patients with choroidal VGAMs present with life
threatening, often medically intractable heart failure.
Patients with mural VGAMs typically present with
enlarging head circumference, hydrocephalus, and
developmental delay.
Treatment
VGAMs are almost exclusively treated via endo-
vascular techniques (1623). Prior to development
of endovascular therapy, open surgical treatment
496 NEUROINTERVENTIONAL MANAGEMENT

Table 25.1 Lasjaunias Subcategories of Vascular Malformation resulted in extremely poor outcomes with mortality
in Children over 90% (24,25). With the development of neurointer-
Subcategory Lesion Location ventional therapeutic techniques, these lesions have
become treatable with significantly improved out-
Arteriovenous shunt VGAM Subarachnoid comes (26). The ultimate goal is to treat the lesion by
DAVF Dural
PAVF Subpial
closure of the fistulas and provide the child with the
AVM Subpial best chance for good neurologic development. How-
Venous malformations Cavernoma NA ever, the short-term goals of an intervention vary
Dysplasia NA depending on the presentation and type of lesion.
Proliferative Moyamoya NA For example, choroidal lesions are often treated in a
Angiopathy NA sequential fashion. The initial goal is to decrease the
Hemangiomas NA shunt in the neonate to minimize the cardiac effects
Source: Adapted from Ref. 1. of the VGAMs and prevent or reverse heart failure
(Fig. 25.1D). Subsequent interventions continue to

(A) (B)

(C) (D)

Figure 25.1 Neonate diagnosed in utero with a Vein of Galen Aneurysmal Malformation (VGAM). At birth the patient presented in
medically intractable heart failure. An axial MRA (A) and sagittal MRI (B) demonstrated a choroidal VGAM. Additionally, the MR
demonstrated scattered foci of susceptibility along the ependymal lining of the lateral ventricles consistent with blood products from
prior bleeds and evidence of subarachnoid blood. (C) A cerebral angiogram obtained at the time of treatment was consistent with the
magnetic resonance (I- imaging, A- angiography) (MRI/A). (D) Post-embolization angiogram demonstrating significantly reduced flow in
the malformation.
 DIAGNOSIS AND MANAGEMENT OF PEDIATRIC CEREBROVASCULAR DISEASE
further reduce the shunt until obliteration is
obtained. Conversely, due to reduced feeding vessels
and the lack of the acute cardiac changes, mural
VGAMs are treated at an older age and often require
fewer total interventions.
When treating a VGAM, it is helpful to establish
a goal and develop a plan prior to beginning the
angiogram. An analysis of the MRI/A can provide
information on the structure of the lesion and the best
method and route to treat the lesion (27). The angio-
gram is performed using appropriate sized catheters,
usually 4 Fr in neonates and infants, via standard
femoral arterial or transumbilical routes (2831).
Special attention is made to minimize blood loss and
contrast dose in the pediatric age group. A micro-
catheter is navigated to the fistula sites. The choice of
embolic agent (n-BCA, coils, and Onyx) is determined
by the angioarchitecture of the fistulas with the goal
to occlude at the site of arteryvein communication.
If the embolization occurs proximally in the artery,
collateral flow will likely occur with persistence or
recurrence of the fistula.
Evidence from case series indicates that VGAMs
can be effectively treated endovascularly, with 60% of
patients of all ages having minimal to no develop-
mental delay at follow-up (15,16,20,21,23). However,
case series outcomes can be misleading depending on
the median age of the group, as individual outcome is
greatly dependant on the age of the patient. Young
patients presenting with cardiac failure are particularly
difficult to treat (1618,32). Patients presenting early in
life with intractable cardiac failure have mortality rates
as high as 62% despite treatment (1623,32). In those
patients presenting at older ages, outcome is consider-
ably better with up to 80% reported as normal in some
large series.
PIAL ARTERIOVENOUS FISTULA
Description
Pial arteriovenous fistulas (PAVFs) are an uncommon
but important type of cerebrovascular disease which
is overrepresented in the pediatric population,
although the exact incidence is unknown (3339). The
lesions are classified within the group of AV shunts
(Table 25.1) (1). PAVFs consist of direct communica-
tion between one or a few arterial feeders and the
venous system within the pia (40). The differentiating
factor between AVM and PAVF is the lack of the tan-
gle of abnormal vessels, the nidus, in PAVF. PAVFs
are differentiated from other lesions by their subpial
location, versus the subarachnoid location of VGAMs
and the dural location of dural arteriovenous fistulas
(DAVFs).
PAVFs commonly present in the very young, up
to half of the patients present within the first 2 years
of life and the rest present as older children or
adults (38). The clinical presentation differs depending
on the patients age (38). Heart failure is a presenting
symptom only in neonates. Heart failure arises due
to similar physiology seen in neonates with VGAM,
excessive blood flow through the shunt lesion (41).
Older children and adults commonly present with
symptoms secondary to mass effect that is age
497
specific, including headaches and enlarging head cir-
cumference (34,35). Patients less commonly present
with seizures or focal neurological deficit, which
may be related to focal venous ischemia. Patients
can also rarely present with acute hemorrhage that
may be intraventricular, intraparenchymal, or subar-
achnoid in location (34). This hemorrhage has been
associated with thrombosis or stenosis of the venous
outflow (42).
PAVFs can be identified on a number of imaging
studies. On computed tomography (CT), an enlarged
venous varix may be evident as a region of iso- or
hypodensity, and if edema or ischemia is present the
brain parenchyma may show an abnormal area of
hypodensity. As with other AV shunts, flow voids and
flow artifact will be evident on MRI/A (Fig. 25.2A, B).
Additionally, the parenchymal changes can be readily
seen on MR sequences and in severe cases, particularly
in neonatal patients, overt encephalomalacia may be
seen. As with VGAMs, the MRA provides a roadmap
of the vascular lesion and can be useful in guiding
future treatment. It should be noted that it can be
difficult to differentiate AVMs from PAVFs on CT or
MRI/A, commonly necessitating the need for catheter
angiography to accurately define the lesion.
On angiography PAVFs share a number of fea-
tures (Fig. 25.2C, D): rapid venous opacification; dis-
proportionately large arterial feeder(s); and direct
filling of a large venous varix, often with a jet phe-
nomenon (36). Commonly, the site of direct artery to
vein transition will be evident as an increase in vessel
caliber. Special attention should be paid to the venous
drainage to determine if subpial venous reflux,
venous outflow obstruction, or sinus obstruction is
present, as these factors may increase the hemorrhage
rate of the lesion.
Treatment
Determining outcome for these rare lesions is difficult.
However, in most cases PAVFs should be treated as
untreated lesions are frequently neurologically devas-
tating or fatal (37). The goal of treatment is interruption
of the artery from the draining vein at the site of the
fistula (Fig. 25.2E, F). Prior to the development of
endovascular techniques, these lesions where effec-
tively treated with surgery (36,38,39). As embolization
technology has developed, this has largely become the
treatment of choice for PAVFs (3335). Endovascular
treatment may be particularly useful for lesions located
in deep locations or in eloquent regions of brain.
A number of overall guidelines exist for treat-
ment of PAVFs. First, when treating PAVFs, an analy-
sis of structure of the lesions must be performed. One
should determine if the architecture allows the place-
ment of a microcatheter into the target, the fistulous
connection itself. If embolization is performed too
proximally, the fistula may remain open and could
recruit new feeding vessels, leading to recurrence of
the lesion. In general, the smallest lesions are often
treated first, followed by the largest. If the smaller
lesions are treated last, the overall flow could be dra-
matically increased in the remaining fistulas, poten-
tially resulting in complications such as hemorrhage.
498 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

(E) (F)

Figure 25.2 A 5-month-old child that presented with enlarging head circumference. (A) An MRI and (B) MRA demonstrated a PAVF
in the right temporal-occipital region. This lesion was evident on cerebral angiography (C, D). (E) Selective embolization of the lesion
with micro-catheter present in the PVAF. (F) Post-embolization angiogram.
 DIAGNOSIS AND MANAGEMENT OF PEDIATRIC CEREBROVASCULAR DISEASE
(A) (B)
Figure 25.3 A 7-year-old patient presenting with altered mental status. (A) A non-contrast head computed tomography (HCT)
obtained at the time of presentation demonstrated a left frontal hemorrhage. (B) A follow-up MRI demonstrated a large left frontal arte-
riovenous malformation (AVM). (C) A cerebral angiogram with a left frontal AVM nidus and early draining vein.
Standard embolic agents, such as NBCA and
detachable coils, have been used effectively for these
lesions (3438). In addition, newer agents such as
Onyx have been used with some success (43). Due to
the rarity of these lesions it is difficult to determine
the overall outcome from the small case series
reported; however, good outcomes are seen in the
majority, 70% or higher, of patients.
Surgery is also a treatment option, particularly
for those lesions in which the angioarchitecture does
not allow endovascular treatment (36,38,39). Again the
goal is interruption of the AV shunt at the fistulous
connection. Like endovascular techniques, small series
report that surgical treatment is effective; however,
surgical treatment may have a higher rate of certain
types of complications, specifically an increase in
venous infarcts.
ARTERIOVENOUS MALFORMATION
Description
Cerebral arteriovenous malformations (AVMs) consist of
an abnormal collection of blood vessels which results in
connections between veins and arteries without inter-
vening capillary beds or brain parenchyma. This group
of abnormal vessels results in AV shunting through
the characteristic feature of an AVM, the nidus, and
enlarged draining vein or veins. AVMs are believed to
be congenital lesions and are found in both adult and
pediatric patients (44,45). AVMs do not typically become
symptomatic in patients until the second to fourth dec-
ade of life (46,47). However, even though most AVMs
do not present until adulthood, these lesions can become
symptomatic in the pediatric age group.
Both pediatric and adult patients present most
commonly with hemorrhage and seizure (48). Studies
on pediatric AVMs show the risk of hemorrhage to be
24% per year, with a resulting 510% mortality rate
499
(C)
and a 50% risk of serious neurological morbidity asso-
ciated with each hemorrhagic event (49,50). Other pre-
senting symptoms in children are rare and include
developmental delay, hydrocephalus, persistent head-
ache, and congestive heart failure or other cardiovas-
cular related symptoms such as syncope.
Because many AVMs present with hemorrhage,
the first imaging study obtained is often a CT study
(Fig. 25.3A). On this initial study a nidus may or may
not be evident and if the patient is in extremis, a CT
angiogram may be performed to provide the surgeon
with some information on the vascular structure of
the lesion. In non-urgent cases where the clinical his-
tory or the CT scan suggest an AVM, or in cases of
unexplained seizure, the study of choice is a MRI/A
to evaluate the brain parenchyma as well as the vas-
cular structure of the lesion (Fig. 25.3B). Some findings
on MR are characteristic of AVMs, such as the pres-
ence of flow voids representing the nidus and the
supplying and draining vessels as well as evidence of
previous hemorrhages or blood products. The next
step is usually a catheter angiogram to define the
lesions (Fig. 25.3C). However, if a large hematoma is
present, the pressure of the blood clot may preclude
full visualization of the AVMs and therefore, if treat-
ment can be safely delayed, a repeat angiogram is
often performed. One important factor to determine is
whether any aneurysms are present in the nidus or on
feeding vessels, as the presence of these lesions may
indicate a higher rate of rebleeding and necessitate
more urgent treatment (5155).
Treatment
As with most vascular lesions, the goal of treatment is
complete obliteration of the AVM. As in adults, the
management strategy of AVMs in the pediatric popu-
lation may include surgical resection, endovascular
embolization, and radiosurgery.
500 NEUROINTERVENTIONAL MANAGEMENT

Traditionally, surgical resection is the treatment PEDIATRIC INTRACRANIAL ANEURYSMS

of choice for definitive cure of the lesion. (56). The
surgical outcome of patients is generally good, with
81 to 95% of pediatric patients having an excellent or
good outcome (5658). Outcome has been associated
with the location and size of the lesion as well as
whether the lesion is diffuse in its nidus angioarchi-
tecture. Long-term follow-up is often needed as there
may be an increased rate of recurrence in pediatric
patients and late recurrences have been seen in this
population (49,58,59).
In modern large series of pediatric AVMs pub-
lished since 2000, there has been in increase in the use
of pre-surgical embolization in patients to a rate as
high as 75% (50,5660). The exact benefit obtained
from pre-operative embolization may vary within the
pediatric population and each case must be evaluated
individually. The surgeon must determine, after a dis-
cussion with the neurointerventionalist, to what
degree the lesion can be embolized and if this reduc-
tion in blood supply, number of feeding arteries, and
size results in a significant benefit compared with the
risk of embolization related complications. As endo-
vascular techniques evolve, further reduction in the
overall complication rate following embolization of
AVMs will likely impact the discussion of the of risk
versus benefit (58,61).
Intraoperative angiography has become a com-
mon adjuvant to AVM surgery in adult patients but
this has not been extensively described nor critically
evaluated in the pediatric population. Ghosh et al.
evaluated the use of intraoperative angiography in
the management of pediatric patients and found
that in 3 of 15 AVM cases, intraoperative angiogram
revealed residual lesion which was then completely
resected (62). In the pediatric population, angiograms
often have to be obtained with general anesthesia;
therefore, obtaining an angiogram while the patient
remains in the operating room has the additional bene-
fit of allowing the patient to be extubated and a neuro-
logic exam obtained immediately post-operatively.
A post-operative angiogram can then be obtained at a
later date.
Like adult patients, radiosurgery with Gamma
Knife or linear-accelerator-based stereotactic systems
have been used in pediatric AVM patients (63). Large
case series have demonstrated an obliteration rate of
35% to 74% (6472). Most studies have demonstrated
that the volume of the lesion was inversely correlated
with obliteration rate.
Description
Intracranial aneurysms are much less common in the
pediatric population than in adults. Other differences
from adult aneurysm populations include different
gender predominance, distribution, location, etiology,
clinical behavior, and often management. The differ-
ences likely reflect not only true characteristics of the
disorders which may underlie aneurysms in this pop-
ulation, but also methodological variables specific to
each series (Table 25.2).
Despite their rarity and differences from adult
aneurysms, pediatric intracranial aneurysms, like
those in adults, present significant risks of both mor-
bidity and mortality which warrant rapid evaluation
and effective treatment. Intracranial aneurysms infre-
quently occur in children, with patients in the first
two decades of life, constituting from 0.6% to 4.6% of
all intracranial aneurysms in large series (7375).
Within the pediatric population, aneurysms are found
less commonly at younger ages. The majority is identi-
fied in adolescents, significantly lower numbers are
found in children, with those in patients under 1year
of age even more rarely identified (76).
Most pediatric aneurysm series demonstrate a
predominance of male patients (Table 25.2). This is in
marked contrast to the overall female to male predom-
inance of 1.6 to 1 observed in adult aneurysm popula-
tions (73). Huang et al. reviewed 750 cases of
aneurysms in patients under the age of 18 reported
between 1939 and 2004. They found an overall male:
female ratio of 1.8:1 (77). The sexual distribution
within the pediatric population has been suggested to
vary with age, however, with male predominance
most marked between childhood and puberty. In this
age range, male to female ratios as high as 2.7:1 to 4:1
have been reported (78,79). At younger ages, some
series report equal male and female occurrence or
even female predominance under the age of 2 years
with an M:F ratio as high as 1:5 (80). While the small
numbers reported at the youngest ages may affect reli-
ability, others have reported an equal to slightly
increased (1.4:1) male to female ratio in aneurysms
presenting in patients under 1year, with an average
presenting age of 5 months (76,81).
Presentation of pediatric aneurysms varies based
on both the age of the patient and the etiology of
the aneurysm. Most series indicate that subarachnoid

Table 25.2 Characteristics of Pediatric Aneurysms

Circulation
Paper Patient # Anr # Age M:F Post ex ICA in ICA MCA ACA Mult Giant
Liang et al., (82) 24 24 < 14 y 1.4 38% 13% 17% 21% 13% 4% 33%
Lv et al., (78) 25 25 17 y 4 60% 4% 20% 16% 0 80%
Hetts et al., (88) 77 103 3 m--18 y 0.9 21% 13% 40% 17% 10% 11% 17%
Huang et al., (77) 19 19 1 m--18 y 2.2 42% 16% 11% 5% 26% 0 37%
Lasjaunias et al., (80) 59 75 8 d--15 y 1.5 31% 12% 27% 21% 9% 12% 0
Agid et al., (85) 33 37 1 d--17 y 0.9 30% 14% 27% 14% 15% 8% 30%
Proust et al., (79) 22 25 16 y 2.7 9% 0 36% 36% 18% 12% 12%
Review., (Huang et al.) (77) 1.8 17% 20%
Abbreviations: Anr, Aneurysm; M:F, male to female ratio; Mult, multiple aneurysms; Post, posterior; ex ICA, extradural internal carotid
artery; in ICA, intradural internal carotid artery; ICA, internal carotid artery; MCA, middle cerebral artery; ACA, anterior cerebral artery.
 DIAGNOSIS AND MANAGEMENT OF PEDIATRIC CEREBROVASCULAR DISEASE
hemorrhage is the presenting feature in from 80% to
over 90% of the pediatric population, with nearly half
of patients presenting with good grade (77,79,82,83).
Others suggest a more age-dependent presentation
with patients under 6 years of age most often presen-
ting with hemorrhage, while in children between
6 and 11, nonhemorrhagic neurological deficits and
headache assume increasing importance. After age 11,
hemorrhage again becomes the dominant presentation,
assuming the more typical adult presentation with
subarachnoid hemorrhage by late teenage years (80,84).
Throughout the pediatric age range however, nonhe-
morrhagic neurological deficits, often the result of mass
effect, are more prominent than is the case in adult
series. This difference from adults likely reflects the
increased number of large and giant aneurysms in the
pediatric population (82).
The distribution of pediatric intracranial aneur-
ysms also differs from that observed in the adult
population. The most common pediatric aneurysm
location in most series is the internal carotid artery
(ICA) bifurcation, involved in approximately 25% of
all reported cases, significantly higher than the 4.5%
of adult aneurysms which occur in this location
(77,79,85). The anterior communicating artery is the
second most common aneurysm location in pediatric
patients, representing approximately 20% of cases.
This is only half the frequency of aneurysms reported
in this location in adults (73). The frequency of pedia-
tric anterior communicating artery aneurysms is
nearly equaled by that of the middle cerebral artery
(MCA) bifurcation in some series, a location typically
less common than that of the anterior communicating
artery in adult populations (73,86,87).
Despite the anterior location of most pediatric
aneurysms, increased occurrence in the posterior cir-
culation has been noted in most pediatric series. This
contrasts with the 5.5% frequency of posterior fossa
aneurysms reported in adult series (73,86,87). Huangs
review indicated a 17% rate of posterior circulation
aneurysms in the 706 cases published between the
years 1939 and 2005. More recent series however sug-
gest a higher frequency of occurrence in these loca-
tions. Hetts et al. found that 21% of aneurysms
in their population were located in the posterior circu-
lation. Higher frequencies of occurrence are corro-
borated by others including Agid et al. who found
29.7% posterior circulation aneurysms, Lasjaunias
et al. who reported 39%, Liang at 38%, and Lv whose
population consisted of 60% posterior circulation
aneurysms (78,80,85,88). Better detection may account
for the higher numbers in more recent series, perhaps
reflecting more widespread use of noninvasive imag-
ing modalities. Nevertheless, selection and referral
bias, as reflected by increasing numbers of studies
conducted at centers for endovascular treatment may
also play a role. In virtually all pediatric series, the
basilar artery has been the most common posterior
aneurysm location.
The etiology of intracranial aneurysms in the
pediatric population is much more diverse than
reported in adults, with decreased numbers of saccu-
lar aneurysms, by far the most common type occur-
ring in adults. While saccular aneurysms represent
the majority of reported cases in pediatric patients,
501
pediatric aneurysms are often found to be associated
with a predisposing condition. Although often diffi-
cult to reliably diagnose, dissection, infection, trauma,
(particularly blunt trauma), and familial or genetic
conditions account for significant numbers of pediatric
aneurysms in many series. Specific frequencies vary
among series and many series do not specify etiology
or specifically exclude infectious or traumatic aneur-
ysms. Nevertheless, these major etiologies appear to
underlie the vast majority of pediatric aneurysms (89).
For example, the series of both Hetts et al. and
Agid et al. found saccular or berry aneurysms to be
most common with a frequency of 46% in both series.
This was followed in frequency by nontraumatic dis-
secting aneurysms (30% and 19% respectively),
trauma (15% and 14%), and inflammatory causes (12%
and 8%). In contrast, Lasjaunias et al.s review of 75
aneurysms in 59 patients found dissecting aneurysms
represented the most common etiology (42%) with an
additional 3% classified as chronic (persisting) post-
traumatic aneurysms. Saccular aneurysms comprised
32% of the series, while 8% were identified as infec-
tious aneurysms (84,88).
The distribution of aneurysms has been shown to
differ based on etiology. For example, aneurysms asso-
ciated with dissection or trauma appear to be overre-
presented in the posterior circulation. Lasjaunias found
that 78% of vertebrobasilar aneurysms were associated
with dissection, while both Agid and Hetts found that
over half of their posterior circulation aneurysms were
associated with dissection or trauma (80,84,88).
Saccular aneurysms represent the most common
type of pediatric anterior circulation aneurysms in the
majority of reports. Although uncommon, infectious
aneurysms most often involve the anterior circulation,
with most patients known to have an infectious focus
such as endocarditis. Human immunodeficiency virus
(HIV) was the second most common infection related
etiology in several more recent series (80,85,88).
In adult patients, approximately 35% of aneur-
ysms are classified as giant aneurysms (>2.5cm). The
frequency is substantially increased in children with
approximately 20% of pediatric aneurysms meeting
size criteria for giant aneurysms. In adults, approxi-
mately 40% of giant aneurysms are found in the carotid
distribution, 25% in the anterior and middle cerebral
arteries, and 30% in the vertebrobasilar territory. Giant
intracranial aneurysms of children demonstrate a
greater degree of predilection for the posterior circula-
tion (Fig. 25.4AF). In Lvs series, for example 80% of
posterior circulation aneurysms were classified as giant
aneurysms (77,78,88).
A number of rare congenital and hereditary
conditions have been associated with an increase in
the risk of intracranial aneurysm. Most commonly,
these conditions include coarctation of the aorta,
autosomal-dominant polycystic kidney disease, and
fibromuscular dysplasia. Although less frequently
associated with intracranial aneurysms, Marfans
syndrome, EhlersDanlos syndrome, most often
type IV, pseudoxanthoma elasticum as well as
selected phakomatoses, including neurofibromatosis
(NF1), and tuberous sclerosis, have also been associ-
ated with intracranial aneurysms developing at an
early age (9094).
502 NEUROINTERVENTIONAL MANAGEMENT

[H]

(A) (B) (C)

Tra>Sag

(D) (E) (F)

Figure 25.4 Pediatric aneurysm. A 9-year-old male presents with mild diplopia on far right lateral gaze. (A) Unenhanced and
enhanced (B) CT scans demonstrate hyperdense homogeneously enhancing mass anterior to brainstem. (C) Sagittal computed tomog-
raphy angiography (CTA) shows aneurysm of basilar artery with mass effect on pons. (D) Coronal-enhanced T1-weighted MR and axial
MRA (E) show aneurysm. (F) Lateral view of left vertebral digital subtraction angiography (DSA) injection.

Treatment their natural history. Although data from adult series

The evaluation of a suspected aneurysm in pediatric
should be guided by a high index of suspicion, parti-
cularly in cases of unexplained headaches. The imaging
evaluation usually begins with unenhanced CT scan
(Figs. 25.4A, 25.5A, 25.6A). If the scan is normal and sub-
arachnoid hemorrhage is suspected, lumbar puncture
should be performed. MR and MRA may also be helpful
for the evaluation of unruptured aneurysms (Figs. 25.4DE,
25.5BC, 25.6B). While MRA avoids radiation exposure,
it cannot exclude small aneurysms under 5mm in diame-
ter. Computed tomography angiography (CTA) may also
be useful in the evaluation of pediatric aneurysms, partic-
ularly in cases where MR is not diagnostic (Fig. 25.4BC).
While radiation exposure is a justifiable concern, the
information gained may be used to target angiographic
evaluation. Digital subtraction angiography is generally
indicated for the evaluation of intracranial aneurysms in
the pediatric population (Figs. 25.4F, 25.5D, 25.6CE). The
study should evaluate other potential causes of intra-
cranial hemorrhage, including AVMs, vasculitis, and
DAVFs. In appropriate cases, endovascular treatment is
performed at the time of the diagnostic angiogram.
Similar to management decisions in adults, those
for pediatric aneurysms are often difficult and compli-
cated by the lack of accurate information concerning
are often used as a guide, it is unclear that such data
can be generalized to the pediatric population, partic-
ularly the very young. In addition, the range of etiolo-
gies underlying pediatric aneurysms often raises further
questions concerning the use of adult data, which is
usually obtained from series composed exclusively of
saccular aneurysms. The heterogeneity of etiologies,
morphology, and clinical manifestations has major
implications for treatment strategies (95).
Management choices for unruptured intracranial
aneurysms in the pediatric population involve not
only consideration of etiology and natural history, but
also the longer patient life spans and increased cumu-
lative risk compared with adults. Treatment options
include following without immediate treatment in
asymptomatic cases, surgical treatment, and endovas-
cular treatment. As in all cases, the risks and benefits
associated with each management option are para-
mount. In addition, because prevention of future hem-
orrhage is an important goal, durability of closure is
of particular concern in the pediatric population.
Prior to the development of endovascular techni-
ques, surgical treatment was the only treatment avail-
able; however, endovascular treatment has evolved to
play an increasing role in the management of pediatric
aneurysms. Nevertheless, as is the case with natural
 DIAGNOSIS AND MANAGEMENT OF PEDIATRIC CEREBROVASCULAR DISEASE 503

(A) (B)

(C) (D)

Figure 25.5 Traumatic aneurysm. A 10-month-old patient with history of head trauma. (A) Unenhanced CT demonstrates occipital
bone fracture as well as subarachnoid hemorrhage centered in the posterior fossa and fourth ventricle. (B) MRA on hospital day 3
demonstrates aneurysm at the origin of right posterior inferior cerebellar artery (PICA) (arrow). (C) Repeat MRA on day 7 shows
increase in aneurysm size (D) which was confirmed on DSA.

history studies, far less data are available concerning
outcomes of treatment in pediatric aneurysms com-
pared with that of adults.
Sanai et al. reported a series of 32 pediatric
patients ranging in age from 2 months to 18 years har-
boring a total of 43 aneurysms which were multiple
in 8 of the patients. Thirteen patients harboring 15 aneur-
ysms underwent microsurgical treatment with complete
obliteration in 93.3% and new neurologic deficits in
7.7%. Sixteen patients harboring 19 aneurysms were
treated endovascularly with a 78.9% rate of complete
obliteration and 6.3% new neurologic deficits. No
mortality occurred in either group. Importantly, recur-
rence of the treated aneurysm was not observed in the
microsurgical group although de novo aneurysm for-
mation occurred in 6.7%. A 15.8% recurrence rate was
observed in the endovascular group with a de novo
aneurysm formation rate of 15.8%. Etiologies were not
specified, making it impossible to draw conclusions
based on etiology based therapy. Nevertheless, there
were more incidents of treatment failure and/or
aneurysm recurrence in the endovascular group and
given the importance of minimizing recurrence in this
population, the authors suggest that in most cases of
pediatric aneurysms, microsurgical intervention is
superior (96).
Stiefel et al. reviewed 12 pediatric patients harbor-
ing 13 ruptured aneurysms ranging in age from less
than 1month to 16 years of age. They found that while
either treatment can be equally effective, surgical inter-
vention should usually be the first-line treatment.
They recommend coil embolization only if surgery is
not a viable option or if the aneurysm is located at the
basilar apex (97).
Agid et al. reviewed 37 aneurysms in 33 patients
under age 17 (85). Surgically treated patients (9) had a
504 NEUROINTERVENTIONAL MANAGEMENT

44% good recovery, 44% significant morbidity, and
11% mortality. Endovascular treatment demonstrated
an identical mortality but 77% good recovery and 23%
significant morbidity. Conservative management in 11
patients resulted in 64% good recovery and 36%
mortality. These authors recommended endovas-
cular approach whenever possible. Nevertheless, they
emphasized the goals of both alleviating acute
symptoms and preventing future hemorrhage. For the
latter, longer-term follow-up information will be
necessary.
Hetts et al.s relatively large experience with 103
aneurysms in 77 pediatric patients found low treatment-
related morbidity and mortality in both surgical and
endovascular treatment groups (88). The overall infarc-
tion rate was higher with surgical treatment at 14% than
in endovascular treatment (7%). Nevertheless, they
emphasized the need for availability of both treatment
modalities as exemplified by a 21% retreatment rate in
the endovascular group and a 10% crossover rate from
endovascular to surgical treatment.
Krings et al. formulated treatment recommen-
dations more focused on aneurysm etiology and
morphology. They recommended endosaccular coil
treatment only for the classical berry-type aneur-
ysms. In many instances, particularly in younger
patients with fusiform aneurysms, parent vessel
occlusion may be well tolerated due to robust lepto-
meningeal collateral routes (Fig. 25.6). Other options
including flow reversal, surgical options, or com-
bined treatment with bypass and parent vessel occlu-
sion should also be contemplated (89).

(A) (B) (C)

(D) (E)

Figure 25.6 A 3-month-old male with irritability and poor feeding. (A) Unenhanced CT demonstrates frontal lobe hematoma (arrow)
and subarachnoid hemorrhage. (B) Sagittal T2-weighted MR shows relationship of anterior cerebral artery (ACA) aneurysm (arrow)
to hematoma (arrowhead). (C) Lateral view of internal carotid injection demonstrates aneurysm (arrow). (D) Microcatheterization of
ACA with coils placed distal, proximal, and within the aneurysm (arrow). (E) Post-embolization view demonstrates ACA occlusion.
Delayed views (not shown) showed collateral filling of distal ACA.
 DIAGNOSIS AND MANAGEMENT OF PEDIATRIC CEREBROVASCULAR DISEASE
CONCLUSIONS
Vascular malformations are rare but significant prob-
lem in the pediatric population. Effective treatment of
these lesions requires a detailed understanding of the
natural history, pathophysiology, and structure of the
lesions. This allows one to attack the lesion at the site of
pathology thereby minimizing risks and maximizing
the chance of success. Also, in treating these lesions, the
physician must understand the unique character of the
pediatric patient, specifically the size of the patient
which may limit some treatment options, and the need
for a significant durable strategy given the long lifespan
of the pediatric patient. The complexity of these lesions
leads itself to a multidisciplinary approach, with a team
including neurosurgeons, neurologists, neurointerven-
tionalists, and pediatric critical care physicians.
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 26
Diagnosis and management of uncommon and genetic
cerebrovascular diseases
Rebecca N. Ichord
INTRODUCTION
Stroke and cerebrovascular disease (CVD) in childhood
is the subject of rapidly growing awareness and research
in the past decade. Advances in availability and tech-
nical quality of noninvasive brain and vascular imaging
with magnetic resonance imaging (MRI), and magnetic
resonance angiography (MRA) have greatly expanded
the capacity to detect and characterize CVD in infants
and children. Concurrent rapid growth in the techniques
and discoveries of molecular biology and genetics pro-
vide great opportunities to understand the basic mole-
cular and cellular biology of numerous inherited and
malformative vascular disorders affecting the develop-
ing nervous system. Neurointerventionalists are increas-
ingly being asked to participate in the diagnosis, and
sometimes the treatment, of children and adults with
uncommon congenital and inherited forms of CVD. This
chapter provides an overview of inherited and congeni-
tal cerebrovascular disorders for which expertise of an
interventional neuroradiologist may be requested for
comprehensive diagnosis or treatment. Each disorder is
briefly summarized with illustrative images. In most
conditions, treatment includes supportive and medical
measures that are common across the age spectrum and
among different diseases. Acquired cerebrovascular
disorders in children and young adults such as throm-
boembolic disease, focal cerebral arteriopathy, vasculitis,
and dissection comprise a large proportion of the spec-
trum of childhood-onset CVD, and are beyond the scope
of this chapter. Excellent comprehensive reviews of the
general approach to diagnosis and treatment of these
disorders are available elsewhere (13).
GENETIC CV DISORDERS PRESENTING
IN NEWBORNS AND INFANTS
PHACES
The syndrome known as PHACES was first described
as an association of facial cutaneous capillary heman-
giomas with intracranial vascular anomalies and pos-
terior fossa brain malformations (4). A more complete
description of the clinical features provided the
acronym PHACE which refers to Posterior fossa mal-
formations, facial Hemangioma, Arterial anomalies,
Cardiovascular anomalies and Eye defects (5). Subse-
quently, patients with this constellation of anomalies
were also found to have midline ventral cleft defects
(oral-facial or sternal), leading to the designation
PHACES. Recently a consensus statement was pub-
lished proposing criteria for the diagnosis of PHACE/
PHACES as either Definite or Possible, as follows:
(1) Definite PHACE: segmental hemangioma or heman-
gioma >5cm on the face or scalp plus one major criterion
or two minor criteria; (2) Possible PHACE: segmental
hemangioma >5cm on the face or scalp plus one minor
criterion. Major criteria include major anomalies, and
minor criteria include minor anomalies, in one of the
involved organ systems (cerebrovascular, cardiovascular,
ocular), as detailed in the consensus statement (6).
The spectrum of clinical features in PHACES is
broad, summarized in Table 26.1. The facial heman-
gioma is usually apparent in infancy, and is often the
first clue to diagnosis of this syndrome. In a multicenter
prospective study of 108 infants with facial heman-
giomas, 31% had features of PHACE, most commonly
cerebrovascular (91%) and cardiovascular (67%) (7).
Females are disproportionately affected (>80%), leading
to the suggestion that the disorder is x-linked with pre-
natal male lethality. Cerebral vascular anomalies may
be asymptomatic for many years, or may present with
ischemic stroke. Typically, however the arteriopathy is
static or progressive, in contrast to that of acquired
pediatric cerebral arteriopathies such as in moyamoya
syndrome (MMS) or sickle cell anemia. The combination
of cardiovascular with cerebrovascular anomalies is
especially important, as surgical repair of cardiovascular
anomalies such as coarctation may have ramifications
for the coexisting cerebrovascular anomalies. The spec-
trum of cerebrovascular anomalies was described in a
series of 70 patients with PHACE syndrome (8). These
anomalies are typically ipsilateral to the facial heman-
gioma. The cerebrovascular anomalies in this study
were classified into subtypes with their prevalence in
the cohort as follows: arterial dysgenesis (56%), arterial
narrowing (39%), arterial nonvisualization (20%), prim-
itive embryonic carotid-vertebrobasilar connections (20%),
and anomalous arterial course or origin (47%), most
commonly involving the internal carotid artery and its
embryonic branches.
Radiologic features are varied, in keeping with the
broad spectrum of arterial anomalies and the occurrence
of ischemic injury. The latter may include overt ischemic
stroke in large vessel territories, clinically covert infarcts
in watershed or hypoperfusion zones, or diffuse chronic
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES 509

Table 26.1 Clinical Features in PHACES

Major Feature Spectrum of Findings

Posterior fossa anomalies
Hemangiomas
Arterial anomalies
of the brain
Cardiovascular anomalies
Eye abnormalities
Midline ventral cleft anomalies
Dandy-Walker malformation, cerebellar hypoplasia
Large facial hemangiomas
Cervical and intracranial carotid artery hypoplasia or atresia; ectasia and/or tortuosity;
anomalous origins; aberrant or persistent fetal carotid-vertebral connections; intracranial aneurysms;
sinus pericranium; intracranial hemangioma; dural arteriovenous malformation
Aortic coarctation, aortic ectasia or aneurysm; aortic or tricuspid valve anomalies; tetralogy of Fallot;
anomalous pulmonary veins; dextrocardia; double aortic arch; atrial septal defect, ventricular
septal defect
Congenital cataracts, choroidal hemangiomas, cryptophthalmos, exophthalmos, colobomas,
posterior embryotoxin, optic atrophy, microphthalmos, strabismus, and optic nerve hypoplasia
Anomalies of sternum development, including cleft, pit, partial or complete agenesis

(A) (B) (C)

Figure 26.1 PHACES in a 2-month-old infant. Brain MRA (A) and neck MRA (B) show markedly tortuous right ICA (*); absent left
internal carotid artery, replaced by extensive network of collaterals below the skull base (**), and contribute to reconstitution of the left
supraclinoid left internal carotid artery. The vertebral arteries are markedly tortuous. T2 brain MRI (C) shows left periorbital and facial
hemangioma (?).

ischemic changes such as leukoencephalopathy or focal
or global atrophy. Illustrative images from several
typical cases are shown in Fig. 26.1.
The pathogenesis and genetic basis of PHACE
syndrome are unknown. The appearance of the cerebro-
vascular abnormalities is quite clearly one of dysgenesis,
and not degenerative. The predominant involvement
of the carotid circulation and its embryonic branches
has led to the proposition that there is a defect in angio-
genesis arising from neural crest cells (9).
Treatment of the cerebrovascular manifestations of
PHACE is supportive and symptomatic. Corticosteroids
have been used topically or systemically to promote
involution of the hemangiomas. Propranolol shows
promise in the treatment of disfiguring or life-threatening
hemangiomas, and is currently being evaluated in a
clinical trial (10). Treatment for ischemic injury and overt
stroke is guided by the same principles as for ischemic
stroke in children from any cause, as described in exist-
ing published guidelines and reviews (1,3).
Incontinentia Pigmenti
Incontinentia pigmenti (IP), also known as Bloch-
Sulzberger syndrome, a neurocutaneous syndrome
caused by mutations in the NF-kB essential modulator
(NEMO) gene. Diagnosis rests on recognition of the
typical cutaneous lesions, and confirmed by identifying
a NEMO mutation (11).
Cardinal clinical features include vesicular-bullous
skin rash, following Blashkos lines, evolving to reticular
pattern of hyperpigmentation and later atrophic skin
lesions with hypopigmentation, and absence of hair
and sweat glands. Brain involvement is seen in 3050%
of affected infants, manifest in a previously well term
newborn beginning between 1 and 6 weeks of age as
an acute monophasic encephalopathy with seizures and
altered mental status (1214). The acute clinical syn-
drome is self-limited, evolving over 510 days, and then
stabilizes. It is associated with cerebral necrosis, some-
times hemorrhagic. The encephalopathy may precede
the appearance of the rash, and resembles other condi-
tions such as herpes encephalitis, hemorrhagic infarction
from ischemia with coagulopathy, stroke, hypoxic-
ischemic encephalopathy or trauma. Appropriate diag-
nostic studies are necessary to eliminate other causes
of this pattern of neonatal encephalopathy. Long-term
neurologic sequelae are common including epilepsy,
microcephaly, motor or cognitive impairment, and optic
atrophy. Other ectodermal systems may be affected
510 NEUROINTERVENTIONAL MANAGEMENT
including hair (scalp, eyebrows, eyelashes), nails, and
teeth. Retinopathy with features of microangiopathy has
also been described. Recurrent episodes of acute encep-
halopathy with new foci of cerebral injury are rare, but
may occur (15). The disease can present in older ages,
even adults (16), where the skin lesions may be subtle
and late-stage. This diagnosis should be considered
in women with a combination of late-stage cutaneous
lesions along with hair, nails, dental lesions, and unex-
plained multiple fetal losses.
MRI findings in infants and children have been
described for both acute and chronic stages (12,14,15).
Acutely there are usually multiple foci of T2 hyper-
intensity and restricted diffusion involving gray
matter or white matter. All brain regions may be
affectedcerebral hemispheres, corpus collosum,
internal capsule and deep gray nuclei, cerebellum and
brainstem. Lesions evolve to atrophy, gliosis and cystic
encephalomalacia in the chronic stage. Lesion size and
extent are highly variable, ranging from punctuate to
holohemispheric. Among neonates, regions of injury
typically do not typically conform to large artery
vascular territories or classic vascular watershed zones.
However, in older infants large-vessel territory ische-
mic infarcts have been reported (17).
The inheritance and molecular biology of IP
have been characterized. It is inherited as an x-linked
dominant disorder due to mutation of NEMO. There
is extensive phenotypic variation, related in part to
variations in the specific mutation, and in part to lyoniza-
tion. The disorder can be seen in males with mosaicism
or chromosome duplications (XXY). The mechanism
of cerebral injury is uncertain. Disordered signaling in
NF-kB may affect multiple cellular systems, resulting in
disturbed angiogenesis and inflammatory responses.
Microangiopathy affecting arterial or venous circulation
or both has been proposed as a mechanism for cerebral
injury (13,18).
Treatment is supportive, with attention to identi-
fying and treating acute symptomatic seizures and
subsequently providing developmental assessments
and interventions. Antithrombotic therapy has not
typically been used due to the tendency for hemor-
rhagic transformation of white matter injury in very
young infants, and the lack of evidence for thrombosis
as a part of the pathogenesis.
Sturge-Weber Syndrome
Sturge-Weber syndrome (SWS) is a neurocutaneous
disorder characterized by a triad of facial cutaneous
capillary malformation (port wine stain) affecting V1
trigeminal distributions associated with ipsilateral
leptomeningeal angioma and ocular choroidal vascular
malformation (19,20). Patients with only two of the
triad components are considered to have partial or
variant SWS (21).
Children with SWS are typically identified at birth
by the presence of the facial port wine stain. Neurologic
symptoms are referable to focal cortical degeneration
in the vicinity of the leptomeningeal angiomatosis,
usually ipsilateral to the facial port wine stain, and may
not appear until several months or years of age. Most
often epilepsy is the predominant clinical neurologic
symptom, and may be associated with variable focal
neurologic deficits such as hemiparesis, hemisensory
loss, cortical visual impairment, and neurocognitive
dysfunction which sometimes evolve in stuttering
fashion resembling stroke-like episodes. Chronic head-
aches of migrainous quality are common. Seizures may
be refractory, sometimes associated with progression of
focal cortical degeneration in the region of the angio-
matosis. Involvement of other organs is limited to ocu-
lar disease, primarily glaucoma.
Radiologic findings in SWS vary with age. The
brain parenchyma typically appears normal on com-
puted tomography (CT) or MRI in the neonatal period
and early infancy. MRI with contrast is usually neces-
sary early in life to demonstrate the angiomatosis, which
appears as robust leptomeningeal enhancement over the
occipital and parietal regions ipsilateral to the facial port
wine stain. Over time cortical degeneration subjacent to
the angioma is evident in the form of atrophy, gliosis,
and laminar necrosis with calcification (Fig. 26.2). The
vascular lesion is not appreciable on MR angiogram or
venogram, or on catheter angiogram, except as a relative
paucity of normal cortical draining veins.
The genetic defect in SWS has not been defined.
Inheritance is sporadic. It is thought to result from a
somatic mutation causing a defect in embryogenesis
involving the vascular plexus of the cephalic end of
the neural tube (22). The pathophysiology of neurologic
manifestations is considered to be chronic ischemia of
the cortex underlying the angiomatous malformation
due to local vascular congestion and stasis. Disturbed
cortical excitability in this ischemic and degenerating
region is the basis for epilepsy in these patients.
Treatment is targeted to each of the major organ
systems affected. Laser therapy is effective for the facial
port-wine stain, and long-term medical and surgical
interventions are usually needed to manage glaucoma.
Neurologic treatment rests on careful and aggressive
treatment of seizures with antiepileptic medications (23).
In some children, surgery is considered when epilepsy
becomes medically refractory and is associated with
progressive loss of neurologic function. Headaches are
common, and require long-term management with med-
ical and supportive interventions. Chronic daily aspirin
has been proposed to mitigate the progressive ischemic
degeneration (24).
Capillary Malformation-Arteriovenous
Malformation Syndrome
Capillary malformation-arteriovenous malformation
syndrome (CM-AVM) and Parkes-Weber syndrome
(PWS) are closely related disorders in which cutane-
ous capillary malformations are the cardinal feature,
typically small and multifocal in CM-AVM, or large
confluent or patchy with soft tissue or bony hyper-
trophy in PWS. A mutation involving the transcription
factor, p120-Ras GTPase-activating protein encoded by
RASA1 gene has recently been described in this auto-
somal dominantly inherited disorder (25). Cerebral
vascular malformations including AVM, AV fistula or
vein of Galen malformation have been reported to
affect up to 30% of patients. This association suggests
an important role for RASA1 in angiogenesis.
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES 511

Menkes Syndrome hemorrhagic complications (26,27). The disease is

Menkes syndrome is an inherited multisystem disorder
due to copper deficiency resulting from mutations in
the copper-transporting ATPase gene ATP7A. Affected
children are abnormal from birth due to growth retar-
dation, chronic severe and progressive encephalopathy
and refractory epilepsy, abnormal skin and hair (brittle
sparse hair), and severe autonomic insufficiency. There
is variable systemic and cerebral vascular dysgenesis
and degeneration, resulting in ectasia, aneurysms or
stenosis, which predispose children to ischemic or
usually fatal in the first three years of life. Diagnosis is
suspected by recognition of the typical pili torti abnor-
malities of hair, the finding of low serum copper and
ceruloplasmin levels, and can be confirmed by gene
mutation analysis. Radiologic findings are variable,
and include delayed or disordered myelination, white
matter vasogenic or cytotoxic edema, basal ganglia
ischemic changes or calcification (28). Vascular imaging
shows marked diffuse vascular intracranial and extrac-
ranial tortuosity, ectasia, and sometimes stenosis (29).
Treatment with copper supplements starting in the first

(A) (B) (C)

Figure 26.2 Sturge-Weber syndrome. A 6-month old with seizures and left facial port wine stain. Axial T2 MRI (A) shows left
hemisphere diffuse cortical atrophy and numerous small abnormal veins (?). Axial T1-post contrast exam (B) shows diffuse abnormal
leptomeningeal enhancement (*). Five-year old child with focal epilepsy. Axial CT (C) shows prominent areas of increased signal with
mineralization in the right frontal and left temporal and occipital lobes with volume loss (?).

Table 26.2 Telangiectasias and Capillary Malformation Syndromes

Extra-CNS vascular
Syndrome/MIM abnormalities
Syndromes evident at birth or early infancy
Sturge-Weber syndrome V1 facial capillary angioma
(port-wine stain), glaucoma
Capillary malformation-AVM Small, multifocal cutaneous
syndrome (CM-AVM) capillary malformations,
MIM# 608354 randomly distributed;
soft-tissue AVMs of face
and limbs
Parkes-Weber syndrome Large cutaneous capillary
MIM#608355 malformations, often with
subjacent soft-tissue AV fis-
tulas causing limb soft-tissue
and bone hypertrophy
Syndromes evident in childhood or adolescence
Hereditary hemorrhagic Mucocutaneous telangiecta-
telangiectasia (HHT) sia, pulmonary or liver AVM
MIM# 187300
Cerebral cavernous
malformation (CCM)
MIM# 116860
Abbreviations: MIM#, Mendelian inheritance in man #; AVM, arteriovenous malformation; AVF, arteriovenous fistula.
CNS vascular
abnormalities
Leptomeningeal angioma
Vein of Galen malformation,
cerebral AVM, cerebral
AVF
Similar to CM-AVM
Cerebral AVM
Cerebral cavernous
malformations, single or
multiple
Inheritance, Genetic
defect
Sporadic, suspected
somatic mutation
Germ line mutations in the
RASA1 (, (p120-Ras
GTPase- activating protein)
autosomal dominant
inheritance
Germline mutations in
RASA1 (p120-Ras GTPase-
activating protein), autoso-
mal dominant inheritance
Autosomal dominant
inheritance
Sporadic or familial
(autosomal dominant).
Multiple genes identified
(CCM2/malcavernin,
PDCD10)
512 NEUROINTERVENTIONAL MANAGEMENT

week of life has been described as beneficial in some
cases. Otherwise, treatment is symptomatic and sup-
portive or palliative.
GENETIC CV DISORDERS PRESENTING IN
CHILDHOOD
Neurofibromatosis
Neurofibromatosis type I (NF-1) is a common inheri-
ted disorder estimated to affect 1 per 3,000 in the
population. Diagnosis requires the presence of
at least two of seven features: six or more cafe au lait
macules, axillary freckling, two or more neurofibro-
mas, two or more Lisch nodules (iris hamartomas),
sphenoid dysplasia or thinning of long bone
cortex, or a first-degree relative diagnosed with NF-I
(3032). The phenotype is varied, most commonly
involving skin, bone, and less commonly optic
pathway gliomas. The spectrum of vascular disease
is broad, referred to by some investigators as NF-1
vasculopathy, and includes the following types of
lesions: renal artery stenosis or hypoplasia leading to
renovascular hypertension, cervical and intracranial
arterial hypoplasia, moyamoya, aneurysms especially
of internal carotid artery, cervical vertebral arteriove-
nous malformation, coarctation of the thoracic or
abdominal aorta, focal or long-segment stenosis
involving mesenteric, subclavian, iliofemoral arteries
(31) (Fig. 26.3) for illustrative images.
As would be expected from this spectrum of
lesions, the clinical manifestations are variable, typi-
cally occurring in adolescence or adulthood, and may
include ischemic stroke or transient ischemic attack,
or aneurysmal intracranial hemorrhage. Many patients
harbour these lesions with no overt symptoms. The
prevalence and natural history of vascular disease in
patients with NF-1 is estimated at 0.46% (30,33,34).
This is likely an underestimate, as the data available
come from retrospective institutional case series. In a
recent published series of data from 419 children with
NF-1, 6% had cerebral arteriopathy which led to overt
stroke months to years after diagnosis in 47% of
cases, and which was progressive in 35% (30). Unilat-
eral moyamoya was the most common type of cere-
bral arteriopathy in these series. Patients with optic
pathway gliomas were more likely to have cerebral
arteriopathy than those without gliomas.

(A) (B) (C)

(D) (E) (F)

Figure 26.3 NF1 vasculopathy. A 13-year-old girl with optic pathway glioma and known left internal carotid (ICA) and middle cerebral
artery (MCA) hypoplasia developed dense right hemiparesis and aphasia, which resolved within 6 hours after treatment with IV fluids
and pressor administration. MRI T2 sequence (A) shows known right optic pathway glioma (*), and MRA (B, C) with markedly attenu-
ated left internal carotid and middle cerebral arteries. Perfusion-weighted MRI with arterial spin label (D) confirms marked cerebral
hypoperfusion in left hemisphere. Catheter cerebral angiogram shows normal right ICA and MCA (E), and diffusely narrow left ICA with
supraclinoid occlusion (F).
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES
The genetic defect has been identified as a mutation
of the NF-1, a tumor suppressor gene which encodes the
protein neurofibrin, and is important in regulating cell
proliferation and differentiation. It is inherited as an
autosomal dominant disorder with high penetrance.
Neurofibrin is expressed in vascular endothelium and
smooth muscle. The precise pathophysiologic mecha-
nism connecting defective neurofibrin to vasculopathy
is uncertain. The histopathology of NF-1 vasculopathy
as described in autopsy and surgical pathologic exa-
mination involves fibromuscular dysplasia (FMD) of
large and medium arteries. Additionally, arteries may be
compressed or occluded due to local invasion or com-
pression, most notably the terminal carotid or circle of
Willis (COW) by optic pathway gliomas, and the cervical
vertebral or carotid arteries by plexiform neurofibromas
in the neck (31). It has been suggested that neurofibrin
deficiency disrupts angiogenesis, causing neointimal
vascular smooth muscle proliferation, and the spectrum
of vascular dysplasia affecting multiple organs (35,36).
Treatment of NF-1 vasculopathy is challenging,
and must be tailored to the specific lesions and
secondary morbidities such as stroke or hemorrhage.
Routine surveillance imaging for vascular disease in
NF-1 has not been recommended due to its relative
rarity and lack of evidence to guide selection of patients
and timing of such imaging. Advances in surgical and
interventional techniques available to manage complex
vascular lesions have been successfully applied to
patients with aneurysms and steno-occlusive disease (31).
A variety of strategies have been used, including surgical
bypass or revascularization procedures for moyamoya
vasculopathy, angioplasty and stenting for extracranial
occlusive lesions, surgical clipping and or endovascular
embolization or stenting for aneurysms.
Alagille Syndrome
Alagille syndrome (AGS) is a dominantly inherited
multi-system disorder caused by defects in Jagged1
(JAG1), a ligand in the Notch signaling pathway (37).
Figure 26.4 Alagille syndrome. Brain MRA shows lack of flow-related signal in the supraclinoid right internal carotid artery (*) and
stenosis involving the proximal right A1 and M1 segments; also focal narrowing and irregularity of the supraclinoid left internal carotid
artery (**) extending to the proximal A1 and M1 segments. The left superficial temporal anastomosis is apparent (?).
513
The clinical manifestations of AGS include cholestasis,
congenital heart defects primarily involving the pulmo-
nary arteries, butterfly vertebrae, posterior embryotoxin
and facial dysmorphism, and CVD (38). The diagnosis
of AGS is based on the presence of consistent disease
in 3 out of the 5 main systems involved, although there
is extensive phenotypic variability not explained by
genotype variability (39).
Vascular disorders include aneurysms and steno-
occlusive disease of the internal carotid arteries and circle
of Willis (including moyamoya vasculopathy), renal,
abdominal aorta, celiac, superior mesenteric and sub-
clavian arteries, and are among the leading causes of
death and chronic disability in these patients (40)
(Fig. 26.4). The incidence, natural history and patho-
physiology of CVD in AGS are incompletely understood.
Retrospective cohort studies report a 14% incidence of
intracranial hemorrhage, accounting for 25% of mort-
ality (38). In other single-center studies, CVD was repor-
ted in up to 35% of patients (40,41). These included
ischemic stroke, intracerebral hemorrhage, and pre-stroke
cerebrovascular lesions (aneurysms, carotid steno-
occlusive lesions, carotid dolichoectasia). Studies pub-
lished to date suggest that CVD manifestations in AGS
vary with age, with steno-occlusive disease and ische-
mic stroke predominating in younger children, while
intracranial hemorrhage and cerebral aneurysm present
more commonly in older children and young adults.
AGS is inherited as an autosomal dominant dis-
order. The cerebral arteriopathy in AGS is related to
mutations in JAG1, a ligand in the Notch signaling
pathway, which is an evolutionarily conserved inter-
cellular signaling system fundamental to regulating
vascular development (42). JAG1 is expressed in all
major arteries in mouse embryos, and Notch ligands
and receptors are widely expressed in vascular endo-
thelium and supporting cells. Beyond artery and vas-
cular smooth muscle differentiation, Notch signaling
also has a crucial role in the sprouting and branching
of new blood vessels in angiogenesis. Inactivation of
Notch signaling prevents the transition of a primitive
514 NEUROINTERVENTIONAL MANAGEMENT
vascular plexus to a highly branched network of
vessels.
Treatment of the cerebrovascular disorders in
AGS is supportive and symptomatic. There is no con-
sensus concerning screening asymptomatic patients
with neuroimaging, and practices vary widely. Diag-
nostic screening and treatment are further complicated
by the coexistence in many patients of advanced
liver disease often requiring transplantation, or severe
congenital heart defects, which may increase the risk
of ischemic stroke or hemorrhage in the presence of
cerebral vasculopathy. Surgical and medical treatment
strategies have been used successfully in AGS as for
similar cerebral vascular lesions in other conditions.
Williams Syndrome
Williams syndrome is a genetic disorder characterized
by cardiovascular disease, distinct facies, short stature,
cognitive deficiency, distinct behavioural profile, and
disturbed calcium metabolism. Cardiovascular disease
is an elastin arteriopathy, and manifests as supra-
valvular aortic stenosis and pulmonic stenosis in a
large majority of patients, and renovascular hyperten-
sion in a subset of patients. A minority of patients
have a cerebral steno-occlusive vasculopathy, resulting
in multifocal stenosis of the vessels of the circle of
Willis, including moyamoya-like vasculopathy (43).
CVD may be asymptomatic, or may cause headache,
cognitive decline, transient ischemic attack or stroke.
Treatment of CVD is supportive and symptomatic, and
is often complicated by the coexistence of heart disease,
heart failure, and hypertension. The diagnosis is usu-
ally suspected based on clinical features, and can be
confirmed by genetic testing. Medical treatment using
antiplatelet agents to prevent thrombotic occlusion in
abnormal vessels, and surgical treatment in the form of
revascularization procedures have been reported.
Williams syndrome is inherited as an autosomal
dominant condition, but occurs most often as a de
novo mutation. The molecular defect has been charac-
terized as a mutation of one of multiple genes in a
segment of the genome referred to as the Williams-
Beuren syndrome critical region (WBSCR), which
encodes the transcription factor elastin (44). It has been
proposed that defective elastin function disturbs vessel
wall remodeling, with resultant aberrant smooth muscle
cell proliferation and migration, and neointimal
hyperplasia (45).
Cerebral Cavernoma Malformations
Cerebral cavernoma malformations (CCMs) are
vascular malformations comprised of a cluster of
dilated capillaries with no intervening pia mater or
brain tissue (46). They have a propensity to bleed,
varying from recurrent minute capillary leak of blood
elements to large mass-occupying hematomas. This
results in varying symptomatology, depending on
location and magnitude of hemorrhage, and may
include focal deficits, headache, and seizures. Age at
symptom onset spans the age spectrum, from early
infancy to late adulthood (47). Lesions may be single
or multiple, and may occur throughout the neuraxis.
Diagnosis can be made based on the typical
appearance of these lesions on MRI, where gradient
echo or susceptibility-weighted sequences provide
sensitive and specific identification of these lesions
(in the absence of acute hemorrhage) (Fig. 26.5). They
do not typically appear on catheter angiogram. Treat-
ment depends entirely on the clinical presentation.
Asymptomatic lesions typically are left untreated.
Headaches and epilepsy are treated medically. Surgi-
cal excision may be offered in cases where there has
been significant hemorrhage or where a specific lesion
can be determined to be the cause of medically refrac-
tory symptomatic focal epilepsy. Cavernomas are not
typically amenable to endovascular treatment.
CCMs may be sporadic, or may be inherited as an
autosomal dominant disorder with variable penetrance.
Several disease-causing genetic mutations have been
identifiedCCM1 also known as KRIT1, CCM2, CCM3
also known as PDCD10which encode proteins invol-
ved in angiogenesis (48).
Hereditary Hemorrhagic Telangiectasia
Hereditary hemorrhagic telangiectasia (HHT) is a
genetically heterogeneous disorder defined by the
presence of telangiectasias of the skin and mucosa,
and angiodysplasias affecting the lung, brain, and
liver (49). Angiodysplasias represent a spectrum of
arteriovenous malformations (AVM), arteriovenous
fistula, and angiomas, and may affect multiple organ
systems, notably the lungs, liver, brain, and spinal
cord. Epistaxis is the most common and earliest onset
symptom. Other symptoms include recurrent gastro-
intestinal hemorrhage, sometimes severe enough to
require transfusion, intracerebral hemorrhage, anemia
due to recurrent hemorrhage, migraine-type recurrent
headaches, and pulmonary hypertension, high-output
heart failure, paradoxical embolus leading to ischemic
stroke or brain abscess. Clinical diagnostic criteria
have been proposed based on four features: epistaxis,
mucocutaneous telangiectasia, visceral vascular
lesions, and positive family history. The diagnosis is
considered definite if three criteria are fulfilled, and is
considered possible or suspect if two criteria are
fulfilled (50). Pulmonary AVMs may be detected by
delayed appearance of bubble contrast on echocardio-
gram in the left atrium, or by lower than normal
oxygen saturation on pulse oximetry. Radiographic
features are typical of the type and location of AVMs,
with additional findings depending on related hemor-
rhage or ischemic stroke (Fig. 26.6).
HHT is inherited as an autosomal dominant dis-
order. It is caused by mutations in one of several
genes from the TGF-b family of signaling factors,
which are involved in regulating a multitude of
cellular functions. Multiple subtypes of HHT have been
defined, distinguished by the gene mutation present.
HHT1 involves mutations in ENG encoding endoglin.
HHT2 involves mutations in ACVRL1 encoding ALK1.
A third HHT syndromeHHT in association with
juvenile polyposis (JPHT)involves mutations in
MADH4. HHT3 and HHT4 involve mutations not
fully characterized which map to chromosomes
5q and 7p. HHT1 and HHT2 are most common, and
differ phenotypically only in that pulmonary and
cerebral AVMs predominate in HHT1, while hepatic
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES 515

(A) (B)

(C) (D)

Figure 26.5 Cerebral cavernous malformation. A 4-year-old child developed partial complex seizures from right frontal lobe focus.
Brain MRI T2 sequence (A) and corresponding T1 sequence (B) show a symptomatic large right frontal cavernoma and small asympto-
matic cavernoma in left perisylvian region. Susceptibility sequence (C) shows extensive perilesional blood products. Epilepsy remitted
after resection of the symptomatic lesion, shown on post-resection MRI (D).

