uprightdoc wrote:According to the leaky blood brain barrier therory, lesions are a sign of breach or disruption of the blood brain and CSF barrier. In this regard, the classic lesions of MS are typically supratentorial (above the posterior fossa), periventricular and perivenular (Dawson's fingers). Many MS signs and symptoms, however, are often from infratorial structures (within the posterior fossa) such as the brainstem and cerebellum. The only lesions that I have found that clearly correlate with the signs and symptoms is optic neuritis and lesions in the optic nerve. It hard to explain arm and leg weakness according to classic lesions. Moreover, many patients have no lesions or obvious signs of disruption of the blood brain barrier. Some patients without lesions have more progressive conditons and greater disability.
Aside from optic neurtitis, do you know of any cases where the lesions correlate with the signs and symptoms?
Happy to offer a possible explanation for this, just my speculation, nothing I've seen in the literature on it.
I think you are suggesting and I agree that what we are seeing on MRI is not necessarily the whole picture of what is going on.
With some imaging modes, we are probably seeing places where there BBB is injured and there is an active inflammatory state.
I would expect that there would also be relatively more damage in the CNS near these areas than farther away, but if the theory is correct that CD4+ T-cells are targeting myelin, I don't see any reason that if they cross into the CNS, they can't go almost anywhere in the CNS through the CNS circulatory system, CSF.
I know zip about this circulation, but it may also in some way be tied to the types of problems that are seen in CCSVI in which the left jugular almost always causes my flow disturbances than the right side and more issues with the left transverse sinus which sometimes isn't even there. Could the location of the problems associated with CCSVI explain the injury that occurs to the veins? I don't know. I'm not even suggesting this is the case as much as asking if it is and if so, does this help explain the geography of injury?
The other factor here may be that until fairly recently, we couldn't see lesions in gray matter so we assumed they were not there. Now that it is being examined, we are seeing both lesions and atrophy (presumably because nerves are dying) and has a much greater correlation with disability that white matter lesions which almost seem to have no relationship with disability.
Is "many" the right characterization of the number of people who show no lesions? I agree that white matter lesions tell us nothing about disability.
But, what if the process is as Prof Hayes found in her mice? A breach in the BBB allows immune cells that don't belong in the CNS to migrate there and cause damage to nerves through demyelination? Even after the BBB injury is healed, you've still got these immortal T-cells wrecking havoc because there is an insufficient amount of calcitriol to cause them to undergo programmed cell death.
RRMS then becomes a phase when there is ongoing or at least relapsing injury to the BBB which does show up nicely on MRI and SPMS and PPMS are states where the problem is solely the activity of the immune system in the CNS and the BBB is intact?
That works for me, but then there is way more about all this than my mind can get a handle on. :>)