Applied Radiology

Dr. Goyal and Dr. Willinsky are in the Department of Medical Imaging at the Toronto Hospital, Western Division, in Toronto, Ontario, Canada.

V ascular diseases of the venous system in the central nervous system (CNS) are less well understood than the arterial disorders, and often, venous disorders are considered late in the differential diagnosis. The onset of venous diseases often is insidious. With the ability to recognize the signs of venous abnormalities on imaging, the radiologist may be the first to suggest the appropriate diagnosis. Commonly encountered venous disorders in clinical practice which have radiological significance are venous occlusive disease and venous thrombosis, Sturge-Weber syndrome, dural arteriovenous fistula and venous congestive encephalopathy, cavernomas, and developmental venous anomalies (DVAs).

Venous occlusive disease

Occlusive disease of the cerebral veins or sinuses may be the result of trauma, invasion by tumor, infection or thrombosis in hypercoagulable states; occasionally no cause is discernible. Cerebral vein thrombosis is a frightening event because of the severity of
clinical manifestations and the high mortality rate, estimated to be 5 to 30%. ^1,2 Clinically, the disease can have a variable presentation ranging from a subtle headache to impaired consciousness. Broadly speaking, the symptoms are either related to raised intracranial pressure (ICP), taking the form of headache, nausea and vomiting, and papilledema, or are due to a venous infarct and/or bleed within the brain parenchyma.

Depending on the location of the infarct and/or bleed, the clinical presentation may be focal neurological deficit, seizure, or altered level of consciousness. Most often, presentation is acute, with symptoms present for less than 7 days. Rarely, however, a subacute or chronic presentation is seen in the form of benign intracranial hypertension (pseudotumor cerebri). Common predisposing conditions include infection (such as mastoiditis which most often results in transverse sinus thrombosis), polycythemia, malignancy, peurperium, dehydration, oral contraceptive use, inflammatory bowel disease, head injury, and diabetes mellitus. ² In clinical practice, the most commonly seen conditions are peurperium and dehydration. These two groups of patients also represent the group in which the disease is obviously preventable in most situations. No predisposing factor can be found in approximately 30% of patients. ²

Diagnosis often is based on imaging, and in this scenario the radiologist would be the first person to consider the condition. Findings of venous occlusive disease, although subtle, are quite characteristic on CT. These include the presence of hyperdense venous sinuses or the "cord sign" on a noncontrast CT scan. On a post-contrast scan, the "empty delta sign" is seen in cases of superior sagittal sinus thrombosis, which represents the enhancing menin geal venous tributaries and other collateral venous channels around the non-enhancing sinus. ³

Another common manifestation is the presence of hemorrhagic infarcts. These typically have a non-arterial distribution, and may be bilateral in cases of thrombosis of midline structures such as the superior sagittal sinus (bilateral parasagittal infarcts) or straight sinus (bilateral thalami) (figure 1). Also, venous hemorrhagic infarcts typically are associated with significant perifocal edema and mass effect. Consequently, venous infarcts may simulate hemorrhage within a tumor (figure 2A).

Maintaining a high index of suspicion, correlating with the clinical scenario, and obtaining additional investi-
gations such as MRI may be useful in differentiating venous infarcts from other causes of hemorrhages. The location of the lesion may be another indicator of a venous infarct. For example, the presence of a hemorrhagic lesion within the lateral part of the temporal lobe should raise the suspicion of transverse sinus thrombosis, as this part of the brain drains into the transverse sinus via the vein of Labbe (figures 2-4).

MR allows direct visualization of the major venous channels and is now the imaging modality of choice for suspected venous thrombosis. Thrombus often is visualized on spin-echo MR imaging within the vascular channels (figures 3A,3B,4C). An MR venogram allows excellent visualization of the major sinuses (figure 4D). Detection of cortical vein thrombosis in the absence of involvement of the sinuses may be difficult on MR; however, the diagnosis of a venous infarct may be suggested on the basis of imaging features.

Angiography, although still considered the gold standard, is rarely performed. Indications for angiography include suspected cortical vein thrombosis or when therapeutic intervention is planned. Findings on angiography include filling defects within the veins, venous occlusion, presence of venous collaterals, and a pseudophlebitic pattern of the veins draining the normal brain parenchyma (figure 2C). In cases of chronic thrombosis, there may be evidence of recanalized sinuses which demonstrate an irregular outline.

