title: Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis.
abstract: BACKGROUND
  It has been proposed by Zamboni and colleagues that multiple sclerosis is caused by chronic cerebrospinal venous insufficiency, a term used to describe ultrasound-detectable abnormalities in the anatomy and flow of intra- and extracerebral veins. We conducted a meta-analysis of studies that reported the frequency of chronic cerebrospinal venous insufficiency among patients with and those without multiple sclerosis.
  
  
  METHODS
  We searched MEDLINE and EMBASE as well as bibliographies of relevant articles for eligible studies. We included studies if they used ultrasound to diagnose chronic cerebrospinal venous insufficiency and compared the frequency of the venous abnormalities among patients with and those without multiple sclerosis.
  
  
  RESULTS
  We identified eight eligible studies: all included healthy controls, and four of them also included a control group of patients with neurologic diseases other than multiple sclerosis. Chronic cerebrospinal venous insufficiency was more frequent among patients with multiple sclerosis than among the healthy controls (odds ratio [OR] 13.5, 95% confidence interval [CI] 2.6-71.4), but there was extensive unexplained heterogeneity among the studies. The association remained significant in the most conservative sensitivity analysis (OR 3.7, 95% CI 1.2-11.0), in which we removed the initial study by Zamboni and colleagues and added a study that did not find chronic cerebrospinal venous insufficiency in any patient. Although chronic cerebrospinal venous insufficiency was also more frequent among patients with multiple sclerosis than among controls with other neurologic diseases (OR 32.5, 95% CI 0.6-1775.7), the association was not statistically significant, the 95% CI was wide, and the OR was less extreme after removal of the study by Zamboni and colleagues (OR 3.5, 95% 0.8-15.8).
  
  
  CONCLUSIONS
  Our findings showed a positive association between chronic cerebrospinal venous insufficiency and multiple sclerosis. However, poor reporting of the success of blinding and marked heterogeneity among the studies included in our review precluded definitive conclusions.
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ont. laupacisa@smh.ca
authors.forename: Andreas
authors.initials: A
authors.lastname: Laupacis
authors.forename: Erin
authors.initials: E
authors.lastname: Lillie
authors.forename: Andrew
authors.initials: A
authors.lastname: Dueck
authors.forename: Sharon
authors.initials: S
authors.lastname: Straus
authors.forename: Laure
authors.initials: L
authors.lastname: Perrier
authors.forename: Jodie M
authors.initials: JM
authors.lastname: Burton
authors.forename: Richard
authors.initials: R
authors.lastname: Aviv
authors.forename: Kevin
authors.initials: K
authors.lastname: Thorpe
authors.forename: Thomas
authors.initials: T
authors.lastname: Feasby
authors.forename: Julian
authors.initials: J
authors.lastname: Spears
mesh_terms: D001921:Brain / Q000098:blood supply; D002550:Cerebral Veins / Q000000981:diagnostic imaging; D006801:Humans; D007601:Jugular Veins / Q000000981:diagnostic imaging; D009103:Multiple Sclerosis / Q000150:complications*; D013116:Spinal Cord / Q000098:blood supply; D018608:Ultrasonography, Doppler; D014689:Venous Insufficiency / Q000150:complications*