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Multiple Sclerosis International
Volume 2013 (2013), Article ID 598093, 6 pages
Review Article

The Evidence for Hypoperfusion as a Factor in Multiple Sclerosis Lesion Development

1Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5
2College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia

Received 7 November 2012; Revised 8 February 2013; Accepted 19 March 2013

Academic Editor: Bianca Weinstock-Guttman

Copyright © 2013 Bernhard H. J. Juurlink. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The evidence that hypoxia is a precipitating factor in causing early MS lesions includes increased protein levels of hypoxia-inducible factor-1α; presence of the D-110 hypoxia-inducible protein; increased expression of hypoxia-inducible genes in lesions as well as in adjacent normal-appearing white matter (NAWM); loss of myelin-associated glycoprotein in myelin of early MS lesions; a 50% reduction of blood flow through NAWM with areas of lowest blood flow having the greatest probability of lesion development. Why MS-like lesions develop following hypoxemic insults in some individuals but not in others is likely dependent upon the presence of immune predisposing factors that are governed genetically. Hypoperfusion may be due to decreased arterial supply, restricted venous return, or a combination of these. There are clinical trials ongoing or planned to treat chronic cerebrospinal venous insufficiency (CCSVI) through angioplasty. I suggest that it is important that clinical trials addressing vascular issues in MS should examine how the vascular intervention affects white matter perfusion and determine whether the extent of perfusion recovery and maintenance of this recovery is related to functional recovery and maintenance of functional recovery. Consideration should also be given to the possibility of arterial problems playing a role in hypoperfusion in some MS patients.