Vol 22.5 Neuroimaging.2016

Continuum: Lifelong Learning in Neurology—Neuroimaging, Volume 22, Issue 5, October
2016
Issue Overview
Neuroimaging October 2016;22(5)
Continuum: Lifelong Learning in Neurology® is designed to help practicing neurologists stay
abreast of advances in the field while simultaneously developing lifelong self-directed learning
skills.
Learning Objectives
Upon completion of this Continuum: Lifelong Learning in Neurology Neuroimaging issue,
participants will be able to:
 Understand basic MRI physics and technology and how to acquire and interpret MRIs
 Describe the foundation and utility of multimodal CT and MRI and collateral imaging in all
stages of ischemic stroke diagnosis and management
 Discuss the significance of neuroimaging in the management of patients presenting with

hemorrhagic stroke, the various neuroimaging tools available to clinicians to aid in
management, and the common neuroimaging findings that help identify the underlying
etiology of hemorrhagic stroke
 Accurately use structural and functional neuroimaging protocols in the evaluation and
treatment of patients with focal and generalized seizure disorders and identify the limitations
and potential diagnostic indications of neuroimaging investigations in people with epilepsy
 Recognize the imaging features of common congenital malformations and discuss how their
appropriate identification can impact diagnosis and treatment
 Discuss the role of neuroimaging in the diagnosis and management of neuro-ophthalmic

disorders
 Recognize the usefulness of MRI sequences in characterizing tumor types and discuss the
usefulness of posttreatment MRIs in distinguishing tumor recurrence from treatment-related
changes such as pseudoprogression and pseudoresponse
 Identify the imaging characteristics of common and less often encountered intracranial cysts
and differentiate benign entities from pathologic processes
 Discuss the utility of different imaging modalities in diagnosing pathologic lesions in the
sellar and parasellar regions
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

 Recognize the imaging features of common spinal cord disorders, including disorders of the
spine that secondarily affect the spinal cord
 Recognize neuroimaging characteristics of central nervous system demyelinating disorders
 Recognize which neuromolecular imaging tests are clinically available and what the
indications are in different disorders
 Discuss the clinical uses of ultrasound examination in cerebrovascular, neurodegenerative,

and peripheral nervous system diseases
 Discuss the recent potential safety concerns associated with the use of gadolinium-based
contrast agents
 Understand the basics of the Federal Anti-Kickback Statute and Stark Law in relation to
physician investment or ownership in a variety of health care enterprises
 Discuss potential safety risks associated with MRI scans performed on patients with
implanted medical devices, current US Food and Drug Administration (FDA) safety labeling
for objects in the MRI environment, and advantages and challenges of magnetic resonance
conditional devices
Core Competencies
This Continuum: Lifelong Learning in Neurology Multiple Sclerosis and Other Demyelinating
Diseases issue covers the following core competencies:
 Patient Care and Procedural Skills
 Medical Knowledge
 Practice-Based Learning and Improvement
 Interpersonal and Communication Skills
 Professionalism
 Systems-Based Practice
Disclosures
CONTRIBUTORS
Laszlo L. Mechtler, MD, FAAN, Co-Guest Editor

Medical Director, DENT Neurologic Institute; Director, DENT Headache, Neuro-Oncology, and
Imaging Centers, Amherst, New York; Professor of Neurology and Oncology, University at
Buffalo; Chief of Neuro-Oncology, Roswell Park Cancer Institute, Buffalo, New York
a
Dr Mechtler has received personal compensation for serving as board advisor for Supernus Pharmaceuticals, Inc;
for serving as guest editor of Current Pain & Headache Reports and Neurologic Clinics; as a speaker for Allergan,
Pernix Therapeutics, and Teva Pharmaceutical Industries Ltd; and as a consultant for Green Grass Advisors. Dr
Mechtler provided expert consultation for legal testimony for DOPF, P.C.
b
Dr Mechtler reports no disclosure.

Joshua P. Klein, MD, PhD, FANA, FAAN, Co-Guest Editor
Chief, Division of Hospital Neurology, Department of Neurology, Brigham and Women’s
Hospital; Associate Professor of Neurology and Radiology, Harvard Medical School, Boston,
Massachusetts
a
Dr Klein has received personal compensation as a coauthor and editor and for serving on the editorial board of
McGraw-Hill and as a consultant for Advance Medical and Best Doctors, Inc. Dr Klein has given expert medical
testimony for Anaesthesia Associates of Massachusetts and HeplerBroom LLC.
b
Dr Klein reports no disclosure.
Ajay Abad, MD
Neuro-oncologist, Roswell Park Cancer Institute; Clinical Assistant Professor of Neurology,
University at Buffalo, Buffalo, New York
a
Dr Abad has provided expert medicolegal testimony on tumor treatment field therapy.
b
Dr Abad reports no disclosure.
Bela Ajtai, MD, PhD

Neurologist, Neuroimager, DENT Neurologic Institute, Amherst, New York; Clinical Assistant
Professor of Neurology, University at Buffalo, Buffalo, New York
a
Dr Ajtai has received personal compensation for speaking engagements from Allergan and Novartis AG.
b
Dr Ajtai reports no disclosure.
Andrei V. Alexandrov, MD, RVT

Semmes-Murphey Professor and Chairman, Department of Neurology, University of Tennessee
Health Science Center, Memphis, Tennessee
a
Dr Alexandrov serves on the editorial board of the Journal of Neuroimaging.
b
Dr Alexandrov reports no disclosure.
Mirza A. Baig, DO
Neurologist, Neuroimaging Fellow, DENT Neurological Institute, Amherst, New York
a,b
Dr Baig reports no disclosures.
Konstantin Balashov, MD, PhD, FAAN

Professor, Department of Neurology, Robert Wood Johnson Medical School, Rutgers University,
New Brunswick, New Jersey
a
Dr Balashov has served on the editorial boards of BMC Neurology and Neuroimmunology and Neuroinflammation,
as chairperson of the health care advisory committee of the New Jersey chapter of the National Multiple Sclerosis
Society, and as a consultant for Sanofi Genzyme and Teva Pharmaceutical Industries Ltd. Dr Balashov has received
research/grant support and personal compensation for speaking engagements from Teva Pharmaceutical Industries
Ltd and research/grant support from Biogen and the National Multiple Sclerosis Society.
b
Dr Balashov reports no disclosure.
John A. Bertelson, MD
Assistant Professor of Neurology, Dell Medical School, University of Texas at Austin; Clinical
Assistant Professor of Psychology, University of Texas at Austin, Austin, Texas
a
Dr Bertelson has served on the medical advisory board of BrainGear and has provided expert medicolegal
testimony on cases related to brain trauma.
b
Dr Bertelson reports no disclosure.
Riley Bove, MD
Assistant Professor of Neurology, University of California San Francisco, San Francisco,
California
a
Dr Bove receives research/grant support from the National Institutes of Health and the National Multiple Sclerosis
Society.
b
Dr Bove reports no disclosure.

Gregory D. Cascino, MD, FAAN
Whitney MacMillan Junior Professor of Neuroscience, Mayo Clinic College of Medicine;
Enterprise Director of Epilepsy, Mayo Clinic, Rochester, Minnesota
a
Dr Cascino serves on the board of directors of the American Academy of Neurology and as an associate editor of
Neurology. Dr Cascino receives royalties from Mayo Medical Ventures and UpToDate, Inc.
b
Dr Cascino reports no disclosure.
Robert Fenstermaker, MD, FACS, FAANS

Chair, Department of Neurosurgery, Roswell Park Cancer Institute; Professor, Department of
Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo,
Buffalo, New York
a
Dr Fenstermaker serves on the board of directors of and owns stock or stock options in MimiVax, LLC; receives
personal compensation for meeting organization from prIME Oncology; and receives research/grant support from
the Roswell Park Alliance Foundation.
b
Dr Fenstermaker reports no disclosure.
Joseph V. Fritz, PhD

Chief Executive Officer, DENT Neurologic Institute, Amherst, New York
a
Dr Fritz serves as a consultant for Allergan.
b
Dr Fritz reports no disclosure.
Ankur Garg, MD
Assistant Professor of Neurology; Director, Endovascular Surgical Neuroradiology Fellowship,
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
a
Dr Garg serves on the membership committee of the Society of Vascular and Interventional Neurology.
b
Dr Garg reports no disclosure.
Ryan Hakimi, DO, MS

Director, Greenville Health System Neuro ICU; Director, Greenville Health System Inpatient
Neurology Service Line; Clinical Associate Professor, University of South Carolina-Greenville,
Greenville, South Carolina
a
Dr Hakimi has served on the board of directors and annual program committee of the American Society of
Neuroimaging, on the editorial boards of the International Journal of Neurology and Neurotherapy and the
International Journal of Neural Science and Brain Research, and on the annual program committee and as cochair
of the fundraising committee of the Neurocritical Care Society.
b
Dr Hakimi reports no disclosure.
Joseph S. Kass, MD, JD, FAAN

Associate Professor of Neurology, Psychiatry, and Medical Ethics; Director, Neurology
Residency Program; Chief of Neurology Service, Ben Taub General Hospital, Baylor College of
Medicine, Houston, Texas
a
Dr Kass has received personal compensation for expert testimony in legal cases involving personal injury,
defamation, and malpractice.
b
Dr Kass reports no disclosure.
Samuel Lapalme-Remis, MDCM, MA, FRCPC

Epilepsy Fellow, Mayo Clinic, Rochester, Minnesota
a,b
Dr Lapalme-Remis reports no disclosures.
David S. Liebeskind, MD, FAAN

Professor of Neurology; Director, Neurovascular Imaging Research Core,
University of California Los Angeles, Los Angeles, California
a
Dr Liebeskind has served as an associate editor of the Journal of Neuroimaging and as a consultant to the imaging
core laboratories of Medtronic and Stryker. Dr Liebeskind receives royalties from UpToDate, Inc, and
grant/research support from the National Institutes of Health.
b
Dr Liebeskind reports no disclosure.

Michelle P. Lin, MD, MPH
Vascular Neurology Fellow, Johns Hopkins University School of Medicine, Department of
Neurology, Baltimore, Maryland
a,b
Dr Lin reports no disclosures.
Jennifer W. McVige, MA, MD

Neurologist, Department of Neuroimaging and Headache Medicine for Adults and Children;
Director of Concussion Center, DENT Neurologic Institute; Amherst, New York; Assistant
Professor of Neurology, University at Buffalo, Buffalo, New York
a
Dr McVige has received personal compensation for speaking engagements from Avanir Pharmaceuticals, Inc, and
Teva Pharmaceutical Industries Ltd, and receives research/grant support from the Harry Dent Family Foundation
Inc.
b
Dr McVige reports no disclosure.
Robert S. Miletich, MD, PhD, FAAAS

Professor, Interim Chair, Residency Program Director, Medical Director of the Nuclear Medicine
Technologist Program, Department of Nuclear Medicine, University at Buffalo, Buffalo, New
York; President, University Nuclear Medicine, Inc, Buffalo, New York
a
Dr Miletich serves on the editorial board of the Journal of Neuroimaging and receives research/grant support from
the William E. Mabie, DDS, and Grace S. Mabie Fund.
b
Dr Miletich reports no disclosure.
Bennett Myers, MD
Associate Clinical Professor, University at Buffalo, Buffalo, New York; Attending Neurologist,
DENT Neurologic Institute, Amherst, New York
a
Dr Myers has served on the scientific advisory board of Biogen and has received personal compensation for
speaking engagements from Biogen, Novartis AG, and Teva Pharmaceutical Industries Ltd. Dr Myers has provided
expert medical testimony on brachial plexopathy as a complication of scalene nerve block.
b
Dr Myers reports no disclosure.
Nandor K. Pinter, MD
Research Fellow, DENT Neurologic Institute, Amherst, New York; Radiologist, Department of
Neuroradiology, National Institute of Clinical Neurosciences, Budapest, Hungary
a
Dr Pinter receives research/grant support from the Harry Dent Family Foundation Inc.
b
Dr Pinter reports no disclosure.
Marcus Ponce de Leon, MD, FAAN

Residency Program Director, Department of Neurology, Madigan Army Medical Center,
Tacoma, Washington; Assistant Professor, Uniformed Services University of Health Sciences,
Bethesda, Maryland
a,b
Dr Ponce de Leon reports no disclosures.
Ernst-Wilhelm Radue, MD
Professor Emeritus, Consulting Neurologist, Chief Executive Officer of Biomedical Research
and Training, Basel, Switzerland
a
Dr Radue has served as a consultant for Neurologische und Psychiatrische Universitäts Klinik Basel, has received
personal compensation for speaking engagements from Novartis AG and Sanofi Genzyme, and receives royalties
from Springer-Verlag GmbH.
b
Dr Radue reports no disclosure.
Rachel V. Rose, JD, MBA

Attorney, Rachel V. Rose Attorney at Law PLLC; Affiliated Faculty, Baylor College of
Medicine, Houston, Texas
a
Ms Rose serves on the editorial board of BC Advantage and receives book royalties from the American Bar
Association.

b
Ms Rose reports no disclosure.
Karanbir Singh, MD
Attending Neurologist, Director of Neurology/Neuroimaging, Apex Hospital, Jalandhar, Punjab,
India
a,b
Dr Singh reports no disclosures.
Gabriella Szatmáry, MD, PhD

Director of Neuro-Ophthalmology, Director of Neuroimaging, Hattiesburg Clinic, Hattiesburg,
Mississippi
a,b
Dr Szatmáry reports no disclosures.
Georgios Tsivgoulis, MD, PhD, MSc, RVT

Associate Professor of Neurology, Second Department of Neurology, University of Athens
School of Medicine, Attikon University Hospital, Athens, Greece; Visiting Associate Professor
of Neurology, Director of Stroke Research, Department of Neurology, University of Tennessee
Health Science Center, Memphis, Tennessee
a
Dr Tsivgoulis serves on the editorial boards of Stroke and the Journal of Neuroimaging and has received
research/grant support from the European Regional Development Fund.
b
Dr Tsivgoulis reports no disclosure.
Horst Urbach, MD
Professor, Director Department of Neuroradiology, University Medical Center, Freiburg,
Germany
a
Dr Urbach serves as coeditor of Clinical Neuroradiology and on the editorial board of Neuroradiology and has
received personal compensation for speaking engagements from Bracco, Stryker, and UCB SA.
b
Dr Urbach reports no disclosure.
Matthias Weigel, PhD

Senior Physicist, Radiological Physics, Department of Radiology, University Hospital Basel;
Department of Biomedical Engineering, University of Basel, Basel Switzerland
a
Dr Weigel has received personal compensation for speaking engagements from the European Society for Magnetic
Resonance in Medicine and Biology, the Magnetic Resonance Compact University Hospital Erlangen, and
Vereinigung Südwestdeutscher Radiologen und Nuklearmediziner and royalties from the University Medical Center
of the University of Freiburg for a patent for dynamic motion correction in MRI.
b
Dr Weigel reports no disclosure.
Roland Wiest, MD
Professor of Neuroradiology, Institute of Diagnostic and Interventional Neuroradiology,
Inselspital, University of Bern, Bern, Switzerland
a
Dr Wiest receives research/grant support from the Swiss National Foundation.
b
Dr Wiest reports no disclosure.
Eduardo E. Benarroch, MD, FAAN

Professor of Neurology, Mayo Clinic, Rochester, Minnesota
a,b
Dr Benarroch reports no disclosures.
Adam G. Kelly, MD
Associate Professor of Neurology, University of Rochester Medical Center;
Chief of Neurology, Highland Hospital, Rochester, New York
a
Dr Kelly has received research support from the Donald W. Reynolds Foundation.
b
Dr Kelly reports no disclosure.
a
Relationship Disclosure
b
Unlabeled Use of Products/Investigational Use Disclosure

Methods of Participation and Instructions for Use
Continuum: Lifelong Learning in Neurology® is designed to help practicing neurologists stay
abreast of advances in the field while simultaneously developing lifelong self-directed learning
skills. In Continuum, the process of absorbing, integrating, and applying the material presented is
as important as, if not more important than, the material itself.
The goals of Continuum include disseminating up-to-date information to the practicing
neurologist in a lively, interactive format; fostering self-assessment and lifelong study skills;
encouraging critical thinking; and, in the final analysis, strengthening and improving patient
care.
Each Continuum issue is prepared by distinguished faculty who are acknowledged leaders in
their respective fields. Six issues are published annually and are composed of review articles,
case-based discussions on ethical and practice issues related to the issue topic, coding
information, , and comprehensive CME and self-assessment offerings, including a self-
assessment pretest, multiple-choice questions with preferred responses, and a patient
management problem. For detailed instructions regarding Continuum CME and self-assessment
activities, visit aan.com/continuum/cme.
The review articles emphasize clinical issues emerging in the field in recent years. Case reports
and vignettes are used liberally, as are tables and illustrations. Video material relating to the
issue topic accompanies issues when applicable.
The text can be reviewed and digested most effectively by establishing a regular schedule of
study in the office or at home, either alone or in an interactive group. If subscribers use such
regular and perhaps new study habits, Continuum’s goal of establishing lifelong learning patterns
can be met.

LIFELONG LEARNING IN NEUROLOGY ®
Neuroimaging
Volume 22 Number 5 October 2016
CONTRIBUTORS
Laszlo L. Mechtler, MD, FAAN, Co-Guest Editor
Medical Director, DENT Neurologic Institute; Director, DENT Headache,
Neuro-Oncology, and Imaging Centers, Amherst, New York;
Professor of Neurology and Oncology, University at Buffalo;
Chief of Neuro-Oncology, Roswell Park Cancer Institute, Buffalo, New York
aDr Mechtler has received personal compensation for serving as board advisor for Supernus
Pharmaceuticals, Inc; for serving as guest editor of Current Pain & Headache Reports and
Neurologic Clinics; as a speaker for Allergan, Pernix Therapeutics, and Teva Pharmaceutical
Industries Ltd; and as a consultant for Green Grass Advisors. Dr Mechtler provided expert
consultation for legal testimony for DOPF, P.C.
bDr Mechtler reports no disclosure.
Joshua P. Klein, MD, PhD, FANA, FAAN, Co-Guest Editor

Chief, Division of Hospital Neurology, Department of Neurology, Brigham and Women’s
Hospital; Associate Professor of Neurology and Radiology, Harvard Medical School,
Boston, Massachusetts
aDr Klein has received personal compensation as a coauthor and editor and for serving on
the editorial board of McGraw-Hill and as a consultant for Advance Medical and Best
Doctors, Inc. Dr Klein has given expert medical testimony for Anaesthesia Associates of
Massachusetts and HeplerBroom LLC.
bDr Klein reports no disclosure.
Ajay Abad, MD
Neuro-oncologist, Roswell Park Cancer Institute; Clinical Assistant Professor
of Neurology, University at Buffalo, Buffalo, New York
aDr Abad has provided expert medicolegal testimony on tumor treatment field therapy.
bDr Abad reports no disclosure.
Bela Ajtai, MD, PhD

Neurologist, Neuroimager, DENT Neurologic Institute, Amherst, New York;
Clinical Assistant Professor of Neurology, University at Buffalo,
Buffalo, New York
aDr Ajtai has received personal compensation for speaking engagements from Allergan
and Novartis AG.
bDr Ajtai reports no disclosure.
aRelationship Disclosure
bUnlabeled Use of Products/Investigational Use Disclosure
Continuum (Minneap Minn) 2016;22(5) www.ContinuumJournal.com

CONTRIBUTORS continued
Andrei V. Alexandrov, MD, RVT
Semmes-Murphey Professor and Chairman, Department of Neurology,
University of Tennessee Health Science Center, Memphis, Tennessee
aDr Alexandrov serves on the editorial board of the Journal of Neuroimaging.
bDr Alexandrov reports no disclosure.
Mirza A. Baig, DO
Neurologist, Neuroimaging Fellow, DENT Neurological Institute,
Amherst, New York
a,bDr Baig reports no disclosures.

Professor, Department of Neurology, Robert Wood Johnson Medical School,
Rutgers University, New Brunswick, New Jersey
aDr Balashov has served on the editorial boards of BMC Neurology and Neuroimmunology
and Neuroinflammation, as chairperson of the health care advisory committee of the
New Jersey chapter of the National Multiple Sclerosis Society, and as a consultant for
Sanofi Genzyme and Teva Pharmaceutical Industries Ltd. Dr Balashov has received
research/grant support and personal compensation for speaking engagements from
Teva Pharmaceutical Industries Ltd and research/grant support from Biogen and the
National Multiple Sclerosis Society.
bDr Balashov reports no disclosure.
John A. Bertelson, MD
Assistant Professor of Neurology, Dell Medical School, University of Texas at
Austin; Clinical Assistant Professor of Psychology, University of Texas at Austin,
Austin, Texas
aDr Bertelson has served on the medical advisory board of BrainGear and has provided
expert medicolegal testimony on cases related to brain trauma.
bDr Bertelson reports no disclosure.
Riley Bove, MD
Assistant Professor of Neurology, University of California San Francisco,
San Francisco, California
aDr Bove receives research/grant support from the National Institutes of Health and the
National Multiple Sclerosis Society.
bDr Bove reports no disclosure.
www.ContinuumJournal.com October 2016

Gregory D. Cascino, MD, FAAN
Whitney MacMillan Junior Professor of Neuroscience, Mayo Clinic College of
Medicine; Enterprise Director of Epilepsy, Mayo Clinic, Rochester, Minnesota
aDr Cascino serves on the board of directors of the American Academy of Neurology and as an
associate editor of Neurology. Dr Cascino receives royalties from Mayo Medical Ventures and
UpToDate, Inc.
bDr Cascino reports no disclosure.
Robert Fenstermaker, MD, FACS, FAANS

Chair, Department of Neurosurgery, Roswell Park Cancer Institute;
Professor, Department of Neurosurgery, Jacobs School of Medicine
and Biomedical Sciences, University at Buffalo, Buffalo, New York
aDr Fenstermaker serves on the board of directors of and owns stock or stock options in
MimiVax, LLC; receives personal compensation for meeting organization from prIME
Oncology; and receives research/grant support from the Roswell Park Alliance Foundation.
bDr Fenstermaker reports no disclosure.
Joseph V. Fritz, PhD

Chief Executive Officer, DENT Neurologic Institute, Amherst, New York
aDr Fritz serves as a consultant for Allergan.
bDr Fritz reports no disclosure.
Ankur Garg, MD
Assistant Professor of Neurology; Director, Endovascular Surgical Neuroradiology
Fellowship, University of Oklahoma Health Sciences Center,
Oklahoma City, Oklahoma
aDr Garg serves on the membership committee of the Society of Vascular
and Interventional Neurology.
bDr Garg reports no disclosure.
Ryan Hakimi, DO, MS

Director, Greenville Health System Neuro ICU; Director, Greenville Health System
Inpatient Neurology Service Line; Clinical Associate Professor, University of South
Carolina-Greenville, Greenville, South Carolina
aDr Hakimi has served on the board of directors and annual program committee of the
American Society of Neuroimaging, on the editorial boards of the International Journal of
Neurology and Neurotherapy and the International Journal of Neural Science and Brain
Research, and on the annual program committee and as cochair of the fundraising
committee of the Neurocritical Care Society.
bDr Hakimi reports no disclosure.

Joseph S. Kass, MD, JD, FAAN
Associate Professor of Neurology, Psychiatry, and Medical Ethics;
Director, Neurology Residency Program; Chief of Neurology Service,
Ben Taub General Hospital, Baylor College of Medicine, Houston, Texas
aDr Kass has received personal compensation for expert testimony in legal cases involving
personal injury, defamation, and malpractice.
bDr Kass reports no disclosure.
Samuel Lapalme-Remis, MDCM, MA, FRCPC

Epilepsy Fellow, Mayo Clinic, Rochester, Minnesota
a,bDr Lapalme-Remis reports no disclosures.
David S. Liebeskind, MD, FAAN

Professor of Neurology; Director, Neurovascular Imaging Research Core,
University of California Los Angeles, Los Angeles, California
aDr Liebeskind has served as an associate editor of the Journal of Neuroimaging and as
a consultant to the imaging core laboratories of Medtronic and Stryker. Dr Liebeskind
receives royalties from UpToDate, Inc, and grant/research support from the National
Institutes of Health.
bDr Liebeskind reports no disclosure.
Michelle P. Lin, MD, MPH

Vascular Neurology Fellow, Johns Hopkins University School of Medicine,
Department of Neurology, Baltimore, Maryland
a,bDr Lin reports no disclosures.

Neurologist, Department of Neuroimaging and Headache Medicine for Adults
and Children; Director of Concussion Center, DENT Neurologic Institute;
Amherst, New York; Assistant Professor of Neurology, University at Buffalo,
Buffalo, New York
aDr McVige has received personal compensation for speaking engagements from Avanir
Pharmaceuticals, Inc, and Teva Pharmaceutical Industries Ltd, and receives research/grant
support from the Harry Dent Family Foundation Inc.
bDr McVige reports no disclosure.

Professor, Interim Chair, Residency Program Director, Medical Director of the
Nuclear Medicine Technologist Program, Department of Nuclear Medicine,
University at Buffalo, Buffalo, New York; President, University Nuclear Medicine,
Inc, Buffalo, New York
aDr Miletich serves on the editorial board of the Journal of Neuroimaging and receives
research/grant support from the William E. Mabie, DDS, and Grace S. Mabie Fund.
bDr Miletich reports no disclosure.
Bennett Myers, MD
Associate Clinical Professor, University at Buffalo, Buffalo, New York;
Attending Neurologist, DENT Neurologic Institute, Amherst, New York
aDr Myers has served on the scientific advisory board of Biogen and has received
personal compensation for speaking engagements from Biogen, Novartis AG,
and Teva Pharmaceutical Industries Ltd. Dr Myers has provided expert medical testimony
on brachial plexopathy as a complication of scalene nerve block.
bDr Myers reports no disclosure.
Nandor K. Pinter, MD
Research Fellow, DENT Neurologic Institute, Amherst, New York; Radiologist,
Department of Neuroradiology, National Institute of Clinical Neurosciences,
Budapest, Hungary
aDr Pinter receives research/grant support from the Harry Dent Family Foundation Inc.
bDr Pinter reports no disclosure.

Residency Program Director, Department of Neurology, Madigan Army Medical
Center, Tacoma, Washington; Assistant Professor, Uniformed Services University
of Health Sciences, Bethesda, Maryland
a,bDr Ponce de Leon reports no disclosures.
Ernst-Wilhelm Radue, MD
Professor Emeritus, Consulting Neurologist, Chief Executive Officer of Biomedical
Research and Training, Basel, Switzerland
aDr Radue has served as a consultant for Neurologische und Psychiatrische Universitäts
Klinik Basel, has received personal compensation for speaking engagements from Novartis
AG and Sanofi Genzyme, and receives royalties from Springer-Verlag GmbH.
bDr Radue reports no disclosure.
Rachel V. Rose, JD, MBA

Attorney, Rachel V. Rose Attorney at Law PLLC; Affiliated Faculty,
Baylor College of Medicine, Houston, Texas
aMs Rose serves on the editorial board of BC Advantage and receives book royalties
from the American Bar Association.
bMs Rose reports no disclosure.

Karanbir Singh, MD
Attending Neurologist, Director of Neurology/Neuroimaging, Apex Hospital,
Jalandhar, Punjab, India
a,bDr Singh reports no disclosures.

Director of Neuro-Ophthalmology, Director of Neuroimaging,
Hattiesburg Clinic, Hattiesburg, Mississippi
a,bDr Szatmáry reports no disclosures.
Georgios Tsivgoulis, MD, PhD, MSc, RVT

Associate Professor of Neurology, Second Department of Neurology,
University of Athens School of Medicine, Attikon University Hospital, Athens,
Greece; Visiting Associate Professor of Neurology, Director of Stroke Research,
Department of Neurology, University of Tennessee Health Science Center,
Memphis, Tennessee
aDr Tsivgoulis serves on the editorial boards of Stroke and the Journal of Neuroimaging and
has received research/grant support from the European Regional Development Fund.
bDr Tsivgoulis reports no disclosure.
Horst Urbach, MD
Professor, Director, Department of Neuroradiology, University Medical Center,
Freiburg, Germany
aDr Urbach serves as coeditor of Clinical Neuroradiology and on the editorial board of
Neuroradiology and has received personal compensation for speaking engagements from
Bracco, Stryker, and UCB SA.
bDr Urbach reports no disclosure.
Matthias Weigel, PhD

Senior Physicist, Radiological Physics, Department of Radiology, University
Hospital Basel; Department of Biomedical Engineering, University of Basel,
Basel Switzerland
aDr Weigel has received personal compensation for speaking engagements from the
European Society for Magnetic Resonance in Medicine and Biology, the Magnetic Resonance
Compact University Hospital Erlangen, and Vereinigung Südwestdeutscher Radiologen und
Nuklearmediziner and royalties from the University Medical Center of the University of
Freiburg for a patent for dynamic motion correction in MRI.
bDr Weigel reports no disclosure.

Roland Wiest, MD
Professor of Neuroradiology, Institute of Diagnostic and Interventional
Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
aDr Wiest receives research/grant support from the Swiss National Foundation.
bDr Wiest reports no disclosure.
SELF-ASSESSMENT AND CME TEST WRITERS

Eduardo E. Benarroch, MD, FAAN
Professor of Neurology, Mayo Clinic, Rochester, Minnesota
a,bDr Benarroch reports no disclosures.
Adam G. Kelly, MD
Associate Professor of Neurology, University of Rochester Medical Center;
Chief of Neurology, Highland Hospital, Rochester, New York
aDr Kelly has received research support from the Donald W. Reynolds Foundation.
bDr Kelly reports no disclosure.

Volume 22 n Number 5 n October 2016

www.ContinuumJournal.com
Denotes Online-Only Article

Neuroimaging
Guest Editors: Laszlo L. Mechtler, MD, FAAN; Joshua P. Klein, MD, PhD, FANA, FAAN
Editor’s Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1377
REVIEW ARTICLES
Introduction to Magnetic Resonance Imaging for Neurologists . . . . . . . . . . . . . 1379
Ernst-Wilhelm Radue, MD; Matthias Weigel, PhD;
Roland Wiest, MD; Horst Urbach, MD
Imaging of Ischemic Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1399
Michelle P. Lin, MD, MPH; David S. Liebeskind, MD, FAAN
Imaging of Hemorrhagic Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1424
Ryan Hakimi, DO, MS; Ankur Garg, MD
Imaging for Adults With Seizures and Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . 1451
Samuel Lapalme-Remis, MDCM, MA, FRCPC; Gregory D. Cascino, MD, FAAN
Imaging of Congenital Malformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1480
Imaging in Patients With Visual Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1499
Imaging of Brain Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1529
Mirza A Baig, DO; Joshua P. Klein, MD, PhD, FANA, FAAN;
Laszlo L. Mechtler, MD, FAAN
Imaging of Intracranial Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1553
Bela Ajtai, MD, PhD; John A. Bertelson, MD
Imaging of Pituitary and Parasellar Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 1574
Robert Fenstermaker, MD, FACS, FAANS; Ajay Abad, MD
Imaging of Spinal Cord Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1595
Karanbir Singh, MD; Laszlo L. Mechtler, MD, FAAN;
Joshua P. Klein, MD, PhD, FANA, FAAN
Imaging of Central Nervous System Demyelinating Disorders . . . . . . . . . . . 1613
Positron Emission Tomography and Single-Photon Emission
Computed Tomography in Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1636
Volume 22 n Number 5 www.ContinuumJournal.com 1373

Ultrasound in Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1655

Georgios Tsivgoulis, MD, PhD, MSc, RVT; Andrei V. Alexandrov, MD, RVT
Potential Safety Issues Related to the Use of Gadolinium-based
Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1678
Nandor K. Pinter, MD; Joshua P. Klein, MD, PhD, FANA, FAAN;
MEDICOLEGAL ISSUES
Legal Implications of Physician Investment and Ownership
in Health Care Enterprises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1685
Rachel V. Rose, JD, MBA; Joseph S. Kass, MD, JD, FAAN
PRACTICE ISSUES
Safety Considerations in Magnetic Resonance Imaging of Patients
With Implanted Medical Devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1691
Coding in Neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e1
Joseph V. Fritz, PhD; Bennett Myers, MD
SELF-ASSESSMENT AND CME

Learning Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1375
Instructions for Completing Postreading Self-Assessment and CME Test
and Tally Sheet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1699
Postreading Self-Assessment and CME Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1701
Postreading Self-Assessment and CME Test—Preferred Responses . . . . . . 1721
Eduardo E. Benarroch, MD, FAAN; Adam G. Kelly, MD
Patient Management Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1731
Patient Management Problem—Preferred Responses . . . . . . . . . . . . . . . . . . . 1738
Riley Bove, MD
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1747
List of Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Back Cover
1374 www.ContinuumJournal.com October 2016

Learning Objectives
Upon completion of this Continuum: Lifelong Learning in Neurology
Neuroimaging issue, participants will be able to:
Understand basic MRI physics and technology and how to acquire and interpret MRIs
s
Describe the foundation and utility of multimodal CT and MRI and collateral imaging
s
in all stages of ischemic stroke diagnosis and management

Discuss the significance of neuroimaging in the management of patients presenting
s
with hemorrhagic stroke, the various neuroimaging tools available to clinicians to aid
in management, and the common neuroimaging findings that help identify the underlying
etiology of hemorrhagic stroke
Accurately use structural and functional neuroimaging protocols in the evaluation
s
and treatment of patients with focal and generalized seizure disorders and identify
the limitations and potential diagnostic indications of neuroimaging investigations
in people with epilepsy
Recognize the imaging features of common congenital malformations and discuss how their
s
appropriate identification can impact diagnosis and treatment

Discuss the role of neuroimaging in the diagnosis and management
s
of neuro-ophthalmic disorders
Recognize the usefulness of MRI sequences in characterizing tumor types and discuss the
s
usefulness of posttreatment MRIs in distinguishing tumor recurrence from treatment-related

changes such as pseudoprogression and pseudoresponse
Identify the imaging characteristics of common and less often encountered intracranial
s
cysts and differentiate benign entities from pathologic processes

Discuss the utility of different imaging modalities in diagnosing pathologic lesions in the sellar
s
and parasellar regions

Recognize the imaging features of common spinal cord disorders, including disorders
s
of the spine that secondarily affect the spinal cord

Recognize neuroimaging characteristics of central nervous system demyelinating disorders
s
Recognize which neuromolecular imaging tests are clinically available and what the
s
indications are in different disorders

Discuss the clinical uses of ultrasound examination in cerebrovascular, neurodegenerative,
s
and peripheral nervous system diseases

Discuss the recent potential safety concerns associated with the use of gadolinium-based
s
contrast agents
Understand the basics of the Federal Anti-Kickback Statute and Stark Law in
s
relation to physician investment or ownership in a variety of health care enterprises

Discuss potential safety risks associated with MRI scans performed on patients with
s
implanted medical devices, current US Food and Drug Administration (FDA) safety labeling
for objects in the MRI environment, and advantages and challenges of magnetic resonance
conditional devices
Core Competencies
This Continuum: Lifelong Learning in Neurology Neuroimaging issue
covers the following core competencies:
Patient Care and Procedural Skills

s
Medical Knowledge
s
Practice-Based Learning and Improvement

s
Interpersonal and Communication Skills

s
Professionalism
s
Systems-Based Practice
s

Editor’s Preface
* 2016 American Academy
A Volume With Intensity of Neurology.
and Density
This issue of Continuum was day to assist in our patients’
developed by Guest Editors neurologic diagnoses.
Dr Laszlo L. Mechtler and The issue then takes
Dr Joshua P. Klein to pro- a whirlwind tour of the
vide us with the most up-to- neuroimaging of spe-
date tools to enhance what cific clinical syndromes,
we all do multiple times a disorders, and neuroan-
day: order, personally re- atomic regions. The first
view, and interpret our pa- of these articles is by
tients’ neuroimaging studies Drs Michelle P. Lin and
within the context of their David S. Liebeskind, who
clinical presentations. From discuss the imaging of
the start, I want to men- patients with ischemic
tion how indebted I am to stroke, immediately fol-
Dr Mechtler, Continuum’s This issue is densely lowed by a discussion of
associate editor of neuro- packed with practical the imaging of hemor-
imaging, for successfully information that will rhagic stroke by Drs
lobbying that a neuroimag- be relevant to all of us Ryan Hakimi and Ankur
ing issue was overdue in the as we decide which Garg. Next, Drs Samuel
Continuum curriculum, and imaging studies to Lapalme-Remis and
I also want to sincerely thank perform (and when) Gregory D. Cascino re-
Dr Klein for taking on the and is intensely view the many imaging
task of co-guest editorship illustrated with considerations in evalu-
with Dr Mechtler. This issue, ating adults with sei-
instructive example
the product of their collab- zures and epilepsy, and
oration, is densely packed
neuroimages Dr Jennifer W. McVige
with practical information throughout discusses and provides
that will be relevant to all of each article. many illustrative imaging
us as we decide which imag- examples of congenital
ing studies to perform (and when) and is malformations. Dr Gabriella Szatmáry
intensely illustrated with instructive exam- then reviews the imaging aspects of pa-
ple neuroimages throughout each article. tients with symptoms related to dysfunc-
The issue begins with an introduction tion anywhere along the visual pathway.
to MRI for neurologists by Drs Ernst- Drs Mirza A. Baig, Joshua P. Klein,
Wilhelm Radue, Matthias Weigel, Roland and Laszlo L. Mechtler review the imag-
Wiest, and Horst Urbach. Although the ing features of brain tumors, followed
complicated nature of this topic makes by a review of the imaging of intracranial
the word primer a bit of a misnomer, cysts by Drs Bela Ajtai and John A.
a careful reading of the authors’ expla- Bertelson and a discussion of the imaging
nation of this very complex topic will characteristics of pituitary and parasellar
provide neurologist readers with a con- disorders by Drs Robert Fenstermaker
ceptualization (which most of us do not and Ajay Abad. Drs Karanbir Singh, Laszlo
have) of the physics underlying MRI and L. Mechtler, and Joshua P. Klein next re-
its various sequences that we review every view the imaging features of many spinal
Continuum (Minneap Minn) 2016;22(5):1377–1378 www.ContinuumJournal.com 1377

Editor’s Preface
cord disorders, and Dr Konstantin facilities as an apropos example. In the

Balashov provides us with an up-to-date Practice Issues article, Dr Marcus Ponce
review of the imaging features that assist de Leon discusses the current consider-
in our contemporary diagnosis of central ations we all need to be aware of with
nervous system demyelinating disorders. regard to the safety of MRI of patients with
The preceding articles primarily em- implanted medical devices. Drs Joseph V.
phasize structural neuroimaging mo- Fritz and Bennett Myers next review (in
dalities, especially MRI. However, other the Coding article, which is online only in
neuroimaging modalities, each with a this issue) the imaging codes, indications,
place in our diagnostic armamentarium, and documentation requirements neurol-
are of relevance to neurologic practice. ogists need to be aware of with regard to
Dr Robert S. Miletich reviews the rele- neuroimaging of our patients.
vance of positron emission tomography As with every Continuum issue, sev-
(PET) and single-photon emission com- eral opportunities exist for CME. After
puted tomography (SPECT) studies in reading the issue and taking the Post-
a variety of neurologic syndromes, in- reading Self-Assessment and CME Test
cluding dementia, brain tumors, epi- written by Drs Eduardo E. Benarroch and
lepsy, movement disorders, and stroke. Adam G. Kelly (including a generous
Drs Georgios Tsivgoulis and Andrei V. number of questions related to interpre-
Alexandrov review ultrasound as a diag- tation of neuroimages), you may earn
nostic modality in neurology, including its up to 12 AMA PRA Category 1 Creditsi
role in assessment of cerebrovascular toward self-assessment and CME. The
disease and movement disorders and its Patient Management Problem, written by
evolving role in diagnosis of peripheral Dr Riley Bove, describes the case of a
nervous system disorders. 45-year-old man presenting with sub-
In the final review article of the issue, acute bilateral lower extremity weakness
Drs Nandor K. Pinter, Joshua P. Klein, and sensory loss. By following this patient’s
and Laszlo L. Mechtler provide us with case and answering multiple-choice ques-
a summary of the current information tions corresponding to decision points
regarding potential safety issues related (also including a number of neuroimag-
to the use of gadolinium-based contrast ing decisions and interpretation of imag-
agents, an issue that all neurologists need ing features) along this patient’s course,
to have on their radar despite (or perhaps you will have the opportunity to earn up
because of) the limited information to 2 AMA PRA Category 1 CME Credits.
currently available about this develop- I thank Drs Mechtler and Klein and
ing topic. each of their outstanding expert contrib-
This issue also presents the first Med- utors for creating such a comprehensive
icolegal Issues article in the newly re- and highly illustrated issue to inform our
named “Ethical and Medicolegal Issues” most up-to-date approaches to the order-
section, where articles about medicolegal ing, performance, and interpretation of
themes will generally alternate with the neuroimaging studies that, following
Continuum’s previously standard Ethical our neurologic histories and examinations,
Issues articles, under the associate editor- form such an important part of the diag-
ship of Dr Joseph S. Kass. In this issue’s nostic process in so many of our patients.
debut of this feature, Ms Rachel V. Rose
and Dr Kass review the legal implications
of physician investment and ownership VSteven L. Lewis, MD, FAAN
in health care enterprises, using imaging Editor-in-Chief

Review Article
Introduction to Magnetic
Address correspondence to
Dr Ernst-Wilhelm Radue,
Biomedical Research and
Training, University Eye Hospital
Resonance Imaging for Basel, Mittlere Strasse 91,

CH-4031 Basel, Switzerland,
ernst-wilhelm.radue@usb.ch.
Neurologists Relationship Disclosure:

Dr Radue has served as a
consultant for Neurologische
und Psychiatrische
Ernst-Wilhelm Radue, MD; Matthias Weigel, PhD; Roland Wiest, MD; Universit.ts Klinik Basel,
Horst Urbach, MD has received personal
compensation for speaking
engagements from Novartis
AG and Sanofi Genzyme, and
ABSTRACT receives royalties from
Springer-Verlag GmbH.
Purpose of Review: In neuroradiology, highly sophisticated methods such as MRI Dr Weigel has received
are implemented to investigate different entities of the central nervous system and personal compensation for
to acquire miscellaneous images where tissues display varying degrees of speaking engagements from
the European Society for
characteristic signal intensity or brightness. Compared to x-ray, CT, and ultrasound, Magnetic Resonance in
MRI produces clearer images of tissues, body fluids, and fat. The basics of MRI may Medicine and Biology, the
be unknown to neurologists; this article introduces MRI physics, techniques, and Magnetic Resonance Compact
University Hospital Erlangen,
interpretation guidelines. and Vereinigung
Recent Findings: This article discusses the basics of MRI to provide clinicians with Südwestdeutscher
the scientific underpinning of MRI technology and to help them better understand Radiologen und
Nuklearmediziner and
image features and improve their diagnosis and differential diagnosis by combining royalties from the University
MRI characteristics with their knowledge of pathology and neurology. Medical Center
Summary: This article will help neurologists deepen their knowledge and under- of the University of Freiburg
for a patent for dynamic
standing of MRI by introducing the basics of MRI physics, technology, image motion correction in MRI.
acquisition, protocols, and image interpretation. Dr Wiest receives research/
grant support from the Swiss
National Foundation. Dr
Continuum (Minneap Minn) 2016;22(5):1379–1398. Urbach serves as coeditor of
Clinical Neuroradiology
and on the editorial board of
Neuroradiology and has
INTRODUCTION sound). However, MRI produces im- received personal compensation
for speaking engagements from
This article provides a short, but ages that are related to the magnetic Bracco, Stryker, and UCB SA.
comprehensive, overview of MRI for properties of, and molecular interac- Unlabeled Use of
neurologists, including the physics tions within, the tissues under obser- Products/Investigational
Use Disclosure:
underlying this imaging modality, the vation. Since these interactions are Drs Radue, Weigel, Wiest, and
basics of image acquisition, and the complex and manifold, MRI has be- Urbach report no disclosures.
come a powerful and versatile imaging * 2016 American Academy
approach to imaging interpretation of Neurology.
with MRI. modality that can distinguish a large
number of very different tissue contrasts.
A PRIMER ON MRI PHYSICS
MRI is a noninvasive imaging modality Important Physical Features
that provides excellent soft tissue That Create MRI Images
contrast for normal and pathologic The physics of MRI can be understood
structures of tissues such as cartilage, best by following a number of steps
muscles, brain, and spinal cord as well and thereby investigating the underly-
as fat and body fluids. Medical imaging ing physics and technology. These
modalities often produce image con- steps also reflect the physics of an
trasts that are related to the different MRI measurement cycle.
absorption and reflection of waves in Polarization. The human body con-
body tissues (eg, x-ray, CT, ultra- sists of approximately 1027 molecules,

Introduction to MRI
KEY POINT
h MRI produces images which is an unfathomably large num- suffers from low signal (and low signal
that are related to the ber. Each molecule consists of a few to noise ratio, as described later in
magnetic properties of, to thousands of atoms. Many nuclei of this article).
and molecular interactions these molecule-bound atoms rotate Excitation and precession. Initially,
within, the tissues around their axis; they have a so-called at rest, the net magnetization resides
under observation. spin.1Y3 Spinning nuclei always gener- parallel to the B0 field in the equi-
ate a nuclear magnetic (dipole) mo- librium position; this is called the
ment. Thus, each spinning nucleus equilibrium magnetization M0.1Y3 How-
behaves like a tiny bar magnet with a ever, an MRI scanner is able to gener-
magnetic north pole and south pole. It ate a second magnetic field, B1, that
has become common in MRI literature oscillates in the radiofrequency range.
to refer to these nuclear magnets in a The spins are able to absorb energy
simplified way as spins.1Y3 Because of from this B1 field, and, thus, they are
their high natural abundance in the tipped or flipped out of the equilib-
human body and because they have the rium position. This process is called
strongest magnetic moment, the nuclei excitation; the spins and, accordingly,
of hydrogen atoms are commonly used the net magnetization are excited.1Y3 The
for clinical MRI. A hydrogen nucleus angle by which the spins/magnetization
consists of only one proton. There- are rotated is termed the flip angle. Flip
fore, the following discussion focuses angles are usually between 0 degrees
on spins of hydrogen nuclei/protons. and 90 degrees.
Although the human body contains As soon as the spins leave the
roughly 1027 magnetic hydrogen nu- equilibrium position, they start to
clei, ie, spins, humans do not seem to undergo a rotating motion around
be magnetic. Why? Because all the the external B0 field called precession,
spins are randomly orientated in the much like a spinning top under the
body; they cancel each other, and there- effect of gravity. The precession fre-
fore their net magnetization is 0.1Y3 quency of the spins is depicted by the
The basic idea of MRI is to put the Larmor equation.1Y3 The Larmor equa-
patient into a very strong and static tion states that the precession fre-
magnetic field, the so-called main field quency is directly proportional to the
B0. This static B0 field is generated by strength of the magnetic field. Thus,
the MRI scanner and is approximately the higher the magnetic field, the
30,000 to 140,000 times stronger than higher the precession frequency (ie,
the earth’s magnetic field. As a conse- the faster the spins rotate). Contrary
quence, the spins begin to orient in to this, the lower the magnetic field,
space and to align with the B0 field. the lower the precession frequency
However, compared to compass and the slower the spins rotate.
needles in the earth’s magnetic field, The basic statement of the Larmor
spins align not only parallel but also equation would not be of such great
antiparallel to the external static B0 importance in MRI if all spins experi-
field. 1Y3 The numbers are almost enced the same magnetic field as
equal; only a tiny excess of spins is determined by the nominal value of
additionally aligned parallel to the B0 the scanner’s B0 field (eg, 1.5T or 3T)
field, leading to a tiny but measurable and therefore automatically had the
macroscopic net magnetization, or same Larmor frequency. This is not
M 0 . Since this effect of so-called the case for several reasons. First, the
polarization is so weak, MRI is an B0 main field of an MRI scanner can
imaging modality that permanently never be built perfectly constant in

space as it has spatial inhomogenei-
ties. Second, human body tissues also
generate a tissue-characteristic magne-
tization called susceptibility, which
distorts the external B0 field. Hence,
the spin’s Larmor frequency slightly
changes with position due to B0
inhomogeneity and tissue susceptibil-
ity effects.1Y3 The third reason is that
an MRI scanner can generate spatially
varying magnetic fields that are used
for spatial encoding. These so-called
gradient fields are discussed later in
the article.
So far, it has been roughly said that
the B1 excitation field oscillates in the
radiofrequency range; however, to be
FIGURE 1-1 In MRI, any magnetization vector M
more accurate, the B1 oscillation (orange arrow) is decomposed into a
frequency has to match quite precisely longitudinal component Mz parallel to
the z-axis (blue arrow) and into a transverse
the Larmor precession frequency of the component Mxy (green arrow) in the x-y-plane.
spins. The two frequencies have to be
in resonance. Otherwise, the spins
cannot absorb the radiofrequency en- netization components occur and pre-
ergy, and they are not excited.1Y3 A cess in the x-y-plane. Generally,
good analogy for this observation of moving or rotating magnetic moments
mandatory resonance is a child’s swing. or vectors induces electrical currents
The child must move synchronously or in electrical coils. Thus, the precessing
in resonance with the swing to increase excited spins induce an electrical
its amplitude. The modality’s full name, voltage in radiofrequency receiver
written out as nuclear magnetic reso- coils placed around the human body,
nance imaging, directly originates similar to a generator producing
from this effect.1Y3 electricity.1Y3 Since the effect is very
Magnetization is a vector quantity, weak, the measured radiofrequency
ie, it possesses a magnitude and a signal is tiny and must be amplified by
direction (Figure 1-1). As has already a dedicated radiofrequency receiver/
been pointed out, the initial direction amplifier chain. However, the radio-
of the net magnetization is parallel to frequency coils and radiofrequency
the external B0 field. By definition, this amplifier chain also measure and
is the z-axis of the scanner’s coordi- generate noise, which is usually of
nate system; it is also called the similar magnitude to the desired ra-
longitudinal direction. Orthogonal to diofrequency signal. For this reason,
the longitudinal z-direction is the MRI inherently suffers from a low signal
transverse plane, spanned by the to noise ratio. If the MRI images
orthogonal x-axis and y-axis. In MRI, become too noisy (ie, if the signal to
any magnetization vector is de- noise ratio gets too low), diagnosis is
composed into a longitudinal and a no longer feasible.
transverse component (Figure 1-1). Modern radiofrequency coils for
Measurement with radiofrequency MRI are usually close to the patient’s
coils. After excitation, transverse mag- body to improve the reception of the

Introduction to MRI
KEY POINT
h T1-weighted MRI uses radiofrequency signal. Since the mea- sponds to an exponential asymptotic
T1 relaxation times to sured noise is directly correlated to curve (Figure 1-2). Thus, T1 does not
generate fundamental the sensitivity volume of the radio- directly depict the time when the re-
images with characteristic frequency receiver coil, small radio- laxation is completed, but is a mea-
tissue signal frequency coils produce a higher sure of the speed of the relaxation or
intensities or tissue signal to noise ratio than the scanner’s recovery of the longitudinal magneti-
brightness. As a rule of large body coil. Furthermore, modern zation component (Figure 1-2).
thumb, the more phased-array coils take advantage of T1 relaxation times are not only
aqueous a tissue is, the this; they consist of a matrix of several highly tissue characteristic, but they
higher the T1 is. Fat has small radiofrequency coils of high also depend on the B0 field strength
short T1.
signal to noise ratio, combining them of the scanner.1,2,4 They also alter with
to be sensitive to a larger body volume. structural changes of the tissue, which
At the end of the radiofrequency re- makes T1 highly sensitive for patho-
ceiver chain, the signal is further logic changes of body tissue; T1-
postprocessed by a computer to re- weighted MRI uses T1 relaxation times
construct the magnetic resonance to generate fundamental images with
(MR) image.1Y3 characteristic tissue signal intensities
Relaxation. Nature always strives or tissue brightness (Figure 1-2). T1
for equilibrium, ie, for a uniform relaxation times are roughly between
distribution of energy. Consequently, half a second and a few seconds for
in MRI, the excited spins want to get liquids. As a rule of thumb, the more
rid of their energy such that the net aqueous a tissue is, the higher the T1
magnetization resides as a pure longi- is. Fat has short T1.
tudinal magnetization in the equili- A second relaxation takes place that
brium position again. This effect is leads to a decay or relaxation of the
called relaxation.1Y4 Two different generated transverse component
types of relaxation occur in MRI, which toward 0, which can be considerably
is another reason magnetization vec- faster than the recovery of the longi-
tors are always regarded as a longitu- tudinal component.1Y4 Remember that
dinal magnetization component and a the macroscopic net magnetization is
transverse magnetization component. the sum of a multitude of spins. For
With the equilibrium magnetization each spin, the Larmor equation holds
being excited, the longitudinal com- true. Since the molecules and spins
ponent is reduced (flip angle between are in permanent thermal motion on
0 and 90 degrees) or becomes exactly a microscopic scale, their magnetic
0 (a 90-degree flip angle). Then the moments interact with each other.
process of longitudinal relaxation To put it simply, a given spin influ-
immediately starts: the longitudinal ences the local magnetic field the
magnetization grows back to its nor- neighboring spins “see”; accordingly,
mal size in the equilibrium state. their Larmor precession frequencies
However, this is not an immediate change constantly. As a consequence,
process, because the spins need time the precessing transverse magnetiza-
to transfer their excess of energy to tion components of the spins get out
the environment in the tissue. To be of sync or out of phase.1Y4 The in-
more accurate, the speed of the dividual components fan out in the
longitudinal relaxation is specific for a transverse plane, leading to a decay of
given tissue and takes place with a the transverse net magnetization with
characteristic relaxation time T1.1Y4 the characteristic and tissue-specific
Furthermore, this T1 relaxation corre- relaxation time T2 (Figure 1-3). The T2

FIGURE 1-2 Longitudinal relaxation or T1 recovery curves of the (longitudinal) magnetization
component Mz shown for two tissues with different T1 but the same proton
density. In this example, tissue 1 has a short T1 (eg, body fat, orange curve),
whereas tissue 2 has a long T2 (eg, CSF, blue curve). Based on such different recovery curves,
T1-weighted images can be acquired; two representative examples are shown. The left image
was acquired with a shorter repetition time than the right image, leading to a stronger T1
weighting. As is typical for a T1-weighted brain image, white matter is brighter than gray
matter because of the shorter T1. CSF has the longest T1 and is therefore very dark.
FIGURE 1-3 Transverse relaxation or T2 decay curves of the (transverse) magnetization

component Mxy shown for two tissues with different T2 but the same proton
density. In this example, tissue 1 has a short T2 (eg, body fat, orange curve),
whereas tissue 2 has a long T2 (eg, CSF, blue curve). Based on such different decay curves,
T2-weighted images can be acquired. Three representative examples are shown, with
increasing echo time from left to right, leading to an increase in T2 weighting from left to right
accordingly. As is typical for a T2-weighted brain image, gray matter is brighter than white
matter because of the longer T2. CSF has the longest T2 and is therefore very bright.

Introduction to MRI
KEY POINT
h T2 alters with structural relaxation is an exponential decay; tion, the Larmor frequency also
or metabolic changes thus, similar to T1, T2 does not di- changes linearly along the gradient’s
of the tissue, which rectly depict the time when the direction accordingly. This effect is
makes it highly sensitive relaxation is completed but is a mea- exploited in three ways for spatial
for pathologic changes sure of the speed of relaxation or encoding. First, during radiofrequency
of body tissue; decay (Figure 1-3). excitation, a gradient can be turned
T2-weighted MRI uses T2 T2 relaxation times are approxi- on, the so-called slice selection (two-
relaxation times to mately between 50 milliseconds and dimensional acquisition) or slab selec-
generate fundamental 100 milliseconds for aqueous soft tion (three-dimensional acquisition)
images with tissues and roughly 1 to 2 seconds gradient.1Y5 Consequently, according
characteristic tissue
for liquids. T2 also alters with struc- to the resonance condition mentioned
signal intensities or
tural or metabolic changes of the earlier in the article, only spins are
tissue brightness.
tissue, which makes it highly sensitive excited (and therefore generate signal)
for pathologic changes of body tissue; where the linearly changing precession
T2-weighted MRI uses T2 relaxation frequencies in space match the range
times to generate fundamental images of radiofrequency excitation frequen-
with characteristic tissue signal inten- cies: This defines the desired slice or
sities or tissue brightness (Figure 1-3). slab. Second, during the measurement,
Because of the random nature of a gradient can be turned on, the so-
the thermal motion, the spin interac- called read or frequency-encoding
tions are random, and, thus, the T2 gradient.1Y5 Then, the spin locations
decay is irreversible.1Y4 However, an along this read gradient are encoded
additional, reversible effect leads to into the signal via the spins’ spatially
further decay of transverse magnetiza- dependent Larmor frequency. Third,
tion. Inhomogeneities of the scanner’s between excitation and measurement,
B0 field and varying susceptibility ef- a gradient can be turned on, the so-
fects of the tissues, as discussed earlier called phase-encoding gradient.1Y5
in the article, also change the Larmor Thus for a duration of time, the spins
frequency according to the Larmor along this phase-encoding gradient
equation. These effects are fixed in precess with different Larmor frequen-
space on a macroscopic scale and are, cies and therefore acquire different
therefore, reversible by using so-called phases. As phases, the different angles
spin echoes.4 The combined relaxation of transverse magnetization compo-
of the irreversible T2 part and the nents in the x-y-plane are indicated
reversible part is termed T2*.1Y5 (Figure 1-1). Repetitive measurement
cycles with different phase-encoding
Spatial Encoding gradients allow encoding spin locations
So far, basic MR physics, signal gener- into phase changes. Generally, three
ation, and measurement as well as gradient coils also reside within the
relaxation effects have been discussed. scanner, one each for the x-, y-, and
However, to reconstruct a full image, z-direction.
the measured MR signal needs to be The measured signal containing
assigned to the corresponding loca- the spatial encoding is stored into a
tion in the patient’s body where it was raw data space called k-space. After-
generated; spatial encoding is ward, the main step in image recon-
needed.1Y5 To achieve this, so-called struction is to make use of the Fourier
gradient coils are employed that gen- transform. It facilitates decoding of
erate a linear magnetic field in space. the k-space data such that it as-
In accordance with the Larmor equa- signs signal intensities to their correct

KEY POINTS
location again, resulting in the re- echo sequences are more robust in h Errors caused by B0
constructed image. signal behavior, they are slower than inhomogeneities,
The complexity of the spatial GRE sequences. A faster spin echo susceptibility effects,
encoding and the MR signal genera- variant, the turbo or fast spin echo body motion, or wrong
tion makes MRI prone to errors in sequence, generates more than one parameter settings on
these procedures, eg, caused by B0 echo per excitation and is one of the the scanner can manifest
inhomogeneities, susceptibility ef- workhorses in clinical MRI.4,5 in the image as artifacts
fects, body motion, or wrong parame- Important MRI sequence parame- (structures displayed that
ter settings at the scanner. Such ters that can usually be influenced by do not reflect reality), or
effects can manifest in the image as the user at the scanner are the echo the image may be
blurred. Identifying and
artifacts, ie, structures are displayed time (TE) and the repetition time
avoiding such artifacts is
that do not reflect the reality, or the (TR). TE defines the time from the
of great importance
image may be blurred. Identifying and excitation until the signal is measured in MRI.
avoiding such artifacts is of great in the transverse plane.1Y5 This is of
importance in MRI. h Important MRI sequence
importance because the longer the TE
parameters that can
defined by the user, the longer the usually be influenced by
MRI Sequences tissue-specific T2 decay takes place. the user at the scanner
Generally, radiofrequency excitation, Hence, the acquired image displays a are the echo time and
the switching of spatial encoding gra- stronger T2 weighting. TR defines the the repetition time.
dients, waiting times for relaxation, time between repetitive measurement h Echo time defines the
and signal measurements follow an cycles or excitations.1Y5 If the defined time from the excitation
exact and predefined timing pattern TR is short compared to the charac- until the signal is
that is called the (MRI) sequence. teristic T1 relaxation times of the in- measured in the
Some parts of the sequence timing vestigated tissues, the corresponding transverse plane. This is
may be influenced by the user. The longitudinal magnetizations cannot of importance because
exact sequence timing pattern deter- fully recover before the next excita- the longer the echo time
mines the characteristic brightness of tion, which represents a T1 weighting defined by the user, the
the different tissues in the reconstructed of the magnetization. As a result, the longer the tissue-specific
images due to proton density and T1 image that is reconstructed is also T2 decay takes place.
and T2 weighting. Hence, the acquired
T1 weighted.
image displays a stronger
Dozens, hundreds, or perhaps T1 and T2 weighting are dominant
T2 weighting.
thousands of different MRI sequences or strong signal weightings in MRI and
exist, depending on how the different therefore facilitate images with excel- h Repetition time defines
types and variants that were published the time between
lent tissue differentiation. Morpho-
repetitive measurement
within the past 40 years are counted logic acquisitions with both low T1
cycles or excitations.
and classified. In practice, MRI sequences weighting and low T2 weighting usually
are frequently classified as being either bring out the third fundamental MRI h If the defined repetition
time is short compared to
a gradient recalled echo (GRE) or a spin weighting: proton density weighting.1Y5
the characteristic T1
echo sequence.4,5 Basically, GRE se- This weighting is proportional to the
relaxation times of the
quences use a radiofrequency excita- number of spins/protons in the tissue. investigated tissues, the
tion pulse, apply the spatial encoding, Proton density weighting is weak com- corresponding longitudinal
and directly measure the excited mag- pared to T1 and T2 weighting, partic- magnetizations cannot
netization, as described earlier in the ularly in the brain. fully recover before the
article. Spin echo sequences apply a next excitation, which
second radiofrequency pulse after exci- Magnetization Preparation represents a T1 weighting
tation and before the measurement, the The flexibility and versatility of tissue of the magnetization.
so-called refocusing pulse. It reverses brightness and appearance in MRI can As a result, the image
or refocuses the B0 inhomogeneity and be increased manifold by employing that is reconstructed
susceptibility effects. Whereas spin additional radiofrequency and gradient is also T1 weighted.

Introduction to MRI
KEY POINTS
h T1 and T2 weighting are pulses. These magnetization prepara- sional motion is of a random nature,
dominant or strong tions introduce dedicated weightings the introduced phase change is dif-
signal weightings in MRI into the initial equilibrium magnetiza- ferent for each individual spin; hence,
and therefore facilitate tion before the actual excitation pulse the net transverse magnetization is
images with excellent or make the already excited magneti- attenuated.6 By contrast, f low in a
tissue differentiation. zation sensitive to some physical vessel is a coherent motion; thus, the
h Diffusion represents effects. Both have a direct impact on introduced phase change for each in-
water motion in the the tissue brightness and appearance dividual spin is the same and pro-
tissue on a microscopic in the later reconstructed image. portional to its speed. Consequently,
scale; it is determined by Among important variants are inflow velocities can be measured from
the tissue microstructure version recovery, diffusion, flow veloc- the phase change of the net trans-
and also reflects ity, and perfusion preparations. An verse magnetization.
metabolism. The inversion recovery preparation uses Direct perfusion-weighted imaging
resulting apparent an initial 180-degree radiofrequency is also feasible by administering con-
diffusion coefficient is
pulse to invert the longitudinal mag- trast agents to the patient. MRI con-
tissue-specific and is a
netization along the z-axis. Afterward, trast agents cause a strong reduction
measure of the mobility
of the water molecules
characteristic T1 recovery takes place of the local T1 and T2 relaxation times
in the tissue. toward equilibrium for all tissues; in the blood and where the contrast
however, all longitudinal magnetiza- agent molecules are able to diffuse,
h The principal advantage
tions have one moment in time when which may also depend on the whether
of MRI is the ability
to investigate
their magnitude is 0, depending on the blood-brain barrier is intact. Addi-
tissue-dependent the tissue’s T1. If the excitation tional postprocessing techniques and
responses to a magnetic follows in such a moment, the corre- models allow quantitative perfusion
field in multiple planes sponding tissue appears dark in the values to be derived. Prominent exam-
without the use of image (tissue nulling). Important ples of perfusion-weighted imaging are
ionizing radiation. types are short tau inversion recovery dynamic contrast-enhanced imaging
(STIR), in which fat is dark, and fluid- (T1-weighted) and dynamic susceptibil-
attenuated inversion recovery (FLAIR), ity contrast (T2-weighted) imaging.
in which fluids such as CSF are dark. Generally, apart from perfusion-
By using particular gradient patterns, weighted imaging, contrast agents may
MRI sequences can also be made sen- add further information about tissue
sitive to motion effects, such as diffu- damage and are able to brighten up
sion and flow in the tissue.6 These vessels in the body.
particular gradient patterns alter the
phase of transverse magnetization IMAGE ACQUISITION AND
components in dependence of mo- MAGNETIC RESONANCE
tion. Diffusion represents water mo- PROTOCOLS
tion in the tissue on a microscopic The principal advantage of MRI is the
scale; it is determined by the tissue ability to investigate tissue-dependent
microstructure and also reflects metab- responses to a magnetic field in multi-
olism.6 The resulting apparent diffu- ple planes without the use of ionizing
sion coefficient (ADC) is tissue-specific radiation. Basic knowledge about the
and is a measure of the mobility of the brain’s anatomy and typical landmarks
water molecules in the tissue. Diffu- is mandatory for reading MRI.
sional motion is exceptionally sensi- To acquire the appropriate slicing
tive to pathologic tissue changes, and, localizer scans using fast echo, acquisi-
thus, diffusion-weighted imaging (DWI) tions in three orthogonal planes are
is extremely well suited as an early recommended. Axial imaging ac-
marker for stroke imaging. Since diffu- quisitions should be placed in the

midsagittal line oriented along the ium detect venous thrombosis; T1-
anterior and posterior commissure and T2-weighted fat-suppressed
or alternatively along the genu and sequences along the cervical arteries
splenium of the corpus callosum. detect dissections of the arteries.
Coronal acquisitions should be ori- Vascular malformations require time-
ented along the principle targets resolved ultrafast angiograms of the
of the examination, ie, in an 18- to affected vessels with a temporal reso-
30-degree angulation perpendicular lution greater than 1.0 second.
to the long axis of the hippocampus to Specialized high-resolution proto-
assess temporal lobe atrophy or mesio- cols are also recommended when
temporal sclerosis, along the pituitary searching for epileptogenic lesions in
stalk in cases of sellar pathology, or patients with (focal) epilepsy syn-
along the main axis of the optic nerves dromes, since conventional protocols
in orbital pathology. Sagittal slices may miss the abnormalities in approxi-
should be oriented along the midline mately 50% of cases.7 Six sequences are
of the corpus callosum. The appropri- considered as essential, encompassing
ate sequences should follow predefined T1-weighted, high-resolution T1-
and standardized protocols. However, weighted, T2/STIR, FLAIR in coronal
during acquisition, changes may be and axial acquisitions, and GRE/SWI se-
necessary to follow unexpected pathol- quences of 3 mm or more. In patients
ogies, and one should not rely on in whom there is a concern for lepto-
protocols that may be hampered by meningeal inflammation and infiltra-
inadequate slice thickness or lack of tion, standard routine protocols may
DWI, GRE/T2*, or susceptibility- be complemented by postcontrast
weighted imaging (SWI) sequences. FLAIR. For differentiation between
For standard acquisitions, the authors inflammatory pseudotumoral lesions
recommend DWI/ADC, T1-weighted, and CNS tumors, DWI, perfusion imag-
T2-weighted, and FLAIR sequences as ing, and MR spectroscopy may be of
a basic standard, with optional acquisi- additional value (Figure 1-4).
tions of time-of-flight, SWI, and T1- Beyond lesion analysis, standard
weighted gadolinium sequences with a clinical routine MRI protocols embody
spatial resolution between 3 mm and a wealth of information about the
5 mm (depending on field strength) functional state of the brain. DWI,
with at least one high-resolution three- for example, is now part of most rou-
dimensional acquisition with isotropic tine protocols. Diffusion is restricted
voxels (each side of the voxel equals the in tissue with a dense cellular matrix
same length, here 1.0 mm 1.0 mm or in the presence of cytotoxic edema
1.0 mm) (Table 1-1). with subsequent lowering of the ADC
A stroke protocol for MRI should (Figure 1-5).
encompass DWI, FLAIR, T2*/SWI, dy- While DWI is frequently employed
namic susceptibility contrast perfu- to detect the core of an ischemic
sion, and time-of-flight or first-pass stroke8 or a brain abscess,9 it may also
gadolinium MR angiography (MRA). aid in the differential diagnosis between
In cases of hemorrhage, additional seizure-related diffusion restriction and
T1-weighted sequences may be help- an ischemic stroke,10 in tumefactive
ful to inform about the onset of the multiple sclerosis lesions,11 in glioma
hemorrhage. Venous time-of-flight an- and lymphoma,12 and in the prognos-
giograms and FLAIR and T1-weighted tic assessment of coma13 and traumatic
sequences with and without gadolin- brain injury.14,15

1388
TABLE 1-1 Routine Magnetic Resonance Imaging Protocols
CE
Sequence DWI/ADC T2-Weighted T1-Weighted FLAIR SWI ToF CE MRA Perfusion T1-Weighted FLAIR+CE
Magnetic Axial Axial Axial Coronal Axial Optional Sagittal 3-D
www.ContinuumJournal.com
resonance GRE
screening
Stroke Axial Axial Axial Optional Intracranial and Axial Axial Axial
extracranial
Trauma Axial Axial Sagittal Axial Axial
Multiple sclerosis Axial 3 mm or 3-D Sagittal 3-D Sagittal 3-D Sagittal 3-D
GRE GRE and
T1-weighted
spin echo
Epilepsy Axial T2/STIR axial/ 3-D GRE FLAIR axial/ Axial
coronal coronal
Introduction to MRI
Glioma Axial Axial 3-D GRE Axial Optional Sagittal 3-D

GRE and
T1-weighted SE
Infections Axial Axial Axial/sagittal Axial Sagittal 3-D Coronal
GRE and
T1-weighted SE
Neurodegenerative Axial Axial 3-D GRE Coronal Axial Axial Optional: ASL Optional
disorders
3-D = three-dimensional; ADC = apparent diffusion coefficient; ASL = arterial spin labeling; CE = contrast-enhanced; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion
recovery; GRE = gradient recalled echo; MRA = magnetic resonance angiography; SE = spin echo; STIR = short tau inversion recovery; SWI = susceptibility-weighted imaging; ToF = time of
flight.

October 2016
FIGURE 1-4 Signal characteristics of a tumefactive demyelinating lesion. A, Faint fluid-attenuated inversion recovery
(FLAIR) hyperintensity; B, C, diffusion restriction and decreased apparent diffusion coefficient (ADC) imaging.
D, Cerebral blood flow maps indicate hyperperfusion. E, Follow-up MRI (ADC map) after 24 hours indicates
lesion expansion and ADC signal drop following acute demyelination.
MRI may aid also in the differenti- rhage), calcifications, hemorrhagic con-
ation between vasogenic tumoral tusions in traumatic brain injury, or
edema and tumor infiltration,16 in altered blood oxygenation due to stroke
treatment selection of patients or status epilepticus (Figure 1-7).19Y20
experiencing wake-up strokes with Perfusion imaging in acute stroke
undefined onset, 17 and in assess- has been shown to be a good predic-
ment of various CSF pathologies, tor of the ischemic penumbra21 but
such as meningitis, meningeal carci- may also aid in the differentiation
nomatosis, stroke, and hemorrhage18 between ischemic and postictal
(Figure 1-6). hypoperfusion22 or in migraine attacks
SWI is used to assess disorders with atypical aura symptoms.23 Typical
associated with hemoglobin break- perfusion findings in different clinical
down (eg, parenchymal hemorrhage, scenarios can be seen in Figure 1-8. In
cerebral amyloid angiopathy, cavernous neuro-oncology, cell density and
malformations, subarachnoid hemor- prominent vascularization reflect
FIGURE 1-5 Patterns of diffusion-weighted imaging (DWI) restrictions in various neurologic disorders. A, Right middle
cerebral artery (MCA) territory infarction; B, Creutzfeldt-Jakob disease (cortical, basal ganglia); C,
symmetrically cortical in hypoxic-ischemic encephalopathy (HIE); D, cortical mixed cytotoxic and vasogenic
pattern in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS).

Introduction to MRI
FIGURE 1-6 Coronal fluid-attenuated inversion recovery (FLAIR) imaging indicating three characteristic patterns of
hyperintensity. A, Bilateral hippocampal and parahippocampal swelling in tick-borne encephalitis; B,
bithalamic and diencephalic edema due to venous thrombosis of the internal cerebral veins; C, dirty CSF
sign in a patient with subarachnoid hemorrhage (SAH). Note the hyperintensity due to expansion of blood
into the sulcal space.
heterogeneous patterns of malignancy 10 to 15 minutes because of a stroke

than can be prognostically assessed by or in an otherwise uncooperative
combinations of DWI and perfusion patient, or as an elective structural or
imaging24 to differentiate tumor pro- functional imaging study, which may
gression and therapy-related effects.25 last around 1 hour and requires ex-
tensive postprocessing procedures af-
GENERAL CONSIDERATIONS terward. The underlying disorder may
FOR IMAGE INTERPRETATION be misdiagnosed if, for example, an
The way MRI is used in clinical prac- uncooperative patient is studied with
tice strongly depends on the clinical a rigidly applied stroke protocol in an
needs and context of application, emergency setting. Imaging findings
whether as an emergency MRI within may be so subtle that only with the
FIGURE 1-7 Advanced MRI applications for ischemic stroke. A, Axial susceptibility-weighted imaging (SWI) indicates
location and thrombus length in the left middle cerebral artery (arrow); B, digital subtraction angiography
indicates vessel occlusion of the left internal carotid artery (arrow); C, SWI indicates prominent veins due to
increased oxygen extraction (paramagnetic effect) (arrow); D, perfusion imaging ([time-to-maximum; max delay] longer than
6 s indicated in red) (arrow) corresponds to the area with prominent vessels on SWI.

FIGURE 1-8 Perfusion imaging indicating abnormal cerebral blood flow maps in different neurologic disorders. A, Patient
with postictal hypoperfusion in the left temporal lobe presenting with aphasia. B, Patient with hypoperfusion
(exceeding the vascular territories) in the right temporal and occipital lobe during a migraine attack with
headache. C, Patient with clinical presentation of frontotemporal dementia and a symmetric pattern of reduced cerebral
blood flow in the frontal lobes. Arrows indicate brain areas with regional perfusion decrease.
appropriate clinical information will diffusion), then switching to T2/FLAIR

a lesion be found or correctly inter- sequences and T1-weighted se-
preted (Figure 1-9). quences with and without contrast to
To interpret images correctly, read- get a first overview of suspected
ing and analysis of the MRI should pathologies. In a second step, the
incorporate a systematic approach. remaining sequences should be ana-
This may encompass a structured lyzed in the context of the suspected
sequence of reading, first inspecting pathology, eg, perfusion imaging, SWI,
the DWI/ADC sequences (especially in and vascular sequences if a vascular
cases where the main findings can be disorder is suspected. A systematic
expected from facilitated or restricted approach should consider fixed reading
FIGURE 1-9 Imaging of a 76-year-old man with right-sided hemichoreic movements for several weeks. A, Axial fluid-attenuated
inversion recovery (FLAIR) sequence is unremarkable. B, Axial cerebral blood volume map shows a slight elevation
in cerebral blood volume in the left lentiform nucleus (arrow). C, Axial three-dimensional time-of-flight magnetic
resonance angiogram (MRA) shows diminished signal of the left internal carotid (arrow) and middle cerebral artery suggesting a
high-grade proximal internal carotid artery stenosis.

Introduction to MRI
KEY POINTS
h A systematic approach procedures, for example, from inside decline, or epileptic seizures. MRI
should consider fixed to outside or vice versa, from gray indicates intraaxial or extraaxial
reading procedures, for matter to white matter and CSF, or pathology, a space-occupying effect,
example, from inside to from suspected pathology to general gadolinium enhancement.
outside or vice versa, inspection on a slice-by-slice basis. It vasogenic edema, and midline shift,
from gray matter to cannot be emphasized enough that & Vascular: Sudden onset of a
white matter and CSF, the peripheral parts of the images neurologic deficit. MRI information
or from suspected
need to beinspected carefully; most may include vascular territory and
pathology to general
pathologies present in the periphery DWI lesion with ADC reduction.
inspection on a
slice-by-slice basis.
may be missed if those areas are & Infections: Headache, fever, focal
not examined carefully by the image neurologic deficit, or increased
h If a lesion is detected, it
reader. If possible, images should
should first be classified cells in CSF. MRI findings include
by broad category, eg,
be read twice, either by the neurora-
swelling of cerebral sulci or
tumoral lesion, vascular diologist and the neurologist or by
two specialized readers, to enable con- meningeal enhancement.
pathology, infection,
or degeneration. sistency checks of the suspected find- & Degenerative diseases: Cognitive
ings, with the final goal to identify decline, epileptic seizures. MRI may
and interpret structural lesions. If a indicate focal or generalized atrophy,
lesion is detected, it should first be no gadolinium enhancement, and
classified by broad category, eg, tumoral no focal lesions.
lesion, vascular pathology, infection, If no lesion is found, one should care-
or degeneration. Depending on the fully reanalyze the images and take into
underlying pathology, typical presen- consideration that a lesion may have
tations and imaging features may be been overlooked. A lesion may be
taken into account: overlooked because of an insufficient
& Cerebral tumors: Slowly progressive spatial resolution or insufficient contrast
focal clinical deficit, cognitive to the surrounding tissue (Figure 1-10)
FIGURE 1-10 Focal cortical dysplasia type IIB. A, Coronal two-dimensional fluid-attenuated inversion recovery (FLAIR)
turbo spin echo sequence with a slice thickness of 2 mm; B, coronal reformation of a three-dimensional
FLAIR sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE)
sequence; C, sagittal three-dimensional FLAIR SPACE sequence (1 mm 1 mm 1 mm voxel). Despite a higher
signal to noise ratio, the funnel-shaped hyperintensity is hardly visible on the two-dimensional sequence (A, arrow).
Multiplanar coronal reformation (B) of the three-dimensional FLAIR sequence helps locate the lesion, which is typically
found in the depth of a sulcus (B, C, arrows).

or because of misleading clinical infor- lesion to be detected, it must be at least
mation or a lack of clinical informa- 2 voxels (volume element defined by
tion. In some instances, a lesion may the slice thickness and the in-plane
not yet be visible, eg, during an early resolution) in size. If a lesion is less
manifestation of an acute spinal in- than 2 voxels in size, it may easily be
farction (Figure 1-11) or in the case missed because of partial volume effects.
of a lesion that is responsible for the Two-dimensional sequences have
clinical symptoms but hidden among a higher in-plane resolution and a
many others. higher signal to noise ratio than three-
Although lesion detectability is de- dimensional sequences26; however,
pendent on the contrast to noise ratio, they rarely cover the entire brain with
ie, the signal to noise ratio of the lesion a slice thickness of 1 mm to 2 mm.
versus the signal to noise ratio of the Three-dimensional sequences are gen-
surrounding tissue, in most cases, for a erally acquired in sagittal orientation
FIGURE 1-11 A 31-year-old man with sudden onset of pain and paraplegia below the level of
T10. A, Initial MRI with T2-weighted fast spin echo and sagittal diffusion-weighted
imaging (not shown) was unremarkable. B, Follow-up axial imaging 3 days later shows
a left-sided posterolateral spinal infarct. The insets in panel B are the axial images at the positions
shown by the thick white lines in the sagittal T2-weighted fast spin echo (left) and diffusion-weighted
(right) images. The thin white lines represent the range that is covered by the axial sequences.

Introduction to MRI
KEY POINTS
h Image interpretation and can be reformatted in any plane brain (epidural, subdural, subarach-
should always depend using a multiplanar reformation tool. noid space), cortex, white matter,
on the combination and This multiplanar reformation helps to ventricular ependymal, and ventricular
integration of imaging find subtle (epileptogenic) lesions space. The location of a lesion is
features and clinical (Figure 1-10). On the other hand, appropriately assessed with the lesion
information. high in-plane resolution may be needed cut perpendicular to its surface and
h Since location is a highly to show the details of a lesion and make
considering the effect on the surround-
relevant parameter for a specific diagnosis (Figure 1-12).
ings (Figure 1-13). In most cases, an
diagnosis, a strong Image interpretation should always
effort should be made
appropriate reformation of a three-
depend on the combination and inte-
to categorize a lesion dimensional sequence (eg, FLAIR,
gration of imaging features and clinical
with respect to its
information. While the signal intensity magnetization-prepared rapid ac-
topography. quisition gradient-echo imaging
may be a specific characteristic for a
h The signal intensity of [MPRAGE]) is considered helpful.
suspected lesion (eg, the high DWI
a lesion may provide The signal intensity of a lesion may
information about its
signal of epidermoid cysts, abscesses,
and infarctions), a combination of provide information about its compo-
composition. A
lesion is classified as several imaging parameters are of sition. A lesion is classified as hypoin-
hypointense, isointense, crucial importance to narrow the tense, isointense, or hyperintense as
or hyperintense as differential diagnosis. A checklist of compared to the gray matter if not
compared to the gray otherwise stated. T1-hyperintense le-
characteristic imaging features to be
matter if not
otherwise stated.
analyzed ahead of image interpreta- sions consist of fat, blood in the
tion are summarized in Table 1-2. methemoglobin stage, or proteina-
h T1-hyperintense lesions
Since location is a highly relevant ceous fluid, or show contrast enhance-
consist of fat, blood in
the methemoglobin parameter for diagnosis, a strong ment. Blood vessels typically are void
stage, or proteinaceous effort should be made to categorize a of any signal (flow void); they may,
fluid, or show contrast lesion with respect to its topography. however, show a paradoxical enhance-
enhancement. Try to exactly locate a lesion with ment on noncontrast T1-weighted
respect to: the spaces covering the GRE sequences.
FIGURE 1-12 High-resolution T2-weighted short tau inversion recovery (STIR) sequence
(0.45 mm 0.45 mm 2 mm) shows a nodule within a cyst (A, arrow)
suggestive of the scolex of the cysticercus. Ringlike contrast enhancement of
the lesion supports the diagnosis (B).

KEY POINT
The signal intensity of lesions that h MRI produces images
TABLE 1-2 Characteristic Imaging are T1 isointense, T1 hypointense, and that represent signal
Features to Be
T2 hypointense, isointense, or hyperintensities of tissue that
Analyzed Ahead of
Image Interpretation intense is related to the cellularity of are dependent on
these lesions. Lesions with a high relaxation time and
cellularity (high nucleus to cytoplasm spatial resolution.
b Location
Intraaxial, extraaxial ratio) show a relatively high signal on
(epidural, subdural, CSF space) T1-weighted images and a relatively
Lobe, gyrus, ventricular system
low signal on T2-weighted images
(Figure 1-14).
Gray matter, white matter
DWI provides information about
(central, peripheral,
U fiber involvement) the mobility of free water protons
b Morphology
within a lesion, complementing SWI
and T2-weighted sequences, which
Exophytic component
reveal whether a lesion contains calci-
Cystic component fication or blood degradation prod-
Encapsulated process ucts. Sometimes additional application
Central necrosis of CT may be necessary to confirm
Calcifications the diagnosis of a calcification or a
Hemorrhage cavernous malformation or to show
the osseous structures more clearly
Perifocal edema
(Figure 1-15).
b Signal Intensity
Interpretation of pathologic imag-
Spin density, T1 relaxation, ing features require a fundamental
T2 relaxation
knowledge of normal anatomy and
Susceptibility signal and their variants. Careful con-
Diffusion (water mobility) sideration of the localization of le-
Flow (flow void) sions, space-occupying effects, signal
b Delineation abnormalities of T1 and T2, and
contrast enhancements help deter-
b Contrast Enhancement
mine whether a correct diagnosis is
Blood-brain barrier disturbance
made based on MRI.
Vessels
b Effect on Environment CONCLUSION
Space occupying MRI produces images that represent
signal intensities of tissue that are
Not space occupying
dependent on relaxation time and spa-
Space giving
tial resolution. Pathologic structures are
Bone destruction identified by specific tissue behavior
Bone remodeling mainly related to different relaxation
b Growth Pattern times. Combined with knowledge of
clinical symptoms and signs, and recog-
Infiltrative
nition of suspected localization and
Multiplicity
etiology, careful assessment and inter-
Metastases pretation of MRI scans is an essential
diagnostic skill.

Introduction to MRI
FIGURE 1-13 Ganglioglioma with remodeling of the adjacent bone. A, Axial fluid-attenuated
inversion recovery (FLAIR) MRI; B, coronal T2-weighted fast spin echo sequence;
C, CT shows a tiny cortical partially calcified lesion with exophytic growth/bony
remodeling (A, B, C, arrows).
FIGURE 1-14 T2 lesions with relative hypointensity suggestive for highly cellular lesions such
as lymphoma (A, arrow), vestibular schwannoma, or, as in this case,
meningioma (B, arrow) and metastasis (C, arrow).
FIGURE 1-15 A 12-year-old girl with a teratoma in the pineal region. A clue to the diagnosis is
the mixture of fat and calcified elements on T2-weighted (A) and T1-weighted
(B) images. Fat is hyperintense on T1-weighted and T2-weighted images;
calcification may show different signal intensities. A complementary CT scan (C )
helps to differentiate fat as hypodense (blue arrow) and calcification as strongly
hyperdense (open arrow).

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2. McRobbie DW, Moore EA, Graves MJ,
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Prince MR. MRI from picture to proton.
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Review Article
Imaging of Ischemic
Dr David S. Liebeskind,
Neurovascular Imaging
Research Core, UCLA
Stroke Department of Neurology,

Neuroscience Research
Building, 635 Charles E.
Young Dr S, Suite 225,
Michelle P. Lin, MD, MPH; David S. Liebeskind, MD, FAAN Los Angeles, CA 90095,
davidliebeskind@yahoo.com.
Relationship Disclosure:
ABSTRACT Dr Lin reports no disclosure.
Dr Liebeskind has served as
Purpose of Review: This article provides an overview of cerebrovascular hemody- an associate editor of the
namics, acute stroke pathophysiology, and collateral circulation, which are pivotal in Journal of Neuroimaging
the modern imaging of ischemic stroke that guides the care of the patient with stroke. and as a consultant to the
imaging core laboratories
Recent Findings: Neuroimaging provides extensive information on the brain and of Medtronic and Stryker.
vascular health. Multimodal CT and MRI delineate the hemodynamics of ischemic Dr Liebeskind receives
stroke that may be used to guide treatment decisions and prognosticate regarding royalties from UpToDate, Inc,
and grant/research support
expected outcomes. Mismatch imaging with either CT or MRI may identify patients from the National Institutes
with salvageable regions who are at risk and likely to benefit from reperfusion therapy, of Health.
even if they are outside the standard time window. Imaging of collateral circulation and Unlabeled Use
of Products/Investigational
determination of collateral grade may predict greater reperfusion, lower hemorrhage Use Disclosure:
risk, and better functional outcome. Current neuroimaging technology also enables Drs Lin and Liebeskind report
the identification of patients at high risk of hemorrhagic transformation or those who no disclosures.
may be harmed by treatment or unlikely to benefit from it. * 2016 American Academy
of Neurology.
Summary: This article reviews the use and impact of imaging for the patient with
ischemic stroke, emphasizing how imaging builds upon clinical evaluation to establish
diagnosis or etiology, reveal key pathophysiology, and guide therapeutic decisions.
Continuum (Minneap Minn) 2016;22(5):1399–1423.
INTRODUCTION weighted imaging (DWI) with apparent

Advanced imaging technologies have diffusion coefficient (ADC) maps, gradi-
dramatically changed the approach to ent recalled echo (GRE), susceptibility-
ischemic stroke management. While the weighted imaging (SWI), fluid-attenuated
“time is brain” mantra has led to efficient inversion recovery (FLAIR), magnetic
stroke delivery on a system/population resonance angiography (MRA), and
level, modern neuroimaging provides perfusion-weighted MRI. As stroke is
rapid profiling of patient-specific tissue dynamic, any of these single imaging
viability, vessel status, and cerebral per- depictions reflects only a snapshot in
fusion that have further enhanced treat- time in the evolution of infarct growth.
ment decisions and stroke outcomes.1Y6 Combinations of these modalities and
Noninvasive multimodal CT and MRI the serial evaluation of disease course
enable prompt diagnosis, identify treat- provide real-time data to reflect the in-
able underlying causes of stroke, en- dividual patient course.
hance selection of candidates for No standardized imaging protocols
reperfusion therapy within or outside for acute stroke currently exist, other
of standard windows, and predict out- than joint statements from professional
comes. Multimodal CT includes CT societies.7,8 Nevertheless, the aim of
angiography (CTA) and CT perfusion, neuroimaging in acute stroke is to pro-
whereas multimodal MRI includes pa- vide rapid information on tissue and
renchymal sequences such as diffusion- vessels to enhance rational decisions

Ischemic Stroke
KEY POINTS
h Advanced neuroimaging for reperfusion therapy without causing clinicians to make more individualized
can provide real-time harm from delays. Such imaging pro- (rather than population-based) thera-
information on the state tocols are therefore dependent on peutic decisions. Key hemodynamic
of the brain parenchyma available resources, local experience, parameters are defined in Table 2-1.
and neurovasculature, and clinician preference. Without Arterial occlusion, as in ischemic stroke,
which may guide proper clinical context or adequate causes decreased cerebral blood flow
treatment outside of expertise, imaging may be misleading, and cerebral perfusion pressure. In
current time windows. introduce harm, and waste time and 1985, Powers and Raichle described
h Every image serves to resources, yet imaging often acceler- three stages of hemodynamic compro-
answer specific clinical ates clinical decision making. mise10; Figure 2-111 and Figure 2-212
questions to guide The following sections describe ce- show stage 1 compensatory cerebral
treatment decisions. rebrovascular hemodynamics, acute autoregulation that maintains constant
h Advances in stroke pathophysiology, and collateral cerebral blood flow via maximal dila-
neuroimaging in stroke circulation, which are pivotal in the mod- tion of small arteries and arterioles and
are built on the basis of ern imaging of ischemic stroke. Clinical recruitment of collaterals, producing
hemodynamics; and image-based patient selection for a compensatory increase in cerebral
accounting for these IV thrombosis and intraarterial thrombec- blood volume, thereby offsetting the
variables allows tomy and prognostication are discussed potential prolongation of time parame-
physicians to make more
in conjunction with case scenarios. ters such as mean transit time, time to
individualized (rather
peak, and time to maximum (Tmax).
than population-based)
PATHOPHYSIOLOGY OF ACUTE Mean transit time is defined as the aver-
therapeutic decisions.
ISCHEMIC STROKE age of the transit time of blood through
The 3- to 4.5-hour time window for IV a given brain region. The transit time
thrombolysis following onset of stroke of blood through the brain paren-
symptoms is derived from population chyma varies depending on the dis-
studies9 that do not account for the tance traveled between arterial inflow
marked variations in individual patients’ and venous outflow and is measured
parenchymal or vascular anatomy, path- in seconds. Tmax is the time to peak
ophysiology, and cerebral reserve, all of of the residue function, indicating a
which are important factors that influ- delay in contrast bolus arrival between
ence stroke outcome. Advances in mul- the arterial input function and the
timodal CT/MRI for stroke are founded tissue. A Tmax of 0 reflects normal
on the basis of hemodynamics and ac- blood supply in normal tissue without
count for how such variables enable delay. Conversely, a Tmax greater than
TABLE 2-1 Hemodynamic (Computed Tomography/Magnetic Resonance Perfusion) Parameters

in Cerebral Ischemic Infarct
Time Parameters
(MTT,a TTP, Tmax) Cerebral Blood Volumea Cerebral Blood Flowa
Ischemic penumbra Mildly increased Mildly increased or normal Mildly decreased
Infarct core Markedly increased Mildly decreased Markedly decreased
MTT = mean transit time; Tmax = time to maximum; TTP = time to peak.
a
Cerebral blood volume (CBV) is the total volume of blood in a given unit of brain volume (mL/100 g). Cerebral blood flow (CBF) is the
volume of blood moving through a given unit of brain volume per unit time (mL/100 g/min). Mean transit time (MTT) is the average
transit time of blood through a given brain region in seconds. The central volume principal is defined as CBF = CBV/MTT.

FIGURE 2-1 Schematic of cerebral autoregulation. Arterioles dilate or constrict in response to
changes in blood pressure and intracranial pressure to maintain a constant
cerebral blood flow.
Data from Lassen N, Physiol Rev.11 physrev.physiology.org/content/39/2/183.short.
0 is often associated with an acute tissue oxygenation decrease and, ulti-

ischemic lesion owing to arterial delay. mately, bioenergetic cell death.12
When mean transit time is increased, Symptom onset is only an approxi-
as in ischemic stroke, red blood cells mation of stroke onset from vessel oc-
spend a longer time within oxygen- clusion. Clinical symptoms are observed
permeable capillaries; this allows for an below a certain threshold of cerebral
increase in oxygen extraction from the blood flow. At very low cerebral blood
capillary network by the brain tissue. flow, cerebral infarction occurs within
In stage II, when maximal autoregu- minutes; at higher levels of cerebral
latory vasodilation is exhausted, oxygen blood flow, it may take hours before
extraction fraction (the percent of the infarction occurs because tissue viabil-
oxygen extracted from the blood by ity is dependent on the degree and the
tissue during its passage through the duration of cerebral blood flow, as dem-
capillary network) is increased to main- onstrated in Figure 2-3.13,14 Collateral
tain brain tissue oxygenation and me- flow is the intervening factor that deter-
tabolism necessary for cellular viability. mines how long the patient can be
In stage III, when the autoregulatory asymptomatic before stroke evolves
range of cerebral perfusion pressure after occlusion.4 The perfusion-diffusion
reduction is overwhelmed at the ische- mismatch model was based on these
mic core, it results in a decrease of ce- ischemic stages. Ischemic core refers
rebral blood volume and an ensuing to areas in which irreversible cell in-
decrease in cerebral blood flow until it jury has occurred. The ischemic pen-
crosses the threshold when collaterals umbra refers to tissue at risk of
fail, with venous collapse leading to infarction if reperfusion does not

Ischemic Stroke
KEY POINTS
h The ischemic
penumbra refers to
tissue at risk of
infarction if reperfusion
does not occur in a
timely manner. This
dysfunctional but
salvageable tissue has
been the target of all
reperfusion and
neuroprotection therapies.
h The cerebral collateral
circulation exists to
protect the brain
against ischemia and
sustain the penumbra.
FIGURE 2-2 Stroke pathophysiology. Illustration of the changes in cerebral variables during a
progressive decrease in cerebral perfusion pressure and progression through
various stages of impaired cerebral circulation. In stage I, cerebral autoregulation
enables vascular dilation and collateral recruitments, leading to increased cerebral blood volume
(CBV) to maintain cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2).
In stage II, oxygen extraction fraction (OEF) is increased to sustain CMRO2 with gradual decrease
in CBV and collateral failure. In stage III, OEF is exhausted and CMRO2 has declined, leading
to cell death and irreversible infarct. Cerebrovascular reserve (CVR) decreases progressively with
hemodynamic failure.
Modified with permission from Nemoto E, et al, Stroke.12 B 2002 American Heart Association, Inc.
stroke.ahajournals.org/content/34/1/2.short.
occur in a timely manner. This dys- the time course of ischemic injury, stroke
functional but salvageable tissue has severity, imaging findings, and thera-
been the target of all reperfusion and peutic opportunities.4,15 In ischemic
neuroprotection therapies. stroke, occlusion or stenosis of an arte-
rial segment impairs blood flow to the
COLLATERAL CIRCULATION downstream territory and increases fluid
HEMODYNAMICS AND ANATOMY shear stress; mechanical stimulation of
The cerebral collateral circulation exists the vessel wall causes cytokine release
to protect the brain against ischemia and vascular remodeling to dilate the
and sustain the penumbra. It is a dy- vessel, leading to recruitment of collat-
namic system that can preserve cerebral erals.5,16 All segments of the cerebral
blood flow to the brain when the pri- circulation, from arterial inflow routes
mary vessels fail. Collateral perfusion to the microcirculation and down-
varies across individuals and influences stream venous channels, are involved

in sustaining collateral perfusion,
whereas arterial anastomoses provide
alternative routes to rapidly shunt
flow around an arterial occlusion.17
Figure 2-4 shows principal sites of
compensatory collateral anastomoses:
(1) large artery communications be-
tween the extracranial and intracranial
circulations, (2) completeness of the
circle of Willis, and (3) leptomeningeal
anastomoses providing cortical surface
perfusion.16 In the setting of acute or
chronic occlusions, these connections
can supply sufficient blood flow to large
FIGURE 2-3 Schematic of ischemic thresholds. When
portions of the affected territory through local cerebral blood flow falls below
shunting and retrograde flow. Neverthe- 22 mL/100 g/min, reversible paralysis
(penumbra) occurs. Duration to irreversible infarct is
less, regardless of the robustness of col- dependent on local cerebral blood flow (arrows). Even
laterals on presentation, collaterals will profound ischemia is reversible for a brief time. Arrows
represent varied time intervals when penumbra becomes
eventually fail without prompt reperfusion. ischemic core as dependent on cerebral blood flow.
Modified with permission from Jones TH, et al, J Neurosurg.13
CLINICAL INDICATIONS FOR B 1981 American Association of Neurological Surgeons.
NEUROIMAGING IN ACUTE thejns.org/doi/abs/10.3171/jns.1981.54.6.0773.
ISCHEMIC STROKE
When ordering neuroimaging for acute the stroke ischemic or hemorrhagic?
stroke management, key questions to (2) What’s the size and location? (3)
always consider when deciding the op- What’s the cause of stroke? (4) Is
timal imaging to obtain include: (1) Is the patient a candidate for IV tissue
FIGURE 2-4 Schematic of the collateral circulations. A, Extracranial arterial collateral circulation. Shown are anastomoses
from the facial (1), maxillary (2), and middle meningeal (3) arteries to the ophthalmic artery and dural
arteriolar anastomoses from the middle meningeal artery (4) and occipital artery through the mastoid foramen
(5) and parietal foramen (6). Intracranial arterial collateral circulation in B, frontal and C, lateral views. Shown are the
posterior communicating artery (1), leptomeningeal anastomoses between anterior and middle cerebral arteries (2) and
between posterior and middle cerebral arteries (3), the tectal plexus between posterior cerebral and superior cerebellar
arteries (4), anastomoses of distal cerebellar arteries (5), and the anterior communicating artery (6).
Reprinted with permission from Liebeskind DS, Stroke.16 B 2003 American Heart Association, Inc. stroke.ahajournals.org/content/34/9/2279.long.

Ischemic Stroke
KEY POINT
h Collateral flow in plasminogen activator (tPA)? (these modalities for acute stroke evaluation
ischemic stroke is a could be answered with noncontrast are summarized in Table 2-2.
dynamic process and CT or MRI); (5) Is there a large vessel
will eventually fail if occlusion? (6) Is the patient a candi- PATIENT SELECTION FOR
timely reperfusion is date for intraarterial thrombectomy? INTRAVENOUS THROMBOLYSIS
not established. (these could be answered using CTA/ A targeted clinical assessment (history,
MRA or digital subtraction angiography neurologic examination, laboratory
[DSA]); (7) Is there an ischemic penum- values) remains the cornerstone (and
bra? (this could be assessed using CT initial step) of stroke evaluation and
or MR perfusion). selection for IV tPA. The National Insti-
Advantages and disadvantages of tutes of Health Stroke Scale (NIHSS)
various noninvasive neuroimaging score provides important information
TABLE 2-2 Advantages and Disadvantages of Noninvasive Neuroimaging Modalities

for Acute Stroke
Neuroimaging Modality Advantages Disadvantages

Parenchyma
Noncontrast CT Fast acquisition time, widely Limited sensitivity to infarct size,
available, sensitive to hemorrhage location of early ischemia
Diffusion-weighted MRI Sensitive to early ischemia, fast Lack of availability, patient
acquisition time, high conspicuity contraindications (eg, metals,
of lesion claustrophobia), long acquisition time
Vasculature
CT angiography Quantify vascular disease burden Potential renal toxicity, allergy to contrast
(eg, degree with stenosis, agents; radiation exposure; provides no
length of clot, characteristics of information on direction or velocity of flow
plaques), fast acquisition time
Magnetic No contrast Overestimates stenosis, sensitive to motion
resonance angiography and other technical artifacts, long
acquisition time, patient contraindications
(eg, metals, claustrophobia)
Ultrasound (carotid or Flow data, portable, low cost User dependent, time consuming,
transcranial Doppler) technical constraints
Tissue Perfusion
CT perfusion Fast acquisition time Potential renal toxicity, allergy to contrast
agents; radiation exposure; qualitative
Magnetic Good spatial resolution Qualitative; patient contraindications (eg,
resonance perfusion metals, claustrophobia), requires gadolinium
Positron emission Gold standard for cerebral blood Requires multiple radiotracers with very
tomography (PET) flow measures, provides quantitative short half-lives, thus impractical in acute
measures of physiologic parameters settings; low resolution, limited availability
(oxygen extraction fraction
and metabolism)
CT = computed tomography; MRI = magnetic resonance imaging.

about the severity of stroke and prog-
nosis and influences decisions about
acute treatment. Initial stroke imaging
can be done using either noncontrast
head CT or MRI to differentiate hem-
orrhagic (15%) from ischemic stroke
and determine the size (whether it is
more than one-third of the middle
cerebral artery [MCA] territory) and
location. The choice is based on the
available infrastructure and staff, as well
as the experience of the stroke team.
Imaging of the Ischemic Core

The ischemic core may be imaged using
noncontrast CT and various MRI se-
quences, including DWI, ADC mapping,
and FLAIR.
Computed tomography. Noncon-
trast CT is the most widely used first-
line imaging tool in patients with acute FIGURE 2-5 Alberta Stroke Program Early CT Score
(ASPECTS) scoring scheme. The upper row
stroke and is recommended as an ini- demonstrates axial CT cuts of the ganglionic
tial mode of imaging to assist in ASPECTS level (M1YM3, insula [I], lentiform nucleus [L],
making decisions for IV tPA.7 Acquisi- caudate nucleus [C], and posterior limb of the internal capsule
[IC]). The lower row demonstrates M4YM6.
tion of further imaging, such as MRI
Reprinted with permission from Puetz V, et al, Int J Stroke.18
or CTA, should not delay administra- B 2009 SAGE Publications. wso.sagepub.com/content/4/5/354.abstract.
tion of IV thrombolysis. Early ischemic
changes on noncontrast CT appear as
hypodensity (cytotoxic edema), loss ganglionic ASPECTS region (M4YM6). KEY POINT
of gray-white differentiation, cortical The caudate nucleus is assessed in both h Noncontrast CT is the
swelling, and loss of sulcation (efface- the ganglionic level (head of caudate) most widely used
ment of brain sulcus from tissue swell- and supraganglionic level (body and tail first-line imaging tool
ing). Ischemic changes in the anterior of caudate). To compute the ASPECTS, in patients with acute
circulation can be quantified topo- stroke and is
a single point is subtracted from 10 for
recommended as an
graphically with the Alberta Stroke evidence of early ischemic change in
initial mode of imaging
Program Early CT Score (ASPECTS), a each of the 10 ASPECTS regions. A to assist in making
simple 10-point pretreatment noncon- score of 10 reflects a normal CT scan; a decisions for IV tissue
trast CT score that divides the MCA score of 0 indicates diffuse ischemic in- plasminogen activator.
territory into 10 regions and identifies volvement throughout the complete MCA
patients with stroke who are unlikely to territory.19 Figure 2-6 demonstrates an
have good outcome from thrombolysis example of a malignant ischemic infarct
(Figure 2-518). Any ischemic lesion on (hypodense) of the entire left MCA ter-
axial CT cuts at the level of the caudate ritory with hemorrhagic conversion
head or below is adjudicated to a (hyperdense), corresponding to poor
ganglionic ASPECTS region (M1YM3, collaterals on angiography.
insula, caudate nucleus, lentiform nu- The use of noncontrast CT to de-
cleus, internal capsule); ischemic le- tect hemorrhage has the advantage
sions above the level of the caudate of fast acquisition and wide availabil-
head are adjudicated to a supra- ity (Table 2-2). However, noncontrast

Ischemic Stroke
minutes after ischemia).21 When com-

bined in various sequences (DWI/ADC/
FLAIR/GRE), MRI alone captures an
enormous amount of information on
stroke severity and chronicity. DWI mea-
sures the net movement of water in tis-
sue due to molecular motion and shows
hyperintense ischemic tissue changes
within minutes to a few hours after arte-
rial occlusion due to a reduction of the
ADC. The ADC reduction occurs primar-
ily in the intracellular space associated
with disruption of membrane ionic
homeostasis and cytotoxic edema.
In terms of clinical interpretation, an
increased signal on DWI (described as
hyperintense) followed by a decreased
ADC map represents irreversible ische-
mia, ie, an infarcted brain region; the
combination of DWI and ADC maps
with T2-weighted images allows acute
lesions to be distinguished from sub-
acute or older acute ischemic stroke
lesions. When a lesion is hyperintense
FIGURE 2-6 Collaterals and outcome. Poor collaterals in a case of left middle
cerebral artery occlusion (A) are followed by extensive ischemia on both DWI and the ADC map and
and hemorrhagic transformation (B) after recanalization with hypointense on the exponential im-
marginal reperfusion. In another case of left middle cerebral artery occlusion,
robust collaterals (C) are followed by complete recanalization (D) and age, the phenomenon is referred to as
good clinical outcome. T2 shine-through, which may be seen
Reprinted with permission from Liebeskind DS, et al, Stroke.15 B 2014 American Heart with late subacute infarcts or chronic
Association, Inc. stroke.ahajournals.org/content/45/7/2036.short. ischemic lesions.
The extent (size) and pattern of the
DWI lesion are important therapeutic
CT has a specificity of 56% to 100% and and prognostic biomarkers. Patients
poor sensitivity (20% to 75%) for de- with a smaller diffusion core (70 mL or
tecting early ischemic changes (within less) treated with IV/intraarterial throm-
a 6- to 8-hour window), particularly in bolysis have a significantly better out-
patients with posterior fossa ischemia.20 come than patients with a larger core.22
DWI is a better choice of imaging modal- The pattern of DWI lesion helps to iden-
ity to show early ischemic brain injury tify stroke etiology. For example, an
(within less than 6 hours from onset) isolated lenticulostriate lesion points
with sensitivity of 91% to 100% and to lacunar infarct. Multiple lesions in
specificity of 86% to 100%.21 different vascular territories suggest a
Magnetic resonance imaging. In the cardioembolic/aortoembolic source,
late 1980s, DWI and time-of-flight MRA whereas scattered lesions in one vas-
were transformative advancements in cular territory are associated with large
vascular neurology as they enabled artery atherosclerosis as demonstrated
rapid diagnosis of stroke and determi- in Figure 2-7.
nation of etiology to allow timely treat- Comparing the signal intensities on
ment (DWI signals appear within a few DWI, ADC, and FLAIR images can help

KEY POINTS
h Comparing the signal
intensities on
diffusion-weighted,
apparent diffusion
coefficient, and
fluid-attenuated
inversion recovery
images can help
distinguish acute,
subacute, and chronic
stroke. Positive signals
on diffusion-weighted
imaging without
FIGURE 2-7 Stroke mechanisms on diffusion-weighted MRI. Diffusion-weighted
imaging (DWI) lesion patterns in acute ischemic stroke, including isolated
corresponding
lenticulostriate infarction (A), bilateral middle cerebral artery lesions caused by fluid-attenuated
cardioembolism (B), and borderzone ischemia caused by right internal carotid artery inversion recovery
hypoperfusion (C).
hyperintensity imply
Reprinted with permission from Liebeskind DS, Ann Neurol.5 B 2009 American Neurological Association. that the stroke occurred
onlinelibrary.wiley.com/doi/10.1002/ana.21787/abstract.
less than 4.5 hours
before imaging.
distinguish acute, subacute, and chronic Vascular signs on parenchymal im- h Hyperdense middle
stroke (Figure 2-823). Positive signals aging. While noncontrast CT and MRI cerebral artery sign on
on DWI without corresponding FLAIR are paramount in imaging brain paren- noncontrast CT and
hyperintensity imply that the stroke chyma, a number of clinically relevant blooming artifact on
occurred less than 4.5 hours before vascular signs indicate vessel patency or gradient recalled echo
imaging (sensitivity of 62%, specificity suggestions of thrombus. For example, MRI may indicate red
of 78%).24 ADC values are reduced in the the hyperdense MCA sign on noncon- cellYpredominant
occlusive thrombus.
first 7 to 10 days, then pseudonormalize trast CT and blooming artifact on GRE
(the period in the evaluation of stroke MRI (Figure 2-1029) may indicate red
when ADC is normal), and finally in- cellYpredominant occlusive thrombus,
crease. 25 Figure 2-8 shows serial which may or may not be associated with
imaging across four time points, dem- a poor outcome.29 FLAIR sequences
onstrating the DWI, ADC, and FLAIR may show vascular hyperintensities
temporal signal changes. Given the tem- due to slow retrograde flow in the lep-
poral relationship of MRI sequences, tomeningeal vessels feeding the cortex
concurrent viewing of MRI sequences (Figure 2-11)30; these findings may be
may help select patients with an unclear an important clue to the presence of
“last known well time” or wake-up stroke a proximal arterial occlusion and good
for acute reperfusion treatment as dem- retrograde collateral flow, which is a
onstrated in Case 2-1. favorable prognostic indicator asso-
MRI is also helpful to rule out intra- ciated with smaller ischemic lesion
cranial hemorrhage and predict hemor- volume on MRI and milder clinical se-
rhagic transformation. GRE/SWI is more verity.31 Furthermore, high ASPECTS
sensitive than CT for the detection of on noncontrast CT in a known MCA
chronic hemorrhage, particularly chronic occlusion may be seen as a marker of
microbleeds.27 The extent of micro- robust collateral flow.32 Some patients
bleeds is a biomarker of the severity of with stroke with poor collateral flow
the underlying vascular disease and is exhibit extensive ischemic changes
associated with an increased risk of (low ASPECTS), whereas those with
spontaneous intracranial hemorrhage.28 more robust collaterals may reveal only

Ischemic Stroke
FIGURE 2-8 Serial multimodal MRI for ischemic infarct. Example of temporal changes in
diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC),
and fluid-attenuated inversion recovery (FLAIR) images along with admission
noncontrast CT for a 54-year-old man imaged serially with MRI at 2.9 hours, 2.4 days, 42 days,
and 111 days after onset. Admission National Institutes of Health Stroke Scale score was 1,
3-month modified Rankin Scale score was 2. Both DWI and ADC are readily abnormal by
admission, whereas FLAIR shows subtle signs of abnormality (arrowhead). Noncontrast CT appears
normal. Regions of ADC appear pseudonormal on the subacute scan, increasing by 1 month
(arrows). DWI appears hyperintense across all time points. FLAIR lesion volume appears largest at
2.4 days as a result of edema before stabilizing its infarct size at 42 days.
Reprinted with permission from Wu O, et al, Neuroimag Clin N Am.23 B 2011 Elsevier, Inc. www.sciencedirect.com/
science/article/pii/S1052514911000220.
Case 2-1
A 71-year-old woman woke up with mild aphasia and right hemiparesis, with a National Institutes
of Health Stroke Scale score of 7. Noncontrast CT showed old lacunes, but no hemorrhage.
Diffusion-weighted images and apparent diffusion coefficient map showed subtle new left centrum
semiovale diffusion changes without corresponding fluid-attenuated inversion recovery (FLAIR)
signals (Figure 2-926). Vessel imaging with time-of-flight magnetic resonance angiography (MRA)
showed occlusion of the left middle cerebral artery (Figure 2-9). Perfusion maps showed relatively
preserved cerebral blood flow and cerebral blood volume but marked prolongation of transit times
(mean transit time and time to maximum [Tmax]), suggesting a target mismatch pattern (Figure 2-9).
Given the large mismatch pattern and proximal M1 occlusion, the patient underwent intraarterial
thrombectomy and achieved thrombolysis in cerebral infarction (TICI) 2b status reperfusion
(near-complete to complete recanalization). She recovered rapidly postprocedurally with a modified
Rankin Scale score of 1 at 2-year follow-up.
Continued on page 1409

Continued from page 1408
FIGURE 2-9 Imaging of the patient in Case 2-1, who was selected for late reperfusion. Diffusion-weighted
imaging/apparent diffusion coefficient (DWI/ADC) shows new left centrum semiovale
diffusion changes without corresponding fluid-attenuated inversion recovery (FLAIR) signals.
Red arrow points to DWI lesion; blue arrow points to the corresponding ADC hypointensity. Time-of-flight
magnetic resonance angiography (TOF MRA) shows occlusion of left middle cerebral artery (yellow arrow).
Perfusion maps show relatively preserved cerebral blood flow (CBF) and cerebral blood volume (CBV), but
marked prolongation of transit times (MTT and Tmax), suggesting a target mismatch pattern.
3-D = three-dimensional; FMT = first moment transit time; MTT = mean transit time; Tmax = time to maximum.
Reprinted with permission from Rowley HA, Stroke.26 B 2013 American Heart Association, Inc. stroke.ahajournals.org/content/44/
6_suppl_1/S53.full.
Comment. Multimodal CT/MRI can help identify a favorable target mismatch profile in patients with
an unclear last known well time (eg, wake-up stroke) and help make the decision to extend acute
reperfusion treatment beyond the standard window of 3 to 4.5 hours.
Case modified with permission from Rowley HA, Stroke.26 B 2013 American Heart Association, Inc. stroke.ahajournals.org/content/44/6_suppl_1/S53.full.
marginal changes or no change (high hemorrhagic transformation.33 DWI/

ASPECTS).32 perfusion-weighted MRI and CT perfu-
sion are imaging modalities commonly
Imaging of Penumbral Tissue and used to rapidly identify patients with
Diffusion-Perfusion Mismatch stroke with persistent penumbra
Perfusion imaging gives a snapshot thought to be optimal candidates for
of stroke pathophysiology. It esti- reperfusion therapies.7 Table 2-1 de-
mates the relative volumes of penum- fines key perfusion-diffusion para-
bral regions that may be salvaged with meters and their trends. While no
timely reperfusion therapy and of standardized perfusion parameter cur-
infarcted core that cannot be sal- rently exists, a Tmax longer than 6 sec-
vaged and conveys a higher risk of onds is a commonly used threshold

Ischemic Stroke
reversal of a penumbra correlate with

improved clinical outcomes.
The target mismatch profile (small
DWI lesion volume, large perfusion-
weighted MRI lesion volume) and the
malignant profile (large DWI lesion
volume, large perfusion-weighted
MRI lesion volume), as defined by
the Diffusion and Perfusion Imaging
Evaluation for Understanding Stroke
Evolution (DEFUSE) study, are key
patterns to look for when reviewing
FIGURE 2-10 Hyperdense middle cerebral artery sign and blooming perfusion imaging to identify optimal
artifact. A, Noncontrast head CT showing a right candidates for later thrombolysis with-
hyperdense middle cerebral artery (red arrow). B,
Gradient recalled echo (GRE) MRI demonstrates blooming artifact (white out causing additional harm.35 Target
arrow) in left middle cerebral artery. Both signs suggest thrombosis. mismatch is associated with good out-
Reprinted with permission from Liebeskind DS et al, Stroke.29 B 2011 American come; a malignant mismatch profile is
Heart Association, Inc. stroke.ahajournals.org/content/42/5/1237.short.
associated with severe intracranial
hemorrhage and poor outcome after
reperfusion.35 Figure 2-12 shows im-
KEY POINT that identifies ischemic tissue that portant mismatch patterns.
h Diffusion-weighted is likely to be irreversibly injured
imaging/perfusion- PATIENT SELECTION FOR
if reperfusion does not occur.34 A
weighted MRI and CT INTRAARTERIAL THROMBECTOMY
mismatch is considered significant if
perfusion are imaging
the penumbra is at least 20% of the Clinically, after the question of whether
modalities commonly
used to rapidly identify ischemic core volume.34 In general, hemorrhage exists has been estab-
patients with stroke both the presence of a penumbra and lished and tPA has been administered,
with persistent
penumbra thought
to be optimal
candidates for
reperfusion therapies.
FIGURE 2-11 Fluid-attenuated inversion recovery (FLAIR)

vascular hyperdensity. FLAIR image of M2
segmental occlusion of the middle cerebral
artery demonstrates vascular hyperintensity immediately
proximal to the occlusion (A, arrow) caused by slow flow
and serpiginous vascular hyperintensity distal to the
occlusion (B, arrow) from slow retrograde collateral flow.
Reprinted with permission from Liebeskind DS, Ann Neurol.5 B 2009
American Neurological Association. onlinelibrary.wiley.com/doi/10.1002/
ana.21787/abstract.

FIGURE 2-12 Mismatch profiles. Baseline and follow-up diffusion-weighted imaging (DWI), perfusion-weighted MRI, and magnetic
resonance angiography (MRA) scans for patients with different MRI profiles. Arrows point to the occlusion on MRA.
Lesion volumes represent the total lesion volume (volumes from each brain slice are summed). The colored scale
on the perfusion-weighted MRI maps indicates the degree of delay (in seconds) of gadolinium arrival relative to the arrival of
the arterial input. Color within the ventricles on the perfusion-weighted MRI maps is an artifact and is not included in the
perfusion-weighted MRI volume. At 30 days, the mismatch profile patient had a modified Rankin Scale score of 2 and National
Institutes of Health Stroke Scale score of 2; the malignant profile patient died from intracranial hemorrhage on hospital day 3.
MCA = middle cerebral artery; NIHSS = National Institutes of Health Stroke Scale; PWI = perfusion-weighted MRI; tPA = tissue
plasminogen activator.
Modified with permission from Albers GW, et al, Ann Neurol.35 B 2006 American Neurological Association. onlinelibrary.wiley.com/doi/10.1002/ana.20976/abstract.

Ischemic Stroke
KEY POINT
h A malignant the next step is to evaluate whether the Many comprehensive stroke centers
mismatch profile is patient may qualify for intraarterial with streamlined endovascular exper-
associated with severe thrombectomy for large vessel occlu- tise consider endovascular therapy up
intracranial hemorrhage sive stroke. Clinical inclusion criteria to 12 hours after onset of symptoms
and poor outcome for endovascular therapy for acute for anterior circulation stroke and up to
after reperfusion. stroke are mainly extrapolated from 24 hours for posterior circulation
successful thrombectomy trials and stroke. Ongoing randomized clinical
operator experience. The 2015 update trials (A Phase IIa Safety Study of In-
of the American Heart Association/ travenous Thrombolysis With Alteplase
American Stroke Association guideline, in MRI-Selected Patients [MR WITNESS],
published after the five positive DWI or CTP Assessment With Clinical
endovascular randomized clinical trials Mismatch in the Triage of Wake-Up
(Multicenter Randomized Clinical Trial and Late Presenting Strokes Under-
of Endovascular Treatment for Acute going Neurointervention [DAWN], and
Ischemic Stroke in the Netherlands DEFUSE 3) are evaluating the feasibil-
ity of image-based patient selection
[MR CLEAN],36 Endovascular Treat-
for extended therapeutic windows.
ment for Small Core and Anterior Cir-
Key exclusion criteria commonly used
culation Proximal Occlusion With
in prior endovascular trials were rapidly
Emphasis on Minimizing CT to Recan-
improving NIHSS score of less than 4,
alization Times [ESCAPE],37 Extending
glucose lower than 50 mg/dL or higher
the Time for Thrombolysis in Emergency than 400 mg/dL, systolic blood pres-
Neurological DeficitsYIntra-Arterial sure higher than 185 mm Hg, diastolic
[EXTEND-IA], 38 Solitaire With the blood pressure higher than 110 mm Hg,
Intention for Thrombectomy as PRIMary international normalized ratio (INR)
Endovascular Treatment [SWIFT
higher than 3, platelet count less than
PRIME],39 Randomized Trial of Revas-
cularization With Solitaire FR Device 50,000 cells/6L, intracranial hemor-
Versus Best Medical Therapy in the rhage, or ischemic stroke within the
Treatment of Acute Stroke Due to past 3 months.
Anterior Circulation Large Vessel Oc- Society joint statements recom-
clusion Presenting Within 8 Hours of mend three major vascular imaging strat-
Symptom Onset [REVASCAT]40) in- egies7: (1) noncontrast CT with CTA with
cludes recommendations of patients or without CT perfusion, (2) noncon-
who should receive endovascular in- trast CT with DSA, and (3) MRI (DWI,
terventions: those who are 18 years of FLAIR, GRE/SWI with or without
age or older; have a baseline modified perfusion-weighted MRI and arterial
Rankin Scale score of 1 or less, an spin labeling) with or without MRA. Of
NIHSS score of 6 or more, internal the three options, noncontrast CT with
carotid artery or M1 occlusion and re-
CTA with or without CT perfusion from
ceived tPA, and an ASPECTS of 6
aortic arch to vertex is a favored strategy
or higher; and start treatment within
for selecting intraarterial thrombec-
6 hours of symptom onset (Class I;
Level of Evidence A).8 Furthermore, tomy candidates as CT is fast and
those who had contraindications to IV widely available. 41
thrombolysis, such as those on anti-
coagulation, or who showed no im- Imaging of Occlusion
provement after tPA or early clinical Identification of an occluded large
deterioration after tPA from early re- vessel provides additional therapeutic
currence of stroke should be consid- and prognostic information. Vari-
ered for intraarterial thrombectomy. ous noninvasive vascular imaging

KEY POINTS
modalities are compared in Table 2-2. collateral grading scales exist, the h When combined with
CTA is the most widely used nonin- most commonly used is the one pro- CT perfusion, CT
vasive test for identifying major intra- posed by the American Society of angiography can rapidly
cranial vessel occlusion with 98.4% Interventional and Therapeutic Neu- generate quantitative
sensitivity, 98.1% specificity, and 98.2% roradiology (ASITN) and the Society and qualitative
accuracy, with high interobserver reli- of Interventional Radiology (SIR). The parameters that enable
ability for large vessel occlusions when ASITN/SIR collateral grading system is discrimination between
compared with DSA.42,43 CT-based a 5-point scale (0 = worst, 4 = best). normal tissue,
techniques provide a more accessible The grades are defined and corre- penumbra, and
and expedient assessment for grading infarcted core.
sponding angiographic findings de-
collateral flow in the acute setting than scribed in Figure 2-13.49 h In the absence of
conventional angiography. In particu- Many noninvasive ways to image recanalization, collateral
lar, when combined with CT perfusion, collaterals exist.17 Traditional static blood flow is the
CTA can rapidly generate quantitative determinant of
CTA and MRA are limited in their abil-
penumbral survival.
and qualitative parameters that enable ity to assess collateral flow as the
discrimination between normal tissue, image attainment is delayed, with h High collateral
penumbra, and infarcted core.44 How- grade predicts greater
relatively low flow leading to under-
ever, CTA and CT perfusion are limited reperfusion, better
estimation of collateral quality.
functional outcome,
by radiation and contrast. Time-of- Multiphase CTA and arterial spin la- and lower
flight MRA is another widely used beling MRA are newer dynamic imag- hemorrhage risk.
noninvasive vessel imaging technique ing acquisitions that allow dynamic
without radiation or contrast (sensitiv- h Low Alberta
assessments of flow comparable to
Stroke Program Early
ity 84% to 87%, specificity 85% to 98%).43 conventional DSA.47,50 Multiphase CTA CT Score (ASPECTS)
It is limited by flow artifact, which may has been tested for its clinical utility correlates with low
result in overestimation of vessel steno- in the ESCAPE study with good inter- collateral grades.
sis, and motion artifacts as some pa- rater reliability.37,51
h Standardized perfusion
tients with stroke may not be able to Furthermore, with noncontrast CT, methods and thresholds
follow commands. a low ASPECTS correlates with low are needed to reliably
collateral grades, as described in the determine the core and
Imaging of Collaterals
Solitaire With the Intention for penumbra and facilitate
In the absence of recanalization, col-
Thrombectomy (SWIFT)46 and Inter- the clinical use and
lateral blood flow is the determinant of dissemination of
ventional Management of Stroke III
penumbral survival. Good collaterals these techniques.
(IMSIII) trials.4,45 FLAIR sequences re-
are associated with greater reperfu-
veal slow reverse collateral flow in
sion, better median NIHSS score at
day 7, and better modified Rankin arterial segments beyond an occlusion,
Scale score at day 90. Conversely, poor which is a reliable marker for the pres-
collaterals are associated with symp- ence of collateral flow (Figure 2-11).30
tomatic hemorrhage.45Y47 Recanalization and reperfusion
The gold standard of imaging of col- clearly influence stroke outcome.36Y40
lateral circulation is conventional DSA Thrombolysis in cerebral infarction (TICI)
because of the complex configuration is a commonly used angiographic score
and often diminutive caliber of collat- for revascularization/reperfusion in
eral vessels. However, its applicability neurointervention for acute ischemic
is limited by its invasive nature, rela- stroke.49 Figure 2-1452 describes the
tively long acquisition and procedural angiographic findings of TICI scores.
times, and low accessibility; thus, it is Case 2-2 demonstrates image-based
not practical as the first-line imaging patient selection for intraarterial
study for general use.48 While many thrombectomy and outcomes.

Ischemic Stroke
FIGURE 2-13 American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology
collateral grade on pretreatment angiography. Grade 0 or no collaterals in right middle cerebral artery
(MCA) occlusion, marginal grade 1 collaterals in left MCA occlusion, grade 2 or partial collaterals in left
MCA occlusion, grade 3 or slow but complete collaterals in right MCA occlusion, and grade 4 or rapid and complete
collaterals in right MCA occlusion.
Modified with permission from Liebeskind DS, et al, Stroke.15 B 2014 American Heart Association, Inc. stroke.ahajournals.org/content/
45/7/2036.short.
FIGURE 2-14 Examples of the thrombolysis in cerebral infarction (TICI) score in a case of proximal MCA occlusion.
TICI 0 shows no recanalization/reperfusion of the primary occluded vessel (arrow). TICI 1 shows partial
reperfusion beyond the initial occlusion but no filling of distal middle cerebral artery branches. TICI 2a
and TICI 2b correspond to partial (less than 50%) and near-complete (more than 50% but less than full) reperfusion
beyond the occlusion site, respectively. TICI 3 indicates complete reperfusion of the entire middle cerebral
artery territory.
Reprinted with permission from Mokin M, et al, Neurosurg Focus.52 B 2014 American Association of Neurological Surgeons. thejns.org/doi/full/
10.3171/2013.10.FOCUS13374.

Case 2-2
A 76-year-old man with atrial fibrillation who was on warfarin presented at 6:30 PM with acute-onset
right-sided hemiparesis and aphasia with a last-known well time of 5:00 PM. He had an initial National
Institutes of Health Stroke Scale score of 12 and an international normalized ratio (INR) of 1.2.
Noncontrast CT showed no hemorrhage and was positive for a hyperdense middle cerebral artery sign,
and his Alberta Stroke Program Early CT Score was 10. IV tissue plasminogen activator was started, and he
was transferred to a nearby comprehensive stroke center. Upon arrival, CT angiography and CT perfusion
were performed (Figure 2-15), which showed a region of reduced cerebral blood flow (42 mL) and a
region supplied by collateral hypoperfusion (time to maximum [Tmax] more than 6 seconds) of 149 mL.
Initial cerebral angiography showed a left proximal middle cerebral artery occlusion with robust grade 4
collateral filling. A stent was used with two passes; recanalization (thrombolysis in cerebral infarction
[TICI] 2b status) was achieved in 55 minutes. A follow-up MRI brain at 24 hours showed a striatocapsular
diffusion lesion and complete reperfusion on Tmax. The patient had no residual deficits at 90 days.
FIGURE 2-15 Imaging of the patient in Case 2-2 who was selected for intraarterial thrombectomy. CT perfusion of
proximal left middle cerebral artery occlusion using RAPID software. CT perfusion demonstrates a small
ischemic core in the striatocapsular region as reduced cerebral blood flow with automated
segmentation of ischemic core (magenta, relative cerebral blood flow less than 30% of normal brain) (A). The area
supplied by collaterals is indicated by a large time to maximum (Tmax) perfusion lesion with automated segmentation of
tissue at risk (green, Tmax greater than 6 seconds) (B). Recanalization was achieved. Follow-up imaging at 24 hours
indicates a striatocapsular diffusion lesion (C ) and complete reperfusion on Tmax (D).
Reprinted with permission from Menon BK, et al, Stroke.51 B 2015 American Heart Association, Inc. stroke.ahajournals.org/content/46/6/1453.full.
Comment. The case illustrates the acute management of large vessel occlusion stroke in the
‘‘drip-and-ship’’ system of care and clinical and image-based selection for IV tissue plasminogen
activator and intraarterial thrombectomy. The patient had a relatively mild clinical deficit because of
robust collaterals. Collateral status at the time of arterial occlusion in acute ischemic stroke has a
profound effect on stroke severity, infarct volume, recanalization, and functional outcome.
Case modified with permission from Menon BK, et al, Stroke.51 B 2015 American Heart Association, Inc. stroke.ahajournals.org/content/
46/6/1453.full.

Ischemic Stroke
COMPARISON OF IMAGE-BASED based selection criteria building on

SELECTION CRITERIA IN RECENT prior trials and clinical experience
ENDOVASCULAR TRIALS showed benefit of endovascular treat-
In 2014Y2015, five randomized clini- ment of stroke when patients were
cal trials (MR CLEAN,36 ESCAPE,37 carefully selected and treated in a
EXTEND-IA,38 SWIFT PRIME,39 and timely manner. Details of these trials
REVASCAT40) using various image- are listed in Table 2-3. Key similarities
TABLE 2-3 Summary of Image-based Patient Selection Across 2014–2015 Intraarterial

Thrombectomy Trials for Acute Ischemic Stroke Secondary to Large
Vessel Occlusion
Time Window
Number of (Symptom Onset
Study Title Country; Year Patients Enrolled to Groin Puncture)
Multicenter Randomized Clinical Trial Netherlands; N = 500 6 hours
of Endovascular Treatment for Acute 2010Y2014
Ischemic Stroke in the Netherlands
(MR CLEAN)36
Endovascular Treatment for Small Canada, United N = 316 12 hours
Core and Anterior Circulation States, South Korea,
Proximal Occlusion With Emphasis on Ireland,
Minimizing CT to Recanalization United Kingdom;
Times (ESCAPE)37 2013Y2014
Extending the Time for Thrombolysis Australia, N = 70 6 hours (90 minutes
in Emergency Neurological New Zealand; from image to
DeficitsYIntra-Arterial (EXTEND IA)38 2012Y2014 groin puncture)
Solitaire With the Intention for United States; N = 197 6 hours (90 minutes
Thrombectomy as Primary Endovascular 2012Y2014 from image to
Treatment Trial (SWIFT PRIME)39 groin puncture)
Randomized Trial of Revascularization Spain; 2012Y2014 N = 206 8 hours

With Solitaire FR Device Versus Best
Medical Therapy in the Treatment of
Acute Stroke Due to Anterior Circulation
Large Vessel Occlusion Presenting Within
8 Hours of Symptom Onset (REVASCAT)40
ASPECTS = Alberta Stroke Program Early CT Score; CT = computed tomography; CTA = computed tomography angiography;
DSA = digital subtraction angiography; DWI = diffusion-weighted imaging; MR = magnetic resonance; MRA = magnetic resonance
angiography; NCT = noncontrast computed tomography; rCBF = relative cerebral blood flow; TICI = thrombolysis in cerebral infarction (score);
Tmax = time to maximum.
a
Imaging entry criteria were revised midway through the study. After imaging entry criteria revision, sites could enroll based on ASPECTS
findings only but were still encouraged to obtain perfusion imaging and use this information if available. A total of 71 patients were
enrolled under the initial imaging entry criteria and 125 patients under the revised imaging entry criteria.

were the confirmation of a proximal highest odds of good functional out-
occlusion (mostly with CTA) and use come used CT/magnetic resonance (MR)
of a newer generation of stent retriever. perfusion to select patients with both a
Four of the trials (all except for MR small core in farct and large penumbral
CLEAN) used imaging to exclude pa- tissue (EXTEND-IA, SWIFT PRIME) or the
tients with a large ischemic core or poor presence of moderate to good collat-
collateral grades.41 The trials with the eral circulation (ESCAPE). Key differences
Minutes to
Parenchymal Vascular Recanalization Reperfusion Reperfusion at
Imaging Selection Imaging Selection (TICI 2b/3) (Range) 24 Hours
NCT CTA/MRA/DSA 58.7% 332 (279Y394) 75.4%
versus 32.9%
NCT (ASPECTS Q6) Multiphase CTA 72.4% Not reported Not reported
(collateral filling of
Q50% of middle
cerebral artery-pia)
CT/MR diffusion-perfusion; Tmax CTA/MRA 86.0% 248 (204Y277) 89% versus 34%
96-second delay perfusion volume
and rCBF or DWI for ischemic core
(using RAPID software); included
mismatch ratio 91.2, absolute mismatch
volume 910 mL, ischemic core G70 mL
NCT (ASPECTS Q7) CT/MR CTA/MRA 88.0% Not reported Reperfusion at
diffusion-perfusion; Tmax 27 hours; 83%
910-second delay perfusion volume versus 40%
and rCBF or DWI for ischemic core
(RAPID)a; Included mismatch ratio
91.8, absolute mismatch volume
Q15 mL, ischemic core e50 mL
NCT (ASPECTS Q7) CTA/MRA 66.0% 355 (269Y430) Not reported

Ischemic Stroke
were the choice of imaging modali- down positioning despite persisting

ties and ischemic-penumbral thresh- proximal arterial occlusion. Use of ad-
olds. Multiphase CTA and ASPECTS vanced imaging for early diagnosis and
were used to exclude patients with treatment of acute ischemic stroke also
poor collaterals and large ischemic facilitates prognostication, rehabilita-
core in ESCAPE. CT/MR perfusion and tion planning, and early secondary
an automated postprocessing protocol stroke prevention.
with a priori thresholds to determine
ischemic core and penumbra were IMAGING OF MINOR STROKE AND
used in EXTEND-IA and SWIFT PRIME. TRANSIENT ISCHEMIC ATTACK
However, debate remains over the pre- The ABCD2 (age, blood pressure, clin-
cise CT perfusion thresholds for pa- ical features, duration, presence of
tient selection.53 Clearly, standardized diabetes mellitus) clinical risk predic-
perfusion methods and thresholds are tion score is commonly used to triage
needed to reliably determine the core patients with suspected transient ische-
and penumbra to facilitate clinical use mic attack (TIA) for hospital admission
and dissemination of these techniques. (threshold at 4 or higher) versus outpa-
tient follow-up within 7 days; however,
IMAGING OF POST-REPERFUSION studies have called into question its
MANAGEMENT ability to reliably stratify patients at
high risk for stroke.55 A meta-analysis
Post-reperfusion therapy care is essen-
tial because approximately 25% of pa- involving 13,766 TIA admissions re-
tients may have neurologic worsening vealed that ABCD2 score did not reli-
during the first 24 to 48 hours after ably determine those at low versus high
stroke and it is difficult to predict which risk of early recurrent stroke: 20% of
patients will deteriorate.54 A dedicated patients with an ABCD2 score of less
stroke unit with nursing expertise is than 4 had more than 50% carotid
pivotal in the management of patients stenosis or atrial fibrillation, and 35%
with acute stroke. Key components of to 41% of TIA mimics had an ABCD2
medical therapy for acute stroke beyond score of 4 or more.55 Perhaps incor-
thrombolysis include blood pressure porating an imaging screen, such as
modulation, antiplatelet and statins, perfusion imaging, may improve its
cardiac monitoring, respiratory support, predictive power.
normothermia, and normoglycemia.8,54 Furthermore, patients with rapidly
The dynamic nature of ischemic stroke improving symptoms or who have low
and response to reperfusion can be cap- NIHSS scores often are excluded from
tured by serial multimodal CT/MRI, com- acute reperfusion therapy; however,
paring the change in ischemic lesion almost one-third of cases will go on to
patterns from baseline over ensuing days sustain substantial disability.56 Perfu-
and weeks. Clinical response to reperfusion imaging (perfusion-weighted MRI
sion can sometimes be difficult to cap- or CT perfusion) can identify this sub-
ture. Early neurologic deterioration group of patients with high-risk minor
maybe due to tPA failure, recurrent strokes or unstable TIA who are likely
stroke, or hemorrhagic transformation. to decline because of asymptomatic
Conversely, rapidly improved symp- vascular stenosis who may benefit from
toms may not be from successful higher-intensity treatment.57 Case 2-3
recanalization but rather due to im- demonstrates the utility of multimodal
proved cerebral perfusion from head- MR for unstable TIA.