AVMs predominate in HHT2. ALK1 and endoglin are
thought to participate in the regulation of angiogene-
sis via modulation of vascular endothelial prolifera-
tion and differentiation.
Management in HHT involves appropriate sub-
specialists to address target-organ manifestations in a
comprehensive manner. Coordinated care may involve
cardiologists for the pulmonary vascular lesions,
gastroenterologists for hepatic involvement, neurolo-
gists and neurosurgeons for cerebral involvement, and
interventional radiologists for endovascular treatment
of AVMs. Screening imaging and endovascular treat-
ment of pulmonary AVMs is commonly performed
and is considered safe and effective. There is no con-
sensus concerning the role of screening or surveil-
lance imaging for asymptomatic cerebral vascular
516 NEUROINTERVENTIONAL MANAGEMENT
Figure 26.6 Hereditary hemorrhagic telangiectasia. An 8-year-old child with left frontal intracranial hemorrhage (?), seen on head CT
(A); cerebral angiogram (B) showed arteriovenous malformation (?).
malformations, and for that matter the utility and
indications for treating asymptomatic cerebral AVMs.
There is limited data regarding the incidence, natural
history and rate of hemorrhage with these lesions.
Rapid advances in the methods available to detect and
treat cerebral AVMs including endovascular, surgical,
and radiation modalities provide expanded options
to patients and their families. Currently treatment of
asymptomatic cerebral AVMs is dictated by local insti-
tutional practice and expertise and patient preference.
In the case of symptomatic lesions, standard treatment
with supportive measures as well as definitive endo-
vascular and surgical therapies is appropriate, and can
be life-saving.
Microcephalic Primordial Dwarfism
Microcephalic primordial dwarfism comprises a group
of disorders characterized by prenatal-onset growth
retardation with microcephaly, distinct cranio-facial
dysmorphic features, with or without skeletal dysp-
lasia. Among these disorders, two subtypes have
been reported to be associated with intracranial vascu-
lar diseaseSeckle syndrome (51,52) and Majewski
osteodysplastic primordial dwarfism type II (MOPD
type II) (53). Cerebrovascular disorders may include
moyamoya-type vasculopathy and cerebral aneur-
ysms. Aneurysms have been reported to be multiple,
saccular, and associated with moyamoya-type occlusive
arteriopathy. Associated hypertension in some patients
has led to the speculation that there is a systemic
arteriopathy. The clinical presentation of cerebrovascular
disorders in these patients includes the spectrum to
be expected with these vascular lesions, including tran-
sient ischemic attack, ischemic stroke, and aneurysmal
subarachnoid hemorrhage. The prevalence of CVD has
been estimated in MOPD type II to be as high as 25%.
Treatment is the same as for any patient with these
vascular diseases, and includes aspirin and revas-
cularization surgery for moyamoya-type arteriopathy,
aggressive antihypertensive management where indi-
cated, and surgical or endovascular treatment of
aneurysms.
GENETIC CV DISORDERS PRESENTING
IN ADOLESCENCE AND YOUNG ADULTHOOD
Inherited Small Vessel Diseases: CADASIL,
CARASIL, and Related Disorders
Advances in the molecular biology of vascular disease
have led to the definition of several inherited diseases
affecting cerebral medium and small vessels (54,55).
The best known example of this group of disorders is
cerebral autosomal-dominant arteriopathy with sub-
cortical infarcts and leukoencephalopathy (CADASIL).
The clinical features typically include migraine-like
headaches, multifocal subcortical white matter lacunar
infarcts with diffuse leukoencephalopathy, and
vascular dementia with adult onset. Mutations have
been identified in a subset of patients involving the
NOTCH3 signaling system, which is important in
angiogenesis (56). There is wide variation in pheno-
type and marked genetic heterogeneity. While median
age of onset is in the mid40s, onset in patients as
young as age 8 years has been reported. The radio-
logic appearance is distinct, with T2/FLAIR hyper-
intensity affecting subcortical white matter diffusely
in a confluent pattern, often with scattered micro-
bleeds. Retinal vasculopathy is common, characterized
by arteriolar narrowing, arteriolar wall thickening and
fibrosis. CARASIL, cerebral recessive arteriopathy
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES
with subcortical infarcts and leukoencephalopathy,
resembles the CADASIL phenotype. It has been
associated with mutations in the HTRA-1 gene, which
is part of the TGF-b cell signaling family. Retinal
vasculopathy with cerebral leukodystrophy (RVCL)
is another inherited small vessel vasculopathy with
onset in the fourth and fifth decade. It presents with
progressive vision loss due to retinal vascular degen-
eration, and evolves to include multiple lacunar
strokes and vascular dementia. The genetic defect
involves mutations in the TREX1 gene. Treatment
of these disorders is supportive or palliative. In most
cases the course is one of relentless progression
ending in severe dementia and death.
Fabrys
Fabrys disease is an x-linked recessive lysosomal stor-
age disease due to defective or deficient a-galactosidase
A activity (57). Although metabolic disturbance begins
in childhood, most individuals are asymptomatic until
adult years. Multiple target organs are involved, with
progressive dysfunction especially involving heart and
kidney, beginning in childhood. The skin is involved as
well, giving the distinct angio-keratoma lesions typical
of Fabrys disease. CVD appears in adulthood as multi-
focal small vessel territory ischemic stroke. Inheritance is
X-linked, with earlier-onset and more severe clinical
phenotype in males compared to females. Diagnosis is
suspected on the basis of clinical features, and can be
confirmed by the finding of deficient enzyme activity
in peripheral leukocytes, or by identifying the genetic
mutation. Treatment is symptomatic, targeting specific
end-organ involvement. Antiplatelet agents and statins
have been used for secondary stroke prevention. Enzyme
replacement therapy became available in 2001 using a
recombinant a-galactosidase A, and has been shown to
have efficacy in clinical trials.
Retinal Vasculopathy with Leukodystrophy
Retinal vasculopathy with leukodystrophy has been
defined to encompass a spectrum of diseases involv-
ing both retinal and cerebral angiopathy, and which
includes the disorder previously known as HERNS
Hereditary Endotheliopathy with Retinopathy, Nephro-
pathy, and Stroke. These are autosomal dominantly
inherited diseases characterized by adult-onset visual
loss due to retinal vascular disease, and a progressive
encephalopathy due to multifocal large and small-vessel
ischemic injury with a diffuse obliterative angiopathy.
They are associated with mutations in the TREX1 gene,
which encodes a 35 exonuclease.
Hereditary Angiopathies Due To COL4A1
Mutations
Hereditary angiopathy with nephropathy, aneur-
ysm, and muscle cramps (HANAC) is an inherited
connective tissue disorder manifest as multicystic
nephropathy, myopathy with cramps, retinal angio-
pathy, and both large vessel and small vessel cere-
bral angiopathy (58). The spectrum of neurovascular
disease in HANAC includes intracranial aneurysms
and periventricular leukoencephalopathy attributed to
517
micro-angiopathy, lacunar stroke, and dilated peri-
vascular spaces. It is due to basement membrane defects
arising from mutations in the COL4A1 gene. It is inher-
ited as an autosomal dominant disease with variable phe-
notype. Cerebrovascular lesions are
clinically asymptomatic in most patients (59).
Previous descriptions of clinical syndromes
ascribed to COL4A1 mutations were limited to prenatal
onset intracerebral hemorrhage (60). In such patients,
the clinical presentation may be an acute neonatal ence-
phalopathy with altered mental status and seizures. In
other patients, clinical presentation may be adult onset
intracerebral hemorrhage in small vessel territories in
the absence of hypertension or other risk factors for
hemorrhage. These patients also have retinal vasculo-
pathy and periventricular leukoencephalopathy. On the
other end of the age spectrum this genetic defect
has been reported in patients presenting with infantile
hemiplegia associated with a porencephaly from remote
prenatal or perinatal intracerebral hemorrhage (60).
It has been suggested that individuals with this genetic
mutation are generally asymptomatic until a precipi-
tating factor such as trauma (including the trauma of
birth), hypertension or administration of anticoagulation
occurs and triggers the hemorrhage (61). Treatment in
this disorder is targeted to organ-specific symptoms.
Neonates with intracerebral hemorrhage rarely undergo
angiography or surgical interventions. Rather their care
is focused on optimizing recovery and rehabilitating
chronic neurodevelopmental impairments.
IDIOPATHIC NON-FAMILIAL ARTERIOPATHIES
AND VASCULAR MALFORMATIONS
Fibromuscular Dysplasia
Fibromuscular dysplasia (FMD) comprises a group of
disorders presenting in childhood through middle age
with noninflammatory, nonatherosclerotic arteriopathy
causing stenosis of large and medium vessels, most
commonly the renal and carotid arteries (62). Affected
arteries have focal or multifocal segmental stenosis,
sometimes associated with aneurysms or dissection,
and resulting in hypertension in the case of renal
artery involvement, and stroke or hemorrhage in the
case of craniocervical involvement. Three subtypes
have been defined on the basis of histopathologic fea-
tures: intimal, medial, or adventitial fibroplasia. With
medial fibroplasia there is segmental thickening and
collagen deposition in the media, resulting in alter-
nating segments of stenosis and dilatation, sometimes
aneurysms, and giving the appearance of string of
beads on angiography. Medial fibroplasia is the
most common, accounting for 8090% of cases, with a
female predominance, and presenting in the third or
fourth decade of life, most commonly with hyperten-
sion. With intimal fibroplasia there is collagen deposi-
tion in the intima, resulting in segmental concentric
arterial stenosis appearing as a band-like constriction
or a long segment tubular stenosis, and may also
be associated with aneurysms. Estimates of incidence
and the full spectrum of FMD are complicated by the
heterogeneity of the disorder, clinically silent disease
in many cases, and the variability of radiologic
518 NEUROINTERVENTIONAL MANAGEMENT

appearance. Catheter angiography is considered the
gold standard for diagnosis of FMD. The finding of
string of beads is considered highly characteristic of
FMD, but is not always clearly evident with noninva-
sive imaging modalities such as MRA.
The prevalence of cervical or intracranial carotid
disease in FMD combined with disease in other terri-
tories is uncertain because it is often asymptomatic,
and has been estimated in 928% of patients (63).
Carotid involvement in FMD predominantly affects the
cervical carotid in adult forms of this disease. Intra-
cranial disease is more common when FMD presents
in childhood, where it is predominantly of the intimal
type (64). The spectrum of CVD due to FMD in children
is broad, and includes ischemic stroke due to focal
intracranial stenosis, moyamoya disease (MMD), and
subarachnoid hemorrhage due to aneurysms (6567)
(Fig. 26.7). FMD is the most common cause of reno-
vascular hypertension of childhood onset (64,68,69). An
association between FMD and moyamoya is further
supported by the finding that a subset of patients, up to
8%, with idiopathic moyamoya has renovascular hyper-
tension. In one case from this series, histopathologic
analysis of the affected renal artery disclosed intimal-
type FMD (70). To date there are have been no system-
atic prospective studies evaluating the prevalence and
characteristics of cervical or cerebral involvement in
childhood onset FMD presenting as renovascular
hypertension.
Treatment of FMD is directed at specific lesions
and depends on symptoms. Hypertension is managed
with medication, and in many cases with endovas-
cular interventions. Percutaneous transluminal balloon
angioplasty (PTA) is commonly performed for renal
artery stenosis with generally favorable results in
adults, and mixed results in children (62,71,72). It has
been recommended that patients with renovascular
hypertension due to FMD should undergo screening
vascular imaging of the cervical and cerebral circulation
because of the association with steno-occlusive disease
or aneurysms (62). Along the same lines, serial long-
term surveillance imaging of affected vessels has been
suggested because of the progressive nature of FMD
and the risk of developing aneurysms. Recommen-
dations for treatment of asymptomatic steno-occlusive
cervical carotid or vertebral disease center on the use
of antiplatelet agents for stroke prophylaxis. The use of
antithrombotic agents must be tempered and modified
as needed by results of on-going surveillance vascular
imaging, as these patients are at risk for development
of aneurysms and dissection in any affected vessels
(mesenteric, aorta, cervical, cerebral, pulmonary).
Angioplasty for symptomatic cervical carotid or vertebral
steno-occlusive disease has been reported with

(A) (B) (C) (D)

(E) (F) (G)

Figure 26.7 Fibromuscular dysplasia. A 15-year-old boy with renovascular hypertension since age 2, presented with right hemiparesis
and aphasia. Head CT (A) on admission shows acute left MCA infarct (?). Axial FLAIR MRI 10 months later (B). Brain MRA at age 10
(C) shows bilateral left > right moyamoya type vasculopathy. Brain MRA 10 months after acute stroke (D) shows absence of flow in left
ICA, and natural synangiosis from left external carotid artery (ECA) (*). Catheter angiogram concurrent with MRA, right internal carotid
artery injection (E), left ECA injection (F). Abdominal aortogram (G) shows high grade aortic stenosis and tortuosity.
 DIAGNOSIS AND MANAGEMENT OF UNCOMMON AND GENETIC CEREBROVASCULAR DISEASES 519

favorable results, although published data for this
approach are limited to small series and case reports.
Treatment of cerebral aneurysms in patients with FMD
is governed by principles and guidelines similar to that
for aneurysms of other etiologies, and may involve the
use of endovascular or surgical approaches (62,63).
Revascularization surgery has been performed in cases
of MMD related to FMD, though the timing and indi-
cations are controversial (1,73,74).
Moyamoya Disease (Fig. 26.8)
Moyamoya disease (MMD) refers to a progressive
cerebral arteriopathy of idiopathic or unknown cause
involving distal intracranial internal carotid artery
stenosis with collateral formation (75). Moyamoya
syndrome (MMS) refers to moyamoya-type vasculop-
athy associated with a known predisposing condition
or secondary to cranial irradiation for malignancy or
systemic disease such as hemoglobinopathy. It is typi-
cally bilateral, and presents in childhood with headache,
transient ischemic attacks or overt ischemic stroke.
Rarely the initial clinical symptoms include epilepsy
or extrapyramidal movement disorders. It may have
a more indolent course, manifest as neurocognitive
impairment or frank vascular dementia in late child-
hood, adolescence, or young adulthood. Many asso-
ciated conditions and genetic disorders have been
described with MMS, some of which are described in
preceding sections of this chapter. Additional condi-
tions reported to be associated with MMS include
trisomy 21, tuberculous meningitis, HIV, autoimmune
thrombocytopenia, and hemolytic anemia.
The radiologic features of MMD/MMS and
moyamoya variant vasculopathy evolve as the disease
progresses in six stages described by Suzuki, begin-
ning with terminal carotid artery stenosis without
collateral vessel formation, to high grade stenosis with
extensive collateral formation around the circle of
Willis and skull base, to complete occlusion with dis-
appearance of collaterals (76). Associated cerebral
ischemic injury is common and highly variable, and

(A) (B) (C)

(D) (E) (F)

Figure 26.8 Moyamoya disease. A 4-year-old boy presents with acute left hemiparesis. Brain MRI T2 (A and B) and diffusion
weighted imaging (C) show acute right middle cerebral artery (MCA) stroke (?) and diffuse leukoencephalopathy (*). MRA on presen-
tation (D) shows complete occlusion of terminal carotid arteries bilaterally (>), and disease in both posterior cerebral arteries (?).
Extensive collateral formation can be seen on T2 sequence (A). By two years after bilateral pial synangiosis procedures, transient
ischemic attacks remit. Five years after initial presentation MRI shows chronic generalized volume loss and focal encephalomalacia
appear on T2 sequence (E), and extensive reconstitution of flow in both MCAs at site of surgery (F).
520 NEUROINTERVENTIONAL MANAGEMENT
may include mild diffuse hemisphere volume loss,
multifocal deep white matter microinfarcts, diffuse
leukoencephalopathy, cortical infarcts corresponding
to small arterial branch occlusions, or complete proxi-
mal or circle of Willis large vessel territory strokes
(77). The arteriopathy by definition involves both car-
otid arteries and their main branches, although it may
be asymmetric, beginning initially unilaterally and
then later becoming bilateral. In a minority of cases it
may also involve the posterior circulation and entire
circle of Willis (Fig. 26.8). Intracranial hemorrhage is
part of the spectrum in a minority of patients with
MMD/MMS, and may be parenchymal or subarach-
noid, attributed to rupture of small collaterals or
aneurysms.
The pathophysiology of MMD and MMS is uncer-
tain, and likely multifactorial (78). About 10% of idio-
pathic MMD is familial. Genetic factors undoubtedly
play a role, as evidenced by the association of MMS
with specific genetic syndromes such as NF1, trisomy
21, Alagille and Williams syndrome. In these diseases,
specific gene mutations can be linked to disordered
angiogenesis, as is seen with disordered NOTCH signal-
ling in AGS caused by mutations in JAG1 (79). Inflam-
matory and degenerative processes that alter the integrity
of vascular endothelial function or trigger intimal or
medial proliferation and fibrosis are invoked in cases of
MMS related to systemic diseases such as hemoglobin-
opathy, cranial irradiation or infectious arteritis.
Treatment of MMD/MMS involves a combination
of medical and surgical approaches. Diagnosis is
typically suspected from the appearance of ischemic
injury and abnormal flow-voids on T2 MRI sequences.
It is confirmed based on typical steno-occlusive findings
on angiography. Current MR technology, especially
with 3T imaging, is usually sufficiently specific and sen-
sitive to confirm the diagnosis. The extent and severity
of stenosis can be overestimated by MRA. Catheter
angiography is necessary for confirmation in some cases,
particularly in the evaluation of suspected aneurysmal
subarachnoid hemorrhage, and is necessary for assess-
ment and planning of surgical interventions. Medical
interventions for acute ischemic symptoms are sympto-
matic and supportive, involving optimizing perfusion and
oxygenation, followed by aggressive rehabilitation (1).
Antiplatelet agents are typically used in patients with
ischemic injury to minimize thrombotic occlusion in sten-
otic vessels and artery-to-artery embolization. Because of
the propensity to hemorrhage, the use of thrombolysis
and systemic anticoagulation are considered to be high
risk interventions for acute stroke due to moyamoya
arteriopathy. Surgical interventions in the form of direct
or indirect revascularization procedures are widely used
and considered to be beneficial for secondary stroke
prevention in patients with MMD/MMS (74,8083).
Aneurysms are treated with surgical or endovascular
approaches (84,85).
Decisions as to which patients are appropriate
surgical candidates for revascularization, and when in
the progression of their disease to perform surgery,
however, remain controversial. Some of this contro-
versy arises from differences among providers in the
definition of the disease, while some is related to the
lack of controlled trials evaluating the safety and effi-
cacy of surgical intervention, particularly in certain
diseases such as hemoglobinopathy. Endovascular
interventions in moyamoya vasculopathy have been
reported in small series or case studies, mostly in
adults, and with mixed results (8688). Safety and
long-term benefit are as yet not established. Many
other nonsurgical treatment dilemmas exist in this
condition with little to no evidence on which to base
decisions (89). Chronic and progressive problems with
headache and hypertension are common. The safe use
of renal angioplasty to treat medically refractory reno-
vascular hypertension in patients with coexistent moya-
moya vasculopathy is especially problematic, as a rapid
drop in systemic blood pressure may precipitate cere-
bral ischemia.
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 27
Endovascular treatment of spinal vascular malformations
Mayumi Oka and Kieran Murphy
INTRODUCTION
In 1960s and 1970s, interventional neuroradiological
techniques for the treatment of spinal vascular lesions
were developed when understanding of these lesions
deepened because of the advances in selective spinal
angiography techniques and increased knowledge.
Two groups of authors contributed the initial and greater
part of the development of selective spinal angiography.
Djindjian et al. reported their first 50 cases of trans-
arterial embolization in 1973 (1). Di Chiro and Doppman
described their own techniques and experiences in spinal
angiography. Aminoff and Logue contributed to an early
understanding of the pathophysiology of spinal vascular
malformations (2) and established the clinical grading
system (3). Later, Kendall and Logue recognized the
dural arteriovenous fistula (dAVF) as a different entity
from arteriovenous shunts involving the spinal cord (4).
These are uncommon and complex pathologies, and the
terminology has changed over the years. We will define
the terminology of lesions and describe clinical mani-
festation, imaging findings, and management of each
lesion; all are best treated by multidisciplinary approach.
CLASSIFICATION
Nomenclature for spinal vascular malformations has
caused confusion and controversy among clinicians,
and multiple classification systems have been pro-
posed until today (57). In 1978, Hurth et al. reported
the first large series (8), which presented a summary
of 150 cases divided into two groups: extramedullary
malformations fed by the posterior spinal artery and
intramedullary malformations fed by the anterior
spinal artery. Their classification was aimed at a surgical
approach focusing on the position of lesions relative to
the spinal cord, rather than the type of shunts. As noted
before, dAVFs were recognized as a distinctly different
pathology from other spinal vascular malformations
only in 1977 (4). Their classification likely included most
of the dAVFs in the group of extramedullary malfor-
mations. In 1985, Riche et al. presented their classification,
close to the modern understanding of these lesions (9),
and distinguished five different types of vascular mal-
formations: (i) intramedullary or mixed arteriovenous
malformation (IM-AVM), (ii) retromedullary AVM,
(iii) extramedullary arteriovenous fistula (AVF) supplied
by the spinal arteries, (iv) extramedullary dAVF with med-
ullary venous drainage, and (v) complex malformations
(disseminated and metameric AVM). Since then, many
authors have suggested modified or new classifications,
and there has been drastic advancement in diagnostic
modalities and our knowledge of spinal vascular malfor-
mations. However, the classification proposed by Riche
et al. still retains the basic concept of spinal vascular
malformations with the exception of retromedullary
AVMs, which are simply included with IM-AVM in the
present classification.
Most authors categorize pathologies on the basis of
angioarchitecture and location of lesions. Table 27.1 sum-
marizes classification of spinal vascular malformations.
Most spinal vascular malformations can be divided into
two different types of shunts: AVFs or AVMs. Locations
of the lesions are categorized as: (i) (intradural) intra-
medullary, (ii) (intradural) perimedullary, (iii) dural, and
(iv) extradural (epidural and paraspinal). A combination
of morphological/hemodynamic and topographic infor-
mation, usually provided by angiography, is used to
classify these lesions. Differentiation of AVF and AVM
can be difficult at times, and interpretation of angio-
graphic images is not free from subjective judgment.
Spinal vascular malformations are also a mixture of
congenital and acquired lesions, etiology still needs to be
elucidated, and the information will be incorporated in a
future classification. For now, a simplified classification
with less controversy may ease communication between
clinicians from different specialties.
Certain genetic or hereditary syndromes/disorders
are known to be associated with spinal vascular malfor-
mations. Rodesch et al. proposed the classification of
intradural spinal vascular malformations based on
genetics or biological features (7). They primarily distin-
guish AVFs and AVMs, and secondarily divide them
into three categories. The first group consists of single
shunts associated with genetic or hereditary disorders,
mainly hereditary hemorrhagic telangiectasia (HHT)
or RenduOslerWeber disease. These are usually
single-hole macro-AVFs and affect the pediatric popula-
tion (10). The second group comprises genetic, nonheredi-
tary, multiple AV shunts with potential metameric links.
These include Cobbs syndrome, KlippelTrenaunay
syndrome, and Parkes Weber syndrome (or Klippel
TrenaunayWeber syndrome). The third group is made
of single lesions consisting of a majority of spinal vascu-
lar malformations, while the first two groups comprise
16% of spinal cord AVMs in a series of 19 patients at one
authors institution (11). These are categorized as com-
plex lesions in the classification by other authors (12,13)
524 NEUROINTERVENTIONAL MANAGEMENT
Table 27.1 Classification of Spinal Vascular Malformations
Location Type
Dural AVF
Perimedullary AVF
Intramedullary AVM
Extradural AVF, AVM
Abbreviations: AVF, arteriovenous fistula; AVM, arteriovenous malformation; ASA, anterior spinal artery; PSA, posterior spinal artery.
and as such require careful investigation of the entire
pathology and determination of the lesion responsible
for clinical symptoms. The aim of treatment should be
symptomatic relief rather than complete cure in most
cases.
clinical manifestations
Spinal vascular malformations are uncommon lesions.
Mourier et al. studied 210 patients treated for an
AVM of the spinal cord. The patients were classified
into dAVF (38%), IM-AVMs (45%), and perimedullary
AVFs (PM-AVFs) (17%) (14). In a series of 186
spinal vascular malformations by Biondi et al. dAVF,
IM-AVM, and PM-AVF comprised 38%, 24%, and
39%, respectively (15). These authors suggest that dis-
tribution of their cases was largely influenced by a
referral base and the nature of their institution being
a tertiary care center. Most reports suggest a much
higher rate of dAVFs, ranging from 60% to 80% of
spinal vascular malformations (4).
There are two main forms of presentations of
spinal vascular malformations: one is progressive
myelopathy of gradual onset and the other is sudden
onset of neurological deficit or worsening of existing
symptoms, usually secondary to hemorrhage (16). The
less common form is an acute deterioration without
hemorrhage, which is thought to be due to thrombosis
of the draining vein of the lesion itself (8).
Intradural spinal arteriovenous shunts (AVMs
and AVFs) have a high rate of hemorrhage reported
in the literature, ranging from 30% to 50% (8,1618).
Hemorrhages occur as a spinal subarachnoid hemor-
rhage (SAH) or hematomyelia. Direct destruction of
neural tissue by hematoma (hematomyelia) accounts
for more severe clinical signs than those secondary to
SAH. Symptoms of SAH depend on the level of rup-
ture; however, acute onset of pain, stabbing back
pain, is universal with or without myelopathy or
radiculopathy. When the lesion is closer to the cranio-
cervical junction, signs and symptoms resemble those
of intracranial SAH and cause a special diagnostic
dilemma. Angiography negative for intracranial
aneurysms when examining a patient with SAH needs
further investigation for cervical spinal vascular mal-
formation. It should be noted that, in a series related
to spinal vascular malformations, of 150 patients 55%
occurred in children less than 15 years of age (8).
This result is concordant with the findings observed
by Rodesch et al. in which 70% of the pediatric
population in their series of intradural spinal vascular
malformations (excluding dAVFs) manifested hemor-
rhagic episodes (19). In contrast to intradural AV
shunts, dAVFs are not typically associated with spinal
SAH or hematomyelia (2022). The exception to this
rule being cervical dAVF (23,24). These are more
Feeder Drainage
Radiculomeningeal Radicular vein
ASA and/or PSA Perimedullary vein
ASA and/or PSA Medullary or perimedullary vein
Commonly segmental Epidural and/or paraspinal
typically present with complications related to venous
hypertension and impaired cord venous drainage.
Besides spinal SAH and hematomyelia, symptoms
of spinal vascular malformations are those of non-
specific myelopathy or radiculopathy. Combination of
paraparesis, sensory abnormalities, sphincter disturban-
ces, and pain, which is often radicular in distribution,
develops with highly variable speeds of progression.
Stepwise progression, with incomplete recovery of
symptoms between events, is common (8) and not
directly correlated with the level of shunts. Progressive,
slow deterioration of neurological status is a classic
feature of spinal vascular malformations, often attrib-
uted to chronic venous hypertension, and eventually
results in ischemic hypoxia of the spinal cord. Inter-
mittent, transient worsening of symptoms have been
documented with exercise, cough, or certain postures
(16,22,25). Pregnancy is attributed to causing aggra-
vation of the disease in a minority of cases (8,15).
In 1974, Aminoff and Logue reported a series of 60
patients with spinal vascular malformations in which
dural and intradural AV shunts were all mixed, as it
was before dAVF was differentiated from others (3,16).
Ten percent of patients presented with SAH. Severe
locomotor disability occurred in 19% of patients within
six months of onset and in 50% within three years. Only
9% of their patients were able to walk independently
after three years. Some authors established a clinical
grading system of the three major symptoms associated
with spinal vascular malformations: problems with gait,
micturition, and defecation (3). Gait disturbances were
graded as follows:
(i) onset of leg weakness, abnormal stance or gait,
without restriction of locomotor activity; (ii) diminished
exercise tolerance; (iii) requirement for one stick or
some support for walking; (iv) requirement for crutches
or two sticks for walking; and (v) unable to stand, con-
fined to bed or wheelchair. Disturbances of micturition
have been classified as mildhesitancy, urgency or
frequency; moderateoccasional urinary incontinence
or retention; and severetotal urinary incontinence or
persistent retention. Disordered control of defecation
has been similarly classified as mildconstipation;
moderateoccasional fecal incontinence or severe
intractable constipation; severefecal incontinence.
Delay in diagnosis is a particular problem of
spinal vascular malformations, especially for those
who present with nonspecific, slowly progressive
radiculopathy or myelopathy, or diabetes. The dura-
tion from onset of symptoms to initial treatment
averaged 2.7 years with dAVFs and 4.2 years with
intradural AVMs in the series by Rosenblum et al. (18).
The time from first symptoms to diagnosis was
less than 1 year in 26%, 1 to 10 years in 60%, and
more than 10 years in 14%. Others reported similar
results.
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 525

(A) (B) (C) (D)

Figure 27.1 PM-AVF, type I. A 28-year-old male presented with left lower extremity weakness. MRI of the thoracolumbar spine showed
central hyperintensity of the cord on T2-weighted images and central enhancement on postgadolinium images (not shown). Myelogram
(A) shows serpentine filling defect consistent with prominent draining vein at the lower thoracic levels. Left T11 intercostal artery
injection (B) reveals the mildly prominent radiculomedullary artery and the anterior spinal artery. The arterial basket, connection
between the anterior spinal artery and the posterior spinal artery, is outlined (long arrow). A fistula (arrowhead) is noted immediately
distal to the basket; a draining vein is seen faintly on this image. Lateral projection (C) of same injection shows the anterior spinal
artery (small arrows) and the fistula (large arrow). Later image (D) shows the artery (arrow) and draining veins (double arrow) posterior
to the spinal cord. Abbreviations: PM-AVF, perimedullary arteriovenous fistula; MRI, magnetic resonance imaging.

IMAGING radiculomedullary artery (or radiculopial artery) that

Early reports indicated that myelography demonstrates
high rate of positive findings in patients with spinal
vascular malformations. Hurth reported typical vascu-
lar filling defects (Fig. 27.1A) in 61%; nonspecific,
abnormal findings (complete or partial obstruction of
contrast column, or an enlarged cord) in 30%; and
normal myelogram in only 9% of their series (8). In a
series of dAVFs, dilated vessels were present in all 25
patients on supine myelogram (26). However, magnetic
resonance imaging (MRI) has become the modality of
choice in evaluation of myelopathy, radiculopathy,
or spinal SAH, since it can demonstrate other more
common pathologies such as disc herniation, spinal
stenosis, vertebral lesion, intra-or extramedullary neo-
plasm, and discitis/osteomyelitis. It can still be difficult
to differentiate infectious or inflammatory myelitis or
intramedullary mass (neoplasm or hematoma) from
myelopathy caused by vascular malformations when
not associated with significant flow voids.
MRI and magnetic resonance angiography
(MRA) often suggest and make a diagnosis of spinal
vascular malformations, spinal angiography is essen-
tial when lesions are being considered for treatment.
The use of dynamic contrast-enhanced gadolinium
MR angiography has led to a major improvement of
the diagnostic accuracy of MRI/MRA in malformation
detection. Exact level of origin identification is now
routine. This technique has been reported by Farb
et al. (27). Selective spinal angiography should focus
on several points with future therapy in mind when
performed: (i) first to differentiate dAVFs from
intradural AV shunts, (ii) to determine the exact level
of shunt (by vertebral levels for surgical option),
(iii) identify all feeders and relationship with the
is not directly feeding the fistulacontinuity of spinal
artery axis, and (iv) presence of aneurysm and venous
varix, and their relationship with symptoms (comp-
ression, rupture, etc.). Each level needs to be selected,
and angiographers must be attentive to vascular blush
in the hemivertebra, which implies that the dorsal
spinal branch has been injected (Fig. 27.2A, B). The
ventral and dorsal spinal branches can have separate
origins from the aorta, especially when there is a com-
mon trunk for multiple levels (28). When the angio-
gram is negative after intercostal and lumbar artery
injections, vertebral, deep cervical, ascending cervical,
and internal iliac arteriogram should be performed.
SPINAL DAVFS
Terms for dAVF include epidural angiomatous mal-
formations (4), dorsal extramedullary AVM, type I, and
intradural dorsal AVF (5). These are the most common
types of spinal vascular malformation (29).
Pathophysiology
The dAVFs are shunts between the dural branch
(radiculomeningeal artery) of the dorsospinal artery
and radicular vein (Fig. 27.3), which normally drains
the perimedullary vein. The fistula is located within
the dural sleeve of the exiting spinal nerve root. The
fistula drains into the perimedullary venous system
via radicular veins in a retrograde fashion. The patho-
physiology of neurological symptoms is attributed to
chronic venous hypertension caused by retrograde
flow in the perimedullary vein, which normally drains
the cord via the coronal venous plexus (2,4). Slow
but high-pressure retrograde venous flow into the
526 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 27.2 Left T9 intercostal artery injection demonstrated a normal dorsospinal artery with blush in the left hemivertebra.

(A) (B) (C) (D)

Figure 27.3 Spinal dAVF. A 39-year-old male with paraplegia. Sagittal proton density MRI (A) shows flow voids along the posterior
aspect of the thoracic cord. Early arterial phase of right T5 intercostal arteriogram (B) shows a shunt (small arrow) between the radicu-
lomeningeal branch of the dorsospinal artery and the radicular vein (large arrow). Later image shows a shunt (arrow) and venous drain-
age into the perimedullary vein in both cranial and caudal directions (long arrows) (C, D). Abbreviations: dAVF, dural arteriovenous
fistula; MRI, magnetic resonance imaging.

valveless coronal venous plexus limits venous drain-
age of the spinal cord by the normal radial veins and
results in a decreased arteriovenous gradient, even-
tually leading to congestive cord ischemia, which may
or may not be reversible. The result of these patholog-
ical changes is irreversible necrotizing myelopathy
first described by Foix and Alajouanine (30)also
called angiodysgenetic myelomalacia or subacute
necrotic myelitis, where the neural tissue may liquefy
and produce a cavity (31).
Spinal dAVF is an acquired disease, although the
etiology is still unknown (32). Infection, trauma, syringo-
myelia, and surgery have been mentioned as an associa-
tion or cause in the form of case reports (29,33). Venous
thrombosis is the leading pathogenesis of cranial dAVFs
(31) and is also considered to be a potential cause of
spinal dAVFs. However, there was no association
between multiple prothrombotic factors and spinal
dAVFs, comparing 40 patients with dAVF and 119
control patients (34).
Clinical Manifestations
Spinal dAVFs commonly affect middle-aged to elderly
males with 45:1 male to female ratio. Most patients
are in their fourth to seventh decades. Patients usually
present with gradually progressive myelopathy, which
affects lower extremity and sphincter functions.
Common initial symptoms are pain (1639%), lower
extremity weakness (2955%), and sensory disturbance
(2447%). Sphincter dysfunction was seen in about
10% of patients. Symptoms can progress slowly and
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS
continuously, or in stepwise fashion. Most patients
have a combination of motor, sensory, and sphincter
symptoms by the time diagnosis is made, paraparesis
in 78% to 100%, sensory disturbance in 69% to 90%,
urinary incontinence in 80% to 89%, disturbed defeca-
tion in more than 80%, and disturbed sexual function
in about a third of patients, though this symptom
is often concealed by patients (2022,35,36). Pain is
a common but nonspecific symptom that manifests
as a backache or radicular pain. This pain is often
attributed to degenerative lumbar diseases or poly-
radiculopathy before dAVFs are suspected. Sensory
disturbances start with tingling paresthesia or hyper-
esthesia in the feet and progress to proximal level.
Flaccid and spastic paraparesis are equally common (20).
Hemorrhage is uncommon and SAH is seen almost
exclusively with cervical dAVFs, only one lumbar dAVF
with SAH (37) and one hematomyelia in thoracic dAVF
to date (38).
Delay in making a diagnosis of dAVF is common,
ranging from months to often several years with a
median length of 10.5 to 27 months, because of the non-
specific and insidious nature of symptoms (20,21,26).
Van Dijk in his report suggested that recent advances
in diagnostic imaging, mainly MRI and MRA, and
wide availability of the scanner may have shortened
the delay in diagnosis of dAVFs. In their series, 30 out
of 49 patients (61%) presented with dAVFs.
Imaging
MRI should be the first imaging modality performed
when any spinal vascular malformation is suspected.
Although myelogram can demonstrate enlarged veins
in most dAVFs (26), the myelogram must be obtained
in a supine position since most of the veins are
located dorsal to the spinal cord. This maneuver may
not be done unless the diagnosis is already sus-
pected. MRI findings commonly seen in patients with
dAVFs, listed in order of frequency, are (i) central
hyper-intensity of the cord on T2-weighted images
(85100%), (ii) mild gadolinium enhancement, and
(iii) vascular flow voids posterior to the spinal cord
and mild expansion of the cord (Fig. 27.4) (26,39,40).
Central hyperintensity on T2-weighted images reaches
the tip of conus in a majority of cases (26). Peripheral
hypointensity surrounding central hyperintensity has
been described by Hurst et al. which is more cons-
picuous on true T2-weighted or gradient-echo images
but subtle on fast spin echo (FSE) T2-weighted
images. The authors hypothesize that the finding is
due to slow flow of blood containing deoxyhemoglobin
within distended veins (41). One must be familiar
with the normal MR appearance of the spine; it can be
difficult to differentiate an abnormally dilated coronal
venous plexus from prominent but normal veins on
todays high-field MRI. Cerebral spinal fluid pulsation
artifact should not be mistaken as abnormal flow voids.
With recent advances in MRA techniques, first-pass
contrast-enhanced MRA is reported to identify the level
of fistula within one level with a relatively high rate
of accuracy ranging from 75% to 100% (39,42,43). Also,
ever advancing multidetector row CT angiography has
demonstrated precise localization of dAVFs in all eight
patients (44).
527
Conventional catheter spinal angiography, how-
ever, is indispensable for choosing treatment options
and is still the gold standard to evaluate the vascular
pathology of the spine. The above-mentioned noninva-
sive imaging techniques may play a role in reducing
the length of catheter angiography, thus decreasing
contrast load and radiation dose, especially in those
with renal insufficiency and severe atherosclerotic
disease (39). Because of particular demographics of
patients affected by this disease, there are few false-
negative angiograms mainly because of occlusion of
the origin of feeding intercostals or lumbar arteries,
severe atherosclerosis, or aortic aneurysm (45).
Arterial feeders are commonly located in the
midthoracic to upper lumbar level with more than
80% seen between T5 and L2, and two-thirds on the
left (2022). In one series, sacral dAVF was common
(18%) (46). In case of negative spinal angiography,
after selective intercostal and lumbar artery injections,
a selective lateral sacral artery injection should be per-
formed. Multiple feeders to the fistula are seen in
as low as 10% to as high as 60% (20,22,46). Multiple
dAVFs are an uncommon entity with a few case
reports of double dAVFs in the literature, and their
incidence is less than 2% of all spinal dAVFs (4749).
Cervical dAVFs
Cervical dAVFs are an uncommon subgroup of
dAVFsapproximately 2.5% of all spinal dAVFs (37)
(Fig. 27.5). Although they have the same morphology
and pathophysiology as thoracolumbar dAVFs, one
needs to be aware of particular characteristics of cervi-
cal dAVFs. In patients with myelopathy, motor and
sensory symptoms are not always localized in the
lower extremity. Hemiparesis or quadriparesis are as
common as paraparesis (23). Myelopathy at a cervical
level can also include brain stem signs such as cranial
neuropathy or dyspnea (50). The most important dif-
ference is that they have a much higher rate of SAH
when compared with their thoracolumbar counterpart.
Recent literature reviews reported a 30% to 45% inci-
dence of SAH in cervical dAVFs (24,37). The presence
of a varix and superiorly directed venous drainage
were significantly associated with SAH. In a review of
41 patients with cervical dAVFs, superiorly directed
drainage was seen in 60% (12 out of 20) of the SAH
group, which is much higher than 10% in the non-
SAH group, and reaching the cranium in 50% of cases
(10 of 20). Venous varix was noted in 35% and 5%
of the SAH and non-SAH group, respectively (24).
Authors also noted high prevalence of feeders from
the right vertebral artery (68%). Venous drainage is
via the coronal venous plexus, epidural or intra-
cranial. Purely epidural venous drainage is associated
with myelopathy due to mass effect, rather than
venous congestion as seen in most dAVFs (51).
Treatment
Spinal dAVF is an infrequent but potentially treatable
cause of myelopathy. As all the other spinal vascular
malformations, dAVF is best managed by a multi-
disciplinary team of neurologists, neurosurgeons, and
interventional neuroradiologists. Interruption of the
528 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

(E) (F) (G) (H)

Figure 27.4 Spinal dAVF. A 34-year-old male with scoliosis presented with acute deterioration of bilateral lower extremity weakness
and urinary incontinence, which has been present over a year. His main complaint prior to this event was back pain. T2-weighted
images of the thoracolumbar spine (A, B) demonstrate flow voids dorsal to the cord and abnormal high signal in the spinal cord from
T4 to the conus. Contrast enhancement is noted in the lower thoracic cord (C). The T10 intercostal angiogram (D) shows a fistula
between the radiculomeningeal artery and the radicular vein (arrow). Later image (E) shows dilated perimedullary veins in both cranial
and caudal directions, down to the conus (arrow). Glue embolization with NBCA was performed (F). Glue penetrates the fistula (short
arrow) and occludes the proximal segment of the draining vein (large arrow). Control angiogram performed after embolization reveals
residual fistula fed by right T9 (G) and T11 (H) intercostal artery branches; contribution to the fistula from these feeders were not seen
prior to embolization of T10. Two feeders were embolized with glue subsequently and final angiogram showed no residual fistula.
Abbreviations: dAVF, dural arteriovenous fistula; NBCA, N-butyl 2-cyanoacrylate.

feeding artery only is not sufficient to eliminate the
fistula and often results in recurrenceas in cranial
dAVFs, the fistula recruits nearby arteries or else
existing microfeeders grow. Resection of draining
veins, which was once thought to be the pathology of
dAVFs by means of stripping dilated coronal venous
plexus, can cause a devastating outcome. It is now
known that treatment should focus on the fistula and
disconnecting the vein from the AVF. Meta-analysis
of surgical studies demonstrated 97.9% technically
successful results, 55% overall improvement, and 33%
rate of improvement in micturition function (52). The
same authors analyzed results of embolization and
found a 46% technical success rate; however, there
were not enough data on the outcome of the embo-
lization series. Generally, approximately one-half to
two-thirds of patients report improvement in motor
function, one-tenth of patients experience worsening,
and the remainder becomes stable. Function of the
sphincter does not recover as much as motor strength;
improvement is seen in one-third, stability of symp-
toms in one-third, and continuous deterioration in
one-third (53).
Jellema et al. noted that leg pain and muscle
spasms were difficult symptoms to alleviate. In their
series of 44 patients, the majority of patients who had
either pain or spasms experienced worsening of the
symptoms despite improvement in motor function (53).
Others noted correlation between the level of fis-
tula and the outcome. Better results were seen when
the lesion was in the lower thoracic region compared
with those in the midthoracic or lumbar levels (36).
Shorter duration of symptoms, less than a year, prior
to treatment appears to correlate with better outcome,
especially with sphincter dysfunction (54).
The optimal treatment for spinal dAVFs is contro-
versial, especially with ever advancing endovascular
techniques. Many authors have addressed the importance
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 529

(A) (B) (C) (D)

Figure 27.5 Cervical dAVF. An 84-year-old male presented with lower extremity weakness and an unsteady gait. Sagittal T2-weighted
image (A) demonstrated T2 hyperintensity in the central cord at mid-to lower thoracic region. Selective injections of all intercostal
and lumbar arteries were negative. Right vertebral artery injection (B, C) demonstrates small AVF fed by the lateral spinal artery or C1
radicular artery. Venous drainage is caudal and could be followed to midthoracic level (D), which corresponds to MRI findings.
Abbreviations: dAVF, dural arteriovenous fistula; AVF, arteriovenous fistula; MRI, magnetic resonance imaging.

(A) (B)

Figure 27.6 Spinal dAVF. A 59-year-old male presented with progressive lower extremity weakness. Selective left T6 intercostal artery
injection shows a plexiform network of vessels at fistula (small arrow) and prominent perimedullary vein (double small arrows).
A radiculomedullary artery arises from the same level (long arrow). Abbreviation: dAVF, dural arteriovenous fistula. Source: Courtesy
of Philippe Gailloud, Division of Interventional Neuroradiology, Johns Hopkins University (unpublished material).

of a multidisciplinary approach (20,21,53,54). They
have advocated an initial attempt of endovascular ther-
apy when possible, reserving surgery for anatomically
unfavorable lesionsusually implied as the segmental
artery that harbors both the feeder of dAVF and the
artery of Adamkiewicz (Fig. 27.6A, B). Surgery can be
performed immediately after embolization, as it does
not interfere with any surgical technique, if embo-
lization fails or a complex network of dural collaterals
appears as a result of embolization. Those authors
reported no differences in outcomes among those who
were treated by surgery, embolization, or combination
of both.
Endovascular Technique
Those who perform endovascular treatments for
spinal dAVF should know that surgery for these
lesions is relatively straightforward with high success
530 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
rates and low complication rates (52) (Fig. 27.7A, B). If
the fistula does not have optimal anatomy for embo-
lization, or when technical difficulty is encountered
during the procedure, the patient should be referred
for surgery. Case selection is the key for successful
endovascular treatment for dAVFs. Embolization is
contraindicated if the artery of Adamkiewicz, a major
contributor to the anterior spinal artery, arises from
the same dorsospinal artery as a feeding artery of
dAVF. This contraindication occurs in approximately
10% of patients (46,55). We consider visualization of
the radiculopial artery (a contribution to the posterior
spinal artery) also as contraindication to embolization.
Niimi et al. reported 87% technical success in 33 of 38
cases since the introduction of the variable stiffness
microcatheter, and noted that three out of five patients
who had inadequate embolization had a spinal cord
artery arising from the same pedicle as the feeder,
which prevented more aggressive embolization (46).
Navigation of the microcatheter through often
near-normal sized, but invariably tortuous feeder, can
be difficult and stability of the guiding catheter can
play a significant role in wire-catheter navigation.
There are many guiding catheters of different shapes
and variable stiffness suited for intercostals and lumbar
arteries. We perform all endovascular spinal interven-
tion under general anesthesia. The ability to suspend
respiration at the crucial moment gives a more accurate
delivery of embolic material.
The goal of embolization is to have the embolic
material reaching the proximal portion of the draining
vein through the fistula (Fig. 27.8). Proximal occlusion
of the feeding artery may temporarily improve symp-
toms by reducing arterial flow through the fistula, but
will not be a cure. Angiographers need to recognize
the proximal occlusion; failure to do so is the most
common cause of recurrence after embolization, since
postembolization angiogram shows obliteration of
Figure 27.7 Spinal dAVF. A 58-year-old male presen-
ted with progressive lower extremity weakness, which
worsened to complete paraplegia in last 10 days with
no sensation below T6. Sagittal T2-weighted MRI
(A) demonstrates prominent flow voids posterior to the
thoracic cord with abnormal high signal in the cord, which
extends down to the conus (not shown). (B) Spinal
angiogram demonstrates arteriovenous shunt (arrow) at
T6 level, fed by T6 intercostal artery, which shares a
common trunk with T5 and T7. The patient underwent
surgery three days after the angiogram. His strength
improved to three-fifth in both lower extremities, and
improvement in pinprick and bilateral vibration were
observed. However, he still needs self-catheterization at
four months follow-up. Abbreviations: dAVF, dural arte-
riovenous fistula; MRI, magnetic resonance imaging.
dAVF in either case. In case of definite proximal
occlusion, surgery should be considered soon after
embolization. If there is any doubt of glue staying
proximal to the vein, short-term follow-up angio-
graphy should be performed.
N-Butyl 2-cyanoacrylate (NBCA) is the choice of
embolization material today. Use of coils or particles
(mostly polyvinyl alcohol) is not acceptable because
of the well-documented high recurrence rate (56,57).
A mixture of NBCA and ethiodol (often 1:2) is inj-
ected slowly through the microcatheter that is opti-
mally positioned in the feeding artery as close to the
fistula as possible. Speed of injection and ratio of
NBCA to ethiodol varies case by case and requires
operator experience. When there is some distance
between the microcatheter tip and the shunt, the D5
push technique can be useful. D5 solution infused
through the guiding catheter facilitates the advance-
ment of glue.
Following embolization, it is important to docu-
ment: (i) obliteration of dAVFs by injection of segmen-
tal artery at several levels above and below the
treated level (Fig. 27.4G, H) and (ii) patency of the
artery of Adamkiewicz and venous drainage of nor-
mal spinal cord. The overpenetration of glue reaching
beyond the proximal draining vein can be more prob-
lematic than the proximal occlusion of feeding artery,
since it can worsen the venous hypertension, the
results of which may be cord infarct or hemorrhage.
In fact, venous thrombosis should be considered first
if the patients symptoms deteriorate after embo-
lization. In those cases, intravenous heparin should be
immediately started with a bolus and maintained for
24 to 48 hours with possible conversion to anticoagu-
lation. Recurrence of dAVFs can occur by collatera-
lization or recanalization of embolized vessels. The
latter is an infrequent phenomenon when NBCA is
used as an embolic agent.
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 531

(A) (B) (C) (D) (E)

Figure 27.8 Spinal dAVF. A 73-year-old female presented with acute onset of paraplegia and numbness for 12 hours. (A) Right T6
intercostal artery injection shows a radiculomeningeal artery travels down to T7 level and forms a shunt (small arrow) with drainage
into the radicular vein (long arrow). (B) Later image shows prominent perimedullary vein in caudal direction. (C) The microcatheter
injection of the dorsospinal artery depicts more clear images of the feeder (small arrow), the shunt (short arrow), and perimedullary
vein (long arrow). (D) Glue cast (33% NBCA) follows the course of dAVF; it outlines the feeder, shunt, and proximal portion of vein.
(E) Postembolization T6 intercostal angiogram shows no residual. At three months follow-up, she was able to walk with a walker.
Abbreviations: dAVF, dural arteriovenous fistula; NBCA, N-butyl 2-cyanoacrylate.

With the use of modern devices and NBCA,
initial technical success, i.e., adequate embolization,
can be obtained in close to 90% in selected cases.
However, even in experienced hands, 15% to 20% of
dAVFs can recur following an initially successful
embolization.
PERIMEDULLARY ARTERIOVENOUS FISTULAS
First described by Djindjian et al. as intradural extra-
medullary spinal AVMs in 1977, PM-AVFs are also
called type IV spinal cord AVM (58), intradural ventral
AVF (5), intradural direct AVF (18), and spinal cord
AVF (7). Fundamentally, PM-AVFs are abnormal direct
connections between the spinal arteries and medullary
veins without nidus; the fistula is on, not within, the
spinal cord, as the name describes (58).
Type III fistulas are mostly seen in children (59)
and have a high association with HHT or RenduOsler
Weber syndrome (19). An association with Cobb syn-
drome has also been reported (59,60). These syndromes
of vascular malformations are known to begin in early
fetal life (35 weeks). Rodesch et al. divided PM-AVF
into two subtypes: micro-AVF (mAVF) and macro-AVF
(MAVF); the latter corresponds to type III PM-AVF (7).
In their series, five of six MAVFs in children were asso-
ciated with HHT, while there was no HHT association
with mAVF. Authors suggested that presence of type III
AVF in children should prompt a search for HHT, and
patients as well as family members should undergo
screening for pulmonary AVF, which is the main cause
of disability secondary to CNS disorder ischemia due to
right to left shunt, stroke, and abscess.