The first line of management for venous occlusive disease is hydration and administration of heparin (even in the presence of hemorrhage on imaging). Thrombolysis should be considered only if there is deterioration of the clinical status despite therapeutic levels of heparin. Patient selection criteria for thrombolysis are difficult to determine, as the outcome of the disease is variable and dependent on the location of thrombosis. For example, extension into the deep venous system and into the cerebral veins is a poor prognostic sign. ⁴ Conversely, in one series, 71% of patients with cerebral venous thrombosis affecting the dural sinuses made a complete recovery and there was a 10% mortality rate. ¹ In another series of 28 patients presenting with deep vein thrombosis, 37% made a full recovery, 26% had deficits, and 37% died. ⁵ In a series of seven patients who failed a trial of medical therapy, direct thrombolytic therapy resulted in clinical improvement in six patients. ⁶

Sturge-Weber syndrome

Sturge-Weber syndrome is most frequently a sporadic, noninherited abnormality consisting of a facial venular malformation (port-wine stain), letomen ingeal venous angiomatosis, seizures, dementia, hemiplegia, hemianopsia, buphthalmos, and glaucoma. The topography of the facial malformation does not predict the cerebral lesion. The cortical lesion arises from an early thrombosis of the medullary veins, leading to a congestive post-ischemic venous atrophy and eventually calcification.

CT imaging of this disorder demonstrates atrophy and linear gyral calcification (tramtrack on plain films). The findings are more classical on MR, although calcification may be difficult to identify. Typical findings include presence of cerebral atrophy, typically found in the occipital/parietal lobes with T2 darkening (hemosiderin staining), and pial and leptomeningeal enhancement or congestion. ⁷

Cranial dural arteriovenous fistula and venous congestive encephalopathy

Although intracranial dural arteriovenous fistulas (DAVFs) are not strictly considered venous vascular disease, their clinical presentation, as well as the decision regarding patient management options, are most often a result of the venous expression of the disease. Presentation of benign DAVFs often relates to the location of the fistula and includes tinnitus, cranial nerve palsies, and/or signs related to venous hypertension in the orbit. ^8,9

Imaging features of DAVFs are variable and are dependent on the location of the fistula, the resultant effect on the veins, and on the drainage of the surrounding normal brain parenchyma. CT often is nondiagnostic and may show only the effects of the disease, such as parenchymal hematoma, proptosis, or dilated venous channels, rather than the disease itself. Presence of a dural arteriovenous malformation (AVM) usually is obvious on MR by the presence of multiple flow voids in the vicinity of the fistula (figure 5A). Manifestation of venous drainage may be proptosis with a dilated superior ophthalmic vein in the case of cavernous sinus DAVMs, or may be hydrocephalus and an acquired Chiari malformation in posterior fossa fistulae. In patients with neurological deficits due to DAVFs with venous congestive encephalopathy (VCE), MR may show diffuse edema in the white matter in addition to the flow voids (figure 5B). ¹⁰ These patients may present with nonspecific symptoms such as dementia. Rarely, the congested brain may show diffuse enhancement after administration of gadolinium which is different from the enhancement pattern of many neoplasms (figure 6A).

When MR findings suggest a DAVF, selective angiography, including all dural branches, is mandatory. The value of a good quality angiogram performed by an experienced angiographer with selective injection into every dural branch cannot be overstressed. If the clinical suspicion of a DAVF is high, angiography should be performed, even in the absence of MR abnormality.

Intracranial dural arteriovenous fistulae have been grouped into two categories--benign or aggressive--based on the presence or absence of retrograde leptomenin-
geal venous drainage (RLVD) (figures 5C,6B,6C). ^8,11 Aggressive DAVFs with RLVD may have a similar presentation to the benign type, or they may present with an intracranial bleed, progressive neurological deficit, or seizure. ^9,11,12 In 1986, Lasjaunias and coworkers demonstrated that focal neurological deficits are related to the territory of the venous reflux. ¹² Awad and coworkers, in their review of 360 cases from the literature prior to 1990, found that RLVD, venous ectasia, and Galenic venous drainage correlated with intracerebral hematoma (ICH) and nonhemorrhagic neurological deficit (NHND) at presentation. ⁹

A comprehensive classification of DAVFs based on angioarchitecture was first proposed by Djindjian et al in 1977. ¹³ In 1995, this scheme was modified by Cognard et al in a review of their own series of 205 patients. Cognard was able to show a relationship between type and presentation; ¹⁴ a similar but simplified version of this classification was proposed by Borden et al in 1995. ¹⁵ In 1996, Davies et al confirmed the validity of these classification systems by showing a highly significant correlation between either the Borden type or the Cognard type and presentation with either ICH or nonhemorrhagic neurological deficit. ¹⁶

