How PwMS acquire disability

[NHE]

How patients with multiple sclerosis acquire disability
Brain. 2022 Feb 1;awac016.

Patients with multiple sclerosis acquire disability either through: (1) Relapse-associated worsening (RAW), or (2) progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins, and the extent to which multiple sclerosis therapies delay disability accumulation. Using the Novartis-Oxford MS (NO.MS) data pool spanning all multiple sclerosis phenotypes and pediatric multiple sclerosis, we evaluated ∼200,000 EDSS transitions from >27,000 patients with ≤15 years follow-up. We analyzed three datasets: (A) A full analysis dataset containing all observational and randomized controlled clinical trials in which disability and relapses were assessed (N = 27,328); (B) All phase 3 clinical trials (N = 8364); and (C) All placebo-controlled phase 3 clinical trials (N = 4970). We determined the relative importance of RAW and PIRA, investigated the role of relapses on all-cause disability worsening using Andersen-Gill models, and observed the impact of the mechanism of worsening and disease modifying therapies (DMTs) on the time to reach milestone disability levels using time continuous Markov models. PIRA started early in multiple sclerosis, occurred in all phenotypes, and became the principal driver of disability accumulation in the progressive phase of the disease. Relapses significantly increased the hazard of all-cause disability worsening events: Following a year in which relapses occurred (vs a year without relapses), the hazard increased by 31-48%; all p < 0.001. Pre-existing disability and older age were the principal risk factors for incomplete relapse recovery. For placebo-treated patients with minimal disability (EDSS 1) it took 8.95 years until increased limitation in walking ability (EDSS 4) and 18.48 years to require walking assistance (EDSS 6). Treating patients with DMTs delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and by 3.09 years (2.60, 3.72), respectively. In relapsing-remitting multiple sclerosis (RRMS), patients who worsened exclusively due to RAW events took a similar time to reach milestone EDSS values compared with those with PIRA events; the fastest transitions were observed in patients with PIRA and superimposed relapses. Our data confirm relapses contribute to the accumulation of disability, primarily early in multiple sclerosis. PIRA starts already in RRMS and becomes the dominant driver of disability accumulation as the disease evolves. Pre-existing disability and older age are the principal risk factors for further disability accumulation. Using DMTs delays disability accrual by years, with the potential to gain time being highest in the earliest stages of multiple sclerosis.

[ElliotB]

I believe certain specific disability related to walking that I have has been increasing because of a major attack I had almost 10 years ago that I believe damaged nerves so that my muscles in my left leg do not strengthen regardless of the amount of exercise I do. And I do a lot every day and have been for years. Fortunately I have not had any relapses since then, and many of my 'simpler' symptoms have improved or disappeared fully, but not my walking.

[Scott1]

Hi Elliot,
What sort of exercises do you do? I have found that concentrating on eccentric movement rather than concentric movement makes a big difference. Sometimes you need to find the antagonist muscle and work it rather than the one you think is not working. At other times, there can be a 'hard to isolate' muscle that is dominating the pattern of movement and it needs to be manually relaxed before you can re-establish anormal pattern. (e.g flexor digitorum longus can shorten leading to no ankle flexion, tight calves, curling toes and stiffer hamstrings- then, all that ricochets through the limb and up into the torso and you end up with a tight back, sore quads etc). If you can find a good dry needler ( not a fool who pretends to know anatomy - the major issue), the flexor can be released, but then it depends what sort of exercises you follow up with.
Regards,

[ElliotB]

I do a wide variety of exercise for many hours each day (3 to 5 hours per day), 7 days a week. I have been for years. I have no other issues as you mention, no swelling or stiffness either. I don't have drop foot either, but certain specific leg muscles remain weak. Those muscles simply will not strengthen. I had lost a lot of muscle mass in my leg over the past 5-7 years and have fortunately been able to gain some of it back over the past few years. But not enough obviously. But the muscles needed for certain specific movements associated with walking simply will not strengthen at all.

Scott, thank you for your suggestions.

[Scott1]

Hi Elliot,

I find with walking that I always have some muscles that aren't cooperating. Generally it turns out that a perfectly good muscle is doing way more work than it should to compensate for others that aren't. The overworked muscle becomes fatigued. That is the one that hurts but the problem is with the antagonist muscle that doesn't hurt at all. For example, my quads get sore because my glutes and my hamstrings are not doing enough. That affects rectus femoris (near the front of your hip) so my stride length shortens. I can get out of it if I work the antagonist to the muscle that is doing all the work.
The other group that everyone forgets about are the adductors. They impact on the big stringy hamstrings and they will pull the leg inward.
A really long duration Thomas stretch with a weight on the extended leg can release the rectus femoris but the benefit comes from then working the hamstrings by circling the leg in a bicycle action. The adductors can be worked by doing side-lying lifts with a weight on the extended leg.
A good dry needling session and a decent massage also help.
Hope that helps.
Regards,