Classification PM-AVF and Hemorrhagic Telangiectasia

Riche et al. distinguished three types of PM-AVFs (9).
Type I fistulas are slow-flow, simple, single-hole fistu-
las fed by a single feeder, usually the anterior spinal
artery, that is slightly enlarged and often flows a long
distance before ending in a small shunt (Fig. 27.1).
It is drained by a single mildly enlarged vein, often
along the posterior aspect of the cord. Type II fistulas
are more voluminous and are often fed by more than
one spinal artery (Fig. 27.9). One main feeder, usually
the anterior spinal artery, can be identified along with
multiple smaller posterior spinal arteries. Type III fis-
tulas are often referred as giant perimedullary fistulas
(Fig. 27.10). They are rapid and very high-flow giant
fistulas with multiple enlarged feeders. Venous drainage
is markedly dilated, ecstatic, and often appears dysplas-
tic, and a large venous aneurysm or pouch is a charac-
teristic finding at the level of shunt. This subdivision of
PM-AVF (type I, II, and III) is applied in other classifica-
tions; the most commonly used subclassification is type
IV spinal cord AVM (IVa, IVb, and IVc, respectively).
HHT is an autosomal dominant mucocutaneous and
visceral vascular dysplasia with prevalence of 1 to 10
for every 100,000 cases. Diagnosis is made when at
least three clinical criteria are met: epistaxis, telangiec-
tasia, visceral vascular malformations, and an affected
first-degree relative. Two mutations of endoglin
(ENG) on chromosome 9 and of activin-like receptor
kinase (ALK1) on chromosome 12 have been identi-
fied and represent two subtypes of HHT, i.e., HHT 1
and HHT 2, respectively (61). A higher incidence of
pulmonary AVM (40%) with HHT 1, versus 3% for
HHT 2, distinguishes the two types. Telangiectasias of
mucous membranes and skin causes epistaxis and
gastrointestinal symptoms, which are the most com-
mon presentations of the disease. Pulmonary AVM is
perhaps the most important abnormality to detect
because of the relatively high incidence (1020%) of
serious consequences involving the brain (stroke,
abscess). Ten to twenty percent have cerebral AVMs,
which are commonly described as mAVM (nidus less
532 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 27.9 PM-AVF, type II. A 31-year-old male presented with progressive urinary and bowel incontinence, erectile dysfunction, and
spastic paraplegia over several months. Sagittal T2-weighted images (A, B) show expansion and extensive signal abnormality involving
the high-to midthoracic cord and prominent flow voids. Right T5 intercostal artery injection (C) shows a moderate-flow fistula fed by the
posterior spinal artery with reflux into the intrinsic veins. There is no apparent nidus. Later image (D) shows prominent draining veins,
venous drainage through the radicular vein is also noted (arrow). Selective injection of the right T7 intercostal artery (E) demonstrates
the fistula fed by a small feeder. Glue embolization of the right T5 intercostal artery (F) followed by embolization of the T7 was
performed. The patient has shown slow improvement in strength and experiences no more incontinence; however, no change is noted
with erectile dysfunction. Abbreviation: PM-AVF, perimedullary arteriovenous fistula. Source: Courtesy of Philippe Gailloud, Division
of Interventional Neuroradiology, Johns Hopkins University (unpublished material).

than 10mm) or small AVM (13cm). Spinal cord
vascular malformations are seen in 8% of HHT with
neurological manifestations (62). Treatment of PMAVF
in patients with HHT will be the same for those
without HHT; however, the presence of other visceral
organ AVMs and right to left shunt may differ treat-
ment priority and perioperative management, includ-
ing general anesthesia and anticoagulation.
Clinical Manifestations
A large series of spinal AVMs reported various inci-
dences of PM-AVM ranging from 13.5% (11 out of 81)
to as high as 34% (27 out of 80) (6,14,18) of all spinal
AVMs. This variability in many series can be explained
largely by different referral patterns. In one series,
dAVFs comprised only 10% of all spinal AVMs
because dAVFs were treated by physicians in smaller
centers. In a series of 157 intradural spinal AVMs
without including dAVFs, 32 patients were found to
have PM-AVFs (20%) (19).
Patients are younger than those affected by
dAVFs, most present in their second to fourth deca-
des. About two-thirds are younger than 25 years
and one-third less than 15 years (19). Many patients
have months to years of radiculomedullary symptoms,
which are progressive with or without episodes of
acute deterioration. If untreated, complete spinal
transection develops in seven to nine years (63). As in
spinal dAVFs, venous ischemia due to venous conges-
tion is likely the main cause of progressive symptoms
in type I and some type II patients, and venous
thrombosis may play a role in nonhemorrhagic epi-
sodic deterioration. Symptoms seen in some type
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 533

(A) (B) (C) (D)

(E) (F) (G)

Figure 27.10 PM-AVF, type III. A 23-year-old female with known PM-AVF developed acute deterioration of spastic paraplegia with
new bladder and bowel incontinence. At age 18, the diagnosis was made by angiogram (A, B) after an episode of spinal SAH. The
treatment was offered but declined. T12 intercostals artery injection (A) shows a large anterior spinal artery supplying a high-flow fistula
(arrow) and a large venous aneurysm (double arrow). Later image (B) shows opacification of contiguous venous pouches. At the
time of treatment, the venous pouch appears more dysplastic (C). Also noted was an interval development of posterior spinal artery
contribution to the fistula (arrow). (D) A detachable coil was placed first at the site of fistula (arrow), and postcoil angiogram shows a
reduction of flow through the fistula. Glue embolization (E) was performed (90% NBCA) through the coil (large arrow), glue (small
arrow) stays at the fistula without escaping into the venous side. Postembolization angiogram of T12 (F) shows almost complete
obliteration, the posterior spinal artery is visualized. T9 intercostal artery injection (G) demonstrates contiguity of the anterior spinal
artery. Abbreviations: PM-AVF, perimedullary arteriovenous fistula; SAH, subarachnoid hemorrhage; NBCA, N-butyl 2-cyanoacrylate.
Source: Courtesy of Philippe Gailloud, Division of Interventional Neuroradiology, Johns Hopkins University (unpublished material).

II and III patients are multifactorial, i.e., not only
venous hypertension but steal phenomenon and direct
compression are also responsible for development of
disease. A large varix at the level of shunt in type III
patients causes direct compression of the spinal cord
or nerve roots, which may explain asymmetric distri-
bution of signs and symptoms in some patients (60).
Approximately one-third of patients present with
spinal SAH (18,60,63). Hemorrhage likely occurs on
the venous side of malformationsvenous drainage is
commonly seen in the posterior aspect of the cord and
posterior spinal veins are located exclusively in the
subarachnoid space. On the other hand, hematomyelia
is likely a result of rupture of the anterior spinal vein,
which is subpial in location (17). A much higher
incidence of hemorrhage (SAH or hematomyelia) has
been observed in pediatric populations. In one series,
70% of patients under 15 years of age presented with
some type of hemorrhage (19); they also tend to
present with acute symptoms rather than progressive
symptoms of chronic nature. Delay in diagnosis is
unfortunately very common; more than 20 years of
delay has been reported (14,63).
Imaging
Type II and III lesions are easily detected as prominent
serpentine filling defects on myelography or perime-
dullary flow voids, often accompanied by signal abnor-
mality within the cord on MRI (Fig. 27.9A, B). In type
III lesions, integrity and architecture of the spinal cord
can be very difficult to assess because of the large size
of venous outflow and resulting distortion of the cord
(Fig. 27.11). Though early reports questioned the ability
of MRI to diagnose type I lesions (14,60), recent case
series suggested that MRI with MRA is a reliable
modality, particularly because myelotomography is
not available anymore (64). Contrast administration
increases the visualization of perimedullary vessels and
534 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 27.11 PM-AVF, type III (same patient as in Fig. 27.10). Sagittal T2-weighted images of the lumbar spine (A, B) at the time of
presentation demonstrate prominent tortuous flow voids around the distal spinal cord. There is a large flow void suggesting a venous
aneurysm. The cord is distorted by dilated vessels, and it is difficult to evaluate the cord parenchyma (C). Abbreviation: PM-AVF, peri-
medullary arteriovenous fistula.
demonstrates intramedullary enhancement at the level
of signal abnormality.
For all three types of PM-AVFs, only selective spi-
nal angiography can provide the information necessary
to achieve the subclassification of a lesion and to choose
its treatment. The number and size of feeders and
the size and location of the fistula dictate treatment.
Oblique or lateral views are often necessary. The feeders
arise from various levels; however, the fistula itself is
commonly located at the level of conus medullaris rang-
ing from 64% to 75% in reported series, followed by
filum terminale (65). Type III lesions can be seen in the
cervical region.
Some lesions, mostly type II lesions, may be mis-
taken as IM-AVM on angiography because of a pseudo-
nidus appearance caused by reflux of venous flow into
the intrinsic network of congested veins immediately
distal to the shunt (19).
Treatment
Subclassification of PM-AVF does not hold signifi-
cant implications for clinical symptoms or treatment
outcomes, rather indicates therapeutic approaches.
The size of fistula and the size and number of
feeders included in classification are critical infor-
mation, as well as the location of the fistula relative
to the spinal cord. Emergent intervention is not nec-
essary in most of hemorrhagic cases as a high rate of
spontaneous recovery is reported (72% by Rodesch
et al.) (17).
Most authors agree that surgery should be con-
sidered first in type I lesions because of the small size
of the feeder and long distance to the shunt. Trans-
arterial embolization has been attempted in a small
(C)
number of patients, with reported success, when a
lesion was located anterior to the conus medullaris or
spinal cord (64,66). It is reasonable to try an endovas-
cular approach first, in selected patients, as long as
operators recognize proximal occlusion, which results
in the same angiographic appearance as true oblitera-
tion of the shunt. Those with proximal occlusion need
to undergo surgical resection without a long interval
to avoid growth of more complex, recanalized fistula
fed by collaterals.
For type II lesions, some think that embolization
is rarely effective because of multiple feeders and fis-
tulas. Some feeders are transmedullary branches, and
catheterization of those branches may not be techni-
cally possible and may not be safe. Surgery is indi-
cated in most posterolateral AVFs, and embolization
can be performed in conjunction with surgery in
anterior lesions. Resection or clipping of PM-AVF that
is interposed, often hidden deep behind markedly
enlarged veins, is technically difficult (14). Although
surgery may be the treatment of choice in type II
PM-AVFs, reports on the surgical outcome of these
lesions remain scarce.
Type III lesions have multiple large feeders and
giant venous ectasia, which represent high operative
risk. Thus, embolization is the first line of treatment.
Successful obliteration of giant PM-AVF has been
reported with a detachable balloon (14,59); however,
the balloon is not currently available in the U.S. market.
Acrylic glue (NBCA) should be used whenever transar-
terial access to the shunt is achievable. In a series of
22 patients with type III PM-AVF, 15 patients, whose
angiogram showed complete disappearance of the
lesion at the time of embolization, had recovered
completely (14).
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS
Endovascular Techniques
Embolization is performed under general anesthesia.
Ability to control respiration and any patients motion
is critical when visualization of fine vasculature is crit-
ical. The patient is given 5,000 units of heparin at the
beginning and the dose is adjusted to maintain acti-
vated clotting time (ACT) above 250 seconds. Usually,
an hourly bolus of 1,000 second is effective. A non-
glide guiding catheter is placed at the origin of the
feeding artery. A 6-Fr system is used whenever possi-
ble to acquire a better roadmap during navigation of
the microcatheter as well as to add stability to the sys-
tem. A braided microcatheter enables us to use either
coils or liquid adhesive. Some newer small-diameter
microcatheters (e.g., Echelon 10, Micro Therapeutics
Inc., Irvine, California, U.S.) have a large inner diameter
equipped for detachable coil placement, but still come
with an advantage of small outer diameter that makes
navigation easier and allows contrast injection through
a 5-Fr guiding catheter. It is imperative to reach the site
of the fistula, as proximal closure of the feeder results
in development of a more complex, inaccessible lesion.
Embolization should be performed with liquid
adhesive (NBCA mixed with iodized oil). For a type II
lesion with medium-flow, primary glue embolization
is performed with various concentrations of NBCA
(Fig. 27.9F). For very high-flow type III lesions, a glue
injection following placement of coils at the site of fis-
tula prevents glue migration through a high-flow shunt
into the venous side. Placement of coils also assures
accurate deposition of fast glue (Fig. 27.10D, E). Coil
placement at the fistula may not be possible when the
feeder continuously enlarges as it gets closer to the
fistula; in those cases, few coil loops can be positioned
in the proximal venous pouch. Communication with
the anesthesiologist is important during the procedure,
especially, immediately before injection of liquid
adhesive. The anesthesiologist must know the nature of
glue embolization and that any patient motion can
cause disaster or failure of embolization. Since liquid
adhesive is a permanent agent, and failure of embo-
lization usually means losing an access to the lesion in
the best scenario.
Some advocate a provocative test before embo-
lization, including a balloon occlusion test of spinal
arteries and injection of barbiturate or lidocaine. We
do not use neurophysiological monitoring or provocative
tests, rather detailed analysis of a pre-embolization
microcatheter angiogram provides crucial and adequate
information to decide where to deposit and when to
stop injecting glue.
Transient worsening of symptoms after intervention
is common but most return to baseline (60). Worsening of
symptoms can occur during the immediate postembo-
lization period or in the subacute phase (46 weeks) after
embolization. The former is likely a result of progressive
retrograde thrombosis of the draining vein of fistula and
veins of adjacent cord parenchyma due to sudden hemo-
dynamic changes. The latter is secondary to mass effect
and inflammatory changes of thrombosis of a large
venous pouch, which peaks weeks after thrombosis hap-
pens. For the immediate postoperative period, especially
in high-flow fistula, patients will be kept on intravenous
heparinization for 24 to 48 hours to keep the normal
535
draining vein patent. A thrombosis can also occur on the
arterial side (58). When a large varix is obliterated, intra-
venous steroid is used during the hospitalization, which
likely reduces the inflammatory effects of acute throm-
bus. A tapering dose of oral steroid may be added in
selective cases. For patients who develop symptoms in
the subacute phase, again a steroid is often used to
reduce edema and inflammatory changes associated with
thrombus formation.
INTRAMEDULLARY ARTERIOVENOUS
MALFORMATION
IM-AVM is also called type II malformation, glomus
AVM, and angioma arteriovenosum. It consists of
feeding arteries, nidus, and draining veins, as in cere-
bral AVM. The nidus of AVM can be compact, called
glomus type (Fig. 27.12), or more diffuse in appear-
ance involving a longer segment, called juvenile type
(Fig. 27.13). Differentiation of the two types, although
it is widely used, is very loosely defined in the litera-
tures. Though it was a classification based on angio-
graphic findings, it has been used for surgical lesions
that lack a clear plane between the nidus and normal
cord. In our opinion, the juvenile type should be used
specifically to describe IM-AVM with involvement of
neighboring nonneural structures, such as dura, bone,
muscle, subcutaneous tissue, or skin, to avoid confu-
sion, although initial descriptions of the juvenile type
suggest this finding as common and not essential (18).
In a new modified classification by Spetzler, the
juvenile type is called extradural-intradural AVM (5).
Other names applied to this type are metameric angio-
matosis (67) and type III malformation (68). In this
section, this subgroup of IM-AVM is described under
metameric angiomatosis.
Clinical Manifestations
Although IM-AVM is uncommon, it is two to three
times more common than PM-AVFs (14,15). Patients
usually present in the second and third decade of life.
There is slight male predominance in many series. In
a series of 90 patients with intradural AVM/AVFs,
57% were male (8). In the series by Rodesch et al. 57%
of 155 patients with intradural AVM/AVFs were male
but no significant gender difference was seen in the
adult population (17). Approximately, one-half to two-
thirds of patients experience hemorrhage (SAH and/
or hematomyelia) by the time diagnosis is made
(15,17,69). Hemorrhage leads to acute onset of neuro-
logical deficits in two-thirds, the rest only have back
pain (characteristic severe spinal pain with or without
root pain) without deficits (70). Recurrent SAH is seen
in 18% to 30% (15,17). Rodesch et al. found a signifi-
cantly higher risk of hemorrhage in cervical lesions
(65%) compared with thoracolumbar lesions (40%)
(17), concordant with other observations (8), although
their series does not differentiate IM-AVM from
PM-AVF. Other symptoms include back pain, motor
deficits, sensory disturbance, bladder and bowel
incontinence, and impotence. These symptoms usually
develop in a slow progressive fashion. In the Hurth
et al. series, approximately 40% of patients with
untreated or partially treated intradural AVM/AVFs
536 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 27.12 IM-AVM. A 38-year-old female presented with progressive right lower extremity weakness associated with right-sided hip
and back pain over a year. Right T9 intercostal artery injection (A) shows the anterior spinal artery (small arrows) supplying the
intramedullary nidus (long arrow) at the T10T11 level. Later image (B) shows early venous drainage through the perimedullary veins
(double arrows) in both cranial and caudal directions. Lateral projection of same artery shows the anterior spinal artery and fistula in
early phase (C) and drainage veins ventral to the cord in cranial direction (large arrows) and dorsal to the cord in caudal direction
(small arrows) in late phase (D). Right T11 intercostal artery injection (E) reveals small contribution from the posterior spinal artery.
There appears to be a small component of AVF from the right L2 lumbar artery (F). Abbreviations: IM-AVM, intramedullary arterio-
venous malformations; AVF, arteriovenous fistula.

had acceptable neurological conditions after 15 years,
the number is somewhat better in cervical lesions (8).
Imaging
Diagnosis of IM-AVM is easily made by MRI. It dem-
onstrates intramedullary nidus and dilated draining
veins along the spinal cord. It provides important
information of associated abnormalities such as SAH,
myelomalacia, gliosis, cord edema, venous ectasia,
and aneurysm.
IM-AVM distributes uniformly along the longitu-
dinal axis of the spinal cord without thoracolumbar
predominance, unlike dAVFs. IM-AVM has a nidus fed
by anterior spinal (radiculomedullary) or posterior spi-
nal (radiculopial) arteries. It may be supplied directly
by spinal arteries or their branches, such as sulcocom-
missural arteries and pial branches. Multiple arterial
feeders are often present (Fig. 27.14A, B), which can be
extensive, especially in the cervical IM-AVM due to the
presence of an embryological connection of vertebral,
ascending cervical, deep cervical arteries, and external
carotid artery branches. Venous drainage can be ventral
or dorsal to the cord and cranial or caudal in the longi-
tudinal course. IM-AVM nidus can be confined to the
cord parenchyma, or on the pial surface, or both. Intra-
operatively, most AVMs have a varying degree of
extramedullary/subpial component that is accessible to
surgeons (69).
Biondi et al. reported a 20% (14 out of 70)
incidence of aneurysm in IM-AVMs (Fig. 27.13D) (15).
Earlier reports presented a much lower frequency
of spinal aneurysm; however, this is due to mixing of
all vascular malformations, including dAVFs and
PM-AVFs, into one group. Many reports also mis-
interpreted the venous pouch in PM-AVFs as an
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 537

(A) (B) (C)

(D) (E) (F)

(G) (H) (I)

Figure 27.13 A 14-year-old male with port wine stain in midline back over upper thoracic level, severe headache, nuchal rigidity, and
new onset left upper extremity weakness with paraparesis. (A, B) Sagittal and axial T2-weighted images demonstrate flow voids
throughout cord and in adjacent soft tissue and bony structures (including T1 vertebral body on sagittal images). (C, D) Left vertebral
artery injection demonstrated intramedullary spinal cord AVM with ASA supply originating from intradural vertebral artery. (E) Injection
of left T4 intercostal artery shows soft tissue component as well as supply to intramedullary component of AVM, feeding artery
aneurysm on pedicle. (F) Selective injection of intramedullary pedicle followed by glue embolization. (G) Plain film demonstrating
radiopaque glue in pedicle and nidus. (H) Postembolizationno filling of inferior intramedullary supply or aneurysm. (I) Injection of
adjacent intercostals fills soft tissue AVM component. Abbreviations: ASA, Anterior spinal artery; AVM, arteriovenous malformation.
538 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
aneurysm. There were no aneurysms associated with
dAVFs (44 patients) or PM-AVFs (72 patients) in his
series. SAH was present in 100% of patients with
IM-AVMs and associated spinal aneurysm; of those
43% of cases had recurrent SAH. In patients with
IM-AVMs and no spinal aneurysms on the angiogram,
SAH was present in 70% (39 out of 56) with recurrent
SAH in 13 patients (15). Following embolization
of IM-AVM without obliteration of aneurysm, size of
8 out of 11 aneurysms followed the size of an AVM,
suggesting that flow change is an important factor in
the formation and growth of aneurysms (71). It is
important to carefully study the angioarchitecture
of IM-AVM, especially in the early arterial phase, to
differentiate an aneurysm from a venous pouch. These
aneurysms are thought to be flow-related aneurysms
as a result of hemodynamic changes, though under-
lying dysplasia or abnormalities of local vessels are
likely to contribute to aneurysm formation since an
aneurysm is rarely seen in high-flow PM-AVF. Pseu-
doaneurysms related to rupture or dysplastic change
in or near a nidus can be seen; however, it can be
difficult to differentiate the true aneurysm from
the pseudoaneurysm, and the Biondi et al. article did
not differentiate two abnormalities. In the series of
intradural AVM/AVFs by Rodesch et al. true arterial
aneurysms were seen in 49 out of 155 patients (31.6%)
and pseudoaneurysms in 26 patients (17%). Interest-
ingly, there was no increased risk of hemorrhage in
patients with true aneurysms. Pseudoaneurysms were
associated with hemorrhage in all cases (17).
Metameric Angiomatosis
Metameric angiomatosis are complex vascular abnor-
malities involving the spinal cord in various fashions,
extending into or separately affecting the vertebrae, mus-
cle, subcutaneous tissue, and skin along the dermatome.
Juvenile AVM, also referred to as type III vascular mal-
formation, and complex spinal cord AVM are diffuse
Figure 27.14 IM-AVM. A 19-year-old female pre-
sented with mild left lower extremity weakness
and numbness in abdomen and left thigh. Right
T9 angiogram (A) shows the right posterior spinal
artery feeding a nidus at T8 level. Left T8 injection
(B) shows the anterior spinal artery supply to the
nidus. Embolization was performed via right T9
feeder using glue. Abbreviation: IM-AVM, intra-
medullary arteriovenous malformation.
lesions that do not respect tissue boundaries and are
typically seen in young patients. Well-known asso-
ciated syndromes are Cobb syndrome, Klippel
Trenaunay syndrome, and Parkes Weber syndrome.
Cobb syndrome is characterized by intradural AVM/
AVFs and is associated with vertebral, cutaneous,
or paraspinal lesions in the same or adjacent segment
(Fig. 27.13B, C). A cutaneous angioma can be small and
subtle, but it is the hallmark of this syndrome (72).
KlippelTrenaunay syndrome manifests with cutaneous
angioma and limb venolymphatic lesions without AV
shunts (7376), whereas Parkes Weber syndrome has
limb lesions with high-flow shunts (77,78). The limb
lesions also follow the dermatome distribution.
Matsumaru et al. found 16% of metameric vascular mal-
formations in their series of 119 spinal cord AVMs (11).
They include nine Cobb, two KlippelTrenaunay, and
one Parkes Weber syndrome. There were seven cases of
nonsyndromic association with bifocal intradural meta-
meric lesions. Incidence of metameric angiomatosis in
patients with intradural AVM/AVFs is 19% in the series
of Rosenblum et al. 38% in a series of thoracic IM-AVM
by Biondi et al. and 26% in the Hurth et al. series
(excluding HHT).
Obviously, these are extremely rare lesions; there-
fore, optimal specific treatment has not been estab-
lished. Prognosis is generally poor and a complete cure
of lesions should not be a goal of treatment since it is
likely associated with high morbidity, given the com-
plexity of the abnormalities. It should be targeted to
the lesion or site responsible for clinical symptoms, and
it may be the best to leave them alone if patients are
stable and not symptomatic.
Treatment
Because of the known progressive course and poor prog-
nosis, treatment is recommended to prevent the onset
or progression of symptoms. Clinically, patients with
a history of hemorrhage or progressive neurological
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS
deficits should be treated more aggressively to prevent
recurrent hemorrhage or progression of disease process.
Treatment by any methods should aim at obliteration
of AVM; however, some lesions are not curable by
means of surgery or embolization. In these scenarios, the
goal of treatment can be tailored to improve clinical
symptoms or to target specific angioarchitecture such as
aneurysm.
Embolization has become the first line of treatment
in many centers, either as a primary treatment or as a
preoperative adjunct (67,79). A liquid adhesive, NBCA,
should be used as an embolic material, whenever
feasible, especially when embolization is performed as a
sole treatment. In the largest series of glue embolization
of intradural AVM/AVFs by Rodesch et al. which
consisted of 114 patients excluding patients who only
consulted, 69 patients (60%) underwent embolization, 21
(18%) received surgery, and 24 (21%) were considered
untreatable. Among 69 patients, 68 lesions were treated
with acrylic glue, and a good clinical outcome was
achieved (15% asymptomatic, 43% improved, 25%
unchanged) at mean follow-up of 5.6 years. More than
50% reduction in size of AVM/AVF was seen in 86%
of cases. Complications were transient deficits in 10
patients and permanent deficits in 9 (13%)three of
which (4%) suffered a mild disabling deficit, whereas
other six deficits did not limit normal activity. All com-
plications occurred during the embolization through the
anterior spinal artery. No recanalization was noted (80).
Even in one of the most experienced centers for treat-
ment of spinal vascular malformations, a relatively large
number of patients (21%) do not receive any treatment.
All treating physicians need to know the limits of endo-
vascular treatment. Arterial aneurysms on feeders of
IM-AVM should be treated, especially in patients with
a history of hemorrhage. Even partial treatment may
be acceptable to eradicate the aneurysm and reduce risk
of future hemorrhage (81). Preoperative embolization
can be useful to facilitate surgical resection of certain
lesions (8284). There are several papers reporting the
use of Onyx, a hyperviscous liquid embolic agent, with a
longer injection time and reduced risk of catheter adhe-
sion in these lesions. While we have no personal experi-
ence of the use of this material, many who we respect
report that it is safe and effective (85).
Radiosurgery may be an alternative treatment
for symptomatic lesions that are not amenable to sur-
gery or embolization (86,87).
Endovascular Techniques
We perform all IM-AVM embolizations under general
anesthesia. The patient is fully heparinized, and
ACT is monitored during the procedure. A nonglide
guiding catheter will be placed at the origin of the
feeding artery. When an AVM is high flow, a flow-
guided microcatheter can be used; however, in many
instances, a braided microcatheter with support from
a guidewire is needed to navigate through tortuous
spinal arteries. Whenever a posterior spinal axis,
including a radiculopial artery, is one of the promi-
nent feeders, it should be chosen first as a target
since embolization is safer with less risk of morbidity.
The posterior spinal artery supplies the posterolateral
aspect of the cord in radial fashion and multiple
539
circumferential and longitudinal anastomoses exist
between them. As described before, in patients with a
history of hemorrhage, a feeder with aneurysm should
be targeted first. When the anterior spinal artery
(radiculomedullary artery) needs to be embolized,
superselective catheterization in or near the nidus
beyond the longitudinal axis of the artery is essential
to keep any normal branch out of danger (Fig. 27.15),
which usually means catheterization of the sulcocom-
missural artery. Once the catheter tip is in position, a
superselective angiogram should be done to confirm
the absence of normal branches. Embolization is
performed with NBCA mixed with iodized oil, and
dilution of NBCA depends on the angioarchitecture
and flow of the lesion and location of the catheter tip.
We commonly use 30% to 50% of NBCA, unless high-
flow shunt is noted within the nidus, for which higher
concentration of NBCA is used.
After embolization, patients are monitored in the
neurocritical care unit for one day, then in the floor for
another day or two before discharge. IV heparinization
is continued for 24 hours in most of the patients to
prevent progressive thrombosis of normal veins.
EXTRADURAL ARTERIOVENOUS
MALFORMATION/FISTULAS
Extradural AVMs/AVFs are rare lesions that can
cause neurological symptoms. In this group, paraspi-
nal or paravertebral AVM/AVF and epidural AVF are
included, most common form of which is vertebral-
vertebral AVF.
Clinical Manifestations
Several case report and case series are available
(8892), and they provide clinical, angiographic, and
treatment information of 22 cases. One case was
reported twice and was excluded. Extradural AVMs/
AVFs are common in pediatric patients; among
22 cases, 13 patients were less than 17 years of age,
including 6 infants. However, there is no significant
gender prediction (10 male, 12 female). It appears to
occur equally throughout the spinal axis with seven
cervical, ten thoracic, one thoracolumbar, and four
lumbar lesions. Several forms of clinical presentations
were reported but progressive neurological deficits
are the most common presentation. This deficit is
caused by two mechanisms: the first is venous hyper-
tension or congestion secondary to venous reflux into
the perimedullary vein via epidural venous plexus,
which is comparable to the pathophysiology of
dAVFs. The second is direct compression of the spinal
cord or spinal nerves by dilated arterialized veins.
Other symptoms include mass effect on other organs,
one infant presented with difficulty swallowing secon-
dary to compression of esophagus (91), and another
patient with KlippelTrenaunay syndrome was found
to have asymptomatic erosion of cervical vertebrae
caused by high-pressure venous masses (92). High-
flow shunts caused congestive heart failure because of
volume and pressure overload in one neonate (91).
Only one SAH has been reported, angiogram of the
patient showed high-flow shunt with pseudoaneurysm
540 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

(E) (F) (G) (H) (I)

Figure 27.15 IM-AVM. An 83-year-old female with severe neck pain and quadriplegia. (A, B) Right vertebral artery injection shows
PSA feeding pedicle to spinal cord AVM originating from right C4 level. ASA originating from right intradural vertebral artery gave small
component of AVM supply. Note soft tissue AVM at right cervico-occipital level (drainage laterally into neck veins). (CF) Plain and
subtracted images of AP and lateral views of selective injection of feeding pedicle pre-embolization. (G) Lateral plain film after
embolization demonstrating glue in nidus of AVM. (H, I) Postembolization RVA injection, minimal component from ASA remaining.
Abbreviation: IM-AVM, intramedullary arteriovenous malformation; RVA, right vertebral artery.

on venous side (90). There are three patients with Imaging

metameric angiomatosis and two patients with meta-
meric angiomatosis and spinal vascular malformation.
One patient with neurofibromatosis presented with
pain and CT finding of epidural mass through neural
foramen, which led to surgery with assumption of the
lesion being neurofibroma (89). This lesion was later
treated by endovascular method. The association of
neurofibromatosis and AVF has been reported (93).
On the other hand, vertebral-vertebral AVF is
often asymptomatic and rarely causes neurological
deficits. Most patients are found to have a bruit or
experience tinnitus. The largest series of vertebral-
vertebral AVFs by Beaujeux et al. reported that out of
46 patients of this condition, only 3 had neurological
deficits, whereas 21 had tinnitus (94). In their series,
majority were spontaneous (59%), whereas in other
series 100% cases were spontaneous (95). Trauma
was thought to be the cause in 41% of patients.
In half of the cases vertebral-vertebral AVFs are
located in C1 to C2 levels, and C5 is the other com-
mon location.
MRI often provides useful information regarding
geography of lesion, presence of dilated perimedullary
veins, cord compression, and coexisting abnormality
(Fig. 27.16). In the series by Goyal et al. 3 of 10
patients had increased signal within the cord on
T2-weighted images and prominent perimedullary
vessels (89). Two of them had paravertebral AVF with
reflux into perimedullary veins on angiogram. The
author emphasized importance of this finding, since
simple clipping of the radicular vein can alter venous
flow and eliminate symptoms.
Extradural AVM/AVF can be located in the
epidural space, bone, or adjacent soft tissue; there-
fore, any neighboring artery can become feeder
(Fig. 27.17AD). The spinal artery (including radiculo-
medullary and radiculopial arteries) does not contrib-
ute to shunts. Venous drainage involves epidural
venous plexus at some point, which is drained by
paraspinal veins such as azygos or hemiazygos veins
or reflux into the perimedullary veins (Fig. 27.16EH).
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 541

(A) (B) (C) (D)

(E) (F) (G) (H)

(I) (J) (K)

Figure 27.16 Paraspinal AVF. A 28-year-old male presented with progressive lower extremity weakness with vascular malformation
identified in the lumbar region on MRI (AD). Further workup prior to embolization showed asymptomatic pulmonary hypertension.
Pelvic angiogram (E, F) demonstrates high-flow fistula fed by anterior division of the internal iliac artery bilaterally with robust venous
drainage into the internal iliac veins. Left L1 angiogram (G) demonstrates a large lumbar artery feeding the AVM nidus lateral to the
spinal canal. Venous drainage is via the large epidural vein with radicular veins (H, arrows) seen at multiple levels. Nearly all inter-
costals and lumbar arteries from T10 to L4 contribute to AVM or AVF. Following first embolization of a few prominent feeders, he was
asymptomatic for a year. Second embolization was done when he presented with sensory symptoms in the lower extremities. Left L2
lumbar angiogram (I) shows a fast-flow AVM lateral to the spinal canal. Glue embolization was performed in oblique projection that
best demonstrates the proximal segment to prevent reflux (J). Unsubtracted image (K) shows the coil mass, glue cast from current and
prior embolizations. Abbreviations: AVF, arteriovenous fistula; MRI, magnetic resonance imaging; AVM, arteriovenous malformation.
Source: Courtesy of Philippe Gailloud, Division of Interventional Neuroradiology, Johns Hopkins University (unpublished material).
542 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
(C) (D)
Treatment
Extradural AVF/AVM with neurological symptoms
should be treated if feasible. Because of variable
angioarchitecture and involved vessels, treatment
needs to be individualized depending on clinical
symptoms and pathophysiology. If venous congestive
myelopathy is caused by perimedullary venous
reflux, treating arterial side by endovascular app-
roach will not resolve spinal venous hypertension
unless complete obliteration of shunts is achieved.
However, alteration of venous drainage by clipping
of radicular vein will likely eliminate symptoms. The
lesion can be left alone unless systemic symptoms
develop. When symptoms are caused by large
high-pressure veins in the epidural space, lesions
usually have very high flow and feeders are multiple
and dilated. Transarterial embolization using liquid
adhesives is useful with high rate of success (90).
One can use similar method as treating type III
PM-AVF. Placement of coil at the shunt or proximal
venous pouch can facilitate precise deposition of
liquid adhesive without its migration to systemic
Figure 27.17 Paraspinal AVF. An 11-year-old boy
status post chest wall lymphatic malformation
resection at age six and known vascular lesion in
the spine suddenly developed near complete
paralysis and urinary and bowel incontinence. Left
suprascapular artery angiogram (A) shows the
feeder of paraspinal AVF (approximate midline
location is indicated by an arrow pointing an endotra-
cheal tube). Late arterial phase (B) demonstrates a
large venous aneurysm (large arrow) at the level
of T5 and T6, which drains into the epidural vein
on the left (small arrow). Glue embolization was
performed with a microcatheter tip (C, arrow) just
proximal to two main feeding branches of the AVF
using D5 solution push technique. Postembolization
angiogram via the left subclavian artery (D) shows
no contribution from the suprascapular artery. Faint
opacification of the feeder fed by small collaterals
via the superior intercostals artery. Glue cast is out-
lined by small arrows. He underwent second embo-
lization via the T6 intercostal artery (not shown) and
recovered completely. Abbreviation: AVF, arterio-
venous fistula. Source: Courtesy of Philippe Gail-
loud, Division of Interventional Neuroradiology, Johns
Hopkins University (unpublished material).
veins (Fig. 27.16IH). When arterial route is exhausted
or there is single venous drainage with multiple arterial
feeders, transvenous route can be used (89,92), coils in
the epidural space do not appear to cause symptomatic
compression of spinal cord.
Vertebral-vertebral AVF is often neurologically
asymptomatic and indication of treatment should be
thought out as in benign intracranial dAVF. When a
high-flow single-hole fistula is found, often caused
by trauma, placement of detachable coils or balloon at
the shunt or proximal venous pouch is effective in
closing the shunt (Fig. 27.18). This procedure can
be performed via transarterial or transvenous route
(96,97). If it results in incomplete obliteration of the
fistula, sacrifice of the vertebral artery must be consid-
ered. The vertebral artery harboring the fistula needs
to be occluded distal and proximal to the fistula.
ISOLATED SPINAL ARTERY ANEURYSMS
Isolated spinal artery aneurysms without associated
AVM are exceedingly rare and few have been
 ENDOVASCULAR TREATMENT OF SPINAL VASCULAR MALFORMATIONS 543

(A) (B) (C) (D) (E)

Figure 27.18 Vertebral-vertebral fistula. A 23-year-old male presented with proptosis of the right eye two months after a motor vehicle
accident. AP (A) and lateral (B) angiogram of the left vertebral artery show high-flow direct fistula between distal cervical segment of
vertebral artery and vertebral vein. Using transarterial approach, the fistula was embolized with detachable coils (C). Postembolization
AP (D) and lateral (E) angiogram show minimal flow through the coil mass, which continuously decreased over several minutes docu-
mented on repeated angiograms. Also noted is a high-flow carotid cavernous fistula (type I) (not shown).

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 28
Neuroendovascular aspects of cerebrovascular disease in
pregnancy
Bryan A. Pukenas and Robert W. Hurst
INTRODUCTION
Manifestations of cerebrovascular disease in pregnancy
are uncommon and differ significantly in many aspects
when compared to non-pregnant patients. Although
pregnant women are subject to the same cerebro-
vascular disorders seen in the non-pregnant state, the
risks of occurrence and natural history may differ
significantly in pregnancy. In addition, cerebrovascular
disease in pregnancy has major implications not only
for the affected patient but also for the fetus. Moreover,
pregnancy is associated with a number of specific
cerebrovascular disorders which are not commonly
encountered in non-pregnant patients. This chapter will
briefly highlight aspects of cerebrovascular disorders
encountered in pregnancy of neuroendovascular
interest.
Imaging findings in pregnant patients with cerebro-
vasular disease are generally identical to those of their
non-pregnant counterparts. Nevertheless, familiarity
with the risks and benefits of each imaging modality
with regard to mother and fetus is essential (1). Knowl-
edge of the specific imaging findings associated with
pregnancy-related disorders is required for the effective
diagnosis and endovascular management. Lastly, safety
considerations associated with endovascular treatment
in this patient population must take into consideration
risks to both the mother and fetus.
PHYSIOLOGIC ALTERATIONS ASSOCIATED
WITH PREGNANCY
The alteration of risk and the predisposition to specific
cerebrovascular disorders encountered in pregnancy is
in large part due to the significant physiological
changes associated with pregnancy. These physiologi-
cal changes not only impact the predisposition and
occurrence of pregnancy-related cerebrovascular disor-
ders, they must also be taken into consideration when
performing neuroendovascular procedures in gravid
patients. Physiological alterations include changes in
fluid and blood volume, cardiovascular changes, and
hematological parameters.
Maternal fluid volume and composition alters con-
siderably during and after pregnancy. Blood volume
begins to expand in the first trimester, increases by about
1250ml and this volume is maintained until term (2),
peaking at 4045% greater than non-pregnant levels
in the last trimester (3). Increases in total red cell mass
during gestation ranges from 1740% (4). As a result of
the relative increase in fluid volume exceeding that of
erythrocyte production, hemodilution with associated
anemia is present after the first trimester. Believed to
permit compensation for blood loss at delivery, these
physiological adaptations may delay changes in heart
rate or blood pressure until significant amounts of blood
loss have occurred (5,6). Post angiographic monitoring
of pregnant patients must take these features into
account as they may delay recognition of puncture site
or retroperitoneal hematoma.
Cardiovascular changes include increased stroke
volume and heart rate with increase in mass of the
left ventricular wall, resulting in a 3050% increase
in cardiac output (7,8). Compromise of cardiac output
may occur when venous return to the heart is impaired.
This can occur as a result of the enlarged uterus com-
pressing the inferior cava when gravid patients are
placed in the supine position for angiography (9), with
subsequent cerebral and fetal hypoperfusion. Caval
compression in the supine position can also lead to
redirection of venous return into the spinal extradural
vertebral venous system, decreasing the capacity of
the extradural and subarachnoid spaces (10). In order
to avoid these potential complications, patients under-
going angiography should remain as much as possible
in the left lateral decubitus position with fetal moni-
toring if necessary (11).
Elevated pregnancy-related hormone levels
dilate arteries and decrease systemic vascular resist-
ance. The effect gives rise to a decrease in both sys-
tolic and diastolic blood pressure during the first
two trimesters. This is usually followed by a return
to normal values later in pregnancy. While Mag-
netic Resonance (MR) studies have shown no
change in the diameters of intracranial arteries
throughout pregnancy, transcranial Doppler investi-
gations indicate that cerebral perfusion pressure in
the middle cerebral artery increases by over 50%
during gestation, returning to baseline values fol-
lowing delivery. Cerebral hemodynamic changes
have been suggested predate the development of
pre-eclampsia and may contribute to its pathophysi-
ology, possibly allowing early diagnosis (1214). In
addition, blood pressure near the normal range for
a non-pregnant patient may represent abnormal ele-
vation during pregnancy and should be carefully
548 NEUROINTERVENTIONAL MANAGEMENT
monitored as such changes may represent initial find-
ings of pre-eclampsia.
In contrast to arterial pressures, venous pressure
progressively elevates through pregnancy (15). This
elevation of venous pressure, combined with a decrease
in plasma proteins, may predispose to the development
of tissue edema. Despite the increased venous pressure,
venous compliance also increases during pregnancy (15)
resulting in slowing of venous flow and stasis within
the venous system.
As noted, a physiological anemia is present
throughout the majority of pregnancy. Additional
hematologic changes include increases in factors VII,
VIII, IX, X, XII, fibrinogen and plasminogen activator
inhibitors. Activated protein C resistance may occur,
as well as a decrease in a protein S activity. In
addition, levels of antithrombin III decrease, with the
lowest levels found in the third trimester. Overall
hypercoagulability results from the combined eleva-
tions of procoagulant factors and decreased effect of
coagulation inhibitors. The hypercoagulability is likely
exacerbated in the postpartum period as diuresis
begins to return blood volume to pre-pregnancy
levels. These changes may underlie or contribute to
the significant increases in venous thrombotic events
which are associated with pregnancy and are most
marked in the postpartum period (5,13,16). In addi-
tion, the physiologic hypercoagulability associated with
pregnancy may be synergistic to an otherwise asymp-
tomatic hereditary thrombophilia such as factor V
Leiden, prothrombin mutation (G20210A), or protein C
or S deficiency, further adding to a propensity for
intravascular thrombosis.
ISCHEMIC STROKE
Arterial infarct is the most common type of stroke
associated with pregnancy and the puerperium (17).
Estimates of ischemic stroke risk in pregnancy vary,
with reported ranges varying from 11 per 100,000 (18)
to as high as 13 times that expected outside of pregn-
ancy (19). James et al. noted an elevated stroke risk of
34.2 per 100,000 deliveries (20). Nevertheless, the actual
risk of pregnancy-related ischemic stroke remains
controversial and has been found to vary with the popu-
lation at risk. For instance, the stroke risk in African
American women has been found to be twice that of the
overall population of young women (21). Sharshar et al.
demonstrated the incidence of ischemic stroke in preg-
nancy (4.3 per 100,000 deliveries; 95% CI, 2.4 to 7.1)
differs little from that for all women of childbearing age
in occidental countries (22). In addition, Kittner et al.,
in a study of 46 hospitals in Maryland and Washington,
D.C., compared the incidence of ischemic and hemorrha-
gic stroke in pregnancy and 6 weeks postpartum to an
age-matched population of non-pregnant women (23).
They found that risk of cerebral infarction is increased in
the six weeks after delivery (relative risk = 8.7), but not
during pregnancy itself (relative risk = 0.7). James et al.
also noted a predominance of postpartum strokes with
nearly half of strokes (48%) occurring in the postpartum
period, compared with 41% at delivery, and 11% identi-
fied antepartum (20). Other investigators have also
shown the risk of ischemic stroke to be elevated in the
period immediately preceding and including delivery (24).
While reported incidence of ischemic stroke in the peri-
partum period varies, the majority occur in the late
third trimester and in the postpartum period.
Ischemic stroke in pregnancy and the puerperium
is extremely heterogeneous in its etiology (17,25,22,23,26).
Major causes of acute ischemic stroke include cardi-
oembolic stroke, stroke associated with pre-eclampsia
and eclampsia, cerebral vasculopathy, and miscellane-
ous causes. In addition, the high relative risk of ische-
mic stroke during the postpartum period suggests a
causal role for the large decrease in blood volume or
the rapid changes in hormonal status that follow deliv-
ery, perhaps mediated by means of hemodynamic,
coagulative, or vessel-wall changes (23). Lastly, specific
pregnancy-related disorders must be considered. There-
fore, in the peripartum patient, the large number of
potential ischemic stroke causes must always be included
in the differential diagnosis.
Cardioembolic stroke represents a significant
cause of stroke in young adults and in some studies
constitutes a considerable etiology for pregnancy-
related acute ischemic strokes. A significant number
of strokes, particularly in studies from Taiwan, are
associated with rheumatic heart disease, a relatively
uncommon cause in the United States and Europe
(25,26). Nevertheless, because cardioembolic stroke
may represent up to 25% of stroke in young adults,
consideration of cardiac disorders remains paramount
in evaluation of ischemic stroke in all young patients.
In addition, several cardiac conditions including pul-
monary vascular obstructive disease, Marfan syn-
drome with dilated aortic root, severe aortic stenosis,
and severe systemic ventricular dysfunction may
convey sufficient risk to advise that pregnancy be
avoided (27,28).
Peripartum cardiomyopathy is an established
risk for stroke during pregnancy and should be con-
sidered in pregnant patients with stroke and cardiac
failure. The condition is uncommon and its reported
incidence varies amongst populations, ranging from
1 in 299 births in Haiti (29) to 1 in 4,000 live births
in the United States (30). While the cause is unknown,
an autoimmune etiology has been suspected. Certain
populations, including older women and black
women are at higher risk. Presentation includes heart
failure due to left ventricular dysfunction with onset
in late pregnancy or the postpartum period occurring
in patients without pre-existing heart disease. Left
ventricular thrombus may be present, conveying a
high risk of acute ischemic stroke. The diagnosis is
one of exclusion (3134).
In older populations atrial fibrillation is rela-
tively common and is a major cause of cardioembolic
stroke in the elderly. However, atrial fibrillation in
young patients is relatively uncommon in the absence
of underlying structural heart disease. Atrial fibril-
lation in pregnancy, particularly if associated with
other cardiac symptoms including heart failure or
heart murmur should raise a question of cardiomyo-
pathy or rheumatic heart disease (35).
Infective endocarditis is uncommon in preg-
nancy. Nevertheless up to 65 percent of embolic
events in infective endocarditis involve the central
nervous system, and of all patients with infective
endocarditis, neurologic complications develop in
 NEUROENDOVASCULAR ASPECTS OF CEREBROVASCULAR DISEASE IN PREGNANCY
20 to 40 (36). Consequently, a high index of suspicion
should be maintained in pregnant patients presenting
with acute arterial infarcts or hemorrhagic stroke
which may be associated with risk factors or symp-
toms of infective endocarditis (37).
Uncommon cardiac causes of stroke have also
been reported in association with pregnancy including
coronary artery dissection (38,39).
Arterial dissection has been identified as the
cause of up to 8% of arterial ischemic strokes in preg-
nancy (17). Dissection usually involves the cervico-
cerebral arteries, most commonly the internal carotid
artery; however, vertebral artery dissection has also
been reported in association with pregnancy (40). Both
ischemic and hemorrhagic stroke may result from
pregnancy-related dissections. Known predisposing
factors include fibromuscular dysplasia, tortuosity of
the carotid arteries, and underlying connective tissue
disorders. An association has also been found with
reversible cerebral vasoconstriction syndrome and
reversible posterior leukoencephalopathy syndrome (41).
While straining at the time of delivery has been postu-
lated as a contributing factor, dissection has also been
reported after caesarian delivery and in association
with breast feeding (4245) (see chapter on dissection).
Although no large prospective studies regarding
thrombolysis in the pregnant patient have been per-
formed, both intravenous and intra-arterial thrombo-
lysis have been used for treatment of acute ischemic
stroke during pregnancy. While recent obstetric deliv-
ery is considered a relative contraindication, tissue
plasminogen activator (tPA) is not teratogenic and
does not cross the placenta (46). Nevertheless, concern
remains regarding the effect of thrombolytic medica-
tions on the placenta itself, possibly resulting in pre-
mature labor, placental abruption, or fetal demise (47).
Leonhardt et al. reviewed the use of thrombolytic
therapy in pregnancy including that for treatment of
acute stroke. They concluded that thrombolytic ther-
apy should not be withheld in pregnant patients in
case of life-threatening or potentially debilitating
thromboembolic disease (46).
Intra-arterial thrombolysis using tPA has also
been reported to successfully treat stroke during preg-
nancy (4850). While little data exist, the lower doses
utilized likely convey a decreased risk of systemic
hemorrhage which might be further lowered by the
use of mechanical clot lysis or clot extraction devices.
Consequently, it appears that similar to the case with
intravenous thrombolytic therapy, intra-arterial stroke
treatment should not be withheld from pregnant
patients when the benefits outweigh the potential
risks to the fetus.
HEMORRHAGIC STROKE IN PREGNANCY
Nontraumatic intracranial hemorrhages associated
with pregnancy carry significant morbidity and mor-
tality for both mother and fetus. Most common
causes of nontraumatic intracranial hemorrhage in the
pregnant patient include arteriovenous malformations,
aneurysms, and pre-eclampsia (see below). Conse-
quently, presentation with nontraumatic intracranial
hemorrhage should prompt a search for structural
lesions. Other less common causes should also be
549
considered including vasculitis, cavernous malforma-
tions, hematologic causes, and medications (17,51).
The incidence of perimesencephalic subarachnoid
hemorrhage during pregnancy does not appear
increased, although studies are limited (52).
Intracranial hemorrhage follows arterial infarct
and venous thrombosis as the most common stroke type
associated with pregnancy (17). Subarachnoid hemor-
rhage is a significant contributor to intracranial hemor-
rhage during pregnancy. Batemen et al. studied the
frequency, risk factors, and outcome of intracerebral
hemorrhage in pregnancy and the postpartum period,
comparing the rates of intracerebral hemorrhage (ICH)
in pregnant/postpartum with those of non-pregnant
women (51). The pregnancy-related ICH rate of 7.1 per
100,000 at-risk person-years was higher than the 5.0 per
100,000 person-years found for non-pregnant women.
Similar to the timing of ischemic strokes, most of the
increased risk was attributable to ICH that occurred in
the postpartum period. In addition, the mortality associ-
ated with pregnancy-related ICH was 20.3% and
accounted for 7.1% of maternal death. A number of
independent risk factors for ICH were identified includ-
ing advanced maternal age, African American race,
hypertensive diseases, coagulopathy, and tobacco abuse.
Sharshar et al. in a study of 348,295 deliveries also found
evidence that pregnancy is associated with an increased
risk of cerebral hemorrhage, most in the postpartum
period. The authors also emphasized the poor outcomes
associated with pregnancy-related ICH and identified
the most common etiology as eclampsia, followed by
cerebrovascular malformations and aneurysms (22).
Kittner et al. also found an increased risk of postpartum
hemorrhage, identifying a relative risk of 28.3 compared
with the non-pregnant state (53).
INTRACRANIAL ANEURYSMS
The most common cause of nontraumatic subarachnoid
hemorrhage is ruptured intracranial aneurysms. Aneur-
ysm rupture during pregnancy, similar to that in the
non-pregnant patient is associated with high rates of
rebleeding if left untreated and with high maternal and
fetal mortality (54). Outcomes have been related to mat-
ernal Hunt and Hess score at presentation (55).
While some have demonstrated no increased risk
in aneurysmal subarachnoid hemorrhage during preg-
nancy, labor, or the puerperium (56), others have shown
a period of increased risk for both subarachnoid and
intraparenchymal hemorrhage during late pregnancy
and the postpartum period (24).
Others have reported the incidence of sympto-
matic aneurysm in pregnancy to be in the range of
one in 1,10025,000, exceeding the risk of rupture in
non-pregnant patients. By some estimates, the risk of
aneurysm rupture during pregnancy is increased five
times that in age-matched controls, complicating up
to 0.05% of all pregnancies (5759). In addition, up to
50% of aneurysm ruptures in women under 40 may
be associated with pregnancy (60,61). While some
studies support an equal risk throughout pregnancy,
others suggest that rupture is more common in late
pregnancy (57,62). Many of the physiologic changes
associated with pregnancy, including an increase
cardiac output, blood volume and cerebral perfusion,
550 NEUROINTERVENTIONAL MANAGEMENT
have been suggested to predispose to the growth and
rupture of intracranial aneurysms during pregnancy (63).
The International Study of Unruptured Intra-
cranial Aneurysms (ISUIA) aimed to assess the natural
history of unruptured intracranial aneurysms and to
measure the risk associated with their repair (64).
While many aspects of the study have engendered
controversy, the results from this large study are
often useful in guiding management and counseling
patients harboring unruptured aneurysms. The ISUIA
results suggest a very low hemorrhage rate in the
short term for most small unruptured aneurysms
affecting the anterior circulation. Nevertheless, Marshman
et al. caution that pregnancy may represent a condi-
tion where extrapolation of ISUIA results suggesting
relatively low rupture rates for small unruptured ane-
urysms may be potentially inappropriate and may
underestimate rupture rates (65). This might be parti-
cularly relevant should risks progressively increase
throughout gestation as a result of the physiological
changes accompanying pregnancy. Consequently, many
pregnant women might feel that such risk justifies
small aneurysm obliteration, in some cases even prior
to attempting to conceive. Each case must be discu-
ssed on an individual basis (65).
Both surgical and endovascular treatment must
be entertained as management options for intracranial
aneurysms associated with pregnancy. Increasing num-
bers of reports documenting both decision-making and
technical aspects for successful endovascular treatment
of intracranial aneurysms during pregnancy and imme-
diately postpartum have appeared (54,6671). Indica-
tions for treatment have included rapid aneurysm
growth and acute rupture. Recommendation has also
been made for treatment of relatively large asympto-
matic aneurysms discovered during pregnancy (72).
Emphasis has been placed on the timing of treatment
with respect to delivery in late pregnancy including
the high early re-rupture rate of untreated aneurysms.
Under some circumstances emergency cesarean section
followed by aneurysm treatment has been recom-
mended (55). Anesthetic management during endovascular
coiling of pregnant patients including pathophysiol-
ogy, and perioperative management should also be well
understood by the anesthesiology team (73). In addition,
the risk of radiation exposure to the fetus must be
minimized by abdominal shielding, minimizing fluoro-
scopic exposure to the uterus, and low pulse frequency
settings. Studies indicate that with proper precautions,
even relatively prolonged endovascular cases can be
performed with acceptable risk to the fetus (65).
ARTERIOVENOUS MALFORMATIONS
As is the case in the non-pregnant patient, significant
morbidity and mortality is associated with arterio-
venous malformations (AVM) rupture during preg-
nancy (63). In addition, pregnancy may convey up
to four-fold increased risk of AVM rupture when
compared to the non-pregnant patient (74,75). How-
ever, more recent studies have cast doubt upon this
contention suggesting no increased risk during preg-
nancy (7678). Although based on limited data,
recommendations have been made that evaluation
and treatment of pregnant women with intracranial
hemorrhage due to rupture of an AVM should be sim-
ilar to that in the non-pregnant state. Cesarean section
has been recommended in some cases (79).
INTRACRANIAL VENOUS THROMBOSIS IN
PREGNANCY
Cerebral venous sinus thrombosis (Fig. 28.1) commonly
presents in the third decade, with a female predomi-
nance of 1.5 to 5 to 1 found in most studies (80). Preg-
nancy, particularly the postpartum period, clearly
represents a state of increased risk for intracranial
venous thrombosis, in some series constituting the
predisposing condition for up to 25% of cases (81,82).
The hypercoagulable and hormonal changes associated
with pregnancy have been suggested predispose to the
development of venous thrombosis throughout the
body, including the intracranial venous system (16).
Clinical presentation, diagnosis, treatment decisions,
and technique are more fully reviewed elsewhere in
this volume.
ENDOVASCULAR TREATMENT OF CEREBRAL
VENOUS THROMBOSIS
Similar to the case in the non-pregnant population,
endovascular treatment has been reported useful in
pregnancy-related dural sinus thrombosis. Indications
have included patients who progress or fail to respond
to medical therapy or those presenting with severe
neurological deficits (83,84). Techniques have included
endovascular administration of thrombolytic medica-
tion, mechanical clot disruption and clot removal
using rheolytic thrombectomy (83,8590).
PRE-ECLAMPSIA AND ECLAMPSIA
Pre-eclampsia and eclampsia are multisystem disorders
unique to pregnancy. They affect 5% to 8% pregnancies
and are responsible for up to 20% of pregnancy-related
maternal mortality (91). The condition represents an
important cause of both ischemic and hemorrhagic
stroke during pregnancy and the postpartum period
(17,22,23,26,92) and may initially appear during preg-
nancy or in the postpartum period. It is most common
during the first pregnancy and in pregnancies with
multiple gestations.
Clinical diagnosis of pre-eclampsia in an other-
wise healthy female is based on the appearance of
new hypertension and proteinuria at or after 20 weeks
gestation. The onset may also be associated with
severe headache, hyperreflexia, and visual disturban-
ces making it necessary to differentiate the condition
from other causes of intracranial hemorrhage which
may warrant consideration of neuroendovascular therapy.
Progression to eclampsia, which occurs in 12% of
severe pre-eclampsia, is indicated by the development
of seizures in a pregnant or recently delivered woman
that cannot be attributed to other causes. The cause
remains unknown; however, hypotheses focus on
abnormal placental function in early pregnancy
(91,93).
 NEUROENDOVASCULAR ASPECTS OF CEREBROVASCULAR DISEASE IN PREGNANCY 551

(A) (B)

Study

(C) (D)

Figure 28.1 Dural venous sinus thrombosis. A 19-year-old female 1 week postpartum with severe headache and papilledema. (A) Sagittal
T1-weighted images at midline and left parasagittal (B) demonstrate clot within superior sagittal sinus, straight sinus, and left transverse
sinuses (arrows). (C) Axial Fluid attenuated inversion recovery (FLAIR) image shows high signal intensity clot within left transverse sinus
(arrow). (D) Sagittal venogram shows absent flow in superior sagittal sinus (arrow).

