Chronic Cerebrospinal Venous Insufficency Not Cause of Multiple Sclerosis: Hypothesis Rest in Peace

In 2009, Zamboni and colleagues¹ reported that the presence of multiple stenoses of the extra-cranial venous drainage system-a disorder they called chronic cerebrospinal venous insufficiency (CCSVI)-was significantly associated with MS. The venous blockages were present in all MS patients they studied by ultrasound and on catheter venography. These blockages were not seen in healthy control participants. The investigators thus speculated that venous blockages have a central role in the pathogenesis of MS, and that treatment with venoplasty would ameliorate the disease. Venoplasty was hailed as a “cure” for MS-and many patients funded their own (and in many cases expensive) treatment before independent validation studies on CCSVI had been completed.

In a recent multi-center study from Canada, Traboulsee and colleagues² performed a blinded case-control study of the prevalence of extra-cranial venous narrowing on both catheter venography and ultrasound in patients with multiple sclerosis, their siblings, and unrelated healthy controls (177 participants in total). The hypothesis was that if CCSVI as an entity exists and is MS causative, it should be present at the greatest extent in MS patients, at a lower frequency in their unaffected siblings (due to the sharing of MS genetic risk factors), and at a significantly lower incidence in healthy disease-free individuals. The results of this investigation showed that 1 of 65 (2%) people with MS fulfilled catheter venography criteria for CCSVI--a figure very similar to that of unaffected siblings (1 of 46 [2%]) and unrelated controls (1 of 32 [3%]).
 

Key Points

o CCSVI is not more prevalent in patients with MS as reported in the Zamboni paper. CCSVI is neither specific or causative for MS.

o Ever since the publication of the Zamboni paper there has been skepticism in the MS community about CCSVI. The notion that a venous anomaly was present in 100% of individuals with MS raised eyebrows, and further, a theory that a venous anomaly could cause MS flies in the face of decades of evidence highlighting the importance of the immune system in the disease. The Canadian study is well conducted: it puts a final nail in the coffin for the hypothesis that CCSVI is MS causative. It is now absolutely clear that no reason exists to further investigate or treat for CCSVI.