What is the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis in the etiology of multiple sclerosis (MS)?

Updated: Oct 08, 2019
  • Author: Christopher Luzzio, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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A controversial hypothesis proposes a vascular rather than an immunologic cause for some cases of MS. In 2008, Paolo Zamboni described an association between MS and chronic cerebrospinal venous insufficiency (CCSVI). [42]

The CCSVI hypothesis posits that stenosis of the main extracranial venous outflow pathways results in compromised drainage and a high rate of cerebral venous reflux. The CCSVI hypothesis has been linked with the potential effects of iron deposition in the brain parenchyma, which some authors suggest is modestly to strongly predictive of disability progression, lesion volume accumulation, and atrophy in some patients with MS. [43, 44]

A small, open-label study suggested that internal jugular vein and azygous vein angioplasty had a positive effect on MS symptoms in patients with CCSVI. [45] A meta-analysis found a positive association between CCSVI and MS, but poor reporting of the success of blinding and marked heterogeneity among studies of CCSVI precluded definitive conclusions. [46]

Because of the potential danger of such experimental procedures in treating this unproven vascular condition, the US Food and Drug Administration (FDA) has issued a warning. See FDA issues alert on potential dangers of unproven treatment for multiple sclerosis.

Given the paucity of supporting evidence, most MS experts also question the CCSVI hypothesis and do not recommend this therapy. Nevertheless, CCSVI has received widespread attention in the lay press and MS support groups, so physicians should be prepared for inquiries from patients on this highly controversial subject.

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