HELLP syndrome, consisting of the combination
of hemolysis, elevated liver enzymes, and low platelet
levels, occurs in 4% to 12% of women with pre-
eclampsia or eclampsia. The condition is associated
with mortality of up to 25% with over half of dea-
ths being the result of intracranial hemorrhage or
stroke. Additional complications which may affect the
CNS include disseminated intravascular coagulation,
hypoxic-ischemic encephalopathy, and cardiopulmonary
arrest (94,95).
Pre-eclampsia and eclampsia share many imaging
features with posterior reversible encephalopathy
and hypertensive encephalopathy (Fig. 28.2). In fact,
approximately 10% of patients with characteristic imag-
ing features of posterior reversible encephalopathy
demonstrate these features in the setting of pre-eclampsia
or eclampsia (96). Neuroimaging findings include very
early MR changes of posterior sulcal hyperintensity and
leptomeningeal enhancement. These changes have been
described to precede the development of other changes
by days, suggesting the usefulness of contrast-enhanced
MR in the diagnosis (97). MR imaging shows T1 hypoin-
tense, T2 hyperintense areas primarily located in parietal
and occipital regions. Occasional involvement of deep
brain structures may be present. Most demonstrate no
evidence of diffusion restriction indicating areas of
vasogenic edema. Areas of diffusion restriction may be
present and suggest that areas of cytotoxic edema may
occur as well. Hemorrhage may also be present (98101).
Magnesium sulfate is usually given intravenously
to decrease the risk of seizures and management often
includes concomitant use of antihypertensives (93,102).
Currently, there is no role for neuroendovascular diag-
nosis or management of the spectrum of pre-eclampsia/
eclampsia.
REVERSIBLE CEREBRAL VASOCONSTRICTION
SYNDROME
The phenomenon of reversible cerebral arterial
segmental vasoconstriction was first described in 1988
and is also referred to as Call Fleming syndrome,
benign cerebral angiitis, or thunderclap headache (103).
When the condition is identified in pregnancy and the
puerperium, it has been referred to as postpartum
angiopathy (Fig. 28.3) (104106).
552 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 28.2 Posterior reversible encephalopathy syndromeeclampsia. A 36-year-old pregnant female with hypertension and new
onset seizures. (A) Unenhanced CT shows vasogenic edema pattern of bilateral occipital regions with less involvement of temporal
regions bilaterally. (B) T2 and FLAIR (C) images confirm bilateral involvement. (D) DWI shows no restricted diffusion. (E) Unenhanced
and enhanced (F) axial T1-weighted images show no hemorrhage and only minimal cortical enhancement.

Reversible cerebral vasoconstriction syndrome
(RCVS) predominately affects females between the ages
of 20 and 50 years. The syndrome has been associated
with several conditions characterized by elevated
female hormone levels including oral contraception use,
hormone treatment for infertility, pregnancy, and the
puerperium (107,108). A broad range of medications has
also been associated with the syndrome including
bromocriptine, phenylpropanolamine, pseudoephed-
rine, selective serotonin reuptake inhibitors, and other
vasoactive drugs (109). Other conditions associated
with RCVS include migraine, hypercalcemia, porphyria,
pheochromocytoma, and postcarotid endarterectomy (110).
Some cases have no apparent predisposing factors.
The etiology of RCVS is unknown; however,
the condition may share aspects of pathophysiology
which also underlie posterior reversible leukoen-
cephalopathy, pre-eclampsia and/or eclampsia, and
likely comprises a spectrum of disorders characterized
by prolonged but reversible, cerebral vasospasm
(105,108,111,112).
Patients with RCVS typically present with
sudden, severe, (thunderclap) headaches which
may persist for weeks prior to spontaneous resolu-
tion. Focal neurological deficits may develop from
ischemia caused by severe intracranial vasoconstric-
tion. Although deficits are most often transient they
may persist or only partially resolve. Death has rarely
been reported as a result of RCVS. Recurrence of the
syndrome appears to be exceedingly rare. The clinical
presentation shares features with a number of poten-
tially devastating neurological conditions which must
be excluded prior to making the diagnosis. These include
meningitis, encephalitis, vasculitis, cerebral venous throm-
bosis, arterial dissection, pituitary apoplexy, intracranial
hemorrhage and post subarachnoid hemorrhage vaso-
spasm (105,113,114).
Neuroimaging may demonstrate areas of focal cer-
ebral ischemia best seen on MRI. While not charac-
teristic, superficially located subarachnoid hemorrhage,
usually over the convexities, and intraparenchymal
hemorrhage have also been described (101,115).
 NEUROENDOVASCULAR ASPECTS OF CEREBROVASCULAR DISEASE IN PREGNANCY 553

(A) (B) (C)

(D) (E)

Figure 28.3 Postpartum vasculopathy. A twenty-four-year old female with severe postpartum headache. (A) Axial CT scan shows
subarachnoid hemorrhage involving region of incisura (arrow). (B) Axial FLAIR MR confirms subarachnoid hemorrhage in same area
as visualized on CT. (C) Lateral view of left vertebral artery injection demonstrates severe narrowing with cutoff of PICA (arrow).
(D) Left and right (E) carotid injections also demonstrate areas of abrupt narrowing (arrows) compatible with postpartum vasculo-
pathy. Two-month follow-up after treatment with calcium channel blockers (not shown) showed resolution of areas of narrowing.

Magnetic Resonance Angiography (MRA) and Com-
puted Tomography Angiogram (CTA) demonstrate
areas of segmental vasoconstriction involving any of the
intracranial arterial distributions. Angiography confirms
multiple segmental areas of vasoconstriction. Diagnosis
rests on resolution of the vasoconstriction as demon-
strated on follow-up neuroimaging, usually within 3
months of onset (103,110,
113,115,116). Transcranial Doppler may be useful in
following the course and resolution of vasoconstriction.
Treatment recommendations have included
removal of potential precipitating factors, blood
pressure control, and the use of calcium channel
blockers (113,114). Currently, except for angio-
graphic diagnosis, there is little role for endovas-
cular procedures in the management of RCVS.
However, a recent retrospective review found no
evidence of that calcium channel blockers improved
outcome or were superior to symptomatic treatment.
Glucocorticoids were ineffective in preventing
clinical deterioration and a trend towards worse out-
comes was noted with glucocorticoid treatment (117),
Currently, except for angiographic diagnosis, there is
little role for endovascular procedures in the manage-
ment of RCVS.
INTRACRANIAL NEOPLASMS
The incidence of intracranial malignant neoplasms
in the gravid patient may be 3.6 per million live
births (118). Tumor histology includes gliomas (both
high and low grade), meningiomas, melanoma meta-
stasis, epidermoids, hemangioblastomas, as well as others
(119,120). Presenting symptoms, as the general popu-
lation, may consist of signs of intracranial hyper-
tension, hemorrhage, or seizure (121). Hemorrhagic
lesions to be considered include melanoma and cho-
riocarcinoma metastasis (Fig. 28.4). Treatment strat-
egies should be tailored according to tumor grade
and location, fetal gestational age, and associated
554 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

(C) (D)

Figure 28.4 Choriocarcinoma metastases. A 29-year-old female with headache and multiple hemorrhagic lesions on unenhanced CT
(not shown). (A) Sagittal unenhanced T1-weighted image shows hemorrhagic lesion. Note incomplete rim of hypointensity. (B) FLAIR
image demonstrates edema while gradient image (C) confirms hemorrhagic nature of lesion. (D) Enhanced T1-weighted image shows
rim enhancement (arrow). Although superficially resembling a cavernous malformation, the incomplete rim of hypointensity, edema in
the absence of acute hemorrhage and enhancement indicates the metastatic nature of the lesion.

risk to mother and fetus (120). Several studies have
demonstrated low complication rates to mother and
fetus in properly selected patients (119,122,123).
CONCLUSION
In addition to the cerebrovascular disorders affecting
normal young adults, the pregnant patient is at risk
for conditions specific to pregnancy and the post-
partum period. Familiarity with these disorders, their
diagnosis and management is essential for neuroendo-
vascular decision making in the pregnant patient.
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 29
Percutaneous vertebral augmentation
Bryan A. Pukenas and Mary E. Jensen
INTRODUCTION
Vertebral body augmentation encompasses a group of
minimally invasive therapies that fortify vertebral body
insufficiency fractures due to osteoporosis, osteolytic
conditions, or minor trauma. Percutaneous vertebro-
plasty is the best-known augmentation procedure, with
a proven track record of safety and efficacy. A similar
procedure called kyphoplasty, also known as balloon-
assisted vertebroplasty, has recently gained popularity.
Evolving techniques such as lordoplasty and the uses of
new devices such as steerable needles, vertebral body
stents (Synthes, West Chester, Pennsylvania, U.S.),
deployable grafting systems (OptiMesh, Spineology,
St. Paul, Minnesota, U.S.), and permanent structural
implants (StaXx Fracture Repair System, Spine Wave,
Inc., Shelton, Connecticut, U.S.) are being promoted. The
fundamental goal of all these procedures is to provide
improved compressive strength to the vertebral body
and prevent its further collapse through the introduction
of a stabilizing material. The major clinical benefit of ver-
tebral augmentation is pain relief, the mechanism of
which is unclear. Other clinical benefits such as res-
toration of the vertebral body height and reduction of
kyphotic angulation have been suggested, although not
proven.
Although early vertebroplasty reports focused
mainly on its use in the treatment of painful vertebral
hemangiomas and bony metastases, the majority of the
current literature addresses augmentation procedures
in osteoporotic crush fractures, since these fractures
respond particularly well. This chapter will focus pri-
marily on the clinical and technical aspects of vertebral
augmentation in the treatment of osteoporotic and
malignant vertebral fractures.
BIOMECHANICS OF VERTEBRAL BODY
AUGMENTATION
The loss of substantive bone tissue from primary or
secondary osteoporosis, tumor erosion, or osteonecro-
sis may lead to vertebral collapse when the axial load is
more than the involved vertebral body can withstand.
Polymethylmethacrylate (PMMA), an acrylic polymer
noted for its excellent compressive strength (but poor
shear strength), has long been used by spine surgeons
for vertebral packing following tumor debulking (13).
During the PMMA preparation phase, liquid and pow-
dered acrylic components are mixed together to create
a dough, which is then used to fill the surgically
created void. The material cures in a matter of minutes
to form dense cement. The curing process is an exo-
thermic reaction, thus generating significant heat.
Extensive research on PMMA as a suitable material
for vertebroplasty has been published. Biomechanical
testing of PMMA injected into osteoporotic vertebral
bodies demonstrates an increase in the force by almost
200% to compress treated vertebrae when compared
with an untreated control group (4). Even when altered
by the addition of opacification agents or antibiotic pow-
ders (5), or by changing the monomer to polymer ratio
(6), the compressive strength easily surpasses that of an
unadulterated osteoporotic vertebral body. When verte-
brae are compressed past the point of initial failure,
injected specimens are more likely to resist continued
deformation than native vertebrae (7), thereby maintain-
ing spinal axis alignment. When PMMA is applied
directly to tumor tissue, the acrylic causes necrosis at the
PMMA/tumor interface, probably from direct cytotoxic
effects and tissue coagulation caused by the exothermic
polymerization process (8).
Despite the extensive biomechanical research that
has been published, the mechanism of pain relief asso-
ciated with vertebroplasty remains unclear. Many theo-
ries have been proposed. The mechanical, vascular,
chemical, and/or thermal effects of PMMA may cause
destruction of nerve endings in adjacent sensitive tis-
sues or incite tumor necrosis. Stabilization of microfrac-
tures and decreased mechanical stresses applied to the
affected vertebrae may also play a role (9). However, if
this vertebral strengthening effect is the cause of the
therapeutic response, one would expect to find the
degree of pain relief to be proportional to the total
amount of injected acrylic and the extent of vertebral
filling. To date, there has been no correlation between
pain relief and the volume of PMMA used (9), and the
physiological explanation of the analgesic effect associ-
ated with vertebroplasty remains obscure.
HISTORY OF PERCUTANEOUS VERTEBRAL
AUGMENTATION IN OSTEOPOROTIC
VERTEBRAL COMPRESSION FRACTURES
In 1987, Galibert et al. (10) described the percutaneous
application of acrylic polymer (PMMA) to vertebral
body defects associated with painful hemangiomas,
with resultant good control of pain. Other small series
followed with emphasis on the treatment of hemangio-
mas or metastases (1113). In 1991, the first report of
vertebroplasty in the osteoporotic spine was published.

Debussche-Depriester (14) reported five patients suffer-
ing from painful osteoporotic vertebral compression
fractures (VCFs), all of whom showed complete, imme-
diate relief of pain after vertebroplasty with no or mini-
mal residual discomfort.
Vertebroplasty was virtually unknown in North
America until the early 1990s; Dion and Jensen suc-
cessfully treated the first patient in the United States,
and the first article focusing on the technical aspects
of vertebroplasty was published in 1997 by the
authors (15). In this small clinical trial, 29 patients
with 47 osteoporotic VCFs, who had failed conserva-
tive medical therapy, underwent vertebroplasty.
Ninety percent of this cohort experienced significant
pain relief as evidenced by patients verbal expression
of perceived pain and analgesic use. In 1998, Dera-
mond et al. (16) reported the results of vertebroplasty
on 80 patients with osteoporotic fractures, with rapid
and complete relief of pain in greater than 90% of
cases. Follow-up of 1 month to 10 years showed pro-
longed analgesic effect, and only a single complication
was reported. Vertebroplasty was enthusiastically
accepted by interventional radiologists and embraced
by the elderly population.
On the basis of the positive outcomes seen with
vertebroplasty, kyphoplasty was introduced by Reiley,
an orthopedic surgeon. In 2001, Lieberman et al.
reported early clinical improvement of pain and func-
tion with this new alternative approach to VCF treat-
ment (17). As a result, kyphoplasty gained significant
popularity, primarily in the surgical community. Like
vertebroplasty, kyphoplasty involves the placement of
one or two needles into the vertebral body. An addi-
tional step consists of the placement of expandable bone
tamps within the vertebral body in order to create of a
cavity, with the intent of restoring vertebral body height
and minimizing kyphosis (17,18). With this procedure,
more viscous PMMA is injected into a known volume
of space. Although fewer complications have been
reported, disadvantages include the use of more com-
plicated equipment, increased cost (17), and although
not required, the frequent use of general anesthesia (18).
The first open prospective vertebroplasty study
was not published until 1999 (19); no control group
was used and the follow-up period ended at six
months. Since then, several retrospective (20,21) and
prospective non-randomized studies (2224) have
shown statistically significant improvement in pain
and function, particularly ambulation. These results
were confirmed in a prospective study using a conser-
vatively managed control group (25) and a prospective
randomized control study (26), also using a conserva-
tively managed control group. However, more recent
prospective randomized controlled trials have shown
similar improvements in pain and disability for osteo-
porotic compression fractures in both vertebroplasty
and sham procedure groups (27,28).
VERTEBROPLASTY IN OSTEOPOROTIC
COMPRESSION FRACTURES
In 1995, an estimated 700,000 vertebral fractures
occurred in elderly individuals as a sequela of osteopo-
rosis (29). The lifetime risk of a clinically detected VCF
is 15.6% for white females and 5% for white males (30).
PERCUTANEOUS VERTEBRAL AUGMENTATION 559
Osteoporotic VCFs most likely occur in postmeno-
pausal Caucasian and Asian females. Although the
majority of fractures result from age-related bone loss,
underlying factors that may contribute to osteoporosis
include steroid therapy, early oophorectomy, hypogo-
nadism in males, hyperthyroidism, chronic obstructive
pulmonary disease, immobility, anticonvulsant use,
smoking, and alcohol consumption. Twenty percent of
females and 40% of males presenting with vertebral or
hip fractures have one of these associated conditions
(31). Both low bone mass and a history of previous
fracture independently predict the risk of subsequent
fracture, with a seven-fold increased risk in females
with low bone mass and a 25-fold risk in females with
low bone mass and a single fracture (32).
A vertebral fracture may be defined as reduction
in vertebral height by 15% or greater, or classified by
degree and type of deformity (wedge, biconcavity, or
compression) (33). The most common locations for the
development of a compression fracture are the T8,
T12, L1, and L4 levels (34,35). The physiologic thoracic
kyphosis places the greatest axial load at T8, and the
thoracolumbar spinal junction is frequently affected
because of the change in mobility between the rela-
tively restricted thoracic spine and the more freely
moving lumbar vertebrae (34).
Although many fractures are asymptomatic, clini-
cally detected VCFs are associated with some degree of
pain in 84% of patients (36). Most fractures occur spon-
taneously (59%) (34), or are associated with trivial
strain or exertion (35). Pain is often described as intense
and deep, localized to the level of the involved verte-
bra, and exacerbated by palpation over the affected
site (35,36). Pain is often position dependent with
reduction or relief when supine, while weight bearing
or bending causes the most discomfort. In some cases,
pain may be referred to adjacent levels of the vertebrae
as far removed as four levels, or radiate to the flank or
along the ribs (35). Frank radicular pain involving the
legs is uncommon (35) and may be caused by foraminal
stenosis due to a retropulsed bone fragment or severe
vertebral collapse.
Pain associated with VCFs is usually self-limiting,
lasting from two weeks to three months. For this rea-
son, treatment of acute fractures has been largely con-
servative, with current medical therapy emphasizing
pain control using narcotic and/or anti-inflammatory
medications and bed rest (37). However, extended bed
rest and narcotic use in the elderly is not without risk,
and the decision to treat sooner rather than later should
be on the basis of the patients overall medical condi-
tion, degree of infirmity, and rapidity of improvement.
Surgery is rarely indicated, and internal fixation is
reserved for patients with gross deformity, instability,
or neurological deficits (38).
Local application of heating pads and ice packs,
massage therapy, or trigger point injections may be use-
ful. Other treatments, such as back bracing, physical
therapy, and exercise, are introduced once the patient is
capable of bearing weight. Patients should be evaluated
by their primary care physician, gerontologist, or endo-
crinologist for initiation of preventive medical therapy
[bisphosphonates, calcitonin, or if not contraindicated,
hormonal replacement therapy (HRT)] to prevent new
fractures.
560 NEUROINTERVENTIONAL MANAGEMENT
Quality of life and functional status are severely
affected by vertebral osteoporosis. Elderly females
with symptomatic fractures demonstrate significant
performance impairments in physical, functional, and
psychosocial testing when compared with a control
group with no fractures (39). A late consequence of
the disease is the development of progressive kypho-
sis, which may lead to chronic pain and disability,
decreased exercise tolerance, fear of falling, early sati-
ety, weight loss, and depression (36). Clearly, osteopo-
rosis of the spine and its clinical consequences are
important health care and public health issues that
deserve attention.
CONSEQUENCES OF CONSERVATIVE THERAPY
Before vertebroplasty, VCFs were essentially the only
fracture not treated orthopedically. As noted above,
initial treatment usually is conservative, consisting
of immobilization and narcotic analgesia. Although
conservative therapy implied safe, it is neither
benign nor risk-free, and its complications are well
documented (4042).
Narcotic analgesia, commonly used in conjunc-
tion with bed rest in the treatment of acute and
chronic nonmalignant musculoskeletal pain (40,43),
may lead to adverse drug reactions (ADRs) in over
70% of individuals, with the elderly more likely to
suffer severe ADR such as confusion.
Immobilization encompasses enforced bed rest,
use of braces or corsets, and pain causing protective
limitations of motion. During bed rest, virtually every
organ system is adversely affected, and these effects
tend to be more pronounced in older patients who
have less reserve than younger ones. Bone density
declines approximately 2% per week (40), with the
most dramatic changes seen in the first 12 weeks of
immobilization. Muscle strength declines 10% to 15%
per week and the rate of recovery from disuse is
slower than the rate of loss (41). Decreased endurance
is seen with a sense of fatigue and reduced patient
motivation, setting up a vicious circle of greater inac-
tivity. Muscle and ligament complexes are affected,
resulting in muscular shortening and contracture for-
mation (41). There is abundant evidence that early
active mobilization after initial stabilizationa benefit
of both vertebroplasty and kyphoplastyis the key to
contracture prevention. Early mobilization also leads
to the prevention of pressure sores, the prevalence of
which tends to increase significantly with age. Cardio-
vascular effects include increased heart rate, shorter
diastolic times, and reduced coronary blood flow.
Overall cardiac output, stroke volume, and left ventric-
ular function decline as well as cerebral perfusion (41).
Depending on the length of bed rest, it may take 20 to
72 days to restore pre-bed rest cardiac function.
The lungs suffer from decreased ciliary clearance,
less effective coughing, atelectasis, and a predilection for
pneumonia. Respiratory capacity decreases by 25% to
50% from deconditioning of the respiratory muscles and
restrictive impairment (42). In one study of patients
immobilized by pelvic fracture, the incidence of deep
vein thrombosis (DVT) was 61%, with proximal DVT
occurring in 29%. Pulmonary embolism is seen in 2% to
12% of patients and is fatal in 0.5% to 10% (44). Patients
are at increased risk of genitourinary calculus formation,
incontinence, urinary tract infections, and urosepsis.
Gastrointestinal effects include reduced appetite, consti-
pation, and fecal impaction, all exacerbated by the
administration of narcotics. Even the central nervous
system is not immune; patients at bed rest exhibit higher
levels of anxiety, depression, insomnia, and pain intoler-
ance (42).
A prospective study of 498 hospitalized patients
(70 years or older), low mobility (defined as bed rest
or ability to transfer to chair) and intermediate mobi-
lity (defined as ambulation one to two times with total
assistance) were independent predictors of several
poor hospital outcomes at discharge (45). When com-
pared with high mobility (defined as ambulation two
or more times with partial or no assistance) patients,
the low and intermediate mobility patients showed
decline in activities of daily living, new institutionali-
zation, and death. The contribution of low mobility to
these outcomes remained statistically significant in
multivariate analyses even after controlling for age,
sex, severity of illness, and comorbidities. In a study
of vertebroplasty in an affected inpatient population
(46), treatment facilitated a rapid discharge as well as
long-term improvement in refractory pain. In addi-
tion, vertebroplasty leads to greater decreases in anal-
gesic requirement when administered earlier in
hospitalization. A recent retrospective study compar-
ing kyphoplasty versus conservative therapy in the
Austrian population demonstrated 1.62 times greater
readmission rate and 1.09 times higher length of stay
in the conservatively treated group when compared to
the kyphoplasty group (47). In addition, Gerling et al.
demonstrated that cement augmentation of refractory
osteoporotic VCFs improves survival for up to two
years when compared to conservative pain manage-
ment, regardless of age, gender, number of fractures,
or comorbidities (48). In a study of the Medicare pop-
ulation, those with VCFs who underwent vertebral
augmentation had a 60.8% adjusted survival rate ver-
sus 50% in the conservatively managed group (49).
In short, conservative treatment leads to adverse
outcomes associated with low mobility and bed rest,
which may be viewed as iatrogenic events leading to
complications such as functional decline. Restoring mobi-
lity quickly and minimizing narcotic use should be major
goals of compression fracture therapy, and vertebral
augmentation has been suggested to be effective for both.
PATIENT SELECTION CRITERIA
The primary goal of vertebroplasty is to alleviate pain
and improve mobility; vertebral body stabilization for
prevention of further collapse is a secondary goal. Treat-
ment is directed toward affected patients who have
failed a reasonable course of medical therapy. Selection
criteria are outlined in detail in the American College
of Radiology (ACR) Standards Guidelines for the
Performance of Percutaneous Vertebroplasty (50). All
practitioners should be familiar with this documents
content. In short, appropriate candidates have been
noted to include patients with painful VCF refractory to
medical therapy, with failure defined as no or minimal
pain relief following the administration of prescription
analgesics for an unspecified time period; patients who

are unable to ambulate because of the pain; painful VCF
associated with osteonecrosis (Kummells disease) (51);
and unstable VCF that demonstrates movement at the
wedge deformity. Patients with multiple compression
deformities, who are at risk for pulmonary compromise,
gastrointestinal dysfunction, or altered center of gravity
if further collapse occurs, are also specified in the ACR
document, although no data to support this position are
available.
Absolute contraindications are few. Patients with
asymptomatic stable fractures or those who are clearly
improving with conservative treatment should not be
candidates. There is no evidence to support prophylac-
tic vertebroplasty in osteopenic patients with no acute
fracture. Systemic infection, osteomyelitis, uncorrect-
able coagulopathies, and allergic sensitivity to any of
the required components are other contraindicated con-
ditions. Although traumatic compression fracture of
nonosteoporotic vertebra is considered an absolute con-
traindication in the ACR guidelines, a recent study has
shown a positive clinical outcome from vertebroplasty
in patients suffering from thoracolumbar burst frac-
tures (52).
Relative contraindications are not defined and are
often operator specific. Patients with significant spinal
canal compromise from retropulsed fragments, verte-
bra plana, or chronic fractures may be candidates, but
relief is variable. Radicular pain or radiculopathy
involving the lower extremities is an infrequent finding
with VCFs, and an appropriate search for other com-
pressive pathology unrelated to the collapse should be
performed prior to vertebroplasty.
PATIENT SCREENING AND EVALUATION
A clinical coordinator, such as a nurse, nurse practi-
tioner, or experienced assistant, is invaluable for the
smooth operation of a busy vertebroplasty service. The
coordinator can collect pertinent information, such as a
pain history, other relevant medical conditions or
previous surgeries, current analgesic use, and radiolog-
ical studies, prior to scheduling an appointment. In
many cases, non-candidates are discovered early on
and can be redirected. Requiring a referral from an
individuals primary care physician also helps to elimi-
nate inappropriate patients who are self-referred.
Potential candidates for treatment should fulfill rele-
vant clinical and radiological criteria, and the informa-
tion should be appropriately documented in the
patients medical record. Inevitably, the practitioner
will be faced with the previously treated patient who
experiences a new VCF and demands an immediate
vertebroplasty. Following the same screening methods
used for evaluation of the initial fracture will ensure
that the practitioner considers all potential pathologic
processes prior to performing a second procedure.
History of Present Illness
A detailed history concentrating on the patients back
pain, mobility, relevant medication use (including anal-
gesics, steroids, bisphosphonates, calcitonin, HRT), and
general medical condition is obtained. Presenting symp-
toms, indications for the procedure, pertinent medical
and surgical history, a list of all current medications,
PERCUTANEOUS VERTEBRAL AUGMENTATION 561
history of allergies, and detailed documentation of failed
medical therapy are recorded. Use of visual analog
scales for determining pain level, dermatome drawings
for pain localization, or questionnaires are useful for
collecting data.
Patients with atypical back pain should be eval-
uated for a concomitant disease process. Any condition
that results in bacteremia, e.g., urinary tract infection,
may seed the spinal column resulting in discitis or epi-
dural abscess.
Neurological and Physical Examination
A focused physical and neurological examination to
identify painful vertebral levels and evaluate for possi-
ble radicular symptoms or neurological deficits is man-
datory. Sites of point tenderness to percussion or
palpation and positional trigger points are identified.
In patients with multiple acute or subacute compres-
sion fractures, the site of point tenderness often corre-
lates with the pain generator that should be targeted at
the initial treatment. A lack of preoperative spinous
process tenderness does not preclude clinical success of
vertebroplasty (53). Patients with diffuse or nonfocal
pain, low back pain that radiates to the hip or iliac
crest, or lumbar radiculopathy may have other pathol-
ogy such as facet or disc disease, which should first be
excluded. Evaluation of the patients ability to lie prone
without pulmonary compromise is recommended, par-
ticularly in individuals with known chronic obstructive
pulmonary disease. A detailed physical examination is
indicated when significant concurrent illnesses are
suspected.
Radiological Evaluation
Osteoporotic postmenopausal females with a docu-
mented new or subacute fracture on conventional
radiographs and who meet the clinical criteria may
proceed to vertebroplasty without other imaging.
Occasionally, plain films will show intravertebral gas-
filled clefts indicating the presence of avascular
necrosis (51,54). Kyphotic movement at the fracture
site on flexion/extension films also may be associated
with a cleft (55). Bony sclerosis and osteophyte forma-
tion are indicative of healed chronic fractures.
Adjunctive imaging is indicated in patients with
single or multiple fractures of uncertain age, when
serial conventional radiographs are unavailable, or
when a marrow-replacement disease process, such as
multiple myeloma, is suspected. For all practical pur-
poses, most patients have had magnetic resonance
imaging (MRI) as part of their diagnostic evaluation
prior to referral. MRI and/or bone scan imaging are
very useful for identifying active fractures (56,57) and
predicting outcome (54,5861). Uncomplicated VCFs
typically exhibit decreased signal on T1-weighted
sequences (Fig. 29.1A) and increased or inhomogene-
ous signal on T2-weighted sequences (Fig. 29.1B) (62).
Edema within the pedicle has been reported in both
benign and pathologic compression fractures, and is
not specific for malignancy (63). Fluid-filled clefts are
readily identified but their presence is underestimated
when compared to vertebroplasty findings, with only
50% of clefts seen on MRI (54). Subacute or chronic
562 NEUROINTERVENTIONAL MANAGEMENT
(A) (B)
Figure 29.1 T1-weighted sagittal image (A) shows low signal intensity involving the L3 vertebral body in addition to the inferior end-
plate of L5 and the superior endplate of L2. The corresponding areas on the T2-weighted image (B) show mild hyperintensity, which is
inhomogeneous. STIR sequence (C) clearly identifies edema at all three levels. Abbreviation: STIR, short-tau inversion recovery.
painful fractures may demonstrate normal (fatty) mar-
row signal intensity on T1-and T2-weighted images.
A limited MR study consisting of T1 (Fig. 29.1A)
and short-tau inversion recovery (STIR) (Fig. 29.1C)
sagittal images may be the only study needed to spot
vertebral body edema. Although MRI is sensitive for
the detection of acute compression fractures, the dura-
tion of vertebral body edema with respect to the pres-
ence of pain is unknown. Three recent studies (5961)
have correlated clinical outcomes with preprocedural
MR findings. Patients whose fractures showed exten-
sive bone marrow edema were more likely to exhibit
a positive clinical response to vertebroplasty than
those patients whose fractures did not display edema.
However, the lack of edema did not preclude a posi-
tive response, and these individuals should not be
automatically deemed ineligible for vertebroplasty.
Bone scans (Fig. 29.2) and MRIs are usually posi-
tive in the first three to four months, but bone scintig-
raphy has been shown to be more accurate than MRI
in the detection of older fractures (57). In patients sus-
pected of having active VCFs with no obvious acute
fracture on MRI, bone scintigraphy is often the next
study performed. In evaluating the use of scintigraphy
in preprocedural evaluation of patients being consid-
ered for vertebroplasty, Maynard et al. (58) found that
a high percentage of patients (94%) achieved nearly
(C)
complete pain relief after treatment of those levels
that showed increased uptake of tracer, even in
patients with multiple fractures of uncertain age. One
pitfall of bone scanning is that activity in chronic facet
disease may be confused with activity in a partially
collapsed vertebral body on a routine scan (Fig. 29. 3).
In these cases, SPECT scanning can localize the tracer
uptake within the vertebral body as opposed to the
adjacent facet joints.
In patients with complex or severe fractures,
computed tomography (CT) prior to vertebroplasty
may be used to evaluate the integrity of the posterior
wall of the vertebral body, to locate fracture lines
involving the vertebral body and pedicles, to detect
intravertebral gas-filled clefts, and to assess posterior
displacement of fragments (Fig. 29.4). Canal compro-
mise from retropulsed bone is not considered an abso-
lute contraindication provided there is no cord or
nerve root compression resulting in neurological
symptoms or dysfunction.
In ambiguous cases, fluoroscopic examination of
the painful sites may reveal an alternative explanation
for back pain. One common finding is in patients with
low back pain radiating to the hip who demonstrate
facet arthropathy and point tenderness over the joint.
Diagnostic facet injection can be performed first as
part of the screening process.

Figure 29.2 Anterior and posterior whole body bone scan images show intense focal uptake of tracer at the L4 level consistent with a
compression fracture.
Preprocedure Preparation and Counseling
Vertebroplasty is usually performed on an outpatient
basis. Important preprocedure instructions should be
given at the time of the evaluation or the night prior
to the procedure. Patients are asked to receive nothing
by mouth after midnight. Depending on operator pref-
erences, patients may take their morning medications
with a small amount of water. Transdermal narcotic
patches need not be removed, unless in the working
field. A responsible adult must be available to transport
the patient home after completion of the observation
period. Informed consent is obtained in all cases.
Risks cited should include infection, bleeding, frac-
ture, extravasation of acrylic into the surrounding epi-
dural or paravertebral veins resulting in worsening
pain or paralysis, pulmonary compromise, and death.
The potential need for immediate surgical intervention
should be discussed, and surgical backup at the time
of the procedure must be available. Preprocedural
PERCUTANEOUS VERTEBRAL AUGMENTATION 563
labwork includes a complete blood count, partial
thromboplastin time (PTT), prothrombin time (PT),
and international normalized ratio (INR).
Elderly patients often have chronic conditions
that require special consideration. When indicated,
preprocedure laboratory testing may also include elec-
trolytes and renal function, and sedimentation rate.
On an outpatient basis, individuals taking Cou-
madin can be given low-molecular-weight heparin
(LMWH) subcutaneously once or twice a day. LMWH
can be neutralized with protamine sulfate (64) at the
time of the procedure and immediately reinstituted on
its completion, followed by resumption of Coumadin
therapy. This process eliminates the need for a lengthy
hospitalization but requires coordination with the
patients primary care physician. It is important to note
that protamine sulfate does not fully neutralize the
anti-Xa effect of LMWH, even in excess (64).
Vertebroplasty should be avoided in patients
with known infections, fevers, or elevated white blood
564 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 29.3 Anterior (A) and posterior (B) bone scan images show increased tracer activity throughout the whole vertebral body at L3,
but focal uptake most notable overlying the posterior and lateral aspects of the vertebral hemispheres at L4. This patient was found to
have a new compression fracture at L3 and significant degenerative joint disease at L4 and L5.

(A) (B)

Figure 29.4 Coronal (A) and sagittal (B) reconstructions of a lumbar CT showing an intraosseous air-filled cleft with mild sclerosis
along the inferior border. Note the vertical fracture through the posterior third of the vertebral body with gas in the disc spaces and ret-
ropulsion of the posterior fracture fragment into the spinal canal. Abbreviation: CT, computed tomography.

count (unless due to steroid use). Patients with chronic
obstructive pulmonary disease or asthma may have dif-
ficulty in breathing when lying prone, and anesthesia-
managed conscious sedation may be required. General
anesthesia is usually not indicated, except in the unco-
operative or unstable patient.
TECHNICAL ASPECTS OF VERTEBROPLASTY
Different techniques have evolved on the basis of the
predominant European (16,65,66) and North American
(15,6769) experiences. Descriptions of the procedure
abound primarily in the radiology literature; variations
in technique are mostly minor and related to the avail-
ability of the products and equipment utilized, and the
operators training and personal style. However, there
is no substitute for hands-on experience, and inter-
ested operators are strongly encouraged to attend one
of the many educational courses currently available.
Equipment Requirements and Operator Skills
Needle placement within the vertebral body has been
described using standard fluoroscopy (15,16,65), CT
guidance (66,70), or CT fluoroscopy (71). Regardless of
the modality used to position the needle, acrylic injection
into the trabecular space is, in essence, a venous emboli-
zation and should be performed under continuous (72)
or intermittent (73) fluoroscopic observation. Operators
should strive to use the highest quality fluoroscopy
available, with multiple levels of magnification and
small focal spot sizes. Use of a biplane digital angiogra-
phy unit is ideal; biplane monitoring of fluoroscopic
images decreases procedural time and enables orthogo-
nal visualization of the acrylic injection. However, a
high-quality single-plane unit that can rapidly move
from the lateral to the anteroposterior (AP) positions
will suffice. Low-quality analog fluoroscopy portable
units are to be avoided as the image quality is usually
too poor for adequate visualization of bony landmarks
and acrylic flow.
In addition to a high-quality imaging chain, the
operator should possess appropriate cognitive and
technical skills to ensure quality and safety of the
study. These skills include but are not limited to
knowledge of the radiographic anatomy of the spine
and associated structures on both CT and fluoroscopy;
formal training in radiation physics, equipment, and
techniques to minimize exposure to self and patient;
skill in CT or fluoroscopic-guided biopsy procedures
of the spine, including radiographic triangulation; and
knowledge of proper embolization technique.
Patient Preparation and Monitoring
From start to finish, a dedicated nurse or other trained
professional, whose primary responsibility is to establish
and maintain venous access, administer conscious seda-
tion, monitor the patients physiologic status, and main-
tain the medical record, must be present. Treatment of
patients with decreased respiratory excursion when in
the prone position can be problematic because of unsat-
isfactory oxygenation. Patients with respiratory compro-
mise may require supplemental oxygen or anesthesia
support. Performing the procedure in the decubitus
PERCUTANEOUS VERTEBRAL AUGMENTATION 565
position or in a myelogram suite with the table tilted
and the patient semierect are other options. As with any
invasive procedure, equipment and medications for
emergency resuscitation should always be immediately
available.
The patient is placed prone on the angiography
table, and in addition to providing oxygen via nasal
cannula, physiological monitors including electrocar-
diography (EKG) leads; pulse oximeter; and blood
pressure cuff are attached. Additional conscious seda-
tion may be given in the form of fentanyl and midazo-
lam in small increments.
To minimize infection risk, the procedure is per-
formed under strict sterile conditions. All personnel
in the room don surgical caps and masks, and the
operators and their assistants wear sterile gowns and
gloves. The level to be treated is identified under flu-
oroscopy and marked, and the overlying skin surface
is sterilely prepped and draped. Since they are in
close approximation to the surgical field, the image
intensifiers are covered with sterile bags. Prophylactic
antibiotic therapy, either given intravenously and/or
mixed with the acrylic polymer, has been advocated
(15,16,6769).
Pedicle Targeting
The pedicle to be punctured is isolated under AP fluo-
roscopy. In the simple bulls-eye approach to the
pedicle, the fluoroscopic tube is either in a straight AP
position or obliqued slightly. In this approach, the
largest surface area of the pedicle is presented for tar-
geting and its entire cortical circumference is easily
seen. This approach is most likely to be used in the
upper and midthoracic vertebral bodies (Fig. 29.5) as
the pedicles jut posteriorly from the vertebral body at
a 90o angle in the axial plane. The needle is advanced
until its tip is positioned in the midportion of the ipsi-
lateral vertebral hemisphere. The use of a steerable
needle will often allow for acrylic filling of the entire
vertebral body via a single pedicle approach. If using
a bipedicular technique, the contralateral pedicle is
targeted in similar fashion.
Puncture of the pedicle using the more oblique
scotty-dog view will result in a steeper lateral-to-
medial needle track with the final needle position near
the midline of the vertebral body (Fig. 29.6). From this
location, it is more likely that a single transpediculate
injection will fill the central portion of the vertebra
between the pedicles, minimizing the need for a con-
tralateral puncture. This approach is more technically
challenging since the pediculate cortex is not as well
seen as it is in the bulls-eye view, and the surface area
is smaller, particularly in the thoracic spine. If the needle
is positioned too laterally, it may traverse the transverse
process or the thoracic cavity with subsequent fracture
or pneumothorax. However, the unipediculate approach
results in a shorter procedure time, diminished risk as
only one needle is placed, and better visualization dur-
ing injection since only a single injected bolus of acrylic
is observed (74).
With either approach, the puncture site should
avoid the medial and inferior borders of the pedicles.
Tracks in these locations can result in a breach of the corti-
cal wall and entry into the spinal canal or neural foramen.
566 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C)

(D) (E) (F)

Figure 29.5 The pedicle to be traversed is first anesthetized using a 25-G spinal needle (A, B). In this illustration, the anesthesia nee-
dle tip is slightly inferior, and the actual puncture site will be made higher on the pedicle to parallel the superior endplate fracture (C, D).
Note the difficulty in visualizing the inferior aspect of the pedicles on the lateral view (D) due to overlapping bony edges from the
ribs, and burnout from the lung fields. After vertebroplasty (E, F), the PMMA is noted to fill a cavity superior to the inferior endplate.
Abbreviation: PMMA, polymethylmethacrylate.

Once the angle of approach is determined, the
skin, subcutaneous soft tissues, and pediculate perios-
teum are anesthetized with 7 to 10 cc of bupivacaine
hydrochloride (0.25%) (Abbott Laboratories), using a
2-inch, 1825-guage spinal needle (depending on oper-
ator preference). Prior to removing this needle, AP
and lateral fluoroscopy should show the tip of the
needle approximating the same location on the pedicle
in the superiorinferior plane. If there is a discrepancy
between the two and the patient is in the true lateral
position, then the AP tube should be adjusted in
either the cranial or caudal direction until the needle
tip approximates the same location on the pedicle as
on the lateral view. A small skin incision is made
with a number 11 scalpel blade to allow easy passage
of the vertebroplasty needle.
Positioning of the Needle
A variety of disposable vertebroplasty needles or tro-
cars are available for use, and there are no perform-
ance comparison studies among the different products
that might guide selection. These devices generally
range in size from 10 to 15G; injection of acrylic is dif-
ficult through smaller gauge needles, although 15-G
needles have been used particularly in the cervical
region. Important features for consideration include
the availability of different stylet tip shapes and
 PERCUTANEOUS VERTEBRAL AUGMENTATION 567

(A) (B) (C)

(D) (E) (F)

Figure 29.6 In the scotty-dog approach, the AP tube is obliqued approximately 208 (A). The needle is advanced through the pedicle (B)
and is positioned in the midline (C), in the anterior one-third of the vertebral body (D). In this patient, a large cavity was filled within the
central portion of the L4 vertebral body (E, F). A small amount of PMMA has decompressed into the needle track (arrow) but remains
within the vertebra. Abbreviations: AP, anteroposterior; PMMA, polymethylmethacrylate.

cannula sizes and lengths, radiolucency of the handle,
locking of the stylet within the cannula, and com-
patibility of the cannula Luer lock hub with various
injection devices and methacrylates. Specialty needles
are also available with beveled cannulas to direct
acrylic flow or with curved tips to reach specific loca-
tions in the vertebral body (Fig. 29.16A,B).
The needle is advanced until the stylet tip abuts
the cortical surface in the superior to midpoint portion
of the pedicle. Depending on the shape of the pedicle,
the needle should enter at the widest point, away
from the medial and inferior borders. With hourglass-
shaped pedicles, the operator may need to choose the
extreme superior or inferior aspect for entrance. The
angle of approach on the lateral view is determined
by the degree of endplate compression or anterior
wedging. Often the course of the needle will parallel
that of the superior endplate (Fig. 29.5D), in which
case the stylet tip position will begin more superiorly
on the pedicle. On the AP view, the needle should
traverse the pedicle and vertebral body from lateral to
medial (Fig. 29.5C); otherwise, it may abut or exit the
lateral wall of the vertebral body.
The stylet tip of the needle should be positioned
precisely before a cortical break is made. Positioning
is best made with a diamond-point stylet, as beveled
stylets have a tendency to slip off the pedicle. Once
the track is started, repositioning becomes difficult as
the stylet has a tendency to slide into the initial divot.
In this situation, changing the angle of approach by
rotating the AP tube slightly may present a better
entrance point, or the contralateral pedicle can be
used instead. A slight back-and-forth twisting motion
is used to advance the tip through the cortex, with fre-
quent fluoroscopic checks in both the AP and lateral
planes as the needle traverses the pedicle. Alterna-
tively, a small sterile orthopedic hammer can be used
to tap gently on the needle handle, advancing the tip
in small increments. Once within the trabecular bone,
less pressure is required to advance the needle and
568 NEUROINTERVENTIONAL MANAGEMENT
care must be taken not to pierce the endplates or ver-
tebral wall. Use of the single-bevel stylet often will
deflect the needle tip in the direction opposite to the
bevel, allowing minor adjustments in either plane.
The needle is advanced using continuous or intermit-
tent lateral fluoroscopy until the stylet tip is placed in
the anterior one-third to one-quarter of the vertebral
body. The closer the tip is to the midline on the AP
view, the further anterior it may be positioned on the
lateral view. Because the stylet tip projects beyond the
end of the cannula, the final cannula tip position will
be slightly more posterior.
Placement of a Contralateral Needle
Many experienced practitioners position a single nee-
dle in the midportion of the vertebral body and per-
form only a single injection of acrylic, filling the
midportion of the body (Fig. 29.6C). If the initial nee-
dle placement is within the lateral aspect of the hemi-
vertebra, the acrylic will more than likely remain in
the ipsilateral hemivertebra. The use of newer curved,
steerable needles makes complete unipedicular filling
of the vertebral body routinely possible. Those who
use straight needles often prefer to fill the entire verte-
bra at a single sitting and will place a second needle if
the initial fill pattern is deemed unsatisfactory or
incomplete. Whether this procedure is necessary for a
good clinical result is a matter of debate. An in vitro
study by Tohmeh et al. (75), evaluating PMMA aug-
mentation of osteoporotic vertebrae from a single or
bipedicular approach, showed no significant differ-
ence in height changes between either augmented
group; specifically, preferential deformation of the sin-
gle-side augmented group was not noted. In a retro-
spective clinical study by Kim et al. (74), use of a
unipediculate approach resulted in filling of both ver-
tebral halves from a single puncture site with no stat-
istically significant difference in clinical outcome from
that of bipediculate vertebroplasty.
The bipediculate approach presents unique chal-
lenges. One problem is the obscuration of the basiver-
tebral plexus during injection by overlapping needles.
Changing the lateral obliquity makes the visualization
around the single needle easy, but the presence of a
second trocar makes observation of this critical area
difficult. Waiting to place the second needle after
completion of the first injection is one solution, and if
acrylic fills the contralateral hemisphere, the second
injection is not needed. If both needles are placed at
the same time, the contralateral stylet remains in place
during the initial ipsilateral acrylic injection; other-
wise, the material will track through the trabecular
space and egress out the contralateral needle. The first
needle can be removed prior to injection of the second
hemivertebra. Another technical difficulty is observing
acrylic flow during contralateral injection because of
the presence of PMMA in the ipsilateral hemisphere.
Potential solutions include adding extra barium sul-
fate to the acrylic mixture used during the contrala-
teral injection so that it is seen through the ipsilateral
acrylic cast; using final images of the ipsilateral injec-
tion displayed on an adjacent monitor as a guide by
looking for acrylic extending outside of the existing
cast; or injecting under a combination of lateral and
AP oblique views. Use of road-mapping technique is
not advised as respiratory and bowel gas movement
makes precise visualization impossible.
The initial technical description of vertebroplasty
(15) advocated the use of vertebrography prior to
acrylic injection as a safety feature. Injection of small
amounts of contrast into the vertebral body confirms
the cannula location within the trabecular space, eval-
uates potential routes of acrylic extravasation, and
clearly defines the location of the basivertebral plexus,
which channels much of the vertebral venous outflow
into the anterior internal epidural venous plexus. On
the lateral view, the egress point of this plexus is seen
as a bony depression located anterior to the posterior
vertebral body margin between the pedicles, which
may not be easily visualized in osteoporotic bone. The
location of this vascular junction is critically impor-
tant, as extravasation of acrylic into the epidural veins
is the major cause of neurological complications in
vertebroplasty.
Controversy exists over the need for vertebrogra-
phy, particularly in the hands of experienced practi-
tioners (76,77). Gaughen et al. (78) retrospectively
evaluated the safety and efficacy of vertebroplasty
performed in two patient populations, one in which
venography was performed and the other without
venography. No significant differences in frequency or
amount of venous extravasation, or in clinical out-
come between the two groups were found. However,
this study was done at a major medical center by
senior interventionalists with extensive experience,
and its conclusions may not be valid for all operators.
In short, some operators may find the vertebro-
gram helpful, as it easily identifies the location of the
needle tip, visualizes the exact point where the basi-
vertebral plexus exits the vertebral body, outlines the
epidural and paraspinal venous system, and may
predict PMMA flow characteristics and possible sites
of egress (76). However, contrast that extravasates
through fracture lines into the paravertebral spaces
may obscure visualization and make injection of
PMMA difficult to see (Fig. 29.8B). The decision to
perform vertebrography either consistently, on a
case-by-case basis, or not at all is left to the individ-
ual operator.
Biomaterial Preparation
A variety of bone filler substances have been used in the
treatment of vertebral body disease. Currently there are
two biomaterials approved for use in vertebroplasty in
the United States: PMMA, and a non-resorbable bioac-
tive composite material (Cortoss, Orthovita, Malvern,
Pennsylvania, U.S.). There are several commercially
available PMMA products that are used for vertebro-
plasty, all with different handling characteristics. PMMA
consists of two componentsa fine-grained powdered
polymer and a volatile liquid monomer. When the two
substances are combined, an exothermic chemical reac-
tion begins that leads to progressive polymerization of
the mixture to its solid state. Cortoss consists of two
components as well a resin composition and a rein-
forcing particle composition. Users should be familiar
with cement characteristics prior to starting a vertebro-
plasty service. Bench testing is the recommended way to

evaluate the material to ensure that the resultant mixture
can be injected effectively through a needle and visual-
ized fluoroscopically. This testing is best done at a for-
mal course in which acrylic preparation and injection is
performed on either cadavers or anatomic models.
The major parameters of these biomaterials that
impact its use in vertebroplasty are polymerization time
and opacification. The polymerization time, or curing
rate, varies among the different products, and the slurry
may be suitable for injection from as little as 5 minutes
to close to 35 minutes. The polymerization time of any
PMMA can be prolonged by refrigerating the kit prior to
its use, cooling the procedure room, or by chilling the
prepared acrylic in an ice bath. The use of radiofre-
quency energy is another technique to alter polymeriza-
tion time. For acrylics with longer curing times, the
powdered polymer component needs to dissolve com-
pletely in the liquid monomer before injection. If
adequate solvation time (12 minutes after mixing) is
not allowed, the pressure from injection may cause the
monomer to leach out of the mixture, leaving a powder
plug in the cannula.
The second parameter of great significance is
opacification. As most clinically relevant complications
are due to the migration of acrylic into the extraoss-
eous spaces, fluoroscopic visualization of the material
during injection is of paramount importance. Visual-
ization is influenced by the amount of barium sulfate,
tantalum (79), or iodine (80) within the product, size
of the patient, location of the treated vertebral body,
and quality of the imaging chain. The percent of
radiopaque material varies between products, and
operators must be knowledgeable about their chosen
materials opacification characteristics. Sterile barium
sulfate for use in vertebroplasty is commercially avail-
able and users should be prepared to supplement
their mix with extra barium sulfate if necessary. Anti-
biotic powders for infection prophylaxis may be
added to the polymer (81). Added substances should
be thoroughly mixed with the powdered polymer first
to guarantee homogeneity of the slurry.
Certain caveats applyany alteration of the
manufacturers product or mixing instructions, either
by adding substances or changing the powder to
liquid ratio, may change the consistency and/or poly-
merization time of the material. Readers are cautioned
that any altered material is no longer FDA-approved.
Biomaterial Injection
Injection of the biomaterial slurry is performed using
either 1-mL Luer lock syringes or commercially available
cement delivery systems. The 1-mL syringes are inex-
pensive, require minimal storage space, and allow exqui-
site tactile feedback during injection, which improves
flow control; however, their use places the operators
hands close to or within the radiation field. Commer-
cially available injection devices are self-contained
systems, with a reservoir into which the PMMA is
loaded and a twist-type or trigger-activated plunger
that advances the material into the tubing. The systems
are attached to the cannula hub via high-pressure tub-
ing. Each turn of the plunger or pull on the trigger
delivers a consistent amount of acrylic through the can-
nula. Some newer systems also incorporate push button
PERCUTANEOUS VERTEBRAL AUGMENTATION 569
controls far removed from the working cannula. Injec-
tion devices increase the distance between the operator
and the X-ray tube, thus minimizing the dose to the
hands, especially in the AP plane (82). With a delivery
system, only a single connection of the tubing to the
cannula hub is necessary, resulting in less exposure of
the acrylic to the atmosphere and of the hubs Luer lock
threads to the acrylic. Unfortunately, the tactile feed-
back with delivery systems is diminished and the oper-
ator has to rely more on visual cues, such as crowding
of the barium particles in the cannula, to detect com-
promised acrylic flow. In addition, pressure buildup in
the system resulting in sudden expulsion of acrylic
from the cannula tip is more likely with injection devi-
ces than 1-mL syringes. Regardless of the system used,
operators should practice first on models or cadavers to
become familiar with the tactile feedback and visual
cues used during biomaterial injection.
The injection of biomaterial into the trabecular
space is an embolization procedure, and all injections
should be visualized using continuous or near conti-
nuous fluoroscopic monitoring. Some authors have
advocated injection of small aliquots (0.10.2cc) using
intermittent fluoroscopy (73,83). However, as with any
vascular embolization, direction of flow can shift sud-
denly as the embolization progresses. Small amounts of
material can move quickly into unintended vascular
spaces without recognition (82). Embolization of acrylic
to the pulmonary system is particularly problematic
because the material does not remain in the field of
view, and deposition into the lungs may not be sus-
pected until the patient becomes symptomatic. Further-
more, small aliquots are difficult to measure with
injection devices and the amount perceived to be deliv-
ered may be different from what is actually delivered
because of compliance in the system. Lateral imaging is
used primarily to ensure that epidural extravasation of
cement does not occur; intermittent AP fluoroscopy
monitors any lateral paravertebral extravasation. Both
AP and lateral imaging is used to assess for intradiscal
flow of biomaterial. As the acrylic exits the cannula, it
permeates the trabecular space, giving the appearance
of a concentrically expanding cloud (Fig. 29.7). Alterna-
tively, it may seep along intraosseous cracks, leak
through endplate fractures, or fill an internal cavity
(Fig. 29.6). In some instances, vertebral body expansion
with reduction of kyphotic and wedge angulation will
occur (Fig. 29.8) (8486). The cannula is withdrawn
slightly whenever injection becomes difficult, creating a
space for acrylic flow. When using an injector, forward
pressure is removed prior to needle withdrawal to
avoid sudden PMMA deposition into a new space.
Typically, the injection is terminated when the acrylic
reaches the posterior one-quarter of the vertebral
body to avoid embolization of the basivertebral plexus
(Fig. 29.7). Good pain relief occurs with filling of two-
thirds of the vertebral body (74), and overzealous
attempts at complete vertebral filling risks complication
for little clinical gain.
Failure of the acrylic to egress from the cannula
tip may be due to obstruction from bony trabeculae,
or from a blockage within the 1-mL syringe, injector
tubing, or cannula. Compaction occurs when contin-
ued injection against a relative obstruction forces the
liquid monomer out of the slurry. The resultant plug
570 NEUROINTERVENTIONAL MANAGEMENT

(A) (B)

Figure 29.7 Multiple adjacent compression fractures were treated at one sitting. All three needles were placed followed by sequential
PMMA injection. Note the cloud-like, wispy pattern of trabecular filling. The embolization is terminated when the PMMA reaches the
posterior quarter of the vertebral body. Abbreviation: PMMA, polymethylmethacrylate.

