OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been implicated in the pathogenesis of multiple sclerosis (MS). This comprehensive meta-analysis of case-control studies investigates the association of CCSVI with MS. METHODS: Through Medline, EMBASE and Cochrane database searches, case-control ultrasound studies comparing CCSVI frequency among patients with MS and healthy controls were identified. RESULTS: We identified 19 eligible studies including 1250 patients with MS and 899 healthy controls. The pooled analysis showed that CCSVI was associated with MS [odds ratio (OR) 8.35; 95% confidence interval (CI) 3.44-20.31; p < 0.001) with considerable heterogeneity across studies (I (2) = 80.1%). This association was substantially attenuated in sensitivity analyses excluding studies that were carried out by the group that originally described CCSVI, included investigators who had also been involved in publications advocating endovascular procedures for CCSVI treatment, or were conducted in Italy. Our most conservative sensitivity analysis combining different exclusion criteria yielded no association of CCSVI with MS (OR 1.35; 95% CI 0.62-2.93; p = 0.453) without any heterogeneity (I (2) = 0%). CONCLUSION: There is considerable heterogeneity across different case-control studies evaluating the association of CCSVI and MS. The greatest factor contributing to this heterogeneity appears to be the involvement of investigators in other publications supporting endovascular procedures as a novel MS treatment.

1st Department of Neurology 'Eginition' Hospital School of Medicine University of Athens Athens Greece

2nd Department of Neurology 'Attikon' Hospital School of Medicine University of Athens Athens Greece

2nd Department of Neurology 'Attikon' Hospital School of Medicine University of Athens Iras 39 Gerakas Attikis 15344 Athens Greece and International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

Department of Hygiene Epidemiology and Medical Statistics School of Medicine University of Athens Athens Greece

Department of Neurology Ruhr University St Josef Hospital Bochum Germany

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"Liberation treatment" for chronic cerebrospinal venous insufficiency in multiple sclerosis: the truth will set you free