In DAVFs, aneurysmal venous drainage has a higher incidence of bleeding on presentation compared to those without aneurysmal enlargement. ^9,14 Sinosal drainage with retrograde flow in the venous sinuses but no cortical venous drainage can result in raised intracranial pressure. ¹⁴ Davies et al, in their study of the natural history of the DAVF, confirmed the benign course of those DAVFs that have sinosal drainage only and the aggressive course of those with cortical venous drainage. ¹⁶

The presence or absence of retrograde leptomeningeal venous drainage is an important determinant in treatment planning. The sine qua non in management of DAVFs is that those with RLVD must be cured and those without may be followed clinically or partially treated for symptom palliation. ^8,11 Treatment involves either surgical disconnection of the refluxing vein or obtaining the same result by the endovascular route. The most commonly used embolic agents include polyvinyl alcohol (PVA) and N-butyl cyanoacrylate (NBCA).

Cavernomas

Cavernomas are the only true venous malformations. Their incidence is 0.4% and they can be found in the brain or spinal cord. ¹⁷ About 80% are supratentorial, with the frontal and temporal lobes being the most frequent sites. ¹⁸ They are angiographically occult, except in rare instances at the time of a bleed where venous "puddling" has been demonstrated. Cavernomas have a strong association with developmental venous anomalies (DVAs). ^19,20 Fundamentally stable, they can grow by confluence of vascular spaces often related to intralesional bleeds or thrombosis. In the familial forms, which are often multiple, an anomaly of endothelial growth factor has been identified. Additionally, there is an autosomal dominant inheritance.

MR has been found to be a sensitive tool in the diagnosis of cavernomas. They typically are seen as well-defined, lobulated lesions with a central core of reticulated, mixed signal intensity surrounded by a rim of signal hypointensity (figures 7-9). Use of the correct imaging sequences is key to the diagnosis. A gradient-echo sequence which enhances the magnetic susceptibility effects should be a part of the imaging protocol of every patient with a bleed. On this sequence, cavernomas are seen as black lesions. Size measurement is inaccurate on this sequence due to the "blooming effect" (figure 10). ²¹

Cavernomas produce symptoms either by hemorrhage (figure 11) or thrombosis. Hemorrhage outside the cavernoma generally is not observed at surgery, even in the face of a perilesional bleed evident at MR. Subacute blood seen outside the hemosiderin ring on MR is found, at surgery, to be contained by a thin capsule. Hemosiderin staining in the adjacent parenchyma has been found at autopsy, suggesting diapedesis or "slow ooze" of blood products through the endothelial lining. The presence of significant mass effect indicates either leaking of blood into potential spaces within the cavernoma or acute thrombosis. Perilesional bleeds may result from extravasation into the potential crevasses in the periphery of the lesion; perilesional edema is likely related to the sudden expansion of the lesion, compromising local blood flow.

Turjman et al demonstrated the value of MR in identifying a cavernoma as the underlying cause of an intracerebral hematoma. ²² It is not our present practice to perform angiography when cavernomas are discovered on MR. Serial MR images demonstrate that cavernomas can be dynamic lesions with active and regressive changes. Additionally, serial MR images are helpful in cases of an acute intracerebral hematoma, wherein the cavernoma may be seen on a follow-up study though it was completely obscured by the bleed in the original study.

Zabramski grading has alerted us to the various morphologies of cavernomas. ²³ From our analysis, however, this grading has not been useful in predicting future bleeds. ²⁴ Gender or multiplicity was not associated with higher bleeding rates. In our series we did find a high bleeding rate (10.9%) in the posterior fossa. ²⁵ Therapeutic options, as of now, are limited to surgery. Endovascular techniques have no established role, and radiation, including stereotactic radiotherapy, has not proven to be useful.

Developmental venous anomalies (DVAs)

DVAs originally were classified as malformations and often were referred to as venous angionias. It has become clear that DVAs represent extreme variations of the venous drainage of the cerebral or cerebellar hemispheres. They drain normal brain, and the circulation time is normal. Their association with cavernomas is well known, and the cavernomas may account for the symptomatology seen when these entities are discovered. ²⁶ A recent study described the prospective hemorrhage rate of 0.34% per year for DVAs. ²⁶ The authors felt that this represented a complication of an underlying but as yet undetected cavernoma. AR