(A) (B)

Figure 29.8 This 70-year-old male presented with an acute wedge compression fracture of the L3 vertebral body (A). Following
filling of an intraosseous cavity with PMMA, the fracture is reduced and the height is restored (B). The density surrounding the
anterior inferior border of the vertebral body (arrows) is from contrast extravasation into the surrounding tissues during vertebrogra-
phy. Abbreviation: PMMA, polymethylmethacrylate.

will obstruct the cannula lumen, necessitating its
removal. Compaction is best identified by the lack of
movement of PMMA into the vertebra, with crowding
of the constrained barium particles within the can-
nula. If repositioning of the cannula tip slightly poste-
riorly does not result in better flow, then the syringe
or delivery system is disconnected and evaluated for
plug formation. If no obstruction is present, the can-
nula is cleared with the stylet under fluoroscopic
observation and injection resumes.
Small acrylic leaks through endplate fractures
are acceptable, but large amounts of PMMA within
the disc space may act as a wedge causing fracture of
the adjacent vertebra (87). If the acrylic preferentially
flows to a paravertebral or epidural vein, the needle is
repositioned more posteriorly and the material is
allowed to thicken. Injection is terminated if continued
venous filling occurs.
Occasionally, partially solidified PMMA will dis-
connect from the needle tip during withdrawal and
deposit in the subcutaneous soft tissues. This retained
fragment may become a source of pain or infection.
Decompression of PMMA along the needle track has
been seen with needle removal after filling large intra-
osseous cavities. Several techniques can be employed
to prevent subcutaneous deposition. Prior to needle
removal, a 360o twisting motion is performed to sepa-
rate any stream of acrylic that may be attached to the
material within the cannula dead space. The needle is
withdrawn slightly and the needle track is observed
for retrograde acrylic movement. It may be left in place
until the acrylic hardens as long as connection between
the intraosseous bolus and the needle has been broken.
If necessary, redirection and advancement of the needle
across the acrylic core will separate the two (88).
If inadequate filling of the vertebral body requires
a contralateral puncture, then the procedure is repeated
on the opposite side. Otherwise, the skin incision is
cleaned and dressed with small adhesive bandages,
and the patient is transferred to the recovery room for
further observation and care.
POSTPROCEDURAL CARE
In the outpatient setting, most post vertebroplasty
patients are observed for two hours prior to discharge.
Individuals remain supine for one hour and are grad-
ually allowed to sit up and/or stand over the next
hour under direct nursing or physician supervision.
Ambulatory patients are discharged to the care of a
responsible adult after recovery. In many instances,
patients experience some immediate pain relief either
from the residual effects of the local anesthetic or
from the procedure, or a combination of both. Patients
are advised that focal pain at the puncture sites is
common and may last up to 48 hours. Pain medication
may be taken as needed; however, they are encoura-
ged to gradually limit narcotic use so that efficacy
can be determined. Nonsteroidal anti-inflammatory
agents such as acetaminophen or ibuprofen may be
substituted.
Prior to discharge, patients are evaluated for chest
or back pain, new neurological dysfunction, dyspnea, or
other potential complications of the procedure. Most sig-
nificant complications are due to extraosseous acrylic
PERCUTANEOUS VERTEBRAL AUGMENTATION 571
deposition, and patients quickly become symptomatic.
Early recognition is vital so that appropriate treatment
can be instituted, and suspected complications should
be treated as emergencies. For this reason, immediate
access to CT scanning and surgical backup is an absolute
requirement for any vertebroplasty service.
Bandages placed over the puncture sites may be
removed the next day, and skin incisions are kept
clean and dry. Follow-up either by direct contact or
telephone interview should be done within 48 hours
and at 7 days following the procedure.
Patients are to notify the physician of redness or
discharge at the operative site, recurrent or new back
pain, chest pain, or shortness of breath, or unexplained
fever or neurological symptoms. Any new symptom
requires prompt clinical evaluation. New back pain may
indicate recurrent or new fracture, unrecognized facet
pain, or epidural abscess. Chest pain may be the result
of rib fractures or unsuspected pulmonary embolization
of acrylic. All neurological symptoms require immediate
CT scanning to search for misplaced PMMA, and sus-
pected osteomyelitis or abscess is best investigated
with MRI.
For people who have been immobilized for a long
period of time, a gradual increase of activity is recom-
mended. Some individuals who experience rapid clini-
cal improvement may attempt to return to full activity
only to develop new vertebral fractures or fall and
break a hip or a wrist. A short course of physical ther-
apy with continued use of a brace may be helpful.
Patients who are not receiving preventative medical
therapy are referred to endocrinology or geriatrics for
further evaluation and implementation of appropriate
treatment.
CLINICAL OUTCOMES
Hundreds of articles concerning vertebral augmenta-
tion have been published in the last 20 years and
numerous studies have addressed the clinical out-
comes of patients treated with percutaneous vertebro-
plasty. Most reports describe vertebral augmentation
as a successful therapy for the relief of the pain associ-
ated with VCFs caused by either osteoporosis or
tumor involvement. The earliest literature consisted of
small, retrospective, uncontrolled case series introduc-
ing the technique, and claiming excellent results for
the patients involved (1014). Since that time, larger
case series have been published (9,15,16,1924,53,58,
65,66,8991), most demonstrating immediate and con-
siderable improvement in pain and patient mobility
following treatment (15,16,1926). A prospective, non-
randomized study of 79 consecutive patients with
osteoporotic compression fractures, of whom 55 (70%)
were treated with vertebroplasty and 24 (30%) with
conservative therapy, the vertebroplasty group sho-
wed statistically significant reduction in pain and
improvement in physical functioning at 24 hours over
the conservative treatment group (25). In addition,
24% of the treated patients were able to cease all anal-
gesia after 24 hours compared to none in the conser-
vative treatment group.
A prospective trial of vertebroplasty versus best
medical therapy (26) examined 40 patients with acute
osteoporotic compression fractures who were
572 NEUROINTERVENTIONAL MANAGEMENT
randomized to vertebroplasty or conservative therapy,
with crossover for the medically treated group allowed
at six weeks. The vertebroplasty group showed statisti-
cally significant improvement in pain and mobility, and
reduction in medication use immediately after vertebro-
plasty. None of the patients randomized to medical
therapy showed significant improvement, and 16 of the
19 patients were offered vetebroplasty. This postmedical
therapy vetebroplasty group also showed statistically
significant improvement in all three parameters imme-
diately following the procedure. At 12 weeks, both
groups showed statistically significant durability of the
therapeutic response.
It is well documented that the natural history of
healing compression fractures is comprised of gradual
improvement in pain over 2 to 12 weeks with variable
return of function. What is not described as natural
history is sudden improvement in pain and return in
functionthe hallmark picture of a positive therapeu-
tic response with vertebroplasty. Most of the patients
enrolled in the initial vertebroplasty studies did not
undergo treatment until all noninvasive therapeutic
options had been exhausted. These patients acted as
their own internal controls, as vertebroplasty was per-
formed at a point in their clinical course in which if
improvement associated with healing were to occur, it
should have happened. It is therefore unlikely that the
rapid marked improvement in clinical findings follow-
ing vertebroplasty was associated with the natural
course of the disease.
It may also be argued that patients treated medi-
cally are just as likely to have a long-term positive out-
come similar to that of the treated population, a finding
noted in the Diamond study (25). However, equality in
long-term outcomes does not negate the early positive
effects of a successful vertebroplasty. The potential com-
plications associated with conservative therapy are more
likely to happen early in the course of a patients immo-
bilization, leading to physiological losses from which the
patient may not recover.
Another consideration is that the positive out-
comes seen in vertebroplasty are due to the placebo
effect. Most vertebroplasty reports have consistently
shown positive responses in the range of 80% to 90%
for osteoporotic fractures, regardless of cohort demo-
graphics, etiology of osteoporosis, geographic location,
or type of institution where the procedure was
performed. However, the recent INvestigational Verte-
broplasty Efficacy and Safety Trial (INVEST) trial, a
randomized controlled trial comparing vertebroplasty
versus a simulated vertebroplasty (sham) procedure,
demonstrated that improvements in pain and pain-
related disability associated with osteoporotic com-
pression fractures were similar between the two
groups (27). Many have cited flaws with this study.
Initially, a very low recruitment rate required liberali-
zation of the inclusion criteria. As a result, the study
was powered for statistical significance in two catego-
ries: a 3-point difference between groups on the
Roland-Morris Disability Questionnaire and a 1.5 dif-
ference on the visual analog scale. There was a higher
cross-over rate amongst the sham group compared to
the vertebroplasty group (43% versus 12%). The study
excluded the inpatient population with acute fracture
pain, and mandated four weeks of medical therapy
prior to enrollment, effectively excluding those with
subacute fractures (92). Acute compression fractures
usually heal within six weeks, but only 32 percent of
the subjects in this study were treated within that time
frame (93). Additionally, those with maximal back
pain tend to have greater symptom relief after verte-
broplasty (94), but they are also the least likely to par-
ticipate in a randomized study (93).
At the same time, Buchbinder et al. reported no
beneficial effect of vertebroplasty compared to a sham
procedure at 1 week, 3, or 6 months after treatment (28).
Like the INVEST trial, this study has also sparked
controversy in the literature. Due to low enrollment
rates, neither the INVEST trial nor the Buchbinder
study was powered to perform subgroup analysis (93).
There was inconsistent use of edema on MRI in both
studies to assess for acute fractures and neither study
contained a non-interventional control group (92). Frac-
ture morphology was also not described, and those
with gas-filled clefts and pathologic fractures are more
likely to have improvement in pain scores after verte-
broplasty (93). Both studies excluded patients with
pathologic fractures, a population who tend to experi-
ence more pain reduction after vertebroplasty (95,96).
Following the Kallmes and Buchbinder studies, the
VERTOS II (97) open-label randomized control trial was
published and examined whether vertebroplasty had
additional value compared with optimum conservative
pain treatment in patients with acute vertebral fractures.
This study demonstrated the importance of patient
selection when performing vertebroplasty. In patients
with acute osteoporotic vertebral fractures who had per-
sistent severe pain, vertebroplasty performed at a mean
56 weeks after onset of symptoms resulted in faster and
greater pain relief than did conservative treatment. Inter-
estingly, in more than half of the patients who initially
qualified for the study, pain spontaneously decreased to
bearable levels, with a visual Analog Scale (VAS) score
lower than 5 thereby precluding inclusion and perhaps
strengthening some of the arguments related to patient
selection in the Kallmes and Buchbinder studies.
Patients who underwent vertebroplasty experienced sig-
nificant pain relief and used a lower class of drugs than
did those receiving conservative treatment, and pain
relief was sustained throughout follow-up. In the conser-
vatively managed group, pain relief was slower and less
than with vertebroplasty, and pain treatment required
tended to increase during the first month. The authors
also noted that election of optimum pain treatment and
the psychological effect of care and daily attention
accounted for the decrease in VAS score in the conserva-
tive treatment group during the first week (97).
In summary, despite the overall general endorse-
ment in the literature, two recent randomized controlled
studies have demonstrated no benefit of vertebroplasty
over a sham procedure for osteoporotic VCF. One
open-label randomized control study has demonstrated
immediate and sustainable (at least to a year) pain
relief after vertebroplasty that is significantly greater
than that achieved with conservative treatment, at an
acceptable cost. Already, VERTOS IV, a randomized
sham control trial using the same strict criteria as the
VERTOS II trial is in the preliminary stages in an
attempt to assess pain relief compared to a sham inter-
vention in patients with an acute osteoporotic VCF (98).

TREATMENT OF VCFS ASSOCIATED WITH
NEOPLASTIC DISEASE
Malignancies involving the spinal axis are not uncom-
mon in the cancer population. Each year, approxi-
mately 5% of cancer patients will develop spinal
metastases, although not all will become clinically rel-
evant (99). Malignant cells may access the spinal col-
umn by direct extension from a paravertebral tumor
or via hematogenous, lymphatic, or perineural spread
(100). Pain arises from tumor impingement on nerve
roots or the spinal cord, or from periosteal irritation
caused by cortical erosion and vertebral collapse.
Treatment options include medical therapy, systemic
chemotherapy, radiation therapy, chemoembolization,
transarterial embolization, surgery, or a combination
of modalities. Radiation therapy is highly effective in
many patients, but relief may be delayed by two
weeks, and minimal if any bone strengthening is not
recognized for up to two to four months (101). Exten-
sive multifocal disease is most likely to be treated by
radiation therapy, or conventional medical therapy
consisting of immobilization and corticosteroid medi-
cation or narcotic analgesia. Conservative treatment
is associated with multisystem complications as dis-
cussed earlier in this chapter.
Unlike osteoporotic VCFs, surgery may be indi-
cated in selected individuals. Patients with compressive
neurological symptoms from single or adjacent level dis-
ease with a life expectancy of six months or greater are
often considered for surgical intervention. Most techni-
ques consist of anterior decompression and stabilization
by replacement of the affected vertebral bodies with
PMMA, with the addition of pedicle screws, cages, or
distraction rods as needed (13). However, there is a sig-
nificantly increased perioperative morbidity and mortal-
ity in surgical patients who have received previous
chemotherapy, radiation therapy, or steroids (2,3).
A variety of minimally invasive techniques have
been effective as primary or adjunctive treatment of vas-
cular metastases. Percutaneous transarterial emboliza-
tion may be used for preoperative devascularization
(102,103), delivery of chemotherapeutic agents (104),
and pain palliation (105,106) through shrinkage of tumor
bulk. Direct percutaneous puncture with instillation of a
cytotoxic material such as absolute ethanol (107) has
also been described. However, with the exception of sur-
gery, none of these therapies restore strength and stabil-
ity to the spinal column, and patients remain at risk for
vertebral collapse. Vertebroplasty of metastatic lesions
presumably palliates pain and provides structural stabil-
ity to the spine through the solidification of the osteo-
lytic lesion. In addition, there may be some cytotoxic
effect of PMMA that results in tumor necrosis and
shrinkage (108). In some patients, vertebroplasty may
facilitate surgery by providing stabilization of the ante-
rior column in an otherwise nonsurgical candidate.
Novel methods for palliation of neoplastic vertebral
lesions including injection of cement and samarium
(109) have also been described.
Patient Selection
Because of the variety of therapeutic choices available
to this patient population, the decision to treat is
PERCUTANEOUS VERTEBRAL AUGMENTATION 573
made by a multidisciplinary team and takes into con-
sideration the local and general extent of the disease,
the patients medical condition, response to previous
therapy, general state of health, and life expectancy.
In general, patients suffering from significant
focal, mechanical pain unresponsive to analgesia are
potential candidates for vertebroplasty (16,65,110,111).
Blastic metastases with an osteolytic component may
be considered for vertebroplasty. Patients with mini-
mal or no pain but impending or frank vertebral col-
lapse due to extensive vertebral involvement may also
be treated for spinal stabilization.
Absolute contraindications for vertebroplasty in
malignancies are the same as for osteoporotic VCFs.
Relative contraindications unique to neoplastic disease
also exist. In many of the early studies, patients with
cortical osteolysis were excluded from treatment for
fear of causing canal compromise (112); however, fur-
ther studies show that these lesions can be success-
fully treated provided there is no significant epidural
involvement (9,16). Extensive destruction and signifi-
cant collapse leading to height loss of 70% or more is
a relative contraindication. Severely compressed verte-
brae are technically difficult to treat, and compression
of the cord or nerve roots by displaced fracture frag-
ments and/or significant epidural tumor bulk may be
made worse with the injection of PMMA. Disease
involving the posterior elements cannot be treated
with PMMA; instead, vascular tumors may be injected
in a manner similar to that described for hemangio-
mas (113), with N-butyl cyanoacrylate prior to surgical
removal.
Imaging Evaluation
Spinal MRI is the most common study obtained in
patients with malignant disease. MRI is extremely use-
ful for identifying the extent of the disease, including
the location and number of involved vertebrae, the
presence of canal compromise, and the compression
of neural structures (Fig. 29.9A). However, MRI does
not adequately visualize the bony cortex, and CT is
better at defining the degree of osseous destruction
and cortical involvement (Fig. 29.9B) as well as identi-
fying displaced fragments that may encroach upon
the canal. In those who cannot undergo MRI, the
addition of intrathecal contrast in conjunction with
preoperative CT scanning may provide valuable infor-
mation about the presence of epidural disease. In
patients with severe vertebral destruction or lesions in
difficult locations such as the cervical spine, CT can
be utilized for treatment planning, needle placement,
and in some cases, acrylic injection.
Preprocedure plain films also play an important
role in lesion evaluation as it allows the operator to
assess the visibility of the bony cortex, particularly the
appearance of the pedicles. Since most vertebral
bodies are entered via the transpedicular route under
fluoroscopic guidance, poor definition of the pedicles
may alter the approach or necessitate the need for
needle placement under CT.
Patients with multiple myeloma or lymphoma
may have plain film findings identical to osteoporotic
patients (Fig. 29.14A). Individuals who present with an
osteoporotic fracture but who do not fit the clinical
574 NEUROINTERVENTIONAL MANAGEMENT

(A) (B) (C) (D)

Figure 29.9 This 65-year-old male with renal cell carcinoma was evaluated for acute back pain and was found to have an L1 meta-
static deposit on MRI (A). Note the marked tumor involvement of the vertebral body, and the left pedicle and lamina with epidural
extension into the left lateral recess. (B) CT confirms the osseous destruction and better demonstrates the cortical erosion at the lateral
recess. CT after vertebroplasty (C) shows PMMA within the tumor located in the vertebral body with extension into the lateral recess.
The needle track through the right pedicle was sealed with PMMA. Lateral plane film (D) shows the PMMA bulging into the spinal canal
(arrows). The PMMA within the needle track can also be seen (open arrow). The patient developed a radiculopathy that responded
completely to a short course of oral steroids. Abbreviations: MRI, magnetic resonance imaging; CT, computed tomography; PMMA,
polymethylmethacrylate.

picture of primary or secondary osteoporosis (e.g., most
males, African-American females) should be evaluated
with MRI and biopsy, if necessary.
Special Considerations in the Performance of
Vertebroplasty for Malignant Disease
The basic principles that guide the injection of acrylic
into osteoporotic VCFs also apply to neoplastic lesions.
However, there are certain technical issues that are
unique to the treatment of patients with tumor involve-
ment. Cancer-ridden individuals are often more uncom-
fortable in the prone position than osteoporotic patients
and may require large amounts of narcotic analgesia
or general anesthesia. In addition, these people are
more prone to infection as a side effect of chemo-
therapy or radiation treatments, and prophylactic intra-
venous injection of a broad spectrum antibiotic prior to
vertebroplasty is recommended. The addition of antibi-
otic powder mixed with the PMMA may also prove
beneficial.
As noted above, the traditional approach for
thoracic and lumbar vertebrae is via the transpedicular
route. However, with tumor involvement the bony
landmarks often are not seen, making the transpedicu-
lar approach problematic. One technique is to estimate
the location of the affected pedicle using the medial
and lateral borders of the adjacent pedicles as markers.
As long as the needle tip remains lateral to the
medial border of the adjacent pedicles, the needle will
not pass through the spinal canal. If the transpedicular
approach is not viable, the posterolateral approach for
lumbar or lower thoracic vertebrae or the intercostope-
dicular approach for upper thoracic vertebrae may
be used.
Unlike osteoporosis, the cervical spine is often
involved with malignant processes. The anterolateral
approach for cervical lesions may be done under fluoro-
scopic guidance alone (114) or with the use of CT.
Fluoroscopic visualization of the lower cervical verte-
brae may be difficult because of the overlying shoulder
density. Placement of the needle using CT guidance
allows the operator to observe and avoid major vascular
structures. Injection of PMMA under CT is problematic,
as the 3D movement of the acrylic cannot be adequately
monitored without excessive table movement. There
have been recent reports of injection of minute aliquots
of PMMA using CT-fluoroscopy (71,115). A study of 500
CT-guided vertebroplasties demonstrated a 30 day mor-
tality of 0.4% (pulmonary embolism in 1/251 patients)
and procedural-related morbidity rate of 2.8% (7/251
patients) (116). PMMA injection should be done under
continuous or frequent intermittent fluoroscopic moni-
toring whenever possible, and should not be performed
unless the posterior wall of the vertebral body can
be seen.
Vertebrography is not routinely performed in
neoplastic vertebrae. Unlike osteoporosis, the signifi-
cant cortical destruction and bony erosion present
with tumors lead to substantial leakage of contrast
into the canal and paravertebral spaces. Contrast can-
not be readily removed from these spaces and its
presence may obscure visualization, impeding or pre-
venting cement injection.
The larger vertebroplasty trocars (1011G) read-
ily accept smaller (15G or less) biopsy systems for
sampling of tumor, or a specialized vertebroplasty
trocar with a biopsy cannula can be used (Fig. 29.10).
Some authors advocate using small 15-G trocars for
acrylic injection of cervical lesions, or in vertebrae
with extensive destruction or extreme vascularity. Use
of small needles may decrease the risk of hematoma
formation or leakage of acrylic out of the needle
track.
Because of the variable density of tumor tissue rel-
ative to osteoporotic bone, the acrylic pattern may
appear spotty and discontinuous. One exception is mul-
tiple myeloma, where the affected vertebrae may fill in

Figure 29.10 This patient underwent a biopsy prior to vertebro-
plasty. Note the hollow cannula (arrow) extending outside of the
trocar. The biopsy cannula is inserted in place of the stylet when
the trocar is located at the posterior wall of the vertebral body.
The trocar is then advanced to the anterior third of the vertebral
body, the biopsy cannula is removed and the tissue core is
retrieved.
a similar manner as osteoporotic fractures. Hypervascu-
lar tumors may demonstrate free arterial flow through
the cannula once the stylet is removed, and the operator
should be prepared to deposit acrylic material within
the track during needle withdrawal to prevent excess
bleeding (Fig. 29.9C). There has been one reported case
of tumor displacement into the canal as a result of ver-
tebroplasty (117). The introduction of intrathecal con-
trast immediately prior to treatment may allow the
operator to identify tumor displacement during acrylic
injection.
Routine postprocedure CT scanning is recom-
mended in malignant lesions. Studies provide informa-
tion about the distribution of the acrylic (Fig. 29.9C)
and may show changes in position of the tumor mass,
cement leakage, intratumoral epidural cement, iatro-
genic fracture or hematoma, or other unsuspected com-
plications. It also provides a permanent record for
comparison to future studies.
PERCUTANEOUS VERTEBRAL AUGMENTATION 575
Vertebroplasty and Adjunctive Therapies
Radiation therapy is typically used concomitantly with
vertebroplasty (9,110,118,119). The timing of the radia-
tion therapy does not affect the vertebroplasty response
(118) and the radiation does not affect the integrity of the
acrylic. Most investigators advocate initial treatment
with vertebroplasty because of its immediate analgesic
effect and improved spinal stability (9,65,110,118), fol-
lowed by radiation therapy.
Transarterial or direct puncture embolization of a
particulate or liquid agent may be useful in reducing
frank epidural disease or posterior element involve-
ment. Recent reports of radiofrequency ablation of
tumor followed by vertebroplasty have shown positive
results in a small number of patients (120,121).
Clinical Outcomes
As noted above, percutaneous vertebroplasty was ini-
tially described in 1987 as a treatment for painful ver-
tebral hemangiomas (10). In 1989, Kaemmerlen et al.
reported the first series limited to 20 patients with
malignant disease (11). Eighty-five percent had sub-
stantial pain relief in less than 48 hours, and one com-
plication was reported. No recurrent local pain or
secondary vertebral body collapse was observed in an
average follow-up period of 2.8 months.
In 1996, Weill et al. (89) reported their experience
with vertebroplasty in 37 patients. Seventy-three per-
cent of patients had complete or marked relief in pain,
which remained stable at six months, and in 65% of
patients at one year. Recurrence of pain in five patients
was attributed to the development of adjacent meta-
static vertebral lesions. Five (13.5%) local complications
were notedthree patients developed sciatica and two
patients with treated cervical vertebrae experienced
dysphagia. Three patients were successfully treated
with steroid therapy, while one patient required surgi-
cal removal of epidural cement.
The same year, Cotten et al. (9) published a pro-
spective study focusing on patient outcomes in
37 patients with 40 involved vertebrae. The efficacy of
the treatment was evaluated by a different physician
from the one who performed the procedure, and the effi-
cacy criterion was the change in the pain score on the
McGill-Melzack verbal scale (05 scale). Patients were
evaluated at 48 hours, 3 months, and 6 months following
vertebroplasty, with a mean follow-up period of 4.2
months. All patients received radiation therapy 12 to 22
days following the procedure. Thirty-six patients (97.3%)
reported some pain relief within the first 48 hours; 13.5%
were pain-free, 55% showed substantial improvement,
and 30% were moderately improved. The extent of verte-
bral body filling was compared to the degree of pain
relief and no correlation was found. Of 40 vertebral
bodies, 29 (72.5%) demonstrated leakage of PMMA out-
side of the vertebral body, but the majority of leaks were
clinically silent. Three patients (8.1%) developed radicu-
lar pain from leaks into the neural foramen, and two of
these patients required decompressive surgery for relief.
The beneficial effects of vertebroplasty appeared to be
durable. All patients who were available for reevaluation
had sustained or increased pain relief at one month,
with 88.9% at three months and 75% at six months.
576 NEUROINTERVENTIONAL MANAGEMENT

In addition, no new or progressive vertebral collapse

was seen in the injected vertebrae.
Deramond et al. (16) reported their experience in
101 patients treated for spinal malignancies. Eighty
percent of patients had moderate to complete pain
relief following vertebroplasty, with a 10% reported
complication rate. Fifty percent of treated vertebrae
had osteolysis of the posterior wall, yet radicular pain
accounted for only 4% of the complications. The
remaining complications were associated with the
patients primary disease.
The North American literature on vertebroplasty
outcomes in metastatic lesions is not as extensive as the
European literature. In the first report by Barr et al.
(111), 8 of 48 patients suffered from metastatic disease,
of which 50% described substantial pain relief follow-
ing vertebroplasty. Seven of eight patients (87.5%) dem-
onstrated no further collapse of the treated vertebrae at
follow-up. In 2003, Fourney et al. (122) described a
larger series of 56 patients. Eighty-four percent of
patients noted marked or complete pain relief following
vertebroplasty or kyphoplasty, and no patient had wor-
sening symptoms or suffered a complication. Asympto-
matic acrylic leakage occurred in 9% of vertebroplasty
patients and none in the kyphoplasty patients. Median
follow-up was 4.5 months, and reductions in visual
analog pain scores remained significant up to one year.
In a systematic review of vertebroplasty in patients
with spinal metastasis, Chew, et. al. (72) found a serious
complication rate of 0% to 11.5%, and mortality for the
procedure ranged from 0% to 7%. All of these series
point out the difficulty in determining the efficacy and Figure 29.11 This patient complained of leg pain following verte-
durability of vertebroplasty in a patient population suf- broplasty done at an outside institution. CT showed PMMA within
fering from malignancies. Many patients are too ill to the L2L3 neural foramina bilaterally, causing nerve root com-
attend follow-up sessions or have died. Also, the addi- pression. The patient responded to steroid therapy. Note the
tion of radiation therapy or other concomitant therapies PMMA located within the paravertebral veins draining into the
cloud the picture as to the long-term benefits derived IVC (open arrow). Abbreviations: CT, computed tomography;
PMMA, polymethylmethacrylate; IVC, inferior vena cava.
from vertebroplasty. The initial pain relief easily could
be ascribed to the effects of vertebroplasty, but its role in
the durability of the pain relief versus that of the addi-
tional therapy remains uncertain.

COMPLICATIONS
The number of percutaneous augmentation procedures
being performed around the world is steadily increas-
ing. Neophyte operators are most likely to experience
complications during their learning phase. Complica-
tions are best avoided by awareness of the factors that
contribute to their occurrence. Often, it is the overzea-
lous quest for complete vertebral body filling that
results in complications (117).
The primary cause of a symptomatic vertebro-
plasty complication is the passage of acrylic into adja-
cent spaces via fracture lines or cortical destruction
(Fig. 29.9D), along the needle track, or into the epidural
and paravertebral venous complexes (9,16,65,110,118).
Acrylic material located within the epidural venous Figure 29.12 The history is unknown of this woman who pre-
plexus or foraminal veins may cause spinal cord or sented for a chest film. A midthoracic level vertebroplasty is seen
nerve root compression, with resultant radiculopathy or through the cardiac silhouette in addition to extensive pulmonary
myelopathy (Fig. 29.11). Migration of small amounts of PMMA in the apices and the right hilum. Lateral film (not shown)
PMMA through the epidural or paravertebral venous demonstrated six other vertebroplasty sites. Abbreviation: PMMA,
system to the pulmonary vasculature (Fig. 29.12) is usu- polymethylmethacrylate. Source: Courtesy of Jonas Goldstein,
ally without clinical significance, but symptomatic pul- M.D., Asheville, North Carolina, U.S.
monary embolus and death have been reported (123).
 PERCUTANEOUS VERTEBRAL AUGMENTATION 577

Perivertebral acrylic is usually asymptomatic, although

dysphagia from esophageal compression after a cer-
vical vertebroplasty for malignancy has occurred (118).
Acrylic within the disc space may decrease its cushion-
ing ability, leading to focal fractures at adjacent end-
plates (87).
More often than not, PMMA leakage is asympto-
matic, even in malignant lesions. Cotten et al. (9) demon-
strated acrylic leaks by CT, both venous and cortical, in
29 of 40 patients with osteolytic metastases or myeloma.
Most of these leaks were asymptomatic, but two of eight
foraminal leaks produced nerve root compression that
required decompressive surgery. In a later series, Cotten
et al. (65) reported that 1 patient, of 258 treated, experi-
enced spinal cord compression that required surgery. Of
13 patients with radicular pain, only 3 required surgical
decompressions, while 10 responded to local anesthetic
infiltration or medical therapy. Deramond et al. (16)
noted a single transient neurological complication in 80
patients with osteoporotic fractures. Review of all major
vertebroplasty series shows that the complication rate
ranges from 1% to 10%; Murphy and Deramond (110)
divided it further into 1.3% for osteoporosis, 2.5% for
hemangiomas, and 10% for neoplastic disease. Fortu-
nately, most patients with radicular symptoms respond
to anti-inflammatory or narcotic analgesics or local anes-
thetic infiltration. But if significant neurological compro- Figure 29.13 This 80-year-old female with a T11 compression
mise were to occur, surgical colleagues must be available fracture underwent vertebroplasty at an outside institution. Fol-
lowing the procedure, she complained of incontinence and leg
for immediate consultation or intervention. Vertebro-
weakness. Spiral CT with axial reconstruction shows decompres-
plasty should only be performed at sites where surgical sion of PMMA along the needle track through the subarachnoid
backup is available. space. MRI (not shown) demonstrated application of the PMMA
Complications also may occur from inappropriate along the lateral aspect of the conus. Abbreviations: CT, com-
needle positioning. Improper placement of the cannula puted tomography; PMMA, polymethylmethacrylate; MRI, mag-
tip within or near the basivertebral plexus places the netic resonance imaging.
patient at risk for deposition of PMMA into the epidural
venous plexus. Advancement of the needle through the
anterior vertebral body wall could damage the aorta or
inferior vena cava. Use of the paravertebral approach generalized association between acrylic injection and
may injure the intercostal or lumbar artery. Also, leakage systemic cardiovascular derangement (125).
of PMMA into the paravertebral space through the nee- One theoretical complication is thermal injury to
dle track is more common with vertebrae that are adjacent neurological structures during acrylic poly-
accessed through the vertebral body rather than the merization. There have been no clinical reports of this
pedicle. Transgression of the dura may lead to a sympto- phenomenon and its possibility appears unlikely on
matic cerebrospinal fluid (CSF) leak or decompression the basis of in vitro tests, which showed no significant
of PMMA into the thecal sac after cannula removal temperature rise in the spinal canal with vertebro-
(Fig. 29.13). Pneumothorax is a potential complication of plasty (126), and in vivo animal experiments, which
thoracic vertebroplasty. showed no spinal cord damage from PMMA located
Other complications that have occurred, as repor- adjacent to the dural sac in dogs (127).
ted in the literature or through personal knowledge, Exposure to methylmethacrylate and the radia-
include fracture of the transverse process or pedicle, tion used for its application are potential occupational
paravertebral hematoma, epidural abscess, pneumo- hazards to physicians, staff, and patients. Cloft et al.
thorax, rib fractures, CSF leak, seizure or respiratory studied the exposure of medical personnel to methyl-
arrest from oversedation, and acute disc extrusion. methacrylate vapor during vertebroplasty (128).
Severely osteoporotic patients may sustain rib fractures A vertebroplasty exposes the physician to less than 5
(15) or sternal fractures from lying prone on the proce- ppm (parts per million) of methacrylate vapor, well
dure table. Padding the table, performing the puncture below the allowable limit of 100ppm per eight hours
with the patient in the decubitus position, or advancing set by Occupational Safety and Health Administration
the needle through the bone with the use of a hammer (OSHA). Exposure to the patient and other personnel
may help to decrease the chance of a rib fracture. is presumed to be even lower as they are usually fur-
Hemodynamic compromise has been associated ther away from the acrylic mixing area. However,
with packing of the acetabulum with PMMA during hip even though vapor exposure is negligible, some peo-
replacement surgery. Transient systemic hypotension ple may experience an idiosyncratic reaction or
during acrylic injection in vertebroplasty has been asthma exacerbation in response to the pungent smell
reported (124), but a large retrospective study of the car- of the material. Radiation doses to the operator have
diovascular effects of PMMA in vertebroplasty found no already been described in the technical aspects portion
578 NEUROINTERVENTIONAL MANAGEMENT
of this chapter. When stringent radiation safety practi-
ces are followed, operators can perform up to 500 ver-
tebroplasties in a year before reaching the extremity
dose limit (82). Patient peak skin doses in vertebro-
plasty have also been studied (129). In 61 treated
patients, the mean peak skin dose was 684mGy, and
in only 1 patient did peak skin dose exceed 2Gy. At
no time did the peak dose ever exceed 3Gy even
though more than one level was treated in many of
these individuals.
New fractures following vertebroplasty often
occur and may represent the natural history of osteo-
porosis rather than a complication of the procedure.
However, the issue of increased risk for fracture at an
adjacent level has been raised in the literature. Grados
et al. (21) found a slight but statistically significantly
increased risk of vertebral fracture in the vicinity of
an augmented vertebra when compared to a vertebral
fracture in the vicinity of an untreated fracture. Lin
et al. (87) evaluated a small group of patients who
developed adjacent endplate fractures following verte-
broplasty and found a higher proportion than those
who did not have an acrylic leak into the adjacent
disc space. These results must be considered with cau-
tion as association does not necessarily mean causa-
tion, and avoiding treatment of fractures that involve
the endplate may change the clinical response (130). It
has been suggested that the location and degree of
height restoration of the treated level (131), or filling
of an intraosseous cavity (132) may play a role in the
development of adjacent fractures.
In summary, complications are most commonly
associated with (i) poor visualization owing to inad-
equate fluoroscopic equipment, poor patient coopera-
tion (the moving target), or unsatisfactory acrylic
opacification; (ii) operator error, such as inappropriate
patient selection; lack of knowledge of the radio-
graphic spinal anatomy, particularly bony and venous;
poor fluoroscopic-triangulation skills; unfamiliarity
with equipment, devices, and PMMA; and poor embo-
lization technique; (iii) lack of patient monitoring; and
(iv) improper aseptic technique. By recognizing and
avoiding these potential pitfalls, and thoroughly edu-
cating oneself prior to performing vertebroplasty, oper-
ators will markedly decrease their chances of causing a
significant complication.
KYPHOPLASTY
In 2001, a new technique for percutaneous augmentation
of osteoporotic VCFs called kyphoplasty was descri-
bed in the literature (17). In kyphoplasty, the vertebral
body is accessed in a similar manner as vertebroplasty,
but a balloon catheter (KyphX Inflatable Bone Tamp,
Kyphon, Inc., Sunnyvale, California, U.S.) is used to
create a space within the hemivertebra prior to acrylic
injection (Fig. 29.14). Kyphoplasty is quite similar to ver-
tebroplasty, differing only in the use of the balloon, and
has been referred to as balloon-assisted kyphoplasty.
Theoretical advantages of kyphoplasty over verte-
broplasty include the potential for vertebral body height
restoration, reduction of kyphotic angulation of the
spine, and lower rate of acrylic leakage into adjacent soft
tissues. The realization of these benefits, however, has
not been established in clinical studies.
Although several papers have been published
(133142), the clinical outcome data are not as extensive
as for vertebroplasty. The majority of the kyphoplasty lit-
erature addresses outcomes in the treatment of acute or
subacute fractures, usually defined as vertebral levels
that are edematous on MRI or show tracer uptake on
nuclear medicine studies. However, similar positive out-
comes in pain relief and improved mobility regardless of
fracture age have been described. In one study (140),
patients with fractures over four months old had nearly
as favorable clinical outcomes (87% response) as patients
with fractures less than ten weeks old (90% response).
However, most series describe a positive clinical res-
ponse rate that is very similar to what is seen in verte-
broplasty-treated populations. All these reports have
been hampered by the same methodologic flaws that
associated with the majority of the vertebroplasty litera-
ture. Recently, the FREE study (143) compared the effi-
cacy and safety of kyphoplasty versus conservative
therapy in patients with acute painful vertebral frac-
tures secondary to osteoporosis, multiple myeloma,
and osteolytic metastatic tumors. The authors noted
improvements in quality of life and disability measures
the kyphoplasty group, but differences in the two
groups diminished at one year. In addition, the rate of
subsequent fracture was numerically higher but not
statistically significant in the kyphoplasty group.
Complications associated with kyphoplasty are
similar to those seen in vertebroplasty. Six major com-
plications in 531 patients (1.1%) treated with kypho-
plasty were reported in a multicenter collection of
patients, four of which were neurological complica-
tion. Nussbaum et al. (144) evaluated vertebroplasty
and kyphoplasty complications reported to the FDA
and found a number of kyphoplasty complications
not reported elsewhere. Eighteen cases involving spi-
nal canal intrusion were reported, of which thirteen
cases required surgical decompression and five cases
resulted in permanent neurological deficit. Kypho-
plasty has also been reported to be associated with
adjacent fracture formation, occurring primarily
within a two-month window following the treatment
(145) (Fig. 29.15).
CONTROVERSIES IN VERTEBRAL BODY
AUGMENTATION PROCEDURES
The major controversy between kyphoplasty and verte-
broplasty groups relates to height restoration, kyphosis
correction, and safety. Currently, there are multiple stud-
ies that show improved height and reduced kyphosis
can occur with both techniques. There are no data to
support that these changes provide any additional clini-
cal benefit. Kyphoplasty proponents state that the risk of
PMMA extravasation is diminished due to the creation
of a cavity, thus making kyphoplasty safer than verte-
broplasty. However, studies have shown that the rate of
leakage is similar, and in both instances the rate of clini-
cal relevant complication due to leakage remains small.
Because of additional equipment, anesthesia, and
hospital costs, kyphoplasty has been estimated to cost
10 to 20 times more than vertebroplasty. It is possible
that certain subgroups of patients may drive more
benefit from one particular procedure. Features that
might affect choice of procedure include degree of
 PERCUTANEOUS VERTEBRAL AUGMENTATION 579

(A) (B) (C)

(D) (E) (E)

Figure 29.14 Kyphoplasty performed on a patient with a T12 compression fracture from biopsy-proven multiple myeloma. With the
exception of the superior endplate compression, the vertebral body looks normal. After positioning of the balloons (A, B) they are sym-
metrically inflated (C, D), resulting in lifting of the superior endplate (arrows). After the created cavities are filled with PMMA and the
cannulas are removed (E, F), the superior endplate returns to its original position. Abbreviation: PMMA, polymethylmethacrylate.

compression deformity, age of the fracture, and the
presence of neoplastic involvement, but the benefits of
kyphoplasty relative to vertebroplasty in such sub-
groups currently remain totally undefined. With the
considerable added financial expense of kyphoplasty,
a significant clinical benefit over vertebroplasty would
have to be proven to justify this cost.
Sacroplasty
Sacral insufficiency fractures are another cause of lower
back, hip, and leg pain in the elderly. These fractures
are usually difficult to diagnose as the symptoms are
nonspecific or radicular in nature, and the imaging
findings are less obvious than those found with VCFs.
Plain radiographs are often nondiagnostic or difficult
to interpret because of the curvature of the sacrum and
overlying bowel gas. MRI may show marrow edema,
and cortical disruption and bony sclerosis may be
detected on CT. The H-or butterfly-pattern of uptake
in the sacrum on bone scintigraphy is typical of frac-
tures of the body of the sacrum that involve the sacral
alae (146). Like vertebroplasty, medical treatment is
usually limited to immobilization and analgesics.
In 2002, Garant (147) first described sacroplasty.
A natural extension of vertebroplasty, sacroplasty,
involves the injection of acrylic into the sacral alar frac-
ture site under fluoroscopic control (148). The operator
is faced with unique technical challenges. The sacrum
is a thin, curved bone, and localization of the needle
tip with respect to the fracture line, the sacral foramina,
and the inner cortex on the pelvic side is often prob-
lematic. Poor visualization of the sacral foramina dur-
ing acrylic injection is a significant hazard.
When performed under fluoroscopy, the needle
is placed either through the dorsal cortex along the
short axis of the sacrum (147) or in the plane of the
long axis of the upper sacrum between the foramina
and the sacroiliac joint (149). Contrast injection to con-
firm trocar placement and positioning of 20-G Chiba
580 NEUROINTERVENTIONAL MANAGEMENT

Figure 29.15 This elderly lady underwent an L4 kypho-

plasty (A) and showed clinical improvement. Six weeks
later, she developed new back pain. Lateral plain film
(B) shows new compression fractures from T12
(A) (B) through L3.

(A) (B) (C)

Figure 29.16 Sacroplasty was performed for pain control on this patient with widespread multiple myeloma lesions. Both sacral ala
were injected. Various areas of involvement were injected from a single puncture site with the use of a (A, B) curved cannula (Cardinal
Medical, Inc., Chicago, Illinois, U.S.). Coronal CT reconstructions following sacroplasty (C) shows PMMA throughout the sacral ala with-
out compromise of the neural foramina. Abbreviation: PMMA, polymethylmethacrylate.

