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Posted by on Apr 15, 2011 in Neurology

CCSVI: Nonspecific Marker for General Neurologic Disease?

CCSVI: Nonspecific Marker for General Neurologic Disease?


Chronic cerebrospinal venous insufficiency (CCSVI)a much-ballyhooed marker for multiple sclerosis and a possible target for treatmentappears to be neither a particularly sensitive nor specific indicator of the disease. This conclusion is based on a new study from the University of Buffalo, where hemodynamics of the transcranial and extracranial veins were assessed by echo-color Doppler ultrasound in 336 people with various neurologic conditions (including MS) and 163 healthy controls.

The essential take-away of this quasi-blinded study is this: That although the prevalence of CCSVI (established by meeting 2 of 5 criteria) was statistically significantly higher in individuals with MS than in healthy controls (62.5% vs 25.5%; P < .001), this difference was not significant between patients with MS and those with a wide variety of other neurologic diseases (62.5% vs 45.8%; P = .131). There was also a substantial percentage of so-called borderline CCSVI cases in each of the study subgroups (18 cases among healthy controls and 30 cases among patients with MS), making the condition a potentially difficult one to establish with comfortable certainty. (Read on for other technical caveats when attempting to measure CCSVI.)

Study Subgroup


CCSVI,** %

Healthy controls



Clinically isolated syndrome



Other neurologic diseases






In the Buffalo study, the highest calculated sensitivity for CCSVI as a potential marker for MS was 62.5%, and the highest calculated specificity was 77.3%. These values are considerably lower than the hard-to-believe calculations offered by Paolo Zamboni (100% and 100%), the Italian vascular surgeon who, in 2009, resurrected this messer, the idea that MS has a vascular cause. The Buffalo authors concluded,

Our findings are consistent with an increased prevalence of CCSVI in MS but with a modest sensitivity/specificity. Our findings point against CCSVI having a primary [emphasis added] causative role in the development of MS.

In an accompanying editorial, Fox and Rae-Grant of the Cleveland Clinic importantly note that the 5 ultrasound criteria for CCSVI proposed by Zamboni “have yet to be validated against a criterion standard.” Moreover, they advise that the use of balloon venoplasty to treat presumed CCSVI in MS “should be restricted to a blinded, controlled clinical trial using carefully chosen clinical endpoints and appropriate patient safety oversight.”

But the docs aren’t entirely dismissive of the possibility that CCSVI could figure importantly in the pathogenesis of MS: “It behooves the clinical research community to carefully pursue CCSVI to its end,” they advise. To that end, the US and Canadian MS Societies awarded a total of $2.4 million in grants to various groups last year to study CCSVI.

In a measured comment at MedPage Today (taped at the ongoing annual meeting at the AAN), Fox also advised that a number of factors (technician pressure on the blood vessel, patient hydration, machine knob settings) can dramatically affect whether CCSVI is detected or diagnosed. He charged that Zamboni did not provide sufficient information on these types of parameters to ensure that his impressive results can be reliably tested or replicated. When questioned about the possible alternative of MR venography to assess CCSVI, Fox warned that the technique is probably not sufficiently sensitive to detect the venous-flow changes that are assumed to be associated with the purported CCSVI. Consequently, he implied, we should stick with ultrasound for now and establish the methods and criteria for detecting CCSVI (if it even exists beyond that of an epiphenomenon).

* Borderline cases excluded from “no CCSVI” group.

** Borderline cases included in “no CCSVI” group.

Image of neck veins from Gray’s Anatomy (1918).

Addendum: Also to further muddy the waters, the CCSVI rates in the Buffalo study between healthy controls and patients with other neurologic diseases were not significantly different (P = .39).

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.