Case 2-3
An 82-year-old man with hypertension presented with two episodes of
aphasia, each lasting 30 minutes. His initial National Institutes of Health
Stroke Scale (NIHSS) score was 0, and his ABCD2 score was 4. Diffusion-weighted
imaging (DWI) showed no evidence of acute infarction (Figure 2-16A58);
perfusion-weighted MRI showed hypoperfusion on the time-to-peak map
(Figure 2-16B) in the entire left middle cerebral artery territory (arrows). On
hospital day 2, he was noted to have sudden-onset right hemiplegia and
aphasia, with an NIHSS score of 18, as observed by his neurointensive care
unit nurse, with clear time of onset at 6:00 AM. His head position was
flattened, and he was given 2 L of 0.9% normal saline with improved
symptoms to an NIHSS score of 12. He was given IV tissue plasminogen
activator and underwent intraarterial thrombectomy with marked clinical
improvement and a postprocedural NIHSS score of 0. He was discharged
home with dual antiplatelet therapy, atorvastatin, and amlodipine.
FIGURE 2-16 Identifying high-risk transient ischemic attack using multimodal MRI
in the patient in Case 2-3. A, Diffusion-weighted imaging (DWI)
showing no evidence of acute infarction. B, Perfusion-weighted MRI
showing significant hypoperfusion on the time to peak map of the entire left
middle cerebral artery territory (arrows).
Reprinted with permission from Sorensen AG, Ay K, Neuroimag Clin N Am.58 B 2011, Elsevier.
www.sciencedirect.com/science/article/pii/S1052514911000141.
Comment. This patient’s clinical symptoms were consistent with transient

ischemic attack. DWI has limited sensitivity (90%) for very small infarcts,
particularly in the brainstem. In addition, a short episode of ischemia that is
not severe enough to cause permanent tissue injury may cause symptoms in
the absence of lesions detected by DWI. The combined use of DWI and
perfusion-weighted MRI may improve the sensitivity for detection of tissue
ischemia and, more important, ‘‘tissue at risk’’ penumbra that calls for prompt
workup of the transient ischemic attack to offer patients appropriate intensity
of treatment as in this patient. The diagnostic utility of perfusion-weighted
MRI remains to be confirmed in large prospective studies.
Case modified with permission from Sorensen AG, Ay H, Neuroimaging Clin N Am.58 B 2011 Elsevier.

Ischemic Stroke
CONCLUSION 6. Liebeskind DS, Alexandrov AV. Advanced

multimodal CT/MRI approaches to hyperacute
Neuroimaging provides extensive in- stroke diagnosis, treatment, and monitoring.
formation on the brain and vascular Ann N Y Acad Sci 2012;1268:1Y7. doi:10.1111/
health. Every image serves to answer j.1749-6632.2012.06719.x.
specific clinical questions that en- 7. Wintermark M, Sanelli PC, Albers GW, et al.
Imaging recommendations for acute stroke
hance treatment decisions, building
and transient ischemic attack patients: a joint
upon the clinical evaluation. Factors statement by the American Society of
such as patient age, premorbid status, Neuroradiology, the American College of
the patient’s wishes and expectations Radiology and the Society of NeuroInterventional
of good outcome, and time from onset Surgery. J Am Coll Radiol 2013;10(11):828Y832.
doi:10.1016/j.jacr.2013.06.019.
remain important. Use of advanced
neuroimaging technologies in routine 8. Powers WJ, Derdeyn CP, Biller J, et al. 2015
American Heart Association/American Stroke
care of the patient with ischemic stroke Association focused update of the 2013
will accelerate translational research in guidelines for the early management of
the field, train a new generation of patients with acute ischemic stroke regarding
clinical neuroimagers, and, most impor- endovascular treatment: a guideline for
healthcare professionals from the American
tant, optimize patient outcomes. With
Heart Association/American Stroke Association.
recent overwhelming evidence sup- Stroke 2015;46(10):3020Y3035. doi:10.1161/
porting image-based patient selection STR.0000000000000074.
for acute reperfusion therapy to opti- 9. Lees KR, Bluhmki E, von Kummer R, et al.
mize stroke outcome and avoid harm, Time to treatment with intravenous
a need for standardization and auto- alteplase and outcome in stroke: an
updated pooled analysis of ECASS, ATLANTIS,
mation of perfusion imaging para-
NINDS, and EPITHET trials. Lancet
meters to facilitate dissemination of 2010;375(9727):1695Y1703. doi:10.1016/
the technology clearly exists. S0140-6736(10)60491-6.
10. Powers WJ, Raichle ME. Positron emission
ACKNOWLEDGMENTS tomography and its application to the study
Dr Liebeskind receives grant support of cerebrovascular disease in man. Stroke
from the National Institutes of Health/ 1985;16(3):361Y376. doi:10.1161/
01.STR.16.3.361.
National Institute of Neurological Dis-
orders and Stroke (K24NS07227). 11. Lassen NA. Cerebral blood flow and oxygen
uptake. Physiol Rev. 1959;39(2):183Y238.
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Review Article
Imaging of
Dr Ryan Hakimi, University of
South Carolina-Greenville,
Greenville Health System
Neuroscience Associates, 200
Patewood Dr, #350,
Greenville, SC 29615,
Hemorrhagic Stroke
hakimiry1@gmail.com.
Ryan Hakimi, DO, MS; Ankur Garg, MD
Dr Hakimi has served on the
board of directors and annual
program committee of the ABSTRACT
American Society of
Neuroimaging, on the Purpose of Review: Hemorrhagic stroke comprises approximately 15% to 20%
editorial boards of the of all strokes. This article provides readers with an understanding of the indications
International Journal of and significance of various neuroimaging techniques available for patients presenting
Neurology and Neurotherapy
and the International Journal with hemorrhagic strokes of distinct causes.
of Neural Science and Brain Recent Findings: The most common initial neuroimaging study is a noncontrast
Research, and on the annual head CT, which allows for the identification of hemorrhage. Once an intracranial hem-
program committee and as
cochair of the fundraising orrhage has been identified, the pattern of blood and the patient’s medical history,
committee of the Neurocritical neurologic examination, and laboratory studies lead the practitioner to pursue further
Care Society. Dr Garg serves on neuroimaging studies to guide the medical, surgical, and interventional management.
the membership committee of
the Society of Vascular and Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses,
Interventional Neurology. the subsequent neuroimaging pathway necessary to better evaluate and care for these
Unlabeled Use of patients is variable based on the etiology.
Products/Investigational
Use Disclosure:
With an increasing incidence and prevalence of atrial fibrillation associated with the
Drs Hakimi and Garg report aging population and the introduction of three new direct factor Xa inhibitors and one
no disclosures. direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use
* 2016 American Academy continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold
of Neurology.
increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an
ICH associated with oral anticoagulant use have a higher mortality rate than those with
primary ICH. Despite the reduced incidence of hypertension-related ICH over the past
decade, it is expected that the incidence of ICH will continue to increase.
Summary: Neuroimaging studies are integral to the identification of hemorrhagic
stroke, determination of the underlying etiology, prevention of hematoma expansion,
treatment of acute complications, and treatment of the underlying etiology, if indicated.
Neuroimaging is essential for prognostication and thus directly impacts patient care.
INTRODUCTION United States has a stroke every

For the purpose of this review, non- 40 seconds, and someone dies of stroke
traumatic intracranial hemorrhage and every 4 minutes.1 Hemorrhagic stroke
hemorrhagic stroke are used inter- comprises approximately 15% to 20%
changeably and are defined as any of these strokes,2 and its incidence is
spontaneous intraparenchymal, sub- reported to be approximately 15 per
arachnoid, or intraventricular hemor- 100,000 to 40 per 100,000 person-years.
rhage. The neuroimaging of traumatic High rates of associated morbidity,
intracranial hemorrhage is not covered mortality, and disability exist. In fact,
in this review. the 30-day mortality of hemorrhagic
Stroke continues to be one of the stroke has been reported to be as high
leading causes of mortality and mor- as 61%, with only 20% of survivors
bidity in the United States and costs achieving full functional independence
the nation approximately $34 billion at 6 months.3 The initial management
annually. On average, someone in the of hemorrhagic stroke centers on early

KEY POINTS
identification, determination of the as a hyperdense lesion on head CT. h Head CT without
underlying etiology, prevention of he- However, as time passes, the lesion contrast has distinct
matoma expansion, treatment of acute will become isodense with the brain advantages over other
complications such as mass effect and parenchyma, typically after 1 week,5 neuroimaging tools as
obstructive hydrocephalus, and treat- at which time the sensitivity of CT is the initial screening
ment of the underlying etiology, if in- lower than that of MRI. In addition to test for hemorrhagic
dicated. Neuroimaging is the key determining the location of hemor- stroke, including wide
determinant of all these components rhage, CT imaging also helps identify availability, lower cost,
of care and hence plays a crucial role in intraventricular extension, assess the ease of identification
hemorrhagic stroke management. extent of cerebral edema and mass effect, of hemorrhage, high
sensitivity and specificity,
and estimate hemorrhage volume.
SIGNIFICANCE OF IMAGING and applicability
Calculation of the volume of blood
IN HEMORRHAGIC STROKE in patients with
on head CT is most easily performed hemodynamic instability
MANAGEMENT using the ABC/2 method, wherein the and claustrophobia.
Neuroimaging is the key starting point dimensions of the hematoma are mea-
in the evaluation of patients with hem- h Calculation of hematoma
sured in centimeters to create a volume
volume allows for
orrhagic stroke. As such, this article in milliliters. First, the longest axis improved communication
describes the various structural neuro- measured (in centimeters) is labeled between medical
imaging modalities (CT, MRI, and trans- A, then a perpendicular to line A is providers and can be easily
cranial color-coded duplex) as well as drawn and labeled B; then, the number accomplished by using
the various vascular neuroimaging of slices on which contiguous blood is the ABC/2 method.
modalities (CT angiography [CTA], noted multiplied by the slice thickness h Approximately,
magnetic resonance angiography (in centimeters) is labeled C. The one-third of patients
[MRA], digital subtraction angiography product of these three dimensions with hemorrhagic stroke
[DSA], and transcranial Doppler [TCD] divided by two is the estimated blood will have hematoma
ultrasound) relevant to the evaluation volume (Figure 3-16).7 However, the expansion on follow-up
and management of patients with hem- slice thickness on most standard head CT within the
orrhagic stroke from various etiologies. head CT protocols is 0.5 cm. There- first 3 hours of
fore, for simplicity, one can multiply symptom onset.
Identification of Hemorrhage A and B by the number of slices on h Presence of a spot
The possibility of hemorrhagic stroke which contiguous blood is noted, then sign on head CT
should be considered in any patient divide by four. angiography is
who presents with signs or symptoms Calculation of the hematoma vol- indicative of active
of acute neurologic dysfunction. Usu- ume allows for improved communica- hemorrhage and
ally the first diagnostic modality used predictive of hematoma
tion between medical providers and
growth; it may favor
in such situations is a noncontrast for prognostication when combined
admittance to the
head CT because of its distinct advan- with the physical examination to cal- intensive care unit even
tages over other neuroimaging tools, culate the ICH Score using the vari- if the patient is not
such as MRI, in emergent situations. ables in Table 3-18 and Figure 3-2. intubated and appears to
The high sensitivity and specificity of Approximately one-third of patients be clinically stable.
CT for identifying acute blood, along will have hematoma expansion on
with its lower cost, feasibility in unsta- follow-up head CT within the first
ble patients, and wide availability, 3 hours of symptom onset.9 The use
make it the first neuroimaging modal- of a head CTA or a contrast-enhanced
ity of choice in most acute situations. head CT (when CTA is not available)
Rapid neuroimaging using CT or can allow for earlier identification of
MRI is recommended to distinguish such patients via the spot sign, wherein
ischemic stroke from an intracerebral contrast is identified within the hem-
hemorrhage (ICH).4 Acute ICH is seen orrhage, suggesting active bleeding

Hemorrhagic Stroke
FIGURE 3-1 Calculating the intracranial hemorrhage volume. Since the standard CT slice
thickness for brain imaging is 0.5 cm, for ease of calculation, one can multiply
A and B by the number of slices on which contiguous blood is noted, then
divide by four.
6
Image modified from Alberts M, Stroke Belt Consortium. B 2006 National Stroke Association.
a
TABLE 3-1 Determination of the Intracerebral Hemorrhage Score
Component ICH Score Points

Glasgow Coma Scale 3Y4 2
5Y12 1
13Y15 0
ICH volume (mL) Q30 1
G30 0
Intraventricular hemorrhage Yes 1
No 0
Infratentorial originb Yes 1
No 0
Age (years) Q80 1
G80 0
Total ICH Score 0Y6
ICH = intracerebral hemorrhage.
a
Reprinted with permission from Hemphill JC III, et al, Stroke.8 B 2001 American Heart
Association, Inc. stroke.ahajournals.org/content/32/4/891.short.
b
Includes all interior cerebral areas below the undersurface of the temporal and occipital
lobes extending to the upper cervical cord; includes the cerebellum.

(Case 3-1).10 A dynamic spot sign has
also been reported on CT perfusion im-
aging, with a higher predictive value.11
However, the utility of CT perfusion
imaging in a patient with hemorrhagic
stroke is unclear at this time. Head CTA
can further identify underlying vascular
lesions that may then guide therapy
and influence the patient’s outcome.
Head CT imaging has several limi-
tations. It poorly visualizes the poste-
rior fossa contents (ie, the brainstem
and cerebellum) because of beam-
FIGURE 3-2 Prognostication of intracerebral hemorrhage
hardening artifact. In addition, the (ICH) based on the ICH Score. The ICH Score
hyperattenuation of acute blood on comprises two patient-related factors (age and
Glasgow Coma Scale score) and three neuroimaging findings
head CT is based on the protein con- (size of hematoma, location, intraventricular component).
tent of whole blood (ie, hemoglobin). 8
Reprinted with permission from Hemphill JC III, et al, Stroke. B 2001
Therefore, in patients who are anemic, American Heart Association, Inc. stroke.ahajournals.org/content/32/4/891.short.
in particular those with serum hemo-

globin less than 10 g/dL, hyperattenuation from tumor or infectious process is KEY POINT
may be limited, resulting in a reduced suspected; and the need for a magnetic h Hyperattenuation of
ability to identify the ICH. Similarly, in resonance (MR) or CT venogram when acute blood on head CT
is based on the protein
patients with very elevated hemoglobin ICH from cerebral venous thrombosis
content of whole blood
values, such as those with polycythemia is suspected. (ie, hemoglobin).
or significant hemoconcentration, the Therefore, in patients
vasculature may appear abnormally Guidance for Additional Tests with serum hemoglobin
hyperdense, making accurate diagnosis In addition to helping guide further less than 10 g/dL,
of ICH more challenging.12,13 neuroimaging, the initial head CT find- hyperattenuation may
ings may indicate the need for addi- be limited, resulting in
Guidance for Further tional testing, such as a lumbar reduced ability to
Neuroimaging puncture to assess for SAH or infection, identify intracerebral
echocardiography to assess for hyper- hemorrhage. Similarly, in
The identification and pattern of patients with very
blood on the initial head CT can guide tensive heart disease or endocarditis,
or body imaging in the search for a elevated hemoglobin
subsequent neuroimaging. This may values, such as those with
primary malignancy.
include the need for a repeat head polycythemia or significant
CT after a few hours to assess for Guidance for Acute Emergent
hemoconcentration, the
worsening hemorrhage, edema, or vasculature may appear
Treatment abnormally hyperdense,
midline shift; the need for CTA or
An emergent head CT is integral in the making accurate diagnosis
DSA in case of subarachnoid hemor- evaluation of a patient who has a of intracerebral
rhage (SAH) or ICH from suspected depressed level of consciousness. Dis- hemorrhage challenging.
arteriovenous malformation or arterio- covery of an ICH with intraventricular
venous fistula; the need for brain MRI extension and resultant obstructive hy-
without contrast in the case of ICH from drocephalus in a patient who is coma-
suspected hemorrhagic transformation tose or severely encephalopathic may
of is chemic stroke or ICH from lead to placement of an external ventri-
cerebral amyloid angiopathy; the need cular drain with dramatic improvement
for brain MRI with contrast when ICH in the patient’s clinical examination

Hemorrhagic Stroke
Case 3-1
An 84-year-old man was transferred for a right frontal intracerebral hemorrhage (ICH). He initially
presented to the emergency department of his local hospital for left-sided facial droop and dysarthria.
A head CT was obtained (Figure 3-3A). The patient became unconscious immediately after the
initial head CT and was intubated. An emergent head CT angiogram was obtained, which showed
extension of the ICH and a spot sign, suggesting active hemorrhage (Figure 3-3B). He was
subsequently transferred, and his examination on arrival revealed a Glasgow Coma Scale score of 6.
The patient would not open his eyes to noxious stimulation, but would localize on his right upper
extremity. A repeat head CT a few hours later showed further expansion of the ICH and significant
midline shift (Figure 3-3C). The family chose to pursue comfort care measures, based on the patient’s
advanced age and marked neurologic deterioration.
FIGURE 3-3 Imaging of the patient in Case 3-1. A, Initial head CT. B, An emergent head CT angiogram was obtained,
showing extension of the intracerebral hemorrhage and a spot sign (arrow), suggesting active
hemorrhage. C, A repeat head CT a few hours later showed further expansion of the intracranial
hemorrhage and significant midline shift (line and arrow).
Comment. This case demonstrates two key points: (1) a significant risk of hemorrhage
expansion exists within the first few hours; and (2) a spot sign on head CT angiography can predict
hematoma expansion. This information can be used in prognostication and subsequent medical
decision making.
KEY POINT at times (Case 3-2). Similarly, findings Neuroimaging With Magnetic
h MRI is more suggestive of elevated intracranial pres- Resonance Imaging
sensitive than CT in sure may indicate the need for hyper- Unlike CT imaging, which uses x-rays
identifying subacute ventilation and hyperosmolar therapy. to produce cross-sectional images and
hemorrhagic stroke.
hence involves radiation exposure, MRI
Guidance for Prognostication uses magnetic fields and radio waves
In addition to the ICH Score described to produce images. Modern 1.5T MRI
above, the Fisher scale (Table 3-214) machines are equally sensitive at iden-
and modified Fisher scale (Table 3-315), tifying acute symptomatic ICH as CT.5
which are based on the initial non- In addition, MRI is more sensitive than
contrast head CT, are used when com- CT at identifying subacute ICH. Similar
municating about SAH. to CT imaging, the appearance of ICH

Case 3-2
A 54-year-old woman with a history of hypertension, hypothyroidism, and rheumatoid arthritis was brought
to the hospital for subarachnoid hemorrhage (SAH). According to her husband, she was in her usual state
of health while riding in his truck that afternoon when she suddenly grabbed her head and said that it felt
like somebody touched her. She immediately returned to baseline and had no further symptoms. Later
that evening, she was found unconscious on her bathroom floor. An initial noncontrast head CT showed
SAH with an extensive intraventricular component (Figure 3-4A). On initial examination, she was intubated
and had a Glasgow Coma Scale score of 5. An external ventricular drain (EVD) was emergently placed by
a neurosurgeon, following which her clinical examination quickly improved to a Glasgow Coma Scale score
of 11 without any other intervention. A post-EVD placement CT showed decreased intraventricular blood
and amount of
hydrocephalus but
increased midline
shift posteriorly
(Figure 3-4B).
Comment. This
patient’s neurologic
examination
improved
significantly after
placement of an
EVD because
obstructive
hydrocephalus was
relieved. This
demonstrates how
CT imaging can
guide emergent
procedures,
leading to clinical
improvement. FIGURE 3-4 Imaging of the patient in Case 3-2. A, An initial noncontrast head CT showing
subarachnoid hemorrhage with extensive intraventricular component (yellow
arrows) B, CT postjexternal ventricular drain placement showing decreased
intraventricular blood (yellow arrows) and hydrocephalus, but increased midline shift
posteriorly (red line and arrow).
KEY POINTS
on MRI evolves over time, as shown between the two most common etiol-
in Table 3-4. h Susceptibility-weighted
ogies of ICH: arterial hypertensive
MRI is the most sensitive
Susceptibility-weighted imaging vasculopathy and cerebral amyloid modality for detecting
(SWI) which is a high-resolution three- angiopathy. small amounts
dimensional gradient recalled echo Limitations associated with MRI, of intraparenchymal
(GRE) MRI sequence, is most sensitive other than cost, center on logistic hemorrhage.
in detecting small amounts of hemor- and patient-specific characteristics.17 h MRI allows for distinction
rhage. This is followed by the more The most common logistic limitation between the two most
traditional two-dimensional GRE associated with MRI is the ability to common etiologies of
T2*-weighted imaging.16 Other MRI obtain the study in a timely fashion. hemorrhagic stroke:
sequences, such as T1, T2, and fluid- Common patient-specific limita- arterial hypertensive
attenuated inversion recovery (FLAIR), tions of MRI include the presence of vasculopathy and
provide supportive information. Most a pacemaker or ferromagnetic foreign cerebral amyloid
important, MRI allows for distinction object, claustrophobia, and large angiopathy.

Hemorrhagic Stroke
a
TABLE 3-2 Fisher Scale for Subarachnoid Hemorrhage
Fisher Scale
Grade Findings on Admission CT
1 No blood visualized
2 Diffuse deposition or thin layer of blood with all vertical layers
being G1 mm thick
3 Localized clots and/or vertical layers of blood Q1 mm thick
4 Diffuse or no subarachnoid hemorrhage, presence of
intraparenchymal or intraventricular blood
a
Reprinted with permission from Fisher CM, et al, Neurosurgery.14 B 1980 Congress of Neurological
Surgeons. journals.lww.com/neurosurgery/Abstract/1980/01000/Relation_of_Cerebral_Vasospasm_
to_Subarachnoid.1.aspx.
body habitus. Claustrophobia and be able to lie flat and still for the
large body habitus have, to some duration of the study without respira-
degree, been overcome by the advent tory compromise, as motion significantly
of open and semiopen MRI scanners, degrades the diagnostic information
but these may not be available at gained from an MRI.
many centers. The duration of the Studies ordered through the
study also poses some patient-specific emergency department are typically
limitations in patients with more exten- ordered to be performed emergently,
sive ICH who may develop hemody- and most centers cannot accommodate
namic instability. The patient must also numerous emergent MRI studies. One
a
TABLE 3-3 Modified Fisher Scale for Subarachnoid Hemorrhage
Frequency, % (n)
Delayed Cerebral
Grade Criteria Patients, % Ischemia Infarction
0 No subarachnoid hemorrhage 5 0 (0/15) 0 (0/15)
(SAH) or intraventricular
hemorrhage (IVH)
1 Minimal/thin SAH, no IVH 30 12 (10/83) 6 (5/83)
in both lateral ventricles
2 Minimal/thin SAH, with IVH 5 21 (3/14) 14 (2/14)
in both lateral ventricles
3 Thick SAH,b no IVH in 43 19 (22/117) 12 (14/117)
both lateral ventricles
4 Thick SAH,b with IVH in 17 40 (19/47) 28 (13/47)
both lateral ventricles
All patients 100 20 (54/276) 12 (34/276)
a
Reprinted with permission from Claassen J, et al, Stroke. 15
B 2001 American Heart Association, Inc. stroke.ahajournals.org/content/32/
9/2012.short.
b
Completely filling Q1 cistern or fissure.

TABLE 3-4 Appearance of Intracerebral Hemorrhage onaNoncontrast Computed Tomography
and Magnetic Resonance Imaging by Stages
T1-Weighted T2-Weighted T2*-Weighted

Stage Phase of Blood Noncontrast CT MRI MRI MRI
Hyperacute Oxyhemoglobin Smooth, Hypointense or Hyperintense Marked
hyperdense isointense hypointensity
Acute Deoxyhemoglobin Hyperdense with Isointensity Hypointense Marked
(12Y48 hours) fluid levels or slight with hypointensity
hypointensity hyperintense
with thin perilesional rim
hyperintense
rim in the
periphery
Early subacute Methemoglobin Hypodense Hyperintensity Hypointensity Hypointensity
(72 hours) intracellular region of edema
with mass effect
Late subacute Methemoglobin Less intense with Hyperintensity Hyperintensity Hypointensity
(3Y20 days) extracellular ringlike profile
Chronic Hemosiderin Isodense or Hypointensity Hypointensity Hyperintense or
(9 weeks) and ferritin modest confined isointense core
hypodensity surrounded by
hypointense rim
a
Reprinted with permission from Macellari F, et al. Stroke.2 B 2014 American Heart Association, Inc. stroke.ahajournals.org/content/45/
3/903.long.
strategy developed by the authors at and reported within 4 hours KEY POINT
Oklahoma University Medical Center to of order. h Establishing a hospital
alleviate this challenge is to establish & Level 3 brain MRI: Indicated protocol for obtaining
priority levels for brain MRI studies when the findings of the study MRI scans based on
based on how the study is expected to will supplement the plan of care, priority levels may be a
such as in a patient with an very practical and
impact the plan of care for a particular
acute ischemic stroke and low efficient way to triage
patient:
National Institutes of Health patients for MRI and
& Level 1 brain MRI: Indicated only Stroke Scale score who is may result in better use
when the findings of the study will of limited resources.
outside of the thrombolysis or
determine whether the patient will
interventional window. The MRI is
need a surgical or endovascular expected to be completed and
intervention. The MRI is expected reported within 24 hours
to be completed and reported of order.
within 90 minutes of order.
A retrospective analysis of the imple-
& Level 2 brain MRI: Indicated mentation of this strategy at our insti-
only when the findings of the study
will determine the patient’s tution indicated that the vast majority of
disposition, such as discharge to neurosciences patients obtained their
home, admit to floor, or admit to ordered MRI study within the pre-
the intensive care unit. The MRI scribed time indicated by the ordered
is expected to be completed level (unpublished data).

Hemorrhagic Stroke
KEY POINTS
h Modern CT Most MRI scanners currently avail- in this situation is that the amount of
angiography has very able for clinical purposes are 1.5T contrast administered can be kept
high sensitivity and scanners; however, 3T MRI scanners much lower (as low as 5 mL to 10 mL
specificity in detecting are increasingly available. The higher while assessing a single vessel of inter-
arterial lesions of the magnetic field produced by 3T MRI est) as compared to CTA, where the
brain and is largely scanners provides exceptional anatomic amount of contrast administered is
replacing digital details and may be beneficial for various much higher (usually 70 mL to 100 mL).
subtraction angiography pathologies in the brain, including ICH.
for diagnostic purposes. In addition, a 3T MR angiogram may Digital Subtraction Cerebral
However, the sensitivity supplant the need for invasive DSA in Angiography
of CT angiography is some instances.
lower than digital Conventional angiography, or DSA, is
subtraction angiography the most invasive neuroimaging tech-
Computed Tomography
for aneurysms smaller nique used in the assessment of pa-
Angiography and Magnetic
than 3 mm and
Resonance Angiography tients with ICH. The technique involves
intracranial dissections. placing a femoral sheath introducer in
CTA is performed by combining the IV
h In patients with either the right or left common femoral
administration of iodinated contrast
marginally elevated artery followed by the introduction and
material and CT scanning to evaluate
creatinine where advancement of a catheter into the
angiographic data are
vascular-related conditions, such as
aneurysms or stenoses. With the in- artery of interest under direct fluoros-
critical, digital
creasing availability of multislice CT copy. Contrast is then injected through
subtraction angiography
may be preferred over scanners, CTA has largely replaced the catheter, and images are obtained
CT angiography as the invasive DSA for diagnostic purposes using time-controlled x-rays. The im-
amount of contrast in a number of clinical scenarios. Disad- ages are subtracted from a precontrast
administered can be vantages of CTA include radiation expo- image, hence the term digital subtrac-
kept much lower sure and contrast administration with tion angiography.
with digital subsequent risk of contrast-induced ne- The sensitivity and specificity of
subtraction angiography. phropathy and serious allergic reaction. DSA exceed 99% in identifying vascu-
h The sensitivity and However, MRA of the head uses time- lar abnormalities in patients with ICH.
specificity of digital of-flight imaging and does not require It continues to be the gold standard
subtraction angiography contrast administration, therefore elim- study in a variety of clinical scenarios.
exceed 99% in inating the risk of a serious allergic However, it has an approximately 1%
identifying vascular reaction and contrast-induced ne- combined risk of complications, such
abnormalities in
phropathy. In addition, radiation expo- as stroke, vessel dissection, vessel
patients with
sure is avoided. The sensitivity and perforation, contrast allergic reaction,
hemorrhagic stroke.
specificity of 1.5T MRA is lower than contrast-induced nephropathy, and
that of modern multislice CTA studies. groin hematoma, as well as exposes
At most centers, a brain CT angio- patients to radiation. Because of its
gram is obtained in the emergency limited availability and risks, noninva-
department following the diagnosis of sive imaging, such as CTA and MRA,
ICH on initial head CT. In patients has largely replaced DSA as the initial
with renal insufficiency or known modality of choice in assessing the
serious allergic reaction to iodinated cerebral vasculature.18
contrast, an MR angiogram can be
obtained. In patients with marginally Transcranial Doppler
elevated creatinine where angiogra- Ultrasound and Transcranial
phic data would affect clinical decision Color-Coded Duplex
making, DSA can be considered in TCD is a noninvasive blind insonation
place of CTA. The advantage of DSA of blood flow within large intracranial

KEY POINT
arteries, producing spectral waveforms imperative to have appropriately trained h The role of transcranial
and determination of physiologic he- sonographers performing TCD studies Doppler in the imaging
modynamic variables. 19 TCD with under the auspices of an accredited of hemorrhagic stroke is
brightness-mode (B-mode) imaging, laboratory, as incorrectly obtained false- most robust
also known as imaging TCD, transcra- positive data could result in patient in the detection of
nial color-coded duplex, transcranial morbidity as a consequence of unneces- cerebral vasospasm
sary hemodynamic augmentation or in patients with
duplex sonography, and triplex imag- subarachnoid
neurointerventional procedures, while
ing, adds anatomic visualization of the hemorrhage.
false-negative data could result in
vasculature and surrounding structures
clinicians missing the window of op-
using the gray scale of B-mode. portunity to prevent the patient from
Transcranial Doppler ultrasound. having delayed cerebral ischemia.22
The role of TCD in the imaging of One additional calculation that is
hemorrhagic stroke is most robust in routinely obtained as part of a TCD
the detection of cerebral vasospasm study is the Gosling pulsatility index,
in patients with SAH. TCD measures which is defined as the difference of
systolic and diastolic velocities in large the peak systolic velocity minus the
intracranial arteries, allowing for cal- end diastolic velocity, divided by the
culation of mean flow velocities, mean velocity. Although elevated
which, when elevated, correlate with pulsatility index values have been
the severity of vasospasm. Specifi- shown to correlate with increased
cally, TCD can detect vasospasm days intracranial pressure in some patients,
b e f or e c l i n i c a l m a ni f e s t a t i o n s , pulsatility index values cannot be used
allowing the clinician to initiate hemo- in isolation to determine which pa-
dynamic augmentation to prevent tients have increased intracranial pres-
delayed cerebral ischemia.20,21 Fur- sures to warrant hyperosmolar
thermore, serial TCD examination al- therapy or external ventricular drain
lows for evaluation of the efficacy placement.23 However, trends in the
of the treatment provided, whether pulsatility index values can be useful
medical or neurointerventional, to as supportive information when intra-
guide subsequent care. TCD can also cranial pressure monitoring is not
identify severe vasospasm, which available or suboptimal. 24,25 De-
places the patients at highest risk for pressed pulsatility index values, on
delayed cerebral ischemia, and help the other hand, in the setting of
identify which patients would benefit vasospasm are felt to represent distal
the most from intraarterial vasodila- vascular dilation that occurs as a
tors and angioplasty to prevent delayed compensatory mechanism to prevent
cerebral ischemia. tissue ischemia and may correlate
The chief benefits of TCD in SAH with the risk of symptomatic large
include that the patient is not exposed vessel vasospasm following aneurys-
to ionizing radiation, it does not mal SAH.23
require administration of potentially Transcranial color-coded duplex.
nephrotoxic contrast agents, and, In addition to the capabilities of TCD
most important, it can be done at the for monitoring of vasospasm, transcra-
bedside. As with any ultrasound-based nial color-coded duplex allows for
modality, the study quality is highly bedside monitoring of parenchymal
dependent on the quality of the sono- hematoma expansion. Using the B-mode
grapher’s technique and the institu- component of transcranial color-coded
tion’s scanning protocol. Therefore, it is duplex, two-dimensional visualization

Hemorrhagic Stroke
of the hematoma is obtained in the underlying structural cause or medical

form of a hyperechoic mass.26 cause. Common structural causes of
Using this technique, the sonogra- secondary ICH include a vascular mal-
pher can also assess for the presence formation, tumor, hemorrhagic trans-
or absence of intraventricular exten- formation of an ischemic infarction,
sion as well as midline shift.26 More- vasculitis, or cerebral venous throm-
over, calculation of ICH volume using bosis. Common medical causes of
transcranial color-coded duplex has secondary ICH include infection,
shown close agreement with that coagulopathy, and sympathomimetic
calculated via head CT. The volume drug use.2
of ICH using transcranial color-coded
duplex can be calculated as demon- Arterial Hypertensive
strated in Figure 3-5. However, as the Vasculopathy
hematoma begins to degrade, typi- Arterial hypertensive vasculopathy is
cally beyond day 5, its hyperechoic the most common cause of nontrau-
signature also diminishes, reducing the matic ICH and is most often associated
sharply demarcated margins of the with long-standing arterial hyperten-
hematoma.26 sion.27 It most commonly affects the
lenticulostriate branches arising from
DISEASE-SPECIFIC STATES AND the middle cerebral arteries, the tha-
NEUROIMAGING lamic perforators arising from the
Classification of ICH can most easily posterior communicating and posteri-
be thought of as primary and second- or cerebral arteries, and the perforat-
ary based on the etiology. Primary ICH ing arteries off of the basilar artery.
is caused by arterial hypertensive vas- Therefore, a propensity for hemorrhage
culopathy and, to a lesser degree, exists in specific anatomic locations
cerebral amyloid angiopathy. Second- (Figure 3-628). Chronic hypertension
ary causes of ICH are numerous; how- imparts an increased relative risk of
ever, they can be classified into an ICH of 3.68 to 5.55.29
FIGURE 3-5 Measurement of major longitudinal (L) and sagittal (S) diameters in the axial plane
and coronal plane (C) using transcranial color-coded duplex sonography.
26
Reprinted with permission from Pérez ES, et al, Stroke. B 2009 American Heart Association, Inc.
stroke.ahajournals.org/content/40/3/987.short.

FIGURE 3-6 Common sites of spontaneous intraparenchymal hemorrhage secondary to chronic hypertension.
28
Illustration reprinted from Qureshi AI, et al, N Engl J Med. B 2001 Massachusetts Medical Society. www.nejm.org/doi/full/10.1056/
NEJM200105103441907.
6
Complete image reprinted from Alberts M, Stroke Belt Consortium. B 2006 National Stroke Association.
Patients typically present with neu- Cerebral Amyloid Angiopathy KEY POINT
rologic dysfunction ranging from focal h It is important to
In a patient presenting with ICH, sever-
exclude secondary
neurologic deficits to altered level of al clinical factors (such as advanced age
causes of hemorrhagic
consciousness and is dependent on the and history of cognitive decline) and stroke through vascular
location and size of the ICH. The initial neuroimaging factors help make the neuroimaging even
neuroimaging findings (volume and diagnosis of cerebral amyloid angi- when it is suspected
location of the ICH) in combination opathy as the underlying cause of to be caused by
ICH. The neuroimaging findings in- arterial hypertensive
with the neurologic examination have
clude the cortico-subcortical location vasculopathy.
been shown to determine the patient’s of the hematoma, the presence of
prognosis and guide subsequent med- microbleeds in the cortical regions,
ical and surgical management.29,30 and superficial siderosis, which are
It is important to exclude second- best seen on SWI and GRE (T2*) MR
ary causes of ICH through vascular sequences (Figure 3-7). Cerebellar,
neuroimaging even when the ICH is brainstem, and deeper lesions are
suspected to be caused by chronic less likely to be from cerebral amyloid
hypertension. The same concept ap- angiopathy.31 Boston and modified
plies to patients presenting with ICH Boston criteria (Table 3-532) can be
in the setting of coagulopathy or particularly useful when considering
sympathomimetic drug use. a diagnosis of cerebral amyloid

Hemorrhagic Stroke
FIGURE 3-7 Imaging characteristics of cerebral amyloid angiopathy on CT and MRI. CT (A) and MRI (B) of an 84-year-old
woman who presented with an acute spontaneous left parietal intracerebral hemorrhage (ICH) (cortical
location) (A, B, yellow arrows). MRI shows the characteristic microbleeds suggestive of cerebral amyloid
angiopathy as the underlying cause of spontaneous ICH (B, red oval ). CYE, MRIs of a 94-year-old man who presented
with a very small spontaneous left frontal hemorrhage (C, yellow arrow). The gradient recalled echo (GRE) and
susceptibility-weighted images demonstrate significant cortical microbleeds (more prominent on the right side; C, D, E, red
ovals) and superficial siderosis (more prominent on the left side) indicating cerebral amyloid angiopathy as the cause of the
patient’s spontaneous ICH.
angiopathyas the underlying cause of of SAH include arteriovenous malforma-

ICH. Cerebral amyloid angiopathy is tion or fistula (Case 3-3 and Case 3-4),
a consequence of deposition of intracranial dissection (Case 3-5), cere-
amyloid-" peptide in the vascular bral venous thrombosis, reversible ce-
walls of leptomeningeal and cortical rebral vasoconstriction syndrome,
vessels resulting in decreased vascular vasculitis (Case 3-6), and use of sym-
compliance; it accounts for 5% to 20% pathomimetic drugs. Neuroimaging
of ICHs.33 plays a key role in management of
these patients, helping to identify SAH
Subarachnoid Hemorrhage and guiding the etiology, treatment,
Excluding trauma, aneurysmal rupture and prognostication. Imaging can also
is the most common cause of SAH. help tremendously when SAH happens
Other potential underlying etiologies in the setting of trauma. For example,

TABLE 3-5 Boston and Modified Boston Criteria for Diagnosis of Cerebral Amyloid Angiopathy
in Patients With Intracerebral Hemorrhagea,b
Classic Boston Criteria Modified Boston Criteria

Definite CAA Full postmortem examination No modification compared with the
demonstrating: classic Boston criteria
& Lobar, cortical,

c
or cortico-subcortical
hemorrhage
& Severe CAA with vasculopathy

& Absence of other diagnostic lesiond
Probable CAA Clinical data and pathologic tissue No modification compared with the
with supporting (evacuated hematoma or cortical classic Boston criteria
pathology biopsy) demonstrating:
& Lobar, cortical,

c
or cortico-subcortical
hemorrhage
& Some degree of CAA in specimen

& Absence of other diagnostic lesiond
Probable CAA Clinical data and MRI or CT demonstrating: Clinical data and MRI or CT demonstrating:
c
& Multiple hemorrhages restricted to & Multiple hemorrhagesc restricted
lobar, cortical, or cortico-subcortical to lobar, cortical, or cortico-subcortical
regions (cerebellar hemorrhage allowed) regions (cerebellar hemorrhage allowed)
& Age Q55 years OR
& Absence of other cause of hemorrhaged Single lobar, cortical, or cortico-subcortical

hemorrhage and focale or disseminatedf
superficial siderosis
& Age Q55 years

& Absence of other caused of hemorrhage
or superficial siderosis
Possible CAA Clinical data and MRI or CT demonstrating: Clinical data and MRI or CT demonstrating:
& Single lobar, cortical, or & Single lobar,ccortical, orecortico-subcorticalf

cortico-subcortical hemorrhagec hemorrhage and focal or disseminated
superficial siderosis
& Age Q55 years & Age Q55 years

& Absence of other cause of hemorrhaged & Absence of other caused of hemorrhage
or superficial siderosis
CAA = cerebral amyloid angiopathy; CT = computed tomography; MRI = magnetic resonance imaging.
a
Adapted from Linn J, et al, Neurology.32 B 2010 American Academy of Neurology. www.neurology.org/content/74/17/1346.long.
b
Reprinted with permission from Domingues R, et al, Neurol Clin.5 B 2015 Elsevier Inc. www.sciencedirect.com/science/article/pii/
S0733861914001170.
c
The term hemorrhage referred, in the pathologic validation, to lobar intracerebral hemorrhage (ICH). However, some authors suggest
that multiple lobar cerebral microbleeds, without lobar ICH, may be considered as probable cerebral amyloid angiopathy.
d
Other causes of ICH that question the diagnosis of cerebral amyloid angiopathy are excessive warfarin dose (international normalized
ratio [INR] higher than 3.0; INR 3.0 or lower or other nonspecific laboratory abnormalities are permitted for diagnosis of possible cerebral
amyloid angiopathy), antecedent of head trauma or ischemic stroke, hemorrhagic transformation of an ischemic stroke, arteriovenous
malformation, central nervous system tumor or vasculitis, blood dyscrasia, or coagulopathy.
e
Siderosis restricted to three or fewer sulci.
f
Siderosis affecting at least four sulci.

Hemorrhagic Stroke
Case 3-3
A 46-year-old woman with a history of untreated hypertension was admitted to the hospital for abrupt-onset
severe headache that persisted for 3 days (Hunt and Hess Scale grade 2). A noncontrast head CT showed a
small subarachnoid hemorrhage in the prepontine cistern (Figure 3-8A; Fisher grade 1 [Table 3-2]). A head CT
angiogram was next obtained, which showed a basilar apex aneurysm adjacent to the area of hemorrhage
(Figure 3-8B). The aneurysm was emergently treated by balloon-assisted coiling. Figure 3-8C shows the
basilar apex aneurysm on digital subtraction angiography. Figure 3-8D depicts the digital subtraction
angiographic three-dimensional reconstruction of the aneurysm.
Figure 3-8E shows the final results of the acutely performed balloon-assisted coiling (notice the contrast filling
at the base of the aneurysm, suggestive of small residual aneurysm). The patient returned a few months later
and underwent Y-stent remodeling and further coiling that resulted in complete radiographic occlusion of
the aneurysm (Figure 3-8F).
Comment. The case illustrates the critical role of neuroimaging in the identification,
prognostication, and management of patients with aneurysmal subarachnoid hemorrhage.
FIGURE 3-8 Imaging of the patient in Case 3-3. A, Noncontrast head CT showing a small subarachnoid hemorrhage in
the prepontine cistern (Fisher grade 1) (yellow arrow). B, Head CT angiography showing a basilar apex
aneurysm adjacent to the area of hemorrhage (red circle). C, Basilar apex aneurysm on digital subtraction
angiography (red oval ). D, Digital subtraction angiography three-dimensional reconstruction of the aneurysm (green
oval). E, Final results of the acutely performed balloon-assisted coiling (note the contrast filling at the base of the aneurysm,
suggestive of small residual aneurysm) (yellow arrow). F, The patient was brought back a few months later and underwent
Y-stent remodeling and further coiling that resulted in complete radiographic occlusion of the aneurysm (red oval) (note the
stent tines in the bilateral posterior cerebral and basilar arteries) (yellow arrows).

Case 3-4
A 76-year-old man with a history of poorly controlled diabetes mellitus, significant coronary artery
disease, and hypertension presented to the hospital with acute-onset headache, encephalopathy, and
decreased level of consciousness. A head CT showed diffuse extensive subarachnoid hemorrhage
(Figure 3-9A; Fisher grade 3 [Table 3-2]). An external ventricular drain was emergently placed without
any immediate subsequent clinical improvement. A head CT angiogram was next obtained, which was
suggestive of a midbasilar artery aneurysm. Emergent digital subtraction angiography was performed,
which confirmed a blister aneurysm at the midbasilar artery, above the origin of the right anterior
inferior cerebellar artery (Figure 3-9B). A blister aneurysm is a small aneurysm arising from a nonbranching
segment of an artery and suspected to originate from a dissection. The aneurysm was acutely treated
endovascularly by deploying two overlapping intracranial stents across the lesion in the hope of slowing
the flow to the aneurysm. However, no stagnation of flow in the aneurysm was noted. The patient died a
few days later of rehemorrhage from this aneurysm.
Comment. This case demonstrates that a very small aneurysm can be the source of large diffuse
subarachnoid hemorrhage.
FIGURE 3-9 Imaging of the patient in Case 3-4. A, Head CT showing a diffuse extensive
subarachnoid hemorrhage (Fisher grade 3) (oval). B, Emergent digital subtraction
angiography was performed, which confirmed a blister aneurysm (arrow) at the
midbasilar artery, above the origin of the right anterior inferior cerebellar artery.
if the SAH is located over the frontal especially within 6 hours of hemor-
poles and the patient is found to have rhage.34 In a patient with a clinical
a basilar apex aneurysm, the aneurysm history highly suggestive of SAH but
is likely an incidental finding and the negative head CT, further options in-
SAH is from the trauma itself. These clude lumbar puncture to assess for
determinations for SAH in the setting of xanthochromia, MRI to assess for
trauma have significant ramifications in SAH, and CTA or DSA to identify the
determining the urgency of treatment. presence of an aneurysm or other
A noncontrast head CT is highly sen- etiology. CTA is slowly replacing DSA
sitive in detecting subarachnoid blood, as the first-line technique for the

Hemorrhagic Stroke
Case 3-5
A 47-year-old man with a history of type 2 diabetes mellitus, hypertension, and coronary artery disease was
transferred for further management of subarachnoid hemorrhage (SAH). According to the patient’s wife, he
had complained of constipation, went to the bathroom, and felt a ‘‘pop’’ in his head while having a bowel
movement. This was followed by a severe headache and generalized weakness. He was initially taken to his
local hospital by emergency medical services, and his condition declined further en route. A noncontrast head
CT revealed SAH (Figure 3-10A, Fisher grade 4 [Table 3-2]). Upon transfer to the authors’ hospital, his
neurologic examination revealed a Glasgow Coma Scale score of 3, as the patient was comatose and
intubated and would not open his eyes or move his extremities to noxious stimulation. An emergent head CT
angiogram was obtained but did not reveal an underlying cause of SAH (Figure 3-10B). An external
ventricular drain was placed by the neurosurgery team. Digital subtraction angiography was then performed,
which revealed an intracranial dissection involving the right posterior cerebral artery (Figure 3-10C). This was
also confirmed on superselective angiography of the right posterior cerebral artery (Figure 3-10D) and
three-dimensional cine rotational angiography (Figure 3-10E). No definitive treatment of intracranial
dissection could be performed. The patient had a complicated intensive care unit course over the next few
days, which included a nonYST-elevation myocardial infarction, continued increased intracranial pressure,
and multiple bilateral acute ischemic strokes secondary to cardioembolism. His family made the decision
to provide comfort care only, and he expired shortly thereafter.
Comment. This case illustrates an uncommon cause of SAH, intracranial dissection, and is an
example of the limitations of head CTA in identifying the etiology of SAH.
FIGURE 3-10 Imaging of the patient in Case 3-5. Noncontrast head CT revealing a subarachnoid hemorrhage (Fisher
grade 4) (A, oval). An emergent head CT angiogram does not reveal an underlying cause of subarachnoid
hemorrhage (B). Digital subtraction angiography from the left vertebral artery showing an intracranial
dissection involving the right posterior cerebral artery (C, arrow). Findings were also confirmed on superselective
angiography of the right posterior cerebral artery (D, arrow) and three-dimensional cine rotational angiography (E, oval).

Case 3-6
A 48-year-old woman with a history of frequent migraines and hypertension developed a sudden-onset
severe headache while performing yoga. She was evaluated at an outside facility and discharged to
home. Two days later, her husband noted that she was talking gibberish and had gait imbalance. After
multiple visits to the local emergency department over the course of a few days, a head CT was obtained,
which showed a small subarachnoid hemorrhage (SAH) in the high left frontal region (Figure 3-11A,
FIGURE 3-11 Imaging of the patient in Case 3-6. A, After multiple visits to the local
emergency department over a few days, a head CT was finally obtained,
which showed a small subarachnoid hemorrhage in the high left frontal
region (Fisher grade 1) (yellow arrow). Brain MRI and CT angiography were obtained. B,
Gradient recalled echo (GRE) MRI sequence showing small subarachnoid hemorrhage in
the left frontal region (yellow arrow). C, Fluid-attenuated inversion recovery (FLAIR) images
reveal vasogenic edema in the cerebellar hemispheres bilaterally (red ovals). CT angiography
showed multifocal segmental areas of narrowing, worst in the distal branches of the right
middle cerebral artery (not shown). D, Digital subtraction angiography was then performed,
which confirmed these findings (yellow arrow and oval ).

Hemorrhagic Stroke

Fisher grade 1 [Table 3-2]). She was then transferred to the authors’ hospital for further management.
Her neurologic examination did not reveal any deficits. Her urine drug screen was positive for cannabinoids.
Brain MRI and CT angiography were obtained. The gradient recalled echo (GRE) MRI sequence images
showed small SAHs in the bilateral frontal regions (Figure 3-11B), and fluid-attenuated inversion recovery
(FLAIR) images revealed vasogenic edema in the cerebellar hemispheres bilaterally (Figure 3-11C). The CT
angiogram showed multifocal segmental areas of narrowing, worst in the distal branches of the right
middle cerebral artery. Digital subtraction angiography was then performed, which confirmed the
findings (Figure 3-11D). The differential diagnosis included reversible cerebral vasoconstriction syndrome
(RCVS) versus vasculitis. Given the absence of any history and laboratory findings indicating a vasculitic
process and the presence of findings on MRI suggestive of posterior reversible encephalopathy syndrome
(PRES), the diagnosis of RCVS was thought to be most likely the cause of her hemorrhage. She was
started on verapamil for treatment of RCVS and migraine prevention.
Comment. This case illustrates the value of multimodal neuroimaging. Initially the CT scan was
able to identify SAH, differentiating the current symptoms from her frequent migraines. The MRI
confirmed the presence of hemorrhage and also identified changes suggestive of PRES that were not
evident on head CT.
KEY POINTS diagnosis and treatment planning of identified a secondary bleeding source
h A noncontrast head CT cerebral aneurysms, but DSA is still in 56%.35 In contrast, DSA is of limited
is highly sensitive in required in patients with diffuse SAH diagnostic utility in the evaluation of
detecting subarachnoid
and negative initial CTA.34 The SAH parenchymal ICH except in younger
blood, especially within
literature has described perfusion im- patients who are not hypertensive with
6 hours of hemorrhage.
aging to assess for delayed cerebral atypical hemorrhage locations on head
h In a patient with a clinical ischemia and functional MRI (fMRI)/ CT.36,37 Figure 3-12 illustrates clinical
history highly suggestive
positron emission tomography (PET) examples of primary and secondary
of subarachnoid
to assess the physiologic, functional, intraventricular hemorrhages.
hemorrhage but
negative head CT, further
and cognitive sequelae after SAH.34
DSA continues to be the best modal- Intracerebral Hemorrhage
options include lumbar
puncture to ity to assess for aneurysms smaller Secondary to Cerebral
assess for xanthochromia, than 3 mm, intracranial dissections, Venous Thrombosis
MRI to assess for and reversible cerebral vasoconstric- Cerebral venous thrombosis is throm-
subarachnoid tion syndrome. bosis of the venous sinuses and veins
hemorrhage, and CT in the brain. Cortical vein thrombosis
angiography or digital Isolated Intraventricular refers to cerebral venous thrombosis
subtraction angiography Hemorrhage involving only a small cortical vein, as
to identify the presence opposed to venous or lateral sinus
Isolated intraventricular hemorrhage
of an aneurysm or thrombosis, which implies involve-
other etiology.
in the absence of an identifiable
parenchymal or subarachnoid compo- ment of one of the large cerebral
venous sinuses. The clinical course of
nent is an uncommon presentation of
cerebral venous thrombosis can be
intracranial hemorrhage, accounting extremely variable and insidious, mak-
for approximately 3% of intracranial ing it difficult to diagnose early on.
hemorrhage.35 The diagnostic neuro- Neuroimaging can play a crucial role
imaging evaluation of such patients in early identification and treatment.
is variable and only described in case However, identification of the throm-
series. However, in a pooled meta- bus in the sinuses can easily be
analysis of isolated patients with in- overlooked on CT and MRI scans
traventricular hemorrhage who when detailed clinical history of the
underwent DSA, cerebral angiography patient is not available.

KEY POINTS
h The clinical course of
cerebral venous
thrombosis can be
extremely variable and
insidious, making it
difficult to diagnose
early on. Neuroimaging
can play a crucial role in
early identification
and treatment.
h The appearance of the
thrombus on MRI is time
specific: isointense on
T1 and hypointense on
T2 in the acute phase,
hyperintense on T1 and
T2 in the subacute
phase, and isointense
on T1 and hyperintense
on T2 in the
chronic phase.
FIGURE 3-12 Examples of primary versus secondary intraventricular hemorrhage (IVH). A,

Noncontrast head CT of a 66-year-old man who had been on chronic
anticoagulation with warfarin secondary to aortic valve replacement and
presented with IVH (oval). International normalized ratio (INR) was 2.4 on presentation.
He was administered IV vitamin K and prothrombin complex concentrate to reverse the
anticoagulation. Further workup, including head CT angiography, brain MRI, and digital
subtraction angiography, did not reveal any underlying abnormality (primary IVH). BjD, A
26-year-old man who collapsed after a bowel movement. B, C, Noncontrast head CT
showed IVH (arrows). D, Digital subtraction angiogram of the left vertebral artery reveals a
dissecting aneurysm at the left anterior inferior cerebellar artery (secondary IVH) (oval).
The appearance of the thrombus niques can further aid in diagnosing

on MRI is time specific: isointense on cerebral venous thrombosis. While the
T1 and hypointense on T2 in the acute CT venogram involves administration of
phase, hyperintense on T1 and T2 in iodinated contrast medium, MR venog-
the subacute phase, and isointense on raphy can be performed without the
T1 and hyperintense on T2 in the chronic need for contrast using two-dimensional/
phase.38 MR and CT venography tech- three-dimensional time-of-flight as well

Hemorrhagic Stroke
KEY POINT
h Radiologic classification as two-dimensional/three-dimensional exceeding 30 percent of the infarcted
of hemorrhagic phase contrast techniques. Case 3-7 il- area with some mild space-occupying
transformation of lustrates some of the common neuro- effect, and parenchymal hematoma
ischemic stroke can radiologic findings of cerebral venous type 2 represents dense blood clot(s)
help with prognostication thrombosis. It is important to differen- exceeding 30 percent of the infarct
and in making tiate normal anatomic structures and volume with significant space-occupying
decisions regarding variations, such as hypoplastic or atretic effect (Figure 3-1441).
holding or continuing venous sinus or arachnoid granula- Classifying the hemorrhagic trans-
antithrombotic therapy. tions, from the presence of thrombus formation into these neuroimaging sub-
before initiating treatment of cerebral categories is clinically relevant for two
venous thrombosis. important reasons. First, only parenchy-
mal hematoma type 2 has been found
Hemorrhagic Transformation to independently cause clinical deterio-
of Ischemic Stroke ration and impair prognosis.41 Second,
Patients with ischemic stroke, especially the decision to hold antithrombotic ther-
those who receive IV thrombolysis or apy can be individualized based on this
undergo endovascular treatment, are at classification, as in the common clinical
risk of hemorrhagic transformation. practice to hold antithrombotic therapy
Hemorrhagic transformation of ischemic only in the setting of parenchymal hema-
stroke is considered to be symptomatic toma type 1 and type 2.
if it is associated with clinical decline,
specified as an increase in National Intracerebral Hemorrhage
Institutes of Health Stroke Scale score Secondary to Oral
of 4 or greater.39 Radiographically, Anticoagulants and
hemorrhagic transformation has been Sympathomimetic Drugs
categorized into four different sub-
With the aging population, the inci-
types: hemorrhagic infarction type 1
dence of oral anticoagulant use con-
and type 2 and parenchymal hematoma
type 1 and type 2.40 Hemorrhagic infar- tinues to rise, primarily based on the
ction type 1 is defined as small pete- increase in diagnosis of atrial fibrillation.
chiae along the margins of the infarct, Since the introduction of the newer
while hemorrhagic infarction type 2 rep- direct factor Xa inhibitors, it is expected
resents more confluent petechiae within that the total number of patients on
the infarcted area but without space- oral anticoagulants will greatly in-
occupying effect. Parenchymal hema- crease, despite reduced usage of war-
toma type 1 is defined as blood clot not farin. Patients on oral anticoagulants
Case 3-7
A 29-year-old woman with a history of ulcerative colitis on immunosuppressive therapy presented to a
referring hospital with new-onset persistent headaches. A noncontrast head CT at that time was
unremarkable (Figure 3-13A). Two days later, she was brought in encephalopathic with the same
persistent headache. A head CT with and without contrast was performed at this time, which now
showed a large right temporoparietal intracerebral hemorrhage with significant cerebral edema and a
midline shift of 10 mm (Figure 3-13B). The contrast-enhanced images also showed absence of contrast
opacification at the right sigmoid sinus, suggestive of cerebral venous thrombosis as the underlying
cause of the hemorrhage (Figure 3-13C). Upon transfer, a head magnetic resonance venogram was also
obtained, which revealed extensive cerebral venous thrombosis involving the right internal jugular vein

FIGURE 3-13 Imaging of the patient in Case 3-7. A, An initial noncontrast head CT was unremarkable, but 2 days later,
the patient was brought in encephalopathic with the same persistent headache. B, A head CT with and
without contrast was performed and shows a large right temporoparietal intracerebral hemorrhage
(yellow arrow) with significant cerebral edema (green arrow) and a midline shift of 10 mm (double red arrow). C,
Contrast-enhanced images also show absence of contrast opacification at the right sigmoid sinus (arrows), suggestive of
cerebral venous thrombosis as the underlying cause of hemorrhage. D, A head magnetic resonance venogram reveals
nonvisualization of the right internal jugular vein and the right transverse and sigmoid sinuses (oval), suggestive of extensive
cerebral venous thrombosis on the right side. The left venous sinuses are well visualized (arrow). E, MRI reveals significant
right-sided mastoiditis (oval).
and the right transverse and sigmoid sinuses (Figure 3-13D). The patient was treated with heparin
despite the presence of intracerebral hemorrhage (standard treatment). Significant right-sided
mastoiditis was also noted on the MRI (Figure 3-13E); hence an otorhinolaryngology consult was
obtained. It was felt that the mastoiditis was a consequence of cerebral venous thrombosis in this case
rather than the cause. Despite IV heparin and hypertonic therapy, the cerebral edema failed to improve
and her clinical examination deteriorated, leading to hemicraniectomy. Her clinical condition gradually
improved, and she was later discharged to an inpatient rehabilitation facility.
Comment. This case illustrates a typical clinical and radiographic presentation of cerebral venous thrombosis.

Hemorrhagic Stroke
have a sevenfold to tenfold increased to guide the diagnostic evaluation for

risk for ICH. Furthermore, patients who the underlying etiology.
have an ICH associated with oral anti-
coagulant use have a higher mortality Intracerebral Hemorrhage
rate than those with primary ICH.42 It is Secondary to a Neoplastic
expected that the incidence of ICH will or Infectious Process
continue to increase; therefore, depen- The literature on ICH secondary to
dence on neuroimaging will increase underlying infectious or neoplastic
FIGURE 3-14 Radiographic classification of hemorrhagic transformations. A,

Hemorrhagic infarction type 1 with scattered heterogeneous petechiae
along the margins of the infarct (red oval ); B, hemorrhagic infarction
type 2 with more confluent but still heterogeneous petechiae within the infarcted area
(red oval); C, parenchymal hematoma type 1 with a homogeneous hematoma
covering less than 30% of the infarcted area (yellow arrows) and only mild
space-occupying effect (straight blue line); D, parenchymal hematoma type 2 with a
dense hematoma greater than 30% of the lesion volume ( yellow arrows) with
significant space-occupying effect (straight blue line).
41
Modified with permission from Berger C, et al, Stroke. B 2001 American Heart Association, Inc.
stroke.ahajournals.org/content/32/6/1330.full.

KEY POINT
processes is limited to case reports process. Differentiating an infectious h Intracerebral hemorrhage
and series from single centers. The from a neoplastic process based on can also be secondary
most common primary central ner- neuroimaging findings requires knowl- to an underlying brain
vous system infection associated with edge of the clinical history. Findings tumor, either primary or
ICH reported in the literature is suggestive of an underlying infectious metastatic. Overall,
herpes encephalitis. Bacterial endocar- process include a hypointense T2 primary brain tumors are
ditis43 and human immunodeficiency rim around a lesion, leptomeningeal reported to have a lower
virus (HIV)44 are also known risk factors enhancement, the presence of diffu-
rate of intracerebral
for ICH. ICH can also be secondary to hemorrhage as
sion restriction suggesting a cerebral compared to
an underlying brain tumor, either pri- abscess, the presence of subdural em- brain metastases.
mary or metastatic. The literature on pyema, or the presence of mycotic an-
ICH from an underlying neoplastic eurysm (aneurysm arising from infection
process is also very limited. Overall, of the arterial wall). Most brain tumors
primary brain tumors are reported to
are isointense to hypointense on T1 and
have a lower rate of ICH as compared
hyperintense on T2 MRI sequences.
to brain metastases.45 When exclud-
Meningiomas are usually isointense on
ing pituitary adenoma, large retro-
both T1 and T2 MRI sequences. The
spective studies have identified
cystic/necrotic areas usually associated
hemorrhage in 14.6% of autopsy cases
with malignant tumors such as glio-
of patients with brain tumors, with
5.4% being macroscopic. 46 Also, blastoma multiforme are markedly
among the primary brain tumors, ex- hypointense on T1-weighted and hyper-
cluding pituitary adenomas, pilocytic intense on T2-weighted images. On
astrocytoma has the highest hemor- contrast-enhanced MRI, low-grade tu-
rhage rate. The primary determinant mors do not typically exhibit contrast
of hemorrhagic brain metastases is enhancement, while high-grade tumors
the underlying tumor pathology. Thy- often exhibit significant enhancement
roid papillary carcinoma, hepatocellu- because of the blood-brain barrier dis-
lar carcinoma, melanoma, and renal ruption. DSA can sometimes exhibit
cell carcinoma have the highest pro- characteristic tumor blush in the case of
pensity for hemorrhage.45Y47 highly vascular tumors such as
Cerebral edema that is disproportion- hemangioblastomas. Case 3-8 illustrates
ate to the size of ICH on noncontrast some of the neuroradiologic findings
head CT is usually indicative of an in a patient with ICH secondary to
underlying neoplastic or infectious metastatic brain disease.
Case 3-8
An 85-year-old man with a history of hypertension and heart disease was admitted to the stroke
service following an intracerebral hemorrhage manifested by a transient episode of expressive
aphasia. Head CT (Figures 3-15A and 3-15B) and gradient recalled echo (GRE) MRI (Figures 3-15C and
3-15D) showed two distinct areas of hemorrhage, a large left frontal hemorrhage and a smaller right
posterior temporal hemorrhage. Heterogeneous hypointense/hyperintense T2/fluid-attenuated
inversion recovery (FLAIR) (Figures 3-15E and 3-15F) signal and relatively hypointense T1 signal
consistent with an acute hematoma were seen, while the postcontrast images demonstrated contrast
enhancement. Because of concern for a metastatic process, contrast CT of the chest, abdomen, and
pelvis and positron emission tomography (PET) CT were obtained. PET CT (Figure 3-15G) revealed

Hemorrhagic Stroke
FIGURE 3-15 Imaging of the patient in Case 3-8. Head CT (A, B) and gradient recalled echo (GRE) MRI (C, D) show two
distinct areas of hemorrhage, a large left frontal hemorrhage and a smaller right posterior temporal
hemorrhage (A, B, yellow arrows). Heterogeneous hypointense/hyperintense T2/fluid-attenuated inversion
recovery (FLAIR) signal (and relatively hyperintense T1 signal [not shown]) are consistent with a subacute hematoma
(C, D, red ovals), while the postcontrast images (E, F ) demonstrate contrast enhancement (E, F, yellow arrows). Because
of the concern for a metastatic process, contrast CT of the chest, abdomen, and pelvis (not shown) and positron
emission tomography (PET) CT were obtained. PET CT (G) reveals diffuse metastatic disease with multiple lesions noted in
the soft tissue, adrenal glands, lungs, and bones (yellow ovals).
diffuse metastatic disease with multiple lesions noted in the soft tissue, adrenal glands, lungs, and
bones. The patient was later discharged to hospice.
Comment. This case illustrates some of the radiologic features that can be seen in intracerebral
hemorrhage secondary to an underlying neoplastic process. This helps guide further neuroimaging,
management, prognostication, and counseling in these situations.
CONCLUSION in technology, more and more patients

Neuroimaging plays a crucial role in are undergoing noninvasive testing.
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Review Article
Imaging for Adults With

Dr Gregory D. Cascino,
Department of Neurology,
Mayo Clinic, 200 First Street
Seizures and Epilepsy SW, Rochester, MN 55905,

gcascino@mayo.edu.
Samuel Lapalme-Remis, MDCM, MA, FRCPC; Dr Lapalme-Remis reports no
disclosure. Dr Cascino serves
Gregory D. Cascino, MD, FAAN on the board of directors of
the American Academy of
Neurology and as an associate
editor of Neurology. Dr Cascino
ABSTRACT receives royalties from
Purpose of Review: This article discusses structural and functional neuroimaging Mayo Medical Ventures and
UpToDate, Inc.
findings in patients with seizures and epilepsy. The indications for neuroimaging in
Unlabeled Use of
these patients and the potential diagnostic utility of these studies are presented. Products/Investigational
Recent Findings: Patients presenting with new seizures typically require urgent Use Disclosure:
imaging to rule out a critical underlying cause. MRI is the structural neuroimaging Drs Lapalme-Remis and
Cascino report no disclosures.
procedure of choice in individuals with epilepsy. Specific epilepsy protocols should be
considered to increase the diagnostic yield of neuroimaging in patients with structural of Neurology.
lesions associated with focal or generalized seizures. Common epileptogenic path-
ologic processes include mesial temporal sclerosis, malformations of cortical develop-
ment, focal encephalomacia, primary brain tumors, vascular malformations, and
neurocysticercosis. Functional neuroimaging studies are usually restricted to the
evaluation of patients with drug-resistant focal epilepsy who are being con-
sidered for surgical treatment.
Summary: The role of neuroimaging in epilepsy depends on the appropriate clini-
cal indication. In patients without known epilepsy presenting with acute seizures,
structural imaging is essential to rule out an underlying etiology (eg, subdural
hematoma) that may require a specific therapeutic intervention. In individuals with
new or previously uninvestigated epilepsy, MRI serves multiple purposes, including
identifying a causative focal lesion and helping to diagnose the epilepsy type. In a
significant number of patients with epilepsy, the MRI results are normal or reveal
indeterminate findings. For patients with drug-resistant focal epilepsy, functional
neuroimaging techniques, such as fludeoxyglucose-positron emission tomography
(FDG-PET), ictal single-photon emission computed tomography (SPECT), or functional
MRI (fMRI), may assist in surgical planning, especially in patients with MRI-negative
epilepsy, whose prognosis for a seizure-free outcome after surgery is worse than for
patients with an epileptogenic lesion on structural MRI.
INTRODUCTION nosed when any of the following three

The International League Against Epi- conditions are met:
lepsy (ILAE) defines a seizure as “a & The patient has at least two
transient occurrence of signs and/or unprovoked seizures occurring
symptoms due to abnormal excessive more than 24 hours apart.
or synchronous neuronal activity in the & The patient has a single
brain.”1 Seizures indicate brain dysfunc- unprovoked seizure and, upon
tion that may be associated with a focal review of clinical data (which may
or widespread pathology. A practical include imaging data), his or her
clinical definition of epilepsy or a sei- physician estimates that the
zure disorder proposed by the ILAE2 is a likelihood of further seizures over
disease of the brain that may be diag- 10 years is 60% or greater.

Seizures and Epilepsy
KEY POINT
h In the acute setting, & The diagnosis of an epilepsy (2) assessment of patients with epilepsy
the primary purpose of syndrome is confirmed. who are either newly diagnosed or who
structural neuroimaging Once a patient has been determined have long-standing epilepsy but were
in patients with new-onset to have epilepsy or seizures, classifica- never previously investigated with an
seizures is to identify a tion is needed to guide further inves- appropriate imaging modality, and (3)
treatable underlying tigations, treatments, and prognosis. presurgical evaluation of patients with
disease process. According to the proposed 2010 ILAE pharmacoresistant epilepsy.
classification of seizures and epilepsy,
seizures may be classified as general- URGENT ASSESSMENT OF THE
ized, focal, or unknown.3 The classifi- ADULT WITH NEW-ONSET SEIZURES
cation of epilepsies is more complex, Adults presenting with a first seizure
owing to the wide variety of described require urgent medical assessment.
electroclinical syndromes and other This typically occurs in an emergency
epilepsies; one key element is the department or inpatient setting and
underlying cause of epilepsy. Etiologies may be undertaken by an emergency
can be divided into three categories: physician or other non-neurologist,
presumed genetic (previously called sometimes with neurologist consulta-
idiopathic), structural/metabolic (previ- tion. The seizure may represent the first
ously called symptomatic), or unknown event in what will later become epilepsy.
cause (previously called cryptogenic). In the acute setting, however, the ob-
Epilepsy is, therefore, a disease ei- jective is not to diagnose epilepsy but
ther intrinsic to the brain itself or caused to establish whether the seizure was
by a structural or metabolic insult to the provoked by an underlying process that
brain. It is not surprising that imaging further threatens the patient. The sei-
of the seizure-prone brain frequently zure may be the sentinel event in an
reveals abnormalities. Brain imaging undiagnosed systemic disease that
plays an essential role in the workup brings the patient to medical attention
of seizures; it may help confirm the (Case 4-1). Finding an acute structural
seizure or epilepsy type, establish the or metabolic cause for the first sei-
etiology of seizures and direct further zure provides important prognostic
investigations, determine appropriate information to guide triage. Patients
medical treatments, provide information with a first seizure due to stroke,
about prognosis, screen patients for trauma, or central nervous system
epilepsy surgery, and, once a decision infection have a nearly 9 times greater
to investigate a patient for surgery is likelihood of death in the subsequent
made, provide structural and functional 30 days compared to those with un-
data about normal and epileptic tissues provoked seizures.4
that guide decisions to proceed and iden- In the acute setting, the primary
tify what portions of the brain to resect. purpose of structural neuroimaging in
No single imaging study can be ex- patients with new-onset seizures is to
pected to accomplish all of these objec- identify a treatable underlying disease
tives, nor are they all appropriate for a process. An American Academy of
given patient. The purpose of neuroim- Neurology (AAN) evidence-based liter-
aging depends on the clinical scenario. ature review of emergency department
In this review of epilepsy neuroimaging patients presenting with seizure5 con-
in adults, the role of neuroimaging is cluded that one-third to one-half of
presented in three different clinical adult emergency department patients
contexts: (1) urgent assessment of presenting with their first seizure had
patients with new-onset seizures, a head CT abnormality; in 9% to 17%

Case 4-1
A 24-year-old woman with a prior history of urticaria and asthma presented to the emergency
department with a 2-day history of recurrent focal motor seizures involving her right arm that lasted
1 to 2 minutes each. She also reported a moderate left retroorbital headache over this time period.
The patient was alert and oriented. Her heart rate was 110 beats/min and blood pressure was 145/105.
Neurologic examination was unremarkable with the exception of decreased sensation in the medial
aspect of the left hand and right foot. On review of systems, the patient reported a several-week
history of worsening nausea, diarrhea, and weight loss. Approximately 1 month previously, she
had experienced pain and decreased sensation in the distribution of first the left ulnar nerve,
then the right tibial nerve. She had sought medical attention for these symptoms but no diagnosis
was made.
A CT scan of the head was emergently performed and revealed subarachnoid hemorrhage (SAH)
most prominent over the left frontal convexity (Figure 4-1). CT angiogram was unremarkable. Blood
work revealed an eosinophil level of 9500/2L, moderately elevated troponins, an international
normalized ratio (INR) of 1.6, and creatinine of
1.4 mg/dL. CT of the abdomen showed hepatic
and renal infarcts. Eosinophilic granulomatosis
with polyangiitis (Churg-Strauss syndrome) was
suspected, and the patient was loaded with IV
fosphenytoin for her seizures and given
high-dose IV corticosteroids. She was referred to
rheumatology for further treatment after
medical stabilization.
Comment. This patient had systemic
symptoms and mononeuritis multiplex for over
1 month, but the diagnosis of her autoimmune
vasculitis was only made after she developed
seizures and a convexity SAH was discovered
on CT scan, leading to further investigations.
Although her level of consciousness was
normal, red flags included focal-onset seizures,
focal abnormalities on neurologic examination,
headache, hypertension, tachycardia, and
recent history of systemic and neurologic
symptoms. SAH in Churg-Strauss syndrome
represents a rare complication of a rare FIGURE 4-1 Unenhanced head CT of the patient in Case 4-1
showing extensive convexity subarachnoid
disease, but this patient illustrates the hemorrhage, most prominent over the left
importance of obtaining head imaging in frontal lobe and adjacent to the left precentral gyrus, the
patients with unexplained seizures, cause of this patient’s focal motor seizures.
especially when history and examination Courtesy of Carlos Torres, MD, and Michel Shamy, MD, University of Ottawa.
identify one or more red flags.
of all patients, CT findings led to an subdural hematoma, spontaneous in-

acute change of management. The tracranial hemorrhage, stroke, tumor,
panel concluded that emergency CT and brain abscess. Patients with abnormal
scan is possibly useful and may be neurologic examinations, predisposing
considered in all adults with their first histories, or focal seizure onset had a
seizure (Level C evidence). The most higher likelihood of an abnormal CT,
common imaging abnormalities that prompting a Level B recommenda-
led to a change in immediate man- tion that CT should be considered in
agement were traumatic brain injury, such patients.

KEY POINT
h Urgent neuroimaging Urgent neuroimaging following a Among patients presenting with a
following a seizure is seizure is most important with the fol- first generalized seizure, a group of
most important with lowing red flags: recurrent seizures; patients exists who will have returned
the following red flags: focal-onset seizure; persistently altered to baseline and for whom a clear
recurrent seizures; level of consciousness; focal abnormal- provoking factor has been excluded.
focal-onset seizure; ities on neurologic examination; head- These patients do not have epilepsy,
persistently altered level ache; recent head trauma; fever; unless an individual patient’s EEG or
of consciousness; focal hypertension or other vital sign abnor- other clinical data later suggest that
abnormalities on mality; travel to area endemic for he or she is at high risk for recurrent
neurologic examination; cysticercosis; anticoagulant use; and seizures. For these patients, imaging
headache; recent
history of stroke, bleeding disorder, provides benefit, although the urgency
head trauma; fever;
hydrocephalus, human immunodefi- is lower.
hypertension or other
vital sign abnormality;
ciency virus (HIV), immunosuppression, According to the 2007 AAN-American
travel to area endemic malignancy, or other significant concur- Epilepsy Society (AES) Practice Parameter
for cysticercosis; rent illness.5,6 on the evaluation of apparent un-
anticoagulant use; and CT is the mainstay of urgent brain provoked first seizures in adults, the
history of stroke, imaging.7 CT scanning time is rapid, yield of CT or MRI is approximately
bleeding disorder, scanners are widely available, and the 10% and thus imaging should be con-
hydrocephalus, human use of CT is cost-effective in the acute sidered (Level B evidence).8 Neuroim-
immunodeficiency virus, setting. Furthermore, CT is sensitive aging also provides useful prognostic
immunosuppression, for pathologies that are among the information. A separate 2015 AAN-AES
malignancy, or most common causes of acute structural evidence-based guideline found that
other significant
seizures: intracranial blood, gross trau- among patients with an unprovoked first
concurrent illness.
ma, hydrocephalus, and large structural seizure, those with brain imaging abnor-
lesions, such as arteriovenous malfor- malities had a hazard ratio for a
mations (AVMs), tumors, or abscesses. subsequent seizure within 1 to 4 years
Table 4-1 presents pathologies and of 2.44 compared to patients with
associated CT abnormalities found in normal brain imaging, providing Level
patients with provoked seizures. B evidence for increased risk of the
Depending on clinical suspicion, iodine development of epilepsy.9
contrast may increase yield with inclu-
sion of CT angiogram, venogram, or ASSESSMENT OF PATIENTS WITH
contrast-enhanced brain CT studies. ESTABLISHED EPILEPSY
MRI also plays a role in the emer- Of the patients who present with an
gent evaluation of seizures, although unprovoked first seizure, 21% to 45%
the evidence-based review was unable will develop epilepsy in the subse-
to make recommendations because of quent 2 years.3 These patients are
limited data. In patients with red flags, typically referred to a neurologist,
an inconclusive CT scan should prompt who will initiate investigations, includ-
consideration of an emergent brain ing imaging studies. It should be
MRI. MRI provides greater soft tissue noted that in patients with the recent
contrast and may identify pathologies onset of seizures, the line between
missed on CT,7 such as small or hy- patients with established epilepsy and
peracute stroke, embolic shower, cere- those with seizures due to an ongoing
bral venous sinus thrombosis, low-grade structural or metabolic insult may be
tumors, small metastases, posterior blurred. For example, a patient may
reversible encephalopathy syndrome appear to have presumed genetic epi-
(PRES), herpes simplex virus enceph- lepsy, only to be later found to have
alitis, or leptomeningeal disease. a potentially treatable autoimmune

TABLE 4-1 Key Head CT Findings in Etiologies Associated With New-Onset Seizures Due
to Acute Structural, Metabolic, Infectious, or Autoimmune Causes
Noncontrast Contrast CT, CTA,

Acute Pathology CT Findings or CTV Findings Comment
Arterial stroke Dense artery (ie, middle Contrast-enhanced CT: Can CT findings vary greatly
cerebral artery) sign show enhancing vessels based on acuity of stroke
acutely; patchy or gyriform
Loss of gray-white
enhancement may occur
differentiation
in subacute phase
Hypodensity in arterial
CTA: Arterial cutoff
territory with sulcal
effacement
Intracerebral Area of parenchymal CTA: Spot sign may Area of hemorrhage may
hemorrhage hyperdensity with mass indicate active bleeding give strong indication of
effect; clot may have underlying etiology
hypodense areas if
actively bleeding
Intraventricular
hyperdensity in dependent
areas if intraventricular
hemorrhage
Epidural hematoma Hyperdense extraaxial
lens-shaped hematoma that
does not cross suture lines
Subdural hematoma Crescent-shaped extraaxial May cause seizures either in
collection acute or subacute period
Density varies depending
on age of the hemorrhage
Aneurysmal Hyperdensity in basal CTA: Causative aneurysm
subarachnoid cisterns may be seen as an arterial
hemorrhage outpouching, typically at a
May be intraventricular
site of bifurcation
hemorrhage
Convexity Hyperdensity in CTA: Angiopathy may be Underlying causes may
subarachnoid convexity sulci identified depending on include amyloid angiopathy,
hemorrhage underlying etiology venous occlusion, vasculitis,
or reversible cerebral
vasoconstriction syndrome
Cerebral venous May be normal CTV: Empty delta sign of Essential to consider in
thrombosis enhancing dura around young patients with
Subtle venous
a nonenhancing new-onset headache
hyperdensity
sinus thrombus and seizures, especially in
Parenchymal edema may postpartum period
be present and follow
venous territory pattern MRI/MRV should be
performed if venous
thrombosis is suspected
and CT imaging is negative

TABLE 4-1 Key Head CT Findings in Etiologies Associated With New-Onset Seizures Due to
Acute Structural, Metabolic, Infectious, or Autoimmune Causes Continued from page 1455

Arteriovenous Hyperdense calcification CTA: Uniform enhancement Can cause seizure without
malformation and tangle of vessels of tangle of vessels acute hemorrhage
without mass effect
If seizure caused by acute
hemorrhage, typical
arteriovenous malformation
morphology may be obscured
Cavernous May be normal if cavernous CTA: Typically does not May cause seizures with or
malformation malformation is small or show enhancement without hemorrhage
has never hemorrhaged
May be hyperdense from
calcification
After recent hemorrhage,
area of hyperdensity with
associated mass effect and
hypodense edema
Posterior reversible Subtle patchy hypodensities CTA: May show arterial MRI should be performed
encephalopathy with a predilection for tapering and constriction if PRES is suspected and CT
syndrome (PRES) parietooccipital lobes is negative
Traumatic head injury Wide variety of findings CTA: A traumatic arterial Trauma can cause acute
depending on nature of dissection may appear as a seizures by multiple
trauma or injury narrowed and eccentric mechanisms
lumen with increased
Skull fractures may be
external diameter of the
visible on bone window
artery and can be associated
May include subarachnoid with ischemic stroke within
hemorrhage, subdural the affected arterial territory
hematoma, or epidural
hematoma
Cerebral contusions appear
as petechial hemorrhages
Diffuse axonal injury can
cause diffuse swelling with
sulcal effacement
Herpes simplex virus Often normal in early stage Contrast-enhanced CT: MRI should be performed
encephalitis Negative or late patchy if herpes simplex virus
Can show hypodensity
enhancement encephalitis is suspected
and slight mass effect in
and CT is negative
temporal lobe or insula
Meningitis Often normal Contrast-enhanced CT: CT scan cannot reliably
Enhancement over the exclude meningitis
Mild ventricular brain surface extending
enlargement may be into the sulci
present

TABLE 4-1 Key Head CT Findings in Etiologies Associated With New-Onset Seizures Due to
Acute Structural, Metabolic, Infectious, or Autoimmune Causes Continued from page 1456

Abscess CT picture evolves depending Contrast-enhanced CT:
on abscess stage Limited or no enhancement
in early stages; increase
CT may be negative in early
in ring enhancement as
cerebritis or show slight
abscess develops
hypodense mass that
becomes more delineated
as abscess develops
Leptomeningeal May be normal Contrast-enhanced CT: MRI with gadolinium
carcinomatosis May be normal; should be performed
Hydrocephalus with
enhancement of sulci or if suspected
transependymal flow may
basal cisterns
be present Imaging differential
diagnosis includes
sarcoidosis or infectious
meningitic process
(eg, tuberculosis)
Brain metastasis CT findings depend on Contrast-enhanced Although large metastases
tumor type, but masses CT: Usually show may be seen on CT, MRI
usually isodense or enhancement; pattern is needed to further
hypodense to gray matter depends on tumor type characterize lesions
and may identify
Mass effect, perilesional smaller masses not
edema, and possible appreciated on CT
hyperdense hemorrhagic
component may be present
High-grade glioma Typically shows hypodense Contrast-enhanced CT: MRI is needed to
central mass (necrosis) Irregular rim-enhancing further characterize
surrounded by an area pattern lesion prior to biopsy
of higher density, with mass or resection
effect and edema surrounding
the tumor
CT = computed tomography; CTA = computed tomography angiography; CTV = computed tomography venography; MRI = magnetic
resonance imaging; MRV = magnetic resonance venography.
disease. Clinicians must therefore remain patients with acute seizures, imaging
alert for clues pointing to underlying dis- helps establish etiology. If a structural
ease in all epilepsy patients. abnormality is found, serial imaging can
The purposes of neuroimaging in determine whether the lesion is static
patients with new or established epi- or progressive.
lepsy are manifold. In ambiguous cases Imaging may also assist in estab-
without EEG abnormalities, a relevant lishing the diagnosis of certain epilepsy
imaging finding may tip the balance of syndromes, which can have prognos-
probabilities and lead a physician to tic and treatment implications. The
conclude that a patient has epilepsy or 2014 AAN Quality Measurement Set
that an apparently generalized epilepsy Epilepsy Update, which seeks to ad-
is likely to be of focal onset. As in dress gaps in outpatient epilepsy care,

KEY POINTS
h Virtually all adult recommends that epilepsy care pro- CT should only be performed as an
patients with epilepsy viders measure the percentage of all alternative to MRI in resource-poor
should have at least one visits in which seizure type and epilepsy settings or when technical barriers
MRI in the course of etiology or syndrome are either inves- to MRI exist, such as a patient with a
their evaluation. tigated or documented. MRI is a key pacemaker. CT may be useful as an
h A tailored specific brain testing modality that may be ordered or adjunct in limited cases, for example,
MRI epilepsy protocol reviewed for this purpose.10,11 in the evaluation of cortical calcifica-
study in individuals with Finally, in patients who have pharma- tions. Skull-base CT may identify a
focal seizures should be coresistant epilepsy and are potential temporal encephalocele, an increas-
performed to improve surgical candidates, imaging has a differ- ingly appreciated cause of temporal
detection of common ent set of applications that are discussed epilepsy sometimes seen in patients
pathologic findings later in this article. with a history of head trauma.15
underlying the In the nonurgent setting, MRI is the MRI is especially helpful in patients
epileptogenic zone. most useful diagnostic imaging modal- with focal seizures. A tailored specific
h A three-dimensional ity. It became clear early in its adop- brain MRI epilepsy protocol study in
T1-weighted volumetric tion that the sensitivity and specificity individuals with focal seizures should
acquisition with of MRI for focal epilepsy surpasses any be performed to improve detection of
isotropic voxel size of other imaging technique, although its common pathologic findings underly-
1 mm or 1.5 mm
yield varies considerably depending ing the epileptogenic zone (Table 4-2).
enables the flexible
on the underlying pathology, magnetic Given its superior sensitivity over 1.5T,
reconstruction of
images; this is especially
field strength (ie, 1.5T versus 3T), MRI especially in malformations of cortical
helpful for the sequences used, and experience of the development,16 use of a 3T MRI is recom-
evaluation of structural interpreting radiologist.12 CT scan is mended. T1-weighted, T2-weighted,
lesions such as focal insensitive, especially in patients with and fluid-attenuated inversion recovery
cortical dysplasias. a normal neurologic examination. The (FLAIR) sequences in coronal or oblique-
yield of CT is often less than 30% in coronal, axial, and sagittal planes should
unselected patients with epilepsy, and be acquired. A three-dimensional T1-
it may fail to pick up abnormalities in weighted volumetric acquisition with
approximately 50% of patients with isotropic voxel size of 1 mm or 1.5 mm
small structural lesions detectable on enables the flexible reconstruction of
MRI. Its sensitivity is especially poor in images; this is especially helpful for the
mesial temporal sclerosis because of evaluation of structural lesions such as
the proximity of the implicated struc- focal cortical dysplasias.17
tures to the bony temporal fossa.13 Additional tailoring is helpful when
Virtually all adult patients with epi- a specific etiology in suspected. For ex-
lepsy should have at least one MRI in ample, in patients with suspected mesial
the course of their evaluation. The 1997 temporal lobe epilepsy, coronal slices
ILAE Commission Report on Recom- perpendicular to the long axis of the
mendations for Neuroimaging of Pa- hippocampus are crucial; if a lesion
tients With Epilepsy recommends an containing hemosiderin or calcium is
imaging study for all adult patients suspected, T2* gradient recalled echo
with epilepsy, with only the possible (GRE) or susceptibility-weighted im-
exclusion of patients with a definite aging (SWI) will improve yield.18
electroclinical diagnosis of a genetic
generalized epilepsy syndrome, such MAGNETIC RESONANCE
as juvenile myoclonic epilepsy. 14 IMAGING
In practice, however, even these In both generalized and focal epilepsy,
patients are frequently imaged at MRI is the most helpful structural
epilepsy centers. imaging modality.

KEY POINT
TABLE 4-2 Standard Magnetic Resonance Imaging Epilepsy Protocola h Mesial temporal
‘‘Three-Dimensional Epilepsy Study’’ Used at Mayo Clinic lobe epilepsy is the
most common
b Imaging Sequences surgically remediable
epileptic syndrome.
Scout
Sagittal T1-weighted fluid-attenuated inversion recovery (FLAIR)
Axial two-dimensional T2-weighted fast spin echo with fat saturation
Coronal two-dimensional FLAIR with fat saturation
Sagittal sampling perfection with application-optimized contrasts using
different flip angle evolutions (SPACE) double inversion recovery (DIR)
Sagittal magnetization-prepared rapid-acquisition gradient-echo
(MPRAGE) imaging
Small-field-of-view coronal SPACE FLAIR
Axial diffusion-weighted imaging (DWI)
Axial susceptibility-weighted imaging (SWI)
a
3T, 1.5-mm temporal lobe sections.
Generalized Epilepsy seizure disorders. Mesial temporal lobe

Although imaging is most helpful with epilepsy is the most common surgically
focal epilepsy, adults with generalized remediable epileptic syndrome.20 Me-
epilepsy also have a high rate of MRI sial temporal sclerosis, which encom-
abnormalities and, as a general rule, passes hippocampal sclerosis, is the
should undergo MRI at least once. A most frequent pathology associated
prospective MRI study of patients with with pharmacoresistant mesial tempo-
presumed genetic generalized epilepsy ral lobe epilepsy. In addition to hippo-
revealed abnormalities in 24% of pa- campal sclerosis, patients with mesial
tients, although 88% of these were temporal sclerosis have pathologic
thought to be nonspecific. The most changes in other mesial temporal lobe
common abnormalities were reduced structures, such as the amygdala and
hippocampal volumes, basal ganglia entorhinal cortex. Hippocampal sclero-
abnormalities, ventricular abnormali- sis is identified in approximately 40%
ties, and diffuse cortical atrophy.19 of temporal lobe specimens surgically
resected for epilepsy.21 Mesial tempo-
Focal-Onset Epilepsy ral sclerosis may coexist with another
It is with focal epilepsy that MRI is most epileptogenic lesion, so-called dual
useful. Focal seizures are due to an pathology. Pathologically, hippocampal
abnormality in a specific region of the sclerosis is characterized by neuronal
brain, which is often visible on struc- cell loss, gliosis, and granule cell dis-
tural imaging. The nature of this lesion persion.22 Many patients with mesial
has critical implications for prognosis temporal sclerosis had febrile sei-
and treatment. zures or other cerebral insults early
Mesial temporal sclerosis. MRI is in life23; however, the nature of these
pivotal in the diagnostic evaluation associations remains controversial. Pa-
and treatment of patients with focal tients with intractable mesial temporal

KEY POINT
h Thin coronal slices lobe epilepsy are often good surgi- of normal variation or patient position-
through the long axis cal candidates, with reported rates ing, simple visual inspection can be
of the hippocampus of seizure freedom in the 60% to misleading in subtle cases; quantitative
improve MRI detection 80% range.24,25 hippocampal volumetric studies in pa-
of typical abnormalities Structural MRI is sensitive for the tients with mesial temporal sclerosis are
in individuals with detection of mesial temporal sclerosis most objective and can improve yield.27
pathologically verified (Case 4-2 and Table 4-326). Thin Increased signal intensity is seen on
mesial temporal sclerosis. coronal slices through the long axis T2-weighted and decreased intensity
of the hippocampus improve detec- on T1-weighted images. Loss of inter-
tion of typical abnormalities in in- nal hippocampal structure may also be
dividuals with pathologically verified seen. Less-specific associated findings
mesial temporal sclerosis. Most specific include asymmetry of the lateral ven-
is hippocampal atrophy, in which the tricle horns and atrophy of the ipsilat-
natural oval shape of the hippocampus eral anterior temporal lobe, fornix, or
is lost and becomes flattened. Because mammillary body.
Case 4-2
A 32-year-old right-handed man presented with recurrent and unprovoked clinical events associated
with a rising abdominal sensation, word-finding difficulties, and loss of awareness. He had a history of
a prolonged febrile seizure in childhood. A routine EEG showed left anterior temporal sharp waves.
Brain MRI showed left hippocampal formation atrophy with increased signal intensity alteration
(Figure 4-2). He was diagnosed as experiencing focal dyscognitive seizures and started on an
antiepileptic drug with an initial reduction in seizure frequency. The focal seizures ultimately were
shown to be refractory to multiple antiepileptic drugs.
FIGURE 4-2 MRI findings of of the patient in Case 4-2 with mesial temporal sclerosis. A, Oblique-coronal T1-weighted
brain MRI reveals unilateral hippocampal formation atrophy involving the left temporal lobe (arrow). B,
Coronal fluid-attenuated inversion recovery (FLAIR) sequence shows prominent increased left hippocampal
signal intensity (arrow). C, Axial T1-weighted brain MRI reveals unilateral hippocampal formation atrophy involving the left
temporal lobe (arrow).
Comment. This patient has a drug-resistant focal seizure disorder related to mesial temporal
sclerosis, indicating a potentially surgically remediable epileptic syndrome.
A comprehensive presurgical evaluation, including long-term video-EEG monitoring, is required for
seizure localization. Individuals with focal seizures associated with mesial temporal sclerosis may be
good candidates for epilepsy surgery and are likely to experience a seizure-free outcome.

KEY POINTS
TABLE 4-3 Magnetic Resonance Imaging Characteristics of h Because of normal

Mesial Temporal Sclerosisa variation or patient
positioning, simple
Feature Description visual inspection can be
misleading in subtle
Hippocampal The most specific and reliable feature, hippocampal
atrophy atrophy, is defined by comparing the hippocampal cases of hippocampal
circumference on each side on all available coronal slices. atrophy; quantitative
Small asymmetries can be present because of normal hippocampal volumetric
variation or a tilted position in the scanner, and should studies in patients with
not be considered abnormal. It is important to evaluate mesial temporal
the shape of the hippocampus as well. A normal sclerosis are most
hippocampus is oval. In the presence of hippocampal objective and can
sclerosis, it becomes flattened and usually inclined. improve yield.
Increased T2 In isolation, increased T2 signal may be insufficient to h When a patient with
signal diagnose hippocampal sclerosis. focal-onset epilepsy is
T2 mapping (relaxometry) is an objective method for found to have a normal
measuring abnormal T2 signal, which may be difficult to MRI, an undetected
detect visually. focal cortical dysplasia is
typically considered to
Loss of internal This is usually associated with atrophy and hyperintense
structure T2 signal. The loss of normal internal hippocampal be the most likely
structure is a consequence of neuronal loss and gliosis underlying lesion.
with a collapse of pyramidal cell layers that is h Key MRI features of
characteristic of hippocampal sclerosis. focal cortical dysplasia
Other features Asymmetry of the horns of the lateral ventricles (which is type I include blurring of
variable and may lead to false lateralization) and atrophy of the the gray-white junction,
anterior temporal lobe (which is nonspecific) may be present. abnormal gyral or sulcal
patterns, lobar or
Atrophy of the fornix and mammillary body ipsilateral to
the hippocampal sclerosis may also be present. sublobar hypoplasia or
atrophy, and subcortical
a
Reprinted with permission from Cendes F, Continuum (Minneap Minn).26 B 2013 American Academy white matter volume
of Neurology. journals.lww.com/continuum/Fulltext/2013/06000/Neuroimaging_in_
loss with increased
Investigation_of_Patients_With.11.aspx.
T2/decreased T1 signal.
Malformations of cortical develop- neurons with or without balloon cells

ment. Focal cortical dysplasia is an (focal cortical dysplasia type II), or
abnormality of neocortical develop- association with another lesion type
ment and may be found in the tempo- (focal cortical dysplasia type III), such
ral lobes (20% of temporal lobe as hippocampal sclerosis or vascular
epilepsy) or any other region of the malformations. Further subclassifica-
cortex (Figure 4-3 and Table 4-428). It tions are based on specific pathologic
represents approximately one-fourth of characteristics.28
focal epilepsies and is strongly epilep- MRI characteristics of focal cortical
togenic, leading to intractable epilepsy dysplasia vary by type and subtype.30
in approximately three-fourths of pa- For example, cortical thickness may
tients.29 Pathologically, focal cortical be decreased in focal cortical dysplasia
dysplasia is highly variable and may be type I but increased in focal cortical
characterized by aberrant lamination dysplasia type II. MRI may also fail to
of the neocortex (focal cortical dyspla- pick up focal cortical dysplasia pathol-
sia type I), presence of dysmorphic ogy altogether because of insufficient

FIGURE 4-3 Coronal T1 inversion recovery (A, B) and coronal (C, D) and axial (E, F )
fluid-attenuated inversion recovery (FLAIR) images showing typical changes
of focal cortical dysplasia type IIb (arrows). Diagnosis was confirmed in
the postoperative histopathology in a patient with refractory focal seizures with
temporoinsular symptomatology. Note area of cortical thickening and loss of sharpness of the
cortico-subcortical transition (blue arrows) and cortico-subcortical signal changes (increased
FLAIR signal and decreased T1 signal) below the area of cortical thickening that extends
toward the ventricle (transmantle sign) (red arrows).
Reprinted with permission from Cendes F, Continuum (Minneap Minn).26 B 2013 American Academy of
Neurology. journals.lww.com/continuum/Fulltext/2013/06000/Neuroimaging_in_Investigation_of_Patients_With.11.aspx.

TABLE 4-4 Summary Classification and Magnetic Resonance Imaging Findings of Focal
Cortical Dysplasiaa,b
Type of Focal Histologic

Cortical Dysplasia Characteristics MRI Features
Ia Abnormal radial cortical Mild hemispheric hypoplasia; areas with thin cortex;
lamination blurring of the gray-white matter junction; abnormally
shaped sulci and sometimes deep sulci; MRI results are
Ib Abnormal tangential often negative; MRI cannot differentiate these subtypes
cortical lamination
Ic Abnormal radial and
tangential cortical
lamination
IIa Dysmorphic neurons Gradient of morphologic changes: from dysplastic
without balloon cells lesions that can be easily identified by conventional
MRI techniques to minor structural abnormalities,
including small areas of discrete cortical thickening or
blurring of the gray-white matter interface that often
go unrecognized; sometimes subtle hyperintense T2
signal in the subcortical and deep white matter
IIb Dysmorphic neurons with Increased T2 or fluid-attenuated inversion recovery
balloon cells (FLAIR) signal in the subcortical white matter underneath
the focal cortical dysplasia; transmantle sign (tapering
of abnormal white matter signal from cortex to ventricle
surface); blurring of the gray-white matter junction;
increased cortical thickness; deep sulci; abnormal
cortical gyration and sulcation
IIIa Architectural abnormalities Variable combination of MRI features of focal cortical
associated with dysplasia described above and the associated lesion,
hippocampal sclerosis which is most frequently in the same lobe/region
IIIb Architectural abnormalities
adjacent to tumors
IIIc Architectural abnormalities
adjacent to vascular
malformation
Architectural abnormalities
IIId
adjacent to lesions acquired early
in life (eg, trauma, ischemic injury,
encephalitis)
MRI = magnetic resonance imaging.
a
Data from Blümcke I, et al, Epilepsia.28 onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2010.02777.x/full.
b
Reprinted with permission from Cendes F, Continuum (Minneap Minn).26 B 2013 American Academy of Neurology. journals.lww.com/
continuum/pages/articleviewer.aspx?year=2013&issue=06000&article=00011&type=abstract.
resolution or suboptimal sequence selec- Key MRI features of focal cortical

tion. When a patient with focal-onset dysplasia type I include blurring of the
epilepsy is found to have a normal MRI, gray-white junction, abnormal gyral
an undetected focal cortical dysplasia or sulcal patterns, lobar or sublobar
is typically considered to be the most hypoplasia or atrophy, and subcor-
likely underlying lesion (Case 4-3). tical white matter volume loss with

KEY POINT
h Focal cortical dysplasia
type II often shows
Case 4-3
A 33-year old woman had sleep-related hypermotor epilepsy that was associated
apparent increased
with drug-resistant focal seizures. Routine EEG recordings were unremarkable.
cortical thickness (better
Brain MRI showed a right hemisphere focal abnormality consistent with a
seen on T1-weighted
malformation of cortical development (Figure 4-4). The patient subsequently
sequences), blurring of
underwent a focal cortical resection for pharmacoresistant epilepsy after
the gray-white junction,
long-term intracranial EEG monitoring. She experienced a reduction in
and an increased T2
seizure frequency. The pathologic findings revealed focal cortical dysplasia.
and decreased T1 signal
Comment. This patient had drug-resistant focal epilepsy related to a
in the subcortical
malformation of cortical development.
white matter.
FIGURE 4-4 Sagittal T1-weighted brain MRI of the patient

in Case 4-3 shows a focal lesion in the right
hemisphere consistent with polymicrogyria
(arrow).
increased T2/decreased T1 signal. Focal dysplasia type IIa (dysmorphic neu-

cortical dysplasia type II often shows rons without balloon cells).28
apparent increased cortical thickness Other malformations of cortical
(better seen on T1-weighted sequences), development associated with epi-
blurring of the gray-white junction, and lepsy include tuberous sclerosis,
an increased T2 and decreased T1 schizencephaly, periventricular nodular
signal in the subcortical white matter. heterotopia, subcortical heterotopia,
The increased signal may taper off in polymicrogyria, lissencephaly, sub-
the white matter closer to the ventricle; cortical band heterotopia, and
this is the so-called transmantle sign,31 hemimegalencephaly (Figure 4-5, Fig-
seen almost exclusively in focal cortical ure 4-6, and Figure 4-7). These typi-
dysplasia type IIb (dysmorphic neu- cally present early in life and may
rons with balloon cells). Type IIb may be associated with developmental
also be more often associated with delay; however, as with focal cortical
deep sulci and abnormal gyral and dysplasia, patients with milder forms
sulcal patterns and is more easily of some malformations of cortical
identified on MRI than focal cortical development may have normal or

FIGURE 4-5 Tuberous sclerosis. Head CT shows subependymal calcifications (A). Oblique-coronal T1-weighted (B) and
axial fluid-attenuated inversion recovery (FLAIR) (C ) brain MRIs show multiple cortical tubers (B, C, arrow).
near-normal cognitive development etiologies is a common cause of epi- KEY POINT

and present later in life only with focal lepsy (Figure 4-8). In patients presenting h In patients presenting
epilepsy.32 to a first-seizure clinic, encephalomalacia to a first-seizure clinic,
Encephalomalacia. Encephalomalacia encephalomalacia
and gliosis were the most common pre-
and gliosis were the
due to remote brain injuries of various sumed epileptogenic MRI lesions.33 On
most common
presumed epileptogenic
MRI lesions.
FIGURE 4-6 Imaging of a patient with drug-resistant focal

epilepsy and bilateral periventricular gray
matter heterotopias. Oblique-coronal
T1-weighted brain MRI shows the heterotopic gray
matter (arrows).

quences may show hypointensity, sug-

gesting remote hemorrhage.
The location of encephalomalacia
gives a clue as to its etiology. Involvement
of the bifrontal or temporal poles sug-
gests remote traumatic brain injury.
Unsurprisingly, posttraumatic epilepsy
is most often localized to the temporal
lobes, where it frequently coexists with
mesial temporal sclerosis.34 Areas of
encephalomalacia corresponding to an
arterial territory suggest remote ische-
mic stroke. Gliosis from congenital
stroke, whether venous, arterial, or hem-
orrhagic, is often associated with a
porencephalic cyst and may be strongly
epileptogenic.35
Low-grade primary brain tumors.
Intracranial tumors are an important
cause of epilepsy. Most tumors fol-
lowed in epilepsy clinics are static or
slow growing, evolving over years or
FIGURE 4-7 Imaging of a patient with drug-resistant decades. Aggressive primary tumors
focal epilepsy and septooptic dysplasia. and metastases may also cause seizures,
Oblique-coronal T1-weighted brain MRI reveals
perisylvian polymicrogyria (arrow) in the right cerebral but the need for treatment of the tumor
hemisphere and absence of the septum pellucidum. itself requires a different approach.
Low-grade gliomas typically cause focal
seizures as their presenting symptom,
MRI, gliosis appears as an area of T1 and epilepsy is medically intractable in
hypointensity and T2/FLAIR hyperin- about half of patients. Gangliogliomas
tensity with associated volume loss. and dysembryoplastic neuroepithelial
When caused by trauma, T2* GRE se- tumors, also referred to as DNETs,
FIGURE 4-8 Imaging of a patient with prior traumatic brain injury (hit in the head with a baseball) and focal epilepsy. A,
Oblique-coronal T1-weighted brain MRI shows a region of encephalomalacia related to a prior hemorrhage
(arrow). B, Sagittal T1-weighted brain MRI shows the focal abnormality (arrow). C, Axial fluid-attenuated
inversion recovery (FLAIR) sequence shows encephalomalacia and gliosis (arrow).

KEY POINT
are the most frequently encountered they may display variability on imaging, h Gangliogliomas and
primary brain tumors in patients with typical MRI characteristics include cor- dysembryoplastic
focal seizure disorders. tical location, absence of mass effect, or neuroepithelial tumors
Gangliogliomas are discrete tumors edema, with some tumors displaying a are the most frequently
composed of abnormal neuronal and classic pseudocystic or multicystic encountered primary
glial cells with a predilection for the “bubbly” appearance that is hypointense brain tumors in
temporal lobes, where they frequently on T1-weighted images and hyperintense patients with focal
cause intractable epilepsy in children on T2-weighted images.38 seizure disorders.
or young adults. On MRI, they are Diffuse low-grade gliomas, which in-
typically isointense to gray matter clude grade II astrocytomas, oligoden-
without mass effect and commonly drogliomas, and oligoastrocytomas,
associated with a cystic component.36 also cause seizures in a high propor-
Dysembryoplastic neuroepithelial tution of patients. These seizures are
mors are static or slowly progressive difficult to fully resect and can prog-
benign tumors most often found in ress to higher-grade tumors, threat-
superficial cortical regions of the frontal ening patient survival. 39 On MRI,
or temporal lobes and usually cause low-grade gliomas are typically iso-
epilepsy as their sole manifestation intense to hypointense on T1-weighted
(Figure 4-9). Rare cases of malignant images and hyperintense on T2-weighted
transformation are reported.37 Although images, usually without edema or mass
FIGURE 4-9 Imaging of a patient with focal epilepsy.

Axial fluid-attenuated inversion recovery
(FLAIR) sequence shows a focal lesion
in the right parietooccipital lobe consistent with a
dysembryoplastic neuroepithelial tumor that was confirmed
at surgery.

effect. Most low-grade gliomas do not with sclerotic brain tissue; they are
enhance with gadolinium, although likely formed in utero but continue to
this can be seen with oligodendro- evolve throughout life. Although their
gliomas. About one-fifth of low-grade most feared complication is intracere-
gliomas contain calcifications, which bral hemorrhage, AVMs may cause
appear as hyperintense T1 and hypo- seizures outside the context of acute
intense T2 signals.40 bleeding in approximately 30% of pa-
Meningiomas (Figure 4-10) are com- tients (Figure 4-11).42 On MRI, AVMs
mon extraaxial, usually benign, tumors. may appear as a tangle of flow voids.
Although they are often asymptomatic Gliosis adjacent to and within the AVM
and can be found incidentally on MRI, may appear as T2/FLAIR hyperintensity.
seizures caused by meningiomas are T2* GRE or SWI may identify hemosid-
well described. It is essential not to erin from prior bleeding. The flow
dismiss a meningioma as a possible dynamics of the AVM can be evaluated
cause of seizures, as resection cures with time-resolved magnetic reso-
epilepsy in a majority of cases. On the nance angiography (MRA), although
other hand, patients without preoper- conventional angiography is the gold
ative seizures not infrequently have standard.43
new-onset seizures after resection.41 Cavernous malformations (often re-
Classic MRI findings include intense ferred to as cavernous hemangiomas
homogenous gadolinium enhancement or cavernomas) are composed of im-
and the presence of a dural tail. mature multilobulated endothelium-
Intracranial vascular abnormalities lined caverns that may evolve over
including vascular malformations and time (Figure 4-12). The most common
cavernous malformations. AVMs are vascular anomalies associated with
dynamic bundles of abnormal vessels epilepsy are cavernous malformations.
linked to each other via fistulae without Seizures are the most common clin-
intervening capillary beds interposed ical presentation, although asymptom-
atic cavernous malformations are often
seen incidentally. They are thought
to cause epilepsy due to perilesional
hemosiderin deposition. The “pop-
corn” appearance of a multicystic lesion
with various signal intensities due to
the variable age of blood products
is classic. GRE sequences should in-
dicate a hypointense hemosiderin
ring. Resection is curative of epilepsy
in only about 75%, suggesting that the
epileptogenic zone may extend be-
yond the borders of the lesion as seen
on MRI.44
FIGURE 4-10 Imaging of a patient with focal epilepsy Central nervous system infections
of right temporal lobe origin related to
a meningioma. Oblique-coronal including neurocysticercosis and tu-
T1-weighted brain MRI following gadolinium berculosis. Neurocysticercosis is a par-
administration shows a skull base meningioma involving
the right cavernous sinus. asitic infection caused by Taenia solium
larvae, which can infect the brain, and is

FIGURE 4-11 Imaging of a patient with focal epilepsy
related to an arteriovenous malformation.
Sagittal T1-weighted brain MRI following
gadolinium administration shows a focal lesion in the left
cerebral hemisphere consistent with an arteriovenous
malformation.
the most common cause of acquired

epilepsy in endemic regions of the de-
veloping world.45 MRI findings depend
on the life stage of the invading parasite.
During the vesicular stage, the living
parasite may be visualized with a scolex
(head) discernible within a thin-walled
cyst containing fluid isointense to CSF.
As the cyst begins to degenerate and
the colloidal vesicular stage develops,
gadolinium ring enhancement and a
parenchymal inflammatory response
characterized by edema surrounding
the cyst develop. Further changes occur
through the granular nodular stage until
the cyst reaches the nodular calcified
stage, which is the final chronic state of
a nonviable parasite. This stage is
characterized by resolution of edema
and hypointensity on T1- and T2-
weighted images that is easily missed
on MRI unless GRE sequences are used FIGURE 4-12 Imaging of a patient with focal epilepsy
to identify blooming; CT scan is supe- related to a cavernous malformation.
Axial T1-weighted brain MRI shows a
rior for detection at this stage and focal lesion in the left cerebral hemisphere consistent with
shows the lesions as nonenhancing a cavernous malformation (arrow).
hyperdense calcified nodules.

The World Health Organization dom with antiepileptic drugs. The

indicated in 2015 that there were remaining one-third have pharma-
9.6 million new cases of Mycobac- coresistant or drug-resistant epilepsy.48
terium tuberculosis in the world.46 A patient is defined as pharmaco-
Approximately 1% of all individuals resistant after he or she has been tried
infected with tuberculosis and 5% to on a sufficient dose of two appropriate
10% of those with extrapulmonary antiseizure medications yet continues
disease have central nervous system to have seizures.49 Further attempts to
involvement, which may cause seizures achieve seizure control with medica-
or epilepsy. Central nervous system tions are overwhelmingly likely to fail.50
involvement may include meningitis, Such patients should be referred to an
intracranial tuberculoma, brain ab-
epilepsy center for further evaluation.
scess, spinal tuberculoma, Pott disease, Patients with pharmacoresistant fo-
or vasculopathy (Figure 4-13 and
cal epilepsy may be candidates for re-
Figure 4-14).47
section of an epileptogenic lesion.
Approximately half of all patients who
EVALUATION OF PATIENTS undergo epilepsy surgery will remain
WITH PHARMACORESISTANT seizure free after 10 years,51 although
EPILEPSY this proportion is higher in some patient
Approximately two-thirds of patients groups. Imaging provides important
with epilepsy will achieve seizure free- data in predicting surgical success;
FIGURE 4-13 Imaging of a patient from India with

headache, focal epilepsy, and chronic
meningitis. Oblique-coronal T1-weighted
brain MRI following gadolinium administration shows
a focal enhancing lesion in the left cerebral hemisphere
with thickening of the dura (arrow). The diagnosis of
tuberculosis was made on axillary lymph node biopsy.

KEY POINT
h Imaging provides
important data in
predicting surgical
success; among the
factors cited as
improving surgical
outcome in a 2015
Cochrane Review were
concordance of
preoperative MRI and
EEG findings, the
presence of mesial
temporal sclerosis or
tumor, the absence of
focal cortical dysplasia
or malformation of
cortical development,
and an abnormal
preoperative MRI.
FIGURE 4-14 Imaging of a patient from Somalia who

presented with headache, nausea, somnolence,
focal weakness, and seizures. Axial
T2-weighted brain MRI shows a focal lesion with significant
mass effect and vasogenic edema in the right cerebral
hemisphere. An intracranial tuberculoma was removed.
among the factors cited as improving seizure onset; this electroclinical cor-
surgical outcome in a 2015 Cochrane relation reinforces the epileptogenicity
Review were concordance of preopera- of an imaging abnormality.
tive MRI and EEG findings, the presence The required imaging modalities are
of mesial temporal sclerosis or tumor, highly individualized. In right-handed
the absence of focal cortical dysplasia or patients with clear mesial temporal scle-
malformation of cortical development, rosis of the right temporal lobe concor-
and an abnormal preoperative MRI.52 dant with symptomatology and EEG
Indeed, absence of an MRI abnor- data, a single MRI may be sufficient
mality presents a challenge to resec- for temporal lobectomy. In other pa-
tion. Patients with focal epilepsy but tients, especially with extratemporal
no apparent MRI abnormality have or MRI-negative epilepsy, identifying
been referred to as being “nonlesional.” and resecting the seizure focus is more
Because these patients often do have challenging and can require multiple
brain lesions not discernable on MRI complementary imaging approaches.
but identified on postsurgical pathology,
the alternative term MRI-negative epi- Magnetic Resonance Techniques
lepsy has been proposed.53 Structural MRI remains the mainstay
In the evaluation of patients who of presurgical planning. In addition to
are pharmacoresistant, imaging may identifying and characterizing lesions,
be either structural or functional. It MRI establishes the location of the
supplements symptomatology and lesion as well as its proximity and rela-
EEG to establish the likely location of tion to important anatomic structures

KEY POINT
h Functional MRI may containing potentially eloquent cortex, functional topography. 55 Invasive
map sensory and motor for example, the precentral gyrus presurgical electrocortical stimulation
functions, which may containing the motor strip or the mapping is the gold standard in such
be unpredictable when calcarine cortex containing the primary situations, however.
eloquent cortex is visual cortex. Failure to consider such Diffusion tensor imaging. Diffusion
adjacent to or even structures can lead to devastating defi- tensor imaging (DTI) is an emerging
contained within a cits following resection. magnetic resonance technique used to
lesion, causing Some cortical functions, such as identify important structures for surgery
altered anatomic or language and verbal memory, are less that also has a role in epilepsy diagnosis.
functional topography. consistently localized in the same area DTI measures the characteristics and
of cortex across different patients. direction of water diffusion within the
Predictive localization of language is brain, which can be used to map white
even more perilous in patients with matter tracts in three dimensions
epilepsy, given the higher prevalence of (called tractography) as well as offer
atypical localizations due to cortical information on parenchymal micro-
reorganization.54 structural changes.
Functional magnetic resonance Tractography is a method of non-
imaging. Functional MRI (fMRI) is a invasively identifying white matter
noninvasive test that can localize spe- tracts such as the corticospinal tracts
cific functions within an individual or the optic radiations. If performed
patient. fMRI detects relative changes prior to surgery and integrated into neu-
in focal blood oxygen levels that occur ronavigation systems, DTI tractography
over time while the patient is given a offers the possibility of predicting the
protocoled computerized task testing likelihood of a postoperative deficit or
specific brain functions that is alter- even guiding the surgeon away from
nated with rest or control tasks. Since critical areas. In epilepsy surgery, per-
focal areas of the brain must increase haps its most promising application at
their neural activity more to perform present is in identifying the Meyer loop
the task relative to other areas, a time prior to an anterior temporal resec-
series can be produced in which each tion, which causes a contralateral
voxel reflects a correlation with the superior quadrantopia in approxi-
task at that moment and is represented mately 10% of patients.57
visually with high spatial resolution Epileptogenic zones represent dis-
onto the brain.55 If protocoled lan- eased tissue, and a variety of micro-
guage tasks are given during the fMRI, structural changes occur in these regions
language function can be lateralized that alter water diffusion and can give
and localized to guide resection. fMRI rise to DTI abnormalities. Although
is, to some extent, replacing the inva- beyond the scope of this review, DTI
sive Wada test (intracarotid amobarbital is a promising experimental technique
test) for language lateralization. The that may help in the future to identify
two tests agree in 94% of patients with the epileptogenic zone in patients who
clear left-hemisphere language domi- are MRI negative.
nance, although agreement is lower
in patients with atypical language FUNCTIONAL NEUROIMAGING
localizations.56 fMRI may map sensory Positron emission tomography (PET)
and motor functions, which may be and single-photon positron emission
unpredictable when eloquent cortex tomography (SPECT) are functional neu-
is adjacent to or even contained within roimaging modalities that may localize
a lesion, causing altered anatomic or a focal abnormality for surgical planning

KEY POINT
in patients with pharmacoresistant epi- pine receptors has been found to be h In most patients
lepsy. A decaying radioactive tracer decreased in epileptogenic regions, with temporal lobe
tagged to a physiologic ligand is admin- with the area of 11C-FMZ tracer uptake epilepsy, temporal
istered intravenously and binds to tar- appearing smaller on 11C-FMZ-PET hypometabolism has
geted areas. As it decays, it emits gamma than the corresponding area of hy- been found to accurately
rays that are detected by a scanner, and pometabolism seen on FDG-PET. lateralize to the temporal
their location can be visually depicted In theory, this would suggest that lobe with EEG
and mapped onto structural images. a resectable lesion could be more abnormalities and is
Depending on the nature of the probe, precisely delineated using this tech- associated with good
surgical outcomes,
the concentration of the tracer in certain nique. In practice, however, 11C-FMZ-
even when MRI
regions can reveal differential localiza- PET presents technical challenges for
is negative.
tion of specific physiologic functions. clinical use60 and results have been in-
consistent; its role in presurgical work-
Positron Emission Tomography up is not established.
PET scans in epilepsy most frequently
use fludeoxyglucose (FDG) as a ligand Single-Photon Emission
to measure differential glucose con- Computed Tomography
sumption as a surrogate for metabolism. SPECT measures cerebral blood flow
A key concept is that FDG-PET mea- via the injection of a radiotracer such as
sures interictal brain metabolism and technetium-99m-hexamethylpropylene
that the epileptogenic zone is hypomet- amine oxime (99mTc-HMPAO) with
abolic when not seizing, for reasons rapid uptake within the brain (30 to
that have not been clearly elucidated. 60 seconds from injection) but a long
FDG-PET has been found to be half-life. The area of rapid uptake re-
most useful in temporal lobe epilepsy. flects regional blood flow at the time of
In most patients with temporal lobe the injection, providing a snapshot of
epilepsy, temporal hypometabolism cerebral activity at that moment. The
has been found to accurately later- long half-life allows time for data ac-
alize to the temporal lobe with EEG quisition scanning within 4 hours of
abnormalities and is associated with the injection.
good surgical outcomes, even when In practice, in contrast to PET,
MRI is negative (Case 4-4). 58 PET SPECT identifies the location of ictal
does not provide a clearly delineated activity that is characterized by in-
lesion to the surgeon, as the region creased cerebral perfusion. To achieve
associated with hypometabolism usually this, the radiotracer must be prepared
extends beyond the epileptogenic zone. in advance and be ready at bedside in
FDG-PET is less sensitive in patients with an epilepsy monitoring unit. It is then
extratemporal epilepsy (Figure 4-16).59 injected as soon as possible (within
In addition to FDG, other ligands seconds) following the onset of a
have been used for PET, each mea- seizure. An ictal SPECT scan is then
suring different physiologic functions performed and compared to an
and having signature findings in dif- interictal study in the same patient.
ferent epilepsies. These are less widely Although logistic barriers make ac-
used than FDG-PET and most remain quisition challenging, when success-
experimental. For example, flumazenil fully performed, ictal/interictal SPECT
ligands with a carbon-11 tracer (11C- comparison identifies a region of ictal
FMZ) bind to central +-aminobutyric hyperperfusion that is well correlated
acid (GABA)-A benzodiazepine recep- with the ictal focus in a majority of
tors. The concentration of benzodiaze- patients.61 Success depends on the

Case 4-4
A 27-year-old woman with a history of drug-resistant focal seizures
associated with focal dyscognitive seizures presented for a presurgical
evaluation. Routine EEG recordings revealed left temporal spike
discharges. Brain MRI epilepsy protocol did not reveal a structural lesion.
Video-EEG monitoring showed left temporal lobe seizures.
Fludeoxyglucose-positron emission tomography (FDG-PET) indicated left
temporal hypometabolism (Figure 4-15).
FIGURE 4-15 Fludeoxyglucose positron emission

tomography (FDG-PET) of the patient in
Case 4-4 shows left temporal focal
hypometabolism (arrow). The patient has left temporal
lobe epilepsy and a normal brain MRI.
Comment. The PET scan in this patient supported the diagnosis of left
temporal lobe epilepsy. Individuals with a negative brain MRI and a focal
PET temporal lobe abnormality may have a surgically remediable epileptic
syndrome and may be appropriate candidates for epilepsy surgery.
FIGURE 4-16 Fludeoxyglucose positron emission tomography (FDG-PET) of a patient with MRI-negative frontal lobe epilepsy. There is
prominent right frontal lobe hypometabolism (arrow).

KEY POINT
speed with which the radiotracer was data normalization and compar- h Subtraction ictal
injected following seizure onset; yield ison with a control group using statis- single-photon emission
improves as this time lag is reduced.62 tical parametric mapping analysis computed tomography
SPECT is especially helpful in MRI- (Figure 4-18).64 coregistered to MRI
negative epilepsy; together with scalp (SISCOM) allows
EEG data and symptomatology, it may CONCLUSION improved localization
point to a region to be either invasively Epilepsy is a highly variable and indi- of the epileptogenic
monitored or resected. Subtraction ictal vidual disease. The nature and loca- zone in patients with
SPECT coregistered to MRI (SISCOM) tion of the disease within an focal epilepsy.
allows improved localization of the individual’s brain, the underlying anat-
epileptogenic zone in patients with omy and function of that brain, and
focal epilepsy (Case 4-5).63 the interaction between the disease
Statistical ictal SPECT coregistered and brain are all unique to each pa-
to MRI (STATISCOM) is similar to tient. This extreme diversity demands
SISCOM with the additional step of individualized approaches to diagnosis
Case 4-5
A 44-year-old man presented with focal seizures associated with behavioral
arrest and staring. His brain MRI was negative. Routine EEG showed
bitemporal interictal epileptiform discharges. A subtraction ictal single-photon
emission computed tomography (SPECT) coregistered to MRI (SISCOM) study
was performed at the time of a habitual clinical seizure (Figure 4-17). Ictal
EEG supported the diagnosis of right temporal lobe epilepsy.
FIGURE 4-17 Subtraction ictal single-photon emission

computed tomography (SPECT)
coregistered to an MRI (SISCOM) of the
brain shows a region of focal hyperperfusion over the
right posterior temporal head region (arrow). The patient
has MRI-negative right temporal lobe epilepsy.
Comment. The SISCOM study in this patient showed a focal region of

hyperperfusion in the right temporal lobe. The SISCOM technique permits
ictal neuroimaging in epilepsy.

FIGURE 4-18 Statistical ictal single-photon emission computed tomography (SPECT) coregistered to MRI (STATISCOM)
shows a left medial temporal lobe region of hyperperfusion (yellow-red color) in a patient with left temporal
lobe epilepsy.
and treatment. Neuroimaging in epi- 2. Fisher RS, Acevedo C, Arzimanoglou A,

et al. ILAE official report: a practical
lepsy is accordingly complex, and its clinical definition of epilepsy. Epilepsia
role depends on clinical context. Of- 2014;55(4):475Y482. doi:10.1111/epi.12550.
ten, different imaging modalities must 3. Berg AT, Berkovic SF, Brodie MJ, et al.
be correlated with each other and to Revised terminology and concepts for
clinical, laboratory, and EEG data be- organization of seizures and epilepsies:
report of the ILAE Commission on
fore a treatment plan emerges.
Classification and Terminology, 2005Y2009.
Evolving imaging techniques such Epilepsia 2010;51(4):676Y685. doi:10.1111/
as 7T MRI, which shows a resolution j.1528-1167.2010.02522.x.
closer to the gold standard of patho- 4. Hesdorffer DC, Benn EK, Cascino GD,
logic specimens and is especially pro- Hauser WA. Is a first acute symptomatic
mising for the detection of focal cortical seizure epilepsy? Mortality and risk for recurrent
seizure. Epilepsia 2009;50(5):1102Y1108.
dysplasia missed on conventional MRI,65 doi:10.1111/j.1528-1167.2008.01945.x.
provide optimism that we will continue
5. Harden CL, Huff JS, Schwartz TH, et al;
to improve diagnosis and reduce the pro- Therapeutics and Technology Assessment
portion of patients labeled MRI negative. Subcommittee of the American Academy
As new imaging techniques emerge and of Neurology. Reassessment: neuroimaging
in the emergency patient presenting with
our understanding of epilepsy deepens, seizure (an evidence-based review): report
it is hoped that more patients will achieve of the Therapeutics and Technology
seizure freedom in the future. Assessment Subcommittee of the American
Academy of Neurology. Neurology
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Review Article
Imaging of Congenital
Dr Jennifer W. McVige, DENT
Neurologic Institute, 3980
Sheridan Dr, Headache and
Concussion Center, 6th Floor,
Amherst, NY 14226,
jmcvige@dentinstitute.com.
Malformations
Relationship Disclosure: Jennifer W. McVige, MA, MD
Dr McVige has received
personal compensation for
speaking engagements from
Avanir Pharmaceuticals, Inc, ABSTRACT
and Teva Pharmaceutical
Industries Ltd, and receives Purpose of Review: Intracranial congenital malformations are anomalies of brain
research/grant support from development caused by genetic and environmental influences. This article discusses
the Harry Dent Family common intracranial congenital malformations, presents the associated neuroimag-
Foundation Inc.
Unlabeled Use of
ing findings, and discusses how appropriate identification of intracranial anomalies
Products/Investigational can impact diagnosis and treatment.
Use Disclosure: Recent Findings: Advances in neuroimaging techniques and genetic research have
Dr McVige reports
no disclosure.
led to a better understanding of the pathogenesis of many congenital malformations,
* 2016 American Academy adding insight into their clinical relevance and the intricate relationship between critical
of Neurology. periods of development, genetic predisposition, and environmental insults. When one
malformation is discovered, a high likelihood of more malformations exists. In some
instances, the intracranial anomalies will lead to the diagnosis of a particular neurologic
syndrome, which may, in turn, lead to modification of a plan of care.
Summary: Knowledge of congenital malformations and their appearance on imaging
sequences is essential to improve clinical outcomes and quality of life for patients.
INTRODUCTION the location and type of malformation

Neuroimaging is an invaluable tool to affect brain, motor, or cognitive devel-
further knowledge regarding dysmor- opment can alter patient treatment,
phic brain development and how it outcomes, and, ultimately, quality of
affects cognition, motor function, and life. Frequently, these malformations
are something we may search for in
behavior. The development of the brain
patients with developmental delays or
involves a complex cascade of genetic
genetic disorders. Other times, they
material signaling the formation of
are found incidentally on pediatric or
intricate structures at critical periods of adult neuroimaging, which makes for
time. This process can be influenced interesting retrospective patient eval-
and disrupted by environmental factors uations to assess the degree to which
or by inherited or de novo genetic the malformation has affected the
mutations. The type of disruptive insult patient (Case 5-1).
(eg, hemorrhage or infection) is not The classification of congenital
as important as the timing (in regard malformations is challenging because
to structural development) and the many brain structures develop simul-
genetic susceptibility of the fetus.1 taneously and no two malformations
Advances in the field of neuroimag- are exactly alike.2 Thus, it is rare for
ing have dramatically changed the way one anomaly to occur in isolation. If
we evaluate and assess patients with an anomaly is discovered, the neu-
cognitive and developmental delays. roimager must always look for further
Identifying intracranial congenital abnormalities.3 For example, a single
anomalies and understanding how patient may present with agenesis of

Case 5-1
A 39-year-old woman presented with headaches that had been occurring 3 to 4 times a week for the
past 5 years. The pain was described as pressing in the bifrontal or bioccipital area escalating to a
10/10 on the pain scale, and the headaches were often associated with nausea and photophobia. She
had not had a head injury or recent illness. On physical examination, the patient showed delayed
cognitive functioning. She was slow to answer questions, became confused easily, and had difficulty
with fine motor tasks. A brain MRI without contrast showed agenesis of the corpus callosum
(Figure 5-1A) and gray matter heterotopia (Figure 5-1B). Diffusion tractography confirmed complete
agenesis of the corpus callosum (Figure 5-1C).
A further history revealed that the patient had always struggled intellectually. She attended special
education classes and was held back a grade in middle school. She had trouble retaining a job. She had
episodes of staring spells her whole life, which her family referred to as her ‘‘absent moments.’’
Sleep-deprived EEG and 24-hour ambulatory EEG were normal. Her headaches were successfully treated
with prophylactic topiramate, as well as sumatriptan and naproxen for abortive care.
Three years later, she returned after experiencing two partial seizures, involving left arm flexion
and shaking for 1 minute. She had a repeat sleep-deprived EEG that showed a few scattered
spike-and-wave complexes in the right temporal parietal region. She was then started on
levetiracetam. The topiramate was not increased because she reported concentration issues at 75 mg.
FIGURE 5-1 Imaging of the patient in Case 5-1. A, Sagittal T1-weighted MRI showing complete agenesis of the corpus
callosum (black arrows). B, Coronal T1-weighted 1-mm MRI slices with contrast showing agenesis of the
corpus callosum and an area of gray matter heterotopia (white arrow) in the right periventricular area. C,
Diffusion tensor imaging showing dysgenesis of the corpus callosum. There are no clear organized transverse pathways;
therefore, the corpus callosum did not fully form.
Comment. Congenital anomalies can be discovered incidentally during a neurologic workup. This
patient was found to have agenesis of the corpus callosum and gray matter heterotopia, which can
increase the risk for seizures, but she originally presented for headaches. Two EEGs initially revealed no
evidence of seizure activity. The patient was educated about her increased risk for seizures, and the signs
and symptoms were reviewed. Her headaches were successfully treated, and 3 years later, when she did
develop seizures, she was able to seek appropriate help because she had been previously educated.
the corpus callosum, holoprosencephaly, The development of the nervous

and polymicrogyria (Figure 5-2). At times, system involves closure of the neu-
certain patterns of multiple anomalies ropore and eventually the neural tube.
can suggest a genetic syndrome; other Cells in the neuroectoderm rely on
times, the patterns are sporadic. signals to initiate cell recognition and

Congenital Malformations
FIGURE 5-2 Imaging of a 42-year-old man with lobar holoprosencephaly, partial agenesis of the corpus callosum, and
polymicrogyria. The patient had a past history of complex partial seizures and developmental delays. Axial
T1-weighted (A) and axial fluid-attenuated inversion recovery (FLAIR) (B) MRIs showing frontal lobar
holoprosencephaly or failure of the frontal lobes to fully separate (A, B, white arrows). Sagittal FLAIR MRI (C) showing partial
agenesis of the corpus callosum (yellow arrows = small portion of remaining corpus callosum; red arrows = where the
corpus callosum did not form).
KEY POINT adhesion to proceed to closure of the ANOMALIES OF THE DORSAL

h The old stepwise neural tube through a process of neu- PROSENCEPHALON (FOREBRAIN)
theories of rulation. Previous theories suggesting a Malformations in this anatomic location
neurodevelopment have
stepwise cephalad to caudal process involve agenesis of the corpus callosum
been replaced by the
have been refuted and replaced with and cerebral cortical malformations.
idea that simultaneous
the idea of some level of simultaneous These are supratentorial changes in the
developmental
processes occur in
development, with ultimate closure of cortex or changes in the fibers that con-
different regions. This the anterior neuropore at 25 days and nect two parts of the cortex together.
explains why it is the posterior neuropore at 27 to 28 days
common to find gestational age. This may account for Agenesis of the Corpus Callosum
multiple intracranial the frequent discovery of comorbid
The cerebral commissures, which con-
anomalies in one patient. malformations.4,5 When the anterior
nect two areas of cortex, form from the
neuropore closes, three subdivisions
are formed: the prosencephalon (fore- dorsal prosencephalon. These include
brain), mesencephalon (midbrain), the anterior commissure, hippocampal
and rhombencephalon (hindbrain). commissure, and the corpus callosum.
The rhombencephalon will ultimately They are derived from the same com-
divide into the metencephalon (which missural plate and develop from the
will form the pons and the cerebellum) lamina reunions of His in the fetus from
and the myelencephalon (which will 8 to 20 weeks gestation.6 Anomalies of
form the medulla).2 the cerebral commissures occur in 1.8
It has been challenging to classify of 10,000 live births and are some of
congenital malformations because the most common developmental brain
they rarely occur in isolation, and the abnormalities. The incidence is in-
timing of their development during creased in children born prematurely,
gestation has been debated. The fol- children born to mothers of advanced
lowing are some of the more common maternal age, and children with genetic
congenital anomalies, discussed using or other neurologic disorders.3
a classification system suggested by The corpus callosum is the largest
Barkovich and Raybaud.3 and most easily identified commissure.

