title: Chronic cerebrospinal venous insufficiency and multiple sclerosis: a comprehensive meta-analysis of case-control studies.
abstract: OBJECTIVE
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second 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.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Sergentanis
authors.affiliation: Department of Neurology, Ruhr University, St Josef-Hospital, Bochum, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.affiliation: Second Department of Neurology, 'Attikon' Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voumvourakis
authors.affiliation: First Department of Neurology, 'Eginition' Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Triantafyllou
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Psaltopoulou
authors.affiliation: Department of Neurology, Ruhr University, St Josef-Hospital, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Department of Neurology, Ruhr University, St Josef-Hospital, Bochum, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Krogias
keywords: chronic cerebrospinal venous insufficiency; meta-analysis; multiple sclerosis; ultrasound