Vascular malformations of the central nervous system

Authors

Robert J Singer, MD

Christopher S Ogilvy, MD

Guy Rordorf, MD Section Editor

Jose Biller, MD, FACP, FAAN, FAHA Deputy Editor

John F Dashe, MD, PhD

Last literature review version 17.1: January 2009 | This topic last updated: January 24,
2009 (More)

INTRODUCTION — Cerebral vascular malformations occur in 0.1 to 4.0 percent of the general
population [1,2] . Four general subtypes of congenital malformations have been described:

Developmental venous anomalies

Capillary telangiectasias

Cavernous malformations

Arteriovenous malformations

Developmental venous anomalies are most common in autopsy series, with an incidence of 2
percent [3,4] . This is followed by arteriovenous malformations (1 percent), capillary
malformations (telangiectasias, 0.7 percent), and cavernous malformations (0.4 percent).
Developmental venous anomalies and capillary telangiectasia are usually benign, while cavernous
malformations and arteriovenous malformations have a greater tendency toward neurologic
sequelae.

This topic will review our understanding of the natural history and treatment of these three
lesions, which continues to evolve with our burgeoning imaging capabilities and clinical
experience.

Cerebral and spinal cord arteriovenous malformations are discussed separately. (See "Brain
arteriovenous malformations" and see "Disorders affecting the spinal cord", section on Vascular
malformations).

DEVELOPMENTAL VENOUS ANOMALIES — Developmental venous anomalies (DVAs), also known

as venous angiomas, are composed of a radially arranged configuration of medullary veins
separated by normal brain parenchyma (most commonly white matter). These small venous
conduits empty into a central, dilated superficial or deep vein that drains the normal brain.
Microscopically, the venous structures appear largely normal with rare degenerative changes
consisting of thickening and hyalinization. The lesions do not occur in the diencephalon,
brainstem, or spinal cord.

DVAs most often are solitary, although multiple lesions have been described in association with
other clinical syndromes (eg, the blue rubber bleb nevus syndrome) [5] . DVAs also may occur
concurrently with cavernous malformations [6] . A second cerebrovascular anomaly has been
reported in approximately 19 percent of this patient population [7] .

Clinical presentation — DVAs are considered benign lesions, although they may uncommonly
present with seizures, progressive neurologic deficits, and hemorrhage [8-10] . Headache is the
most common presenting complaint, followed by seizures and sensory-motor phenomena.
However, a direct correlation between these symptoms and the existence of a DVA has not been
firmly established [11,12] . In a ten-year prospective clinical and magnetic resonance imaging
study, a symptomatic hemorrhage rate of 0.34 percent per year was observed [11] . The
hemorrhages were usually benign, although fatal intracranial hemorrhages have been described
[10] .

The most informative study retrospectively reviewed patients with presentations that could be
directly linked to vascular complications of DVAs but not to other pathologies [13] . Cases with
cavernous malformations were excluded because of the known association with DVAs. Seventeen
patients were identified, and a review of the literature published after the introduction of MRI
identified another 51 cases fulfilling the same criteria.

From these 68 cases, two major pathophysiologic categories of symptomatic DVAs were identified
[13] : Mechanical compression of intracranial structures by a component of the DVA was seen in
14 patients (21 percent). The most common associated symptoms were hydrocephalus, tinnitus,
brainstem deficits, hemifacial spasm, and trigeminal neuralgia Flow-related symptoms were
present in 49 patients (72 percent), with two subcategories:

- Increased inflow in 19 patients (28 percent), typically related to an arteriovenous

malformation (AVM) draining via dilated and ectatic medullary veins through a DVA, resulting in
headaches, neurologic deficits, seizures, and coma, usually secondary to parenchymal and/or
intraventricular hemorrhage

- Restricted outflow, either by an anatomic obstruction (eg, stenosis or thrombosis of the DVA
or its draining vein) in 26 patients (38 percent) or by a physiologic obstruction (eg, increased
venous pressure secondary to a distal arteriovenous shunt or AVM) in four patients (6 percent).
These mechanisms were associated with variable combinations of neurologic deficits, headaches,
seizures, and altered mentation. The clinical picture in several cases resembled that caused by
cerebral venous thrombosis, with increased intracranial pressure, venous congestive edema,
and/or intraparenchymal or subarachnoid hemorrhage No obvious alteration attributable to the
DVA was found to explain symptoms in six cases (9 percent)
Diagnosis — Cerebral angiography is considered the gold standard for the diagnosis of DVAs, but
they are usually identified with contrast enhanced cross-sectional imaging modalities such as
computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance
angiography (MRA).