It is divided into five sections and Abnormalities can involve a complete
develops ventral to dorsal. From anteri- agenesis (all sections) (Figures 5-1A
or to posterior, the sections of the and 5-1C) (Case 5-2) or partial agenesis
corpus callosum are the rostrum, (Figure 5-2C and Figure 5-4). If the
genu, body, isthmus, and splenium.2 anterior portion is not developed, it is
Case 5-2
A 9-year-old girl presented with her mother, who had concerns that the child was having episodes
of memory lapses intermittently over the prior 4 to 5 years. During these episodes, the patient would
go to change her clothes, forget which clothes were previously worn, and put on the dirty clothes again.
At times during the episodes, she would forget where the bathroom was in the house and wander
around. In addition, she experienced frequent staring spells and episodes with ‘‘gasping for air.’’ A family
history existed of her father having seizures, but the patient and her mother had no contact with the
father or his biological family.
She was born full term by normal vaginal delivery with no complications. From a developmental
standpoint, her motor skills were delayed; she did not sit up until 11 months and did not walk until
17 months. Her speech was also very delayed. At the time of presentation, she was in a fourth grade
special education classroom and was receiving occupational therapy, physical therapy, and speech
therapy. According to her mother she was functioning at a kindergarten level.
Examination revealed a soft-spoken young girl with dysmorphic facies of low-set ears and wide-spaced
teeth. She displayed cognitive function much lower than her chronologic age, with slowed and imprecise
fine motor skills and trouble on gross motor tests of tandem gait, hopping on one foot, and running.
Sleep-deprived EEG showed slowing but no sharp wave activity. Brain MRI revealed complete
agenesis of the corpus callosum (Figures 5-3A and 5-3B) with enlargement of the occipital and
temporal horns of the lateral ventricles consistent with colpocephaly (Figure 5-3C). Chromosomal testing
was normal, but a complete microarray was denied by insurance. Repeat EEG with long-term
monitoring for 3 days showed one ictal event during an awake state with behavioral arrest, then eye
blinking and right leg rhythmic shaking. The ictal EEG showed 4-Hz generalized delta wave slowing with
spike-and-wave complexes.
She was started on levetiracetam and titrated up to a therapeutic dose. Her seizures abated.
FIGURE 5-3 Imaging of the patient in Case 5-2. Sagittal T1-weighted (A) and coronal inversion recovery (B) brain MRIs
showing agenesis of the corpus callosum (A, B, arrows). Axial fluid-attenuated inversion recovery (FLAIR)
MRI showing agenesis of the corpus callosum and colpocephaly (C, arrows).


Comment. This patient was known to have an increased risk for seizures given the congenital
anomalies of agenesis of the corpus callosum and colpocephaly found on the brain MRI. A decision
was made to perform long-term EEG monitoring, despite the previous unremarkable EEG, because of
a high clinical suspicion of seizures and the presence of congenital anomalies on MRI. This was pivotal
in diagnosing her with generalized epilepsy and improving her quality of life.
KEY POINT usually associated with an insult, such with callosal abnormality. In addition
h Dysgenesis or agenesis as infection or vascular event. If the to MRI, diffusion tensor imaging (DTI)
of the anterior corpus posterior portion is not developed or tractography can be used to identify
callosum is usually (Figure 5-4A), it usually is associated abnormalities in the callosal pathways.
associated with an
with arrested development.7 Intracranial anomalies associated
insult, such as infection
Fetal ultrasound is used to screen with callosal agenesis include abnormal
or vascular event.
Dysgenesis of the
for abnormalities in utero, which can increased cortical folding, delayed
posterior corpus be helpful, but when evaluating for sulcation, cerebellar and brainstem
callosum is usually agenesis of the corpus callosum, fetal anomalies, dysplastic deep gray matter,
associated with ultrasound has a false-positive rate up and heterotopias. Callosal agenesis with
arrested development. to 20%.7 Prenatal MRI has proven to interhemispheric cyst development is
be much more sensitive and should be a special subtype that involves a series
used if a suspicion for callosal abnor- of syndromes.3 Other commonly asso-
mality exists. In a 2012 study, prenatal ciated syndromes include Aicardi syn-
MRI was able to detect additional drome, Dandy-Walker malformation,
abnormalities in 22.5% of cases.8 Ante- Chiari type II malformation, and fetal
natal imaging is recommended in these alcohol syndrome.6
cases as well to evaluate for coexisting
anomalies. In a review of the literature, Cerebral Cortical Malformations
Santo and colleagues7 found associated Cortical development can be affected
brain abnormalities in 45.8% of cases by anything that inhibits neuronal or
FIGURE 5-4 Sagittal T1-weighted MRI (A), axial fluid-attenuated inversion recovery (FLAIR) MRI (B), and brain CT (C) of a
5-year-old boy with spastic triplegic cerebral palsy and seizures after a suspected stroke in utero. He was
found to have partial agenesis of the corpus callosum. Only the splenium of the corpus callosum is seen
(A, arrow). There is ex vacuo enlargement of the lateral ventricles (B). The anterior portion of the corpus callosum is not
visualized (C, yellow arrow), and there is a hypodensity in the right frontal area consistent with a chronic infarct (C, red arrow).

KEY POINTS
glial proliferation, migration, or cortical pensity for seizure disorder or cog- h Cortical malformations
organization. This can include gene nitive delays. can be seen on fetal
mutations, insult from infection or bleed- Lissencephaly. Lissencephaly is a dis- ultrasound by 20 weeks
ing, exogenous toxins (eg, alcohol or order of neuronal migration and refers to gestational age.
drugs), and endogenous toxins (eg, a decrease in the gyral and sulcal forma- Prenatal and postnatal
metabolic disorders).3 These can be tion of the brain, or a smooth appear- CT can miss up to 30%
identified via prenatal ultrasound by ance. Pathology has shown a four-layer of findings, thus
20 weeks gestational age or postnatal cortex rather than a six-layer cortex.12 prenatal or postnatal
ultrasound, but many subtle findings Complete lissencephaly (Figure 5-5), or MRI is the imaging
are easily missed. Even CT can miss as the absence of gyral formation, is re- modality of choice.
many as 30% of abnormalities.3 Fetal ferred to as agyria.13 h In lissencephaly, the
and postnatal MRI have a higher sen- Incomplete lissencephaly, or pachy- brain has decreased
sitivity.9,10 Cortical malformations can gyria (Figure 5-6), is defined as the sulci and gyri, resulting
also be frequently found on MRI in presence of a thickened cortex with in a smooth cortex. It
may be described as
children with developmental delays. a few broad flat gyri where the gray-
complete (agyria) or
Kulak and colleagues11 found congen- white junction is indistinct. This is
incomplete (pachygyria).
ital brain anomalies on MRI in 10.7% more likely to be localized and asym- In pachygyria, the cortex
of children assessed with spastic cere- metric. The disorder is associated with has thickened flat gyri.
bral palsy, including schizencephaly, the LIS1or DCX gene mutation 40% to
agenesis of the corpus callosum, poly- 75% of the time.3 Patients typically have
microgyria, holoprosencephaly, and hypotonia, developmental delays, and
lissencephaly as well as cerebral atro- seizures in the form of infantile
phy. MRI is an important tool that can spasms. Band heterotopia, or double
be used for both diagnostic and prog- cortex syndrome, is the mildest form
nostic purposes; the findings may alert of lissencephaly and looks like gray
the physician to an increased pro- matter separated by a band of white
FIGURE 5-5 Coronal T2-weighted MRI (thin 3-mm slices)

of a 30-year-old man with seizures and right
parietotemporal incomplete lissencephaly
and hemiatrophy (arrow).

KEY POINT
h Polymicrogyria is an
irregular cortex with
several small
convolutions in the sulci
and gyri. It is most
commonly located in
the bilateral perisylvian
fissures but can be seen
in a number of locations.
FIGURE 5-6 Pachygyria and schizencephaly in a 24-year-old man with seizures. A, Coronal
fluid-attenuated inversion recovery (FLAIR) MRI showing pachygyria with
bilateral parietal open-lip schizencephaly lined with heterotopic gray matter (red
arrows). B, Axial T2-weighted MRI showing pachygyria (white arrows) with bilateral
parietal schizencephaly.
matter appearing in layers. This occurs ciated with genetic mutations within the
predominantly in females and is fre- homeobox gene PAX6. Polymicrogyria
quently associated with seizures.3 Cob- is most commonly located in the
blestone lissencephalies (lissencephaly
type 2), which have a pebbly appear-
ance, are associated with congenital
muscular dystrophies.5 DTI measures
of high fractional anisotropy have been
shown to be a sensitive measure to detect
dysplastic cortex in lissencephalies.12 DTI
is a specialized MRI sequence that can
detect areas of abnormal cortex not
visualized on standard MRI sequences.
Localizing and assessing the extent of
dysmorphology can aid in prognosis
and the development of a plan of care.
Polymicrogyria. Polymicrogyria is
an irregular cortex with several small
convolutions giving the appearance of
tiny miniature gyri on top of each
other and is due to abnormal migra-
FIGURE 5-7 Axial T1-weighted MRI
tional and postmigrational develop- showing polymicrogyria
ment (Figure 5-7; see Figures 5-12C, and hemiatrophy of the
right frontal lobe (red arrow) with cavum
5-12D, and 5-12E for additional exam- velum interpositum (yellow arrow).
ples).5,14 Polymicrogyria may be asso-

KEY POINTS
bilateral perisylvian fissures (61%) but ventricle to the pial surface of the h Diffusion tensor
can be seen in a number of locations.5 cortex. The gray matter is disorganized imaging measures of
Research with ultrahigh-field 7T MRI and without the proper cortical layers, fractional anisotropy
compared to 3T imaging has revealed and the septum pellucidum is typically can be used to detect
that conventional imaging has many absent.5,9 The clefts are classified as microstructural damage
limitations; many bilateral manifesta- unilateral (60%) or bilateral (40%) in many congenital
tions were discovered with higher and open lip (visible) (Figure 5-6, malformations. Small
magnet strength that were thought to abnormalities that
Figure 5-8, and Figure 5-9) or closed
are missed on MRI
be less pervasive based on conventional lip (barely visible). One-third of all
can be better seen with
imaging. Approximately 78% to 87% cases will have a nonYcentral nervous diffusion tensor imaging.
of patients with polymicrogyria have system associated abnormality (eg, gas-
h Schizencephaly is a gray
epilepsy. Neuroimaging can assist with trointestinal or orthopedic). Most cases
matterYlined cleft
localization of the seizure foci and aid in are sporadic, but some familial cases extending from the
presurgical assessments. High-field have been described.5 Again, MRI is ependyma of the
magnets have also shown cortical drain- more sensitive than CT. Magnetic ventricle to the pial
ing veins associated with the malfor- resonance angiography (MRA) and CT surface of the cortex.
mation, which may play a role in angiography can be used, as they have The gray matter is
pathogenesis.14 A study by Trivedi demonstrated some cases of middle disorganized and
and colleagues15 showed that DTI cerebral artery occlusion as a cause. without the proper
measures of high fractional anisotropy For more information on hetero- cortical layers, and the
septum pellucidum is
are a sensitive index that can be used topia and cortical dysplasia, refer to
typically absent.
in clinical practice to detect micro- the article ‘‘Imaging for Adults With
structural damage. Seizures and Epilepsy’’ by Samuel
Schizencephaly. Schizencephaly Lapalme-Remis, MDCM, MA, FRCPC,
(split brain) is a gray matterYlined cleft and Gregory D. Cascino, MD, FAAN,16
extending from the ependyma of the in this issue of Continuum.
FIGURE 5-8 Axial fluid-attenuated inversion recovery (FLAIR) (A) and coronal T2-weighted (B)
MRIs of an 8-year-old boy with right hemiplegia and intellectual delays. He
was found to have left frontal open-lip schizencephaly (A, arrow). The
schizencephaly is lined with gray matter.

combined with elevated maternal levels

of "-fetoprotein and low maternal levels
of estriol. MRI may play a role in assess-
ing viability, for research purposes, or
to assess for the possibility of organ
donation, if that is desired. The high
early mortality seen in these patients is
responsible for infrequent imaging.
Holoprosencephaly
Holoprosencephaly involves the failure
of differentiation and midline cleavage
of the prosencephalon. Holo- means
single and describes the failure of the
division of the forebrain into two hemi-
spheres. Clear cytogenetic causes exist
for 45% of affected patients; the sonic
hedgehog (SHH ) gene is the most
Coronal T2-weighted MRI widely studied.3 Prognosis and clinical
FIGURE 5-9
of a 31-year-old man with presentation vary greatly, so subtypes
a history of concussion, headaches,
and episodes of inattention. He was incidentally are described on a continuum by the
found to have open-lip schizencephaly in the right terms alobar, semilobar, and lobar to
temporal lobe (arrow). The combination of
temporal lobe schizencephaly with concussion
describe the malformation by decreas-
involving episodes of inattention raises the ing level of severity.
suspicion for possible seizure activity. The differential diagnosis of
holoprosencephaly on neuroimaging
includes a disorder called hydranen-
KEY POINT ANOMALIES OF THE VENTRAL cephaly, which is a fusion of the words
h Anencephaly is the PROSENCEPHALON (FOREBRAIN) anencephaly and hydrocephalus.
absence of the Hydranencephaly is characterized by
Malformations in this region include
forebrain, skull, and near-absence of the cerebral cortex
scalp. It occurs when the anencephaly and holoprosencephaly,
and basal ganglia with retained pres-
cephalic end of the which describe varying degrees of
ence of the falx. In hydranencephaly,
neural tube fails to close severity of cortical dysgenesis. Anen- the brain parenchyma typically begins
or reopens after closure. cephaly is a complete absence of the to form correctly, but a vascular, trau-
It is usually not majority of the cerebral cortex and the matic, or infectious insult occurs.18 This
compatible with life. skull, while holoprosencephaly is is a severe form of porencephaly, in
the absence of different parts of the which the brain parenchyma is re-
cerebral cortex. placed by CSF (Figure 5-10).17
Hydranencephaly and alobar holo-
Anencephaly prosencephaly need to be differentiated
Anencephaly is the absence of the on postnatal ultrasounds and MRI. In
forebrain, skull, and scalp. Females are alobar holoprosencephaly, there is fu-
affected more often than males (3:1 to sion of the thalami and the frontal lobe
4:1). It occurs when the cephalic end of tissue, as well as a dorsal cyst. In hy-
the neural tube fails to close or reopens dranencephaly, there is no fusion of
after closure17 and is usually not com- cerebral hemispheric tissue, and abnor-
patible with life. Fetal ultrasound is mal remnants of supratentorial brain
typically used to diagnose anencephaly, parenchyma are present. The presence

FIGURE 5-10 Axial T1-weighted MRI (A, B) of a 34-year-old man with seizures, intellectual
delays, and a history of hypothermia reveals a diagnosis of hydranencephaly. A
small amount of brain tissue (A, white arrow) can be seen in the right frontal
lobe without gray and white differentiation. There is a partial falx (A) with presence of the
midbrain as well as some posterior occipital and left temporal brain parenchyma (B).
of a falx and the absence of thalamic common form of holoprosencephaly.

fusion can help exclude holoprosen- In this form, no midline differentiation
cephaly as a diagnosis.19,20 exists; the basal ganglia are fused; and
Alobar holoprosencephaly (Figure the sagittal sinus, falx, and olfactory sys-
5-11) is both the most severe and most tem are absent. In extreme forms, the
FIGURE 5-11 Alobar holoprosencephaly on axial head CT in an 11-month-old girl. A lack of

definition of the frontal lobes can be seen (A, B, red arrows), with probable
fusion of the thalami (A, yellow arrow) and absence of a falx.
Courtesy of Richard Sherry, MD.

KEY POINT
h Holoprosencephaly globes and orbits are fused, resulting prosencephaly appears to look like the
describes the failure of the in cyclopia.3 Patients are rarely imaged ace of spades.
division of the forebrain with MRI and CT postnatally because If the third ventricle is fully formed,
into two hemispheres. many of these children are stillborn or the frontal horns are present, and the
Subtypes are described as have a short life expectancy. Fetal posterior corpus callosum (including the
alobar, which is the most ultrasound is most commonly used. splenium) is formed, then the malfor-
severe, with no midline In semilobar and lobar holopros- mation can be described as lobar.3 The
differentiation and fused encephaly (Figures 5-2A and 5-2B), mildest form of lobar holoprosencephaly
basal ganglia; semilobar, the brain is more developed and the is septooptic dysplasia (Figure 5-12),
with an ‘‘ace of spades’’ abnormal facial anomalies are mild or which includes hypoplastic optic nerves
appearance; and lobar,
absent. The severity of the holopros- and the absence of the septum pellu-
with some development
encephaly depends on the extent of cidum, which gives the frontal horns a
of the hypothalamus,
frontal regions, and
the development of the hypothalamus, boxlike appearance.9 The diagnosis and
anterior corpus callosum. low frontal regions, and anterior corpus differentiation of holoprosencephaly
callosum.3 On imaging, semilobar holo- is challenging on fetal MRI. Thin-slice
FIGURE 5-12 Septooptic dysplasia in a 20-year-old man with nystagmus, intellectual delays, vision loss, and complex partial
seizures with a history of septooptic dysplasia. Neuroimaging reveals optic nerve and optic chiasm hypoplasia,
absence of the septum pellucidum, and polymicrogyria. Axial T2-weighted MRI showing bilateral optic
nerve hypoplasia (A, arrows). Axial fluid-attenuated inversion recovery (FLAIR) MRI showing absent septum pellucidum
(B, arrow). Sagittal FLAIR (C ), axial FLAIR (D), and diffusion tensor imaging (DTI) on MRI (E) show polymicrogyria in the
left frontal lobe (C, D, E arrows). Note the lack of symmetry in the frontal lobes on the DTI.

KEY POINTS
coronal sequences and postnatal MRI h Dandy-Walker
are more helpful for refined diagnosis. malformation and
related disorders are
ANOMALIES OF THE MIDBRAIN spectrum disorders that
AND HINDBRAIN involve varying degrees
The midbrain remains as part of the of cerebellar hypoplasia,
brainstem, and the hindbrain becomes mega cisterna magna,
the cerebellum. This occurs due to the and retrocerebellar
anterior-posterior patterning of the arachnoid cysts.
isthmus organizer, which causes the se- h On neuroimaging,
cretion of signaling molecules from pat- Joubert syndrome
terning centers.21 Disorders in these can be identified by
areas have been challenging to iden- thickened and
elongated superior
tify with the limitations of conventional
cerebellar peduncles
CT and MRI. The advent of high- FIGURE 5-13 Sagittal fluid-attenuated
inversion recovery (FLAIR) that give the appearance
resolution thin-slice MRI and DTI has MRI of Dandy-Walker of a molar tooth.
shed light on the extent and pattern malformation showing enlarged posterior
fossa, elevated tentorium cerebelli (arrow),
of dysmorphology. Disorders in this and hypoplasia of the cerebellar vermis.
region include Dandy-Walker mal-
formation and related disorders termed
Dandy-Walker variants as well as
Joubert syndrome. variant is a term used to describe a
milder form of the disorder (Figure 5-14
Dandy-Walker Malformation and Figure 5-15).
and Related Disorders
Dandy-Walker malformation and re- Joubert Syndrome
lated disorders are the most preva- Joubert syndrome is a rare autosomal
lent posterior fossa malformations. recessive disorder that can be asso-
Other variant-related disorders in this ciated with abnormal SHH gene-
in this area include cerebellar hypopla- mediated cell proliferation. Neonatal
sia, mega cisterna magna (10 mm or patients present with tachypnea and
more diameter on sagittal sequences), apnea, while older patients present
and retrocerebellar arachnoid cysts. It with hypotonia, cerebellar ataxia, and
is now believed that these malfor- oculomotor apraxia.23 There may also
mations occur on a spectrum due to be systemic involvement to varying
mesenchymal-neuroepithelial signaling degrees. Neuroimaging is essential for
deficits.21 The classic Dandy-Walker a diagnosis. The molar tooth sign is a
malformation is described as an en- pathognomonic neuroimaging find-
larged posterior fossa, an ele- ing for this disorder (Figure 5-16) that
vated tentorium cerebelli, hypoplasia describes thickened and elongated su-
of the cerebellar vermis, and a dilated perior cerebellar peduncles that give
cystic fourth ventricle (Figure 5-13). the appearance of a molar tooth.24,25
The cerebellar hemispheres are usually Brainstem abnormalities and suprat-
small, and callosal anomalies are found entorial involvement, such as callosal
in 20% of patients.22 Most children dysgenesis, cephaloceles, hippocampal
present in the first year of life with malrotation, migrational disorders, and
increased intracranial pressure, macro- ventriculomegaly, are seen in 30% of
cephaly (90% to 100%), and cognitive patients.24 DTI and fiber tractography
delays (one-third). 21 Dandy-Walker show the absence of decussation of

FIGURE 5-14 Axial noncontrast CT (A) and sagittal T2-weighted MRI (B) showing severely
enlarged cisterna magna communicating with a large supracerebellar cistern
and cistern of the velum interpositum. The tentorium is elevated. The large
retrocerebellar cystic area does not communicate with the fourth ventricle (B, arrow) and the
fourth ventricle is not dilated, so this is classified as a Dandy-Walker variant.
FIGURE 5-15 Sagittal fluid-attenuated inversion

recovery (FLAIR) MRI (3-mm slices)
of a 25-year-old man who
experienced a traumatic brain injury at 5 years old.
Prominent cerebellar atrophy and hypoplasia
(arrow) can be seen, mainly affecting the inferior
cerebellar vermis and the cerebellar hemispheres (not
shown). Agenesis of the posterior corpus callosum
can also be seen. This was diagnosed as
cerebellar hypoplasia.

FIGURE 5-16 Joubert syndrome in a 5-year-old boy with difficulty walking and frequent falls.
Ataxia and hypotonia were found on examination, and the patient was
diagnosed with Joubert syndrome based on imaging findings. A, Axial
fluid-attenuated inversion recovery (FLAIR) MRI showing thickening and elongation of the
superior cerebellar peduncles, which is termed the molar tooth sign (arrow). B, Sagittal
T1-weighted MRI showing midbrain hypoplasia (arrow).
the corticospinal tracts and the supe- tury, but advances in neuroimaging and
rior cerebellar peduncles at the level neurosurgery have allowed for a greater
of the pontomesencephalic junction understanding of the pathophysiology
of the lower brainstem.24 and definition of the disorder through-
out a lifespan. This knowledge pro-
ANOMALIES OF THE voked changes in the labeling system,
CRANIOCERVICAL JUNCTION creating Chiari malformation variants
Anomalies in the craniocervical junction defined as types 0 to IV (Figure 5-18
can occur when the space between and Figure 5-19) (Table 5-1).2,26Y30
the cerebellum, posterior occipital The extent of cerebellar tonsillar exten-
area, and upper cervical area is com- sion has been shown to decrease with
promised. Varying degrees of severity age31 and increase with the presence of
hydrocephalus or a mass lesion. There-
exist; however, studies have identified
fore, the diagnostic criteria can change
several unique characteristics that may
with age; for example, Chiari type I
help to predict outcome.
malformation is defined as cerebellar
tonsillar extension of 5 mm or more in
Chiari Malformation
individuals 15 years of age and older and
Chiari malformation refers to the caudal 6 mm or more in individuals younger
displacement of at least one of the than 15 years of age (Table 5-2).26,27
cerebellar tonsils through the foramen The pathophysiology of Chiari mal-
magnum as measured below the basion- formation is multifactorial, with proven
opisthion line (from the base of the genetic and physiologic causes. Chiari
clivus to the base of the foramen mag- malformation may be part of a larger
num) on sagittal MRI (Figure 5-17). The syndrome, such as craniosynostosis
pathologist Hans Chiari first described or connective tissue disorders (eg,
this disease at the end of the 19th cen- Ehlers-Danlos syndrome), or caused by

FIGURE 5-17 Chiari type I malformation measurements. A, Sagittal cerebellar tonsillar descent is measured
as a horizontal line drawn from the tip of the clivus to the undersurface of the suboccipital
bone. A vertical line is drawn from the foraminal line to the end of the caudal projection of
the cerebellar tonsils. There is also syringohydromyelia seen at the C7 level (arrow). B, Coronal foraminal
horizontal line is drawn across the foramen magnum beneath the occipital bone. Cerebellar tonsillar lines
are measured 90 degrees from the foraminal line to the most caudal projection of tonsillar descent on both
the right and left.
intracranial pressure changes. The devel- hydrodynamic theories exist that pro-
opment of Chiari malformation is be- pose a cause for the development
lieved to be related to the size and shape of Chiari malformation through pres-
of the posterior cranial vault. Several sure gradients. One of those theories
FIGURE 5-18 Chiari type 0 malformation.

Sagittal T2-weighted
MRI of the cervical and FIGURE 5-19 Chiari type II
thoracic spine showing crowding at malformation. Sagittal
the foramen magnum and the presence T2-weighted MRI of
of syringohydromyelia at T2-T3 and cervical spine showing cerebellar
T3-T4 (arrow). Cerebellar tonsils do vermian and medullary descent along
not extend more than 3 mm. with cervical medullary kinking (arrow).

TABLE 5-1 Classification of the Types of Chiari Malformations
Type Classification
0 Cerebellar tonsillar extension G3 mm with syringomyelia and/or obstruction/
compression of structures in the posterior fossa. Slight tilt of the pons
and medulla.
I Elongation of tonsils and medial inferior lobes of cerebellum
into cone-shaped projections. Measures of cerebellar tonsillar extension
are Q5 mm at 15 years of age or older and Q6 mm at younger than
15 years of age; may be associated with syringomyelia (30Y70%).
1.5 Caudal displacement of the cerebellar tonsils with herniation. Caudal
displacement of the brainstem and fourth ventricle. Bulbocervical
kinking without spina bifida.
II Displacement of inferior vermis, pons, and medulla oblongata with elongation
of the fourth ventricle. Almost always associated with myelomeningocele
(usually lumbar). Cervicomedullary kinking (in 70% of cases), syringohydromyelia
(in 50% of cases), dysgenesis of the corpus callosum (in 70Y90% of cases),
and hydrocephalus in most cases. Also tectal beaking and colpocephaly.
III The entire cerebellum herniates into the cervical canal, often with high
cervical or suboccipital encephalocele. Also tectal beaking and
cervicomedullary kinking.
IV Cerebellar hypoplasia or agenesis; remnants of the cerebellum can be
present. Normal-sized brain and brainstem.
was developed by Heiss and col- cause the formation of a syrinx in some
leagues,32 who demonstrated intraop- cases (30% to 70% in Chiari type I
eratively that the cerebellar tonsils act malformation).20 A syrinx is a CSF-
like pistons that descend in systole and filled cavity with gliosis. Hydromyelia
ascend in diastole. The hydrodynamic refers to dilation of the central spinal
theories suggest that this pressure may canal and syringomyelia to the lateral
a
TABLE 5-2 Measurement of Chiari Type I Malformations
Tonsillar Descent
(in Reference to Classification of Chiari
Basion-Opisthion Line) Type I Malformation
G3 mm Normal (cerebellar tonsillar ectopia)
3Y5 mm Borderline Chiari type I malformation (can
be abnormal if co-occurring pathologies exist,
eg, syringohydromyelia or clinical symptoms)
Q5 mm Chiari type I malformation in patients
15 years of age or older
Q6 mm Chiari type I malformation in patients
younger than 15 years of age
a
Reprinted with permission from McVige JW, Leonardo J, Neurol Clin.26 B 2014 Elsevier Inc.

KEY POINTS
h The degree of cavitation of the spinal cord, thus toms and respond better to decom-
cerebellar tonsillar syringohydromyelia is a combination pressive surgery. Other anatomic
herniation in Chiari type I of both (Figure 5-18). abnormalities can also be seen with
malformation does not Chiari type I malformations are the Chiari type I malformation, including a
always correlate with the most commonly occurring Chiari mal- cervical syrinx, platybasia (abnormal skull
severity of symptoms. formations, with a prevalence of 0.56% base flattening), basilar invagination
The size of the posterior to 1.0%.20 The most common presenting (upward projection of the odontoid pro-
fossa, however, has been symptom is a prototypic Valsalva- cess through the foramen magnum), and
shown to be predictive of induced or exertional headache located Klippel-Feil syndrome (vertebral fusion).
severity and response to in the posterior occipital or upper cer- Neuroimaging has played a crucial
decompression surgery.
vical area (Figure 5-20). Associated role in the effort to refine diagnostic
h Measuring the signs may present as cranial nerve dys- criteria and predict good candidates
degree of cerebellar function, brainstem compression, cer- for surgical intervention. MRI can be
tonsillar herniation on ebellar abnormalities, or spinal cord used to measure the degree of tonsil-
sagittal and coronal
injury. The degree of cerebellar tonsillar herniation (Figure 5-17). Tradition-
MRI as well as using
lar herniation does not always corre- ally, sagittal views are used, but adding
cine-MRI CSF flow scans
can be helpful in
late with the severity of symptoms; coronal images can provide a better
evaluating the degree of however, the size of the posterior evaluation of each cerebellar tonsil
severity of Chiari type I cranial vault has been shown to be separately. Cine-MRI can also be used
malformation. predictive in Chiari type I malforma- to measure the CSF flow both anterior
tion. Badie and colleagues33 found and posterior to the cerebellum and
that patients with a smaller posterior brainstem (Figure 5-21). Abnormal
cranial fossa present earlier with symp- flow at C2-C3 has been found to
correlate with the presence of a
syrinx,34 and a greater improvement
in clinical outcome after decompres-
sion surgery was found in individuals
who had a syrinx.35 New research has
shown that DTI measures of low frac-
tional anisotropy in Chiari type I mal-
formation correlate with the degree of
microstructural abnormalities.36 Single-
photon emission computed tomogra-
phy (SPECT) scans, which can assess
for the presence of chemical altera-
tions in the brain parenchyma, can also
be used to assess for aberrant neuro-
ectodermal development.
CONCLUSION
Neuroimaging advances in the assess-
ment of congenital malformations have
helped to provide insight into the
FIGURE 5-20 Imaging of a 5-year-old girl with pathophysiology and temporal course
occipital Valsalva-induced headaches
refractory to medical management, of many disorders. MRI sequences
found to have a Chiari type I malformation without remain the gold standard for the evalu-
syringomyelia. Her sagittal T2-weighted MRI shows
cerebellar tonsillar descent to the C2 lamina and a ation of most congenital malformations,
small posterior fossa with peglike tonsils (arrow). although advanced techniques, such as
DTI, cine-MRI, and SPECT, are helpful

FIGURE 5-21 A 28-year-old man with left upper extremity radicular signs found to have
Chiari malformation and a large multilevel syringohydromyelia. A, Sagittal short
tau inversion recovery (STIR) MRI shows disk protrusion and spinal cord
compression at C5-C6 (arrow). B, Cine-MRI showing very limited CSF flow posterior and
anterior to the cerebellar tonsils (arrow).
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Review Article
Imaging in Patients
Dr Gabriella Szatmáry,
Hattiesburg Clinic, P.A., 415 S
28th Ave, Hattiesburg, MS
With Visual Symptoms 39401, gszatmary@yahoo.com.

Dr Szatmáry reports
Gabriella Szatmáry, MD, PhD no disclosure.
Unlabeled Use of
Use Disclosure:
ABSTRACT Dr Szatmáry reports
no disclosure.
Purpose of Review: This article presents an imaging-based approach to the dif-
ferential diagnosis of visual symptoms. of Neurology.
Recent Findings: Many neurologic disorders may present with visual symptoms.
Therefore, neurologists must be familiar with the array of pathophysiologic processes
that cause visual symptoms. Orbital imaging is challenging owing to the small struc-
tures and different tissue interfaces within and surrounding the orbital compartment.
Some of the emerging three-dimensional MRI sequences are promising and compare
well with high-resolution two-dimensional sequences in the orbits.
Summary: The diagnosis of patients with visual symptoms can be challenging and
often requires in-depth knowledge of neuroanatomy that is well depicted by various
imaging methods. Neurologists are expected to be familiar with the latest imaging
techniques that play an important role not only in diagnosing diseases but also
in determining disease pathogenesis. Close collaboration with the neuroimager,
ophthalmologist, and, when available, neuro-ophthalmologist, is recommended when
caring for patients with visual symptoms.
INTRODUCTION alone may suffice (Case 6-1). This

Neuroimaging has become one of article focuses on the most common
the most powerful diagnostic tools in neuro-ophthalmologic disorders neu-
neuro-ophthalmology as it provides rologists encounter in clinical practice.
visualization of structural damage to
the orbits and central nervous system. CONVENTIONAL AND
MRI is the modality of choice because ADVANCED IMAGING
it is noninvasive and radiation free and Neuroimaging of the orbit is challeng-
provides full field-of-view imaging and ing because of the different tissues
soft tissue contrast. However, CT may within and surrounding the bony orbit
be helpful in the evaluation of calcified that give rise to two major types of
lesions, such as aneurysms, optic artifacts: chemical shift at the fat-water
nerve head drusen, optic nerve sheath interface that causes misregistration
meningiomas, and retinoblastomas and magnetic susceptibility at the bone-
(Figure 6-1). MRIs of the brain and air interface that causes signal loss
orbits in a patient with a visual symp- and distortion (Figure 6-3A). The or-
tom are usually ordered together to bital structures are buried in fatty
assess the entire visual system, including tissues, which show hyperintense sig-
orbital and intracranial compartments. nal on both T1- and T2-weighted
However, some localizing symptoms sequences (due to fat having short
and signs (Table 6-11) suggest an T1 and long T2 values). The routinely
orbital disease for which orbital MRI used fat-suppression MRI methods

Visual Symptoms
KEY POINTS
h CT may be helpful in
the evaluation of
calcified lesions, such
as aneurysms, optic
nerve head drusen,
optic nerve sheath
meningiomas,
and retinoblastomas.
h The orbital structures
are buried in fatty
tissues, which show
hyperintense signal
on both T1- and
T2-weighted sequences
(due to fat having short Head CT without contrast is helpful in the differential diagnosis of intracranial and
FIGURE 6-1
T1 and long T2 values). intraorbital lesions by demonstrating calcification, such as in supraclinoid internal
carotid aneurysm (A, arrow), optic nerve head drusen (bilateral) (B, arrows),
and retinoblastoma (C, arrow).
a
TABLE 6-1 Symptoms and Signs Suggestive of Orbital Disease (Localizing)
and Either Intracranial or Orbital Disease (Nonlocalizing)
b Localizing
Proptosis
Conjunctival injection, chemosis
Eye pain
Enophthalmos
Gaze-evoked amaurosis
Eyelid retraction, lid lag
Unilateral optic disc swelling
Choroidal and retinal folds
Optociliary shunt vessels
Numb cheek syndrome
b Nonlocalizing
Bilateral optic disc swelling
Papilledema
Diplopia
Headache
Relative afferent pupillary defect, Adie tonic pupil
Visual field defect
a
Modified with permission from Szatmáry G, Neurol Clin.1 B 2008 Elsevier Inc. www.sciencedirect.
com/science/article/pii/S0733861908001187.

Case 6-1
A 55-year-old woman presented with a 2-month history of progressive right eye symptoms, including
pain, recurrent episodes of transient visual loss on right gaze (ie, gaze-evoked amaurosis) and, more
recently, bulge. Examination showed 2-mm
proptosis and mild esotropia of her right
eye in primary position that worsened
on right gaze. Afferent visual system
examination was normal. MRI of the orbits
was obtained. Sagittal T1-weighted MRI
showed a hypointense extraconal mass
adjacent to or arising from the lacrimal
gland (Figure 6-2A, arrow). Coronal
T2-weighted image showed a hyperintense
extraconal mass inferiorly and medially
displacing the lateral rectus muscle
(Figure 6-2B, arrow), and axial T1-weighted
contrast-enhanced MRI with fat
suppression demonstrated an intensely
and homogeneously enhancing mass
(Figure 6-2C).
The patient underwent surgical
exenteration of the right orbit for
high-grade adenoid cystic carcinoma,
followed by radiation. Postsurgical image
2 years later demonstrated intracranial
recurrence (Figure 6-2D).
Comment. This patient presented with FIGURE 6-2 Imaging of the patient in Case 6-1. A,
Sagittal T1-weighted MRI shows a
right eye pain, proptosis, and gaze-evoked hypointense extraconal mass adjacent to or
amaurosis suggesting an orbital lesion, and arising from the lacrimal gland (arrow). B, Coronal
T2-weighted MRI shows a hyperintense extraconal mass
MRI of the orbits confirmed a lesion in the inferiorly and medially displacing the lateral rectus muscle
vicinity of the lacrimal gland. The imaging (arrow). C, Axial T1-weighted contrast-enhanced MRI with
differential diagnosis of a lacrimal gland fat suppression demonstrates an intensely and homogeneously
enhancing mass (arrow). D, Postsurgical MRI 2 years after
lesion includes pleomorphic adenoma, orbital exenteration for adenoid cystic carcinoma demonstrates
which is the most common benign tumor; intracranial recurrence (arrows).
however, malignant transformation of the
lesion may occur. Adenoid cystic carcinoma
is the most frequent malignant tumor arising from the lacrimal gland. CT may show calcification in
both lesions, but associated bone erosion and infiltration of adjacent structures occurs only in malignancy.
This lesion showed intense enhancement, and although it was fully resected, it recurred distant from
the primary site, most likely by perineural/perivascular spread.
(eg, inversion recovery sequences obscured by partial volume averaging

such as short tau inversion recovery effect in images obtained at a slice
[STIR] and selective partial inversion thickness greater than the structure
recovery) have a long scan time and itself. Some of the resolution-related
may have insufficient fat suppression, difficulties are overcome by high-
which may give rise to false pathology resolution (0.5 mm to 1 mm) isotropic
and obscuration of underlying pathol- three-dimensional sequences with the
ogy (Figures 6-3B and 6-3C). Also, the added advantage of multiplanar recon-
orbital structures are small and often structions, eg, magnetization-prepared

Visual Symptoms
hold examination (VIBE), a motion

robust fat-suppressed T1-weighted
gradient recalled echo (GRE) acquisition
that has recently demonstrated superior
image quality when evaluating the
orbits compared with MPRAGE and
conventional two-dimensional turbo
spin-echo sequences (Figure 6-3D).3
MRI is a sensitive technique, but its
specificity is relatively low; therefore,
different disease processes can cause
similar imaging appearances. Even
diffusion-weighted imaging (DWI),
originally thought to be specific for an
ischemic etiology, has been reported to
show reduced diffusivity (suggesting
axonal degeneration) in several dif-
ferent disease processes, including
ischemic, inflammatory, and traumatic
optic neuropathy; papilledema; and
Orbital artifacts and advanced sequences. tumors of the optic nerve and sheath.
FIGURE 6-3
Chemical shift artifact causes misregistration at The time-spatial labeling inversion
fat-water interfaces, such as the optic nerve and pulse (Time-SLIP) technique with bal-
sheath, as seen on this coronal T2-weighted MRI (A, arrow);
magnetic susceptibility artifact arises at the interface of anced steady-state free precession
tissues with markedly varied magnetic susceptibilities (bSSFP) sequences is an advanced
(paranasal sinuses-bony orbit) and may be caused by highly
magnetic materials near the orbit, such as dental appliances, as imaging method that is capable of
seen on this axial T2 fluid-attenuated inversion recovery demonstrating to-and-fro pulsations
(FLAIR) fat-suppressed MRI (B, arrow), or by incomplete fat
suppression, as seen on this axial T1-weighted fat-suppressed of the CSF and has been able to
MRI, involving the intraconal and temporal soft tissue address the pathophysiology of some
(C, arrows). Three-dimensional radial volumetric interpolated
breath-hold examination (VIBE) is a gradient recalled echo (GRE) CSF flow-related disorders.4
sequence and normally shows increased vascular markings
along the optic nerves, imitating pathologic contrast
enhancement (D, arrow).
VISUAL LOSS
Imaging plays an important role in
KEY POINT the complex differential diagnosis
rapid-acquisition gradient-echo imaging of neurologic causes of visual loss
h MRI is a sensitive
technique, but its
(MPRAGE) with water excitation. How- by confirming or excluding the pres-
specificity is relatively ever, three-dimensional sequences, ence of a compressive/infiltrative,
low; therefore, different which provide faster acquisition, higher inflammatory/infectious, hereditary, me-
disease processes spatial resolution, and fewer motion chanical (elevated intracranial or in-
can cause similar artifacts, still have not replaced conven- traocular pressure), toxic/metabolic,
imaging appearances. tional high-resolution two-dimensional traumatic, or vascular lesion and by
sequences because these provide bet- monitoring disease activity and poten-
ter image quality, higher contrast to tial complications.
noise and signal to noise ratios, and The causes of visual loss can be
higher diagnostic confidence.2 A pro- divided topographically into orbital
mising technique is three-dimensional and intracranial processes. Diseases
radial volumetric interpolated breath- of the orbits are best assessed by

dividing the orbit into compartments,
which include the globe, intraconal
(extraoptic, optic nerve, and sheath),
extraocular muscle cone (the cone-
shaped compartment enclosed by the
extraocular rectus muscles from the
orbital apex to the globe), and extra-
conal (including lacrimal gland, extra-
conal fat, and eyelid) (Figure 6-45).
Intracranial causes of visual loss can
be divided by lesion location into
prechiasmal, chiasmal, and retro-
chiasmal etiologies.
FIGURE 6-4 Diseases of the orbits are best assessed by
ABNORMALITIES OF THE dividing the orbit into compartments, which
OPTIC NERVE include the globe, intraconal (blue arrow;
extraoptic, optic nerve, and sheath), extraocular muscle
Optic nerve disease is suspected cone (white arrow; cone refers to the cone-shaped
compartment enclosed by the extraocular rectus muscles
when a patient presents with decreased from the orbital apex to the globe), and extraconal (green
vision and, on examination, is noted arrow; including lacrimal gland, extraconal fat, and eyelid).
to have abnormal visual acuity or color 5
Modified with permission from Youssem D, Radiology Assistant. www.
vision, a relative afferent pupillary radiologyassistant.nl/en/p489ca7c544b19/orbita-pathology.html.
defect, a swollen optic nerve (or nor-

mal fundus), or a monocular visual
field deficit.6 pseudotumor cerebri syndrome) in- KEY POINTS
clude: (1) empty or partially empty h Imaging plays an
Mechanical Causes sella, (2) flattening of the posterior important role in the
The most common bilateral optic nerve aspect of the globe (with or without complex differential
protrusion into the globe), (3) disten- diagnosis of neurogenic
disease neurologists are consulted on is
visual loss by confirming
swollen optic nerves from mechanical tion of the optic nerve sheath (perioptic
or excluding the
causes. The differential diagnosis of subarachnoid space) with or without a
presence of a
a swollen optic nerve includes papillitis tortuous optic nerve, and (4) transverse compressive/infiltrative,
or anterior optic neuritis, ischemic or venous sinus stenosis (Case 6-2).7 The inflammatory/infectious,
infiltrative optic neuropathy, pseudo- presence of three out of four of these hereditary, mechanical
papilledema secondary to optic disc imaging criteria supports the diagnosis (elevated intracranial or
drusen, or asymmetric true papilledema. of pseudotumor cerebri syndrome, es- intraocular pressure),
The term papilledema should only be pecially in the so-called pseudotumor toxic/metabolic,
used when the optic nerve swelling is cerebri syndrome without papilledema traumatic, or vascular
secondary to proven raised intracranial (neither papilledema nor abducens lesion and by monitoring
pressure and usually manifesting as nerve palsy is present) and in probable disease activity and
pseudotumor cerebri syndrome when potential complications.
bilateral symmetric swelling. A helpful
imaging sign of pseudopapilledema opening CSF pressure is lower than h The most common
due to optic nerve head drusen is 250 mm. However, it should be recog- bilateral optic nerve
hyperdensity due to calcification at nized that these imaging signs are disease that the
epiphenomena and do not indicate a neurologist is consulted
the optic nerve head on CT head
on is swollen optic
without contrast (Figure 6-1B). Neu- causal relationship to the underlying
nerves from
roimaging signs that are useful process; they are usually nonspecific
mechanical causes.
to support the clinical diagnosis of manifestations of elevated intracranial
papilledema due to idiopathic intra- pressure (ICP) (Figure 6-6). Perhaps
cranial hypertension (IIH, ie, primary the only exception is transverse sinus

Visual Symptoms
Case 6-2
A 23-year-old woman was referred for a neurologic evaluation by an optometrist for bilateral severe
optic nerve swelling. She reported transient visual obscurations simultaneously in both eyes and
bilateral pulsatile tinnitus for 1 month. She had no headaches or diplopia. On examination, her body
mass index was 55 kg/m2 and her visual acuity was 20/20 in the right eye and 20/25 in the left eye with
normal color vision and no relative afferent pupillary defect. She had peripheral temporal visual field
loss in both eyes and severe symmetric bilateral optic nerve swelling with optic disc hemorrhages
(Figure 6-5A).
Brain MRI showed the following findings: Sagittal T1-weighted MRI showed a partial empty sella
(Figure 6-5B); coronal T2-weighted MRI showed dilation of the optic nerve sheaths (Figure 6-5C);
axial three-dimensional contrast-enhanced fast-spoiled GRE-weighted sequence showed flattening,
protrusion, and enhancement of the optic discs (Figure 6-5D); axial three-dimensional contrast-enhanced
magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence showed tortuosity of
the intraorbital optic nerves (Figure 6-5E); and magnetic resonance venography (MRV) showed lateral
transverse sinus stenosis, bilaterally (Figure 6-5F). Lumbar puncture opening pressure in the lateral
decubitus position was 440 mm CSF, and CSF profile was normal. Her visual symptoms improved
following lumbar puncture, and she was started on acetazolamide.
Imaging of the patient in Case 6-2. A, Severe symmetric optic nerve swelling
FIGURE 6-5 with optic disc hemorrhages (only the right eye is shown). B, Sagittal T1-weighted
MRI shows partial empty sella (arrow). C, Coronal T2-weighted MRI shows dilation
of the optic nerve sheaths. D, Axial three-dimensional contrast-enhanced fast-spoiled gradient
recalled echo (GRE)-weighted sequence shows flattening, protrusion, and enhancement of the
optic discs (arrows). E, Axial three-dimensional contrast-enhanced magnetization-prepared
rapid-acquisition gradient-echo sequence (MPRAGE) shows tortuosity of the intraorbital optic
nerves (arrows). F, Magnetic resonance venography (MRV) shows lateral transverse sinus stenosis,
bilaterally (arrows).

Comment. Some patients with pseudotumor cerebri syndrome have no headaches; thus, by the
time they seek medical attention, permanent visual dysfunction has often occurred. The imaging
findings in this case, even before lumbar puncture, suggested the diagnosis of idiopathic intracranial
hypertension in a patient with a typical phenotype for this condition.
stenosis, as stenting of the stenotic significantly smaller, which is a likely KEY POINTS
sinus (or both sinuses) seems to suffi- contributor to the intracranial hyper- h Neuroimaging signs that
are useful to support the
ciently lower the ICP, suggesting that tension in patients with IIH.8
clinical diagnosis of
venous hypertension has a causal rela- For patients with the typical pheno-
papilledema due to
tionship to intracranial hypertension. It type for IIH (young obese female), the
idiopathic intracranial
is still debated whether bilateral or recommendation is to obtain a brain hypertension (ie, primary
unilateral dysfunction of the transverse MRI with and without contrast to con- pseudotumor cerebri
sinus is required to cause elevated ICP. firm normal brain parenchyma and ab- syndrome) include: (1)
Other imaging findings that suggest sence of hydrocephalus and to exclude empty or partially empty
chronically elevated ICP are meningo- abnormal meningeal enhancement. For sella, (2) flattening of the
celes at various apertures of the cranial patients with an atypical phenotype, posterior aspect of the
vault (Figure 6-7) and acquired cere- additional magnetic resonance venog- globe (with or without
bellar tonsillar ectopia. In some patients raphy (MRV) is recommended. Cranial protrusion into the
with IIH, ICP is spontaneously lowered MRV may be obtained without contrast; globe), (3) distention of
however, when an intrinsic venous sinus the optic nerve sheath
by the development of a CSF leak
(perioptic subarachnoid
(rhinorrhea, otorrhea); when the leak lesion is suspected, then MRV both
space) with or without a
is patched, symptoms of raised ICP with and without contrast should be
tortuous optic nerve, and
develop (Figure 6-7D). Tain and col- obtained (Figures 6-7E and 6-7F). The (4) transverse venous
leagues investigated the underlying eti- imaging differential diagnosis of sec- sinus stenosis.
ology of IIH by using velocity-encoded ondary pseudotumor cerebri syndrome
h Imaging findings that
phase-contrast MRI to determine the includes cerebral venous sinus or bilat-
suggest chronically
craniospinal canal compliance distribu- eral jugular vein thrombosis, middle elevated intracranial
tion. They found that normally the ear or mastoid infection, previous pressure are
spinal canal contribution is larger than intracranial infection or subarachnoid meningoceles at various
the cranial; however, in patients with hemorrhage, giant arachnoid granula- apertures of the cranial
IIH, the spinal canal contribution is tion, and dural arteriovenous fistula of vault and
acquired cerebellar
tonsillar ectopia.
Imaging of a 46-year-old man with a history of cryptococcal meningitis who presented

FIGURE 6-6 with acute simultaneous painless visual loss bilaterally. Fundus examination
shows severe symmetric optic nerve swelling with peripapillary hemorrhages (A).
Contrast-enhanced T1-weighted fat-suppressed MRI shows optic nerve protrusion into the globes
and enhancement suggesting papilledema (B, arrows).

Visual Symptoms
KEY POINTS
h For patients with the
typical phenotype for
hypertension (young
obese female), the
recommendation is to
obtain a brain MRI with
and without contrast to
confirm normal brain
parenchyma and absence
of hydrocephalus and
to exclude abnormal
meningeal enhancement.
For patients with an
a typical phenotype,
additional magnetic
resonance venography
is recommended.
h When a patient does
not have the typical
phenotype for
hypertension or when FIGURE 6-7 Imaging findings that support the diagnosis of intracranial hypertension include
meningoceles with enlargement of CSF-filled structures, such as Meckel caves (A,
CSF is not entirely arrow) and internal auditory canals (B), hyperintensity of the optic nerve head on
normal, then spinal diffusion-weighted imaging (DWI) (C, arrow) corresponding to papilledema, and spontaneous
abnormalities, such as CSF leakage at the olfactory recess bilaterally, greater on the left (D, arrow). A differential
diagnostic imaging finding of transverse sinus stenosis is signal loss due to arachnoid granulation
spinal leptomeningeal as seen on this contrast-enhanced magnetization-prepared gradient-echo sequence (MPRAGE)
lymphoma, should be (E, arrow) and magnetic resonance venography (MRV) head images (F, arrow); when it is giant
considered and imaging and bilateral, it can cause substantial obstruction resulting in venous and, subsequently,
intracranial hypertension.
of the entire spinal axis
should be performed.
h Optic nerve glioma is the transverse sinus leading to venous glioma is one of the optic pathway
one of the optic and, in turn, intracranial hypertension. gliomas, and when it is bilateral, it is
pathway gliomas, and However, when these causes are ruled pathognomonic for neurofibromatosis
when it is bilateral, it
out, especially when the patient does type 1. Histologically, especially in chil-
is pathognomic for
not have the typical phenotype for IIH dren, optic nerve glioma is most often
neurofibromatosis
type 1.
or when CSF is not entirely normal, a low-grade tumor, usually pilocytic
then spinal abnormalities, such as spi- astrocytoma, but high-grade tumors
nal leptomeningeal lymphoma, should do occur. On MRI, the optic nerve is
be considered and imaging of the entire typically elongated and has a central
spinal axis should be performed. T2-hyperintense homogeneous linear
core (representing intraneural growth)
Compressive/Infiltrative and surrounding peripheral T2 hyper-
Causes intensity (representing perineural
Patients with optic nerve glioma and growth), called gliomatosis. Optic nerve
optic nerve sheath meningioma usually glioma may show variable enhance-
present with painless gradual visual loss ment on MRI (Figure 6-8D).
or an abnormal optic nerve (atrophy or Patients with optic nerve sheath me-
swelling) that is incidentally found on ningiomas may be observed to have
examination (Figure 6-8). Optic nerve optociliary shunt vessels and choroidal

KEY POINTS
h In the imaging-based
differentiation of optic
nerve sheath
meningioma, helpful
clues are calcification or
enhancement of the
optic nerve sheath,
often with compression
of the optic nerve. Each
of these features has
been labeled as the
tram-track sign.
Sometimes optic nerve
sheath meningioma
may cause bony
erosion, hyperostosis, or
pneumatization of the
adjacent bone.
h The imaging differential
diagnosis of meningeal
FIGURE 6-8 Optic nerve glioma in the right eye of a enhancement includes
10-year-old girl who was negative for
neurofibromatosis. A, Severe chronic optic disc low intracranial pressure
swelling in the right eye. B, On axial T2-weighted fat-suppressed (pachymeningeal
MRI, hyperintensity and elongation of the right intraorbital involvement), infectious
optic nerve is seen (arrow). C, Intense homogenous enhancement
on coronal contrast-enhanced T1-weighted image (arrow) (lesion or neoplastic meningitis,
was isointense on T1-weighted image without contrast [not and dural metastasis.
shown]). D, MRI of another patient with neurofibromatosis
type 1 shows no contrast enhancement of the enlarged
intracranial optic nerve due to optic nerve glioma on coronal
contrast-enhanced T1-weighted image (arrow).
folds on funduscopy. Optic nerve sheath tous, leukemic, lymphomatous, or pri-

meningiomas arise either primarily mary brain tumorYrelated) is suggested
from arachnoid cap cells of the optic by enhancement of the affected layer.
nerve sheath or secondarily from in- Tumor cells can reach the subarach-
tracranial extension of anterior skull noid space through blood, by growing
base meningiomas of the tuberculum along nerve or vascular sheaths, or by
or diaphragma sellae, or anterior clinoid migration from a tumor adjacent to
process (Case 6-3). In the imaging-based CSF. The imaging differential diagnosis
differentiation of optic nerve sheath of meningeal enhancement includes
meningioma, helpful clues are calcifica- low ICP (pachymeningeal involve-
tion or enhancement of the optic nerve ment), infectious or neoplastic menin-
sheath, often with compression of the gitis, and dural metastasis. Perineural
optic nerve (Figure 6-10). Each of spread affects 3% to 5% of patients
these features has been labeled the with cancer (Figure 6-12).9 Perineural
tram-track sign. Sometimes optic nerve spread along the optic nerve causes not
sheath meningiomas may cause bony only optic nerve sheath coverage with
erosion, hyperostosis, or pneumatiza- tumor cells but also neoplastic invasion
tion of the adjacent bone (Figure 6-11). along the Virchow-Robin spaces
On imaging, neoplastic meningeal or (mesenchymal septa), resulting in
leptomeningeal disease (carcinoma- demyelination, axonal beading, and

Visual Symptoms
Case 6-3
A 75-year-old woman was referred to the neuro-ophthalmology clinic for a 2-month history of visual
loss. Her symptoms began with progressive visual loss in her left eye, which led over 2 to 3 weeks
to blindness in that eye. She reported only mild left frontal headaches at onset but subsequently
noted bilateral retroorbital pain independent of eye movement. Six weeks after her symptoms began
in the left eye, she developed gradual central visual loss in the right eye. She denied jaw claudication,
scalp tenderness, diplopia, transient visual obscurations, or pulsatile tinnitus. She reported flulike
symptoms 1 week prior to the onset of her initial visual loss.
On examination in neuro-ophthalmology clinic, her visual acuity was 20/100 in the right eye and
she had no light perception in the left eye. She was not able to identify any of the Ishihara color plates
with both eyes and had a left relative afferent pupillary defect. Extraocular movements were full. Fundus
examination showed a small crowded normal-appearing right optic nerve and left optic atrophy.
Review of her previous imaging showed that an MRI scan of the brain 2 weeks after the onset of
her visual loss in the left and prior to the visual loss in her right eye demonstrated enlarged and
hyperintense prechiasmal left and subtle central hyperintensity in the right optic nerve on coronal
T2-weighted images (Figure 6-9A), with corresponding enhancement in the left greater than right
intracanalicular and intracranial
segments on contrast-enhanced
fat-suppressed T1-weighted
images in the coronal (Figure 6-9B)
and axial planes (Figure 6-9C).
MRI done at the time of her
neuro-ophthalmology visit
showed progression and more
obvious enhancement of the
right optic nerve on coronal
T1-weighted fat-suppressed
images (Figure 6-9D).
Laboratory evaluation
showed a normal sedimentation
rate, C-reactive protein,
angiotensin-converting enzyme
level, and vitamin B12 level, as
well as normal blood cell counts
and a negative Venereal
Disease Research Laboratory
(VDRL) test. Lumbar puncture
showed a cell count of 0, FIGURE 6-9 Imaging of the patient in Case 6-3. Two weeks after visual
loss in the left eye and before visual loss in the right eye,
protein level of 46 mg/dL, and coronal T2-weighted MRI shows enlarged and hyperintense
glucose level of 63 mg/dL, with prechiasmal left and subtle central hyperintensity in the right optic nerve
positive myelin basic protein, (A, arrows); contrast-enhanced fat-suppressed T1-weighted image in the
coronal (B, arrow marks enhancing right central optic nerve) and axial (C, red
negative oligoclonal bands, and arrow marks enhancing left optic nerve) planes (fat-suppression artifacts in the
a normal IgG index. Two weeks medial orbits marked by white arrows in panel C). Two months after
later, her visual acuity presentation, coronal T1-weighted fat-suppressed MRI shows progression
and more obvious enhancement of the right optic nerve (D, arrow), and
deteriorated to 20/200 in the 4 months from initial presentation, severe enlargement and enhancement
right eye, and 4 weeks after of both optic nerves in the coronal (E) and axial (F) planes and additional
that, she had no light perception involvement of the optic chiasm and left optic tract (F, arrows) is seen.
in either eye.

Follow-up imaging 4 months after her initial presentation showed severe enlargement and
enhancement of both optic nerves in the coronal (Figure 6-9E) and axial planes (Figure 6-9F), with
additional involvement of the optic chiasm and left optic tract.
Comment. The course of this patient’s visual loss, despite the fact that she had no optic disc
swelling, suggests that she had a malignancy affecting her optic nerves, either metastatic or primary.
Glioblastoma of the optic nerve was the greatest likelihood, but sarcoidosis or, less likely, lymphoma or
Wegener granulomatosis was also a possibility. The least likely etiology was metastatic malignancy with
carcinomatous meningitis, because when blindness occurs in this setting, it is usually associated with
mental status and CSF changes. The fact that she had mildly elevated myelin basic protein in the absence
of oligoclonal bands suggested breakdown of myelin. The patient underwent a biopsy of the left
intracranial optic nerve and meninges. The biopsy confirmed World Health Organization grade IV
glioblastoma. MRI of the orbit performed before onset of visual loss in the right eye already showed
subtle signal changes, heralding visual loss in the then asymptomatic eye.
Imaging of a 42-year-old woman who presented

FIGURE 6-10 with painless blurred vision in the right eye for
8 months, worse a few minutes after starting to
exercise and returning to baseline within 1 hour after exercise. MRI
of her orbits showed mildly enlarged isointense right optic nerve
involving the posterior intraorbital segment on coronal T1-weighted
imaging (A); compression of the right optic nerve by thickened
optic nerve sheath on coronal short tau inversion recovery (STIR)
sequence (B, arrow); and enhancement and thickening of
the dura (C, white arrow) and the right optic nerve sheath
(C, yellow arrow) in the posterior orbit and the optic canal, and
enlargement and intense enhancement of the right
optic nerve and sheath complex posterior to the optic canal
(D, arrow) on axial contrast-enhanced T1-weighted fat-suppressed
imaging. The diagnosis was anterior clinoid meningioma with orbital
extension versus primary optic nerve sheath meningioma with
intracranial extension.

Visual Symptoms
linating) etiologies. In demyelinating op-

tic neuritis, a patient typically presents
with eye pain provoked by eye move-
ments (in about 95% of cases) and either
a normal optic nerve appearance or
mild optic nerve swelling (Figure 6-14A).
MRI of the brain with and without
contrast should be obtained, because
it currently is the best predictor of
present and future risk of multiple
sclerosis (MS). On MRI with STIR, T2
FIGURE 6-11 Bilateral anterior clinoid meningiomas fluid-attenuated inversion recovery
presenting with unilateral gradual (FLAIR), or T2-weighted imaging with
right-sided visual loss. Contrast-enhanced
fat-suppressed MRI orbits axial (A) and coronal (B) images fat suppression, optic nerve hyperin-
demonstrate asymmetrically pneumatized anterior clinoid tensity is seen in the vast majority of
process (A, B, white arrows) at the level of the prechiasmal
optic nerves and extraaxial dural-based right-sided greater
the cases (Figure 6-14), and on
than left-sided lesions (A, B, yellow arrows), which on the contrast-enhanced T1-weighted imag-
right encase the intracavernous and supraclinoid internal ing with fat suppression, abnormal
carotid artery, compress the optic nerve, and extend into
the sella turcica. enhancement is typically seen in 94%
of affected nerves.10 If the enhancing
optic nerve segment is longer than
KEY POINT degradation of the optic nerve itself.9 17 mm or the canalicular segment of
h In acute optic neuritis, The imaging differential diagnosis of the optic nerve is involved, then poor
MRI with short tau perineural optic nerve enhancement baseline visual acuity, threshold
inversion recovery, includes leptomeningeal disease, optic perimetry, and color vision are ex-
T2 fluid-attenuated
nerve sheath meningioma, and pected. Simultaneous optic nerve
inversion recovery, or
perineuritis (Figure 6-13). or chiasmal enhancement in both
T2-weighted imaging
with fat-suppression eyes, even if only one eye is symptom-
Inflammatory Causes atic, should warrant careful evalua-
sequence shows optic
nerve hyperintensity in The diagnosis of acute optic neuritis is tion for neuromyelitis optica (NMO)
the vast majority of made clinically and is nonspecific as it (Figure 6-15). Elongated (three or
patients, and on can be the result of various infectious more vertebral body segments in
contrast-enhanced and noninfectious (including demye- length) continuous T2-hyperintense
T1-weighted imaging
with fat suppression,
abnormal enhancement
is seen in 94% of
affected nerves. If the
enhancing optic nerve
segment is longer than
17 mm or the canalicular
segment of the optic
nerve is involved, then
poor baseline visual
acuity, threshold
perimetry, and color
FIGURE 6-12 Imaging of a 75-year-old man with history of cardiac transplantation and
vision are expected.
squamous cell carcinoma who presented with left facial numbness followed by
diplopia. On examination, a left cranial nerve V and VI palsy was found. Note
the perineural spread into the left Meckel cave (A, arrow) and cavernous sinus on coronal
T1-weighted imaging without (A) and with contrast (B) and left lateral rectus atrophy and
decreased enhancement due to chronic denervation from cranial nerve VI palsy (C, arrow).

KEY POINTS
infiltration of the leptomeninges may h Sarcoid lesions tend to
result in intraparenchymal masses. be isointense relative to
When granulomas coalesce, they form gray matter on
large masslike lesions, particularly in T1-weighted imaging
the region of the floor of the third and hypointense on
ventricle and optic chiasm. Sarcoid le- T2-weighted imaging;
sions tend to be isointense relative to on contrast-enhanced
gray matter on T1-weighted images and MRI, intense meningeal
hypointense on T2-weighted images; enhancement most
on contrast-enhanced MRI, intense commonly involves
the basal meninges
meningeal enhancement most com-
and sulci. However,
monly involves the basal meninges and
leptomeningeal
Perineuritis as the first
sulci. However, leptomeningeal granu- granulomas may go
FIGURE 6-13 lomas may go unnoticed on nonY
manifestation of Lyme unnoticed on
disease in a 48-year-old contrast-enhanced MRI.
woman presenting with right eye pain, nonYcontrast-enhanced MRI.
worse on eye movement, followed by The most frequent causes of infec-
h In perineuritis, optic
bilateral lower motor neuron facial nerve tious optic neuritis include Lyme dis-
palsy. Coronal contrast-enhanced nerve function is
T1-weighted fat-suppressed image ease, syphilis, tuberculosis, and West preserved, but optic
shows optic nerve sheath enhancement Nile virus. In perineuritis, optic nerve nerve sheath
(white arrow) and enlargement of the
right medial and inferior rectus muscles function is preserved, but optic nerve inflammation is marked
(yellow arrows), suggesting myositis. sheath inflammation is marked by by thickening and
Reprinted with permission from Szatmary G, thickening and enhancement, which enhancement, which
Neurol Clin.1 is best seen on contrast-enhanced is best seen on
B 2008 Elsevier Inc. www.sciencedirect.com/
T1-weighted images with fat suppres- contrast-enhanced
science/article/pii/S0733861908001187.
sion (Figure 6-13). Autoimmune and T1-weighted MRI with
paraneoplastic optic neuropathy may fat suppression.
spinal cord lesions, called longitudinally cause nonspecific optic nerve enhance- h In hereditary,
extensive transverse myelitis, are char- ment on imaging. toxic-metabolic,
acteristic of NMO (Case 6-4). traumatic, and vascular
Sarcoid optic neuropathy usually Hereditary, Toxic/Metabolic, optic neuropathies,
Traumatic, and Vascular Causes neuroimaging is usually
presents with acute to subacute onset
normal or may show
of monocular visual loss that is often In hereditary, toxic-metabolic, trau-
some nonspecific
painful owing to the optic nerve and matic, and vascular optic neuropathies, findings involving the
lacrimal gland inflammation. Neuro- neuroimaging is usually normal or optic nerve or optic
logic manifestations occur in 5% to may show some nonspecific findings disc, including
16% of affected patients during the involving the optic nerve or optic disc, T2 hyperintensity
course of the disease, typically first including T2 hyperintensity and en- and enhancement.
manifesting as pituitary dysfunction hancement. In traumatic, vascular, and
(eg, anterior pituitary failure or diabetes inflammatory processes, DWI hyper-
insipidus), suggested by a thick intensity with or without apparent dif-
and enhancing infundibulum on MRI fusion coefficient (ADC) hypointensity
(Figure 6-17).11 Several mechanisms has been noted. Septooptic dysplasia
exist by which sarcoidosis can affect may be associated with MRI findings
the brain, such as compression by non- of optic atrophy (small optic nerve
caseating masses, inflammation, and and relatively enlarged optic nerve
infiltration. On MRI, the granulomatous sheath), agenesis of the septum pel-
infiltration of the dura mater causes lucidum or corpus callosum, and
plaquelike or nodular thickening on the hypoplastic anterior or ectopic poste-
infundibular stalk and optic chiasm, and rior pituitary gland. In Leber hereditary

Visual Symptoms
FIGURE 6-14 Optic neuritis as the first presentation of multiple sclerosis. A 40-year-old
woman presented with right eye pain, worse with eye movement, and visual
loss in the right eye. A, Optic nerve swelling in the right eye (upper) and normal
disc in the left eye (lower) is shown on fundus photos. B, A long segment of hyperintensity on
diffusion-weighted imaging (DWI) (arrow), and C, enhancement of the optic nerve (arrow) on
coronal contrast-enhanced T1-weighted fat-suppressed image. D, Axial T2 fluid-attenuated
inversion recovery (FLAIR) image shows a small linear periventricular perpendicular white
matter hyperintensity (arrow) with enhancement (not shown) consistent with an active
demyelinating plaque. E, Hypointensity (arrow) is shown on apparent diffusion coefficient
mapping, corresponding to DWI hyperintensity on panel B and, F, a long enhancing optic
nerve segment in the orbit (arrow) on axial contrast-enhanced imaging.
optic neuropathy, MS-like white matter transection of the optic nerve can
lesions have been described.12 be seen. A GRE sequence, such as
Vascular etiologies include ante- susceptibility-weighted imaging (SWI),
rior ischemic optic neuropathy, either is the most sensitive for trauma-
arteritic or nonarteritic; posterior is- related changes of the brain; how-
chemic optic neuropathy; and central ever, it has significant artifacts in the
or branch retinal artery or vein occlu- bony orbits, particularly in the narrow
sion. In giant cell arteritis, in addition optic canal where the optic nerve is
to ischemic optic neuropathy, ischemic most vulnerable.
stroke has been described. In Susac
syndrome, diagnosed by the clinical ABNORMALITIES OF THE
triad of branch retinal artery occlusion, OPTIC CHIASM
sensorineural hearing loss, and enceph- If a patient presents with binocular
alopathy, MS-like pericallosal T2 hy- visual symptoms, typically due to bi-
perintense lesions have been observed. temporal hemianopia, especially when
In traumatic optic neuropathy, it is associated with ocular motility or
imaging is usually normal, or, rarely, pupil abnormality, then perisellar

KEY POINTS
h In the imaging
evaluation of a sellar or
extrasellar lesion,
determine the epicenter
of the lesion (in, above,
below, or lateral to the
sella) and analyze the
lesion for signal
characteristics
(identification of cystic
or solid components,
calcification, and
flow voids).
h In children, the triad
of proptosis, skull
lesion, and diabetes
insipidus suggests
Hand-Schuller-Christian
syndrome, a variant
of Langerhans
cell histiocytosis.
FIGURE 6-15 Optic neuritis as the first presentation of neuromyelitis optica (NMO). A
26-year-old woman presented with severe visual loss in the left eye (A, arrows)
without improvement and 2 years later in the right eye (B, arrows), which
worsened 6 months later (C, arrows) as shown on contrast-enhanced T1-weighted coronal
(upper row) and axial (lower row) images as enlargement and a long segment of enhancement
of the left (A, arrows) and right (B, C, arrows) optic nerve. The patient could distinguish hand
motion in the right eye and had light perception vision in the left eye, and vision did not
improve; NMO antibody was positive.
etiology with involvement of the optic signal characteristic similar to acute

chiasm or intracranial optic nerves blood products, such as postoperative
should be suspected. In the imaging fat packing.
evaluation of a sellar or extrasellar le- Lesions primarily involving the in-
sion, the epicenter of the lesion fundibulum include Rathke cleft cyst
should be determined (in, above, arising from the pars intermedia,
below, or lateral to the sella) and the neurosarcoidosis (Figure 6-17), Lang-
lesion should be analyzed for signal erhans cell histiocytosis (a small
characteristics (identification of cystic solid lesion similar to sarcoidosis),
or solid components, calcification, and lymphocytic hypophysitis, eosino-
flow voids). philic granuloma, granular cell tumor,
Lesions primarily arising from the metastases, and choristoma (the
sella include pituitary adenoma, ab- presence of ganglion cells within an
cess, and hyperplasia (in hypothyroid- endocrine pituitary tumor). In chil-
ism, or lymphocytic in pregnancy). A dren, the triad of proptosis, skull
pituitary adenoma may undergo spon- lesion, and diabetes insipidus sug-
taneous decrease in size due to spon- gests Hand-Schuller-Christian syn-
taneous hemorrhage or infarction, drome, a variant of Langerhans
called pituitary apoplexy, which is a cell histiocytosis.
medical and potentially surgical emer- Lesions primarily arising from
gency. On imaging, apoplexy must the suprasellar region, mainly the
be differentiated from tissues with hypothalamus, include neoplastic (eg,

Visual Symptoms
Case 6-4
A 28-year-old Honduran man with a past medical history of celiac disease presented to the emergency
department with sudden onset of painful visual loss in his right eye. He described discomfort in his
right eye that worsened with eye movement for a couple of days prior to the onset of visual loss. He had
no prior ophthalmic or neurologic history.
MRI with orbital views obtained 2 days after onset showed mild enlargement and intrinsic hyperintensity
of the posterior orbital and intracanalicular segments of the right optic nerve on coronal short
tau inversion recovery (STIR) sequences
(Figure 6-16A) with enhancement on
contrast-enhanced T1-weighted images in
the coronal (Figures 6-16B) and axial
(Figure 6-16C) planes. Brain MRI was normal.
He was treated with IV methylprednisolone
for idiopathic optic neuritis. His neuromyelitis
optica (NMO)-IgG antibody was positive;
hence, he was initiated on azathioprine and
oral prednisone.
Six months after the visual loss, the patient
developed numbness and weakness in his
arms, and a sagittal T2-weighted cervical spine
image demonstrated an elongated
segment of cord hyperintensity, consistent
with longitudinally extensive transverse
myelitis due to NMO (Figure 6-16D),
with associated enhancement on
contrast-enhanced T1-weighted sequence, FIGURE 6-16 Imaging of the patient in Case 6-4. MRI of
confirming an acute lesion. orbital views 2 days after onset of visual loss
in the right eye shows mild enlargement
Comment. Clinical clues to the diagnosis and intrinsic hyperintensity of the posterior orbital segment
of NMO are the patient’s nonwhite race of the right optic nerve on coronal short tau inversion
and past medical history of an autoimmune recovery (STIR) sequence (A, arrow). Contrast-enhanced
T1-weighted fat-suppressed MRI shows enhancement of
disease; therefore, his NMO antibody level the right optic nerve in the orbital apex in the coronal
was checked after presentation with (B, arrow) and the optic canal in the axial (C, arrow) planes.
Sagittal T2-weighted MRI of the cervical spine (D) demonstrates
optic neuritis and was positive. Visual an elongated segment of cord hyperintensity from C1-C2
function, apart from mild dyschromatopsia, through C3-C4, consistent with longitudinally extensive
recovered following treatment with IV transverse myelitis.
methylprednisolone.
optic pathway glioma, meningioma philic granuloma; and arachnoid cysts.

[Figure 6-18], germinoma, cranio- Arachnoid cysts are benign conge-
pharyngioma) and non-neoplastic nital CSF-containing structures that
etiologies. Suprasellar non-neoplastic arise anywhere within the arachnoid
lesions include inflammatory-infectious membrane; in the suprasellar region,
etiologies, such as sarcoidosis, tuber- they may displace and compress the
culosis (involves the basal meninges chiasm and stalk and flatten the pitu-
and is typically T2 hypointense), and itary tissue. On imaging, they have the
cysticercosis; vascular lesions such as an same signal as CSF on all MRI se-
aneurysm (when thrombosed on imag- quences, show no restriction on
ing, it can mimic a craniopharyngioma) DWI (which differentiates them from
(Figure 6-19); hamartoma; eosino- other CSF-containing structures such

Neurosarcoidosis and sarcoid optic neuropathy. A 30-year-old woman
FIGURE 6-17 presented with headaches and weight gain. Sagittal T1-weighted MRI shows
thickening of the optic chiasm (A, arrow) and superior infundibulum with
associated contrast enhancement on the midsagittal image (B, arrow) and plaquelike
thickening and enhancement of the tentorium cerebelli (C, arrow). Fundus photos
obtained 2 years after initial presentation demonstrate severe optic atrophy and arterial
attenuation (D), severe bilateral optic nerve enhancement involving the intraorbital and
intracranial segments (E, F, white arrows), exotropia, and left greater than right eye
proptosis and enlargement of the lacrimal glands (E, yellow arrow) in the axial (E) and
coronal planes (F) on contrast-enhanced T1-weighted fat-suppressed images.
as epidermoid), and no enhancement plaque in the optic tract (Figure 6-20).

or calcification. When an isolated complete homony-
Parasellar and infrasellar lesions mous hemianopia without other
primarily cause diplopia and not neurologic symptoms is identified, a
visual loss; they are therefore discussed primary visual cortical (striate cortex)
in the diplopia section of this article. lesion is suspected, most frequently
from a posterior cerebral artery infarc-
RETROCHIASMAL LESIONS tion or hemorrhage.
A retrochiasmal lesion is suspected In posterior cortical atrophy, visual
when a patient presents with bino- symptoms dominate and areas of cog-
cular visual symptoms (although pa- nition are not affected or only minimally
tients may interpret symptoms as affected at onset. Progressive visuospa-
monocular, involving only the eye tial symptoms due to involvement of
with the temporal visual field defect) the dorsal stream (parietal lobe) visual
and, on examination, homonymous pathway and cortical vision loss develop
hemianopia is identified (a relative af- over time (Figure 6-21), and most
ferent pupillary defect is present in patients will progress to Alzheimer
optic tract lesions only). Rarely, MS pre- disease or other types of dementia,
sents with an isolated demyelinating such as dementia with Lewy bodies,

Visual Symptoms
KEY POINT
h Blow-out fracture of the
orbit usually
involves the thinnest
orbital walls.
FIGURE 6-18 Olfactory groove meningioma presenting as bilateral sequential visual loss in a
54-year-old woman, first in the left eye followed by the right eye. Brain MRI
demonstrates a large bilateral anterior cranial fossa lesion, which on sagittal
three-dimensional T1-weighted sequence is hypointense (A), on axial T2-weighted sequence
hyperintense (B), on coronal T2 fluid-attenuated inversion recovery (FLAIR) fat-suppressed
sequence mildly hyperintense (C, white arrow) with surrounding significant hyperintensity
consistent with vasogenic edema (C, yellow arrow). Contrast-enhanced three-dimensional
axial magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence at the
level of the anterior cranial fossa shows diffuse intense enhancement (D), at the level of
the optic canal with extension into the orbits (E, red arrows), which is confirmed on coronal
reconstruction (F, blue arrows).
corticobasal syndrome, or Creutzfeldt- trast should be done; a protocol

Jakob disease. recommendation includes axial sec-
tions of less than 1 mm angled along
DIPLOPIA the course of the optic nerve and
Diplopia is a nonlocalizing symptom; coronal and sagittal reformations of
thus, the lesion could be anywhere 1-mm thickness.
along the efferent visual pathway. If Ocular restriction, and thus restric-
orbital pathology is suspected, a pro- tive myogenic diplopia, is seen in orbital
tocol recommendation for an MRI fracture and thyroid eye disease. Blow-
study of the orbits with and without out fracture of the orbit usually in-
contrast study is coronal T1-weighted, volves the thinnest orbital walls,
coronal STIR (or T2-weighted fat- including the orbital floor nasal to the
suppressed), axial DWI and ADC infraorbital groove, which may also
map, and axial and coronal contrasted cause infraorbital nerve contusion, and
T1-weighted fat-suppressed sequences the orbital plate of the ethmoid bone,
with high resolution (2.5 mm to 3 mm). which is usually less symptomatic be-
If MRI cannot be performed, then a cause of greater ability to fuse horizon-
CT of the orbits with or without con- tal rather than vertical incongruence.

KEY POINTS
h On imaging of
blow-out fracture of the
orbit, enophthalmos,
air in the lids, and a
teardrop sign due to
prolapsed tissue through
the fracture can be seen.
h In thyroid eye disease,
the acute inflammatory
stage is signified by
increased water
content of the involved
muscles, resulting
in T2 hyperintensity. The
chronic stage is marked
by fibrosis and fat
accumulation seen as
T1 hyperintensity.
Suprasellar and parasellar aneurysms with

FIGURE 6-19 compression of the optic nerve and chiasm.
Sagittal T1-weighted parasagittal image
shows a round mixed-signal extraaxial lesion indenting
the intracranial optic nerve (A, arrow), corresponding to
hypointense flow void on coronal T2-weighted image
(B, arrow) and peripheral enhancement on axial
contrast-enhanced T1-weighted sequence (C ) due to
central thrombosis with compression of the right side of
optic chiasm (C, arrow). Imaging of a different patient with
bilateral parasellar aneurysms demonstrates hypointense
signal with widening of the cavernous sinuses (D, arrows).
On imaging, enophthalmos, air in marked by stretching of the optic

the lids, and a teardrop sign due to nerve by increased retrobulbar fat.
prolapsed tissue through the fracture This MRI-based staging is important
can be seen (Figure 6-22). Another regarding treatment as in the acute
weak point of the bony orbit is the
narrow optic canal (3 mm to 4 mm
wide and 5 mm long), where contu-
sion of the optic nerve can occur.
Thyroid eye disease causes spindle-
shaped enlargement without tendinous
involvement of the extraocular muscles,
most frequently the inferior and me-
dial recti. The acute inflammatory stage
is signified by increased water content
of the involved muscles, resulting in
T2 hyperintensity. The chronic stage is Optic tract lesion as the first manifestation
FIGURE 6-20
marked by fibrosis and fat accumulation of multiple sclerosis. Sagittal T2-weighted
parasagittal image demonstrating oval-shaped
seen as T1 hyperintensity and may hyperintensity (A, arrow) corresponding to enhancement on
result in clinical worsening of restric- axial contrast-enhanced T1-weighted image (B, arrow).
tion (Figure 6-23). Chronicity is also

Visual Symptoms
of malignancy. If the extraocular mus-

cles are involved in the orbital apex,
risk of compressive optic neuro-
pathy exists (Figure 6-24). Orbital
cellulitis spreading from the adja-
cent ethmoid air cell is an infectious
cause of diplopia; it usually begins as
subperiosteal abscess and, when it
involves the medial rectus muscle,
manifests as diplopia.
Idiopathic orbital inflammation,
also called orbital pseudotumor, is a
FIGURE 6-21 Posterior cortical atrophy. A 65-year-old
woman presented with getting lost in heterogeneous group of disorders
familiar surroundings followed by decreased that usually present with painful prop-
memory for recent events. MRI obtained a few years after tosis and diplopia13; it can be diffuse
presentation shows posterior dominant cortical atrophy on
sagittal T1-weighted (A) and axial T2-weighted (B) sequences or localized to a single extraocular
(A, B, white arrows), predominantly involving the occipital muscle, which is called myositis. On
and inferior parietal lobes, and secondary ex vacuo
enlargement of the posterior horns of the lateral ventricles MRI, T2 hypointensity relative to
(A, yellow arrow). uninvolved muscles, enlargement and
marked contrast enhancement, and,
KEY POINT stage steroids are more likely to be ef- occasionally, bone destruction are
h IgG4-related disease of fective. Other extraocular myopathies, seen. IgG4-related disease of the orbit
the orbit may present such as neuromyotonia, myotonia, and may present with myositis or may
with myositis or may superior oblique myokymia, do not involve other orbital (dacryoadenitis)
involve other orbital or intracranial tissues (eg, pachymen-
cause imaging abnormalities. Meta-
(dacryoadenitis) or
static lesions to the orbit may also ingitis, hypophysitis).14 Histologically,
intracranial tissues
cause restrictive diplopia, and this it is a fibroinflammatory process with a
(pachymeningitis,
hypophysitis). may involve one or multiple muscles. propensity to form pseudotumors by
Infrequently, diplopia is the first sign inflammatory infiltrate with IgG4-rich
FIGURE 6-22 Orbital floor and medial blow-out fracture in a patient with trauma. A, Coronal
CT at the midorbital level, bone windows view, shows fracture involving the
infraorbital foramen, orbital emphysema (white arrow), and fracture of the
lamina papyracea with opacification of the adjacent ethmoid sinus (red arrow). B, Coronal
T1-weighted and, C, fluid-attenuated inversion recovery (FLAIR) MRIs show inferior dislocation
of the right inferior rectus muscle, but no entrapment, and herniation of the extraconal fat
into the adjacent ethmoid sinus, called the teardrop sign (B, C, yellow arrows).

Thyroid eye disease in a 50-year-old woman with a remote history of Hashimoto
FIGURE 6-23 thyroiditis who presented with vertical diplopia; laboratory findings were
consistent with Graves disease. Prior to treatment with IV methylprednisolone, sagittal
T1-weighted brain MRI demonstrates isointensity and enlargement (A, arrow), and coronal
T2-weighted fat-suppressed image shows hyperintensity of the left inferior rectus muscle (B, arrow),
with intense homogenous enhancement shown on contrast-enhanced T1-weighted image (C,
arrow). Two months after treatment, mixed T1 hyperintensity and isointensity (D, arrow), decreased
T2 hyperintensity (E, arrow), heterogeneous enhancement (F, arrow), and mildly decreased size of
the left inferior rectus muscle can be seen as compared to panel B and panel C, respectively.
FIGURE 6-24 Breast cancer metastases to multiple extraocular muscles. A, Coronal T1-weighted
image through the anterior orbit shows enlargement and hypointensity of the right
superior and medial rectus muscles (arrows). B, Coronal T2-weighted fat-suppressed image through
the posterior orbits shows enlargement and hyperintensity of additional muscles bilaterally with
crowding in the left orbital apex with risk of compressive optic neuropathy (arrow). C, Axial
contrast-enhanced T1-weighted image shows intense heterogeneous enhancement of the
enlarged muscles with suggestion of bilateral orbital apex crowding (arrows).

Visual Symptoms
KEY POINT
h MRI findings in plasma cells, giving rise to elevation nial nerve deficits and regression of
Tolosa-Hunt syndrome of IgG4 level in serum. MRI abnormalities should occur within
include inflammation Any disorder that causes chronic 2 to 8 weeks of treatment.
marked by enlargement denervation of an extraocular muscle Carotid-cavernous fistulas are abnor-
and enhancement of may manifest as disuse atrophy, such mal connections between the carotid
the cavernous sinus, as due to perineural spread of head arterial system and cavernous sinus
superior orbital fissure, and neck squamous cell carcinoma to venous system, and they can be di-
or orbital apex; the cavernous sinus (Figure 6-12). vided based on etiology (traumatic
narrowing of the The clinical diagnostic criteria of versus spontaneous), velocity of blood
intracavernous internal Tolosa-Hunt syndrome include one or flow (high versus low) and anatomy
carotid artery; and
more episodes of unilateral orbital pain (direct versus dural or internal carotid
enlargement of the
lasting for an average of 8 weeks if left versus external carotid). A carotid-
optic nerve and
extraocular muscles.
untreated, followed by third, fourth, or cavernous fistula usually presents with
sixth cranial nerve palsy, which begins monocular or binocular eye redness
within 2 weeks of the onset of orbital due to arterialized conjunctival vessels
pain. MRI findings in Tolosa-Hunt syn- (Case 6-5). Other symptoms and
drome include inflammation marked signs include diplopia, pulsatile tinni-
by enlargement and enhancement of tus, headaches, and ocular bruits. On
the cavernous sinus, superior orbital brain MRI, carotid-cavernous fistula is
fissure, or orbital apex; narrowing of the often missed, even though enlarge-
intracavernous internal carotid artery; ment and small vessels within the
and enlargement of the optic nerve and cavernous sinus are almost always seen
extraocular muscles (Figure 6-25). even without contrast.15 The superior
However, these findings are not spe- ophthalmic vein runs beneath the su-
cific to Tolosa-Hunt syndrome and may perior rectus muscle and collects blood
be seen with other etiologies, such as from the face via the angular vein.
lymphoma, sarcoidosis, and meningi- Normally, it has an antegrade flow
oma. Corticosteroids are the treatment toward the cavernous sinus; however,
of choice, and they provide significant in carotid-cavernous fistula, reversal
pain relief within 24 to 72 hours of ini- of flow from the cavernous sinus to
tiation. Moreover, improvement of cra- the orbit is suggested by flow void
FIGURE 6-25 Tolosa-Hunt syndrome. This patient presented with episodic progressive left
eye pain, followed in 1 week by diplopia. Axial T2-weighted MRI shows
widening and mild hypointensity (A, arrow), and on contrast-enhanced
T1-weighted image, enhancement in the left cavernous sinus, superior orbital fissure, and orbital
apex in the axial (B, arrow) and coronal planes and narrowing of the intracavernous internal
carotid artery (C, arrow).

KEY POINTS
(arterialized blood) that is usually ance, showing T2 hyperintensity and no h In carotid-cavernous
accompanied by enlargement of the calcium signal on MRI), and aneurysm fistula, reversal of flow
ipsilateral or bilateral superior oph- (Figure 6-19). Extrasellar lesions that from the cavernous
thalmic vein (Figure 6-27). In chronic primarily arise from the infrasellar space sinus to the orbit is
carotid-cavernous fistula, an abnor- (skull base or sphenoid sinus) may suggested by flow void
mal connection between the two cause diplopia and include inflamma- (arterialized blood)
cavernous sinuses can develop and that is usually
tion (eg, sphenoid sinus mucocele,
accompanied by
result in bilateral cavernous sinus which typically remodels the adjacent
enlargement of
findings and enlargement of the bone), chordoma, chondrosarcoma, the ipsilateral or
ipsilateral cortical veins (corkscrew meningioma, squamous cell carcinoma, bilateral superior
vessels) (Figure 6-27). On DWI se- and metastases (Figure 6-12). ophthalmic vein.
quences, superior ophthalmic vein and Patients with dorsal midbrain syn- h Lemierre syndrome is
cavernous sinus hyperintensity with drome (Parinaud syndrome) usually diagnosed when
corresponding ADC hypointensity (re- report diplopia and headaches; on ex- bilateral cavernous
striction) suggests thrombosis of these amination, vertical supranuclear gaze sinus thrombosis due to
structures. Lemierre syndrome is diag- palsy, convergence insufficiency, septic emboli, usually
nosed when bilateral cavernous sinus convergence-retraction nystagmus on from a parapharyngeal
thrombosis due to septic emboli, usu- attempted upgaze, and light-near dis- source, is identified.
ally from a parapharyngeal source, sociation is found (Figure 6-28).
is identified.
Other parasellar lesions that can ANISOCORIA
cause diplopia and include meningi- Anisocoria is the main sign of an ef-
oma, schwannoma (a dumbbell appear- ferent pupillomotor lesion affecting
Case 6-5
A 71-year-old woman was referred by an optometrist for binocular horizontal diplopia that she noted
upon awakening 3 weeks prior to presentation. She developed pulsatile tinnitus in the left ear the day
before her diplopia developed. Her past medical history was significant for coronary artery bypass
surgery 2 months before diplopia onset and severe left retroorbital headaches that developed 2 months
prior to the surgery but resolved following it.
On examination, visual acuity was 20/25 in the right eye and 20/20 in the left eye, with normal color
vision and pupillary reaction and full confrontation visual fields. External eye examination showed
injection due to arterialization of conjunctival vessels in the right greater than left eye (Figure 6-26A)
and mild chemosis. Intraocular pressures were high normal at 20 mm Hg, bilaterally. Ocular motility
showed large esotropia, which increased on right gaze and decreased on left gaze, consistent with an
isolated right abduction deficit.
MRI of the orbits demonstrated mild enlargement of the superior ophthalmic veins bilaterally with flow
void suggestive of reversal of flow (arterialization) on coronal contrast-enhanced T1-weighted fat-suppressed
images (Figure 6-26B). Magnetic resonance angiography (MRA) of her neck with contrast showed
abnormally increased intracranial vascular markings in the left compared with right cavernous sinus (Figure
6-26C). Axial T2-weighted MRI showed abnormal small flow voids in the left cavernous sinus (Figure 6-26D)
and larger right than left intracavernous internal carotid arteries. MRA of her head without contrast
confirmed the abnormal vessels in the left cavernous sinus that were best demonstrated on the source
images (Figure 6-26E).
Four-vessel cerebral angiogram and venogram demonstrated a chronically thrombosed left
cavernous sinus and a carotid-cavernous fistula with alternative venous drainage primarily through the
left ophthalmic vein with cross-filling to the right ophthalmic vein and veins over the left side of the face.

Visual Symptoms
FIGURE 6-26 Imaging of the patient in Case 6-5. A, External photograph of patient
showing hyperemia of both eyes due to arterialized conjunctival
vessels. B, MRI orbits in coronal contrast-enhanced T1-weighted
fat-suppressed image demonstrate mild enlargement of the superior ophthalmic veins
bilaterally with flow void (arrows) suggestive of reversal of flow (arterialization). C, Neck
magnetic resonance angiogram with contrast shows abnormally increased intracranial
vascular markings in the left compared with right cavernous sinus (arrow). D, Coronal
T2-weighted MRI shows abnormal small flow voids in the left cavernous sinus (arrow) and
larger right than left intracavernous internal carotid arteries (yellow arrows). E, Head
magnetic resonance angiogram without contrast (source images) confirm the abnormal
vessels in the left cavernous sinus (arrow).
Comment. A right sixth nerve palsy likely developed in this patient due to shunting of blood from
left to right, resulting in congestion in the right cavernous sinus and enlargement of the right
intracavernous internal carotid artery. Following coiling of the fistula, this patient’s pulsatile tinnitus
resolved but her diplopia persisted, although her ocular misalignment mildly improved.
KEY POINT either the sympathetic or parasym- suspected site of injury based on asso-
h In a suspected Horner pathetic pathways. The purpose of ciated symptoms, signs, and the result
syndrome, an imaging
obtaining an imaging study in a patient of pupil pharmacologic testing. A
evaluation can be
lengthy and costly with sympathetic (Horner syndrome) simplified imaging approach that was
because of the long or parasympathetic (oculomotor nerve found to be efficacious and cost-
oculosympathetic palsy) pupillomotor defect is to evalu- effective is a single contrast-enhanced
pupillomotor pathway; ate for the underlying etiology, in modified brain and cervical MRI
therefore, the imaging particular to exclude a life-threatening extending to the T2 vertebral body
study should be chosen cause. In a suspected Horner syndrome, level.16 In an isolated Horner syn-
according to the
an imaging evaluation can be lengthy drome, when chronicity or causation
suspected site of injury
and costly because of the long to trauma can be clearly established,
based on associated
symptoms, signs, and oculosympathetic pupillomotor path- imaging is not required. In children,
the result of pupil way; therefore, the imaging study even in isolated Horner syndrome, imag-
pharmacologic testing. should be chosen according to the ing of the entire oculosympathetic

Right carotid-cavernous sinus fistula in a 75-year-old
FIGURE 6-27 woman. A, Sagittal T1-weighted right parasagittal
image shows hypointense vascular structures in the
right cavernous sinus and superior clivus (arrow). B, Coronal
T2-weighted anterior orbital image shows enlargement and flow void
in the right greater than left superior ophthalmic veins (arrows). C,
Coronal contrast-enhanced T1-weighted image shows widening of
the right cavernous sinus with abnormal vessels (arrow). D, Axial
T2-weighted image of the brain demonstrates increased number and
tortuous course of right hemispheric cortical veins, suggesting
recruitment of these vessels (arrow).
FIGURE 6-28 Parinaud syndrome due to pineoblastoma. A 49-year-old man presented with a
1-week duration of progressive headache and double vision. Sagittal
T1-weighted MRI of the brain revealed a 2.5-cm hypointense mass in the posterior
third ventricle in the region of the pineal gland (A, arrow), which on axial T2-weighted image was
mildly hyperintense and caused obstructive hydrocephalus suggested by ventriculomegaly and
transependymal flow (B, arrow). The arrow in panel C points to intense enhancement of the lesion.

Visual Symptoms
KEY POINT
h The most common pathway is recommended to exclude or thyroid enlargement) or intracranial
cause of a postganglionic treatable causes, such as malignancies cause (eg, paranasal sinusitis, sphenoid
Horner syndrome is a (eg, neuroblastoma, astrocytoma), Chiari sinus mucocele, purulent otitis media,
vascular process (eg, type 1 malformation, syringomyelia, mandibular or dental abscess, trigemi-
internal carotid artery and hypoplastic carotid artery, unless nal herpes zoster, skull base trauma, or
dissection), although it the site of injury can be clinically iatrogenic causes, such as tonsillectomy
may also be associated determined. If localization on a clinical or extensive middle ear or Gasserian
with migraine, cluster or pharmacologic basis suggests a ganglion surgery) (Case 6-6). The most
headache, or Raeder central Horner syndrome (first order), common cause of a postganglionic
paratrigeminal syndrome imaging should be obtained to rule out a Horner syndrome is a vascular process
(oculosympathetic and brainstem lesion (encephalitis, infarc- (eg, internal carotid artery dissection),
trigeminal or other
tion as part of Wallenberg syndrome, although it may also be associated
cranial nerve palsy).
pontine tumor or hemorrhage, or a with migraine, cluster headache, or
cervical spinal cord lesion, such as Raeder paratrigeminal syndrome
syringomyelia or hematomyelia, glioma, (Horner syndrome and ipsilateral facial
or ependymoma). If localization points to pain in the distribution of the ophthal-
a preganglionic second-order Horner mic division of the trigeminal nerve).
syndrome, imaging should be obtained The other cause of anisocoria is in-
to rule out any lower cervical and upper volvement of the parasympathetic
thoracic lesion, such as pachymeningitis, pupillomotor fibers that can be affected
spinal arthritis (rarely), ruptured inter- anywhere along their pathway. The
vertebral disc, cervical rib, lung apex preganglionic (before the relay in the
(Pancoast) tumor, mediastinal lymph- ciliary ganglion) pupillomotor fibers
adenopathy and tumor, aneurysm (eg, join the somatomotor fibers as they
aortic, subclavian, or common carotid arise from the Edinger-Westphal nucleus
artery), and surgical cervical or thoracic and go through the cavernous sinus,
interventions (eg, cervical sympathec- superior orbital fissure, and the inferior
tomy, thyroidectomy, or direct jugular division of the third nerve to enter and
vein or carotid artery puncture). If relay in the ciliary ganglion; from there,
postganglionic Horner syndrome (third via the short posterior ciliary nerves,
order) is suspected, imaging should they terminate in either the ciliary body
be obtained to rule out either an ex- for accommodation or iris sphincter
tracranial cause (eg, internal carotid muscle for pupillomotor function.
artery dissection, lymphadenopathy, From the imaging perspective, the most
nasopharyngeal or esophageal cancer, important etiology to consider in the
Case 6-6
A 48-year-old man with a past medical history of hypertension and metabolic syndrome was referred to
the neuro-ophthalmology clinic for a 1-week history of persistent left retroorbital headaches and an
enlarged right pupil. On the day of headache onset, the patient had a CT of the head without contrast in
an emergency department that was read as normal. The anisocoria resolved in 4 to 5 days, but the
headache persisted.
On examination, his visual acuity was 20/20 and color vision was 1/10 (congenital dyschromatopsia)
on Ishihara color plates in both eyes. His palpebral fissures were 9 mm in the right eye and 8 mm in
the left eye, his pupils were equal with normal reaction to light and accommodation, and his motility
and ophthalmoscopy were normal. He denied having a recent car accident or neck manipulation.
Laboratory evaluation, including erythrocyte sedimentation rate, C-reactive protein, and complete
blood cell counts, was normal.

Re-review of his initial CT scan of the head without contrast at the level of the odontoid demonstrated
enlargement of the left internal carotid artery with a central area of hypodensity and peripheral
hyperdensity (Figure 6-29A), and at the same level axial T2-weighted (Figure 6-29B, arrow) and
diffusion-weighted images (Figure 6-29C) demonstrated peripheral hyperintensity and a central area
of hypointensity in the left internal carotid artery. Sagittal T1-weighted (Figure 6-29D) and coronal
T2-weighted fluid-attenuated inversion recovery (FLAIR) fat-suppressed (Figure 6-29E) sequences
demonstrated peripheral hyperintensity and central hypointensity in the cervical segment of the left
internal carotid artery. Axial apparent diffusion coefficient mapping showed hypointensity in the vessel
wall corresponding to the hyperintensity on diffusion-weighted imaging, consistent with restriction in the
wall of the internal carotid artery (Figure 6-29F). He was diagnosed with a spontaneous left internal
carotid artery dissection and treated with aspirin 325 mg/d. He was not anticoagulated because of the
spontaneous clinical improvement. His headache subsided, and subtle ptosis resolved in 8 weeks.
FIGURE 6-29 Imaging of the patient in Case 6-6. Head CT without contrast at the level of the
odontoid demonstrates enlargement of the left internal carotid artery with a central
area of hypodensity and peripheral hyperdensity (A, arrow). At the same level,
axial T2-weighted (B, arrow) and diffusion-weighted (C, arrow) images demonstrate peripheral
hyperintensity and a central area of hypointensity in the left internal carotid artery. Sagittal
T1-weighted (D, arrow) and coronal T2 fluid-attenuated inversion recovery (FLAIR) fat-suppressed
sequences demonstrate peripheral hyperintensity and central hypointensity in the cervical segment of
the left internal carotid artery (E, arrow). Axial apparent diffusion coefficient mapping (F) shows
hypointensity in the vessel wall corresponding to the hyperintensity on diffusion-weighted imaging,
consistent with restriction in the wall of the internal carotid artery (arrow).
Reprinted with permission from Szatmáry G, Curr Pain Headache Rep.17 B 2016 Springer Science+Business Media.
link.springer.com/article/10.1007/s11916-016-0582-8.
Comment. Although the patient’s anisocoria resolved and only subtle partial ptosis was seen on
neurologic evaluation, his history was suggestive of a Horner syndrome. Retrospective review of his CT
head showed signs of left internal carotid artery dissection, and diffusion-weighted imaging
showed an acute injury in the vessel wall.

Visual Symptoms
KEY POINT
h From the imaging subarachnoid space is compressive, but because the pupillomotor fibers are
perspective, in patients usually by a posterior communicating immediately beneath the epineurium
with involvement artery aneurysm (with or without rup- within the oculomotor nerve, it usually
of the parasympathetic ture). Initially, mydriasis may be absent, is present. In an unresponsive patient
pupillomotor fibers, the
most important etiology
to consider in the
subarachnoid space is
compressive, usually
by a posterior
communicating artery
aneurysm (with or
without rupture).
Initially, mydriasis may
be absent, but because
the pupillomotor fibers
are immediately
beneath the epineurium
within the oculomotor
nerve, it usually
is present.
FIGURE 6-30 Acute simultaneous Streptococcus pneumoniae and West Nile virus
meningoencephalitis in a 57-year-old man admitted to the hospital with a
2-day history of fever and headaches, leading to unresponsiveness. External
photographs of extraocular movements demonstrate a complete left third cranial nerve palsy
with pupil involvement (A). MRI orbits (contrast-enhanced T1-weighted fat-suppressed image)
shows enhancement of the left third cranial nerve (B, C, D, E, arrows) on axial image (B) and
three consecutive coronal slices at the level of the cavernous sinus (C), orbital apex (D), and
posterior orbit (E).
18
Reprinted with permission from Szatmary G, Leis AA, J Neuroimaging. B 2015 John Wiley & Sons, Inc.
onlinelibrary.wiley.com/doi/10.1111/jon.12125/abstract.

KEY POINT
with a dilated and nonreactive pupil, patients with neuro-ophthalmic symp- h The most common
infectious causes, either viral or bac- toms, usually by excluding a structural causes of a compressive
terial as part of meningitis or mass lesion. Emerging imaging tech- cavernous sinus lesion
lesion with resultant herniation syn- niques are promising to aid in the are intracavernous
drome, must be considered. In infec- discovery of the underlying etiology, internal carotid artery
tious third nerve palsy, brain MRI may such as in idiopathic intracranial hy- aneurysm, meningioma,
show thickening and enhancement of pertension, by identifying causally clival chordoma,
the subarachnoid portion of the oculo- related imaging findings. pituitary tumors with
motor nerve even without meningeal parasellar extension,
enhancement (Figure 6-3017). Sub- pituitary apoplexy,
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Review Article
Imaging of Brain Tumors

Dr Laszlo L. Mechtler,
DENT Neurologic Institute,
3980 Sheridan Dr, Ste 300,
Mirza A. Baig, DO; Joshua P. Klein, MD, PhD, FANA, FAAN; Amherst, NY 14226,
lmechtler@dentinstitute.com.
Laszlo L. Mechtler, MD, FAAN Relationship Disclosure:
Dr Baig reports no disclosure.
Dr Klein has received
ABSTRACT personal compensation as a
coauthor and editor, and for
Purpose of Review: Neuroimaging is an essential tool for the diagnosis and man- serving on the editorial board
agement of brain tumors. of McGraw-Hill and as a
consultant for Advance
Recent Findings: Advances in neuroimaging have allowed for noninvasive visualiza- Medical and Best Doctors, Inc.
tion of tumors and have changed how brain tumors are diagnosed and treated. Dr Klein has given expert
Presurgical planning with the use of functional MRI (fMRI) and diffusion tensor MRI medical testimony for
Anaesthesia Associates of
helps to preserve eloquent regions of the brain and fiber tracts, thereby decreasing Massachusetts and
patients’ postsurgical morbidity. With the use of susceptibility-weighted imaging (SWI) HeplerBroom LLC.
filtered phase images, diffusion-weighted studies, and perfusion imaging techniques, Dr Mechtler has received
deciphering posttreatment effects versus tumor progression can be facilitated. serving as board advisor for
Summary: With recent advancements and novel approaches, various MRI techniques Supernus Pharmaceuticals,
can be used to help diagnose and assist in presurgical planning and posttreatment Inc; for serving as guest editor
of Current Pain & Headache
management of brain tumors. Reports and Neurologic
Clinics; as a speaker for
Continuum (Minneap Minn) 2016;22(5):1529–1552. Allergan, Pernix Therapeutics,
Industries Ltd; and as a
consultant for Green Grass
Advisors. Dr Mechtler provided
INTRODUCTION anatomic MRI with a gadolinium-based expert consultation for legal
Patients with tumors of the central ner- IV contrast agent, which is a technique testimony for DOPF, P.C.
Unlabeled Use of
vous system (CNS) may present with that is highly sensitive for detecting Products/Investigational
a wide variety of neurologic symptoms and characterizing tumors. MRI is Use Disclosure:
more sensitive than CT for detecting Drs Baig, Klein, and Mechtler
and signs, including seizures, head- report no disclosures.
aches, mental status changes, and focal tumors and tumor progression. How- * 2016 American Academy
deficits. Neurologists should be familiar ever, because of its nonspecificity, MRI of Neurology.
with the neuroimaging findings asso- is unable to differentiate tumors from
ciated with tumors so that treatment non-neoplastic tumorlike lesions such
planning is initiated without delay. as infectious abscesses, inflammatory
Treatment of tumors with surgery, ra- masses, and tumefactive demyelination.
diation therapy, or chemotherapeutic Advances in MRI technology have
agents can alter their imaging appear- yielded improvements in both high-
ance so that distinguishing treatment- resolution anatomic imaging and
related changes from tumor recurrence methods of evaluating physiology and
can be challenging. This article de- function. The incorporation of se-
scribes how certain MRI sequences can quences such as diffusion-weighted
be useful in characterizing tumor types imaging (DWI), diffusion tensor imag-
and discusses how tumor recurrence ing (DTI), magnetic resonance (MR)
can be distinguished from treatment- spectroscopy, and perfusion imaging
related changes, such as pseudoprog- as part of the mainstream clinical
ression and pseudonormalization, imaging protocol has provided neu-
through the evaluation of posttreat- rologists and neuro-oncologists with a
ment MRIs. window of opportunity to noninva-
The current standard of neuroim- sively assess the in vivo biological
aging for brain tumor evaluation is behavior of brain neoplasms.

Brain Tumors
KEY POINT
h The most common An estimated 25,000 primary malig- if a patient presents with sudden onset
primary malignant brain nant and 53,000 nonmalignant tumors of focal deficits from an underlying
and central nervous are expected to be diagnosed in the neoplasm, then an acute complication
system tumor United States in 2016. The prevalence should be suspected, such as a hemor-
is glioblastoma. of primary malignant CNS tumors is rhage in the core of the tumor.3 Meta-
61.9 per 100,000, compared to a non- static disease must be suspected in
malignant prevalence rate of 177.3 patients with a CNS neoplasm present-
per 100,000. In 2016, 16,000 deaths in ing with systemic signs such as fever and
the United States will result from tu- weight loss.4
mors of the CNS. As seen in Figure 7-1,1 When a tumor is suspected, neu-
the most commonly occurring malig- roimaging is crucial for diagnosis and
nant CNS tumor is glioblastoma, and preoperative planning as well as for
the most common nonmalignant pri- posttreatment evaluation and follow-up.
mary tumor is meningioma.2 One-half Based on signal characteristics, initial
of all benign primary brain tumors are evaluation of intracranial lesions on
meningiomas. MRI includes determination of whether
Intraaxial lesions are those that the mass is actually a neoplasm. De-
arise from cells in the brain, in con- spite the high resolution and tissue
trast to extraaxial lesions, which arise contrast provided by MRI, clinicians
from the nerves, meninges, and other should be cognizant that neuroimag-
structures outside of the brain. CNS ing is not yet a substitute for tissue
neoplasms present with various symp- diagnosis and, therefore, caution must
toms. The location of the tumor, of always be taken when interpreting
course, determines which symptoms imaging findings.
are most likely to manifest. Generally, MRI with and without gadolinium
symptomatology arises over a sub- is the imaging test of choice. How-
acute to chronic time period. However, ever, CT remains useful due to its wide
FIGURE 7-1 Distribution of all primary brain and central nervous system tumors by
histology groupings.
Modified from Ostrom QT, et al, Neuro Oncol.1 B 2015 The Centers for Disease Control.
neuro-oncology.oxfordjournals.org/content/17/suppl_4/iv1.full.

KEY POINTS
availability and relatively low cost. MAGNETIC RESONANCE h MRI with gadolinium is
Table 7-1 compares the use of differ- IMAGING TECHNIQUES the imaging test of
ent diagnostic modalities and se- The sequences discussed here repre- choice in patients with
quences for tumor imaging. MRI sent manipulation of the properties of suspected central nervous
contrast enhancement on T1- the hydrogen atom as it aligns with system neoplasm.
weighted images represents break- the background magnetic field of the h Contrast enhancement
down of the blood-brain barrier MR apparatus. Then pulses of radio on T1-weighted images
where gadolinium has leaked out. waves from the magnetic field gradi- represents breakdown
However, this finding is not synony- ents are utilized to excite the nuclear of the blood-brain
mous with a malignant brain tumor. spins. Pulse sequence variation param- barrier where
Vasogenic edema can be subtle on eters cause contrast between tissues, gadolinium has
contrast-enhanced T1-weighted im- which is essential in determining a neo- leaked out.
ages, but is easily noted on T2- plastic process from normal anatomy.
weighted images because of the high
sensitivity to changes in water con- T1-weighted and T2-weighted
tent of the brain. Fluid-attenuated Sequences
inversion recovery (FLAIR) imaging Brain tumors are generally hypointense
is a type of T2-weighted imaging on T1-weighted images and hyperintense
sequence in which CSF signal is on T2-weighted images, reflecting in-
suppressed in order to better evalu- creased water content of the neo-
ate regions adjacent to the ventricles plasm as well as vasogenic edema. As
or sulci.5 delineated in Table 7-2, short T1 (ie,
TABLE 7-1 Comparison of Tumor Imaging With Different

Diagnostic Modalities
Imaging Technique Utility in Brain Tumor Imaging

CT Mass effect, herniation, hydrocephalus,
hemorrhage, calcifications
Precontrast and postcontrast Enhancement characteristics, necrosis, extent
T1-weighted imaging of the enhancing portion of the tumor
T2-weighted/T2-weighted Peritumoral edema (vasogenic and
fluid-attenuated inversion infiltrative), nonenhancing tumor
recovery (FLAIR)
T2* susceptibility-weighted Blood products, calcifications, radiation-induced
imaging (SWI) chronic microhemorrhages
Diffusion-weighted imaging Reduced ADC in highly cellular portions of
(DWI)/apparent diffusion tumor, postoperative injury
coefficient (ADC)
Diffusion tensor imaging (DTI) Tractography for surgical planning/navigation
Perfusion imaging Tumor/tissue vascularity
Magnetic resonance spectroscopy Metabolic profile
Functional MRI (fMRI) Preoperative functional mapping, research
into treatment effects

Brain Tumors
KEY POINT
h T2 hypointensity (ie, T1 hyperintensity) and short T2 (ie, iron, hemosiderin, deoxyhemoglobin,
short T2) in brain tumors T2 hypointensity) signals are due to the and melanin. In addition, hypointensities
can represent presence of certain tissue substances, on T2-weighted images can be due to
hemosiderin, melanin, states, or molecules. However, impor- calcification, high nucleus to cytoplasm
calcification, dense tant exceptions to this generalization ratio (ie, primitive neuroectodermal tu-
cellularity, mucin, high exist. Tumors that are hypointense on mors, lymphoma), dense cellularity,
protein, or vascular T2-weighted images include neoplasms fibrocollagenous stroma, very high
flow void. that have paramagnetic effects such as protein concentration, and signal flow
TABLE 7-2 Short T2 and Short T1 Signals in Brain Tumors
b Short T2 (Hypointensity on T2-Weighted Images)

Iron with necrosis (glioblastoma multiforme)
Hemosiderin (chronic bleed)
Deoxyhemoglobin (acute bleed)
Melanin (melanoma)
Ferritin
Calcification (oligodendroglioma)
High nucleus to cytoplasm ratio (primitive neuroectodermal tumors, lymphoma)
Dense cellularity
Macromolecule content
Fibrocollagenous stroma (meningioma)
Mucin (colon carcinoma)
High protein content (craniopharyngioma)
Flow void (hemangioblastoma, glioblastoma multiforme)
Air
b Short T1 (Hyperintensity on T1-Weighted Images)
Methemoglobin (subacute blood)
Melanin (melanoma)
Manganese
Calcium
Iron
Copper
High protein (colloid cyst, craniopharyngioma)
Fat (lipoma, dermoid)
Cholesterol
Paramagnetic agent (gadolinium)
Flow-related enhancement in tumor vessel
Calcium

KEY POINT
voids from rapid flow. Hyperintensity Susceptibility-weighted Imaging h T1 hyperintensity (ie,
on T1-weighted images within brain Susceptibility-weighted imaging (SWI) short T1) in brain
tumors can be due to methemoglobin; uses postprocessing to accentuate dif- tumors can represent
melanin; some forms of calcification; ferences in susceptibility effect between methemoglobin,
naturally occurring ions associated with tissues. The susceptibility effect refers high protein, fat,
cellular necrosis such as manganese, to a material’s ability to disperse (such melanin, gadolinium,
iron, and copper; and high protein, as in the case of calcium) or concen- and cholesterol.
cholesterol, fat, gadolinium, and flow- trate (as is the case with iron or
related enhancement in tumor vessels. gadolinium) in the main magnetic field
The most common neuroimaging find- within which it is located. SWI is
ings for the CNS tumors discussed in extremely sensitive for detecting iron
this article are outlined in Table 7-3. and blood products and is particularly
TABLE 7-3 Magnetic Resonance Imaging Characteristics of Brain Tumors
Type of Brain Tumor Magnetic Resonance Imaging (MRI) Characteristics

Grade I astrocytoma Cystic component is hypointense on T1-weighted and hyperintense on
T2-weighted images
Solid component is isointense on T1-weighted and hyperintense on

T2-weighted images
Heterogeneous enhancement of solid component and the wall of the
cystic component
Grade II astrocytoma Hypointense on T1-weighted and hyperintense on T2-weighted images
Diffusion is not restricted
No enhancement (if present, relate to oligodendroglioma)
Bulging of gray and white matter
Spectroscopy shows mild N-acetylaspartate (NAA) reduction and
increased choline
Perfusion MRI shows normal or reduced cerebral blood volume (CBV) values
Grade III astrocytoma Usually hypointense on T1-weighted and heterogeneously hyperintense on
T2-weighted images
Diffusion is not restricted
Enhancement is inhomogeneous and can be absent as well
Perfusion MRI can be helpful to identify more aggressive lesions
Magnetic resonance spectroscopy will show high choline peak with reduced NAA
Gliomatosis cerebri Hypointense on T1-weighted and hyperintense on T2-weighted images
(World Health
Organization grade III) No restricted diffusion on diffusion-weighted imaging (DWI)
Absent or minimal enhancement

Perfusion MRI shows low values of cerebral blood volume
Magnetic resonance spectroscopy will show marked increase in myo-inositol and
reduced NAA

Brain Tumors
TABLE 7-3 Magnetic Resonance Imaging Characteristics of Brain Tumors Continued from page 1533

Grade IV astrocytoma Hypointense on T1-weighted images, hyperintense on T2-weighted images,
inhomogeneous due to necrotic areas
Marked perilesional vasogenic edema
No restricted diffusion on DWI
Enhancement is predominantly peripheral with ringlike appearance
Lesion extends far from the areas of enhancement
Newly formed pathologic vessels seen as signal voids in T2-weighted images
Perfusion MRI shows marked increase of CBV inside solid component
Magnetic resonance spectroscopy will show a considerable increase of choline
peak, marked reduction of NAA and the appearance of lactate and lipids, due
to the presence of the necrotic areas
Oligodendroglioma Hypointense on T1-weighted images, heterogeneously hyperintense on
T2-weighted images
Heterogeneous enhancement
Magnetic resonance spectroscopy peaks may show high choline
Values of CBV perfusion cannot be used to assess the real grading since they are
high even in low-grade forms (confounding factor)
Ependymoma Heterogeneous signal (necrosis, calcification, methemoglobin, hemosiderin,
vascularity)
Isointense/hypointense on T1-weighted images and isointense/hyperintense
on T2-weighted images
Enhancement is usually dyshomogeneous
Central nervous system In patients who are immunocompetent
(CNS) lymphoma
Isointense/hypointense compared to gray matter on T1-weighted and
T2-weighted images
Homogeneous enhancement
Due to high cellularity, diffusion is restricted
Magnetic resonance spectroscopy shows increased choline and lipid peaks
Perfusion shows CBV values lower than expected in high-grade glial gliomas
In patients who are immunocompromised, signal may be heterogeneous
because of hemorrhage and necrosis
Isointense/hypointense compared to gray matter on T1-weighted and
T2-weighted images
Mild perilesional edema
Predominantly peripheral enhancement with a necrotic core

TABLE 7-3 Magnetic Resonance Imaging Characteristics of Brain Tumors Continued from page 1534

Central neurocytoma Solid components isointense on T1-weighted images while the cystic ones
are hypointense
On T2-weighted images, heterogeneous, predominantly hyperintense with
bubblelike appearance
Variable enhancement with gadolinium
Strong choline peak on spectroscopy
Meningioma Isointense/hypointense to the cortex on T1-weighted images, isointense to
gray matter, but with variable signal on T2-weighted images
At periphery, dilatation of the subarachnoid spaces and invagination of the
cortex from compressive effect
After contrast injection, there is early enhancement, diffuse and marked with
the exclusion of cystic or calcified components
Magnetic resonance spectroscopy shows alanine peak without NAA peak
CNS metastasis Isointense/hypointense on T1-weighted images (except if mucinous)
Heterogeneously hyperintense on T2-weighted images (except mucoepidermoid
type when markedly hypointense)
Peritumoral edema seen as hypointense signal on T1 and hyperintense on
T2-weighted images
Enhancement is variable, more frequently ringlike
Peak of choline on spectroscopy
High values of CBV on perfusion with increased permeability due to the
presence of pathologic neovascularization
useful for detecting microhemorrhages are more conspicuous on SWI as

rhages that are below the resolution of compared to GRE.6
T1- and T2-weighted images. SWI is
more sensitive in comparison to con- Diffusion-weighted Imaging
ventional imaging techniques for Molecular mobility is the essential con-
showing small vessels, calcification, trast mechanism used in DWI and is
and microhemorrhages in brain tu- reflected in a measurement of the ap-
mors. The use of SWI is especially parent diffusion coefficient (ADC).
useful in the evaluation of postradia- Restricted diffusion represents non-
tion microhemorrhages.6 isotropic (anisotropic) molecular move-
T2*-weighted gradient recalled echo ment. Anisotropy refers to the lack of
(GRE) is another technique less sen- uniformity in different crystallograph-
sitive to the susceptibility effects of ic orientations. The greater the den-
iron contained in hemosiderin. The rea- sity of structures impeding water
sons are that SWI has a high contrast to mobility, the lower the ADC; there-
noise ratio and is acquired at higher fore, ADC is considered a noninvasive
spatial resolution than T2*-weighted indicator of cellularity or cell density.
GRE sequences. Therefore, microhemor- DWI is an echo planar imagingYbased

Brain Tumors
KEY POINTS
h Diffusion-weighted sequence that can acquire a sufficient biopsy, and provide prognostic infor-
imaging is extremely number of images in milliseconds.7 mation.12 Thus, perfusion imaging, to-
sensitive in detecting Increased ADC implies unrestricted gether with conventional MRI, should
acute ischemia, cerebral water motion, and decreased ADC be considered in the diagnosis and
abscess, hypercellularity, indicates restricted diffusional motion.8 monitoring of brain tumors before,
and postoperative Therefore, the DWI to ADC ratio is during, and after therapy.
brain injury. extremely sensitive in detecting pathol- Delayed contrast enhancement and
h Magnetic resonance ogies such as acute ischemia, abscess, dynamic susceptibility contrast-enhanced
spectroscopy of hypercellularity, and postoperative MR perfusion imaging are used in re-
malignant brain tumors brain injury. Recent findings indicate search settings for the differentiation of
typically shows an that in gliomas, the higher the World recurrent tumor from treatment-related
increase in the choline Health Organization ( WHO) tumor changes. It is not yet routinely used by
peak, a decrease in the grade, the lower the ADC.8 clinicians but appears to show promise.
N-acetylaspartate peak, DWI sequences have been adapted
an increase of the Magnetic Resonance
to perform DTI by acquiring data in six
choline to creatine ratio, Spectroscopy
or more directions. DTI allows for
and the presence of
a lactate peak.
visualization of the location, orienta- MR spectroscopy is a powerful tech-
tion, and anisotropy in the white matter nique that offers unique metabolic
tracts of the brain and spinal cord. DTI information regarding brain tumor biol-
can be used to provide maps of white ogy that is not available from anatomic
matter fiber tracts (tractography) in imaging. Tumors have a characteristic
tissues adjacent to tumors.9,10 By eluci- spectrographic appearance, which in-
dating the anatomic relationship of cludes an increase in the choline peak, a
motor and sensory pathways to tumor decrease in the N-acetylaspartate (NAA)
tissue, DTI can assist in surgical plan- peak, an increased choline to creatine
ning to limit surgical morbidity.10 ratio, and, in some cases, the presence
of a lactate peak.13,14 Spectroscopic
Perfusion Imaging imaging improves the specificity of
Perfusion imaging measures the degree brain tumor imaging because it not
of tumor angiogenesis and capillary only enables biochemical assessment
permeability, both of which are impor- of tumor dynamics, but also can show
tant biological markers of malignancy, residual or recurrent tumor beyond the
grading, and prognosis, particularly in margins of the tumor seen on structural
gliomas. The most robust quantitative images. This is well demonstrated in
variable derived is relative cerebral Figure 7-2 with a previously biopsy-
blood volume (rCBV), which can be cor- proven oligoastrocytoma that recurred
related to tumor angiogenesis. Cellular 1 year later and demonstrated on
studies have demonstrated a strong repeat biopsy to be anaplastic astrocy-
positive correlation between tumor, toma. In the preoperative phase, MR
rCBV, and astrocytoma grading. Low- spectroscopy has the ability to differ-
grade astrocytomas have significantly entiate high-grade gliomas from low-
lower average rCBV than anaplastic grade gliomas and glioblastoma-related
astrocytoma or glioblastoma. rCBV edema from metastases-related edema,
maps may be used to select biopsy sites to help refine preoperative differential
for enhancing and nonenhancing tu- diagnosis (eg, abscess, tuberculoma
mors by highlighting a ‘‘hot’’ (ie, hyper- versus tumefactive demyelinating le-
vascular) area.11 Perfusion imaging has sion), and to diagnose meningioma
been used to characterize glioma WHO and primary CNS lymphoma. In the
grade and tumor genotype, guide perioperative phase, MR spectroscopy

FIGURE 7-2 Imaging of a 31-year-old woman who underwent surgery 1 year previously for an oligoastrocytoma located
in the superior aspect of the left middle frontal gyrus. On a 3T magnet, a routine follow-up T1-weighted
MRI confirms a postoperative cavity (A, arrow), but a postcontrast T1-weighted MRI shows a new area of
enhancement just anterior to the cavity (B, arrow). Fluid-attenuated inversion recovery (FLAIR) MRI shows an enlarging area
of hyperintensity, or long T2 (C, arrow). Preoperative MR spectroscopy (D, E) shows decreased N-acetylaspartate (NAA)
and an increase in the choline peak (E, arrow) in the area of progression, consistent with tumor recurrence. When the voxel
is placed posterior to the cavity, the MR spectroscopy is normal (F, G, arrow). Functional MRI (fMRI) in the sagittal plane,
using descriptive naming, indicates activation in the left premotor cortex just below the enhancing lesion (H, arrow).
Right-hand activation was found adjacent to the posterior margin of the postoperative cyst that was normal on MR spectroscopy
(I, arrow). These test results aided the neurosurgeon in the resection of the enhancing lesion and adjacent T2-weighted
hyperintensities without postoperative residual neurologic deficits. Pathology was consistent with an anaplastic astrocytoma.
can help localize the site for stereotac- changes in the vessels of the brain, al-
tic biopsy and determine the extent of lowing for an estimation of brain activity
resection; multivoxel MR spectroscopy in a noninvasive manner. The increased
can also predict radiotherapy volumes. blood flow is matched by an increase
Finally, in the postoperative phase, MR in oxygen extraction so that the con-
spectroscopy can assist in monitoring centration of deoxyhemoglobin is in-
malignant transformation of low-grade creased. Since deoxyhemoglobin is
tumors, monitoring response to treat- paramagnetic, a change occurs in
ment, and differentiating recurrent glio- the T2* signal. This change, referred
blastoma multiforme from radiation to as blood oxygen level dependent
necrosis. The limitations of conventional contrast (BOLD), is detected by the
MR spectroscopy restrict its use to me- MRI sequence.15
tabolites in relatively high concentra- fMRI is used primarily for preopera-
tions and to enzyme reactions with a tive localization of eloquent brain re-
half-life of approximately 1 second.14 gions prior to tumor resection in an
Functional Magnetic attempt to minimize intraoperative mor-
Resonance Imaging bidity. fMRI reliably images the primary
fMRI is a neuroimaging technique that motor and sensory areas of the cortex.
can depict dynamic blood oxygenation The ability to identify speech areas may

Brain Tumors
KEY POINT
h On perfusion imaging, make the Wada test for speech and mem- gliomas. Histologically, glioblastomas
low-grade astrocytomas ory laterality someday obsolete.16 are often necrotic, show vascular pro-
have a lower mean liferation, and are highly pleomorphic.
relative cerebral blood GLIOMAS They are heterogeneous, and a single
volume than do Gliomas are tumors arising from glial tumor may exhibit different histologic
anaplastic astrocytomas cells, including astrocytes, oligodendro- features at different sites. Imaging
or glioblastomas. cytes, ependymal cells, and cells of the features, in addition to immunohisto-
choroid plexus. As shown in Figure 7-1, chemical staining, may provide clues to
an estimated 50% of all primary brain help correlate overall tumor prognosis
tumors are astrocytomas.5 The histo- (Figure 7-3).5 Studies have shown that
logic features in grading of gliomas rCBV can predict the time to progres-
include necrosis, vascular proliferation, sion or survival in patients with glioma.17
mitotic index, and nuclear atypia.4 Patients with high pretreatment rCBV
Although grading of gliomas is ideally have lower survival rates when com-
based on histologic evaluation, a sig- pared to patients with lower pretreat-
nificant correlation exists between ment rCBV; longer survival in the latter
rCBV and glioma grade, allowing for case is more than 15 months.17 These
a noninvasive method for estimating data are helpful in designing individu-
tumor grade.17 Low-grade astrocyto- alized treatment plans.
mas have lower mean rCBV values than
do anaplastic astrocytomas or glioblas- GRADE I ASTROCYTOMA
tomas. This relationship between rCBV Astrocytomas are common intracranial
and tumor grade is consistent with neoplasms in children and young
other studies demonstrating that mi- adults. About 75% of astrocytomas are
crovascular density in low-grade astro- juvenile pilocytic astrocytomas, which
cytomas is lower than in anaplastic are WHO grade I tumors.5 Juvenile
astrocytomas or glioblastomas. pilocytic astrocytomas typically occur
Glioblastoma is the most highly vas- in the cerebellar hemispheres and pro-
cularized glioma, comprising 66% of all duce symptoms of elevated intracranial
FIGURE 7-3 Oligoastrocytoma. A, Axial T2 fluid-attenuated inversion recovery (FLAIR) MRI shows a region of abnormal
hyperintensity centered within the right insula (arrow). Minimal mass effect can be seen on surrounding
structures. B, Axial T1 postcontrast image shows minimal enhancement of the lesion (arrow). C, Apparent
diffusion coefficient map shows no hypointensity and, therefore, no evidence of hypercellularity.

pressure, headache, and ataxia.4 They
may be associated with neurofibromatosis TABLE 7-4 Cortical-Based
type 1, especially if the optic pathways Masses With a Cyst
are involved. These tumors are usually and Nodule
amenable to surgical resection.
Optic nerve gliomas are juvenile b Common
pilocytic astrocytomas arising from the Ganglioglioma
optic nerve, chiasm, or optic tract and
Metastasis
almost exclusively affect children and
teenagers. Abnormal signals are ob- b Less Common
served throughout the visual pathway, Pilocytic astrocytoma
including the optic tracts, lateral genic-
Pleomorphic
ulate body, and optic radiations. They
xanthoastrocytoma
are often asymptomatic early on and
usually present with progressive visual Glioblastoma multiforme
loss. On imaging, juvenile pilocytic as- b Rare
trocytomas are well circumscribed with Hemangioblastoma
a large cystic component and an en-
hancing mural nodule. The cyst is often Papillary glioneuronal tumor
isointense to CSF on all sequences, al- Ganglioglioma
though cysts with high protein content Schwannoma
may be hyperintense to CSF on certain
sequences.4 The cystic component is
hypointense on T1-weighted images cell astrocytomas may be indistinguish-
and hyperintense on T2-weighted im- able from subependymal nodules his-
ages, and the solid component is iso- topathologically. On MRI, they appear
intense on T1-weighted images and larger in size and show progressive in-
hyperintense on T2-weighted images. crease in size during serial imaging,
After gadolinium, the wall of the cyst unlike subependymal nodules. Sub-
shows heterogeneous enhancement.2 ependymal giant cell astrocytomas
Other cortical-based masses with a cyst may require surgical resection if they
and nodule are listed in Table 7-4 along show rapid growth and cause obstruc-
with their incidence. tive hydrocephalus.10 Rapamycin is
the pharmacologic therapy used for
SUBEPENDYMAL GIANT CELL shrinking or stabilizing subependymal
ASTROCYTOMAS giant cell astrocytomas.
Subependymal giant cell astrocytomas
(often referred to as SEGAs) are benign GRADES II AND III
intraventricular tumors without ana- ASTROCYTOMAS
plastic potential composed of variably For grade II astrocytomas, known as
sized astrocytic-appearing cells with diffuse astrocytomas, patients have an
variable signal intensity on both CT average survival time of 5 to 6 years,
and MRI (Figure 7-4), depending on while with grade III astrocytomas,
the degree of calcification. Subepen- known as anaplastic astrocytomas, pa-
dymal giant cell astrocytomas are seen tients have an average survival time
in 6% to 16% of patients with tuberous of 2.5 years (Case 7-1). Histologically,
sclerosis complex.18 They arise from these tumors lack pleomorphic cells,
subependymal cells and project into necrosis, or vascular proliferation, al-
the lateral ventricle adjacent to the sep- though mitoses may be seen in ana-
tum pellucidum. Subependymal giant plastic astrocytomas. 4 For diffuse

Brain Tumors
FIGURE 7-4 Subependymal giant cell astrocytoma. A 30-year-old man presented with a history of epilepsy, tuberous sclerosis,
obsessive-compulsive disorder, and neurofibromatosis. MRI of the brain demonstrated numerous cortical-based
T2 hyperintense lesions supratentorially and bilaterally, many of which also exhibited prominent calcification.
These were felt to be representative cortical tubers/hamartomas, consistent with the history of tuberous sclerosis. A, Hypointense
lesion on T1-weighted image (arrow); B, homogeneous contrast enhancement of the lesion on postcontrast T1-weighted
image; C, the lesion is hypointense on fluid-attenuated inversion recovery (FLAIR) image. The mass lesion, (B, arrow) located
within the left lateral ventricle anteriorly at the level of the foramen of Monro, exhibits intense contrast enhancement but no
obstruction of CSF flow. In view of the patient’s history, this likely represents a subependymal giant cell astrocytoma.
astrocytoma, any focus of elevated common and the most lethal of astro-
rCBV is concerning for malignant cytomas, with a median survival of
transformation. A nonenhancing ana- 15 months. Grade IV astrocytomas are
plastic astrocytoma behaves like a low- slightly more common in men over
grade tumor, whereas presence of the age of 50 and almost always occur
enhancement is associated with risk in the cerebral hemispheres. On imag-
of recurrence and shortened survival, ing studies, the tumor may appear as a
with behavior similar to that of a discrete mass with neoplastic cells
glioblastoma (grade IV).19 spread along white matter pathways
Grade II gliomas appear T1 hypo- throughout the brain by the time of
intense and T2 hyperintense. Diffusion diagnosis.5 In adults older than the age
is not restricted, and no enhancement of 50, 60% of glioblastomas arise de
is seen after contrast administration. A
novo. Secondary glioblastoma multi-
swelling and thickening of both white
forme typically develops in patients
and gray matter also occurs. In grade II
under the age of 45 through malignant
tumors, MR spectroscopy shows mild
progression from a low-grade astrocy-
NAA reduction and mildly increased
toma or anaplastic astrocytoma.
choline, and perfusion MRI does not
Glioblastomas have heterogeneous
show elevated rCBV. In contrast,
enhancing patterns with central non-
grade III tumors will have increased
enhancing areas representing necrotic
rCBV values on perfusion MRI and a
tissue. T2-weighted and FLAIR MRI
higher choline peak and a lower NAA
show extensive vasogenic edema
peak on MR spectroscopy.
within the white matter (Figure 7-6).
GRADE IV ASTROCYTOMAS Glioblastomas may spread from one
(GLIOBLASTOMA) hemisphere to the other via the cor-
Grade IV astrocytomas, commonly pus callosum, producing a butter-
known as glioblastomas, are the most fly appearance.20

Case 7-1
A 75-year-old right-handed man presented with a 7-month history of progressive cognitive issues with
word finding and memory difficulties that had worsened over 4 to 5 weeks. MRI of the brain, with and
without contrast, demonstrated a mass lesion in the left occipital lobe extending to the splenium of
the corpus callosum with prominent restricted diffusion and areas of ring enhancement and
hemorrhagic products (Figure 7-5).
A biopsy confirmed anaplastic astrocytoma (World Health Organization grade III). The patient
underwent surgical resection and completed treatment with temozolomide and concurrent radiation
therapy. The patient then started treatment with adjuvant temozolomide. His condition continued
to worsen, and bevacizumab was added but was later discontinued due to side effects. One year later,
three repeat MRI studies were performed in January, March, and April of that year, which
demonstrated enlargement of the splenium of the corpus callosum and increased prominence of the
white matter changes, suggesting progression of disease (Figure 7-5). Continued treatment versus
hospice care was discussed with the patient and his family, and the decision was made for continued
treatment. IV bevacizumab was administered every 2 weeks, and metronomic (ie, a regimen of
drugs administered in low doses at regular intervals over an extended period of time) dosing of
temozolomide was initiated. One month later, the patient opted for hospice care; he died shortly thereafter.
FIGURE 7-5 Imaging of the patient in Case 7-1. Axial T1-weighted postcontrast MRI shows
prominent areas of T1 hypointensity (white ovals) adjacent to the posterior horn of
the left lateral ventricle. On sagittal T1-weighted postcontrast MRI, a mixed
pattern with subtle linear and curvilinear areas of enhancement (white arrows) can be seen
adjacent to the posterior horn of the left lateral ventricle extending into posterior temporoparietal
white matter and the splenium, which is increased in size. Prominent areas of fluid-attenuated
inversion recovery (FLAIR) hyperintensities are noted throughout the white matter in both
cerebral hemispheres (red ovals). Diffusion-weighted imaging (DWI) demonstrates restricted
diffusion in these regions (white arrowheads), indicative of hypercellularity.

