In response to a comment concerning dogma in the field of MS, I am going to publish a series of posts that are designed to “challenge the dogma”.
Dogma: persistent demyelination is a pathological features of non-relapsing progressive MS, i.e. secondary and primary progressive MS.
Dogma: persistent demyelination is a pathological features of non-relapsing progressive MS, i.e. secondary and primary progressive MS.
Question for Dr K: What is the evidence that there a sufficient number of demyelinated axons in non-relapsing progressive MS for remyelination therapeutic strategies to work?
dog·ma (dôg
m
, d
g-)
n. pl. dog·mas or dog·ma·ta (-m-t)
-t)
An authoritative principle, belief, or statement of ideas or opinion, especially one considered to be absolutely true.
Does this imply that remyelination therapies won't work in progressive MS?
Who is Dr K and what is the answer to that question?
Dr K is part of Team G, but has G thrown him a curve ball?The real answer is unknown, just parts of a jigsawWhat no opinion from VV?
Re: "Who is Dr K?"Dr K = Dr Klaus Schmierer; he is an expert in MS pathology and correlating it with MRI:1: Petzold A, Tozer DJ, Schmierer K. Axonal damage in the making: neurofilament phosphorylation, proton mobility and magnetisation transfer in multiple sclerosis normal appearing white matter. Exp Neurol. 2011 Dec;232(2):234-9. 2: Schmierer K, Thavarajah JR, An SF, Brandner S, Miller DH, Tozer DJ. Effects of formalin fixation on magnetic resonance indices in multiple sclerosis cortical gray matter. J Magn Reson Imaging. 2010 Nov;32(5):1054-60. 3: Schmierer K, Parkes HG, So PW, An SF, Brandner S, Ordidge RJ, Yousry TA, Miller DH. High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis. Brain. 2010 Mar;133(Pt 3):858-67. 4: Schmierer K, Parkes HG, So PW. Direct visualization of remyelination in multiple sclerosis using T2-weighted high-field MRI. Neurology. 2009 Feb 3;72(5):472. 5: Schmierer K, Wheeler-Kingshott CA, Tozer DJ, Boulby PA, Parkes HG, Yousry TA, Scaravilli F, Barker GJ, Tofts PS, Miller DH. Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation. Magn Reson Med. 2008 Feb;59(2):268-77. 6: Schmierer K, Tozer DJ, Scaravilli F, Altmann DR, Barker GJ, Tofts PS, Miller DH. Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain. J Magn Reson Imaging. 2007 Jul;26(1):41-51. 7: Schmierer K, Wheeler-Kingshott CA, Boulby PA, Scaravilli F, Altmann DR, Barker GJ, Tofts PS, Miller DH. Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage. 2007 Apr 1;35(2):467-77. 8: Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol. 2004 Sep;56(3):407-15.
Re: "What is the evidence that there a sufficient number of demyelinated axons in non-relapsing progressive MS for remyelination therapeutic strategies to work?"I am not sure if we can answer this question at present, which is why I have asked an expert in the field. This is a very important question and has direct relevance to what phase of the disease remyelination strategies should be targeting. The fact that Biogen-Idec is targeting early relapsing MS, and not progressive MS, with their anti-LINGO trial tells us something already.
Re "What no opinion from VV?"Questions: When were the four types of MS introduced and why? Was it on the eve of the first DMT? Do they really correspond to different causes and/or mechanisms of damage?I think you agree that while there is a perfect correspondence of brain lesions to the venous system, no such matching can be made for the spinal lesions. This means that the latter are NOT caused by something in the blood, NOR by the blood itself (energy of flow).The observation above is sufficient enough to differentiate cerebral and spinal lesions, and consequently cerebral and spinal MS. The question that should be made is how can two different kind of lesions co-exist in the same disease entity. And if someone had to choose, which of the two would consider closer to progressive MS?
