Engorgement of Deep Medullary Veins in Neurosarcoidosis: A Common-Yet-Underrecognized Cerebrovascular Finding on SWI

Discussion

Deep medullary veins constitute the major draining route of cerebral white matter.¹² They have a typical perpendicular arrangement relative to the long axis of the lateral ventricles and a radial distribution along the atria and frontal horns, with a fine and uniform caliber and several zones of convergence that lead to the subependymal veins and ultimately the dural sinuses.¹³

In this study, we found that DMVE is a common finding in neurosarcoidosis, though not as yet recognized as a distinct cerebrovascular manifestation.⁵ It was significantly more common in men, consistent with cerebrovascular manifestations of sarcoidosis being more frequent in this group.⁵ DMVE came to our attention owing to its conspicuity on SWI, a sequence that is now widely available and was originally developed as a means for MR venography.¹⁴ A recent review showed 1 case with mild periatrial DMVE in a typical radial configuration on SWI; however, the presence of engorgement itself was not described.⁵

The pathophysiology of engorgement is uncertain but does not appear to be directly caused by downstream venous occlusion because dural sinuses and deep cerebral veins were patent in almost all our patients. Although there was no evident cortical thrombosis, we did notice a relative paucity of cortical veins along the cerebral hemispheres in some patients from both groups, which raised the question of whether abnormalities in the cortical veins could explain the appearance of DMVE. We did not find a significant difference in the number of visualized cortical veins between groups, but this could be an effect of sample size, and a difference may manifest itself in a larger population. Previous studies have proposed congestion of deep medullary veins as a potential indirect sign of dural sinus thrombosis.^{12,15⇓–17} However, other than 2 cases published by Taoka et al¹² and D'Amore et al,¹⁷ most reports do not convincingly demonstrate the characteristic parallel or radial anatomy seen in our patients. Comparison with such studies is limited because they lacked SWI. In our cohort, 1 patient with DMVE had chronic nonocclusive thrombus in the torcula, and we do not know whether it may have contributed to vascular engorgement. Thrombus can also show prominent hypointense signal on SWI¹⁸ and could potentially be difficult to distinguish from venous engorgement solely on the basis of that sequence. Although attributing our finding to venous engorgement rather than thrombosis was relatively straightforward based on its SWI appearance and lack of “blooming” artifacts, we also confirmed it by the corresponding contrast enhancement.

There was a higher incidence of perivascular space involvement in the group of patients with DMVE than in those without. Neurosarcoidosis is thought to spread to the CNS via the hematogenous route and has a tendency to disseminate along perivascular spaces, though the reason for this particular distribution is unknown.¹⁹ Recent studies have drawn attention to the presence of a glial-based vascular or “glymphatic” pathway for cerebral clearance of solutes and metabolic by-products that is heavily dependent on aquaporin-4 water channels.^{20⇓⇓⇓–24} In vivo and ex vivo experiments have shown rapid periarterial influx of CSF driven by arterial pulsations into the brain parenchyma, subsequent exchange with interstitial fluid, and final paravascular clearance along draining veins.²³ Whether the glymphatic system plays a role in patients with neurosarcoidosis who have parenchymal or perivascular disease has not been established to date, and we do not know whether such a pathway could have influenced the development of DMVE. There is also significant controversy regarding the direction of interstitial fluid clearance and the specific anatomic space where it occurs, with other studies demonstrating primarily intramural outflow along the basement membranes of arteries and not veins.²⁵ This is an area of intense research,²⁶ and it is likely that evidence of the role of the glymphatic system in the pathogenesis of autoimmune and inflammatory disorders of the CNS will continue to accumulate in the near future.

Histopathologically, granulomatous infiltration of arterial and venous walls and perivascular tissues in neurosarcoidosis can be indistinguishable from primary CNS angiitis.⁵ Notably, venous involvement is more common around the ventricles,²⁷ territory drained by the medullary veins. In some cases, there may be an inflammatory infiltrate with extensive endothelial damage in the absence of granulomas.²⁸ These pathologic alterations may result in narrowing or obliteration of the vessel lumina¹⁹ and may possibly contribute to the engorged appearance of deep medullary veins through some degree of venous impedance.

Previous reports of primary CNS angiitis have shown a similar pattern of radial enhancement of deep medullary veins.^29,30 However, it is difficult to assess how much of the linear enhancement in those patients was related to venous engorgement versus perivascular disease because no SWI was performed and findings resolved after treatment. In our study, contrast enhancement was likely a combination of perivascular disease superimposed on engorged vessels. While most patients with DMVE did not show discrete perivascular nodular enhancement, small intramural or transmural changes may have been present but beyond the capabilities of conventional MR imaging to resolve. Furthermore, there was no difference in leptomeningeal enhancement between patients with and without DMVE, and those with marked leptomeningeal disease burden were not more likely to fall into either category.

Deep medullary veins can also be prominent in ischemic stroke, in which mild prominence of deep medullary veins has been linked to hypoperfusion and poor outcomes.^31,32 In that setting, they are presumed to be a manifestation of an increased regional oxygen extraction fraction leading to elevated deoxyhemoglobin in the draining veins. Studies have also suggested that this finding may be a predictor of hemorrhagic transformation in patients treated with intravenous tissue plasminogen activator.^33,34 A similar appearance has also been described in Moyamoya disease, in which it has been correlated with severity.³⁵ However, this so-called “brush sign” is relatively subtle, and none of the published cases have shown the degree of tortuosity and engorgement that was evident in our patients, in whom the process appears to be longstanding and potentially irreversible. Therefore, it is unlikely that the presence of DMVE is a direct result of perfusion changes in neurosarcoidosis. Nevertheless, we did not perform perfusion imaging, and additional research may be worthwhile.

Intracranial hemorrhage is rare in neurosarcoidosis and typically presents as microhemorrhages, likely a reflection of small-vessel disease.^5,7,36 Hemorrhage is thought to result from destruction of the vessel wall by granulomatous inflammation, and 1 previous report documented venous rupture on histopathology.³⁶ In our study, most patients with DMVE had microhemorrhages. These were significantly more common in this group and did not seem to be an effect of patient age. Notably, there was 1 instance of macrohemorrhage that occurred in a patient with DMVE.

Hydrocephalus is seen in 10% of patients with neurosarcoidosis and is associated with high mortality.^6,37 It can result from decreased CSF resorption, obstruction from meningeal or subependymal disease, or adhesions with ventricular entrapment.^2,38,39 We found that hydrocephalus was much more frequent in patients with DMVE, and it is possible that these are manifestations of a more aggressive sarcoid phenotype. We did explore whether patients with DMVE had worse neurologic outcomes, but there was no significant difference in modified Rankin Scale scores at initial evaluation or follow-up.

The main limitations of this study are inherent in its retrospective nature, with heterogeneity in follow-up times and treatment paradigms. Studies were performed on different field magnets, which likely had an effect on the conspicuity of DMVE. Additionally, conventional postcontrast MR imaging likely underestimates vascular/perivascular disease in the background of engorged enhancing vessels. Finally, sample size was relatively small, and it is possible that specific clinical associations may come to light in larger studies.

In conclusion, DMVE is a frequent manifestation of neurosarcoidosis and was seen in about one-third of patients. It does not appear to be secondary to venous thrombosis in most patients and could be an indirect effect of venous and perivenous inflammation resulting in increased venous impedance. In our cohort, this finding was associated with an increased prevalence of microhemorrhages and hydrocephalus, but patients with this finding did not have worse neurologic outcomes. Being a relatively common finding, DMVE might prompt the reader to consider a diagnosis of neurosarcoidosis in challenging cases.