Blood brain barrier compromise with endothelial inflammation may lead to autoimmune loss of myelin during multiple sclerosis.

Multiple sclerosis is an autoimmune disease characterized by multifocal areas of inflammation and demyelination within the central nervous system. The mechanism that triggers the disease remains elusive. However, recent findings may indicate that multiple sclerosis, at its source, could be a hemodynamic disorder. It has been found that multiple sclerosis patients exhibit significant stenoses in extracranial veins draining the central nervous system (in azygous and internal jugular veins), which are associated with significant pressure gradients measured across strictures. Such anatomic venous abnormalities were not found in the control group of healthy subjects. In this review, it is hypothesized that pathological refluxing venous flow in the cerebral and spinal veins increases the expression of adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1), by the cerebrovascular endothelium. This, in turn, could lead to the increased permeability of the blood-brain barrier. Inflamed and activated endothelium could secrete proinflammatory cytokines, including GM-CSF and TGF-beta In these settings, monocytes could transform into antigen-presenting cells and initiate an autoimmune attack against myelin-containing cells. Consequently, a potential therapeutic option for multiple sclerosis could be pharmacotherapy with either substances that strengthen the tight-junctions barrier, or with agents that reduce the expression of adhesion molecules. In addition, surgical correction could be an option in some anatomical variants of pathologic venous outflow. We are optimistic that a hemodynamic approach to the multiple sclerosis pathogenesis can open a new chapter of investigations and treatment of this debilitating neurologic disease.