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Editorial Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis – A Medical, Sociological and Media Controversy Aaron Miller Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis and Professor of Neurology, Mount Sinai School of Medicine Abstract In 2009, Zamboni et al. coined the term “chronic cerebrospinal venous insufficiency” (CCSVI). On the basis of transcranial and extra-cranial colour-coded Doppler ultrasonography, they operationally defined CCSVI as occurring when at least two out of five “abnormalities” were present. They claimed to find CCSVI in 100 % of 109 individuals with multiple sclerosis (MS) and in none of 177 healthy controls. Zamboni’s group subsequently reported an uncontrolled treatment trial of cerebral venoplasty, which was termed the “liberation procedure” and claimed that the procedure benefited people with MS. The Zamboni reports were received with considerable skepticism, regarding both their biological plausibility and the claims of 100  % sensitivity, specificity, positive predictive value and negative predictive value. No investigators have subsequently been able to replicate the Zamboni observations. Although some additional reports have indicated finding venous abnormalities in more MS patients than in other groups, most have either found no association of CCSVI with MS, or else have found substantial numbers of controls, either healthy or with other neurological disease, to have the abnormalities. The original Zamboni reports were widely publicised in the mainstream media, especially in Canada and sparked a raging controversy in the social media. Patients clamoured for trials of cerebral venoplasty and others demanded its availability or travelled around the globe to undergo the procedure. The Canadian Institutes of Health Research have now solicited proposals for a Phase I/II clinical trial. At this point, additional scientific studies, including many funded by the National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada, are moving toward completion and will hopefully allow a proper judgment of the validity of the concept of CCSVI in relation to MS. In the meantime, it is important that physicians remain respectful of patients’ views, but that they are not reticent about expressing their own professional opinions based on available evidence, while emphasising the importance of proper scientific research. Keywords Chronic cerebrospinal venous insufficiency, liberation procedure, cerebral venoplasty, multiple sclerosis, social media, Canadian Institutes of Health Research, National Multiple Sclerosis Society, Multiple Sclerosis Society of Canada Disclosure: Aaron Miller has received research support from Acorda, Teva, Novartis, Genentech, Genzyme, Sanofi and Biogen Idec, has acted as a consultant to Sanofi, Biogen Idec, GlaxoSmithKline, EMD Serono, Daiichi Sankyo, Merck Serono, Novartis, ONO, Acorda, BioMarin, Avanir, Chelsea Therapeutics, Nuron Biotech and La-Ser, and is on the speakers’ bureau for Biogen Idec, Pfizer, EMD Serono, Teva and Acorda. Received: 29 November 2011 Accepted: 12 December 2011 Citation: European Neurological Review, 2012;7(1):10–12 Correspondence: Aaron Miller, Mount Sinai School of Medicine, 5 East 98th Street, 1st Floor, New York, NY 10029, US. E: Beginning with the publication of a paper by Paolo Zamboni in 2009 1 that claimed an association between a number of cerebral venous ‘abnormalities’ and multiple sclerosis (MS), the international MS community has been embroiled in a debate, unprecedented in scope and controversy. The original Zamboni paper defined ‘chronic cerebrospinal venous insufficiency’ (CCSVI) as the presence of two or more of five criteria they described as abnormalities of the venous system draining the brain and spinal cord based exclusively on examination by transcranial and extracranial colour-coded Doppler examination. The initial Zamboni study evaluated 109 MS patients and 177 healthy controls and the investigators reported the occurrence of CCSVI in every MS patient and in none of the controls. In other words, the authors claimed that the presence of CCSVI was 100 % sensitive, 100 % specific, and had 100 % positive predictive value and 100 % negative predictive value for MS. This paper was followed later in 2009 by a report by the Zamboni group of an uncontrolled treatment trial of cerebral venoplasty in 65 patients with MS. 2 The authors observed that patients receiving the 10 intervention, which was termed ‘liberation procedure’, were significantly more likely to be relapse-free post-operatively than pre-operatively and to have fewer gadolinium enhanced lesions post-operatively. In addition the authors noted that, based on the multiple sclerosis functional composite (MSFC) score, the cohort improved at one year. The findings of the Zamboni group were subsequently catapulted to international attention by a series of reports in the mainstream media, especially in Canada. Understandably excited by the undeniable appeal of the prospect of obtaining dramatic improvement or even a ‘cure’ of their MS, patients around the world began to seek the procedure and to demand it where it was not readily available, again particularly in Canada. The controversy and dialogue spread rapidly through the social media, with numerous reports of subjective symptomatic improvement by individuals with MS who had undergone the procedure. Skepticism in the Scientific Community The initial Zamboni reports were met with considerable skepticism by most of the MS scientific and professional community. Like any © TOUCH BRIEFINGS 2012