Brain Tumors

Comment. This case demonstrates the nuances of managing patients with a central nervous
system neoplasm such as an anaplastic astrocytoma. Typically, an anaplastic astrocytoma does not
demonstrate restricted diffusion. This patient’s tumor was a typical and suggestive of malignant
transformation and the presence of hemorrhagic products. The presence of enhancement predicted
higher risk of recurrence and shortened survival for the patient, findings which are similar to
glioblastoma (grade IV).19
Gliomatosis cerebri is a type of ma- provement or stabilization. This is

lignant astrocytoma, generally WHO thought to be a treatment-related phe-
grade III, with extensive tumor infiltra- nomenon termed pseudoprogression,
tion without a discrete mass or necrosis. most likely due to reactive inflammation,
T2-weighted sequences show a edema, and abnormal vessel permeabil-
hyperintense infiltrating mass with ity. Some studies note improved survi-
small ventricles and effaced cortical val in the setting of pseudoprogression,
sulci. With gadolinium, small areas of which may correlate with the extent of
patchy enhancement may occur. 21 the patient’s innate immune response
Gliomatosis cerebri commonly pre- to the tumor.22 Most pseudoprogres-
sents in people younger than 40 years sion occurs within 3 months of the
of age. With radiation and chemo- end of radiation therapy. However,
therapy, survival may be prolonged to pseudoprogression occurring after
nearly 3 years.5 this 3-month period but within the first
In some patients with high-grade year is not uncommon, particularly in
glioma, MRIs performed shortly after tumors with O-6-methylguanine-DNA
concurrent chemotherapy and radia- methyltransferase (MGMT ) promoter
tion therapy show an increase in the methylation.23 No single imaging tech-
area of contrast enhancement. However, nique has been validated to recognize
subsequent imaging demonstrates im- and adequately establish a diagnosis of
FIGURE 7-6 Glioblastoma. A 60-year-old man with headaches and recent personality changes presented with altered
mental status. A, Axial fluid-attenuated inversion recovery (FLAIR) MRI shows a large left frontal nodular and
cystic mass with surrounding T2 hyperintensity. B, T1-weighted precontrast MRI shows a large
hypointense cystic lesion in the left frontal lobe with an open margin at the two o’clock position (arrow). C, T1-weighted
postcontrast MRI demonstrates an irregular rim of enhancement. The internal contents of the cyst contain necrotic debris and
are nonenhancing. The overlying cortical sulci and underlying frontal horn of the left lateral ventricle are effaced, and
rightward shift of midline structures can be seen with subfalcine herniation of the genu of the corpus callosum (not shown).

pseudoprogression from true progres- criteria were published (summarized in
sion; therefore, at present, the diagno- Table 7-5), updating the Macdonald
sis is made based on suspicion and criteria (for glioblastoma published in
comparison to follow-up studies.24 1990) in several important ways while
Another treatment-related imaging maintaining a reliance upon the prod-
phenomenon is pseudoresponse, uct of perpendicular diameters of
which is due to the use of antiangio- contrast-enhancing lesions as an indi-
genic agents such as bevacizumab. cator of tumor size and status.27 Pro-
Pseudoresponse is characterized by a gression occurs when any of the RANO
marked decrease in the enhancing criteria in Table 7-5 are present.
portion of the lesion as early as 1 to
2 days after initiation of therapy and TREATMENT FOLLOW-UP:
is associated with radiologic response RADIATION NECROSIS
rates of 25% to 60%.25 However, en- VERSUS RECURRENT OR
largement of the nonenhancing por- RESIDUAL TUMOR
tion of the lesion on T2-weighted Distinguishing radiation necrosis from
sequences is observed on follow-up recurrent tumor has significant thera-
scans. With antiangiogenic therapy, this peutic implications. Patients with recur-
phenomenon may explain why overall rent tumors may benefit from further
survival increases are modest at best, surgical management with or without
despite the perception (by imaging) of adjuvant chemotherapy, as opposed to
an excellent initial response to treatment. patients with radiation necrosis, who
Not surprisingly, both phenomena may be treated conservatively with
(pseudoprogression and pseudo- steroids or antiangiogenic agents.28
response) have the potential to con- Delayed radiation necrosis and re-
found the imaging assessment of CNS current tumor can both appear
neoplasms.26 In 2010, the Response as a new or enlarging lesion with
Assessment in Neuro-Oncology (RANO) surrounding edema, and conventional
a
TABLE 7-5 Response Assessment in Neuro-Oncology Criteria
Complete Response Partial Response Stable Disease Progressive Disease

T1 (gadolinium None Q50% decrease G50% decrease to Q25% increase
enhancement G25% increase
present)
T2/FLAIR Stable or decrease Stable or decrease Stable or decrease Stable or increaseb
New lesion None None None Presentb
Corticosteroids None Stable or decrease Stable or decrease NA
Clinical status Stable or increase Stable or increase Stable or increase Decreaseb
Requirement All of the above All of the above All of the above Anyb
for response conditions are met conditions are met conditions are met
for at least 4 weeks for at least 4 weeks
on follow-up MRI on follow-up MRI
FLAIR = fluid-attenuated inversion recovery; MRI = magnetic resonance imaging; NA = not applicable.
a
Modified with permission from Wen PY, et al, J Clin Oncol.27 B 2010 American Society of Clinical Oncology. jco.ascopubs.org/content/28/11/1963.long.
b
Progression occurs when any of the criteria are present.

Brain Tumors
KEY POINT
h On perfusion imaging, contrast-enhanced CT and MRI are not OLIGODENDROGLIOMAS
mapping of cerebral reliable in discriminating the two. Path- Oligodendrogliomas arise from oligo-
blood volume can ologically, radiation necrosis, shows dendrocytes and represent about 5%
reveal differences in features of extensive endothelial injury to 10% of primary CNS tumors in adults.
vascularity and may and fibrinoid necrosis, whereas recur- Oligodendrogliomas generally show
help differentiate rent tumor is characterized by vascular some calcification and are less avidly
radiation necrosis from proliferation. MRI-based rCBV mapping contrast enhancing than gliomas. Pa-
recurrent tumor. can reveal differences in vascularity and tients demonstrating a codeletion of
may help differentiate one process from chromosomal arms 1p and 19q have a
the other.21 Radiation necrosis appears better prognosis. Patients without this
as a heterogeneously hypointense codeletion have a poorer prognosis and
lesion on T1-weighted images and a are less responsive to chemotherapy.5
hyperintense lesion on T2-weighted The tumor is most often T1 hypo-
images with inhomogeneous peripheral intense and heterogeneously T2
enhancement after contrast adminis- hyperintense; calcifications, if present,
tration. Hypointensity on T2* sequences are hyperdense on CT and hypointense
such as GRE or SWI may reflect the on T2* images (Figure 7-7). With con-
presence of hemorrhage or blood trast, the lesion shows heterogeneous
breakdown products. Additionally, rCBV enhancement. MR spectroscopy may
values are generally lower in radia- show elevated choline. rCBV is less re-
tion necrosis compared to recurrence liable to assess the grade of oligoden-
of neoplastic disease. Radiation necrosis drogliomas since rCBV may be elevated
may develop distant from the original even in low-grade forms.2
tumor site, while this is less common in Astrocytomas and oligodendro-
tumor recurrence. gliomas cannot be differentiated from
FIGURE 7-7 Oligodendroglioma. A 56-year-old man presented with intermittent numbness and shaking sensations of the
right hand and intermittent episodes of unresponsiveness experienced for the past 2 months. Biopsy confirmed a
diagnosis of World Health Organization grade II oligodendroglioma in the left insular area. Due to the high
MIB-1 index, which was 11% focally, the patient underwent concurrent chemotherapy and radiation followed by temozolomide
treatment. The lesion within the left insula is hypointense on T1-weighted sequence (A, arrow), hyperintense on T2-weighted
sequence (B), and hyperintense on diffusion-weighted imaging (DWI) (C, arrow) from T2 shine-through versus hypercellularity.
This lesion would be hypercellular in comparison to a lower-grade oligodendroglioma. Subtle mass effect on the left lateral
ventricle and minimal left-to-right midline shift can be seen. This minimal subfalcine herniation versus an epileptic event may
explain the patient’s intermittent alteration in consciousness.

one another based on imaging alone, ing of the entire neuraxis with MRI is
although some characteristics exist that essential (Figure 7-8). Calcification and
favor oligodendrogliomas, such as cor- microhemorrhage are observed in
tical involvement, presence of calcifica- about one-half of ependymomas.4
tion, heterogeneous signal (including Ependymomas appear heteroge-
the presence of an intratumoral cyst in neous due to the concurrent presence
some cases), and subtle patchy enhance- of necrosis, calcification, methemoglo-
ment. For low-grade tumors, including bin, hemosiderin, and hypervascularity.
astrocytomas and oligodendrogliomas, They most often appear T1 isointense
every new MRI should be compared to hypointense and T2 isointense to
with previous studies over as long of a hyperintense. Cystic and hemorrhagic
time period as possible to detect the components are rare. Enhancement with
presence of gradual interval growth. gadolinium is usually heterogeneous.5
EPENDYMOMAS PRIMARY CENTRAL NERVOUS

Ependymomas arise from epen- SYSTEM LYMPHOMA
dymal cells lining the ventricles. Other Primary CNS lymphoma comprises 3%
intraventricular masses are listed in of all intracranial neoplasms and is the
Table 7-6. Since they tend to fill the most common intracranial neoplasm
fourth ventricle and expand through in patients with acquired immunodefi-
the foramen of Luschka, foramen of ciency syndrome (AIDS). In such pa-
Magendie, and foramen magnum, they tients, primary CNS lymphoma is linked
present primarily with signs of increased with Epstein-Barr virus infection.
intracranial pressure and hydrocepha- While biopsy is recommended to
lus.5 These tumors often cause ‘‘meta- confirm diagnosis, treatment is medi-
stases,’’ which spread from the fourth cal and not surgical. Chemotherapy
ventricle to the spinal canal via CSF and radiation may benefit patients who
and produce distant spinal metastatic are immunocompetent, whereas in pa-
foci along the CSF spaces without tients with human immunodeficiency
intervening lesions. Therefore, imag- virus (HIV ), the prognosis is poor.5
The tumor behavior and hence the
imaging appearance of CNS lymphoma
are different in patients who are immu-
TABLE 7-6 Intraventricular nocompetent versus those who are
Masses
immunocompromised.
b Ependymoma In patients who are immunocom-
petent, lymphoma is mostly unifocal
b Subependymoma
with defined or lobulated margins. In
b Subependymal giant cell more than 80% of cases, the lesion is
astrocytoma close to the ventricular ependyma or to
b Central neurocytoma the meningeal surface. In 20% to 40%
b Choroid plexus papilloma
of cases, multiple lesions occur. In-
volvement of the basal ganglia, thala-
b Meningioma mus, and corpus callosum is typical.
b Ectopic pinealoma Perilesional edema is usually present
b Epidermoid tumor but less prominent than that in malig-
nant gliomas or metastases. No calcifi-
b Neuroepithelial cysts
cation or hemorrhage occurs, and
necrosis is rare.5

Brain Tumors
KEY POINT
h Lymphomas are
hypercellular tumors
with a high nuclear to
cytoplasmic ratio;
therefore, primary central
nervous system lymphomas
often show reduced
diffusivity on iffusion-
weighted imaging.
FIGURE 7-8 Ependymoma. A, Sagittal T1-weighted MRI of the brain shows a somewhat
heterogeneously hypointense midline expansile mass (arrow), extending
inferiorly from the fourth ventricle into the foramen magnum. B, Axial
T2 fluid-attenuated inversion recovery (FLAIR) MRI shows the hyperintense mass within the
fourth ventricle (arrow).
In patients with AIDS, lymphoma is pressure and cerebellar dysfunction.

most frequently multifocal. The le- Hemangioblastomas are WHO grade I
sions tend to be smaller, each with and may be associated with von Hippel-
more irregular margins, and are not Lindau syndrome, in which case they
necessarily in contact with the epen- occur throughout the CNS as well as in
dyma or meningeal surfaces. More ex- the retina.4 The cystic component of
tensive perilesional edema often the tumor is T1 hypointense and T2
occurs, as well as possible hemorrhage hyperintense; the solid pial compo-
and necrosis. With gadolinium, periph- nent of the tumor is T1 isointense
eral rim enhancement often can and slightly T2 hyperintense. Inside
be seen.3 the solid component, serpiginous
Lymphomas are hypercellular tumors flow voids may be seen. Following con-
with a high nuclear to cytoplasmic trast administration, a marked enhance-
ratio; therefore, primary CNS lym- ment of the subpial nodule without
phoma frequently shows reduced dif- enhancement of the cyst wall can be
fusivity on DWI. Because intratumoral seen. In patients with known or sus-
hemorrhages occur much more fre- pected von Hippel-Lindau syndrome,
quently in high-grade gliomas, GRE imaging of the entire spine, as well as
and SWI sequences can help distin- examination of the retina, is necessary
guish primary CNS lymphoma from to assess for multiple lesions.4
high-grade gliomas.29
PRIMITIVE NEUROECTODERMAL
HEMANGIOBLASTOMA TUMORS (MEDULLOBLASTOMA)
Hemangioblastoma is a benign tumor Primitive neuroectodermal tumors,
composed of an overgrowth of capil- which were formerly called medullo-
laries. It most commonly occurs in blastomas, occur in children and
the posterior fossa and may produce young adults and arise from the prim-
symptoms of increased intracranial itive neuroectoderm of the cerebellar

KEY POINTS
vermis in the fourth ventricle. These adjacent to the region of the foramen h On perfusion imaging,
tumors present with signs of increased of Monro.5 meningiomas show
intracranial pressure or cerebellar dys- The solid components of the tumor elevated blood volume
function. Imaging of the entire neuraxis are T1 isointense, while the cystic com- due to their
is important as these tumors can me- ponents are hypointense; T2 signal is hypervascularity.
tastasize throughout the CNS.5 This heterogeneous and predominantly Capillaries within a
neoplasm is T1 isointense to hypo- hyperintense with a bubblelike appear- meningioma are highly
intense and T2 isointense. The tumor ance, as seen on the images in Case 7-2. permeable due to
shows avid enhancement with gadolin- Calcifications are hypointense on T2, the lack of a
ium in about 90% of cases. Due to high and flow voids from pathologic vas- blood-brain barrier.
cellularity, restricted diffusion may be cularization may be seen. Variable en- h Meningiomas may be
shown. MR spectroscopy shows ele- hancement with gadolinium and a associated with a
vated choline and reduced NAA. Due strong choline peak on MR spectros- mutation in chromosome
to possible leptomeningeal metastasis, copy can be seen.4 22 or as part of
neurofibromatosis type 2.
which occurs in about 33% of patients
at diagnosis, the MRI study should in- MENINGIOMA
clude the brain and the entire spine.4 Meningiomas are highly vascular, extra-
axial tumors that are generally benign.
GANGLIOGLIOMA Meningiomas account for 20% of pri-
Gangliogliomas are slow-growing tu- mary CNS neoplasms. They derive their
mors that occur in children and young blood supply primarily from the menin-
adults and may undergo malignant geal arteries with tumor capillaries that
transformation.5 Gangliogliomas are gen- lack a blood-brain barrier. Roughly 95%
erally cystic, with or without a solid com- of meningiomas are supratentorial, but
ponent, and have a variable degree of they can be found anywhere along the
enhancement and calcifications.2 Gang- dura. Meningiomas are hypervascular on
liogliomas are commonly found in pa- perfusion MRI, with highly permeable
tients with medically refractory seizures. capillaries.4 Meningiomas can occur as a
They are usually cystic masses with well- result of a mutation in chromosome
defined margins, are rarely solid, and are 22 or as part of neurofibromatosis
T1 isointense to hypointense and T2 type 2. Symptoms are produced by
hyperintense. Calcifications appear as compression of adjacent tissues by
areas of hypointensity in T2 and T2* the tumor. 5 Seizures may occur due
sequences. With contrast, the enhance- to its contact with the gray matter.
ment pattern is heterogeneous with On MRI, most meningiomas uni-
various intensity and nodular or mul- formly and avidly enhance with con-
tinodular morphology. The lesion is trast and may produce significant
usually surrounded by mild vaso- surrounding edema (Figure 7-10). A
genic edema.4 heterogeneous pattern of enhance-
ment in a meningioma and significant
CENTRAL NEUROCYTOMA peritumoral edema are clues that the
Central neurocytomas are benign tu- tumor is more aggressive.30 A dural
mors arising within the lateral ventricles tail may be observed and refers to
with a cystic component and variable enhancement of the meninges flanking
degrees of enhancement. The solid the tumor. Meningiomas may also be
component of the tumor is isointense accompanied by hyperostosis of overly-
to gray matter on T2-weighted images, ing bone or with cyst formation.4
and internal flow voids may be seen. CT Meningiomas are isointense or slightly
frequently demonstrates calcification hypointense to the cortex in T1

Brain Tumors
Case 7-2
A 17-year-old boy presented with a 6-week history of headache. The patient’s headaches were continuous
and were made worse by changes in position, coughing, and sneezing. He denied nausea or vomiting.
Neuroimaging showed an intraventricular mass in the right lateral ventricle with internal flow voids from
pathologic vascularization, typical of central neurocytoma. Solid components were isointense on
T1-weighted images (Figure 7-9), while the cystic components were hypointense.
The patient underwent resection with relief of his symptoms. The tumor was found to be an atypical
neurocytoma, and microscopic evaluation showed delicate vascular subdivisions, which were granular.
The tumor had Homer Wright rosettes and perivascular pseudorosettes, and no calcifications were noted.
The tumor was synaptophysin positive, and tumor cells were negative for epithelial membrane
antigen, p53. MIB-1 fraction index (indicates proliferative rate) was 4%. No necrosis was noted.
FIGURE 7-9 Imaging of the patient in Case 7-2. A, Diffusion-weighted imaging (DWI) hyperintensity (arrow)
represents hypercellularity. B, On fluid-attenuated inversion recovery (FLAIR) image, signal is
heterogeneous, predominantly hyperintense with a bubblelike appearance. C, The solid
components of the tumor are T1 isointense, while the cystic components are hypointense.
Comment. This case demonstrates that although central neurocytomas are benign tumors arising
within the lateral ventricles, patients may be very symptomatic, as in this patient, who presented with
severe headaches.
sequences, with variable signal on T2 MR angiography documents the re-

sequences. At the periphery of the lationship between the meningioma and
tumor, a dilatation of the subarachnoid venous and arterial vascular structures.
spaces and invagination of the cortex For surgical planning, it is important
can be seen due to the compressive and to identify infiltration or occlusion of
displacing effect of meningiomas.8,30 and the adjacent venous sinus.
After contrast injection, early en-
hancement, diffuse and marked with HEMANGIOPERICYTOMA
the exclusion of cystic or calcified com- Hemangiopericytoma is an aggressive
ponents, can be seen. MR spectroscopy extraaxial tumor arising from the peri-
shows an alanine peak without an cytes of the meninges and accounts
NAA peak.2 for less than 1% of all intracranial

FIGURE 7-10 Meningioma. A 50-year-old man with seizures was found to have an
extraaxial mass on MRI with a dural tail. Axial T1-weighted (A) and
T1-weighted postcontrast (B) images of the brain showing an isointense and
avidly enhancing extra axial mass (white arrow) arising from the dura overlying the left cavernous
sinus. Axial CT (C ) shows mild hyperattenuation (hyperdensity) of the lesion relative to the
surrounding brain (red arrow). Coronal T1-weighted postcontrast MRI (D) further demonstrates
the contiguity of the mass with the dura overlying the left cavernous sinus.
neoplasms. These tumors adhere to the tumor, tubular and serpiginous struc-
dura, so a dural tail may be present in tures may exist, which appear as flow
addition to homogeneous enhance- voids and result from extensive neovas
ment, but no calcification is demon- cularization. With contrast, marked and
strated on CT. 4 The mass is T1 heterogeneous enhancement can be
isointense and heterogeneous and T2 seen due to the hypervascularity as
isointense to hyperintense. Inside the well as possible areas of necrosis.2

Brain Tumors
CENTRAL NERVOUS SYSTEM perfusion imaging with increased per-

METASTATIC DISEASE meability due to the presence of
Brain metastases outnumber primary pathologic neovascularization.
neoplasms by at least 10 to 1 and occur Metastatic lesions tend to be multi-
in 20% to 40% of patients with cancer. ple. However, solitary lesions do occur
Subsequent median survival is less than and can present a diagnostic challenge.
6 months.31 An estimated 170,000 new In such cases, perfusion MRI may be
cases of brain metastases occur in the useful to detect peritumoral rCBV. Spe-
United States each year.32 The tumor cifically, the T2 hyperintense region sur-
cells spread via the bloodstream, and rounding enhancing brain metastases
therefore these lesions are more likely represents pure vasogenic edema,
to be deposited at end-arterial terri- while in glial tumors, this often repre-
tories such as the cortical gray-white sents a combination of vasogenic edema
junction. Lung cancer accounts for and infiltrative neoplastic cells. Perfu-
50% of all brain metastases, followed sion MRI with rCBV map may help to
by breast cancer, melanoma, and renal differentiate pure vasogenic edema
cell carcinoma. Approximately one- from infiltrative edema.21
third of patients with a metastatic CONCLUSION
brain lesion do not have a known pri-
mary malignancy.5 MRI with gadolinium is the imaging
Metastases are variable in appear- study of choice in patients with a sus-
ance but are typically T1 isointense to pected CNS neoplasm. The most com-
hypointense, except if they are mucin- mon neuroimaging findings for the
ous, in which case they will be T1 CNS tumors discussed in this text are
hyperintense. Metastases most often outlined in Table 7-3. Contrast-
demonstrate heterogeneous T2 hyper- enhanced T1-weighted images show
intensity. In some metastatic lung breakdown of the blood-brain barrier.
mucoepidermoid metastases, a marked This is useful in characterizing a my-
hypointense signal on T2 can be seen. riad of CNS pathologies and does not
Generally, metastatic lesions show no necessarily imply that the mass is ma-
restricted diffusion. Peritumoral edema lignant4; stroke, abscesses, or demy-
is shown as an area of hypointense sig- elination, in addition to neoplasm,
nal on T1-weighted images and will show contrast enhancement with
hyperintense signal on T2-weighted gadolinium. DWI is used to assess for
images. After contrast injection, enhance- ischemia and hypercellularity within
ment is variable in morphology and a lesion, and, in particular, can help
frequently ringlike due to the presence
differentiate abscesses from malignant
of central necrosis. It is important to
gliomas.3 Perfusion imaging provides
use a sufficient dose of gadolinium and
quantitative estimates of rCBV, which
late acquisition of images (at least
10 minutes after gadolinium is admin- reflects the microvasculature and an-
istered) and to acquire thin slices ( less giogenesis associated with the mass.
than 3 mm) or volumetric acquisitions. Higher rCBV tends to correlate well
Interpreters must pay close attention with the grade of neoplasm; low-grade
to subcortical micrometastases, which astrocytomas have lower values and
are sometimes difficult to differentiate anaplastic astrocytomas or glioblas-
from small pial vessels. An increased tomas have higher values. rCBV map-
choline peak can be seen on MR spec- ping can reveal differences in vascularity
troscopy with high values of rCBV on and may help differentiate radiation

necrosis from recurrent tumor. rCBV 9. Brandsma D, Stalpers L, Taal W, et al. Clinical
features, mechanisms, and management of
mapping and MR spectroscopy can pseudoprogression in malignant glioma.
help to differentiate a solitary metastatic Lancet Oncol 2008;9(5):453Y461.
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Review Article
Imaging of Intracranial
Dr Bela Ajtai, DENT Neurologic
Institute, 3980 Sheridan Dr,
Amherst, NY 14226,
Cysts bajtai@dentinstitute.com.
Dr Ajtai has received personal
Bela Ajtai, MD, PhD; John A. Bertelson, MD compensation for speaking
engagements from Allergan
and Novartis AG. Dr Bertelson
has served on the medical
ABSTRACT advisory board of BrainGear
and has provided expert
Purpose of Review: Intracranial cysts are common findings on both CT and MRI. medicolegal testimony on
The majority of intracranial cysts are benign and incidental and without clinical cases related to brain trauma.
significance. However, a minority are due to infectious, neoplastic, or other path- Unlabeled Use of
ologic processes. Use Disclosure:
Recent Findings: Neuroimaging, in particular brain MRI, can readily identify in- Drs Ajtai and Bertelson report
tracranial cysts. It can often be difficult to characterize the likely histopathology of no disclosures.
intracranial cysts based solely on their signal intensity, even when using contrast. * 2016 American Academy
of Neurology.
However, with the knowledge that most intracranial cysts occur within a fairly narrow
anatomic distribution, a concise and specific differential diagnosis can often be de-
veloped based primarily on location. The first location-based question to consider
regarding intracranial cysts is whether the lesion is intraaxial or extraaxial. Intraaxial
cysts should be further characterized as intraparenchymal or intraventricular, and
extraaxial cysts should be identified as either midline or nonmidline. Signal charac-
teristics using CT, MRI, or both can help further characterize the cystic process.
Summary: Neurologists should be familiar with the characteristic patterns of in-
tracranial cysts to distinguish between benign and pathologic processes. A systematic
approach to the assessment of intracranial cysts based on location and appearance
should greatly narrow the differential diagnosis.
INTRODUCTION Additional factors to consider in-

Intracranial cysts are commonly iden- clude whether cysts are single or
tified on both CT and MRI of the multiple and are found in the supra-
brain. Choroid plexus cysts alone may tentorial or infratentorial region. This
be found in up to 50% of autopsy article discusses select intracranial
studies,1 and hippocampal sulcal rem- cysts based on their typical anatomic
nant cysts may be even more com- distribution(s) (Table 8-1). However,
mon.2 While many intracranial cysts it should be noted that certain types
are benign, others can represent in- of intracranial cysts can be seen in a
fectious, neoplastic, or other patho- variety of locations, sometimes within
logic processes. A systematic approach the same patient.
to intracranial cysts based on location
can significantly facilitate the correct INTRAAXIAL CYSTS
identification of such findings. Cysts (PARENCHYMAL)
should be characterized as follows: Intraaxial cysts are cysts that are
& Intraaxial or extraaxial completely surrounded by central ner-
& If intraaxial, determine whether vous system (CNS) parenchyma. This
intraparenchymal or intraventricular group includes cysts of developmental
& If extraaxial, determine whether origin as well as cystic lesions resulting
midline or nonmidline from other pathologic processes.

Intracranial Cysts
KEY POINTS
h Intracranial cysts are TABLE 8-1 Partial Differential Diagnosis of Intracranial Cysts Based
common and often on Typical Location
conspicuous incidental
findings, usually without Location Examples
clinical significance.
Intraaxial (parenchymal) Dilated Virchow-Robin spaces, choroid fissure cysts,
Both location and signal neuroglial cysts, hippocampal sulcal remnant cysts,
characteristics can be porencephalic cysts, neoplasms,a brain abscesses
very helpful to
differentiate benign Intraaxial (ventricular) Choroid plexus cysts, ependymal cysts, colloid cysts
from pathologic processes. Extraaxial (midline) Pineal cysts, neurenteric cysts, cavum septum
h Dilated Virchow-Robin pellucidum, cavum vergae, cavum velum
interpositum, dermoid cysts, Rathke cleft cysts
spaces are
cystic-appearing Extraaxial (nonmidline) Arachnoid cysts,a epidermoid cysts, neurocysticercosisa
findings commonly a
Can be seen in multiple anatomic distributions.
found within subcortical
regions. These incidental
findings can usually
(but not always) be
distinguished from
Dilated Virchow-Robin Spaces appearance and, on fluid-attenuated
chronic lacunar Also known as enlarged or prominent inversion recovery (FLAIR) images, by
infarctions by their lack perivascular spaces, dilated Virchow- the absence of a surrounding thin rim
of adjacent gliotic tissue. Robin spaces demonstrate typical CSF of gliotic hyperintensity (Figure 8-1E).
signal characteristics. The most com- Occasionally, however, even Virchow-
mon, type I Virchow-Robin spaces, are Robin spaces may exhibit a thin T2-
typically seen at the level of the anterior hyperintense rim, and these can be
commissure in the basal ganglia region particularly difficult to differentiate
(Figure 8-1A). Type II Virchow-Robin from chronic lacunar infarctions.
spaces are found in the hemispheric
white matter, most prominently within Choroid Fissure
the centrum semiovale (Figure 8-1B). Neuroepithelial Cysts
Another common location for Virchow- Choroid fissure neuroepithelial cysts
Robin spaces is within the midbrain are well-demarcated cysts that are seen
(Figure 8-1C) at the mesencephalic- along the choroid fissure dorsal to the
diencephalic and pontomesencephalic hippocampus. On axial images, they are
junctions, referred to as type III typically seen alongside the midbrain.
Virchow-Robin spaces.3 Depending on their size, they may exert
In certain cases, diffuse promi- mild local mass effect but do not cause
nence of the perivascular spaces is any clinical symptoms. They exhibit
seen throughout the CNS parenchyma. CSF signal characteristics, appearing
This is especially common in the T1 and FLAIR hypointense and T2
basal ganglia region. Best depicted on hyperintense (Figure 8-2).
T2-weighted sequences, this imaging
appearance has been traditionally re- Neuroglial Cysts
ferred to as état criblé (Figure 8-1D). Neuroglial cysts are well-demarcated in-
While both Virchow-Robin spaces traparenchymal cysts exhibiting CSF-like
and chronic lacunar infarctions com- signal and no contrast enhancement.
monly occur in the basal ganglia and Microscopically, the wall is composed
other subcortical regions, Virchow- of glial processes and end-feet. Typical
Robin spaces can usually be distin- locations include the frontal and tem-
guished based on their morphologic poral lobe white matter (Figure 8-3).

FIGURE 8-1 Perivascular (Virchow-Robin) spaces. A, Type I; axial T2-weighted MRI demonstrates perivascular
spaces (arrows) of various sizes bilaterally at the level of the anterior commissure (arrowheads).
B, Type II; axial T2-weighted MRI reveals hyperintense perivascular spaces in the centrum
semiovale bilaterally. These are seen longitudinally (arrows) and in cross section (arrowheads). C, Type III; axial
T2-weighted MRI reveals hyperintense perivascular spaces in the midbrain at the tegmentum-cerebral
peduncle border (arrows). D, État criblé; axial T2-weighted MRI demonstrates diffuse prominence of the
perivascular spaces in the basal ganglia region bilaterally. E, Axial fluid-attenuated inversion recovery (FLAIR)
image demonstrates a dilated Virchow-Robin space (arrow) in the left basal ganglia. Note the lack of
surrounding T2-hyperintense signal.
These cysts are usually small, but in multiples, are often seen bilaterally, KEY POINT
extreme cases, they may be very large and are located along the length of h Hippocampal sulcal
and exert mass effect (Figure 8-4). the hippocampal body (Figure 8-5). remnant cysts are
They are most easily visualized on T2- extremely common and
Hippocampal Sulcal weighted coronal or axial sequences. benign findings that
Remnant Cysts do not indicate
While enlargement of the hippocam-
hippocampal atrophy
Also known as hippocampal sulcus pal fissure correlates with hippocam-
or other pathologic
remnant cavities, hippocampal sulcal pal atrophy, hippocampal sulcal processes.
remnant cysts are generally consid- remnant cysts are benign findings
ered to be remnants of the primitive and are not associated with Alz-
hippocampal sulcus, a structure that is heimer disease or other degenera-
typically obliterated through normal tive disorders.
development. These cysts are ex-
tremely common, with reported fre- Porencephalic Cysts
quencies ranging from 26% to 93%.2 Literally meaning “hole in the brain,”
They are small cysts that occur in porencephaly refers to the late effects

Intracranial Cysts
KEY POINTS
h Porencephalic cysts are
lined by gliotic tissue
and often communicate
directly with the
ventricular system.
h While classically
considered to be a
condition acquired
during the perinatal
period, cystic
encephalomalacia
can occur due to any
encephaloclastic process
throughout the lifespan.
FIGURE 8-2 Choroid fissure neuroepithelial cyst. A, Coronal T2-weighted MRI demonstrates
a cyst (arrow) arising from the choroid fissure, superior to the hippocampus. B,
Axial fluid-attenuated inversion recovery (FLAIR) sequence reveals the same cyst
(arrow) in the medial temporal lobe, lateral to the midbrain.
of a destructive process of the brain during the perinatal period, cystic

(eg, trauma, infection, ischemia, or encephalomalacia can occur due to
hemorrhage) ultimately resulting in any encephaloclastic process through-
cystic degeneration and encepha- out the lifespan.
lomalacia (Case 8-1). Porencephalic
cysts are lined by gliotic tissue and Neoplasms
often communicate directly with the Primary and metastatic CNS neo-
ventricular system. While classically plasms can present with a variety of
considered to be a condition acquired imaging characteristics, sometimes with
FIGURE 8-3 Small neuroglial cyst. Axial T1-weighted (A) and coronal T2-weighted (B) MRIs
demonstrate a well-circumscribed intraparenchymal cyst (arrow), anteriorly in
the left temporal lobe. It follows CSF signal characteristics.

KEY POINT
h An important imaging
feature that
distinguishes brain
abscesses from
metastasis is that brain
abscesses exhibit
T2-hyperintense signal
imaging due to
restriction of diffusion.
FIGURE 8-4 Large neuroglial cyst. Axial T2-weighted (A) and axial fluid-attenuated inversion
recovery (FLAIR) (B) sequences demonstrate a prominent cyst in the left anterior
temporal and posterior frontal lobes. It follows CSF signal characteristics. Some
septation within the cyst (A, B, arrowheads) can be seen. Note the mass effect on the left
cerebral peduncle (A, B, arrows).
prominent cystic components. For more

information on neuroimaging of neo-
plasms, refer to the article ‘‘Imaging of
Brain Tumors’’ by Mirza A. Baig, DO;
Joshua P. Klein, MD, PhD, FANA, FAAN;
and Laszlo L. Mechtler, MD, FAAN,4 in
this issue of Continuum.
Brain Abscesses
Brain abscesses are cystic (often multi-
cystic) often intraparenchymal lesions
that may form as a result of an infectious
process (usually bacterial or fungal).
The inflammatory purulent collection
is enclosed in a fibrous capsule. They
tend to exhibit ring enhancement and
are surrounded by a copious amount of
T2-hyperintense vasogenic edema. These
features are very similar to the imaging
FIGURE 8-5 Hippocampal sulcal
appearance of neoplastic lesions, espe- remnant cysts. Axial
cially metastases. An important imaging fluid-attenuated inversion
recovery (FLAIR) (A) and coronal
feature, however, that distinguishes T2-weighted (B) MRIs demonstrate small
them from metastasis is that brain bilateral cavities within the temporal
abscesses exhibit T2-hyperintense sig- lobes, medial to the lateral ventricles,
consistent with hippocampal sulcal
nal on diffusion-weighted imaging remnant cysts (A, B, arrows).
(DWI) due to restriction of diffusion.

Intracranial Cysts
Case 8-1
A 25-year-old man with a history of polysubstance abuse sustained severe traumatic brain injury
secondary to a fall from a two-story building. His Glasgow Coma Scale score immediately following
the fall was 3. The initial hospitalization was prolonged, and he required tracheostomy and
percutaneous endoscopic gastrostomy procedures. He recovered, but with epilepsy and severe
cognitive and behavioral impairment, including aggressive outbursts. A subsequent MRI of the brain
obtained years after
the injury for
posttraumatic
seizures showed cystic
encephalomalacia
within the temporal
lobes bilaterally
(Figure 8-6).
Comment. Any
destructive
(encephaloclastic)
process during the
lifespan, including
trauma, may result in
cystic degeneration
and encephalomalacia
that is readily
detectable with
imaging studies in the
chronic stage. The
cystic component of FIGURE 8-6 Imaging of the patient in Case 8-1 showing a posttraumatic porencephalic cyst.
Axial fluid-attenuated inversion recovery (FLAIR) (A) and coronal T2-weighted
porencephaly (B) MRIs demonstrate cystic encephalomalacia within the temporal lobes
demonstrates signal bilaterally. Note the hyperintense signal on the FLAIR image, which corresponds to gliotic
tissue adjacent to the porencephalic cyst. Ex vacuo dilatation of the temporal horns of the
characteristics of CSF lateral ventricles bilaterally can also be seen.
on all sequences. The
degree of T2-weighted
hyperintensity in the
pericystic tissue may
vary, representing
gliosis. If the cyst
formation happens
very early in
development, gliosis
may be absent
(Figure 8-7).
Enhancement or
diffusion restriction is
not associated with
these lesions.
FIGURE 8-7 Porencephalic cyst from early development. Coronal T2 (A) and T1 (B) inversion
recovery sequences demonstrate a prominent cavitary lesion in the right
frontal lobe. It exhibits CSF signal characteristics. Both arrows point to the
opening of the cyst to the surface. Note the absence of surrounding gliosis.

KEY POINT
This constellation of imaging features the subtypes is practically not neces- h The constellation of
(ie, ring enhancement, significant sur- sary. They are T1 hypointense and T2 imaging features
rounding edema, and T2-hyperintense hyperintense and typically (in 60% to including ring
signal/restricted diffusion on DWI) in- 80% of cases) exhibit hyperintense enhancement,
dicates the presence of an abscess signal on DWI (Figure 8-8). Hemor- significant surrounding
until proven otherwise. It is to be rhage may occasionally be associated edema, and
noted that abscesses may form in with choroid plexus cysts, best seen T2-hyperintense signal/
other compartments as well (eg, the as hypointensity on gradient recalled restricted diffusion on
epidural space, subarachnoid space, echo (GRE), T2*, or susceptibility- diffusion-weighted
and ventricles). weighted imaging (SWI) sequences. imaging indicates the
presence of an abscess
On noncontrast CT, they typically ex-
INTRAAXIAL CYSTS (VENTRICULAR) until proven otherwise.
hibit a hyperdense appearance. Cho-
Intraaxial cysts are cysts that are en- roid plexus cysts are usually small (2 mm
closed in the cerebral ventricular system. to 8 mm) and bilateral. Rarely, they may
exceed 2 cm in diameter.
Choroid Plexus Cysts
Choroid plexus cysts are benign cysts Ependymal Cysts
that tend to arise from the glomus of Ependymal cysts are benign cysts typi-
the choroid plexus; hence, they are most cally located in the body of the lateral
commonly found in the atria of the ventricle. They exhibit CSF-like signal
lateral ventricles. The term choroid and are surrounded by a thin wall (Fig-
plexus xanthogranuloma is sometimes ure 8-9). While usually small (2 mm to
used to refer to these cysts; although 3 mm in diameter), in rare cases, epen-
histopathologically there may be dymal cysts can be up to 8 cm to 9 cm
differences, they share imaging char- in diameter and may cause consider-
acteristics, and distinction between able expansion of the involved ventricle
FIGURE 8-8 Choroid plexus cyst. Axial fluid-attenuated inversion recovery (FLAIR) (A) and
diffusion-weighted (B) MRIs demonstrate choroid plexus cysts in the atria of the
lateral ventricles bilaterally (A, B, arrows). These are characteristically
hyperintense on diffusion-weighted imaging.

Intracranial Cysts
KEY POINTS
h In almost every case, Colloid Cysts
colloid cysts are located In almost every case, colloid cysts are
in the anterior one-third located in the anterior one-third of the
of the third ventricle, third ventricle, adjacent to the fora-
adjacent to the foramen men of Monro (Figure 8-10). The
of Monro. signal characteristics of colloid cysts
h Most often, colloid cysts depend on their content. Most often,
are hyperintense on they are hyperintense on T1-weighted
T1-weighted and and hypointense on T2-weighted im-
hypointense on ages based on their mucus or protein
T2-weighted images content. If, however, the protein con-
based on their mucus or tent of a colloid cyst is low, it may
protein content. If, cause an isointense signal on T1- and
however, the protein T2-weighted images and the cyst may
content of a colloid cyst
escape detection. Careful review of all
is low, it may cause an
pulse sequences can help to avoid
isointense signal on
T1- and T2-weighted
this. As another caveat, if a colloid cyst
FIGURE 8-9 Ependymal cyst. Axial
images and the cyst T2-weighted image is less than 5 mm in diameter, it may
may escape detection.
demonstrates a large be missed because of the slice place-
intraventricular cyst with CSF signal
characteristics causing expansion of the ment of the 5-mm-thick slices of a
body of the right lateral ventricle. Note conventional MRI study. Colloid cysts
the thin cyst wall (arrow) in the are nonenhancing, but their epithelial
ventricular cavity.
lining may appear as a thin rim of
enhancement after gadolinium admin-
segment. For a review of diagnostic istration. The cysts are derived from
imaging of ependymal cysts, refer to the tela choroidea neuroepithelium and
Salzman’s comprehensive work.5 are histologically benign, yet they may
FIGURE 8-10 Colloid cyst. Axial T2-weighted (A) and T1-weighted (B) MRIs reveal a round
circumscribed cyst (A, B, arrows) anteriorly in the third ventricle at the level of
the foramen of Monro. The cyst exhibits typical T2 hypointense and T1
hyperintense signal.

KEY POINTS
become life threatening. Obstruction cysts, in particular those with a diame-
h Although histologically
of the foramen of Monro by a colloid ter larger than 1.5 cm, can be symp-
benign, colloid cysts
cyst, which can happen suddenly, may tomatic through mass effect on the may lead to severe
result in acute hydrocephalus, coma, adjacent structures, namely the quadri- symptoms, such as
and death (typically due to herniation geminal plate and the cerebral aque- acute hydrocephalus
or neurogenic cardiac dysfunction with duct (Figure 8-12). Symptoms can and even death,
subsequent cardiac arrest). include Parinaud syndrome, headache, because of their
The above-described cysts represent vertigo, diplopia, and, occasionally, sud- propensity to cause
den death (due to pineal apoplexy). obstruction of CSF
the main forms of intraventricular cysts.
Pineal cysts are composed of an outflow at the level of
It is to be noted that, rarely, arachnoid
outer layer of connective tissue, a the foramen of Monro.
cysts and epidermoid cysts (described
in detail later in this article) can also middle layer of pineal parenchyma, h Intraventricular cystic
and an inner layer of gliotic tissue. lesions mainly include
appear in intraventricular location.
On MRI, pineal cysts are well demar- choroid plexus cysts,
cated and usually ovoid. The cystic fluid colloid cysts, and
EXTRAAXIAL CYSTS (MIDLINE) ependymal cysts.
can vary in composition, so imaging
This section describes cysts that are characteristics are also highly variable. Rarely, arachnoid cysts
outside the CNS parenchyma and and epidermoids can
The signal of the cysts is typically sim-
located in the midline of the neuraxis. also be found in
ilar or slightly hyperintense to CSF on intraventricular
T1- and T2-weighted images.6 On locations.
Pineal Cysts FLAIR sequences, they usually only
Pineal cysts are the most common cys- partially attenuate and thus tend to
tic lesions found within the pineal gland appear relatively hyperintense. With
(Figure 8-11), reported to be seen in gadolinium, the cyst wall may exhibit
over 20% of healthy controls when thin, faint, and often incomplete en-
using high-resolution MRI. 6 These hancement. With delayed imaging (1 to
non-neoplastic lesions are generally 1.5 hours after contrast administra-
small (usually smaller than 10 mm in tion), homogenous enhancement may
diameter) and asymptomatic. Larger be seen, likely due to diffusion of the
FIGURE 8-11 Pineal cyst. Axial fluid-attenuated inversion recovery (FLAIR) (A) and sagittal
T2-weighted (B) MRIs demonstrate a pineal cyst (A, B, arrows) that is T2
hyperintense and also relatively hyperintense on FLAIR. It does not cause
compression of the cerebral aqueduct.

Intracranial Cysts
KEY POINTS
h Simple pineal cysts are cysts. Contrast-enhanced, diffusion-
usually asymptomatic weighted, and other MRI sequences are
and tend not to expand often necessary to characterize these
with time. However, lesions. However, imaging often does
serial imaging may be not allow one to definitely distinguish
necessary to distinguish between these, and follow-up imaging
simple pineal cysts is suggested if the pineal region cyst is
from pineocytomas, large (larger than 15 mm) or exhibits an
pineoblastomas, and atypical signal or enhancement pattern.
other more aggressive
processes. Neurenteric Cysts
h On imaging, neurenteric Neurenteric cysts are rare endodermal-
cysts classically Extremely large pineal derived cysts, most commonly found
FIGURE 8-12
appear as small cyst (arrow) in a pediatric
patient. On axial and
in the spinal canal. They are thought
well-circumscribed
coronal images, this could be confused to arise from the primitive neurenteric
lesions within the with cavum velum interpositum; however,
the sagittal image helps to clarify.
canal and ultimately arise along the
prepontine or
premedullary cisterns or
remnants of the notochord. Intracra-
in the spinal canal. nial neurenteric cysts are usually mid-
contrast material into the cyst cavity. line in the posterior fossa, particularly
Calcification may be seen. anterior to the brainstem. Supratentorial
Other pineal lesions. Pineocytomas neurenteric cysts comprise 25% to 30%
are less common cystic-appearing le- of intracranial neurenteric cysts and are
sions of the pineal gland and can be very most commonly seen adjacent to the
difficult to distinguish from a pineal cyst frontal lobes.7
based on imaging alone. Multiple other On imaging, neurenteric cysts classi-
lesions with cystic components exist that cally appear as small well-circumscribed
can localize to the pineal gland and lesions within the prepontine or pre-
adjacent structures, in particular, pineo- medullary cisterns or in the spinal canal
blastomas, astrocytomas, and arachnoid (Figure 8-13). The fluid contents vary
FIGURE 8-13 Histologically proven neurenteric cyst. Sagittal T1-weighted (A) and
T2-weighted (B) MRIs of the cervical spine reveal a circumscribed cyst (A, B,
arrows) anterior to the cervical cord, just below the cervicomedullary junction.
Because of this, slight posterior displacement of the cord occurs. The cyst is isointense/slightly
hyperintense to CSF on T1-weighted and hyperintense to CSF on the T2-weighted image.

KEY POINT
significantly (clear and colorless to thick h The position of the
and mucoid), so the appearance on fornices (ventral versus
MRI can vary markedly. Nonetheless, dorsal displacement)
neurenteric cysts are usually hyper- helps to distinguish
intense on T2-weighted, isointense to between cavum
hyperintense on T1-weighted, and vergae and cavum
hyperintense to CSF on FLAIR sequences. velum interpositum.
Contrast enhancement is uncommon.7
Cavum Septum Pellucidum

The septum pellucidum is a thin,
originally two-layered membranous
midline structure. It represents under-
developed medial walls of the two
telencephalic vesicles next to each
FIGURE 8-14 Cavum septum
other, separating the two anterior pellucidum. Axial
horns of the lateral ventricles. It T1-weighted MRI reveals
consists of an ependymal lining to- enlargement of the normally virtual space
between the two layers of the septum
ward the ventricles and contains neu- pellucidum (arrow).
ronal and glial cell elements. It is
bordered by the corpus callosum and campal commissure, and its roof and
the column and body of the fornix. posterior wall are formed by the
During normal development, the two posterior body and the splenium of
layers of the septum pellucidum are the corpus callosum, respectively. It is
initially separate and enclose a cavum. not known whether this space is just a
This is typically still seen at birth. With posterior extension of the cavum sep-
further development, the two layers tum pellucidum or it develops sepa-
tend to fuse into a single septum, and rately and just communicates with the
the incidence of a cavum is 15% by cavum septum pellucidum. Indeed, a
6 months of age.8 Often, a cavum cavum septum pellucidum and cavum
septum pellucidum is an incidental find- vergae are usually found together
ing (Figure 8-14), but it must be noted (Figure 8-15). 9 While an isolated
that persistence of the cavum may also cavum vergae is seen in one-third of
indicate a congenital disorder that in- newborns, it typically disappears before
terferes with brain development. The the cavum septum pellucidum and
cavum septum pellucidum may also rarely persists into adulthood. Given its
develop as a result of repetitive brain anatomic borders, the cavum vergae,
trauma, such as occurs in boxers. It when enlarged, is found beneath the
rarely requires intervention, but may, posterior body of the corpus callosum
rarely, cause obstruction at the level of and causes downward displacement of
the foramen of Monro, necessitating the fornix. The latter is a finding that
neurosurgical intervention. helps to distinguish a cavum vergae
from a cavum velum interpositum,
Cavum Vergae which causes an opposite upward
The origin of the cavum vergae is displacement of the fornices.
somewhat controversial. This space is
posterior to the columns of the fornix. Cavum Velum Interpositum
Its lateral borders are the crus of the The ependymal roof of the third
fornix, its inferior border is the hippo- ventricle is covered by a pia mater

Intracranial Cysts
KEY POINT
h Epidermoid and commissure.10 Given its anatomic bor-
dermoid cysts represent ders, it is sometimes called cavum
a group of inclusion fornicis or cavum of the fornix. If a
cysts derived from the cavum velum interpositum forms (or is
ectoderm. Besides being expanded by an arachnoid cyst),
epidermal cells, dermoid caudal displacement of the internal
cysts also contain cerebral veins and anterior and supe-
dermis derivatives, rior displacement of the fornix occur
including sebaceous and
(Figure 8-16). The latter feature helps
sweat gland cells, hair
to distinguish a cavum velum inter-
follicles, and
even adipocytes.
positum from a cavum vergae, which
causes downward fornix displacement.
A cavum velum interpositum is usually
an incidental finding and does not re-
quire treatment. For a review of the
anatomy, embryology, and pathology
FIGURE 8-15 Cavum septum of cavum septum pellucidum, cavum
pellucidum and cavum
vergae. Axial vergae, and cavum velum interpositum,
T1-weighted MRI demonstrates cavum refer to Tubbs and colleagues.11
septum pellucidum anteriorly (arrow)
and, as a continuation of this, cavum
vergae posteriorly between the crus of Dermoid Cysts
the fornix (double arrow).
Epidermoid and dermoid cysts repre-
sent a group of inclusion cysts derived
bilayer, commonly referred to as tela from the ectoderm. Besides epidermal
choroidea. The choroid plexus of the cells, dermoid cysts also contain der-
third ventricle and the internal cerebral mis derivatives, including sebaceous
veins are located between the layers of and sweat gland cells, hair follicles,
the tela choroidea. The cavum velum and even adipocytes. They are typically
interpositum forms when the layers of encountered in the midline (eg, the
the tela choroidea separate. The resul- sellar, parasellar, or frontonasal region)
tant cavum is situated between the crus and the posterior fossa (eg, the vermis
of the fornix and the hippocampal or the cavity of the fourth ventricle).
FIGURE 8-16 Cavum velum interpositum. Sagittal fluid-attenuated inversion recovery (FLAIR) (A), axial T2-weighted (B), and
coronal T2-weighted (C ) MRIs reveal the cavity of a prominent cavum velum interpositum. As a distinguishing
feature from cavum vergae, the fornices are displaced superiorly (A, B, C, arrows).

KEY POINT
The lipid content of dermoids results segment of the neural tube. The h Dermoid cysts may
in a T1-hyperintense signal; this T1 Rathke pouch (a remnant of the cavity rupture; in such cases,
hyperintensity is eliminated by using of the craniopharyngeal duct) eventu- noncontrast
fat-suppression techniques. On T2- ally loses its connection with the T1-weighted images
weighted images, dermoids are hetero- pharynx and forms the anterior pituitary. reveal hyperintense fat
geneous, and their signal ranges from The anterior wall of the pouch gives content dispersed in the
hypointense to isointense to hyper- rise to the pars distalis, and the subarachnoid space.
intense. Occasionally, hair may even posterior wall develops into the pars
be discerned within the cyst as areas intermedia. Normally only minimal
of curvilinear hypointensity. Dermoid residual space (the Rathke cleft) re-
cysts do not enhance with gadolinium mains. Rathke cleft cyst refers to the
and are histologically benign. They may cystic enlargement of this residual
rupture, however, and in such cases, space. Therefore, its location is sellar
noncontrast T1-weighted images reveal or, if larger, also suprasellar. A Rathke
hyperintense fat content dispersed in cleft cyst may be purely suprasellar as
the subarachnoid space (Figure 8-17). well. The major differential diagnosis,
Associated abnormal meningeal en- besides pituitary adenoma, is cranio-
hancement due to chemical meningitis pharyngioma, which arises from the
may also be noted at times. epithelium within the cleft.
The signal characteristics of a Rathke
Rathke Cleft Cysts cleft cyst depend on the cyst contents
The development of the pituitary (eg, protein, mucopolysaccharides,
gland begins when the ectoderm at cholesterol); therefore, they are vari-
the roof of the primary oral cavity able (Figure 8-18 and Figure 8-19).
(stomodeum) forms an upward invag- Rathke cleft cysts may exhibit low, in-
ination (Rathke pouch) and joins the termediate, or high signal on T1- and
downward-protruding infundibular T2-weighted images. They tend to be
process of the rostral diencephalic hyperintense on FLAIR. About 77% of
FIGURE 8-17 Dermoid cyst. A, Axial T1-weighted image reveals a mostly T1-hyperintense lesion (long
arrow) in the lateral ventricle. This has been partially resected. Note the scattered
T1-hyperintense foci (short arrows) in the subarachnoid space, representing spilled contents
of this dermoid cyst due to its previous rupture. B, Axial T2-weighted image reveals mixed hyperintense and
hypointense signal in the cyst (arrow). C, A more caudal axial T1-weighted image reveals additional
numerous T1-hyperintense foci of spilled cyst contents. Because of the hydrocephalus caused by the cyst, a
previously placed shunt is seen across the right hemisphere.

Intracranial Cysts
FIGURE 8-18 Rathke cleft cyst. Axial T2-weighted (A), coronal T2-weighted (B), and sagittal T1-weighted postcontrast
(C ) MRIs demonstrate a circumscribed T2-hyperintense and T1-hypointense nonenhancing cyst
(A, B, C, arrows) in the approximate location of the pars intermedia of the pituitary gland.
Rathke cleft cysts may exhibit hy- Arachnoid Cysts

KEY POINTS
h Rathke cleft cysts are
perintense intracystic nodules on T1- Arachnoid cysts are extraaxial CSF-
intrasellar lesions that weighted images and hypointense filled cysts lined by arachnoid mem-
arise from the pars nodules on T2-weighted images.12 brane. Considering their structure, the
intermedia. They should Occasionally, thin peripheral enhance- term intraarachnoid cyst would be
be distinguished from ment may be seen. more appropriate, as these cysts are
craniopharyngiomas formed between the layers of the
and other lesions. An EXTRAAXIAL CYSTS arachnoid membrane. 13 Arachnoid
intracystic nodule that (NONMIDLINE) cysts are frequent incidental findings
is T1 hyperintense
This section reviews cysts that are on MRI. They account for 1% of all
and T2 hypointense
outside the CNS parenchyma and intracranial mass lesions.14 The most
is considered
pathognomonic of typically not located in the midline of common locations are the middle cra-
Rathke cleft cysts. the neuraxis. nial fossa (Figure 8-20), sylvian fissure,
h Arachnoid cysts are
frequent incidental
findings on MRI. They
account for 1% of all
intracranial mass lesions.
The most common
locations are the middle
cranial fossa, sylvian
fissure, posterior fossa,
suprasellar region,
and vertex.
FIGURE 8-19 Prominent Rathke cleft cyst. Coronal (A) and sagittal (B) T1-weighted MRIs
reveal a T1-hyperintense prominent cyst (A, B, arrows) in the pars intermedia
of the pituitary gland.

FIGURE 8-20 Arachnoid cyst in the middle cranial fossa. Axial T1-weighted (A), fluid-attenuated inversion
recovery (FLAIR) (B), and diffusion-weighted (C ) MRIs reveal an extraaxial cyst (A, B, C, arrows)
with CSF signal characteristics anteriorly in the right middle cranial fossa. This exerts mass
effect on the right anterior temporal lobe.
posterior fossa (Figure 8-21), supra- nal on T1-weighted images relative to

sellar region, and vertex (Figure 8-22). the CSF. Hemorrhage into the cyst can
The signal characteristics of arachnoid also alter the signal. Flow phenomena,
cysts follow that of the CSF: they are such as pulsation or turbulence, may
hypointense on T1-weighted and FLAIR also change the signal within the cyst.
images and hyperintense on T2-weighted Arachnoid cysts do not enhance with
images. This pattern may, at times, be gadolinium. The imaging protocol for
altered by the chemical composition of suspected arachnoid cysts must also
the arachnoid cyst fluid. The fluid is include DWI to differentiate them from
secreted by the cyst wall, and when its epidermoid cysts. Epidermoid cysts
protein content is higher, the cyst may typically exhibit signal characteristics
exhibit slightly more hyperintense sig- very similar to arachnoid cysts; however,
FIGURE 8-21 Retrocerebellar arachnoid cyst versus enlarged cisterna magna. These entities
are, at times, hard to differentiate on sagittal images. A, On axial images,
arachnoid cysts result in lateral displacement of the falx cerebelli (arrow). B,
In the case of enlarged cisterna magna, the falx cerebelli remains in the
midline (arrowheads).

Intracranial Cysts
FIGURE 8-22 Convexity arachnoid cyst. Axial fluid-attenuated inversion recovery (FLAIR) (A), sagittal FLAIR (B), and coronal
T2-weighted (C ) MRIs demonstrate a small arachnoid cyst (A, B, C, arrows) dorsal to the right frontal lobe.
KEY POINTS unlike arachnoid cysts, they are they are slightly hyperintense to CSF.
h In cases of enlarged hyperintense on DWI.15 Although usu- Occasionally, epidermoid cysts appear
retrocerebellar spaces, a
ally seen in nonmidline extraaxial loca- hyperintense to the brain tissue on
midline position of the
tions, arachnoid cysts can also be seen T1-weighted images, which is felt to
falx cerebelli favors an
enlarged cisterna magna in midline locations and within the be caused by increased triglyceride
over a retrocerebellar ventricles. Retrocerebellar arachnoid and fatty acid content. These are rare
arachnoid cyst. cysts are, at times, difficult to distin- and referred to as white epidermoid.16
h Epidermoid cysts, like guish from an enlarged cisterna magna. On T2-weighted images, epidermoids
choroid plexus cysts, The position of the falx cerebelli can are isointense or slightly hyperintense
exhibit T2 hyperintense guide the differential diagnosis in these to CSF. On FLAIR, the signal of the
signal on cases (Figure 8-21). cystic contents is not suppressed
diffusion-weighted completely; therefore, it tends to
images. This Epidermoid Cysts appear hyperintense relative to the
feature helps to Epidermoid cysts (also known as con- suppressed (hypointense) CSF signal.
differentiate them from Most important, on DWI, epidermoids
genital keratin cysts, squamous epi-
arachnoid cysts.
thelial cysts, or ectodermal inclusion exhibit bright signal, due to restricted
h The differential diagnosis cysts) are usually congenital and result diffusion.15 As outlined earlier, this
of intracranial cystic from abnormal inclusion of epidermal imaging feature distinguishes them
lesions with restricted
cells of the ectoderm during neural from arachnoid cysts (Figure 8-23).
diffusion (bright signal
tube closure. They may also form as The differential diagnosis of intracra-
imaging) includes acquired lesions due to accidental nial cystic lesions with restricted diffu-
epidermoid cysts, traumatic epidermal cell inoculation sion (bright signal on DWI) includes
choroid plexus cysts, to deeper structures, including iatro- epidermoid cysts, choroid plexus cysts,
and abscesses. genic causes, such as skin sutures or and abscesses. Epidermoids do not
lumbar puncture. The cysts are com- enhance with gadolinium.
posed of epidermal cells. Congenital
epidermoid cysts are typically off- Neurocysticercosis
midline in the basal cisterns or Neurocysticercosis, caused by infec-
cerebellopontine angle (40% to 50%). tion by the larval form of the parasite
However, epidermoids can also be Taenia solium, is a common cause of
intraventricular and occasionally within epilepsy and other neurologic sequelae
the parenchyma. Their typical signal in endemic regions. T. solium is a
is T1 hypointense to the brain tissue, cestode (tapeworm) that infects
but, in the majority (75%) of cases, humans, with pigs serving as an

FIGURE 8-23 Epidermoid cyst. Axial T1 (A), T2 (B), and fluid-attenuated inversion recovery
(FLAIR) (C ) MRIs reveal a prominent cyst (A, B, C, arrows) in the suprasellar
region. It is T1 hypointense, T2 hyperintense, and, on the FLAIR image,
isointense to the parenchyma. The cyst exhibits prominent mass effect on the thalami and
distorts the third ventricle (A, B, C, arrowheads). Axial diffusion-weighted imaging (D) reveals
that the cyst is strikingly hyperintense (arrow), which distinguishes it from an arachnoid cyst.
intermediate host. Cysticercosis oc- intestinal mucosa, where they enter

curs as a result of fecal-oral contami- the vasculature. Ultimately, some of
nation by ingesting eggs that were them become lodged in the intracra-
released in the feces of a human with nial capillaries.
an intestinal tapeworm. Ingested eggs In the brain, neurocysticercosis cysts
hatch and embryonic cysts cross the can occur within the parenchyma,

Intracranial Cysts
KEY POINTS
h Neurocysticercosis can subarachnoid space, or the ventricles. ventricles and is frequently associated
produce cystic lesions Neurocysticercosis can manifest with with hydrocephalus. Rarely, it can
of varying signal single or multiple lesions. While usually result in stroke via involvement of
characteristics, including small, large lesions can exert mass perforating arteries or other
abnormal enhancement. effect on adjacent structures. Obstruc- vascular structures.
As the intracystic parasite tive hydrocephalus can sometimes & Disseminated neurocysticercosis,
degenerates, large cystic develop, particularly as a result of resulting from innumerable cysts.
lesions with adjacent This is a rare phenomenon whereby
intraventricular cysts. Table 8-2 sum-
inflammation can
marizes the MRI findings, disease cystic lesions due to T. solium are
evolve into small
stage, and underlying pathology of found throughout the body, in
calcified nodules.
neurocysticercosis. Figure 8-24 dem- addition to the more common
h Once a cyst is identified locations within the brain and
and its location
onstrates the various stages of neuro-
cysticercosis lesions, and Case 8-2 subarachnoid spaces.
confirmed, it should be
assessed for size, effect reveals typical imaging findings of a & Spinal neurocysticercosis, a rare
on adjacent structures, patient with a distant history of variant that generally presents as one
and heterogeneity neurocysticercosis. or more extramedullary lesions.
of signal. Variants of cysticercosis include:
& Racemose neurocysticercosis, DIAGNOSIS OF INTRACRANIAL
characterized by a multilobular CYSTS BASED ON IMAGING
cluster of cysts without a visualized CHARACTERISTICS
scolex. This variant tends to occur Once a cyst is identified and its loca-
outside the parenchyma, in the tion confirmed, it should be assessed
subarachnoid space, or in the for size, effect on adjacent structures,
TABLE 8-2 Stages and Pathology of Neurocysticercosis and Imaging Correlate
Stage Pathology MRI Findings

Vesicular Living larva (scolex) within a thin-walled Cystic fluid contents: Similar to CSF
cyst, no significant pericystic edema
Scolex: On T1-weighted imaging, isointense to
hypointense versus white matter; on T2-weighted
imaging, isointense to hyperintense versus white matter
Pericyst: Minimal to no increased fluid-attenuated
inversion recovery (FLAIR) signal
Minimal to no enhancement
Colloidal Degenerating scolex with clear to Cyst contents: FLAIR isointense to hyperintense to CSF
vesicular proteinaceous intracystic fluid,
Cyst wall: Increased enhancement
prominent pericystic inflammatory reaction
Pericyst: Increased T2-weighted and FLAIR signal
Granular Progressive cyst involution, Similar to above
nodular granulomatous nodule develops,
edema starts to decrease
Calcified Calcified nodule, edema resolved Hypointense on T2-weighted and gradient recalled
nodular echo (GRE)/susceptibility-weighted imaging (SWI)
Pericyst: Minimal to no increased FLAIR signal
CSF = cerebrospinal fluid; MRI = magnetic resonance imaging.

FIGURE 8-24 Imaging of a 67-year-old man with neurocysticercosis. Axial fluid-attenuated inversion recovery (FLAIR) (A), axial
contrast-enhanced T1-weighted (B), and coronal contrast-enhanced T1-weighted (C) MRIs demonstrate multiple
cystic lesions of various stages of neurocysticercosis. In the anterior left frontal lobe, note the thin-walled cyst,
intracystic scolex surrounded by fluid that attenuates on FLAIR, lack of enhancement, and lack of pericystic FLAIR hyperintensity
consistent with vesicular-stage neurocysticercosis (A, B, arrowheads). In contrast, the dorsolateral left frontal lobe cyst is
associated with enhancement and prominent adjacent FLAIR hyperintensity consistent with either the colloidal vesicular or
granular nodular stages of neurocysticercosis (A, B, thin arrows). Panel C demonstrates multiple intracranial neurocysticercosis
cysts, including a cluster of two cysts adjacent to the superior sagittal sinus (thick arrow).
and heterogeneity of signal. Many erogeneous signal characteristics would

cysts occur in isolation (eg, arachnoid be more concerning for pathologic
cysts), whereas some occur in pairs processes such as neoplasm or an
or multicyst clusters. While any intra- infectious process. Table 8-3 presents
cranial cyst must first be considered in imaging characteristics that should
the appropriate clinical context, some be considered when assessing intra-
general rules of thumb can assist in cranial cysts.
developing a concise differential
based on certain imaging characteris- CONCLUSION
tics. For example, small thin-walled Intracranial cysts are frequently en-
nonenhancing parenchymal cysts countered on routine CT and MRI
whose intracystic fluid attenuates on studies. While most intracranial cysts
FLAIR sequences may represent be- are benign entities (either normal
nign entities such as parahippocampal variant anatomy or benign congenital
cysts or prominent perivascular lesions), a minority of cystic lesions
spaces. In contrast, the presence of represent pathologic processes. An
calcification, contrast enhancement, or awareness of the anatomic predispo-
intracystic contents demonstrating het- sition of these findings, along with
Case 8-2
An 85-year-old woman who was originally from Mexico presented with deterioration in gait, decline in
verbal output, and increasing incontinence 6 years after the placement of a ventriculoperitoneal shunt
for communicating hydrocephalus due to neurocysticercosis. Imaging showed ventriculomegaly and
scattered subarachnoid calcifications (Figure 8-25). When compared to prior imaging (not included
here), the repeat CT of the head demonstrated stable calcifications but mild progression in
ventriculomegaly. An adjustment in her shunt settings resulted in mild improvement in her gait,
without significant improvement of her other symptoms. Continued on page 1572

Intracranial Cysts
FIGURE 8-25 Imaging of the patient in Case 8-2 who had a distant history of
neurocysticercosis. Coronal (A) and axial (B) head CT demonstrate scattered
subarachnoid calcifications (A, B, thin arrows). This patient had a history of
communicating hydrocephalus, likely related to neurocysticercosis, requiring treatment with a
ventriculoperitoneal shunt (A, open arrow).
Comment. Intraventricular and subarachnoid cysts may be a complication of neurocysticercosis that

results in hydrocephalus (obstructive or communicating), which is well depicted on imaging studies with
CT or MRI. Neuroimaging is of great value for long-term monitoring of such patients and for guiding
decisions for surgical management, if needed.
TABLE 8-3 Imaging Characteristics of Intracranial Cysts
Findings Examples
Cyst contents Heterogeneous Neurocysticercosis (intracystic scolex), sometimes arachnoid cyst (if CSF flow
artifact exists)
Homogenous Choroid fissure cyst, arachnoid cyst, neuroglial cyst, porencephalic cyst,
ependymal cyst, colloid cyst
Signal identical Arachnoid cyst, neuroglial cyst, porencephalic cyst, ependymal cyst, choroid
to CSF fissure cyst
Cyst wall Not visualized Hippocampal remnant cyst, choroid fissure neuroepithelial cyst, neuroglial
cyst, often arachnoid cyst
Thin wall Pineal cyst, ependymal cyst, choroid plexus cyst
MRI sequences Diffusion Epidermoid, choroid plexus cyst, brain abscess
restriction
Contrast Neoplasm, infection (such as neurocysticercosis, brain abscess), sometimes
enhancement pineal cyst
Calcification Neurocysticercosis (chronic stage)
CSF = cerebrospinal fluid; MRI = magnetic resonance imaging.

their imaging appearance, can greatly anatomy. Salt Lake City, UT: Amirsys,
2013:737Y770.
facilitate the correct characterization of
8. Shaw CM, Alvord EC Jr. Cava septi pellucidi
intracranial cysts. The accurate recogni- et vergae: their normal and pathological
tion of a prominent but benign process states. Brain 1969;92(1):213Y223.
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servative management, rather than an 9. Nakajima Y, Yano S, Kuramatsu T, et al.
Ultrasonographic evaluation of cavum
aggressive and potentially unnecessary septi pellucidi and cavum vergae. Brain
surgical intervention. Dev 1986;8(5):505Y508. doi:10.1016/
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Review Article
Imaging of Pituitary
Dr Robert Fenstermaker,
Department of Neurosurgery,
Roswell Park Cancer Institute,
Elm and Carlton Streets,
Buffalo, NY 14263,
Robert.Fenstermaker@
and Parasellar
RoswellPark.org.
Dr Fenstermaker serves on
Disorders
the board of directors of and
owns stock or stock options Robert Fenstermaker, MD, FACS, FAANS; Ajay Abad, MD
in MimiVax, LLC; receives
meeting organization from
prIME Oncology; and receives
ABSTRACT
research/grant support from Purpose of Review: This article reviews sellar and parasellar anatomy and the
the Roswell Park Alliance appearance of normal bone and soft tissue components on both CT and MRI.
Foundation. Dr Abad has
provided expert medicolegal Pituitary gland structure and function are discussed with respect to hormone secretion,
testimony on tumor along with clinical syndromes caused by perturbations in hormone levels. Syndromes
treatment field therapy. and specific diseases in the sellar and parasellar regions are discussed along with
Unlabeled Use of
characteristic clinical features and imaging findings.
Use Disclosure: Recent Findings: Bone and calcifications are best visualized with CT scans, while soft
Drs Fenstermaker and Abad tissues are better defined using MRI. Some lesions have characteristic enhancement
report no disclosures.
patterns with contrast; the presence of delayed contrast uptake further narrows
of Neurology. the differential.
Summary: Lesions that commonly occur in the sellar and parasellar region include
benign and malignant tumors, cysts, vascular pathology, inflammatory processes, and
abscesses. Knowledge of sellar and parasellar anatomy and attention to the use and
interpretation of various imaging modalities can be of great assistance to the clinician
when formulating a differential diagnosis for lesions in this region.
INTRODUCTION imaging findings. Benign lesions in-

The anatomy of the sella turcica and clude pituitary microadenomas and
parasellar region is complex, with a macroadenomas, craniopharyngiomas,
high concentration of critical soft dural-based meningiomas, hypotha-
tissue structures encased in a delicate lamic hamartomas, and schwannomas.
bony architecture with extensive dural Primary germ cell tumors, mesenchymal
investment. Effective imaging in this tumors (chordomas, chondrosarcomas,
region is critical for diagnosis and and plasmacytomas), metastases from sys-
surgical planning. In this article, sellar temic cancers, and astrocytomas comprise
and parasellar anatomy and the ap- the majority of malignant tumors. Cystic
pearance of normal bone and soft lesions consist of dermoid/epidermoid
tissue components on both CT and cysts, Rathke cleft cysts, arachnoid cysts,
MRI are reviewed. Pituitary gland and pituitary abscesses. Vascular anoma-
structure and function are discussed lies include arteriovenous malformations,
with respect to hormone secretion, aneurysms, thromboses, and hemor-
along with clinical syndromes caused rhage. Finally, neurosarcoidosis, lympho-
by perturbations in hormone levels. cytic hypophysitis, and Langerhans cell
Syndromes and specific diseases in histiocytosis comprise the most com-
the sellar and parasellar regions are mon inflammatory lesions that occupy
discussed along with characteristic the sellar region.

KEY POINTS
ANATOMY OF THE sellar and parasellar regions is shown h The pituitary gland is
SELLAR REGION in Figure 9-1.1 ectodermal in origin.
The pituitary gland resides within the h The blood-brain barrier
sella turcica, suspended in place by ANATOMY OF THE
is absent at the
the pituitary stalk, or infundibulum. It PARASELLAR REGION
neurohypophysis and
consists of the anterior lobe, also The parasellar region includes struc- median eminence.
known as the adenohypophysis, and tures encompassing the sella turcica,
the posterior lobe, also known as the the hypothalamus superiorly, the optic
neurohypophysis. During embryogen- chiasm anteriorly, the sphenoid sinus
esis, the neurohypophysis originates inferiorly, and the left and right cavern-
from neural ectoderm, whereas the ous sinuses laterally. Portions of the in-
adenohypophysis arises from the Rathke ternal carotid arteries and cranial nerves,
pouch, an invagination of the oral ecto- specifically the oculomotor (III), troch-
derm. The adenohypophysis consists lear (IV), abducens (VI), and the first two
of five subtypes of secretory cells that divisions of the trigeminal nerve (V1 and
release corresponding hormones: V2), pass through the cavernous si-
somatotrophs (growth hormone), nuses, as shown in the coronal plane
gonadotrophs (follicle-stimulating and in Figure 9-2A.2 Figure 9-2B shows the
luteinizing hormone), corticotrophs sella turcica and pituitary gland in the
(adrenocortical-stimulating hormone), sagittal plane.
thyrotrophs (thyroid-stimulating hor-
mone), and prolactotrophs (prolactin). IMAGING CHARACTERISTICS
These cells are stimulated by the hypo- High-resolution MRI is the modality of
thalamus, which sends releasing hor- choice when evaluating soft tissues and
mones to the adenohypophysis, in turn CSF spaces within the sella turcica and
driving pituitary signaling of target parasellar region. On T1-weighted im-
organs. The neurohypophysis includes aging, the anterior lobe of the pituitary
the infundibulum and the pars nervosa, is isointense relative to gray matter,
a collection of axon terminals originat- whereas the neurohypophysis is nor-
ing from the hypothalamus that store mally hyperintense. The latter is re-
oxytocin and vasopressin. These hor- ferred to as the pituitary bright spot.
mones are released directly into the This high signal intensity can be absent
systemic circulation via the hypophy- in patients with diabetes insipidus,
seal portal system. Between the two suggesting that this signal characteris-
lobes of the pituitary gland lies the tic may be due to stored vasopressin.3
Rathke cleft, a potential space that can Coronal views are particularly infor-
give rise to pathology. mative when evaluating the sellar and
Other notable structures include parasellar regions, normal structures,
the median eminence of the hypothal- and associated pathology. The neuro-
amus, a bulge along the inferior hypophysis and median eminence are
border where the blood-brain barrier devoid of a blood-brain barrier and hence
is absent and hypothalamic releasing take up contrast. Otherwise, areas of
hormones enter the circulation, and contrast enhancement generally reflect
the pars intermedia, a nonfunctional an underlying abnormality. Figure 9-34
collection of cells found at the border demonstrates representative sagittal
of the adenohypophysis and neurohy- and coronal MRIs of the sella turcica
pophysis involved in the production and parasellar region.
of melatonin during embryogenesis. Plain film radiography and CT
The anatomic composition of the scans show normal bony architecture

Pituitary and Parasellar Disorders
FIGURE 9-1 Anatomy of the sellar and parasellar regions.

CN = cranial nerve.
1
Reprinted with permission from Netter F. The Netter collection of medical illustrations. B Elsevier,
Inc. www.netterimages.com.
FIGURE 9-2 Normal anatomy of the sellar and parasellar regions surrounding the pituitary gland in the coronal (A) and
sagittal (B) planes.
2
Reprinted with permission from Di Ieva A, et al, Nat Rev Endocrinol. B 2014 Rights Managed by Nature Publishing Group.
www.nature.com/nrendo/journal/v10/n7/abs/nrendo.2014.64.html.

KEY POINT
h Sellar and parasellar
bony structures and
calcifications are best
visualized on CT.
FIGURE 9-3 Coronal (A) and sagittal (B) MRIs of the sella and suprasellar cistern. A, The
optic chiasm is outlined in green, the internal carotid arteries are outlined in orange,
and the cavernous sinuses are outlined in yellow. B, The pituitary is outlined in red,
the optic chiasm in green, and mammillary body in yellow. The supraoptic and infundibular
recesses are marked in blue.
I = infundibulum; IR = infundibular recess; P = pituitary; SOR = supraoptic recess.
4
Modified with permission from Dr Frank Gaillard, Radiopaedia.org, rID: 17529.
and areas of calcification in greater Headaches

detail than MRI scans. The detection of Large midline mass lesions in the supra-
calcifications and structural aberra- sellar space can cause obstruction of the
tions due to mass lesions, including foramen of Monro on one or both sides
bone remodeling, erosion, invasion, and a resultant noncommunicating hy-
and destruction, is helpful when drocephalus with elevated intracranial
formulating a differential diagnosis.
Figure 9-4 displays the bony architec-
ture of this region as seen on a sagit-
tal CT scan.
CLINICAL SYMPTOMS OF
SELLAR/PARASELLAR LESIONS
Patients with sellar or parasellar mass
lesions often present with characteristic
symptoms and highly specific asso-
ciated clinical signs.
Visual Changes
Lesions causing compression of the
optic chiasm can produce bitemporal
visual field loss. Cavernous sinus lesions
can cause ipsilateral extraocular muscle
weakness and resultant diplopia due
to involvement of the oculomotor, FIGURE 9-4 Sagittal view of the sellar and parasellar
region with associated bony landmarks.
trochlear, or abducens nerves cours-
ing through this space.

KEY POINT
h Obstruction of the pressure. Associated headaches are ing on the hormone that is secreted in
foramen of Monro diffuse with frontal predominance excess (Table 9-1). Large nonfunctional
by suprasellar mass and may be exacerbated when leaning and functional pituitary adenomas can
lesions can cause forward or lying supine. Parasellar also cause failure of the normal gland
noncommunicating lesions often precipitate unilateral due to compression.
hydrocephalus. supraorbital or retroorbital headaches.
Obliterating lesions with associated BENIGN TUMORS
bony invasion can cause CSF rhinorrhea. Benign tumors in the sellar and parasellar
regions are often discovered inciden-
Hormonal Abnormalities tally on neuroimaging. Clinical symp-
Functional pituitary adenomas re- toms are often due to mass effect,
sult in hormonal hypersecretion, with resulting in compression of adjacent
characteristic clinical features depend- structures, including the optic chiasm
TABLE 9-1 Clinical Symptoms and Laboratory Abnormalities in Patients With a Functional
Pituitary Adenoma Associated With Hypersecretion of Specific Hormones
Hormone Effector Hormone Clinical Symptoms Testing

Prolactin None Amenorrhea Prolactin 9200 ng/mL (definitive)
Lactation (excessive in
females, infrequent in males)
Loss of axillary/pubic hair
Gynecomastia
Thyroid-stimulating Thyroxine Hyperthyroidism High TSH despite elevated
hormone (TSH) T3/free T4
Nervousness/irritability/
anxiety/difficulty sleeping
Thin skin/brittle hair/
increased perspiration
Muscular weakness/goiter
Adrenocorticotropic Cortisol Cushing disease High ACTH despite elevated
hormone (ACTH) cortisol; high 24-hour
Hyperglycemia/diabetes
urine cortisol
insipidus/glycosuria/obesity
Skin changes (striae,
bruising, hirsutism)
Osteoporosis/avascular
necrosis of the
femoral head
Immunosuppression/
infection
Follicle-stimulating Estrogen/ Premature menopause Low serum estradiol
hormone/luteinizing testosterone (females) or testosterone
hormone
Testosterone failure (males)

KEY POINTS
and pituitary gland. In some cases, the validated tools that group lesions h Pituitary adenomas are
associated mass effect causes CSF flow together based on size, laterality, ex- often nonfunctional and
obstruction, which can precipitate head- tension into adjacent spaces, and en- discovered incidentally.
aches, nausea, and visual changes related casement of the internal carotid
h Dynamic MRI detects
to elevations in intracranial pressure. artery; both systems are depicted in delayed contrast uptake
Figure 9-6.2 Given their benign nature, in functional adenomas.
Pituitary Adenomas pituitary adenomas do not invade the
h Expansile sellar lesions
Pituitary adenomas are sellar masses lumen of the internal carotid artery.
compress the optic
that can be functional (excessive hor- Frequently, the normal gland and chiasm, causing
mone secretion) or nonfunctional hypothalamic stalk are displaced in a bitemporal hemianopia.
(symptoms due to mass effect). Func- rostral direction and to one side or
tional adenomas cause hypersecretion another by the tumor mass.
of specific hormones produced in the On CT scans, pituitary adenomas
adenohypophysis (Table 9-1). appear hyperdense relative to brain
Pituitary adenomas are classified by parenchyma. Extension of these le-
size, with microadenomas measuring sions can also cause bony erosion and
less than 1 cm in size by definition. reactive changes, but pituitary adenomas
Signal characteristics on MRI are vari- rarely invade or destroy the surround-
able, but these lesions are often hypo- ing bone. On MRI, signal character-
intense on T1-weighted imaging and istics are highly variable, ranging from
hyperintense on T2-weighted or fluid- isointense to hyperintense on both
attenuated inversion recovery (FLAIR) T1- and T2-weighted sequences. Micro-
imaging. For example, in patients with adenomas frequently do not enhance
Cushing disease with excess adrenocor- intensely with contrast.
ticotropic hormone secretion, standard
contrast-enhanced imaging techniques Craniopharyngiomas
may not be adequate for tumor detec- Craniopharyngiomas are benign supra-
tion. In such cases, dynamic MRI may sellar tumors that originate from the
be more effective at detecting an un- pars tuberalis, which partially encircles
derlying microadenoma, with delayed the infundibulum like a collar. During
contrast uptake and progressively more embryologic development, the Rathke
prominent contrast enhancement over pouch separates from the posterior
a period of seconds to minutes.5 pharynx to form the adenohypophysis;
Macroadenomas are larger than the anterior wall of the Rathke pouch
1 cm in diameter. These tumors fre- forms the pars distalis and pars tuber-
quently extend beyond the sella into alis, while the posterior wall gives rise to
the suprasellar cistern, taking on an the pars intermedia. The occurrence of
hourglass shape. They may be discov- craniopharyngiomas is bimodal in age
ered incidentally on CT or MRI. They distribution. They arise most commonly
can cause dysfunction of the oculo- in children between 5 and 14 years of
motor nerve due to mass effect within age and later in life between 50 and
the cavernous sinus. Anterior compres- 74 years of age.6 Patients with cranio-
sion of the optic chiasm often results in pharyngiomas often present with bitem-
a bitemporal hemianopia (Case 9-1). poral visual deficits, beginning with an
Lateral extension results in encase- inferior quadrantanopia with compres-
ment of the adjacent segment of the sion of the superior portion of the optic
internal carotid artery coursing through chiasm, eventually leading to a com-
the cavernous sinus. The Hardy and plete bitemporal hemianopia with on-
Knosp classification systems are both going expansion.

Case 9-1
A 35-year-old man presented to his primary care physician’s office after involvement in a low-speed
motor vehicle accident while changing lanes. Subsequently, he developed a mild frontal headache and
was evaluated in the emergency department several hours later. Further questioning revealed that he
had recently been bumping into things frequently while walking. Review of systems revealed markedly
diminished libido over the past few months. On examination, his visual fields were restricted in the
periphery in both eyes. An MRI revealed a 2 cm 3 cm 2 cm sellar mass that was mildly hyperintense
on T1-weighted imaging (Figure 9-5A). Serum prolactin was markedly elevated at 4020 mcg/L. He
was started on cabergoline, a potent dopamine receptor (D2) antagonist, 0.25 mg 2 times a week,
with partial reduction in tumor volume. He then underwent endonasal endoscopic surgical resection of
the mass. The pathology was consistent with a benign pituitary macroadenoma. He tolerated the
procedure well and experienced gradual improvement in his peripheral vision over the next several
weeks. The postoperative MRI of his brain is shown in Figure 9-5B.
Comment. This case demonstrates the clinical consequences of an expansile mass lesion in the
sellar region.
FIGURE 9-5 Imaging of the patient in Case 9-1. A, Sagittal T1-weighted postcontrast brain
MRI demonstrating a homogenously enhancing pituitary mass (arrow). B, The
same mass is seen postoperatively (arrow) in the T1-weighted MRI with contrast.
KEY POINT On imaging, craniopharyngiomas Meningiomas

h On CT, have features that help distinguish Meningiomas develop in the subdural
craniopharyngiomas them from other sellar masses. They space from arachnoid cap cells and
have a calcified cystic
are usually composed of both solid and can arise from either sellar or para-
rim and a solid
cystic components with fluid that is sellar dura. The tuberculum sellae and
component with
reticular enhancement.
high in protein and lipid content. Cal- planum sphenoidale (Figure 9-8) are
cifications in the cystic rim occur in common sites of origin; others in-
up to 80% of cases and can be vis- clude the greater wings of the sphenoid
ualized on a noncontrast head CT. bones (Figure 9-98), the cavernous
Cystic fluid is often hyperintense on sinuses, optic nerve sheaths, and the
both T1- and T2-weighted MRI se- clival dura mater. Tumors of the tuber-
quences (Case 9-2). The rim and solid culum sella typically cause bitemporal
component both enhance with con- visual deficits with compression of
trast, the solid component often taking the optic chiasm. More lateral lesions
on a reticular enhancement pattern.7 can cause unilateral vision loss with

FIGURE 9-6 Hardy and Knosp classification systems used to characterize pituitary macroadenomas. Hardy classification system:
Grade 0; intact with normal contour; grade I, intact with bulging floor; grade II, intact, enlarged fossa; grade III,
invasive with localized sellar destruction; grade IV, invasive with diffuse destruction. Suprasellar tumors can be
symmetric, occupying the suprasellar cistern only (A), the recess of the third ventricle (B), the whole anterior portion of the third
ventricle (C ); or asymmetric and intracranial extradural (D) or extracranial extradural (E) occupying the cavernous sinus. Knosp
classification system; Grade 0 is no cavernous sinus involvement; grade 1 indicates compression against the medial wall of the
cavernous sinus restricted to a hypothetical line extending between the centers of the two segments of the internal carotid artery;
grade 2 extends beyond this line without passing a line tangent to the lateral margins of the artery itself; grade 3 confers tumor
extension laterally to the internal carotid artery within the cavernous sinus; grade 4 describes total encasement of the
intracavernous portion of the carotid artery.
2
Reprinted with permission from Di Ieva A, et al, Nat Rev Endocrinol. B 2014 Rights Managed by Nature Publishing Group. www.nature.com/nrendo/journal/
v10/n7/abs/nrendo.2014.64.html.
compression of the optic nerve, other are often isointense or hypointense. KEY POINT
cranial nerve deficits, and headaches Sphenoid wing meningiomas may h Parasellar meningiomas
are dural-based lesions
with involvement of the cavernous demonstrate the classic dural tail that
originating from the
sinus. Less commonly, larger meningi- is often seen with lesions along the tuberculum sellae,
omas can cause partial complex sei- calvaria and skull base. Typically, me- planum sphenoidale,
zures by way of contact with mesial ningiomas homogenously enhance anterior clinoid process,
temporal cortex. with contrast, although cystic change or sphenoid wing.
On imaging, approximately 20% of can occur as well. More aggressive In contrast to pituitary
adenomas, meningiomas
meningiomas contain calcifications, atypical or anaplastic lesions may have
involving the sella turcica
which can be visualized on a noncon- associated rim enhancement and areas usually do not produce
trast head CT scan.9 On T1- and T2- of necrosis with brain invasion and bony expansion of
weighted MRI sequences, meningiomas resultant vasogenic edema. this structure.

Case 9-2
A 28-year-old woman presented with progressive headaches with frontal
predominance and peripheral visual loss. Her examination was notable for
a bitemporal superior quadrantanopia. MRI showed a large suprasellar
cystic lesion with a faint contrast-enhancing rim (Figure 9-7).
She underwent partial resection of the lesion, which was found to be a
craniopharyngioma, and postoperatively she developed diabetes insipidus,
hypothyroidism, and hypocortisolism. Additionally, she sustained a
perioperative right thalamic stroke resulting in left-sided hemibody
numbness and tingling. After an extended stay in an inpatient
rehabilitation unit, she was discharged with no visual field deficits and
full return of sensation on her left side. She required continuing
supplemental levothyroxine and hydrocortisone for pituitary insufficiency.
FIGURE 9-7 Imaging of the patient in Case 9-2.

Sagittal T1-weighted image with
contrast shows a cystic lesion with a
faint rim of enhancement (arrow).
Comment. This case demonstrates the clinical consequences of mass

effect of otherwise benign lesions such as a craniopharyngioma and
complications that can arise from surgical resection of craniopharyngiomas,
which can become adherent to surrounding parasellar structures.
Hypothalamic Hamartomas abnormalities. They can also cause

Hypothalamic, or tuber cinereum, gelastic seizures, which are epileptic
hamartomas are congenital lesions that events characterized by involuntary
arise from the floor of the third ventri- and uncontrolled bouts of spontane-
cle. They are benign in nature; symp- ous laughter, a clinical hallmark of this
toms associated with these lesions are tumor type. They are sometimes diffi-
invariably due to mass effect with ex- cult to distinguish from surrounding
pansion (Figure 9-10), often disrupting brain parenchyma given their isoin-
the hypothalamic-pituitary-adrenal ax- tense appearance on both T1- and
is and causing downstream endocrine T2-weighted sequences.

FIGURE 9-8 A 47-year-old woman presented with progressive vision loss in the left eye. Brain
MRI revealed a homogenously enhancing mass in the region of the tuberculum
sellae, as seen on a representative midline sagittal T1-weighted image with
contrast (A, arrow) and planum sphenoidale compressing the left optic nerve. She underwent
resection of the mass, found to be a meningioma after pathologic review. Postoperative
midsagittal T1-weighted image of the same region (B).
Schwannomas tor (III), trochlear (IV), abducens (VI),

Schwannomas are benign lesions that or the first two divisions of the trigem-
arise from Schwann cells. In the inal nerve (V1 and V2), all of which
parasellar region, they often involve traverse the cavernous sinus. The first
cranial nerves, specifically the oculomo- and second divisions of the trigeminal
FIGURE 9-9 Axial T1-weighted contrast MRI demonstrates a meningioma arising from the
medial portion of the greater sphenoid wing, seen axially (A) with extension to
parasellar region and middle cranial fossa (arrow) best visualized coronally (B).
This patient presented with olfactory hallucinations and partial complex seizures.
8
Reprinted with permission from Poh Sun G. B 2011 Dr. Goh Poh Sun. learningneuroradiology.blogspot.com/2011/
10/case-61-sphenoid-wing-meningioma.html.

KEY POINT
h Schwannomas, like germ cell tumors tend to grow more ra-
functional adenomas, pidly and cause more symptoms, although
demonstrate delayed they are somewhat sensitive to platinum-
contrast uptake. based chemotherapy. In comparison,
germinomas are slower growing and
more sensitive to radiation and chemo-
therapy. Both germinomas and non-
germinomatous germ cell tumors occur
along the midline and can occupy the
suprasellar cistern in the region of the
infundibulum. These tumors are typi-
cally hyperdense on CT and mildly
hyperintense on T2-weighted MRI
Hypothalamic sequences. They are isointense on
FIGURE 9-10
hamartomas (as seen T1-weighted imaging and homogenously
on this sagittal
T1-weighted MRI [arrow]) are typically
enhance with the administration of
well circumscribed and noninvasive; contrast (Figure 9-11).
associated symptoms arise from mass
effect or hypothalamic-pituitary-adrenal
axis dysfunction. Mesenchymal Tumors
Modified with permission from Dr Frank Gaillard,
Mesenchymal tumors involve cellular
Radiopaedia.org. rID: 16891.4 precursors of connective or lymphatic/
vascular tissues and include chondrosar-
comas, chordomas, and plasmacytomas.
nerve have the highest preponderance Chondrosarcoma. In contrast to
of schwannomas in this region. Imaging midline chordomas, chondrosarcomas
characteristics of schwannomas are sim-
ilar to those of meningiomas, making the
two lesions difficult to distinguish. Like
meningiomas, they often contain calci-
fications visible on CT. Given their benign
nature with slow growth over time, they
can also cause bony erosion and hyper-
ostosis. Schwannomas also enhance with
contrast, but uptake is often delayed in
comparison to meningiomas, best visu-
alized on a dynamic MRI scan.10
MALIGNANT TUMORS
Malignant tumors are characterized by an
often rapid pace of growth, invasiveness, FIGURE 9-11 A characteristic germinoma,
solid in appearance with
and the degree of bony erosion. They involvement of the
often have characteristic imaging features infundibular stalk and adjacent floor of the
that portend their malignant nature. third ventricle, is demonstrated in this sagittal
postcontrast T1-weighted MRI of the sellar
region (arrow). Germinomas are often
Primary Germ Cell Tumors hyperintense on T2-weighted imaging and
typically enhance with contrast.
Primary germ cell tumors include both
germinomas and nongerminomatous Radiopaedia.org, rID: 17966.4
germ cell tumors. Nongerminomatous

KEY POINT
are paramedian mass lesions that h Intralesional calcifications,
typically arise from the petrooccipital if present, are a
fissure. With expansion, they can ele- characteristic feature of
vate the pituitary gland. Unlike benign chondrosarcomas. The
cystic lesions with calcifications in the thumb sign is a common
periphery, over 50% of chondrosar- radiographic feature of
comas have calcifications that are best clival chordomas when
visualized on CT.11 T2-weighted MRI viewed in the
sequences often demonstrate a chon- sagittal plain.
droid matrix (Figure 9-12).
Chordoma. Chordomas are believed
to arise from remnants of the primitive
notochord and occur along the midline,
a feature that distinguishes them from
FIGURE 9-13 Clival chordoma with
paramedian chondrosarcomas. They are characteristic thumb
aggressive lesions that invade and design, whereby the mass
stroy the skull base.12 On T1-weighted itself looks like a thumb compressing the
brainstem posteriorly on sagittal
sequences, they are heterogeneously T1-weighted imaging.
hyperintense, and when visualized in Modified with permission from Dr Frank Gaillard,
the sagittal plane, they may take on the Radiopaedia.org, rID: 4308.4
shape of a thumb, referred to as the
thumb sign (Figure 9-13). Chordomas
often enhance intensely with contrast, within the clivus with sellar extension re-
reflecting their aggressive nature. sembling nonfunctional macroadenomas.
Plasmacytoma. Plasmacytomas are Over time, they sometimes extend into
uncommon tumors that can present the neighboring cavernous or sphenoid
sinuses. Symptoms arise primarily due
to mass effect but these may be inci-
dentally found (Case 9-3); plasma-
cytomas rarely cause hormonal shifts,
with modest elevations in serum pro-
lactin reported. These tumors can be
the presenting feature of multiple my-
eloma, and are histologically composed
of abnormal plasma cells with a high
proportion of 0 light chain immuno-
globulins. Although plasmacytomas fre-
quently precede the development of
multiple myeloma, a number of cases in
which patients with sellar plasmacytomas
have not gone on to develop multiple
myeloma have been reported.13 On
MRI, plasmacytomas enhance homo-
genously with contrast (Figure 9-14).
FIGURE 9-12 Chondrosarcoma of the Metastatic Tumors

apex of petrous part of
temporal bone with Metastatic tumors can arise in both
characteristic imaging findings, including sellar and parasellar locations. The most
central calcifications and demonstration of a common primary malignancies that
chondroid matrix architecture on coronal
T1-weighted contrast MRI (arrow). metastasize to these areas are breast
and lung adenocarcinoma, followed by

Case 9-3
A 44-year-old man presented with increasing
headaches and neck pain after sustaining
injury to the back of his head during a hockey
game. On examination, no evidence of
papilledema, visual field deficits, or abnormalities
of extraocular movements were seen. MRI with
contrast revealed a large and highly vascular
clival lesion, extending into the cavernous sinuses
bilaterally (Figure 9-14). He underwent
endoscopic resection of the mass, which was
found to be a plasmacytoma on subsequent
pathologic analysis. He received a course of
external beam radiation therapy thereafter,
with prolonged disease control.
Comment. This case shows the typical
imaging features of a sellar plasmacytoma,
an uncommon tumor that can present within
the clivus with sellar extension.
FIGURE 9-14 Imaging of the patient in

Case 9-3. Axial T2-weighted MRI
shows a large well-circumscribed
isointense lesion occupying both the sellar and
bilateral parasellar regions (arrow).
KEY POINT thyroid carcinoma. Sellar metastases signal peripherally toward the dural
h Optic gliomas are can cause diabetes insipidus due to sheath.15 Contrast enhancement is
exophytic lesions that variable. The definitive treatment is
diminished levels of vasopressin and
cause optic nerve
visual field deficits due to compression surgical resection, which usually re-
enlargement, often in
of the optic chiasm. sults in complete vision loss in the
the proximal segment
affected eye.
just anterior to the
Astrocytomas Hypothalamic gliomas. When
optic chiasm.
Astrocytomas in the sellar and parasellar combined with optic gliomas, hypotha-
regions involve the optic nerve and lamic gliomas comprise 15% of
hypothalamus and are usually infiltra- supratentorial tumors in children. Hy-
tive in nature as reflected in associated pothalamic gliomas often occur in
imaging studies. patients with NF1 or in those without
Optic nerve gliomas. While optic this diagnosis but with a family history
nerve gliomas can occur sporadically, they of NF1. Hypothalamic gliomas are rare
are more commonly a manifestation of and histologically consistent with ju-
neurofibromatosis type 1 (NF1). Optic venile pilocytic astrocytomas. They
gliomas are exophytic lesions that cause appear hypointense on T1-weighted
optic nerve enlargement, often in the images and hyperintense on T2-
proximal segment just anterior to the weighted images. They contain both
optic chiasm (Figure 9-1514). With cystic and solid components, with the
significant expansion, they can impinge latter enhancing following administra-
upon the pituitary stalk. On T2- tion of contrast (Figure 9-1616).
weighted sequences, optic gliomas are Pituicytomas. Pituicytomas are rare
hyperintense centrally, with a fading of glial tumors arising from specialized

KEY POINT
h Pituicytomas can cause
central diabetes
insipidus with sufficient
mass effect.
FIGURE 9-15 Optic glioma. Axial T1-weighted MRI with contrast, with characteristic optic
nerve enlargement and hyperintensity (A, white arrow) and chiasmal
involvement (A, black arrow). These areas appear isointense on a
corresponding T2-weighted axial image (B).
14
Reprinted from Grier J, Batchelor T, Oncologist. B John W. Henson, MD. Used with permission.
cells found in the neurohypophysis and Dermoid Cysts

contiguous infundibulum. They are Dermoid cysts arise from developmental
infiltrative and expansile in nature, anomalies in which a small portion of
appearing heterogeneously hyper- embryonic ectoderm is ensnared in
intense on T2-weighted images. They the closing neural tube, usually bet-
are isointense and poorly visualized ween the fifth and sixth weeks of ges-
on T1-weighted images; however, a tation. They are most common in male
bright spot is sometimes seen that cor- children. Dermoid cysts are midline
responds to the intact, but displaced,
neurohypophysis, which is a characteris-
tic radiographic finding (Figure 9-1717).18
Pituicytomas are often asymptomatic.
With sufficient compression of the neuro-
hypophysis and subsequent reduction
in antidiuretic hormone production, they
can cause diabetes insipidus. Table 9-2
summarizes radiographic features of pri-
mary malignant tumors in the sellar and
parasellar spaces across common imag-
ing modalities.
CYSTS Sagittal T1-weighted

FIGURE 9-16 contrast MRI shows a
Cystic lesions in the sellar region are hypointense ovoid
typically midline in location and well-circumscribed lesion (arrow)
developmental in origin. They are typ- consistent with a hypothalamic glioma.
ically slow growing, and symptoms arise Reprinted with permission from Kaltsas G, et al,
16
Endocr Relat Cancer. B 2008 Society for
due to associated mass effect and, less Endocrinology. erc.endocrinology-journals.org/
commonly, rupture and dissemination content/15/4/885.long.
of cystic contents.

lesions occupying the suprasellar cis-

tern that contain a mixture of stratified
squamous epithelial cells, hair follicles,
and sweat and sebaceous structures.
They are essentially intermediate lesions
with epidermal appendages characteris-
tic of teratomas and epithelial cells that
compose the entirety of an epidermoid
cyst. Symptoms arise due to mass effect
and resultant compression of the optic
chiasm (bitemporal hemianopia) or
cyst rupture causing a chemical men-
ingitis with associated headaches, nau-
FIGURE 9-17 Pituicytoma occupying the sea, and vomiting.
sella as seen on a contrast
T1-weighted MRI (arrow), As with craniopharyngiomas, calcifica-
with a characteristic bright spot in the tions can be found in the walls of der-
superior portion of the mass representing a
compressed and deviated neurohypophysis. moid cysts on CT. The cystic cavity is
Modified with permission from Dr Natalie Yang,
often hypodense on CT, given the high
Radiopaedia.org rID: 2650.17 fat content, and correspondingly hy-
perintense on T1-weighted sequences.19
TABLE 9-2 Imaging Characteristics of Malignant Sellar and Parasellar Lesions
T1 With
Tumor Region CT T1 T2 Contrast
Primary germ Suprasellar cistern Hyperdense Isointense Hyperintense Homogenous
cell tumors (infundibulum)
Mesenchymal
tumors
Chondrosarcomas Parasellar Intralesional Variable Hyperintense Heterogeneous
calcification (chondroid matrix) (septations)
Chordomas Parasellar Hyperdense, Foci of Heterogeneously Heterogeneous
(clival) lytic bony hyperintensity hyperintense (honeycomb
destruction (blood/mucus) (thumb sign) appearance)
Astrocytomas
Optic gliomas Parasellar Optic nerve Isointense/ Centrally Variable
enlargement hypointense hyperintense enhancement
compared to
contralateral
optic nerve
Hypothalamic Sellar Hypodense Hypointense Hyperintense Solid component
gliomas enhances
Pituicytomas Sellar Homogenous Isointense Heterogeneous Intense contrast
enhancement (pituitary (hypo/isointense) enhancement
bright spot)

KEY POINTS
Dermoid cysts rarely enhance with con- T2-weighted images. Epidermoid cysts h Dermoid cysts occur
trast, although leptomeningeal en- are positive on diffusion-weighted im- at the midline, while
hancement can occur following rupture aging (DWI), an important feature epidermoid cysts are
of the cyst and subsequent release of when formulating a differential diag- usually paramedian.
its contents. nosis.20 Figure 9-18 shows key radio- h Epidermoid cysts
graphic features of both dermoid and are bright on
Epidermoid Cysts
epidermoid cysts. diffusion-weighted
Epidermoid cysts are parasellar lesions
imaging, consistent with
commonly occurring off midline, but Rathke Cleft Cysts restricted diffusion.
they can also arise in the suprasellar cis- The Rathke pouch is a developmental
tern. They are slow growing and benign h Rathke cleft cysts have a
structure that forms during the characteristic
in nature, arising either during embryo- fourth week of embryogenesis. It is an intraluminal nodule.
genesis at the time of neural tube closure outgrowth of the primitive oral cavity.
or due to trauma, often in a postsurgical The Rathke cleft forms from the lumen
setting. Unlike congenital dermoid cysts, of this primitive outgrowth; a Rathke
epidermoid cysts are composed solely of cleft cyst is an anomaly that forms when
stratified squamous epithelial cells, with the cleft does not regress, with an inci-
fluid that contains cholesterol crystals dence as high as 1 in 5 people. The wall is
and keratin. This fluid is caustic, and composed of ciliated columnar epithe-
rupture of epidermoid cysts can cause lial cells, and an intraluminal nodule is
local inflammation and resultant dam- often visible on imaging. On CT, a Rathke
age to surrounding tissues. cleft cyst appears mildly hyperdense. The
The capsule of an epidermoid cyst cystic fluid is often high in protein, ap-
is often calcified, and its contents are pearing hyperintense on both T1- and
characteristically hypodense on CT. T2-weighted images (Figure 9-19), al-
They appear hypointense on T1- though protein content (and thus in-
weighted images and hyperintense on tensity) can vary.21
FIGURE 9-18 Dermoid cysts (A, arrow) often contain peripheral calcifications best visualized
on CT, while epidermoid cysts (B, arrow) often appear bright on
diffusion-weighted imaging.
4
Panel A modified with permission from Dr Frank Gaillard, Radiopaedia.org, rID: 17956. Panel B modified with
permission from Dr Frank Gaillard, Radiopaedia.org, rID: 15137.4

KEY POINTS
sella is filled with CSF (Figure 9-21).
h With an empty sella, the
The infundibulum traverses the sella
infundibulum traverses
and enhances with contrast; if visible
the sella and enhances
on MRI, this is known as the infundibu-
with contrast; if visible
lum sign.22
on MRI, this is known as
the infundibulum sign.
VASCULAR LESIONS
h Carotid-cavernous Vascular lesions include abnormalities
fistulas cause high-flow
that arise from the carotid artery cours-
shunting of blood and
ing through the cavernous sinus and
external carotid
artery enlargement.
aneurysmal lesions that arise from the
circle of Willis surrounding the pitui-
tary stalk.
Sagittal T2-weighted MRI Carotid-Cavernous Fistulas

FIGURE 9-19
showing a Rathke cleft Arteriovenous fistulas in the parasellar
cyst with characteristic
intracystic nodule (arrow). region involve high-flow shunting of
Modified with permission from Dr Frank
blood between the internal carotid ar-
Gaillard, Radiopaedia.org, rID: 16835.4 tery and adjacent cavernous sinus, caus-
ing retrograde venous flow. This results
in venous congestion and associated en-
Arachnoid Cysts largement of veins, including the supe-
Arachnoid cysts are slow-growing le- rior ophthalmic vein. Increased pressure
sions that can be found in both the in the orbital veins can cause proptosis,
sellar and parasellar regions. They can orbital edema, and congestion with re-
cause adaptive bony changes similar sultant enlargement of the extraocular
to benign meningiomas in addition to muscles in addition to cranial nerve
mass effect. CT scans often demon- palsies and elevated intracranial pres-
strate bony erosion if present. Arach- sure. CT angiography (CTA) often
noid cysts are isointense relative to CSF demonstrates subarachnoid vein en-
on T1- and T2-weighted images, and, largement and increased tortuosity
unlike epidermoid cysts, they are not
positive on DWI (Figure 9-20).
Empty Sella
Empty sella occurs when the pituitary
gland is compressed due to elevated
intracranial pressure or an arach-
noid diverticulum. In addition to flat-
tening of the gland, this can lead to
enlargement and remodeling of the
sella turcica. Idiopathic intracranial
hypertension is a primary cause; how-
ever, in many cases, the empty sella is
an incidental finding of unknown
cause. Preexisting tumors, radiotherapy Sagittal T2-weighted
to the sellar region, prior surgery, or FIGURE 9-20 MRI showing an
hemorrhage can also cause pituitary arachnoid cyst with a
fluid-filled cavity appearing isointense
compression and a resultant empty with adjacent CSF in the lateral
sella. The empty sella is best visualized ventricle (arrow).
on MRI. On T2-weighted images, the

bral angiography remains the gold
standard for evaluation of arterio-
venous malformations.
Cerebral Artery Aneurysms
Aneurysms arising within the circle of
Willis can impinge on the adjacent
optic chiasm, causing bitemporal he-
mianopia and other visual field defects.
As with other vascular lesions, aneu-
rysms are best visualized using cerebral
angiography. Alternatively, CTA and MR
angiography (MRA) are noninvasive
modalities used to visualize aneurysms
Empty sella with when monitoring them over time
FIGURE 9-21 flattening of the (Figure 9-22). CTA allows clearer
pituitary gland, best
visualized on a sagittal MRI given the visualization of vessels and aneurysms,
presence of CSF (arrow). while MRA is more prone to false-
positive results.
due to venous congestion and an Pituitary Apoplexy

enlarged external carotid artery. Retro- In certain situations, adenomas of the
grade venous drainage and associated pituitary gland may hemorrhage spon-
edema are seen on MRI in patients taneously, a condition known as pitui-
with carotid-cavernous fistulas.23 Cere- tary apoplexy. Apoplexy can also occur
FIGURE 9-22 Intracavernous internal carotid artery aneurysm. A, Axial T2-weighted MRI clearly
shows a large ovoid T2 hypointensity within the right cavernous sinus. Flow
void is seen within the cavity of the lesion and heterogeneous signal, consistent
with turbulent blood flow (arrow). B, Magnetic resonance angiography (MRA) delineates the
vasculature in this region and the site of origin of the aneurysm from its parent vessel (arrow).

KEY POINT
h Both Langerhans cell with long-standing use of bromocrip- occurs in pregnant women in the
histiocytosis and tine to treat an underlying prolactinoma. peripartum phase of their pregnancy
pituicytomas can cause In women of childbearing age, hemor- and h a s b e e n a s s o c i a t e d w i t h
diabetes insipidus. rhagic infarction of the gland can occur paraneoplastic syndromes in which the
in the postpartum period, also known as immune response targets pituitary anti-
Sheehan syndrome. Other causes of gens. The presentation on imaging is
apoplexy include sudden changes in in- subtle, notable primarily on MRI with
tracranial pressure, trauma, cerebral an- appearance of a thickened pituitary
giography, and prior radiation therapy. stalk (Figure 9-24).25 More recently,
On CT, the sellar contents appear autoimmune hypophysitis has been
hyperdense due to hemorrhage. They described as a complication of therapy
are correspondingly hyperintense on with certain immune checkpoint in-
T1-weighted sequences, and enhance- hibitors, such as ipilimumab. This is at
ment is often variable and more prom- least partially reversible following dis-
inent in the periphery (Figure 9-23). continuation of the drug.
On DWI, solid infarcted components
are often positive, consistent with re- Langerhans Cell Histiocytosis
stricted diffusion.24 Langerhans cell histiocytosis is a rare
disorder that involves the deposition
INFLAMMATORY LESIONS of granulomatous tissue anywhere along
Inflammatory lesions are usually gran- the hypothalamic-pituitary-adrenal axis.
ulomatous in terms of histology; asso- Diabetes insipidus is a clinical hallmark,
ciated symptoms arise from infiltration occurring in almost 25% of patients
of the pituitary stalk or adenohypophysis. with Langerhans cell histiocytosis, al-
though it is rarely the presenting
Lymphocytic Hypophysitis symptom because of widespread
Lymphocytic hypophysitis is a rela- extrapituitary involvement.26 In cases
tively rare condition. It most commonly of pituitary involvement, thickening of
the pituitary stalk can be seen on T1-
weighted images. In patients with
associated diabetes insipidus, the pos-
terior pituitary often does not enhance.
Neurosarcoidosis
Neurosarcoidosis is an inflammatory
condition characterized by the pres-
ence of noncaseating granulomas within
the central nervous system, potentially
involving the leptomeninges, pituitary
gland, and brain parenchyma. Associated
symptoms often wax and wane and
can include headache, cranial nerve
FIGURE 9-23 Sagittal T1-weighted palsies, visual loss, endocrinopathies
noncontrast MRI showing
pituitary apoplexy such as diabetes insipidus and hypothy-
(hyperintensity) with residual blood visible roidism, seizures, weakness, sensory
in the sella (arrow), extending into the
suprasellar cistern.
changes, back and extremity pain,
and incontinence.
Radiopaedia.org, rID: 17664.4 Although evidence of disease, in-
cluding areas of abnormal contrast

and sometimes accompanied by men-
ingeal enhancement.
CONCLUSION
The sella and parasellar spaces in-
volve the interplay of complex vascular,
nervous, and bony structures, and per-
turbations in the overall architecture can
have significant clinical consequences.
This article reviewed associated anatomy
and imaging characteristics of a variety
of benign and malignant pathologic
lesions in this region. The use of var-
FIGURE 9-24 Sagittal T1-weighted ious imaging modalities, specific radio-
contrast MRI showing
iatrogenic lymphocytic graphic features of these lesions, and
hypophysitis (arrow) due to ongoing the location of lesions all help in for-
ipilimumab use.
mulating a differential diagnosis.
Radiopaedia.org, rID: 8916.4
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Review Article
Imaging of Spinal
Dr Joshua P. Klein,
Department of Neurology,
Room AB-124, Brigham and
Cord Disorders Women’s Hospital, 75 Francis

St, Boston, MA 02116,
jpklein@partners.org.
Karanbir Singh, MD; Laszlo L. Mechtler, MD, FAAN; Relationship Disclosure:
Dr Singh reports no
Joshua P. Klein, MD, PhD, FANA, FAAN disclosure. Dr Mechtler has
received personal
compensation for serving as
board advisor for Supernus
ABSTRACT Pharmaceuticals, Inc; for
Purpose of Review: Spinal cord disorders are common and can be caused by a serving as guest editor of
Current Pain & Headache
myriad of pathologies. Confidently interpreting spine imaging studies is an essential Reports and Neurologic
skill for neurologists as many spinal cord disorders can produce significant disability Clinics; as a speaker for
if not diagnosed and treated correctly. Allergan, Pernix Therapeutics,
Recent Findings: Advances in imaging have revolutionized the care of patients Industries Ltd; and as a
with spinal cord disorders by allowing noninvasive visualization of normal and consultant for Green Grass
abnormal structures. Advisors. Dr Mechtler
provided expert consultation
Summary: This article summarizes the imaging patterns of common spinal cord disorders. for legal testimony for DOPF,
P.C. Dr Klein has received
Continuum (Minneap Minn) 2016;22(5):1595–1612. personal compensation as a
coauthor and editor and for
serving on the editorial board
of McGraw-Hill and as a
consultant for Advance
INTRODUCTION laminae. The laminae from either side Medical and Best Doctors, Inc.
fuse posteriorly to form the spinous Dr Klein has given expert
The spinal cord serves as a conduit for medical testimony for
information traveling between the processes. The transverse process and a Anaesthesia Associates of
superior articular process originate from Massachusetts and
brain and the peripheral nervous sys- HeplerBroom LLC.
tem. The spinal cord lies within the the junction of each pedicle and lamina. Unlabeled Use of
spinal canal, and the canal itself is An inferior articular process originates Products/Investigational
from the inferior laminar surface of Use Disclosure:
bounded by the vertebrae of the spinal Drs Singh, Mechtler, and Klein
column. Understanding the relation- each vertebra and forms the facet joint report no disclosures.
ship between the spinal cord and with the superior articular process of * 2016 American Academy
of Neurology.
surrounding spinal structures is cru- the vertebra below it. The posterior
cial for accurate interpretation of spi- longitudinal ligament lies anterior to
nal cord imaging studies. the spinal canal and extends longitudi-
nally along the vertebral bodies. The
REVIEW OF SPINE AND SPINAL ligamentum flavum lies posterior to
CORD ANATOMY the spinal canal and extends longitudi-
The spinal column is composed of seven nally between the laminae of adjacent
cervical, twelve thoracic, five lumbar, vertebrae (Figures 10-1A and 10-1B).
and five sacral vertebrae. Adjacent cer- The anterior longitudinal ligament lies
vical, thoracic, and lumbar vertebrae at the anterior aspect of the spine and
articulate at intervertebral disks and is unrelated to the spinal canal.
zygapophysial facet joints that permit Spinal nerve roots originate from the
some movement, whereas the sacral spinal cord and exit through neural
vertebrae are fused en bloc and are thus foramina. Each neural foramen is sur-
immobile. The spinal canal lies within rounded anteriorly by a vertebral body
the vertebrae and is enclosed anteriorly and intervertebral disk, superiorly and
by vertebral bodies and intervertebral inferiorly by a pedicle, and posteriorly
disks, anterolaterally by vertebral pedi- by a facet joint (Figure 10-1C). In the
cles, and posterolaterally by vertebral cervical spine, the spinal nerve roots

Spinal Cord Disorders
FIGURE 10-1 Spinal anatomic landmarks. A, Sagittal T2-weighted MRI showing vertebral body (a), intervertebral disk (b),
posterior longitudinal ligament (c), pachymeninges and ligamentum flavum (d), and CSF in subarachnoid
space (e). B, Axial T2-weighted MRI showing CSF in subarachnoid space (a), vertebral body (b), posterior
longitudinal ligament (c), pachymeninges (d), ligamentum flavum (e), spinous process (f), lamina (g), transverse process (h),
and pedicle (i). C, Parasagittal T2-weighted MRI showing pedicle (a), inferior articular process (b), zygapophyseal (facet) joint (c),
superior articular process of lower vertebral body (d), intervertebral disk (e), exiting nerve root in the neural
foramen (f), and vertebral body (g).
KEY POINTS exit above the corresponding verte- PRINCIPLES OF SPINAL

h In the cervical spine, bra, except for the C8 nerve root, which CORD IMAGING
the spinal nerve roots
does not have a corresponding verte- MRI is the imaging modality of choice in
exit above the
bral body and exits below the C7 and most diseases of the spinal cord. Radio-
corresponding vertebra.
Caudal to the C8 nerve above the T1 vertebrae. Caudal to the graphs fail to provide visualization of
root, the spinal nerve C8 nerve root, the spinal nerve roots the spinal cord and are only used to
roots exit below exit below their corresponding verte- examine the spinal column. CT and
their corresponding bral body. CT myelography allow for visualiza-
vertebral body. The vertebral body level differs from tion of the spinal cord but do not
h The vertebral body level the spinal cord dermatomal level. provide adequate resolution of inter-
differs from the spinal During embryonic development, the nal structures. CT provides excellent
cord dermatomal level. vertebral column grows more rapidly visualization of bony structures and is
During embryonic than the spinal cord. As a result, at particularly useful in cases of trauma
development, the birth the newborn spinal cord termi- or in spinal diseases that affect bone.
vertebral column grows nates near the L3 vertebral body, and High-resolution positron emission
more rapidly than the by 2 months of age, the spinal cord tomography (PET) has some role in
spinal cord.
reaches the adult position near the L1 evaluating spinal cord lesions ana-
h MRI is the imaging vertebral body. The most caudal part of tomically and metabolically. Conven-
modality of choice in the spinal cord is the conus medullaris. tional angiography can be used to
most diseases of the
The nerve roots arising from the conus assess vascular malformations as well
spinal cord.
medullaris descend in the spinal canal as as highly vascular spine and spinal
the cauda equina and exit at their cord tumors.
corresponding vertebral level. The filum The introduction of MRI has been
terminale extends from the conus one of the most important advances
medullaris caudally as a continuation in diagnosis and management of spi-
of the pia mater, ultimately inserting nal cord disorders. The advantages of
into the coccyx. MRI are its multiplanar capabilities,

KEY POINTS
superior resolution compared to CT, trast should be administered when the h The short tau inversion
and the variety of protocols available. differential diagnosis includes infec- recovery protocol
The mainstay of spinal cord MRI is tion, neoplasm, inflammation, or de- suppresses fat signal
the T2-weighted sequence. Images myelination.1 Whole spine imaging and improves the
are obtained in sagittal and axial may be necessary in some cases where visualization of edema,
planes. The short tau inversion recov- concern exists for diffuse or multiple hemorrhage, and other
ery (STIR) protocol suppresses fat sig- spinal abnormalities, as in metastatic pathologies on
nal and improves the visualization of disease, infection, and trauma. T2-weighted images.
edema, hemorrhage, and other pa- h IV contrast should be
thologies on T2-weighted images. CONGENITAL AND administered when the
T1-weighted images help to further DEVELOPMENTAL SPINAL differential diagnosis
characterize pathology and are partic- CORD DISORDERS includes infection,
ularly useful when compared to T1 neoplasm, inflammation,
Syringomyelia refers to a fluid-filled
postcontrast images. Gradient recalled or demyelination.
cyst in the spinal cord parenchyma or
echo (GRE) or susceptibility-weighted cystic expansion of the central canal with h Syringomyelia refers to
images (SWI) are sensitive to detecting disruption of ependyma, whereas hydro- a fluid-filled cyst in the
hemorrhage, calcification, and vascular spinal cord or cystic
myelia refers to cystic expansion of the
flow voids. Diffusion-weighted imag- expansion of the
central canal with ependymal lining pre-
central canal with
ing (DWI) sequences can be used to served. These lesions have imaging char- disruption of ependyma,
look for cytotoxic edema in ischemic acteristics of CSF (ie, T1 hypointensity whereas hydromyelia
lesions and high cellularity in tumors and T2 hyperintensity), distinguishing refers to cystic
and abscesses. Newer imaging tech- them from other lesions. In cases of expansion of the central
niques such as diffusion tensor imaging cystic expansion of the central canal, canal with ependymal
(DTI) and perfusion imaging hold great the differentiation between syringo- lining preserved.
promise for further evaluation of spinal myelia and hydromyelia is difficult, as
cord lesions. the integrity of ependymal lining is not
In most cases, localizing a potential well evaluated radiologically. Cervical
spinal cord lesion clinically and obtain- syringomyelia and hydromyelia are
ing focused imaging of that region of frequently associated with Arnold-
the spine is the best approach. IV con- Chiari malformations (Figure 10-2).
FIGURE 10-2 Chiari type I malformation with cervical syrinx. A, Sagittal T2-weighted MRI showing a Chiari type I
malformation with a 10 mm cerebellar tonsillar ectopia (arrow) and a cervical syrinx starting at the
level of the C4YC5 intervertebral disk and extending inferiorly into the upper thoracic cord. B,
Axial T2-weighted MRI showing the syrinx (arrow). C, Sagittal T1-weighted MRI showing the syrinx (arrow)
following CSF signal characteristics.

KEY POINT
h In multiple sclerosis, Other congenital spinal cord disor- Multiple Sclerosis
the plaques are most ders include spina bifida, diastema- Myelitis is common in multiple sclerosis
often small, ovoid, tomyelia, and tethered cord. Spina (MS) and is the presenting event in 20%
well-demarcated T2 bifida is caused by incomplete closure to 40% of patients with MS,2,3 and over
hyperintense lesions and of the developing neural tube that may 85% of patients with MS experience
are typically in the allow portions of the spinal cord or clinical deficits related to myelitis dur-
periphery of the nerve roots to exit the spinal canal, ing the course of their disease.4 De-
cord, extending
forming a myelomeningocele. Diaste- myelinating plaques occur more
longitudinally for
fewer than three
matomyelia refers to an abnormal lon- frequently in the cervical cord than in
vertebral segments. gitudinal bifurcation of the spinal cord the thoracic cord. MS plaques are most
due to a bony or cartilaginous septum often small, ovoid, well-demarcated T2
in the spinal canal. A tethered cord hyperintense lesions and are typically
results from an abnormally taut filum in the periphery of the cord, extending
terminale or from other lesions, such as longitudinally for fewer than three
a lipoma, that exert tension on the vertebral segments (Figure 10-3). The
inferior aspect of the spinal cord.1 lesions preferentially affect myelinated
structures, such as the posterior col-
INFLAMMATORY DEMYELINATING umns and corticospinal tracts, but may
DISEASES OF THE SPINAL CORD not respect white and gray matter
Inflammatory myelopathies are the spi- boundaries.5 Acute plaques may enhance
nal cord lesions most frequently encoun- with contrast and can be associated
tered by neurologists. Knowing the with mild cord swelling. Enhancement
imaging characteristics of different may last for 2 to 8 weeks. In the chronic
inflammatory conditions affecting the stage of MS, spinal cord atrophy can
spinal cord can help differentiate be- develop, which reflects both axonal and
tween these disorders. neuronal loss. T1 hypointense and
FIGURE 10-3 Multiple sclerosis. A, Sagittal short tau inversion recovery (STIR) MRI showing a
well-demarcated hyperintense lesion in the anterior spinal cord at the level of
the C3YC4 (red arrow) vertebral body and another discrete hyperintense
lesion in the posterior spinal cord at the level of the C5 vertebral body (yellow arrow). These
lesions extend for one to two vertebral segments longitudinally. B, Axial T2-weighted MRI
showing an eccentric hyperintense lesion in the left posterolateral cord (green arrow).

KEY POINTS
cavitating cord lesions are rare in MS.6,7 Rarely, T2 hyperintensity may be seen h In neuromyelitis optica,
Sagittal STIR images and axial GRE in the anterior spinal cord as well.11 spinal cord lesions are
images are more sensitive for plaque usually centrally located
detection than conventional spin echo MYELOPATHY FROM and involve more than
T2-weighted images. Image analysis INFECTIOUS DISEASES one-half of the
techniques have been developed and, A delay in diagnosing spinal infections cross-sectional area of
with high-resolution MRI, can be used may have devastating consequences as the cord. Unlike multiple
they can progress to cause myelopathy. sclerosis lesions,
to measure spinal cord cross-sectional
MRI is the imaging modality of choice neuromyelitis optica
area. Spinal cord cross-sectional area is
for spinal infection. CT can be helpful lesions typically extend
reduced in patients with MS compared for more than three
to healthy controls and correlates with for detecting and delineating bony des-
vertebral segments
clinical disability.8 truction and reactive sclerosis, although
in length.
infections can be missed before bone
destruction occurs. Spinal infections h Etiologies of
Neuromyelitis Optica longitudinally extensive
demonstrate the signal characteristics
In neuromyelitis optica (NMO), spinal transverse myelitis
of vasogenic edema on MRI, specifically
cord lesions are usually centrally located include venous
hyperintensity on T2-weighted and hypertensive myelopathy
and involve more than one-half of the hypointensity on T1-weighted images. as well as a variety of
cross-sectional area of the cord. Unlike These signal abnormalities are seen in autoimmune, infectious,
MS lesions, NMO lesions typically ex- the intervertebral disks along with adja- neoplastic, and
tend for more than three vertebral cent vertebra. There is usually evidence metabolic conditions.
segments in length.9 Acutely, the cord of destruction of the cortical rim of
is edematous, and lesions often enhance h Diffuse enhancement is
adjacent vertebrae that is best appreci- seen in infectious
with contrast. Lesions may appear T1 ated on CT but can also be seen on T1- processes that have not
hypointense, which is a less common
weighted sagittal images. In most cases, evolved into an abscess,
feature of spinal lesions in MS.6,7 Other
involvement of adjacent paravertebral whereas rim
etiologies of longitudinally extensive enhancement and a
structures is seen (Figure 10-5). Dif-
transverse myelitis include venous hy- nonenhancing core are
fuse enhancement is seen in infec-
pertensive myelopathy as well as a more suggestive
tious processes that have not evolved
variety of autoimmune, infectious, neo- of an abscess.
into an abscess, whereas rim enhance-
plastic, and metabolic conditions.
ment and a nonenhancing core are
more suggestive of an abscess. MRI is
Nutritional Deficiencies useful for monitoring evolution during
Vitamin B12 (cobalamin) deficiency is treatment of spinal infections. Reduc-
the most common cause of myelopa- tion of bone marrow edema and con-
thy from a nutritional deficiency. Cop- trast enhancement is a sign of healing.12
per and folate deficiencies can mimic Untreated infective spondylodiscitis
clinical and radiographic features of can evolve into an epidural abscess and
vitamin B12 deficiency. MRI is the imag- produce myelopathy, either by com-
ing modality of choice to evaluate for pression of the cord or by causing
spinal cord involvement in these dis- ischemia to the cord. Epidural abscesses
orders. The lesions appear as abnormal associated with spondylitis tend to be
hyperintensity in the posterior col- located in the anterior aspect of the
umns on T2-weighted images. On axial spinal canal, and epidural abscesses not
T2-weighted images, the lesions may associated with spondylitis tend to be
resemble an inverted V or inverted located in the posterior aspect of the
rabbit ears (Case 10-1).10 These lesions spinal canal.13 These lesions are best
do not enhance and can resolve if the visualized with contrast-enhanced MRI,
nutritional deficiency is treated early. which has a specificity and sensitivity

Case 10-1
A 57-year-old man with a remote history of a partial gastrectomy presented with progressive
numbness in his feet and hands, which he had experienced for the past 6 months and had caused
progressive difficulty with ambulation. In addition, he reported numbness in the perineal area. On
examination, the patient had decreased sensation to light touch, vibration, and proprioception, as
well as abnormally brisk deep tendon reflexes in all extremities. No extensor plantar responses were
observed. Motor examination was normal. He had a high-stepping gait with a positive Romberg sign.
Serum vitamin B12 level and MRI of the brain and lumbar spine were normal. Hemoglobin was low at
11.6 g/dL (normal 14 g/dL to 18 g/dL). MRI of the cervical spine with contrast showed nonexpansile
nonenhancing T2 hyperintensity in the posterior columns extending longitudinally from the C2 to C6
vertebral levels (Figure 10-4). A serum copper level was 26 mcg/dL (normal 70 mcg/dL to 175 mcg/dL).
The patient was treated with IV copper followed by oral copper replacement therapy. His neurologic
symptoms mildly improved over a period of months.
FIGURE 10-4 Imaging of the patient in Case 10-1 with copper deficiency myelopathy. A, Sagittal
short tau inversion recovery (STIR) MRI showing a hyperintensity extending from
the C2 to C6 vertebral body level with relative sparing of the anterior cord (arrow).
B, Axial T2-weighted MRI demonstrating an inverted V-shaped hyperintensity in the posterior
cord (arrow).
Comment. This is a case of copper deficiency myeloneuropathy. The most common neurologic
manifestation is myeloneuropathy with sensory ataxia. Associated anemia usually occurs, which can
be microcytic, normocytic, or macrocytic. Common examination findings include impaired light touch,
vibration, and proprioceptive sensation; hyperreflexia; and a Romberg sign. Superimposed
neuropathy can lead to decreased reflexes and loss of pain and temperature sensation. Copper
deficiency should be suspected in patients with a history of gastric bypass, zinc ingestion, or
malabsorption from enteropathies who present with subacute progressive myelopathy, neuropathy,
or myeloneuropathy. The diagnosis is made by documentation of low copper or ceruloplasmin
concentration in the serum. Spinal cord imaging is indicated in patients who develop myelopathy,
and the involvement of posterior columns (inverted V sign on axial images) (Figure 10-4) is supportive
of the diagnosis. Copper supplementation usually halts neurologic deterioration. Early diagnosis
and treatment is imperative as improvement in symptoms is variable.

FIGURE 10-5 Infective spondylodiscitis. A, Short tau inversion recovery (STIR) MRI showing extensive hyperintensity
involving the L3 and L4 vertebral bodies and the intervertebral disk. B, Axial T2-weighted MRI showing
spread of hyperintensity to the paravertebral areas (arrow). C, Sagittal T1-weighted MRI showing the lesion
to be hypointense with destruction of cortical rim of the L3 and L4 vertebrae (straight arrows showing cortical rim
destruction and curved arrow showing a normal cortical rim). D, Sagittal T1-weighted postcontrast MRI showing the lesion
to be avidly enhancing. E, Axial T1-weighted precontrast and F, axial T1-weighted postcontrast MRIs demonstrating
enhancement of the paravertebral structures (F, arrow), signifying paravertebral spread of infection.
of more than 90%.14 Spinal epidural bacteria, intramedullary infections are KEY POINT
abscesses are mostly hyperintense on usually caused by viruses.19 Viral myelitis h Viral myelitis can be
T2-weighted sequences. On T1-weighted can be caused by direct viral infiltration caused by direct viral
infiltration of the
sequences, spinal epidural abscesses of the cord or by postviral immunologic
cord or by postviral
can be hypointense, isointense, or sequelae. Herpes virus, poliovirus,
immunologic sequelae.
slightly hyperintense relative to the cytomegalovirus, and human immu- Herpes virus, poliovirus,
spinal cord, with marked peripheral or nodeficiency virus (HIV) are the typi- cytomegalovirus,
diffuse enhancement.13,15 Reduced cal pathogens. On MRI, viral myelitis and human
diffusivity on DWI may be helpful to appears as a T2 hyperintense lesion in a immunodeficiency virus
confirm the presence of an abscess.16 nonvascular distribution with or with- are the typical pathogens.
Imaging of the entire spinal axis is out cord expansion or enhancement.13
recommended to assess for multiple Pyogenic spinal cord infections are rare,
sites of infection.17,18 but tuberculosis can involve the cord,
In contrast to extramedullary infec- mostly as spinal leptomeningitis and
tions that are most often caused by rarely as intraspinal tuberculomas.20

KEY POINTS
h The borderzone Similar to tuberculosis, syphilis can nous embolization results from frag-
between the larger injure the neuraxis in a variety of ways. ments of nucleus pulposus that enter
segmental anterior Chronic untreated syphilis can lead to the spinal arterial circulation and is
radicular arteries in the tabes dorsalis, with dorsal column de- estimated to cause up to 5% cases of
midthoracic region is myelination and spinal cord atrophy. spinal cord infarctions.23
vulnerable to Syphilitic meningomyelitis can pro- Spinal cord infarctions represent 1%
hypoperfusion, and the duce spinal cord expansion and abnor- of all strokes and 5% to 8% of acute
area supplied by the mal T2 hyperintensity.21 myelopathies.24 MRI is the diagnostic
radicular arteries modality of choice to evaluate for spinal
arising from the artery VASCULAR LESIONS AFFECTING cord infarctions. DWI is sensitive for
of Adamkiewicz (lower THE SPINAL CORD detection of acute infarctions and may
thoracic) is vulnerable
Vascular lesions in the spinal cord are demonstrate changes before other se-
to embolic or
thrombotic strokes.
uncommon but important to recog- quences, as in the brain.25 Subacute
nize. Ischemic lesions of the cord are infarctions appear hyperintense on
h Hyperintensity within neurologic emergencies, and other T2-weighted images and hypointense
adjacent vertebrae may
vascular lesions can be disabling if on T1-weighted images. Abnormal con-
indicate concurrent
bone infarction,
they remain undiagnosed. trast enhancement in the affected cord
whereas adjacent may appear during this time. The
prolapsed disk space
Ischemic Lesions involvement of the anterior cord with
may signify Ischemic injuries to the spinal cord sparing of the posterior columns is
fibrocartilaginous are relatively uncommon as the cord suggestive of spinal cord infarct as these
embolism as a is perfused by a highly collateralized mostly occur in the anterior spinal
cause of infarct. arterial supply. An anterior and pos- artery territory. Typically, the lesions
terior system provides blood supply are bilateral and fairly symmetric and
to the spinal cord as follows. A single appear as a pencil-like hyperintense sig-
anterior spinal artery runs the length nal on sagittal T2-weighted images. The
of the cord in the anterior median owl’s eye appearance may be seen on
fissure, and paired posterior spinal axial T2 images due to involvement of
arteries run in the posterolateral sulci. the anterior gray matter (Figure 10-6).
The anterior spinal artery supplies the Hyperintensity within adjacent verte-
anterior two-thirds of the spinal cord, brae may indicate concurrent bone in-
while the posterior spinal arteries farction, whereas an adjacent prolapsed
supply the posterior one-third. Seg- disk space may signify fibrocartilagi-
mental radicular arteries feed these nous embolism as a cause of infarct.26
spinal arteries. While the posterior When aortic dissection is a suspected
spinal artery receives flow from 10 to cause of spinal cord infarction, thoraco-
16 posterior radicular branches, the abdominal CT angiogram (CTA) or
anterior spinal artery has fewer, but magnetic resonance angiogram (MRA)
larger, anterior radicular arteries feed- should be obtained.
ing into it. This makes the anterior cord
more susceptible to embolic events. Arteriovenous Malformation
The borderzone between the larger Spinal arteriovenous malformations
segmental anterior radicular arteries in (AVMs) include dural arteriovenous fis-
the midthoracic region is vulnerable to tulas and intramedullary AVMs. Dural
hypoperfusion, and the area supplied arteriovenous fistulas constitute more
by the radicular arteries arising from than 70% of spinal AVMs and most com-
the artery of Adamkiewicz (lower monly occur in the lower thoracic
thoracic) is vulnerable to embolic or region. 27 Shunting of arterial blood flow
thrombotic strokes.22 Fibrocartilagi- in these malformations may cause

FIGURE 10-6 Spinal cord infarct. A, Axial T2-weighted MRI showing hyperintensities involving the anterior cord
bilaterally with sparing of the posterior columns (owl’s eye appearance). B, Sagittal short tau
inversion recovery (STIR) MRI showing a linear hyperintensity involving the anterior cord at the
C6YC7 intervertebral disk level (arrow).
progressive myelopathy resulting from on T2-weighted images, is suggestive

venous congestion and venous hyper- of a spinal dural arteriovenous fistula
tension.28 MRI is the imaging modality (Figure 10-7).29 Spinal cord edema, ap-
of choice to evaluate these lesions. pearing as hyperintensity on T2-weighted
Dilated surface venules, appearing as images, is a possible associated finding
enlarged tortuous vascular flow voids and can be longitudinally extensive. If
FIGURE 10-7 Spinal dural arteriovenous fistula. A, Sagittal T2-weighted MRI showing flow voids (arrows) in
the subarachnoid CSF space. B, Sagittal T1-weighted precontrast and C, sagittal T1-weighted
postcontrast MRIs demonstrating longitudinally extensive enhancement of dilated vascular
channels at the posterior aspect of the spinal canal (C, arrow).

