Monday, 15 February 2016

Age dictates Progression

Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers GC, Muraro PA.The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler. 2016 . pii: 1352458516630396. [Epub ahead of print]

BACKGROUND:The multiple sclerosis (MS) clinical course and relapses frequency before progression vary widely.
OBJECTIVE:To investigate the influence of age on the MS phenotype.
METHODS: Among 751 primary progressive (PP = 217) and secondary progressive (SP = 534) MS patients from the London Ontario database, we assessed the relationship of age on the relapse frequency and on the progressive phase evolution, and the impact of relapses on the age at onset of progression.
RESULTS: Age at onset did not influence the early attacks frequency, but patients younger at onset had larger number of total attacks before progression (age = 27.4, 31.0 and 32.8 mean years; ⩾4, 2-3 and 1 relapses, respectively) and longer latency to SP. Although frequent early relapses predicted younger age at SP onset, patients with no attacks (primary progressive multiple sclerosis (PPMS)), or 1, 2-3 and ⩾4 relapses during the relapsing-remitting phase started progressing at similar age (38.6, 41.3, 41.4 and 39.2 mean years, respectively). The age at onset of progressive phase did not affect its evolution.
CONCLUSIONS:Age strongly influences the phenotype before progression. Relapsing-remitting patients younger at onset are more likely to display a predominantly inflammatory course, yet relapses number does not affect the age at onset of progression.

This conclusion is not new and suggests that progression whether primary or secondary starts at a similar age, so whereas relapsing remitting starts at a younger age than progressive MS but the disability associated with progression occurs at the same time suggesting that neural reserve may fade as we get older and also possibly suggests that the process that dictates this may be independent of relapses. However in animals it is clear that progression can occur after one attack, two attacks, four attacks and this depends on the strain sex and age, but to think that the occurrence of attacks does not influence this as suggested in the paper is misleading. Depending on the strain the occurrence of progressive disability is absolutely dependent on the amount of nerve loss and damage already accumulated. We know that progresion is associated with nerve loss and that inflammation drives nerve loss so to think that this aspect does not have to be dealt with because the number of relapses do not dictate the age of onset of progression. Why an age related thing we know that we need to start wearing biifocals/varifocals from our mid 40s so what happens in age. Two things that have been shown to be age dependent are the ability to clear up debris by macophages and the other is neural plasticity, so as you repair potentials wain your progression may increase. However importantly the two issues above can both be manipulated.

Why the picture of the flower. Its there for the party pooper who doesn't want to see pictures of flowers:-)

12 comments:

  1. Quick question;
    If relapse rate does not impact progression, how does that fit with this idea that progression is simply the loss of axonal reserve? Wouldn't we expect someone with multiple relapses (ie more destroyed nerves) to run out of reserve earlier than someone without?

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  2. People with PPMS are not having obvious relapses, one way to see it it is like lighting a touch paper on a firework with a match sometimes it is the first one that gets the firework going, maybe the second one or third one.

    You create the damaged environment that conditions the progression and a relapse can be a very differnt thing.

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  3. I'm just wondering: Isn't it possible that progression is always there, right from the beginning, but that it only becomes apparent when there's a hit in a vital area, an area that cannot be compensated for? For example, in the spine? This might explain why "PPMS" tends to be associated with spinal lesions? I mean, I thought about 85% of lesions in the brain are asymptomatic, so progression of an asymptomatic lesion will also be asymptomatic?

    Beautiful flowers! :o)

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    1. Yes it can be there from the beginning and probably is

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    2. Then... why is important use of DMT if all at 40s will have SPMS?

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    3. Good point what does it say about the Canadian data or :-)

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  4. A couple of observations. I know a woman who had aggressive MS at Uni and was SPMS at 22 (in a wheelchair). I also know MSers in their 50s who are RRMS and taking interferon. I was diagnosed in my early 40s, had Campath (Alemtuzumab) soon after diagnosis of RRMS and 10 years on am considered as MS inactive (as measured by MRI and EDSS). So it's difficult to believe that MSers start progression at a similar age. If this is true, what's the point of highly effective treatments / brain health initiative? According to the research above we all go progressive at the same age regardless!

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    Replies
    1. good point. As every the MS data reports on the population and not the individual some do better others do worse

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    2. Reminds me of a very wise comment an excellent doctor I saw recently made: "Average doesn't cut it for the individual."

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  5. Conclusion: RR is worst than PPand SP

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  6. "Two things that have been shown to be age dependent are the ability to clear up debris by macophages and the other is neural plasticity, so as you repair potentials wain your progression may increase."

    The most important: "However importantly the two issues above can both be manipulated."

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  7. Then why alemtuzumab cohord has 5% patients going in to SP? this number should be around 50% being a 10+ years cohord. Switching off inflammation and preventing brain atrophy seems to have a positive outcome preventing SP onset?

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