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Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo studyG. Comi, M.A. Battaglia, A. Bertolotto, M. Del Sette, A. Ghezzi, G. Malferrari, M. Salvetti, M. Sormani, E. Stolz, L. Tesio, G.L. Mancardi on behalf of the CoSMo study group
Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) has been recently described as a condition characterized by chronically impaired cerebral venous drainage associated to multiple sclerosis (MS). Subsequent studies failed to confirm the association between CCSVI and MS and even questioned whether CCSVI exist at all. The CoSMo study is a large, multicenter case-control study promoted by the Italian MS Foundation to investigate the relationship between CCSVI and MS.
Materials and method: This study was conducted in 35 Italian clinical centers. 1871 subjects aged 18-55 years were enrolled (55 were excluded for major protocol violations) so that the final analysis was based on 1816 subjects: 1202 with MS (72.6% Relapsing Remitting, 13.5% Secondary Progressive, 5.2% Primary Progressive and 8.7% Clinically Isolated Syndromes), 382 healthy controls (HC) and 232 subjects with other neurological diseases (OND). An informed consent was obtained for all the enrolled subjects. Eco Color Doppler (ECD) was performed according to a pre-defined protocol and all sonologist were specifically trained to standardized ECD criteria for CCSVI. The exam was recorded and sent for a central blind evaluation performed by one of 3 expert central sonologists. These had blind access to the ECD imaging. The diagnosis was compared between the local and one central sonologist. In case of agreement, a final report was issued. In case of disagreement, the ECD examination was sent independently to the other two central sonologists and the diagnosis made by a majority. Centralized data collection and monitoring was managed by an independent CRO. The results presented here include 1678 examinations with completed local and central assessment.
Results: The prevalence of CCSVI was 3.24% (95% Confidence Interval (CI)= [2.35%; 4.45%]) in MS patients, 1.98% (95%CI= [0.96%; 4.03%]) and 2.80% (95%CI=[1.29%; 5.98%]) respectively in HC and in patients with OND. The difference between MS patients and HC was not statistically significant (OR=1.66, 95%CI= [0.73;3.77], p=0.28), as well as the difference between MS patients and OND patients (OR=1.16 [0.48,2.78], p=0.99). There was no association between CCSVI and any MS subtype.
Conclusion: The prevalence of CCSVI detected in a multicenter setting by a shared local and central assessment was very low and not significantly associated with MS. These results do not support the role of CCSVI as a potential causal factor in the development of MS.
Dr. Battaglia has no conflicts of interest to declare. Dr A. Bertolotto has been on steering committees in clinical trials sponsored by Biogen Idec, Roche, and has received speaker honoraria from Biogen Idec, Merck Serono, TEVA, Bayer Schering, Sanofi-aventis, and Novartis; and has received research support from Biogen Idec, Bayer Schering, Merck Serono, Sanofi-Aventis, from the Italian Multiple Sclerosis Society, and the European Union Sixth Framework Programme. Dr. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering and Serono Symposia International Foundation. He is member of the Board of the Italian MS Foundation. Dr. M. Del Sette has no conflicts of interest to declare. Dr A. Ghezzi received honoraria for speaking from Bayer-Schering, Biogen-Dompè, Merck-Serono, Novartis, Sanofi-Aventis and Allergan, for consultancy from Actelion, Merck-Serono, Teva and Novartis, received support for participation to
National and International Congresses from Bayer-Schering, Biogen-Dompè, Merck- Serono, Novartis and Sanofi-Aventis. Dr G. Malferrari has no conflicts of interest to declare. Dr. GL Mancardi received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, Sanofi-Aventis, Novartis and Merck Serono Pharmaceuticals. He is member of the Board of the Italian MS Foundation. Dr. M Salvetti declares grant support from Bayer-Schering, Merck-Serono, Sanofi-Aventis and Biogen Idec. Dr. MP Sormani has received consulting fee or honoraria from Biogen Idec, Merck Serono, Actelion, Synthon and TEVA. Dr. E. Stolz has received lecture fees from Boehringer Ingelheim, Bracco and Sanofi-Aventis and support from Schering. Dr. L. Tesio is member of the Board of the Italian MS Foundation.