Blood Brain Barrier Compromise with Endothelial Inflammation may Lead to Autoimmune Loss of Myelin during Multiple Sclerosis(clickable)
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.
Dr Simka's research is going forward; this paper was written before they did the doppler study and found the vascular problems in all of their patients. The team is now working through the hospital ethics committee to see about actual venograms to assess the source of the reflux. I am not sure, but I believe they intend to treat people at some point as well.
Dr Simka's review is very important in that it supports the work out of Ferrara. He is saying I have reviewed the literature and I agree this might be an issue while adding an additional element of how it may be possible for this pathology to tie in to autoimmunity rather than JUST being a mechanical thing. If such a case turned out to be true, treatment would possibly be both stents and immune suppression if the autoimmune element of this was self perpetuating once the CCSVI was treated.
That having been said we have no evidence that in absence of CCSVI a person would have on going autoimmunity: no one has researched that at this point!! more work needs to be done.
My personal belief is that there will not be shown to be an autoimmune element to worry about; that if the venous reflux is stopped all of these things, looking at Dr Simkas work above, the ICAM1, the adhesion etc would stop and it would be a moot point.
But importantly this is a peer coming out and saying this is plausible, put me down as supporting this as well. We need all of these we can get....