Computed tomography — Nonenhanced CT scans do not usually demonstrate DVAs unless there is
an associated cavernous malformation. After contrast administration, the enlarged vein is all that
is typically identified. CT angiography (CTA) has also been used to identify DVAs [14] .

Magnetic resonance imaging and angiography — MRI typically shows medullary veins converging
on the dilated transcerebral vein. A characteristic "sunburst" pattern is seen on enhanced T1-
weighted images. MRA usually demonstrates the dilated venous channel with variable depiction of
the smaller medullary veins.

Angiography — As mentioned, cerebral angiography usually is not needed for the diagnosis of DVA
since axial imaging sequences on MRI often suffice to make the diagnosis. In atypical cases,
angiographic findings are pathognomonic; during the late capillary or venous phase there is a
paucity of normal veins in the region of the lesion and a characteristic "caput medusae"
appearance of the radially arranged small medullary veins (show radiograph 1). The arterial phase
is typically normal.

Treatment — DVAs should be treated conservatively in the vast majority of cases, with associated
symptoms such as headaches and seizures managed medically [12] . Surgery may be required in
the rare patient with hemorrhage associated with a DVA or with uncontrolled seizures [10] .

In patients who undergo surgery, preoperative contrast enhanced imaging is required to identify
an associated cavernous malformation [6] . Venous infarction has been reported with DVA
resection [15] ; thus, it is reasonable to simply evacuate the hematoma and leave the DVA in situ.
Radiosurgical and endovascular techniques do not have a defined role in the management of these
lesions.

CAPILLARY TELANGIECTASIAS — Capillary telangiectasias are small lesions most commonly found
in the pons, middle cerebellar peduncles, and dentate nuclei. Multiple lesions are common.

The lesions are composed of small, dilated capillaries devoid of smooth muscle or elastic fibers.
The intervening brain is often normal; it may also demonstrate areas of microhemorrhage or
gliosis. A common histopathological feature of these lesions is a dilated efferent system, probably
representing a venous channel.

An argument has been made for these lesions representing the early stage in the spectrum of
development of cavernous malformations and other "mixed" vascular malformations [16,17] .
Although not proven, angiogenesis is believed to play a role in lesion evolution. Most
telangiectasias represent an angiodysplastic phenomenon resulting from faulty embryogenesis of
the vascular wall and have been associated with angiomatous phacomatoses such as Osler-Weber-
Rendu (hereditary hemorrhagic telangiectasia), Louis-Bar (ataxia-telangiectasia), and Wyburn-
Mason (unilateral retinocephalic vascular malformation) syndromes [18] . (See "Hereditary
hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)", section on Cerebral AVMs and
section on Unilateral disease).

Clinical presentation — Capillary telangiectasias are usually clinically silent, found incidentally on
neuroimaging studies or at postmortem examination. Rare symptomatic cases occur [19] ;
headache, nausea, and seizures have been described in patients with these lesions, although a
causal relationship is unclear.

Diagnosis — MRI is the most sensitive imaging modality for the identification of capillary
telangiectasias. Low signal intensity "black dots" on T1 and T2-weighted imaging are suggestive,
although not diagnostic of these lesions.

Telangiectasias can be identified in the late arterial/early capillary phase of angiography as a faint
blush with an associated venous channel. Thus, these lesions can be distinguished from DVAs that
are visualized during the venous phase of the study.

Treatment — Capillary telangiectasias are nonoperable lesions.

CAVERNOUS MALFORMATIONS — Cavernous malformations (CMs) are also referred to as

cavernous angiomas, cavernous hemangiomas, or cavernomas. They may occur sporadically or in a
familial pattern [20] . In these populations, de novo lesions have been demonstrated on serial
MRIs. The de novo development of CMs after brain biopsy and after radiosurgery confirms the
evolutionary nature of the lesions [21] .

Three genetic loci (CCM1, CCM2, and CCM3) responsible for familial cavernous malformations
have been reported. Nearly all familial cases of cerebral cavernous malformation among Hispanic
Americans have been linked to a founder mutation of CCM1 localized to 7q [22-24] . Familial cases
in white non-Hispanic families have been linked to CCM2 at 7p15-p13 [25] and CCM3 at 3q25.2-
q27 [25,26] .