When were the four types of MS introduced and why. Types of MS.It is simply a descriptive in clinical course. They were not thought to be fundementally different at first. However the realisation that progression was not responding to immunologicals (1990s) indicated that different mechanisms could be occurring.Are there different causes?Identical twins do not always have the same clinical course. Are there differnt mechanisms of damage, yes no doubt of this or they would all respond in the same way.
"I think you agree that while there is a perfect correspondence of brain lesions to the venous. No such matching can be made for the spinal lesions" No I do not agree.What about grey matter lesions? Especially those adjacent to the menigeal surface? Spinal cord are are around venules? So brain and Spinal MS, which are both around the venous sytem, as distinct entities makes no logical sense. There is nothing fundementally, pathologically different of lesions in brain and spinal cord.They can both be associated with progressive deteriorationBrain lesions will of course produce different symptoms to spinal cord lesions but that does not warrant a belief of spinal verse brain MS as two mutually exclusive mechanisms.However, why not write, in your own words, your thesis in a concise and digestible way (5-10 printed pages max) that takes modern histology/pathology and imaging and responses to therapy into account and publish it. There are plenty of review journals where this can go If it gets past the peer review process then we can discuss it.or you can discuss it on your blog and if you send the link maybe we and others can comment on it.
The thesis i describe belongs to Dr. F.Schelling, i have sent you the link to his website. All readers of this blog can easily find it.Identical twins are not structurally identical, only genetically. If i am using the term right, they differ in phenotype.Difference in DMT response is an insufficient argument to support the existence of a different damage mechanism in progressive MS. The reason is that DMT only seem to reduce MRI activity and ARR, criteria that are poorly related to disability progression.Gray matter lesions also form around veins that drain down to the straight sinus, as is the case with all white matter lesions. Isn't it so?On the other hand, spinal lesions DO NOT expand according to some venular pathway (Thron, Armin, K.: Vascular Anatomy of the Spinal Cord. Neuroradiological Investigations and Clinical Syndromes. Wien, Springer, 1988). Also, arteries and veins in the spinal cord lesions are affected on the their peripheral parts, that is by something OUTSIDE the blood stream (Dr Schelling's thesis has detailed references to support that).Mechanisms of brain and spinal lesion formation are not mutually exclusive but the exact opposite. They work together and eventually lead to progressive state.You 've said before that there is no data to support the idea of Dr. Schelling. Yet, i was diagnosed with whatever he foresaw, and following his idea only, i am reaching one year relapse,fatigue,headache-free. And i am NOT the only one.
I am aware of the paper written by Dr Schelling because you sent me the link (http://www.ms-info.net/evo/msmanu/984), when I asked you to write you views last time.Either you are Dr Schelling or they are not really your views, because you have added nothing to story in the paper. If you are basing your ideas on one single source, it is not the best research approach.I and some colleagues that I sent it to, read all 125 pages of it, but we did want to spend time discussing this. This is why I suggest that YOU condense this down into a readable amount and put your own views into this. I am sure that none of our readers havegot the tme or energy to read this (120+ pages is too much. Also as I have said to you before Your view needs to brought into the noughties as I believe none of the subject matter of Schelling was post 1990 and most of it was pre 1900s. Therefore 21 years of knowledge is essentially ignored and none of the modern pathology or magnetic resonance imaging, epidemeology, genetics, responses to therapy are part of this. Without this update and some real effort from yourself it is not a plausible effort worth speanding the time on. So you could spend your time researching this.
"I was diagnosed with whatever he (schelling foresaw), and following his idea only, i am reaching one year relapse,fatigue,headache-free. And i am NOT the only one. Explain his idea in a condensed fashion and people may want to read it. Then maybe we can get a pathologist to really address the references sources on which the ideas are based. But this is for a written paper and not the blog
"arteries and veins in the spinal cord lesions are affected on the their peripheral parts, that is by something OUTSIDE the blood stream" Outside the blood stream? I have seen spinal cord lesions along veins.Write your hypothesis in a digestable format and then get it peer reviewed and published. Then we can discuss this I have not got time to have one to ones and neither has G.