needles at the sacral foramina for localization may be
useful safeguards (147). Placement of the trocar under
CT guidance with acrylic injection under direct fluoro-
scopic visualization (148,150) or performance of the
entire procedure under CT fluoroscopy (151) has also
been described.
Acrylic injected along the short axis has a ten-
dency to pool as a round collection at the needle tip
with only a short length of PMMA deposited along
the fracture (149). Placement of needles at each sacral
segment may be required to adequately fill the frac-
ture (147,148). As the injection is viewed in a frontal
oblique view, extravasation into the pelvis may not be
detected. The long-axis approach places a vertical col-
umn of acrylic along the fracture line. With this
approach, only one needle per sacral ala is needed.
Since the ventral border of the sacrum is visualized
during the lateral injection, extraosseous extravasation
is more readily identified (149). With either approach,
acrylic is deposited along the track from anterior to
posterior in the short-axis approach and from superior
to inferior in the long-axis approach.
In the case studies and small series reported to
date (147,148,150,152), almost all patients reported
marked or complete relief of pain following sacroplasty.
This technique has also been used in sacral fractures
associated with hemangiomas (153) and metastatic
lesions (152,154) (Fig. 29.16). Although technically more
challenging than vertebroplasty, sacroplasty is another
tool in the radiologists kit of advanced augmentation
procedures.
SUMMARY
Percutaneous vertebral augmentation has advanced
from an obscure technique reserved for a few special
cases to a highly utilized procedure that consistently
benefits a significant number of patients worldwide.
The practice of vertebral augmentation continues to
grow in size and scope, fostering new developments,
research, and products. While the recent INVEST (27)
and Buchbinder et. al. (28) studies have shown no sig-
nificant difference for vertebroplasty compared to a
sham procedure in osteoporotic VCFs, a more strin-
gent randomized sham-controlled study will further
assess the efficacy of this procedure in the acute set-
ting. Regardless, vertebroplasty and kyphoplasty have
been vital to the growth of minimally invasive spine
practices, and beneficial to suffering patients.
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 30
Neurocritical care management of endovascular patients
Monisha A. Kumar and Joshua M. Levine
INTRODUCTION
In order to best care for interventional neuroradiology
and endovascular neurosurgery patients, familiarity
with the procedures performed, the devices employed,
and the diseases treated is imperative. Neurocritical
care of the endovascular patient focuses on anticipation
and avoidance of complications coupled with post-
procedural hemodynamic stabilization, comprehensive
neurological evaluation, and integrated neuromonitor-
ing. It is a multidisciplinary effort involving inter-
ventional radiologists, endovascular neurosurgeons and
neurologists, neurointensivists, anesthesiologists, and
intensive care unit (ICU) nurses. Communication between
these individuals is vital to quality care of these patients.
Endovascular therapy is aimed at the treatment
of cerebrovascular disorders, head and neck neo-
plasms, and spinal vascular malformations. Employed
devices include microcoils, balloons, stents, embolec-
tomy devices, as well as embolic material such as
N-butyl-cyanoacrylate (glue), Onyx (Microtherapeu-
tics Inc., Irvine, California), and polyvinyl alcohol
(PVA) particles. Some of the patients may be com-
pletely asymptomatic from the diseases for which they
are being treated, while others may be neurologically
devastated. Awareness of potential hazards and post-
procedural complications facilitates good care of the
neurovascular patient.
Complications typically occur within the first 1224
hours after endovascular procedures (13). Much of the
ICU management is focused on serial monitoring to
pre-empt or mitigate potential complications. Ongoing
communication with anesthesiologists and the interven-
tional radiology team can alert the ICU team to irregu-
larities during the case and prepare them for imminent
crises. Post-procedural problems can be divided into
neurological, site-related, and critical care complications.
This chapter will begin with neurological complications
pertinent to treatments of different diseases, and then it
will discuss access site and critical care issues relevant
to post-procedure management. Treatment for many of
the post-procedural complications is largely supportive;
where specific therapies are recommended, they will be
discussed in detail.
NEUROLOGICAL COMPLICATIONS
Significant advances in non-invasive imaging have
obviated the need for diagnostic angiography in some
circumstances; diagnostic angiography is now reser-
ved for highly complex cerebrovascular cases. Despite
the increased complexity of endovascular patients,
the safety of neuroradiological procedures has impro-
ved steadily over the past several decades. A study
from Mayo Clinic reported a decrease in the rate of
neurological complications from diagnostic angiogra-
phy from 3.8% between the years 1980 and 1988 to
0.57% between the years 1997 and 2003 (3). Recent
advances, such as safer contrast agents, smaller cathe-
ters, hydrophilic guidewires, and digital imaging sys-
tems are likely responsible for the improved safety
profile of diagnostic cerebral angiography. Increased
opportunity for operator training and wider body of
experience may also contribute to improving compli-
cation rates.
The main neurological complications include
vessel perforation or rupture, intracranial hemorrhage,
arterial dissections, strokes, and transient ischemic
attack (TIA). In a study over 19,000 diagnostic angio-
graphic procedures spanning three decades, neurologi-
cal complications occurred in 2.3% of patients, of which
93% were transient (3). Stroke or permanent disability
occurred in 0.14% of patients and mortality occurred in
0.06%. Hemiparesis and aphasia were the most fre-
quently identified neurological symptoms. More recent
studies describe neurological complications occurring in
00.3% of patients undergoing diagnostic cerebral
angiography (46). However, one study observed silent
infarctions on diffusion-weighted imaging in 12/107
(11.1%) of patients (7).
Advanced age is a consistently identified risk factor
for neurological complication after cerebral angiography
(2,4,8,9). Other identified risk factors may include com-
orbid cardiovascular disease (2,9), longer fluoroscopy
duration (2,10,11), ischemic stroke indication (8,9,12,13),
and trainee-performed procedures (2,711). Interventi-
onal procedures, in contrast to diagnostic evaluations,
result in a higher likelihood of iatrogenic complications
(14,15). This is most likely due to an increased number of
manipulations, including catheter exchanges and micro-
catheter placement, longer procedural duration, as well
as a more distal site of catheterization.
Treatment of procedure-related stroke is focused
on restoration of distal perfusion. This may be
achieved by anti-thrombotic medications, local throm-
bolysis, or mechanical thrombectomy. If ischemia is
detected early, and the territory at risk appears large,
treatment may involve return to angiography suite for
 NEUROCRITICAL CARE MANAGEMENT OF ENDOVASCULAR PATIENTS
local thrombolysis and/or thrombectomy. Intravenous
tissue plasminogen activator (tPA) may be a thera-
peutic option for ischemic stroke within 4.5 hours;
however, it is contraindicated in those patients who
had an arterial puncture at a non-compressible site
within the previous seven days (16). Potential benefit
must be weighed against possible risks. Blood pres-
sure augmentation may be an alternative or adjunctive
treatment option. Administration of intravenous crys-
talloid solutions and vasopressor therapy may assist
in titration of blood pressure to improved neurological
function. Vascular and/or perfusion imaging may
guide treatment decisions.
The incidence of arterial dissection after diagnostic
cerebral angiography ranges between 0.14% and 0.3%
(4,5,13). Arterial dissections can result in either ischemic
injury or intracranial hemorrhage, though the vast
majority are clinically asymptomatic (3,6). If suspected,
vascular imaging can isolate the artery involved, deter-
mine the extent of the lesion, and identify the location of
dissection (intracranial or extracranial). Those resulting
in ischemic injury may be treated with aspirin alone if
mild, or may require acute endovascular intervention if
a large territory is at risk.
It may be difficult to differentiate significant vas-
cular occlusion from intracranial bleeding; although
depressed mental status and headache may herald hem-
orrhage. Urgent brain imaging with computed tomogra-
phy (CT) is mandatory for any patient with a
neurological decline in the ICU after an endovascular
procedure. Emergent endotracheal intubation and
mechanical ventilation should be performed if the
patient is unable to protect his airway. For patients with
intracranial hemorrhage, reversal of anticoagulation is
imperative; in the case of heparin administration, treat-
ment with protamine (1mg for every 100 U of initial
heparin dose) should result in normalization of the acti-
vated partial thromboplastin time (aPTT). Complications
of protamine administration may include anaphylaxis,
hypotension, and pulmonary hypertension.
Arteriovenous Malformations
Approximately one-half of patients with brain arteriove-
nous malformations (AVMs) present with intracerebral
hemorrhage, although patients probably present more
commonly with seizures (1720). Controversy exists
about the true risk of AVM rupture (21); lifetime risk
has been estimated by subtracting the patients age
from 105 (22). The only prospective study to determine
hemorrhagic risk cited a 2% annual risk of rupture;
however, the risk of rupture was significantly higher
among those patients who had bled previously (19).
Risk factors for rupture include increasing patients
age, deep brain location, and exclusive deep venous
drainage (19,2327). AVM size, multiple associated
aneurysms, perforating feeding vessels, and compro-
mised venous outflow are additional factors that may
contribute to the risk of rupture (2831). Posterior fossa
AVMs pose an increased risk of hemorrhagic presenta-
tion and well as increased mortality and morbidity
given their location (32).
Recent reports cite rates of persistent neurological
complications of 1.63% and mortality rates of 11.6%
(3335) from endovascular embolization. Intracranial
587
hemorrhage is the gravest complication from AVM
embolization; ICU management of post-procedural
hemorrhage involves understanding of the causes of
treatment-related bleeding.
The pathophysiological processes underlying post-
procedural hemorrhage are complex. The theory of
normal perfusion pressure breakthrough suggests that
sudden redistribution of blood that would normally
transit the high flow AVM is redirected to arteries of
the nearby brain parenchyma that have been chronically
depleted of blood flow. These arterioles, maximally
dilated as a result of chronic hypoperfusion, fail to vaso-
constrict after embolization has restored a more normal
flow pattern. Therefore, hemorrhage ensues from lack
of autoregulation. For this reason, treatment of AVMs
occurs in a gradual, staged fashion to best decrease the
risk of embolization-related hemorrhage.
An alternate theory suggests that capillaries prolif-
erate as a result of neovascularization; the increased
density of these often abnormal capillaries may predis-
pose to hemorrhage. Occasionally, with reduction of the
afferent high volume blood flow to the AVM from emboli-
zation, flow in the enlarged draining veins diminishes
and blood stagnates (36,37). This passive hyperemia and
local edema (38) may place the patient at extremely high
risk for venous infarction and hemorrhage.
Management of the post-embolization patient in
the ICU focuses on serial neurological examination,
blood pressure control, and intravascular volume man-
agement. Ensuring central head position and avoidance
of internal jugular vein catheterization may minimize
the risk of compromised venous outflow. Adequate
hydration may minimize the risk of venous thrombosis.
Ideally, procedure-related intracerebral hemor-
rhages are pre-empted or avoided. Pre-procedural single
photon emission computed tomography (SPECT) imag-
ing with cerebral blood flow (CBF) mapping may assist
in the identification of patients at risk for re-rupture
(39,40). Pre- and post-procedural imaging may identify
asymptomatic patients with localized edema, who may
have a higher risk of re-rupture from impaired venous
drainage. Optical blood flow measures, Xenon CT, trans-
cranial Doppler ultrasound (TCD) and CT perfusion
may help to identify the ideal blood pressure in individ-
ual patients. Frequently, however, systolic blood pres-
sure goals are arbitrarily set at < 140mmHg; for those at
high risk of re-rupture, it may be kept below 120mmHg
(or 90% of pre-procedural blood pressure). Short courses
of prophylactic anti-epileptic drugs and continuous elec-
troencephalographic surveillance may identify and treat
patients at risk for seizures, which are associated with
severe hypertension and may precipitate hemorrhage.
Ischemic stroke is another serious complication
of AVM embolization. Post-embolization flow shifts
can result in a cerebrovascular steal phenomenon and
result in ischemia. Ischemic stroke should be treated
as mentioned above, although treatment options may
be limited as these patients may be at higher risk of
bleeding.
Other complications of interventional AVM treat-
ments are rare. Glue embolization may cause perma-
nent adhesion of the microcatheter to the vessel wall
(41). Pulmonary emboli (PE) and acute respiratory dis-
tress syndrome (ARDS) have also been reported from
the use of embolic agents. The risk of PE is increased
588 NEUROINTERVENTIONAL MANAGEMENT
in high flow fistulas (4244). ARDS should be treated
according to ARDSnet protocol. Treatment options for
PE may be limited in the acute setting if anticoagula-
tion is contraindicated. Unexplained hypoxemia in
conjunction with a sinus tachycardia should prompt
CT evaluation of the chest for PE.
Dural Arteriovenous Fistulas
Dural arteriovenous fistulas (dAVFs), acquired artery
to vein shunts within the dura mater, constitute 10-
15% of intracranial AVMs. (45). Symptomatology is
location-based, and may include pulsatile tinnitus,
exophthalmos, cranial nerve palsies, and cognitive
impairment. Some patients may experience venous
infarction, hemorrhage or death. Carotid cavernous fis-
tulas (CCFs) are abnormal arteriovenous shunts
between the carotid artery and the cavernous sinus.
These lesions may occur spontaneously, or they may
develop after trauma, infection or sinus thrombosis.
Neurological complications may arise during and
after treatment of dAVFs because of anastomoses
between dural arteries and arteries supplying cranial
nerves and the retina. Sudden increased flow into the
superior ophthalmic vein or a cortical vein may lead to
visual loss or other neurological deficits. Sudden venous
occlusion may cause venous congestion, venous infarc-
tion, and hemorrhage. Ophthalmological consultations
should be obtained before and after treatment proce-
dures, or at the least in the event of a visual complaint.
Patients should be monitored for focal deficits in the
ICU after the procedure.
Spinal Vascular Malformations
Spinal vascular malformations are rare, but likely under-
diagnosed conditions that may result in progressive par-
aparesis. Mechanisms of spinal cord injury include acute
hemorrhage (either intramedullary or subarachnoid)
or subacute venous congestion leading to a progressive
myelopathy. Alternative theories include circulatory
steal phenomena, due to the space-occupying nature of
these lesions. Most are treated without incident and may
not require ICU-level care post-procedure.
The most serious complication of spinal AVM
embolization is spinal cord infarction. In this event,
patients should be transferred to the intensive care
unit. Patients with infarcts of the cervical or high thora-
cic spinal cord may warrant endotracheal intubation
and mechanical ventilation due to respiratory failure.
Blood pressure augmentation and CSF diversion with a
lumbar drain may preserve function in an ischemic but
not yet infarcted spinal cord. Selective hypothermia has
been reported to minimize motor loss in animal models
(46,47,) but is of unproven efficacy in humans. Patients
may experience neurogenic shock characterized by
hypotension and bradycardia. Hypotension should be
treated with IV crystalloid solutions and vasopressors
if needed. Bradycardia may be treated with atropine,
and if required, transcutaneous or transvenous pacing.
Patients may develop autonomic instability or
dysreflexia, a phenomenon characterized by discrete
episodes of flushing, diaphoresis, headache, and bra-
dycardia. Though more typical of traumatic spinal
cord injury, this may be seen in cervical and high-
thoracic spinal cord infarction. Symptomatic brady-
cardia should be treated with intravenous atropine or
epinephrine according to advanced cardiac life sup-
port (ACLS) protocol; prolonged sinus pauses may
warrant placement of a permanent pacemaker. Con-
sultation with cardiologist may help determine in
which patients pacemaker placement would be benefi-
cial. Care must be taken to avoid skin breakdown.
Patients should be log-rolled every 2 to 3 hours and
special beds may be ordered to prevent formation of
decubitus ulcers.
Cerebral Aneurysms
Endovascular treatment of intracranial aneurysms has
flourished over the last few decades. Level I evidence
supports endovascular treatment of ruptured cerebral
aneurysms (48). However, the management of unrup-
tured intracranial aneurysms (UIAs) is less clear. The
risk of rupture of an UIA depends on the size and
location of the aneurysm, patients age, history of prior
subarachnoid hemorrhage, (SAH) familial aneurysm
syndrome or other conditions that may increase the
likelihood of rupture. Complications associated with
instrumentation of cerebral vasculature can be grave,
and since most patients with UIAs are asymptomatic,
treatments should be safe.
In the International Study of Unruptured Intracra-
nial Aneurysms, aneurysm rupture occurred in 6% of
surgical patients; intracerebral hemorrhage and ische-
mic infarction occurred 4% and 11%, respectively (49).
Perioperative hemorrhage was 2% in the endovascular
cohort, and cerebral infarction occurred in 5%. In a
retrospective study of over 2,500 UIAs across multiple
centers, endovascular treatment was associated with
significantly fewer adverse events (13.2% vs. 6.6%,
p < 0.05) as compared to surgical intervention (15).
Surgical patients were more likely to have neurological
complications, cranial nerve palsies, mechanical ventila-
tion, red blood cell transfusions, gastrostomy, and post-
operative infections.
The procedural complication rate from endovas-
cular treatment of ruptured intracranial aneurysms
varies between 5.3 and 17.6% (5052). Complications
may include aneurysm rupture, thromboembolism, coil
migration, parent vessel injury, and post-treatment hem-
orrhage. Risk factors for increased rates of complication
include large aneurysm size, wide-neck morphology,
balloon remodeling, and stent deployment (51).
The ICU management of subarachnoid hemor-
rhage patients is quite complex and is summarized in
the following paragraphs. The early ICU pre-treatment
phase focuses on the prevention of re-bleeding. The
later ICU post-treatment phase is centered on treat-
ment of delayed cerebral ischemia (DCI) and other
potential medical and neurological complications.
The most threatening complication during the
early management period is aneurysmal re-bleeding; the
greatest risk occurs in the first 24 hours (48,53). Medical
measures, such as sedation, pain control, and blood
pressure reduction, are employed to minimize the risk
of re-bleeding until procedural treatment of the aneur-
ysm can be performed. Intravenous antihypertensive
medications commonly administered include nicar-
dipine, labetalol, and esmolol. When lowering blood
 NEUROCRITICAL CARE MANAGEMENT OF ENDOVASCULAR PATIENTS
pressure in patients with chronic hypertension or
elevated intracranial pressure, caution must be exercised
as aggressive measures may result in cerebral ischemia.
Blood pressure lability may itself result in aneurysm re-
bleeding as rapid changes in transmural pressure may
cause rupture. An early short course of antifibrinolytic
therapy (e.g., epsilon aminocaproic acid, tranexamic
acid) may reduce the rate of early re-bleeding without
incurring an increased risk of stroke (54).
Hydrocephalus occurs in 2030% of patients with
SAH (5557). It can occur at any point during the course
of the disease process. Intraventricular hemorrhage,
comorbid hypertension, posterior aneurysm location,
and high Hunt and Hess grade are risk factors for its
development (56). A ventriculostomy should be placed
when hydrocephalus is associated with an altered level
of consciousness as CSF diversion often leads to an
improved level of arousal. Rapid or frequent drainage of
CSF via a ventriculostomy prior to aneurysm treatment
should be avoided as it may result in transmural pres-
sure gradients across the wall of the aneurysm and may
increase the likelihood of re-rupture.
Although seizures are commonly associated with
SAH, their impact on the disease is not well defined.
Exposure to phenytoin is associated with poor long-
term cognitive outcome (58). It may be reasonable to
treat with prophylactic anti-epileptic drug (AED) prior
to treatment of the aneurysm, as a seizure-related surge
in blood pressure may result in re-bleeding. Once the
aneurysm is secured, discontinuation of prophylactic
AEDs may be considered, especially if continuous
electroencephalography (EEG) monitoring is available.
Cardiac complications of SAH are common.
Cardiac arrhythmias occur in 50100% of patients (59);
of these, 5% are life-threatening and should be treated
according to standard ACLS protocols. (60). A reversible
cardiomyopathy, neurogenic stunned myocardium,
occurs in 1331% of SAH patients (61,62). Reported risk
factors include female sex, younger age, smaller body
surface area, anterior aneurysm location, higher clinical
SAH grade, and prior cocaine or amphetamine use
(61,63). Presenting signs of neurogenic stunned myocar-
dium range from sinus tachycardia to frank cardiogenic
shock. Echocardiography should be obtained urgently
when this condition is suspected. Typical findings
include hypokinesis or akinesis of the apical segment of
the left ventricle with preservation of function at the
base (6466) (Tako-Tsubo pattern). spasm may be evident in patients who never manifest
Treatment of neurogenic stunned myocardium is
largely supportive as this condition is transient and
reverses within days (67,68). Cardiac catheterization is
not required as cardiac dysfunction is not due to coro-
nary artery obstruction. Administration of intravenous
crystalloids may suffice if symptoms are mild. Vasopres-
sors and/or inotropes may be used for more significant
cardiac dysfunction. It may be beneficial to opt for a
non-catecholamine inotrope, such as milrinone, as cate-
cholamines are implicated in the pathogenesis of the
myocardial injury. Dynamic left ventricular outflow
obstruction should be excluded prior to using inotropes.
Diuretics should be employed judiciously as volume
depletion is associated with poor outcome after SAH.
Intra-aortic balloon counter-pulsation may be considered
when cardiogenic shock is present and refractory to vas-
opressor therapy. Rare complications of neurogenic
589
stunned myocardium include left ventricular free-wall
rupture and formation of intracardiac thrombus.
Hyponatremia, often attributed to cerebral salt
wasting, occurs in 1030% of SAH patients and may
be associated with poor outcome (6971). Risk factors
for hyponatremia include hydrocephalus, anterior com-
municating artery aneurysms and poor clinical grade
(71,72). It is a hypovolemic hyponatremia resulting from
renal sodium loss. cerebral salt wasting (CSW ) is distin-
guished from the syndrome of inappropriate antidiuretic
hormone (SIADH) by determination of intravascular vol-
ume status, which is difficult in practice. Regardless of
the etiology, the treatment of hyponatremia in SAH
patients is administration of salt. Most cases can be
treated by enteral sodium chloride and intravenous iso-
tonic crystalloid. Fluid restriction should be avoided as
volume contraction has been linked to vasospasm
(73,74). Fludrocortisone may help correct the hyponatre-
mia and minimize the need for volume resuscitation (73).
After successful treatment of the ruptured aneur-
ysm, patients remain at risk for potentially devastating
cerebral ischemia. Narrowing, of the large arteries, or
angiographic vasospasm, is associated with DCI, pre-
sumably from reduced cerebral perfusion. Although
angiographic vasospasm and DCI are associated, not
all angiographic vasospasm results in DCI and not all
DCI results from vasospasm. Angiographic vasospasm
is seen in 2170% of patients, with a typical onset 35 days
after hemorrhage, maximal narrowing at 68 days and
resolution over 24 weeks (75,76). In about one-half
of cases, angiographic vasospasm is manifested by the
occurrence of DCI. DCI accounts for most morbidity
and 50% of mortality in patients who survive the initial
hemorrhage.
A wide variety of diagnostic tests exist to monitor
for vasospasm or compromised cerebral perfusion.
TCD is a widely used screening method for vasospasm.
It is a safe, portable, non-invasive tool that may be per-
formed repeatedly, even continuously, at the patients
bedside. Surveillance protocols may suggest alternate
day or even twice daily diagnostic examinations. The
chief limitation of TCD is that it measures CBF velocities
in limited segments of large intracranial vessels. Contin-
uous electroencephalography is a promising means of
detecting cerebral ischemia (74); however, the gold
standard for detection of arterial narrowing is catheter-
based cerebral angiography (77). Angiographic vaso-
clinical symptoms; in these patients, treatment may not
be warranted. Non-invasive angiographic techniques
including computed tomography angiogram (CTA ) and
magnetic resonance angiography (MRA) are being used
more commonly in lieu of catheter angiography for the
diagnosis of vasospasm (7880).
The use of novel diagnostic tests for the detec-
tion of DCI is becoming more widespread. Xenon CT
and SPECT provide quantitative blood flow infor-
mation (81,82). Near infrared spectroscopy (NIRS) can
be used to non-invasively estimate CBF through the
intact skull. Cerebral microdialysis (CMD) is a techni-
que which enables quantification and analysis of
markers of brain tissue ischemia, such as lactate, pyru-
vate, and glutamate as well as markers of cell injury,
such as glycerol (83,84). The partial pressure of brain
tissue oxygenation (PbtO2) may be monitored via a
590 NEUROINTERVENTIONAL MANAGEMENT
Clark-type electrode placed directly into brain paren-
chyma and may enhance diagnosis of DCI (85,86).
Hemodynamic augmentation to improve CBF is
the mainstay of DCI treatment; although its efficacy has
been studied with only one randomized controlled trial.
The main components of this therapy include induced
hypertension, induced hypervolemia, and hemodilution
(triple H therapy). Triple H therapy has been used
to treat DCI but should not be used prophylactically
(87,88). Avoidance of hypovolemia and hypotension
is clearly supported by the literature (89,90). However,
support for aggressive hypervolemia is less strong.
Induced hypertension using vasopressors for DCI has
been shown to be efficacious by a number of studies
(9193). Hemodilution is the least well-studied compo-
nent of triple H therapy. It is thought to result in rheo-
logical improvements in CBF; however, it may come at a
cost to cerebral oxygen delivery.
Intracranial hypertension should be treated
aggressively. Systemic and metabolic insults such as
fever, acidosis, electrolyte imbalance, hypoglycemia,
and hypoxia should be avoided and treated promptly
if they do occur. Infection, sepsis and the systemic
inflammatory immune response syndrome (SIRS) have
all been shown to increase the risk of vasospasm and
DCI (94,95). Efforts should be made to maintain serum
glucose within a normal range. Conflicting results
have been reported regarding the utility of intrave-
nous magnesium sulfate (9698). Optimal hemoglobin
concentration is unknown though both anemia and
red blood cell transfusion are associated with harm in
the SAH population (99,100).
The only medication that is known to reduce
the risk of poor outcome after SAH is oral nimo-
dipine, an L-type dihydropyridine calcium channel
blocker (101). Administration of 60mg of nimodipine
orally every 4 hours for 21 days is warranted unless
contraindicated.
Catheter-based treatments of cerebral vasospasm
are discussed in a previous chapter. Intra-arterial admin-
istration of vasodilators reverses angiographic vaso-
spasm and results in clinical improvement (102104).
The combination of intra-arterial vasodilators and
balloon angioplasty has been reported in the literature;
it is unknown whether combination therapy is superior
to either single therapy (105,106).
Many novel approaches to the treatment of cerebral
vasospasm and DCI are currently being evaluated. Sta-
tins may mitigate the development of a cerebral vasculo-
pathy. Free radical scavengers and endothelin-receptor
antagonists appear to reduce radiographic vasospasm
and DCI but have not been shown to consistently
improve outcomes (107109). Cisternal fibrinolysis with
urokinase has been shown to reduce vasospasm and
improve outcome, but further study is needed (110).
Treatment with high dose methylprednisolone to reduce
the inflammatory component of vasospasm did not
reduce the incidence of vasospasm, but did improve
functional outcome at 1 year (111).
Acute Ischemic Stroke
Endovascular management of acute ischemic stroke
focuses on timely recanalization of the occluded vessel
in order to reinstitute perfusion to ischemic, but
viable, brain tissue. Endovascular therapy is utilized
in approximately 0.3% of hospitalized acute stroke
cases (112). Interventional treatment has evolved sig-
nificantly over the past few years. Treatment of large
intracranial vessel occlusion still remains a challenge.
Outcome is primarily dictated by vessel recanaliza-
tion. Patients may be treated with local thrombolysis
and/or a wide array of mechanical thrombectomy
devices. Reports of mechanical thrombectomy with
fully recoverable intracranial stents are now being
reported in the literature (113).
The rate of symptomatic intracerebral hemorrhage
(ICH) (sICH) after systemic thrombolysis with IV tPA
is 6.4% (16). The reported rates of sICH after intra-arte-
rial thrombolysis alone vary between 10% and 15%,
and (114,115) the rates of sICH in trials of intravenous
followed by intra-arterial thrombolysis are 6.39.9%
(116118). The rates of sICH with embolectomy alone
are 9.9% (119) and intravenous tPA followed by
mechanical embolectomy are 6.7% (119). Intra-arterial
and combination IA/IV therapy have a higher risk of
hemorrhagic transformation than IV alone (114) as
these patients usually have larger strokes and get
treated later in their hospital course.
Abnormal hemostasis often excludes patients
from systemic thrombolysis, but these patients may be
candidates for interventional treatment. In a substudy
of the Multi Mechanical Embolus Removal in Cerebral
Ischemia (MERCI) trial, 35 patients with abnormal
coagulation profiles underwent endovascular interven-
tion for acute ischemic stroke and had similar rates of
revascularization (thrombolysis in myocardial infarc-
tion (TIMI) 2 to 3: 60% vs. 65%), mortality (40% vs.
38%), and sICH (8.6% vs. 8.5%) as compared to those
without abnormal hemostasis (120). However, those
patients with normal hemostasis had better clinical
outcomes overall likely due to a better state of general
health.
Intracerebral hemorrhage from hemorrhagic
transformation after interventional treatment is
associated with poor outcome (116,117,119,121124).
Major risk factors for hemorrhagic transformation
include a higher NIH Stroke Scale (NIHSS) score
and early signs of infarction on the pre-treatment CT
scan (122,125). Signs of intracerebral hemorrhage
may include decreased level of consciousness, head-
ache, vomiting, or worsening focal deficit. Acute
elevations in blood pressure may also herald neuro-
logical complication. The development of any of
these signs should prompt CT evaluation. Lab stud-
ies that should be concomitantly obtained include a
complete blood count, coagulation profile, and fibri-
nogen level. Treatment of a thrombolysis-related
hemorrhage should be initiated urgently. Creation of
a clinical practice guideline or treatment algorithm
for the reversal of thrombolysis facilitates adminis-
tration of blood products in a timely fashion. Cryo-
precipitate, fresh frozen plasma and/or platelets
should be administered to patients with a fibrinogen
level < 100mg/dL. Neurosurgical consultation should
be sought, although there is no clear indication for
surgical intervention.
Subarachnoid hemorrhage is a recognized but less
well studied complication of endovascular stroke ther-
apy. It may occur in up to 7.7% of intra-arterial therapy
 NEUROCRITICAL CARE MANAGEMENT OF ENDOVASCULAR PATIENTS
(IAT) patients (126). Risk factors for SAH include
rescue angioplasty after thrombectomy, distal middle
cerebral artery (MCA) occlusion and hypertension.
Treatment is supportive.
Malignant cerebral edema complicates 10% of
MCA territory strokes. One-third of patients with mas-
sive cerebral edema may experience neurological wor-
sening within the first 24 hours. The prognosis of MCA
strokes associated with malignant edema is poor, with a
mortality rate of up to 80% (127,128). Serial neurological
examinations are mandatory. In the event of neurolo-
gical decline, a CT scan should be performed urgently.
Rapid sequence intubation should be initiated if the
patient becomes less responsive and is unable to protect
his airway. Placement of an intracranial pressure (ICP)
monitor may be considered to guide osmotherapy.
Decompressive hemicraniectomy (DHC) should be con-
sidered in patients with massive MCA-territory infarc-
tion who are less than 60 years of age. DHC has been
studied in three European trials and in a pooled meta-
analysis (129). Two of the studies were stopped prema-
turely due in part to an evident benefit from surgery.
Indications for surgery are described in Table 30.1. Sur-
gery not only improves mortality, but also improves
functional outcome, regardless of which hemisphere is
involved (129). Time to surgery did not seem to affect
outcome, although the study was underpowered to
definitively address this issue. The probability of sur-
vival after DHC increased from 28% to 80% and the
probability of achieving a good functional outcome
(modified Rankin score of 3) doubled.
Anaphylactoid reactions and angioedema are
other important complications of thrombolytic therapy
with recombinant tissue plasminogen activator (rt-PA).
Patients should be intubated urgently. Emergent crico-
thyroidotomy may be necessary if the trachea cannot
be intubated (130,131). The incidence of rt-PA-associ-
ated anaphylaxis has been reported in up to 1.9% of
Table 30.1 Eligibility Criteria for the Pooled Analysis of Decom-
pressive Hemicraniectomy Trials
Inclusion Criteria
Age 1860
Symptoms suggestive of middle cerebral infarction (MCA)
infarction
National Institute of Health Stroke Scale score (NIHSS) > 15
Decreased level of consciousness or a score of 1 point on
NIHSS 1a
Infarction > 50% MCA territory by CT or volume 145 cm3 by
diffusion weighted image magnetic resonance image (DWI
MRI)
Inclusion within 45hr from symptom onset
Written informed consent by patient or legal representative
Exclusion Criteria
Pre-stroke modified Rankin score (mRS) 2
Fixed and dilated pupils
Significant contralateral ischemia
Space occupying hemorrhagic transformation ( parenchymal
hematoma 2 (> 30% of the infarcted area with significant
space-occupying effect, or clot remote from infarcted area)
(PH2))
Life expectancy < 3 yr
Other serious illness that could affect outcome
Known coagulopathy or systemic bleeding disorder
Contraindication to general anesthesia
Pregnancy
591
stroke patients (130,132,133). Rarely, rt-PA may cause
myocardial rupture or cardiac tamponade in patients
who have an acute coronary syndrome prior to or
concomitant with stroke (134).
A pre- and post-procedure NIHSS should be per-
formed for all patients admitted to the ICU with acute
ischemic stroke. Orotracheal intubation is warranted
in any patient with an altered level of consciousness
or with bulbar dysfunction and airway compromise.
Hypoxia should be avoided; patients with stroke
should receive supplemental oxygen. A clinical cardio-
vascular examination, cardiac enzyme laboratory tests
and a 12-lead electrocardiogram (ECG) should be per-
formed on all stroke patients (135). Continuous teleme-
try monitoring should be performed for at least 24
hours to identify atrial fibrillation. Patients with cardiac
or pulmonary dysfunction should receive X-ray evalua-
tion of the chest. Fever should be treated with antipy-
retic medications as it is associated with increased
infarct size, severity, and mortality.
The management of arterial hypertension during
the acute stroke period remains controversial. Current
American Stroke Association guidelines cite Level I
evidence recommending treatment of hypertension
(systolic blood pressure (SBP) > 185 or diastolic blood
pressure (DBP) > 110) prior to treatment with intrave-
nous tPA (135). For a period of 24 hours after tPA
administration, systolic blood pressure should be
maintained less than 180 mmHg and diastolic blood
pressure less than 105 mmHg. However, for those
patients who have not received IV tPA, the guidelines
are less clear.
Cerebral Venous Thrombosis
Cerebral venous thrombosis (CVT) affects 3 to 4 per
million adults and 7 per million children in the United
States (136). Up to 75 percent of those affected are
women (136). Causes and risk factors associated with
CVT include pregnancy and the post-partum state,
oral contraceptive use, head injury, infections of the
sinuses and meninges, hereditary and acquired throm-
bophilias, and hematological conditions. The most
common but least specific symptom is severe head-
ache. Seizures occur in 40% of patients; these can
range from focal motor seizures to frank status epilep-
ticus (136). Focal neurological findings may be present
and may range from mild weakness to coma or her-
niation syndromes.
Current recommendations for acute treatment of
this disease state that anticoagulation is probably effec-
tive, and that 3 months of treatment, followed by an
antiplatelet agent, is reasonable in the absence of trial
data (137). In patients with radiographic evidence of
venous congestion and a worsening clinical state, endo-
vascular therapy may be warranted (138,139). Patients
with progressive cerebral edema may require endotra-
cheal intubation and mechanical ventilation. These
patients may also require intracranial pressure monitor-
ing and osmotic therapy for intracranial hypertension.
Placement of intracranial pressure monitors would
require temporary discontinuation of anticoagulation;
this may not be ideal in the face of ongoing thrombo-
sis. Osmotic therapy with mannitol may result in rela-
tive hypovolemia which could exacerbate thrombosis;
592 NEUROINTERVENTIONAL MANAGEMENT
hypertonic saline administration may be preferable.
Patients with multiple areas of venous infarction and
hemorrhage may require hematoma evacuation and/or
DHC for refractory elevations in ICP.
Intracranial Atherosclerosis
Intracranial atherosclerosis accounts for approximately
10% of all ischemic strokes (45). In general, intracra-
nial atherosclerosis occurs in the setting of widespread
atherosclerosis. In the United States, there is a higher
incidence among Asians (4244), African-Americans (45)
and Hispanics (46). Diabetes, hypercholesterolemia, cig-
arette smoking, and hypertension are other associated
risk factors (140,141).
Patients with intracranial atherosclerosis should be
treated with lifestyle modification, statins, angiotensin-
converting enzyme inhibitors, and antithrombotics
(45,137). Endovascular revascularization may be consid-
ered for severe symptomatic intracranial stenosis (> 70%
luminal narrowing).
The acute complications of these endovascular inter-
ventions are vessel rupture, ischemic stroke, and thrombo-
sis of the stent. Any neurological change should mandate a
CT scan and vascular imaging of the stented segment. Diag-
nosis and treatment follow that of acute ischemic stroke.
Extracranial Carotid Disease
Carotid artery stenting (CAS) is a viable treatment for
carotid artery stenosis. The classic neurological compli-
cation of CAS is intracerebral hemorrhage from cerebral
hyperperfusion syndrome. It is characterized by unilat-
eral headache, face and eye pain, seizure or focal neuro-
logical signs that occur due to ipsilateral cerebral
edema. Hyperperfusion syndrome is due to a significant
increase in CBF in tissues with altered autoregulation
from chronic oligemia. Comparisons between pre- and
post-procedural blood flow measures may help predict
who will develop hyperperfusion. Some centers meas-
ure CBF with SPECT, or 133 Xe computed tomography
(XeCT) or TCD to establish whether hyperperfusion is
present (40,142144). Post-procedural imaging, includ-
ing MRA and MR perfusion, may be helpful as well.
Treatment of the syndrome centers on strict blood pres-
sure control. There are no published cases of cerebral
hyperperfusion syndrome below a SBP of 135mmHg
(145). One study of post-operative carotid endarterec-
tomy (CEA) patients managed with 48 hours of contin-
uous sedation, mechanical ventilation, and regional
CBF measurements avoided cerebral hyperperfusion
syndrome in the total cohort; it is unclear whether this
is applicable to post-CAS patients (146).
Hypotension and bradycardia represent other
common complications of CAS. The postulated mech-
anism involves increased baroreceptor sensitivity from
distension of the internal carotid artery. Proximity of
the lesion to the carotid bifurcation, eccentric stenosis,
echogenic plaque, and calcification of the carotid
bifurcation may be associated with post-procedural
hypotension (142,147,148). Elderly women and those
with underlying cardiac disease may be at risk for
prolonged hypotension. Hypotension may be treated
adequately with IV fluids or Trendelenburg position
in some; others may require vasopressor therapy.
Anticholinergic medications such as atropine or glyco-
pyrrolate may increase heart rate; however, access to
transcutaneous pacing should be available (148,149).
Ischemic stroke may complicate CAS and should be
approached as previously described.
Head and Neck Tumors
Interventional neuroradiology of the head and neck
includes image-guided biopsies, vessel occlusion, and
local delivery of chemotherapy. Indications for image-
guided biopsies are pre-vertebral fluid collections, spinal
and paraspinal inflammations and abscesses, deep cervi-
cal malignancies, and tumors of the vertebral body and
skull base. The main indication for vessel occlusion is
emergency control of hemorrhage that is often caused by
neoplastic invasion of vascular structures. Other indica-
tions for endovascular intervention to reduce hemorrhage
risk include treatment of tumors such as hemangioma
of the hard palate, juvenile angiofibroma, hemangioperi-
cytoma, malignant fibrous histiocytoma, and glomus
tumor (150). Intra-arterial administration of chemother-
apy is indicated as adjuvant treatment of oropharyngeal
squamous cell carcinoma or palliative care for other head
and neck malignancies. Major complications of treatment
include stroke, blindness, or cranial nerve palsies. Treat-
ment focuses on serial monitoring post-procedure as well
as hemodynamic modulation.
Epistaxis is a common medical condition altho-
ugh it only accounts for 0.46% of emergency medical vis-
its (151). The majority of patients seeking
medical attention for epistaxis can be treated with nasal
packing (151,152). Nasal packing may cause nasal
trauma, a vagal response, aspiration, infection, airway
obstruction, hypoxia, myocardial infarction, and rarely
death (152). A fraction of patients may require endovas-
cular treatment, which has been gaining increased
acceptance as a reasonable alternative to surgery. Com-
plications of embolization can range from minor (head-
ache, facial pain, numbness, edema, paresthesiae) to
major (facial scarring, stroke, monocular blindness, and
sialadenitis requiring surgery). Minor complications may
occur in up to 29% of cases, whereas major complications
have been reported in < 2% (152). Head of bed should be
elevated to 30 degrees to minimize risk of aspiration.
Patients should be monitored for respiratory distress.
Bag-mask ventilation may be contraindicated in patients
with nasal packing; early identification of airway issues
should prompt placement of orotracheal tube.
MEDICAL COMPLICATIONS
Access Site Complications
Access site complications may include local throm-
bosis, distal embolization, arterial dissection, retro-
peritoneal hemorrhage, pseudoaneurysm, or AVF.
Hemostasis has traditionally been established by local,
manual compression. Mechanical clamp devices and
arterial closure devices have been developed as expedi-
ent and convenient alternatives to manual compression.
Use of larger bore sheaths, significant anticoagulation,
hematoma formation, or dual antiplatelet therapy may
warrant mechanical clamp compression. Arterial punc-
ture closure devices (APCDs) that employ a collagen
 NEUROCRITICAL CARE MANAGEMENT OF ENDOVASCULAR PATIENTS
plug, clips, or sutures, may eliminate the need for com-
pression. APCDs theoretically allow for earlier patient
mobilization and shorter hospitalization. Evidence
regarding the efficacy and safety of newer closure
devices largely derives from studies of percutaneous
coronary interventions (PCI). Controversy exists as to
whether APCDs may increase the risk of local vascular
complications.
Post-catheterization pseudoaneurysm (PSA) is one
of the most common vascular complications of angiogra-
phy (Fig. 30.1). The incidence of PSA after diagnostic
angiography is 0.52% (153), whereas after intervention
it may be as high as 7.7% (154). A PSA may be diag-
nosed by auscultation of a systolic bruit over the catheter
insertion site; alternatively, it can be identified by ultra-
sound or CT scan. The majority of PSAs are identified
within 3 days of sheath removal (155). The chief determi-
nant of PSA formation is inadequate manual compres-
sion. Other risk factors include large bore arterial
sheaths, antithrombotic use, age > 65 years, obesity,
hypertension, peripheral arterial disease, hemodialysis,
cannulation of the superficial femoral artery and
increased complexity of interventions (155,156).
Although most PSAs resolve over a few days
without incident, femoral nerve compression, venous
thrombosis, claudication, or rarely, limb ischemia may
occur (156,157). The most serious complication of a
PSA is rupture. Risk factors for rupture include size
greater than 3 cm, the presence of symptoms, large
hematoma size and expansion (158160). Local skin
necrosis may develop as well. Retroperitoneal exten-
sion may occur if the arterial puncture is above the
inguinal ligament.
Most hematomas are managed conservatively
with cystalloid administration and/or blood
(A)
Figure 30.1 (A) AP injection demonstrates early filling of pseudoaneurysm (arrowheads) of common femoral artery with (B) delayed
stagnation of contrast in the lesion (arrowheads). Lesion was treated with thrombin injection followed by complete resolution (not shown).
593
transfusion. Occasionally, surgical intervention may be
required. Abdominal compartment syndrome (161,162)
and compartment syndrome of the thigh (157) have
been reported. Alternatives to surgical intervention
include ultrasound-guided compression repair, ultra-
sound-guided thrombin injection (UGTI), coil insertion,
fibrin adhesives, or balloon occlusion. UGTI has
become the treatment of choice for post-catheterization
PSAs (163165). If a PSA is large enough to cause skin
necrosis, nerve compression or ischemic compromise,
surgical intervention may be preferable to UGTI. The
success rate of UGTI ranges from 91% to 100%
(155,156,163), although deep vein thrombosis (DVT),
PE, and arterial thrombosis are potential complications
in up to 4% of patients (166). Allergic reactions to
bovine thrombin have also been reported (155,167,168).
Arteriovenous fistulae may occur when ongoing
bleeding from the arterial puncture site forms a tract
with the prior venous puncture site. Risk factors for fis-
tula development include peripheral arterial disease,
diabetes mellitus, female sex, small diameter vessel
lumen, large bore sheath, or a long catheter dwell time
(169171). Definitive surgical repair may be required as
fistulae tend to expand over time.
Although the transfemoral route is the most com-
monly used vascular access route, alternative routes
such as the axillary (172), brachial (173,174,) and radial
(175) approaches are being used with success. In addi-
tion to the complications noted above, the transfemoral
approach requires uncomfortable manual compression,
bed rest and an increased length of stay compared to
the transbrachial approach, which is commonly used
for outpatient procedures. The transbrachial approach
is better tolerated; it carries a risk of local hematoma,
upper limb ischemia, and median nerve damage. The
(B)
594 NEUROINTERVENTIONAL MANAGEMENT
transradial approach may be associated with even fewer
complications than the brachial approach and does
not restrict use of antithrombotic medications, although
radial artery vasospasm and need for local vasodilators
may limit its utility (176). At the first signs of vascular
compromise, removal of the catheter and consultation
with a vascular surgeon may be indicated.
INTENSIVE CARE UNIT COMPLICATIONS
The risk of major non-neurological complication after
diagnostic cerebral angiography is very low 00.3%
(2,4,5,13). One significant ICU complication is acute
renal failure, which may ensue from contrast-induced
nephropathy (CIN), renal atheroemboli, or renal hypo-
perfusion. Other complications may include choles-
terol emboli syndrome, and reactions to radiocontrast
media (RCM) or other medications administered dur-
ing the interventional procedure.
Contrast-Induced Nephropathy
Contrast-induced nephropathy is generally defined as
an increase in serum creatinine concentration of > 0.5
mg/dL or a rise of 25% from baseline within 48 hours
after contrast administration (177). The incidence of
CIN in the general population has been estimated at
less than 2%. Patients with chronic renal impairment,
diabetes mellitus, congestive heart failure, and
advanced age are at higher risk, with an incidence of
2030% (177179). CIN has been associated with
increased morbidity, extended hospital length of stay,
and increased healthcare costs.
In patients at risk for CIN, iso-osmolal (290mos-
mol/kg) agents may be preferable because of a lower
risk of CIN (180), although non-ionic low osmolal
(500850mosmol/kg) agents are administered for the
majority of radiological procedures using IV contrast
media. Peri-procedural administration of isotonic sal-
ine may help decrease the risk of CIN (177,181); isotonic
sodium bicarbonate solution does not confer additional
benefit (181,182), although controversy exists regarding
its utility. N-acetylcysteine and theophylline have been
used to counteract the RCM-related vasoconstriction
although their efficacy is unclear (177,183). Ascorbic
acid, fenoldopam, calcium channel blockers, and post-
procedural hemodialysis do not appear to be beneficial;
peri-procedural hemofiltration may be beneficial (177).
Prevention is the mainstay of treatment, once CIN devel-
ops the management is largely supportive.
Cholesterol Embolization Syndrome
Cholesterol embolization syndrome (CES) is systemic
atheroembolism caused by disruption of aortic athero-
matous plaques. Cutaneous manifestations of this syn-
drome include blue toes, livedo reticularis, and digital
gangrene. Stroke, visual loss and ischemic bowel are
other potential sequelae. A prospective evaluation of
over 1700 patients undergoing left heart catheterization
at 11 hospitals found an incidence of 1.4% (184). In this
study, 48% of patients with CES had cutaneous mani-
festations and 64% had renal failure. The in-hospital
mortality was 16%; an elevated C-reactive protein was
the only identified predictor of death. Blood eosinophil
count was significantly higher pre- and post-procedure
among those who developed CES. Surgical interven-
tion may play a role in the treatment of spontaneous
CES; its role in procedure-related CES is unclear.
Treatment depends on the organ systems involved
and is mainly supportive.
Anaphylaxis/Allergy
Reaction to iodinated contrast occurs in up to 1%
of patients (169171) and may be either chemotoxic
or hypersensitivity-type. Chemotoxic reactions include
flushing, warmth, nausea, emesis, vaso-vagal syncope
and seizures. Development of these symptoms is depen-
dent upon dose and infusion rate, and is attributed to
fluid shifts resulting from infusion of a hypertonic solu-
tion. Hypersensitivity reactions are largely independent
of dose and infusion rate. Signs of immediate hypersensi-
tivity reactions include pruritis, urticaria, angioedema,
bronchospasm, wheezing, laryngeal edema, stridor,
hypotension, shock, and altered consciousness.
Elderly patients have a higher risk of mortality
from contrast exposure than do younger patients
(185). Prior hypersensitivity reaction to RCM increases
the risk of another reaction. Asthma and other atopic
diseases may increase the risk of immediate hyper-
sensitivity reactions by more than three-fold. Shellfish
or seafood allergy is not an independent risk factor
for immediate hypersensitivity reactions; it carries the
same risk as other food allergies. Premedication with
corticosteroids and H1 antihistamines reduces the inci-
dence of a severe reaction, such as bronchospasm or
shock to < 1%. High-risk patients may benefit from
non-ionic contrast.
Severe reactions should be treated like anaphy-
laxis, with immediate administration of intravenous epi-
nephrine (1:10,000 or 0.1mg/mL). Early endotracheal
intubation should be performed; a surgical airway may
be necessary. IV fluid should be administered; patients
with persistent hemodynamic compromise should be
started on an epinephrine infusion (210mcg/min).
Antihistamines and IV glucocorticoids are routinely
administered and treatments with nebulized albuterol
should be given. Diphenhydramine for pruritis and rani-
tidine may be administered as well.
Thrombocytopenia
Thrombocytopenia from any cause has been associated
with increased risk of ischemic events, bleeding and red
blood cell transfusions after PCI (186). It is a possible
complication of treatment with unfractionated heparin
and glycoprotein (GP) IIb/IIIa inhibitors, which are
often administered during interventional procedures.
Thrombocytopenia associated with GP IIb/IIIa
occurs with an incidence of 0.5%5.6% (186,187).
It results from complexes of the drug bound to plate-
let glycoproteins which are then targeted for destruc-
tion by macrophages. The resulting thrombocytopenia
is severe, with the nadir platelet count often less than
20,000 per cubic milliliter (188). Abciximab causes
more cases of thrombocytopenia than either tirofiban
or eptifibatide, which directly block GP IIb/IIIa (189).
Symptoms may occur within hours of exposure, or
may present several weeks after treatment. Platelet
 NEUROCRITICAL CARE MANAGEMENT OF ENDOVASCULAR PATIENTS
transfusion should be administered if there is severe
bleeding, or if an invasive procedure is required (190).
Once GPIIb/IIIa-related thrombocytopenia has occurred,
re-administration of the offending medication at a later
date is not recommended as recurrent thrombocytopenia
might prove even more severe.
Heparin-induced thrombocytopenia (HIT) is a pro-
thrombotic immune disorder caused by platelet-activat-
ing antibodies that recognize heparin-platelet factor 4
(PF4) complexes (191,192). In contrast to GP IIb/IIIa
antagonists, HIT does not produce severe thrombocyto-
penia or increase bleeding risk, but does increase the
risk of thrombosis. HIT should be suspected when the
platelet count falls to < 50% of the baseline level or an
absolute number of < 150,000/microL between days 5
and 14 of heparin exposure.
Clinical complications of HIT include both venous
and arterial thromboses. Venous thromboses are four
times more common than arterial thromboses, but stroke
is a significant predictor of mortality (193). Myocardial
infarction accounts for 35% of arterial thromboses;
amputation from arterial thrombosis of a limb may be
required in as many as 20% of patients with HIT (191).
Concomitant prothrombotic risk factors that are often
present include diabetes mellitus, malignancy, systemic
lupus erythematosus, antiphospholipid antibody syn-
drome, indwelling catheters, and trauma (193).
If HIT is strongly suspected, immediate discon-
tinuation of all heparin sources is mandatory and
should be accomplished prior to the demonstration of
HIT antibodies. Anticoagulation with direct thrombin
inhibitors should be initiated to treat the thrombotic
sequelae. Monitoring for thrombosis is imperative.
Treatment with low molecular weight heparin does
not fully eradicate the risk of HIT and is discouraged.
CONCLUSION
The ICU management of interventional neuroradiology
patients is varied and complex. It is imperative that
those involved with the care of these patients be
aware of the diseases encountered, available treatments,
and potential complications. Ongoing communication
between neurosurgeons, neurointerventionalists, neu-
rointensivists, neuroanesthesiologists, and neuro-ICU
nurses is a must as rapid deterioration may occur at any
time.
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Anesthesia for interventional neuroradiology
Dimitry Baranov and W. Andrew Kofke
Anesthesiology is a specialty, which emerged and has
evolved to serve primarily the needs of surgical
patients in the operating theater environment. Until not
that long ago, anesthesia for out-of-OR remote locations
had been often viewed by many anesthesiologist as a
mere diversion from their primary responsibilities in
the main OR. Indirect evidence of this somewhat dis-
dainful attitude can be found in many classical text-
books of anesthesia where provision of anesthesia care
for a wide variety of non-surgical procedures in remote
locations would be covered in one small chapter.
Whereas anesthesia for each subspecialty of surgery
would have its own chapter, such radically different
disciplines as interventional neuroradiology, endos-
copy, and cardiac electrophysiology were lumped
together under some vague and euphemistic moniker
like, Anesthesia at remote locations (16). It would be
incomplete to neglect mentioning that the practitioners
in those non-surgical specialties often reciprocated in
this attitude by making little effort to accommodate
unique requirements of anesthetized patients in their
practice, treating anesthesia as no more but a pesky
necessity otherwise of little consequence to their rou-
tines. Unlike surgery, however, until recently very few
non-surgical professions had perceived or wanted anes-
thesia to become an essential component to progress in
their specialties. Symbolically, the previous 2006 edition
of this very textbook had no chapter on anesthesia.
This kind of unawareness among non-surgical profes-
sions is most likely due to the relatively minor fraction
of these patients who required anesthesia care in the
past, which in turn provided relatively insignificant
occupation and income opportunities for most anesthe-
sia providers. However, with advances in procedural
complexity and increasing severity of patient illness,
this reality has been undergoing rapid and dramatic
transformation in recent years.
The significant growth in the number of new
non-surgical interventions being performed on a pro-
gressively larger proportion of patients, who otherwise
would require surgery, has dramatically increased the
need for anesthesia services in these areas. Neurointer-
ventional radiology is an example par excellence for
this trend. The increasing complexity and often inva-
siveness of neuroradiological interventions often neces-
sitate general anesthesia and advanced monitoring
techniques traditionally used during surgery. More-
over, a growing number of patients undergoing these
procedures are in critical condition requiring advanced
forms of cardiopulmonary and neurological life
31
support, which is largely an unfamiliar territory for
most neurointerventionalists, unlike it is for anesthesi-
ologists. But despite a fast growing need for anesthesi-
ologists participation in the peri-procedural care of
these patients there are comparatively few reviews or
studies to be found in the anesthesiology literature on
the general principles and specific aspects of anesthesia
care for different procedures in modern neurointerven-
tional practice. This chapter is intended to address this
scarcity of relevant information on anesthesia care for
neurointerventional procedures based on the authors
cumulative experience working in this field and review
of available relevant literature. The main goal of this
chapter is to serve as a concise reference source for
anesthesia providers with little exposure to working in
neuroradiology suite regarding the nature and the
anesthetic requirements for most frequently performed
neurointerventional procedures, and also for neuroin-
terventionalists who would like to have a better under-
standing of what is going on the other side of the
curtain.
This chapter is divided into two major sections:
1. General principles of anesthesia care for neuroin-
terventional procedures.
2. Anesthesia management for specific procedures.
GENERAL PRINCIPLES OF ANESTHESIA
MANAGEMENT FOR INTERVENTIONAL
NEURORADIOLOGY
Although most standards of anesthesia care for patients
undergoing neuroradiological interventions are identi-
cal to those practiced in operating rooms, there are
some distinct differences. Those challenges specific to
anesthesia for interventional neuroradiology procedures
have been discussed in the literature (26) and can be
summarized as follows:
1. Minimizing factors leading to decreased safety of
anesthesia care administration in unfamiliar envi-
ronment, outside of the operating room (1,35).
2. Providing adequate anesthesia to patients who do
not experience typical levels of surgical stimulation
during the procedure. Designing anesthetic regi-
mens, which allow rapid recovery to allow periodic
intra-procedural and immediate post-procedural
neurologic examination
3. Designing anesthetic regimens facilitating neuro-
physiologic monitoring modalities during proce-
dures (7).
602 NEUROINTERVENTIONAL MANAGEMENT
4. Minimizing patients movements to improve imag-
ing quality and avoid potential rupture or dissec-
tion during endovascular procedures.
5. Anticipating and treating procedure-specific compli-
cations (e.g., intracranial hemorrhage and intracra-
nial circulatory arrest from aneurysm rupture) (8).
6. Monitoring and managing hemodynamics to facili-
tate specific procedure goals and minimize poten-
tial side effects (e.g., cerebral hypoperfusion during
temporary vascular occlusion).
7. Management of critically ill patients, especially
those on life support (Fig. 31.1).
8. Managing anticoagulation.
9. Radiation safety of anesthesia providers (9,10).
Safety of Anesthesia Care in Interventional
Neuroradiology
We believe that the issue of possible reduced anesthe-
sia safety, related to the remote location, in patients
undergoing neuroradiology intervention should be
central to every anesthesia provider working with
these patients. There are multiple factors which may
potentially diminish the safety of anesthesia care in the
neuroradiology suite as compared to the standardized
Figure 31.1 Example of the complexity in a neuroradiology suite in a complicated neurointensive care patient undergoing a neurointer-
ventional procedure. Patient is intubated with a ventriculostomy, Licox, and 11 intravenous infusions related to cardiomyopathy, pulmo-
nary edema, pneumonia, nutritional support, and vasospasm.
operating room environment. These factors have been
discussed in a number of recent excellent reviews
on patient safety for anesthesia in any out-of-OR loca-
tion (1,3). Notably, a recent report from evaluation of
closed claims indicates a higher proportion of respi-
ratory events in remote anesthetics associated with
successful litigation (Fig. 31.3) (1). A summary of these
factors follows with an emphasis on the specifics of
working in the neuroradiology suite:
1. Neuroradiology team members, including neurointer-
ventionalists, nurses and technicians, are less likely to
understand various aspects of anesthesia management
compared to members of typical operating room (OR)
teams. Surgeons and surgical nurses routinely
work together with anesthesiologists in managing
surgical patients, common surgical emergencies and
complications. The vast majority of surgical proce-
dures are performed with an anesthesiologist being
present in the room, whereas in neuroradiology,
fewer patients may require anesthesiologist presence
(depending on the patient population and institu-
tion). As a result the typical OR team is more likely
to recognize potentially serious intraoperative events
related to anesthesia management than those in the
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
neuroradiology suite. Also, less experience in treat-
ing life-threatening complications on routine basis
can lead to limited effectiveness of assistance
available to the anesthesia provider in case of
emergencies.
2. Limited access to the patient and patients airway during
procedures (Fig. 31.2). The typical neuroradiology set
up includes two C-arm fluoroscopes positioned
around the patients head. In addition, during
acquisition of 3D images, a single fluoroscope rotates
around the head, which makes access to the airway
very limited. Also, a significant part of the procedure
is typically done with the lights off, potentially
further impairing direct patient observation and per-
formance of other essential tasks including medica-
tion preparation and administration. In case of loss
of the airway in a sedated patient or accidental extu-
bation, immediate access to the patients airway is
obviously essential.
3. Significant delay in available help. Most modern
ORs have established procedures in place to
rapidly mobilize and deploy available nearby
highly skilled individuals in case of intraopera-
tive anesthetic or surgical emergencies. Often a
team of designated surgical personnel trained in
(A)
(C)
Figure 31.2 Example of a patient undergoing circumferential imaging in neuroradiology. Care must be taken to avoid dislodging of vas-
cular line, airway, and ventilator circuits. Note the distance of the airway from any provider.
603
crisis resource management (11) is constantly
available to address these emergencies on a very
short notice. This is not a customary practice for
most neuroradiology suites, which are typically
located away from the main OR and rely on the
hospital rapid response team or cardiac arrest
teams to help in an emergency (11). Neither
of these teams are reliably comprised of individ-
uals well versed in management of intraopera-
tive catastrophes related to anesthesia or the
procedure.
4. Lack of familiarity with the physical set-up of the neuro-
radiology suite on the part of the anesthesia provider who
may only occasionally rarely work in this environ-
ment. It is often the practice in many anesthesia
departments to assign their members to remote loca-
tions based on scheduling needs without regard to
their previous exposure to this environment. This
approach, which works well in an OR suite, presup-
poses that most OR set-ups are very similar requiring
only minimal adjustment from any given anesthesia
provider. Of course this is far from reality, especially
considering that many anesthesiologists have had
only limited exposure to working in out-of-OR envi-
ronments during their training. Indeed, fiscal
(B)
604 NEUROINTERVENTIONAL MANAGEMENT
Resp event
Inadeq O2/CO2
Regional block
50
40
30
%
20
10
0 O2 or CO2 irregularities also noted. Chart based on data from
Remote OR
constraints continue to make specific resident train-
ing in this area difficult to develop.
5. Other factors include reduced maintenance of
anesthesia equipment, decreased availability of
anesthesia technician support, and less reliable
restocking of anesthesia supplies and medications.
Many of these issues, and others, have been
formally addressed by the American Society of Anes-
thesiologists (12), creating a set of inviolate standards
for the management of anesthetized patients in remote
locations.
Although it is primarily the responsibility of each
individual anesthesia provider to understand and pre-
pare for these challenges in order to provide a high
level of safety in anesthesia care, an organizational
approach to address these factors on the institutional
level is imperative to minimize preventable morbidity.
High levels of cooperation between interventional neu-
roradiology and anesthesia teams and their leaders are
critical to improve safety for these procedures, espe-
cially where it concerns the prevention and treatment
of acute life-threatening complications. Simulation-
based crisis team training for multidisciplinary pro-
viders is a novel and effective approach in building
high level of coordination between various services,
particularly those who are not intimately familiar with
each others routines (1317). The field of simulation-
based multidisciplinary team crisis training is under-
going rapid development primarily in emergency med-
icine and surgical-based specialties (18). Although
experience with simulation-based procedural training
Figure 31.3 Mechanisms of injury associated with successful liti-
gation, comparing OR with remote locations. Eighty-seven claims
were reviewed for remote location lawsuits versus 3,287
reviewed for operating room (OR) lawsuits. Although lacking a
denominator, this report suggests a predisposition for respiratory
anesthesia-related morbidity in remote locations. Overall propor-
tion of claims based on respiratory events as noted. The propor-
tion of events, as a component of respiratory events, related to
Metzner et al. (1).
for radiologists has been reported in the literature
(1923), the authors are unaware of any interdiscipli-
nary team crisis resource management (CRM) training
involving radiology services. However, logically it
makes sense to use this type of training to increase
safety of care in anesthetized patients undergoing inter-
ventional neuroradiology procedures.
Anesthesia Planning and Administration in
Interventional Neuroradiology
Basic principles of pre-operative assessment, prepara-
tion for and delivering anesthesia care in interventional
neuroradiology are similar to those in surgical patients.
However, a number of unique challenges typical for
these procedures require certain changes in standard
approach while planning for anesthesia in these
patients. This section will address general principles of
anesthetic design and management of patients for neu-
rointerventional procedures.
In order to plan and prepare for anesthesia for
most patients in the neuroradiology suite, the anesthe-
sia provider needs to address a numbers of questions:
1. What kind of anesthesia will be used: general or
sedation (MACmonitored anesthesia care)?
2. Does the nature of the procedure or patient condi-
tion call for any monitoring in addition to stand-
ard anesthesia monitoring?
3. Will any form of neurophysiologic monitoring be
used during the case, and how will it impact the
choice of anesthetic agents?
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
The ability to provide a confident answer to
these questions is often the function of experience in
working in interventional neuroradiology and famili-
arity with the routines and preferences of the specific
neurointerventionalist and the practice as a whole.
However, in the authors experiences it is of utmost
importance to have open lines of communication
between all members of the team taking care of these
patients. A thorough preoperative discussion between
anesthesia, interventional neuroradiology and some-
times neurophysiology services regarding the exact
nature of the procedure, its critical stages, desired
hemodynamic targets, patient positioning, type of
monitoring, etc. is the best way to receive and inte-
grate all the information necessary for anesthesia plan-
ning and eliminate any potential misunderstanding.
Anesthesia Choice: General vs. Sedation
Unlike for many surgical procedures, there is little
consensus regarding the choice of anesthesia type for
many neurointerventional procedures. The choice
between sedation or general anesthesia, even for most
invasive procedures involving placements of endovas-
cular stents and aneurysm coiling, is mainly made
based on the preferences of the neurointerventional
team. It is important to understand that pharmaco-
logic decrements in the sensorium is a continuum,
more akin to a dimmer switch, so that specifically
defining when a patient has transitioned from being
sedated to being under general anesthesia can be diffi-
cult. Naturally, the overall patient condition, degree of
cooperation and availability of anesthesia services
bear strong impact on this decision-making process
regarding the desired depth of anesthesia. But in the
absence of prospective randomized studies comparing
outcomes for patients undergoing certain procedure
either under general anesthesia or sedation, it is rea-
sonable to assume that most procedures in stable
cooperative patients can be performed safely under
both types of anesthesia. Patients who are uncoopera-
tive, critically ill, or with an endangered or uncertain
airway generally require general anesthesia.
Sedation
Sedation, also called monitored anesthesia care (MAC),
is an acceptable choice for many adult patients without
or with minimal to moderate neurological deficits
undergoing a variety of neurointerventional proce-
dures. It is typically performed for diagnostic angio-
graphy as a sole procedure or the initial diagnostic
part of interventional procedures, such as aneurysm
coiling, stents placement, arteriovenous malformation
(AVM) embolizations, etc. Sedation has its advantages
and disadvantages compared to general anesthesia.
The advantages include greater hemodynamic stabil-
ity, ability to perform neurologic examination intra-
operatively, and potentially shorter discharge and
turn-over times between cases. However, producing
optimal conditions for neurointerventional procedures
using sedation is often a daunting task akin to finding
ones way between Scylla and Charybdis. Light seda-
tion is often inadequate to alleviate patients discomfort
605
and can lead to excessive, potentially dangerous,
movements. On the other hand, any attempts to
deepen sedation without airway support may make
things even worse due to increasing patients unco-
operativeness, associated with lack of conscious con-
trols, hypercapnea, hypoxemia, and unacceptable
degree of head movements due to snoring or partially
obstructed breathing. In patients with pre-existing neu-
rologic deficits, even if well compensated, even light
sedation often results in the loss of compensatory
mechanisms and unmasking of neurologic deficits,
accompanied with loss of cooperativeness and some-
times overt agitation. In the absence of anesthesiolo-
gist-administered sedation, any attempts to deepen
sedation may then lead to the loss of the airway and
arterial desaturation, potentially requiring rapid
response team call and emergency endotracheal intu-
bation. Moreover, inability to provide adequate seda-
tion with lack of patient cooperation can result, often
after prolonged struggle, in the procedure cancellation
unless an anesthesiologist is already involved or
immediately available to change to general anesthesia.
The notion that an anesthesiologist will necessarily be
available on short notice to then oversee continuation
of the procedure, in the current era of finance-
constrained health reform, is becoming increasingly
unlikely.
The sedation regimen should allow for rapid
change in the depth of sedation between different
stages of neurointerventional procedures. For exam-
ple, during diagnostic angiography, the insertion of a
groin sheath can be associated with significant pain
and discomfort to the patient at which stage a deeper
level of sedation is warranted, with an eye on avoid-
ing airway obstruction. During diagnostic angiogra-
phy the sedation is typically lightened to allow the
patient to become readily arousable and to be volun-
tarily apneic if necessary. If the neurointerventionalist
decides to use an arterial sealing device on sheath
removal, it might be necessary to briefly deepen seda-
tion again to offset significant discomfort associated
with its use. Other procedures may require frequent
neurological evaluations, necessitating very light lev-
els of sedation, while keeping patients comfortably
sedated in between. This flexibility in readily chang-
ing the depth of sedation is harder to maintain using
a traditional sedation based on bolus administration
of midazolam and fentanyl. Pump-controlled infusion
of a single or a combination of ultra-short acting med-
ication, such as propofol, remifentanil, and dexmede-
tomidine, allows for rapid transition between different
levels of sedation. In the authors experience, use of
intravenous boluses of midazolam and fentanyl, in
combination with infusion of propofol, adjusted to the
desired depth of sedation, reliably produces good
results in the vast majority of these patients. In
patients with a moderate degree of neurologic deficit,
in whom the treatment team expects a higher risk of
loss of cooperation and potential loss of the airway,
but who nonetheless are not viewed as suitable candi-
dates for general anesthesia, the infusion of dexmede-
tomidine or a combination of dexmedetomidine with
remifentanil has been used with a good rate of suc-
cess. The main advantage of dexmedetomidine is that
it produces sedation associated with ability to arouse
606 NEUROINTERVENTIONAL MANAGEMENT
(2426). However, like other sedatives it can also pro-
duce airway obstruction.
Despite all the advantages afforded by these newer
drugs, the process of setting up multiple infusion pumps
is somewhat cumbersome (Fig. 31.1) and requires thor-
ough attention to details (e.g., increased intravenous tub-
ing length) to avoid potentially disastrous medical
errors. Prior experience in the administration of these
newer anesthesia drugs in the well-controlled environ-
ment of the main OR is desirable before using them for
sedation for neurointerventional procedures where
immediate patient access may be impeded by bulky
equipment.
Standard anesthesia monitoring combined with
side stream capnography via nasal cannulae for moni-
toring respiration should be used in all patients. Many
sedated patients breathe through their mouths, which
can result in desaturation and decreased ability to
monitor end tidal CO2. In these patients the use of a
non-rebreathing oxygen mask in combination with
nasal cannulae capnography improves oxygenation
and ability to capture CO2 in the sample line. Capnog-
raphy is now recognized as standard of care for all
sedated patients (27). The use of a nasopharyngeal air-
way in combination with deep (typically propofol
based) sedation in spontaneously breathing patients
may help to minimize head movements due to breath-
ing and snoring. Moreover, the anesthesia circuit can
be connected to the nasopharyngeal airway in one or
both nares to apply continuous positive airway pres-
sure to attenuate airway obstruction and/or hypoxe-
mia. One important caveat to remember is that use of
antiplatelet and heparin therapy can result in signifi-
cant airway bleeding following even minor trauma
during nasal airway insertion. In these patients every
precaution should be taken to use the most atraumatic
insertion technique, or avoid the use of a nasophar-
yngeal airway altogether. The need for invasive arte-
rial pressure monitoring is decided based on the
procedure goals and the patients medical status.
There is no clear consensus in the professional
literature regarding who can administer sedation for
patients in general or those undergoing neurointer-
ventional procedures. However, recent practice
guidelines for sedation and analgesia by non-anes-
thesiologists, published by the American Society of
Anesthesiologists, recommends that any form of
sedation should administered by a designated pro-
vider present throughout the procedure with no
other responsibilities (28). In cases of moderate seda-
tion the person providing sedation should be trained
in basic life support and someone trained in advanced
life support should be immediately available. For deep
sedation a person with advanced life support training
and able to secure the airway should be present in the
procedure area all the time. Obviously, administration
of sedation by trained anesthesia providers meets all
these criteria.
General Anesthesia
General anesthesia is routinely employed for more
invasive, complex, and prolonged procedures where
cooperation or strict immobility during the procedure
is mandatory (e.g., ensure maintenance of the
angiographers roadmap). Although many of these
procedures could possibly be performed under seda-
tion, general anesthesia has many potential benefits
over sedation.
General anesthesia virtually eliminates head move-
ments during critical stages of the procedure, due to
ability to institute brief periods of apnea in paralyzed
ventilated patients under general anesthesia. This
results in better imaging quality and eliminates the
need for additional angiographic runs, thus reducing
radiation exposure, amount of contrast, and time spent
on the diagnostic procedure. Any delays associated
with managing the sedated patients discomfort and
lack of cooperation are minimized. The risk of a sudden
airway obstruction, frequently associated with pro-
found desaturations which can be seen with deep seda-
tion, is eliminated as a complication in the intubated
anesthetized patient with a secured airway. Clearly the
risk of difficult/impossible airway induction or emer-
gence of anesthesia is ever present, but with proper pre-
operative preparation it is much easier to manage a
difficult airway than in the case of the loss of the native
airway during sedation with a limited patient access,
emergency, chaotic conditions, and significant time
delays. However, the recovery from general anesthesia
can take longer compared to sedation and typically
requires longer time to discharge home in the outpa-
tient settings. Nonetheless general anesthesia is feasible
in ambulatory outpatients expected to go home after an
uncomplicated procedure (29).
There are many approaches to how to design
an appropriate general anesthesia regimen for inter-
ventional neuroradiology patients with no clear
advantage of one drug or anesthesia technique over
another, with a notable exception of nitrous oxide.
Nitrous oxide should be avoided due to inherent
potential for intra-arterial air embolism present in
neurointerventional procedures. Nitrous oxide will
expand any intravascular bubbles (3032). Otherwise
various combinations of inhalational agents with intra-
venous agents, opioids and benzodiazepines, pure
TIVA (total intravenous anesthesia) techniques, with
or without neuromuscular blockade have been used
with good results.
Currently there is no indication that any of the
anesthetic agents in use reliably confer neuroprotec-
tion in patients undergoing neurointerventional pro-
cedures although there are encouraging data from
studies in subhuman primates given barbiturates for
focal temporary ischemia (3335). Notably, thiopental
is no longer available and substitutes such as pro-
pofol and etomidate are not well characterized as
neuroprotectants.
When choosing particular anesthetic agents one
must take into account a number of the following con-
siderations. Most neurointerventional procedures are
associated with an increased risk of neurologic injury,
mainly as a result of thromboembolic complications,
unintended vascular occlusion or vascular rupture.
Therefore the use of short acting agents, with low
potential for context sensitivity (i.e., duration of prior
use has less impact on emergence time) should be
used to allow rapid emergence and neurologic evalua-
tion. Slow emergence from general anesthesia can be
an indication of neurologic injury that needs to be
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
emergently addressed either surgically or neurointer-
ventionally. Obviously the inability to determine
whether the slow emergence is due to long acting
anesthetic agents or to some new neuronal injury in
these patients is likely to make the early detection and
therapy of neurologic injury more difficult.
In patients with intracranial hypertension, the
anesthetic choice may be important. Volatile agents
and nitrous oxide (36) will either have no effect or
promote an increase in intracranial pressure (ICP)
(3745) whereas drugs which decrease cerebral meta-
bolic rate with a coupled decrease in blood flow and
volume will tend to decrease ICP. These drugs include
barbiturates (4650), propofol (40,51,52), and etomi-
date (5355). Even though these drugs decrease ICP
their effects to decrease blood pressure can actually
cause a decrease in cerebral perfusion pressure so
their use in this context is never straightforward.
Neurophysiological monitoring is being increas-
ingly used during various neurointerventions in order
to enable early detection of neuronal damage in anes-
thetized patients unsuitable for neurologic examination.
Many anesthetic agents affect various neurophysio-
logic monitoring modalities in a way similar to that
observed with evolving neurologic injury, which can
interfere with the ability to diagnose new neurologic
deficits intraprocedurally (7). A thorough understand-
ing how different anesthetic agents affect various
modes of neurophysiologic monitoring is essential to
designing appropriate anesthetic in these patients. The
anesthesiologist has to be cognizant of these effects and
communicate with the neurophysiologic monitoring
team to arrive at an optimum anesthetic.
Neurointerventional procedures, unlike surgery
are not associated with a significant level of nocicep-
tion. As a result, many patients under general anes-
thesia will tend to have low blood pressure with the
depth of anesthesia typically employed in surgery. An
attempt to maintain blood pressure by lightening
anesthesia can lead to a sudden emergence associated
with rapid increases in blood pressure and tachycar-
dia and potentially dangerous movements even in the
presence of moderate levels of neuromuscular block-
ade. Use of reasonably deep anesthesia with a vaso-
pressor support, e.g., phenylephrine infusion, would
allow stable hemodynamics with a minimal risk of
emergence during critical stages of the procedure. Use
of processed electroencephalogram (EEG) monitors,
e.g., bispectral index (BIS) (5659), might be of some
benefit but is controversial within the anesthesia com-
munity (59,60).
Patients undergoing neurointerventional proce-
dures under general anesthesia traditionally have
their tracheas intubated following administration of
neuromuscular blocking drugs. This approach allows
reliable control of the airway throughout the pro-
cedure and especially in the case of an intracranial
catastrophe. Additionally, in paralyzed, ventilated
patients under general anesthesia ventilation can be
paused for a brief period providing complete lack of
movement for the best image quality. However other
approaches to the airway management can be consid-
ered in the light of recent reports on the successful
use of a laryngeal mask airway with positive pressure
ventilation in anesthetized, paralyzed patients for
607
cerebral aneurysm coiling (61). One potential benefit
of this approach is to reduce side effects of direct lar-
yngoscopy. However, it is potentially more hazardous
in patients with a high risk of aspiration, and higher
potential for laryngospasm and loss of the airway.
Sedation Vs. General Anesthesia
Routinely, the majority of higher invasiveness neuro-
interventions involving ablations of intracranial
malformations, stent placement or stroke revasculari-
zation have been performed under general endotra-
cheal anesthesia. However, successful use of a variety
of conscious sedation protocols in combination with
local anesthesia for some of these procedures in
selected populations of patients has been reported
(6267). Authors of these reports cite a number of
advantages related to using sedation over general
anesthesia in these patients, with the main emphasis
being on reducing anesthesia time, namely induction
and emergence from general anesthesia, minimizing
side effects of general anesthesia, and keeping their
patients ready for neurologic evaluation. Being able to
detect immediate neurologic deterioration or improve-
ment following certain neurointerventions is unques-
tionably of great value and can allow implementation
of necessary changes to the treatment plan without
having to wait for the patient to emerge from general
anesthesia.
However, there are many potential drawbacks to
using sedation over general anesthesia for these proce-
dures with the most salient being dangerous move-
ment at an inopportune time during a procedure (e.g.,
during intracranial vascular instrumentation) with risk
of rupture or dissection. Another very important con-
cern is the lack of a secured airway in sedated
patients. Many reports indicate that sedation was per-
formed by nurses. In case of intracranial catastrophe,
an ever present and not insignificant risk, loss of
consciousness is likely to be accompanied by the loss
of the airway and precipitous desaturation. In the
absence of trained anesthesia providers the time
between initial desaturation and reliable control of the
airway can be unacceptably long in otherwise salvage-
able patients. Indeed, in patients with evolving neuro-
logic damage hypoxemia is known to exacerbate the
ultimate adverse outcome (6871). Even in those cases
when anesthesia is delivered by anesthesiologist it
might take significant amount of time to secure a sud-
denly lost airway in sedated patients in neuroradiol-
ogy suite due to multiple factors discussed in this
chapter earlier. It also could be argued that with the
routine availability of the experienced neuroradiology
anesthesia service the induction of general anesthesia
is only marginally longer than a set-up for nursing
sedation and that the average procedure time can
actually be reduced due to the absence of periodic
sedation failures. Many patients prove to be subopti-
mal for sedation only after they received sedatives
and it often takes significant amount of time to arrive
at optimal level of sedation to be able to perform pro-
cedures in these patients. It also stands to reason that
patients under general anesthesia compared to sedation
are less likely to move during critical manipulation
reducing the risk of vascular damage. Also, complete
608 NEUROINTERVENTIONAL MANAGEMENT
lack of motion easily achievable under during general
anesthesia can make those manipulations easier and
faster.
Current lack of prospective randomized trials on
difference in outcomes in controlled populations of
patients undergoing various neurointerventions under
sedation or general anesthesia leaves it an open ques-
tion. It is up to the treatment team to decide in coop-
eration with the anesthesiologist whether general
anesthesia or sedation is to be used in every particu-
lar patient. Neither approach per se is likely to be
the crucial factor to determine the outcome of the
treatment.
Hemodynamic Management
Assuring adequate brain tissue perfusion and avoid-
ing intracranial bleeding complications are two main
challenges and goals of hemodynamic management
for neurointerventional procedures. Proactive manip-
ulation of arterial pressure through intravenous
administration of various vasopressors and vasodila-
tors in combination with appropriate anesthetics is
the cornerstone of this management. Basic principles
of cerebral hemodynamic management employed for
treating patients in neurocritical care unit are appli-
cable for patients undergoing neurointerventional
procedures.
For patients in danger of cerebral hypoperfusion,
such as patients with cerebral vasospasm, carotid
artery atherosclerotic disease, and acute stroke, or dur-
ing temporary occlusion of cerebral vessels deliberate
hypertension is often employed. In the absence of clini-
cal end points for this therapy, such as neurologic
improvement or cerebral blood flow (which is not yet
available as a monitor), the targeted increase in arterial
blood pressure is arbitrarily chosen, preferably in con-
sultation with the neurointensivist, stroke physicians,
and/or neurointerventionalists. Typically an increase
of 2040% above baseline blood pressure is advocated
if the baseline is known. Alternatively keeping mean
arterial pressure between 90 to 120 mmHg is an accep-
table target range in these patients. Conversely mild
deliberate hypotension is induced in patients in danger
of vascular wall rupture or re-bleeding, following subar-
achnoid hemorrhage (SAH) in patients with ruptured
unsecured cerebral aneurysm or bleeding AVM. Addi-
tionally, in patients undergoing AVM embolization with
glue, temporary slowing of cerebral blood flow, pro-
duced by induced hypotension, can enhance the preci-
sion of glue delivery and minimize the risk of stroke.
The choice of hypotensive agents is governed by the
patients hemodynamics, co-morbidities and anesthesia
provider experience with using these agents. Nicardi-
pine and esmolol are currently popular reasonably short
acting hypotensive drugs.
Anticoagulation
Basic principles of anticoagulation for neurointerven-
tional procedures are reviewed in detail elsewhere in
this book (chapter 11). From the anesthesiologists per-
spective it is important to understand that proper and
timely administration of anticoagulation agents is crit-
ical to the success of many neurointerventions.
Miscommunications between neurointerventional
team and anesthesia provider regarding administra-
tion of heparin can and have resulted in severe life-
threatening complications. An established protocol
addressing two way communication about administer-
ing heparin and double checking the dose with
another member of the team (e.g., nurse) may mini-
mize these kind of errors. It is also important to recog-
nize that anticoagulation with multiple agents renders
patients very prone to persistent bleeding following
even smallest oral and airway trauma.
In case of severe bleeding complications or fol-
lowing completion of certain procedures heparin
reversal with protamine may be requested by neuroin-
terventionalists. Doses of protamine employed are
usually too small to produce hypotension or allergic
reaction, but caution needs to be exercised regarding
the known risk of hypotension (72,73) and allergic
reactions (74) with protamine.
Neurointerventional Complications Management
Complications can arise during neurointerventional
procedures that may require immediate attention by
the anesthesiologist and the neurointerventional team.
A brief summary follows:
Intracranial Hemorrhage
This can arise from rupture of an AVM or fistula,
aneurysm rupture, or rupture/dissection of an instru-
mented intracranial artery. An AVM hemorrhage may
not be at systemic pressure but is still serious. Intracra-
nial arterial hemorrhage can be associated with circu-
latory arrest. This effect of an intracranial arterial
hemorrhage was nicely depicted by Eng and Lam who
observed intracranial circulatory arrest with aneuris-
mal rupture during induction of anesthesia with trans-
cranial Doppler monitoring (8). The paradigm they
followed in managing that event consisted of injection
of propofol, hyperventilation, and mannitol adminis-
tration and should provide a general template for
managing this problem during a neurointerventional
procedure. In addition, if a ventriculostomy is in place,
that can be used to decompress the brain to further
aid in rapidly decreasing this life-threatening level of
acute intracranial hypertension. A similar approach
can likely be employed for acute AVM rupture. Rapid
neurosurgical consultation and computed tomography
(CT) scanning will likely follow for the possibility of
surgical decompression.
Anaphylaxis
This is a known complication of radiocontrast dye
administration (75,76) and some anesthetic drugs
(7779). The therapy generally consists of cessation
of inciting drugs, epinephrine, inhaled bronchodila-
tors, H1 and H2 histamine antagonists, and gluco-
corticoids, along with titrated ventilation, oxygen,
and vasopressor support (7780). Similar but not as
severe are anaphylactoid reactions which are associ-
ated with histamine release but not the more serious
IgE mast cell interaction associated with anaphylaxis
(75,76,78,79).
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
ANESTHESIA FOR SPECIFIC PROCEDURES
Detailed approaches to anesthesia for neuroradiologic
procedures have been reviewed (8183). A brief sum-
mary of the basic principles follow.
Diagnostic Angiography
Diagnostic angiography for intracranial, head and neck
vascular malformations and vascularized tumors is the
most frequently performed neurointerventional proce-
dure. Although it is diagnostic in nature and could be
characterized as of low invasiveness in nature, the
anesthetic challenges of this procedure should not be
underestimated.
Procedure Stages
The diagnostic angiography has at least two distinct
stages. The first stage of intra-arterial (typically fem-
oral artery) sheath insertion can be associated with
considerable patient discomfort. The second stage is
related to intra-arterial contrast dye injection and
rarely causes significant pain other than warm
flushed sensation in the perfused area. During this
stage it is important, however, to minimize patient
movement to obtain high image quality. This is usu-
ally achieved by instructing the patient to hold his/
her breath and remain immobile during the contrast
injection. In cooperative neurologically intact adult
patients, diagnostic angiography can often be per-
formed using only local anesthesia for sheath inser-
tion and no or only minimal intravenous sedation
with or without anesthesiologists involvement (nurs-
ing sedation). Indeed large numbers of institutions
employ this approach thus avoiding a need to co-
ordinate their schedule with the anesthesia depart-
ment and potentially saving time on turn-over time
between cases. However, an increasing proportion of
diagnostic angiography procedures are performed in
patients with significant underlying disease includ-
ing cerebrovascular disease, critically ill patients, or
in patients who are unlikely to cooperate during the
procedure, such as patients with neurologic deficits
and children. Indeed, in many of these patients the
use of certain forms of light sedation, based primar-
ily on intravenous benzodiazepines and opioids, can
paradoxically unmask underlying neurologic disease,
through abolishing compensatory mechanisms, and
make them significantly less cooperative. Addition-
ally, many patients bring a high level of expectation
when it comes to a degree of discomfort related to a
diagnostic procedure. Many patients are well aware
of and request what they consider superior propo-
fol sedation, a drug which can be administered only
by anesthesia providers, or personnel trained in air-
way management and advanced life support. An
experienced anesthesiologist should be typically
most qualified to deal with these challenges. Based
on the experience in our and others institutions,
those practices which have anesthesia services sched-
uled for every patient undergoing neurointerventional
procedure, including diagnostic angiography, are less
likely to experience the failure of sedation, patient dis-
satisfaction, aborting procedures and loss of time
609
related to waiting for availability of anesthesia services
or rescheduling the patient for another time.
Anesthetic Technique and Design
The choice is typically between various degrees of
sedation and general anesthesia.
Sedation
See general discussion on sedation in previous sec-
tions. An acceptable level of sedation in most patients
can be easily achieved by bolus titration of midazolam
and short acting opioids, such as fentanyl. Propofol
infusion affords a better control in changing the depth
of sedation throughout the procedure and rapid
recovery to allow quicker discharge for outpatients
(84,85). Use of other medications such as remifentanil
(86,87) and dexmedetomidine (24) might be warranted
by a patients neurologic and hemodynamic status.
Droperidol is occasionally used for its dissociative
qualities but is also occasionally associated with sig-
nificant dysphoria (8890). Supplemental oxygen and
capnography in combination with standard monitor-
ing should be used in all patients. Equipment for
emergency airway and resuscitation should be imme-
diately available.
General Anesthesia
See general anesthesia section in general discussion
section. General anesthesia for the diagnostic angiog-
raphy is used in either critically ill patients who are
already intubated, cannot tolerate any form of seda-
tion without need for a secure airway, or patients in
whom a desired level of cooperation cannot be
achieved with sedation. It also can be used in those
patients who will definitely require neurointerven-
tional therapy following the diagnostic angiography.
Use of short acting intravenous or inhalational anes-
thetics will allow faster emergence to assess the neu-
rologic status.
Diagnostic angiography is not generally associ-
ated with a significant amount of post-operative
pain, although some discomfort is experienced as
patients must stay in supine position without bend-
ing the leg on the side of the sheath insertion for pro-
tracted periods of time. There is seldom need for the
use of long acting opioids. Diagnostic angiography
under simple sedation or propofol sedation is rarely
associated with significant postoperative nausea and
vomiting (91,92). Prophylactic use of antiemetics is
not recommended.
Standard anesthesia monitoring combined with
capnography is sufficient for most cases, unless
patients conditions warrant more advanced forms of
hemodynamic monitoring.
Anesthesia for Endovascular Management of
Cerebral Aneurysm
Although there is no clear consensus regarding opti-
mal management of unruptured or ruptured cerebral
aneurysm, an increasing number of indications and
strategies for the endovascular treatment of this
610 NEUROINTERVENTIONAL MANAGEMENT
condition have been proposed in recent years (93,94).
See the extended discussion on this topic in the chap-
ter on cerebral aneurysms (chapter 16). Ruptured cer-
ebral aneurysms are usually associated with a higher
likelihood of co-morbidities and critical illness than
that in patients with unruptured aneurysms. There
are a number of different approaches to endovascular
embolization of cerebral aneurysms, depending on
their anatomy and location, and neurointerventional-
ist preferences, which require modification of anes-
thesia techniques employed. Traditionally aneurysms
are secured by placement of platinum coils via intra-
arterial microcatheter into the cavity of the aneur-
ysm, with subsequent thrombus forming around the
coils. Depending on the aneurysm anatomy various
stents may be used to prevent coil extrusion in the
intravascular lumen. Recently a liquid embolization
material, Onyx HD 500 (ev3, Irvine, California, U.S.)
has been used as an alternative for aneurysmal abla-
tion. This technique requires temporary parent vessel
occlusion with an inflatable balloon across the aneur-
ysm neck while the liquid agent is injected inside the
aneurysm via a specially designed microcatheter. The
balloon stays inflated until polymerization of Onyx
takes place, to prevent leakage into the cerebral cir-
culation (9598).
Procedure Stages
The procedure can be divided in two stagesthe diag-
nostic stage and the intervention stage. The diagnostic
stage is typically not different from conventional diag-
nostic angiography. Depending on the availability of
previous imaging studies the patient may or may not
need the diagnostic stage. In follow-up cases to eva-
luate previously coiled aneurysms, or asymptomatic
small size aneurysms, which were left un-coiled for
observation, the diagnostic angiography stage may
not be followed by coiling. These patients, from the
anesthesia perspective, can be managed similarly to
patients undergoing routine diagnostic angiography. If
the decision is made to proceed with the intervention
the neurointerventional team would usually move
away the fluoroscopy equipment to facilitate an unen-
cumbered anesthesia access to the patient. This allows
the anesthesia team to make required adjustments,
e.g., transition to general anesthesia with endotracheal
intubation and arterial line placement and monitoring,
which typically are deemed necessary for anesthesia
management during aneurysm embolization. Depend-
ing on the aneurysm location, embolization technique,
and institutional routines and capabilities, neuro-
physiologic monitoring can be employed during the
intervention. Following the embolization, whenever
possible the patient should undergo emergence in an
expeditious manner to allow early neurological assess-
ment. Endovascular aneurysm treatment carries a risk
of intracranial bleeding or brain ischemia. Hemorrha-
gic complications happen either as a result of sponta-
neous aneurysm rupture or secondary to aneurysm or
vascular wall damage during microcatheter or stent
positioning, or coil placement. Ischemic complications
can result from temporary balloon occlusion, throm-
boembolism, arterial dissection, stent malpositioning,
or embolic material exiting in the vascular lumen.
Appropriate preparation should be made by the anes-
thesia team to handle these potentially catastrophic
emergencies.
Preoperative preparation should involve stand-
ard anesthesia evaluation, discussion with the neuro-
interventionalist regarding the exact technique, need
for neuroprotection during potential periods of vascu-
lar occlusion (it is these authors understanding that
no current so-called neuroprotective anesthesia techni-
que have been proven to be efficacious), goals for
hemodynamic management, and whether and what
modality of neurophysiologic monitoring may be
employed during the procedure. Neurologic evalua-
tion, whenever possible, is performed to appreciate
patients sedation and general anesthesia needs. Sites
for monitoring neuromuscular blockade are deter-
mined, to facilitate appropriate dosing and titration of
neuromuscular blocking drugs. Intraoperative man-
agement of patients arriving from intensive care unit
(ICU) is discussed with the neurointensivist, with an
emphasis on ventilator settings and ICP management,
especially in patients with ventriculostomy in place.
Notably, in patients with a ventriculostomy set
to drain at a specific level, over- or under-draining
can result when the neurointerventionalist raises or
lowers the table without communicating this to anes-
thesia. One approach to deal with this is to simply
monitor ICP and when it increases to a predetermined
threshold, drain CSF in a more controlled manner.
These patients who have a subarachnoid hemorrhage
often arrive with a ventriculostomy in place and the
team has to be familiar with the safe use of an extra-
ventricular drain (EVD) (Fig. 31.4)
Anesthesia Technique
General principles used in the anesthesia management
of neurosurgical patients, and for intraoperative cere-
bral aneurysm patients in particular are applied when
designing the anesthesia plan for the endovascular
treatment of cerebral aneurysm (99,100). Traditionally,
most patients with cerebral aneurysms undergo endo-
vascular treatment under general anesthesia with
endotracheal intubation and use of neuromuscular
blockade. However, successful use of conscious seda-
tion and local anesthesia for coiling of unruptured
aneurysm in a large number of patients has been
recently reported (101). All patients were evaluated
preoperatively and were deemed as suitable candi-
dates, whereas patients with anatomically difficult
lesions, lack of cooperation and restlessness were
excluded. Indeed, the optimal approach to anesthesia
management of these patients remains unsettled, as
discussed earlier in this chapter. Many neurointerven-
tionalists may be uncomfortable with having an
awake/sedated patient during aneurysm treatment or
stent placement and this fact must also be taken into
consideration while deciding on choice of anesthesia
technique.
Unlike in patients with unruptured aneurysm,
we believe general endotracheal anesthesia is the
anesthetic of choice for most patients with ruptured
aneurysm and SAH, or for patients with anatomically
complicated unruptured aneurysms. Many patients
with ruptured aneurysm arrive from the ICU, where
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY 611