KEY POINTS
h Catheter angiography is left untreated, the spinal cord may Likewise, cavernous malformations are
required in cases of eventually become necrotic and atrophic. sometimes associated with other vascu-
suspected vascular Intramedullary AVMs are less com- lar lesions, in particular developmental
malformations to mon than dural arteriovenous fistulas. venous anomalies. Cavernous malforma-
further characterize MRI shows intramedullary flow voids tions are angiographically occult (not
the lesion and and dilated draining veins, which are seen on conventional angiography, CTA,
plan treatment. associated with aneurysms and have or MRA), in contrast to AVMs.
Contrast-enhanced an increased risk of hemorrhage.
CT angiogram or Three-dimensional heavily T2- SPINAL CORD TUMORS
magnetic resonance weighted sequences, such as balanced Most spinal cord tumors are primary;
angiogram can be
steady-state free precession, can aid in intramedullary metastases are rare
helpful to focus the
the detection of spinal AVMs as they (1% to 2%).35,36 Approximately 90% of
search for a spinal
arteriovenous
are less susceptible to pulsation arti- primary spinal cord tumors are glial in
malformation using facts that may simulate flow voids on origin. Ependymomas represent about
catheter angiography. standard T2-weighted images. 30,31 60% of spinal cord tumors, and astro-
Catheter angiography is required in cytomas represent 30%.37 Hemangio-
h Hemosiderin-sensitive
sequences, such as
cases of suspected spinal AVMs to blastomas account for 2% to 8% of
gradient recalled echo and further characterize the lesion and plan spinal cord tumors.38 The thoracic
susceptibility-weighted treatment. Early venous filling, due to cord is the most common location of
imaging, are particularly bypass of the capillary bed, is the key spinal cord tumors (50% to 55%),
sensitive for the diagnosis angiographic feature of an AVM. followed by the lumbosacral cord
of small cavernous Contrast-enhanced CTA or MRA can be (25% to 30%) and the cervical cord
malformations. helpful to focus the search for a spinal (15% to 25%).38 Spinal cord tumors
h Ependymomas AVM using catheter angiography.31,32 most often produce cord expansion
represent about 60% of and do not reliably respect gray and
spinal cord tumors, and Cavernous Malformations white matter boundaries.39
astrocytomas represent Cavernous malformations (often also re- Ependymomas are the most com-
30%. Hemangioblastomas ferred to as cavernous angiomas) are mon intramedullary spinal neoplasm in
account for 2% to 8% of much less frequent in the spinal cord adults (Table 10-1). Ependymomas
spinal cord tumors. than in the brain. On T2-weighted MRI, typically are solitary tumors and arise
cavernous malformations have a het- from the ependymal lining of the cen-
erogeneous hyperintense center, sur- tral canal of the spinal cord, causing
rounded by a rim of hypointensity, diffuse enlargement of the cord over
which gives them the characteristic pop- several levels and an associated syrinx
corn appearance. These lesions exhibit in 50% of cases.40 Myxopapillary ependy-
heterogeneous signal on T1-weighted momas of the filum terminale are a
images as well. The heterogeneity on histologic variant accounting for about
T1- and T2-weighted sequences results 13% of all ependymomas and about
from intracavernous vascular channels 80% of ependymomas located in the
containing hemoglobin in various conus medullaris and filum terminale.41
stages of degradation. Hemosiderin- Spinal ependymomas are also associ-
sensitive sequences, such as GRE and ated with neurofibromatosis type 2.42
SWI, are particularly sensitive for the Cellular ependymomas are centrally
diagnosis of small cavernous malform- located and tend to be hyperintense
ations.33 About 47% of patients with on T2-weighted images. Hemosiderin
spinal cord cavernous malformations is commonly seen as an area of T2 hy-
have additional angiomas elsewhere in pointensity, showing a cap sign in 20%
the neuraxis; thus, consideration of fur- to 64% of cord ependymomas. On
ther imaging of the brain is warranted.34 T1-weighted images, the tumors are

KEY POINT
TABLE 10-1 Characteristics of Spinal Ependymomas and Astrocytomas h Contrast enhancement

of spinal astrocytomas
Characteristics Ependymoma Astrocytoma does not predict
tumor grade.
Percent of spinal 60% 30%
cord tumors
More common in Adults Children
Predilection for Yes No
cauda equina
Location within Central Eccentric
spinal cord
Demarcation Well circumscribed Poorly demarcated
Enhancement Homogenous Variable (none or patchy)
Hemorrhage Common Uncommon
Clinical presentation Central cord syndrome or Asymmetric Brown-SéquardY
cauda equina syndrome like syndrome
isointense to slightly hypointense About 85% to 90% of astrocytomas

compared to normal spinal cord. About are low grade, whereas 10% to 15% are
80% of cellular ependymomas exhibit high grade (mostly anaplastic). Glio-
homogenous contrast enhancement, blastoma multiforme constitutes 0.2%
and minimal or no enhancement is to 1.5% of all spinal cord astrocyto-
rare (Figure 10-8).40 mas.44 In general, astrocytomas have
Myxopapillary ependymomas ap- poorly demarcated margins, although
pear as isointense to hypointense low-grade astrocytomas may be well de-
masses on T1- and T2-weighted images. fined. Spinal astrocytomas are T1
They tend to be extramedullary and hypointense to isointense and T2
can span several vertebral segments. hyperintense. They are usually eccentric
At times mucin accumulation may cause as they arise from the cord parenchyma
myxopapillary ependymomas to be and not the central canal (Figure 10-10).
hyperintense on T1- and T2-weighted Mild to moderate patchy enhancement
images. Prominent enhancement is is common. Lack of enhancement has
seen (Figure 10-9) on T1-weighted post- been reported in up to 30% of intra-
contrast images.40 CSF dissemination medullary astrocytomas.45 Contrast en-
may occur with higher-grade tumors. hancement does not predict tumor
Most ependymomas are nondisruptive; grade.46 The astrocytomas can disrupt
therefore, tractography may show the white matter tracts, which can be
tumors displacing fiber tracts rather seen on tractography. CSF dissemination
than interrupting them.43 of astrocytomas may occur, hence im-
Astrocytomas are the most com- aging of the entire neuraxis is indicated.
mon intramedullary spinal neoplasm in Hemangioblastomas account for
children (Table 10-1) and arise in the 2% to 8% of spinal cord tumors and
cervical spinal cord in approximately are rare in children.38 They are associ-
60% of patients. Tumors spanning the ated with von Hippel-Lindau syndrome
spinal cord, referred to as holocord in 25% of cases.47 On MRI, these tu-
tumors, can occur with pilocytic astro- mors appear T2 hyperintense and T1
cytomas but are extremely rare.40 hypointense. Hemorrhage into the

FIGURE 10-8 Cellular ependymoma. A, Sagittal short tau inversion recovery (STIR) image
showing a discrete expansile hyperintense mass at the level of the C3YC4
vertebral body (arrow). B, Axial T2-weighted view shows the lesion to be
hyperintense and centrally located. C, Sagittal T1-weighted precontrast image showing isointense
signal in the area of lesion. D, Sagittal T1-weighted postcontrast image showing homogenous
enhancement of the lesion (arrow).
tumor may distort the lesion’s signal angiography may demonstrate enlarged
characteristics leading to mixed inten- feeding arteries and draining veins. The
sities on T1- and T2-weighted sequences. tumor alternates between a growth
Homogenous contrast enhancement is phase and a quiescent phase with no
seen in most cases. The presence of growth. Hence, imaging surveillance
dilated vessels may cause these tumors is recommended.40
to be mistaken for vascular malforma- Other less common primary spinal
tions. Hemangioblastomas are com- cord tumors include gangliogliomas,
monly associated with a syrinx (30% oligodendrogliomas, paragangliomas,
to 60%), which, when present, helps melanocytomas, lipomas, primary central
differentiate them from a vascular mal- nervous system lymphomas, and primi-
formation. A spinal cyst with an enhanc- tive neuroectodermal tumors.
ing mural nodule is also a frequent Metastases to the spinal cord paren-
feature of a hemangioblastoma. Spinal chyma are rare and carry a very poor

FIGURE 10-9 Myxopapillary ependymoma. A, Sagittal T2-weighted MRI showing a slightly
hyperintense discrete mass lesion at the terminus of the conus medullaris (arrow). B,
Sagittal T1-weighted precontrast MRI showing the lesion to be slightly hyperintense
as well. C, Sagittal T1-weighted postcontrast MRI showing avid enhancement of the lesion. D, Axial
T1-weighted precontrast MRI showing a slightly hyperintense mass lesion. E, Axial T1-weighted
postcontrast MRI showing avid enhancement.
prognosis. Metastatic lesions can occur effect on the spinal cord. These include
anywhere in the spinal cord, nerve roots, extramedullary/intradural tumors (with
or meninges. On MRI, metastatic lesions schwannomas, neurofibromas, and
are typically T1 isointense and T2 meningiomas being typical) and
hyperintense, with extensive vasogenic extradural spine tumors (mostly verte-
edema surrounding the mass. Homog- bral body tumors). Tumors of the sur-
enous enhancement or rim enhance- rounding paraspinal structures may
ment most often occurs. In contrast to occasionally invade the spinal canal
primary intramedullary neoplasms, me- and cause myelopathy.
tastases are rarely associated with Metastatic disease to the vertebral
peritumoral cysts.48 bodies and epidural space is a com-
mon cause of spinal cord compression
MYELOPATHY FROM and myelopathy. The spine is the
EXTRAMEDULLARY SPINE most common site for bone metasta-
TUMORS ses, which are present in 60% to 70%
Tumors of the spine outside the spinal of patients with systemic cancer.
cord can cause myelopathy by mass Metastatic lesions can be osteolytic,

KEY POINT
h Changes in the spinal
cord in degenerative
disease occur from
compression by disk
herniation or osteophytes.
Early diagnosis and
appropriate treatment
are important to prevent
irreversible damage to
the spinal cord.
FIGURE 10-10 Spinal astrocytoma. A, Sagittal short tau inversion recovery (STIR) MRI
showing a discrete hyperintense expansile mass at the level of the C3YC4
vertebral body. B, Axial T2-weighted image showing a hyperintense lesion
infiltrating into the left side of the spinal cord. This lesion was T1 isointense and did
not enhance with contrast (images not shown).
osteoblastic, or mixed. MRI is the symptoms caused by degenerative disk

imaging modality of choice to evalu- disease and facet arthropathy. 49
ate these lesions. CT enables detection Changes in the spinal cord in degener-
of cortical destruction, but metastatic ative disease occur from compression
lesions without bone destruction may by disk herniation or osteophytes.
be missed on CT. MRI helps define Early diagnosis and appropriate treat-
bone involvement, epidural tumor, and ment are important to prevent irre-
cord compression/injury. It is important versible damage to the spinal cord.50
to differentiate metastatic spine disease MRI is the imaging modality of choice
from spinal infection. The involvement to evaluate degenerative disk disease
of intervertebral disks is common in as well as spinal cord involvement,
spinal infections and less common in which appears as increased signal on
vertebral metastases, since the avascu- T2-weighted images at the level of
lar disk is resistant to tumor invasion. As compression (Figure 10-11). Recently,
a result, the involvement of sequential a specific pattern of spinal cord
vertebrae is more common in spinal enhancement was described that
infections and uncommon in metasta- reliably differentiates myelopathy
ses. Skip lesions are more common due to external cord compression
with metastases. The common pattern from myelitis due to tumor or inflam-
of gadolinium enhancement in meta- mation in the cord. Transverse pan-
static lesions is heterogenous, with cakelike gadolinium enhancement
rim enhancement being common in just caudal to the site of maximal
spinal infections. stenosis and at the rostrocaudal mid-
point of T2 hyperintensity suggested
SPONDYLOTIC MYELOPATHY spondylosis as the cause of myelopa-
One of the most common indications thy (Figure 10-11).51
for spine imaging is to evaluate neck Aside from identifying the cause,
and back pain as well as radicular MRI also serves as a guide for surgical

intervention and prognosis. In pa- MYELOPATHY FROM
tients undergoing surgery for cervical SPINE TRAUMA
spondylotic myelopathy, MRI indica- In an acute setting, CT is the primary
tors of poorer outcome include the imaging modality used to assess trau-
presence of low T1 signal, focal in- matic spine injury. CT can be performed
creased T2 signal, and segmentation rapidly with high spatial resolution and
of T2 signal changes.52 In many cases, is much less sensitive to patient motion
no changes are seen in the spinal cord than MRI. CT is more sensitive than
despite clinical signs of myelopathy. DTI MRI for detection of cortical bone
may be used in such cases, as decreases disruption due to fractures and can
in fractional anisotropy have been found show subtle misalignment resulting
at compression sites in spinal cords that from subluxation of facets or vertebral
appear normal.53 Persistent enhance- bodies. MRI, however, can demons-
ment for months to years following de- trate ligament and cord injury, dis-
compressive surgery is common.51 placed disk fragments, and intraspinal
FIGURE 10-11 Spondylotic myelopathy. A, Sagittal T2-weighted MRI showing posterior

disk protrusion at the C4YC5 intervertebral disk level, causing severe spinal
canal stenosis. Hyperintensity is seen within the cord at the C4 to C7
vertebral body level, signifying cord injury with edema. B, Axial T2-weighted MRI showing
posterior disk protrusion causing severe spinal canal stenosis with cord compression. T2
hyperintensity is seen within the cord (arrow). C, Sagittal T1-weighted precontrast and D,
sagittal T1-weighted postcontrast MRIs showing transverse pancakelike enhancement
within the spinal cord just caudal to the site of maximal stenosis (D, arrow).

KEY POINTS
h CT is more sensitive hematomas that are not well seen on These advanced techniques are tools
than MRI for detection CT. Focal areas of spinal cord contusion that can be used by neurologists and
of cortical bone and swelling are best demonstrated as neuroimagers to help answer sophisti-
disruption due to hyperintensities on T2-weighted images. cated questions about spinal cord
fractures and can show GRE and SWI sequences are more sen- lesions and pathology. Overall, these
subtle misalignment sitive for detecting hemorrhagic axonal new advancements have the potential
resulting from shear injury.54 On occasion, DWI has to remarkably impact the ease and
subluxation of facets or detected spinal cord injury not seen on confidence of detecting and diagnos-
vertebral bodies. MRI, conventional sequences.55 DTI can be ing spinal cord disorders.
however, can used to detect spinal cord longitudinal
demonstrate ligament tract integrity in acute trauma as well. CONCLUSION
and cord injury, displaced Early detection of compressive mye- This article aimed to provide a review
disk fragments, and
lopathy from trauma is essential as it is of imaging of spinal cord disorders
intraspinal hematomas
a neurosurgical emergency. Posttrau- as well as disorders of the spine that
that are not well
seen on CT.
matic cord edema spanning more than secondarily affect the cord. Under-
two vertebral segments, or presence of standing the imaging features of these
h Diffusion tensor hemorrhage within the cord, is associ- lesions is essential in the practice of
imaging enables
ated with a worse prognosis.56 neurology as many of these disorders
qualitative and
quantitative assessment
are neurologic or neurosurgical emer-
of the integrity of white ADVANCES IN SPINAL gencies, and early intervention may
matter tracts of the CORD IMAGING prevent devastating consequences.
spinal cord. MRI is the modality of choice for diag-
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Review Article
Imaging of Central
Dr Konstantin Balashov,
Rutgers University, Robert
Wood Johnson Medical
Nervous System School, Department of

Neurology, 125 Paterson St,
6th Floor, Ste 6200,
Demyelinating New Brunswick, NJ, 08901,

kbalashov@yahoo.com.
Disorders Dr Balashov has served on

the editorial boards of
BMC Neurology and
Neuroimmunology and
Konstantin Balashov, MD, PhD, FAAN Neuroinflammation, as
chairperson of the health care
advisory committee of the
New Jersey chapter of the
ABSTRACT National Multiple Sclerosis
Purpose of Review: This article focuses on neuroimaging in multiple sclerosis (MS), Society, and as a consultant for
Sanofi Genzyme and Teva
the most common central nervous system (CNS) demyelinating disorder encountered Pharmaceutical Industries Ltd.
by practicing neurologists. Less common adult demyelinating disorders and incidental Dr Balashov has received
subclinical white matter abnormalities that are often considered in the differential research/grant support and
diagnosis of MS are also reviewed. speaking engagements from
Recent Findings: Advancements in neuroimaging techniques, eg, the application of Teva Pharmaceutical Industries
ultrahigh-field MRI, are rapidly expanding the use of neuroimaging in CNS demyelinating Ltd and research/grant support
from Biogen and the National
disorders. Probably the most important recent findings include the detection of cortical Multiple Sclerosis Society.
lesions and CNS atrophy even in early stages of MS. The key development for practic- Unlabeled Use of
ing neurologists is the growing impact of MRI on the diagnostic criteria for MS and Products/Investigational
Use Disclosure:
neuromyelitis optica (NMO) spectrum disorders. Dr Balashov reports
Summary: MRI serves as an important component of the diagnostic criteria for MS no disclosure.
and other major CNS demyelinating disorders, and it has been established as a * 2016 American Academy
reliable and sensitive indicator of disease activity and progression. In addition, rapidly of Neurology.
advancing neuroimaging techniques are helping to improve our understanding of
disease pathogenesis.
INTRODUCTION in MS clinical trials. Even so, MRI has

The development of new neuroimaging some disadvantages, including its high
technologies has revolutionized the cost and limited ability to reflect the
approach to diagnosis and manage- underlying pathogenesis of demyelinat-
ment of neurologic disorders. Among ing lesions. This article focuses on the
other neuroimaging techniques, MRI is use of MRI in MS, the most common
considered a reliable noninvasive indi- CNS demyelinating disorder encoun-
cator of demyelinating processes in the tered by practicing adult neurologists.
central nervous system (CNS). MRI has Other, less common, adult demyelin-
a very high sensitivity for subclinical ating disorders that are considered in
disease activity compared to clinical the differential diagnosis of MS are
examination and serves as an important also reviewed.
component of current diagnostic criteria
for multiple sclerosis (MS)1 and neuro- NEUROIMAGING IN MULTIPLE
myelitis optica (NMO) spectrum disor- SCLEROSIS
ders.2 In the past 2 decades, MRI has To better understand neuroimag-
become the standard outcome measure ing in MS, it is helpful to briefly review

CNS Demyelinating Disorders
KEY POINTS
h Important concepts in MS pathogenesis and its major clin- relapses as compared with relapsing-
the diagnosis of multiple ical forms. remitting MS. Since 1993, more than
sclerosis are the 10 disease-modifying therapies have
dissemination in time Definition of Multiple Sclerosis been proven to be partially effective
and dissemination in MS is a chronic disorder of the CNS. for relapsing-remitting MS.
space of lesions. The cause of MS is not known. The
h The term clinically word sclerosis originates from the Clinically Isolated Syndrome
isolated syndrome was Greek word for hard and usually and Radiologically Isolated
introduced to describe a means a replacement of the normal Syndrome
first episode of organ-specific tissue with connective The term clinically isolated syndrome
neurologic symptoms tissue. No specific laboratory or imag- (CIS) was introduced to describe a first
that lasts at least 24 hours ing test, including tissue biopsy and episode of neurologic symptoms that
and is caused by genome sequencing, can establish lasts at least 24 hours and is caused by
inflammation and whether a patient has MS. Therefore, inflammation and demyelination in
demyelination in one or
MS is a clinical diagnosis. The name of one or more sites in the CNS. Patients
more sites in the central
the disease underlines the fact that with CIS and two or more asymptom-
nervous system.
patients with MS have multiple CNS atic lesions on brain MRI have a more
h The term radiologically lesions. The important concepts in the than 85% probability of progression to
isolated syndrome and
diagnosis of MS are the dissemination clinically definite MS.4 Several clinical
its diagnostic criteria
in time and dissemination in space of trials have proven the efficacy of
were introduced to
describe patients with no
lesions.1 The early phase of the dis- selected disease-modifying therapies
prior history of ease is associated with CNS inflamma- in delaying the progression to MS in
neurologic disability but tion, increased permeability of the patients who presented with CIS and
with demyelinating blood-brain barrier, and destruction asymptomatic lesions on brain MRI
lesions incidentally found of oligodendrocytes leading to axonal that were characteristic of MS. How-
on MRI that are similar demyelination. In contrast, the neuro- ever, the definition of “characteristic
to those commonly seen degenerative component, comprising of MS” differed from one clinical trial
in multiple sclerosis. axonal loss and brain/spinal cord atro- to another. A common practice is to
phy, may be subtle at the beginning rely on the definition of the Betaferon/
but becomes more and more obvious Betaseron in Newly Emerging Multi-
as the disease progresses. Both genetic ple Sclerosis for Initial Treatment
and environmental factors contribute to (BENEFIT) study, which requires at
MS. Up to 90% of patients with MS will least two clinically silent lesions of at
be diagnosed with the relapsing- least 3 mm on a T2-weighted brain MRI,
remitting form of the disease, charac- at least one of which is ovoid, peri-
terized by occasional clinical relapses ventricular, or infratentorial, to decide
(exacerbations) and associated with the whether to start disease-modifying ther-
appearance of asymptomatic and symp- apy in a patient with CIS.5
tomatic contrast-enhancing demyelinat- The term radiologically isolated
ing lesions on MRI. Relapsing-remitting syndrome (RIS) and its diagnostic
MS eventually evolves into the second- criteria were introduced to describe
ary progressive form of MS, which is patients with no prior history of
characterized by increasing neurologic neurologic disability but with demye-
disability progression with or without linating lesions incidentally found on
overlapping relapses.3 Approximately MRI that are similar to those com-
10% of patients with MS are diagnosed monly seen in MS (Table 11-1).6
with the primary progressive form of Patients with RIS, especially those with
MS and have more rapid disability spinal cord lesions, have a high prob-
progression and no self-limiting ability of progressing to either CIS or

KEY POINTS
TABLE 11-1 Proposed Diagnostic Criteria for Radiologically h When monthly brain
Isolated Syndromea scans with optimized
imaging protocols are
All six components (AYF) listed below are necessary for a diagnosis of performed, MRI reveals,
radiologically isolated syndrome on average, 35 new
lesions per one clinical
A. The presence of incidentally identified CNS white matter abnormalities exacerbation reported
meeting the following MRI criteria: by the patient with
1) Ovoid, well-circumscribed, and homogenous foci with or without multiple sclerosis.
involvement of the corpus callosum h MRI factors affecting
2) T2 hyperintensities measuring 93 mm and fulfilling Barkhof criteria lesion detection include
for dissemination in spaceb patient positioning,
selection of pulse
3) CNS white matter anomalies not consistent with a vascular pattern
sequences, spatial
B. No historical accounts of remitting clinical symptoms consistent with resolution, coil
neurologic dysfunction technology, contrast
C. The MRI anomalies do not account for clinically apparent impairments medium, and MRI
in social, occupational, or generalized area of functioning magnet strength;
therefore, patients
D. The MRI anomalies are not due to the direct physiologic effects should use the same
of substances (eg, recreational drug abuse, toxic exposure) or a
MRI facility for
medical condition
follow-up imaging.
E. Exclusion of individuals with MRI phenotypes suggestive of leukoaraiosis
or extensive white matter pathology lacking involvement of the
corpus callosum
F. The CNS MRI anomalies are not better accounted for by another
disease process
CNS = central nervous system; MRI = magnetic resonance imaging.
a
Modified with permission from Okuda DT, et al, Neurology.6 B 2008 American Academy of
Neurology. www.neurology.org/content/72/9/800.long.
b
Barkhof criteria for dissemination in space require the presence of at least three out of four of
the following components on brain MRI: a gadolinium-enhancing lesion, a juxtacortical
lesion, an infratentorial lesion, or three or more periventricular lesions.
MS. The question of whether to treat a noninvasive and reproducible tool.

patients with RIS continues to be a The 2010 McDonald criteria for the di-
debatable topic. agnosis of MS heavily rely on MRI to
prove the dissemination in space and
Why MRI Is So Important in dissemination in time features of the
Multiple Sclerosis disease. This makes it possible to diag-
MRI is the best surrogate marker of MS nose MS with only one clinical episode
activity and disease progression. Al- of disease.1 In addition, MRI helps in
though in some cases MRI is not the differential diagnosis of MS and is
necessary to diagnose MS, patients with commonly used in MS clinical trials.
MS and normal CNS imaging are ex-
tremely rare. When monthly brain scans MRI Protocol for Multiple
with optimized imaging protocols are Sclerosis
performed, MRI reveals, on average, MRI factors affecting lesion detection
35 new lesions per one clinical exacer- include patient positioning, selection
bation reported by the patient.7 MRI is of pulse sequences, spatial resolution,

KEY POINT
h In general, coil technology, contrast medium, and demic clinical practice. In 2015, an
increased MRI magnet MRI magnet strength; therefore, patients updated MRI protocol for MS was pub-
strength leads to an should use the same MRI facility for lished by the Magnetic Resonance Im-
increase in the number follow-up imaging. Still, MRI protocols aging in Multiple Sclerosis (MAGNIMS)
of identifiable multiple do vary, and MRI machines are replaced network (Table 11-2).10 In addition, a
sclerosis lesions. from time to time. Currently, the vast separate MRI protocol has been sug-
majority of radiology centers use 1.5T gested by the Consortium of Multiple
or 3T MRI machines. Recent analysis Sclerosis Centers (CMSC) and is ex-
shows no significant difference be- pected to be published soon.11 Both
tween 1.5T and 3T MRI for initial the MAGNIMS and CMSC protocols sug-
MS diagnosis using the 2010 McDonald gest imaging with no gap and a voxel
criteria.8 The number of 7.0T MRI size of 3 mm 1 mm 1 mm for brain
machines installed in major academic MRI. Both protocols suggest a single
centers is growing, with a total of ap- dose (0.1 mmol/kg) of gadolinium-
proximately 20 machines in the United based contrast medium with a mini-
States alone. In general, increased MRI mum delay of 5 minutes after contrast
magnet strength leads to an increase in injection. However, the two protocols
the number of identifiable MS lesions. have different lists of core/mandatory
For example, cortical lesions not seen sequences for brain MRI. It is important
on 1.5T MRI can be found in up to 97% to note that intracranial gadolinium
of patients with MS on 7.0T MRI.9 deposition in postmortem brain sam-
Discussion on a standardized MRI pro- ples has been reported in patients who
tocol to compare disease activity in had repeated (between 4 and 29) brain
patients studied at different MRI facili- MRIs with IV contrast in the 10-year
ties is ongoing. The ideal protocol interval prior to death. The clinical sig-
would combine acceptable sensitivity/ nificance of this finding is not clear at
specificity and feasibility for detection this time.12 For further discussion on
of demyelinating lesions in nonaca- intracranial gadolinium deposition,
TABLE 11-2 Brain MRI Sequences for Baseline Evaluation of Patients

With Multiple Sclerosis Suggested by the Magnetic
Resonance Imaging in Multiple Sclerosis Networka
b Mandatory Sequences
Axial proton density and/or T2 fluid-attenuated inversion recovery
(FLAIR)/T2-weighted
Sagittal two-dimensional or three-dimensional T2 FLAIR
Two-dimensional or three-dimensional contrast-enhanced T1-weighted
b Optional Sequences
Unenhanced two-dimensional or high-resolution isotropic
three-dimensional T1-weighted
Two-dimensional and/or three-dimensional dual inversion recovery
Axial diffusion-weighted imaging
a
Modified with permission from Rovira À, et al, Nat Rev Neurol.10 B 2015 Macmillan Publishers
Limited. www.nature.com/nrneurol/journal/v11/n8/full/nrneurol.2015.106.html.

KEY POINTS
refer to the article “Potential Safety location and hyperintense (bright) on h A ‘‘multiple sclerosisY
Issues Related to the Use of Gadolinium- T2-weighted imaging, they are best specific lesion’’ does not
based Agents” by Nandor K. Pinter, MD; seen on fluid-attenuated inversion exist. The most
Joshua P. Klein, MD, PhD, FANA, FAAN; recovery (FLAIR) images with suppres- remarkable features of
and Laszlo L. Mechtler, MD, FAAN,13 in sion of hyperintense T2 signal coming early multiple sclerosis
this issue of Continuum. from the CSF (Figure 11-1). Lesions in plaques are their
Because of its thin structure and the optic nerve and spinal cord are perivenular location
multiple imaging acquisition artifacts, common in MS (Figure 11-2). and the self-limited
spinal cord MRI is more challenging An “MS-specific lesion” does not contrast-enhancing
than brain MRI; it is considered to be phase.
exist. The most remarkable features of
mandatory in patients if the brain MRI is early MS plaques are their perivenular h The perivenular location
nondiagnostic or if the presenting location and the self-limited contrast- explains the classic
symptoms are at the level of the spinal enhancing phase associated with a bro- ovoid shape of multiple
cord.10 The procedure should be car- sclerosis lesions.
ken blood-brain barrier (Figure 11-1).
ried out on an MRI machine with a So-called central veins can be seen in h The average duration of
minimum field strength of 1.5T. The the majority of contrast-enhancing MS multiple sclerosis lesion
spinal cord MRI protocol suggested lesions (more than 73% to 92%) on 7.0T contrast enhancement is
approximately 3 weeks.
by the CMSC includes sagittal T1- brain MRI.14,15 The perivenular location
weighted imaging; proton density, explains the classic ovoid shape of MS
short tau inversion recovery (STIR), lesions on two-dimensional images in
or phase-sensitive inversion recovery early disease before lesions start to
axial T2- or T2*-weighted imaging merge together. Some of lesions are
through suspicious lesions; and, in arranged perpendicular to the lateral
some cases, postcontrast gadolinium- ventricle in a triangular configuration
enhanced T1-weighted imaging. The known as Dawson fingers (Figure 11-3).
spinal cord MRI protocol suggested However, the perivenular distribution
by MAGNIMS is quite similar but does of lesions may occasionally be seen in
not include T2* imaging. STIR se- other demyelinating disorders, such as
quences block fat signal, improving NMO spectrum disorders15 and Susac
imaging of both the spinal cord and syndrome.16 Recent studies suggest
optic nerves. A follow-up brain MRI that many MS lesions show focal signal
with gadolinium is recommended to (eg, linear enhancement of the central
demonstrate disease dissemination in vein alone or perivenular hyperintense
time as part of the MS diagnostic criteria signal on T2 FLAIR or T2* images) up
or ongoing clinically silent disease ac- to 2 months before the full-size paren-
tivity in patients with an established chymal enhancement is noted on post-
diagnosis. To fulfill the 2010 McDonald contrast T1-weighted imaging.17 The
diagnostic criteria, brain imaging 3 to average duration of MS lesion contrast
6 months after the baseline scan is enhancement is approximately 3 weeks,
recommended in patients with CIS.10 which may help in the differential diag-
nosis of MS versus neoplastic lesions,
Unique MRI Features of but approximately 4% of MS lesions
Multiple Sclerosis Lesions enhance for more than 3 months. MS
The hallmark of MS is focal demyelin- lesions may reveal central or complete/
ation (ie, lesions or plaques) associ- incomplete peripheral ring enhance-
ated with pathologic changes due to ment (Figure 11-418 and Figure 11-5).
various degrees of inflammation, mye- This is not unique to MS and can be
lin loss, axonal injury, and gliosis. As seen in other diseases, eg, sarcoidosis,
many MS lesions are in a periventricular abscesses, or brain tumors.

FIGURE 11-1 Imaging of the natural evolution of an active multiple sclerosis (MS) lesion. The axial brain MRIs of a patient
with relapsing-remitting MS are shown. The active symptomatic lesion (*) is hypointense on T1-weighted images
and enhancing on T1-weighted images postcontrast. A fluid-attenuated inversion recovery (FLAIR)
sequence helps to distinguish a small demyelinating lesion (white arrows) from the CSF signal, which is isointense to MS lesion
signal on T2- and T1-weighted images. A central vein of the lesion (black arrow) is seen on 3T MRI. In most cases, central veins are
not visible on conventional MRI.
FIGURE 11-2 Imaging of spinal cord and optic nerve lesions in multiple sclerosis (MS). Sagittal
cervical spine MRIs depict multiple cervical cord lesions in a 40-year-old man.
The active lesion at C5 level (A, B, arrows) is associated with cord edema
(A, turbo inversion recovery magnitude) and contrast enhancement (B, T1-weighted postcontrast
with fat suppression). Orbit MRI of a 28-year-old man with optic neuritis and MS (C). Axial
postcontrast T1-weighted image with fat suppression is shown. Note the contrast-enhancing left
optic nerve (C, arrow).

KEY POINTS
It is estimated that 10% to 30% of in up to 97% of patients with MS on h Chronic foci of T1
hyperintense T2-weighted MS lesions ultrahigh-field MRI (Figure 11-620). hypointensity (ie, seen
are also seen on T1-weighted imaging The cortical lesion volume correlates on repeated MRIs done
as areas of low signal intensity com- with neurologic disability.9 The find- several months apart)
pared with normal white matter and are ing of at least one cortical lesion was are now called
known as black holes. Both acute and reported in 36% of patients with CIS persistent black holes.
chronic MS lesions may be hypointense and represented a high risk of conver- h Multiple sclerosis is not
on T1-weighted imaging, however with sion to clinically definite MS.21 It re- exclusively a white
different reasons. Most new lesions mains to be seen whether cortical lesions matter disease. Cortical
become isointense as inflammation can be detected in other CNS demye- lesions can be seen in
abates. In contrast, chronic foci of T1 linating disorders using a similar tech- up to 97% of patients
hypointensity (ie, seen on repeated nique. Because of the low accuracy of with multiple sclerosis
MRIs done several months apart) are on ultrahigh-field MRI.
conventional-strength MRI (eg, using
now called persistent black holes and double inversion recovery sequences) h Some patients with
represent areas with pathologically in detecting them,22 cortical lesions are multiple sclerosis may
confirmed severe tissue destruction.19 not included in the 2010 McDonald have focal
Large plaques and ring-enhancing le- leptomeningeal contrast
diagnostic criteria.1
sions are more likely to evolve to T1 enhancement.
In a 2015 study, leptomeningeal con-
hypointensity than smaller plaques in trast enhancement was detected in 25% h Acute demyelinating
both the acute and chronic stages of MS. of patients (39% of enrolled patients lesions with restricted
MS is not exclusively a white matter diffusion have been
had progressive MS) on 3T postcontrast
disease. Cortical lesions can be seen reported in a number of
FLAIR brain images compared to 2.7%
patients with multiple
of healthy subjects (Figure 11-7).23
sclerosis on brain and
This feature is more common in pro- spinal cord MRI.
gressive MS compared to relapsing-
remitting MS. Enhancing leptomeningeal
foci remained stable for many years.
However, the prevalence of focal lepto-
meningeal enhancement was less than
1% in another MS imaging study (13% of
enrolled patients had progressive MS).24
Most MS lesions do not reveal re-
stricted diffusion on MRI. If increased
signal is seen on diffusion-weighted imag-
ing, it would not be associated with
decreased signal on apparent diffusion
coefficient mapping in the majority of
MS lesions. It would, therefore, repre-
sent T2 shine-through. However, acute
demyelinating lesions with restricted
FIGURE 11-3 Imaging of multiple
sclerosis lesions. Axial diffusion have been reported in a num-
fluid-attenuated ber of patients with MS on brain and
inversion recovery (FLAIR) image of a
27-year-old woman with relapsing-remitting spine MRI (Figure 11-4).18,25,26 These
MS shows multiple hyperintense lesions have restricted diffusion at the
periventricular lesions. Some of the lesions
are arranged perpendicular to the lateral hyperacute/acute phase presumably due
ventricle in a triangular configuration, known to local hypercellularity or a hypoxic-
as Dawson fingers (white arrows). Some ischemic process, which is then con-
lesions have an ovoid shape and juxtacortical
location (red arrows). verted to increased diffusion due to
evolving vasogenic edema. White matter

FIGURE 11-4 Recurrent acute demyelinating lesions with restricted diffusion in

relapsing-remitting multiple sclerosis. On initial MRI, an acute demyelinating
lesion (Lesion 1A, arrows) adjacent to the body of the left lateral ventricle
exhibits restricted diffusion (hypointense pixels on apparent diffusion coefficient [ADC] map,
hyperintense signal on diffusion-weighted imaging [DWI]) in conjunction with faint ring
enhancement (hyperintense signal on T1-weighted imaging postcontrast). Follow-up MRI 65 days
later reveals a second ring-enhanced acute demyelinating lesion with restricted diffusion in the right
frontal lobe (Lesion 1B, arrows) and a third periventricular acute demyelinating lesion with
restricted diffusion in the left parietal lobe that does not enhance (Lesion 1C, arrows).
Reprinted with permission from Balashov KE, Lindzen E, Mult Scler.18 B 2012 SAGE Publications. msj.sagepub.com/
content/18/12/1745.short.
lesions with restricted diffusion are is an acute inflammatory demyelinat-

commonly seen in stroke, hypercellular ing disorder with rapid neurologic
tumors, and CNS infections such as worsening that classically presents
herpes encephalitis. Unfortunately, not with multiple alternating ringlike layers
all acute demyelinating lesions with of normal and abnormal T1 and T2
restricted diffusion are contrast- intensity in the cerebral white matter
enhancing, complicating the differential or, less commonly, in the basal gan-
diagnosis between stroke and acute MS glia, pons, cerebellum, and spinal cord
lesions in young patients. (Figure 11-827).28 The Marburg variant
Several types of demyelinating leis another type of MS that is character-
sions exist that are currently consid- ized by rapid progression and severe
ered as rare and aggressive variants of disease course that may lead to death
MS. Concentric sclerosis (Baló disease) within 1 year.

KEY POINT
h Tumefactive demyelinating
lesions are often defined
as brain lesions more
than 2 cm in diameter.
They may appear in
patients either with or
without multiple sclerosis.
FIGURE 11-5 Brain MRI of a young patient with multiple

sclerosis who has two tumefactive lesions.
Axial fluid-attenuated inversion recovery
(FLAIR) (A) and postcontrast T1-weighted (B) images are shown.
There are two patterns of contrast enhancement, heterogenous
(B, red arrow) and open ring (B, yellow arrow).
Tumefactive demyelinating lesions different degrees of mass effect/edema,

are often defined as brain lesions more may have complete or incomplete
than 2 cm in diameter. They may appear peripheral ring enhancement, and
in patients either with or without MS typically do not involve the cortical
(Figure 11-5).29 On MRI, they have area. Most patients presenting with
FIGURE 11-6 Imaging of cortical lesions in multiple sclerosis (MS). Axial brain MRIs of a patient with secondary progressive
MS performed on 7T MRI. Different cortical lesion types (subpial and leukocortical) can be seen (arrows).
In each rectangle, the left image is fast low-angle shot T2* and the right image is turbo spin echo.
Reprinted with permission from Mainero C, et al, Neurology 2009.20 B 2009 American Academy of Neurology. www.neurology.org/content/73/
12/941.short.

FIGURE 11-7 Leptomeningeal contrast enhancement in multiple sclerosis. A, Postcontrast

T2-weighted fluid-attenuated inversion recovery (FLAIR) images of four patients
with multiple sclerosis (MS). Foci of high signal (boxes) on 3T postcontrast
T2-weighted FLAIR images indicate leptomeningeal enhancement. From left to right: a 54-year-old
woman with relapsing-remitting MS, a 51-year-old woman with primary progressive MS, a
38-year-old woman with relapsing-remitting MS, and a 62-year-old man with primary progressive
MS. The findings are magnified in the corresponding boxes (arrows). Enhancement was not present on
precontrast T2-weighted FLAIR scans (not shown). Extracerebral tissues have been masked for clarity.
B, Longitudinal assessment of leptomeningeal enhancement. High signal indicating leptomeningeal
enhancement within a parietal sulcus (arrows) was stable over 4 years in a 55-year-old man with
relapsing-remitting MS. C, Signal intensity on different MRI sequences. Three foci of leptomeningeal
enhancement are visible on postcontrast T2-weighted FLAIR scans (left column), but not on the
corresponding precontrast T2-weighted FLAIR (middle column). In the right column, postcontrast
T1-weighted images show minimal abnormal signal that would not routinely be classified as
enhancement. The first row shows images of a 42-year-old woman with relapsing-remitting MS; the
second row shows images of a 30-year-old woman with relapsing-remitting MS; and the third

KEY POINTS
Continued from page 1622 h Focal spinal cord lesions
row shows images of a 61-year-old woman with primary progressive MS. D, Association with are seen in 80% to 90%
meningeal vessels. A high-resolution 7T MRI of a 51-year-old woman with primary progressive of patients with multiple
MS shows that leptomeningeal enhancement is perivascular. T2*-weighted gradient recalled sclerosis.
echo (GRE) scans showing a, the vessel (red arrow) as it appears before contrast injection; b,
bright signal around the vessel 5 minutes after contrast injection; c, an enlarging area of bright h Longitudinal transverse
signal 20 minutes postcontrast; and d, partially resolving signal 40 minutes postcontrast,
reflecting mixing with the slightly less bright CSF. Other vessels did not show the same finding.
myelitis that extends
over three or more
Reprinted with permission from Absinta M, et al, Neurology.23 B 2015 American Academy of Neurology.
vertebral bodies in
www.neurology.org/content/85/1/18.short.
length is rare in multiple
sclerosis and should
tumefactive demyelinating lesions and in MS and may raise the suspicion of an raise the suspicion of a
no prior history of demyelinating NMO spectrum disorder, sarcoidosis, neuromyelitis optica
disease will eventually be diagnosed acute demyelinating encephalomyelitis, spectrum disorder,
with an NMO spectrum disorder or malignancy, or infection. sarcoidosis, acute
MS.30 Occasionally, these patients may Increased gray and white matter CNS demyelinating
undergo stereotactic brain biopsy to encephalomyelitis,
atrophy is a well-established phenome- malignancy, or infection.
exclude malignancy. non in MS (Figure 11-9). Interestingly,
Focal spinal cord lesions are seen in h Increased gray and
thalamic volumes are decreased even
80% to 90% of patients with MS.31 white matter central
in RIS,32 and upper cervical cord atrophy nervous system atrophy
Spinal cord lesions may affect both gray
is significant in CIS.33 Decreased spinal is a well-established
and white matter and do not respect
anatomic gray-white matter boundaries. cord gray matter volume correlates bet- phenomenon in
ter with MS disability than brain gray multiple sclerosis.
Most lesions are found in the cervical
cord (Figure 11-2). MS lesions may be matter, brain white matter, or spinal h Decreased spinal cord
focal and well demarcated or present cord white matter volumes.34 However, gray matter volume
atrophy rates can be confounded by a correlates better with
as diffuse areas of mildly increased signal
number of influences, such as treatment- multiple sclerosis
on T2-weighted images. Longitudinal
disability than brain gray
transverse myelitis that extends over induced pseudoatrophy effect, genetics,
matter, brain white
three or more vertebrae in length is rare and vascular risk factors, and are not yet matter, or spinal cord
white matter volumes.
FIGURE 11-8 Baló concentric sclerosis in a 32-year-old woman who

presented with fever, slurred speech, and right hemiparesis.
Axial T1-weighted (A) and T2-weighted (B) brain images
show multiple lesions with alternating T1 hypointense and isointense rings
(A) and alternating T2 hyperintense and isointense rings (B).
Reprinted with permission from Wang L, Liu Y-H, Lancet.27 B 2010
Elsevier Ltd. www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61876-6/abstract.

FIGURE 11-9 Imaging of brain atrophy in a 60-year-old man with secondary progressive
multiple sclerosis. Axial brain fluid-attenuated inversion recovery (FLAIR) (A) and
T1-weighted (B, C) images are shown. Multiple merged periventricular
demyelinating lesions are hyperintense on FLAIR. Some lesions are hypointense on T1-weighted
images (black holes). The third ventricle is dilated (C, white arrow). The lateral sulci (C, black
arrows) are very prominent.
recommended for diagnostic and prog- are important MS diagnostic criteria

nostic purposes in clinical practice.10 (Table 11-3) that are occasionally seen
The dissemination in space and on the same MRI (Case 11-1). Of course,
dissemination in time of CNS lesions many caveats are familiar to neurologists
TABLE 11-3 MRI Dissemination in Time and Dissemination in

Space Criteria Included in 2010 McDonald Diagnostic
Criteria for Multiple Sclerosisa
b Evidence for Dissemination in Space

At least one T2 lesionb in at least two out of four areas of the central
nervous system:
Periventricular
Juxtacortical
Infratentorial
Spinal cordc
b Evidence for Dissemination in Time
New T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, with
reference to a baseline scan, irrespective of the timing of the baseline MRI
OR
Simultaneous presence of asymptomatic gadolinium-enhancing and
nonenhancing lesions at any time
a
Modified with permission from Polman CH, et al, Ann Neurol.1 B 2011 American Neurological
Association. onlinelibrary.wiley.com/doi/10.1002/ana.22366/abstract.
b
Gadolinium enhancement of lesions is not required for dissemination in space.
c
If subject has a brainstem or spinal cord syndrome, the symptomatic lesions are excluded and
do not contribute to lesion count.

KEY POINT
Case 11-1 h Only approximately

25% of white matter
A 35-year-old man presented with a
lesions will remain
chief complaint of blurred vision in
evident on conventional
his left eye and left retroorbital pain
T2-weighted imaging
that increased upon eye movement.
6 months after
His examination showed findings
lesion onset.
consistent with left optic neuritis.
The rest of the neurologic
examination was normal. However,
his brain MRI revealed both
contrast-enhancing and nonenhancing
asymptomatic lesions in both
periventricular and juxtacortical areas
(Figure 11-10), fulfilling dissemination
in space and dissemination in time
criteria for multiple sclerosis (MS). The
patient was treated with IV steroids
for 3 days, followed by improvement
in his visual symptoms. After blood
tests for common MS mimics were FIGURE 11-10 Imaging of the
patient in Case 11-1
negative, the patient was diagnosed with relapsing-remitting multiple sclerosis
(MS). Axial postcontrast T1-weighted
with relapsing-remitting MS and brain MRI shows both contrast-enhancing
started on disease-modifying therapy. (white arrows) and nonenhancing (black
Comment. This patient was arrows) white matter lesions in both
periventricular and juxtacortical areas.
diagnosed with relapsing-remitting Therefore, dissemination in space and
MS based on only one clinical event dissemination in time criteria (Table 11-3)
and one brain MRI as per the 2010 are fulfilled. Note that nonenhancing
lesions have an ovoid shape with
revised McDonald diagnostic criteria. well-demarcated borders, which is typical
This case illustrates the high sensitivity for MS lesions.
of MRI for subclinical MS activity.
and neuroradiologists. For example, le- the center of the lesions but sur-
sions adjacent to the frontal horns of the rounded by a rim of activated microglia,
lateral ventricles are not specific to begins to increase.38 This may be as-
patients with MS.35 Only approximately sociated with increased volume of
25% of white matter lesions will remain nonenhancing lesions seen on MRI.
evident on conventional T2-weighted
images 6 months after lesion onset.36 Nonconventional MRI
New MS lesions may demonstrate Techniques in Multiple Sclerosis
seasonal dependence. Interestingly, new A detailed discussion of new imaging
brain lesions are seen on T2-weighted techniques for MS is outside the scope
imaging 2 to 3 times more often in of this article, and the advantages
March through August than during the of ultrahigh-field MRI are described pre-
rest of the year.37 viously. Other nonconventional imag-
The frequency of clinical relapses ing techniques include new contrast
and occurrence of active plaques de- materials, such as ultrasmall superpa-
cline as patients age. At approximately ramagnetic iron oxide; magnetic reso-
47 years of age, the proportion of slowly nance spectroscopy; positron emission
expanding smoldering plaques, defined tomography (PET) imaging; diffusion
as lesions without inflammatory cells in tensor imaging; magnetization transfer

KEY POINTS
h Areas of white matter in imaging; and susceptibility-weighted that are often associated with a positive
patients with multiple imaging (SWI), which may help to im- laboratory test for antiYaquaporin-4 IgG
sclerosis may have prove our knowledge of MS pathogen- antibodies. Diagnostic criteria for NMO
axonal injury and esis and serve as sensitive biomarkers spectrum disorders were published in
microglia activation of subclinical disease activity to aid in 2015.2 In contrast to MS, NMO spec-
despite normal imaging predicting disease progression. The trum disorders have a higher preva-
characteristics on sensitivity and specificity of these lence in Asia compared to North
conventional MRI, methods for diagnosis and differen- America and Europe. Lesions seen on
underlying the concept tial diagnosis of individual patients re- MRI in NMO spectrum disorders
of normal-appearing main to be determined.10,19,31 overlap with those of MS. However, the
white matter.
Areas of white matter in patients with lesion distribution in NMO spectrum
h Classic MRI findings in MS may have axonal injury and microglia disorders is different from MS. In con-
neuromyelitis optica activation despite normal imaging char- trast to MS, lesions adjacent to the
spectrum disorders acteristics on conventional MRI, under- lateral ventricles and juxtacortical le-
include lesions extending lying the concept of normal-appearing sions involving subcortical U fibers are
over half the length of white matter. Nonconventional MRI not common in NMO spectrum disor-
the optic nerve or in the
can be useful for assessment of the ders. The cortical lesions reported in
optic chiasm, area
evolution of normal-appearing white MS are absent in NMO spectrum disor-
postrema of the dorsal
matter damage.19 ders.15 Classic MRI findings in NMO
medulla, or periependymal
brainstem area. Spinal
Technologic advancements have led spectrum disorders include lesions
cord lesions in to rapid progress in optical coherence extending over half the length of the
neuromyelitis optica tomography (OCT). The majority of optic nerve or in the optic chiasm, area
spectrum disorders patients with MS have demyelinating postrema of the dorsal medulla, or
usually present as lesions in the optic nerves. OCT mea- periependymal brainstem area. Spinal
transverse myelitis or sures the thickness of the retinal nerve
cord lesions in NMO spectrum disor-
focal spinal cord atrophy fiber layer, ganglion cell and inner
ders usually present as transverse
extending over three or plexiform layer, and inner nuclear layers
myelitis or focal spinal cord atrophy
more contiguous in the eye. The thickness of each layer is
changing because of retrograde degen- extending over three or more contigu-
vertebral segments.
eration of optic nerve axons. Atrophy in ous vertebral body segments in length
the ganglion cell and inner plexiform (Figure 11-11). In contrast to MS
layer of the retina as measured by OCT plaques, which are nearly exclusively
correlates with both gray and white centered on a small vein (92%) and
matter atrophy as measured by con- show a characteristic hypointense rim
ventional brain MRI.39 (23%), white matter changes in patients
with NMO spectrum disorders are
NEUROIMAGING IN OTHER nonspecific in appearance and are only
CENTRAL NERVOUS SYSTEM infrequently associated with a blood
DEMYELINATING DISORDERS vessel as seen on 7.0T brain MRI.15
Some demyelinating disorders, includ-
ing NMO spectrum disorders, acute Acute Disseminated
disseminated encephalomyelitis, and Encephalomyelitis
progressive multifocal leukoenceph- Acute disseminated encephalomyelitis
alopathy, may mimic MS on MRI. (ADEM) is typically a monophasic
demyelinating disorder (Case 11-2).
Neuromyelitis Optica and However, a clinical presentation con-
Neuromyelitis Optica sistent with ADEM may also be the
Spectrum Disorders first manifestation of MS. ADEM may
NMO spectrum disorders are inflam- be very difficult to differentiate from a
matory demyelinating CNS disorders first MS attack based on MRI. Certain

periventricular and subcortical white
matter in the parietooccipital or fron-
tal lobes, the corpus callosum, thalamus,
and basal ganglia (Figure 11-1342).
Lesions are often bilateral and asymmet-
ric and exert no mass effect. Contrast
enhancement, including an open-ring
pattern, can be seen in selected cases.
PML lesions are often difficult to dif-
ferentiate from MS lesions clinically and
on MRI. Typical MRI features of PML in
patients treated with natalizumab are
summarized in Table 11-4.43
INCIDENTALLY FOUND WHITE

MATTER ABNORMALITIES
In addition to RIS, other white matter
hyperintensities may be incidentally
FIGURE 11-11 Extensive spinal cord found on T2-weighted brain MRI of
lesions in a 42-year-old
woman with subjects with no prior history of focal
neuromyelitis optica (NMO). A sagittal neurologic symptoms. Two major
spinal short tau inversion recovery (STIR)
MRI shows a large area of hyperintense
types of non-RIS white matter hyper-
cord signal and cord expansion extending intensities are commonly encountered
from the level of C3 to the level of C6-7 in general neurologic clinical practice
and from the level of T1 to the level of T5.
(Figure 11-14). The first type presents
as small (usually less than 6 mm in size)
features are more typical for ADEM, in- and randomly distributed white matter
cluding simultaneous enhancement of lesions in nonelderly subjects, with
all demyelinating lesions, significant gray increased prevalence rate (4% to 59%)
matter or basal ganglia involvement, in patients with migraine, especially
and acute longitudinal myelitis. In con- migraine with aura.44 The second type
trast, multiple periventricular lesions, is very common in patients older than
the absence of a diffuse bilateral lesion 65 years (but can also be seen in
pattern, and presence of black holes are middle-aged subjects), hypothesized
MRI characteristics more typical for MS. to be linked to cerebral small vessel
The appearance of new lesions in disease, and typically seen around the
different locations on follow-up MRI anterior horns of the lateral ventricles,
strongly suggests MS.41 along their lateral borders, and around
the posterior horns of the ventricles.45
Progressive Multifocal This second type of white matter hy-
Leukoencephalopathy perintensity appears more often in pa-
Progressive multifocal leukoencepha- tients with neurologic disability, eg,
lopathy (PML) has been reported in dementia or gait ataxia. Similar to the
patients with human immunodeficiency first type, the second type of white mat-
virus (HIV) or other patients who are im- ter hyperintensity can be incidentally
munosuppressed, such as some patients found in subjects with no focal neuro-
with MS treated with natalizumab, di- logic symptoms. The exact etiology and
methyl fumarate, or fingolimod. PML pathogenesis of white matter hyperin-
imaging findings consist of patchy areas tensities of both types is not clear.
of low T1 signal and high T2 signal in These lesions are nonenhancing and

Case 11-2
An 18-year-old woman developed a
fever followed 4 days later by decreased
responsiveness. Clinical examination revealed
that she was lethargic and not oriented to time
and place and had weakness in all four limbs.
Brain MRI showed nonenhancing white matter
T2 hyperintensities without well-demarcated
borders in periventricular, cortical, subcortical,
corpus callosal, thalamic, and brainstem areas
(Figure 11-12A). An extensive T2-hyperintense
nonenhancing signal abnormality was seen
throughout the cervical cord (Figure 11-12B).
CSF examination showed a mildly increased
white blood cell count and no abnormal
oligoclonal bands. Her blood screen was
negative for common causes of transverse
myelitis (eg, Lyme disease, neuromyelitis FIGURE 11-12 Imaging of the patient in Case 11-2 with
acute disseminated encephalomyelitis
optica [NMO]). Based on clinical presentation, (ADEM). A, Axial fluid-attenuated inversion
MRI, and laboratory tests, she was diagnosed recovery (FLAIR) brain MRI shows poorly demarcated T2
with acute disseminated encephalomyelitis hyperintensities in cortical, subcortical, and brainstem areas. B,
Sagittal short tau inversion recovery (STIR) spinal cord MRI
(ADEM) and treated with IV steroids, shows T2 hyperintense signal abnormality throughout the
followed by clinical improvement. cervical cord (arrows).
Comment. Early clinical and imaging
features of ADEM may overlap with those of other central nervous system demyelinating disorders
such as multiple sclerosis and paraneoplastic encephalitis, and it is often difficult to differentiate
between them. In contrast to many other central nervous system demyelinating disorders, ADEM is
typically a monophasic event. The level of contrast enhancement in ADEM may vary. Patients with
nonenhancing ADEM lesions, as in this patient, are well-described.40
usually do not present as the well- MRI (Table 11-5). Many of these
demarcated ovoid lesions typical for disorders (eg, systemic lupus erythe-
patients with MS, CIS, or RIS. At this matosus, Behçet disease, and Sjögren
time, no established approach to man- syndrome [Figure 11-1546]), may pres-
agement of asymptomatic white matter ent with a relapsing-remitting clinical
hyperintensities exists, apart from offer- pattern, abnormal oligoclonal bands
ing laboratory blood tests to rule out in the CSF, and a good response to IV
common treatable causes of demyelin- steroids, features typical for patients
ating disease (eg, vitamin B12 defi- with MS. Additional causes of lesions
ciency) (Table 11-5), assessment for that can mimic CNS demyelinating
hypertension and diabetes mellitus, disease include postradiation myelopa-
and follow-up MRI to exclude rapid thy, human T-cell lymphotropic virus
progression of lesions. type 1 (HTLV-1)Yassociated myelopathy/
tropical spastic paraparesis; glioma;
OTHER DEMYELINATING CNS lymphoma; cerebral autosomal
DISORDERS THAT CAN MIMIC dominant arteriopathy with subcortical
MULTIPLE SCLEROSIS infarcts and leukoencephalopathy
In addition to ADEM, NMO spectrum (CADASIL); antiphospholipid syn-
disorders, and PML, other demyelinating drome; CNS vasculitis; central pontine
disorders can mimic MS clinically or on or extrapontine myelinolysis; chronic

lymphocytic inflammation with pontine
perivascular enhancement responsive
to steroids (CLIPPERS); stroke; Whip-
ple disease; paraneoplastic encepha-
lopathies; copper, vitamin B12, and
vitamin E deficiencies; infections with
CNS involvement (eg, brucellosis, his-
toplasmosis, toxoplasmosis, actinomy-
cosis, HIV); Marchiafava-Bignami disease;
late-onset Alexander disease; autosomal
dominant leukodystrophy; and posteri-
or reversible encephalopathy syndrome
(PRES). Thorough clinical, laboratory,
and neuroimaging data, along with
longitudinal clinical and MRI follow-up,
are sometimes needed before the cor-
rect diagnosis emerges.
FIGURE 11-13 An early progressive
multifocal
CONCLUSION leukoencephalopathy
(PML) diagnosed in a 25-year-old patient
Patients with MS and other CNS demy- with multiple sclerosis who was treated
elinating disorders present unique diag- with natalizumab. An axial brain MRI
shows a fluid-attenuated inversion recovery
nostic and management challenges in (FLAIR) hyperintense lesion in the left frontal
neurologic clinical practice. In the ab- lobe. The lesion demonstrates the classic
appearance of PML including a sharply
sence of definite diagnostic tests, MRI demarcated peripheral border along the
serves as an important component of subcortical U fibers (white arrow) and
a hazy, ill-defined central border
diagnostic criteria. This diagnostic tool (red arrow).
has been established as a reliable and
Reprinted with permission from Honce JM, et al,
sensitive surrogate biomarker of dis- Mult Scler Int.42 B 2015 Justin M. Honce et al.
ease activity and progression and is www.hindawi.com/journals/msi/2015/809252/abs/.
commonly used as one of the key
TABLE 11-4 Typical MRI Features of Early Progressive Multifocal

Leukoencephalopathy in Patients With Multiple
Sclerosis Treated With Natalizumaba
Features Characteristics
Location Subcortical locationb in the prime site, thereby
involving U fibers; cortex and basal ganglia are
often involved; often bilateral
Size Usually 93 cm
Borders Sharp toward the gray matter, ill-defined toward
the white matter
Mode of extension Lesions increase in size and new lesions appear
Mass effect No mass effect in small or large lesions
T2-weighted imaging Always hyperintense

TABLE 11-4 Typical MRI Features of Early Progressive Multifocal

Leukoencephalopathy in Patients With Multiple
Sclerosis Treated With Natalizumaba Continued from page 1629
Features Characteristics
T1-weighted imaging Typically hypointenseb; no reversion of signal
intensity; hyperintensity is suggestive of progressive
multifocal leukoencephalopathyYimmune
reconstitution inflammatory syndrome
Fluid-attenuated Always hyperintense; better appreciated on
inversion recovery (FLAIR) T2-weighted imaging
Diffusion-weighted Always hyperintenseb,c; larger lesions show a
imaging hyperintense rim at the lesion’s edge
Perilesional Smalla punctate T2-hyperintense lesions in the
immediate vicinity of the main lesion are often present
Enhancement Frequent enhancement, punctate or rimlike
Atrophy No atrophy in the early phase
a
Modified with permission from Yousry TA, et al, Ann Neurol.43 B 2012 American Neurological
Association. onlinelibrary.wiley.com/doi/10.1002/ana.23676/abstract.
b
Common features for small progressive multifocal leukoencephalopathy lesions.
c
Due to T2 shine-through effect.
FIGURE 11-14 Incidentally found white matter hyperintensities on brain MRI. Axial
fluid-attenuated inversion recovery (FLAIR) images show type 1 white matter
hyperintensities (A, arrows) in a 30-year-old woman and type 2 white matter
hyperintensities in a 58-year-old woman (B, arrows). Nonspecific frontal capping adjacent to the
frontal horns of lateral ventricles can be seen on both images (circles).

TABLE 11-5 Selected Central Nervous System Demyelinating Disorders That Can Mimic
Multiple Sclerosis on MRI
Disease Comments
Lyme neuroborreliosis Nervous system involvement is common. Neuroborreliosis is frequently
indistinguishable from multiple sclerosis (MS) on both clinical and
radiologic grounds.
Neurosarcoidosis Sarcoidosis involving the CNS has a predilection for the leptomeninges.
Other areas of involvement include cranial nerves, spinal cord, optic chiasm,
hypothalamus, periventricular white matter, ventricular ependyma, and
pituitary gland. Periventricular and other multifocal white matter lesions
are common. Some lesions may have peripheral ring enhancement on
postcontrast T1-weighted imaging.
Systemic lupus erythematosus CNS involvement in SLE was reported in up to 70% of patients. Patients
(SLE) may have different neurologic manifestations, including seizures, stroke
syndromes, movement disorders, headache, transverse myelitis, cranial
neuropathy, and peripheral neuropathy. MRI in patients with SLE may
reveal multiple types of while matter lesions, including small punctate
lesions predominantly in the periventricular and subcortical white
matter, demyelinating plaques in brain and brainstem, optic nerve
lesions, and spinal cord lesions extending over multiple vertebral
bodies. (The latter finding may also raise suspicion of a neuromyelitis
optica [NMO] spectrum disorder.)
Behçet disease Behçet disease is an inflammatory vascular disease with multiple symptoms,
including ulcers in the mouth and on the genitals and inflammation in parts
of the eye. Behçet disease with neurologic involvement (neuro-Behçet
disease) involves the CNS in 5Y50% of cases. Typical symptoms of
neuro-Behçet disease are headache, paresthesia, diplopia, ophthalmoplegia,
cerebellar ataxia, and hemiplegia. MRI may show enhancing meningeal,
periventricular, cortical, basal ganglia, and brainstem lesions; sinus
thrombosis; and longitudinally extensive spinal cord lesions.
Sjögren syndrome Sjögren syndrome is an autoimmune connective tissue disease in which
immune cells attack and destroy the exocrine glands that produce tears and
saliva. It affects mostly women, with the average age of onset in the late
forties. CNS involvement has been estimated to affect 5Y20% of patients.
The spectrum of CNS involvement is wide, with neuropsychiatric and spinal
cord symptoms (inflammatory myelopathy) observed most often. (The latter
finding may also raise suspicion of an NMO spectrum disorder.) Brain MRI
may show diffuse or focal MS-like lesions and isolated optic neuritis.
Vitamin B12 deficiency Neurologic lesions seen on spinal cord MRI due to subacute combined
and nitrous oxide degeneration are well described. Abnormal contrast enhancement has
inhalation-induced myelopathy been described in some spinal cord lesions. This syndrome is sometimes
seen in patients with borderline vitamin B12 deficiency who have recently
been anesthetized (or exposed due to recreational use) with nitrous oxide.
Patients with vitamin B12 deficiency may also have multiple focal and
confluent T2-weighted white matter hyperintensities on brain MRI, which,
in some cases, improve after initiation of hydroxocobalamin therapy.
Susac syndrome Susac syndrome is a very rare disorder that classically presents with
encephalopathy, branch retinal artery occlusion, and hearing loss. In
addition to callosal atrophy, patients with Susac syndrome may show
CSF-isointense lesions within the central part of the corpus callosum.

TABLE 11-5 Selected Central Nervous System Demyelinating Disorders That Can Mimic
Multiple Sclerosis on MRI Continued from page 1631
Disease Comments
Leber hereditary optic Leber hereditary optic neuropathy is a maternally inherited mitochondrial
neuropathy disorder with painless subacute bilateral visual loss, typically presenting in
the second and third decades. Some patients with Leber hereditary optic
neuropathy may have clinical features (eg, clinical relapses) indistinguishable
from MS. This subtype of Leber hereditary optic neuropathy, also known
as Harding disease, is very rare but coexists about 50 times more frequently
than expected by chance. All patients with Harding disease and 25% of
patients with Leber hereditary optic neuropathy, mostly female patients,
have an MRI appearance typical of MS.
Neurosyphilis Syphilis is a sexually transmitted disease caused by Treponema pallidum.
Invasion of the CNS occurs early in the course of untreated syphilis.
Tabes dorsalis is a classic late manifestation of untreated syphilis. Brain
MRI may also reveal nonspecific white matter lesions and contrast
enhancement in cerebral gummas and leptomeninges.
Adrenoleukodystrophy and Adrenoleukodystrophy and its less severe form, adrenomyeloneuropathy,
adrenomyeloneuropathy may have onset of symptoms in adolescence or adulthood. Most often,
the disease has an X-linked recessive hereditary pattern characterized
by adrenal insufficiency and demyelination of the CNS with abnormal
accumulation of very-long-chain fatty acids in cholesterol esters and
sphingolipids. The periphery of the CNS lesions may enhance on
postcontrast T1-weighted images.
CNS = central nervous system; CSF = cerebrospinal fluid; MRI = magnetic resonance imaging.
FIGURE 11-15 Multiple sclerosisYlike lesions in Sjögren syndrome. Axial brain T2-weighted image of a patient with Sjögren
syndrome at disease onset with ovoid lesions (A, arrows), with subsequent spinal cord involvement 2 years later
(B, arrow) and cerebral dissemination clearly visible in the axial fluid-attenuated inversion recovery (FLAIR)
sequence (C) despite intensive immunosuppressive treatment.
Reprinted with permission from Massara A, et al, Rheumatology.46 B 2010 British Society for Rheumatology.
rheumatology.oxfordjournals.org/content/49/8/1540.full.

outcome measures in MS pharmaceu- Ann Neurol 2011;70(1):182Y183.
doi:10.1002/ana.22490.
tical clinical trials. In addition, rapidly
9. Harrison DM, Roy S, Oh J, et al. Association
advancing neuroimaging techniques
of cortical lesion burden on 7-T magnetic
help to improve our understanding of resonance imaging with cognition and
disease pathogenesis. disability in multiple sclerosis. JAMA Neurol
2015;72(9):1004Y1012. doi:10.1001/
ACKNOWLEDGMENTS jamaneurol.2015.1241.
The author wishes to thank Joan 10. Rovira À, Wattjes MP, Tintoré M, et al.
Evidence-based guidelines: MAGNIMS
Moore; Yaritza Rosario; Lawrence consensus guidelines on the use of MRI in
Golbe, MD; Yeva Fernandez, MD; and multiple sclerosis-clinical implementation in
Christopher Renner, MD, for their the diagnostic process. Nat Rev Neurol
valuable comments and suggestions 2015;11(8):471Y482. doi:10.1038/
nrneurol.2015.106.
to improve the quality of the article.
11. Traboulsee A, et al. Revised recommendations
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Review Article
Positron Emission
Dr Robert S. Miletich, University
at Buffalo, 105 Parker Hall, 3435
Main St, Buffalo, NY 14214,
miletich@buffalo.edu.
Dr Miletich serves on the
Tomography and
editorial board of the Journal
of Neuroimaging and receives
research/grant support from
Single-Photon Emission
the William E. Mabie, DDS,
and Grace S. Mabie Fund.
Unlabeled Use of
Computed Tomography
in Neurology
Use Disclosure:
Dr Miletich reports no disclosure.
of Neurology. Robert S. Miletich, MD, PhD, FAAAS
ABSTRACT
Purpose of Review: Positron emission tomography (PET) and single-photon emission
computed tomography (SPECT) are now available for routine clinical applications in
neurology. This article discusses their diagnostic use in dementia, brain tumors, epilepsy,
parkinsonism, cerebrovascular disease, and traumatic brain injury.
Recent Findings: Neuromolecular imaging, also known as nuclear neurology, involves
clinical imaging of both basal regional physiology (perfusion, metabolism, and transport
mechanisms) and specific neurochemical physiology (currently, only the dopamine
transporter). This article serves as an introduction to neuromolecular imaging, review-
ing the literature supplemented by the author’s experience.
Summary: Neurologic PET and SPECT are no longer restricted to the research realm.
These modalities have high diagnostic accuracy.
INTRODUCTION radiopharmaceuticals for positron

This article discusses the clinical ap- emission tomography (PET) and
plication of neuromolecular imaging, single-photon emission computed to-
also known as nuclear neurology, mography (SPECT). In the author’s
focusing on tomographic methods experience, medical insurance usually
that are currently available and acces- reimburses for both the radiopharma-
sible in routine clinical care, if regional ceuticals and the imaging tests reviewed
expertise exists. Planar scintigraphy in this article.
methods, in which a two-dimensional SPECT utilizes standard nuclear
image is created of a three-dimensional medicine cameras for which tomo-
object, such as in nuclear cisterno- graphic methods are enabled. SPECT
graphy or spine bone scans, are not capability is ubiquitous, as all nuclear
reviewed in this article. The focus is medicine departments in nearly every
on literature from the past 5 years hospital in the United States have such
supplemented by the author’s clinical cameras. The most common radioiso-
experience. Clinical neuromolecular topes used in SPECT are technetium
imaging examines the central nervous 99m (99mTc), iodine 123 (123I), thallium
system distribution of US Food and 201 (201Tl), and indium 111 (111In).
Drug Administration (FDA)Yapproved These radioisotopes are incorporated

KEY POINT
into molecules that trace a physiologic sured as it is on the biomarker itself.1 h Neuromolecular imaging
process. Physiologic processes that can Neuromolecular imaging is specialized can measure some
be measured in the clinical arena with testing requiring specific expertise. As aspect of a pathologic
SPECT include cerebral perfusion with much can be gained diagnostically from process within the brain,
exametazime Tc 99m or bicisate Tc the visual interpretation of these im- but it can also measure
99m, dopamine transporter (DAT) ages by competent interpreters as from the physiologic effects of
concentrations with ioflupane I 123, statistically rigorous methodology. Vi- that pathology on the
brain tumor uptake with thallous chlo- sual interpretation is the typical experi- functioning of cerebral
ride Tl 201, and CSF hydrodynamics ence in the clinical realm. parenchyma. Both
with diethylenetriamine pentaacetic To review all potential applications types of measurements
provide useful
acid (DTPA) In 111. of neuromolecular imaging would re-
diagnostic information.
PET requires specialized cameras, quire review of all neurologic disor-
as the physical process requires coin- ders; this article reviews the most
cident detection of two high-energy common indications for which clinical
511-keV photons. The only widely reimbursement exists: dementia, brain
available radioisotope for clinical tumors, epilepsy, parkinsonism, cere-
PET is fluorine 18 (18F), which, be- brovascular disease, and traumatic
cause of its long half-life of 110 minutes, brain injury (TBI). Table 12-1 lists indi-
can be disseminated from regional cations and the type of neuromolecular
distribution centers. Other radioiso- imaging used in these disorders.
topes that may be used clinically
have much shorter half-lives, requir- DEMENTIA
ing on-site or local production; these With the aging populations of indus-
are not reviewed in this article. The trial and postindustrial societies
only physiologic process that can throughout the world, age-related dis-
be assessed clinically by PET is cere- orders, including neurodegenerative
bral glucose metabolism with disorders and specifically Alzheimer
fludeoxyglucose F 18 (FDG). disease (AD), are becoming public
Neuromolecular imaging can mea- health epidemics. Effective therapies
sure some aspect of a pathologic for neurodegenerative disorders have
process within the brain, but it can not been developed because the basic
also measure the physiologic effects pathophysiology of the disorders is
of that pathology on the functioning not understood. Clinical trials of new
of cerebral parenchyma. Both types of therapies are confounded by the pres-
measurements provide useful diagnos- ence of multiple diseases that show
tic information. Because of the nearly phenotypically similar clinical pre-
stoichiometric relationship between sentations. Currently, the field is
regional neuronal synaptic activity, searching for biomarkers that can
regional perfusion, and regional glu- properly diagnose these diseases, par-
cose metabolism, measuring the latter ticularly in the early stages when
two provides information about re- abortive therapy will be most effective.
gional brain activity. Currently neu- Neuromolecular imaging provides the
romolecular imaging can assay a potential for sensitive imaging bio-
number of physiologic processes clin- markers in dementia. Two indications
ically. These assays can serve as bio- for neuromolecular imaging exist in
markers for the disease process. dementia: early diagnosis and differ-
However, the diagnostic accuracy for ential diagnosis.
any imaging biomarker is as depen- With the realization that neurode-
dent on how the biomarker is mea- generative dementia has a prodromal

PET and SPECT
KEY POINT
h Positive positron
emission tomography TABLE 12-1 Indications for Clinically Available Neuromolecular
Imaging Tests
amyloid imaging is a
biomarker of brain
amyloid-" deposition,
Disorder Indications PET SPECT
and fludeoxyglucose Dementia Early diagnosis, differential FDG Bicisate,
positron emission diagnosis exametazime
tomography Brain tumors Grading, staging, tumor FDG Thallium
hypometabolism in the localization, mass lesion
temporal and parietal diagnosis, tumor recurrence
cortices and MRI atrophy versus treatment effect, therapy
in the temporal and efficacy evaluation, malignant
parietal lobes are degeneration diagnosis,
biomarkers of neuronal prognostication
degeneration or injury. Epilepsy Episodic neurologic syndrome FDG Bicisate,
diagnosis, localization of exametazime
seizure focus
Parkinsonism Early diagnosis, differential FDG Ioflupane,
diagnosis bicisate,
exametazime
Cerebrovascular disease Cellular viability, cellular Bicisate
ischemia
Traumatic brain injury Injury identification FDG Bicisate
FDG = fludeoxyglucose; PET = positron emission tomography; SPECT = single-photon emission
computed tomography.
phase, a new diagnostic category called loid imaging is a biomarker of brain

mild cognitive impairment (MCI) amyloid-" deposition, and FDG-PET
gained wide acceptance. In the past hypometabolism in the temporal and
30 years, the importance of neuro- parietal cortices and MRI atrophy in
imaging in the diagnosis of dementia the temporal and parietal lobes are
has also been accepted.2 As such, a biomarkers of neuronal degeneration
joint task force was convened by the or injury.
National Institute on Aging (NIA) and Reviews have summarized diagnos-
the Alzheimer’s Association (AA) to tic accuracy for both perfusion SPECT
revise the classic 1984 National Insti- and FDG-PET in the diagnosis of AD.
tute of Neurological and Communica- Perfusion SPECT has been reported to
tive Disorders (NINCDS)YAlzheimer’s have sensitivities of 65% to 85% and
Disease and Related Disorders Associa- specificities of 72% to 87%. FDG-PET
tion (ADRDA) criteria for the diagnosis sensitivities of 75% to 99% and spec-
of AD in both dementia and MCI.3,4 ificities of 71% to 93% have been
These criteria now include core clinical reported. In general, PET has higher
features and biomarkers of the patho- diagnostic accuracy (an average of
physiologic process. The latter includes 10% higher) than SPECT.5 Another
two classes of evidence: biomarkers of review essentially replicated these
brain amyloid-" deposition and bio- findings, with FDG-PET in AD versus
markers of neuronal degeneration or controls showing 89% to 99% sensitiv-
injury. In imaging, positive PET amy- ities and 60% to 87% sensitivities.6

KEY POINT
Cerebral perfusion SPECT has variable research radiopharmaceutical carbon h Patterns of central
efficacy in distinguishing AD from 11Ylabeled Pittsburgh Compound B nervous system
other diseases, usually less effective (11C-PiB), this diagnostic accuracy is dysfunction shown on
than in comparisons of AD with dependent on age as an age-related in- neuromolecular imaging
healthy controls. For distinguishing AD creased prevalence of amyloid tracer usually develop early in
from healthy controls, exametazime uptake exists, with up to 40% of asymp- the disease course of
SPECT had 76% sensitivity and 85% tomatic people over 70 years of age dementia, facilitating
specificity. These values were 80% and having high cortical PiB uptake.6,13 early diagnosis.
80% for frontotemporal dementia, 75% Amyloid imaging also shows little sig-
and 72% for vascular dementia, and nificant change over time and is poorly
70% and 76% for dementia with Lewy correlated with clinical progression of
bodies (DLB).7 SPECT had 79% accu- disease, in contrast to atrophy on MRI
racy for distinguishing AD from other and cerebral perfusion and metabo-
dementing illnesses.6 Overall, the few lism worsening with disease progres-
recent publications on MCI have shown sion. A potential application of amyloid
intermediate changes between demen- imaging is prognosticating AD develop-
tias and healthy controls.8 Nonetheless, ment in patients with MCI or even in
because neuromolecular imaging cap- asymptomatic individuals, but this has
tures the functional status of the brain, not been established.13 Given the un-
it has the capability for early diagnosis certainties of the pathophysiologic pro-
(Case 12-1) and differential diagnosis cess of AD, it remains unclear what
(Figure 12-2) in MCI. the diagnostic certainty for amyloid im-
Three amyloid imaging markers, aging will be. Although it is likely that
florbetapir, flutemetamol, and flor- amyloid imaging will have very good
betaben, have been approved by the negative predictive value, a likely poor
FDA, all tagged by 18F. Amyloid imag- positive predictive value may hinder its
ing has shown high correlation between usefulness.
regional amyloid tracer uptake and post- It has been proposed that examina-
mortem insoluble amyloid deposits. tion of the dopamine system with
Patients with AD have 50% to 90% higher DAT agents can help in the differential
gray matter concentrations of amyloid diagnosis of AD from DLB or PD
tracers than controls. Amyloid imaging dementia,12 but few studies have been
may be useful in the differential diagnosis published at this time.
of dementia as amyloid accumulations A comprehensive meta-analysis re-
in frontotemporal lobar degeneration view of literature from January 1990 to
are low, similar to healthy controls.8 March 2010 that examined diagnostic
However, amyloid imaging’s specificity biomarkers for AD, including CSF,
is not fully defined at this time and clinical features, MRI, SPECT, and
more research is needed. For instance, FDG-PET, showed that as compared
approximately 25% of patients with to controls without dementia, FDG-
Parkinson disease (PD) with dementia PET had the highest area under the
and DLB had positive amyloid scans, receiver operating characteristic curve
similar to AD.12 Although the FDA has (AUROC) at 0.96, with 90% sensitivity
approved amyloid imaging agents, and 89% specificity. FDG-PET was also
Medicare has not approved these stud- best in discriminating AD from other
ies for reimbursement outside of the dementias, with 0.91 AUROC, 92%
research setting. Although 80% to 100% sensitivity, and 78% specificity. The
sensitivity and specificity have been performance of SPECT, MRI, and CSF
reported using the amyloid imaging phosphorylated tau concentrations

PET and SPECT
Case 12-1
A 67-year-old man developed confusion postoperatively following endovascular repair of an
abdominal aortic aneurysm. The confusion cleared, but he and his wife noted short-term memory
problems that progressively worsened over the subsequent year. He also developed difficulties with
calculations and multitasking. His wife noted that he no longer did well under pressure situations. He was
a retired attorney and remained independent in activities of daily living. Past medical history was
significant for hypercholesterolemia, hypertension, and vitamin B12 and vitamin D deficiencies. All
four disorders had been medically corrected or controlled by the time of the fludeoxyglucose positron
emission tomography (FDG-PET) scan; MRI showed moderate diffuse atrophy. He had recently scored
25 out of 30 on the Mini-Mental State Examination (MMSE) and had been diagnosed with amnestic
mild cognitive impairment. FDG-PET/CT revealed mild diffuse atrophy on CT and a selective pattern of
association cortex hypometabolism, worst posteriorly. Severe decreases were shown in the lateral
parietal cortex (Figure 12-1A) and medial parietal cortex (Figure 12-1B). Severe hypometabolism in the
inferior temporal cortex, moderate hypometabolism in lateral temporal cortex, and mild decreases
in frontal cortex were also present.
FIGURE 12-1 Imaging of the patient in Case 12-1. Fludeoxyglucose positron emission
tomography (FDG-PET)/CT with fused CT in gray scale and PET in color scale
in the transverse (A) and sagittal (B) planes. Severe hypometabolism can be
seen in the medial parietal cortex (A, down-pointing arrow; B, arrow), and lateral parietal
cortex (A, horizontal arrows). Bright intensity or hot coloration (white, yellow) in PET
indicates high tracer localization and thus higher amounts of glucose metabolism. Low
intensity or cold coloration (black, orange) indicates low amounts.
Comment. This case demonstrates the use of FDG-PET/CT in supporting the diagnosis of prodromal
Alzheimer disease in mild cognitive impairment. Recent literature analyzing diagnostic testing, disease
risk factors, and postmortem pathology have revealed that besides Alzheimer disease, mild cognitive
impairment can result from multiple other disorders, individually or as comorbidities.9Y11 FDG-PET/CT
revealed association cortex dysfunction in a pattern unique to Alzheimer disease. This pattern had no
CT correlate in that the atrophy seen was diffuse.
were similar to one another, with neuromolecular imaging diagnosis of

AUROC of 0.85 to 0.86.14 AD has been hypometabolism or hy-
AD is a global brain disorder. The poperfusion in the temporal and parie-
often-stated criteria for making the tal cortices. Although this certainly is

KEY POINTS
h Each dementing illness
has its own pattern
of central nervous
system dysfunction on
neuromolecular
imaging, facilitating
differential diagnosis.
h The typical imaging
pattern for Alzheimer
disease is a posteriorly
dominant asymmetric
association cortex
hypofunction, worst in
temporal and parietal
cortices, with important
involvement of the
medial parietal cortex.
Function is better
preserved in primary
cortex and subcortical
gray matter structures.
FIGURE 12-2 Two examples of the neurodegenerative patterns of Alzheimer disease (A, B)
and frontotemporal lobar degeneration (C, D) in cerebral perfusion bicisate
single-photon emission computed tomography (SPECT) from transverse
(A, C) and sagittal planes (B, D). Regions of maximal involvement in the medial parietal
cortex (A, red arrow; B, arrow), lateral temporal and parietal cortices (A, white arrows),
medial frontal cortex (D, arrow), and polar and lateral frontal cortex (C, arrows) can be seen.
Images are of a 70-year-old woman (A, B) and an 85-year-old man (C, D) both with a 1-year
history of short-term memory impairment. Both had been diagnosed with mild cognitive
impairment and maintained intact affairs of daily living. Bright intensity or hot coloration
(white, yellow) in SPECT indicates high tracer localization and thus higher amounts of cerebral
perfusion. Low intensity or cold coloration (black, purple, blue-green) indicates low amounts.
needed, it is an inadequate characteri- In the previously mentioned literature,

zation of the array of changes that are neuromolecular imaging specificities
seen functionally on neuromolecular are often lower than the sensitivities.
imaging in AD. These findings include This is because other disorders have a
a widespread, but posteriorly domi- predilection for affecting the temporal
nant, asymmetric association cortex and parietal cortices. In the author’s
hypofunction with relative preservation clinical practice, the biggest confounder
of function in the primary cortices. is small vessel disease.15
Many disorders cause decreased func-
tion of the association cortex, which is BRAIN TUMORS
called the global brain impairment Approximately 50,000 people are diag-
pattern. Many global brain impairment nosed with primary brain tumors in
subpatterns exist, which help distin- the United States annually and
guish between the different disorders. 140,000 with metastatic brain tumors.

PET and SPECT
KEY POINTS
h The biological behavior Gliomas were the first human neo- active organ in the body. It is easy to
of tumors is reflected plasm for which the diagnostic utility misinterpret these studies in the ab-
in their glucose of FDG-PET was shown by the sence of sufficient training and expe-
metabolic profile. Giovanni Di Chiro group in 1982.15 rience. In the management of patients
The foundation for this was laid by with brain tumors, MRI remains the
h The interpretation of
fludeoxyglucose positron
Otto Warburg in the 1930s, who standard imaging modality, in particu-
emission tomography showed increasing glucose utilization lar using contrast-enhanced sequences.
requires multimodal and glycolysis in many different body These have high sensitivity but often
cross-correlation. cancers with increasing malignancy low specificity. This often leads to the
and anaplasia. This is now coined the diagnostic conundrum of assessing
Warburg theory, and it remains the the presence of treatment effect ver-
basis for the use of FDG-PET in sus tumor recurrence in patients with
oncology. Having a noninvasive mea- known brain tumors. This is the most
sure of the biological behavior of common indication for FDG-PET in
tumors is critical for rational manage- the author’s experience. As such, the
ment of these disorders. interpretation of FDG-PET requires
The indications for FDG-PET in multimodal cross-correlation. More
brain tumors include tumor grading, diagnostic information is extracted
tumor staging, tumor localization, the from PET by correlating it to MRI.
differential diagnosis of cerebral mass FDG-PET is complementary to MRI
lesions, distinguishing between tumor in that it adds value in defining the
recurrence versus treatment effect, biological behavior of the lesion field.
therapy efficacy evaluation, early diag- Much of the formative work on the
nosis of malignant degeneration, and efficacy of FDG-PET in brain tumors
prognostication.15,16 The author’s ex- was published decades ago by the Di
perience is that FDG-PET is a useful Chiro National Institutes of Health
technique for all of these indications. group. More recent work has replicated
Therapy must be titrated for the this earlier work and has shown the
tumor grade. Targeted therapies re- high diagnostic accuracy of FDG-PET
quire knowledge of tumor location for grading tumors, assessing tumor
and spread. MRI is very sensitive to progression, and distinguishing tumor
structural changes but often is not recurrence versus treatment effect in
specific and may not distinguish where previously treated patients with brain
neoplasm actually resides within a le- tumors.17 For example, using tumor
sion bed. It often cannot distinguish FDG uptake that is greater than or
tissue inflammation or necrosis from equal to 0.6 times the values in gray
neoplasm, a distinction needed for matter or 1.5 times the values in white
therapy evaluation or planning. Low- matter resulted in 94% sensitivity and
grade gliomas quite often undergo 77% specificity for distinguishing high-
malignant degeneration to a higher- grade from low-grade neoplasms.16 For
grade tumor. Timely diagnosis of such the diagnosis of tumor recurrence ver-
transformation can improve outcomes. sus treatment effect, sensitivities of
Finally, because FDG-PET is an assay of 80% to 86% and specificities of 40% to
high fidelity for the tumor’s biological 88% have been reported in the litera-
behavior, a more accurate prognosis is ture (Case 12-2).16 This wide range
thus provided. of reported values may be because
It is true that FDG-PET is not easy of variability of interpretative skills, as
to interpret given that the milieu is discussed previously. By characteriz-
the cerebrum, the most metabolically ing the biological behavior of brain

Case 12-2
A 57-year-old woman who underwent resection of a left occipital lobe glioblastoma multiforme 2 years
previously, followed by concurrent chemoradiation and 24 cycles of adjuvant temozolomide, was found to
have a new contrast-enhancing lesion on MRI 2 months after completion of her last cycle of temozolomide.
Fludeoxyglucose positron emission tomography (FDG-PET)/CT was requested for evaluation of tumor
recurrence versus
treatment effect. PET
(Figures 12-3A and
12-3C) clearly revealed
a 7-mm hypermetabolic
focus at the MRI
contrast-enhancing site
(Figure 12-3D). CT
showed a faint cortical
hypoattenuation
(Figure 12-3B). The
surrounding cortex was
hypometabolic. These
findings were consistent
with tumor recurrence
in the right medial
parietal cortex,
contralateral to the
original neoplasm.
Stereotactic radiosurgery
was planned.
Comment. This case
illustrates a number of
points. Small lesions
can be assessed with
modern PET/CT
cameras because of
improved spatial
resolution. PET is rarely
read in isolation of any
other modalities. To
extract the maximum
amount of diagnostic
information from
functional imaging,
cross-correlation to
structural imaging is
needed. The
interpretation of FIGURE 12-3 Multimodal imaging of the patient in Case 12-2 with fludeoxyglucose
positron emission tomography (FDG-PET) (A), CT (B), fused PET and CT
brain tumor studies (C ), and gadolinium-enhanced T1-weighted MRI (D). A 7-mm focus of
is based both on hypermetabolism is seen (A, C, arrows) at the site of MRI enhancement (D, arrow). Mild
tumor bed changes hypoattenuation can be seen at this site on CT (B, arrow). This focus is surrounded by
hypometabolic cortical ribbons. The findings are consistent with recurrence of high-grade
and the effects on the glioma and diaschisis of neighboring gray matter. In panel A, darker intensity indicates
cerebral parenchyma. higher amounts of glucose metabolism. In panel C, bright intensity or hot coloration (white,
yellow) indicates higher amounts of glucose metabolism.

PET and SPECT
KEY POINT
h Neuromolecular imaging tumors, FDG-PET provides prognostic geous as compared to FDG,18 and no
has proven usefulness information. For example, high FDG PET agents are FDA approved for
in the noninvasive uptake in glioblastomas was associ- amino acid imaging.
identification of the ated with a 29% 1-year survival, while SPECT with [201Tl]thallous chloride
epileptic zone in low FDG uptake was associated with a is also a useful neuromolecular imaging
candidates for resective 94% 1-year survival.18 This essentially technique for brain tumors. Although
epileptic surgery. replicates the findings reported by the sensitivities and specificities are not
the Di Chiro group 30 years ago. as high as those of FDG-PET, they have
Another camp of opinion exists in been reported in the 80% range, indi-
the literature that denigrates the ef- cating a useful diagnostic test. SPECT
fectiveness of FDG-PET in providing with [201Tl]thallous chloride has been
useful clinical management informa- recommended for assessment of glio-
tion in brain tumors. This group has blastoma progression.19 Thallium is
discouraged use of FDG-PET for as- treated as a potassium analogue by
sessment of glioblastoma progression19 the blood-brain barrier and, as such,
or for assessing tumor progression gains entry into the brain only with
versus treatment effect following ra- blood-brain barrier disruption. This
diosurgery.20 These negative pro- simplifies interpretation, as it becomes
nouncements may be related to the a matter of hot spot identification.
interpretative difficulties posed by
evaluating glucose metabolism within EPILEPSY
the brain. FDG-PET diagnosis is not Epilepsy affects 1% to 2% of the popu-
made simply by the presence or ab- lation. At least 30% of patients with
sence of tumoral FDG. It is a multi- epilepsy will fail to adequately respond
modal cross-correlative evaluation that to antiepileptic drugs. Surgical treat-
assesses magnitude, pattern, morphol- ment remains an option in these pa-
ogy, location, and even temporal be- tients. Two main indications exist for
havior of this uptake relative to the neuromolecular imaging in epilepsy.
structural changes shown on MRI. Also One is to assist in the differential
critical in this evaluation are the effects diagnosis of episodic syndromes that
on the surrounding parenchyma. High may or may not be due to epilepsy. The
diagnostic accuracy exists with the second is to help localize the epilepto-
proper interpretative scheme. genic zone in candidates for surgical
Because of reported difficulties resection of a seizure focus. The first
with FDG, a movement for imaging indication has become an integral part
brain tumors with radioactive amino of the author’s clinical practice; unfor-
acids has developed, primarily in tunately, no well-characterized pub-
Europe. Given the greater contrast of lished data exist on this use of
uptake between neoplasm and brain neuromolecular imaging. However,
parenchyma, imaging with radioactive the presurgical evaluation indication
amino acids is easier to read. How- is well established.22Y24
ever, the grading capability of these Neuromolecular imaging has proven
images has been questioned in the usefulness in the noninvasive iden-
literature.21 In the opinion of this tification of the epileptic zone in can-
author, with an experienced neuro- didates for resective epileptic surgery.
molecular imager, FDG provides high This localization requires a multi-
diagnostic accuracy. No other PET and modal investigation that includes elec-
SPECT tracers have been definitively trophysiology, structural imaging, and
shown to be diagnostically advanta- functional imaging and may include

KEY POINTS
invasive neurosurgical diagnostic tech- tion can be seen based on the timing of h Ictal single-photon
niques. Interictal FDG-PET and both the bicisate injection relative to seizure emission computed
ictal and interictal SPECT are now onset: focal ictal activation, lobar or tomography and interictal
routinely performed in surgical epilepsy even more widespread ictal activation, positron emission
centers throughout the world. Neuro- widespread ictal deactivation, and focal tomography can help
molecular imaging has high sensitivity, ictal deactivation. The first has the localize seizure foci in the
with ictal SPECT at 96%, interictal greatest fidelity for epileptic zone char- presurgical evaluation
SPECT at 44%, postictal SPECT at 75%, acterization, but diagnostic information of candidates for
and interictal FDG-PET on modern is present in each pattern. epilepsy surgery.
equipment up to 90% for temporal lobe For many patients, noninvasive h A computer-generated
epilepsy and 67% for extratemporal techniques may be sufficient to guide combination of ictal
epilepsy (Case 12-3).16 surgery for the site of surgical resec- single-photon emission
The combination of interictal and tion. However, if localization is not computed tomography
ictal SPECT, with or without MRI, possible, neuromolecular imaging may (SPECT), interictal
SPECT, and MRI often
using standard computer imaging be able to regionalize or lateralize the
provides precise
technology increases the diagnostic epileptogenic zone, which can mini-
localization of
accuracy of epileptic zone localization. mize the extent of subsequent invasive seizure foci.
This image processing is done at diagnostic techniques. Neuromolecular
surgical epilepsy centers throughout imaging is particularly useful when MRI h The greatest challenge
in performing ictal
the world. Many different systems have is either normal or shows multiple
single-photon emission
been developed. Subtraction ictal lesions, any one of which could be the computed tomography
SPECT coregistered to MRI (SISCOM), epileptic zone. for imaging in epilepsy
developed at the Mayo Clinic, is the Neuromolecular imaging is also use- is in injecting radiotracer
most widely known, but other method- ful in epileptic syndromes, such as in as close to the time
ologies exist.25 During ictus, seizure epileptic spasms with the EEG pattern of seizure onset
foci demonstrate hyperperfusion. The of hypsarrhythmia. The underlying pa- as possible.
purpose of combining the ictal and thology is variable and can be due to
interictal SPECT images is to identify either multifocal or unifocal cortical
this site of ictal-activated hyperperfu- lesions, resection of which may cure
sion. This is done by subtracting the or control epilepsy.24 Other syndromes
interictal image volume from the ictal with similar considerations are tuber-
image volume. The difference is ictal ous sclerosis, Sturge-Weber syndrome,
activation. All of these techniques various congenital malformations, and
require three-dimensional registration even Rasmussen encephalitis. The goal
of image sets, followed by propor- in all of these is to identify a resectable
tional normalization, which then allows epileptic zone.
algebraic manipulation of the interictal
and ictal images. The final product is PARKINSONISM
parametric images of ictal activation The clinical diagnosis of PD is incor-
(Figures 12-4C and 12-4D). Even ictal rect 20% of the time.26 Misdiagnosis is
deactivation parametric images can be even greater for the atypical parkinso-
created. Examining both ictal activation nian syndromes. This differential diag-
and ictal deactivation parametric im- nosis problem arises because of the
ages can provide diagnostic informa- large number of disorders causing
tion. The greatest challenge in parkinsonism.27 These include the
performing ictal SPECT is in injecting Lewy body diseases of PD and DLB;
radiotracer as close to the time of sei- the atypical parkinsonian syndromes
zure onset as possible. Four different multiple system atrophy (MSA), pro-
patterns of ictal activation and deactiva- gressive supranuclear palsy (PSP),

PET and SPECT
Case 12-3
A 54-year-old woman with increasing frequency of seizures presented as a candidate for epilepsy
surgery. Her symptomatology was stereotypic, with an aura of fear followed by loss of contact
with her right hand, oral automatisms, and left hand dystonic posturing, all lasting 2 to 3 minutes.
MRI revealed no temporal structural abnormality, but showed small occipital areas of
cortical dysplasia. EEG revealed interictal sharp waves and intermittent rhythmic delta
activity in the right
temporal region.
Fludeoxyglucose
positron emission
tomography (FDG-PET) in
transverse (Figure 12-4A)
and coronal planes
(Figure 12-4B) revealed
right temporal
hypometabolism in
both allocortex and
neocortex. Ictal
activation images
(Figures 12-4C and
12-4D) revealed focal
ictal activation in the
right anterior medial
temporal lobe. Invasive
electrophysiologic
studies were deemed
unnecessary given the
correlative diagnostic
information.
Comment. This case
illustrates the key role
neuromolecular imaging
plays in the presurgical
evaluation of patients
with epilepsy. When
all diagnostic information
is congruent, expensive
and invasive diagnostics,
such as subdural
electrode grids or depth FIGURE 12-4 Neuromolecular imaging of the patient in Case 12-3 includes ictal
fludeoxyglucose positron emission tomography (FDG-PET) (A, transverse;
electrodes, can B, coronal), and ictal activation images (C, transverse; D, transverse, 5 mm
often be avoided. dorsal to C). There is glucose hypometabolism in the right temporal lobe (arrows, A, B).
The ictal activation images were generated from ictal and interictal bicisate single-photon
emission computed tomography (SPECT) images. Both SPECT images are put into the
same stereotactic space of the MRI, followed by proportional normalization, which then
allows subtraction of the interictal image volume from the ictal image volume, leaving
those regions that show increased perfusion due to ictus. The ictal activation images help
to identify the location of seizure foci. The only coloration in panel C and panel D indicates
the ictal activation. The processed SPECT is registered to a fluid-attenuated inversion
recovery (FLAIR) sequence MRI, which is displayed in gray scale. In panel A and panel B,
bright intensity or hot coloration (red, yellow) in PET indicates high tracer localization and
higher amounts of glucose metabolism. Low intensity or cold coloration ( purple, blue)
indicates low amounts. In panel C and panel D, red and orange indicate high ictal
activation. No color indicates no ictal activation.

corticobasal degeneration, and other mine, induced in earlier stages of the
types of frontotemporal dementia; Lewy body diseases, will result in
and the secondary parkinsonian syn- hyperperfusion or hypermetabolism
dromes caused by drugs, vascular within the striatum (Figure 12-5).
disease, or normal pressure hydro- This hyperfunction may also be seen
cephalus. Even tremor disorders, such from neuroleptic medication. All the
as essential tremor, can enter the other parkinsonism disorders typi-
differential diagnosis. cally cause hypofunction in the stria-
The indications for neuromolecular tum. Only ioflupane I 123 provides a
imaging include the early diagnosis direct measure of the loss of dopamine
and differential diagnosis of parkin- innervation to the striatum.
sonism. Currently, four radiotracers The differential diagnostic utility of
are clinically available in the United neuromolecular imaging results from
States with proven utility for these in- the different patterns seen for differ-
dications. These include exametazime ent disorders. This is the principle
and bicisate for cerebral perfusion used in the clinic for visual interpreta-
SPECT, ioflupane for DAT imaging, tion of these studies. It also underlies
and FDG for regional glucose metab- the published neuromolecular imag-
olism. Each neuromolecular imaging ing literature. For validation, these
type will show changes that reflect a patterns must be compared to some
hypodopaminergic state. The perfu- gold standard. Very few studies have
sion and metabolism tracers will also used the best gold standard, which is
show regional dysfunction from dis- postmortem tissue confirmation. In
ease involvement in other neuronal lieu of tissue diagnosis, most studies
elements. The deficiency of dopa- have used consensus clinical criteria
FIGURE 12-5 Two different 65-year-old men with stage 3 Parkinson disease, one scanned
with fludeoxyglucose positron emission tomography (FDG-PET) (A) and the
other with bicisate single-photon emission computed tomography (SPECT) (B).
Both were withdrawn from dopaminergic therapy prior to neuromolecular imaging. Mild
hypermetabolism (A, arrows) and hyperperfusion (B, arrows) can be seen in the striatum.
This is often worse in the posterior inferior lenticular nuclei (A). This hyperfunction is absent
in the neurodegenerative atypical parkinsonian syndromes, but it is seen in dementia with
Lewy bodies. Bright intensity or hot coloration (red, yellow) indicates high tracer localization
and thus higher amounts of glucose metabolism (A) and perfusion (B). Low intensity or cold
coloration (black, blue) indicates low amounts.

PET and SPECT
KEY POINTS
h Differential diagnostic developed by professional organiza- the past 5 years, with this literature
information for tions, along with detailed patient being mature but indicating a role for
parkinsonism is provided follow-up for 0.5 to 3 years following perfusion SPECT in these disorders.
by the pattern of striatal the imaging. Such methodology has Beyond visual interpretation, a
and cortical uptake proven adequately valid upon direct number of studies have used comput-
of neuromolecular examination.28 There have also been erized methods for analyzing FDG-
imaging tracers. two types of image analysis in the liter- PET images of parkinsonism. These
h The identification of loss ature, visual examination of images by an methods have included voxel-based
of dopamine transporter expert versus applied computer method- methods in which statistical analysis
and the pattern of that is applied to each volume element, or
ology. The former replicates what occurs
loss help to distinguish voxel, of the image, comparing the
in the clinic, while the second is a field
neurodegenerative results to a database of normal sub-
parkinsonism from
in development. Not surprisingly, the jects.29 Other techniques have applied
secondary parkinsonism reported findings of the two methodol- multivariate analyses to define neuro-
caused by drugs and ogies are very similar because both begin nal networks based on how brain
even from tremor with the same information: the images. regions covary together.33 Although
disorders such as With clinical diagnosis consensus there have been reported findings of
essential tremor. criteria as gold standard, FDG-PET is a similar nature as that reported with
able to distinguish PD from atypical visual analysis, it is the author’s opin-
parkinsonian syndromes with greater ion that this computerized analysis
than 90% accuracy, using expert visual field needs to mature further before
analysis.27,29,30 Visual analysis of FDG- there can be any consideration for its
PET can also discriminate between the usefulness in the clinical arena.
atypical parkinsonian syndromes MSA, Ioflupane I 123 has been shown by
PSP, and corticobasal degeneration, histopathology in animals and humans
with greater than 75% sensitivity and to bind to the DAT on presynaptic
90% specificity overall.27,31 Concor- dopamine terminals. Loss of this bind-
dance with clinical diagnosis was ing is a surrogate marker of the loss of
reported of 80% for MSA, 93.3% for nigrostriatal terminals.34,35 A high cor-
PSP, and 100% for corticobasal degen- relation (R = 0.65) exists between DAT
eration in 136 parkinsonian patients.29 imaging and the density of dopamine
Another study using similar method- neurons in the substantia nigra. Par-
kinsonism can be a difficult differential
ology reported sensitivities/specific-
diagnosis.27 The identification of loss
ities of 77%/97% for MSA, 74%/95%
of DAT and the pattern of that loss
for PSP, and 75%/92% for corticobasal
help to distinguish neurodegenerative
degeneration in 95 parkinsonian pa- parkinsonism from secondary parkin-
tients.30 The one recent study that used sonism caused by drugs and even from
postmortem tissue diagnosis as the tremor disorders such as essential
gold standard reported concordance tremor (Figure 12-6). DAT imaging
of FDG-PET with tissue diagnosis in using visual analysis has been reported
seven patients with PSP and one patient to help distinguish vascular parkinson-
with corticobasal degeneration.32 More ism from PD with a 94% accuracy.36
study is needed on this, particularly Each neurodegenerative process can
with regard to concordance to post- have its own pattern, creating the
mortem gold standards, but the find- potential to distinguish between them.
ings to date support the usefulness of Atypical parkinsonian syndromes and
FDG-PET in parkinsonism diagnosis. early DLB tend to have more homog-
Little has been published on the role enous and more symmetric involve-
of perfusion SPECT in parkinsonism in ment of the caudate and putamen than

KEY POINTS
h Perfusion and
metabolism imaging
indirectly demonstrate
the hypodopaminergic
state by showing its
synaptic consequences.
h Dopamine transporter
imaging directly
demonstrates the
hypodopaminergic
state by showing loss
of dopaminergic
nerve terminals.
FIGURE 12-6 Ioflupane I 123 imaging of the dopamine transporter. A, Imaging of a

55-year-old man with a 5-year history of worsening hand tremor,
worse on the right. There is normal ioflupane distribution through the
cerebrum, making essential tremor the likely diagnosis. B, Imaging of a 39-year-old
woman with a 1-year history of worsening tremors. Two findings are noted.
Diminished contrast between the striatum and the rest of the brain due to decreased
striatal uptake; these decreases are worse in the putamen, particularly posteriorly,
than in the caudate. These findings are consistent with neurodegenerative
parkinsonism. Although Parkinson disease is the most likely diagnosis, other atypical
parkinsonian syndromes, such as multiple system atrophy, progressive supranuclear
palsy, corticobasal degeneration, or frontotemporal dementia cannot be entirely
ruled out. Bright intensity (white) indicates high tracer localization and thus higher
dopamine transporter concentrations. Low intensity (black) indicates low amounts.
PD. PD tends to have a posterior to tion; the latter is a particularly good

anterior gradient of improving uptake indicator of whether tissue is critically
within the striatum. However, a consid- hypoperfused (the presence of in-
erable overlap exists in the intrastriatal creased oxygen extraction fraction
patterns, making distinction from other means that the tissue is not receiving
neurodegenerative parkinsonism diffi- sufficient blood to its energy require-
cult.31 Given the phenotypic overlap of ments). Three stages of hemodynamic
DLB and AD, DAT imaging has poten- compromise have been defined exper-
tial usefulness in this distinction. DAT imentally using 15O PET tracers for mea-
imaging has 87% sensitivity and 94% suring regional cerebral blood flow,
specificity in distinguishing DLB from blood volume, and oxygen extraction
other dementias or controls. fraction.37 Bicisate SPECT is capable
of defining these three stages as well.
CEREBROVASCULAR DISEASE Stage 0 is the absence of abnormality
SPECT and PET are useful techniques due to presence of collateral flow chan-
for the evaluation of hemodynamic nels. In stage I, a tissue vasodilatation
reserve in patients with severe cere- restores regional flow to normal but
brovascular disease. SPECT allows as- results in increased regional blood
sessment of cerebral perfusion. Using volume and decreased vascular reserve.
oxygen 15 (15O) tracers, PET can mea- Stage II has increased blood volume,
sure cerebral blood flow, cerebral blood decreased vascular reserve, and de-
volume, and oxygen extraction frac- creased blood flow or perfusion.

PET and SPECT
KEY POINT
h Cerebral perfusion Cerebral perfusion SPECT involves in that area, indicating diminished vas-
single-photon emission the simultaneous assessment of two cular reserve (Figure 12-7). The in-
computed tomography physiologic processes, neuronal activ- crease in perfusion after the challenge
involves the simultaneous ity and the state of the vascular tree. is variable; in the author’s experience, it
assessment of two Techniques to disentangle the cere- is between 10% and 50%. This amount
physiologic processes, bral perfusion SPECT signal into neu- of activation is sufficient for diagnos-
neuronal activity and the ronal function versus vascular disease tic purposes.
state of the vascular induce a dilatation in responsive vas- The two main perfusion SPECT
tree. Techniques to cular beds by interventions that pro- radiopharmaceuticals currently in use
disentangle the cerebral voke tissue acidosis. Available options are exametazime Tc 99m and bicisate
perfusion single-photon Tc 99m. Their cellular uptake mecha-
are the carbonic anhydrase inhibitor
emission computed
acetazolamide, which induces a meta- nisms are different, which results in
tomography signal into
bolic acidosis, and inhalation of car- significantly different imaging capa-
neuronal function versus
bon dioxideYenriched gas, which bilities. Only bicisate has a brain
vascular disease induce
a dilatation in responsive induces a respiratory acidosis. The cellYspecific uptake mechanism,
vascular beds by presence of compromised vascular re- based on one or more esterases only
interventions that serve can be determined by compar- expressed within brain cells. The main
provoke tissue acidosis. ing the perfusion before and after the uptake and retention mechanism for
vasodilatory challenge. Because vessels exametazime is glutathione chelation.
in ischemic territories will already be Glutathione is present in all cells of
dilated, the vasodilatory challenge will the body, including inflammatory cells,
result in lesser increase in perfusion meningeal cells, and fibrocytes. Most
FIGURE 12-7 Imaging of a 49-year-old man who had undergone sacrifice of the left internal
carotid artery for aneurysms that could not be treated endovascularly.
Subsequently, the patient had two episodes of right arm shaking. The differential
diagnosis was transient ischemic attacks versus seizure. The possible need for
extracranial-intracranial bypass was discussed. Only heterogeneous multifocal white matter
hypoperfusion is evident on the rest images of the bicisate vascular reserve cerebral activation
perfusion single-photon emission computed tomography (SPECT) study (A), consistent with
small vessel disease. However, after administration of the stress agent acetazolamide, a
clear-cut middle cerebral artery territory hypoperfusion is evident (B, arrow), indicating
vascular reserve compromise. It was likely the right arm shaking episodes were transient
ischemic attacks. In the awake resting state, collateralization and middle cerebral artery tree
vasodilatation are able to compensate for the hindered internal carotid artery flow. These
compensations may not be adequate in states of decreased perfusion pressure (eg, sleep).
Bright intensity or hot coloration (white, yellow) indicates high tracer localization and thus
higher amounts of perfusion. Low intensity (black, purple, blue) indicates low amounts.

of the earlier literature in acute stroke may show higher apparent perfusion
that showed low diagnostic accuracies than bicisate because exametazime is
for perfusion SPECT used exametazime. taken up not just by brain cells but also
Because of the difference of brain cell by other cell types, such as inflam-
uptake mechanisms, brain cell viability, matory cells, fibrocytes, and other mes-
and, thus, reversible ischemia, is only enchymal elements.
reliably revealed by bicisate. SPECT might also be useful in the
In acute stroke, two tissues are evaluation of patients with suspected
threatened: the ischemic core and vascular cognitive impairment. Currently,
the surrounding tissue, the penumbra. the diagnosis of vascular dementia or
Although the fates are initially uncer- vascular cognitive impairment is
tain, much of the ischemic core will go supported by MRI, which identifies
on to infarction while the ischemic tissue structural injury, such as gray or
penumbra retains the potential for white matter infarcts or white matter
salvage. Stroke evolution over time is hyperintensities. These methods are
in major part related to propagation of not sensitive to the presence of active
infarction within these threatened tis- ischemia before tissue injury, particu-
sues. SPECT with either exametazime larly that from small vessel disease.
or bicisate within the first 8 hours of Measuring cerebral hemodynamic re-
acute stroke presentation has a positive serve may facilitate the etiologic diag-
predictive value of 90%, with reported nosis of cognitive impairment and help
sensitivities of 61% to 74% and specific- to address risk factor management.
ities of 88% to 98%.37 Twenty patients However, this application for SPECT
were evaluated with bicisate SPECT remains mostly investigational.41
prior to IV recombinant tissue-type
plasminogen activator (rtPA) therapy.38 TRAUMATIC BRAIN INJURY
Brain regions with bicisate concentra- In the past few years, the public has
tions that were 15% to 53% that of the been made aware of the role of re-
contralateral side went on to infarct petitive TBI in causing long-term mor-
despite rtPA therapy. Values of 45% bidity in athletes of contact sports.
to 83% indicated reversible ischemia This clinical syndrome, called chronic
salvageable from death following traumatic encephalopathy, has most
treatment. Values of 45% to 52% dramatically been demonstrated in
uptake were taken as the threshold former National Football League
for viability and therapy triage. 38 players. 4 2 However, TBI occurs
Exametazime-SPECT 1 hour following throughout the population by various
rtPA therapy in 35 patients was also means, including motor vehicle acci-
predictive of outcome, with hypoper- dents, assaults, and even falls in those
fusion associated with poor outcome.39 with or without gait impairment. Fol-
Bicisate SPECT can also be used in the lowing concussion or mild TBI, patients
acute setting to distinguish a transient often are left with persistent symp-
ischemic attack from an evolving toms that profoundly compromise their
stroke by using a cutoff uptake value quality of life. CT and MRI often show
of 70% or greater relative to the ho- no abnormalities.
mologous region of the contralateral These injuries occur due to differen-
hemisphere.40 In the subacute phase tial brain acceleration and momentum
of stroke, bicisate retains its advantage relative to other tissues. Concussion
over exametazime by its specificity of results from rotational or angular ac-
cell uptake mechanism. Exametazime celeration of the brain. Contusion is

PET and SPECT
KEY POINT
h The regions most often a more forceful process, with actual Bicisate SPECT and FDG-PET have high
involved in traumatic macroscopic schism of tissue. The sensitivity for detecting sites of injury
brain injury include brain impacts surrounding structures, because their imaging signal requires
polar and orbital frontal typically the inner table of the skull, intracellular uptake of radiopharma-
lobes, polar and inferior but the meninges are also involved. ceuticals. Absence of cells or cellular
temporal lobes, and Shear or strain forces also propagate dysfunction results in decreased radio-
dorsal frontal and within the brain itself, again due to a pharmaceutical localization. Regional
parietal lobes. Less differential acceleration or momen- changes have been concordant with
common areas include
tum. White matter shear or strain neuropsychological findings.43 SPECT
the perisylvian regions
injuries are one example. Most of outperformed both CT and MRI and
and inferior cerebellum.
these brain injuries are contrecoup had high positive predictive value and
injuries. Neuromolecular imaging shows near 100% negative predictive value
decreased perfusion and metabolism at for the continued presence of clinical
the sites of brain injury, typically in the symptoms at 3-month intervals after the
polar and orbital frontal and temporal injury.44 In the author’s experience,
lobes, the dorsal vertex of the frontal the location and pattern of physio-
and parietal lobes where glide contu- logic changes on PET and SPECT in
sions occur, and, less commonly, in the mild TBI include wedge defects and
perisylvian regions and inferior cerebel- regional decreases incongruent with
lum. However, injury can potentially levels of perfusion or metabolism else-
occur anywhere in the cerebrum. where in the cerebrum (Figure 12-8).
FIGURE 12-8 Imaging of a 22-year-old man with persistent cognitive and affective
difficulties following a motor vehicle accident 1.5 years ago. His school
performance had deteriorated, and he was anxious with a depressed
mood, not typical for him prior to the accident. A, Bicisate single-photon emission
computed tomography (SPECT) shows hypoperfusion in the orbital frontal cortices,
where subtle parasagittal wedge defects are also seen (arrows). B, Fluid-attenuated
inversion recovery (FLAIR) MRI shows a long T2 lesion in the right inferior temporal
lobe (arrow) and no other findings. Bilateral inferior temporal cortex hypoperfusion can
also be seen where a wedge defect is evident at the site of long T2 (C, arrow). In panel
A and panel C, bright intensity or hot coloration (white, yellow) in SPECT indicates high
tracer localization and thus higher amounts of perfusion. Low intensity or cold
coloration (purple, blue) indicates low amounts.

KEY POINT
CONCLUSION and dementia. Semin Neurol 2013;33(4):
386Y416. doi:10.1055/s-0033-1359312. h Neuromolecular imaging
Neuromolecular imaging is physiologic has high sensitivity for
9. Petersen RC, Aisen P, Boeve BF, et al. Mild
imaging of the cerebrum. Both basal cognitive impairment due to Alzheimer the detection of
physiologic and specific neurochemical disease in the community. Ann Neurol traumatic brain injury
systems can be examined. The litera- 2013;74(2):199Y208. doi:10.1002/ana.23931. and often shows injury
ture has shown high diagnostic accu- 10. Roberts RO, Cha RH, Mielke MM, et al. Risk when CT and MRI
racy in a wide range of disorders, and protective factors for cognitive are negative.
including dementia, brain tumors, epi- impairment in persons aged 85 years and
older. Neurology 2015;84(18):1854Y1861.
lepsy, parkinsonism, cerebrovascular
doi:10.1212/WNL.0000000000001537.
disease, and TBI. Expanding utility in
other disorders will likely be shown in 11. White LR, Edland SD, Hemmy LS, et al.
Neuropathologic comorbidity and cognitive
the future. New radiopharmaceuticals impairment in the Nun and Honolulu-Asia
tracing new and different physiologic Aging Studies. Neurology 2016;86(11):1000Y1008.
processes are expected. doi:10.1212/WNL.0000000000002480.
12. Arnaldi D, Morbelli S, Morrone E, et al.

Cognitive impairment in degenerative
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Review Article
Ultrasound in
Dr Georgios Tsivgoulis,
Second Department of
Neurology, University of
Neurology Athens School of Medicine,

Iras 39, Gerakas Attikis,
Athens, Greece 15344,
tsivgoulisgiorg@yahoo.gr.
Georgios Tsivgoulis, MD, PhD, MSc, RVT;
Andrei V. Alexandrov, MD, RVT Dr Tsivgoulis serves on the
editorial boards of Stroke and
the Journal of Neuroimaging
and has received research/
ABSTRACT grant support from the European
Purpose of Review: Low cost, avoidance of irradiation, and high temporal resolution Regional Development Fund.
Dr Alexandrov serves on the
are inherent advantages of ultrasound imaging that translate into multiple clinical uses in editorial board of the Journal
many domains of neurology. This article presents clinical uses of ultrasound examination of Neuroimaging.
in cerebrovascular, neurodegenerative, and peripheral nervous system diseases. Unlabeled Use of
Recent Findings: Modern treatment and prevention of ischemic stroke rely on prompt Products/Investigational
Use Disclosure:
diagnosis. Ultrasonography has found a place as a noninvasive screening test and Drs Tsivgoulis and
bedside technique that provides estimates of the degree of stenosis as well as Alexandrov report
hemodynamic and structural information about intracranial and extracranial vessels no disclosures.
in real time. Other standard applications of neurosonology include detection of * 2016 American Academy
of Neurology.
vasospasm in patients with subarachnoid hemorrhage, selection of appropriate
candidates for blood transfusion among patients with sickle cell anemia (primary
stroke prevention), right-to-left shunt testing, emboli detection, vasomotor reactivity
assessment, and noninvasive confirmation of cerebral circulatory arrest. Improvement
in image quality permits novel uses of ultrasonography in neurodegenerative and
peripheral nervous system disorders, providing clinically important information that
is complementary to the clinical examination and electrophysiology. Transcranial
parenchymal sonography may assist in the differential diagnosis of movement dis-
orders, while peripheral nerve ultrasound using high-frequency probes may provide
structural information regarding the underlying etiology of entrapment neuropathies.
Summary: The indications for neurosonology are rapidly expanding, increasing its
applicability outside the field of cerebrovascular diseases. Ultrasound testing is a
noninvasive easily repeatable bedside investigation providing clinically relevant
information on a wide spectrum of neurologic disorders.
INTRODUCTION Vascular ultrasound was the first

Excellent safety, very high temporal modality adopted in clinical neurology
and high spatial resolution, real-time for the evaluation of extracranial
evaluation, low cost, and the ability to (1970s) and intracranial (1980s) vascu-
perform examinations at the bedside lature before the widespread availability
are some of the key advantages of of multimodal CT and MRI. Brightness-
medical ultrasound. These advantages mode display (B-mode) consists of a
explain why diagnostic ultrasound has two-dimensional grayscale image de-
revolutionized many medical special- rived from scanning a plane through
ties, including neurology. Several med- the body by an array of transducers.
ical schools in the United States already B-mode has been in clinical use for many
include ultrasound in their curriculum years for the evaluation of the vessel
for all medical students, using it to teach wall and plaques in the extracranial
anatomy and instructing them in how arteries (Figure 13-1). Doppler mode
to scan with portable equipment. makes use of the Doppler effect in

Ultrasound
sonology to describe a variety of non-

invasive imaging and nonimaging
ultrasound techniques that have
established clinical value in evaluating
patients with stroke or those at risk for
stroke. The extracranial internal carotid,
common carotid, external carotid, and
vertebral arteries can be assessed by
cervical duplex (simultaneous presen-
Cervical duplex ultrasound (brightness
tation of B-mode image and Doppler
FIGURE 13-1 waveform) ultrasonography, while the
mode, horizontal plane). The common
carotid artery (CCA) is bifurcating into the middle cerebral, anterior cerebral, pos-
internal carotid artery (ICA) and external carotid artery
(ECA). Note an arterial branch originating from the ECA (red terior cerebral, ophthalmic, intracranial
asterisk). The presence of arterial branch is essential for the vertebral, and basilar arteries can be
ultrasound differentiation between cervical ECA (several
arterial branches) and cervical ICA (no arterial branch). investigated by transcranial Doppler
(TCD) or transcranial color-coded du-
plex sonography. Other specialized
KEY POINT measuring blood flow. Information tests that can be used to ascertain the
h The extracranial internal about blood direction and velocity is pathogenic mechanism of stroke or risk
carotid, common projected on the B-mode image, of stroke recurrence include emboli
carotid, external carotid,
encoded in colors. Spectral Doppler detection with or without contrast
and vertebral arteries
depicts a waveform containing infor- injection, vasomotor reactivity testing,
can be assessed by
mation about velocity, resistance, and and real-time spectral Doppler moni-
cervical duplex
(simultaneous
flow direction. Imaging improvement in toring during treatment or specific
presentation of B-mode has permitted the evaluation maneuvers (eg, head turn, blood pres-
brightness-mode image of the adult brain parenchyma and sure manipulation).
and Doppler waveform) opened new horizons in the imaging
ultrasonography, while of neurodegenerative disorders. Novel Ultrasound Assessment of
the middle cerebral, high-frequency probes have permitted Extracranial Arteries
anterior cerebral, high-quality imaging of peripheral Cervical duplex ultrasonography is a
posterior cerebral, nerves, providing morphologic infor- noninvasive neuroimaging modality
ophthalmic, intracranial mation that is complementary to the for the evaluation of both vessel wall
vertebral, and basilar neurophysiologic findings. However, features and blood flow parameters in
arteries can be it should be noted that despite recent cervical arteries. Cervical duplex ultra-
investigated by technologic advances, neurosonology
transcranial Doppler or
sonography provides real-time infor-
continues to remain highly operator mation about the presence of an
transcranial color-coded
dependent and requires extensive train- atherosclerotic plaque, including its
duplex sonography.
ing to acquire both the required theo- length, composition, protrusion and
retical knowledge and the necessary surface, range of resulting vascular
scanning skills. This article presents a stenosis or occlusion, presence of a
brief and practical overview of the dissection, and other significant imag-
main current applications of ultra-
ing findings in patients with acute
sound in neurology.
ischemic stroke (Table 13-1). Cervical
duplex ultrasonography can directly
CEREBROVASCULAR DISEASES visualize atherosclerotic plaque com-
A major cause of disability and death, position that can be classified based on
ischemic stroke ensues after occlusion its echogenicity. Uniformly hyperechoic
of extracranial or intracranial arteries. carotid plaques are mainly composed
This article uses the term neuro- of fibrotic tissue needed for plaque

KEY POINTS
h Cervical duplex
TABLE 13-1 Applications of Cervical Duplex Ultrasonography in
Patients With Acute Ischemic Stroke ultrasonography can
directly visualize
b Information about plaque composition and surface (eg, lipid, hemorrhage, atherosclerotic plaque
fibrous content, ulceration, superimposed thrombus) composition that can be
classified based on its
b Diagnosis of the degree of carotid artery stenosis (normal, 0Y49%,
echogenicity. Cervical
50Y69%, 70Y99%, near occlusion, occlusion)
duplex ultrasonography
b Diagnosis of the degree of vertebral artery stenosis (G50%, 950%, occlusion) also allows rapid
b Detection of intraluminal thrombus in cervical vessels detection of internal
carotid artery thrombosis
b Diagnosis of subclavian steal syndrome and differentiation
b Diagnosis/suspicion of uncommon causes of stroke (eg, cervical artery between chronic internal
dissection, fibromuscular dysplasia, aortic arch dissection) carotid artery occlusion
with or without preexisting
b Complementary information in the diagnosis of temporal arteritis
atheromatous stenosis.
b Indirect information for distal intracranial vessel occlusion
h Peak systolic velocity,
b Indirect information for heart rate and heart valves end-diastolic velocity,
and the systolic internal
b Diagnosis of other conditions not related to acute stroke (eg, carotid
body tumor) carotid artery/common
carotid artery velocity
ratio are essential
ultrasound parameters
stability. In contrast, heterogeneous be conducted with grayscale (B-mode), for North American
(and predominantly hypoechoic) power-mode, or color Doppler and Symptomatic Carotid
plaques consisting of matrix deposi- spectral Doppler ultrasound, and Endarterectomy Trial
tion, cholesterol accumulation, ne- reported using NASCET ranges of ICA grading ranges of
extracranial internal
crosis, calcification, and intraplaque stenosis (normal, 0% to 49%, 50% to
carotid artery disease.
hemorrhage are considered unstable, 69%, 70% to 99%, near occlusion,
being the source of artery-to-artery occlusion). A characteristic example of h Peak systolic velocity and
embolic strokes.1 severe (70% to 99%) ICA stenosis is end-diastolic velocity
must be assessed in the
Peak systolic velocity, end-diastolic presented in Case 13-1.
prestenotic, stenotic, and
velocity, and the systolic internal ca- Cervical duplex ultrasonography al-
poststenotic segments of
rotid artery (ICA)/common carotid ar- lows rapid detection of ICA thrombosis the vessel, and ultrasound
tery (CCA) velocity ratio are essential and differentiation from chronic ICA interpretation must refer
ultrasound parameters for grading the occlusion with or without preexisting to the North American
percentage of stenosis in extracranial atheromatous stenosis. These acute Symptomatic Carotid
carotid artery steno-occlusive disease. findings may prompt consideration of Endarterectomy Trial
Peak systolic velocity and end-diastolic carotid endarterectomy (Case 13-2). strata of internal carotid
velocity must be assessed in the Ultrasound diagnosis and classifica- artery stenosis.
prestenotic, stenotic, and poststenotic tion of vertebral artery stenosis is more
segments of the vessel. The Society of demanding. Vertebral artery asymme-
Radiologists in Ultrasound Consensus try is common, and a hypoplastic
Conference reached multidisciplinary vertebral artery may terminate in the
agreement on criteria to predict clini- posterior inferior cerebellar artery. An-
cally relevant strata of ICA stenosis atomic variants and abnormalities (eg,
corresponding to the North American stenosis, occlusion) of the contralateral
Symptomatic Carotid Endarterectomy vertebral artery influence vertebral
Trial (NASCET) criteria (Table 13-2).2 artery flow. Severe stenosis in the
All carotid artery examinations should carotid arteries may also affect blood

Ultrasound
TABLE 13-2 Peak Systolic Velocities, End-Diastolic Velocities, and Doppler Spectra With
Varying Degrees of Extracranial Internal Carotid Artery Stenosisa
Peak Systolic
ICA Stenosis Peak Systolic End-Diastolic Velocity ICA/
Range Velocity (cm/s) Velocity (cm/s) CCA Ratio Plaque
Normal G125 G40 G2 None
0Y49% G125 G40 G2 G50% diameter reduction
50Y69% 125Y230 40Y100 2Y4 Q50% diameter reduction
70Y99% 9230 9100 94 Q50% diameter reduction
Near occlusion High/low or Variable Variable Significant, detectable
undetectable lumen
Occlusion Undetectable NA NA Significant, no detectable
lumen
CCA = common carotid artery; ICA = internal carotid artery; NA = not applicable.
a
Modified with permission from Grant EG, et al, Radiology.2 B 2003 Radiological Society of North America. pubs.rsna.org/doi/full/10.1148/
radiol.2292030516.
KEY POINT flow in the vertebral artery due to minimal diastolic blood flow that con-
h Ultrasonography recruitment of collaterals. Vertebral curs with high-resistance bidirectional
may assist in the artery stenoses are most commonly Doppler signal. In B-mode imaging, a
diagnosis of carotid or located in the origin from the subcla- tapered lumen with a characteristic
vertebral artery vian artery (V0 segment) followed by string sign appearance may be shown,
dissection. Cervical
the atlas loop/intracranial segments, as well as a floating intimal flap. The
duplex ultrasonography
while intertransverse segments are less true lumen can be compressed by the
may detect reversed
systolic blood flow commonly affected. Criteria for verte- false lumen thrombus, and subse-
at the origin of the bral artery stenoses are not based on a quently a low-velocity Doppler wave-
vessel and absent or peak systolic velocity cutoff but on form can be recorded. The flow
minimal diastolic focal and significant peak systolic ve- direction in a patent false lumen may
blood flow that locity increase, since tortuosity of the fluctuate from forward to reverse or
concurs with proximal vertebral artery segment, ICA may be bidirectional. If a dissection is
high-resistance lesions, and vertebral artery asymmetry found ascending from the proximal
bidirectional may result in relatively high velocities. CCA, it indicates aortic dissection. In
Doppler signal. The velocity increase should be found patients with a distal cervical ICA
over a relatively short segment of the dissection (that has not descended to
vertebral artery with normal or de- the proximal ICA), a retromandibular
creased prestenotic and poststenotic high-velocity signal may be the only
velocities.7 Elongated and multiple ste- sign of dissection.8
noses in the vertebral artery may not Ultrasound detection of vertebral
produce focal velocity elevations, which artery dissection in the V2 through V4
could be a source of false-negative cer- segments (Figure 13-4) is challenging
vical duplex ultrasonography studies. since no well-defined and predictable
Ultrasonography may assist in the imaging findings have been identified.
diagnosis of carotid artery dissection. Absent blood flow, low bidirectional
Cervical duplex ultrasonography may flow, or low poststenotic velocities can
detect reversed systolic blood flow at be detected at the level of the atlas
the origin of the ICA and absent or loop, a frequent site of dissection. A

Case 13-1
A 58-year-old man with a history of hypertension, hypercholesterolemia, and smoking presented with
recurrent episodes of transient hemiparesis lasting between 20 and 40 minutes over the previous 2 days.
His blood pressure was 178/94 mm Hg, and his ABCD2 score (age, blood pressure, clinical features,
duration, presence of diabetes mellitus) was 4. He reported that he developed symptoms after standing
up or walking for a period longer than 30 minutes. Emergent neurosonology evaluation disclosed the
presence of hypoechoic material in the distal right internal carotid bulb coupled by the absence of flow
in color-mode display on cervical duplex ultrasound (Figure 13-2). Transcranial duplex sonography showed
the presence of collateral flow via ipsilateral ophthalmic artery flow reversal (Figure 13-2), while the
flow in the ipsilateral proximal middle cerebral artery was severely blunted (mean flow velocity of
60 cm/s, pulsatility index of 0.42; normal values being less than 100 cm/s and 0.6 to 1.1, respectively).
The diagnosis of acute internal carotid artery occlusion causing orthostatic hypoperfusion syndrome was
made.3 Digital subtraction angiography confirmed the presence of an acute right internal carotid artery
occlusion. Brain MRI with diffusion-weighted imaging excluded the presence of an acute infarction.
The patient was put in the head-down position and treated with IV isotonic fluids and the combination of
oral aspirin (100 mg) and clopidogrel (75 mg) while his systolic blood pressure was maintained at the
levels of 160 mm Hg to 180 mm Hg for the first 5 days of acute cerebral ischemia. The patient did not
develop any recurrent symptoms during his hospitalization.
FIGURE 13-2 Imaging of the patient in Case 13-1. Acute internal carotid artery occlusion originally
diagnosed by cervical duplex ultrasound (A) and subsequently confirmed by digital
substraction angiography (C). Note the presence of hypoechoic material in the
distal internal carotid artery bulb coupled by absence of flow in color-mode display. Transcranial
color-coded duplex sonography displays the presence of collateral flow via ipsilateral ophthalmic
artery flow reversal (B, detection of retrograde low-resistance flow in ipsilateral ophthalmic artery).
Comment. This case highlights the importance of neurosonology in identifying patients with acute cerebral
ischemia due to hypoperfusion caused by steno-occlusive intracranial or extracranial arterial disease. Acute
blood pressure lowering in this subgroup of patients may be harmful and cause further neurologic
deterioration. Putting the patient in the head-down position and maintaining a moderately elevated blood
pressure level appears to be the preferable therapeutic approach in patients with orthostatic transient ischemic
attacks or strokes caused by cerebral hypoperfusion distal to an extracranial or intracranial large vessel occlusion.4

Ultrasound
Case 13-2
A 64-year-old man with a history of hypertension, diabetes mellitus, coronary artery disease, and
smoking presented with a mild right hemiparesis 12 hours following symptom onset. His National Institute
of Health Stroke Scale (NIHSS) score was 3. Emergent neurovascular ultrasound disclosed the presence of
a heterogeneous plaque with an overlying thrombus in his left internal carotid artery (Figure 13-3)
causing severe stenosis (70% to 99% North American Symptomatic Carotid Endarterectomy Trial
range). Transcranial Doppler monitoring of the ipsilateral proximal middle cerebral artery recorded the
FIGURE 13-3 Imaging of the patient in Case 13-2. Cervical duplex ultrasound (A, B) depicts a
heterogeneous plaque (A, green arrowheads) with an overlying thrombus
(A, white arrowheads) causing a hemodynamically (70% or greater) significant
carotid artery stenosis. Note the presence of aliasing on color-mode display (A) and the
elevated peak systolic velocity (236 cm/s) and end-diastolic velocity (112 cm/s) on spectral
display (B). CT angiography (C, D) confirms ultrasound findings and depicts the presence of an
overlying thrombus protruding in the vessel lumen (C, red circle; D, white arrowhead). The
patient underwent emergent carotid endarterectomy, removing both atherosclerotic plaque
and overlying thrombus (E).

presence of high-intensity transient signals indicative of microembolism in real time. CT angiography
confirmed the ultrasound findings and depicted the presence of a large atherosclerotic plaque with an
overlying thrombus protruding in the left internal carotid artery lumen (Figure 13-3). Brain MRI with
diffusion-weighted imaging showed numerous small foci of restricted diffusion in the territory of
the left middle cerebral artery. Artery-to-artery embolism distal to a symptomatic carotid artery
stenosis was considered as the underlying mechanism of acute cerebral ischemia. The patient underwent
emergent carotid endarterectomy at 29 hours following symptom onset (Figure 13-3). He was discharged
on the fifth day of hospitalization with an NIHSS score of 1.
Comment. This case highlights the importance of neurosonology in identifying patients with
symptomatic carotid artery stenosis causing distal microembolization. These patients carry an
excessively high risk (nearly tenfold) of recurrent stroke5 and should undergo carotid endarterectomy
during the first 14 days after transient ischemic attack or nondisabling stroke.6 Neurosonology is a
noninvasive and inexpensive neuroimaging modality that can be rapidly applied at the bedside of
patients with acute cerebral ischemia; it may provide real-time diagnostic and prognostic information
to help make patient management decisions.
dissection causing stenosis at the V1 or cerebral arteriogram) should be

segment may be detected by ultra- performed even if ultrasound results
sound; absent blood flow may be are inconclusive.
found in the intertransverse segments, Takayasu arteritis presents with
and a localized broadening of a vessel smooth homogenous concentric thick-
diameter at V1 may be seen with se- ening of the arterial wall on B-mode
vere stenosis or occlusion. Direct visu- imaging in proximal cervical vessels
alization of intramural hematoma by (common carotid artery, innominate
ultrasound is rare; it can be easily missed artery, and subclavian artery), which
if no significant stenosis is evident or can be easily identified by cervical
if it is located outside an accessible duplex ultrasonography by the typi-
intratransverse arterial segment.9 When cal macaroni sign (Figure 13-5). In
a clinical suspicion of vertebral artery contrast to atherosclerotic disease,
dissection exists, further imaging work- patients with Takayasu arteritis have an
up (MRI with fat-saturation sequences affected CCA with sparing of the ICA
FIGURE 13-4 Extracranial vertebral artery (VA) segments on cervical duplex ultrasound. VA
origin (V0) from the subclavian artery is displayed on the right panel, the
pretransverse VA segment (V1) located proximally to the C6 transverse process
is displayed in the middle panel, and the transverse VA segment (V2) is displayed in the
left panel.
RVA = right vertebral artery.

