Research Progression Onset


Tuntuncu M et al. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.

Mult Scler. 2012 Jun 26. [Epub ahead of print]

Background:It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases.

Objective:Our aim was to confirm that onset of progressive disease course is more relevant to the patient’s age than the presence or duration of a pre-progression relapsing disease course in MS.

Methods:We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics, age-of-progression-onset and time to Expanded Disability Status Scale of 6 (EDSS6). 

Results: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression.

Conclusions:  Some MSers with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Prof G was talking about childhood MS and saying that Young MSers can show better recovery and the flip side was that be he thought that as you get older, you probably get worse at recovery. This study suggests that progression in MS more relates to your age than disease duration so younger people are more likely to start with RRMS prior to SPMS, whereas as if you are older at onset then the risk that disease is PPMS will increase, but this work shows that sometimes progressive MS does not occur. This may relate to the repair process and as we get older we do not repair evvery thing as well as we were younger. We have reported previously that this could related to immune effects and how well macrophages can clear up myelin damage or how we produce growth factors that facilitate recovery of nerve contacts and nerve pathways. This provides us some clues for treatments.
I was looking at some brain tissues of Progressive MSers with DoctorLove and ProfPaul over the last few days and it is easy to see why Immune therapies directed at lymphoid cells may not be that great at treating progressive MS, as the lesions are predominated by microglia and macrophages.

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  • It depends who you believe!

    Some say lymphocytes are everything…they have their heads firmly in the ground in my opinion.

    Others say that Progression has nothing to do with lymphocytes…maybe they are in the ground also

    However, the lymphocyte directed therapies have not stopped PPMS but can they change the slope of progression? Trials ongoing will attempt to answer this. I have views of the likely outcome, but the facts will speak for themselves

  • -You don't see lymphoid cells in the brain tissue of progressive MSers,
    -lymphocyte directed therapies do not help PPMS,
    -some people start with PPMS without an earlier relapsing phase
    Doesn't all this suggest that progression IS independent of lymphoctyes?

    '38% with RRMS did not develop progression by age 75': Somebody should study these people and find out how they differ from the other 62%.

  • Re: "You don't see lymphoid cells in the brain tissue of progressive MSers."

    This is not correct; MSers with progressive disease have a lot of lymphoid cells in their brains. I think the reasons why someone develops progressive MS rather than relapse-onset disease is unknown at present. But as there is inflammation any effective combination of treatments will need to include an anti-inflammatory drug, hence the recent trial activity in progressive MS with anti-inflammatory drugs (fingolimod, ocrelizumab and natalizumab).

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