G-transducer
NOT connected A-height of
to pressure bag CSF drainage
relative to
tragus

F-pressure tubing
to ventriculostomy B-quantitative
CSF collection
chamber

E-transducer zeroed
at level of tragus

D-pressure tubing to
quantitative CSF
collection chamber

C-CSF
collection
bag

Figure 31.4 Ventriculostomy setup (extraventricular drainEVD). (A) The EVD is typically setup to drain cerebrospinal fluid (CSF)
once a certain CSF pressure is achieved in the head. This is established by setting the level of the EVD at the cmH2O above the
tragus. This represents the popoff pressure and when the CSF pressure exceeds this, CSF drips in the collection chamber. (B) The
quantitative collection chamber is where the CSF drips and can be used to measure the amount of CSF drained. When it fills up, the
stopcock below the chamber is opened to drain into the CSF collection bag. (C) CSF collection bag. (D) Pressure tubing to the quanti-
tative CSF chamber goes from the stopcock on the transducer to the CSF collection chamber. (E) Transducer. This is zeroed at the
level of the tragus. The orientation of the transducer stopcock determines if the CSF drains directly into the CSF collection chamber or
if the intracranial pressure (ICP) is being continuously monitored. Note that if the transducer is not physically connected to the bed,
that raising or lowering the bed will alter the pressure at which CSF drains and can produce under or over drainage. Keeping the trans-
ducer set to monitor averts this problem by providing a continuous ICP number, and when the ICP exceeds a predetermined level the
stopcock can be reoriented to allow CSF drainage at the correct EVD height under direct observation. (F) Pressure tubing to ventricu-
lostomy is the tubing which connects the EVD to the transducer and the drainage system. Typically there is another stopcock in this
tubing which provides an extra layer of safety to prevent overdrainage, particularly during transport. (G) The transducer used for ICP
monitoring, unlike transducers used for hemodynamic pressure monitoring, is not connected to a high pressure flush bags. A high pres-
sure flush is useful to maintain patency of a vascular monitoring line but can introduce suprasystemic pressures into the brain and
should never be connected to an ICP transducer.

they are already intubated and undergoing ventilator
support with a ventriculostomy and possibly already
well sedated. These patients often require only mini-
mal additional anesthesia. No specific anesthetic agent
has an advantage over another, although shorter act-
ing agents may allow faster reversal and shorter times
to neurologic assessment. Use of neuromuscular
blockade allows lighter planes of anesthesia with typi-
cally more hemodynamic stability and reliable immo-
bility. Additionally, some neurointerventionalists may
ask for brief periods of apnea during coil placement
or stent deployment to minimize any head move-
ments. This is more easily achieved in chemically par-
alyzed patients. Choice of specific anesthetic agents is
also guided by anticipated physiologic needs and spe-
cific interventions goals, such cerebral perfusion pres-
sure, ICP and cerebral aneurysm transmural pressure
management, the discussion of which is beyond the
scope of this chapter but can be reviewed in anesthesi-
ology or neuroanesthesiology textbooks.
Anesthesia for Neurointerventional Management
of Vasospasm Following SAH
Symptomatic cerebral vasospasm is a well-recognized
consequence of SAH observed in up to one-third of
all patients with SAH (102108). It is one of the main
causes of mortality and major morbidity in the initial
612 NEUROINTERVENTIONAL MANAGEMENT
survivors of SAH. The traditional treatment consisting
of induced hypertension and volume expansion is
directed at improving blood flow to underperfused
areas of the brain in hope of minimizing brain ische-
mia and preventing stroke (109113). Opinions
recently are shifting away from the use of hemodilu-
tion with most efforts currently focused on induced
hypertension as the most useful medical therapy of
vasospasm (113,114). It is important to point out the
danger of re-bleeding with hypertensive therapy in
patients with unclipped/unembolized cerebral aneur-
ysm or AVM.
Endovascular treatment of persistent vasospasm
has been used as either an alternative to the so-called
triple H therapy in patients who cannot tolerate hyper-
tension and volume expansion or in those patients who
failed to respond to it. Endovascular treatment consists
of intra-arterial vasodilator infusion or balloon angio-
plasty, or a combination of those two techniques
depending on the morphology of the vasospasm (115).
A number of vasodilating agents have been used with
good result, with papaverine (115118) and nicardipine
(115,119123) being most frequently used. The extensive
discussion on the diagnosis and treatment of cerebral
vasospasm can be found in the chapter on cerebral
aneurysm (chapter 17).
Procedure Stages
During the first part of the procedure, diagnostic
angiography is performed to confirm the diagnosis of
the vasospasm and based on the angiographic picture
to decide, which technique to employ. During the
second stage, an intra-arterial infusion microcatheter is
fluoroscopically positioned for direct infusion of vaso-
dilator into the spastic vessel. This may be accompanied
200
150
100
50
0 0
12:45 13:00 13:15 13:30
Figure 31.5 Excerpt from an electronic anesthesia record showing the effects of intra-arterial nicardipine on systemic blood pressure.
Systolic blood pressure highlighted, decreasing from 200 mmHg to 150 mmHg, despite starting on a phenylephrine infusion with the
dose increased during the procedure, producing a partial return to the blood pressure goal.
by decrease in blood pressure (122,124) (Fig. 31.5) and
occasional elevation of ICP (which may be a direct
effect of cerebral vasodilation or reflex vasodilation in
response to the decrease in blood pressure). To avoid
these side effects intra-arterial vasodilators are infused
slowly over prolonged period (about 30min) of time
and infusion may be further slowed down in patients
with significant decrements in cerebral perfusion pres-
sure due to increased ICP or decreased blood pressure.
Systemic vasopressor infusion may be needed during
this time. In the case of angioplasty, the balloon catheter
is advanced into the constricted parts of the vessel,
where it is inflated to dilate the vascular lumen. Follow-
ing the intervention, another set of images is obtained
to demonstrate improvement in cerebral perfusion
(115,125127). Angioplasty may result in a new intra-
cranial hemorrhage secondary to either direct vessel
rupture or dissection or due to reperfusion bleed
(125,128). Thromboembolic complications have also
been reported. In a case of unsecured aneurysm there is
also a risk of a secondary aneurysm rupture.
Anesthesia Preparation and Technique
Most symptomatic cerebral vasospasm patients have a
significant change in neurologic status and tend to be
critically ill. They must be evaluated for presence of
subendocardial injury and myocardial dysfunction sec-
ondary to SAH (129), pulmonary edema secondary to
volume overload or cardiomyopathy (130132), extent
of neurologic deficit, and other co-morbidities. Many
patients arrive from the ICU already intubated, venti-
lated and sedated, and with either ICP pressure probe
or ventriculostomy in place. These patients, often on
infusions of propofol, opioids, or benzodiazepines (as
illustrated in Fig. 31.1), will generally require only
200
150
100
50
13:45 14:00 14:15 14:30 14:45 15:00
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
minimal additional anesthesia. In unintubated patients
general endotracheal anesthesia is typically used. Poten-
tial profound hypotension following induction of gen-
eral anesthesia secondary to myocardial dysfunction
and hypovolemia is occasionally observed in these
patients and should inform the choice of induction
agents. In these patients etomidate may be the induction
agent of choice due to less significant hemodynamic
effects. Use of neuromuscular blockade facilitates
immobility, which can be crucial, especially during bal-
loon angioplasty, while facilitating use of lower anes-
thetic doses to lessen cardiovascular depression.
Hemodynamic and ICP Management
Cerebral perfusion pressure in patients with cerebral
vasospasm usually must be maintained at higher
above normal levels in order to improve perfusion in
the affected areas of the brain. This is achieved by
keeping mean arterial pressure (MAP) above baseline
level and, as possible, keeping ICP in the normal
range. Preoperative discussion with the neuroICU
team and interventional neuroradiology team is help-
ful to determine the target range for MAP and ICP.
Vasopressors, such as phenylephrine, norepinephrine
or epinephrine infusion, are routinely used for main-
taining MAP in the desired range, depending on the
degree of myocardial dysfunction present. The ICP is
managed by draining CSF from the ventriculostomy
in those patients who already have one, especially
for intra-arterial vasodilating therapy. Additional ICP
reducing therapies include mannitol (133135), hyper-
tonic saline (122,124,136,137) and preferential use of
propofol (40,46,138) as the mainstay of the anes-
thetic. Good understanding how to calibrate the
ventriculostomy transducer and to drain CSF safely
is important for anesthesiologist working with neu-
rosurgical patients to avoid potentially serious com-
plication related to use of a ventriculostomy (Fig.
31.4). Hyperventilation should not be used routinely
to avoid potential augmentation of cerebral vaso-
spasm and cerebral ischemia, but can be used in
critical situations, e.g., herniation. All patients
should have blood pressure monitored with an arte-
rial cannula. Use of shorter acting anesthetic agents
facilitates shorter time to neurologic examination
following the procedure, which is desirable.
Embolization of Cerebral Arteriovenous
Malformations
Arteriovenous fistulas or malformations (AVMs) can
be divided into cerebral or pial and dural AVMs.
Their etiology, presentation, clinical manifestations,
and clinical course can be distinctly different and
may require different treatment approaches. Intracra-
nial hemorrhage is one of the main complications of
cerebral AVM and can be associated with high mor-
bidity and mortality. Typically, a multidisciplinary
approach is required in the management of most
AVMs. Interventional neuroradiology plays a big role
in the treatment of these conditions. Many AVMs
will require either neurosurgical excision or radiosur-
gery for definitive treatment. Detailed angiography is
required for both in order to determine the anatomy
613
and indication for those procedures. Endovascular
embolization of AVMs with various embolic agents
often serves as an adjunct to neurosurgery or radio-
surgery. Embolization allows reduction of the AVM
size leading to decreased intraoperative blood loss
and decrease in associated morbidity and mortality.
Certain AVMs can be definitively treated by endo-
vascular embolization alone, although often requiring
a number of sessions weeks or months apart. In
some patients with inoperable AVMs, embolization
reduces the risk of new hemorrhage or re-bleeding
and also alleviates some symptoms unrelated to
bleeding. Different embolization agents are being
used in modern practice, which might have an effect
on anesthesia management. Detailed discussion of
these issues is in the chapter on AVM management
(chapter 18).
Procedure stages are similar to those for cerebral
aneurysm neurointerventional management. Diag-
nostic angiography allows visualization of compli-
cated AVM anatomy before making decision about
optimal position of arterial microcatheter in an arte-
rial feeder to the fistula. Depending on the emboliza-
tion agent used, neurointerventionalist might decide
to use a sodium amytal test immediately before
injecting embolic agent. Temporary anesthesia is pro-
duced in the downstream watershed area with sub-
sequent neurologic examination intended to detect
whether it is associated with any induced transitory
neurologic deficits, akin to a Wada test. This techni-
que allows minimizing the risk of embolic agents
being carried by blood flow and lodged in the func-
tional brain tissues. During the embolization the
neurointerventionalist may ask for reduction in arte-
rial blood pressure by 1015% to minimize the risk
of embolic complications.
Anesthesia preparation and technique is similar to
that outlined for cerebral aneurysm management.
Many AVM embolizations can be done with sedation
of variable depth depending on the stage of the proce-
dure and specific anatomic location of the AVM. In
fact if sodium amytal testing is planned, light sedation
is necessary to allow neurologic testing. On the other
hand, embolization with the liquid embolic agent
Onyx can be associated with considerable degree of
pain and discomfort and requires the patient to
remain absolutely still during the period of emboliza-
tion. Therefore most of these procedures should be
done under general anesthesia. Invasive arterial moni-
toring is typically used for the intraoperative blood
pressure management with vasoactive drugs. Consid-
ering the risk of ischemic and hemorrhagic complica-
tions, preparations should be made for the emergency
airway management of the sedated patient if neces-
sary. Patients with airway anatomy and history pre-
dictive of difficult intubation should be considered for
general anesthesia prospectively. That is to say, the
notion that sedation in a patient with a difficult airway
is safer is not the case because the development of a
need for emergency airway control would be a cata-
strophic situation, further complicating new dynamic
neurologic problems with hypoxemia, hypercapnea,
and cardiovascular instability. Use of short acting
anesthetic agents is encouraged to allow quick emer-
gence from anesthesia and neurologic examination.
614 NEUROINTERVENTIONAL MANAGEMENT
Transarterial Embolization of Vascular Tumors
Transarterial embolization of vascular extracranial
head and neck tumors and of vascular intracranial
tumors (meningiomas, hemangioblastomas, etc.) is
directed at devascularization of these lesions. It is usu-
ally done as a preoperative procedure aimed at mini-
mizing blood loss and improving operative conditions
during definitive surgical resection. Concurrently,
angiographic inspection of the detailed anatomy of
the lesion and its venous outflow can significantly
reduce the risks of operative complications. It is also
performed as a palliative procedure for inoperable
lesions.
Basic stages of these procedures and anesthesia techni-
que are similar to that for AVM embolization and can
be usually performed under sedation, unless Onyx is
being used, which tends to be too painful for sedated
patients to tolerate. In that case, use of general anes-
thesia may be necessary. Of course patient neurologic
status and co-morbidities may be decisive factors
in the choice of anesthetic technique. Decision on the
use of arterial line is done in consultation with the
neurointerventionalist.
Endovascular Treatment of Acute Ischemic
Stroke
For patients with acute ischemic stroke (AIS) time is
brain and achieving fastest possible re-canalization
of occluded vessel and reperfusion of the ischemic
brain tissues can result in dramatically improved out-
comes. Those patients who fail intravenous trial of
thrombolytic therapy are often candidates for either
intra-arterial pharmacological thrombolysis or endo-
vascular mechanical clot retrieval with a number of
devices. Endovascular treatment of AIS is a rapidly
evolving and promising field with many new emerg-
ing technologies, some of which are in development
or trial stages (139,140). From the anesthesiologists
perspective it is important to appreciate the emer-
gency nature of these procedures where every
minute of delay in re-canalization is potentially paid
for with the terminal loss of brain tissue. Also, these
treatments carry substantial potential for hemorrha-
gic intracranial complications (141143) in a popula-
tion with typically significant cardiovascular and
cerebrovascular co-morbidities.
Anesthetic management for endovascular stroke
treatments has recently become the subject of signifi-
cant controversy. Although traditionally GA has been
predominantly used in the past for endovascular treat-
ment of AIS, recently some reports advocated use of
local anesthesia (LA) with minimal sedation as a pre-
ferred alternative (144,145) whereas another report
advocates the use of general anesthesia (146). The
issue related to choice between GA and LA with seda-
tion for endovascular treatment of stroke are similar
to those discussed earlier in this chapter, but the
stakes are higher due to need avoiding delays in per-
forming the procedure, and also the extreme impor-
tance of being able to monitor changes in neurologic
status during these procedures. From this perspective,
LA with sedation has clear advantage over GA. How-
ever, in a number of patients a conversion to GA may
be necessary but can be significantly delayed if anes-
thesia providers were not involved from the start. In
the authors opinion, the dilemma of choosing
between GA and LA with sedation is unnecessary. It
would be preferable to have anesthesia services
involved in the management of these patients from
the very beginning, regardless whether they are ini-
tially managed under LA or GA. This approach would
allow the team to proceed with LA and sedation with-
out delays, while allowing the anesthesiologist to set
up for conversion to GA if necessary. Also, the imme-
diate availability of experienced anesthesia providers
can allow skilful use of light dexmedetomidine, which
may facilitate management of poorly cooperative
patients without resorting to GA. This option is not
available with nursing sedation. Otherwise, all basic
principles of anesthetic management of patients with
cerebral vasospasm outlined earlier should be fol-
lowed. Emphasis is on maintaining target cerebral
perfusion pressure, based on the discussion with the
treatment team. Use of arterial line is desirable, but
not if its placement results in time delays. Non-inva-
sive blood pressure can be sufficient to start the proce-
dure until the arterial line is placed. In some
circumstances, monitoring arterial pressure from the
femoral sheath may provide a solution to difficulty in
placing a peripheral arterial line. Extreme caution
must be exercised to avoid any airway trauma either
with endotracheal intubation or placement of oral/
nasal airways, to avoid persistent mucosal bleeding in
these anti-coagulated patients. In our opinion, the use
of the Glidescope (147149) or similar endoscopic
technologies affords a better atraumatic alternative to
direct laryngoscopy.
Vertebroplasty and Kyphoplasty
In patients with pathologic vertebral fractures due to
osteoporosis, metastatic or osteolytic lesions (such as
multiple myeloma), percutaneous vertebral stabiliza-
tion can be achieved by performing vertebro- or kypho-
plasty, often resulting in dramatic pain relief. It is
usually indicated in patients who have failed conserva-
tive management of their condition. The procedure is
performed by injecting radio-opaque polymethylmetha-
crylate cement into the affected vertebral body under
fluoroscopic guidance. During kyphoplasty an inflat-
able balloon is introduced inside the affected vertebral
body to dilate the cavity and to increase the height of
the fractured vertebra followed by the cement injection.
Consequently, kyphoplasty tends to take longer to
perform than vertebroplasty and can be associated
with substantial amount of brief intense pain and dis-
comfort. Patients are positioned prone on the fluoro-
scopy table with some form of chest and pelvis
support to open the interspinous spaces and improve
visualization.
Vertebroplasty is usually performed under LA
with sedation using standard monitors and side
stream capnography to monitor respiration. Kypho-
plasty can be done under sedation, but often is poorly
tolerated. We prefer to use general endotracheal anes-
thesia, which creates optimal operating conditions and
usually well tolerated by patients. Positioning can be
challenging and airway monitoring is even more
 ANESTHESIA FOR INTERVENTIONAL NEURORADIOLOGY
Figure 31.6 Vertebroplasty in a prone sedated patient. Access to the patient to evaluate neurologic status, pain, and airway integrity
can be a challenge as shown in this photo.
problematic than in the supine patient in the radiol-
ogy suite (Fig. 31.6). It is important to remember that
the procedure is performed in a mostly elderly popu-
lation with multiple co-morbidities and carries a risk
of potentially serious complications related to polyme-
thylmethacrylate cement injection. Cement extravasa-
tion, extrusion of cement and compression of the
spinal cord, pulmonary embolism and hemo/pneumo-
thorax have been reported (150). The anesthesiologist
should be aware of these potential complications and
be prepared to treat them.
SUMMARY
Anesthesia in neuroradiology poses a variety of chal-
lenges to the anesthesia team. These include poten-
tially increased risk related to the remote location and
the numerous neurocritical care issues that may arise,
including ICP issues, intracranial hemorrhage, ana-
phylaxis, and vasospasm, among others. For most pro-
cedures a decision regarding the use of sedation or
general endotracheal anesthesia is needed. Typically,
hard evidence, supporting one mode versus the other,
is absent and the team is guided by individual prefer-
ences and common sense. Good interdisciplinary com-
munication is essential.
615
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ACA. See Anterior cerebral artery
ACAS. See Asymptomatic Carotid
Artery Surgery;
Asymptomatic Carotid
Atherosclerosis Study
Access site complications,
592594
Acculink Carotid Stent, 241
Acquired immune deficiency
syndrome (AIDS). See
Human immunodeficiency
virus
Acrylic glue, 534
ACST. See Asymptomatic Carotid
Surgery Trial
ACTH. See Adrenocorticotropin
ACTH-dependent Cushings
syndrome, 485486
ACTH-secreting pituitary
adenoma, 485486
Acute embolic stroke
MERCI retriever, 245246
Penumbra reperfusion catheters,
244245
Acute ischemic stroke
anesthesia, 614
angiographic evaluation, 405
intra-arterial chemical
thrombolysis
anterior circulation, 405408
posterior circulation, 408
intra-arterial mechanical
thrombolysis
augmented fibrinolysis, 410
endovascular thrombectomy,
408, 410
endovascular
thromboaspiration, 410
thrombus disruption, 410
thrombus entrapment, 410
neurological complications,
590591
patient selection, 404
Adrenocorticotropin (ACTH), 485,
492
Adult-type dural arteriovenous
fistula, 450
Aggressive cranial dural
arteriovenous fistulas, 453,
458459
AGS. See Alagille syndrome
AICA. See Anterior inferior
cerebellar artery
AIDS. See Acquired immune
deficiency syndrome
Alagille syndrome (AGS), 513514
Allcock test, 335
Alligator retrieval device, 408
Index
Alternative reperfusion
strategies, 410
American College of Radiology
(ACR), 104
guidelines, 560561
American Society of
Anesthesiologists, 606
Amobarbital, 258, 262
Amplatz, 234
Anaphylaxis, 594, 608
Anastomotic veins
inferior anastomotic vein of
Labbe, 101
superficial middle cerebral vein,
100101
superior anastomotic vein of
Trolard, 100
Anesthesia
complications
anaphylaxis, 608
intracranial hemorrhage, 608
neurointerventional procedures
anticoagulation, 608
general vs. sedation, 605608
hemodynamic management,
608
planning and administration,
604605
principles of, 601602
safety issues, 602604
neuroradiologic procedures
acute ischemic stroke, 614
cerebral aneurysm, 609611
diagnostic angiography, 609
embolization of cerebral
arteriovenous
malformations, 613
kyphoplasty, 614615
transarterial embolization, 614
vasospasm, 611613
vertebroplasty, 614615
Aneurysms
with BAVMs
classification, 381
clinical implications, 384
epidemiology, 381
pathogenesis, 381384
treatment approaches, 384385
intracranial (see Intracranial
aneurysms)
intracranial collaterals, 8182
pediatric, 500, 502
pediatric intracranial, 500504
saccular, 501
subarachnoid hemorrhage
from aneurysmal rupture,
112113
nonaneurysmal, 113
and saccular aneurysmal
rupture, 110112
traumatic, 503
Angiographically occult vascular
malformations, 188189
Angioinvasive aspergillosis,
215216
AngioJet system, 410, 481482
Angioplasty
balloon, 369371
pharmacological, 369
Angio-Seal, 252
Anterior cerebral artery (ACA)
cerebrovascular variants
management, 9596
neurovascular anatomy, 2528
Anterior choroidal artery, 2324
Anterior communicating artery
(ACoA), 9596
Anterior inferior cerebellar artery
(AICA), 99
Anterior radiculomedullary
arteries, 41
Anticholinergic medications, 592
Anticoagulation
anesthesia, 608
systemic, 478
in vascular access, 230
Aortic arch
cerebrovascular variants
management, 88
embryology of, 1
APA. See Ascending pharyngeal
artery
APCDs. See Arterial puncture
closure devices
Arterial and venous occlusion
testing
complications, 257
CT perfusion imaging, 257
indications, 254
induced hypotension, 255
MR perfusion imaging, 256257
neurophysiological
monitoring, 257
SPECT imaging, 256
stump pressures, 255
TCD, 257
techniques, 254255
xenon CT imaging, 257
Arterial closure devices, 252
Arterial dissections, 121122, 150,
171172
characteristics of, 291
clinical features of, 293
pathophysiology of, 291292
Arterial feeders, 376
Arterial infarct, 548
622 INDEX
Arterial pressure, 255
Arterial puncture closure devices
(APCDs), 592593
Arteriovenous malformations
(AVMs)
extradural
clinical manifestations, 539540
imaging techniques, 540
treatment methods, 542
intramedullary
clinical manifestations,
535536
imaging techniques, 536538
metameric angiomatosis, 538
treatment methods, 538539
neurological complications,
587588
nonaneurysmal subarachnoid
hemorrhage, 113114
in pediatric cerebrovascular
disease, 499500
perimedullary
classification, 531
clinical manifestations,
532533
and hemorrhagic
telangiectasia, 531532
imaging techniques, 533534
treatment methods, 534535
in pregnancy, 550
in vascular malformations,
282285
Ascending pharyngeal artery
(APA), 56, 8, 32, 90
Aspergillus fungal sinusitis, 216
Aspergillus vasculitis, 217
Asymptomatic Carotid Artery
Surgery (ACAS), 170
Asymptomatic Carotid
Atherosclerosis Study
(ACAS), 415
Asymptomatic Carotid Surgery
Trial (ACST), 415
Atherosclerosis, 118121
Atherosclerotic plaque
extracranial carotid angioplasty,
240
intracranial angioplasty, 240
Augmented fibrinolysis, 410
Aviator balloon catheter, 240
AVM. See Arteriovenous
malformation
Bacterial infections, 213
Balloon angioplasty, 369371
Balloon-assisted aneurysm
remodeling, 236237
Balloon-assisted vertebroplasty. See
Kyphoplasty
Balloon catheters
balloon-assisted aneurysm
remodeling, 236237
balloon test occlusion, 237
extracranial carotid angioplasty,
240
high-pressure balloons, 237238,
240
intracranial angioplasty
of atherosclerotic plaque, 240
for cerebral vasospasm, 237
low-pressure balloons, 235236
other applications, 240
Balloon-mounted stents, 241
Balloon remodeling technique,
343345
Balloon test occlusion (BTO), 237,
239
Balt Magic microcatheters, 233
Basal vein of Rosenthal, 101
Basilar artery, 98
Basilar meningitis, 213214
BAVM. See Brain arteriovenous
malformations
BCVI. See Blunt carotid vertebral
injury
Behets disease, 212
Benign cranial dural arteriovenous
fistulas, 452453, 457
Bleomycin, 251
Bloch-Sulzberger syndrome. See
Incontinentia pigmenti
Blood-brain barrier (BBB)
disruption, 179
Blood velocity measurements, 158
Blunt carotid vertebral injury
(BCVI), 126128
Blunt injury, 127128
Bolus contrast CT perfusion,
106108
Borden DAVF classification, 451
Brain arteriovenous malformations
(BAVM)
angioarchitecture
aneurysms, 381385
draining veins, 380381
feeding arteries, 376377
nidus, 377, 380
cerebral angiography, 375
classification
deep, 375376
superficial, 375
epidemiology of, 374
grading systems, 385386
natural history of, 374375
pathogenesis of, 374
selective angiographic
evaluation, 378
superselective angiographic
evaluation, 378
Brainstem injury, 493
Brevital, 259
BTO. See Balloon test occlusion
Bulls-eye approach, 565
CAA. See Cerebral amyloid
angiopathy
CADASIL. See Cerebral autosomal-
dominant arteriopathy with
subcortical infarcts and
leukoencephalopathy
Calcification, 173
Call-Fleming syndrome. See
Reversible cerebral
vasoconstriction syndrome
Capillary hemangioma, 266267
Capillary malformation-
arteriovenous malformation
(CM-AVM) syndrome, 510
Capillary telangiectase.
See Capillary vascular
malformations
Capillary vascular malformations,
187, 280
CARASIL. See Cerebral recessive
arteriopathy with
subcortical infarcts and
leukoencephalopathy
CARAT. See Cerebral Aneurysm
Rerupture after Treatment
Cardioembolic stroke, 548
CaRESS. See Carotid
Revascularization using
Endarterectomy or Stenting
Systems
Carotid and Vertebral Artery
Transluminal Angioplasty
Study (CAVATAS), 419
Carotid angioplasty and stenting
(CAS), 168169
Carotid artery dissection. See also
Extradural dissection;
Intradural dissection
diagnosis detection
computed tomography
angiography, 300
digital subtraction
angiography, 294297
magnetic resonance
angiography, 298300
magnetic resonance imaging,
298300
ultrasonography, 297298
epidemiology, 291
pathogenesis, 291293
pathophysiologic process, 305
prognosis and outcome,
311312
Carotid artery revascularization,
415416
Carotid artery stenting
durability, 426
high-risk features, 427
markers, 426
patient preparation and
procedure overview,
424426
postintervention follow-up, 426
training for carotid stenting, 424
Carotid bifurcation, 89
Carotid body tumors, 270271
Carotid cavernous fistula (CCF)
anatomy of, 316318
classification of, 318
clinical features of, 316
etiology of, 316

