Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis - 15/11/11
, Erin Lillie, MSc a, Andrew Dueck, MD MSc b, c, Sharon Straus, MD MSc a, b, Laure Perrier, MEd MLIS a, d, Jodie M. Burton, MD MSc e, Richard Aviv, MBChB b, f, Kevin Thorpe, MMath a, g, Thomas Feasby, MD h, Julian Spears, MD SM a, bAbstract |
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).
Interpretation |
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.
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| Competing interests: Andreas Laupacis receives honoraria as a member of a data safety monitoring board for studies of two drugs for multiple sclerosis funded by Novartis Pharmaceuticals. Jodie Burton has received unrestricted educational support and honoraria for speaking and educational engagements from Teva Neuroscience Canada, EMD Serono and Biogen Idec Canada. No competing interests declared by the other authors. Disclaimer: Andreas Laupacis is a member of CMAJ’s Editorial Board, and Sharon Straus is an associate editor for CMAJ. Neither was involved in the editorial decision-making process for this article. This article has been peer reviewed. Contributors: Andreas Laupacis, Andrew Dueck, Sharon Straus, Laure Perrier, Jodie Burton, Richard Aviv, Kevin Thorpe, Thomas Feasby and Julian Spears designed the study. Erin Lillie drafted the systematic review protocol, and Laure Perrier conducted the literature searches. Andreas Laupacis and Sharon Straus participated in screening articles for review. Andreas Laupacis, Erin Lillie, Andrew Dueck and Laure Perrier contributed to data abstraction. Andreas Laupacis and Kevin Thorpe supervised the analysis. Erin Lillie performed the meta-analyses and sensitivity analyses, and Andrew Dueck provided input to the sensitivity analyses. Andreas Laupacis drafted the manuscript. All of the authors revised the manuscript and approved the final version submitted for publication. Funding: Funding for this study was provided by the Canadian Institutes of Health Research (grant no. 243347). The study sponsors had no role in the design of the study, the collection, analysis or interpretation of the data, the writing of the report, or the decision to submit the manuscript for publication. |
Vol 183 - N° 16
P. E1203-E1212 - novembre 2011 Ritorno al numero
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