CMAJ: Cerebrospinal venous insufficiency may be linked to MS

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Chronic cerebrospinal venous insufficiency was found to be linked to multiple sclerosis (MS) in a meta-analysis published Oct. 3 in the Canadian Medical Association Journal. However, the researchers noted that the results may not  provide definitive conclusions due to poor reporting of the success of blinding and heterogeneity within studies included in the meta-analysis.

“It has been proposed by Zamboni and colleagues that multiple sclerosis [MS] 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,” Andreas Laupacis, MD, of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital in Toronto, and colleagues wrote.

Laupacis and colleagues searched MEDLINE and EMBASE databases to conduct a meta-analysis to evaluate the frequency of chronic cerebrospinal venous insufficiency among patients with and without MS. The researchers identified eight studies published from 2005 to 2011 to include in the analysis. These studies included a total of 664 patients with MS: 528 healthy controls and 136 controls with neurologic diseases other than MS.

The researchers reported chronic cerebrospinal venous insufficiency to be more frequent among those with MS compared with healthy controls. Chronic cerebrospinal venous insufficiency was also more frequent among patients with other neurologic disease. The researchers reported that there was “extensive unexplained heterogeneity among the studies.”

It was noted that the large amount of heterogeneity prevented a definitive conclusion to be made during the study. However, the authors noted that the source of this heterogeneity was not clear and said that it was “not obviously caused by differences in the definition of chronic cerebrospinal venous insufficiency, patient characteristics or the methodologic quality of the studies.”

Laupacis and colleagues speculated that differences in ultrasound technique could be the culprit for the variations between the studies in the frequency of chronic cerebrospinal venous insufficiency among patients with MS. Reflux in the deep cerebral veins is the most technically challenging to identify with ultrasound.

“An association between chronic cerebrospinal venous insufficiency and multiple sclerosis does not mean that the condition causes multiple sclerosis,” the authors noted. While some studies have noted that chronic cerebrospinal venous insufficiency may be a consequence of MS, it may not be the culprit.

“Further high-quality studies, using identical ultrasound protocols, are needed to definitively determine whether chronic cerebrospinal venous insufficiency is more frequent among patients with multiple sclerosis than among those without it,” Laupacis et al concluded.

"Despite the results of this meta-analysis, we are still far from proving that chronic cerebrospinal venous insufficiency is the cause of multiple sclerosis and embracing the liberation procedure," Robert J. Fox, MD, of the Cleveland Clinic, wrote in an accompanying editorial.

Previously, it was found that performing a "liberation procedure" in MS patients can relapse MS and improved measures of inflammation. However, Fox offered that the procedure is also associated with real risks including death and other life-threatening complications.

"The meta-analysis by Laupacis and colleagues is a good starting point; however, much work remains to be done before we can be certain whether chronic cerebrospinal venous insufficiency is a paradigm shift in the classic sense, as conceived by Thomas Samuel Kuhn, or just another fad," Fox concluded.