Historical overview of CCSVI and multiple sclerosis relationship by Dr. Michael Dake

written for the 10th International Symposium of Endovascular Therapeutics in Barcelona, Spain

http://www.sitesymposium.org

Chronic cerebrospinal venous insuffiency (CCSVI) is a term used to descibe impaired venous drainage from the central nervous system (CNS) caused by abnormalities in anatomy and flow affecting the extracranial veins. Recently, it has been proposed the CCSVI may contribute to the pathogenesis of multiple sclerosis (MS).

It is hypothesized the venous obstruction results in abnormal flow that promotes inflammation at the blood-brain barrier and that this triggers a process marked by a disturbance of hemeostasis within the CNS that leads to demyelination and neurodegeneration. The venous abnormalities of the CCSVI are often diagnosed by ultrasound or magnetic resonance venography, however the prevalence of CCSVI detailed in groups of MS patients and patients without MS varies widely in published reports. Increased standardization of diagnostic studies to evaluate both anatomical and physiological findings associated with CCSVI is needed.

Chronic cerebrospinal venous insufficiency (CCSVI) is recently described condition that may possibly contribute to the symptoms often experienced by patients with MS. The idea the the vascular system is somehow related to the pathological abnormalities of MS was proposed shortly after the characteristic lesions were described. Of the early investigators of the disease, Charcot was the first to describe the obstruction of blood vessels within MS lesions. Indeed, the vascular hypothesis was widely advocated as the most plausible explanation for the pathogenesis of the MS during the late 1800s.

Then, during the mid-20th century, the recognition the these central vascular channels were abnormal cerebral veins fueled enthusiasm for the concept of a vascular etiology. During this period, researchers including Putnam, Marburg, Dow, Fog, Adams, Engeli and others contributed to advancing an understanding of the role of abnormal venous involvement in MS, but over the last 50 years the vascular hypothesis has been eclipsed by emerging evidence that strongly supports a primary autoimmune basis for the disease.

Recently, Zamboni and colleagues revitalized interest in the importance of cerebrospinal venous drainage as a factor that influences the pathogenesis of MS. They described ultrasonographic and venographic evidence of extracranial venous obstruction involving the internal jugular, vertebral, deep cerebral and azygos veins in a remarkably high percentage of patients diagnosed with MS. Comparatively, similar findings were not diagnosed in healthy control subjects and patients with other neurological diseases. They proposed that CCSVI interferes with venous drainage from the CNS, and that this contributes to the development and progression of MS. Moreover, when the stenotic lesions in the internal jugular

and azygo veins were treated endovascularly with balloon angioplasty, they observed in many patients a rapid and often dramatic improvement in a variety of symptoms.

The publication of these findings unleashed an emotionally intense controversy that currently
still forments with boiling points of view. From highly critical reaction that decry the concept of CCSVI as a hoax that provides false hope to vulnerable and desperate, individuals to supportive testimonials from treated patients, the debate surrounding the existence, association and relevance of CCSVI to MS is reflected in the contributions to the medical literature. Although, the vast majority of the articles on the topic consist of commentaries, opinions, interpretations and diatribes, rather than reports of clinical evidence for or against CCSVI, the essence of the recently published independent clinical studies designed to evaluate various aspects of the CCSVI hypothesis do, by and large, reflect the opposing public contentions in the dispute by presenting conflicting results that either pointedly question, or support the existence of CCSVI. At present, our level of understanding is simply insufficient to settle the argument.