Evidence against the Involvement of Chronic Cerebrospinal Venous Abnormalities in Multiple Sclerosis. A Case-Control Study

Ian W Rodger,Dorothy Dilar,Norman B Konyer,Charles H Goldsmith,John Bienenstock,Arlene Franchetto,Judith Coret-Simon,Mary Jane Sayles,David Koff,Luciana Ribeiro,Slobodan Franic,Gary Foster,Ellen Mcdonald,Michael D Noseworthy,Lehana Thabane,Mitchell Levine,Alexander Coret ,John E Paulseth ,Janet C Dwyer

doi:10.1371/journal.pone.0072495

Abstract

ObjectiveMultiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI.MethodsA case-control study was conducted in which 100 MS patients aged between 18–65 y meeting the revised McDonald criteria were randomly selected and stratified into one of four MS subtypes: relapsing/remitting, secondary progressive, primary progressive and benign. Control subjects (16–70 y) with no known history of MS or other neurological condition were matched with the MS cases. All cases and controls underwent ultrasound imaging of the veins of the neck plus the deep cerebral veins, and magnetic resonance imaging of the neck veins and brain. These procedures were performed on each participant on the same day.ResultsOn ultrasound we found no evidence of reflux, stenosis or blockage in the internal jugular veins (IJV) or vertebral veins (VV) in any study participant. Similarly, there was no evidence of either reflux or cessation of flow in the deep cerebral veins in any subject. Flow was detected in the IJV and VV in all study participants. Amongst 199 participants there was one MS subject who fulfilled the minimum two ultrasound criteria for CCSVI. Using MRI we found no significant differences in either the intra- or extra-cranial venous flow velocity or venous architecture between cases and controls.ConclusionThis case-control study provides compelling evidence against the involvement of CCSVI in multiple sclerosis.

Highlights

Multiple sclerosis (MS) is a chronic, demyelinating, neurodegenerative, inflammatory disease of the central nervous system[1,2]
Zamboni and colleagues coined the term chronic cerebrospinal venous insufficiency (CCSVI) to define the vascular condition present in MS patients in which anomalies of the main extracranial cerebrospinal venous architecture interfered with the normal venous drainage from the brain [5,9]
The primary objective of this study was to evaluate the relative prevalence of the five venous abnormalities that define CCSVI, using both Doppler ultrasound and magnetic resonance imaging (MRI) quantitative flow techniques, amongst four sub-groups of MS patients and the matched controls

Summary

Introduction

Multiple sclerosis (MS) is a chronic (and often progressive), demyelinating, neurodegenerative, inflammatory disease of the central nervous system[1,2]. It has been recognized that most MS plaques are situated around perivenular spaces This observation led to the hypothesis that venous hemodynamic problems, including venous reflux, might be central to the underlying MS disease process [3]. The consequences of venous insufficiency in peripheral tissues are well established and include, amongst other things, microhemorrage and iron deposition [4] It was characteristics such as these that led Zamboni and colleagues to hypothesize that MS was associated with abnormalities of the drainage of the cerebral venous system and that, along with vascular iron leakage, were involved in progression of the disease [5,6,7,8,9]. The primary objective of this study was to evaluate the relative prevalence of the five venous abnormalities that define CCSVI, using both Doppler ultrasound and magnetic resonance imaging (MRI) quantitative flow techniques, amongst four sub-groups of MS patients and the matched controls

Methods

Results

Conclusion