Ultrasound
FIGURE 13-5 Cervical duplex ultrasound showing typical macaroni sign in the right common carotid artery (CCA)
of a 32-year old woman with Takayasu arteritis (A, B-mode). The macaroni sign represents smooth,
homogeneous, and moderately echogenic circumferential thickening of the arterial wall (red
arrowheads) that occurs in Takayasu arteritis. Note the elevation of velocities (peak-systolic velocity: 257 cm/s,
end-diastolic velocity: 76 cm/s) due to constriction of CCA lumen in color-mode display (B).
KEY POINT and external carotid artery. More- coded duplex sonography to provide
h Intracranial cerebral over, contrast-enhanced cervical du- real-time flow findings (Figure 13-7)
vasculature can be plex ultrasonography can reliably that are complementary to information
assessed by transcranial
identify vulnerable plaques at the provided by CT angiography (CTA) or
Doppler or transcranial
vessel wall lumen, by providing direct multimodal MRI. TCD is a diagnostic
color-coded duplex
sonography to provide
visualization of intraplaque neovas- method increasingly used for the
real-time flow findings cularization and improving delinea- diagnosis of cerebrovascular diseases
that are complementary tion of plaque ulcers. 10 Takayasu (Table 13-3). TCD identifies intracra-
to information provided arteritis may also present with subcla- nial stenoses, distal emboli, and col-
by CT angiography or vian steal syndrome caused by subcla- lateral flow and helps determine
multimodal MRI. vian artery stenosis. hemodynamic significance of extra-
Giant cell arteritis can present cranial or intracranial steno-occlusive
with stroke symptoms, typically of the lesions, monitor recanalization during
vertebrobasilar territory. In these cases, thrombolytic therapy in real time, deter-
the vertebral artery may rarely show mine the stroke pathogenic mechanism,
hypoechoic wall thickening on cervical and select the next and most appro-
duplex ultrasonography. An examina- priate step in patient management.13
tion of the superficial temporal artery A fast-track insonation protocol
with high-frequency 12-MHz to 15-MHz has been developed for rapid extra-
B - m o de transducers can detect cranial and intracranial artery eval-
hypoechoic circumferential thickening uation in the emergency setting of
(the halo sign) (Figure 13-6).11 The acute ischemic stroke to diagnose large
halo sign is moderately sensitive (68%) artery intracranial steno-occlusive le-
but highly specific (91%) when present sions, recanalization, and reocclusion.14
at the superficial temporal artery and The choice of fast-track insonation
can also be used to guide biopsy as steps is determined by clinical localiza-
well as monitor treatment.12
tion of the ischemic arterial territory.
Ultrasound Assessment of Most studies can be accomplished
Intracranial Arteries within minutes by experienced sonog-
Intracranial cerebral vasculature can be raphers at the bedside in parallel with
assessed by TCD or transcranial color- the neurologic examination in the

FIGURE 13-6 Ultrasound findings in giant cell arteritis. Extracranial duplex ultrasound of the left superficial temporal artery
(STA) shows reduced color filling and vessel-wall thickening in the form of a dark halo (hypoechoic
circumferential thickening) in axial (A, red arrows) and longitudinal (B, blue arrow) planes. Note the normal
color filling in the right STA in axial (C) and longitudinal (D) planes. The ultrasound findings in the left STA wall (unilateral
halo sign) are indicative of giant cell arteritis. The diagnosis is confirmed by magnetic resonance angiography (MRA) (E)
depicting unilateral severe left STA stenosis/obstruction (red arrow) and temporal artery biopsy showed inflammatory
infiltrates (including giant cells) involving the entire vessel wall with marked intimal thickening. Note the normal appearance
of the right STA (E, blue arrow).
emergency department without evaluating patients with acute ischemic

delaying treatment. Overall, bedside stroke with acute proximal arterial oc-
TCD examination in the emergency clusion or stenosis of an intracranial
department had a satisfactory agree- artery (Figure 13-8). Its efficacy de-
ment to brain CTA in the evaluation of pends on symptomatic artery localiza-
patients with acute ischemic stroke. tion, onset-to-insonation time, and
TCD is a highly accurate and reliable acute ischemic stroke severity. TCD
bedside diagnostic examination for can reveal artery occlusion in more
FIGURE 13-7 Depiction of proximal intracranial arteries of the circle of Willis in a healthy individual using
transcranial color-coded duplex sonography (A). The intensity mode, or power mode,
allows better visualization of the arterial flow (B).
ACA = anterior cerebral artery; MCA = middle cerebral artery; PCA = posterior cerebral artery.

Ultrasound
TABLE 13-3 Applications of Transcranial Doppler or Transcranial

Color-Coded Duplex Sonography in Patients With Acute
Ischemic Stroke
b Bedside confirmation of vascular origin of the presenting symptoms and

determination of underlying stroke mechanism
b Fast detection and localization of occlusion/stenosis
b Mapping of the collateral circulation
b Detection of cerebral embolism in real time and quantification of
right-to-left shunt
b Real-time monitoring of recanalization in patients treated with systemic
thrombolysis
b Selection of patients for intraarterial reperfusion procedures
b Monitoring of rescue intraarterial procedures (eg, detection of
reocclusion, air embolism, hyperperfusion syndrome)
b Detection of supratentorial intracerebral hemorrhage at the bedside
following acute reperfusion therapies (application of transcranial
color-coded duplex sonography)
b Potential augmentation of clot lysis and clinical recovery
(sonothrombolysis)
than 90% of patients with acute ische- Ultrasound may also assist in map-
mic stroke treated with recombinant ping of collateral cerebral circulation.
tissue-type plasminogen activator Efficient collateral circulation helps
within 3 hours from symptom onset maintain cerebral perfusion in the set-
when NIHSS score is 10 or more.14 ting of acute ischemic stroke and is
FIGURE 13-8 Transcranial Doppler findings in intracranial stenosis. A, Power-motion-mode transcranial Doppler
depicts the presence of a hemodynamically (70% or greater) significant right proximal middle
cerebral artery stenosis. Note the presence of elevated mean (141 cm/s) and peak (209 cm/s)
systolic flow velocities and the presence of systolic bruit on power-motion-mode (depicted as systolic flow gaps) and
spectral (circles) displays. B, Digital substraction angiography confirmed the diagnosis of severe (79%) proximal
middle cerebral artery stenosis (arrow).

KEY POINTS
associated with reduced infarct volume TIBI flow grades were found to corre- h Transcranial Doppler
and better functional outcome. The late strongly with stroke severity, assesses recanalization
main collateral pathways are the ante- mortality, and clinical improvement. and potential reocclusion
rior and posterior communicating ar- Rapid arterial recanalization is associ- in real time in patients
teries, reversed ophthalmic artery, and ated with better short-term improve- with acute ischemic
reversed basilar artery. These channels ment. On the contrary, slow flow stroke treated with
come into play only if a change occurs improvement and dampened TIBI systemic or intraarterial
in pressure gradients between two flow signals are less favorable prog- reperfusion therapies.
anastomosing arterial systems. TCD nostic signs that indicate the need for h A novel application of
can provide real-time information on further reperfusion therapies, such as neurosonology is the
the blood flow direction and velocity mechanical thrombectomy. TIBI flow assessment of an
intracranial arterial steal
of the collateral pathways. Activation grading can be used in follow-up after
syndrome and evaluation
of a collateral flow pathway implies initial CTA assessment to determine if of vasomotor reactivity
the presence of a flow-limiting lesion the patient still has a persisting occlu- of intracranial arteries.
proximal to the origin of the collateral sion or reocclusion or had full recanali-
channel.15 zation without clinical improvement to
TCD and transcranial color-coded avoid the need for repeat CTA in acute
duplex sonography may assess recan- ischemic stroke within the time frame
alization and potential reocclusion in for mechanical thrombectomy.
real time in patients with acute ische- A novel application of neurosonology
mic stroke treated with systemic or is the assessment of intracranial arterial
intraarterial reperfusion therapies. steal syndrome and evaluation of vaso-
Spontaneous recanalization of a mid- motor reactivity of intracranial arteries.
dle cerebral artery (MCA) occlusion Once a feeding vessel is blocked,
occurs at a rate of approximately 6% compensatory distal vasodilation de-
per hour after symptom onset, and IV creases resistance to attract blood flow
tissue plasminogen activator doubles through collateral channels. Counter-
the chance of complete recanalization intuitively, this hemodynamic phenom-
to almost 13% during the first hour enon may, in turn, lead to further
of treatment, with a median time of perfusion decrease of ischemic brain
35 minutes after the bolus infusion.16 tissues (in which arteries cannot dilate
TCD provides a noninvasive bedside any further). This lack of further dilation
tool for real-time monitoring of arterial may not counteract the steal of blood
recanalization. The thrombolysis in by normally perfused areas that main-
brain ischemia (TIBI) flow-grading tain the capability for vasodilation with
system was developed to evaluate additional stimuli. This hemodynamic
residual flow noninvasively and in real steal phenomenon can be detected on
time in analogy to the thrombolysis in TCD in patients with acute ischemic
myocardial infarction (TIMI) flow stroke and has been termed reversed
grades.17 TIBI grade 5 corresponds Robin Hood syndrome in analogy with
to normal blood flow, grade 4 to stenotic ‘‘rob the poor to feed the rich.’’18
blood flow (accelerated), grade 3 to A TCD vasomotor study is a simple
dampened blood flow (decreased ve- method to assess vasomotor reactivity
locities compared to the contralateral in acute ischemic stroke and can iden-
intracranial artery), grade 2 to blunted tify patients at high risk for stroke in
blood flow (flattened waveform), the setting of symptomatic or asymp-
grade 1 to minimal blood flow (absent tomatic extracranial internal carotid
diastolic flow), and grade 0 to no flow. artery stenosis or occlusion. During this

Ultrasound
KEY POINTS
h The transcranial noninvasive test, TCD is used to mea- benefit from prophylactic transfusion
Doppler bubble sure velocity response to voluntary (Table 13-4).13 Ischemic strokes in
test is more sensitive breath-holding for 30 seconds, which children with sickle cell anemia primar-
than transthoracic induces hypercapnia and serves as a ily result after stenosis of the MCA or
echocardiography (with natural vasodilatory stimulus.19 distal intracranial ICA, and some chil-
or without contrast Another indication for TCD is the dren may develop moyamoya syn-
injection) in detection of noninvasive detection of cerebral em- drome. The Stroke Prevention in
a right-to-left shunt bolization and presence of right-to-left Sickle Cell Anemia (STOP) trial showed
through a patent shunts, such as patent foramen ovale, that time-averaged maximum mean
foramen ovale. as a conduit of paradoxical embolism. velocity greater than 200 cm/s in the
h Transcranial Doppler Microembolic signals can be detected terminal ICA or MCA is associated with
stratifies the risk of during TCD monitoring in patients with a 10% annual risk for stroke.13 Trans-
patients with sickle cell acute ischemic stroke or transient is- fusion to lower hemoglobin S concen-
anemia and those in chemic attacks as signals of high inten- trations to less than 30% of total
need of blood
sity and short duration within the hemoglobin in these children decreases
transfusions for primary
Doppler spectrum; they represent solid time-averaged maximum mean for
stroke prevention. Those
who meet transcranial
or gaseous particles within the blood several weeks, reduces blood coagu-
Doppler criteria for blood flow. Although not causing immediate lation biomarkers,22 and, most impor-
transfusions should stay symptoms, these embolic signals are tant, reduces the relative risk of stroke
on transfusions since clinically important, as they can identify by 92%. Children at risk continue to
these children remain an embolic mechanism and point to the benefit from transfusions and should
at high risk of stroke source of embolism in patients with continue to receive treatment to sustain
if transfusions stroke or transient ischemic attack. the primary stroke prevention benefit,
are discontinued. TCD is the gold standard of detection, as shown in the STOP 2 trial.23 It should
h One of the first quantification, and localization of cere- be noted that not all pediatric strokes
applications of bral embolization in real time. Patients in sickle cell anemia are predicted by
transcranial Doppler in with symptomatic carotid artery steno- TCD as other mechanisms come into
clinical use has been sis and microembolic signals on TCD play, such as artery dissection, embo-
the identification of were found to benefit from early ca- lism, small artery infarction, and
cerebral vasospasm rotid endarterectomy.20 hypercoagulable states.
after subarachnoid
Paradoxical embolism is a possible One of the first applications of TCD
hemorrhage.
mechanism of acute ischemic stroke in in clinical use has been the identifica-
patients with right-to-left shunts. The tion of cerebral vasospasm after sub-
TCD bubble test is equivalent or even arachnoid hemorrhage (SAH). Blood
superior to both transthoracic and extravasation has a toxic effect on
transesophageal echocardiography in brain arteries and leads to lumen
detection of right-to-left shunt through narrowing that, when severe enough,
a patent foramen ovale. 13 Power- can lead to ischemic lesions. TCD can
motion-mode Doppler may further estimate the severity of vasospasm by
increase the yield. TCD criteria for detecting increased blood velocities
grading right-to-left shunts have been in areas of vasospasm (Table 13-4).13
proposed to distinguish incidental Baseline TCD measurements are
from pathogenic right-to-left shunts in obtained, and the patient is monitored
patients with acute ischemic stroke.21 every day or every other day through-
TCD is a validated diagnostic tool for out Day 7 (all grades) and Day 10 (Hunt-
children with sickle cell anemia be- Hess grades 2+) or until vasospasm
tween the ages of 2 and 16 years who resolution. It is recommended that
have not sustained a stroke to identify extracranial internal carotid artery ve-
those at high risk for stroke who could locities be recorded to adjust for

TABLE 13-4 Established Clinical Indications and Expected Outcomes of Transcranial Doppler
Testing in Sickle Cell Anemia, Subarachnoid Hemorrhage, and Brain Deatha
Broad Indication Specific Indications Expected Outcomes

Sickle cell anemia Children Robust first-ever stroke risk reduction based on transcranial
Doppler (TCD) criteria for the need of blood transfusion
and continuing use of blood transfusions.
Subarachnoid Days 2Y5 TCD can detect development of vasospasm days before it
hemorrhage can become clinically apparent. This information can be
used by intensivists to step up hemodynamic management
of these patients.
Days 5Y12 TCD can detect progression to the severe phase of spasm
when development of the delayed ischemic deficit due to
perfusion failure through the residual lumen is the greatest.
This information can help in planning interventions (eg,
angioplasty, nicardipine infusions).
Day 12Yend of ICU stay TCD can document spasm resolution after treatment or
intervention, sustainability of vessel patency, and infrequent
cases of late or rebound vasospasm development at the end
of the second or into the third week after subarachnoid
hemorrhage. At all specific time intervals, TCD is able to detect
changes in resistance to flow that may indicate increase in
the intracranial pressure and necessitate ventriculostomy.
Suspected brain Increased intracranial TCD can rule out cerebral circulatory arrest if positive
death pressure, mass effect, diastolic flow is detected at any intracranial pressure values.
herniation TCD can confirm the clinical diagnosis of brain death by
demonstrating complete cerebral circulatory arrest in both
middle cerebral arteries and the basilar artery. TCD offers
serial noninvasive assessments and can minimize the
number of nuclear flow studies needed to confirm arrest
of cerebral circulation.
a
Modified with permission from Alexandrov AV, et al; American Society of Neuroimaging Practice Guidelines Committee, J Neuroimaging.13
B 2010 American Society of Neuroimaging. onlinelibrary.wiley.com/doi/10.1111/j.1552-6569.2010.00523.x/full.
increased velocities due to hyperdynamic hypertension-euvolemia or invasively

states. By recording velocity in the MCA with balloon angioplasty or intraar-
and the ipsilateral extracranial ICA, a terial vasodilators. Distal vasospasm
Lindegaard ratio between mean flow can be indirectly diagnosed when focal
velocities (MCA/ICA) can be calculated; pulsatile flow (pulsatility index greater
a ratio greater than 6 indicates severe than 1.2) is detected.24 Similar to a
spasm. Secondary findings, such as rapid Lindegaard ratio, a Soustiel ratio (mean
daily mean flow velocity rise (greater flow velocity of basilar artery/extracranial
than 20% or greater than 65 cm/s) and vertebral artery assessed at the first
early appearance of MCA mean flow cervical level) greater than 3 indi-
velocity of greater than 180 cm/s, are cates severe basilar artery vasospasm
associated with adverse outcomes in after SAH.25
patients with SAH. Early recognition Brain death is a clinical diagnosis
of severe vasospasm can lead to the that can be supported by TCD find-
prompt treatment of vasospasm with ings, given the ability of TCD to detect

Ultrasound
KEY POINTS
h Brain death is a clinical cerebral circulatory arrest (Table 13-4). evaluated in three predetermined exam-
diagnosis that can be Increased intracranial pressure causes ination planes: mesencephalic, thalamic,
supported by transcranial increased pulsatility, followed by re- and lateral ventricular (Table 13-5).
Doppler, given the ability duction, elimination, and reversal of The midbrain appears hypoechoic in
of transcranial Doppler to diastolic flow. Finally, a reverberating transcranial sonography and is readily
detect cerebral flow pattern emerges, and, at that point, recognized by its characteristic but-
circulatory arrest. TCD can confirm complete cerebral terfly pattern, surrounded by the hyper-
h The midbrain appears circulatory arrest (Figure 13-9), offering echoic basal cisterns. The substantia
hypoechoic in transcranial a pathophysiologic explanation of clin- nigra appears as a thin hyperechoic
sonography, surrounded ical progression to brain death. TCD has strip with total surface not exceeding
by the hyperechoic basal received a Class A, Level II evidence rat- 0.20 cm2 in normal subjects. In 87% of
cisterns, while the ing for determining cerebral circulatory
substantia nigra appears
patients with Parkinson disease (PD),
arrest/brain death by the American Aca-
as a thin hyperechoic strip the substantia nigra shows increased
demy of Neurology.26 False negatives
with total surface not echogenicity (Figure 13-10) as com-
exist, especially when time has elapsed
exceeding 0.20 cm2 in pared to 12% in controls.28 Hyperecho-
between brain death and TCD examina-
normal subjects. genicity is more pronounced in the side
tion, but specificity remains high (higher
h Increased substantia of the midbrain contralateral to the
than 95%). A recent meta-analysis in-
nigra hyperechogenicity
cluding 22 eligible studies (1671 pa- side of predominance of extrapyramidal
can be detected with symptoms. In a minority of patients
tients total) showed that TCD had a
transcranial parenchymal with PD, around 10%, normal echo-
sonography in
pooled sensitivity and specificity of
90% and 98%, respectively, for the genicity of the substantia nigra is pre-
approximately 90% of
diagnosis of brain death.27 served, a finding that could be because
patients with idiopathic
Parkinson disease.
of a different genetic background or
MOVEMENT DISORDERS secondary parkinsonism.29 Increased
Technologic advances in ultrasound iron deposition and reduction of fer-
have led to improved brain parenchy- ritin levels have been described in
mal imaging that has permitted novel autopsy studies of the substantia nigra
uses of transcranial sonography in neu- of patients with PD; iron is thus be-
rologic disorders. The echogenicity and lieved to bind to alternative proteins
surface of specific brain structures are and result in neurotoxicity locally.30
FIGURE 13-9 Power-motion-mode transcranial Doppler showing reverberating flow in middle cerebral arteries both
in power-motion-mode (red bands corresponding to antegrade flow, blue bands corresponding to
retrograde flow) and spectral displays in a patient with cerebral circulatory arrest.

TABLE 13-5 Standardized Examination Planes and Cerebral Structures to Be Evaluated
in Patients Diagnosed With Movement Disorders
Examination Plane Structure Normal Findings Abnormal Findings

Mesencephalic plane Substantia nigra Echogenicity: weak Size of echoic area 90.2 cm2:
medium hyperechogenicity
Size of echoic area: Size of echoic area 90.25 cm2:
G0.2 cm2 significant hyperechogenicity
Red nucleus Echogenicity: medium Unknown
to significant
Midbrain raphe Echogenicity: medium Reduced echogenicity
to significant (hypoechoic to anechoic)
Thalamic plane Thalamus Echogenicity: hypoechoic Increased echogenicity
to isoechoic (hyperechoic)
Lentiform nucleus Echogenicity: isoechoic Increased echogenicity
(hyperechoic)
Caudate nucleus Echogenicity: isoechoic Increased echogenicity
(hyperechoic)
Third ventricular Age G60 years: G7 mm Age G60 years: 97 mm
diameter
Age 960 years: G10 mm Age 960 years: 910 mm
Lateral ventricular plane Lateral ventricular Age G60 years: G19 mm Age G60 years: 919 mm
diameter
Age 960 years: G22 mm Age 960 years: 922 mm
When extrapyramidal symptoms related with markedly increased risk KEY POINT
become apparent in PD, 60% to 70% for PD development.33 h Substantia nigra
of nigrostriatal neurons have been Neurosonology may provide nonin- hyperechogenicity may
serve as a preclinical
lost. As a consequence, a preclinical vasive information for the differential
marker of idiopathic
diagnosis of PD is critical for the diagnosis of extrapyramidal disorders. parkinsonism.
research and development of neu- Differentiating PD from other neuro-
roprotective therapies. Large-scale degenerative disorders presenting
population screening is not feasible, with parkinsonism, such as multiple
but in relatives of patients with PD, system atrophy, progressive supranu-
who are at higher risk for developing clear palsy, dementia with Lewy bod-
the disease, substantia nigra hyper- ies, and corticobasal degeneration,
echogenicity is present in 45%.31 An- can still be challenging despite re-
other subgroup at risk for PD is markable progress in brain imaging.34
patients with depression; in this group, Definite diagnosis of the aforemen-
an increased incidence of substantia tioned disorders necessitates autopsy,
nigra hyperechogenicity has been de- and, in many instances, clinical diag-
scribed.32 In a cohort of 1847 asymp- nosis is proved erroneous by post-
tomatic subjects over 50 years of age, mortem findings. Correct diagnosis is
substantia nigra hyperechogenicity cor- crucial not only for treatment, but

Ultrasound
KEY POINTS
h Peripheral nerve
ultrasound may offer
structural information
regarding the underlying
etiology of entrapment
neuropathies.
Ultrasound findings are
complementary to
information offered by
neurophysiologic studies.
h Ultrasonography of a
peripheral nerve
examines five parameters:
(1) cross-sectional area
at certain sites of clinical
interest, (2) variability
of the cross-sectional
area along its course,
(3) echogenicity,
(4) vascularity, and
(5) mobility.
FIGURE 13-10 Transcranial sonography in a patient

with idiopathic Parkinson disease at axial
midbrain plane. Note the butterfly
appearance of midbrain (A, red arrow) and the presence
of mild ipsilateral substantia nigra hyperechogenicity
(B, green asterisk; planimetric measurement of substantia
nigra echoic area: 0.227 cm2 [normal reference value
G0.20 cm2, moderate substantia nigra hyperechogenicity
0.20 cm2 to 0.25 cm2, severe substantia nigra
hyperechogenicity 90.25 cm2]).
also for creating homogenous cohorts PNS that is complementary to electro-

for clinical trials. As a consequence, a physiologic studies. Normal peripheral
great need exists for novel noninva- nerves have a tubular form, with alter-
sive diagnostic methods. Transcranial nating hypoechoic (nerve fibers) and
sonography, in conjunction with clin- hyperechoic (perineurium) zones that
ical characteristics, has demonstrated give the impression of a honeycomb
high sensitivity for the differential pattern (Figure 13-11). Five parame-
diagnosis of movement disorders.35 ters of a peripheral nerve are exam-
Transcranial sonography findings in ex- ined: (1) cross-sectional area (CSA) at
trapyramidal disorders are summarized certain sites of clinical interest, (2) va-
in Table 13-6. riability of the CSA along its course,
(3) echogenicity, (4) vascularity, and
PERIPHERAL NERVOUS SYSTEM (5) mobility.
Ultrasonography of the peripheral
nervous system (PNS) is a noninvasive Entrapment Neuropathies
diagnostic method that is increasingly Peripheral nerve ultrasound may be
being used in clinical practice. It pro- particularly useful in the diagnosis of en-
vides a morphologic evaluation of the trapment neuropathies (Table 13-7).36,37

TABLE 13-6 Ultrasound Findings of Brain Parenchyma in Healthy Individuals and in Those With
Neurodegenerative Disease
Increase Increase of
Substantia Lentiform Caudate of Third Lateral
Nigra Nucleus Nucleus Ventricular Ventricular
Condition Hyperechogenicity Hyperechogenicity Hyperechogenicity Diameter Diameter
Healthy individuals Rare Rare Rare Very rare Rare
960 years old
Idiopathic Almost always Rare Often Never Very rare
Parkinson observed
disease
Multiple system Very rare Almost always Often Never Very rare
atrophy observed
Progressive Rare Almost always Almost always Almost Often
supranuclear palsy always
Corticobasal Almost always Almost always Almost always Never Rare
degeneration observed
Dementia with Almost always Rare Almost always Never Often
Lewy bodies observed
Carpal tunnel syndrome. Carpal within normal values.37 One of the KEY POINT
tunnel syndrome is the entrapment latest applications of neuromuscular h The most common
neuropathy that has been most exten- ultrasound is the preoperative detection ultrasound findings seen
sively studied with ultrasound. The in patients with
of persistent median artery or bifid
symptomatic carpal
most common ultrasound findings de- median nerve that have been reported tunnel syndrome include
tected in patients with symptomatic as causes of atypical carpal tunnel enlarged cross-sectional
carpal tunnel syndrome include: syndrome.38 area of the median nerve
& Enlarged CSA of the median nerve Radial neuropathy. The most com- proximal to the edge of
proximal to the edge of the mon causes of compressive neuropa- the flexor retinaculum,
flexor retinaculum thy of the deep motor branch of the increased wrist to forearm
& Increased wrist to forearm radial nerve are repetitive overuse of the swelling ratio,
swelling ratio forearm (repetitive pronation-supination hypoechogenicity and
disturbed fascicular echo
& Hypoechogenicity and disturbed or flexion-extension). The most com-
structure, reduced
fascicular echo structure mon ultrasound findings are CSA en- slippage of the nerve after
& Reduced slippage of the nerve largement of the posterior inferior finger flexion, and
after finger flexion nerve at the proximal portion of increased vascularity.
& Increased vascularity the compression site, hyperemia of
A diagnostic algorithm that takes the nerve, and echo difference of the
into consideration CSA of the median dorsal extensor muscles caused by
nerve at the wrist and the forearm denervation.37,39
presents similar sensitivity and speci- Fibular neuropathy. Entrapment
ficity to electrophysiologic studies.36 neuropathy of the common fibular
However, in some cases of severe and nerve is usually located at the fibular
advanced carpal tunnel syndrome re- head region. Although reduction of mo-
sulting in nerve atrophy, CSA could be tor conduction velocity and presence

Ultrasound
FIGURE 13-11 Median nerve ultrasound. A, Peripheral nerve ultrasound depicts a transverse view of a normal median nerve
(circled with dotted lines) at the wrist. The nerve appears with normal echotexture exhibiting a honeycomb pattern
and with a normal cross-sectional area (CSA) of 0.07 cm2. B, The same nerve is depicted in sagittal
view, exhibiting no signs of entrapment (dotted lines). C, Peripheral nerve ultrasound depicting a transverse view of the wrist of a
patient with carpal tunnel syndrome. The median nerve appears enlarged (circled with dotted lines) (CSA = 0.18 cm2, normal
value G0.11 cm2) and the echotexture has changed to hypoechoic with loss of the regular honeycomb pattern. D, Sagittal view
of the same nerve shows the structural entrapment and consecutive enlargement shortly before the constriction (dotted lines).
of conduction block are frequent elec- method for evaluating cervical root
trophysiologic findings, neuromus- lesions. CSA of the clinically affected
cular ultrasound may add useful cervical nerve roots are increased
diagnostic data concerning the etiology compared to the unaffected sides and
of entrapment: intraneural ganglia, correlate with symptom duration.41
ganglion cyst, neurofibroma, or hema-
toma. Common pathologic ultrasound Brachial Plexopathies
findings include increased CSA of the Ultrasound imaging of the brachial
nerve at the fibular head or proximally plexus is routinely used to perform
and increased fibular to popliteal fossa nerve block, but diagnostic applica-
swelling ratio.37,40 tions are growing fast. High specificity
Cervical radiculopathy. Although and fair sensitivity of ultrasound in
MRI remains the gold standard for brachial plexus pathology has been
diagnosing cervical radiculopathy, so- reported, especially for the detection
nography provides an alternative of mass lesions.42 Ultrasound may

TABLE 13-7 Overview of the Most Common Ultrasound Findings in
Entrapment Neuropathiesa
Entrapment Neuropathy Ultrasound Findings

Carpal tunnel syndrome Cross-sectional area (CSA) 90.11 cm2
Wrist to forearm ratio 91.4
Reduced echogenicity
Increased vascularity
Reduced mobility
Cubital tunnel syndrome CSA 90.09 cm2
Elbow to upper arm ratio 91.4
Increased echogenicity of epineurium
Luxation/subluxation
Radial nerve compression CSA 90.06 cm2
Fibular nerve compression CSA 90.12 cm2
Popliteal fossa to fibular head ratio 91.4
Cervical radiculopathy Side-to-side difference ratio 91.5
a
Modified with permission from Kerasnoudis A, Tsivgoulis G, J Neuroimaging.37 B 2015 American
Society of Neuroimaging. onlinelibrary.wiley.com/doi/10.1111/jon.12261/abstract.
reveal rupture, swelling, or loss of the nerve conduction studies of the phrenic
internal texture of the brachial plexus nerve.44
in traumatic lesions and may assist in
the diagnosis of radiation plexitis, Inflammatory Polyneuropathies
tumor invasion (Pancoast tumor), neu- PNS ultrasound may also offer diag-
rogenic tumors, and Parsonage-Turner nostic information in patients with in-
(also known as neuralgic amyotrophy flammatory polyneuropathies.37 The
or brachial neuritis) and thoracic out- main applications of neurosonology
let syndromes.43 in the diagnostic evaluation of inflam-
matory polyneuropathies are summa-
Phrenic Neuropathies rized below.
Besides enhancing the accuracy of Chronic inflammatory demyelinat-
needle positioning during EMG of ing polyradiculoneuropathy. Brachial
the diaphragm, ultrasound may reveal plexus hypertrophy and multifocal
atrophy (decrease of absolute thickness) peripheral nerve hypertrophy can be
or decreased contractility (decrease in seen on ultrasound images in patients
thickening ratio at maximal inspiration) with chronic inflammatory demyelin-
of the diaphragm, providing additional ating polyradiculoneuropathy (CIDP),
information to diaphragmatic EMG and probably due to recurrent episodes

Ultrasound
of demyelination and remyelination detecting focal nerve enlargement in

that lead to the classic onion-bulb his- MMN and differentiating this condition
tologic appearance of the nerves. In- from amyotrophic lateral sclerosis.48
creased intranerve CSA variability in Peripheral nerve involvement is a
several peripheral nerves has also been common complication of systemic
reported. The degree of correlation vasculitis and presents as a painful
between sonographic and electrophys- sensorimotor polyneuropathy affect-
iologic findings in CIDP still remains ing primarily the lower limbs or as a
unclear, and neither study correlates mononeuritis multiplex. Diffuse thick-
sufficiently with functional disability.45 ening of peripheral nerves, primarily
Nerve ultrasound scores have been de- of the lower limbs, and reduction of
veloped to distinguish CIDP of sub- nerve diameter after corticosteroid
acute or progressive onset from therapy have been described using
Guillain-Barré syndrome (GBS). A sum ultrasound.49 Abnormal ultrasound
score of 2 points or more on the findings have been reported in pa-
Bochum ultrasound score has sensi- tients with paraproteinemia, and path-
tivity of 80% and specificity of 100% ologic values of both of the nerve CSAs
for the distinction of subacute CIDP in various peripheral nerves have been
from GBS. The score is more sensitive found in patients with antiYmyelin-
than both classic electrophysiologic associated glycoprotein antibodies
and clinical parameters in diagnosing (MAG) polyneuropathy.50
the early onset of CIDP.46 In addition,
a distinction of CIDP from multifo- CONCLUSION
cal motor neuropathy (MMN) or TCD and cervical duplex ultrasonogra-
multifocal acquired demyelinating phy are two easily repeatable nonin-
sensory and motor neuropathy vasive diagnostic tests that can be
(MADSAM) can be made with the performed at the bedside and may
Bochum ultrasound score. provide hemodynamic information in
Guillain-Barré syndrome. Both pe- real time. Both tests broaden the
ripheral nerve and cervical root pa- abilities of stroke physicians to rapidly
thology during the early stage of GBS evaluate patients with stroke, deter-
have been described with ultrasonog- mine the likely mechanism of stroke,
raphy, but nerve ultrasound findings and decide on acute reperfusion and
seem to show no significant correla- secondary prevention therapies. Tran-
tion to electrophysiologic findings or scranial parenchymal sonography has
functional disability in patients with recently been developed as a valuable
GBS.47 However, increased CSF protein supplementary tool in the diagnosis
and reduced compound muscle action and differential diagnosis of move-
potential amplitudes in motor conduc- ment disorders by providing reliable
tion studies appear to predict both the structural information on the substantia
functional outcome and the develop- nigra, basal ganglia, and ventricular
ment of pathologic nerve ultrasound system. Peripheral nerve ultrasound is
changes in GBS.37 a noninvasive and readily available
Other neuropathies. Nerve ultra- modality that may offer structural in-
sound abnormalities in MMN appear as formation regarding the underlying
a multifocal pattern of nerve enlarge- etiology of entrapment neuropa-
ment at sites with or without clinical or thies that is complementary to the
electrophysiologic abnormalities. Nerve findings offered by neurophysio-
ultrasound is a useful method for logic studies.

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Review Article
Potential Safety Issues

Laszlo L. Mechtler, DENT
Neurologic Institute, 3980
Sheridan Dr, Ste 300,
Amherst, NY 14226,
lmechtler@dentinstitute.com.
Related to the Use of
Dr Pinter receives
research/grant support from
the Harry Dent Family
Gadolinium-based
Foundation Inc. Dr Klein has
received personal compensation
as a coauthor and editor and
for serving on the editorial
Contrast Agents
board of McGraw-Hill and as Nandor K. Pinter, MD; Joshua P. Klein, MD, PhD, FANA, FAAN;
a consultant for Advance
Medical and Best Doctors, Inc.
Dr Klein has given expert
medical testimony for
Anaesthesia Associates of ABSTRACT
Massachusetts and
HeplerBroom LLC. Purpose of Review: This article reviews recent research on gadolinium deposit
Dr Mechtler has received formation in the brain linked to contrast-enhanced MRI studies.
serving as board advisor for
Recent Findings: Human and animal studies have confirmed the presence of
Supernus Pharmaceuticals, Inc; gadolinium in the brain following the serial administration of gadolinium-based con-
for serving as guest editor of trast agents. This is a relatively new and growing field of research primarily driven by
Current Pain & Headache
Reports and Neurologic Clinics;
concerns regarding unknown and potentially harmful side effects of gadolinium-based
as a speaker for Allergan, contrast agents. Retrospective observational in vivo studies in humans demonstrated
Pernix Therapeutics, and Teva T1 shortening effects in the brain parenchyma resulting from gadolinium exposure.
Pharmaceutical Industries Ltd;
and as a consultant for Green
These studies were followed by postmortem human and animal studies. Evidence
Grass Advisors. Dr Mechtler exists that gadolinium may cause deposits in the brain and that this may occur in-
provided expert consultation dependently of impaired renal function and in the presence of an intact blood-brain
for legal testimony for
DOPF, P.C.
barrier. Gadolinium deposition has been linked primarily with the use of linear, rather
Unlabeled Use of than macrocyclic, gadolinium-based contrast agents.
Products/Investigational Summary: The formation of gadolinium deposits and its implications have been the
Use Disclosure: focus of only a small number of research groups. The currently available data must be
Drs Pinter, Mechtler, and
Klein report no disclosures. verified, and the potential factors that may be linked to this phenomenon and the
* 2016 American Academy clinical significance must be explored. Depending on future findings, changes in the
of Neurology. clinical application of gadolinium-based contrast agents may be expected.
INTRODUCTION agents have been associated with neph-

Every drug has its potential side effects. rogenic systemic fibrosis.1 Nephrogenic
This is just as true for contrast agents systemic fibrosis is a potentially fatal
used in imaging studies, such as iodine- systemic fibrosing disease that develops
based contrast agents used in x-ray and in patients with severely impaired renal
CT and gadolinium-based contrast function following the administration
agents used in MRI, as for therapeutic of gadolinium. It almost exclusively
drugs. Beside the well-known adverse occurs when the glomerular filtration
reactions that are more general and rate is under 30 mL/min. The vast
more or less the same regardless of the majority of the reported unconfounded
type of contrast medium, such as hyper- single-agent cases have been related
sensitivity reactions, the contrast agents to contrast agents with a linear
have unique side effects as well. For molecular structure (gadodiamide 78%,
example, gadolinium-based contrast gadopentetate dimeglumine 20%,

KEY POINT
gadoversetamide less than 20%), while The first article concluding that these h Nephrogenic systemic
those with macrocyclic structure have hyperintensities (observed in the den- fibrosis is a potentially
been associated with only a few cases, tate nucleus and globus pallidus) were fatal systemic fibrosing
if any. Table 14-1 provides a summary likely related to prior gadolinium-based disease that develops in
of the molecular names, molecular contrast agent administration rather patients with severely
structures, and brand names of the than other pathologies, including prior impaired renal function
nine gadolinium-based contrast agents radiation therapy, was published in following the
approved by the US Food and Drug 2014 by Kanda and colleagues.2 This administration of
gadolinium. It almost
Administration (FDA). Nephrogenic work stimulated new investigational
exclusively occurs when
systemic fibrosis was first reported efforts and discussion, which goes on the glomerular filtration
10 years ago and triggered quick action mostly in the pages of Radiology and rate is under 30 mL/min.
from the medical community. Since Investigative Radiology in the form of
then, with the routine application of research articles and letters, often in a
renal function testing and the applica- passionate tone.3,4
tion of protocols for gadolinium-based
contrast agent administration, it has DISCUSSION
been virtually eliminated. The precursors of the Kanda study were
However, a new concern is rising animal and human in vitro and in vivo
regarding gadolinium-based contrast studies on gadolinium retention. Since
agents. Studies have reported a link 1992, animal studies have shown in-
between hyperintensities in the brain creased gadolinium retention in tis-
on nonenhanced T1-weighted scans sues, especially bone, with the less
and a history of prior gadolinium- stable linear forms of gadolinium-
based contrast agent exposure; in based contrast agents.5,6 Human stud-
subsequent studies, gadolinium reten- ies also tested gadolinium retention
tion was detected in postmortem in vivo and ex vivo in bone. Often cited
examinations of the same brain areas. is the work by White and colleagues7
TABLE 14-1 Currently Available Magnetic Resonance Imaging Contrast Agents on the Market
in the United States
Gadolinium Chelate Structure Product Manufacturer

Gadobenate dimeglumine Linear-ionic MultiHance Bracco Imaging S.p.A.; Italy
Gadoteridol Macrocyclic-nonionic ProHance Bracco Imaging S.p.A.
Gadobutrol Macrocyclic-nonionic Gadavist Bayer AG; Germany
Gadopentetate dimeglumine Linear-ionic Magnevist Bayer AG
Gadoxetate disodium Linear-ionic Eovist Bayer AG
Gadodiamide Linear-nonionic Omniscan GE Healthcare; United States
Gadoterate meglumine Macrocyclic-ionic Dotarem Guerbet; France
Gadoversetamide Linear-nonionic Optimark Mallinckrodt Pharmaceuticals;
Ireland-United States
Gadofosveset trisodium Linear-ionic Ablavara Lantheus Medical Imaging, Inc;
Massachusetts, United States
a
Previously Vasovist, Epix Pharmaceuticals.

Safety of Gadolinium-based Agents
KEY POINTS
h Studies have from 2006, a study of bone specimens previous work by Frenzel and col-
demonstrated of total hip arthroplasty with removal leagues,10 that the hyperintensities were
dose-dependent of the femoral head. This work dem- likely due to dechelation and gadolin-
hyperintensities in the onstrated the existence of gadolinium ium retention in brain parenchyma,
dentate nucleus and deposits as well as the possible link although they added that it was not
globus pallidus on between the molecular structure of possible “to distinguish between de-
T1-weighted images in gadolinium-based contrast agents and posits of chelated or dechelated in-
patients with a history their differences in tendency to create soluble form of gadolinium.” The
of gadolinium-based residues in tissues in human speci- investigators also stated that the phe-
contrast material mens. The study found that the linear nomenon is particularly associated with
administration.
gadodiamide left 2 to 4 times more gadodiamide. Quatrocchi and col-
h T1 hyperintensities gadolinium in the bone than the mac- leagues11 came to the same conclu-
have been linked rocyclic gadoteridol. The explanation sion about dose dependency in the
to the use of linear was proposed to be the lower thermo- case of the linear gadodiamide. They
gadolinium-based
dynamic stability of the open-chain provided possible explanations for the
contrast agents.
chelate of gadolinium in gadodiamide. phenomenon, assuming that gado-
h The physical presence Just as with nephrogenic systemic fibro- linium may not penetrate an intact
of gadolinium deposits sis, the molecular structure of the blood-brain barrier.
has been demonstrated
gadolinium-based contrast agents Kanda and colleagues12 next com-
following exposure to
seemed to make a difference in the pared the linear gadopentetate
linear gadolinium-based
contrast agents.
amount of gadolinium deposited in bone, dimeglumine and the macrocyclic
and, again, linear gadolinium-based gadoteridol and found that T1 hyper-
contrast agents were in the crosshairs. intensities were linked to the use of
Another precursor of the Kanda the linear gadolinium-based contrast
study was a study on dentate nucleus agent. The study included 360 sub-
hyperintensities by Kasahara and col- jects, 233 of which were excluded,
leagues8 in 2011. This study concluded partly on the basis of pulsation artifacts
that the imaging abnormalities may be arising from the sigmoid sinus and
linked to a history of brain radiation; obscuring posterior fossa structures.
however, in this case, gadolinium-based Of the remaining 127 subjects, only
contrast agent administration was not nine showed hyperintensity on nonY
accounted for. contrast-enhanced T1-weighted scans,
Following these studies, Kanda and although the subject selection may
colleagues 2 demonstrated dose- have had an effect on the final results.
dependent hyperintensities in the Radbruch and colleagues13 con-
“dentate nucleus and globus pallidus on firmed these findings in a study of
T1-weighted images in patients with a 100 patients; again, the dose-dependent
history of gadolinium-based contrast ma- phenomenon of signal abnormality
terial administration” (Figure 14-1). This in the globus pallidus and dentate
effect was independent of renal func- nuclei was observed with the history
tion, and the cutoff value for the hyper- of multiple administrations of gado-
intensities was a history of six or more pentetate dimeglumine, but not with
contrast-enhanced MRI scans. Shortly that of the macrocyclic gadoterate.
after, other studies demonstrated the The physical presence of gadolinium
same phenomenon and related aspects. deposits has also been demonstrated
Errante and colleagues9 also re- following exposure to linear gadolinium-
ported dose-related T1 signal change based contrast agents.14,15 Using induc-
in patients with normal renal function. tively coupled plasma mass spectrometry,
The authors concluded, referring to a transmission electron microscopy, and

KEY POINT
h Studies confirmed the
presence of gadolinium
deposits in the neural
tissue with normal renal
function and found that
a significant amount of
gadolinium passed
through the intact
blood-brain barrier.
FIGURE 14-1 Hyperintense signal in the globus pallidus (A) and dentate nuclei (C) on
nonenhanced T1-weighted MRI scans, along with T2-weighted scans of the
same levels (B, D). The circles on the T1-weighted scans indicate the
region-of-interest samples for signal intensity measurements.
Reprinted with permission from Kanda T, et al, Radiology.2 B 2013 Radiological Society of North America.
pubs.rsna.org/doi/abs/10.1148/radiol.13131669.
light microscopy, McDonald and col- dose-dependent relationship” in the

leagues14 analyzed postmortem neu- gadolinium-based contrast agent group.
ronal tissues from the dentate nuclei, Kanda and colleagues15 found gadolin-
pons, globus pallidus, and thalamus of ium deposits in deceased patients by
13 patients who had undergone at least analyzing specimens from the globus
four gadolinium-based contrast agentY pallidus, dentate nuclei, frontal lobe
enhanced brain MRIs compared to a cortex, frontal lobe white matter, and
control group of 10 patients. They con- cerebellar white matter. In a prospec-
firmed the presence of gadolinium de- tive animal study conducted by Bayer
posits in the neural tissue with normal Healthcare researchers,16 T1 shorten-
renal function and found that a signifi- ing in the deep cerebellar nuclei of rats
cant amount of gadolinium passed was demonstrated to occur with linear
through the intact blood-brain barrier. gadolinium-based contrast agents but
The deposits showed a “significant not with macrocyclic gadolinium-based

KEY POINT
h A growing body of contrast agents. In another animal cases. Also, macrocyclic gadolinium-
literature exists with study with repeated administration of based contrast agent administration
data suggesting that the linear gadodiamide and the mac- was not recorded in those patients
linear gadolinium-based rocyclic gadoterate meglumine, authors who had normal-appearing dentate nu-
contrast agents are from the Guerbet Research and Inno- clei. This suggests that not only the type
more likely to create vation Department found that “repeated of gadolinium-based contrast agent but
MRI changes and that administrations of linear gadodiamide also other underlying factors may be
actual gadolinium to healthy rats were associated with responsible for this phenomenon.
deposits in the neural progressive and persistent abnormal
tissue are responsible T1[-weighted] signal hyperintensity in CONCLUSION
for the abnormal
the deep cerebellar nuclei and with The recent observation that abnormal
imaging findings.
gadolinium deposit in cerebellum, in hyperintensities in the brain on non-
contrast to the macrocyclic gadoterate enhanced T1-weighted scans are likely
meglumine.”17 related to a history of serial gadolinium-
More recently, low levels of both based contrast agent administration has
linear and macrocyclic gadolinium- raised a new concern regarding the use
based contrast agents were detected and safety of gadolinium-based contrast
in postmortem bone and brain tissue agents, although the observation that
by Murata and colleagues.18 However, gadolinium creates deposits in tissues is
the authors acknowledge that, al- not new.7 A growing body of literature
though their results “suggest the exists with data suggesting that linear
possibility that there may be differen- gadolinium-based contrast agents are
tial gadolinium deposition among mac- more likely to create these MRI changes
rocyclic agents, this is not supported by and that actual gadolinium deposits in
animal and in vitro studies.” Neverthe- the neural tissue are responsible for the
less, this remains the only postmortem abnormal imaging findings.20 A few
human study to date that aimed to studies have raised the possibility that
detect macrocyclic agents as well as macrocyclic gadolinium-based contrast
linear agents. agents may produce this effect as well;
In their 2015 work, Adin and col- however, these results have been ques-
leagues19 also found that hyperin- tioned on a methodologic basis.18,21
tensity of dentate nuclei depends on The currently available in vivo clinical
the gadolinium dose; they found that studies are all retrospective observa-
after four or more contrast-enhanced tional studies, each with its own limi-
MRI scans and a total dose of 77 mL tations. Therefore, it is too early to
gadolinium, a significant increase in the draw clinical conclusions regarding this
likelihood of developing hyperintense phenomenon. It seems that gadolin-
dentate nuclei existed. However, as ium deposits do occur in the brain, but
noted by Kanda and colleagues,3 in sufficient data do not exist to imply any
some cases no T1 shortening was ob- clinical significance. As a free molecule,
served, even with a history of as many gadolinium is highly toxic; therefore, a
as 12 contrast-enhanced MRI studies. justified concern surrounds this issue.22
This may be explained by the use of The potential and yet unknown harm
macrocyclic gadolinium-based contrast that may be linked to these deposits
agents in the study, although, of the explains why so much attention is
80 cases with hyperintense dentate focused on this topic. Diverse research
nuclei, macrocyclic gadolinium-based teams and carefully designed studies
contrast agent administration during with minimized selection and funding
follow-up was recorded in only three bias will be necessary to assess any

KEY POINT
clinical relevance of gadolinium deposit gadopentetate, gadoteridol, gadoterate,
and gadodiamide in mice and rats. Invest h Following existing
formation. Presumably, the focus will Radiol 1995;30(6):372Y380. guidelines and ordering
be on extraneural tissues as well. The contrast-enhanced
7. White GW, Gibby WA, Tweedle MF.
development of safer and more effec- Comparison of Gd(DTPA-BMA) (Omniscan) scans only when
tive gadolinium-based contrast agents versus Gd(HP-DO3A) (ProHance) relative clinically indicated can
or other contrast agents should also to gadolinium retention in human bone minimize the number of
tissue by inductively coupled plasma mass
continue; academic, commercial, and potential adverse effects
spectroscopy. Invest Radiol 2006;41(3):
private institutions should all be in- 272Y278. of gadolinium-based
cluded to foster this process.20 contrast agents.
8. Kasahara S, Miki Y, Kanagaki M,
From the clinical standpoint, the et al. Hyperintense dentate nucleus on
possibility of a new side effect may have unenhanced T1-weighted MR images is
associated with a history of brain irradiation.
the benefit of reminding the clinical Radiology 2011;258(1):222Y228.
community to be mindful when refer- doi:10.1148/radiol.10100508.
ring patients for imaging studies. Fol- 9. Errante Y, Cirimele V, Mallio CA, et al.
lowing existing guidelines and ordering Progressive increase of T1 signal intensity
contrast-enhanced scans only when of the dentate nucleus on unenhanced
magnetic resonance images is associated
clinically indicated can minimize the with cumulative doses of intravenously
number of potential adverse effects. administered gadodiamide in patients
with normal renal function, suggesting
dechelation. Invest Radiol 2014;
ACKNOWLEDGMENTS 49(10):685Y690. doi:10.1097/
RLI.0000000000000072.
The authors would like to thank Ashley
10. Frenzel T, Lengsfeld P, Schirmer H, et al.
Adamo for her review of this article. Stability of gadolinium-based magnetic
resonance imaging contrast agents in human
serum at 37 degrees C. Invest Radiol
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\
Introduction to Magnetic Resonance

Imaging for Neurologists
Ernst-Wilhelm Radue MD; Matthias Weigel PhD; Roland Wiest MD; Horst Urbach MD.
Continuum (Minneap Minn). August 2016; 22 (5 Neuroimaging): 1379Y1398.
Abstract
Purpose of Review:
In neuroradiology, highly sophisticated methods such as MRI are implemented to investigate
different entities of the central nervous system and to acquire miscellaneous images where tissues
display varying degrees of characteristic signal intensity or brightness. Compared to x-ray, CT,
and ultrasound, MRI produces clearer images of tissues, body fluids, and fat. The basics of
MRI may be unknown to neurologists; this article introduces MRI physics, techniques, and
interpretation guidelines.
Recent Findings:
This article discusses the basics of MRI to provide clinicians with the scientific underpinning
of MRI technology and to help them better understand image features and improve their diagnosis
and differential diagnosis by combining MRI characteristics with their knowledge of pathology
and neurology.
Summary:
This article will help neurologists deepen their knowledge and understanding of MRI by
introducing the basics of MRI physics, technology, image acquisition, protocols, and
image interpretation.
Key Points
& MRI produces images that are related to the magnetic properties of, and molecular
interactions within, the tissues under observation.
& T1-weighted MRI uses T1 relaxation times to generate fundamental images with
characteristic tissue signal intensities or tissue brightness. As a rule of thumb, the more
aqueous a tissue is, the higher the T1 is. Fat has short T1.
* 2016 American Academy of Neurology.

& T2 alters with structural or metabolic changes of the tissue, which makes it highly
sensitive for pathologic changes of body tissue; T2-weightedMRI uses T2 relaxation
times to generate fundamental images with characteristic tissue signal intensities or
& tissue brightness.
& Errors caused by B0 inhomogeneities, susceptibility effects, body motion, or wrong
parameter settings on the scanner can manifest in the image as artifacts (structures displayed
that do not reflect reality), or the image may be blurred. Identifying and avoiding such
artifacts is of great importance in MRI.
& Important MRI sequence parameters that can usually be influenced by the user at the scanner
are the echo time and the repetition time.
& Echo time defines the time from the excitation until the signal is measured in the transverse
plane. This is of importance because the longer the echo time defined by the user, the
longer the tissue-specific T2 decay takes place. Hence, the acquired image displays a
stronger T2 weighting.
& Repetition time defines the time between repetitive measurement cycles or excitations.
& If the defined repetition time is short compared to the characteristic T1 relaxation times of
the investigated tissues, the corresponding longitudinal magnetizations cannot fully
recover before the next excitation, which represents a T1weighting of the magnetization.
As a result, the image that is reconstructed is also T1 weighted.
& T1 and T2 weighting are dominant or strong signal weightings in MRI and therefore
facilitate images with excellent tissue differentiation.
& Diffusion represents water motion in the tissue on a microscopic scale; it is determined
by the tissue microstructure and also reflects metabolism. The resulting apparent
diffusion coefficient is tissue-specific and is a measure of the mobility of the water
molecules in the tissue.
& The principal advantage of MRI is the ability to investigate tissue-dependent responses to
a magnetic field in multiple planes without the use of ionizing radiation.
& A systematic approach should consider fixed reading procedures, for example, from
inside to outside or vice versa, from gray matter to white matter and CSF, or from
suspected pathology to general inspection on a slice-by-slice basis.
& If a lesion is detected, it should first be classified by broad category, eg, tumoral lesion,
vascular pathology, infection, or degeneration.
& Image interpretation should always depend on the combination and integration of
imaging features and clinical information.
& Since location is a highly relevant parameter for diagnosis, a strong effort should be made
to categorize a lesion with respect to its topography.
& The signal intensity of a lesion may provide information about its composition. A lesion is
classified as hypointense, isointense, or hyperintense as compared to the gray matter
if not otherwise stated.
& T1-hyperintense lesions consist of fat, blood in the methemoglobin stage, or
proteinaceous fluid, or show contrast enhancement.
& MRI produces images that represent signal intensities of tissue that are dependent on
relaxation time and spatial resolution.
Imaging of Ischemic Stroke

Michelle P. Lin, MD, MPH; David S. Liebeskind, MD, FAAN. Continuum (Minneap Minn).
October 2016; 22 (5 Neuroimaging):1399Y1423.

Abstract
Purpose of Review:
This article provides an overview of cerebrovascular hemodynamics, acute stroke pathophysiology,
and collateral circulation, which are pivotal in the modern imaging of ischemic stroke that
guides the care of the patient with stroke.
Recent Findings:
Neuroimaging provides extensive information on the brain and vascular health. Multimodal CT
and MRI delineate the hemodynamics of ischemic stroke that may be used to guide treatment
decisions and prognosticate regarding expected outcomes. Mismatch imaging with either CT or
MRI may identify patients with salvageable regions who are at risk and likely to benefit from
reperfusion therapy, even if they are outside the standard time window. Imaging of collateral
circulation and determination of collateral grade may predict greater reperfusion, lower
hemorrhage risk, and better functional outcome. Current neuroimaging technology also enables
the identification of patients at high risk of hemorrhagic transformation or those who may be
harmed by treatment or unlikely to benefit from it.
Summary:
This article reviews the use and impact of imaging for the patient with ischemic stroke,
emphasizing how imaging builds upon clinical evaluation to establish diagnosis or etiology,
reveal key pathophysiology, and guide therapeutic decisions.
Key Points
& Advanced neuroimaging can provide real-time information on the state of the brain
parenchyma and neurovasculature, which may guide treatment outside of current
time windows.
& Every image serves to answer specific clinical questions to guide treatment decisions.
& Advances in neuroimaging in stroke are built on the basis of hemodynamics; accounting
for these variables allows physicians to make more individualized (rather than
population-based) therapeutic decisions.
& The ischemic penumbra refers to tissue at risk of infarction if reperfusion does not occur
in a timely manner. This dysfunctional but salvageable tissue has been the target
of all reperfusion and neuroprotection therapies.
& The cerebral collateral circulation exists to protect the brain against ischemia and sustain
the penumbra.
& Collateral flow in ischemic stroke is a dynamic process and will eventually fail if timely
reperfusion is not established.
& Noncontrast CT is the most widely used first-line imaging tool in patients with acute
stroke and is recommended as an initial mode of imaging to assist in making decisions for
IV tissue plasminogen activator.
& Comparing the signal intensities on diffusion-weighted, apparent diffusion coefficient,
and fluid-attenuated inversion recovery images can help distinguish acute, subacute, and
chronic stroke. Positive signals on diffusion-weighted imaging without corresponding
fluid-attenuated inversion recovery hyperintensity imply that the stroke occurred less than
4.5 hours before imaging.

& Hyperdense middle cerebral artery sign on noncontrast CT and blooming artifact on
gradient recalled echo MRI may indicate red cellYpredominant occlusive thrombus.
& Diffusion-weighted imaging/perfusion weighted MRI and CT perfusion are imaging
modalities commonly used to rapidly identify patients with stroke with persistent
penumbra thought to be optimal candidates for reperfusion therapies.
& A malignant mismatch profile is associated with severe intracranial hemorrhage and poor
outcome after reperfusion.
& When combined with CT perfusion, CT angiography can rapidly generate quantitative
and qualitative parameters that enable discrimination between normal tissue, penumbra,
and infarcted core.
& In the absence of recanalization, collateral blood flow is the determinant of
penumbral survival.
& High collateral grade predicts greater reperfusion, better functional outcome, and lower
hemorrhage risk.
& Low Alberta Stroke Program Early CT Score (ASPECTS) correlates with low
collateral grades.
& Standardized perfusion methods and thresholds are needed to reliably determine the core
and penumbra and facilitate the clinical use and dissemination of these techniques.
Imaging of Hemorrhagic Stroke

Ryan Hakimi, DO, MS; Ankur Garg, MD. Continuum (Minneap Minn).
Abstract
Purpose of Review:
Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides
readers with an understanding of the indications and significance of various neuroimaging
techniques available for patients presenting with hemorrhagic strokes of distinct causes.
Recent Findings:
The most common initial neuroimaging study is a noncontrast head CT, which allows for the
identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern
of blood and the patient’s medical history, neurologic examination, and laboratory studies lead
the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and
interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection
of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for
these patients is variable based on the etiology.
With an increasing incidence and prevalence of atrial fibrillation associated with the aging
population and the introduction of three new direct factor Xa inhibitors and one direct thrombin
inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase.
Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral
hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use
have a higher mortality rate than those with primary ICH. Despite the reduced incidence of
hypertension-related ICH over the past decade, it is expected that the incidence of ICH will
continue to increase.

Summary:
Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of
the underlying etiology, prevention of hematoma expansion, treatment of acute complications,
and treatment of the underlying etiology, if indicated. Neuroimaging is essential for
prognostication and thus directly impacts patient care.
Key Points
& Head CT without contrast has distinct advantages over other neuroimaging tools as the
initial screening test for hemorrhagic stroke, including wide availability, lower cost,
ease of identification of hemorrhage, high sensitivity and specificity, and applicability in
patients with hemodynamic instability and claustrophobia.
& Calculation of hematoma volume allows for improved communication between medical
providers and can be easily accomplished by using the ABC/2 method.
& Approximately, one-third of patients with hemorrhagic stroke will have hematoma
expansion on follow-up head CT within the first 3 hours of symptom onset.
& Presence of a spot sign on head CT angiography is indicative of active hemorrhage and
predictive of hematoma growth; it may favor admittance to the intensive care unit
even if the patient is not intubated and appears to be clinically stable.
& Hyperattenuation of acute blood on head CT is based on the protein content of
whole blood (ie, hemoglobin). Therefore, in patients with serum hemoglobin less than
10 g/dL, hyperattenuation may be limited, resulting in reduced ability to identify
intracerebral hemorrhage. Similarly, in patients with very elevated hemoglobin values,
such as those with polycythemia or significant hemoconcentration, the vasculature
may appear abnormally hyperdense, making accurate diagnosis of intracerebral
hemorrhage challenging.
& MRI is more sensitive than CT in identifying subacute hemorrhagic stroke.
& Susceptibility-weighted MRI is the most sensitive modality for detecting small amounts
of intraparenchymal hemorrhage.
& MRI allows for distinction between the two most common etiologies of hemorrhagic
stroke: arterial hypertensive vasculopathy and cerebral amyloid angiopathy.
& Establishing a hospital protocol for obtaining MRI scans based on priority levels may be a
very practical and efficient way to triage patients for MRI and may result in better use
& of limited resources.
& Modern CT angiography has very high sensitivity and specificity in detecting arterial
lesions of the brain and is largely replacing digital subtraction angiography for diagnostic
purposes. However, the sensitivity of CT angiography is lower than digital subtraction
angiography for aneurysms smaller than 3 mm and intracranial dissections.
& In patients with marginally elevated creatinine where angiographic data are critical,
digital subtraction angiography may be preferred over CT angiography as the amount of
contrast administered can be kept much lower with digital subtraction angiography.
& The sensitivity and specificity of digital subtraction angiography exceed 99% in
identifying vascular abnormalities in patients with hemorrhagic stroke.
& The role of transcranial Doppler in the imaging of hemorrhagic stroke is most robust in
the detection of cerebral vasospasm in patients with subarachnoid hemorrhage.
& It is important to exclude secondary causes of hemorrhagic stroke through vascular
neuroimaging even when it is suspected to be caused by arterial hypertensive vasculopathy.
& A noncontrast head CT is highly sensitive in detecting subarachnoid blood, especially
within 6 hours of hemorrhage.

& In a patient with a clinical history highly suggestive of subarachnoid hemorrhage but
negative head CT, further options include lumbar puncture to assess for xanthochromia,
MRI to assess for subarachnoid hemorrhage, and CT angiography or digital
subtraction angiography to identify the presence of an aneurysm or other etiology.
& The clinical course of cerebral venous thrombosis can be extremely variable and
insidious, making it difficult to diagnose early on. Neuroimaging can play a crucial role in
early identification and treatment.
& The appearance of the thrombus on MRI is time specific: isointense on T1 and
hypointense on T2 in the acute phase, hyperintense on T1 and T2 in the subacute phase,
and isointense on T1 and hyperintense on T2 in the chronic phase.
& Radiologic classification of hemorrhagic transformation of ischemic stroke can help
with prognostication and in making decisions regarding holding or continuing
antithrombotic therapy.
& Intracerebral hemorrhage can also be secondary to an underlying brain tumor, either
primary or metastatic. Overall, primary brain tumors are reported to have a lower rate of
intracerebral hemorrhage as compared to brain metastases.
Imaging for Adults With Seizures

and Epilepsy
Samuel Lapalme-Remis, MDCM, MA, FRCPC; Gregory D. Cascino, MD, FAAN.
Continuum (Minneap Minn). October 2016; 22 (5 Neuroimaging):1451Y1479.
Abstract
Purpose of Review:
This article discusses structural and functional neuroimaging findings in patients with seizures
and epilepsy. The indications for neuroimaging in these patients and the potential diagnostic
utility of these studies are presented.
Recent Findings:
Patients presenting with new seizures typically require urgent imaging to rule out a critical
underlying cause. MRI is the structural neuroimaging procedure of choice in individuals with
epilepsy. Specific epilepsy protocols should be considered to increase the diagnostic yield of
neuroimaging in patients with structural lesions associated with focal or generalized seizures.
Common epileptogenic pathologic processes include mesial temporal sclerosis, malformations of
cortical development, focal encephalomacia, primary brain tumors, vascular malformations,
and neurocysticercosis. Functional neuroimaging studies are usually restricted to the evaluation
of patients with drug-resistant focal epilepsy who are being considered for surgical treatment.
Summary:
The role of neuroimaging in epilepsy depends on the appropriate clinical indication. In patients
without known epilepsy presenting with acute seizures, structural imaging is essential to rule out
an underlying etiology (eg, subdural hematoma) that may require a specific therapeutic
intervention. In individuals with new or previously uninvestigated epilepsy, MRI serves multiple
purposes, including identifying a causative focal lesion and helping to diagnose the epilepsy type.

In a significant number of patients with epilepsy, the MRI results are normal or reveal indeterminate
findings. For patients with drug-resistant focal epilepsy, functional neuroimaging techniques,
such as fludeoxyglucose-positron emission tomography (FDG-PET), ictal single-photon emission
computed tomography (SPECT), or functional MRI (fMRI), may assist in surgical planning,
especially in patients with MRI-negative epilepsy, whose prognosis for a seizure-free outcome after
surgery is worse than for patients with an epileptogenic lesion on structural MRI.
Key Points
& In the acute setting, the primary purpose of structural neuroimaging in patients with
new-onset seizures is to identify a treatable underlying disease process.
& Urgent neuroimaging following a seizure is most important with the following red flags:
recurrent seizures; focal-onset seizure; persistently altered level of consciousness;
focal abnormalities on neurologic examination; headache; recent head trauma; fever;
hypertension or other vital sign abnormality; travel to area endemic for cysticercosis;
anticoagulant use; and history of stroke, bleeding disorder, hydrocephalus, human
immunodeficiency virus, immunosuppression, malignancy, or other significant
concurrent illness.
& Virtually all adult patients with epilepsy should have at least one MRI in the course of
their evaluation.
& A tailored specific brain MRI epilepsy protocol study in individuals with focal seizures
should be performed to improve detection of common pathologic findings underlying the
epileptogenic zone.
& A three-dimensional T1-weighted volumetric acquisition with isotropic voxel size of
1 mm or 1.5 mm enables the flexible reconstruction of images; this is especially helpful
for the evaluation of structural lesions such as focal cortical dysplasias.
& Mesial temporal lobe epilepsy is the most common surgically remediable epileptic syndrome.
& Thin coronal slices through the long axis of the hippocampus improve MRI detection of
typical abnormalities in individuals with pathologically verified mesial temporal sclerosis.
& Because of normal variation or patient positioning, simple visual inspection can be
misleading in subtle cases of hippocampal atrophy; quantitative hippocampal volumetric
studies in patients with mesial temporal sclerosis are most objective and can improve yield.
& When a patient with focal-onset epilepsy is found to have a normal MRI, an undetected
focal cortical dysplasia is typically considered to be the most likely underlying lesion.
& Key MRI features of focal cortical dysplasia type I include blurring of the gray-white
junction, abnormal gyral or sulcal patterns, lobar or sublobar hypoplasia or atrophy, and
subcortical white matter volume loss with increased T2/decreased T1 signal.
& Focal cortical dysplasia type II often shows apparent increased cortical thickness
(better seen on T1-weighted sequences), blurring of the gray-white junction, and an
increased T2 and decreased T1 signal in the subcortical white matter.
& In patients presenting to a first-seizure clinic, encephalomalacia and gliosis were the most
common presumed epileptogenic MRI lesions.
& Gangliogliomas and dysembryoplastic neuroepithelial tumors are the most frequently
encountered primary brain tumors in patients with focal seizure disorders.
& Imaging provides important data in predicting surgical success; among the factors cited as
improving surgical outcome in a 2015 Cochrane Review were concordance of
preoperative MRI and EEG findings, the presence of mesial temporal sclerosis or tumor,
the absence of focal cortical dysplasia or malformation of cortical development, and an
abnormal preoperative MRI.

& Functional MRI may map sensory and motor functions, which may be unpredictable
when eloquent cortex is adjacent to or even contained within a lesion, causing altered
anatomic or functional topography.
& In most patients with temporal lobe epilepsy, temporal hypometabolism has been found to
accurately lateralize to the temporal lobe with EEG abnormalities and is associated
with good surgical outcomes, even when MRI is negative.
& Subtraction ictal single-photon emission computed tomography coregistered to MRI
(SISCOM) allows improved localization of the epileptogenic zone in patients with
focal epilepsy.
Imaging of Congenital Malformations

Jennifer W. McVige, MA, MD. Continuum (Minneap Minn). October 2016;
22 (5 Neuroimaging):1480Y1498.
Abstract
Purpose of Review:
Intracranial congenital malformations are anomalies of brain development caused by genetic and
environmental influences. This article discusses common intracranial congenital malformations,
presents the associated neuroimaging findings, and discusses how appropriate identification of
intracranial anomalies can impact diagnosis and treatment.
Recent Findings:
Advances in neuroimaging techniques and genetic research have led to a better understanding
of the pathogenesis of many congenital malformations, adding insight into their clinical relevance
and the intricate relationship between critical periods of development, genetic predisposition,
and environmental insults. When one malformation is discovered, a high likelihood of more
malformations exists. In some instances, the intracranial anomalies will lead to the diagnosis of a
particular neurologic syndrome, which may, in turn, lead to modification of a plan of care.
Summary:
Knowledge of congenital malformations and their appearance on imaging sequences is essential
to improve clinical outcomes and quality of life for patients.
Key Points
& The old stepwise theories of neurodevelopment have been replaced by the idea that
simultaneous developmental processes occur in different regions. This explains why it is
common to find multiple intracranial anomalies in one patient.
& Dysgenesis or agenesis of the anterior corpus callosum is usually associated with an
insult, such as infection or vascular event. Dysgenesis of the posterior corpus callosum is
usually associated with arrested development.
& Cortical malformations can be seen on fetal ultrasound by 20 weeks gestational age.
Prenatal and postnatal CT can miss up to 30% of findings, thus prenatal or postnatal MRI
is the imaging modality of choice.

& In lissencephaly, the brain has decreased sulci and gyri, resulting in a smooth cortex. It
may be described as complete (agyria) or incomplete (pachygyria). In pachygyria, the
cortex has thickened flat gyri.
& Polymicrogyria is an irregular cortex with several small convolutions in the sulci and gyri.
It is most commonly located in the bilateral perisylvian fissures but can be seen in a
number of locations.
& Diffusion tensor imaging measures of fractional anisotropy can be used to detect
microstructural damage in many congenital malformations. Small abnormalities that are
missed on MRI can be better seen with diffusion tensor imaging.
& Schizencephaly is a gray matterYlined cleft extending from the ependyma of the ventricle
to the pial surface of the cortex. The gray matter is disorganized and without the proper
cortical layers, and the septum pellucidum is typically absent.
& Anencephaly is the absence of the forebrain, skull, and scalp. It occurs when the cephalic
end of the neural tube fails to close or reopens after closure. It is usually not compatible
with life.
& Holoprosencephaly describes the failure of the division of the forebrain into two
hemispheres. Subtypes are described as alobar, which is the most severe, with no midline
differentiation and fused basal ganglia; semilobar, with an ‘‘ace of spades’’ appearance;
and lobar, with some development of the hypothalamus, frontal regions, and anterior
corpus callosum.
& Dandy-Walker malformation and related disorders are spectrum disorders that involve
varying degrees of cerebellar hypoplasia, mega cisterna magna, and retrocerebellar
arachnoid cysts.
& On neuroimaging, Joubert syndrome can be identified by thickened and elongated
superior cerebellar peduncles that give the appearance of a molar tooth.
& The degree of cerebellar tonsillar herniation in Chiari type I malformation does not
always correlate with the severity of symptoms. The size of the posterior fossa, however,
has been shown to be predictive of severity and response to decompression surgery.
& Measuring the degree of cerebellar tonsillar herniation on sagittal and coronal MRI as
well as using cine-MRI CSF flow scans can be helpful in evaluating the degree of severity
of Chiari type I malformation.
Imaging in Patients With Visual

Symptoms
Gabriella Szatmáry, MD, PhD. Continuum (Minneap Minn). October 2016;
Abstract
Purpose of Review:
This article presents an imaging-based approach to the differential diagnosis of visual symptoms.
Recent Findings:
Many neurologic disorders may present with visual symptoms. Therefore, neurologists must be
familiar with the array of pathophysiologic processes that cause visual symptoms. Orbital

imaging is challenging owing to the small structures and different tissue interfaces within and
surrounding the orbital compartment. Some of the emerging three-dimensional MRI sequences are
promising and compare well with high-resolution two-dimensional sequences in the orbits.
Summary:
The diagnosis of patients with visual symptoms can be challenging and often requires in-depth
knowledge of neuroanatomy that is well depicted by various imaging methods. Neurologists
are expected to be familiar with the latest imaging techniques that play an important role not only
in diagnosing diseases but also in determining disease pathogenesis. Close collaboration with
the neuroimager, ophthalmologist, and, when available, neuro-ophthalmologist, is recommended
when caring for patients with visual symptoms.
Key Points
& CT may be helpful in the evaluation of calcified lesions, such as aneurysms, optic nerve
head drusen, optic nerve sheath meningiomas, and retinoblastomas.
& The orbital structures are buried in fatty tissues, which show hyperintense signal on both
T1- and T2-weighted sequences (due to fat having short T1 and long T2 values).
& MRI is a sensitive technique, but its specificity is relatively low; therefore, different
disease processes can cause similar imaging appearances.
& Imaging plays an important role in the complex differential diagnosis of neurogenic
visual loss by confirming or excluding the presence of a compressive/infiltrative,
inflammatory/infectious, hereditary, mechanical (elevated intracranial or intraocular
pressure), toxic/metabolic, traumatic, or vascular lesion and by monitoring disease
activity and potential complications.
& The most common bilateral optic nerve disease that the neurologist is consulted on is
swollen optic nerves from mechanical causes.
& Neuroimaging signs that are useful to support the clinical diagnosis of papilledema due
to idiopathic intracranial hypertension (ie, primary pseudotumor cerebri syndrome)
include: (1) empty or partially empty sella, (2) flattening of the posterior aspect of the
globe (with or without protrusion into the globe), (3) distention of the optic nerve sheath
(perioptic subarachnoid space) with or without a tortuous optic nerve, and (4) transverse
venous sinus stenosis.
& Imaging findings that suggest chronically elevated intracranial pressure are meningoceles
at various apertures of the cranial vault and acquired cerebellar tonsillar ectopia.
& For patients with the typical phenotype for idiopathic intracranial hypertension (young
obese female), the recommendation is to obtain a brain MRI with and without
contrast to confirm normal brain parenchyma and absence of hydrocephalus and to
exclude abnormal meningeal enhancement. For patients with an a typical phenotype,
additional magnetic resonance venography is recommended.
& When a patient does not have the typical phenotype for idiopathic intracranial
hypertension or when CSF is not entirely normal, then spinal abnormalities, such as spinal
leptomeningeal lymphoma, should be considered and imaging of the entire spinal
axis should be performed.
& Optic nerve glioma is one of the optic pathway gliomas, and when it is bilateral, it is
pathognomic for neurofibromatosis type 1.
& In the imaging-based differentiation of optic nerve sheath meningioma, helpful clues
are calcification or enhancement of the optic nerve sheath, often with compression
of the optic nerve. Each of these features has been labeled as the tram-track sign.

Sometimes optic nerve sheath meningioma may cause bony erosion, hyperostosis, or
pneumatization of the adjacent bone.
& The imaging differential diagnosis of meningeal enhancement includes low intracranial
pressure (pachymeningeal involvement), infectious or neoplastic meningitis, and
dural metastasis.
& In acute optic neuritis, MRI with short tau inversion recovery, T2 fluid-attenuated inversion
recovery, or T2-weighted imaging with fat-suppression sequence shows optic nerve
hyperintensity in the vast majority of patients, and on contrast-enhanced T1-weighted
imaging with fat suppression, abnormal enhancement is seen in 94% of affected nerves. If
the enhancing optic nerve segment is longer than 17 mm or the canalicular segment of
the optic nerve is involved, then poor baseline visual acuity, threshold perimetry, and color
vision are expected.
& Sarcoid lesions tend to be isointense relative to gray matter on T1-weighted imaging and
hypointense on T2-weighted imaging; on contrast-enhanced MRI, intense meningeal
enhancement most commonly involves the basal meninges and sulci. However,
leptomeningeal granulomas may go unnoticed on nonYcontrast-enhanced MRI.
& In perineuritis, optic nerve function is preserved, but optic nerve sheath inflammation is
marked by thickening and enhancement, which is best seen on contrast-enhanced
T1-weighted MRI with fat suppression.
& In hereditary, toxic-metabolic, traumatic, and vascular optic neuropathies, neuroimaging
is usually normal or may show some nonspecific findings involving the optic nerve or
optic disc, including T2 hyperintensity and enhancement.
& In the imaging evaluation of a sellar or extrasellar lesion, determine the epicenter of the
lesion (in, above, below, or lateral to the sella) and analyze the lesion for signal
characteristics (identification of cystic or solid components, calcification, and flow voids).
& In children, the triad of proptosis, skull lesion, and diabetes insipidus suggests
Hand-Schuller-Christian syndrome, a variant of Langerhans cell histiocytosis.
& Blow-out fracture of the orbit usually involves the thinnest orbital walls.
& On imaging of blow-out fracture of the orbit, enophthalmos, air in the lids, and a teardrop
sign due to prolapsed tissue through the fracture can be seen.
& In thyroid eye disease, the acute inflammatory stage is signified by increased water
content of the involved muscles, resulting in T2 hyperintensity. The chronic stage is
marked by fibrosis and fat accumulation seen as T1 hyperintensity.
& IgG4-related disease of the orbit may present with myositis or may involve other orbital
(dacryoadenitis) or intracranial tissues (pachymeningitis, hypophysitis).
& MRI findings in Tolosa-Hunt syndrome include inflammation marked by enlargement
and enhancement of the cavernous sinus, superior orbital fissure, or orbital apex;
narrowing of the intracavernous internal carotid artery; and enlargement of the optic nerve
and extraocular muscles.
& In carotid-cavernous fistula, reversal of flow from the cavernous sinus to the orbit is
suggested by flow void (arterialized blood) that is usually accompanied by enlargement of
the ipsilateral or bilateral superior ophthalmic vein.
& Lemierre syndrome is diagnosed when bilateral cavernous sinus thrombosis due to septic
emboli, usually from a parapharyngeal source, is identified.
& In a suspected Horner syndrome, an imaging evaluation can be lengthy and costly
because of the long oculosympathetic pupillomotor pathway; therefore, the imaging
study should be chosen according to the suspected site of injury based on associated
symptoms, signs, and the result of pupil pharmacologic testing.
& The most common cause of a postganglionic Horner syndrome is a vascular process
(eg, internal carotid artery dissection), although it may also be associated with migraine,

cluster headache, or Raeder paratrigeminal syndrome (oculosympathetic and
trigeminal or other cranial nerve palsy).
& From the imaging perspective, in patients with involvement of the parasympathetic
pupillomotor fibers, the most important etiology to consider in the subarachnoid space is
compressive, usually by a posterior communicating artery aneurysm (with or without
rupture). Initially, mydriasis may be absent, but because the pupillomotor fibers are
immediately beneath the epineurium within the oculomotor nerve, it usually is present.
& The most common causes of a compressive cavernous sinus lesion are intracavernous
internal carotid artery aneurysm, meningioma, clival chordoma, pituitary tumors with
parasellar extension, pituitary apoplexy, diencephalic tumor (craniopharyngioma), and
idiopathic granulomatous inflammation (Tolosa-Hunt syndrome).
Imaging of Brain Tumors

Mirza A. Baig, DO; Joshua P. Klein, MD, PhD, FANA, FAAN; Laszlo L. Mechtler, MD,
FAAN. Continuum (Minneap Minn). October 2016; 22 (5 Neuroimaging):1529Y1552.
Abstract
Purpose of Review:
Neuroimaging is an essential tool for the diagnosis and management of brain tumors.
Recent Findings:
Advances in neuroimaging have allowed for noninvasive visualization of tumors and have changed
how brain tumors are diagnosed and treated. Presurgical planning with the use of functional
MRI (fMRI) and diffusion tensor MRI helps to preserve eloquent regions of the brain and fiber
tracts, thereby decreasing patients’ postsurgical morbidity. With the use of susceptibility-weighted
imaging (SWI) filtered phase images, diffusion-weighted studies, and perfusion imaging
techniques, deciphering posttreatment effects versus tumor progression can be facilitated.
Summary:
With recent advancements and novel approaches, various MRI techniques can be used to help
diagnose and assist in presurgical planning and posttreatment management of brain tumors.
Key Points
& The most common primary malignant brain and central nervous system tumor is glioblastoma.
& MRI with gadolinium is the imaging test of choice in patients with suspected central
nervous system neoplasm.
& Contrast enhancement on T1-weighted images represents breakdown of the blood-brain
barrier where gadolinium has leaked out.
& T2 hypointensity (ie, short T2) in brain tumors can represent hemosiderin, melanin,
calcification, dense cellularity, mucin, high protein, or vascular flow void.
& T1 hyperintensity (ie, short T1) in brain tumors can represent methemoglobin, high
protein, fat, melanin, gadolinium, and cholesterol.

& Diffusion-weighted imaging is extremely sensitive in detecting acute ischemia, cerebral
abscess, hypercellularity, and postoperative brain injury.
& Magnetic resonance spectroscopy of malignant brain tumors typically shows an increase
in the choline peak, a decrease in the N-acetylaspartate peak, an increase of the
choline to creatine ratio, and the presence of a lactate peak.
& On perfusion imaging, low-grade astrocytomas have a lower mean relative cerebral blood
volume than do anaplastic astrocytomas or glioblastomas.
& On perfusion imaging, mapping of cerebral blood volume can reveal differences in
vascularity and may help differentiate radiation necrosis from recurrent tumor.
& Lymphomas are hypercellular tumors with a high nuclear to cytoplasmic ratio; therefore,
primary central nervous system lymphomas often show reduced diffusivity on
iffusionweighted imaging.
& On perfusion imaging, meningiomas show elevated blood volume due to their
hypervascularity. Capillaries within a meningioma are highlypermeable due to the lack of
a blood-brain barrier.
& Meningiomas may be associated with a mutation in chromosome 22 or as part of
neurofibromatosis type 2.
Imaging of Intracranial Cysts

Bela Ajtai, MD, PhD; John A. Bertelson, MD. Continuum (Minneap Minn). October 2016;
Abstract
Purpose of Review:
Intracranial cysts are common findings on both CT and MRI. The majority of intracranial cysts
are benign and incidental and without clinical significance. However, a minority are due to
infectious, neoplastic, or other pathologic processes.
Recent Findings:
Neuroimaging, in particular brain MRI, can readily identify intracranial cysts. It can often be
difficult to characterize the likely histopathology of intracranial cysts based solely on their signal
intensity, even when using contrast. However, with the knowledge that most intracranial
cysts occur within a fairly narrow anatomic distribution, a concise and specific differential
diagnosis can often be developed based primarily on location. The first location-based question to
consider regarding intracranial cysts is whether the lesion is intraaxial or extraaxial. Intraaxial
cysts should be further characterized as intraparenchymal or intraventricular, and extraaxial cysts
should be identified as either midline or nonmidline. Signal characteristics using CT, MRI, or
both can help further characterize the cystic process.
Summary:
Neurologists should be familiar with the characteristic patterns of intracranial cysts to
distinguish between benign and pathologic processes. A systematic approach to the assessment
of intracranial cysts based on location and appearance should greatly narrow the
differential diagnosis.

Key Points
& Intracranial cysts are common and often conspicuous incidental findings, usually without
clinical significance. Both location and signal characteristics can be very helpful to
differentiate benign from pathologic processes.
& Dilated Virchow-Robin spaces are cystic-appearing findings commonly found within
subcortical regions. These incidental findings can usually (but not always) be
distinguished from chronic lacunar infarctions by their lack of adjacent gliotic tissue.
& Hippocampal sulcal remnant cysts are extremely common and benign findings that do not
indicate hippocampal atrophy or other pathologic processes.
& Porencephalic cysts are lined by gliotic tissue and often communicate directly with the
ventricular system.
& While classically considered to be a condition acquired during the perinatal period, cystic
encephalomalacia can occur due to any encephaloclastic process throughout the lifespan.
& An important imaging feature that distinguishes brain abscesses from metastasis is that
brain abscesses exhibit T2-hyperintense signal on diffusion-weighted imaging due to
restriction of diffusion.
& The constellation of imaging features including ring enhancement, significant
surrounding edema, and T2-hyperintense signal/restricted diffusion on
diffusion-weighted imaging indicates the presence of an abscess until proven otherwise.
& In almost every case, colloid cysts are located in the anterior one-third of the third
ventricle, adjacent to the foramen of Monro.
& Most often, colloid cysts are hyperintense on T1-weighted and hypointense on
T2-weighted images based on their mucus or protein content. If, however, the protein
content of a colloid cyst is low, it may cause an isointense signal on T1- and T2-weighted
images and the cyst may escape detection.
& Although histologically benign, colloid cysts may lead to severe symptoms, such as acute
hydrocephalus and even death, because of their propensity to cause obstruction of CSF
outflow at the level of the foramen of Monro.
& Intraventricular cystic lesions mainly include choroid plexus cysts, colloid cysts, and
ependymal cysts. Rarely, arachnoid cysts and epidermoids can also be found in
intraventricular locations.
& Simple pineal cysts are usually asymptomatic and tend not to expand with time. However,
serial imaging may be necessary to distinguish simple pineal cysts from pineocytomas,
pineoblastomas, and other more aggressive processes.
& On imaging, neurenteric cysts classically appear as small well-circumscribed lesions
within the prepontine or premedullary cisterns or in the spinal canal.
& The position of the fornices (ventral versus dorsal displacement) helps to distinguish
between cavum vergae and cavum velum interpositum.
& Epidermoid and dermoid cysts represent a group of inclusion cysts derived
from the ectoderm. Besides epidermal cells, dermoid cysts also contain dermis
derivatives, including sebaceous and sweat gland cells, hair follicles, and
even adipocytes.
& Dermoid cysts may rupture; in such cases, noncontrast T1-weighted images reveal
hyperintense fat content dispersed in the subarachnoid space.
& Rathke cleft cysts are intrasellar lesions that arise from the pars intermedia. They
should be distinguished from craniopharyngiomas and other lesions. An intracystic
nodule that is T1 hyperintense and T2 hypointense is considered pathognomonic of
Rathke cleft cysts.

& Arachnoid cysts are frequent incidental findings on MRI. They account for 1% of all
intracranial mass lesions. The most common locations are the middle cranial fossa,
sylvian fissure, posterior fossa, suprasellar region, and vertex.
& In cases of enlarged retrocerebellar spaces, a midline position of the falx cerebelli favors
an enlarged cisterna magna over a retrocerebellar arachnoid cyst.
& Epidermoid cysts, like choroid plexus cysts, exhibit T2 hyperintense signal on
diffusion-weighted images. This feature helps to differentiate them from arachnoid cysts.
& The differential diagnosis of intracranial cystic lesions with restricted diffusion (bright
signal on diffusion-weighted imaging) includes epidermoid cysts, choroid plexus
cysts, and abscesses.
& Neurocysticercosis can produce cystic lesions of varying signal characteristics, including
abnormal enhancement. As the intracystic parasite degenerates, large cystic lesions
with adjacent inflammation can evolve into small calcified nodules.
& Once a cyst is identified and its location confirmed, it should be assessed for size, effect on
adjacent structures, and heterogeneity of signal.
Imaging of Pituitary and Parasellar

Disorders
Robert Fenstermaker, MD, FACS, FAANS; Ajay Abad, MD. Continuum (Minneap Minn).
Abstract
Purpose of Review:
This article reviews sellar and parasellar anatomy and the appearance of normal bone and soft
tissue components on both CT and MRI. Pituitary gland structure and function are discussed
with respect to hormone secretion, along with clinical syndromes caused by perturbations in
hormone levels. Syndromes and specific diseases in the sellar and parasellar regions are discussed
along with characteristic clinical features and imaging findings.
Recent Findings:
Bone and calcifications are best visualized with CT scans, while soft tissues are better
defined using MRI. Some lesions have characteristic enhancement patterns with contrast; the
presence of delayed contrast uptake further narrows the differential.
Summary:
Lesions that commonly occur in the sellar and parasellar region include benign and malignant
tumors, cysts, vascular pathology, inflammatory processes, and abscesses. Knowledge of
sellar and parasellar anatomy and attention to the use and interpretation of various imaging
modalities can be of great assistance to the clinician when formulating a differential diagnosis for
lesions in this region.
Key Points
& The pituitary gland is ectodermal in origin.
& The blood-brain barrier is absent at the neurohypophysis and median eminence.

& Sellar and parasellar bony structures and calcifications are best visualized on CT.
& Obstruction of the foramen of Monro by suprasellar mass lesions can cause
noncommunicating hydrocephalus.
& Pituitary adenomas are often nonfunctional and discovered incidentally.
& Dynamic MRI detects delayed contrast uptake in functional adenomas.
& Expansile sellar lesions compress the optic chiasm, causing bitemporal hemianopia.
& On CT, craniopharyngiomas have a calcified cystic rim and a solid component with
reticular enhancement.
& Parasellar meningiomas are dural-based lesions originating from the tuberculum sellae,
planum sphenoidale, anterior clinoid process, or sphenoid wing. In contrast to
pituitary adenomas, meningiomas involving the sella turcica usually do not produce bony
expansion of this structure.
& Schwannomas, like functional adenomas, demonstrate delayed contrast uptake.
& Intralesional calcifications, if present, are a characteristic feature of chondrosarcomas.
The thumb sign is a common radiographic feature of clival chordomas when viewed in the
sagittal plain.
& Optic gliomas are exophytic lesions that cause optic nerve enlargement, often in the
proximal segment just anterior to the optic chiasm.
& Pituicytomas can cause central diabetes insipidus with sufficient mass effect.
& Dermoid cysts occur at the midline, while epidermoid cysts are usually paramedian.
& Epidermoid cysts are bright on diffusion-weighted imaging, consistent with
restricted diffusion.
& Rathke cleft cysts have a characteristic intraluminal nodule.
& With an empty sella, the infundibulum traverses the sella and enhances with contrast; if
visible on MRI, this is known as the infundibulum sign.
& Carotid-cavernous fistulas cause high-flow shunting of blood and external carotid
artery enlargement.
& Both Langerhans cell histiocytosis and pituicytomas can cause diabetes insipidus.
Imaging of Spinal Cord Disorders

Karanbir Singh, MD; Laszlo L. Mechtler, MD, FAAN; Joshua P. Klein, MD, PhD,
FANA, FAAN. Continuum (Minneap Minn) 2016;22(5):1595Y1612.
Abstract
Purpose of Review:
Spinal cord disorders are common and can be caused by a myriad of pathologies. Confidently
interpreting spine imaging studies is an essential skill for neurologists as many spinal cord
disorders can produce significant disability if not diagnosed and treated correctly.
Recent Findings:
Advances in imaging have revolutionized the care of patients with spinal cord disorders by
allowing noninvasive visualization of normal and abnormal structures.
Summary:
This article summarizes the imaging patterns of common spinal cord disorders.

Key Points
& In the cervical spine, the spinal nerve roots exit above the corresponding vertebra.
Caudal to the C8 nerve root, the spinal nerve roots exit below their corresponding
vertebral body.
& The vertebral body level differs from the spinal cord dermatomal level. During embryonic
development, the vertebral column grows more rapidly than the spinal cord.
& MRI is the imaging modality of choice in most diseases of the spinal cord.
& The short tau inversion recovery protocol suppresses fat signal and improves the
visualization of edema, hemorrhage, and other pathologies on T2-weighted images.
& IV contrast should be administered when the differential diagnosis includes infection,
neoplasm, inflammation, or demyelination.
& Syringomyelia refers to a fluid-filled cyst in the spinal cord or cystic expansion of the
central canal with disruption of ependyma, whereas hydromyelia refers to cystic
expansion of the central canal with ependymal lining preserved.
& In multiple sclerosis, the plaques are most often small, ovoid, well-demarcated T2
hyperintense lesions and are typically in the periphery of the cord, extending
longitudinally for fewer than three vertebral segments.
& In neuromyelitis optica, spinal cord lesions are usually centrally located and involve
more than one-half of the cross-sectional area of the cord. Unlike multiple sclerosis
lesions, neuromyelitis optica lesions typically extend for more than three vertebral
segments in length.
& Etiologies of longitudinally extensive transverse myelitis include venous hypertensive
myelopathy as well as a variety of autoimmune, infectious, neoplastic, and
metabolic conditions.
& Diffuse enhancement is seen in infectious processes that have not evolved into an abscess,
whereas rim enhancement and a nonenhancing core are more suggestive of an abscess.
& Viral myelitis can be caused by direct viral infiltration of the cord or by postviral
immunologic sequelae. Herpes virus, poliovirus, cytomegalovirus, and human
immunodeficiency virus are the typical pathogens.
& The borderzone between the larger segmental anterior radicular arteries in the midthoracic
region is vulnerable to hypoperfusion, and the area supplied by the radicular arteries
arising from the artery of Adamkiewicz (lower thoracic) is vulnerable to embolic or
thrombotic strokes.
& Hyperintensity within adjacent vertebrae may indicate concurrent bone infarction,
whereas adjacent prolapsed disk space may signify fibrocartilaginous embolism as a
cause of infarct.
& Catheter angiography is required in cases of suspected vascular malformations to
further characterize the lesion and plan treatment. Contrast-enhanced CT angiogram or
magnetic resonance angiogram can be helpful to focus the search for a spinal
arteriovenous malformation using catheter angiography.
& Hemosiderin-sensitive sequences, such as gradient recalled echo and susceptibility-weighted
imaging, are particularly sensitive for the diagnosis of small cavernous malformations.
& Ependymomas represent about 60% of spinal cord tumors, and astrocytomas represent
30%.Hemangioblastomas account for 2% to 8% of spinal cord tumors.
& Contrast enhancement of spinal astrocytomas does not predict tumor grade.
& Changes in the spinal cord in degenerative disease occur from compression by disk
herniation or osteophytes. Early diagnosis and appropriate treatment are important to
prevent irreversible damage to the spinal cord.

& CT is more sensitive than MRI for detection of cortical bone disruption due to
fractures and can show subtle misalignment resulting from subluxation of
facets or vertebral bodies. MRI, however, can demonstrate ligament and cord
injury, displaced disk fragments, and intraspinal hematomas that are not well seen
on CT.
& Diffusion tensor imaging enables qualitative and quantitative assessment of the integrity
of white matter tracts of the spinal cord. Visualization of white matter tracts may
help differentiate destructive from nondestructive lesions.
Imaging of Central Nervous System

Demyelinating Disorders
Konstantin Balashov, MD, PhD, FAAN. Continuum (Minneap Minn). October 2016;
Abstract
Purpose of Review:
This article focuses on neuroimaging in multiple sclerosis (MS), the most common central
nervous system (CNS) demyelinating disorder encountered by practicing neurologists. Less
common adult demyelinating disorders and incidental subclinical white matter abnormalities that
are often considered in the differential diagnosis of MS are also reviewed.
Recent Findings:
Advancements in neuroimaging techniques, eg, the application of ultrahigh-field MRI,
are rapidly expanding the use of neuroimaging in CNS demyelinating disorders. Probably the
most important recent findings include the detection of cortical lesions and CNS atrophy
even in early stages of MS. The key development for practicing neurologists is the growing
impact of MRI on the diagnostic criteria for MS and neuromyelitis optica (NMO)
spectrum disorders.
Summary:
MRI serves as an important component of the diagnostic criteria for MS and other major CNS
demyelinating disorders, and it has been established as a reliable and sensitive indicator of
disease activity and progression. In addition, rapidly advancing neuroimaging techniques are
helping to improve our understanding of disease pathogenesis.
Key Points
& Important concepts in the diagnosis of multiple sclerosis are the dissemination in time and
dissemination in space of lesions.
& The term clinically isolated syndrome was introduced to describe a first episode of
neurologic symptoms that lasts at least 24 hours and is caused by inflammation and
demyelination in one or more sites in the central nervous system.

& The term radiologically isolated syndrome and its diagnostic criteria were introduced
to describe patients with no prior history of neurologic disability but with demyelinating
lesions incidentally found on MRI that are similar to those commonly seen in
multiple sclerosis.
& When monthly brain scans with optimized imaging protocols are performed, MRI
reveals, on average, 35 new lesions per one clinical exacerbation reported by the patient
with multiple sclerosis.
& MRI factors affecting lesion detection include patient positioning, selection
of pulse sequences, spatial resolution, coil technology, contrast medium, and MRI
magnet strength; therefore, patients should use the same MRI facility for
follow-up imaging.
& In general, increased MRI magnet strength leads to an increase in the number of
identifiable multiple sclerosis lesions.
& A ‘‘multiple sclerosisYspecific lesion’’ does not exist. The most remarkable features of
early multiple sclerosis plaques are their perivenular location and the self-limited
contrast-enhancing phase.
& The perivenular location explains the classic ovoid shape of multiple sclerosis lesions.
& The average duration of multiple sclerosis lesion contrast enhancement is approximately
3 weeks.
& Chronic foci of T1 hypointensity (ie, seen on repeated MRIs done several months apart)
are now called persistent black holes.
& Multiple sclerosis is not exclusively a white matter disease. Cortical lesions can be seen in
up to 97% of patients with multiple sclerosis on ultrahigh-field MRI.
& Some patients with multiple sclerosis may have focal leptomeningeal contrast
enhancement.
& Acute demyelinating lesions with restricted diffusion have been reported in a number of
patients with multiple sclerosis on brain and spinal cord MRI.
& Tumefactive demyelinating lesions are often defined as brain lesions more than 2 cm in
diameter. They may appear in patients either with or without multiple sclerosis.
& Focal spinal cord lesions are seen in 80% to 90% of patients with multiple sclerosis.
& Longitudinal transverse myelitis that extends over three or more vertebral bodies in length
is rare in multiple sclerosis and should raise the suspicion of a neuromyelitis optica
spectrum disorder, sarcoidosis, acute demyelinating encephalomyelitis, malignancy,
or infection.
& Increased gray and white matter central nervous system atrophy is a well-established
phenomenon in multiple sclerosis.
& Decreased spinal cord gray matter volume correlates better with multiple
sclerosis disability than brain gray matter, brain white matter, or spinal cord white
matter volumes.
& Only approximately 25% of white matter lesions will remain evident on conventional
T2-weighted imaging 6 months after lesion onset.
& Areas of white matter in patients with multiple sclerosis may have axonal injury and
microglia activation despite normal imaging characteristics on conventional MRI,
underlying the concept of normal-appearing white matter.
& Classic MRI findings in neuromyelitis optica spectrum disorders include lesions
extending over half the length of the optic nerve or in the optic chiasm, area
postrema of the dorsal medulla, or periependymal brainstem area. Spinal cord
lesions in neuromyelitis optica spectrum disorders usually present as transverse
myelitis or focal spinal cord atrophy extending over three or more contiguous
vertebral segments.

Positron Emission Tomography and
Single-Photon Emission Computed
Tomography in Neurology
Robert S. Miletich, MD, PhD, FAAAS. Continuum (Minneap Minn). October 2016;
Abstract
Purpose of Review:
Positron emission tomography (PET) and single-photon emission computed tomography
(SPECT) are now available for routine clinical applications in neurology. This article discusses
their diagnostic use in dementia, brain tumors, epilepsy, parkinsonism, cerebrovascular disease,
and traumatic brain injury.
Recent Findings:
Neuromolecular imaging, also known as nuclear neurology, involves clinical imaging of both
basal regional physiology (perfusion, metabolism, and transport mechanisms) and specific
neurochemical physiology (currently, only the dopamine transporter). This article serves as
an introduction to neuromolecular imaging, reviewing the literature supplemented by the
author’s experience.
Summary:
Neurologic PET and SPECT are no longer restricted to the research realm. These modalities have
high diagnostic accuracy.
Key Points
& Neuromolecular imaging can measure some aspect of a pathologic process within the
brain, but it can also measure the physiologic effects of that pathology on the functioning
of cerebral parenchyma. Both types of measurements provide useful diagnostic
information.
& Positive positron emission tomography amyloid imaging is a biomarker of brain
amyloid-A deposition, and fludeoxyglucose positron emission tomography hypometabolism
in the temporal and parietal cortices and MRI atrophy in the temporal and parietal
lobes are biomarkers of neuronal degeneration or injury.
& Patterns of central nervous system dysfunction shown on neuromolecular imaging
usually develop early in the disease course of dementia, facilitating early diagnosis.
& Each dementing illness has its own pattern of central nervous system dysfunction on
neuromolecular imaging, facilitating differential diagnosis.
& The typical imaging pattern for Alzheimer disease is a posteriorly dominant asymmetric
association cortex hypofunction, worst in temporal and parietal cortices, with important
involvement of the medial parietal cortex. Function is better preserved in primary cortex
and subcortical gray matter structures.

& The biological behavior of tumors is reflected in their glucose metabolic profile.
& The interpretation of fludeoxyglucose positron emission tomography requires
multimodal cross-correlation.
& Neuromolecular imaging has proven usefulness in the noninvasive identification of the
epileptic zone in candidates for resective epileptic surgery.
& Ictal single-photon emission computed tomography and interictal positron emission
tomography can help localize seizure foci in the presurgical evaluation of candidates for
epilepsy surgery.
& A computer-generated combination of ictal single-photon emission computed
tomography (SPECT), interictal SPECT, and MRI often provides precise localization of
seizure foci.
& The greatest challenge in performing ictal single-photon emission computed tomography
for imaging in epilepsy is in injecting radiotracer as close to the time of seizure
onset as possible.
& Differential diagnostic information for parkinsonism is provided by the pattern of striatal
and cortical uptake of neuromolecular imaging tracers.
& The identification of loss of dopamine transporter and the pattern of that loss help to
distinguish neurodegenerative parkinsonism from secondary parkinsonism caused by drugs
and even from tremor disorders such as essential tremor.
& Perfusion and metabolism imaging indirectly demonstrate the hypodopaminergic state by
showing its synaptic consequences.
& Dopamine transporter imaging directly demonstrates the hypodopaminergic state by
showing loss of dopaminergic nerve terminals.
& Cerebral perfusion single-photon emission computed tomography involves the
simultaneous assessment of two physiologic processes, neuronal activity and the state of
the vascular tree. Techniques to disentangle the cerebral perfusion single-photon
emission computed tomography signal into neuronal function versus vascular disease
induce a dilatation in responsive vascular beds by interventions that provoke
tissue acidosis.
& The regions most often involved in traumatic brain injury include polar and orbital frontal
lobes, polar and inferior temporal lobes, and dorsal frontal and parietal lobes. Less
common areas include the perisylvian regions and inferior cerebellum.
& Neuromolecular imaging has high sensitivity for the detection of traumatic brain injury
and often shows injury when CT and MRI are negative.
Ultrasound in Neurology
Georgios Tsivgoulis, MD, PhD, MSc, RVT; Andrei V. Alexandrov, MD, RVT.
Continuum (Minneap Minn). October 2016; 22 (5 Neuroimaging):1655Y1677.
Abstract
Purpose of Review:
Low cost, avoidance of irradiation, and high temporal resolution are inherent advantages of
ultrasound imaging that translate into multiple clinical uses in many domains of neurology. This
article presents clinical uses of ultrasound examination in cerebrovascular, neurodegenerative,
and peripheral nervous system diseases.

Recent Findings:
Modern treatment and prevention of ischemic stroke rely on prompt diagnosis. Ultrasonography
has found a place as a noninvasive screening test and bedside technique that provides
estimates of the degree of stenosis as well as hemodynamic and structural information about
intracranial and extracranial vessels in real time. Other standard applications of neurosonology
include detection of vasospasm in patients with subarachnoid hemorrhage, selection of
appropriate candidates for blood transfusion among patients with sickle cell anemia (primary
stroke prevention), right-to-left shunt testing, emboli detection, vasomotor reactivity assessment,
and noninvasive confirmation of cerebral circulatory arrest. Improvement in image quality
permits novel uses of ultrasonography in neurodegenerative and peripheral nervous system
disorders, providing clinically important information that is complementary to the clinical
examination and electrophysiology. Transcranial parenchymal sonography may assist in the
differential diagnosis of movement disorders, while peripheral nerve ultrasound using
high-frequency probes may provide structural information regarding the underlying etiology
of entrapment neuropathies.
Summary:
The indications for neurosonology are rapidly expanding, increasing its applicability outside
the field of cerebrovascular diseases. Ultrasound testing is a noninvasive easily repeatable
bedside investigation providing clinically relevant information on a wide spectrum of
neurologic disorders.
Key Points
& The extracranial internal carotid, common carotid, external carotid, and vertebral arteries
can be assessed by cervical duplex (simultaneous presentation of brightness-mode
image and Doppler waveform) ultrasonography, while the middle cerebral, anterior
cerebral, posterior cerebral, ophthalmic, intracranial vertebral, and basilar arteries can be
investigated by transcranial Doppler or transcranial color-coded duplex sonography.
& Cervical duplex ultrasonography can directly visualize atherosclerotic plaque composition
that can be classified based on its echogenicity. Cervical duplex ultrasonography also
allows rapid detection of internal carotid artery thrombosis and differentiation between
chronic internal carotid artery occlusion with or without preexisting atheromatous stenosis.
& Peak systolic velocity, end-diastolic velocity, and the systolic internal carotid
artery/common carotid artery velocity ratio are essential ultrasound parameters for
North American Symptomatic Carotid Endarterectomy Trial grading ranges of
extracranial internal carotid artery disease.
& Peak systolic velocity and end-diastolic velocity must be assessed in the prestenotic,
stenotic, and poststenotic segments of the vessel, and ultrasound interpretation must refer
to the North American Symptomatic Carotid Endarterectomy Trial strata of internal
carotid artery stenosis.
& Ultrasonography may assist in the diagnosis of carotid or vertebral artery dissection.
Cervical duplex ultrasonography may detect reversed systolic blood flow at the origin of the
vessel and absent or minimal diastolic blood flow that concurs with high-resistance
bidirectional Doppler signal.
& Intracranial cerebral vasculature can be assessed by transcranial Doppler or transcranial
color-coded duplex sonography to provide real-time flow findings that are
complementary to information provided by CT angiography or multimodal MRI.

& Transcranial Doppler assesses recanalization and potential reocclusion in real time
in patients with acute ischemic stroke treated with systemic or intraarterial
reperfusion therapies.
& A novel application of neurosonology is the assessment of an intracranial arterial steal
syndrome and evaluation of vasomotor reactivity of intracranial arteries.
& The transcranial Doppler bubble test is more sensitive than transthoracic
echocardiography (with or without contrast injection) in detection of a right-to-left shunt
through a patent foramen ovale.
& Transcranial Doppler stratifies the risk of patients with sickle cell anemia and those in
need of blood transfusions for primary stroke prevention. Those who meet transcranial
Doppler criteria for blood transfusions should stay on transfusions since these children
remain at high risk of stroke if transfusions are discontinued.
& One of the first applications of transcranial Doppler in clinical use has been the
identification of cerebral vasospasm after subarachnoid hemorrhage.
& Brain death is a clinical diagnosis that can be supported by transcranial Doppler, given the
ability of transcranial Doppler to detect cerebral circulatory arrest.
& The midbrain appears hypoechoic in transcranial sonography, surrounded by the
hyperechoic basal cisterns, while the substantia nigra appears as a thin hyperechoic strip
with total surface not exceeding 0.20 cm2 in normal subjects.
& Increased substantia nigra hyperechogenicity can be detected with transcranial parenchymal
sonography in approximately 90% of patients with idiopathic Parkinson disease.
& Substantia nigra hyperechogenicity may serve as a preclinical marker of
idiopathic parkinsonism.
& Peripheral nerve ultrasound may offer structural information regarding the underlying
etiology of entrapment neuropathies. Ultrasound findings are complementary to
information offered by neurophysiologic studies.
& Ultrasonography of a peripheral nerve examines five parameters: (1) cross-sectional area
at certain sites of clinical interest, (2) variability of the cross-sectional area along its
course, (3) echogenicity, (4) vascularity, and (5) mobility.
& The most common ultrasound findings seen in patients with symptomatic carpal tunnel
syndrome include enlarged cross-sectional area of the median nerve proximal to the
edge of the flexor retinaculum, increased wrist to forearm swelling ratio, hypoechogenicity
and disturbed fascicular echo structure, reduced slippage of the nerve after finger
flexion, and increased vascularity.

Medicolegal Issues
Legal Implications of
Dr Joseph S. Kass, One Baylor
Plaza M-210, Houston, TX
77030, kass@bcm.edu.
Physician Investment Relationship Disclosure:

Ms Rose serves on the editorial
board of BC Advantage and
and Ownership in receives book royalties from

the American Bar Association.
Dr Kass has received personal
Health Care Enterprises compensation for expert

testimony in legal cases
involving personal injury,
defamation, and malpractice.
Rachel V. Rose, JD, MBA; Joseph S. Kass, MD, JD, FAAN Unlabeled Use of
Use Disclosure:
Ms Rose and Dr Kass report
ABSTRACT no disclosures.
This article presents a case in which a neurology group practice is considering Disclaimer:
investing in an imaging center that is owned by nonphysician investors with the aim This article does not constitute
legal or financial advice on
of referring patients to this imaging center. The article reviews some important legal the part of either the authors
pitfalls in federal law that physicians must be aware of when considering such an or the American Academy
investment and focuses on the general outlines of and exceptions to the Stark Law of Neurology or its affiliates
and is not a substitute for
and the Federal Anti-Kickback Statute. legal advice. Laws and
interpretations of laws are
subject to change. Please
consult a qualified attorney in
your jurisdiction of practice
for legal advice.
Case of Neurology.
A neurology group practice made up of six neurologists who were all
partners in the practice had seen income fall in recent years because of
a decline in EMG reimbursements and a rise in expenditures with a recent
investment in an expensive electronic health record system. In an effort
to increase income for the practice, the group considered investing in
a nearby imaging center with the idea of referring their patients who require
neuroimaging to that center. The investment would be for fair market value,
and the sole current owner of the imaging center was a private equity
firm composed of all nonphysicians. One of the partners in the neurology
group practice was worried that such an investment may run afoul of federal
law and suggested consultation with an attorney. The neurology group
practice was not an Accountable Care Organization.
DISCUSSION
This scenario raises multiple legal issues for all parties involved. Three critical
federal laws must be considered by every party involved in the proposed
transaction: the physician self-referral law (also known as the Stark Law),1 the
Federal Anti-Kickback Statute,2 and the subsequent modifications of these laws
by the Patient Protection and Affordable Care Act,3 commonly referred to as the
Affordable Care Act. When analyzing commercial transactions involving health care
providers, the effect of all three laws should be considered in tandem. Considera-
tion of applicable state laws is also important but is beyond the scope of this article.
Violations of the Stark Law, the Anti-Kickback Statute, or related Affordable Care
Act modifications have serious and far-reaching consequences for physicians and
health care institutions beyond the payment of penalties and refunds. They may

Physician Investment and Ownership
lead to exclusion from Medicare and Medicaid under the Social Security Act.4
Additionally, violations can be used as the basis for False Claims Act violations.5
For example, in 2015, the US Department of Justice resolved a $237 million False
Claims Act judgment involving illegal payments made to referring physicians.6
In United States ex rel. Drakeford v. Tuomey Healthcare System, Inc., Case No.
3:05-cv-02858 (MBS) (D.S.C.), 19 physician contracts executed between physi-
cians and a hospital were found to establish improper financial relationships and
illegal physician referrals, leading to 21,730 false claims. The jury awarded actual
damages of $39,313,065 for the 21,730 false claims, which the district court then
tripled as allowed under the False Claims Act.7
The fundamental purpose of the Stark Law is to mitigate the influence of
financial considerations on physician referrals.8 The Stark Law “[p]rohibits a
physician from making referrals for certain designated health services (DHS)
payable by Medicare to an entity with which he or she (or an immediate family
member) has a financial relationship (ownership, investment, or compensation),
unless an exception applies.”9 A financial relationship is defined as “a direct or
indirect ownership or investment interest” or “a direct or indirect compensation
arrangement.”10 Among the prohibited designated health services are “radiol-
ogy and certain other imaging services.”10
The Stark Law applies to a variety of scenarios and has been implemented in
three phases: Stark I,11 Stark II,12 and Stark III,13 with the Centers for Medicare
& Medicaid Services (CMS) revealing its final changes to the Stark Law in the
Current Year 2016 Medicare Physician Fee Schedule final rule.14 The Stark Law
has a number of exceptions. These exceptions fall into one of three broad
categories: (1) compensation arrangements, such as the publicly traded securities
and mutual fund exception; (2) ownership/investment arrangements, such as
office space and equipment rental, risk-sharing arrangements, and physician
recruitment; and (3) general exceptions, such as the commonly used in-office
ancillary services exception.14 The details of all these very complex exceptions are
beyond the scope of this article, but legal counsel familiar with the intricacies of
the Stark Law can help structure compensation and investment relationships that
are compliant. The Stark Law’s complexity has even led a judge for the US Court
of Appeals for the Fourth Circuit to state that “even for well-intentioned health
care providers, [the Stark Law is] I a booby trap rigged with strict liability and
potentially ruinous exposure.”15 Whereas an Anti-Kickback Statute violation
requires intent, the Stark Law is a strict liability law and does not require that the
government prove the accused intended to violate the law.
The Anti-Kickback Statute extends beyond the referrals that are the domain
of the Stark Law and impacts a multitude of other physician business relationships
in which a federal health care program pays for the procurement of goods and
services. The Anti-Kickback Statute has been interpreted to cover any arrangement
where one purpose of the remuneration was to obtain money for the referral
of services or to induce further referrals.16 Prohibited kickbacks under the Anti-
Kickback Statute include “the knowing and willful solicitation, receipt, offer, or
payment of any remuneration in return for: referring an individual for any items
or services covered by a federal health care program; or purchasing, leasing or
ordering or arranging for, or recommending or arranging for the purchase, lease,
or ordering of any item or service paid for (in whole or in part) by a federal
health care program.”2

Types of arrangements that the Office of the Inspector General has found to
be impermissible include “paying local pharmacies a fee for support services
each time the services result in a referral [specialty pharmacy] to dispense a
specialty drug,”17 “a laboratory’s proposal to enter into agreements with
physician practices to provide all laboratory services for the practices’ patients
and waive all fees for those practices’ patients who are enrollees of certain
insurance plans that require the patients to use a different laboratory,”18 and
“[an] ambulance supplier’s response to a request for proposals (‘RFP’) for the
provision of all emergency ambulance services.”19
Just as the Stark Law has exemptions, the Anti-Kickback Statute has safe
harbors. While exceptions under Stark and safe harbors under the Anti-Kickback
Statute are separate and distinct, they both must be analyzed when considering
the legality of a transaction. Some of the Anti-Kickback Statute safe harbors
include payments to bona fide physician employees, certain investment
interests, and waivers of coinsurance for Medicare services for select in-
dividuals.20,21 It is important to note that if the compensation arrangement is
between a hospital organization and a physician group that qualifies as an
Accountable Care Organization, then compliance with both the Anti-kickback
Statute and the Stark Law may be waived.22
The hypothetical transaction described in this article must be modified to
meet the complex requirements of federal law. First, the transaction should be
analyzed to see if it falls under a Stark Law exception, such as the in-office
ancillary services exception or the physician services exception.23 Stark Law
exceptions include services that meet a number of very specific requirements
with multiple layers of complexity, only some of which can be discussed here.
The physician services exception comes into play when either another physician
in the same group practice or a physician (eg, resident or fellow) under the
personal supervision of another physician in the same group practice personally
provides the referral services.23 For example, if the general neurologist refers a
patient to an interventional neurologist who is a member of the same group
practice to provide a diagnostic angiogram, then the physician services ex-
ception applies.
More germane to the hypothetical scenario is the in-office ancillary services
exception. This exception permits a physician group practice to own, operate,
and receive remuneration for imaging services. To qualify, the neurology group
must be considered a group practice, and certain specific requirements as to
the location and staffing of the neuroimaging center must be met.24,25 A group
practice under the Stark Law requires, among other points, that the physician
group be a single legal entity made up of at least two physicians.26 The in-office
ancillary services exception also specifically prohibits physicians from mandat-
ing that all of their patients go to a facility in which they have an ownership
interest.27 Physicians must also disclose to their patients that they have an
ownership interest in the imaging center. Additionally, Section 6003(a) of the
Affordable Care Act3 imposes a new requirement on physicians who are referring
patients to their group practice for certain imaging services and are relying on the
in-office ancillary services exception. According to the Affordable Care Act and
the Health Care and Education Reconciliation Act of 2010, as of January 1, 2011,
nonradiology physicians who order imaging tests as part of their office practices
are required to make certain disclosures to patients.3,28 Under this provision,

physicians must inform patients in writing at the time of the referral that the
patient may obtain these services from other suppliers and provide a list of
suppliers within 25 miles of the office.
In addition to the Stark Law exceptions, the neurology group must be mindful
of the Anti-Kickback Statute 50-50 Investor Rule when considering how it
structures its investment with the current owners of the imaging center. This rule
states, “no more than 50% of the value of the investment interest of each class of
investments may be held by investors who are in a position to make or influence
referrals to, furnish items or services to, or otherwise generate business for the
entity.”29 Therefore, the fact that a private equity company is composed of non-
referring individuals makes the arrangement legitimate under this Anti-Kickback
Statute safe harbor as long as the neurology group does not own more than a
50% interest in the imaging center. Finally, the physicians’ compensation struc-
ture, such as their profit-sharing arrangements, must also be analyzed in relation
to the Stark Law and Anti-Kickback Statute. The complexities involved in such an
analysis are beyond the scope of this article.
CONCLUSION
Violating the Stark Law, the Anti-Kickback Statute, or its modifications under the
Affordable Care Act may result in devastatingly harsh civil and criminal penalties.
Properly restructuring the neurologists’ investment plan may bring the financial
arrangement into compliance with federal law. The neurology group practice must
ensure that its ownership falls under the appropriate Stark Law exception and Anti-
Kickback Statute safe harbor. The neurologists are obligated to disclose their finan-
cial relationship in the imaging center to their patients and must give their patients
a choice of facilities in which to undergo neuroimaging. The neurologists’ invest-
ment interests and compensation plans from the imaging center’s profits must also
adhere to the provisions of the Stark Law and Anti-Kickback Statute. In addition to
these federal laws, the neurology group’s attorney must also ensure compliance
with applicable state laws. Finally, if the propriety of a particular course of action is
unclear, the neurologists’ attorney may ask for an advisory opinion from the Office
of the Inspector General about the legality of a proposed transaction.
USEFUL WEBSITE
Why Stark, Why Now? A Senate Finance Committee Majority Staff Report. A
helpful tool for keeping up-to-date on changes to the Stark Law.
www.finance.senate.gov/imo/media/doc/Stark%20White%20Paper,%20SFC%
20Majority%20Staff.pdf
REFERENCES
1. Limitation on Certain Physician Referrals, Section 1877 of the Social Security Act, 42 USC §1395nn (1989).
2. Criminal Penalties for Acts Involving Federal Health Care Programs, Section 1128B(b) of the
Social Security Act, 42 USC §1320-aY7b(b).
3. Patient Protection and Affordable Care Act, Pub L 111-148 (2010). www.gpo.gov/fdsys/pkg/
PLAW-111publ148/pdf/PLAW-111publ148.pdf. Published March 23, 2010. Accessed July 28, 2016.
4. Exclusion of Certain Individuals and Entities From Participation in Medicare and State Health
Care Programs. Section 1128(b)(6)(A) of the Social Security Act, 42 USC §1320aY7.

5. United States ex rel Moilan v McAllen Hospitals L.P., No. M-05-cv-263 (SD Tex October 30, 2009);
and Grier R, Frazier S, and Androphy J. False claims act damages in anti-kickback and self-referral
cases. ABA Health eSource (June 2011). www.americanbar.org/newsletter/publications/aba_
health_esource_home/aba_health_law_esource_1106_grier.html. Accessed July 28, 2016.
6. The United States Justice Department. United States resolves $237 million false claims act
judgment against South Carolina hospital that made illegal payments to referring physicians.
www.justice.gov/opa/pr/united-states-resolves-237-million-false-claims-act-judgment-against-
south-carolina-hospital. Published October 16, 2015. Accessed July 28, 2016.
7. Becker S, Carnell H. The Tuomey case: 12 key points. Becker’s Hospital Review. www.
beckershospitalreview.com/legal-regulatory-issues/the-tuomey-case-12-key-points.html.
Published July 16, 2015. Accessed July 28, 2016.
8. American Health Lawyers Association. A public policy discussion: taking the measure of the
Stark Law. www.healthlawyers.org/hlresources/PI/ConvenerSessions/Documents/
Stark%20White%20Paper.pdf. Published 2009. Accessed July 28, 2016.
9. Centers for Medicare & Medicaid Services. Physician self referral. www.cms.gov/Medicare/Fraud-
and-Abuse/PhysicianSelfReferral/index.html?redirect=/physicianselfreferral/11_list_of_codes.asp.
Modified January 5, 2015. Accessed July 28, 2016.
10. Financial Relationship, Compensation, and Ownership or Investment Interest, 42 CFR §411.354(a)(1).
11. Omnibus Budget Reconciliation Act of 1989 (OBRA 1989).
12. Omnibus Budget Reconciliation Act of 1993 (OBRA 1993).
13. US Department of Health and Human Services, Medicare Program; Physicians’ Referrals to Health
Care Entities With Which They Have Financial Relationships (Phase III); 72 Federal Register 51012
(September 5, 2007).
14. US Department of Health and Human Services, Medicare Program; Revisions to Payment Policies
under the Physician Fee Schedule and Other Revisions to Part B for CY 2016, 80 Federal Register
70885, 71300-71341 (November 16, 2015). A pre-publication version of the Final Rule was
released by CMS on October 30, 2015.
15. United States ex rel Drakeford v Tuomey, 792 F3d 364, 395 (4th Cir 2015) (Wynn J, concurring).
16. United States v Borrasi, 639 F3d 774 (7th Cir 2011); United States v McClatchey, 217 F3d 823 (10th Cir
2000); United States v Davis, 132 F3d 1092 (5th Cir 1998); United States v Kats, 871 F2d 105
(9th Cir 1989); United States v Greber, 760 F2d 68 (3d Cir 1985), cert. denied, 474 US 988 (1985).
17. Department of Health and Human Services Office of Inspector General. Re: OIG advisory opinion
no. 14-06. oig.hhs.gov/fraud/docs/advisoryopinions/2014/AdvOpn14-06.pdf. Issued August 7,
2014. Posted August 15, 2014. Accessed July 28, 2016.
18. Department of Health and Human Services Office of Inspector General. RE: OIG advisory opinion
No 15-04. oig.hhs.gov/fraud/docs/advisoryopinions/2015/AdvOpn15-04.pdf. Issued March 18,
2015. Posted March 25, 2015. Accessed July 28, 2016.
19. Department of Health and Human Services Office of Inspector General. Re: OIG advisory
opinion no. 13-18. www.oig.hhs.gov/fraud/docs/advisoryopinions/2013/AdvOpn13-18.pdf. Issued
November 21, 2013. Posted November 27, 2013. Accessed July 28, 2016.
20. Criminal Penalties for Acts Involving Federal Health Care Programs, 42 USC §1320a-7b(b)(3).
21. Criminal Penalties for Acts Involving Federal Health Care Programs, 42 CFR §1001.952(a).
22. King R, Rose R, Merritt M, Okray J. The ABCs of ACOs. Washington, DC: American Bar
Association; 2014, 32Y33.
23. Cornell University Law School Legal Information Institute. 42 CFR 411.355 Y General exceptions
to the referral prohibition related to both ownership/investment and compensation.
www.law.cornell.edu/cfr/text/42/411.355. Accessed July 28, 2016.
24. General Exceptions to the Referral Prohibition Related to Both Qwnership/Investment and
Compensation, 42 CFR §411.355.
25. MLN Matters SE 0441. www.cms.hhs.gov/MLNMattersArticles/downloads/SE0441.pdf. Updated
April 9, 2013. Accessed July 28, 2016.
26. Group Practice, 42 CFR 411.352.

27. General Exceptions to the Referral Prohibition Related to Both Ownership/Investment and
Compensation, 42 CFR 411.355(b)(7).
28. Health Care and Education Reconciliation Act of 2010, Pub L 111-152 (2010). www.gpo.gov/fdsys/pkg/
PLAW-111publ152/pdf/PLAW-111publ152.pdf. Published March 30, 2010. Accessed July 28, 2016.
29. Matyas DE. Anti-kickback and self-referral. American Health Lawyers Association. www.healthlawyers.org/
events/programs/materials/documents/fhl12/matyas.pdf. Published October 2012. Accessed July 28, 2016.

Practice Issues
Safety Considerations
Dr Marcus Ponce de Leon,
Madigan Army Medical
CenterVNeurology,
in Magnetic Resonance 9040A Fitzsimmons

Dr, Tacoma, WA 98431,
marcusponce@yahoo.com.
Imaging of Patients Relationship Disclosure:

Dr Ponce de Leon reports
no disclosure.
With Implanted Unlabeled Use of

Use Disclosure:
Medical Devices
Dr Ponce de Leon reports
no disclosure.
of Neurology.
ABSTRACT
MRI is a valuable tool in the evaluation of patients with neurologic disease. It offers
ease of use and widespread availability; however, MRI can pose significant health
hazards to patients with implantable devices. Accordingly, the US Food and Drug
Administration (FDA) has changed the safety labeling of implantable devices. This
article increases provider awareness by detailing the potential safety risks MRI poses to
patients with implantable devices and reviews the most recent FDA device labeling.
INTRODUCTION
MRI is the most common diagnostic study ordered by neurologists. The ability of
MRI to depict anatomy in great detail and detect a wider range of soft tissue den-
sities than other studies makes it the imaging technique of choice for many
neurologic diseases. Additionally, MRI does not expose the patient to ionizing
radiation or iodinated contrast agents as does CT scanning. However, MRI is not
without risk to the patient. Strong magnetic fields formed by MRI scanners pose
a risk to patients with ferromagnetic and electronic implanted devices. This is an
important consideration since expanding indications and increased life expectancy
translate into a greater number of electronic devices being implanted every year.
This article discusses safety issues involving the use of MRI for patients who have
implanted devices.
Case
A 74-year-old man with diabetes mellitus and hypertension was admitted
for new-onset headaches, nausea, and visual disturbance. Three years prior
to admission, he underwent placement of an implantable cardioverter
defibrillator to treat intermittent symptomatic ventricular tachycardia.
Neurologic examination revealed a left superior quadrantanopia, mild
weakness and hyperreflexia of the left upper and lower extremities, and a
left extensor plantar response. A contrast-enhanced brain MRI was ordered.

Safety Considerations in MRI
DISCUSSION
Approximately 30 million MRI studies are ordered in the United States each year,
and the number of scans grows by 10% annually.1 The number of medical devices
implanted each year is also growing. A 2005 study estimated that up to 75% of
patients with pacemakers will have a medical need for an MRI over the lifetime
of their device.2 Historically, MRIs have been contraindicated for patients with
implanted medical devices, such as cochlear implants, pacemakers, defibrilla-
tors, and deep brain stimulators, secondary to the risks of patient injury and device
malfunction during the procedure. In the past decade, because of advances in
device technology and better understanding of how to mitigate risk, a shift toward
performing MRIs on patients with ferromagnetic and electronic devices has
occurred. However, MRIs continue to pose a safety hazard for this patient
population, and the decision to proceed with an MRI should be based on clinical
necessity and an understanding of potential risks.
Adverse Effects Involving Magnetic Resonance Imaging and

Implanted Medical Devices
MRI scanners produce strong electromagnetic fields that can interact with and
negatively affect implanted devices. Adverse effects include thermal effects, me-
chanical effects, and electromagnetic effects.
Thermal effect. Thermal effect occurs when the radiofrequency generated by
MRI scanners induces currents within electrically conductive materials. This cur-
rent can result in heating of the devices sufficient to injure tissue. Leads associated
with implanted devices pose a particular concern. The US Food and Drug Ad-
ministration (FDA) has noted multiple reports of injuries to patients with
implanted neurologic stimulators caused by heating of electrode tips during MRI
scanning.3 Heating effects have also been demonstrated in patients with cardiac
pacemakers, and several studies have shown increases in serum troponin levels
after MRI scans.4,5 Even patients without devices who retain ‘‘abandoned’’ leads
from previous procedures are at risk from thermal effect.6
Mechanical effect. The static magnetic fields created by MRI scanners strongly
attract metals. Implanted devices contain metal parts and can be moved or shifted
when in contact with the magnetic field. A 2015 study of 19 patients with cochlear
implants who underwent 34 MRI scans showed that four patients experienced
movement of the internal magnet. Three of the patients had their magnet reseated
with manual pressure applied over the scalp, while one required surgical repo-
sitioning.7 Cardiac implantable electronic devices are also susceptible to magnetic
forces. While the ferromagnetic components in cardiac implantable electronic
devices decrease as technology advances, batteries and transformers essential to
device function continue to pose a safety risk. The risk increases with increasing
magnetic field strength, an important consideration as 3T MRI scanners become
more common.
Electromagnetic effect. In addition to adverse effects through heating and
dislodgement of devices, the magnetic field can affect the function of medical
devices. The magnetic field can switch a pacemaker into an asynchronous mode,
disabling its ability to detect and treat tachycardia. Likewise, pacing activity may
be prevented or triggered unnecessarily if the magnet induces current in the
pacemaker leads.8 The battery of an implantable cardioverter defibrillator can be
depleted when the device capacitor is exposed to the magnetic field. Finally,

concern remains that pulsed gradient fields could stimulate the heart and ulti-
mately induce an arrhythmia. While this has not been confirmed in a patient,
gradient field experiments on swine have induced tachycardia.9
Magnetic Resonance Imaging Safety Terminology

To decrease the risk of patient injury and equipment damage, the FDA developed
labeling criteria for objects that enter the magnetic resonance (MR) environment.
Objects are formally defined as MR Safe, MR Conditional, and MR Unsafe and
have green, yellow, and red icons, respectively (Practice Figure 1). The terms MRI
compatible and MRI incompatible are no longer used. MR Safe items are non-
conducting, nonmetallic, and nonmagnetic items that pose no known hazards in
all MRI environments. MR Unsafe items are known to pose hazards in all MRI
environments. MR Conditional items have been demonstrated to pose no known
hazards in specified MRI environments under specified conditions of use. Con-
ditions that define the MRI environment include static magnetic field strength,
radiofrequency fields, spatial gradient magnetic field, time rate of change of the
magnetic field, and specific absorption rate.
Magnetic Resonance Conditional Devices

Prior to 2011, all implantable ferromagnetic and electronic devices were con-
sidered to be MR Unsafe. In practice, many patients with MR Unsafe devices had
MRI scans, and the majority of those patients had no adverse events. However, a
small percentage of patients sustained injuries, damage to an implanted device, or
even death during an MRI scan.10,11 In 2008, the appearance of the first MR
Conditional devices provided patients with a safer option for obtaining an MRI
scan.12 MR Conditional devices can be programmed so that interaction with MRI
scanners is greatly decreased under specific MRI conditions. It is important to
note that MR Conditional devices require significant planning and logistical
support when exposed to the MRI environment. The environmental conditions
required by some devices can prohibit the use of MRI scanners that exceed the
maximum field strength exposure for that device. Or, if the MRI scanner can achieve
a sufficiently low field strength, the image quality may become inadequate.13 In
PRACTICE FIGURE 1 US Food and Drug Administration (FDA) labeling criteria (developed
by the American Society for Testing and Materials International)
for portable objects taken into Zone IV. Square green ‘‘Magnetic
Resonance (MR) Safe’’ label is for wholly nonmetallic objects, triangular yellow
label is for objects with ‘‘MR Conditional’’ rating, and round red label is for
‘‘MR Unsafe’’ objects.

