the whole concept of MRIs being only loosely correlated with progression and/or disability
Because most MS damage occurs around blood vessels, it seemed reasonable that a toxin circulating in the bloodstream leaked out into the brain, even though no researcher could find a trace of it.
In point of fact, thanks to the work of Dejerine , we know that multiple sclerosis is a chronic, diffuse, and interstitial myelitis, in which the irritative process begins with the vascular element. The vessels are the seat of periarteritis and of endoarteritis. Their wall thickens and their lumen is constricted until, in the region of the capillaries, it is almost completely closed. Dejerine himself actually wondered whether these vascular infiltrations, which constitute the most significant manifestations of medullar involvement, might be the only histo-pathological lesions that can explain the genesis of multiple sclerosis.
Well, recently we've seen with MRI studies that there are blood perfusion abnormalities in active, acute MS plaques. Specifically, blood flow is increased in these areas. The idea that MS has something to do with the blood vessels and blood flow is new to me, and I'm not sure what it means.
MS results in intense inflammation within the brain and spinal cord, and there is increasing evidence that this can directly cause conduction and neurological deficits. This PhD project explores the hypothesis that the deficits arise because the nerve fibres passing through inflammatory lesions are relatively starved of oxygen and glucose. The hypothesis is strongly supported by historical evidence, currently largely forgotten, that drugs that open blood vessels (e.g. amyl nitrite) can restore function in MS within an hour. This study proposes to explore the mechanisms underlying such phenomena using several different experimental inflammatory and/or demyelinating models, focusing on the oxygen concentration within the lesions.
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