follow-up, 325
imaging studies of, 319320
indications for treatment, 318319
pathophysiology of, 316318
symptoms and signs of, 318
treatment options
endovascular therapy, 320325
goal of, 320
medical therapy, 320
surgical therapy, 320
Carotid endarterectomy (CEA)
carotid artery revascularization,
415416
embolic protection devices,
419420
extracranial disease
management guideline,
423424
periprocedural risk factors,
416419
stenting trials, 419
vs. trials of angioplasty in
high-risk patients
EVA-3S, 421
ICSS (CAVATAS-2), 422
SAPPHIRE, 420421
SPACE, 421422
vs. trials of angioplasty in
lower-risk patients
CaRESS, 422423
CREST, 423
trials under way, 423
Carotid occlusion, 172173
Carotid plaque imaging, 148150
Carotid Revascularization
Endarterectomy versus
Stenting Trial (CREST),
415416, 423
Carotid Revascularization using
Endarterectomy or Stenting
Systems (CaRESS), 420,
422423
Carotid stenosis, 148
Carotid stenosis index (CSI), 441
Carotid ultrasonography
calcification, 173
carotid occlusion, 172173
extracranial VA, 173174
high bifurcation, 173
tortuosity, 173
CAS. See Carotid angioplasty and
stenting
Catch thrombectomy device, 408
Catheter angiography, 205, 208
Catheters
balloon (See Balloon catheters)
continuous flush systems,
233234
diagnostic, 230231
distal access catheter, 232
flow-guided microcatheters, 233
guide, 232
guidewire-directed
microcatheters, 233
microcatheter, 232233
rotating hemostatic valve,
233234
stopcock, 233234
CAVATAS. See Carotid and
Vertebral Artery
Transluminal Angioplasty
Study
Cavernous sinus, 101
CAVM. See Cerebral arteriovenous
malformations
CCA. See Common carotid arteries
CCF. See Carotid cavernous fistula;
Crotid-cavernous fistula
CCM. See Cerebral cavernoma
malformations (CCM);
Cerebral cavernous
malformation (CCM)
Cerebellar arteries
anterior inferior cerebellar
artery, 99
posterior inferior cerebellar
artery, 99
superior cerebellar artery, 99
upper basilar artery, 99
Cerebral amyloid angiitis, 206
Cerebral amyloid angiopathy
(CAA), 206
Cerebral Aneurysm Rerupture after
Treatment (CARAT), 343
Cerebral aneurysms
anesthesia, 609611
neurological complications,
588590
Cerebral angiogram, 239
Cerebral angiography
brain arteriovenous
malformations, 375
intracranial aneurysms, 328
Cerebral arteriovenous
malformations (CAVM),
7981
Cerebral autosomal-dominant
arteriopathy with
subcortical infarcts and
leukoencephalopathy
(CADASIL), 221, 516517
Cerebral cavernoma malformation
(CCM), 514515
Cerebral cavernous malformation
(CCM)
angiographically occult
vascular malformations,
188189
capillary vascular
malformations, 187
cerebral venous malformations,
187
clinical presentation of,
194195
diagnostic imaging of, 193194
epidemiology of, 189192
histopathology of, 192193
intracranial hemorrhage, 195
management strategy
epilepsy, 196197
INDEX 623
expectant management,
195196
medical management, 196
patients with, 196197
radiosurgical treatment, 198
surgical adjuncts, 198
surgical resection, 196
pathobiology of, 192193
pathogenesis of, 193
Cerebral ischemia, 293294
Cerebral microdialysis (CMD), 589
Cerebral recessive arteriopathy
with subcortical infarcts and
leukoencephalopathy
(CARASIL), 516517
Cerebral spinal fluid analysis,
204, 213
Cerebral vasculitis
cerebral amyloid angiitis, 206
connective tissue disease
vasculitides, 212213
differential diagnosis, 204
infectious vasculitides, 213218
other mimics, 219222
primary angiitis of central
nervous system, 203206
rational approach for diagnosis,
203
reversible cerebral
vasoconstriction syndromes,
218219
systemic vasculitides, 207212
Cerebral vasospasm
endovascular treatment
angioplasty, 369370
balloon angioplasty
technique, 371
systemic endovascular
techniques, 368369
timing of angioplasty, 370371
intracranial angioplasty, 237
pathophysiology of, 367368
Cerebral veins
clinical considerations, 3738
deep venous system, 3637
superficial venous system, 3536
Cerebral venous and dural sinus
thrombosis (CVST)
clinical presentation, 470471
diagnosis
computed tomographic
venography, 475476
computed tomography, 472
digital subtraction
angiography, 476478
magnetic resonance imaging,
472473
magnetic resonance
venography, 473475
epidemiology of, 469
outcomes and treatment
endovascular intervention,
479481
intracranial pressure
management, 481
624 INDEX
Cerebral venous (Continued)
systemic anticoagulation, 478
pathophysiology of, 469470
risk factors, 469470
Cerebral venous malformations, 187
Cerebral venous thrombosis, 550
Cerebral venous thrombosis
(CVT), 7678
neurological complications,
591592
Cerebrovascular lesions, 495
Cerebrovascular variants
management
anterior circulation
anterior cerebral artery, 9596
anterior communicating
artery, 9596
carotid bifurcation, 89
carotid vertebrobasilar
anastomoses, 94
circle of Willis, 9495
common carotid artery, 8889
external carotid artery, 9092
internal carotid artery, 9294
middle cerebral artery, 96
posterior cerebral artery,
9697
aortic arch, 88
posterior circulation
basilar artery, 98
cerebellar arteries, 9899
vertebral artery, 97
vertebrobasilar junction, 9798
venous system
anastomotic veins, 100101
cavernous sinus, 101
deep venous system, 101
dural venous sinuses, 99100
veins of posterior fossa, 101
WADA testing, 101
Cervical DAVFs, 527, 529
Cervical veins, 18
CES. See Cholesterol embolization
syndrome
CFA. See Common femoral artery
CHF. See Congestive heart failure
Cholesterol embolization
syndrome (CES), 594
Choriocarcinoma metastases, 554
Choroidal vein of Galen aneurysmal
malformations, 495
Churg-Strauss syndrome (CSS), 211
CIN. See Contrast-induced
nephropathy
Circle of Willis, 9495
Clinical coordinator, 561
CMD. See Cerebral microdialysis
Coagulopathy, 285
Cobb syndrome, 538
Coccidioidomycosis, 218
Cognard DAVF classification, 451
Coils, embolic material, 246247
Color duplex ultrasonography,
297298
Common carotid artery (CCA)
cerebrovascular variants
management, 8889
external carotid artery
anastomotic network, 12
ascending pharyngeal artery,
56
facial artery, 9
internal maxillary artery,
1112
lingual artery, 6, 9
occipital artery, 910
posterior auricular artery,
1011
superficial temporal artery, 11
superior thyroid artery, 5
internal carotid artery, 12, 1516
Common femoral artery (CFA),
227228
Complex-curve catheters, 231
Computed tomographic
venography (CTV), 475476
Computed tomography
angiography (CTA), 300
Computer-asissted tomography
(CT)
cisternography, 104
clinical applications
ischemia, 116124
nontraumatic hemorrhage,
110115
trauma, 125128
myelography, 104
perfusion technique
bolus contrast, 106108
stable xenon, 108109
Computer-asissted tomography
angiography (CTA), 105
106, 116117
cerebrovascular, 118122
Congestive heart failure (CHF), 417
Connective tissue disease
vasculitides
rheumatoid arthritis, 213
scleroderma, 213
Sjgrens syndrome, 213
systemic lupus erythematosus,
212213
Conservative therapy, 560
Continuous flush systems, 233234
Contralateral carotid occlusion, 418
Contrast-enhanced magnetic
resonance angiography,
138140, 298
Contrast-induced nephropathy
(CIN), 594
Cortical brain arteriovenous
malformations, 375
Cortical vein thrombosis, 473474
Cranial dural arteriovenous
fistulas
classification, 451452
clinical features
aggressive DAVFs, 453
benign DAVFs, 452453
diagnostic imaging
computer tomography, 454
digital subtraction
angiography, 455
MRI/MRA, 454455
radiosurgery, 461
therapeutic considerations,
455461
Craniofacial vascular
malformations, 266
CREST. See Carotid
Revascularization
Endarterectomy versus
Stenting Trial
Crotid-cavernous fistula (CCF),
3738
Cryoglobulinemia, 212
Cryoglobulins, 212
Cryptococcal meningitis, 218
CSI. See Carotid stenosis index
CSS. See Churg-Strauss
syndrome
CTA. See Computed tomography
angiography; Computer-
asissted tomography
angiography
CTV. See Computed tomographic
venography
Curative BAVM embolization,
388, 396
Cushings syndrome, 485
CVST. See Cerebral venous and
dural sinus thrombosis
CVT. See Cerebral venous
thrombosis
DAC. See Distal access catheter
DAVF. See Dural arteriovenous
fistulas; Dural arteriovenous
shunts or fistulae
Decompressive hemicraniectomy
(DHC), 591
Deep brain arteriovenous
malformations, 375376,
379
Deep parenchymal brain
arteriovenous
malformations, 376
Deep venous system
cerebral veins, 3637
cerebrovascular variants
management
basal vein of Rosenthal, 101
internal cerebral vein, 101
vein of Galen, 101
Deep venous thrombosis, 476
Delayed hydrocephalus, 358
Delayed ischemic neurologic
deficit (DIND), 367
Developmental venous anomaly
(DVA), 187
DHC. See Decompressive
hemicraniectomy
Diagnostic angiography, 609
Diagnostic catheters, 230231
Diagnostic US imaging

carotid ultrasonography
calcification, 173
carotid occlusion, 172173
extracranial VA, 173174
high bifurcation, 173
tortuosity, 173
duplex sonography of carotid
and vertebral arteries
arterial dissection, 171172
assessment of vascular
pathology, 170
degree of stenosis, 170
reference values, 170171
revascularization procedures,
171
intracranial arterial occlusion
detection, 159162
cerebral vasospasm, 163165
coiled intracranial aneurysms,
165166
intracerebral venous system,
166167
intracranial atherosclerotic
stenosis, 162163
vascular malformations, 166
microemboli detection, 167168
carotid angioplasty and
stenting, 168169
endovascular treatment of
intracranial aneurysms, 170
percutaneous transluminal
angioplasty, 170
techniques
blood velocity measurements,
158
Doppler display modes, 158
grayscale imaging, 158
transcranial Doppler (TCD),
157158
Digital subtraction angiography
(DSA), 163, 294297,
476478
Dimethyl sulfoxide (DMSO), 390
DIND. See Delayed ischemic
neurologic deficit
Direct CCF. See Carotid cavernous
fistula
Direct chemical thrombolysis, 479
Direct percutaneous puncture, 229
Dissecting aneurysm, 292
Dissection-related stenosis, 241242
Distal access catheter (DAC), 232
Distal embolic protection devices,
234235
Distal feeding artery aneurysm,
384
Distal flow-related aneurysm, 382
DMSO. See Dimethyl sulfoxide
Dominant feeder, 377
Doppler display modes, 158
Double-lumen balloon catheters.
See High-pressure balloon
catheters
DSA. See Digital subtraction
angiography
2D time-of-flight (TOF) MRA
technique, 134136
3D time-of-flight (TOF) MRA
technique, 136137
Dual microcatheter technique, 350
Duplex ultrasonography, 297298
Dural arteriovenous fistulas
(DAVF)
cranial
classification, 451452
clinical features, 452453
diagnostic imaging, 454455,
461
therapeutic considerations,
455461
neurological complications, 588
pathophysiology of, 450451
spinal
classification, 463464
clinical features, 464
diagnostic imaging, 464
therapeutic considerations,
464466
Dural arteriovenous shunts or
fistulae (DAVF), 7879
Dural sinus thrombolysis, 480
Dural venous sinus
inferior sagittal sinus, 100
occipital sinus, 100
sigmoid sinus, 100
straight sinus, 100
superior sagittal sinus, 100
torcular Herophili, 100
transverse sinus, 100
Dural venous sinus thrombosis,
551
Dutch-European Cerebral Sinus
Thrombosis Trial, 480
DVA. See Developmental venous
anomaly
Dynamic magnetic resonance
angiography, 140
ECA. See External carotid artery
Echo time, 137138
Eclampsia, 550551
ECST. See European Carotid
Surgery Trial
EDRFs. See Endothelial-derived
relaxation factors
EFNS. See European Federation of
Neurological Societies
Electrothrombosis, 328
ELST. See Endolymphatic sac
tumor
Embolic agents, 389
Embolic material
coils, 246247
embospheres, 250251
Onyx, 247250
polyvinyl alcohol (PVA)
particles, 250
sclerosing agents, 251
Embolic protection devices (EPD)
carotid endarterectomy, 419420
INDEX 625
distal, 234235
proximal, 235
Embolization
complications
incidence, 396397
ischemic stroke, 397398
periprocedural hemorrhage,
397
pulmonary emboli, 398
curative embolization, 388, 396
historical background, 386
palliative embolization, 388, 396
post-procedural care, 394
preradiosurgical embolization,
388, 395396
presurgical embolization, 388, 395
technique
n-BCA, 392394
Onyx, 394
provocative testing, 392
vessel selection, 391392
tools
embolic agents, 389
guidewires, 388389
microcatheters, 388389
n-butyl cyanoacrylate, 390
Onyx, 390391
PVA particles, 389390
Embospheres, 250251
Endarterectomy versus
Angioplasty in Patients with
Symptomatic Severe Carotid
Stenosis (EVA-3S), 418, 421
Endoluminal reconstructive
strategy, 349353
Endolymphatic sac tumor (ELST),
278281
Endothelial-derived relaxation
factors (EDRFs), 367
Endovascular aneurysm treatment
access-related complications,
358
balloon remodeling technique,
343345
cerebral angiography, 328
coil embolization, 339, 341343
complications
intraprocedural rupture,
355357
thromboembolism, 353355
deconstructive approach, 334336
delayed sequelae of treatment
aneurysm bleeding/
rebleeding, 357358
aneurysm recurrence/
recanalization, 358
endoluminal reconstructive
strategy, 349353
liquid embolic agents, 346347,
349
multiple microcatheter
technique, 346
reconstructive approach, 336, 339
stent-assisted coil embolization,
344346
626 INDEX
Endovascular infusions
intra-arterial infusion of
chemotherapy, 251
intra-arterial thrombolysis, 252
transvenous thrombolysis, 252
vasodilator infusions, 251252
Wada testing, 251
Endovascular management of
tumors
capillary hemangioma, 266267
endolymphatic sac tumor,
278280
hemangiopericytoma, 276278
juvenile angiofibroma, 267269
meningiomas, 271276
paragangliomas, 269271
vascular tumors, 266
Endovascular therapy of CCF
transarterial approach, 320322
transorbital approach, 325
transvenous approach, 323325
Endovascular thrombectomy, 408,
410
Endovascular thromboaspiration,
410
Endovascular US thrombolysis, 176
Enterprise stent, 242, 344, 346, 410
Entry slice phenomenon, 132
EPD. See Embolic protection
devices
Epilepsy, 258
Epilepsy and CCM, 196197
Epistaxis, 285, 592
Ethanol, 251, 283
European Carotid Surgery Trial
(ECST), 170, 415, 441
European Federation of
Neurological Societies
(EFNS), 478, 481
EVA-3S. See Endarterectomy
versus Angioplasty in
Patients with Symptomatic
Severe Carotid Stenosis
ev3 Endovascular. See Onyx
Expectant management, 195196
External carotid artery (ECA), 30, 32
cerebrovascular variants
management
ascending pharyngeal artery,
90
facial artery, 91
internal maxillary artery,
9192
lingual artery, 91
occipital artery, 91
posterior auricular artery, 91
superficial temporal artery, 91
superior thyroid artery, 90
common carotid artery
anastomotic network, 12
ascending pharyngeal artery,
56
facial artery, 9
internal maxillary artery,
1112
lingual artery, 6, 9
occipital artery, 910
posterior auricular artery, 1011
superficial temporal artery, 11
superior thyroid artery, 5
vascular access, 229
Extracranial arterial stenosis, 7576
Extracranial carotid angioplasty,
240
Extracranial carotid artery stenting,
241
Extracranial carotid disease, 592
Extracranial disease management
guideline, 423424
Extracranial fibromuscular
dysplasia, 221
Extracranial vertebral artery,
173174
Extradural arteriovenous
malformation
clinical manifestations, 539540
imaging techniques, 540
treatment methods, 542
Extradural cervical arteries, 293
Extradural dissection
endovascular treatment of,
304305, 307
internal carotid artery, 293294
medical treatment of, 300, 303
surgical treatment of, 303
vertebral artery, 294
Extradural dissection-associated
aneurysms, 307309
Extradural ICA dissection, 293294
Extraspinal extradural system, 40
Extravascular closure devices, 252
Fabrys disease, 517
Facial arteriovenous
malformations, 283
Facial artery, 9, 91
Facial veins, 1819
FDA. See Food and Drug
Administration
Fibromuscular dysplasia (FMD),
219, 517519
Filter-type embolic protection
devices, 419
Flexibility, 240
Flow compensation, 137
Flow-diverting devices, 350353
Flow-guided microcatheters, 233
FMD. See Fibromuscular dysplasia
fMRI. See functional magnetic
resonance imaging
Focused ultrasound (FUS) surgery,
177179
Food and Drug Administration
(FDA), 438
6 French sheath, 344
functional magnetic resonance
imaging (fMRI), 259260
Gateway balloon catheter, 240
GCA. See Giant cell arteritis
GDC. See Guglielmi detachable
coils
General anesthesia, 251, 606609
Genetic cerebrovascular disorders
in adolescence and young
adulthood
Fabrys disease, 517
hereditary angiopathies, 517
inherited small vessel
diseases, 516517
retinal vasculopathy with
leukodystrophy, 517
in childhood
Alagille syndrome, 513514
cerebral cavernoma
malformations, 514
hereditary hemorrhagic
telangiectasia, 514516
microcephalic primordial
dwarfism, 516
neurofibromatosis, 512513
Williams syndrome, 514
in newborns and infants
capillary malformation-
arteriovenous malformation
syndrome, 510
incontinentia pigmenti, 509510
Menkes syndrome, 511512
PHACES syndrome, 508509
Sturge-Weber syndrome, 510
Giant aneurysm, 114
Giant cell arteritis (GCA), 207
Glidewirer, 460
Global injuries, 116
Glomus jugulare, 272
Glomus jugulotympanicum, 272
Glomus tumors. See
Paragangliomas
Glomus vagale, 273
Gradient moment nulling. See Flow
compensation
Grayscale imaging, 158
Guardian II hemostasis valve, 234
Guglielmi detachable coils (GDCs),
329
Guide catheters, 232
Guidewire-directed microcatheters,
233
Guidewires, 234, 388389
Gyral brain arteriovenous
malformations, 375, 379
HANAC. See Hereditary
Angiopathy With
Nephropathy, Aneurysm,
And Muscle Cramps
Headaches, 294
Head and neck tumors, 592
Hemangioma thrombocytopenia
syndrome, 267
Hemangiopericytoma (HPC),
276278
Hemodynamic management, 608
Hemorrhage, 386
Hemorrhagic stroke, 549

Heparin-induced
thrombocytopenia (HIT), 595
Hereditary angiopathies, 517
Hereditary Angiopathy With
Nephropathy, Aneurysm,
And Muscle Cramps
(HANAC), 517
Hereditary Endotheliopathy with
Retinopathy, Nephropathy,
and Stroke (HERNS), 517
Hereditary hemorrhagic
telangiectasia (HHT),
285288, 514516, 531532
HERNS. See Hereditary
Endotheliopathy with
Retinopathy, Nephropathy,
and Stroke
Heterogeneous lesions, 194
Heubners arteritis. See
Meningovascular syphilis
HHT. See Hereditary hemorrhagic
telangiectasia
High-flow lesions, 282
High-lying lesions, 417
High-pressure balloon catheters,
237238, 240
HIT. See Heparin-induced
thrombocytopenia
HIV. See Human
immunodeficiency virus
HPC. See Hemangiopericytoma
Human immunodeficiency virus
(HIV), 218
Hydrocoil Endovascular
Aneurysm Occlusion and
Packing Study (HELPS)
trial, 358
HyperForm balloons, 235236, 336
HyperGlide balloons, 235236, 336,
344, 371
Hyperperfusion, 123124, 442
Hypotension, 592
ICA. See Internal carotid artery
ICAD. See Intracranial
atherosclerotic disease
ICAP-1. See Integrin cytoplasmic
domain-associated protein-1
ICSS. See International Carotid
Stenting Study
Idiopathic epistaxis, 285
Idiopathic non-familial
arteriopathies
fibromuscular dysplasia, 517519
moyamoya disease, 519520
IMA. See Internal maxillary artery
IM-AVM. See Intramedullary
arteriovenous malformation
Incontinentia pigmenti (IP),
509510
Indirect feeder, 376377
Induced hypotension, 255
Infectious vasculitides
angioinvasive aspergillosis,
215216
bacterial infections, 213
human immunodeficiency virus,
218
infectious agents, 218
meningovascular syphilis,
214215
mucormycosis, 216217
mycobacterium tuberculosis,
213214
varicella zoster virus, 217218
Infective endocarditis, 548549
Inferior petrosal sinus sampling
(IPSS)
alternatives to, 493
complications, 492493
contralateral injection, 489
data intrepretation, 492
microcatheter technique, 488
Inferior sagittal sinus (ISS), 100
Inherited small vessel diseases,
516517
Insufflator device, 240
Integrin cytoplasmic domain-
associated protein-1
(ICAP-1), 193
Intensive care unit (ICU)
complications
anaphylaxis, 594
cholesterol embolization
syndrome, 594
contrast-induced nephropathy,
594
thrombocytopenia, 594595
Internal carotid artery (ICA), 12,
1517, 2122
cerebrovascular variants
management
cavernous segment, 93
cervical segment, 92
choroidal segment, 94
communicating segment, 94
lacerum segment, 93
ophthalmic segment, 93
petrous segment, 9293
extradural dissection, 293294
intradural dissection, 294
Internal carotid artery
stenosis, 172
Internal cerebral vein, 101
Internal maxillary artery (IMA),
1112, 1415, 9192
International Carotid Stenting
Study (ICSS), 422
International Study of Unruptured
Intracranial Aneurysm
(ISUIA), 329331, 550
International Study on Cerebral
Vein and Dural Sinus
Thrombosis (ISCVT), 469
International Subarachnoid
Aneurysm Trial (ISAT), 327
Intra-arterial chemical
thrombolysis
anterior circulation, 405408
posterior circulation, 408
INDEX 627
Intra-arterial infusion of
chemotherapy, 251
Intra-arterial mechanical
thrombolysis
augmented fibrinolysis, 410
endovascular thrombectomy,
408, 410
endovascular
thromboaspiration, 410
thrombus disruption, 410
thrombus entrapment, 410
Intra-arterial thrombolysis, 252
Intracarotid amobarbital test,
258259
Intracerebral venous system,
166167
Intracranial aneurysms
balloons and endovascular
treatment, 328329
cerebral angiography, 328
coiled, 165166
coils for endosaccular aneurysm
treatment, 329
complications of endovascular
treatment
intraprocedural rupture,
355357
thromboembolism, 353355
delayed sequelae of treatment
aneurysm bleeding/
rebleeding, 357358
aneurysm recurrence/
recanalization, 358
early beginnings, 327328
electrothrombosis, 328
endovascular aneurysm
treatment
access-related complications,
358
balloon remodeling technique,
343345
coil embolization, 339, 341343
deconstructive approach,
334336
endoluminal reconstructive
strategy, 349353
liquid embolic agents,
346347, 349
multiple microcatheter
technique, 346
reconstructive approach,
336, 339
stent-assisted coil
embolization, 344346
endovascular navigation and
embolization, 328
endovascular treatment of, 170
epidemiology of, 327
magnetic resonance
angiography, 145148
pediatric, 500504
in pregnancy, 549550
ruptured
natural history of, 331332
patient selection, 332333
628 INDEX
Intracranial aneurysms (Continued)
unruptured
natural history of, 329331
patient selection, 333334
Intracranial angioplasty
of atherosclerotic plaque, 240
for cerebral vasospasm, 237
Intracranial arterial occlusion
detection
cerebral vasospasm, 163165
coiled intracranial aneurysms,
165166
intracerebral venous system,
166167
intracranial atherosclerotic
stenosis, 162163
vascular malformations, 166
Intracranial arteriovenous
malformations, 150151
Intracranial atherosclerosis
intracranial collaterals, 7273
neurological complications, 592
Intracranial atherosclerotic disease
(ICAD)
diagnostic studies, 435436
history of, 434
indications for treatment, 435,
437
inflammation role, 445446
intracranial vessel structure, 435
Neurolink system, 438
new concepts and future
trends, 445
percutaneous transluminal
balloon angioplasty, 437438
Pharos, 440
primary stenting, 438
reperfusion syndrome, 442
restenosis after stenting, 442445
stent-assisted angioplasty, 438
surgical treatment, 437
technical stenting procedure,
441442
trials in progress, 440441
Wingspan stent, 438440
Intracranial atherosclerotic
stenosis, 162163
Intracranial collaterals
anatomy of, 5961
aneurysms, 8182
arterial and venous disorders,
6667
cerebral arteriovenous
malformations, 7981
cerebral venous thrombosis,
7678
clinical features of, 6364
dural arteriovenous shunts or
fistulae, 7879
epidemiology of, 6162
extracranial arterial stenosis,
7576
imaging of, 6466
intracranial atherosclerosis,
7273
ischemic stroke, 6772
moyamoya, 7374
pathophysiology of, 6263
tumors, 8283
Intracranial hemorrhage, 115, 318,
549
anesthesia, 608
cerebral cavernous
malformation, 195
Intracranial HPC, 276, 279
Intracranial neoplasms, 553554
Intracranial pressure management,
481
Intracranial saccular aneurysms
flow diversion treatment, 242,
244
stent-coiling of, 242
Intracranial stenting, 241242
Intracranial venipuncture, 229
Intracranial venous thrombosis,
550
Intracranial vessel structure, 435
Intradural dissection
endovascular treatment of,
309311
internal carotid artery, 294
medical treatment of, 309
surgical treatment of, 309
vertebral artery, 294
Intramedullary arteriovenous
malformation (IM-AVM)
clinical manifestations, 535536
imaging techniques, 536538
metameric angiomatosis, 538
treatment methods, 538539
Intramural hematoma, 292
Intraplaque hemorrhage, 150
Intraprocedural rupture, 355357
Intraspinal extradural system,
4041
Intrathecal nitroprusside, 369
Intravascular closure devices, 252
Intrinsic spinal cord arteries, 44
Intrinsic spinal cord veins, 46, 51
Introducer sheaths, 229230
INvestigational Vertebroplasty
Efficacy and Safety Trial
(INVEST) trial, 572
IP. See Incontinentia pigmenti
Ipsilateral intraluminal thrombus,
418
IPSS. See Inferior petrosal sinus
sampling
ISAT. See International
Subarachnoid Aneurysm
Trial
Ischemia
hemorrhagic and stroke-like
conditions
reperfusion and
hyperperfusion, 123124
vasculitis and vasculopathy,
124
hyperacute and acute setting
CT angiography, 116117
nonenhanced CT, 116
perfusion imaging and
comprehensive stroke
evaluation, 117118
subacute and chronic setting
cerebrovascular CTA, 118122
perfusion imaging and
evaluating long-term risk, 122
Ischemic stroke, 6772
embolization complications,
397398
magnetic resonance
angiography, 153154
in pregnancy, 548549
ISCVT. See International Study on
Cerebral Vein and Dural
Sinus Thrombosis
Isolated spinal artery aneurysms,
542543
ISS. See Inferior sagittal sinus
ISUIA. See International Study of
Unruptured Intracranial
Aneurysm
JAF. See Juvenile angiofibroma
JNA. See Juvenile
nasopharyngiomas
Jostent GraftMaster Coronary Stent
Graft, 322
Juvenile angiofibroma (JAF),
267269
Juvenile nasopharyngiomas (JNA),
229
Kasabach Merritt syndrome,
266267
Klippel-Trenaunay syndrome, 538
Kyphoplasty, 578, 614615
Left common carotid artery, 229
Leptospiral arteritis, 218
Leptospirosis, 218
Lidocaine, 262
Lingual artery, 6, 910, 91
Liquid adhesives, 322
Liquid embolic agents, 346347,
349
LMWH. See Low-molecular-weight
heparin
Low-flow lesions, 282
Low-lying lesions, 417
Low-molecular-weight heparin
(LMWH), 563
Low-pressure balloon catheters,
235236
Lymphatic vascular malformations,
280, 282
MAC. See Monitored anesthesia care
Magnetic resonance angiography
(MRA)
clinical applications
arterial dissections, 150
carotid plaque imaging,
148150

carotid stenosis, 148
intracranial aneurysms, 145148
intracranial arteriovenous
malformations, 150151
ischemic stroke, 153154
spinal vascular malformations,
151153
contrast-enhanced, 138140
dissection detection, 298300
dynamic, 140
phase-contrast, 140144
time-of-flight (TOF) technique,
132134
2D, 134136
3D, 136137
echo time, 137138
flow compensation, 137
limitations, 137
ultra high field, 144145
Magnetic resonance venography
(MRV), 473475
Magnetization transfer imaging
(MTI), 136137
Magnetoencephalography (MEG),
260261
Malignant disease, 574575
Mandibular arteriovenous
malformations, 284
Marathon microcatheters, 233
MDCT. See Multidetector CT
Mechanical Embolus Removal in
Cerebral Ischemia (MERCI)
retriever, 245246
Mechanical thrombectomy, 482
Mechanical thrombolysis, 355
Medial fibroplasia, 517
Medical management, 196
MEG. See
Magnetoencephalography
Meningiomas, 271276
Meningovascular syphilis, 214215
Menkes syndrome, 511512
MERCI, 355, 408
Metameric angiomatosis, 538
Methohexital, 259
Microbubbles (MB)-augmented US
thrombolysis, 177
Microcatheters
characteristics, 232233
embolization tools, 388389
flow-guided microcatheters, 233
guidewire-directed
microcatheters, 233
Microcephalic primordial
dwarfism, 516
Micropuncture technique, 229
Microscopic polyangiitis, 212
Microwires, 234
Middle cerebral artery (MCA),
2830, 96
Middle meningeal arteries
(MMAs), 91
Migraine-type headaches, 294
Mikaelsson catheter. See Simmons
1 catheter
Mirage, 233234
Mixed brain arteriovenous
malformations, 375
Mixed cryoglobulinemia, 212
Mixed deep brain arteriovenous
malformations, 376
MMAs. See Middle meningeal
arteries
MMD. See Moyamoya disease
MMS. See Moyamoya syndrome
Modified Mehran system,
443445
MO.MA device, 420, 425
Monitored anesthesia care (MAC).
See Sedation
Monoclonal cryoglobulinemias, 212
MOTSA. See Multiple overlapping
thin slab acquisition
Moyamoya, 7374
Moyamoya disease (MMD), 219,
519520
Moyamoya syndrome (MMS),
519520
MRV. See Magnetic resonance
venography
MTI. See Magnetization transfer
imaging
Mucormycosis, 216217
Multidetector CT (MDCT), 104
Multifocal fibromuscular
dysplasia, 222
Multiholed flush catheters, 231
Multiple microcatheter technique,
346
Multiple overlapping thin slab
acquisition (MOTSA), 136
Mural vein of Galen aneurysmal
malformations, 495
Mycobacterium tuberculosis,
213214
Mynx, 252
Nasal aneurysm, 286
Nasal telangiectasias, 287
NASCET. See North American
Symptomatic Carotid
Endarterectomy Trial
National Institutes of Health
(NIH), 439
National Institutes of Health Stroke
Scale (NIHSS), 404
n-butyl cyanoacrylate (n-BCA),
390, 392394, 530
NC-CT. See Non-contrast-enhanced
computed tomography
NECT. See Nonenhanced CT
Neoplastic disease
clinical outcomes, 575576
imaging evaluation, 573574
for malignant disease, 574575
patient selection, 573
vertebroplasty and adjunctive
therapies, 575
Neurofibrin, 513
Neurofibromatosis, 512513
INDEX 629
Neurofibromatosis type I (NF-1),
512513
NeuroFlo, 71, 82, 177, 369, 410
Neuroform stent, 242, 344346, 410
Neurolink system, 438
Neurological complications
acute ischemic stroke, 590591
arteriovenous malformations,
587588
cerebral aneurysms, 588590
cerebral venous thrombosis,
591592
dural arteriovenous fistulas, 588
extracranial carotid disease, 592
head and neck tumors, 592
intracranial atherosclerosis, 592
spinal vascular malformations,
588
Neuronet device, 408
Neurosarcoidosis, 212
Neurosyphilis, 214215
Neurovascular anatomy
anterior cerebral artery, 2528
anterior choroidal artery, 2324
cerebral veins, 3538
external carotid artery, 30, 32
internal carotid artery, 2122
middle cerebral artery, 2830
ophthalmic artery, 2223
persistent caroticobasilar
anastomoses, 2425
posterior cerebral artery, 3335
posterior communicating artery,
2223
vertebrobasilar system, 3233
NF-1. See Neurofibromatosis type I
Nicardipine, 369
NIH. See National Institutes of
Health
NIHSS. See National Institutes of
Health Stroke Scale
Nimodipine, 369
Nitric oxide (NO), 367
Nonaneurysmal subarachnoid
hemorrhage, 113
Non-contrast-enhanced computed
tomography (NC-CT), 472
Nondeconvolution methods, 107
Nonenhanced CT (NECT), 116
Non-flow-related aneurysm, 382
Noninvasive testing, 259260
Nonlaminar blood flow, 137
Nonthermal effects, 157158
Nontraumatic hemorrhage
aneurysm
nonaneurysmal subarachnoid
hemorrhage, 113
SAH and saccular aneurysmal
rupture, 110112
SAH from aneurysmal
rupture, 112113
arteriovenous malformation,
113114
intracranial hemorrhage, 115
venous occlusive disorders, 115
630 INDEX
Nontraumatic intracranial
hemorrhages, 549
North American Symptomatic
Carotid Endarterectomy
Trial (NASCET), 170, 415
Occipital artery, 911, 91
Occipital sinus, 100
Onyx, 247250, 390391, 394
Onyx HD-500, 346347, 349
Ophthalmic artery, 2223
Osler-Weber-Rendu disease. See
Hereditary hemorrhagic
telangiectasia
Osteoporotic vertebral
compression fractures
kyphoplasty, 578
neoplastic disease
clinical outcomes, 575576
imaging evaluation, 573574
for malignant disease,
574575
patient selection, 573
vertebroplasty and adjunctive
therapies, 575
percutaneous vertebral
augmentation, 558559
vertebroplasty, 559560
PACNS. See Primary angiitis of
central nervous system
Palliative BAVM embolization,
388, 396
PAN. See Polyarteritis nodosa
Papaverine, 369
Paragangliomas, 269271
Paraspinal arteriovenous fistula,
541542
Parkes Weber syndrome, 538
Parodi AntiEmbolism
System, 235
PAVF. See Pial arteriovenous
fistulas
PCA. See Phase-contrast
angiography; Posterior
cerebral artery
PCoA. See Posterior
communicating artery
Pediatric aneurysms, 500, 502
Pediatric diagnostic angiography,
229230
Pediatric intracranial aneurysms,
500504
Penetrating injury, 125127
Penumbra system, 355, 410
Perclose, 252
Percutaneous transluminal balloon
angioplasty (PTA), 170, 434,
437438, 518
Percutaneous vertebral
augmentation. See
Osteoporotic vertebral
compression fractures;
Vertebroplasty
Perfusion CT imaging
arterial and venous occlusion
testing, 257
bolus contrast, 106108
stable xenon, 108109
Perfusion harmonic imaging
(PHI), 162
Perimedullary arteriovenous
fistula (PM-AVF)
classification, 531
clinical manifestations,
532533
and hemorrhagic telangiectasia,
531532
imaging techniques, 533534
treatment methods, 534535
Perimesencephalic hemorrhage,
113
Peripartum cardiomyopathy, 548
Periprocedural hemorrhage, 397
Periprocedural risk factors
age, 416
arch type and arch disease, 418
congestive heart failure, 417
contralateral carotid
occlusion, 418
coronary artery bypass grafting,
416417
high-lying lesions, 417
ipsilateral intraluminal
thrombus, 418
low-lying lesions, 417
postendarterectomy restenosis,
418
radiation-induced carotid
stenosis, 418419
recurrent nerve palsy, 419
severe coronary artery disease,
416
tandem lesions, 417418
Persistent caroticobasilar
anastomoses, 2425
Petrosal sinus sampling (PSS),
486487, 489, 491492
Petrous carotid aneurysm, 288
PHACES syndrome, 508509
Pharmacological angioplasty, 369
Pharmacological testing
indications, 261262
noninvasive alternatives, 262
technique, 262
Pharos, 440
Phase-contrast angiography (PCA),
140144
Phase-contrast magnetic resonance
angiography, 140144
Phenox clot retriever, 408
PHI. See Perfusion harmonic
imaging
Pial arteriovenous fistulas
(PAVFs), 497499
PICA. See Posterior inferior
cerebellar artery
Pipeline device, 242
Pipeline Embolization Device,
350351, 353
PISTE. See Pragmatic ischemic
stroke thrombectomy
evaluation
Pituitary adenomas, 486, 492
Plexal brain arteriovenous
malformations, 376
PM-AVF. See Perimedullary
arteriovenous fistula
PMMA. See
Polymethylmethacrylate
Poiseuilles law, 367
Polyarteritis nodosa (PAN),
208209, 211
Polymethylmethacrylate (PMMA),
558, 568
Polyvinyl alcohol (PVA) particles,
250
Post-catheterization
pseudoaneurysm (PSA), 593
Postendarterectomy restenosis,
418
Posterior auricular artery, 1011, 91
Posterior cerebral artery (PCA),
3335, 9697
Posterior cervical HPC, 281
Posterior communicating artery
(PCoA), 2223
Posterior inferior cerebellar artery
(PICA), 99
Posterior radiculomedullary
arteries, 41
Posterior reversible
encephalopathy syndrome,
552
Postpartum vasculopathy, 553
Powdered contrast agents, 283
Pragmatic ischemic stroke
thrombectomy evaluation
(PISTE), 413
Pre-eclampsia, 550551
Pregnancy
arteriovenous malformations,
550
cerebral venous thrombosis, 550
hemorrhagic stroke, 549
intracranial aneurysms, 549550
intracranial neoplasms, 553554
intracranial venous thrombosis,
550
ischemic stroke, 548549
physiologic alterations, 547548
pre-eclampsia and eclampsia,
550551
reversible cerebral
vasoconstriction syndrome,
551553
Preoperative evaluation, 226227
Preradiosurgical BAVM
embolization, 388, 395396
Presurgical BAVM embolization,
388, 395
Primary angiitis of central nervous
system (PACNS), 203206,
219
Propranolol, 266

Prowler 10, 14 and Plus
microcatheters, 233
Prowler Select Plus microcatheter,
346
Proximal embolic protection
devices, 235
Proximal flow-related aneurysm,
382
Proximally located aneurysm, 383
PSA. See Post-catheterization
pseudoaneurysm
Pseudoaneurysm, 109
Pseudoterminal feeder, 376
PSS. See Petrosal sinus sampling
PTA. See Percutaneous
transluminal balloon
angioplasty
Pterygopalatine venous plexus,
16, 19
Pulmonary emboli, 398
Pulseless disease. See Takayasus
arteritis
PVA particles, 389390
RA. See Rheumatoid arthritis
Radial artery, 228229
Radial force, 240
Radiation-induced carotid stenosis,
418419
Radiation-induced vasculopathy,
220
Radicular arteries, 41
Radiculomedullary arteries, 41
Radiculomedullary spinal cord
veins, 4748
ramped Rf. See Tilted optimized
nonsaturating excitation
(TONE)
RCVS. See Reversible cerebral
vasoconstriction syndrome
Rebleeding, 357358
Recanalization, 358
Recurrent nerve palsy, 419
Reperfusion, 123124
Reperfusion syndrome, 442
Restenosis, 442445
Retinal vasculopathy with
leukodystrophy, 517
Reversible cerebral
vasoconstriction syndrome
(RCVS), 218220, 551553
Rheolytic thrombectomy, 481
Rheumatic pachymeningitis, 213
Rheumatoid arthritis (RA), 213
RHV. See Rotating hemostatic
valve
Rotating hemostatic valve (RHV),
233234
Ruptured aneurysm. See
Subarachnoid hemorrhage
Ruptured intracranial
aneurysms
natural history of, 331332
patient selection, 332333
Rx Accunet, 235
Saccular aneurysmal rupture,
110112
Saccular aneurysms, 501
Sacroplasty, 579581
Safe catheter, 230
Safety and Efficacy of NeuroFlo
Technology in Ischemic
Stroke (SENTIS), 413
SAH. See Subarachnoid
hemorrhage
SAMMPRIS. See Stenting versus
Aggressive Medical
Management for Preventing
Recurrent stroke in
Intracranial Stenosis
SAPPHIRE. See Stenting and
Angioplasty with Protection
in Patients at High Risk for
Endarterectomy
Sarcoidosis, 212
SCA. See Superior cerebellar artery
Scaffolding, 240
Scleroderma, 213
Sclerosing agents, 251, 284
Scotty-dog approach, 565, 567
Secondary cerebral vasculitis
connective tissue disease
vasculitides
rheumatoid arthritis, 213
scleroderma, 213
Sjgrens syndrome, 213
systemic lupus erythematosus,
212213
infectious vasculitides
angioinvasive aspergillosis,
215216
bacterial infections, 213
human immunodeficiency
virus, 218
infectious agents, 218
meningovascular syphilis,
214215
mucormycosis, 216217
mycobacterium tuberculosis,
213214
varicella zoster virus, 217218
systemic vasculitides
Behets disease, 212
Churg-Strauss syndrome, 211
cryoglobulinemia, 212
giant cell arteritis, 207
microscopic polyangiitis, 212
polyarteritis nodosa, 208209,
211
sarcoidosis, 212
Takayasus arteritis, 207210
Wegeners granulomatosis,
211212
Sedation, 605609
Self-expanding stents, 241
SENTIS. See Safety and Efficacy of
NeuroFlo Technology in
Ischemic Stroke
Severe coronary artery disease, 416
Shuttle Select Tuohy-Borst, 230
INDEX 631
sICH. See Symptomatic
intracerebral hemorrhage
Sigmoid sinus, 100
Silk device, 350351, 353
Simmons 1 catheter, 231
Simmons II catheter, 231
Simple-curve catheters, 231
Single photon emission computed
tomography (SPECT), 256,
435436
Sinonasal HPC, 278
Sjgrens (sicca) syndrome, 213
Skin lesions, 189
SLE. See Systemic lupus
erythematosus
Slow flow, 137
SMCV. See Superficial middle
cerebral vein
Solitaire/Solo stent, 410
Sotradecol, 251
SPACE. See Stent-Protected
Angioplasty versus Carotid
Endarterectomy
SPECT. See Single photon emission
computed tomography
Sperficial venous system, 3536
Spetzler-Martin grading system,
385, 387
Spinal cord
arterial blood supply sources, 40
arterial supply on regions
cervical region, 4243
thoracic region, 4344
thoracolumbar region and
cauda equina, 44
arterio-arterial anastomotic
interconnections, 4546
AVMs and vascular neoplasms,
48, 50, 5457
extra- and intraspinal
anastomoses, 4041
intrinsic arteries, 44
radicular supply and superficial
arteries, 4142
venous drainage
extradural and extraspinal
venous spaces, 48
intraparenchymal venous
anastomoses, 46
intrinsic veins, 46
radiculomedullary veins and
transdural course, 4748
on regions, 4647
superficial veins, 46
Spinal dural arteriovenous fistulas
classification, 463464
clinical features, 464
clinical manifestations, 526527
diagnostic imaging, 464
endovascular technique, 529531
imaging techniques, 527
pathophysiology of, 525526
therapeutic considerations,
464466
Spinal radicular arteries, 41
632 INDEX
Spinal vascular malformations
classification, 523524
clinical manifestations, 524
imaging techniques, 525
magnetic resonance
angiography, 151153
neurological complications, 588
Spinnaker Elite microcatheters, 233
Spontaneous arterial dissections,
291
SSS. See Superior sagittal sinus
STA. See Superficial temporal artery
Stable xenon perfusion CT, 108109
Standard embolic agents, 499
Starclose, 252
Stenotic-occlusive disease, 118121
Stent-assisted angioplasty, 438
Stent-assisted coil embolization,
344346
Stenting and Angioplasty with
Protection in Patients at
High Risk for
Endarterectomy
(SAPPHIRE), 416417,
420421
Stenting versus Aggressive
Medical Management for
Preventing Recurrent stroke
in Intracranial Stenosis
(SAMMPRIS), 440441
Stent-Protected Angioplasty versus
Carotid Endarterectomy
(SPACE), 416, 421422
Stents
balloon-mounted, 241
dissection-related stenosis,
241242
extracranial carotid artery
stenting, 241
intracranial saccular aneurysms
flow diversion treatment,
242, 244
stent-coiling of, 242
properties of, 240
self-expanding, 241
vascular, 241
Stiff microcatheters, 233
Stopcock, 233234
Straight sinus, 100
Stroke
cardioembolic, 548
hemorrhagic, 549
ischemic, 115116, 153154
Stroke Outcomes and
Neuroimaging of
Intracranial Atherosclerosis
(SONIA) study, 72
Sturge-Weber syndrome (SWS),
510511
Subarachnoid brain arteriovenous
malformations, 376
Subarachnoid hemorrhage (SAH)
acute ischemic stroke, 590591
from aneurysmal rupture,
112113
pregnancy, 549
and saccular aneurysmal
rupture, 110112
Subclavian steal syndrome,
174175
Sulcal brain arteriovenous
malformations, 375, 378
Sump effect, 397
Superficial brain arteriovenous
malformations. See Cortical
brain arteriovenous
malformations
Superficial middle cerebral vein
(SMCV), 100101
Superficial spinal cord arteries,
4142
Superficial spinal cord veins, 46,
5253
Superficial temporal artery (STA),
11, 14, 91
Superior cerebellar artery (SCA),
99
Superior sagittal sinus (SSS), 100
Superior thyroid artery (SUT), 5,
7, 90
Supplementary feeder, 377
Susceptibility-weighted (SW)
imaging, 194
SUT. See Superior thyroid artery
SWS. See Sturge-Weber syndrome
Sylvian vein, 100101
Symptomatic cerebral vasospasm,
611612
Symptomatic intracerebral
hemorrhage (sICH), 590
Syphilis. See Meningovascular
syphilis
Systemic anticoagulation, 478
Systemic endovascular techniques,
368369
Systemic lupus erythematosus
(SLE), 212213
Systemic sclerosis. See
Scleroderma
Systemic vasculitides
Behets disease, 212
Churg-Strauss syndrome, 211
cryoglobulinemia, 212
giant cell arteritis, 207
microscopic polyangiitis, 212
polyarteritis nodosa, 208209,
211
sarcoidosis, 212
Takayasus arteritis, 207210
Wegeners granulomatosis,
211212
TACIT. See Transatlantic
Asymptomatic Carotid
Interventional Trial
Takayasus arteritis, 207210
Tandem lesions, 417418
TCCS. See Transcranial color-coded
duplex sonography
TCD. See Transcranial Doppler
TcMRgFUS. See Transcranial
magnetic resonance
imaging-guided focused
ultrasound surgery
Technical stenting procedure,
441442
Temporal lobe hematoma, 31
Terminal feeder, 376
Tew classification of BAVM-
associated aneurysms,
381
Therapeutic US imaging
BBB disruption, 179
coagulation, 179
focused ultrasound (FUS)
surgery, 177179
immunization, 179180
US-enhanced thrombolysis in
acute stroke
endovascular, 176
mechanisms for accelerated
thrombolysis, 174176
microbubbles (MB)-
augmented, 177
transcutaneous, 176177
Thermal effects, 157
Thermal index (TI), 157
Thrombectomy
mechanical, 482
rheolytic, 481
Thrombocytopenia, 594595
Thromboembolism, 353355
Thrombus disruption, 410
Thrombus entrapment, 410
TI. See Thermal index
TIAs. See Transient ischemic
attacks
Tilted optimized nonsaturating
excitation (TONE), 136
Time-of-flight (TOF) MRA
technique
2D, 134136
3D, 136137
echo time, 137138
flow compensation, 137
limitations, 137
TONE. See Tilted optimized
nonsaturating excitation
Torcular Herophili, 100
Tortuosity, 173
Tortuous vasculature, 137
Transarterial embolization,
614
Transatlantic Asymptomatic
Carotid Interventional Trial
(TACIT), 423
Transcranial color-coded duplex
sonography (TCCS),
158159, 162
Transcranial Doppler (TCD),
158159, 257
Transcranial low-frequency US
mediated thrombolysis in
brain ischemia (TRUMBI)
trial, 177

Transcranial magnetic resonance
imaging-guided focused
ultrasound surgery
(TcMRgFUS), 180
Transcutaneous US-enhanced
thrombolysis, 176177
Transend-10, 234
Transient ischemic attacks (TIAs),
434
Transtentorial herniation, 481
Transvenous thrombolysis, 252
Transverse sinus (TS), 100
Transverse sinus dural
arteriovenous fistula,
460461
Trauma
blunt injury, 127128
intracranial aneurysms, 128
penetrating injury,
125127
Traumatic aneurysms, 503
Traumatic arterial dissections, 291
Traumatic intracranial aneurysms,
128
Triple H therapy, 590
TS. See Transverse sinus
Type III lesions, 194
Type II malformations, 194. See also
Intramedullary
arteriovenous malformation
(IM-AVM)
Type I lesions, 194
Type IV malformations, 194
UCLA. See University of California,
Los Angeles
UGTI. See Ultrasound-guided
thrombin injection
UIA. See Unruptured intracranial
aneurysms
Ulceration, 120
Ultra high field magnetic
resonance angiography,
144145
Ultrasonography, 297298
Ultrasound-guided thrombin
injection (UGTI), 593
Ultrasound (US) imaging
basics of, 157
bioeffects and safety
contrast agent effects, 158
nonthermal effects, 157158
thermal effects, 157
diagnostic (see Diagnostic US
imaging)
therapeutic uses
BBB disruption, 179
coagulation, 179
focused ultrasound (FUS)
surgery, 177179
immunization, 179180
thrombolysis
endovascular, 176
mechanisms for accelerated
thrombolysis, 174176
microbubbles (MB)-
augmented, 177
transcutaneous, 176177
transcranial Doppler (TCD),
158159
Unilateral headaches, 294
University of California, Los
Angeles (UCLA), 328329,
343
Unruptured intracranial
aneurysms
natural history of, 329331
patient selection, 333334
Unruptured intracranial
aneurysms (UIA), 588
Upper basilar artery, 99
VA. See Vertebral artery
Varicella zoster virus (VZV),
217218
Vascular access
anticoagulation, 230
introducer sheaths, 229230
patient monitoring, 227
sites and techniques
common femoral artery,
227228
direct percutaneous puncture,
229
external carotid artery, 229
left common carotid artery,
229
micropuncture technique, 229
radial artery, 228229
surgical exposure for
intracranial venipuncture,
229
Vascular malformations, 116,
280282, 496, 505, 517520
Vascular stents, 241
Vascular tumors, 266, 614
Vasculitis, 203. See also Cerebral
vasculitis
Vasculitis and vasculopathy, 124
Vasodilator infusions, 251252
Vasopressors, 613
VBJ. See Vertebrobasilar junction
Vein of Galen, 101
Vein of Galen aneurysmal
dilatations (VGAD), 37, 495
Vein of Galen aneurysmal
malformations (VGAM),
37, 495497
Vein of Labbe, 101
Veins of posterior fossa, 101
Venogenesis, 62
Venous aneurysms, 109
Venous drainage
extradural and extraspinal
venous spaces, 48
intraparenchymal venous
anastomoses, 46
intrinsic veins, 46
radiculomedullary veins and
transdural course, 4748
INDEX 633
spinal cord region
cervical region, 4647
lumbar region, 47
thoracic region, 47
superficial veins, 46
Venous occlusive disorders, 115
Venous vascular malformations,
280
Verapamil, 369
Vertebral arteries, 15
Vertebral artery (VA), 97
extracranial, 173174
extradural dissection, 294
intradural dissection, 294
Vertebral artery dissection. See also
Extradural dissection;
Intradural dissection
diagnosis detection
computed tomography
angiography, 300
digital subtraction
angiography, 294297
magnetic resonance
angiography, 298300
magnetic resonance imaging,
298300
ultrasonography, 297298
epidemiology, 291
pathogenesis, 291293
prognosis and outcome, 311312
Vertebral body augmentation
biomechanics of, 558
controversies, 578581
Vertebral-vertebral arteriovenous
fistula, 540, 542543
Vertebrobasilar junction (VBJ),
9798
Vertebrobasilar system, 3233
Vertebroplasty
anesthesia, 614615
clinical outcomes, 571572
complications, 576578
osteoporotic vertebral
compression fractures,
559560
patient screening and evaluation
history of present illness, 561
neurological and physical
examination, 561
preprocedure preparation and
counseling, 563565
radiological evaluation,
561562
patient selection criteria,
560561
postprocedural care, 571
techniques
biomaterial injection, 569, 571
biomaterial preparation,
568569
contralateral needle
placement, 568
equipment requirements and
operator skills, 565
needle positioning, 566568
634 INDEX
Vertebroplasty (Continued)
patient preparation and
monitoring, 565
pedicle targeting, 565566
Vessel occlusion, 592
Vessel selection embolization
technique, 391392
VGAD. See Vein of Galen
aneurysmal dilatation
VGAM. See Vein of Galen
aneurysmal malformations
Viatrac 14 Plus balloon catheter, 240
Vitesse Intracranial Stent Study for
Ischemic Therapy (VISSIT),
440
VZV. See Varicella zoster virus
Wada testing
alternative agents, 259
cerebrovascular variants
management, 101
endovascular infusions,
251
epilepsy, 258
historical background,
258259
noninvasive testing,
259260
technique, 259
Waffle cone technique, 349
Warfarin Aspirin Symptomatic
Intracranial Disease
(WASID), 72,
435, 439
Wedged catheter embolization,
391
Wegeners granulomatosis
(WG), 211212
Williams syndrome, 514
Wingspan stent, 410, 438440
Xenon CT imaging, 257
Neurointerventional Management:
Diagnosis and Treatment
Second Edition

About the book

Neurointerventional Management: Diagnosis and Treatment, Second Edition has been retitled from the
original Interventional Neuroradiology, reflecting the revolutionary changes occurring in this rapidly
advancing field. Since the publication of the first edition, interest in neurointerventional therapy has
developed at an increasing pace. New device development has expanded the range of disorders
amenable to neurointerventional treatment and additional emphasis is present within medical and
surgical specialities on subspecialization in neurointerventional therapy. Physicians from all specialties
involved in the care of disorders of the head, neck, and central nervous system, including neurosurgery,
neuroradiology, and neurology, are currently specializing in neurointerventional therapy.
This book is written by a panel of todays leading experts in the field of neurointerventional therapy
and edited by two neuroendovascular practitioners whose training and experience represent all
three major specialties involved in neurointerventional therapy. The book is intended to provide
the clinical practitioner with background information and specific descriptions of the anatomy,
techniques, disorders, procedures, and decisions more commonly encountered in this field. Each
chapter is illustrated with scientifically concise images, depicting pertinent neuroanatomy, imaging,
neuroendovascular techniques, and related procedures. The new edition includes more diagnostic
aspects of cerebrovascular disease of neurointerventional interest and discusses the treatment of
disorders not covered in the first edition. Nine new chapters address increased interest in the field
and provide in-depth focus on a range of new topics, including normal cerebrovascular variants,
non-shunting cerebrovascular malformations, the endovascular aspects of cerebrovascular disease
in pregnancy, neurocritical care management of endovascular patients, anesthetic management
of neurointerventional procedures, and the diagnosis and management of cerebral vasculitis,
dural venous sinus thrombosis, pediatric cerebrovascular disease, and uncommon and genetic
cerebrovascular diseases.

About the editors

Robert W. Hurst is Professor of Radiology, Neurosurgery, and Neurology at the University of
Pennsylvania Medical School, Philadelphia, and Director of Interventional Neuroradiology at the
Hospital of the University of Pennsylvania, Philadelphia. Following graduation from the United States
Military Academy at West Point, New York, Professor Hurst received his M.D. from the University of
Texas Medical School at Houston. After completing residencies in both neurology and radiology, he
underwent fellowship training in diagnostic neuroradiology and interventional neuroradiology at
the Hospital of the University of Pennsylvania and New York University. Specializing in interventional
neuroradiology, he is board certified in radiology, neuroradiology, neurology, and vascular neurology.
Professor Hurst has served as Consultant, Member, and Chairman of the Neurological Devices Panel
of the U.S. Food and Drug Administration.
Robert H. Rosenwasser is the Jewell L. Osterholm Professor and Chair of Neurological Surgery,
Professor of Radiology, and Director of the Division of Neurovascular Surgery, Interventional
Neuroradiology at Jefferson Medical School, Thomas Jefferson University, Philadelphia, Pennsylvania.
Professor Rosenwasser received his M.D. from Louisiana State University, Shreveport. He completed
a residency in neurosurgery at Temple University Hospital, followed by fellowships in neurovascular
surgery at the University of Western Ontario, Canada, and interventional neuroradiology at New York
University. Professor Rosenwasser is recognized as one of the world leaders uniquely specialized as
both a Cerebrovascular Neurosurgeon and Interventional Neuroradiologist.

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