Does the Evidence Support the Controversial CCSVI Theory of MS?

Though many patients once had high hopes for the CCSVI hypothesis and the endovascular intervention to treat it, recent studies question its validity.

This news article and accompanying video looks at CCSVI, “a radical new theory developing on the cause of multiple sclerosis.”

Italian vascular surgeon Paolo Zamboni developed the CCSVI (Chronic Cerebrospinal Venous Insufficiency) theory of MS, which he says is due to “blockage in the veins in the neck area,” which cause “a reverse flow of blood back into the brain, damaging the nervous system.” Zamboni’s solution is to open the blocked veins using balloon angioplasty or stents. Although these theories have found many supporters among some clinicians and patients desperate for a cure, they have been met with a great deal of skepticism by other researchers and physicians.

Indeed, although the National Multiple Sclerosis Society is “coordinating a worldwide effort to conduct and evaluate research on CCSVI,” this video report notes that the Society’s VP of research characterizes the Zamboni hypothesis as “a long shot” and “cautions patients should only undergo the procedure as part of a clinical trial.”

A quick look at studies on CCSVI in PubMed reveals a murky picture; several studies in Neurology, the Annals of Neurology, and other journals have found no evidence to support this hypothesis, yet several studies and case reports by Zamboni and colleagues say otherwise.

The authors of "Normal CSF Ferritin Levels in MS Suggest against Etiologic Role of Chronic Venous Insufficiency," published in Neurology, suggested that “if the presumed mechanism of venous stasis—related parenchymal iron deposition and neurodegeneration were true, then upregulation of intrathecal iron transport proteins may be expected.” To test this, they examined the “CSF ferritin levels in patients with MS and a range of neurologic disorders.” They found “no significant change of CSF ferritin levels over the 3-year follow-up period,” leading them to conclude that “these data do not support an etiologic role for CCSVI-related parenchymal iron deposition in MS.”

In "Chronic Cerebrospinal Venous Insufficiency and Multiple Sclerosis: Critical Analysis and First Observation in an Unselected Cohort of MS Patients," German researchers reported the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis “cannot represent the exclusive pathogenetic factor in the pathogenesis of MS. In our cohort, only 20% of the patients fulfilled the required neurosonological features of CCSVI. So far, the pathogenetic relevance of these findings remains speculative. Thus, based on the current scientific position we cannot justify invasive ‘therapeutic’ approaches, especially if they are performed outside of clinical trials.”

The authors of “No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis,” published in the Annals of Neurology, “were unable to detect a significant difference of the cerebral and cervical venous drainage between patients with MS and healthy subjects for all except 2 venous indices analyzed,” results that “call into question the existence of CCSVI—certainly in a large proportion of patients with MS—and do not underpin a role of cerebral venous congestion leading to reflux of blood into the CNS in the pathophysiology of MS.”

If you’re looking for a more sympathetic view of CCSVI and its potential role in treatment for MS, check out the following resources:

Characterizing the Manifestation of CCSVI with MR Venography and Flow Quantification: The Role of MRI in Treatment Planning (VIDEO)

E. Mark Haacke, PhD, discusses “the use of MR techniques for flow quantification, measurement of iron deposition, and before/after scanning to validate treatment.”

The Venous Multiple Sclerosis Hypothesis

This website is about the hypothesis of the association of "Chronic cerebrospinal venous insufficiency" (CCSVI) and multiple sclerosis (MS). The goal of this website is “to track development, especially research. CCSVI is currently under research. Examination and treatments are not standard medical methods. Access to treatment for multiple sclerosis must be based on science, not hope. Unfortunately, the research is still in the beginning. There are no scientific publications about ‘stenting’ and thus there is no valid experience on that.”

The CCSVI Alliance

This organization is “is dedicated to educating patients with research-based information, providing tools for patients to advocate for themselves, and supporting medical professionals' exploration of Chronic Cerebrospinal Venous Insufficiency (CCSVI).”

First Blinded Study of Venous Insufficiency Prevalence in MS Shows Promising Results

This news release from the University at Buffalo reported that “more than 55% of multiple sclerosis patients participating in the initial phase of the first randomized clinical study to determine if persons with MS exhibit narrowing of the extracranial veins, causing restriction of normal outflow of blood from the brain, were found to have the abnormality.” Neurologists at the university reported that “the 10.2% of subjects in which results were border line were excluded, the percentage of affected MS patients rose to 62.5%, preliminary results show, compared to 25.9% of healthy controls.” Read the study abstract here.