“The pathology study below suggests that acute MS lesions in children with MS are more damaging that those that are found in adults. The number of transected, cut or shredded, axons (nerve processes) was 50% greater in inflammed MS lesions from children compared to lesions from adults. This may explain why children with MS are more likely to manifest with cognitive problems than adults. We have always put down the cognitive problems in paediatric MS to the fact that paediatric brain is not fully developed, or mature, therefore it can’t deal with the damage. This study suggests that there may be something different about the inflammatory response in children that is more damaging than that which occurs in adults. The latter is something that needs to be looked into; may be a young immune system has more robust and primed inflammatory mechanisms than an older immune system. The other explanation is that this study is biased by MSer selection. The children who had died of MS or needed biopsies were sicker, or had more active disease, compared to the adults MSers studied.”
Giovannoni G. Any evident MRI T2-lesion activity should guide change of therapy in multiple sclerosis – Yes. Mult Scler. 2015 Jan 26. pii: 1352458514566261.
Excerpt (concluding paragraph):
Critics claim that a zero-tolerance strategy would result in the majority of MS patients ending up on so-called highly effective, and potentially more risky, therapies. My response to this criticism is that if they have ongoing inflammation they probably need to be on highly effective therapies. A good analogy is the treat-to-target strategy adopted by rheumatologists to manage rheumatoid arthritis; their treatment algorithms are designed to suppress joint inflammation as much as possible and induce long-term remission with the aim of preventing end-organ, or permanent joint, damage. I don’t understand why MS neurologists would want to manage MS any differently. At least rheumatologists have the option of replacing joints when their treatment strategies fail. Unfortunately, MSologists do not have the luxury of being able to replace the brain and spinal cord; sadly, walking sticks, wheelchairs, beds and coffins await the victims of therapeutic nihilism. Will the non-adoption of a zero-tolerance strategy to focal inflammatory events in MS be viewed as a form of subliminal therapeutic nihilism by the next generation of MS neurologists and patients?
Epub: Pfeifenbring et al. Extensive acute axonal damage in paediatric multiple sclerosis lesions. Ann Neurol. 2015 Jan . doi: 10.1002/ana.24364.
Objective: Axonal damage occurs early in multiple sclerosis (MS) and contributes to the degree of clinical disability. Children with MS more often show disabling and polyfocal neurological symptoms at disease onset than adults with MS. Thus, axonal damage may differ between paediatric and adult MSers.
Methods: We analyzed axonal pathology in archival brain biopsy and autopsy samples from 19 children with early MS. Lesions were classified according to demyelinating activity and presence of remyelination. Axonal density and extent of acute axonal damage were assessed using Bielschowsky’s silver impregnation (axon stain) and immunohistochemistry for amyloid precursor protein (APP) respectively. Axonal injury was correlated with the inflammatory infiltrate as well as clinical characteristics. Results were compared with data from adult MSers.
CoI: multiple
the inflammatory response in children that is more damaging than that which occurs in adults.
Can you explain (I) what the inflammatory response is responding to (or why we can't identify what the response is against) and (ll) is the thing what the immune system is responding to actually causing any damage before the inflammatory response.
Re: " what the inflammatory response is responding to…"
The autoimmune theory states it is responding self-antigens. The infection hypothesis states the inflammation is in response to a virus that has yet to be identified. I personally favour the last hypothesis.
Yes, there is evidence of damage or something happening in the brain and spinal cord weeks to months before a lesion appears. I cover this topic in one of my recent SlideShares: http://multiple-sclerosis-research.blogspot.com/2014/12/canada-why-i-think-ms-is-caused-by-virus.html
Many thanks. Finding the virus will be a major breakthrough. I know you have work underway to try and do this.
Very dangerous wording in your last statement. Prof G."Therapeutic nihilism" is unacceptable because you are suggesting that neurologists exhibiting caution against emerging DMTs are nihilistic as opposed to justifiably prudent. Revise your words, please.
If it looks like a duck, walks like a duck and quacks like a duck, it's a duck.
Perhaps "therapeutic cowardice" may be more appropriate?
I was invited to write the paper with the explicit aim of generating controversy, debate, discussion, etc. which is why I used the phrase subliminal nihilism. It refers to the future not the present; It is a prediction and not a statement about the current state of play. And I am asking a question, not making a statement of fact.
"to make you aware that there are large number of neurologists who don't support the concept of NEDA (no evident disease activity), but prefer to target MEDA (minimal evident disease activity) and still others who don't think we should be monitoring a response, or lack of a response, to therapy with MRI at all"
Is this what is referred to as a postcode lottery – with how disabled you are likely to get depending on which camp your neuro falls in?
You are named on the ABN MS board Prof G – do you have any influence?