Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis Patients Is Challenged
Abstract & Commentary
By Susan Gauthier, DO, MS, Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College. Dr. Gauthier reports no financial relationships relevant to this field of study.
Synopsis: In a study of extracranial and transcranial color-coded sonography, there was no impairment of cerebral venous drainage in patients with multiple sclerosis as compared to healthy controls.
Source: Doepp F, et. al. No cerebral venous congestion in patients with multiple sclerosis. Ann Neurol 2010;68:173-183.
Within the last two years, a new hypothesis regarding multiple sclerosis (MS) has been proposed that directly challenges the widely accepted view that MS is caused by the peripheral activation of auto-reactive lymphocytes. This recent hypothesis is based on an impairment of cerebral venous drainage, which leads to an immune response secondary to the back flow of blood; this has been termed chronic cerebrospinal venous insufficiency (CCSVI) by Zamboni and coworkers.1 The same authors published a small open-labeled study of endovascular angioplasty and reported a modest stabilization in relapsing patients. CCSVI has become a worldwide phenomenon with institutions offering endovascular procedures to patients with MS before any replication of the findings, and certainly well before its relationship (cause or effect) to MS was properly explored. In this recent investigation by Doepp et al, the authors attempted to replicate the original observations made by Zamboni and coworkers.
Fifty-six patients with MS41/56 with relapsing disease and the remaining with secondary progressive MSand 20 age- and sex-matched healthy controls were studied with extracranial and transcranial color-coded sonography in the supine and upright positions. The following variables were measured: cerebral blood flow (arterial blood flow in the internal carotid arteries and vertebral arteries in the supine position), internal jugular vein (IJV) and vertebral vein (VV) flow, IJV valve incompetence, intracranial venous flow, and lastly, assessment of the five CCSVI criteria. The evaluation of IJV and VV flow included analysis of the following: the time-averaged blood flow velocity, their cross-sectional area (CSA), and blood volume flow (BVF). Cerebral blood flow and intracranial venous flow were similar between MS patients and controls. Both groups had a similar supine BVF of both IJV and VV as well as a pattern of a decrease in IJV BVF and an increase in VV BVF with an upright position; however, the decrease of IJV BVF was significantly less as compared to patients. CSA in supine and upright positions was similar between the two groups. Ten patients and 4 controls fulfilled 1 of 5 CCSVI criterion (no statistical difference) and no subjects met more than 2 criteria.
Commentary
Doepp et al found no differences in cerebral blood flow or venous drainage between patients with MS and healthy controls. Therefore, their results directly contradict the work reported by Zamboni and coworkers. Interestingly, there was a higher IJV BVF in MS patients in the upright position, which the authors speculate may be related to autonomic vascular dysregulation. However, this observation suggests a better than normal venous drainage in MS patients, compared to controls. As pointed out by the authors, the work published by Zamboni et al appeared to be almost perfect, which led many within the field to question the results, but unfortunately, CCSVI has gained a great momentum within patient groups due to the potential for a "quick cure" for a chronic disabling disease. The authors of this study postulate that the discrepancy between the studies was due to methodological differences as well as assumptions made by Zamboni et al. Currently, there is little agreement established within the literature regarding normal cerebral venous drainage or the most accurate method to evaluate it. This paper underscores the need to replicate studies, especially when the results may cause a significant shift in the treatment paradigm of a disease. MS remains a complicated disease best controlled by chronic immune-modulation as opposed to endovascular treatment. This paper should discourage physicians from offering endovascular treatment to patients with MS until further research on CCSVI and multiple sclerosis has been completed.
Reference
1. Zamboni P, et. al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392-399.
In a study of extracranial and transcranial color-coded sonography, there was no impairment of cerebral venous drainage in patients with multiple sclerosis as compared to healthy controls.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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