Safety Considerations in MRI
addition to placing requirements on the MRI scanner, MR Conditional devices

must be placed in certain modes during the scan. This action requires individuals
knowledgeable in the programming of the specific device to be present at the
time and location of the scan. These individuals are frequently representatives of
the device manufacturer, thus coordination must occur. For maximum safety,
clinical specialists who manage the conditions for which the device was
implanted should be available while the device is in the MRI mode.
Case Continued
During pre-MRI screening, the patient’s implantable cardioverter
defibrillator was identified as MR Conditional. Radiology personnel arranged
to have a manufacturer’s representative who was knowledgeable in
programming the device on-site for the procedure. After the scan was
completed, the patient reported a sensation of warmth and movement in
the area of the device while he was in the scanner. Interrogation of the
device after the procedure showed that it had not sustained damage, but
the settings had changed. The implantable cardioverter defibrillator was
reprogrammed without incident and an ECG was obtained, which was
normal. The MRI revealed a contrast-enhancing mass involving the right
temporal and frontal lobes consistent with a high-grade glioma. Brain
biopsy confirmed diagnosis of an anaplastic astrocytoma, for which
treatment was begun. Eight months after admission, the implantable
cardioverter defibrillator continued to function normally.
CONCLUSION
MRI in the presence of implantable medical devices is a complex safety issue
impacting millions of patients. Each year, the FDA approves new MR Conditional
devices. Also, advances in technology continue to increase MRI field strengths and
the potential for interaction with medical devices. Health care personnel should
never assume MR safety information about a device, even for MR Conditional
devices, if it is not clearly documented in writing. Rather, the decision to image
should be based on published MR safety information for each device and should
recognize that such information applies only to specifically tested conditions.14
In the case presented in this article, a patient with an implantable cardioverter
defibrillator underwent an MRI and experienced both thermal and mechanical
effects during the procedure that did not cause an injury. The decision to obtain
the MRI was based on clinical necessity and was discussed with the patient. The
case illustrates a situation in which the care team understood and anticipated
potential complications associated with cardiac implantable electronic devices and
MRIs, weighed the risks against the diagnostic value of obtaining the scan, and took
steps to ensure patient safety.
REFERENCES
1. Organization for Economic Cooperation and Development, OECD Health Statistics 2015, July 2015.
The U.S. performs a high number of MRI exams compared to other countries. Compiled by
Peter G Peterson Foundation. pgpf.org/Chart-Archive/0052_MRI-exams. Accessed August 2, 2016.
2. Kalin R, Stanton MS. Current clinical issues for MRI scanning of pacemaker and defibrillator
patients. Pacing Clin Electrophysiol 2005;28(4):326Y328. doi:10.1111/j.1540-8159.2005.50024.x.

3. Konings MK, Bartels LW, Smits HF, Bakker CJ. Heating around intravascular guidewires by
resonating RF waves. J Magn Reson Imaging 2000;12(1):79Y85. doi:10.1002/1522-
2586(200007)12:1G79::AID-JMRI993.0.CO;2-T.
4. Mollerus M, Albin G, Lipinski M, Lucca J. Cardiac biomarkers in patients with permanent
pacemakers and implantable cardioverter-defibrillators undergoing an MRI scan. Pacing Clin
Electrophysiol 2008;31(10):1241Y1245. doi:10.1111/j.1540-8159.2008.01172.x.
5. Naehle CP, Strach K, Thomas D, et al. Magnetic resonance imaging at 1.5-T in patients
with implantable cardioverter-defibrillators. J Am Coll Cardiol 2009;54(6):549Y555.
doi:10.1016/j.jacc.2009.04.050.
6. Langman DA, Goldberg IB, Finn JP, Ennis DB. Pacemaker lead tip heating in abandoned and
pacemaker-attached leads at 1.5 Tesla MRI. J Magn Reson Imaging 2011;33(2):426Y431.
doi:10.1002/jmri.22463.
7. Carlson ML, Neff BA, Link MJ, et al. Magnetic resonance imaging with cochlear implant magnet
in place: safety and imaging quality. Otol Neurotol 2015;36(6):965Y971. doi:10.1097/
MAO.0000000000000666.
8. Roguin A, Schwitter J, Vahlhaus C, et al. Magnetic resonance imaging in individuals with cardiovascular
implantable electronic devices. Europace 2008;10(3):336Y346. doi:10.1093/europace/eun021.
9. Tandri H, Zviman MM, Wedan SR, et al. Determinants of gradient field-induced current in a
pacemaker lead system in a magnetic resonance imaging environment. Heart Rhythm
2008;5(3):462Y468. doi:10.1016/j.hrthm.2007.12.022.
10. Fontaine JM, Mohamed FB, Gottlieb C, et al. Rapid ventricular pacing in a pacemaker patient
undergoing magnetic resonance imaging. Pacing Clin Electrophysiol 1998;21(6):1336Y1339.
doi:10.1111/j.1540-8159.1998.tb00202.x.
11. Irnich W, Irnich B, Bartsch C, et al. Do we need pacemakers resistant to magnetic resonance
imaging? Europace 2005;7(4):353Y365. doi:10.1016/j.eupc.2005.02.120.
12. Sutton R, Kanal E, Wilkoff BL, et al. Safety of magnetic resonance imaging of patients with a
new Medtronic EnRhythm MRI SureScan pacing system: clinical study design. Trials 2008;9:68.
doi:10.1186/1745-6215-9-68.
13. Crane BT, Gottschalk B, Kraut M, et al. Magnetic resonance imaging at 1.5 T after cochlear
implantation. Otol Neurotol 2010;31(8):1215Y1220. doi:10.1097/MAO.0b013e3181ec1d61.
14. Expert Panel on MR Safety, Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document on MR
safe practices: 2013. J Magn Reson Imaging 2013;37(3):501Y530. doi:10.1002/jmri.24011.

Practice Issues
Coding in Neuroimaging Address correspondence to

Dr Joseph V. Fritz, DENT
Neurologic Institute,
Joseph V. Fritz, PhD; Bennett Myers, MD 3980 Sheridan Dr, Amherst,
NY 14226,
Jfritz@dentinstitute.com.
Accurate coding is an important function of neurologic practice. This contribution to Relationship Disclosure:
Continuum is part of an ongoing series that presents helpful coding information Dr Fritz serves as a consultant
along with examples related to the issue topic. Tips for diagnosis coding, Evaluation for Allergan. Dr Myers has
served on the scientific
and Management coding, procedure coding, or a combination are presented, advisory board of Biogen and
depending on which is most applicable to the subject area of the issue. has received personal
compensation for speaking
engagements from Biogen,
INTRODUCTION Novartis AG, and Teva
Pharmaceutical Industries Ltd.
This article reviews Current Procedural Terminology (CPT)1 codes for neuroim- Dr Myers has provided
aging studies along with the indications and documentation required to support expert medical testimony
on brachial plexopathy as
appropriate use criteria. An example vignette is presented to help illustrate cod- a complication of scalene
ing and documentation requirements. Providers are advised to consult with local nerve block.
and national payer coverage determination documents for reimbursement guide- Unlabeled Use of
lines to determine medical necessity. Use Disclosure:
Drs Fritz and Myers report
ADVANCED IMAGING CODES AND APPROPRIATE INDICATIONS no disclosures.
Common CPT codes and typical neurologic indications for MRI, magnetic re- of Neurology.
sonance angiography (MRA), CT, CT angiography (CTA), noninvasive vascular
imaging and ultrasound, and nuclear medicine (positron emission tomography
[PET] and single-photon emission computed tomography [SPECT]) of the brain,
neck, spine, and neurovasculature are summarized in Coding Table 1 through
Coding Table 11,2Y7 based on American Medical Association coding standards.1
Qualifying indications are based on published clinical guidelines from the Centers
for Medicare & Medicaid Services (CMS), payer, and radiology benefits management
system websites,2Y5,8,9 but are not exhaustive and do not ensure payer authorization.
Rules-based software tools are used by many payers and radiology benefits
management systems to check appropriateness prior to authorizing an imaging
study. Commercial tools are also available to help guide the ordering provider.10 In
general, if the imaging study will not alter the care of the patient (regardless of
the results), it will be difficult to justify medical necessity. Similarly, if the clinical
findings alone warrant intervention, it is unlikely that a confirmatory imaging
study will be authorized.
Evidence-based appropriateness recommendations, such as those published by
the American College of Radiology,11 are commonly used in the development of
payer policies. However, significant nuances still remain in local payer imaging
guidelines. Also, detailed considerations of the patient condition and other avail-
able information further complicate appropriateness testing. The Medicare
Access and CHIP (Children’s Health Insurance Program) Reauthorization Act of
2015 (MACRA) includes the directive to implement clinical decision support mech-
anisms tied to appropriate use criteria.12 It is conceivable that CMS will eventually
mandate integration and standardization of clinical guidelines into electronic
medical record systems.
Neurologic conditions representing referring indications are normally described
by the International Classification of Diseases, Tenth Revision, Clinical Mod-
ification (ICD-10-CM) codes G00 to G99.13 Symptom codes draw from coding
sections ‘‘Symptoms, Signs and Abnormal Clinical and Laboratory Findings, Not
Continuum (Minneap Minn) 2016;22(5):e1–e25 www.ContinuumJournal.com e1

Coding in Neuroimaging
Elsewhere Specified’’ (ICD-10-CM codes R00 to R99), ‘‘Injury, Poisoning and

Certain Other Consequences of External Causes’’ (ICD-10-CM codes S00 to T88),
‘‘External Causes of Morbidity’’ (ICD-10-CM codes V00 to Y99), and ‘‘Factors
Influencing Health Status and Contact With Health Services’’ (ICD-10-CM codes
Z00 to Z99). A number of published clinical guidelines list specific diagnostic
codes as prerequisites for imaging. However, given the abundance of ICD-10-CM
codes representing candidate conditions and symptoms, the referring provider is
advised to use electronic medical recordYbased look-up tables or other standard
references to find the appropriate diagnostic codes corresponding to the
qualifying condition or symptom.13,14
DOCUMENTATION REQUIREMENTS
Patient documentation consists of the Evaluation and Management (E/M) visit
note, referral order, CPT and ICD codes, imaging report, and E/M follow-up
visit note. The visit note associated with the imaging order must clearly state
the clinical rationale and symptoms that justify ordering the study, describe
how the results will affect management, discuss other tests that are needed or
have already been performed, list applicable ICD-10-CM codes, and provide
the relevant differential diagnosis. ‘‘Suspected’’ or ‘‘rule out’’ conditions must
be supported by known signs and symptoms and documented with ICD codes
that validate the suspicion.
The referral order must summarize the indications, specify the name and CPT
code(s) for the desired procedure, and associate the relevant diagnostic codes
that are aligned with the payer’s documented clinical guidelines. The CPT code
must match, not approximate, the desired procedure; otherwise, an ‘‘unlisted’’
procedure code should be used.
Once the imaging study has been completed, a report from the reading
physician must be generated, which must contain a description of the study, relate
findings and limitations to the clinical question, and provide an impression with
specific or differential diagnoses. Upon receipt of the imaging report, the referring
provider is responsible for integrating these findings into the patient’s care plan,
documented by a follow-up visit note describing how the imaging results will be
used to update the diagnosis and patient’s care plan.
The referring provider and support staff should become familiar with applicable
payer policies and be sensitive to their specific requirements for medical necessity
determination; otherwise, the authorization process may become more arduous,
with increased demand for time-consuming peer-to-peer reviews. Depending on
the payer, authorization may also require submission of clinical notes or peer-to-
peer reviews. Documentation completeness and consistency also provide the
imaging center with the insight needed to optimize acquisition techniques and
report findings that address the clinical question.
Consequences for improper documentation include authorization delays,
payment denials, audits that may result in retroactive refunds and penalties, and
perceptions of overutilization that may result in financial penalties or exclusion
from some payer networks. Institutions that operate the imaging service are also
negatively impacted when clinical documentation is sparse, with risks of refunds,
patient inconvenience, staff inefficiencies, and suboptimal scan protocols or
interpretations. When ordering imaging studies, these additional recommenda-
tions should be followed:
e2 www.ContinuumJournal.com October 2016

& Do not order imaging before relevant results are obtained from prior
imaging studies, laboratory tests, or progress from current therapies.
& Be mindful of tests that have been determined to be commonly overused.15
Examples include MRI for headaches without associated neurologic
symptoms and imaging patients with back pain before conservative
therapies have been completed, unless symptoms are worsening or results
from EMG or nerve conduction studies are positive.
& Avoid imaging of multiple body parts in one encounter, such as head
and neck MRI, cervical-thoracic-lumbar imaging, or MRI with magnetic
resonance angiography. Combined tests can result in unnecessary costs
or authorization delay if it is clinically apparent that a more targeted study
is sufficient or if the need for additional studies depends on results of
more limited imaging.
& Specify preferred equipment or techniques that are not distinctly defined by
the CPT code (eg, susceptibility-weighted imaging [SWI] for head trauma,
3T MRI for patients with multiple sclerosis [MS], low-dose CT for pediatric
studies, or wide-bore MRI for patients who are claustrophobic).
& Use the ICD-10-CM code Z00.6, Encounter for examination for normal
comparison and control in clinical research program, in either the primary
or secondary position, along with supporting information for research scans
performed under approved clinical evidence determination protocols, if
billing through a Medicare fiscal intermediary. (For more details, visit www.
cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/
MLNMattersArticles/downloads/MM8401.pdf.)
& Additional documentation is required with a PET scan claim for
neurodegenerative disease, including date of symptom onset, diagnosis of
clinical syndrome (normal aging; mild cognitive impairment; mild, moderate,
or severe dementia), Mini-Mental State Examination (MMSE) or similar test
score, presumptive cause (possible, probable, uncertain Alzheimer disease),
any neuropsychological testing performed, results of any structural imaging
(MRI, CT) performed, relevant laboratory tests (vitamin B12, thyroid
hormone), and number and name of prescribed medications.
& When a CT scan and MRI are performed on the same day for the same
anatomic area, the medical record must clearly reflect the medical necessity
for performing both tests.
& When performing postoperative evaluations, the medical rationale must
clearly indicate why additional imaging is needed.
& If the referral is for a condition that is suspected but not known, describe
and provide ICD-10-CM codes for applicable symptoms, findings, laboratory
tests, or prior imaging studies.
& Include supporting data in the clinical and referral notes that will help the
imaging center workflow and ensure they fully understand the patient
condition, for example, prior surgeries, patient obesity, claustrophobia, and
prior imaging studies that should be compared.

Case
A 36-year-old right-handed woman presented with a 2-month history of
the gradual onset of difficulty walking and a 1-week history of numbness
that began in the right foot, which, over the course of 2 minutes, spread
to involve the entire right side of her body. She had visited an urgent
care facility because of the new-onset numbness, where no imaging was
performed. Over the course of the next 24 hours, the numbness largely
resolved, although she had residual numbness in the right foot and
right hand. However, 2 days later, she developed numbness in the left
hand. At that time, she began to experience intermittent electric
shocklike sensations that traveled from her neck down her spine with
neck flexion.
The patient had no bowel, bladder, or bulbar dysfunction. She had no
prior history of similar symptoms, loss of vision in one eye, or double
vision. She did have a brief period of mild ataxia 5 years ago, for which she
did not seek medical attention. Her symptom onset was not preceded by
injury, illness, or trauma. No aggravating or relieving factors were
identified. Her medications included vitamin B12, vitamin C, and vitamin D.
She had no significant past medical history or family history.
On examination, vital signs were normal. Mental status and cranial
nerve examinations were normal and her funduscopic examination was
normal. Muscle strength testing showed mild hip flexion weakness
bilaterally. Sensory examination showed decreased vibration sense in
the fingers and the toes. Reflexes were increased in the biceps, triceps,
knees, and ankles, and she had bilateral Babinski signs. Gait was mildly
unsteady. Specific points of her comprehensive neurologic examination
that were normal and abnormal were documented individually in the record.
Paresthesia of her upper and lower extremities of both sides and gait
disorder were documented using International Classification of Diseases,
Tenth Revision, Clinical Modification (ICD-10-CM) codes R20.2, Paresthesia
of skin, and R26.81, Unsteadiness on feet. Blood work to evaluate for Lyme
disease and inflammatory disorders was negative. Vitamin B12 level was
normal. Complete metabolic profile, complete blood cell count, and
thyroid function tests were normal. Her presentation was worrisome for
myelitis of the cervical spine likely associated with multiple sclerosis (MS).
An MRI of the brain with and without contrast (Current Procedural
Terminology [CPT] code 70553, without contrast material, followed by
contrast material[s] and further sequences) and an MRI of the cervical spine
with and without contrast (CPT code 72156, Magnetic resonance [eg, proton]
imaging, spinal canal and contents, without contrast material, followed by
contrast materials[s] and further sequences; cervical) were ordered. The
possibility of MS affecting the brain and spinal cord, likely of the
relapsing-remitting type, was discussed with the patient and her husband.
A follow-up visit was conducted after MRI scanning was performed. The
MRI brain study revealed multiple periventricular white matter lesions,
some perpendicular to the ventricles. Two lesions were within the corpus
callosum. Two of the periventricular white matter lesions showed abnormal
contrast enhancement. MRI of the cervical spine obtained the same day
revealed an area of bright T2 signal without enhancement at the C3 level.
Continued on page e5

Continued from page e4
Based on the results of the imaging study and the characteristic history,
the patient was diagnosed with relapsing-remitting MS. Diagnosis,
pathophysiology, epidemiology, prognosis, and treatment options were
discussed, including medications taken orally and by injection or infusion.
A follow-up visit was scheduled in 1 week to decide on choice of
immunomodulatory agent. The diagnostic code was changed to
ICD-10-CM code G35, Multiple sclerosis.
DISCUSSION
In the example presented, the clinical documentation clearly described symptoms
correlated with MS affecting both the brain and spine. These suspicions were not
contradicted by laboratory studies. Payers often resist authorizing a cervical spine
study in combination with the brain without additional justification. In this ex-
ample, the history localized the disease process to the cervical spinal cord, most
likely myelitis associated with MS, and was strengthened by the remote history of
an episode of ataxia. Note that the referring indication represented the known
symptoms, collectively coded as paresthesia. The patient’s condition was not
coded as MS until the condition was confirmed by imaging.
CONCLUSION
Proper documentation and coding of the neurologic examination is critical to the
imaging referral process. Payer authorizations depend on such information, and
delays or inaccuracies can significantly impact access to important diagnostic
testing. Clearly stating the clinical rationale and reconsidering the need for multiple
studies can often alleviate the need for time-consuming peer-to-peer conversation.
Increased scrutiny of utilization equates to audits and potentially severe penalties
for those who inappropriately order advanced imaging. These penalties may
include fines, negative publicity through transparency campaigns, additional
authorization hurdles, or removal from certain payer networks. Furthermore,
imaging centers depend on detailed clinical rationale to optimize scan protocols
and image interpretation. Future integration of lengthy, complex, and diverse
clinical guidelines into the electronic medical record environment is expected to
improve utilization and completeness of documentation.

CODING TABLE 1 Current Procedural Terminology Codes and

Indications for MRI of the Brain
Code Descriptor
70551 Magnetic resonance (eg, proton) imaging, brain (including brain stem);
without contrast material
70552 with contrast material(s)
70553 without contrast material, followed by contrast material(s) and
further sequences
b Indications2
Detecting or evaluating extraaxial tumors
Arteriovenous malformations
Cavernous malformations
Small intracranial aneurysms
Cranial nerve lesions
Demyelinating disorders, including multiple sclerosis
Lesions near dense bone
Vestibular schwannomas
Pituitary lesions
Brain radiation injuries
Developmental brain abnormalities (eg neuroectodermal dysplasia)
Subacute central nervous system hemorrhage or hematoma
Acute stroke
Complex partial seizures
Seizures refractory to therapy
Temporal lobe epilepsy
Other atypical seizure disorders
Acute head trauma
Acute intracranial bleeding
Skull fracture or other bone abnormality
Follow-up for hydrocephalus
Focal problem or recent significant change in symptomatology
Brain infections
CT contraindicated

CPT B 2014 American Medical Association.1 All rights reserved. CPT is a registered trademark of
the American Medical Association.

Indications for Magnetic Resonance Angiography
of the Head and Necka
Code Descriptor
70544 Magnetic resonance angiography, head; without contrast material(s)
70546 without contrast material(s), followed by contrast material(s) and
further sequences
70547 Magnetic resonance angiography, neck; without contrast material(s)
further sequences
b Indications2
Determine necessity for surgery in:
Tumor
Aneurysms
Vascular malformations
Vascular occlusion or thrombosis
Suspected transient ischemic attack with carotid bruit and stenosis shown
on Doppler
Prior imaging findings suspicious
b Specify
Carotid arteries
Circle of Willis
Anterior, middle, or posterior cerebral arteries
Vertebral or basilar arteries
Venous sinuses
a
Magnetic resonance angiography (MRA) is typically not appropriate for patients who are
asymptomatic, patients who have a headache (unless accompanied by other symptoms that may
imply intracranial aneurysm, such as blood in CSF), or in addition to diagnostic contrast angiography.


Indications for MRI of the Orbit, Face, and Neck
Code Descriptor
70540 Magnetic resonance (eg, proton) imaging, orbit, face, and/or neck;
without contrast material(s)
further sequences
b Indications2
Tumor
Infection
Soft tissue pathologies
Congenital abnormalities
b Specify
Nasopharynx
Oropharynx
Neck
MRI = magnetic resonance imaging.


Indications for Other MRI Procedures
Code Descriptor
70554 Magnetic resonance imaging, brain, functional MRI; including test
selection and administration of repetitive body part movement and/or
visual stimulation, not requiring physician or psychologist administration
70555 requiring physician or psychologist administration of entire
neurofunctional testing
b Indications3
Brain tumor (preoperative lesion mapping)
Seizure (preoperative lesion mapping)
Posttreatment, procedure, surgery
Code Descriptor
76390 Magnetic resonance spectroscopy
b Indications4
Differentiate recurrent or residual brain tumor from post-therapy changes,
(eg, delayed radiation necrosis)

Indications for Other MRI Procedures
Differentiate brain tumor from other nontumor diagnoses, (eg, abscesses or

other infectious or inflammatory processes)
Cerebrovascular injury
Degenerative diseases
Dementia (including Alzheimer disease)
Epilepsy
Metabolic and mitochondrial diseases
Multiple sclerosis diagnosis and monitoring
Parkinson disease
Code Descriptor
76498 Unlisted magnetic resonance procedure (eg, diagnostic, interventional)
b Example MRI Studies That Would Use CPT Code 76498a
Magnetic resonance neurography
Whole-body MRI
MRI with focused ultrasound (investigational)
Code Descriptor
76376 3D rendering with interpretation and reporting of computed tomography,
magnetic resonance imaging, ultrasound, or other tomographic modality
with image postprocessing under concurrent supervision; not requiring
image postprocessing on an independent workstation
76377 requiring image postprocessing on an independent workstation
b Example MRI Studies That Would Use CPT Code 76376 or 76377
Ventricular and/or hippocampal volume quantitation in dementia
Presurgical planning
Code Descriptor
72159 Magnetic resonance angiography, spinal canal and contents, with or
b Indications2
Spinal arteriovenous malformation
Cervical spine fracture
Known or suspected vertebral artery injury
CPT = Current Procedural Terminology; MRI = magnetic resonance imaging.

a
Use of unlisted procedures is often associated with procedures that payers consider to be not
medically necessary.


Indications for MRI of the Spine
Code Descriptor
72141 Magnetic resonance (eg, proton) imaging, spinal canal and contents,
cervical; without contrast material
thoracic; without contrast material
lumbar; without contrast material
without contrast material, followed by contrast material(s) and further
sequences; cervical
72157 thoracic
72158 lumbar
72159 Magnetic resonance angiography, spinal canal and contents, with or
b Example Indications2
Spinal cord lesion
Syringomyelia
Spinal cord demyelination or inflammation
Spine or spinal cord tumor
Spinal cord infarct
Spinal trauma
Discitis and osteomyelitis
Epidural abscess
Developmental abnormality (eg, spinal dysraphism)
Spinal stenosis
Spinal cord compression
Postoperative scarring
Herniation of disc
CT limited by bone artifacts or iodinated contrast contraindicated


Indications for CT of the Head and Neck
b Head and Brain

Code Descriptor
70450 Computed tomography, head or brain; without contrast material
further sections
Indications2
Acute head trauma
Suspected acute intracranial hemorrhage
Detection or evaluation of calcification
Immediate postoperative evaluation for surgical treatment of tumor or for
surgical treatment of hemorrhage or hemorrhagic lesions
Shunted hydrocephalus or shunt revision
Mental status change
Increased intracranial pressure
Treated/untreated vascular lesions
Acute neurologic deficits
Suspected intracranial infection
Suspected hydrocephalus
Congenital lesions (such as, but not limited to, craniosynotosis,
macrocephaly, and microcephaly)
Evaluating psychiatric disorders
Brain herniation
Suspected mass or tumor
Evaluation for small metallic objects prior to MRI (if plain film inadequate)
Certain conditions related to headache, including
After head injury
Unusual in duration, character, severity, or suddenness of onset
Not responding to medical therapy
Conditions in which magnetic resonance is contraindicated, such as
Diplopia
Cranial nerve dysfunction
Seizures
Apnea


Syncope
Ataxia (including dizziness and vertigo)
Neurodegenerative disease
Developmental delay
Neuroendocrine dysfunction
Encephalitis
Vascular occlusive disease or vasculitis
Aneurysm
Drug toxicity
Cortical dysplasia
Migration anomalies or other morphologic brain abnormalities
Sinusitis
Hearing loss and other otolaryngologic presentations
Nontraumatic neurologic central deficit with suspicion of infarction or bleeding
Foreign body
Thyroid ophthalmopathy or proptosis
b Orbits, Sella, Posterior Fossa, and Maxillofacial Area
Code Descriptor
70480 Computed tomography, orbit, sella, or posterior fossa or outer, middle,
or inner ear; without contrast material
further sections
70486 Computed tomography, maxillofacial area; without contrast material
further sections
Indications for Orbits, Sella, or Posterior Fossa3
Proptosis (exophthalmos)
Progressive vision loss
Decreased range of motion of the eyes
Ocular tumor, especially melanoma
Suspected hyperthyroidism (such as Graves disease)
Trauma

Known or suspected optic neuritis if MRI is contraindicated or is unable to

be performed
Unilateral visual deficit
Suspected orbital pseudotumor
Indications for Face3
Sinonasal or facial tumor
Osteomyelitis
Parotid stones
Trauma, (eg, suspected facial bone fractures)
Facial abscesses
b Soft Tissue of the Neck
Code Descriptor
70490 Computed tomography, soft tissue neck; without contrast material
70492 without contrast material followed by contrast material(s) and
further sections
Indications3
Neck tumor, mass (combination studies if suspected metastases or ongoing
surveillance)
History of cancer with suspected recurrence or metastasis
Skull base tumor, mass, or cancer
Tumors of the tongue, larynx, nasopharynx, pharynx, or salivary glands
Parathyroid tumor presurgical assessment (check payer policy for
prerequisite testing)
Palpable lesions in mouth or throat
Nonthyroid masses (check policy for size and duration prerequisites)
Inflammatory disease or infections
Abscesses of the pharynx and neck
Lymphadenopathy (check policy for size and duration prerequisites)
Preoperative evaluation
Postoperative/procedural evaluation (eg, postYneck dissection)


Vocal cord lesions

Vocal cord paralysis
Evaluation of the parotid and submandibular glands and ducts


Indications for CT Angiography
Code Descriptor
70496 Computed tomographic angiography, head, with contrast material(s),
including noncontrast images, if performed, and image postprocessing
b Indications3
Intracranial aneurysm
Arteriovenous malformation
Vertebral basilar insufficiency
Vascular abnormality visualized on previous brain imaging
Vasculitis
Abnormal laboratory results suggesting acute inflammation or
autoimmune antibodies
History of intracranial aneurysm in parent or sibling
Polycystic kidney disease,
Ehlers-Danlos syndrome
Fibromuscular dysplasia
Neurofibromatosis
Aortic coarctation
Venous thrombosis
Pulsatile tinnitus
Preoperative evaluation for brain/skull surgery
Postoperative/procedural evaluation
Code Descriptor
70498 Computed tomographic angiography, neck, with contrast material(s),
including noncontrast images, if performed, and image postprocessing

Indications for CT Angiography Continued from page e14
b Indications3
Abnormal ultrasound or carotid duplex imaging of the neck
Suspected carotid or vertebral artery dissection in closed head injury
Carotid body tumors, paragangliomas
Pulsatile neck mass
Evaluation before carotid endarterectomy
Evaluation after treatment, intervention, or surgery
b Indications for Brain CTA/Neck CTA combination
Recent stroke or transient ischemic attack
Sudden onset of one-sided weakness
Inability to speak
Vision defects
Severe dizziness
Symptoms of vertebral basilar insufficiency (eg, vision changes, vertigo,
abnormal speech)
Suspected carotid or vertebral artery dissection in closed head injury
CT = computed tomography; CTA = computed tomographic angiography.


Indications for CT of the Spine
Code Descriptor
72125 Computed tomography, cervical spine; without contrast material
72126 with contrast material
further sections
72128 Computed tomography, thoracic spine; without contrast material
further sections
72131 Computed tomography, lumbar spine; without contrast material
further sections


Indications for CT of the Spine Continued from page e15
b Indications3 for Conditions Such as Fracture, Tumor, Cancer, Metastasis,

Postoperative Evaluation, and Cord Compression, Supported By Laboratory
Results, Prior Imaging, and Symptoms Including
Delayed or nonhealing postoperative
Extremity weakness
Abnormal/asymmetric reflexes
Abnormal gait
Abnormal sensory changes along a particular nerve distribution
Cauda equina syndrome
Bowel or bladder dysfunction
New footdrop
Radiculopathy and positive EMG/NCV test
Progression or worsening of symptoms during treatment
Laboratory or prior imaging suggesting new or change in tumor
Muscle weakness
Evidence of metastasis on bone scan or previous imaging study
Prior abnormal or indeterminate imaging that requires further clarification
Changing neurologic status postoperatively
Evidence of surgical infection
b Other Indications Include
Determine the position of fracture fragments
Staging of known tumor
Evaluation of patient undergoing active tumor treatment
If spine MRI is contraindicated for
Preoperative evaluation
Infection
Abscess
Inflammatory disease
Degenerative changes
New-onset back pain
Symptoms related to immune system suppression
Tethered cord
Spinal dysraphism

Indications for CT of the Spine Continued from page e16
Syringomyelia
Ankylosing spondylitis
CT = computed tomography; EMG = electromyography; NCV = nerve conduction velocities.


Indications for Other CT Procedures
b Combination Scans
Cervical/thoracic/lumbar CT
CT myelogram or discogram
Metastatic survey
b Cervical MRI/CT
Unstable craniocervical junction
b Brain CT/Cervical CT
Arnold-Chiari malformation
Code Descriptor
0042T Cerebral perfusion analysis using computed tomography with contrast
administration, including post-processing of parametric maps with
determination of cerebral blood flow, cerebral blood volume, and
mean transit time
Indication4
Identify ischemic brain regions, especially within the first few hours after
stroke onset
Code Descriptor
76497 Unlisted computed tomography procedure (eg, diagnostic, interventional)
Example
CT whole body scanning
Code Descriptor
72285 Discography, cervical or thoracic, radiological supervision and interpretation
62291 Injection procedure for discography, each level; cervical or thoracic
Indication
Cervical and thoracic pain syndromes (check local payer policy)


CODING TABLE 10 Current Procedural Terminology Codes

and Indications for Noninvasive
Vascular Imaging
b General Indications and Conditions2

Significant signs/symptoms of arterial or venous disease, supported by
medical history
Not redundant to other diagnostic procedures that must be performed
Used when invasive correction is contemplated
b Extracranial Arteries (Carotids, Vertebrals)
Code Descriptor
93880 Duplex scan of extracranial arteries; complete bilateral study
93882 unilateral or limited study
Indications
Asymptomatic or symptomatic cervical bruits
Amaurosis fugax
Focal cerebral or ocular transient ischemic attacks, including, but not limited to
Localizing symptoms (eg, sensory loss)
Weakness of one side of the face
Slurred speech
Weakness of a limb
Syncope suggestive of vertebrobasilar or bilateral carotid artery disease
Recent neurologic or cerebrovascular event
Before major cardiac and vascular surgery when a bruit is noted or a history
of previous neurologic or cerebrovascular event exists
After carotid endarterectomy (outside the global period) or follow-up of
previously documented stenoses
Pulsatile neck mass
Evaluation of blunt or penetrating neck trauma
Ocular microembolism (eg, optic nerve/retinal arterial/Hollenhorst plaques/ocular)
b Transcranial Doppler (TCD) Studies
Code Descriptor
93886 Transcranial Doppler study of the intracranial arteries; complete study
93888 limited study
93890 vasoreactivity study
93892 emboli detection without intravenous microbubble injection
93893 emboli detection with intravenous microbubble injection

Vascular Imaging Continued from page e18
Indications2
Hemodynamic effects of severe stenosis or occlusion of the extracranial
(greater than or equal to 60% diameter reduction) and major basal
intracranial arteries (greater than or equal to 50% diameter reduction)
Cerebral vasospasm complicating subarachnoid hemorrhage
Intracranial hemodynamic abnormalities in patients with suspected brain death
Intraoperative and perioperative monitoring of intracranial flow velocity
and hemodynamic patterns during carotid endarterectomy
Evaluation of cerebral embolization
Assessing hemodynamic effects, patterns, and extent of collateral circulation in
patients with known regions of severe stenosis or occlusion
Assessing stroke risk in children 2 to 16 years of age with homozygous sickle
cell anemia
Detecting residual right-to-left shunting after repair/closure of an intracardiac
or intrapulmonary shunt
b Peripheral Artery Examinations
Code Descriptor
93923 Complete bilateral noninvasive physiologic studies of upper or lower
extremity arteries, 3 or more levels (eg, for lower extremity: ankle/
brachial indices at distal posterior tibial and anterior tibial/dorsalis
pedis arteries plus segmental blood pressure measurements with
bidirectional Doppler waveform recording and analysis, at 3 or more
levels, or ankle/brachial indices at distal posterior tibial and anterior
tibial/dorsalis pedis arteries plus segmental volume plethysmography at
3 or more levels), or ankle/brachial indices at distal posterior tibial and
anterior tibial/dorsalis pedis arteries plus segmental transcutaneous
oxygen tension measurements at 3 or more levels), or single level study
with provocative functional maneuvers (eg, measurements with
postural provocative tests, or measurements with reactive hyperemia)
93925 Duplex scan of lower extremity arteries and arterial bypass grafts;
complete bilateral study
Indications
Severe claudication
Rest pain, absent pulses, increasingly severe with elevation
Gangrene or pregangrenous changes of the extremity
Ischemic ulceration of the extremity occurring in the absence of pulses
Aneurysmal disease
Evidence of thromboembolic events


Vascular Imaging Continued from page e19
Blunt or penetrating trauma (including complications of procedures)

Follow-up of grafts or other vascular intervention
Presurgical conduit assessment
b Peripheral Venous Examinations
Code Descriptor
93965 Noninvasive physiologic studies of extremity veins, complete
bilateral study (eg, Doppler waveform analysis with responses to
compression and other maneuvers, phleborheography, impedance
plethysmography)
93970 Duplex scan of extremity veins including responses to compression and
other maneuvers; complete bilateral study
General Indications
Candidate for anticoagulation, thrombolysis, or invasive therapeutic
procedures
Specific Indications Related to Deep Vein Thrombosis
Edema
Tenderness
Inflammation
Erythema
Suspected pulmonary embolus (hemoptysis, chest pain, dyspnea)
Unexplained lower extremity edema status
Post major surgical procedures
Trauma
Unexplained lower extremity pain

Indications for Nuclear Medicine Studies Used
in Neurologya,b
b Brain Positron Emission Tomography (PET) and PET/CT

Code Descriptor
78814 Positron emission tomography (PET) with concurrently acquired
computed tomography (CT) for attenuation correction and anatomical
localization imaging; limited area (eg, chest, head/neck)
78815 skull base to mid-thigh
78816 whole body
78608 Brain imaging, positron emission tomography (PET); metabolic
evaluation
78609 perfusion evaluation
78811 Positron emission tomography (PET) imaging; limited area (eg, chest,
head/neck)
78812 skull base to mid-thigh
78813 whole body
78999 Unlisted miscellaneous procedure, diagnostic nuclear medicine
Tracer HCPCS Codes
A9552 Fludeoxyglucose F-18 FDG
A9555 Rubidium RB-82
A9526 Ammonia N-13
A9586c Florbetapir F-18
A9599c (Generic beta amyloid tracer code)
Modifiers
PI Positron emission tomography (PET) or PET/computed tomography (CT) to
inform the initial treatment strategy of tumors that are biopsy proven or
strongly suspected of being cancerous based on other diagnostic testing
PS Positron emission tomography (PET) or PET/computed tomography (CT)
to inform the subsequent treatment strategy of cancerous tumors when the
beneficiary’s treating physician determines that the PET study is needed to
inform subsequent anti-tumor strategy
Q0 Investigational clinical service provided in a clinical research study that is
in an approved clinical research study
Q1 Routine clinical service provided in a clinical research study that is in an
approved clinical research study


in Neurologya,b Continued from page e21
Indications
Early identification and staging of malignancies, therapy planning, and
treatment
Suspected brain metastatic disease
Epilepsy (presurgical refractory seizures)
Dementia and neurodegenerative disease (Alzheimer versus frontotemporal
dementia)
b Brain Imaging (Nontumor)
Code Descriptor
78600 Brain imaging, less than 4 static views;
78601 with vascular flow
78605 Brain imaging, minimum 4 static views;
78606 with vascular flow
78607 Brain imaging, tomographic (SPECT)
78610 Brain imaging, vascular flow only
Tracer HCPCS Codes
A9521 Technetium Tc-99m exametazime
A9557 Technetium Tc-99m bicisate
A9584 Iodine I-123 ioflupane
A9512 Technetium Tc-99m pertechnetate
Indications5
Differentiation of necrotic tissue from tumor of the brain
Distinguishing Parkinson disease from essential tremor
Parathyroid disease
Infection or inflammatory process (localize abscess)
Lymphoma, to distinguish tumor from necrosis
Neuroendocrine tumors, diagnosis and staging
Presurgical ictal detection of seizure focus (in place of PET)
Suspected dementia (eg, Alzheimer disease, dementia with Lewy bodies,
frontotemporal dementia, and vascular dementia) (consult local payer guidelines)
Indications for ioflupane I-123 injection6
Differentiate essential tremor from tremor due to idiopathic Parkinson
disease, multiple system atrophy, and progressive supranuclear palsy
Differentiate dementia with Lewy bodies from Alzheimer disease

b CSF Flow
Code Descriptor
78630 Cerebrospinal fluid flow; imaging (not including introduction of
material); cisternography
78635 ventriculography
78645 shunt evaluation
78647 tomographic (SPECT)
78650 Cerebrospinal fluid leakage detection and localization
Tracer HCPCS Codes
A4641 Indium In-111 diethylenetriamine pentaacetic acid
A9548 Indium In-111 pentetate
A9512 Technetium Tc-99m pertechnetate
Indications
Hydrocephalus
Symptomatic subarachnoid cysts
Central nervous system shunting tube patency
Suspected CSF leak
b Tumor Imaging
Code Descriptor
78800 Radiopharmaceutical localization of tumor or distribution of
radiopharmaceutical agent(s); limited area
78801 multiple areas
78802 whole body, single day imaging
78803 tomographic (SPECT)
78804 whole body, requiring 2 or more days imaging
Indications by Tracer
HCPCS A9508 Iodine I-123 iobenguane sulfate
Neuroendocrine tumors (pheochromocytoma, neuroblastoma, or
paraganglioma)
HCPCS A9551 Technetium Tc-99m succimer
Tumor detection
HCPCS A9582 Iodine I-123 iobenguane
Neuroblastoma


HCPCS A9524 Iodine I-131 iodinated serum albumin

Tumor imaging
HCPCS A9572 Indium In-111 pentetreotide
Localization of primary and metastatic neuroendocrine tumors bearing
somatostatic receptors
b Miscellaneous Nuclear Medicine
Code Descriptor
78699 Unlisted nervous system procedure, diagnostic nuclear medicine
Examples
Subtraction ictal single-photon emission computed tomography (SPECT)
coregistered to MRI (SISCOM)
Preoperative evaluation of individuals with intractable focal epilepsy to
identify and localize area(s) of epileptiform activity when other
techniques designed to localize a focus are indeterminate
Brain SPECT with and without acetazolamide
Assess cerebral vascular reserve of the arterial blood supply
a
Data from Medicare Coverage Database.2 www.cms.gov/medicare-coverage-database/.
b
Healthcare Common Procedure Coding System (HCPCS) codes for the radiopharmaceutical have
been added to the procedural Current Procedural Terminology code according to the specific
modality and indication.7
c
Use with CPT 78814 or 78811 in clinical trials under the Coverage with Evidence Development
guidelines.
REFERENCES
1. American Medical Association. Current procedural terminology (CPT) 2015. Chicago: American
Medical Association Press, 2015.
2. Medicare Coverage Database. www.cms.gov/medicare-coverage-database/overview-and-quick-
search.aspx. Accessed August 5, 2016.
3. National Imaging Associates, Inc. 2016 NIA clinical guidelines for medical necessity review.
www1.radmd.com/media/332507/_____2016-master-nia-clinical-guidelines.pdf. Accessed June 6, 2016.
4. Anthem. Medical policies: magnetic resonance spectroscopy (MRS).
www.anthem.com/medicalpolicies/policies/mp_pw_a053262.htm. Reviewed May 7, 2015.
5. Aetna. Clinical policy bulletin: single photon emission computed tomography (SPECT).
www.aetna.com/cpb/medical/data/300_399/0376.html. Reviewed June 10, 2016.
6. Drugs.com. Indications and usage for DaTscan. www.drugs.com/pro/datscan.html.
Revised September 2015. Accessed August 5, 2016.
7. Coding Ahead. Coding guidelines and CPT codes for radiopharmaceuticals. www.codingahead.
com/2012/05/coding-guidelines-and-cpt-codes-for.html. Accessed August 5, 2016.

8. Centers for Medicare & Medicaid Services. Medicare national coverage determinations
manual. Chapter 1, part 4 (sections 200Y310.1) coverage determinations. www.cms.gov/
Regulations-and-Guidance/Guidance/Manuals/Downloads/ncd103c1_Part4.pdf. Revised
February 5, 2016. Accessed August 5, 2016.
9. eviCore Healthcare. Radiology tools and criteria. www.carecorenational.com/benefits-management/
radiology/radiology-tools-and-criteria.aspx. Accessed August 5, 2016.
10. Schneider E, Zelenka S, Grooff P, et al. Radiology order decision support: examination-indication
appropriateness assessed using 2 electronic systems. J Am Coll Radiol 2015;12(4):349Y357.
doi:10.1016/j.jacr.2014.12.005.
11. American College of Radiology. ACR appropriateness criteria. www.acr.org/Quality-Safety/
Appropriateness-Criteria. Updated November 2015. Accessed August 5, 2016.
12. American Academy of Neurology. MACRA. www.aan.com/practice/medicare-payment-reform/.
13. Centers for Disease Control and Prevention. International classification of diseases,
tenth revision, clinical modification (ICD-10-CM). www.cdc.gov/nchs/icd/icd10cm.htm
Updated April 29, 2016. Accessed August 5, 2016.
14. ICD-10-CM expert for physicians. The complete official code set, 2016. Salt Lake City, UT:
Optimum360, 2015.
15. Choosing wisely: an initiative of the ABIM Foundation. Clinician lists. www.choosingwisely.org/
clinician-lists/. Accessed August 5, 2016.

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will be awarded for this issue after October 31, 2019.
b 1. The pattern of hyperintensity in the fluid-attenuated inversion recovery

(FLAIR) image shown is most likely to indicate which of the following conditions?

Postreading Test
A. autoimmune encephalitis
B. Creutzfeldt-Jakob disease
C. CSF hypovolemia
D. hypoxic-ischemic encephalopathy
E. subarachnoid hemorrhage
b 2. A 59-year-old man is admitted to the intensive care unit with a subarachnoid
hemorrhage from a ruptured anterior communicating artery aneurysm. As
part of his screening for the development of vasospasm, transcranial Doppler
velocities in the middle cerebral arteries should be compared to velocities in
which of the following vessels?
A. basilar artery
B. contralateral middle cerebral artery
C. contralateral vertebral artery, V4 segment
D. ipsilateral anterior cerebral artery
E. ipsilateral internal carotid artery, extracranial segment
b 3. A 52-year-old man with a history of diabetes mellitus and hypertension is

evaluated after the sudden onset of left hemiparesis. A diffusion-weighted
image obtained 6 hours after the event is shown. Which of the following is
the most likely cause of his symptoms?
Reprinted with permission from Liebeskind DS. Imaging the future

of stroke: I. Ischemia. Ann Neurol 2009;66(5):574Y590. doi:10.
1002/ana.21787. B 2009 American Neurological Association.
A. anterior cerebral artery thrombosis

B. cardioembolic stroke
C. cerebral venous thrombosis
D. internal carotid artery occlusion
E. lacunar infarction

b 4. On magnetic resonance spectroscopy, which of the following patterns
would be most characteristic of a neoplastic process as opposed to other
causes of brain lesions?
A. absence of a lactate peak
B. decreased choline to creatine ratio
C. increase in the choline peak
D. increase in the creatine peak
E. increase in the N-acetylaspartate (NAA) peak
b 5. A 7-year-old girl is seen for headaches. Her headaches are posterior in
location and usually precipitated by physical activity or when she bears
down to have a bowel movement. Her developmental history has been
unremarkable, and neurologic examination is normal. Which of the following
findings is seen on this patient’s sagittal T2-weighted MRI of the brain?
A. Chiari type I malformation

B. Dandy-Walker malformation
C. idiopathic intracranial hypertension
D. Joubert syndrome
E. septooptic dysplasia
b 6. The spot sign on CT imaging of patients with intracerebral hemorrhage
indicates a higher likelihood of which of the following?
A. cavernous malformation as the cause of bleeding
B. early hematoma expansion
C. hypertension as the cause of bleeding
D. neoplastic process as the cause of bleeding
E. venous infarction as the cause of bleeding

Postreading Test
b 7. A 44-year-old man is seen in the emergency department with several days

of progressive quadriparesis. His neurologic history is notable for vision loss
in the right eye 5 years ago, for which he did not seek any medical attention. His
examination shows 20/400 vision in the right eye with associated right optic disc
pallor and a right afferent pupillary defect; 3/5 power in both arms; paralysis of
both legs; and bilateral extensor plantar responses. MRI of the brain shows
minimal nonspecific T2/fluid-attenuated inversion recovery (FLAIR) white
matter hyperintensities not located in periventricular or juxtacortical locations.
Sagittal spinal short tau inversion recovery (STIR) MRI of his cervical spine is
shown. Which of the following is the most likely diagnosis?
A. acute disseminated encephalomyelitis (ADEM)

B. multiple sclerosis
C. neuromyelitis optica (NMO)
D. progressive multifocal leukoencephalopathy
E. Sjögren disease
b 8. Which of the following MRI sequences evaluates for the random movement
of water within tissues?
A. diffusion-weighted imaging (DWI)
B. fluid-attenuated inversion recovery (FLAIR)
C. perfusion-weighted imaging
D. susceptibility-weighted imaging (SWI)
E. time of flight

b 9. A 64-year-old woman is evaluated after awakening with right hemiparesis
and aphasia. A noncontrast CT scan performed immediately upon arrival to
the emergency department 30 minutes following detection of the event
shows a hyperdense left middle cerebral artery and no intracranial bleed. The
results of CT perfusion studies showing cerebral blood flow (CBF), cerebral
blood volume (CBV), mean transit time (MTT), and time to maximum
(Tmax), are shown. Which of the following is the most appropriate
interpretation of the set of images?
Reprinted with permission from Rowley HA. The alphabet of imaging in acute stroke: does it spell improved
selection and outcome? Stroke 2013;44(6 suppl 1):S53YS54. doi:10.1161/STROKEAHA.113.001939. B 2013
American Heart Association, Inc. stroke.ahajournals.org/content/44/6_suppl_1/S53.full.
A. failure to develop collateral circulation

B. a large area of infarction
C. a large intracerebral hemorrhage
D. a large ischemic penumbra
E. vasogenic edema with impending risk of herniation
b 10. Which of the following conditions might result in impaired visualization of
acute cerebral hemorrhage on CT?
A. anemia
B. cardiomyopathy
C. cirrhosis
D. prior skull fracture
E. thrombocytopenia

Postreading Test
b 11. A 45-year-old man is evaluated for progressive gait difficulties, urinary

symptoms, and erectile dysfunction over the past 6 months. Examination
shows a steppage gait, weakness in L5YS1 innervated muscles bilaterally,
lower limb areflexia, loss of all sensory modalities distally in the lower limb,
perianal anesthesia, and reduced anal sphincter tone. MRI of the lumbar
spine is shown. (A, Sagittal T2-weighted image; B, sagittal noncontrast
T1-weighted image; C, sagittal postcontrast T1-weighted image; D, axial
precontrast T1-weighted image at the level of the lesion; E, axial postcontrast
T1-weighted image at the level of the lesion.) Which of the following is the
most likely diagnosis?
A. astrocytoma
B. cavernous malformation
C. dural arteriovenous fistula
D. Hodgkin lymphoma
E. myxopapillary ependymoma

b 12. Multiple observational studies have shown a higher prevalence of
hyperintensities on nonenhanced T1-weighted scans following previous serial
gadolinium-based contrast injections in which of the following brain regions?
A. cerebellar vermis
B. choroid plexus
C. dentate nuclei
D. hippocampi
E. mammillary bodies
b 13. A 43-year-old woman with a known pituitary microadenoma (found

incidentally on an MRI performed for headache 2 years ago) is seen in the
emergency department for severe headache, nausea, and double vision.
Examination is notable for a blood pressure of 70/49 mm Hg, loss of
sensation in the V1 and V2 distributions on the right, and a right-sided cranial
nerve VI palsy. Her sagittal noncontrast T1-weighted brain MRI is shown.
Which of the following is the most likely diagnosis?
Modified with permission from Gaillard F, Radiopaedia.org,

rID: 17664.
A. carotid-cavernous fistula
B. cavernous sinus thrombosis
C. lymphocytic hypophysitis
D. pituitary apoplexy
E. pituitary macroadenoma
b 14. Which of the following types of cancers, when metastatic to the brain, has
the highest likelihood of hemorrhage?
A. colon cancer
B. lung cancer
C. nonmelanoma skin cancer
D. ovarian cancer
E. renal cell carcinoma

Postreading Test
b 15. A 25-year-old man is evaluated for spells characterized by behavioral arrest

and staring, which last 2 to 3 minutes. His neurologic examination is normal.
Brain MRI is also normal. A routine EEG shows bitemporal interictal epileptiform
discharges. Given the failure to respond to two antiseizure medications at
maximal tolerated doses, he undergoes a subtraction ictal single-photon
emission computed tomography (SPECT) coregistered to MRI (SISCOM) to
identify the primary ictal focus. The findings are shown in the figure below.
Which of the following is the mechanism of the abnormality found in this study?
A. disruption of the blood-brain barrier

B. impaired anaerobic glycolysis
C. inflammatory response
D. relative increase in blood flow
E. upregulation of +-aminobutyric acid (GABA)-A receptors
b 16. A 33-year-old woman is evaluated for recent headache and pulsatile
tinnitus over the past 6 weeks. Her headache is constant and increases when
bending forward or coughing. Her body mass index is 30 kg/m2. Neurologic
examination shows bilateral optic disc swelling but is otherwise normal.
Brain MRI shows no mass lesion; however, which of the following MRI
findings is most likely to be present in this patient?
A. compression of the optic nerve sheath
B. enhancement of the pituitary gland
C. flattening of the posterior aspect of the globe
D. pachymeningeal enhancement
E. spinal root sheath diverticula

b 17. A 28-year-old woman is seen in clinic after a recent emergency department
visit for an episode of loss of consciousness, during which she underwent a brain
MRI. She has no history of prior neurologic symptoms, her developmental
history is unremarkable, and her neurologic examination is normal. Which of the
following findings is seen on this patient’s coronal T2-weighted brain MRI?
A. focal cortical dysplasia of the superior temporal gyrus

B. mesial temporal sclerosis
C. open-lip schizencephaly
D. polymicrogyria
E. right temporal lobe ependymoma

Postreading Test
b 18. A 76-year-old woman is evaluated for intermittent memory difficulties over

the past 2 years. She reports occasional difficulties remembering what she was
told several minutes before or remembering names, particularly when she is in
stressful situations. However, she lives independently and is successful as the
chair of the board in her local church. From social media, the patient is aware of
the potential use of amyloid imaging for early diagnosis of Alzheimer disease
(AD) and asks whether she should undergo the procedure. Her neurologic
examination, psychometric testing, and brain MRI are normal. Which of the
following statements applies to amyloid imaging in this setting?
A. amyloid deposits have high positive predictive value as they can be seen in
less than 10% of asymptomatic patients older than 70 years
B . amyloid imaging is clinically indicated in her case given her risk for
developing AD
C. amyloid imaging is unlikely to differentiate AD from frontotemporal
lobar degeneration
D. changes in amyloid burden would correlate with progressive neurologic
deterioration over time
E . a negative amyloid imaging study may have a good negative predictive
value against AD pathology
b 19. A 25-year-old man with tuberous sclerosis complex is seen in follow-up.

On his most recent MRI, a new area of contrast enhancement in the lateral
aspect of the left lateral ventricle is seen (T1-weighted postcontrast image
shown); this abnormality was not present on his prior scan 1 year ago. His
seizure control and neurologic examination are unchanged from prior visits.
Which of the following is the most likely cause of his MRI finding?

A. central neurocytoma
B. choroid plexus papilloma
C. ependymoma
D. subependymal giant cell astrocytoma
E. subependymal nodule
b 20. A 4-year-old-girl is evaluated for spells of transient unresponsiveness
over the past 3 months. Her development is normal, as is her neurologic
examination. EEG shows focal seizures originating in the right temporal lobe.
MRI of the brain shows a lesion located in the right temporal cortex without
associated mass effect, edema, or contrast enhancement. The lesion has a
pseudocystic or ‘‘bubbly’’ appearance that is hypointense on T1-weighted
images and hyperintense on T2-weighted images. Which of the following is
the most likely diagnosis?
A. desmoplastic infantile ganglioglioma
B. dysembryoplastic neuroepithelial tumor
C. pleomorphic xanthoastrocytoma
D. primitive neuroectodermal tumor
E. subependymal glial cell astrocytoma ganglioglioma
b 21. An 18-year-old man is evaluated for the recent onset of intermittent

headaches. His neurologic examination is normal. MRI of his brain is shown.
Which of the following is a possible complication associated with this lesion?
A. pituitary insufficiency
B. seeding to the spinal canal
C. seizure
D. sudden death
E. upward gaze palsy

Postreading Test
b 22. Which of the following imaging characteristics is typical of the classic

Dandy-Walker malformation?
A. absence of the fourth ventricle
B. hypoplasia of the cerebellar vermis
C. inferior displacement of the tentorium
D. microcephaly
E. smaller size of the posterior fossa
b 23. A 30-year-old woman is evaluated for right eye pain and blurred vision
over the past 2 weeks. Examination shows reduced visual acuity and a swollen
optic nerve in the right eye and a temporal field cut in the right eye. The rest
of the neurologic examination is normal. Sagittal T1 precontrast (A) and
postcontrast (B) sequences of her brain MRI are shown. Which is the
following is the most likely diagnosis?
A. Churg-Strauss syndrome
B. CSF leak
C. Lyme disease
D. neurosarcoidosis
E. venous thrombosis
b 24. Which of the following imaging characteristics would be most consistent
with delayed radiation necrosis as opposed to tumor progression in patients
with glioblastoma?
A. enhancement with gadolinium
B . lesion development adjacent to the initial tumor site
C. lower cerebral blood volume levels on perfusion MRI
D. presence of hemorrhage
E . vasogenic edema seen on T2-weighted and fluid-attenuated inversion
recovery (FLAIR) sequences

b 25. A 72-year-old man is evaluated for the sudden onset of left hemiparesis.
On examination 3 hours after symptom onset, he has mild upper motor
neuron distribution weakness in the left upper limb. A fluid-attenuated
inversion recovery (FLAIR) MRI of the brain is obtained within 4 hours of the
event. What do the findings in this study indicate?
Reprinted with permission from Liebeskind DS. Imaging the future of stroke: I. Ischemia. Ann Neurol
2009;66(5):574Y590. doi:10.1002/ana.21787. B 2009 American Neurological Association.
A. cortical laminar necrosis

B . hemorrhagic transformation of a cardioembolic stroke
C. slow retrograde collateral flow proximal to a middle cerebral artery
(MCA) occlusion
D. subarachnoid hemorrhage in the setting of amyloid angiopathy
E . superficial vein thrombosis
b 26. In patients with sickle cell anemia, which of the following imaging findings is
validated as being able to predict individuals at higher risk of stroke?
A. elevated mean flow velocities in the middle cerebral arteries
B. Lindegaard ratio greater than 6
C. macaroni sign on carotid ultrasonography
D. presence of bilateral microembolic signals in the middle cerebral arteries
E. reverberating flow pattern on transcranial Doppler

Postreading Test
b 27. A 72-year-old man with history of hypertension is evaluated for a 2-year

history of intermittent headaches. His neurologic examination is normal.
The arrows on this patient’s T2-weighted MRI (at the level of the anterior
commissure [arrowheads]) point to which of the following findings?
A. amyloid angiopathy
B. dilated Virchow-Robin spaces
C. lacunar infarcts
D. microemboli
E. vasculitis
b 28. High-resolution MRIs of the normal pituitary gland often show an area of
T1 hyperintensity, referred to as the pituitary bright spot. Which of the
following anatomic structures does this correspond to?
A. adenohypophysis
B. median eminence
C. neurohypophysis
D. pituitary stalk
E. Rathke cleft

b 29. A 20-year-old right-handed man is evaluated for spells characterized by
abdominal pain, dysarthria, and bradycardia. His neurologic examination is
normal. An axial fluid-attenuated inversion recovery (FLAIR) image is shown,
with the abnormalities marked with arrows. Which of the following is the
most likely pathologic substrate of these imaging abnormalities?
Reprinted with permission from Cendes F. Neuroimaging in

investigation of patients with epilepsy. Continuum (Minneap
Minn) 2013;19(3 Epilepsy):623Y642. doi:10.1212/01.CON.
0000431379.29065.d3. B 2013 American Academy of
Neurology. journals.lww.com/continuum/Fulltext/2013/06000/
Neuroimaging_in_Investigation_of_Patients_With.11.aspx.
A. aberrant axonal sprouting

B. dysmorphic neurons
C. gliosis
D. immature endothelium-lined caverns
E. proliferation of oligodendrocytes
b 30. Which of the following time frames best approximates the average
duration that an acute multiple sclerosis (MS) lesion is expected to show
contrast enhancement on MRI?
A. 1 week
B. 3 weeks
C. 6 weeks
D. 12 weeks
E. 20 weeks

Postreading Test
b 31. A 42-year-old man is seen in clinic for vision complaints. On additional

questioning, he reports a 1-year history of decreased libido and the recent
onset of gynecomastia. Examination shows subtle restriction of bitemporal
vision. A sagittal postcontrast T1-weighted image from his brain MRI is
shown. Which of the following is the most likely diagnosis?
B. craniopharyngioma
C. dermoid cyst
D. pituitary apoplexy
E. pituitary macroadenoma
b 32. In brain neoplasms, restricted diffusion on diffusion-weighted MRI (ie,
reduced apparent diffusion coefficient) may be indicative of which of the
following?
A. hypercellular nature of a neoplasm
B. intratumor hemorrhage
C. lower grade of glioma
D. metastatic as opposed to primary brain source of neoplasm
E. postradiation necrosis

b 33. A 57-year-old man is evaluated for numbness in his hands and feet and
imbalance that developed over the past 6 months. He has a history of
diabetes mellitus, hypertension, and a previous partial gastrectomy.
Examination shows a sensory ataxia with Romberg signs, areflexia, bilateral
Babinski signs, and absent joint position sense in the fingers and toes. MRI of
the cervical spine is shown. Serum methylmalonic acid levels are normal.
Which of the following is the most appropriate next test in this patient?
A. antiYaquaporin-4 antibodies
B. antinuclear antibodies
C. serum angiotensin-converting enzyme
D. serum ceruloplasmin
E. serum vitamin D
b 34. A 54-year-old woman is seen for 1 week of right eye pain, a bloodshot
appearance to the right eye, and double vision. On examination, she has
proptosis, chemosis, and congestion of the right eye, with impairment of eye
movements in the horizontal and vertical directions. CT angiography of the
brain shows asymmetric contrast enhancement of the cavernous sinuses, with
more marked enhancement on the right; dilation of the right superior
ophthalmic vein is also seen. Which of the following is the most
likely diagnosis?
B. right central retinal vein occlusion
C. right internal jugular vein thrombosis
D. temporal arteritis
E. unruptured right internal carotid artery aneurysm

Postreading Test
b 35. A 12-year-old boy is evaluated for headache, vomiting, and gait disturbance.
Examination shows papilledema, impaired upward gaze, and pupillary
light-near dissociation. Sagittal MRI using T2-weighted (A) and T1-weighted
(B) sequences are shown. Which of the following diagnoses
is most likely?
A. histiocytosis
B. pilocytic astrocytoma
C. pineal cyst
D. pinealoma
E. teratoma
b 36. A 22-year-old man is evaluated for progressive gait disturbance and hand
paresthesia over the past 3 months. Examination shows a sensory ataxia and
severe proprioceptive loss in his hands and feet. MRI of the cervical spine
shows a T1-hypointense and T2-hyperintense cystic mass lesion with a
homogeneous contrast-enhancing nodule associated with dilated vessels and
a syrinx. Which of the following is the most likely diagnosis?
A. arteriovenous malformation
B. cavernous malformation
C. hemangioblastoma
D. myxopapillary ependymoma
E. pilocytic astrocytoma

b 37. A 31-year-old woman is seen for 3 days of worsening vision in the left eye
as well as pain with eye movements. She has had no prior episodes of
neurologic dysfunction. Examination is notable for 20/200 acuity in the left
eye, normal funduscopic appearance of the left optic nerve, and a relative
afferent pupillary defect on the left. Postcontrast fat-suppressed T1-weighted
MRI is shown. Which of the following is the most likely diagnosis?
A. giant cell arteritis

B. Graves disease
C. nonarteritic ischemic optic neuropathy
D. optic nerve glioma
E. optic neuritis
b 38. A 68-year-old man is evaluated for progressive memory difficulties over
the past 2 years. He experiences difficulty recalling names and details from
previous conversations but has remained independent in activities of daily
living. Examination shows 1/3 recall after 5 minutes but is otherwise normal.
Brain MRI demonstrates bilateral hippocampal atrophy. Which of the
following cortical areas are most likely to show reduced metabolism on
fludeoxyglucose positron emission tomography (FDG-PET) scan?
A. anterior cingulate
B. anterior temporal
C. dorsolateral prefrontal
D. medial parietal
E. ventrolateral prefrontal

Postreading Test
b 39. A 62-year-old woman with a history of diabetes mellitus and hypertension

is evaluated for sudden-onset headache and left face and upper limb weakness
that began 3 hours ago. A noncontrast CT scan of the head is shown. Which
of the following is the most likely cause of this patient’s symptoms?
Reprinted with permission from Liebeskind DS, Sanossian N,

Yong WH, et al. CT and MRI early vessel signs reflect clot
composition in acute stroke. Stroke 2011;42(5):1237Y1243.
doi:10.1161/STROKEAHA.110.605576. B 2011 American
Heart Association, Inc. stroke.ahajournals.org/content/42/5/
1237.short.
B. cerebral vein occlusion
C. middle cerebral artery (MCA) thrombosis
D. subarachnoid hemorrhage
E. vasculitis
b 40. A 70-year-old man is referred for carotid ultrasonography after his primary
care provider heard a bruit over the left side of the neck. His ultrasound
shows elevated velocities in the 50% to 69% range. The presence of which of
the following ultrasound findings would be more suggestive of this plaque
being unstable and thus more likely to result in artery-to-artery embolism?
A. concentric thickening of vessel wall (macaroni sign)
B. elevated Lindegaard ratio
C. false lumen with bidirectional flow
D. intraplaque hemorrhage
E. uniform hyperechogenicity

Postreading 2. A 59-year-old man is admitted to the intensive care unit with

a subarachnoid hemorrhage from a ruptured anterior com-
Self-Assessment and municating artery aneurysm. As part of his screening for the
development of vasospasm, transcranial Doppler velocities in
CME Test—Preferred the middle cerebral arteries should be compared to velocities

in which of the following vessels?
Responses A. basilar artery

B . contralateral middle cerebral artery
C. contralateral vertebral artery, V4 segment
D. ipsilateral anterior cerebral artery
Following are the preferred responses to the questions in the E . ipsilateral internal carotid artery, extracranial segment
Postreading Self-Assessment and CME Test in this Continuum
issue. The questions and answer options are repeated, and the The preferred response is E (ipsilateral internal carotid artery,
preferred response is given, followed by an explanation and a extracranial segment). In patients with subarachnoid hemor-
reference with which you may seek more specific information. rhage, transcranial Doppler can be used to monitor velocities
You are encouraged to review the responses and explanations of intracranial vessels as a means of detecting vasospasm.
carefully to evaluate your general understanding of the course Velocities can be increased in the setting of decreased vascular
material. The comments and references included with each caliber (as seen in vasospasm) but can also be elevated in
question are intended to encourage independent study. hyperdynamic states. To control for this possibility, the ratio of
the velocities in the middle cerebral artery and the ipsilateral
Participants who complete the Postreading Self-Assessment
extracranial internal carotid artery (the Lindegaard ratio) can
and CME Test and issue evaluation online at www.aan.com/ be calculated; criteria for the diagnosis of vasospasm based on
continuum/cme may earn up to 12 AMA PRA Category 1 this ratio have been validated. For more information, refer to
Creditsi toward SA-CME. Participants have up to 3 years pages 1666Y1667 of the Continuum article ‘‘Ultrasound in
from the date of publication to earn CME credits. No SA-CME Neurology.’’
will be awarded for this issue after October 31, 2019.
3. A 52-year-old man with a history of diabetes mellitus and hyper-
tension is evaluated after the sudden onset of left hemiparesis. A
1. The pattern of hyperintensity in the fluid-attenuated inver-
diffusion-weighted image obtained 6 hours after the event is
sion recovery (FLAIR) image shown (page 1701) is most
shown (page 1702). Which of the following is the most likely
likely to indicate which of the following conditions?
cause of his symptoms?
A. autoimmune encephalitis
A. anterior cerebral artery thrombosis
B . Creutzfeldt-Jakob disease
B . cardioembolic stroke
C. CSF hypovolemia
C. cerebral venous thrombosis
D. hypoxic-ischemic encephalopathy
D. internal carotid artery occlusion
E . subarachnoid hemorrhage
E . lacunar infarction
The preferred response is E (subarachnoid hemorrhage).

Failure to suppress CSF signal intensity (sulcal hyperintensity) The preferred response is D (internal carotid artery occlu-
on FLAIR images has been reported in patients with abnormal sion). The pattern of the lesion on diffusion-weighted imaging
CSF, such as those with meningitis and subarachnoid hemor- helps to identify the etiology of stroke. In this case, the ab-
rhage. Autoimmune encephalitis, including limbic encephali- normal areas of restricted diffusion suggest borderzone ische-
tis, produces increased FLAIR signal in the medial temporal mia between the territories of the anterior cerebral artery and
lobes. Creutzfeldt-Jakob disease is associated with increased middle cerebral artery caused by right internal carotid artery
FLAIR signal in the cortical ribbon and basal ganglia. Hypoxic- hypoperfusion. The abnormal area extends beyond that of
ischemic encephalopathy typically produces increased FLAIR the anterior cerebral artery. The distribution seen in this patient’s
signal in the white matter. CSF hypovolemia is primarily asso- MRI would be atypical for cardioembolic or aortoembolic stroke
ciated with pachymeningeal enhancement on postcontrast (which would be suggested by multiple lesions in different
images but is not typically associated with changes in FLAIR vascular territories and not confined to a single hemisphere),
MRI. For more information, refer to page 1389 and Figure 1-6C cerebral venous thrombosis, or lacunar infarction. For more
of the Continuum article ‘‘Introduction to Magnetic Resonance information, refer to page 1406 and Figure 2-7C of the
Imaging for Neurologists.’’ Continuum article ‘‘Imaging of Ischemic Stroke.’’
Continuum (Minneap Minn) 2016;22(5):1721Y1730 www.ContinuumJournal.com 1721

Postreading Test—Preferred Responses
4. On magnetic resonance spectroscopy, which of the follow- 7. A 44-year-old man is seen in the emergency department with
ing patterns would be most characteristic of a neoplastic several days of progressive quadriparesis. His neurologic
process as opposed to other causes of brain lesions? history is notable for vision loss in the right eye 5 years ago,
for which he did not seek any medical attention. His exam-
A. absence of a lactate peak ination shows 20/400 vision in the right eye with associated
B . decreased choline to creatine ratio right optic disc pallor and a right afferent pupillary defect; 3/5
C. increase in the choline peak power in both arms; paralysis of both legs; and bilateral ex-
D. increase in the creatine peak tensor plantar responses. MRI of the brain shows minimal non-
E . increase in the N-acetylaspartate (NAA) peak specific T2/fluid-attenuated inversion recovery (FLAIR) white
matter hyperintensities not located in periventricular or jux-
The preferred response is C (increase in the choline peak). tacortical locations. Sagittal spinal short tau inversion recovery
Magnetic resonance spectroscopy is a noninvasive means of (STIR) MRI of his cervical spine is shown (page 1704). Which of
assessing metabolic information about a brain lesion, which the following is the most likely diagnosis?
can assist in diagnosis and in treatment planning. A typical
pattern of findings is associated with a neoplasm, which in- A. acute disseminated encephalomyelitis (ADEM)
cludes an increase in the choline peak, a decrease in the NAA B . multiple sclerosis
peak, and an increased choline to creatine ratio. In some cases, C. neuromyelitis optica (NMO)
a lactate peak can also be seen. For more information, refer to D. progressive multifocal leukoencephalopathy
pages 1536Y1537 of the Continuum article ‘‘Imaging of E . Sjögren disease
Brain Tumors.’’
The preferred response is C (neuromyelitis optica [NMO]).
5. A 7-year-old girl is seen for headaches. Her headaches are This patient is presenting with signs and symptoms of a
posterior in location and usually precipitated by physical cervical myelopathy, which has also been confirmed with MRI.
activity or when she bears down to have a bowel movement. The longitudinally extensive nature of this myelitis is sugges-
Her developmental history has been unremarkable, and tive of NMO, and his prior history of optic neuritis also strongly
neurologic examination is normal. Which of the following favors this diagnosis. In addition, his brain MRI does not show
findings is seen on this patient’s sagittal T2-weighted MRI of the typical changes seen in multiple sclerosis (periventricular
the brain (page 1703)? and juxtacortical lesions). For more information, refer to page
1626 and Figure 11-11 of the Continuum article ‘‘Imaging
A. Chiari type I malformation of Central Nervous System Demyelinating Disorders.’’
B . Dandy-Walker malformation
C. idiopathic intracranial hypertension
D. Joubert syndrome 8. Which of the following MRI sequences evaluates for the
E . septooptic dysplasia random movement of water within tissues?
A. diffusion-weighted imaging (DWI)
B . fluid-attenuated inversion recovery (FLAIR)
The preferred response is A (Chiari type I malformation). C. perfusion-weighted imaging
This patient is presenting with posterior headaches that are D. susceptibility-weighted imaging (SWI)
stereotypically precipitated by exertion and Valsalva maneu- E . time of flight
vers. This is a common pattern of headaches seen with Chiari
malformations. Her MRI shows downward displacement of the
cerebellar tonsils, which is the radiographic feature of this The preferred response is A (diffusion-weighted imaging [DWI]).
disorder. For more information, refer to page 1496 and DWI evaluates the random movement of water molecules
Figure 5-20 of the Continuum article ‘‘Imaging of Congen- within tissues. In various pathologic states, most commonly
ital Malformations.’’ acute ischemia, random water movement is restricted; this can
be reflected in the apparent diffusion coefficient and the
6. The spot sign on CT imaging of patients with intracerebral hem- related DWI sequences. For more information, refer to page
orrhage indicates a higher likelihood of which of the following? 1386 of the Continuum article ‘‘Introduction to Magnetic
Resonance Imaging for Neurologists.’’
A. cavernous malformation as the cause of bleeding
B . early hematoma expansion
C. hypertension as the cause of bleeding
D. neoplastic process as the cause of bleeding
E . venous infarction as the cause of bleeding
The preferred response is B (early hematoma expansion).

A spot sign on CT angiography, CT perfusion studies, or even
postcontrast CT imaging results from active contrast extrava-
sation into the hematoma. If contrast is extravasating from a
vessel, it is highly probable that blood is also extravasating;
this is concerning for an increased risk of hematoma ex-
pansion. For more information, refer to pages 1425 and 1427
of the Continuum article ‘‘Imaging of Hemorrhagic Stroke.’’

9. A 64-year-old woman is evaluated after awakening with right 11. A 45-year-old man is evaluated for progressive gait difficulties,
hemiparesis and aphasia. A noncontrast CT scan performed im- urinary symptoms, and erectile dysfunction over the past 6 months.
mediately upon arrival to the emergency department 30 minutes Examination shows a steppage gait, weakness in L5YS1 innervated
following detection of the event shows a hyperdense left middle muscles bilaterally, lower limb areflexia, loss of all sensory modalities
cerebral artery and no intracranial bleed. The results of CT distally in the lower limb, perianal anesthesia, and reduced anal
perfusion studies showing cerebral blood flow (CBF), cerebral sphincter tone. MRI of the lumbar spine is shown (page 1706).
blood volume (CBV), mean transit time (MTT), and time to (A, Sagittal T2-weighted image; B, sagittal noncontrast T1-
maximum (Tmax), are shown (page 1705). Which of the fol- weighted image; C, sagittal postcontrast T1-weighted image; D,
lowing is the most appropriate interpretation of the set of images? axial precontrast T1-weighted image at the level of the lesion;
E, axial postcontrast T1-weighted image at the level of the
A. failure to develop collateral circulation lesion.) Which of the following is the most likely diagnosis?
B . a large area of infarction
C. a large intracerebral hemorrhage A. astrocytoma
D. a large ischemic penumbra B . cavernous malformation
E . vasogenic edema with impending risk C. dural arteriovenous fistula
of herniation D. Hodgkin lymphoma
E . myxopapillary ependymoma
The preferred response is D (a large ischemic penumbra).
The CT perfusion maps demonstrate relatively preserved CBF
and CBV but marked prolongation of transit times (MTT and The preferred response is E (myxopapillary ependymoma).
Tmax), suggesting a target mismatch pattern consistent with Myxopapillary ependymomas of the filum terminale typically
an ischemic penumbra. Perfusion imaging gives a snapshot of appear as isointense to hypointense masses on T1- and T2-
stroke pathophysiology, estimating the relative volumes of weighted images. They can span several vertebral segments
penumbral regions that may be salvaged with timely reper- and tend to be extramedullary. At times, as in this patient, mucin
fusion therapy and of infarcted core that cannot be salvaged accumulation may cause them to be hyperintense on T1- and
and conveying a higher risk of hemorrhagic transformation. T2-weighted images. Prominent contrast enhancement is seen.
While no standardized perfusion parameter currently exists, Astrocytomas are the most common intramedullary spinal
Tmax greater than 6 seconds is a commonly used threshold neoplasm in children and typically arise in the cervical spinal
that identifies ischemic tissue that is likely to be irreversibly cord. They have poorly demarcated margins; are usually eccen-
injured if reperfusion does not occur. The relative preservation tric; and may show no, mild, or moderate patchy enhancement.
of CBF in this case suggests development of collateral cir- Dural arteriovenous fistulas most commonly occur in the lower
culation. In contrast, an infarct core would be expected to thoracic region, and imaging shows longitudinally extensive
show reduction in both CBF and CBV. For more information, T2-weighted hyperintensity in the central spinal cord with
refer to page 1409 and the second row of Figure 2-9 of the dilated surface venules appearing as enlarged tortuous vas-
Continuum article ‘‘Imaging of Ischemic Stroke.’’ cular flow voids. On T2-weighted imaging, cavernous mal-
formations present as a heterogeneous hyperintense center
surrounded by a rim of hypointensity, giving them the char-
10. Which of the following conditions might result in impaired acteristic popcorn appearance. They may also exhibit heter-
visualization of acute cerebral hemorrhage on CT? ogenous signal on T1-weighted images, reflecting the presence
A. anemia of intracavernous vascular channels containing hemoglobin in
B . cardiomyopathy various stages of degradation. Cauda equina lesions may occur
C. cirrhosis in nonYHodgkin lymphoma (primarily angiocentric) but are
D. prior skull fracture unlikely in Hodgkin lymphoma. For more information, refer to
E . thrombocytopenia page 1605 and Figure 10-9 of the Continuum article ‘‘Imaging
of Spinal Cord Disorders.’’
The preferred response is A (anemia). CT of the brain is the most 12. Multiple observational studies have shown a higher prevalence
widespread method of detecting acute intracranial hemorrhage, of hyperintensities on nonenhanced T1-weighted scans follow-
although there are some limitations to its interpretation. Acute ing previous serial gadolinium-based contrast injections in
blood appears hyperdense on CT, but in patients with anemia, which of the following brain regions?
blood appears less dense; thus, the differentation between
blood and brain tissue may be less apparent. This can result in A. cerebellar vermis
failure to identify acute hemorrhage. The other factors listed B . choroid plexus
above should not clearly limit the diagnostic potential of C. dentate nuclei
noncontrast CT. For more information, refer to page 1427 of D. hippocampi
the Continuum article ‘‘Imaging of Hemorrhagic Stroke.’’ E . mammillary bodies
The preferred response is C (dentate nuclei). Multiple studies
have consistently shown a higher rate of T1 hyperintensities
in various brain locations among patients previously exposed
to gadolinium-based contrast agents. The dentate nucleus, globus
pallidus, and thalamus appear to be especially common locations
for this to occur. The clinical impact of these MRI findings, if one
exists, is not yet certain. For more information, refer to page 1679
of the Continuum article ‘‘Potential Safety Issues Related to the
Use of Gadolinium-based Contrast Agents.’’

13. A 43-year-old woman with a known pituitary microadenoma 15. A 25-year-old man is evaluated for spells characterized by
(found incidentally on an MRI performed for headache 2 years behavioral arrest and staring, which last 2 to 3 minutes. His
ago) is seen in the emergency department for severe neurologic examination is normal. Brain MRI is also normal.
headache, nausea, and double vision. Examination is notable A routine EEG shows bitemporal interictal epileptiform dis-
for a blood pressure of 70/49 mm Hg, loss of sensation in the charges. Given the failure to respond to two antiseizure
V1 and V2 distributions on the right, and a right-sided cranial medications at maximal tolerated doses, he undergoes a
nerve VI palsy. Her sagittal noncontrast T1-weighted brain MRI subtraction ictal single-photon emission computed tomog-
is shown (page 1707). Which of the following is the most raphy (SPECT) coregistered to MRI (SISCOM) to identify the
likely diagnosis? primary ictal focus. The findings are shown in the figure
below (page 1708). Which of the following is the mecha-
A. carotid-cavernous fistula nism of the abnormality found in this study?
B . cavernous sinus thrombosis
C. lymphocytic hypophysitis A. disruption of the blood-brain barrier
D. pituitary apoplexy B . impaired anaerobic glycolysis
E . pituitary macroadenoma C. inflammatory response
D. relative increase in blood flow
The preferred response is D (pituitary apoplexy). This patient E . upregulation of ,-aminobutyric acid (GABA)-A receptors
is presenting with acute onset of headache, cranial nerve
dysfunction, and hypotension. This clinical scenario is sug- The preferred response is D (relative increase in blood flow).
gestive of pituitary apoplexy, especially in a patient with a In patients with focal epilepsy, SISCOM allows improved local-
known pituitary adenoma, since these can occasionally spon- ization of the epileptogenic zone. SPECT uses the injection of a
taneously undergo infarction or hemorrhage. Management of radiotracer with rapid uptake within the brain (30 to 60 seconds
these patients includes blood pressure and circulatory support from injection), but a long half-life, to measure cerebral blood
and consideration of surgical evacuation of the pituitary flow. Regional blood flow at the time of injection is reflected
bleeding. The hypotension seen in this case would be very by the area of rapid uptake, providing a snapshot of cerebral
atypical of the other choices and is a major clue to the diag- activity at that moment. Together with scalp EEG data and
nosis of apoplexy. For more information, refer to pages 1591Y1592 symptomatology, SPECT may point to a region to be either
and Figure 9-23 of the Continuum article ‘‘Imaging of invasively monitored or resected in MRI-negative epilepsy. For
Pituitary and Parasellar Disorders.’’ more information, refer to pages 1473 and 1475 and Figure
4-17 of the Continuum article ‘‘Imaging for Adults With
14. Which of the following types of cancers, when metastatic to Seizures and Epilepsy.’’
the brain, has the highest likelihood of hemorrhage?
16. A 33-year-old woman is evaluated for recent headache and
A. colon cancer
pulsatile tinnitus over the past 6 weeks. Her headache is constant
B . lung cancer
and increases when bending forward or coughing. Her body mass
C. nonmelanoma skin cancer
index is 30 kg/m2. Neurologic examination shows bilateral optic
D. ovarian cancer
disc swelling but is otherwise normal. Brain MRI shows no mass
E . renal cell carcinoma
lesion; however, which of the following MRI findings is most
The preferred response is E (renal cell carcinoma). Among likely to be present in this patient?
the different types of systemic malignancies, rates of metas-
A. compression of the optic nerve sheath
tasis to the brain vary widely; furthermore, when metastasis to
B . enhancement of the pituitary gland
the brain does occur, some types of cancer have a higher
C. flattening of the posterior aspect of the globe
predilection to cause intracranial bleeding. These include thyroid
D. pachymeningeal enhancement
papillary cancer, melanoma, and renal cell carcinoma. For more
E . spinal root sheath diverticula
information, refer to page 1447 of the Continuum article
‘‘Imaging of Hemorrhagic Stroke.’’
The preferred response is C (flattening of the posterior aspect
of the globe). The history and findings are suggestive of idio-
pathic intracranial hypertension (pseudotumor cerebri). Flatten-
ing of the posterior aspect of the globe (with or without protrusion
into the globe) is a neuroimaging sign that is consistent with the
presence of papilledema, such as idiopathic intracranial hyperten-
sion. Other imaging signs that support the diagnosis of idiopathic
intracranial hypertension include an empty or partially empty sella,
distention of the optic nerve sheath (perioptic subarachnoid space)
with or without a tortuous optic nerve, and transverse venous sinus
stenosis. Pachymeningeal enhancement, enhancement of the
pituitary gland, and spinal root diverticula are typically associ-
ated with intracranial hypotension (intracranial hypovolemia).
Idiopathic intracranial hypertension is associated with disten-
sion, not compression, of the optic nerve sheath. For more
information, refer to page 1503 of the Continuum article
‘‘Imaging in Patients With Visual Symptoms.’’

17. A 28-year-old woman is seen in clinic after a recent emergency the differential diagnosis of dementia as amyloid accumulations
department visit for an episode of loss of consciousness, in frontotemporal lobar degeneration are low, similar to healthy
during which she underwent a brain MRI. She has no history of controls. For more information, refer to page 1639 of the
prior neurologic symptoms, her developmental history is un- Continuum article ‘‘Positron Emission Tomography and Single-
remarkable, and her neurologic examination is normal. Which Photon Emission Computed Tomography in Neurology.’’
of the following findings is seen on this patient’s coronal T2-
weighted brain MRI (page 1709)? 19. A 25-year-old man with tuberous sclerosis complex is seen
in follow-up. On his most recent MRI, a new area of contrast
A. focal cortical dysplasia of the superior temporal gyrus enhancement in the lateral aspect of the left lateral ven-
B . mesial temporal sclerosis tricle is seen (T1-weighted postcontrast image shown) (page
C. open-lip schizencephaly 1710); this abnormality was not present on his prior scan 1 year
D. polymicrogyria ago. His seizure control and neurologic examination are un-
E . right temporal lobe ependymoma changed from prior visits. Which of the following is the most
likely cause of his MRI finding?
The preferred response is C (open-lip schizencephaly). This
patient’s imaging shows a cleft in the lateral right temporal A. central neurocytoma
lobe, extending to the cortical surface. The cleft is lined with B . choroid plexus papilloma
cortex, making this lesion most consistent with open-lip C. ependymoma
schizencephaly of the right temporal lobe. Developmental D. subependymal giant cell astrocytoma
anomalies such as this can be found incidentally on neuroim- E . subependymal nodule
aging, but they may aid in diagnosing clinical conditions if The preferred response is D (subependymal giant cell astro-
they are located in eloquent areas. Given the proximity of this cytoma). Patients with tuberous sclerosis complex can have a
anomaly to the mesial temporal area, seizure must be con- variety of neuroimaging findings on MRI. Lesions in ventric-
sidered in the differential diagnosis of this patient’s episode of ular locations such as the one shown here include sub-
transient alteration of awareness. For more information, refer to ependymal nodules and subependymal giant cell astrocytomas.
page 1487 and Figure 5-9 of the Continuum article ‘‘Imaging The fact that this lesion has enlarged over a relatively short time
of Congenital Malformations.’’ frame makes it much more likely to be a subependymal giant
cell astrocytoma than a subependymal nodule. Subependymal
18. A 76-year-old woman is evaluated for intermittent memory
giant cell astrocytomas arise from subependymal cells and
difficulties over the past 2 years. She reports occasional
project into the lateral ventricle adjacent to the septum pellu-
difficulties remembering what she was told several minutes
cidum. Although these lesions are benign, they may require
before or remembering names, particularly when she is in
surgical removal if they grow rapidly or cause secondary phe-
stressful situations. However, she lives independently and is
nomena, such as obstructive hydrocephalus. For more infor-
successful as the chair of the board in her local church.
mation, refer to page 1539 and Figure 7-4B of the Continuum
From social media, the patient is aware of the potential use
article ‘‘Imaging of Brain Tumors.’’
of amyloid imaging for early diagnosis of Alzheimer disease
(AD) and asks whether she should undergo the procedure. 20. A 4-year-old-girl is evaluated for spells of transient unre-
Her neurologic examination, psychometric testing, and sponsiveness over the past 3 months. Her development is
brain MRI are normal. Which of the following statements normal, as is her neurologic examination. EEG shows focal
applies to amyloid imaging in this setting? seizures originating in the right temporal lobe. MRI of the
A. amyloid deposits have high positive predictive value as they brain shows a lesion located in the right temporal cortex with-
can be seen in less than 10% of asymptomatic patients older out associated mass effect, edema, or contrast enhancement.
than 70 years The lesion has a pseudocystic or ‘‘bubbly’’ appearance that is
B . amyloid imaging is clinically indicated in her case given hypointense on T1-weighted images and hyperintense on
her risk for developing AD T2-weighted images. Which of the following is the most
C. amyloid imaging is unlikely to differentiate AD from front- likely diagnosis?
otemporal lobar degeneration A. desmoplastic infantile ganglioglioma
D. changes in amyloid burden would correlate with progres- B . dysembryoplastic neuroepithelial tumor
sive neurologic deterioration over time C. pleomorphic xanthoastrocytoma
E. a negative amyloid imaging study may have a good negative D. primitive neuroectodermal tumor
predictive value against AD pathology E . subependymal glial cell astrocytoma ganglioglioma
The preferred response is E (a negative amyloid imaging
study may have a good negative predictive value against The preferred response is B (dysembryoplastic neuroepithelial
AD pathology). Given its 80% to 100% reported sensitivity, tumor). The most frequently encountered primary brain tumors
it is likely that a normal amyloid imaging study will have very in patients with focal seizure disorders are gangliogliomas and
good negative predictive value against AD neuropathology. dysembryoplastic neuroepithelial tumors. Dysembryoplastic
However, it may have a poor positive predictive value, as its neuroepithelial tumors are most often found in superficial cor-
diagnostic accuracy is dependent on age. An age-related in- tical regions of the frontal or temporal lobes, usually causing
creased prevalence of amyloid tracer uptake exists, with up to epilepsy as their sole manifestation. They are static or slowly
40% of asymptomatic people over 70 years of age having high progressive benign tumors. They may display variability on
cortical Pittsburgh Compound B (PiB) uptake. Amyloid imag- imaging, but typical MRI characteristics include cortical loca-
ing also shows little significant change over time and correlates tion and absence of mass effect or edema; some tumors may
poorly with clinical progression of disease. It may be useful in display a classic pseudocystic or multicystic ‘‘bubbly’’ appearance

that is hypointense on T1-weighted images and hyperintense 23. A 30-year-old woman is evaluated for right eye pain and blurred
on T2-weighted images. Desmoplastic infantile ganglioglioma, vision over the past 2 weeks. Examination shows reduced visual
primitive neuroectodermal tumor, and pleomorphic xantho- acuity and a swollen optic nerve in the right eye and a temporal
astrocytoma typically show contrast enhancement on MRI. The field cut in the right eye. The rest of the neurologic exam-
location and radiologic features of this patient’s lesion are not ination is normal. Sagittal T1 precontrast (A) and postcontrast
consistent with subependymal glial cell astrocytoma. For more (B) sequences of her brain MRI are shown (page 1712). Which
information, refer to pages 1466Y1467 of the Continuum is the following is the most likely diagnosis?
article ‘‘Neuroimaging for Adults With Seizures and Epilepsy.’’
A. Churg-Strauss syndrome
21. An 18-year-old man is evaluated for the recent onset of inter- B . CSF leak
mittent headaches. His neurologic examination is normal. MRI C. Lyme disease
of his brain is shown (page 1711). Which of the following is a D. neurosarcoidosis
possible complication associated with this lesion? E . venous thrombosis
A. pituitary insufficiency
B . seeding to the spinal canal The preferred response is D (neurosarcoidosis). Acute to
C. seizure subacute onset of monocular visual loss that is often painful
D. sudden death is usually the presenting symptom of sarcoid optic neuropathy.
E . upward gaze palsy Granulomatous infiltration of the dura mater causes plaquelike
or nodular thickening on the infundibular stalk and optic
The preferred response is D (sudden death). The imaging chiasm, as seen on this patient’s sagittal T1-weighted MRI,
and location of the lesion shown in this MRI are typical of a which shows thickening of the optic chiasm (A, arrow) and
colloid cyst. Colloid cysts are almost always located in the superior infundibulum with associated contrast enhancement
anterior third of the third ventricle, adjacent to the foramen of in the midsagittal image (B, arrow). Infiltration of the lep-
Monro, and their signal characteristics depend on their tomeninges may result in intraparenchymal masses. There is
content. Most often, they are hyperintense on T1-weighted no diffuse dural enhancement on this patient’s MRI to sug-
images and hypointense on T2-weighted images because of gest a CSF leak, nor is there evidence for venous thrombosis.
their mucus or protein content. Obstruction of the foramen of Whereas Lyme disease and Wegener granulomatosis can affect
Monro by a colloid cyst, which can happen suddenly, may the meninges and cranial nerves, involvement of the infundib-
result in acute hydrocephalus, coma, and death (typically due ulum is more characteristic of neurosarcoidosis, and this clinical
to herniation or neurogenic cardiac dysfunction with subse- and radiologic picture is not suggestive of Churg-Strauss
quent cardiac arrest). The location and features of this lesion syndrome. For more information, refer to pages 1511 and
would not be expected to produce seizures, upward gaze Figures 6-17A and 6-17B of the Continuum article ‘‘Imaging
palsy, pituitary insufficiency, or seeding to the spinal canal. For in Patients With Visual Symptoms.’’
more information, refer to page 1560 and Figure 8-10 of the
Continuum article ‘‘Imaging of Intracranial Cysts.’’ 24. Which of the following imaging characteristics would be
most consistent with delayed radiation necrosis as opposed
22. Which of the following imaging characteristics is typical of to tumor progression in patients with glioblastoma?
the classic Dandy-Walker malformation? A. enhancement with gadolinium
A. absence of the fourth ventricle B . lesion development adjacent to the initial tumor site
B . hypoplasia of the cerebellar vermis C. lower cerebral blood volume levels on perfusion MRI
C. inferior displacement of the tentorium D. presence of hemorrhage
D. microcephaly E . vasogenic edema seen on T2-weighted and fluid-attenuated
E . smaller size of the posterior fossa inversion recovery (FLAIR) sequences
The preferred response is B (hypoplasia of the cerebellar The preferred response is C (lower cerebral blood volume
vermis). Dandy-Walker malformations are a category of levels on perfusion MRI). Distinguishing postradiation ne-
posterior fossa developmental abnormalities thought to arise crosis from tumor progression can be a significant challenge in
from deficits in mesenchymal-neuroepithelial signaling. These a patient who has been previously treated for glioma. Both of
can occur along a spectrum of severity, but the classic Dandy- these processes can manifest significant vasogenic edema, cause
Walker malformation includes enlargement of the posterior enhancement on CT and MRI, and have hemorrhagic compo-
fossa, elevation of the tentorium, hypoplasia of the cerebellar nents. On perfusion MRI, radiation necrosis is more likely to
vermis, and a dilated, enlarged fourth ventricle. Children with demonstrate relatively low cerebral blood volume levels, while
this disorder most commonly present with macrocephaly, not tumor progression may demonstrate increased perfusion. Lesions
microcephaly. For more information, refer to page 1491 of adjacent to the initial site of the tumor could be consistent with
the Continuum article ‘‘Imaging of Congenital Malformations.’’ either process. For more information, refer to pages 1543Y1544
of the Continuum article ‘‘Imaging of Brain Tumors.’’

25. A 72-year-old man is evaluated for the sudden onset of left 27. A 72-year-old man with history of hypertension is evaluated
hemiparesis. On examination 3 hours after symptom onset, for a 2-year history of intermittent headaches. His neurologic
he has mild upper motor neuron distribution weakness in the examination is normal. The arrows on this patient’s T2-weighted
left upper limb. A fluid-attenuated inversion recovery (FLAIR) MRI (at the level of the anterior commissure [arrowheads])
MRI of the brain is obtained within 4 hours of the event (page (page 1714) point to which of the following findings?
1713). What do the findings in this study indicate?
A. amyloid angiopathy
A. cortical laminar necrosis B . dilated Virchow-Robin spaces
B . hemorrhagic transformation of a cardioembolic stroke C. lacunar infarcts
C. slow retrograde collateral flow proximal to a middle cerebral D. microemboli
artery (MCA) occlusion E . vasculitis
D. subarachnoid hemorrhage in the setting of amyloid angiopathy
E . superficial vein thrombosis The preferred response is B (dilated Virchow-Robin spaces).
Dilated Virchow-Robin spaces, a common and usually inci-
The preferred response is C (slow retrograde collateral flow dental finding as in this patient, have typical neuroimaging
proximal to a middle cerebral artery [MCA] occlusion). The features of CSF. Type I Virchow-Robin spaces, as seen in this
FLAIR image of M2 segmental occlusion of the MCA dem- patient, are typically seen at the level of the anterior com-
onstrates vascular hyperintensity immediately proximal to the missure in the basal ganglia region. Dilated Virchow-Robin spaces
occlusion (A, arrow) caused by slow flow, and serpiginous can usually be distinguished from chronic lacunar infarctions
vascular hyperintensity distal to the occlusion (B, arrow) from based on their morphologic appearance and, by the absence
slow retrograde collateral flow. Such findings may be an of a surrounding thin rim of gliotic hyperintensity on fluid-
important clue to the presence of a proximal arterial occlusion attenuated inversion recovery (FLAIR) images, a characteristic
and good retrograde collateral flow, a favorable prognostic sign of infarction. The findings in this patient’s MRI are not
indicator associated with smaller ischemic lesion volume on suggestive of amyloid angiopathy, which is best detected with
MRI and milder clinical severity. The findings are in the vessels gradient recalled echo (GRE) or susceptibility-weighted imag-
and not in the parenchyma or the superficial subarachnoid ing (SWI); in addition, amyloid angiopathy would be hypo-
space. For more information, refer to page 1407 and Figure intense on T2-weighted images. For more information, refer
2-11 of the Continuum article ‘‘Imaging of Ischemic Stroke.’’ to page 1554 and Figure 8-1A of the Continuum article
‘‘Imaging of Intracranial Cysts.’’
26. In patients with sickle cell anemia, which of the following
imaging findings is validated as being able to predict indi- 28. High-resolution MRIs of the normal pituitary gland often
viduals at higher risk of stroke? show an area of T1 hyperintensity, referred to as the pituitary
bright spot. Which of the following anatomic structures does
A. elevated mean flow velocities in the middle cerebral this correspond to?
arteries
B . Lindegaard ratio greater than 6 A. adenohypophysis
C. macaroni sign on carotid ultrasonography B . median eminence
D. presence of bilateral microembolic signals in the middle C. neurohypophysis
cerebral arteries D. pituitary stalk
E . reverberating flow pattern on transcranial Doppler E . Rathke cleft
The preferred response is C (neurohypophysis). The poste-
The preferred response is A (elevated mean flow velocities rior pituitary gland, or neurohypophysis, can often be seen as
in the middle cerebral arteries). Patients with sickle cell a bright or hyperintense region on high-resolution T1-weighted
anemia are at risk for developing a nonatherosclerotic arterio- MRI. This is thought to correspond to vasopressin stored in this
pathy resulting in stenosis of the middle cerebral arteries and region of the gland. Neurologists should be aware of the normal
distal portions of the internal carotid arteries. Detection of anatomic appearance of the sellar and parasellar region in order
elevated mean flow velocities in these vessels is highly pre- to better identify pathology there. For more information, refer to
dictive of stenosis; this, in turn, is predictive of stroke. Trans- page 1575 of the Continuum article ‘‘Imaging of Pituitary and
fusion to a hemoglobin S fraction less than 30% is associated Parasellar Disorders.’’
with reductions in velocities and a dramatic reduction in stroke.
Regarding the other listed options, bilateral microembolic signals
would be potentially suggestive of a cardioembolic source
of stroke. Elevated Lindegaard ratios (middle cerebral artery/
internal carotid artery velocity) are suggestive of vasospasm in
patients with subarachnoid hemorrhage. A reverberating flow
pattern on intracranial ultrasound is seen in patients with
circulatory arrest (ie, in brain death), and the macaroni sign
refers to vessel wall thickening seen in Takayasu arteritis. For
more information, refer to page 1666 of the Continuum
article ‘‘Ultrasound in Neurology.’’

29. A 20-year-old right-handed man is evaluated for spells char- 31. A 42-year-old man is seen in clinic for vision complaints. On
acterized by abdominal pain, dysarthria, and bradycardia. His additional questioning, he reports a 1-year history of decreased
neurologic examination is normal. An axial fluid-attenuated libido and the recent onset of gynecomastia. Examination
inversion recovery (FLAIR) image is shown (page 1715), with shows subtle restriction of bitemporal vision. A sagittal post-
the abnormalities marked with arrows. Which of the follow- contrast T1-weighted image from his brain MRI is shown (page
ing is the most likely pathologic substrate of these imaging 1716). Which of the following is the most likely diagnosis?
abnormalities?
A. aberrant axonal sprouting B . craniopharyngioma
B . dysmorphic neurons C. dermoid cyst
C. gliosis D. pituitary apoplexy
D. immature endothelium-lined caverns E . pituitary macroadenoma
E . proliferation of oligodendrocytes
The preferred response is E (pituitary macroadenoma). This
The preferred response is B (dysmorphic neurons). The patient is presenting with signs and symptoms of bitemporal
image shows the typical findings of cortical dysplasia type II, hemianopia, which is often related to compression of the optic
which include cortical thickening and loss of sharpness of chiasm from a sellar or suprasellar mass lesion. His imaging
the cortico-subcortical transition (blue arrow) and increased shows a large pituitary mass, and his additional symptoms are
FLAIR signal below the area of cortical thickening that extends highly suggestive of hypogonadism, so the most likely cause of
toward the ventricle (transmantle sign, red arrow). The clin- his symptoms and imaging would be a nonfunctional pituitary
ical manifestations may, in part, be explained by involvement adenoma. Pituitary apoplexy and carotid-cavernous fistulas
of the insular cortex. Focal cortical dysplasia type II often usually present more acutely. The imaging shown here is not
shows apparent increased cortical thickness, which is better typical of dermoid cyst. For more information, refer to page
seen on T1-weighted sequences; blurring of the gray-white 1579 and Figure 9-5A of the Continuum article ‘‘Imaging of
junction; and increased T2 signal and decreased T1 signal in Pituitary and Parasellar Disorders.’’
the subcortical white matter. Imaging may demonstrate the
transmantle sign, in which increased signal tapers off in the 32. In brain neoplasms, restricted diffusion on diffusion-weighted
white matter closer to the ventricle, seen almost exclusively MRI (ie, reduced apparent diffusion coefficient) may be indi-
in focal cortical dysplasia type IIb. Gliosis appears as an area cative of which of the following?
of T1 hypointensity and T2/FLAIR hyperintensity with associated
volume loss. For more information, refer to pages 1464Y1466 A. hypercellular nature of a neoplasm
and Figure 4-3F of the Continuum article ‘‘Imaging for Adults B. intratumor hemorrhage
With Seizures and Epilepsy.’’ C. lower grade of glioma
D. metastatic as opposed to primary brain source of neoplasm
E. postradiation necrosis
30. Which of the following time frames best approximates the
average duration that an acute multiple sclerosis (MS) lesion is The preferred response is A (hypercellular nature of a
expected to show contrast enhancement on MRI? neoplasm). Diffusion-weighted imaging is a marker of the
A. 1 week movement of water within an area of the brain. Several
B . 3 weeks different pathophysiologic mechanisms and processes can
C. 6 weeks result in restricted diffusion, including acute ischemia and
D. 12 weeks pyogenic abscess. In brain neoplasms, the presence of re-
E . 20 weeks stricted diffusion is often related to higher cell density (ie,
hypercellularity). In this regard, restricted diffusion is often
The preferred response is B (3 weeks). Enhancement after seen in higher-grade gliomas as opposed to lower-grade
the administration of gadolinium is a hallmark of an acute MS gliomas. For more information, refer to pages 1535Y1536 of
lesion and is thought to represent focal breakdown of the the Continuum article ‘‘Imaging of Brain Tumors.’’
blood-brain barrier in that region. However, other central nervous
system processes can also result in contrast enhancement, so an
understanding of the expected duration of enhancement can
be helpful for diagnostic purposes. The average length of
enhancement of an acute demyelinating lesion from MS is
about 3 weeks; while about 4% of lesions may continue to
enhance after 3 months, longer durations of enhancement may
suggest an alternative etiology. For more information, refer to
page 1617 of the Continuum article ‘‘ Imaging of Central
Nervous System Demyelinating Disorders.’’

33. A 57-year-old man is evaluated for numbness in his hands (as seen in the unaffected contralateral side). Angiography
and feet and imbalance that developed over the past 6 months. would be the next step in this case, so that the exact timing of
He has a history of diabetes mellitus, hypertension, and a venous flow can be seen. For more information, refer to pages
previous partial gastrectomy. Examination shows a sensory 1590Y1591 of the Continuum article ‘‘Imaging of Pituitary
ataxia with Romberg sign, areflexia, bilateral Babinski signs, and Parasellar Disorders.’’
and absent joint position sense in the fingers and toes. MRI of
the cervical spine is shown (page 1717). Serum methylmalonic 35. A 12-year-old boy is evaluated for headache, vomiting, and
acid levels are normal. Which of the following is the most gait disturbance. Examination shows papilledema, impaired
appropriate next test in this patient? upward gaze, and pupillary light-near dissociation. Sagittal
A. antiYaquaporin-4 antibodies MRI using T2-weighted (A) and T1-weighted (B) sequences
B . antinuclear antibodies are shown (page 1718). Which of the following diagnoses
C. serum angiotensin-converting enzyme is most likely?
D. serum ceruloplasmin A. histiocytosis
E . serum vitamin D B . pilocytic astrocytoma
C. pineal cyst
The preferred response is D (serum ceruloplasmin). The history D. pinealoma
and findings are those of a myeloneuropathy. Deficiencies of E . teratoma
copper and folate can mimic the clinical and radiographic
features of vitamin B12 deficiency. MRI is the imaging mo- The preferred response is E (teratoma). The lesion, located
dality of choice to evaluate for spinal cord involvement in in the pineal region, shows increased signal in both T1- and
these disorders. In these deficiencies, lesions appear as ab- T2-weighted images, which is consistent with the presence
normal hyperintensity in the posterior columns on T2-weighted of fat. Teratomas also contain areas of calcification that can
images, as seen in this patient. The lesions may resemble an have different intensities on MRI but are best identified on
inverted V or ‘‘inverted rabbit ears’’ on axial T2-weighted images, CT. The presence of fat is not a feature of pinealoma, pilocytic
as also seen in this patient. The lesions do not enhance, and, if astrocytomas, or histiocytosis. Pineal cysts are isointense with
the nutritional deficiency is treated early, can resolve. Rarely, the CSF. For more information, refer to page 1394 and Figures
T2 hyperintensity may also be seen in the anterior spinal cord. 1-15A and 1-15B of the Continuum article ‘‘Introduction to
This patient’s normal serum methylmalonic acid level argues Magnetic Resonance Imaging for Neurologists.’’
against vitamin B12 deficiency and supports the possibility of
copper deficiency. The history, examination, and MRI findings, 36. A 22-year-old man is evaluated for progressive gait dis-
including the lack of contrast enhancement, are not those of turbance and hand paresthesia over the past 3 months.
neuromyelitis optica (NMO) associated with antiYaquaporin-4 Examination shows a sensory ataxia and severe proprio-
antibodies or immune myelopathies sometimes associated ceptive loss in his hands and feet. MRI of the cervical spine
with positive antinuclear antibodies. The lack of parenchymal shows a T1-hypointense and T2-hyperintense cystic mass
or pial enhancement argues against spinal neurosarcoidosis. lesion with a homogeneous contrast-enhancing nodule
Vitamin D deficiency is not associated with a myeloneuropathy. associated with dilated vessels and a syrinx. Which of the
For more information, refer to page 1599 and Figure 10-4 of following is the most likely diagnosis?
the Continuum article ‘‘Imaging of Spinal Cord Disorders.’’
B . cavernous malformation
34. A 54-year-old woman is seen for 1 week of right eye pain, a C. hemangioblastoma
bloodshot appearance to the right eye, and double vision. D. myxopapillary ependymoma
On examination, she has proptosis, chemosis, and conges- E . pilocytic astrocytoma
tion of the right eye, with impairment of eye movements in
the horizontal and vertical directions. CT angiography of
the brain shows asymmetric contrast enhancement of the The preferred response is C (hemangioblastoma). Heman-
cavernous sinuses, with more marked enhancement on the gioblastomas appear T2 hyperintense and T1 hypointense
right; dilation of the right superior ophthalmic vein is also on MRI. In most cases, homogenous contrast enhancement
seen. Which of the following is the most likely diagnosis? is seen. These tumors may be mistaken for vascular mal-
formations because of the presence of dilated vessels. They
A. carotid-cavernous fistula are commonly associated with a syrinx, and the presence of
B . right central retinal vein occlusion a syrinx helps differentiate them from vascular malformations.
C. right internal jugular vein thrombosis Another typical feature of a hemangioblastoma is a spinal cyst
D. temporal arteritis with an enhancing mural nodule. Myxopapillary ependymomas
E . unruptured right internal carotid artery aneurysm of the filum terminale are a histologic variant of ependymoma
and show prominent contrast enhancement. They appear as
The preferred response is A (carotid-cavernous fistula). Acute isointense to hypointense masses on T1- and T2-weighted images,
onset of proptosis, orbital edema, and venous congestion of tend to be extramedullary, and can span several vertebral
the eye, along with ophthalmoparesis, is very suggestive of a segments. Astrocytomas commonly originate in the cervical
carotid-cavernous fistula. The imaging described here would spinal cord, but, unlike hemangioblastomas and ependymomas
also be supportive of this diagnosis, as it shows prominent that typically have poorly demarcated margins, they are T1
contrast filling of the right cavernous sinus that is not dem- hypointense to isointense and T2 hyperintense and show mild
onstrating the typical delay seen with filling of venous structures to moderate patchy enhancement or a lack of enhancement.

In intramedullary spinal arteriovenous malformations, MRI lobar degeneration. For more information, refer to page 1641
shows intramedullary flow voids and dilated draining veins of the Continuum article ‘‘Positron Emission Tomography
associated with aneurysms. On T2-weighted images, cavern- and Single-Photon Emission Computed Tomography in
ous malformations present as a heterogeneous hyperintense Neurology.’’
center surrounded by a rim of hypointensity, giving them the
characteristic popcorn appearance. They may also exhibit 39. A 62-year-old woman with a history of diabetes mellitus
heterogenous signal on T1-weighted images, reflecting the and hypertension is evaluated for sudden-onset headache
presence of intracavernous vascular channels containing he- and left face and upper limb weakness that began 3 hours
moglobin in various stages of degradation. For more informa- ago. A noncontrast CT scan of the head is shown (page
tion, refer to pages 1605Y1606 of the Continuum article 1720). Which of the following is the most likely cause of
‘‘Imaging of Spinal Cord Disorders.’’ this patient’s symptoms?
37. A 31-year-old woman is seen for 3 days of worsening vision B . cerebral vein occlusion
in the left eye as well as pain with eye movements. She has C. middle cerebral artery (MCA) thrombosis
had no prior episodes of neurologic dysfunction. Examina- D. subarachnoid hemorrhage
tion is notable for 20/200 acuity in the left eye, normal fun- E . vasculitis
duscopic appearance of the left optic nerve, and a relative
afferent pupillary defect on the left. Postcontrast fat-suppressed The preferred response is C (middle cerebral artery [MCA]
T1-weighted MRI is shown (page 1719). Which of the fol- thrombosis). The noncontract head CT demonstrates a right
lowing is the most likely diagnosis? hyperdense MCA, suggesting thrombosis. While noncontrast
A. giant cell arteritis CT and MRI are paramount in imaging the brain parenchyma,
B . Graves disease vessel patency or suggestions of thrombus may be indicated
C. nonarteritic ischemic optic neuropathy by a number of clinically relevant vascular signs. For example,
D. optic nerve glioma blooming artifact on gradient recalled echo (GRE) MRI or the
E . optic neuritis hyperdense MCA sign on noncontrast CT may indicate red
cellYpredominant occlusive thrombus, The imaging feature
The preferred response is E (optic neuritis). This patient’s shown here is not that of arteriovenous malformation and
clinical presentation of several days of progressive monocular would be atypical for subarachnoid hemorrhage. The vessel
visual impairment associated with pain with eye movement is affected is the MCA, not a cerebral vein. For more information,
highly suggestive of acute optic neuritis. The MRI shows en- refer to page 1407 and Figure 2-10A of the Continuum
hancement of the left optic nerve, which is the imaging find- article ‘‘Imaging of Ischemic Stroke.’’
ing commonly associated with this disorder. For more
information, refer to page 1617 and Figure 11-2C of the 40. A 70-year-old man is referred for carotid ultrasonography
Continuum article ‘‘Imaging of Central Nervous System De- after his primary care provider heard a bruit over the left
myelinating Disorders.’’ side of the neck. His ultrasound shows elevated velocities
in the 50% to 69% range. The presence of which of the
38. A 68-year-old man is evaluated for progressive memory dif- following ultrasound findings would be more suggestive of
ficulties over the past 2 years. He experiences difficulty re- this plaque being unstable and thus more likely to result in
calling names and details from previous conversations but artery-to-artery embolism?
has remained independent in activities of daily living. Exam- A. concentric thickening of vessel wall (macaroni sign)
ination shows 1/3 recall after 5 minutes but is otherwise B . elevated Lindegaard ratio
normal. Brain MRI demonstrates bilateral hippocampal atro- C. false lumen with bidirectional flow
phy. Which of the following cortical areas are most likely to D. intraplaque hemorrhage
show reduced metabolism on fludeoxyglucose positron emis- E . uniform hyperechogenicity
sion tomography (FDG-PET) scan?
A. anterior cingulate The preferred response is D (intraplaque hemorrhage).
B . anterior temporal This patient’s ultrasound is consistent with carotid stenosis
C. dorsolateral prefrontal in the moderate range of severity. Some stenotic lesions are
D. medial parietal made up largely of fibrotic tissue and are relatively smooth
E . ventrolateral prefrontal walled, with ultrasound showing relative hyperechoic tissue;
these types of plaques are considered more stable and less
The preferred response is D (medial parietal). The history, likely to result in stroke. Conversely, other ultrasound features
examination, and MRI suggest amnestic mild cognitive impair- can be more suggestive of unstable plaque, including intra-
ment, which is most commonly associated with underlying plaque hemorrhage, calcification, and necrosis. Concentric
Alzheimer disease pathology. The typical FDG-PET pattern for uniform wall thickening is seen in Takayasu arteritis. A false
Alzheimer disease is posteriorly dominant asymmetric associ- lumen with potentially bidirectional flow may be seen in
ation cortex hypometabolism, most notable in temporal and carotid or vertebral artery dissection. An elevated Lindegaard
parietal cortices, with preferential; involvement of the medial ratio is seen in vasospasm secondary to subarachnoid hemor-
parietal cortex. Anterior temporal, anterior cingulate, and pre- rhage, not carotid stenosis. For more information, refer to pages
frontal cortical hypometabolism are seen in frontotemporal 1656Y1657 of the Continuum article ‘‘Ultrasound in Neurology.’’

Patient Management
Dr Riley Bove, University of
California, San Francisco
Sandler Neurosciences Center,
Problem 675 Nelson Rising Ln, San

Francisco, CA 94158,
Riley.Bove@ucsf.edu.
Riley Bove, MD Relationship Disclosure:
Dr Bove receives research/
grant support from the
National Institutes of Health
and the National Multiple
The following Patient Management Problem was chosen to reinforce the Sclerosis Society.
Unlabeled Use of
subject matter presented in the issue. It emphasizes decisions facing the Products/Investigational
practicing physician. As you read through the case you will be asked to Use Disclosure:
complete 12 questions regarding history, examination, diagnostic evaluation,
therapy, and management. For each item, select the single best response. of Neurology.
To obtain CME credits for this activity, subscribers must complete this
Patient Management Problem online at www.aan.com/continuum/cme. A
tally sheet is provided with this issue to allow the option of marking
answers before entering them online. A faxable scorecard is available
only upon request to subscribers who do not have computer access or
to nonsubscribers who have purchased single back issues (send an email
to ContinuumCME@aan.com).
Upon completion of the Patient Management Problem, participants may
earn up to 2 AMA PRA Category 1 Creditsi. Participants have up to 3 years
from the date of publication to earn CME credits. No CME will be awarded
for this issue after October 31, 2019.
Learning Objectives
Upon completion of this activity, the participant will be able to:
& Identify normal anatomic landmarks on brain and spine MRIs
& Formulate a differential diagnosis for lesions on brain and spine MRIs
& Understand the limitations of current imaging techniques
Case
A 45-year-old man living in a rural community develops progressive
weakness in his legs over 8 days, culminating in a fall when exiting his car
in a parking lot. He is brought by a colleague to the emergency
department. A neurologic consultation is requested. On neurologic
examination, the patient demonstrates symmetric mild bilateral lower
extremity weakness, absence of proprioception in the feet bilaterally,
diminished sensation to pinprick in the left abdominal section under the
rib cage, and patellar hyperreflexia. Examination of his cranial nerves and
upper extremities is normal.

Patient Management Problem
b 1. Which would be the most appropriate next step?

A. complete myelogram
B. lumbar puncture
C. lumbar spine MRI
D. nerve conduction studies and EMG
E. thoracic spine MRI
The patient is admitted to the inpatient neurologic service for evaluation.

An urgent thoracic spine MRI with and without contrast is performed.
His noncontrast T1-weighted sagittal MRI is shown in PMP Figure 1.
A postcontrast MRI showed patchy enhancement of the lesion.
PMP FIGURE 1
b 2. Which of the following diagnoses is most compatible with this patient’s

thoracic spine MRI (PMP Figure 1)?
A. epidural abscess
B. hydromyelia
C. longitudinally extensive transverse myelitis
D. multiple sclerosis (MS)
E. syringomyelia

b 3. On PMP Figure 2, which is an axial T2-weighted image at a level below
the patient’s spinal cord lesion, what normal feature is the red arrow
pointing to?
A. lamina
B. pedicle
C. spinous process
D. transverse process
E. vertebral body
PMP FIGURE 2
b 4. On PMP Figure 2, what normal feature is the yellow arrow pointing to?
A. central draining vein of vertebral body
B. lamina
C. pedicle
D. spinous process
E. transverse process
b 5. On PMP Figure 2, what normal feature is the blue arrow pointing to?
A. anterior longitudinal ligament
B. interspinous ligament
C. ligamentum flavum
D. posterior longitudinal ligament
E. supraspinous ligament
Brain MRI is performed and is unremarkable. Lumbar puncture is performed

and shows 45 white blood cells/mm3, 0 red blood cells/mm3, protein 70 mg/dL,
and glucose 52 mg/dL.

b 6. What is the most important next diagnostic test to order in this patient?
A. lumbar MRI
B. serum myelin oligodendrocyte glycoprotein (MOG) antibody
C. serum neuromyelitis optica (NMO) IgG
D. somatosensory evoked potentials
E. spinal angiogram
Serum NMO IgG antibody is sent and is pending. The patient’s history and
images are re-reviewed with a neuroimager to ensure that the thoracic
abnormality does not represent a spinal arteriovenous lesion.
b 7. Which of the following statements is most true about spinal arteriovenous

fistulas (AVFs) compared to spinal arteriovenous malformations (AVMs)?
A. both spinal AVFs and AVMs are typically angiographically occult
B . hemorrhage is rare with both spinal AVMs and AVFs
C. spinal AVFs are characterized by a direct shunt between the artery
and the vein
D. spinal AVFs are characterized by the presence of a nidus of abnormal
vessels between the artery and the vein
E . spinal AVMs are characterized by a direct shunt between the artery
and the vein
The thoracic MRI is reviewed with the neuroimaging team, and no flow
voids suggestive of an arteriovenous lesion are seen. This patient’s brain
MRI is also re-reviewed to assess for any subtle brain findings of an NMO
spectrum disorder, and no abnormalities are seen.
b 8. Although this patient’s brain MRI was unrevealing, which of the following
brain MRI findings, if seen, would be more consistent with an NMO
spectrum disorder than MS?
A. corpus callosum lesions
B. cortical and subcortical lesions
C. hypothalamic and area postrema lesions
D. middle cerebellar peduncle lesions
E. multiple periventricular ovoid lesions
Within several hours of admission, the patient begins to report worsening

lower extremity weakness and difficulty voiding his bladder. Strength is
now 2/5 in both legs diffusely, and bladder scan demonstrates a postvoid
residual of 175 mL.

b 9. What is the most appropriate management of this patient at this time?
A. azathioprine
B. fluoroquinolone antibiotic
C. glatiramer acetate
D. interferon beta
E. IV methylprednisolone
Two days after admission, the patient now reports the onset of a
positional headache, worse with standing. Brain MRI is repeated, and his
coronal postcontrast T1-weighted image is shown (PMP Figure 3).
PMP FIGURE 3
b 10. Which of the following is the most likely explanation for the findings
on this patient’s brain MRI?
A. bacterial meningitis
B. dural enhancement after lumbar puncture
C. IgG4 pachymeningitis
D. posterior reversible encephalopathy syndrome (PRES)
E. venous sinus thrombosis

The patient is diagnosed with an NMO spectrum disorder and treated with a
course of 5 days of IV methylprednisolone, with gradual improvement in his
lower extremity strength. He is discharged to inpatient rehabilitation on a
slow prednisone taper. He is seen in follow-up neurology clinic 1 month later,
manifesting significant improvement in his strength, ambulation, and bladder
function. His NMO IgG antibody has also returned and is positive. Long-term
immunosuppressive therapy is recommended, but he elects to defer further
immunosuppressive treatment at this time.
Three months later, the patient calls reporting a 2-day history of right
retroorbital pain and decreased vision in his right eye. Examination shows
a central scotoma of the right eye and a right afferent pupillary defect.
Orbital MRI is performed, and his coronal T2-weighted image
is shown (PMP Figure 4).
PMP FIGURE 4
b 11. Which of the following is the most accurate interpretation of this

patient’s MRI?
A. normal findings
B. pituitary microadenoma
C. right cavernous sinus thrombosis
D. right nasopharyngeal mass
E. right optic nerve hyperintensity

The patient is treated with IV methylprednisolone for 3 days with good
clinical response. Given this second clinical attack, the patient now agrees to
immunosuppressive therapy and is treated with rituximab. One week later,
he returns to the emergency department reporting a worsening headache
and visual blurring bilaterally that has progressed over the course of several
hours. On examination, blood pressure is 170/90 mm Hg. He is
encephalopathic and has a bilateral visual field defect. An urgent brain MRI
is performed; the FLAIR image is shown (PMP Figure 5).
PMP FIGURE 5
b 12. Which of the following is the most likely explanation for these
imaging findings?
A. posterior circulation stroke
B. posterior reversible encephalopathy syndrome (PRES)
C. progressive multifocal leukoencephalopathy (PML)
D. tumefactive MS
E. vasculitis
The patient is admitted to the inpatient neurology service, where his blood
pressure is aggressively controlled. Over the subsequent 3 days, his
encephalopathy and visual field defects resolve. He is discharged on
hospital day 5. Follow-up imaging obtained 1 month later reveals
complete disappearance of the T2-weighted hyperintensity.

Patient Management
Dr Riley Bove, University of
California, San Francisco
Sandler Neurosciences Center,
675 Nelson Rising Ln, San
Francisco, CA 94158,
Riley.Bove@ucsf.edu.
Problem—Preferred
Dr Bove receives research/
grant support from the
Responses
National Institutes of Health
and the National Multiple Riley Bove, MD
Sclerosis Society.
Unlabeled Use of
Use Disclosure:
Following are the preferred responses for the Patient Management Problem
of Neurology. in this Continuum issue. The case, questions, and answer options are re-
peated, and the preferred response is given, followed by an explanation and
a reference with which you may seek more specific information. You are
encouraged to review the responses and explanations carefully to evaluate
your general understanding of the material. The comment and references
included with each question are intended to encourage independent study.
To obtain CME credits for this activity, subscribers must complete this
Patient Management Problem online at www.aan.com/continuum/cme.
Upon completion of the Patient Management Problem, participants may
earn up to 2 AMA PRA Category 1 CreditsTM. Participants have up to 3 years
from the date of publication to earn CME credits. No CME will be awarded
for this issue after October 31, 2019.
Learning Objectives
Upon completion of this activity, the participant will be able to:
& Identify normal anatomic landmarks on brain and spine MRIs
& Formulate a differential diagnosis for lesions on brain and spine MRIs
& Understand the limitations of current imaging techniques
Case
A 45-year-old man living in a rural community develops progressive
weakness in his legs over 8 days, culminating in a fall when exiting his car
in a parking lot. He is brought by a colleague to the emergency
department. A neurologic consultation is requested. On neurologic
examination, the patient demonstrates symmetric mild bilateral lower
extremity weakness, absence of proprioception in the feet bilaterally,
diminished sensation to pinprick in the left abdominal section under the
rib cage, and patellar hyperreflexia. Examination of his cranial nerves and
upper extremities is normal.

b 1. Which would be the most appropriate next step?
A. complete myelogram
B . lumbar puncture
C. lumbar spine MRI
D. nerve conduction studies and EMG
E . thoracic spine MRI
The preferred response is E (thoracic spine MRI). The patient manifests

signs and symptoms localizable to the thoracic spinal cord, with a
midthoracic sensory level. Therefore, the most appropriate next step is to
image the thoracic spine with MRI,1 although additional concurrent imaging
of the cervical spinal cord would also be reasonable. A follow-up lumbar
puncture will help distinguish between inflammatory and infectious
etiologies, if indicated. Myelography would only be indicated if a
contraindication to MRI existed.
1. Cho TA. Spinal cord functional anatomy. Continuum (Minneap Minn) 2015;21(1 Spinal Cord
Disorders):13Y35. doi:10.1212/01.CON.0000461082.25876.4a.
The patient is admitted to the inpatient neurologic service for evaluation.

An urgent thoracic spine MRI with and without contrast is performed. His
noncontrast T1-weighted sagittal MRI is shown in PMP Figure 1 (page 1737).
A postcontrast MRI showed patchy enhancement of the lesion.
b 2. Which of the following diagnoses is most compatible with this patient’s

thoracic spine MRI (PMP Figure 1, page 1737)?
A. epidural abscess
B . hydromyelia
C. longitudinally extensive transverse myelitis
D. multiple sclerosis (MS)
E . syringomyelia

PMP—Preferred Responses
The preferred response is C (longitudinally extensive transverse myelitis).

This patient’s MRI shows a longitudinally extensive spinal cord lesion, defined
as a lesion longer than three vertebral bodies in length. Although other causes
of a longitudinally extensive spinal cord lesion are possible in this patient
(including a dural arteriovenous fistula), of the options listed, this lesion is most
compatible with a longitudinally extensive transverse myelitis. MS lesions are
typically smaller in the rostral-caudal dimension and also span less of a
cross-sectional area of the spinal cord than lesions from longitudinally extensive
transverse myelitis. Syringomyelia refers to a fluid-filled cyst in the spinal cord
parenchyma or cystic expansion of the central canal with disruption of ependyma,
whereas hydromyelia refers to cystic expansion of the central canal with
ependymal lining preserved1; neither of these findings is demonstrated on this
patient’s MRI. The lesion in this image is intramedullary only, unlike an epidural
abscess, which is an extramedullary lesion that can compress the cord.
1. Singh K, Mechtler LL, Klein JP. Imaging of spinal cord disorders. Continuum (Minneap Minn)
2016;22(5 Neuroimaging):1595Y1612.
b 3. On PMP Figure 2 (page 1738), which is an axial T2-weighted image at

a level below the patient’s spinal cord lesion, what normal feature is the
red arrow pointing to?
A. lamina
B. pedicle
C. spinous process
D. transverse process
E. vertebral body
The preferred response is D (transverse process). Knowledge of normal

vertebral anatomy can be useful in neurologic diagnosis.1 The vertebral
body bears approximately 80% of the load in upright posture and
provides the attachment for the intervertebral disks. The spinal cord
runs posterior to the vertebral body in the spinal canal and is enclosed
and protected by a ring of structures, including the pedicles, transverse
processes, and lamina. The pedicles project posteriorly from the vertebral
body and abut the transverse processes (typically absent in the cervical
spine except in the cases of cervical rib), which run perpendicular to
them, projecting posteriorly and laterally.
1. Cramer GD, Darby SA. Clinical anatomy of the spine, spinal cord, and ANS. 3rd ed.
St. Louis: Elsevier Mosby, 2014.
b 4. On PMP Figure 2 (page 1738), what normal feature is the yellow

arrow pointing to?
A. central draining vein of vertebral body
B. lamina
C. pedicle
D. spinous process
E. transverse process

The preferred response is D (spinous process). Posterior to the transverse
processes, the lamina fuse into the spinous process, closing the posterior
part of the spinal canal.1
1. Cramer GD, Darby SA. Clinical anatomy of the spine, spinal cord, and ANS. 3rd ed. St. Louis:
Elsevier Mosby, 2014.
b 5. On PMP Figure 2 (page 1738), what normal feature is the blue arrow
pointing to?
A. anterior longitudinal ligament
B . interspinous ligament
C. ligamentum flavum
D. posterior longitudinal ligament
E . supraspinous ligament
The preferred response is A (anterior longitudinal ligament). The ligaments

play a major role in maintaining the structural stability of the spine and
preventing injury from hyperextension and hyperflexion. These ligaments
include the intrasegmental system, which holds individual vertebrae
together, and the intersegmental system, which holds multiple vertebrae
together. The long, thick anterior longitudinal ligament runs anterior to the
vertebral bodies from the anterior tubercle of the atlas to the sacrum,
providing stability to the spine.1 Other components of the intersegmental
system include the posterior longitudinal ligament, which runs posterior
to the vertebral bodies, and the supraspinous ligament, which connects
the tips of each spinous process. In the intrasegmental system, the
strongest spinal ligament is the ligamentum flavum. The ligamentum
flavum covers the dura mater, running anterior to and between the
lamina, from the base of the skull to the pelvis. The thin interspinous
ligament connects adjoining spinous processes, connecting anteriorly to the
ligamentum flavum and posteriorly to the supraspinous ligament.
1. Cramer GD, Darby SA. Clinical anatomy of the spine, spinal cord, and ANS. 3rd ed.
St. Louis: Elsevier Mosby, 2014.
Brain MRI is performed and is unremarkable. Lumbar puncture is performed

and shows 45 white blood cells/mm3, 0 red blood cells/mm3, protein
70 mg/dL, and glucose 52 mg/dL.
b 6. What is the most important next diagnostic test to order in this patient?
A. lumbar MRI
B . serum myelin oligodendrocyte glycoprotein (MOG) antibody
C. serum neuromyelitis optica (NMO) IgG
D. somatosensory evoked potentials
E . spinal angiogram

The preferred response is C (serum neuromyelitis optica [NMO] IgG). The

thoracic spine MRI is consistent with a longitudinally extensive transverse
myelitis. NMO is a severe inflammatory neurologic disease; the main clinical
manifestations are simultaneous or successive episodes of optic neuritis
and transverse myelitis. NMO is associated with serum IgG antibodies to
aquaporin-4, which are present in about 75% of patients with NMO. NMO
spectrum disorder is a unifying term to describe the clinical spectrum of
NMO, including aquaporin-4 antibody positive patients with limited forms of
the disease. Compared with other causes of longitudinally extensive
transverse myelitis, NMO is more likely to cause lesions that involve more
than one-half of the spinal cord’s cross-sectional area, enhance, and have a
central or both central and peripheral location in the cord.1 Because
treatment of NMO differs from treatment of MS, establishing a diagnosis
is paramount. Testing for aquaporin-4 antibody is more sensitive in serum
than in CSF.2 Less frequently, MOG antibodies and NMO spectrum
disorders may be associated.3 Lumbar MRI has no role in this scenario, and
somatosensory evoked potentials would add no additional useful information
to the imaging findings in this patient. Spinal angiogram would not be
indicated in this patient without a strong imaging and clinical suspicion for an
arteriovenous abnormality (eg, dural arteriovenous fistula) which is even
more unlikely now in this patient with an inflammatory CSF.
1. Pekcevik Y, Mitchell CH, Mealy MA, et al. Differentiating neuromyelitis optica from other
causes of longitudinally extensive transverse myelitis on spinal magnetic resonance imaging.
Mult Scler 2016;22(3):302Y311. doi:10.1177/1352458515591069.
2. Jarius S, Franciotta D, Paul F, et al. Cerebrospinal fluid antibodies to aquaporin-4 in
neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance.
J Neuroinflammation 2010;7:52. doi:10.1186/1742-2094-7-52.
3. Sepúlveda M, Armangué T, Sola-Valls N, et al. Neuromyelitis optica spectrum disorders:
comparison according to the phenotype and serostatus. Neurol Neuroimmunol Neuroinflamm
2016;3(3):e225. doi:10.1212/NXI.0000000000000225.
Serum NMO IgG antibody is sent and is pending. The patient’s history and
images are re-reviewed with a neuroimager to ensure that the thoracic
abnormality does not represent a spinal arteriovenous lesion.
b 7. Which of the following statements is most true about spinal arteriovenous

fistulas (AVFs) compared to spinal arteriovenous malformations (AVMs)?
A. both spinal AVFs and AVMs are typically angiographically occult
B . hemorrhage is rare with both spinal AVMs and AVFs
C. spinal AVFs are characterized by a direct shunt between the artery and
the vein
D. spinal AVFs are characterized by the presence of a nidus of abnormal
vessels between the artery and the vein
E . spinal AVMs are characterized by a direct shunt between the artery and
the vein

The preferred response is C (spinal AVFs are characterized by a direct shunt
between the artery and the vein). Among spinal arteriovenous lesions,
AVFs are characterized by a direct shunt between the artery and vein, while
AVMs are characterized by the presence of a nidus of abnormal vessels
between the artery and the vein. Both types of lesions may present with
sudden hemorrhage. Conventional angiogram is the most sensitive diagnostic
technique for both lesions. However, if a lesion is not immediately noted
during the procedure, testing may be protracted as the entire spinal cord must
be evaluated segment by segment.1
1. Patsalides A, Knopman J, Santillan A, et al. Endovascular treatment of spinal arteriovenous
lesions: beyond the dural fistula. AJNR Am J Neuroradiol 2011;32(5):798Y808. doi:10.3174/
ajnr.A2190.
The thoracic MRI is reviewed with the neuroimaging team, and no flow
voids suggestive of an arteriovenous lesion are seen. This patient’s brain
MRI is also re-reviewed to assess for any subtle brain findings of an NMO
spectrum disorder, and no abnormalities are seen.
b 8. Although this patient’s brain MRI was unrevealing, which of the following
brain MRI findings, if seen, would be more consistent with an NMO spectrum
disorder than MS?
A. corpus callosum lesions
B . cortical and subcortical lesions
C. hypothalamic and area postrema lesions
D. middle cerebellar peduncle lesions
E . multiple periventricular ovoid lesions
The preferred response is C (hypothalamic and area postrema lesions).

A brain MRI can help to distinguish NMO from MS. The presence of
hypothalamic, periaqueductal gray matter, and area postrema lesions is more
typical of NMO. In contrast, the presence of cortical, U fiber, or Dawson
finger lesions is more suggestive of MS.1
1. Tackley G, Kuker W, Palace J. Magnetic resonance imaging in neuromyelitis optica. Mult Scler
2014;20(9):1153Y1164. doi:10.1177/1352458514531087.
Within several hours of admission, the patient begins to report worsening

lower extremity weakness and difficulty voiding his bladder. Strength is
now 2/5 in both legs diffusely, and bladder scan demonstrates a postvoid
residual of 175 mL.

b 9. What is the most appropriate management of this patient at this time?

