Time to reevaluate the role of venous hemodynamics in MS pathophysiology?

Abstract

Although the cause of multiple sclerosis (MS) is not known, the consensus theory is that genetic predisposition, along with some nongenetic trigger, begins a downward spiral of immune-mediated inflammatory disease activity followed by progressive neurologic deterioration and disability. The nongenetic trigger is the subject of intense basic science as well as epidemiologic research. Paolo Zamboni, an Italian vascular surgeon, and colleagues1,2 have recently challenged the established pathophysiology of MS by postulating a new entity called chronic cerebrospinal venous insufficiency (CCSVI). CCSVI is a theoretical term used to describe a collection of intracranial and extracranial duplex ultrasound findings of CNS venous anomalies present in patients with MS. Zamboni and colleagues hypothesize that insufficient venous drainage results in iron accumulation and enhanced CNS inflammation. The authors studied 109 patients with MS and 177 controls and reported a remarkable 100% sensitivity, specificity, positive and negative predictive value correlating ultrasound findings of abnormal cerebral venous outflow with MS. In another study, Zamboni et al.1 reported MS was associated with venous outflow anomalies with an odds ratio of 43 (95% confidence interval 29–65). Selected patients in both studies underwent unblinded venography that demonstrated venous “twisting,” “membranous obstruction,” and stenosis; however, it was unclear how ultrasound techniques were employed and …