On gross examination, cavernous malformations have a characteristic "mulberry" appearance with

engorged purplish clusters. They vary from 2 mm to several centimeters in diameter. Microscopic
examination reveals that CMs are composed of dilated, thin walled capillaries with a simple
endothelial lining and a thin, fibrous adventitia. Elastic fibers and smooth muscle are not present
in the vessel walls. In the classic description of CMs, there is no intervening brain tissue between
the channels of the lesion [27] . However, this may not be an essential criterion of CMS, as one
histopathologic study of 71 CM cases noted intervening brain parenchyma in 50 (70 percent) [28] ,
and others have also noted intervening brain tissue in some fraction of cases [16,29] .
The immediately surrounding tissue is usually gliotic and hemosiderin-laden due to previous
hemorrhages. It contains dilated capillaries that may represent telangiectasias; this finding
supports the integrative concept of capillary telangiectasias and cavernous malformations
representing two ends of a spectrum in the development of cavernous malformations [16] .
Inflammation, calcification and, rarely, ossification may be identified with CMs, usually in larger
lesions [30] .

Developmental venous anomalies (DVAs) may be associated with CMs. (See "Developmental
venous anomalies" above). In a series of 102 patients, DVAs associated with CMs were found in 23
percent; these occurred more often with lesions in the posterior fossa than the supratentorial
compartment [6] . A later series of 57 patients with CMs found associated DVAs in 25 percent, and
atypical patterns of venous drainage associated with CMs were seen in an additional 35 percent
[31] .

The cerebrum is the most common location for CMs (70 to 90 percent) [32] . They have been
reported throughout the supratentorial compartment, but most commonly are subcortical and
predisposed to the rolandic and temporal areas. Posterior fossa lesions comprise approximately 25
percent of CMs in most large series, with the majority located in the pons and cerebellar
hemispheres. There have been only 36 cases of spinal cord cavernous malformations reported in
the literature [33] .

Clinical presentation — CMs occur with equal frequency in males and females, with a mean age of
30 to 40, although women more commonly present with hemorrhage and neurologic deficits
[34,35] . CMs that are associated with DVAs or atypical venous drainage may be more likely to
present with symptomatic hemorrhage than CMs that are not associated with venous anomalies
[31] . The presentation of CMs is specific to their location. Supratentorial CMs commonly present
with hemorrhage, seizures, and progressive neurologic deficits. Annual bleeding rates of 0.25 to
1.1 percent have been reported in several large series [35,36] . Seizures and progressive
neurologic deficits may be the result of mass effect and secondary compromise of the
microcirculation, or of microhemorrhages with local hemosiderin deposition irritating cortical or
subcortical tissue. Infratentorial CMs commonly present with hemorrhage and progressive
neurologic deficits. Lesions in the brainstem present with cranial neuropathies and long-tract signs
that cause progressive neurologic decline due to the high volume of critical nuclei and fiber tracts
in this area. Thus, the natural history of brainstem lesions is worse than that of lesions in other
areas. The annual bleeding rate for brainstem lesions is 2 to 3 percent per year, with recurrent
hemorrhage rates approaching 17 to 21 percent [21] . Progressive neurologic decline is observed
in 39 percent.

The natural history of asymptomatic lesions is significantly different from CMs presenting with
clinical sequelae. A prospective study of 122 patients (mean age 37 years, range 4 to 82 years)
found that 50 percent were initially asymptomatic [37] . At a mean follow up of 34 months, the
hemorrhage rate in asymptomatic and symptomatic patients was 0.6 and 4.5 percent,
respectively. This study did not find that gender or lesion location influence prognosis, although
others suggest that female gender and infratentorial location are risk factors for subsequent
neurologic disability [36,38] . Lesion size and multiplicity do not appear to influence prognosis.

Diagnosis — Blood flow through CMs is minimal. Thus, they may not be seen on angiography and
often are referred to as "angiographically occult." Other imaging modalities, particularly MRI, play
a more important role in the diagnosis [20] .

