finn wrote:Well, the theory of inflammation being the primary driving force of MS has been the widest health myth in MS research for 40 years, and most treatments in clinical trials at the moment are based on it (including Tovaxin). That is why I do understand your point of view.
Hi finn, I can't guess what the creator of Tovaxin had in mind other than to determine if and for how long the vaccine effect would remove the myelin reactive T cells from the system. And after that point to determine what effect removing those self-reactive T cells would have on MS.
Because for so long our vocabulary regarding the MS process was restricted to "permeable bbb, inflammation, neurodegeneration, lesions and atrophy" I think it got lost in the shuffle that something in the disease process precedes those things.
I have no idea what the future holds, but if in the future it is determined that Campath, HDC and/or Tovaxin stops MS in it's tracks, would it be completely correct for me to say they work by controlling inflammation, or you to say that they work by controlling neurodegeneration? I don't think so because they act at a point prior to the instigation of either inflammation or neurodegeneration. Kind of like removing the fuel before a fire can start as opposed to only concerning ourselves with inflammation and neurodegeneration is like attempts to dampen a fire which is already out of control.
Of course, anything I or anyone else on this site says should always be taken with a grain of salt. Over and above that, I'm about to say things, which I personally think are of a higher logic but which don't align with traditional MS "wisdom"
finn wrote:I believe there is plasticity in MS brain, too, but I doubt its ability to modify the neurodegenerative process of this disease. Of course it may have a modest effect on the clinical course of MS. Animal studies suggest that it takes 15-30% axonal loss before first permanent symptoms appear, and reorganizing pathways in the brain may be able to delay the process.
I don't hint that plasticity has any effect or direct relationship, positive or negative, with inflammation or neurodegeneration but that plasticity has a VASTLY greater ability to mask neurodegeneration than it has ever been given credit. Especially when progression is at a rate which plasticity can match, or almost match.
I think it's always important for us to keep in mind that with MS, involving the brain, spinal cord and optical nerves which for the most part are directly inaccessible to us, we have always been in the position of having to base opinions on what "seems" and not necessarily what "is". Although MRI helps, it isn't perfect and we still can't directly observe the MS process. Postmortem analysis lets us directly observe, but obviously after death and after the end of the MS process and decomposition has begun.
NONE of the information has ever been direct and this really is a situation in which common sense and logic should be aided by, but not directed by research results. That isn't what happened and that's why MS has remained so illusive for all these years.
I think there are at least two kinds of plasticity involved. One involves networks in the brain inherently having far more capacity than normal situations require. For our purposes allows ongoing damage to be masked without the brain actually having to “rewire” itself but instead, slowly obstructing the normally available pathways until reaching a point in which “traffic” (electrical impulses) is so congested that the effects are noticeable (what “seems” to us to be the first symptoms of MS and what would lead someone to seek diagnosis and which currently “seems” to us to be the beginning of the MS process). For some reason my mind always wants to consider this "quick plasticity".
It seems evident that most people only consider plasticity as "re-routing" of the circuits of the brain and is the type of plasticity we are most familiar in the rehabilitation of stroke and brain damage from car accidents, etc.... This is a slower process and is considered to REQUIRE intentional effort to implement. While it seems that intentional nurturing does insure a higher degree of completeness in rehabilitation and does speed rehabilitation, I'm convinced that through the use of necessity this type of plasticity does unintentionally and invisibly happen, especially in younger people.
At least two types of plasticity, each with their separate reservoirs of capacity and types of masking ability.
Hopefully you will consider my ideas on plasticity within the realm of possibility, maybe even within the realm of likelihood.
If you do and if you also agree that the entire accumulated knowledge base of MS “conventional wisdom” is based on indirect knowledge (based on what the picture “seems” to be) then you are ready to consider that, in addition to the traditional ways, there are other logical, possibly more logical, ways to view every aspect of MS.
Consider the RRMS phase. Although researchers admit they don’t know what is responsible for the symptoms and reversal of symptoms, it seems universally accepted that demyelinisation and remyelinisation is the driving force, despite the fact that it is obvious that remyelinisation is a slow process, which might even be slower in those with MS. The idea that remyelinisation might align with the timeline necessary to explain reversal of symptoms in RRMS is illogical.
Although when I mentioned it earlier it was appreciated like a fart in church, it seems much more logical to believe that in the RRMS phase, inflammation itself is initially responsible for the interruption of the nerve’s electrical impulses-the noticed symptoms. There is always permanent damage being done but, dependant on the severity of the inflammation, there are varying degrees of injury. Immediately fatally damage to some axons, mortally wounded but not immediately fatal and damage within the ability to heal. I think this is the reason why during initial relapses certain symptoms completely disappear during remission but after subsequent relapses almost inevitably become permanent. Underlining that, it seems most logical that a relapse portrays inflammation surpassing the combination of speed and ability of plasticity to mask symptoms.
It seems most logical that remission is the elimination or lessening of inflammation, again allowing efficiency of the electrical impulses of the nerves and subsequently allowing the masking ability of plasticity to keep pace.
Continuing the “Lyon hypothesis” into the progressive phase of MS, it might be accurate to consider that plasticity and inflammation still play a part, but like myself they are little worn out and don’t have the capacity they did in the past.
This seems to be an opportune time to point out that after MS has run it’s course for a certain amount of time, at some point in the progressive phase, it’s often been noticed that progression slows. That was a consideration when forming this hypothesis. What could possibly be the reasoning behind that?
Because any process we don’t understand and can’t explain, necessarily seems random, with further knowledge we most often find that it wasn’t really random at all. In the case of why and where inflammation and subsequent lesions form on the brain, at this point let’s go with the flow and consider it totally random because at this time we have no other options.
(of course this isn’t an accurate representation, but it might contain some degree of truth) Consider a brain in the beginning of the MS process as a spinning brain suspended on a string and we are the “monster” throwing darts at it, with the goal of always hitting a previously unaffected spot. In the beginning (the RRMS phase) this game is very successful but with enough time (the SPMS/PPMS phase) it becomes progressively harder to hit an unaffected area with a dart.
The truth in this might involve the fact that lesions are scar tissue, damaged tissue which (talking somewhat out of my arse here) might not lend itself to inflammation as well as
“virgin” tissue, in combination to the likelihood that the progressive phases align with a time when plasticity is reaching the end of certain capacities. I guess my point might be that it’s possible that the progressive phase might not signal an actual change in the disease process, as it “seems” to, but might instead, more sensibly, might be a visual sign that certain capacities have reached or are reaching their limits.
I admit that this is an imperfect hypothesis, which can’t be documented, but it continues to be a work in progress.