A. azathioprine
B . fluoroquinolone antibiotic
C. glatiramer acetate
D. interferon beta
E . IV methylprednisolone
The preferred response is E (IV methylprednisolone). The patient has a

severe and worsening inflammatory myelopathy. It is important to start
steroid therapy to minimize extension of his lesion and symptoms, with
step-up therapy to plasma exchange if indicated.1 A high clinical suspicion of
an NMO spectrum disorder exists; therefore, a disease-modifying therapy
approved for MS (such as an interferon or glatiramer acetate) is not indicated, as
it may exacerbate NMO. As his urinary symptoms are not likely due to an
infection, empiric antibiotics are not indicated. Consideration of preventive
therapy with immunosuppression (eg, azathioprine or rituximab) can await
acute treatment with IV steroids.
1. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: Evaluation of 871 attacks and 1,153
treatment courses. Ann Neurol 2016;79(2):206Y216. doi:10.1002/ana.24554.
Two days after admission, the patient now reports the onset of a
positional headache, worse with standing. Brain MRI is repeated, and
his coronal postcontrast T1-weighted image is shown in PMP Figure 3
(page 1740).
b 10. Which of the following is the most likely explanation for the findings on
this patient’s brain MRI?
A. bacterial meningitis
B . dural enhancement after lumbar puncture
C. IgG4 pachymeningitis
D. posterior reversible encephalopathy syndrome (PRES)
E . venous sinus thrombosis

The preferred response is B (dural enhancement after lumbar puncture).
Postdural puncture headache is characterized by headache that worsens after
sitting or standing and improves after lying down, often with neck stiffness,
tinnitus, hypacusia, photophobia, or nausea. It typically develops within
5 days of dural puncture and resolves either spontaneously within 1 week or
within 48 hours after treatment of the CSF leak (epidural blood patch).
In additional to technical factors, patient risk factors include being female and
having a low body mass index and prior history of headaches. Neuroimaging
reveals dural enhancement, as shown in this patient, which may be
accompanied by low-lying tonsils.1 Dural enhancement seen with IgG4
pachymeningitis is typically more focal.2 Bacterial meningitis would be
characterized on MRI by enhancement in the subarachnoid space and not dura.
This patient’s findings are not suggestive of venous sinus thrombosis or PRES.
1. Bezov D, Lipton RB, Ashina S. Post-dural puncture headache: part I diagnosis, epidemiology, etiology,
and pathophysiology. Headache 2010;50(7):1144Y1152. doi:10.1111/j.1526-4610.2010.01699.x.
2. Lu LX, Della-Torre E, Stone JH, Clark SW. IgG4-related hypertrophic pachymeningitis: clinical features,
diagnostic criteria, and treatment. JAMA Neurol 2014;71(6):785Y793. doi:10.1001/jamaneurol.2014.243.
The patient is diagnosed with an NMO spectrum disorder and treated with a
course of 5 days of IV methylprednisolone, with gradual improvement in his
lower extremity strength. He is discharged to inpatient rehabilitation on a
slow prednisone taper. He is seen in follow-up neurology clinic 1 month later,
manifesting significant improvement in his strength, ambulation, and
bladder function. His NMO IgG antibody has also returned and is positive.
Long-term immunosuppressive therapy is recommended, but he elects to
defer further immunosuppressive treatment at this time.
Three months later, the patient calls reporting a 2-day history of right
retroorbital pain and decreased vision in his right eye. Examination shows a
central scotoma of the right eye and a right afferent pupillary defect.
Orbital MRI is performed, and his coronal T2-weighted image is shown in
PMP Figure 4 (page 1741).
b 11. Which of the following is the most accurate interpretation of this patient’s MRI?
A. normal findings
B . pituitary microadenoma
C. right cavernous sinus thrombosis
D. right nasopharyngeal mass
E . right optic nerve hyperintensity
The preferred response is E (right optic nerve hyperintensity). This patient’s

T2-weighted coronal sequence demonstrates hyperintensity in the right optic
nerve, consistent with right optic neuritis.1
1. Szatmáry G. Imaging in patients with visual symptoms. Continuum (Minneap Minn) 2016;
22(5 Neuroimaging):1499Y1528.

The patient is treated with IV methylprednisolone for 3 days with good

clinical response. Given this second clinical attack, the patient now agrees
to immunosuppressive therapy and is treated with rituximab. One week
later, he returns to the emergency department reporting a worsening
headache and visual blurring bilaterally that has progressed over the
course of several hours. On examination, blood pressure is 170/90 mm Hg. He
is encephalopathic and has a bilateral visual field defect. An urgent brain
MRI is performed; the FLAIR image is shown in PMP Figure 5 (page 1742).
b 12. Which of the following is the most likely explanation for these imaging
findings?
A. posterior circulation stroke
B . posterior reversible encephalopathy syndrome (PRES)
C. progressive multifocal leukoencephalopathy (PML)
D. tumefactive MS
E . vasculitis
The preferred response is B (posterior reversible encephalopathy syndrome

[PRES]). This patient’s MRI is most compatible with PRES. PRES has been
reported in patients with NMO spectrum disorders, with a pattern of bilateral
vasogenic subcortical edema without infarction potentially facilitated by water
flux impairment due to aquaporin-4 autoimmunity.1 Fluid shifts resulting from
steroid use or other medications may be additional contributing factors. PML
has been reported after immunosuppressive therapies including rituximab,2
and MRI findings may be indistinguishable from PRES3; however, the recency
of the treatment makes this less likely in this patient. Tumefactive MS lesions
are typically well circumscribed with an open ring pattern of enhancement
and would not have the pattern seen in this patient. The findings on this patient’s
MRI also extend beyond the posterior circulation, making posterior
circulation ischemia unlikely.
1. Magaña SM, Matiello M, Pittock SJ, et al. Posterior reversible encephalopathy syndrome in
neuromyelitis optica spectrum disorders. Neurology 2009;72(8):712Y717. doi:10.1212/
01.wnl.0000343001.36493.ae.
2. Durali D, de Goër de Herve MG, Gasnault J, Taoufik Y. B cells and progressive multifocal
leukoencephalopathy: search for the missing link. Front Immunol 2015;6:241. doi:10.3389/
fimmu.2015.00241.
3. Berger JR, Neltner J, Smith C, Cambi F. Posterior reversible encephalopathy syndrome
masquerading as progressive multifocal leukoencephalopathy in rituximab treated
neuromyelitis optica. Mult Scler Relat Disord 2014;3(6):728Y731. doi:10.1016/
j.msard.2014.08.004.
The patient is admitted to the inpatient neurology service, where his blood
pressure is aggressively controlled. Over the subsequent 3 days, his
encephalopathy and visual field defects resolve. He is discharged on
hospital day 5. Follow-up imaging obtained 1 month later reveals
complete disappearance of the T2-weighted hyperintensity.

Neuroimaging
* 2016 American Academy of
INDEX American Heart Association/American Stroke

Association guidelines
for management of acute ischemic stroke,
Neurology. All rights reserved.
1412, 1420r
Page numbers in boldface type indicate major for management of spontaneous intracerebral
discussions. Letters after page numbers refer to hemorrhage, 1449r
the following: c = case study; f = figure; American Society of Interventional and Therapeutic
r = reference; t = table. Neuroradiology (ASITN) collateral circulation
grading system, 1413, 1414f
A Amlodipine, 1419c
Amyloid imaging, 1638, 1639
AA (Alzheimer’s Association), 1638 Anencephaly, 1488, 1498r
AAN. See American Academy of Neurology Anisocoria, 1521Y1525
ABC/2 method, to determine intracerebral Anti-Kickback Statute, 1685Y1688, 1689r
hematoma volume, 1425, 1426f Anticoagulant use
ABCD risk prediction score for TIA, 1418 for cerebral venous thrombosis, 1444cY1445c
N-Acetylaspartate (NAA) peak, in brain tumors, as contraindication to tPA, 1412
1533tY1535t, 1536, 1537f, 1540, 1547, 1548 intracranial hemorrhage secondary to, 1424,
Acute disseminated encephalomyelitis (ADEM), 1443f, 1444Y1446, 1450r
1626Y1628, 1628c, 1628f seizures and, 1454
AD. See Alzheimer disease Antiplatelet therapy, 1418, 1419c
ADC. See Apparent diffusion coefficient imaging Apparent diffusion coefficient (ADC) imaging,
ADEM (acute disseminated encephalomyelitis), 1386, 1397r. See also Diffusion-weighted imaging
1626Y1628, 1628c, 1628f image interpretation, 1391, 1392
Adenohypophysis, 1575, 1579, 1592 imaging protocols for, 1387, 1388t
Adenoid cystic carcinoma, 1501c, 1501f in specific conditions
Adrenocorticotropic hormone secretion, 1579 acute disseminated encephalomyelitis, 1634r
Adrenoleukodystrophy, 1632t brain tumor, 1397r, 1531t, 1535Y1536
Adrenomyeloneuropathy, 1632t oligoastrocytoma, 1538f
AES (American Epilepsy Society), 1454 ischemic stroke, 1399, 1405, 1406Y1407,
Affordable Care Act, 1685, 1687, 1688 1408f, 1408cY1409c, 1409f
Agenesis of corpus callosum, 1480Y1481, 1481c, multiple sclerosis, 1512f, 1619, 1620f
1481fY1483f, 1482Y1485, 1483cY1484c, 1497r patients with visual symptoms, 1499
cerebellar hypoplasia and, 1492f anisocoria, 1524cY1525c, 1525f
prenatal detection of, 1484 diplopia, 1518, 1521
septooptic dysplasia and, 1511 optic neuritis, 1514f
spastic cerebral palsy and, 1484f, 1485 spinal cord lesions, 1597
Agyria, 1485 tumefactive demyelinating lesion, 1389f
Aicardi syndrome, 1484 Arachnoid cyst, 1554t, 1566Y1568, 1567fY1568f,
AIDS. See Human immunodeficiency virus 1573r, 1572t
infection cavum velum interpositum expansion by, 1564
Alberta Stroke Program Early CT Score (ASPECTS), differentiation from epidermoid cyst, 1567, 1569f
1405, 1405f, 1407,1409, 1412, 1413, 1416tY1417t, intraventricular, 1561
1418, 1421r pineal, 1562
Alteplase. See Tissue plasminogen activator retrocerebellar, 1491, 1568, 1567f
Alzheimer disease (AD), 1653r sellar region, 1574Y1575, 1580c, 1584f
biomarkers for, 1639 Arterial hypertensive vasculopathy, 1434Y1435,
diagnostic criteria for, 1638 1435f
hippocampal sulcal remnant cyst and, 1555 1573r Arterial spin labeling (ASL), 1386t
neuromolecular imaging in, 1637Y1641, 1640c, Arteriovenous malformations (AVMs)
1640f, 1641f, 1653r on CT, 1456t
posterior cortical atrophy and, 1520 on MRI, 1468, 1469f
Alzheimer’s Association (AA), 1638 seizures due to, 1454
American Academy of Neurology (AAN), 1452 sellar region, 1574
AANYAmerican Epilepsy Society practice spinal, 1602Y1604 1611r
parameter for evaluation of unprovoked first subarachnoid hemorrhage due to, 1436
seizures in adults, 1454, 1477r ASITN (American Society of Interventional and
Quality Measurement Set Epilepsy Update, 1457 Therapeutic Neuroradiology) collateral circulation
American College of Radiology, 1399, 1420r grading system, 1413
American Epilepsy Society (AES), 1454, 1477r ASL (arterial spin labeling), 1388t

Neuroimaging
ASPECTS (Alberta Stroke Program Early CT Score), orbital cellulitis and, 1518
1405, 1405f, 1407,1409, 1412, 1413, 1416tY1417t, pituitary, 1577
1418, 1421r tuberculous, 1470
Astrocytoma Brain death, transcranial Doppler ultrasound in
gliomatosis cerebri, 1533t, 1542, 1552r diagnosis of, 1667Y1668, 1667t, 1668f, 1676r
grade I (pilocytic), 1447, 1506, 1533t, Brain deposits of gadolinium, 1678Y1683, 1681f,
1538Y1539, 1539t, 1586, 1605, 1612r 1683rY1684r
grade II (diffuse), 1467, 1533t, 1539Y1540 Brain metastases, 1447, 1550
grade III (anaplastic), 1533t, 1536, 1537f, on CT, 1457t
1538Y1540, 1541cY1542c, 1541f, 1550, incidence of, 1550, 1604
1552r, 1694c intracerebral hemorrhage secondary to,
grade IV (glioblastoma), 1534t, 1540Y1543 1446Y1447, 1447cY1448c, 1448f, 1450r
intracerebral hemorrhage secondary to, 1447 on MRI, 1396f, 1457t, 1550
MRI characteristics of, 1534tY1535t primary tumors associated with, 1550
oligoastrocytoma, 1467, 1536, 1537f, 1538f seizures due to, 1466
pineal, 1562 Brain tumors, 1529Y1552, 1551rY1552r. See also
sellar region, 1574, 1586Y1587, 1586f, 1588t specific tumors
spinal cord, 1604, 1605, 1605t, 1608f central neurocytoma, 1535t, 1547Y1548,
subependymal giant cell, 1539 1548c, 1548f
Atorvastatin, 1419c on CT, 1457t, 1531t
Atrial fibrillation, 1415c, 1418, 1424, 1444 distinguishing radiation necrosis from, 1543Y1544
AVMs. See Arteriovenous malformations distribution of types of, 1530f
ependymoma, 1545, 1546f
ganglioglioma, 1547
B gliomas, 1538
grade I astrocytoma, 1538Y1539
B0 field (MRI), 1380Y1381 grades II and III astrocytoma, 1539Y1540
inhomogeneity and susceptibility effects on, grade IV astrocytoma, 1540Y1543
1381, 1385 histologic grading of, 1538
B1 field (MRI), 1380, 1381 relative cerebral blood volume in, 1538
Bacterial endocarditis, 1447 subependymal giant cell astrocytoma, 1539
Balanced steady-state free precession (bSSFP) hemangioblastoma, 1546
for spinal arteriovenous malformation, 1604 hemangiopericytoma, 1548Y1549
Time-SLIP technique with, 1502 incidence of, 1530, 1604
Baló concentric sclerosis, 1620, 1623f intraaxial vs. extraaxial, 1530
Band heterotopia, 1464, 1485Y1486 intracerebral hemorrhage secondary to, 1447, 1450r
Beh0et disease, 1631t intraventricular, 1545t
Betaferon/Betaseron in Newly Emerging Multiple meningioma, 1547Y1548, 1549f
Sclerosis for Initial Treatment (BENEFIT) mortality from, 1530
study, 1614 on MRI, 1387Y1389, 1388t, 1397r, 1457t, 1529,
Bevacizumab, 1397rY1398r 1530Y1538, 1537f, 1647
for anaplastic astrocytoma, 1541c characteristics of specific tumors,
for glioblastoma, 1397r, 1552r 1533tY1535t
pseudoresponse to, 1543 comparison of techniques, 1531t
for radiation necrosis, 1552r diffusion-weighted imaging, 1386, 1535Y1536
Bicisate technetium 99m, 1637 functional MRI, 1537Y1538
Blood, on MRI, 1386, 1394. See also Cerebral image interpretation, 1390
blood flow magnetic resonance spectroscopy, 1536Y1537
Blood oxygen level dependent (BOLD) perfusion imaging, 1536
contrast, 1537 susceptibility-weighted imaging, 1533, 1535
Boston and modified Boston criteria for cerebral T1-weighted and T2-weighted sequences,
amyloid angiopathy, 1437t 1531Y1533, 1535, 1532t
Brachial plexopathies, on ultrasound, 1672Y1673, neuromolecular imaging of, 1638t, 1641Y1644,
1677r 1643c, 1643f, 1653rY1654r
Brain abscess, 1554t, 1557 oligodendroglioma, 1544Y1545
on CT, 1453, 1454, 1457t primary CNS lymphoma, 1545Y1546
on MRI, 1457t, 1529, 1550, 1572t primitive neuroectodermal tumor, 1546Y1547
diffusion-weighted imaging, 1387, 1394, seizures due to, 1466Y1468
1397r, 1447, 1536, 1553, 1557, 1559, 1568 Bromocriptine, 1592
MR spectroscopy, 1536 bSSFP. See Balanced steady-state free precession

C PET for presurgical evaluation of patient with
drug-resistant epilepsy, 1460c
urgent assessment of adult with new-onset
CAA. See Cerebral amyloid angiopathy seizure, 1453c
Cap sign of spinal cord ependymoma ultrasound in extracranial internal carotid artery
(on MRI), 1604 stenosis, 1660cY1661c
Carbon 11Ylabeled Pittsburgh Compound B Cauda equina, 1596
(11C-PiB), 1639 Cavernous malformations, 1468
Carotid artery dissection, on ultrasound, 1658, 1675r on CT, 1456t
Carotid artery stenosis, 1391f, 1657 on MRI, 1468, 1469f
on time-of-flight MRA, 1391f susceptibility-weighted imaging, 1429
on ultrasound, 1656, 1657t, 1659cY1661c, 1659f, spinal, 1604
1660f, 1675r Cavernous sinuses, 1517f, 1575, 1577f, 1583f
Carotid-cavernous fistula, 1520Y1523, 1521cY1522c, Cavum fornicis (cavum of the fornix), 1564
1522f, 1523f Cavum septum pellucidum, 1563f, 1564,
parasellar, 1590Y1591 1564f, 1573r
Carpal tunnel syndrome, on ultrasound, 1671, cavum vergae and, 1563Y1564, 1564f
1673t, 1676r Cavum velum interpositum, 1486f, 1554t,
Case studies 1563Y1564, 1564f
agenesis of corpus callosum, 1481c, 1483cY1484c differentiation from cavum vergae, 1564, 1564f
brain tumor differentiation from pineal cyst, 1562f
anaplastic astrocytoma, 1541cY1542c Cavum vergae, 1563, 1564f
central neurocytoma, 1548c CBF. See Cerebral blood flow
coding in neuroimaging, e4cYe5c CBV. See Cerebral blood volume
copper deficiency myelopathy, 1600c Centers for Medicare & Medicaid Services (CMS),
demyelinating disorders 1686, e1
acute disseminated encephalomyelitis, 1628c Central nervous system development, 1481Y1482
multiple sclerosis, 1628c Central neurocytoma, 1535t, 1545t, 1547Y1548,
hemorrhagic stroke, 1428c, 1429c 1548c, 1548f
cerebral venous thrombosis, 1444cY1445c Cerebellar hypoplasia, 1491, 1492f, 1495t
subarachnoid hemorrhage, 1439cY1442c Cerebellar tonsillar herniation. See Chiari
intracranial cysts malformation
neurocysticercosis, 1571cY1572c Cerebral amyloid angiopathy (CAA), 1435Y1436,
porencephalic cyst, 1558c 1450r
ischemic stroke, 1408cY1409c on CT, 1436f, 1437t
tPA therapy, 1415c patient with new-onset seizures, 1455t
transient ischemic attack, 1419c intracerebral hemorrhage due to, 1427, 1434,
neuromolecular imaging 1435Y1436, 1436f
brain tumor, 1643c Boston and modified Boston criteria for
dementia, 1640c diagnosis of, 1437t
epilepsy, 1646c on MRI, 1389, 1429, 1435, 1436f, 1437t
patients with visual symptoms pathophysiology of, 1436
adenoid cystic carcinoma, 1501c, 1501f Cerebral artery aneurysms, 1591, 1591f
carotid-cavernous fistula, 1521cY1522c Cerebral blood flow (CBF), 1420r
Horner syndrome due to internal carotid in frontotemporal dementia, 1391f
artery dissection, 1524cY1525c in intracavernous internal carotid artery
idiopathic intracranial hypertension, aneurysm, 1591f
1504cY1505c in ischemic stroke, 1400Y1401, 1400t,
neuromyelitis optica, 1514c 1401fY1403f, 1404t, 1408Y1409c, 1409f
visual loss, 1508cY1509c collateral circulation for preservation of,
physician investment and ownership in health 1402Y1403, 1413
care enterprises, 1685c intraarterial thrombectomy and, 1415c, 1415f
pituitary and parasellar disorders during migraine attack, 1391f
craniopharyngioma, 1582c in patient with hemichoreic movements, 1391f
pituitary adenoma, 1580c PET imaging of, 1404t, 1649, 1654r
safety of MRI in patient with implanted medical postictal, 1391f
device, 1691c, 1694c SPECT imaging of, 1473, 1649Y1650, 1653r, 1654r
seizures and epilepsy transcranial Doppler ultrasound of, 1432Y1433,
focal cortical dysplasia, 1464c 1662, 1665Y1666, 1675r
mesial temporal sclerosis, 1460c Cerebral blood volume (CBV)

Neuroimaging
in brain metastases, 1550 in extracranial internal carotid artery stenosis,

in brain tumors, 1539, 1553 1657, 1658t, 1665, 1660cY1661c, 1660f
astrocytoma, 1533t, 1536, 1538, 1538, 1551r in giant cell arteritis, 1662, 1663f
glioblastoma, 1536, 1538, 1550 in ischemic stroke, 1655, 1656Y1657, 1657t
gliomas, 1538 in Takayasu arteritis, 1661Y1662, 1662f
gliomatosis cerebri, 1533t in vertebral artery dissection, 1658, 1661, 1661f
meningioma, 1547 in vertebral artery stenosis, 1663Y1664
oligodendroglioma, 1544 Cervical radiculopathy, on ultrasound, 1672,
perfusion imaging of, 1536, 1538, 1544, 1547 1673t, 1677r
vs. radiation necrosis, 1544 Chiari malformation, 1493Y1496, 1498r
in hemorrhagic stroke, 1425 agenesis of corpus callosum and, 1484
in internal carotid artery stenosis, 1391f classification of types of, 1493, 1495t
in ischemic stroke, 1400, 1400t, 1401, 1402f, measurement of, 1495t
1408cY1409c, 1409f on MRI, 1494f, 1496, 1496f, 1497f
PET imaging of, 1649 pathophysiology of, 1493Y1495
SPECT imaging of, 1649Y1650 syringomyelia and, 1494f, 1495t, 1495Y1496,
Cerebral commissures, 1482 1497f, 1498r, 1597, 1597f
Cerebral cortical malformations, 1484Y1487 Chondrosarcoma, 1521, 1574, 1584Y1585, 1585f,
causes of, 1484Y1485 1588t, 1594r
focal cortical dysplasia, 1392f, 1398r, 1458, Chordoma, 1521, 1574, 1585
1461Y1464, 1462f, 1463t, 1464c, 1464f, 1471, clival, 1527, 1585f, 1588t, 1594r
1477rY1478r Choristoma, 1513
lissencephaly, 1464, 1485Y1486, 1485f, Choroid fissure neuroepithelial cyst, 1554, 1554t,
1497r, 1498r 1556f, 1572t
other types of, 1464 Choroid plexus cyst, 1553, 1554t, 1559, 1559f,
polymicrogyria, 1464, 1464f, 1466f, 1481, 1482f, 1561, 1568, 1572t
1485, 1486Y1487, 1486f, 1490f, 1498r Choroid plexus xanthogranuloma, 1559
prenatal detection of, 1485 Chronic inflammatory demyelinating
schizencephaly, 1464,1485, 1486f, 1487, polyradiculoneuropathy (CIDP), on ultrasound,
1487f, 1488f 1673Y1674, 1683r
seizures due to, 1461Y1465 Chronic traumatic encephalopathy, 1656, 1660r
tuberous sclerosis, 1464, 1465f Churg-Strauss syndrome, 1453c
subependymal giant cell astrocytoma and, CIDP (chronic inflammatory demyelinating
1539, 1540f polyradiculoneuropathy), on ultrasound,
Cerebral edema, due to intracerebral hemorrhage, 1673Y1674, 1687r
1425, 1444cY1445c, 1445f, 1447 Clinically isolated syndrome (CIS) and multiple
Cerebral glucose metabolism, PET measurement sclerosis, 1614
of, 1637, 1647 CMS (Centers for Medicare & Medicaid Services),
in brain tumors, 1642, 1643f, 1644 1686, e1
in Parkinson disease, 1647f CMSC (Consortium of Multiple Sclerosis Centers)
in presurgical evaluation for epilepsy, 1646f protocol for MRI, 1616, 1617, 1633r
in prodromal Alzheimer disease, 1640f Cobalamin deficiency, 1599, 1611r, 1628,
Cerebral palsy, congenital brain malformations 1631t, 1640c
and, 1484f, 1485, 1498r Cochlear implant, safety of MRI in patient with,
Cerebral venous thrombosis (CVT), 1390f, 1427, 1692, 1695r
1434, 1436, 1442Y1444, 1443f, 1444cY1445c, Coding in neuroimaging, e1Ye25, e4cYe5c,
1445f, 1450r e24rYe25r
Cerebrovascular disease. See also specific disorders advanced imaging codes and appropriate
collateral circulation in, 1649, 1650f, 1658, indications, e1Ye2
1659c, 1659f CPT codes and indications, e1Ye3, e4cYe5c, e24r
ultrasound of, 1658, 1659c, 1659f, 1662, for CT angiography, e14tYe15t
1664Y1665, 1664t for CT of head and neck, e12tYe14t
hemorrhagic stroke, 1424Y1448, 1448rY1450r for CT of spine, e15tYe17t
ischemic stroke, 1399Y1420, 1420rY1423r for MR angiography of head and neck, e7t
neuromolecular imaging in, 1638t, 1649Y1651, for MRI of brain, e6t
1650f, 1653rY1654r for MRI of orbit, face, and neck, e8t
sellar region, 1588t, 1591Y1593 for MRI of spine, e10t
ultrasound in, 1662Y1674 for noninvasive vascular imaging, e18tYe20t
Cervical duplex ultrasound, 1662f for nuclear medicine studies, e21tYe24t
in carotid artery dissection, 1658 for other CT procedures, e17t

for other MRI procedures, e8tYe9t with new-onset seizures, 1455t
documentation requirements, e2Ye3 subarachnoid hemorrhage, 1429c, 1429f,
ICD-10-CM codes, e1Ye3, e4cYe5c,e25r 1438cY1442c, 1438fY1441f, 1439, 1442,
Collateral circulation 1449r, 1453c, 1453f, 1455t
in acute ischemic stroke, 1400, 1402Y1403, subdural hematoma, 1455t
1420rY1421r herpes encephalitis, 1456t
eventual failure of, 1402, 1403 intracranial cysts, 1553, 1571
grading system for, 1413, 1414f choroid plexus cyst, 1559
hemodynamics and anatomy of, 1402Y1403, neurocysticercosis, 1572c, 1572f
1403f ischemic stroke, 1399, 1404, 1404t,
image-based patient selection for intraarterial 1405Y1406, 1410Y1412, 1422r
thrombectomy, 1413, 1415c, 1416t Alberta Stroke Program Early CT Score,
imaging of, 1408, 1410, 1407f, 1413, 1405, 1405f, 1407Y1409, 1412, 1413,
1414fY1415f, 1415c 1416tY1417t, 1418, 1421r
impact on stroke outcome, 1405, 1406f, 1413, with new-onset seizures, 1455t
1415c, 1421r post-reperfusion management, 1418
in cerebrovascular disease, 1649, 1650f, 1658, to select patients for intraarterial
1659c, 1659f thrombectomy, 1413
ultrasound of, 1658, 1659c, 1659f, 1662, leptomeningeal carcinomatosis, 1457t
1664Y1665, 1664t meningitis, 1456t
in spinal cord ischemic lesions, 1602 patients with visual symptoms, 1499, 1500f
Colloid cyst, 1532t, 1554t, 1560Y1561, 1560f, 1572t diplopia, 1516
Colpocephaly, 1483cY1484c, 1483f, 1495t internal carotid artery dissection,
Computed tomography (CT) 1524cY1525c, 1525f
compared with MRI, 1379 orbital blow-out fracture, 1518f
Current Procedural Terminology codes and pituitary and parasellar disorders, 1575Y1577,
indications for 1577f
head and neck CT, e11tYe14t arachnoid cyst, 1590
other CT procedures, e17t chondrosarcoma, 1584Y1585, 1588t
spinal CT, e15tYe17t chordoma, 1588t
multimodal, 1399 craniopharyngioma, 1580
in specific conditions dermoid cyst, 1588, 1589f
arteriovenous malformations, 1456t epidermoid cyst, 1589
brain abscess, 1457t hypothalamic glioma, 1588t
brain metastasis, 1457t meningioma, 1584
brain tumor, 1457t, 1533tY1535t neurosarcoidosis, 1592Y1593
central neurocytoma, 1547 optic nerve glioma, 1588t
to distinguish radiation necrosis from pituicytoma, 1588t
tumor, 1544 pituitary adenoma, 1579, 1593r
meningioma, 1396f, 1447, 1468, 1547Y1548, pituitary apoplexy, 1591Y1592
1549f, 1581 primary germ cell tumor, 1584Y1585, 1588t
PET and, 1643c, 1644f Rathke cleft cyst, 1589
subependymal giant cell astrocytoma, 1539 schwannoma, 1583Y1584
cavernous malformations, 1395, 1456t posterior reversible encephalopathy
concussion, 1651 syndrome, 1456t
congenital malformations, 1485 seizures and epilepsy
agenesis of corpus callosum, 1484f assessment of patients with established
midbrain and hindbrain anomalies, 1491 epilepsy, 1454, 1457Y1458
schizencephaly, 1487 Churg-Strauss syndrome, 1453c, 1453f
epidural hematoma, 1455t mesial temporal sclerosis, 1458
ganglioglioma, 1396f status epilepticus, 1397r
hemorrhagic stroke, 1425Y1427, 1428c, urgent assessment of new-onset seizure,
1428f, 1431t, 1449r 1452Y1454, 1455tY1457t
cerebral amyloid angiopathy, 1436f, 1437t spinal cord disorders, 1597, 1598
cerebral venous thrombosis, 1442, epidural abscess, 1601
1444cY1445c, 1455t metastatic lesions, 1608
hemorrhagic transformation of ischemic myelopathy from spine trauma, 1609Y1610
stroke, 1446f spinal infections, 1599Y1606
intracerebral hemorrhage secondary to traumatic brain injury, 1456t
brain metastases, 1447, 1447cY1448c Computed tomography angiography (CTA)

Neuroimaging
of arteriovenous malformations, 1456t schizencephaly, 1464,1485, 1486f, 1487,

of carotid-cavernous fistulas, 1590 1487f, 1488f
of cavernous malformations, 1456t seizures due to, 1461Y1465
of cerebral artery aneurysms, 1591 of midbrain and hindbrain, 1491Y1493
Current Procedural Terminology codes and Dandy-Walker malformation and related
indications for, e1, e14tYe15t disorders, 1484, 1491, 1491f, 1492f
in hemorrhagic stroke, 1425, 1427, 1428c, Joubert syndrome, 1491Y1493, 1493f, 1498r
1428f, 1432 of ventral prosencephalon (forebrain), 1488Y1491
with new-onset seizures, 1455t anencephaly, 1488, 1498r
spot sign of hematoma expansion, 1425, holoprosencephaly, 1481, 1482f, 1485,
1427, 1428c, 1428f, 1449r, 1455t 1488Y1491, 1489f
subarachnoid hemorrhage, 1438f, 1439, septooptic dysplasia, 1466f, 1490, 1490f, 1511
1440c, 1440f, 1441cY1442c,1441f, 1442, hydranencephaly, 1488Y1489, 1489f
indications for, e14tYe15t Consortium of Multiple Sclerosis Centers (CMSC)
in ischemic stroke, 1399, 1404, 1404t, 1405, protocol for MRI, 1616, 1617, 1633r
1417t, 1663, 1675r Conus medullaris, 1596
collateral circulation, 1413 Copper deficiency myeloneuropathy, 1599,
with new-onset seizures, 1455t 1600c, 1600f
occluded vessel, 1414f Corpus callosum, 1480Y1481, 1481c, 1481fY1483f,
to select patients for endovascular treatment, 1482Y1484, 1483cY1484c
1415c, 1416 agenesis of, 1480Y1481, 1481c, 1481fY1483f,
transcranial ultrasound and, 1662, 1663 1482Y1484, 1483cY1484c, 1497r
for new-onset seizures, 1455tY1456t cerebellar hypoplasia and, 1492f
in posterior reversible encephalopathy fetal ultrasound detection of, 1484
syndrome, 1456t septooptic dysplasia and, 1511
of schizencephaly, 1487 spastic cerebral palsy and, 1484f, 1485
of spinal arteriovenous malformation, 1604 brain tumor involving
of spinal cavernous malformation, 1608 anaplastic astrocytoma, 1541cY1542c
of spinal cord ischemic lesions, 1604 glioblastoma, 1540
in traumatic brain injury, 1456t lymphoma, 1545
Computed tomography (CT) myelography, 1596 in demyelinating disorders
Computed tomography (CT) perfusion imaging acute demyelinating encephalomyelitis, 1623
in hemorrhagic stroke, 1427, 1449r progressive multifocal leukoencephalopathy,
in ischemic stroke, 1399, 1400t, 1404t, 1409, 1627
1410, 1412, 1413 radiologically isolated syndrome, 1615t
to select patients for endovascular treatment, development and anatomy of, 1482Y1483
1415c, 1416, 1416t intracranial cysts bordered by
in status epilepticus, 1397r cavum septum pellucidum, 1563
in TIA, 1418 cavum vergae, 1563
Computed tomography (CT) venography, 1454 other brain abnormalities related to anomalies
of cerebral venous thrombosis, 1427, of, 1497r
1443Y1445, 1455t holoprosencephaly, 1490
Concussion, 1651 in Susac syndrome, 1631t
Congenital keratin cyst. See Epidermoid cyst Cortical vein thrombosis, 1442. See also
Congenital malformations, 1480Y1497, 1497rY1498r Cerebral venous thrombosis
cerebral palsy and, 1484f, 1485, 1498r Corticobasal degeneration
classification of, 1480, 1482 neuromolecular imaging in, 1647, 1647f
CNS development and, 1481Y1482 posterior cortical atrophy and, 1515
of craniocervical junction: Chiari malformation, ultrasound in, 1669, 1671t
1493Y1496, 1494f, 1495t, 1496f, 1497f Corticosteroids
of dorsal prosencephalon (forebrain), 1482Y1487 for acute disseminated encephalomyelitis, 1628c
agenesis of corpus callosum, 1480Y1481, for brain tumor, 1543t
1481c, 1481fY1484f, 1482Y1484, radiation necrosis, 1543
1483cY1484c, 1485, 1492f, 1511 for Churg-Strauss syndrome, 1453c
cerebral cortical malformations, 1484Y1487 for demyelinating disorders that mimic
lissencephaly, 1464, 1485Y1486, 1485f, multiple sclerosis, 1628Y1629
1497r, 1498r for multiple sclerosis, 1625c
polymicrogyria, 1464, 1464f, 1466f, 1481, for thyroid eye disease, 1519f
1482f, 1485, 1486Y1487, 1486f, for Tolosa-Hunt syndrome, 1520
1490f, 1498r for vasculitis with peripheral neuropathy, 1674

CPT coding. See Current Procedural Terminology neuroglial cyst, 1554Y1555, 1556f, 1557f
coding porencephalic cyst, 1466, 1555Y1556, 1558c,
Craniopharyngioma, 1514, 1527, 1532t, 1565, 1566, 1558f, 1572t
1574, 1579Y1580, 1582c, 1582f, 1588, 1592r intraaxial (ventricular), 1553, 1554t, 1559Y1561
Craniosynostosis, 1493 choroid plexus cyst, 1553, 1554t, 1559, 1559,
Creutzfeldt-Jakob disease, 1389f, 1516 1559f, 1561, 1568, 1572t
CT. See Computed tomography colloid cyst, 1560Y1561, 1572t
CTA. See Computed tomography angiography ependymal cyst, 1559Y1560, 1560f, 1573r
Cubital tunnel syndrome, on ultrasound, 1673t location-based approach to, 1553, 1554t
Current Procedural Terminology (CPT) coding, Cysts, sellar region, 1575, 1587Y1593
e1Ye3, e4cYe5c, e24r arachnoid cyst, 1590, 1590f
codes and indications for CT dermoid cyst, 1587Y1589, 1589f
of head and neck, e11tYe14t empty sella, 1590Y1591, 1591f
other CT procedures, e17t epidermoid cyst, 1589, 1589f
of spine, e15tYe17t Rathke cleft cyst, 1589, 1590f
codes and indications for CT angiography,
e14tYe15t
D
codes and indications for MR angiography of
head and neck, 37t
codes and indications for MRI Dacryoadenitis, 1518
of brain, e7t Dandy-Walker malformation, 1484, 1491, 1491f
of orbit, face, and neck, e8t Dandy-Walker variant, 1491, 1492f
other MRI procedures, e8tYe9t DAT (dopamine transporter) imaging, 1637, 1639,
of spine, e10t 1648Y1649, 1649f, 1654r
codes and indications for noninvasive vascular DAWN (DWI or CTP Assessment With Clinical
imaging, e18tYe20t Mismatch in the Triage of Wake-Up and Late
codes and indications for nuclear medicine Presenting Strokes Undergoing
studies, e21tYe24t Neurointervention) trial, 1412
documentation requirements, e2Ye3 Dawson finger lesions, in multiple sclerosis,
Cushing disease, 1578t, 1579 1617, 1619f
CVT (cerebral venous thrombosis), 1390f, 1427, Deep brain stimulator, safety of MRI in patient
1434, 1436, 1442Y1444, 1443f, 1444cY1445c, with, 1692
1445f, 1450r DEFUSE (Diffusion and Perfusion Imaging
Cysticercosis. See Neurocysticercosis Evaluation for Understanding Stroke Evolution)
Cysts, intracranial, 1553Y1573, 1573r study, 1397r, 1410, 1412, 1421r
extraaxial (midline), 1553, 1554t, 1561Y1566 Dementia
cavum septum pellucidum, 1563, 1563f, 1564f neuromolecular imaging in, 1637Y1641, 1640c,
cavum velum interpositum, 1486f, 1640f, 1641f, 1653r
1563Y1564, 1564f posterior cortical atrophy and, 1515, 1518f
cavum vergae, 1563, 1564f Dementia with Lewy bodies (DLB)
dermoid cyst, 1564Y1565, 1565f, 1573r neuromolecular imaging in, 1639, 1647f, 1654r
neurenteric cyst, 1562, 1562f amyloid imaging, 1638Y1639
pineal cyst, 1561Y1562, 1561f, 1562f, 1573r posterior cortical atrophy and, 1515
Rathke cleft cyst, 1513, 1557t, 1565Y1566, ultrasound in, 1669, 1671t
1566f, 1573r, 1574, 1589, 1590f Demyelinating disorders of CNS, 1389f, 1397r,
extraaxial (nonmidline), 1553, 1554t, 1566Y1570 1613Y1633, 1633rY1635r
arachnoid cyst, 1566Y1568, 1567fY1568f acute disseminated encephalomyelitis, 1626Y1627
epidermoid cyst, 1568, 1569f incidentally found white matter abnormalities
neurocysticercosis, 1468Y1469, 1478r, 1554t, on MRI, 1627Y1628, 1630f
1568Y1570, 1570t, 1571f, 1571cY1572c, multiple sclerosis, 1618Y1631
1572f, 1572t neuromyelitis optica and neuromyelitis optica
imaging characteristics of, 1570Y1571, 1572t spectrum disorders, 1611r, 1613, 1623, 1626,
intraaxial (parenchymal), 1553Y1559, 1554t 1628c, 1631t, 1633r
brain abscess, 1557, 1559 longitudinally extensive transverse myelitis
choroid fissure neuroepithelial cyst, 1554, in, 1511, 1514c 1514f, 1599
1556f, 1572t optic neuritis as first presentation of,
dilated Virchow-Robin spaces, 1554, 1554t, 1555f 1510, 1512f
hippocampal sulcal remnant cysts, 1553, 1554t, other demyelinating disorders that can mimic
1555, 1557f multiple sclerosis, 1628Y1629, 1631tY1632t,
neoplasms, 1556Y1557 1632f

Neuroimaging
progressive multifocal leukoencephalopathy, intracranial cysts

1627Y1628, 1629f, 1629tY1630t, 1635r arachnoid cyst, 1567, 1569f, 1590
tumefactive demyelinating lesions, 1387, 1389f, brain abscess, 1387, 1447, 1536, 1557, 1572
1397r, 1536, 1621Y1623, 1621f, 1634r choroid plexus cyst, 1559, 1559f
Dermoid cyst, 1554t, 1564Y1565, 1565f epidermoid cyst, 1394, 1567, 1568, 1569f,
sellar region, 1574, 1587Y1589, 1589f 1573r, 1589, 1589f
Diabetes insipidus, pituitary disorders and pineal lesions, 1562
craniopharyngioma, 1582c ischemic stroke, 1390f, 1399, 1404t, 1405Y1407,
germinoma, 1593r 1407fY1409f, 1408cY1409c, 1410, 1422r
Hand-Schuller-Christian syndrome, 1513 diffusion-perfusion mismatch, 1409Y1410,
Langerhans cell histiocytosis, 1592 1411f
MRI in, 1575 to select patients for intraarterial
neurosarcoidosis, 1592 thrombectomy, 1410Y1412, 1416t
pituicytoma, 1587 malignancies, 1390
pituitary adenoma, 1578t MELAS, 1389f
sarcoidosis, 1511 multiple sclerosis, 1512f, 1616t, 1619, 1620f
sellar metastases, 1586 natalizumab-induced progressive
Diastematomyelia, 1598 multifocal leukoencephalopathy, 1630t
Diethylenetriamine pentaacetic acid indium patients with visual symptoms, 1502,
111, 1637 1506f, 1512f
Diffusion and Perfusion Imaging Evaluation for arachnoid cysts, 1514
Understanding Stroke Evolution (DEFUSE) carotid artery dissection, 1524cY1535c, 1525f
study, 1410, 1421rY1422r carotid-cavernous fistula, 1520
Diffusion-perfusion mismatch, 1409Y1410 diplopia, 1520
Diffusion tensor imaging (DTI) neuromyelitis optica, 1514c
of brain tumor, 1529, 1531t, 1536, 1551r, 1552r optic neuritis, 1513f
of congenital malformations, 1484, 1486, 1487, pituitary abscess, 1593
1496, 1498r pituitary apoplexy, 1591Y1592
agenesis of corpus callosum, 1481f, 1482Y1484 spinal cord disorders, 1601, 1610
Chiari malformation, 1496, 1498r epidural abscess, 1599Y1601, 1611r
Joubert syndrome, 1491 spinal cord infarction, 1393f, 1602
lissencephaly, 1486 traumatic injury, 1610, 1610r, 1612r
polymicrogyria, 1486Y1487, 1490f TIA, 1419c, 1419f, 1421r
septooptic dysplasia, 1490f Digital subtraction angiography (DSA)
in multiple sclerosis, 1625 of brain tumor, 1442
for presurgical evaluation of patients with in hemorrhagic stroke, 1425, 1427, 1432
drug-resistant epilepsy, 1472, 1479r intraventricular hemorrhage, 1442, 1443f
of spinal cord disorders, 1597, 1610, 1612r subarachnoid hemorrhage, 1438cY1442c,
posttraumatic myelopathy, 1610 1438fY1441f, 1442
spondylotic myelopathy, 1609, 1612r of internal carotid artery occlusion, 1659f
tractography, 1472, 1479r, 1481f, 1484, 1491, in ischemic stroke, 1390f, 1404, 1422r
1531t, 1536, 1551r, 1605, 1612 collateral circulation, 1413Y1414
Diffusion-weighted imaging (DWI), 1386, 1397r occluded vessel, 1414f
image interpretation, 1391, 1392, 1394, 1395 Dilated Virchow-Robin spaces, 1554, 1554t, 1555f
MRI protocols for, 1387, 1388t Diplopia, 1516Y1521
in specific conditions Direct factor Xa inhibitors, 1424, 1444
acute disseminated encephalomyelitis, 1634r Direct thrombin inhibitor, 1424
brain tumor, 1397r, 1529, 1531t, 1535Y1536, Dirty CSF sign of subarachnoid hemorrhage
1553, 1554rY1555r (on MRI), 1390f
astrocytoma, 1534t, 1544f DLB. See Dementia with Lewy bodies
gliomatosis cerebri, 1533t DNET (dysembryoplastic neuroepithelial tumor),
lymphoma, 1546 1466Y1467, 1467f, 1478r
neurocytoma, 1548f Dopamine transporter (DAT) imaging, 1637,
oligodendroglioma, 1544f 1639, 1647, 1648Y1649, 1649f, 1654r
carotid artery stenosis, 1660cY1661c Double cortex syndrome, 1485
Creutzfeldt-Jakob disease, 1389f DSA. See Digital subtraction angiography
diffuse axonal injury, 1397r DTI. See Diffusion tensor imaging
epilepsy, 1459t DWI. See Diffusion-weighted imaging
status epilepticus, 1397r DWI or CTP Assessment With Clinical Mismatch
hypoxic-ischemic encephalopathy, 1389f in the Triage of Wake-Up and Late Presenting

Strokes Undergoing Neurointervention Epidural hematoma, 1455tY1456t
(DAWN) trial, 1412 Epilepsy. See Seizures and epilepsy
Dynamic contrast-enhanced imaging, 1386 Equilibrium magnetization M0 (MRI), 1380
Dynamic susceptibility contrast imaging, 1386 ESCAPE (Endovascular Treatment for Small Core
of brain tumor, 1536, 1551r and Anterior Circulation Proximal Occlusion
in stroke, 1387 With Emphasis on Minimizing CT to
Dysembryoplastic neuroepithelial tumor (DNET), Recanalization Times) trial, 1412, 1413, 1416,
1466Y1467, 1467f, 1478r 1416tY1417t
Excitation (MRI), 1380
Extending the Time for Thrombolysis in Emergency
E Neurological DeficitsYIntra-Arterial (EXTEND-IA)
trial, 1412, 1416, 1417, 1416tY1417t
Echo time (TE) (MRI), 1385
Ectodermal inclusion cyst. See Epidermoid cyst
Edinger-Westphal nucleus, 1524
F
EEG. See Electroencephalogram
18
Ehlers-Danlos syndrome, 1493 F (fluorine 18), 1637
Electroencephalogram (EEG), 1454, 1457, 1471Y1476 Facial nerve palsy, 1511f
neuromolecular imaging and, 1645, 1646c False Claims Act, 1686, 1689r
PET, 1473, 1474f, 1479r, 1645 Fat, on MRI, 1379, 1382, 1383f, 1386, 1387,
SPECT, 1475, 1475c 1394, 1396f
in pharmacoresistant epilepsy, 1471 FDG (fludeoxyglucose) fluorine 18, 1637, 1638t
related to malformation of cortical Fetal alcohol syndrome, 1484
development, 1464c Fibular neuropathy, on ultrasound, 1671Y1672,
related to mesial temporal sclerosis, 1460c 1673t, 1677r
sleep-deprived, in agenesis of corpus callosum, Filum terminale, 1598
1481c, 1483cY1484c myxopapillary ependymoma of, 1604
Empty delta sign of cerebral venous thrombosis Fisher Scale and modified Fisher Scale for
(on CT venography), 1455t subarachnoid hemorrhage, 1428, 1430t, 1449r
Empty sella, 1590, 1591f FLAIR. See Fluid-attenuated inversion recovery
Encephalomalacia, 1465Y1466, 1466f, 1556, imaging
1558c, 1558f Flip angle (MRI), 1380, 1382
Endovascular therapy for ischemic stroke, 1422r Florbetaben, for amyloid imaging, 1639
American Heart Association/American Stroke Florbetapir, for amyloid imaging, 1639
Association guidelines for, 1412 Flow velocity (MRI), 1386
patient selection for, 1410Y1412 Fludeoxyglucose (FDG) fluorine 18, 1637, 1638t
timing of, 1412 Fluid-attenuated inversion recovery (FLAIR)
Endovascular Treatment for Small Core and imaging, 1386, 1394, 1397r
Anterior Circulation Proximal Occlusion With image interpretation, 1391, 1394
Emphasis on Minimizing CT to Recanalization imaging protocols for, 1387, 1388t
Times (ESCAPE) trial, 1412, 1413, 1416, in specific conditions
1416tY1417t acute disseminated encephalomyelitis, 1628f
Entrapment neuropathies, on ultrasound, brain tumor, 1531, 1531t, 1543t
1679Y1672, 1673t astrocytoma, 1540f, 1541f
carpal tunnel syndrome, 1671 central neurocytoma, 1548f
cervical radiculopathy, 1672 ependymoma, 1546f
fibular neuropathy, 1671Y1672 ganglioglioma, 1396f
radial neuropathy, 1671 glioblastoma, 1542f
Eosinophilic granuloma, 1513, 1514 cerebral venous thrombosis, 1390f
Ependymal cyst, 1554t, 1559, 1560, 1560f, congenital malformations
1572t, 1573r, cerebellar hypoplasia, 1492f
Ependymoma, 1534t, 1545, 1545t, 1546f corpus callosum agenesis and colpocephaly,
spinal cord, 1604Y1607, 1605t, 1606f, 1607f, 1612r 1483f
Epidermoid cyst, 1554t, 1568, 1569f, 1573r, Dandy-Walker malformation, 1491f
1589, 1594r holoprosencephaly, 1482f
diffusion-weighted imaging of, 1394, 1567, Joubert syndrome, 1493f
1568, 1569f, 1573r, 1589, 1589f pachygyria and schizencephaly, 1486f
intraventricular, 1560, 1568 partial corpus callosum agenesis, 1484f
sellar region, 1574, 1588Y1589, 1589f schizencephaly, 1487f
Epidural abscess, spinal, 1599, 1602, 1611r septooptic dysplasia, 1490f

Neuroimaging
hemorrhagic stroke, 1429, 1447c, 1448f 7T MRI, 1476, 1479r

secondary to neoplastic process, 1447c, transmantle sign, 1462f, 1463t, 1464
1448f neuropathology of, 1461
subarachnoid hemorrhage, 1441f, 1442c Folate deficiency, 1599
incidentally found white matter Follicle-stimulating hormone secretion, 1575, 1578t
abnormalities, 1630f Forebrain anomalies. See Prosencephalon anomalies
intracranial cysts, 1573 Fosphenytoin, 1453c
arachnoid cyst, 1567, 1568f, 1569f Fourier transform (MRI), 1384
cavum velum interpositum, 1564f Fourth nerve palsy, 1520
choroid fissure neuroepithelial cyst, Frequency-encoding gradient (MRI), 1384
1554, 1556f Frontotemporal dementia, 1391f, 1639, 1641f,
choroid plexus cyst, 1559f 1647, 1649f
dilated Virchow-Robin spaces, 1554, 1555f Functional magnetic resonance imaging (fMRI)
epidermoid cyst, 1568, 1569f to assess language lateralization, 1472, 1479r
hippocampal sulcal remnant cyst, 1557f of brain tumors, 1529, 1531t, 1537Y1538, 1537f
neurocysticercosis, 1571f, 1572t for presurgical assessment of drug-resistant
neuroglial cyst, 1557f epilepsy, 1452, 1472
pineal cyst, 1561Y1562, 1561f of subarachnoid hemorrhage, 1442
posttraumatic porencephalic cyst, 1558f
Rathke cleft cyst, 1565
ischemic stroke, 1399, 1405, 1406, 1407,
G
1408, 1408fY1410f, 1408cY1409c, 1412,
1413, 1421r Gadobenate dimeglumine, 1679t
collateral circulation, 1413, 1421rY1422r Gadobutrol, 1679t
multiple sclerosis, 1616t, 1617, 1618f, 1619, Gadodiamide, 1679t
1619f, 1621f, 1622f, 1624f, 1639r Gadofosveset trisodium, 1679t
natalizumab-induced progressive multifocal Gadolinium-based contrast agents for MRI, 1387,
leukoencephalopathy, 1634f, 1634t 1392, 1633rY1634r
multiple sclerosisYlike lesions in Sjögren adverse effects and safety of, 1633r, 1678Y1683
syndrome, 1632f for agents with linear molecular structure vs.
patient with hemichoreic movements, 1391f macrocyclic structure, 1678Y1679
patients with visual symptoms, 1502f gadolinium brain deposits, 1678, 1680Y1683,
internal carotid artery dissection, 1681, 1683rY1684r
1525c, 1525f nephrogenic systemic fibrosis in patients
olfactory groove meningioma, 1516f with renal dysfunction, 1680
optic neuritis, 1510, 1512f available agents on U.S. market, 1679t
orbital blow-out fracture, 1518f in brain metastases, 1550, 1535t
pituitary adenoma, 1579 in brain tumors, 1532, 1533Y1534, 1535t,
seizures and epilepsy, 1458, 1459t, 1545t, 1547
1460f, 1462f central neurocytoma, 1535t, 1547
arteriovenous malformation, 1468 ependymoma, 1545
dysembryoplastic neuroepithelial tumor, glioblastoma multiforme, 1643f
1467f glioma, 1468
encephalomalacia, 1466, 1466f gliomatosis cerebri, 1542
focal cortical dysplasia, 1392f, 1398r, meningioma, 1468, 1468f
1458, 1463t optic nerve glioma, 1539
tuberous sclerosis, 1465f primary CNS lymphoma, 1545
SPECT imaging and, 1646f, 1652f primitive neuroectodermal tumor, 1546
subarachnoid hemorrhage, 1390f in epilepsy related to arteriovenous
tick-borne encephalitis, 1390f malformation, 1469f
tumefactive demyelinating lesion, 1389f in intracranial cysts
Fluorine 18 (18F), 1637 arachnoid cyst, 1567
Flutemetamol, for amyloid imaging, 1639 colloid cyst, 1560
fMRI. See Functional magnetic resonance imaging dermoid cyst, 1565
Focal cortical dysplasia, 1461Y1465, 1471, epidermoid cyst, 1568
1477rY1479r pineal cyst, 1561
classification of, 1463t in ischemic stroke, 1411f
drug-resistant epilepsy due to, 1464c in leptomeningeal carcinomatosis, 1457t
on MRI, 1392f, 1398r, 1458, 1461Y1465, 1462f, in multiple sclerosis, 1616Y1617, 1624t, 1633r
1463t, 1464f, 1477r in neurocysticercosis, 1470

in spinal metastases, 1608 radiation necrosis, 1544
in spondylotic myelopathy, 1608, 1612r choroid plexus cyst, 1559
in tuberculosis, 1470f hemorrhagic stroke, 1429, 1449r
Gadopentetate dimeglumine, 1679t cerebral amyloid angiopathy, 1435, 1436f
Gadoteridol, 1679t intracerebral hemorrhage secondary to
Gadoversetamide, 1679t brain metastases, 1447c, 1448f
Gadoxetate disodium, 1679t subarachnoid hemorrhage, 1441f, 1442c
Ganglioglioma, 1396f, 1539t, 1547 ischemic stroke, 1399, 1406, 1407Y1408,
seizures due to, 1466Y1467, 1478r 1410f, 1412
spinal cord, 1606 multiple sclerosis, 1599, 1622f
GBS (Guillain-Barré syndrome), on ultrasound, neurocysticercosis, 1469, 1570t
1674, 1677r patients with visual symptoms
Germ cell tumors, primary, 1574, 1584, 1588t idiopathic intracranial hypertension,
Germinoma, 1514, 1584, 1584f, 1593r 1504fY1505c, 1504f
Giant cell arteritis, 1512, 1662, 1663f, 1675r traumatic optic neuropathy, 1512
Glasgow Coma Scale volumetric interpolated breath-hold
in intracerebral hemorrhage, 1426t, 1427f, examination, 1502, 1502f
1428c, 1429c, 1440c seizures and epilepsy, 1458, 1466
in traumatic brain injury, 1558c arteriovenous malformations, 1468
Glioblastoma, 1540Y1543 cavernous malformations, 1468
histology of, 1538 neurocysticercosis, 1469, 1572t
imaging in management of progression, 1653r spinal cord disorders, 1597
PET, 1644 cavernous malformations, 1604
on MR spectroscopy, 1540 multiple sclerosis, 1599
MRI characteristics of, 1397r, 1398r, 1447, posttraumatic myelopathy, 1610
1540Y1542, 1542f, 1551rY1552r Granular cell tumor, 1513
treatment-related pseudoprogression, GRE. See Gradient recalled echo MRI
1542Y1543 Growth hormone secretion, 1575
treatment-related pseudoresponse, 1543 Guillain-Barré syndrome (GBS), on ultrasound,
optic nerve, 1510c 1674, 1677r
prevalence of, 1530
relative cerebral blood volume in, 1536, 1538, 1550
H
Response Assessment in Neuro-Oncology
criteria for, 1543, 1543t
Glioblastoma multiforme, 1539t, 1540 Halo sign of giant cell arteritis (on ultrasound),
on MR spectroscopy, 1537 1662, 1663f
on MRI, 1447, 1532t Hamartoma, 1514, 1540f
neuromolecular imaging of, 1643c, 1643f, 1653r hypothalamic, 1574, 1582, 1584f
spinal cord, 1605 Hand-Schuller-Christian syndrome, 1513
Gliomas, 1538 Headache
on CT, 1457t conditions associated with
grade I astrocytoma, 1538Y1539 agenesis of corpus callosum, 1481c
grade II and grade III astrocytoma, 1539Y1540 Beh0et disease, 1631t
grade IV astrocytoma, 1540Y1543 brain tumor, 1529
histologic grading of, 1538 central neurocytoma, 1548c
MRI characteristics of, 1387, 1388t, 1467Y1468, glioblastoma, 1508c, 1542f
1533tY1534t juvenile pilocytic astrocytoma, 1538
optic nerve, 1506, 1507, 1507f, 1539, 1586 carotid-cavernous fistula, 1521, 1521cY1522c
PET imaging of, 1642 cerebral venous thrombosis, 1444cY1445c,
relative cerebral blood volume in, 1538 1455t
seizures due to, 1466, 1467 Chiari type I malformation, 1496, 1496f
subependymal giant cell astrocytoma, 1539, 1540f Churg-Strauss syndrome, 1453c
Gliomatosis cerebri, 1533t, 1542, 1552r idiopathic intracranial hypertension,
Gradient coils (MRI), 1384 1504cY1505c
Gradient fields (MRI), 1381 infectious meningoencephalitis, 1526f
Gradient recalled echo (GRE) MRI, 1385, 1399 internal carotid artery dissection, 1524cY1525c
imaging protocols for, 1387, 1388t intracranial tuberculosis, 1470f, 1471f
in specific conditions neurosarcoidosis, 1515f, 1592
brain tumor, 1535 orbital disease, 1500t
CNS lymphoma, 1546 Parinaud syndrome, 1521, 1523f, 1561

Neuroimaging
postganglionic Horner syndrome, 1524, 1525c MRI, 1428Y1432, 1431t

schizencephaly, 1488f to provide guidance for acute emergent
seizures, 1454 treatment, 1427Y1428, 1429c
sellar/parasellar lesions, 1577Y1578, 1579 to provide guidance for additional tests, 1427
craniopharyngioma, 1582c to provide guidance for further
dermoid cyst, 1588 neuroimaging, 1427
meningioma, 1580 to provide guidance for prognostication,
pituitary adenoma, 1580c 1427f, 1428, 1428c
plasmacytoma, 1586c transcranial Doppler ultrasound and
subarachnoid hemorrhage, 1438cY1441c transcranial color-coded duplex,
systemic lupus erythematosus, 1631t 1432Y1434, 1434f
migraine incidence of, 1424
perfusion imaging in, 1389, 1391f, 1397r mortality from, 1424
postganglionic Horner syndrome and, 1524 primary vs. secondary causes of intracranial
subarachnoid hemorrhage and, 1441cY1442c hemorrhage, 1434
white matter abnormalities and, 1627, 1635r Heparin, 1444cY1445c
MRI evaluation of, 1392, 1704 Hepatocellular carcinoma, intracerebral
Health Care and Education Reconciliation Act of hemorrhage secondary to, 1447
2010, 1687Y1688, 1690r Herpes simplex virus encephalitis, 1454, 1456t, 1620
Hemangioblastoma, 1539t, 1546 CT in, 1456t
on digital subtraction angiography, 1447 intracerebral hemorrhage and, 1447
on MRI, 1532t, 1546 seizures due to, 1454
spinal cord, 1604, 1605Y1606, 1612r Hippocampal abnormalities
Hemangiopericytoma, 1548Y1549 in generalized epilepsy, 1459
Hemianopia in Joubert syndrome, 1491
bitemporal, 1512, 1579, 1588, 1591 in mesial temporal sclerosis, 1459, 1460, 1460c,
homonymous, 1515 1460f, 1461t
Hemorrhagic stroke, 1424Y1448, 1448rY1450r in tick-borne encephalitis, 1390f
anticoagulant-associated risk of, 1424, 1443f, Hippocampal commissure, 1482, 1563, 1564
1445Y1446, 1450r Hippocampal sclerosis
disease-specific states and imaging of, 1434Y1447 focal cortical dysplasia type IIIa and, 1463t
arterial hypertensive vasculopathy, 1434Y1435 mesial temporal sclerosis and, 1459, 1460,
cerebral amyloid angiopathy, 1435Y1436, 1461t, 1477r
1436f, 1437t Hippocampal sulcal remnant cysts, 1553, 1554t,
hemorrhagic transformation of ischemic 1555, 1557f
stroke, 1399, 1434, 1444, 1446f, 1450r HIV. See Human immunodeficiency virus infection
ICH secondary to cerebral venous thrombosis, Holoprosencephaly, 1481, 1482f, 1485,
1442Y1445, 1444cY1445c, 1445f 1488Y1491, 1489f
ICH secondary to neoplastic or infectious septooptic dysplasia, 1466f, 1490, 1490f, 1511
process, 1446Y1448, 1447cY1448c, 1448f Horner syndrome, 1522Y1524, 1524cY1525c, 1528r
ICH secondary to oral anticoagulants and Human immunodeficiency virus (HIV)
sympathomimetic drugs, 1444Y1446 infection, 1627
isolated intraventricular hemorrhage, intracerebral hemorrhage and, 1447, 1450r
1442, 1443f myelitis and, 1601
subarachnoid hemorrhage, 1436Y1442, primary CNS lymphoma and, 1545, 1546
1438cY1442c, 1438fY1441f progressive multifocal leukoencephalopathy
early management of, 1424Y1425 and, 1627
hypertension-related, 1424 seizures and, 1454
imaging of, 1425Y1434 Hydranencephaly, 1488Y1489, 1489f, 1498r
CT to identify hemorrhage, 1424, 1425Y1427, Hydrogen nuclei, in MRI, 1380
1426f, 1426t, 1427f, 1428c, 1428f, 1431t Hydromyelia, 1494f, 1495Y1496, 1597
CTA or MRA, 1432 Hyperdense middle cerebral artery sign of
spot sign of hematoma expansion on CTA, thrombus (on CT), 1407, 1410f, 1415c, 1455t
1425, 1427, 1428c, 1428f, 1449r, 1455t Hypertension, 1419c, 1691c
to determine hematoma volume, 1425, 1426f asymptomatic white matter abnormalities
to determine ICH Score, 1425, 1426t, 1427f, and, 1628
1428, 1449r carotid artery stenosis and, 1660cY1661c
digital subtraction angiography, 1432 intracerebral hemorrhage due to, 1424
Fisher Scale and modified Fisher Scale for arterial hypertensive vasculopathy, 1429,
subarachnoid hemorrhage, 1428, 1430t, 1449r 1434Y1435, 1435f

secondary to neoplastic process, 1446Y1447, Internal carotid artery (ICA) dissection
1447cY1448c Horner syndrome due to, 1524, 1524cY1525c
subarachnoid hemorrhage, 1429c, 1438cY1441c on ultrasound, 1658, 1675r
intracranial hypertension and, 1503 Internal carotid artery (ICA) stenosis
seizures and, 1454 on time-of-flight MRA, 1391f
in Churg-Strauss syndrome, 1453c on ultrasound, 1657, 1658t, 1659cY1661c,
spinal arteriovenous malformation and, 1603 1660f, 1675r
visual symptoms and International Classification of Diseases, Tenth
anisocoria, 1524cY1525c Revision, Clinical Modification (ICD-10-CM)
subarachnoid oculomotor palsy, 1527 coding, e1Ye2, e4cYe5c, e25r
Hypothalamic glioma, 1586, 1587f, 1588t International League Against Epilepsy (ILAE),
Hypothalamic hamartoma, 1574, 1582, 1584f 1476rY1478r
Hypoxic-ischemic encephalopathy, 1389f classification system of, 1451, 1476r
definition of seizure, 1451, 1476r
recommendations for neuroimaging, 1458
I
Interpretation of magnetic resonance images,
1390Y1395, 1391fY1394f, 1395t, 1396f
123
I (iodine 123), 1636Y1637 Interventional Management of Stroke III (IMSIII)
ICA. See Internal carotid artery trial, 1413
ICD-10-CM (International Classification of Intraarachnoid cyst, 1566. See also Arachnoid cyst
Diseases, Tenth Revision, Clinical Modification) Intracerebral Hemorrhage (ICH) Score, 1425,
coding, e1Ye2, e4cYe5c, e25r 1426t, 1427f, 1428, 1449r
ICH (intracranial hemorrhage), nontraumatic. Intracranial hemorrhage (ICH), nontraumatic.
See Hemorrhagic stroke See Hemorrhagic stroke
ICH (Intracerebral Hemorrhage) Score, 1425, Intraventricular hemorrhage, 1442, 1443f
1426t, 1427f, 1428, 1449r Inversion recovery preparation (MRI), 1386
Idiopathic intracranial hypertension (IIH), Inverted V sign of spinal cord degeneration
1503Y1506, 1504cY1505c, 1527, 1527r, (on MRI), 1600c, 1611r
1590, 1594r Iodine 123 (123I), 1636Y1637
IHH (idiopathic intracranial hypertension), Ioflupane iodine 123, 1637
1503Y1506, 1504cY1505c, 1527, 1527r, Ipilimumab, lymphocytic hypophysitis and,
1590, 1594r 1592, 1593f
ILAE. See International League Against Epilepsy Ischemic core
Image acquisition and MRI protocols, definition of, 1401
1386Y1390, 1388t, 1389fY1391f hemodynamic parameters for, 1400, 1400t
axial, coronal, and sagittal acquisitions, 1386Y1387 imaging of, 1405Y1409, 1416t
epilepsy protocol, 1387 CT, 1405Y1406, 1405f, 1406f, 1408f, 1415f
protocols for standard acquisitions, 1387 MRI, 1406Y1408, 1407fY1409f, 1409c
stroke protocol, 1387 SPECT, 1651
Implantable cardioverter defibrillator, safety of vascular signs on parenchymal imaging,
MRI in patient with, 1691c, 1692Y1693, 1694, 1407Y1409, 1410f
1694c, 1694rY1695r time intervals for penumbra to become, 1403f
Implanted medical devices, safety of MRI in patients Ischemic penumbra
with, 1692Y1694, 1693c, 1694c, 1694rY1695r collateral circulation and survival of, 1402, 1418
IMSIII (Interventional Management of Stroke III) definition of, 1401Y1402
trial, 1413, 1420r hemodynamic parameters for, 1400, 1400t
Indium 111 (111In), 1636Y1637 imaging of
Infections CT angiography, 1413
brain abscess due to, 1557 perfusion imaging, 1389, 1409Y1410,
intracerebral hemorrhage secondary to, 1416t, 1419c
1446Y1447 SPECT, 1651
on MRI, 1388t, 1392 ischemic threshold for, 1403f, 1413, 1418
spinal, 1599Y1602, 1611r Ischemic stroke, 1399Y1421, 1408cY1409c,
Inflammatory polyneuropathies, on ultrasound, 1421rY1423r
1673Y1674 clinical indications for neuroimaging in,
CIDP, 1673Y1674 1403Y1404
Guillain-Barré syndrome, 1674 collateral circulation in, 1399, 1402Y1403,
multifocal motor neuropathy, 1674 1420rY1421r
with vasculitis, 1674 eventual failure of, 1403, 1404
Infundibulum sign of empty sella (on MRI), 1590 grading system for, 1413, 1414, 1414f

Neuroimaging
hemodynamics and anatomy of, 1402Y1403, Larmor equation (MRI), 1380, 1382, 1384
1403f Leber hereditary optic neuropathy, 1511,
image-based patient selection for intraarterial 1528r, 1632t
thrombectomy, 1410Y1412, 1415c, 1416t Lindegaard ratio, 1667, 1676r
imaging of, 1408, 1410, 1410f, 1413, Lipoma, spinal, 1598, 1606
1414fY1415f, 1415c Lissencephaly, 1464, 1485Y1486, 1485f,
impact on stroke outcome, 1405, 1406f, 1497r, 1498r
1413, 1415c, 1420rY1423r Longitudinal magnetization (MRI), 1382,
comparison of image-based selection criteria in 1383f, 1385
recent endovascular trials in, 1416Y1418 Longitudinal relaxation (MRI), 1382, 1383f, 1385.
comparison of imaging modalities for, 1404t See also T1-weighted imaging
CT in, 1399, 1404, 1404t, 1405Y1406, 1410 Luteinizing hormone secretion, 1575, 1578t
Alberta Stroke Program Early CT Score, 1405f, Lyme disease, 1511, 1511f, 1628c, 1631t, e4cYe5c
1405Y1410, 1412, 1413, 1416t, 1421r Lymphocytic hypophysitis, 1513, 1574,
patient with new-onset seizures, 1455t 1592, 1593f
decision for reperfusion therapy in, 1399Y1400 Lymphoma, primary CNS, 1387, 1396f,
factors affecting outcome of, 1400 1545Y1546
hemorrhagic transformation of, 1399, 1399, in HIV/AIDS, 1545
1434, 1444, 1446f, 1450r on MR spectroscopy, 1536
imaging of minor stroke and TIA, 1418 on MRI, 1532, 1532t, 1534t, 1546
imaging of post-reperfusion management vs. multiple sclerosis, 1628
in, 1418 spinal cord, 1606
intravenous thrombolysis for, 1415c spinal leptomeningeal, 1506
patient selection for, 1404Y1410 vs. Tolosa-Hunt syndrome, 1520
time window for, 1400
MRI in, 1387, 1390f, 1399, 1404, 1404t, 1405,
1406Y1408, 1409fY1411f
M
pathophysiology of, 1400Y1402
compensatory cerebral autoregulation, M0 (MRI), 1380
1400, 1403f Macaroni sign of Takayasu arteritis (on ultrasound),
hemodynamic parameters, 1400, 1400t 1661, 1662f
ischemic stages in perfusion-diffusion MACRA (Medicare Access and CHIP
mismatch model, 1401Y1402 Reauthorization Act of 2015), e1, e25r
symptom onset and ischemic thresholds, MADSAM (multifocal acquired demyelinating
1401, 1403f sensory and motor neuropathy), 1674
patient selection for intraarterial Magnetic resonance angiography (MRA)
thrombectomy for, 1410Y1413 of arteriovenous malformation, 1468
Rankin Scale score after, 1408f, 1408c, 1411f, 1413 spinal, 1604
ultrasound in, 1404t, 1656, 1657t, 1662Y1663, of carotid artery stenosis, 1391f
1664t, 1662Y1666, 1675r of carotid-cavernous fistula, 1528r
vascular signs on parenchymal imaging in, of cavernous malformations, 1521c, 1522f, 1528r
1407Y1409 spinal, 1604
blooming artifact, 1407, 1410f of cerebral artery aneurysm, 1591, 1591f
hyperdense middle cerebral artery sign, coding for, 1702, 1708t, 1710t, 1711t
1407, 1410f, 1415c, 1455t Current Procedural Terminology codes and
indications for MRA of head and neck, e7t
of giant cell arteritis, 1663f
J of meningioma, 1548
recommendations for ordering, e2Ye3
Joubert syndrome, 1491Y1493, 1493f, 1498r of schizencephaly, 1487
of spinal cord lesions, 1604, 1608
of stroke, 1387, 1388t
K hemorrhagic, 1425, 1432
ischemic, 1399, 1404, 1404t, 1406,
k-space data (MRI), 1384 1408cY1409c, 1409f, 1411f, 1412Y1413,
1416t
Magnetic resonance imaging (MRI), 1379Y1396,
L 1397rY1398r. See also specific imaging
sequences and protocols
Langerhans cell histiocytosis, 1513, 1574, 1592, 1594r avoiding artifacts in, 1385

compared with other imaging modalities, PET and, 1642
1379, 1386 primary CNS lymphoma, 1545
contrast agents for, 1386 primitive neuroectodermal tumor, 1546
Current Procedural Terminology codes and subependymal giant cell astrocytoma,
indications for 1539, 1540f
brain MRI, e6t treatment-related pseudoprogression,
orbit, face, and neck MRI, e8t 1542Y1543
other MRI procedures, e8tY39t treatment-related pseudoresponse, 1543
spinal MRI, 310t concussion, 1651
frequency of use, 1692 congenital malformations, 1496
functional (See Functional magnetic agenesis of corpus callosum, 1481f, 1481c,
resonance imaging) 1482f, 1485
gadolinium-based contrast agents for, 1387, anencephaly, 1488
1392, 1633rY1634r cerebellar hypoplasia, 1492f
safety of, 1633r, 1678Y1684 Chiari malformation, 1494f, 1496, 1496f, 1497f
image acquisition and protocols for, cortical malformations, 1485
1386Y1390, 1388t, 1389fY1391f Dandy-Walker malformation, 1491, 1491f
image interpretation, 1390Y1395, 1391fY1394f, Dandy-Walker variant, 1492f
1395t, 1396f holoprosencephaly, 1488, 1489f, 1490
consistency checks, 1392 hydranencephaly, 1488Y1489, 1489f
lesion topography, 1394 Joubert syndrome, 1491Y1493, 1493f
overlooking lesions, 1392Y1393 lissencephaly, 1485Y1486, 1485f
signal intensity of lesions, 1394Y1395 midbrain and hindbrain anomalies, 1491
signal to noise ratio, 1393 polymicrogyria, 1486f, 1486Y1487
systematic approach to, 1391Y1392 schizencephaly, 1486, 1487f
for two- vs. three-dimensional sequences, demyelinating disorders
1393Y1394 acute disseminated encephalomyelitis,
typical presentations of lesions, 1392 1626, 1628f
multimodal, 1399 Baló concentric sclerosis, 1623f
physics of, 1379Y1386 incidentally found white matter abnormalities,
excitation and precession, 1380Y1381, 1381f 1627, 1630f
magnetization preparation, 1385Y1386 multiple sclerosis, 1387, 1388t, 1512f,
measurement with radiofrequency coils, 1613Y1631, 1616t, 1618fY1625f
1381Y1382 radiologically isolated syndrome, 1614, 1615t
MRI sequences, 1385 spinal lesions, 1602Y1603, 1603f, 1617, 1618f
polarization, 1379Y1380 neuromyelitis optica, 1626, 1627f
relaxation, 1382Y1384, 1383f progressive multifocal leukoencephalopathy,
spatial encoding, 1384Y1385 1627, 1629f, 1629tY1630t
safety in patients with implanted medical tumefactive demyelinating lesions, 1387,
devices, 1691Y1694, 1694rY1695r 1389f, 1397r, 1529, 1536, 1621Y1623,
Magnetic Resonance Imaging in Multiple Sclerosis 1621f, 1634r
(MAGNIMS) network, 1616Y1617 hemorrhagic stroke, 1428Y1432, 1431t, 1449r
Magnetic resonance imaging (MRI) in specific cerebral amyloid angiopathy, 1389, 1429,
conditions 1435, 1436f, 1437t
brain metastases, 1396f, 1457t, 1535t, 1550 cerebral venous thrombosis, 1442Y1443, 1455t
brain tumor, 1387Y1389, 1388t, 1397r, 1447, intracerebral hemorrhage secondary to brain
1457t, 1531, 1531t, 1530Y1538, 1533tY1535t, metastases, 1447cY1448c, 1448f
1537f subarachnoid hemorrhage, 1441f, 1441cY1442c
anaplastic astrocytoma, 1537f, 1541cY1542c, herpes encephalitis, 1456t
1541f intracranial cysts, 1553, 1571, 1572t
to distinguish radiation necrosis from tumor, arachnoid cyst, 1566, 1567f, 1568f, 1590, 1590f
1543Y1544 brain abscess, 1557
ependymoma, 1545, 1546f cavum septum pellucidum, 1563f, 1564f
glioblastoma, 1397r, 1398r, 1447, 1540Y1543, cavum velum interpositum, 1486f, 1563f
1542f, 1551rY1552r cavum vergae, 1564f
grade II glioma, 1539Y1540 choroid fissure neuroepithelial cyst,
hemangioblastoma, 1546 1554, 1556f
juvenile pilocytic astrocytoma, 1539 choroid plexus cyst, 1559, 1559f
oligoastrocytoma, 1538f colloid cyst, 1560, 1560f
oligodendroglioma, 1544Y1545, 1544f dermoid cyst, 1564Y1565, 1565f

Neuroimaging
dilated Virchow-Robin spaces, 1554, 1555f pituitary abscess, 1593

ependymal cyst, 1560f pituitary adenoma, 1579, 1580c, 1580f, 1593r
epidermoid cyst, 1568, 1569f pituitary apoplexy, 1591, 1592f
hippocampal sulcal remnant cyst, 1555, 1557f plasmacytoma, 1585, 1586c, 1586f
neurocysticercosis, 1571f, 1572f, 1572t primary germ cell tumor, 1584, 1588t
neuroglial cyst, 1556f, 1557f Rathke cleft cyst, 1589, 1590f
pineal cyst, 1561Y1562, 1561f, 1562f schwannoma, 1584
porencephalic cyst, 1558f posterior reversible encephalopathy syndrome,
Rathke cleft cyst, 1565, 1566f, 1589, 1590f 1456t
ischemic stroke, 1387, 1390f, 1399, 1404, 1404t, seizures and epilepsy, 1387, 1388t, 1451Y1476
1405, 1406Y1408, 1409fY1411f arteriovenous malformations, 1468, 1469f
post-reperfusion management, 1418 assessment of patients with established
to select patients for intraarterial epilepsy, 1454
thrombectomy, 1413 cavernous malformations, 1468, 1469f
leptomeningeal carcinomatosis, 1457t CNS tuberculosis, 1468, 1470, 1470f, 1471f
patients with visual symptoms, 1499Y1503 encephalomalacia, 1465Y1466, 1466f, 1556,
adenoid cystic carcinoma, 1501c, 1501f 1558c, 1558f
carotid-cavernous fistula, 1520, 1521c, 1522f, generalized epilepsy, 1459
1523f, 1590 low-grade primary brain tumors, 1466Y1468,
diplopia, 1516 1467f
Horner syndrome, 1522 malformations of cortical development,
idiopathic intracranial hypertension, 1461Y1465, 1462f, 1463t, 1464c, 1464fY1466f
1504cY1505c, 1504f,1506f, 1506 mesial temporal sclerosis, 1458, 1459Y1460,
infectious third nerve palsy, 1526f 1460c, 1460f, 1461t
internal carotid artery dissection, 1524c, 1525f neurocysticercosis, 1468Y1469
multiple sclerosis, 1517f presurgical evaluation of patients with
neuromyelitis optica, 1513f, 1514c, 1514f drug-resistant epilepsy, 1470Y1471
olfactory groove meningioma, 1516f standard epilepsy protocol used at Mayo
optic nerve glioma, 1506, 1507f, 1586 Clinic, 1459t
optic nerve sheath meningioma, 1509f urgent assessment of new-onset seizure,
optic neuritis, 1510Y1511, 1512f 1452, 1455tY1457t
orbital blow-out fracture, 1518f spinal cord disorders, 1596Y1597, 1596f, 1610
orbital metastases, 1520f arteriovenous malformations, 1602Y1604, 1603f
Parinaud syndrome, 1523f astrocytoma, 1608f
perineuritis, 1511, 1511f cavernous malformations, 1604
posterior cortical atrophy, 1518f ependymoma, 1604Y1605, 1605t, 1606f, 1607f
sarcoid optic neuropathy, 1515f metastatic lesions, 1607, 1608
septooptic dysplasia, 1466f, 1490f, 1511 multiple sclerosis, 1598Y1599, 1598f
suprasellar aneurysms with compression of myelopathy from spine trauma, 1609
optic nerve and chiasm, 1517f neuromyelitis optica, 1599
thyroid eye disease, 1517Y1518, 1519f nutritional deficiency myelopathy, 1599,
Tolosa-Hunt syndrome, 1520f 1600c, 1600f
visual loss, 1508cY1509c, 1510f spinal cord infarction, 1393, 1393f, 1602, 1603f
pituitary and parasellar disorders, 1575, spinal infections, 1599
1577f, 1594r spondylotic myelopathy, 1618Y1609, 1609f
arachnoid cyst, 1590, 1590f Magnetic resonance spectroscopy, 1387, e24r
chondrosarcoma, 1584Y1585, 1585f, 1588t of brain tumor, 1529, 1531t, 1536Y1537,
chordoma, 1585, 1585f, 1588t 1551, 1551r
craniopharyngioma, 1579, 1582f astrocytoma, 1533t, 1534t, 1537f, 1540f
dermoid cyst, 1587 central neurocytoma, 1535t, 1547, 1548f
empty sella, 1590Y1591, 1591f CNS lymphoma, 1534t
epidermoid cyst, 1589, 1589f CNS metastasis, 1535t, 1550
hypothalamic glioma, 1586, 1587f, 1588t ganglioglioma, 1396f, 1547
hypothalamic hamartoma, 1582, 1584f gliomatosis cerebri, 1533t
Langerhans cell histiocytosis, 1592 medulloblastoma, 1546
lymphocytic hypophysitis, 1592, 1593f meningioma, 1535t, 1547
meningioma, 1580Y1581, 1583f oligodendroglioma, 1534t, 1544
neurosarcoidosis, 1592 primitive neuroectodermal tumor, 1546
optic nerve glioma, 1586,1587f, 1588t Current Procedural Terminology codes and
pituicytoma, 1586Y1587, 1588f, 1588t, 1594r indications for, e21tY1724t

in multiple sclerosis, 1625 Mesencephalon (midbrain) anomalies,
of spinal cord lesions, 1610 1491Y1493
of tumefactive demyelinating lesions, 1397r Dandy-Walker malformation and related
Magnetic resonance venography (MRV) disorders, 1484, 1491, 1491f, 1492f
in cerebral venous thrombosis, 1427, Joubert syndrome, 1491Y1493, 1493f, 1498r
1443Y1445, 1444f, 1455t Mesenchymal tumors, 1574, 1584Y1585, 1588t
in idiopathic intracranial hypertension, Mesial temporal sclerosis, 1451, 1459Y1460,
1504cY1505c, 1504f, 1506, 1506f 1460c, 1460f
Magnetization preparations (MRI), 1386 CT in, 1458
Magnetization-prepared rapid acquisition encephalomalacia and, 1466
gradient-echo (MPRAGE) imaging, 1394 MRI in, 1458, 1459Y1460, 1461t, 1471, 1477r
in epilepsy, 1459t neuropathology of, 1459
for visual symptoms, 1502 Migraine
intracranial hypertension, 1505c, 1504f, 1506f perfusion imaging in, 1389, 1391f, 1397r
olfactory groove meningioma, 1516f postganglionic Horner syndrome and, 1524
Magnetization transfer imaging, in multiple subarachnoid hemorrhage and, 1441cY1442c
sclerosis, 1625 white matter abnormalities and, 1627, 1635r
Magnetization vector (MRI), 1381, 1381f, 1382 Mild cognitive impairment (MCI), 1638, 1639,
MAGNIMS (Magnetic Resonance Imaging in 1640c, 1653r
Multiple Sclerosis) network, 1616Y1617 Mismatch imaging, in ischemic stroke, 1399
Mastoiditis, due to cerebral venous thrombosis, Mitochondrial encephalopathy, lactic acidosis,
1445f, 1445c and strokelike episodes syndrome
MCI (mild cognitive impairment), 1638, 1639, (MELAS), 1389f
1640c, 1653r MMN (multifocal motor neuropathy), on
Median nerve ultrasound, 1672f ultrasound, 1674
Medicare Access and CHIP Reauthorization Act of Molar tooth sign of Joubert syndrome (on MRI),
2015 (MACRA), e1, e25r 1491, 1493f
Medicolegal issues: physician investment and Mononeuritis multiplex, 1453c, 1674
ownership in health care enterprises, Movement disorders
1685Y1688, 1685c, 1688rY1690r neuromolecular imaging in, 1638t, 1645Y1649,
Medulloblastoma. See Primitive neuroectodermal 1647f, 1649f, 1653r, 1654r
tumor ultrasound in, 1655, 1668Y1670, 1669t, 1670f,
Mega cisterna magna, 1491 1671t, 1676r
Melanocytoma, spinal cord, 1606 MPRAGE imaging. See Magnetization-prepared
Melanoma, 1447, 1532t, 1550 rapid acquisition gradient-echo imaging
MELAS (mitochondrial encephalopathy, lactic MR CLEAN (Multicenter Randomized Clinical Trial
acidosis, and strokelike episodes of Endovascular Treatment for Acute Ischemic
syndrome), 1389f Stroke in the Netherlands), 1412, 1416,
Melatonin, 1575 1416tY1417t
Meningioma, 1547Y1548 MR WITNESS (Study of Intravenous Thrombolysis
diplopia due to, 1521 with Alteplase in MRI-Selected Patients), 1412
on MRI, 1396f, 1447, 1468, 1535t, 1547Y1548, MRA. See Magnetic resonance angiography
1549f MRI. See Magnetic resonance imaging
olfactory groove, 1516f MRV. See Magnetic resonance venography
optic nerve sheath, 1499, 1500, 1506Y1507, MS. See Multiple sclerosis
1509f, 1510, 1511f, 1580 MSA. See Multiple system atrophy
parasellar, 1580Y1581, 1583f Multicenter Randomized Clinical Trial of
prevalence of, 1530 Endovascular Treatment for Acute Ischemic
seizures due to, 1468 Stroke in the Netherlands (MR CLEAN), 1412,
Meningitis 1416, 1416tY1417t
with anisocoria, 1524 Multifocal acquired demyelinating sensory and
carcinomatous, 1507, 1508cY1509c motor neuropathy (MADSAM), 1674
chemical, 1565, 1588 Multifocal motor neuropathy (MMN), on
cryptococcal, 1505f ultrasound, 1674
CT in, 1456t Multiple myeloma, plasmacytoma and, 1585, 1594r
MRI in, 1389 Multiple sclerosis (MS), 1613Y1628, 1628c,
pneumococcal, 1526f, 1528r 1633rY1635r
spinal, 1601 clinically isolated syndrome and, 1614
tuberculous, 1470, 1470f coding for neuroimaging in, e4cYe5c
Mesencephalon (midbrain), 1482, 1491 definition of, 1614

Neuroimaging
dissemination in time and dissemination in in carotid artery stenosis, 1666cY1667c

space features of, 1614, 1615, 1615t, 1617, in ischemic stroke, 1408c, 1431
1624, 1624t, 1625c collateral circulation and, 1413
importance of MRI in, 1615 with hemorrhagic transformation, 1445
MRI features of lesions in, 1617Y1625, to select patients for intraarterial
1618fY1625f thrombectomy, 1410Y1412
MRI protocol for, 1387, 1388t, 1615Y1617, 1616t to select patients for tPA therapy, 1404Y1405,
spinal imaging, 1617 1665
nonconventional imaging techniques in, after tPA therapy, 1411f
1625Y1626 in TIA, 1418, 1419c
optic neuritis as first presentation of, 1510, 1514f Nephrogenic systemic fibrosis,
optic tract lesion in, 1512f, 1513f gadolinium-related, 1678
other demyelinating disorders that can mimic Net magnetization M0 (MRI), 1380
MS, 1628Y1629, 1631tY1632t Neurenteric cyst, 1554t, 1562Y1563, 1562f
primary progressive, 1614 Neurocysticercosis, 1394f, 1478r, 1517, 1554t,
radiologically isolated syndrome and, 1568, 1570tf, 1571f, 1571c, 1572f, 1572t
1614Y1615, 1615t disseminated, 1570
relapsing-remitting, 1614 racemose, 1570
revised McDonald diagnostic criteria for, 1617, seizures due to, 1451, 1454, 1468Y1469
1619, 1624t, 1625c, 1633r spinal, 1570
spinal cord lesions in, 1598Y1599, 1598f, stages and pathology of, 1570t
1611rY1612r, 1617, 1618f, 1623 Neurofibromatosis type 1 (NF1)
treatment-associated progressive multifocal astrocytomas in, 1539, 1540f
leukoencephalopathy in, 1627, 1629f, hypothalamic glioma in, 1586
1629tY1630t, 1635r optic nerve glioma in, 1506, 1507, 1507f, 1586
tumefactive lesions in, 1621 Neurofibromatosis type 2 (NF2)
variants of, 1620 meningioma in, 1547
Baló concentric sclerosis, 1620, 1623f spinal ependymoma in, 1604, 1612r
Marburg variant, 1620 Neuroglial cyst, 1554Y1555, 1556f, 1557f, 1572t
Multiple system atrophy (MSA) Neurohypophysis, 1575
neuromolecular imaging in, 1648, 1649f pituicytoma effects on, 1586Y1587, 1588f
ultrasound in, 1669, 1671t Neuromolecular imaging, 1636Y1653,
Mxy (MRI), 1381, 1381f, 1383f, 1384 1653rY1654r. See also Positron emission
Mycobacterium tuberculosis infection. tomography; Single-photon emission
See Tuberculosis computed tomography
Myokymia, superior oblique, 1521 amyloid imaging, 1638, 1639
Myotonia, 1518 of brain tumors, 1638t, 1641Y1644, 1643c, 1643f
Mz (MRI), 1381, 1381f, 1383f in cerebrovascular disease, 1638t, 1649Y1651,
1650f
Current Procedural Terminology codes for
N
codes and indications for, e21tYe24t
in dementia, 1637Y1641, 1638t, 1640c,
NAA (N-acetylaspartate) peak, in brain tumors, 1640f, 1641f
1533tY1535t, 1536, 1537f, 1540, 1547, 1548 dopamine transporter imaging, 1637, 1639,
Natalizumab-associated progressive multifocal 1647, 1648Y1649, 1649f, 1654r
leukoencephalopathy, 1627, 1629f, in epilepsy, 1638t, 1644Y1645, 1646c, 1646f
1629tY1630t, 1635r in parkinsonian syndromes, 1638t, 1645Y1649,
National Institute of Neurological and 1647f, 1649f
Communicative Disorders (NINCDS)YAlzheimer’s radioisotopes used for, 1636Y1637
Disease and Related Disorders Association of traumatic brain injury, 1638t, 1651Y1652,
(ADRDA) diagnostic criteria for Alzheimer 1652f
disease, 1638 Neuromyelitis optica (NMO) and neuromyelitis
National Institute of Neurological and optica spectrum disorders, 1611r, 1613, 1623,
Communicative DisordersYAlzheimer’s Disease 1626, 1627f, 1628c, 1631t
and Related Disorders Association diagnostic criteria for, 1633r
(NINCDS-ADRDA) diagnostic criteria for differentiation from multiple sclerosis, 1633r
Alzheimer disease, 1638 longitudinally extensive transverse myelitis in,
National Institute on Aging (NIA), 1638 1511, 1514c 1514f, 1599
National Institutes of Health Stroke Scale optic neuritis as first presentation of, 1511, 1513f
(NIHSS) score Neuromyotonia, 1518

Neuropore, 1481Y1482 Orbital blow-out fracture, 1516, 1517, 1518f
Neurosarcoidosis, 1457t, 1515f, 1520, 1528r, Orbital cellulitis, 1518
1592Y1593, 1631t Orbital diseases
mechanisms of effects on brain, 1511 assessing orbital compartments, 1503, 1503f
on MRI, 1511, 1617 visual loss due to, 1502Y1503
in sellar region, 1574, 1592 Orbital metastases, 1518
spinal cord lesions in, 1623 Orbital myositis, 1511f, 1518, 1528r
visual symptoms of, 1508cY1509c Orbital pseudotumor, 1518
infundibulum lesions, 1513 Oxytocin, 1575
optic neuropathy, 1511Y1512, 1515f
suprasellar lesions, 1514
P
Neurosonology. See Ultrasound
Neurosyphilis, 1511, 1602, 1632t
NF1. See Neurofibromatosis type 1 Pacemaker, safety of MRI in patient with, 1429,
NF2. See Neurofibromatosis type 2 1458, 1692, 1694rY1695r
NIA (National Institute on Aging), 1638 Pachygyria, 1485, 1486f
NIHSS. See National Institutes of Health Stroke Pachymeningitis, 1518, 1524
Scale score Papilledema, 1502, 1503, 1505, 1506f, 1586c
NINCDS-ADRDA (National Institute of Neurological Papillitis, 1503
and Communicative DisordersYAlzheimer’s Paraganglioma, spinal cord, 1606
Disease and Related Disorders Association) Parasellar region disorders. See Pituitary and
diagnostic criteria for Alzheimer disease, 1638 parasellar disorders
Nitrous oxide inhalationYinduced myelopathy, Parinaud syndrome, 1521, 1523f, 1561
1631t Parkinson disease (PD)
NMO. See Neuromyelitis optica diagnosis of, 1645, 1654r
Nutritional deficiency myelopathy, 1599, neuromolecular imaging in, 1638t, 1648,
1600c, 1600f 1649f, 1654r
ultrasound in, 1668Y1669, 1670f, 1671t, 1676r
Parkinsonian syndromes
O neuromolecular imaging in, 1638t, 1645Y1649,
1647f, 1649f, 1653r, 1654r
OCT (optical coherence tomography), in multiple ultrasound in, 1668Y1669, 1670f, 1671t, 1676r
sclerosis, 1626, 1634r Patient Protection and Affordable Care Act,
Oculosympathetic pathway imaging, 1522Y1527 1685, 1688r
Oligoastrocytoma, 1467, 1536, 1537f, 1538f PD. See Parkinson disease
Oligodendroglioma, 1467, 1468, 1533tY1534t, Penumbra. See Ischemic penumbra
1544Y1545, 1551r Perfusion-weighted MRI imaging (PWI), 1386, 1397r
on MRI, 1532t, 1533t, 1544, 1544f protocols for, 1387, 1388t, 1389Y1390
spinal cord, 1606 in specific conditions, 1391f
Optic chiasm abnormalities, 1512Y1516, brain tumor, 1536, 1550
1515fY1517f frontotemporal dementia, 1391f
Optic nerve abnormalities, 1503Y1512 ischemic stroke, 1389, 1390f, 1397r, 1399,
compressive/infiltrative causes of, 1506Y1510, 1404, 1404t, 1409, 1410, 1411f
1507f, 1508cY1509c, 1509f, 1510f, 1511f migraine attack, 1391f
hereditary, toxic/metabolic, traumatic, and postictal, 1391f
vascular causes of, 1511Y1512 spinal cord disorders, 1610
inflammatory causes of, 1510Y1511, 1511f, 1514c TIA, 1418, 1419c, 1419f
mechanical causes of, 1503, 1504cY1505c, 1503f Perineuritis, 1510, 1513, 1513f
Optic nerve glioma, 1506, 1507f, 1539, 1586, 1588t Peripheral nervous system (PNS)
Optic nerve sheath meningioma, 1499, 1500, Current Procedural Terminology codes and
1506Y1507, 1509f, 1510 indications for noninvasive vascular imaging
Optic neuritis, 1510Y1511, 1528r of, e18tYe20t
anterior, 1503 ultrasound of, 1670Y1674, 1672f, 1676rY1677r
demyelinating, 1510, 1512f brachial plexopathies, 1672Y1673
as first presentation of multiple sclerosis, entrapment neuropathies, 1670Y1672, 1673t
1512f, 1513f carpal tunnel syndrome, 1671
infectious causes of, 1511 cervical radiculopathy, 1672
Optical coherence tomography (OCT), in fibular neuropathy, 1671Y1672
multiple sclerosis, 1626, 1634r radial neuropathy, 1671
Orbital artifacts, 1502f inflammatory polyneuropathies, 1673Y1684

Neuroimaging
Guillain-Barré syndrome, 1674 imaging characteristics of, 1588t

multifocal motor neuropathy, 1674 mesenchymal tumors, 1584Y1585
with vasculitis, 1674 chondrosarcoma, 1584Y1585, 1585f, 1588t
phrenic neuropathies, 1673 chordoma, 1585, 1585f, 1588t
Periventricular nodular heterotopia, 1464 plasmacytoma, 1585, 1586c, 1586f
PET. See Positron emission tomography metastatic tumors, 1585Y1586
Phase-encoding gradient (MRI), 1384 primary germ cell tumors, 1584, 1588t
Phrenic neuropathies, on ultrasound, 1673, 1677r pituitary and parasellar anatomy, 1575, 1576f
Physics of magnetic resonance imaging, 1379Y1386 pituitary hormone secretion, 1574
excitation and precession, 1380Y1381, 1381f vascular lesions, 1590Y1592
magnetization preparation, 1385Y1386 carotid-cavernous fistula, 1590
measurement with radiofrequency coils, cerebral artery aneurysms, 1591, 1591f
1381Y1382 pituitary apoplexy, 1591Y1592, 1592f
MRI sequences, 1385 Pituitary apoplexy, 1513, 1527, 1591Y1592,
polarization, 1379Y1380 1592f, 1594r
relaxation, 1382Y1384, 1383f Pituitary bright spot (on MRI), 1575, 1588f, 1588t
spatial encoding, 1384Y1385 Plasmacytoma, 1574, 1584, 1585, 1586c, 1586f, 1594r
11
C-PiB (carbon 11Ylabeled Pittsburgh PNS. See Peripheral nervous system
Compound B), 1639 Polarization, MRI and, 1379Y1380
Pineal cyst, 1554t, 156iY1562, 1561f, 1562f Poliovirus myelitis, 1601
1572t, 1573r Polymicrogyria, 1464, 1464f, 1466f, 1481, 1482f,
Pineoblastoma, 1523f, 1562 1485, 1486Y1487, 1486f, 1490f, 1498r
Pineocytoma, 1562 Porencephalic cyst, 1466, 1555Y1556, 1558c,
Pituicytoma, 1586Y1587, 1588f, 1588t 1558f, 1572t
Pituitary adenoma, 1447, 1513, 1565, 1578, 1578t, Positron emission tomography (PET), 1473,
1579, 1580c, 1580f, 1593r 1636Y1653, 1653rY1654r
clinical symptoms and hormonal abnormalities cameras for, 1637
due to, 1578t, 1579 Current Procedural Terminology codes for
Hardy and Knosp classification systems for, codes and indications for, e21tYe24t
1579, 1581f insurance payment for, 1636
pituitary apoplexy due to hemorrhage of, 1592 measurement of cerebral glucose metabolism
Pituitary and parasellar disorders, 1574Y1593, by, 1637
1593rY1594r radioisotope for, 1473, 1636Y1637, 1638t
benign tumors, 1578Y1584 in specific conditions
craniopharyngioma, 1579Y1580, 1582c, 1582f brain tumor, 1638t, 1641Y1644, 1643c, 1643f
hypothalamic hamartoma, 1582, 1584f cerebrovascular disease, 1638t, 1649Y1651
meningioma, 1580Y1581, 1583f dementia, 1637Y1641, 1638t, 1640c, 1640f
pituitary adenoma, 1579, 1578c, 1578f, 1581f epilepsy, 1472Y1473, 1474c, 1474f, 1638t,
schwannoma, 1583Y1584 1644Y1645, 1646c, 1646f
clinical symptoms of, 1577Y1578 intracerebral hemorrhage secondary to brain
headache, 1577Y1578 metastases, 1447cY1448c, 1448f
hormonal abnormalities, 1578, 1578t ischemic stroke, 1404t
visual changes, 1577 multiple sclerosis, 1625
cysts, 1587Y1590 parkinsonian syndromes, 1638t, 1645Y1649,
arachnoid cyst, 1590, 1590f 1647f, 1649f
dermoid cyst, 1587Y1589, 1589f spinal cord disorders, 1596
empty sella, 1590, 1591f subarachnoid hemorrhage, 1442
epidermoid cyst, 1589, 1589f traumatic brain injury, 1638t, 1651Y1652, 1653
Rathke cleft cyst, 1589, 1590f Warburg theory for use in oncology, 1642
imaging characteristics of, 1575Y1577, 1577f Posterior cortical atrophy, 1515, 1518f
inflammatory lesions, 1592Y1593 Posterior reversible encephalopathy syndrome
Langerhans cell histiocytosis, 1592 (PRES), 1442c, 1454, 1456t, 1629
lymphocytic hypophysitis, 1592, 1593f Precession frequency (MRI), 1380, 1384
neurosarcoidosis, 1592 PRES (posterior reversible encephalopathy
pituitary abscess, 1574, 1593 syndrome), 1442c, 1454, 1456t, 1629
malignant tumors, 1584Y1587 Primitive neuroectodermal tumor, 1532, 1532t,
astrocytoma, 1586Y1587 1546Y1547
hypothalamic glioma, 1586, 1587f, 1588t spinal cord, 1606
optic nerve glioma, 1586, 1587f,1588t Progressive multifocal leukoencephalopathy
pituicytoma, 1586Y1587, 1588f, 1588t (PML), 1626

natalizumab-associated, 1627, 1629f, Renal cell carcinoma, 1447, 1550
1629tY1630t, 1635r Repetition time (TR) (MRI), 1385
Progressive supranuclear palsy (PSP), 1676r Response Assessment in Neuro-Oncology
neuromolecular imaging in, 1645, 1649f (RANO) criteria for glioblastoma, 1543, 1543t
ultrasound in, 1669, 1671t Retinoblastoma, 1499, 1500, 1500f
Prolactin secretion, 1575, 1578t, 1580c, 1585 Retrochiasmal lesions, 1515Y1516
Prosencephalon (forebrain), 1482 REVASCAT (Randomized Trial of Revascularization
Prosencephalon (forebrain) anomalies, 1482Y1491 With Solitaire FR Device Versus Best Medical
dorsal, 1482Y1487 Therapy in the Treatment of Acute Stroke Due to
agenesis of corpus callosum, 1480Y1481, Anterior Circulation Large Vessel Occlusion
1481c, 1481fY1484f, 1482Y1484, Presenting Within 8 Hours of Symptom Onset),
1483cY1484c, 1485, 1492f, 1511 1412, 1416, 1416tY1417t
cerebral cortical malformations, 1484Y1487 Reversed Robin Hood syndrome, 1665
lissencephaly, 1464, 1485Y1486, 1485f, Reversible cerebral vasoconstriction syndrome,
1497r, 1498r 1436, 1442, 1442c, 1455t
polymicrogyria, 1464, 1464f, 1466f, Rhombencephalon (hindbrain), 1482
1481, 1482f, 1485, 1486Y1487, 1486f, Rhombencephalon (hindbrain) anomalies,
1490f, 1498r 1491Y1493
schizencephaly, 1464,1485, 1486f, 1487, Dandy-Walker malformation and related
1487f, 1488f disorders, 1484, 1491, 1491f, 1492f
ventral, 1488Y1491 Joubert syndrome, 1491Y1493, 1493f, 1498r
anencephaly, 1488, 1498r RIS (radiologically isolated syndrome) and
holoprosencephaly, 1481, 1482f, 1485, multiple sclerosis, 1614Y1615, 1615t
1488Y1491, 1489f Romberg sign in copper deficiency
septooptic dysplasia, 1466f, 1490, 1490f, 1511 myeloneuropathy, 1600c
hydranencephaly, 1488Y1489, 1489f
Proton density weighting (MRI), 1385
S
Pseudopapilledema, 1503
Pseudotumor cerebri syndrome. See Idiopathic
intracranial hypertension Safety of gadolinium-based contrast agents for
PSP. See Progressive supranuclear palsy MRI, 1633r, 1678Y1683
PWI. See Perfusion-weighted MRI imaging for agents with linear molecular structure vs.
macrocyclic structure, 1678Y1679
gadolinium brain deposits, 1678, 1680Y1683,
R 1681, 1683rY1684r
nephrogenic systemic fibrosis in patients with
Radial neuropathy, on ultrasound, 1671, 1673t renal dysfunction, 1678
Radiofrequency coils for MRI, 1381Y1382 Safety of MRI in patients with implanted medical
Radiologically isolated syndrome (RIS) and devices, 1691Y1694, 1694rY1695r
multiple sclerosis, 1614Y1615, 1615t electromagnetic effect, 1692Y1693
Raeder paratrigeminal syndrome, 1524 mechanical effect, 1692
Randomized Trial of Revascularization With MR Conditional devices, 1693Y1694
Solitaire FR Device Versus Best Medical Therapy safety terminology, 1693, 1693f
in the Treatment of Acute Stroke Due to Anterior thermal effect, 1692
Circulation Large Vessel Occlusion Presenting SAH. See Subarachnoid hemorrhage
Within 8 Hours of Symptom Onset (REVASCAT), Sarcoidosis. See Neurosarcoidosis
1412, 1416, 1416tY1417t Schizencephaly, 1464,1485, 1486f, 1487, 1487f, 1488f
Rankin Scale score, after ischemic stroke, 1408f, Schwannoma, 1521, 1539t
1408c, 1411f, 1412, 1413 sellar region, 1574, 1583Y1584, 1594r
RANO (Response Assessment in Neuro-Oncology) spinal, 1607
criteria for glioblastoma, 1543, 1543t SEGA (subependymal giant cell astrocytoma),
Rasmussen encephalitis, 1645 1539, 1540f
Rathke cleft, 1578, 1593 Seizures and epilepsy, 1451Y1476, 1476rY1479r
Rathke cleft cyst, 1513, 1554t, 1565Y1566, 1566f, assessment of patients with established epilepsy,
1574, 1589, 1590f 1454Y1458
Rathke pouch, 1565Y1566, 1575, 1579, 1589 etiologies of, 1452
Read gradient (MRI), 1384 ILAE classification of, 1452, 1476r
Relaxation (MRI), 1382 ILAE definitions of, 1451Y1452, 1476r
longitudinal (T1), 1382, 1383f MRI assessment of, 1387, 1388t, 1391f,
transverse (T2), 1382Y1384, 1383f 1458Y1470

Neuroimaging
focal-onset epilepsy, 1459Y1470 in spinal cord disorders, 1597

agenesis of corpus callosum, 1481c, cellular ependymoma, 1606f
1483cY1484c copper deficiency myelopathy, 1600f
arteriovenous malformations, 1468, 1469f infective spondylodiscitis, 1601f
cavernous malformations, 1468, 1469f multiple sclerosis, 1598f, 1599
cerebral cortical malformations, 1461Y1465, spinal astrocytoma, 1608f
1462f, 1463t, 1464c, 1464fY1466f spinal cord infarction, 1603f
CNS tuberculosis, 1470, 1470f, 1471f Sickle cell anemia, transcranial Doppler ultrasound
encephalomalacia, 1465Y1466, 1466f, in, 1655, 1666, 1667t
1556, 1558c, 1558f Signal to noise ratio in MRI, 1380, 1381Y1382
low-grade primary brain tumors, 1466Y1468, for two- vs. three-dimensional sequences,
1468f 1393Y1394
mesial temporal sclerosis, 1459Y1460, Single-photon emission computed tomography
1460c, 1460f, 1461t (SPECT), 1636Y1653, 1653rY1655r
neurocysticercosis, 1468Y1469 cameras for, 1637
generalized epilepsy, 1459 Current Procedural Terminology codes for
standard epilepsy protocol used at Mayo codes and indications for, e21tYe24t
Clinic, 1459t insurance payment for, 1636
neuromolecular imaging in, 1638t, 1644Y1645, physiologic processes measured by, 1637
1646c, 1646f, 1653rY1654r radioisotopes used for, 1636Y1637
presurgical evaluation of patients with, 1452, in specific conditions
1470Y1475 brain tumor, 1638t, 1644
diffusion tensor imaging, 1472 cerebrovascular disease, 1638t, 1649Y1651,
functional MRI, 1472 1650f
MRI, 1471Y1472 congenital malformations, 1496
PET, 1472Y1473, 1474c, 1474f, 1644, dementia, 1637Y1641, 1638t
1646c, 1646f epilepsy, 1472, 1473Y1475, 1475f, 1476f,
SPECT, 1472, 1473Y1475, 1475f, 1476f, 1638t, 1645, 1646f
1645, 1646f statistical ictal SPECT coregistered to MRI
prevalence of, 1644 (STATISCOM), 1475, 1476f
urgent assessment of adults with new-onset subtraction ictal SPECT coregistered to MRI
seizures, 1452Y1454, 1453c (SISCOM), 1475, 1475c, 1475f, 1479r,
CT findings in specific etiologies, 1455tY1457t 1645, e24t
Sella turcica, 1575 parkinsonian syndromes, 1638t, 1645Y1649,
Sellar region disorders. See Pituitary and 1647f
parasellar disorders traumatic brain injury, 1638t, 1651Y1652, 1652f
Septooptic dysplasia, 1466f, 1490, 1490f, SIR (Society of Interventional Radiology) collateral
1511Y1512 circulation grading system, 1413, 1414f
Septum pellucidum, 1563 SISCOM (subtraction ictal SPECT coregistered to
absence of MRI), 1475, 1475c, 1475f, 1479r, 1645, et
in holoprosencephaly, 1490 Sixth nerve palsy, 1520, 1522c
in schizencephaly, 1487 Sjögren syndrome, 1628, 1631t, 1632f, 1635r
in septooptic dysplasia, 1466f, 1490f, 1511 Slab selection (MRI), 1384
Septum pellucidum cavum, 1554t, 1563 SLE (systemic lupus erythematosus), 1628, 1631t
1563f, 1573r Slice selection (MRI), 1384
cavum vergae and, 1563Y1564, 1564f Social Security act, 1686, 1688r
Sheehan syndrome, 1592 Society of Interventional Radiology (SIR) collateral
Short tau inversion recovery (STIR) imaging, circulation grading system, 1413, 1414f
1386, 1387 Solitaire With the Intention for Thrombectomy as
in acute disseminated encephalomyelitis, 1628f PRIMary Endovascular Treatment (SWIFT
of Chiari malformation and syringomyelia, 1494f PRIME) trial, 1412, 1416, 1416tY1417t
in epilepsy, 1388t Soustiel ratio, 1667, 1676r
in multiple sclerosis, 1510, 1512f, 1598f, Spatial encoding (MRI), 1384Y1385
1599, 1617 Sphenoid sinus mucocele, 1521, 1524
in neurocysticercosis, 1394f Spin echo MRI, 1384, 1385, 1388t, 1397r
in neuromyelitis optica, 1514c, 1514f, 1627f in epilepsy, 1459t
in patients with visual symptoms, 1501, 1509f in focal cortical dysplasia, 1392f
diplopia, 1516 of ganglioglioma, 1396f
multiple sclerosis, 1510, 1512f in multiple sclerosis, 1599, 1621f
neuromyelitis optica, 1514c, 1514f in patient with visual symptoms, 1502

of spinal infarction, 1393f Stroke imaging
Spina bifida, 1598 for acute ischemic stroke, 1399Y1420,
Spinal cord disorders, 1595Y1610, 1610rY1612r 1420rY1423r
advances in spinal cord imaging, 1610 for hemorrhagic stroke, 1424Y1448,
anatomy of spine and spinal cord, 1595Y1596, 1448rY1450r
1596f MRI, 1387, 1388t, 1389
congenital and developmental disorders, diffusion-weighted imaging, 1386, 1387, 1389f
1597Y1598 digital subtraction angiography, 1390f
infections, 1599Y1602 interpretation of, 1390
epidural abscess, 1599Y1601, 1611r perfusion-weighted imaging, 1389,
infective spondylodiscitis, 1599, 1601f 1389f, 1390f
viral myelitis, 1601 susceptibility-weighted imaging, 1389, 1390f
inflammatory demyelinating diseases, for wake-up stroke, 1389, 1407, 1409f, 1412
1598Y1599 Stroke Prevention in Sickle Cell Anemia (STOP)
multiple sclerosis, 1598Y1599, 1598f, trial, 1666, 1676r
1610rY1611r, 1617, 1618f, 1623 Study of Intravenous Thrombolysis with Alteplase
neuromyelitis optica, 1510, 1514c, 1514f, in MRI-Selected Patients (MR WITNESS), 1412
1599, 1627f Sturge-Weber syndrome, 1645
nutritional deficiencies, 1599, 1600c, 1600f Subarachnoid calcifications, 1571cY1572c, 1572f
intramedullary tumors, 1604Y1607 Subarachnoid cysts, 1572c, e23t
astrocytoma, 1604, 1605, 1605t Subarachnoid hemorrhage (SAH), 1427
ependymoma, 1604Y1605, 1605t, 1606fY1607f aneurysmal, 1433, 1438c, 1438f, 1439, 1439f,
hemangioblastoma, 1604, 1605Y1606 1449r, 1455t
locations of, 1604 in Churg-Strauss syndrome, 1453c, 1453f
metastatic lesions, 1604, 1606Y1607 convexity, 1453f, 1455t
other types of, 1606 due to intracranial dissection, 1436, 1440c, 1440f
myelopathy from extramedullary spine tumors, etiologies of, 1436
1607Y1608 imaging of, 1427, 1436, 1438cY1441c, 1438f,
myelopathy from spine trauma, 1609Y1610 1439, 1439f, 1442
principles of spinal cord imaging, 1596Y1597 CT, 1429c, 1429f, 1438fY1441f, 1439, 1442,
spondylotic myelopathy, 1608Y1609, 1609f 1449r, 1453c, 1453f
vascular lesions, 1602Y1604 in patients with new-onset seizures,
arteriovenous malformation, 1602Y1604, 1603f 1455t, 1456t
cavernous malformation, 1604 digital subtraction angiography,
ischemic lesions, 1602 1438cY1442c, 1438fY1441f, 1439, 1442
blood supply to spinal cord, 1602 Fisher Scale and modified Fisher Scale, 1428,
spinal cord infarction, 1393, 1393f, 1602, 1430t, 1449r
1603f, 1611r MRI, 1389, 1390f
Spinal nerve roots, 1595Y1596 transcranial Doppler ultrasound, 1432Y1434,
Spinal neurenteric cyst, 1554t, 1562Y1563, 1562f 1449r, 1656, 1666Y1667, 1667t, 1676r
Spins (MRI), 1380 posttraumatic, 1433, 1436
Split brain. See Schizencephaly Subclavian steal syndrome, 1657t, 1662
Spondylodiscitis, infective, 1599Y1601, 1601f Subcortical band heterotopia, 1464
Spondylotic myelopathy, 1608Y1609, 1609f Subcortical heterotopia, 1464
Spot sign of hematoma expansion (on CTA), Subdural empyema, 1447
1425, 1427, 1428c, 1428f, 1449r, 1455t Subdural hematoma, 1451, 1453, 1455t, 1456t
Squamous cell carcinoma, 1510f, 1520, 1521 Subependymal giant cell astrocytoma (SEGA),
Squamous epithelial cyst. See Epidermoid cyst 1539, 1540f
Stark Law, 1685Y1688, 1689r Subtraction ictal SPECT coregistered to MRI
Statistical ictal SPECT coregistered to MRI (SISCOM), 1475, 1475c, 1475f, 1479r, 1645, et
(STATISCOM), 1475, 1476f Susac syndrome, 1512, 1617, 1631t, 1633r
Status epilepticus, 1389, 1397r Susceptibility effects on MRI, 1381, 1385
STIR. See Short tau inversion recovery Susceptibility-weighted imaging (SWI), 1389,
(STIR) imaging 1391, 1395, 1397r
STOP (Stroke Prevention in Sickle Cell Anemia) protocols for, 1387, 1388t
trial, 1666, 1676r recommendations for ordering, e2Ye3
Streptococcus pneumoniae meningoencephalitis, in specific conditions
1526f, 1528r brain tumor, 1529, 1531t, 1533Y1535
String sign of carotid artery dissection CNS lymphoma, 1545
(on ultrasound), 1658 radiation necrosis, 1543

Neuroimaging
choroid plexus cyst, 1559 Tethered cord, 1598

hemorrhagic stroke, 1429, 1449r Thallium 201 (201Tl), 1636Y1637
cerebral amyloid angiopathy, 1389, Thallous chloride thallium 201, 1637
1435, 1436f Third nerve palsy, 1520
ischemic stroke, 1390f, 1399, 1407Y1409, 1412 infectious, 1526f, 1527
multiple sclerosis, 1626 subarachnoid, 1527
neurocysticercosis, 1570t Thrombectomy, intraarterial, 1400, 1404, 1408c,
seizures and epilepsy, 1458, 1459t 1420rY1422r
arteriovenous malformation, 1468 American Heart Association/American Stroke
spinal cord disorders, 1597, 1610 Association guidelines for, 1412
cavernous malformation, 1604 patient selection for, 1410Y1415
posttraumatic myelopathy, 1610 timing of, 1412
status epilepticus, 1397r Thrombolysis in Cerebral Infarction (TICI) score,
traumatic optic neuropathy, 1512 1408c, 1413, 1414f, 1415c, 1415f, 1416t
SWIFT PRIME (Solitaire With the Intention for Thumb sign of chordoma (on MRI), 1585,
Thrombectomy as PRIMary Endovascular 1585f, 1588t
Treatment) trial, 1412, 1416, 1416tY1417t Thyroid eye disease, 1516, 1517, 1519f
Sympathomimetic drugs, intracerebral hemorrhage Thyroid papillary carcinoma, intracerebral
due to, 1436, 1444Y1446 hemorrhage secondary to, 1447
Syphilis, 1513, 1606, 1637t Thyroid-stimulating hormone secretion, 1575, 1578t
Syringomyelia, Chiari malformation and, 1494f, TIA (transient ischemic attack), 1418, 1419c,
1495Y1496, 1495t, 1496f, 1498r, 1597, 1597f 1419f, 1420r
Systemic lupus erythematosus (SLE), 1628, 1631t TICI (Thrombolysis in Cerebral Infarction) score,
1408c, 1413, 1414f, 1415c, 1415f, 1416t
Time-of-flight magnetic resonance angiography,
T
1387, 1388t
in ischemic stroke, 1406, 1408cY1409c, 1409f, 1413
T1 (longitudinal relaxation) (MRI), 1382, 1383f in patient with hemichoreic movements, 1391f
effect of contrast agents on, 1386 Time-spatial labeling inversion pulse (Time-SLIP)
inversion recovery preparation, 1386 technique with balanced steady-state free
T1-weighted imaging (MRI) precession, 1502
dynamic contrast-enhanced imaging, 1386 Tissue plasminogen activator (tPA), 1415c, 1419c,
effect of contrast agents on, 1386 1423r, 1675r
image interpretation, 1390 neuroimaging for, 1404, 1405
imaging protocols for, 1387, 1388t CT, 1405
inversion recovery preparation, 1386 post-reperfusion management, 1418
signal intensity of lesion on, 1394Y1395, 1396f SPECT, 1651, 1654r
T1 weighting, 1385 ultrasound, 1665, 1675r
T2 (transverse relaxation) (MRI), 1382Y1384, 1383f patient selection for, 1404Y1405
effect of contrast agents on, 1386 patient selection for intraarterial
T2-weighted imaging (MRI), 1385 thrombectomy after, 1410Y1412, 1411f
201
dynamic susceptibility contrast imaging, 1386 Tl (thallium 201), 1636Y1637
image interpretation, 1390 ToF. See Time-of-flight
imaging protocols for, 1387, 1388t Tolosa-Hunt syndrome, 1520, 1520f, 1527
signal intensity of lesion on, 1395, 1396f Topiramate, 1481f
T2*, 1384 tPA. See Tissue plasminogen activator
T2 shine-through, 1406 TR (repetition time) (MRI), 1383f, 1385
Tabes dorsalis, 1602, 1632t Tractography, 1472, 1479r, 1481f, 1484, 1491,
Taenia solium infection. See Neurocysticercosis 1531t, 1536, 1551r, 1605, 1612r. See also
Takayasu arteritis, on ultrasound, 1661Y1662, Diffusion tensor imaging
1662f, 1675r Tram-track sign of optic nerve sheath meningioma
TBI. See Traumatic brain injury (on MRI), 1507
99m
Tc (technetium 99m), 1473, 1636Y1637 Transcranial color-coded duplex sonography
TCD. See Transcranial Doppler ultrasound to assess intracranial arteries, 1656, 1662, 1663f
TE (echo time) (MRI), 1385 in cerebrovascular disease, 1656, 1659f
Teardrop sign of orbital blow-out fracture (on MRI), in hemorrhagic stroke, 1425, 1432Y1434, 1434f
1520, 1521, 1521f in ischemic stroke, 1663f, 1664t, 1664
Technetium 99m (99mTc), 1473, 1636Y1637 Transcranial Doppler (TCD) ultrasound, in
Temozolomide, 1541c, 1544f, 1552r, 1643c cerebrovascular disease, 1433, 1449r, 1450r,
Teratoma, pineal region, 1396f 1656, 1664Y1668, 1674, 1675rY1676r

bubble test, 1666 in extracranial internal carotid artery stenosis,
carotid artery stenosis, 1660c, 1675r 1657, 1658t, 1659cY1661c, 1659f, 1660f
Current Procedural Terminology codes and in giant cell arteritis, 1662, 1663f
indications for, e18tYe19t in ischemic stroke, 1655, 1656Y1657, 1657t
detection of cerebral embolization and in Takayasu arteritis, 1661Y1662, 1662f
right-to-left shunts, 1666 in vertebral artery dissection, 1658, 1661,
detection of cerebral vasospasm after 1661f
subarachnoid hemorrhage, 1449r, 1666, in vertebral artery stenosis, 1657Y1658
1667t, 1676r Current Procedural Terminology codes and
to diagnose brain death, 1667Y1668, 1667t, indications for noninvasive vascular imaging,
1668f, 1676r e1, e18tYe20t
hemorrhagic stroke, 1425, 1432Y1433 fetal, to screen for congenital malformations,
intracranial arterial steal syndrome, 1665 1484, 1485
ischemic stroke, 1404t, 1662Y1666, 1664t, 1675r anencephaly, 1488
middle cerebral artery stenosis, 1664f holoprosencephaly, 1488, 1490
practice standards for, 1449r indications for, 1655
in sickle cell anemia, 1666, 1667t of intracerebral hemorrhage, 1449r
subarachnoid hemorrhage, 1433, 1449r, 1655, in movement disorders, 1655, 1668Y1671,
1666Y1667, 1667t, 1676r 1669t
vasomotor study, 1665Y1666 for differential diagnosis, 1669Y1671, 1671t
Transient ischemic attack (TIA), 1418, 1419c, Parkinson disease, 1668Y1669, 1671f
1419f, 1420r of peripheral nervous system, 1670Y1674, 1672f
Transmantle sign of focal cortical dysplasia brachial plexopathies, 1672Y1673
(on MRI), 1462f, 1463t, 1464 entrapment neuropathies, 1671Y1672, 1673t
Transverse magnetization (MRI), 1381, 1381f, carpal tunnel syndrome, 1671
1382, 1383f, 1384 cervical radiculopathy, 1672
Transverse relaxation (MRI), 1382Y1384, 1383f. fibular neuropathy, 1671Y1672
See also T2-weighted imaging radial neuropathy, 1671
Transverse venous sinus stenosis, 1503, inflammatory polyneuropathies, 1673Y1674
1504cY1505c, 1504f, 1506f Guillain-Barré syndrome, 1674
Traumatic brain injury (TBI) multifocal motor neuropathy, 1674
chronic traumatic encephalopathy due to, with vasculitis, 1674
1651, 1654r phrenic neuropathies, 1673
concussion, 1651Y1652 prenatal, 1484, 1485
CT in, 1456t spectral Doppler, 1656
MRI in, 1387, 1388t, 1389, 1397r transcranial color-coded duplex
neuromolecular imaging of, 1651Y1653, to assess intracranial arteries, 1656, 1659f,
1652f, 1654r 1662, 1663f
Tuberculosis, 1478r in cerebrovascular disease, 1656, 1659f
on MRI, 1470f, 1471f in hemorrhagic stroke, 1425, 1432Y1434, 1434f
seizures due to, 1468Y1470 in ischemic stroke, 1663f, 1664t, 1665
spinal, 1601Y1602, 1611r transcranial Doppler (TCD), in cerebrovascular
visual symptoms of, 1511, 1514 disease, 1449r, 1450r, 1656, 1662Y1668,
Tuberous sclerosis, 1464, 1465f, 1551r, 1645 1674, 1675rY1676r
subependymal giant cell astrocytoma and, bubble test, 1666
1539, 1540f carotid artery stenosis, 1661c, 1675r
Tumefactive demyelinating lesions, 1387, 1389f, coding for, e18t
1397r, 1529, 1536, 1621Y1623, 1621f, 1634r detection of cerebral embolization and
right-to-left shunts, 1666
detection of cerebral vasospasm after
U
subarachnoid hemorrhage, 1449r, 1666,
1667t, 1676r
Ultrasound, 1379, 1655Y1674, 1675rY1677r to diagnose brain death, 1667Y1668, 1667t,
advantages of, 1655 1668f, 1676r
B-mode, 1655Y1656 hemorrhagic stroke, 1425, 1432Y1434
in cerebrovascular disease, 1656Y1668 intracranial arterial steal syndrome, 1665
assessment of extracranial arteries, 1656Y1662 ischemic stroke, 1404t, 1662Y1666,
assessment of intracranial arteries, 1662Y1668 1664t, 1675r
cervical duplex, 1656f middle cerebral artery stenosis, 1664f
in carotid artery dissection, 1658 practice standards for, 1449r

Neuroimaging
in sickle cell anemia, 1666, 1667t mechanical causes of, 1503Y1506,

subarachnoid hemorrhage, 1433, 1449r, 1504cY1505c, 1505fY1506f
1655, 1666Y1667, 1667t, 1676r due to retrochiasmal lesions, 1515Y1516,
vasomotor study, 1665Y1666 1517f, 1518f
vascular, 1655Y1656, 1656f due to sellar/parasellar lesions, 1577
United States ex rel. Drakeford v. Tuomey craniopharyngioma, 1579Y1580, 1582c
Healthcare System Inc., 1686 meningioma, 1580Y1581
metastatic tumors, 1585Y1586
optic nerve glioma, 1586
V
pituitary adenoma, 1580c
localizing and nonlocalizing signs and
Vascular dementia, 1639, 1651 symptoms, 1500t
Vascular imaging, noninvasive, Current MRI evaluation of, 1499
Procedural Terminology codes and indications conventional and advanced techniques,
for, e18tYe20t 1499Y1502
Vasculitis, 1628, e12t, e14t orbital artifacts, 1502f
in Churg-Strauss syndrome, 1453c Vitamin B12 deficiency, 1599, 1611r, 1628,
intracerebral hemorrhage secondary to, 1434, 1631t, 1640c
1436, 1442c, 1455t Volumetric interpolated breath-hold examination
ultrasound of peripheral neuropathies (VIBE), 1502, 1502f, 1527r
associated with, 1674, 1677r von Hippel-Lindau syndrome, 1546, 1605, 1612r
Vasopressin, 1575, 1586
Vertebral artery dissection, on ultrasound, 1658, W
1661, 1661f
Vertebral artery stenosis, on ultrasound, 1657Y1658
Vertebral column, 1596, 1596f Wada test for language lateralization, 1472, 1479r,
VIBE (volumetric interpolated breath-hold 1538, 1551r
examination), 1502, 1502f, 1527r Wake-up stroke, 1389, 1407, 1409f, 1412
Viral myelitis, 1601 Wallenberg syndrome, 1524
Virchow-Robin spaces, 1573r Warburg theory for use of PET in oncology, 1642
dilated, 1554, 1554t, 1555f Warfarin, 1415c, 1437t, 1443f, 1444
neoplastic invasion of, 1507 West Nile virus infection, 1511, 1526f, 1528r
Visual symptoms, 1499Y1527, 1527rY1528r White matter abnormalities incidentally found on
anisocoria, 1521Y1527 MRI, 1627, 1630f
CT for, 1499, 1500f
differential diagnosis of visual loss, 1502Y1510, X
1500f
diplopia, 1516Y1521
x-axis (MRI), 1381, 1381f
due to optic chiasm abnormalities, 1512Y1515,
1515fY1517f
due to optic nerve abnormalities, 1503Y1512 Y
compressive/infiltrative causes of, 1503,
1506Y1510, 1507f, 1508cY1509c, 1508f, y-axis (MRI), 1381, 1381f
1510f, 1511f
hereditary, toxic/metabolic, traumatic, and
vascular causes of, 1511Y1512 Z
inflammatory causes of, 1510Y1511,
1512fY1515f, 1514c z-axis (MRI), 1381, 1381f

Neuroimaging
List of Abbreviations
11C Carbon 11 MADSAM Multifocal acquired demyelinating sensory
11C-FMZ Flumazenil ligands with a carbon-11 tracer and motor neuropathy
11C-PiB Carbon 11–labeled Pittsburgh Compound B MAG Myelin-associated glycoprotein
15O Oxygen 15 MAGNIMS Magnetic Resonance Imaging in Multiple Sclerosis
18F Fluorine 18 MCA Middle cerebral artery
99mTc Technetium 99m MCI Mild cognitive impairment
99mTc-HMPAO Technetium-99m-hexamethylpropylene amine oxime MMN Multifocal motor neuropathy
111In Indium 111
123I
MMSE Mini-Mental State Examination
Iodine 123
201Tl MOG Myelin oligodendrocyte glycoprotein
Thallium 201
AA Alzheimer’s Association MPRAGE Magnetization-prepared rapid acquisition
AAN American Academy of Neurology gradient-echo imaging
AD Alzheimer disease MR Magnetic resonance
ADC Apparent diffusion coefficient MR CLEAN Multicenter Randomized Clinical Trial of Endovascular
ADEM Acute disseminated encephalomyelitis Treatment for Acute Ischemic Stroke in the Netherlands
ADRDA Alzheimer’s Disease and Related Disorders Association MR WITNESS A Phase IIa Safety Study of Intravenous Thrombolysis
AES American Epilepsy Society With Alteplase in MRI-Selected Patients
AIDS Acquired immunodeficiency syndrome MRA Magnetic resonance angiography
ASITN American Society of Interventional and
Therapeutic Neuroradiology MRI Magnetic resonance imaging
ASPECTS Alberta Stroke Program Early CT Score MRV Magnetic resonance venography
AUROC Area under the receiver operating characteristic curve MS Multiple sclerosis
AVF Arteriovenous fistula MSA Multiple system atrophy
AVM Arteriovenous malformation MTT Mean transit time
B-mode Brightness-mode display
BENEFIT Betaferon/Betaseron in Newly Emerging NAA N-Acetylaspartate
Multiple Sclerosis for Initial Treatment NASCET North American Symptomatic Carotid
BOLD Blood oxygen level dependent Endarterectomy Trial
bSSFP Balanced steady-state free precession NF1 Neurofibromatosis type 1
CADASIL Cerebral autosomal dominant arteriopathy with NIA National Institute on Aging
subcortical infarcts and leukoencephalopathy NIHSS National Institutes of Health Stroke Scale
CCA Common carotid artery
CIDP Chronic inflammatory demyelinating NINCDS National Institute of Neurological and
polyradiculoneuropathy Communicative Disorders
CIS Clinically isolated syndrome NMO Neuromyelitis optica
CLIPPERS Chronic lymphocytic inflammation with pontine OCT Optical coherence tomography
perivascular enhancement responsive to steroids PD Parkinson disease
CMS Centers for Medicare & Medicaid Services PET Positron emission tomography
CMSC Consortium of Multiple Sclerosis Centers
CNS Central nervous system PiB Pittsburgh Compound B
CPT Current Procedural Terminology PML Progressive multifocal leukoencephalopathy
CSA Cross-sectional area PNS Peripheral nervous system
CSF Cerebrospinal fluid PRES Posterior reversible encephalopathy syndrome
CT Computed tomography PSP Progressive supranuclear palsy
CTA Computed tomography angiography
DAT Dopamine transporter RANO Response Assessment in Neuro-Oncology
DAWN DWI or CTP Assessment With Clinical Mismatch in the RCVS Reversible cerebral vasoconstriction syndrome
Triage of Wake-Up and Late Presenting Strokes rCBV Relative cerebral blood volume
Undergoing Neurointervention REVASCAT Randomized Trial of Revascularization With Solitaire FR
DEFUSE Diffusion and Perfusion Imaging Evaluation Device Versus Best Medical Therapy in the Treatment of
for Understanding Stroke Evolution Acute Stroke Due to Anterior Circulation Large Vessel
DLB Dementia with Lewy bodies Occlusion Presenting Within 8 Hours of Symptom Onset
DNET Dysembryoplastic neuroepithelial tumors RIS Radiologically isolated syndrome
DSA Digital subtraction angiography
DTI Diffusion tensor imaging rTPA Recombinant tissue plasminogen activator
DTPA Diethylenetriamine pentaacetic acid SAH Subarachnoid hemorrhage
DWI Diffusion-weighted imaging SIR Society of Interventional Radiology
ECG Electrocardiogram SISCOM Subtraction ictal SPECT coregistered to MRI
EEG Electroencephalogram SPACE Sampling perfection with application-optimized
E/M Evaluation and Management contrasts using different flip angle evolutions
EMG Electromyography
ESCAPE Endovascular Treatment for Small Core and Anterior SPECT Single-photon emission computed tomography
Circulation Proximal Occlusion With Emphasis on STATISCOM Statistical ictal single-photon emission computed
Minimizing CT to Recanalization Times tomography (SPECT) coregistered to magnetic
EVD External ventricular drain resonance imaging
EXTEND-IA Extending the Time for Thrombolysis in Emergency STIR Short tau inversion recovery
Neurological Deficits—Intra-Arterial STOP Stroke Prevention in Sickle Cell Anemia
FDA US Food and Drug Administration SWI Susceptibility-weighted imaging
FDG Fludeoxyglucose
FDG-PET Fludeoxyglucose positron emission tomography SWIFT Solitaire With the Intention for Thrombectomy
FLAIR Fluid-attenuated inversion recovery SWIFT PRIME Solitaire With the Intention for Thrombectomy
fMRI Function magnetic resonance imaging as Primary Endovascular Treatment
GABA γ-aminobutyric acid TBI Traumatic brain injury
GBS Guillain-Barré syndrome TCD Transcranial Doppler
GRE Gradient recalled echo TE Echo time
HCPCS Healthcare Common Procedure Coding System
HIV Human immunodeficiency virus TIA Transient ischemic attack
HTLV-1 Human T-cell lymphotropic virus type 1 TIBI Thrombolysis in brain ischemia
ICA Internal carotid artery TICI Thrombolysis in cerebral infarction
ICD International Classification of Diseases Time-SLIP Time-spatial labeling inversion pulse
ICD-10-CM International Classification of Diseases, Tenth Revision, TIMI Thrombolysis in myocardial infarction
Clinical Modification
Tmax Time to maximum
ICH Intracerebral hemorrhage
ICP Intracranial pressure TOF Time-of-flight
IgG Immunoglobulin G tPA Tissue plasminogen activator
IIH Idiopathic intracranial hypertension TR Repetition time
ILAE International League Against Epilepsy TTP Time to peak
IMSIII Interventional Management of Stroke III
VDRL Venereal Disease Research Laboratory test
INR International normalized ratio
IV Intravenous VIBE Volumetric interpolated breath-hold examination
MACRA Medicare Access and CHIP Reauthorization Act of 2015 WHO World Health Organization

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