Magnetic resonance imaging — MRI usually establishes the diagnosis of cavernous malformation.
Characteristic findings on T-1 and T-2 weighted images include a "popcorn" pattern of variable
image intensities consistent with evolving blood products (show radiograph 2). A dark hemosiderin
ring, best seen on T2 or gradient echo sequences at the periphery of the lesion, is suggestive of
remote hemorrhage (show radiograph 3). Lesions that mimic CMs on MRI include low grade
gliomas, hemorrhagic metastases (particularly melanoma), and choriocarcinoma [33] .

Contrast enhanced images should be obtained once a CM is identified in order to delineate any
potential associated DVAs [6] . Contrast enhanced images often demonstrate DVAs since they are
associated with normal flow. On the other hand, CMs may have only scattered enhancement that
is variable and inconsequential. This is critical in surgical planning since the resection of DVAs may
compromise normal cortical venous drainage patterns and lead to venous infarction [15] .

Computed tomography — CT usually demonstrates a nonspecific, irregular, hyperdense mass with

variable degrees of calcification. A faint perilesional blush with contrast administration is a variable
and nonspecific finding.

Angiography — CMs demonstrate a capillary blush or early draining vein in approximately 10

percent of patients [32] . These findings may be similar to the angiographic appearance of
meningiomas. Digital subtraction angiography appears to be much more sensitive than MRI for
detecting the presence of CM-associated atypical venous drainage [31] .

Treatment — Asymptomatic CMs are observed, irrespective of location. Indications for surgical
resection of accessible symptomatic cerebral and cerebellar lesions include progressive neurologic
deficit, intractable epilepsy, and recurrent hemorrhage. One group reported excellent or good
surgical outcomes in 97 percent of 65 patients with cerebral and cerebellar CMs at a mean follow-
up of one year [32] . A poor outcome was reported in 1.5 percent with an overall mortality of 1.5
percent. In a case series of 168 patients with symptomatic epilepsy attributed to CM, more than
two-thirds of patients were seizure free at three years after surgery [39] . Predictors for good
outcome included mesiotemporal location, size <1.5 cm, and the absence of secondarily
generalized seizures. Another series identified a long preoperative seizure history and poorer
preoperative seizure control as unfavorable prognostic indicators [40] .

Surgically inaccessible lesions — Patients with symptomatic CMs entirely surrounded by eloquent
tissue (eg, rolandic cortex, brainstem, thalamus/basal ganglia) are usually observed despite the
poor natural history associated with untreated brainstem and thalamic lesions.
Stereotactic radiosurgery is a potential alternative to conservative therapy in patients with such
surgically inaccessible lesions, and the available evidence suggests that it does lead to a reduction
in hemorrhage, especially two years or more after radiosurgery [41-44] . Nevertheless, high
complication rates in available published series coupled with clinical experience has dissuaded
many from using stereotactic radiosurgery for the treatment of CMs. (See "Stereotactic cranial
radiosurgery and radiotherapy" and see "Complications of cranial stereotactic radiosurgery",
section on Late reactions).

As an example, one retrospective analysis of 95 patients with 98 lesions found that stereotactic
radiosurgery was associated with a significant drop in the annualized hemorrhage rate from 17 to
5 percent after a two-year post-treatment latency period [42] . However, at an average follow-up
of 5.4 years, the incidence of permanent neurologic deficit and mortality was 16 and 3 percent,
respectively, and these complications were attributed to radiation-induced injury. In addition, the
combined effects of radiation-related injury and clinical progression of the lesion led to a
significant decline in neurologic function during follow-up.

Given the available data, we suggest not using stereotactic radiosurgery for the treatment of CMs.

Brainstem location — Brainstem CMs often are treated due to their aggressive natural history
when there is progressive neurologic deterioration, with or without recurrent hemorrhage, if the
lesion lies near the pial surface or if a non-eloquent tissue corridor exists to the lesion [45] . In one
series of 23 patients with surgically treated brainstem CMs, 46 percent had transient neurologic
deficits, 17 percent had new or worsened deficits, and 83 percent were significantly improved at a
mean follow-up of 3.9 years [33] . In a second retrospective analysis, no or only slight neurologic
deficit was reported in 67 percent of 30 patients treated conservatively compared with 84 percent
of 93 patients treated surgically [21] . Microsurgical techniques are also being used with success in
some centers [46] .

ARTERIOVENOUS MALFORMATIONS — Arteriovenous malformations (AVMs) are the most

dangerous congenital vascular malformations. This topic is discussed separately. (See "Brain
arteriovenous malformations").

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