No I am not talking about football.
There is a lot of talk about whether smouldering lesions are something different, where their origins may be something other than immune attack. Whilst I have no problem with this, based on histology by the pathologists they accumulate over time.
Smouldering lesions are lesions with microglial edge
There are more smouldering lesions evident in progression
Now you can see whatt one person calls a smouldering lesion, which can be seen on MRI with an iron rim and has been there for a while another calls the smoldering lesion a pre-active lesion which is not going to be seen by MRI. When you do histology these are probably the early drivers and has a sick looking oligodendrocyte and microglia and no lymphocytes .
However, there has been some debate in the last couple of days about whether relapses matter. They do and you don’t want them, because with a relapse comes lesions and with lesions comes damage and with damage comes more smouldering lesions. This is the match that lights the fire and once enough fires have been lit they are going to burn for a long long time…maybe for ever.
We see this in the beasties there is nothing smouldering to start with but they certainly appear. Yes this is not MS, but it shows you what matches do and as we know people shouldn’t play with matches.
It is also the case the more fires you have at the beginning of MS the more likely that disability will appear. I guess there is a major window of opportunity to put the fires out. How long is the window open…I am suspecting not that long for some nerve tracts. (Red bettom looks at disability in those starting late with high efficacy treatment), but is early and you can see it is not a flat line. However the more fires you put out the better things will be, you just need differnt fire extinguishers to put out the embers..
Relapses add to permanent disability in relapsing multiple sclerosis patients.Koch-Henriksen N, Sørensen PS, Magyari M.Mult Scler Relat Disord. 2021 May 17;53:103029. doi: 10.1016/j.msard.2021.103029
Objective: Whether relapses have direct effects on permanent disability in multiple sclerosis is still an unsettled issue. We aimed at investigating the cumulative effect of breakthrough relapses on the Expanded Disability Status Scale (EDSS) in relapsing-onset MS patients under disease modifying therapy (DMT).
Methods: From the Danish Multiple Sclerosis Registry we identified all patients in Denmark with relapsing-onset MS who had started DMT and followed them from the first day of treatment. We included patients aged 18-59 with Kurtzke’s EDSS score < 6.0 at entry, and we compared patients with and without relapses during follow-up. Endpoints were 1) annualized increase in EDSS; 2) time to 6-month sustained EDSS-worsening; 3) time to EDSS 6.0; and 4) time to increase in pyramidal- and cerebellar functional systems. Patients with and without relapses after entry were 1:1 matched by sex, EDSS, and age at entry. We analysed EDSS-worsening with adjusted Generalized Linear Models and time to the endpoints with adjusted Cox regression.
Results: We included 1,428 patients with breakthrough relapses and 1,428 without. The adjusted annualized increase in EDSS was 0.179 in patients with relapses (95% CI 0.164 – 9.194) and 0.086 in patients without relapses (95% CI 0.074 – 0.097), but in patients with EDSS ≥ 4.0 at entry there was no difference. The hazard ratio for irreversible worsening of EDSS was 1.83 (95% CI 1.58 – 2.12) and for irreversible increase to EDSS 6.0 or more 1.62 (95% CI 1.25 – 2.10). Irreversible increase in pyramidal and cerebellar functional system scores also happened significantly earlier in patients with breakthrough relapses.
Conclusions: Our results indicate that breakthrough relapses under DMT is associated with increasing permanent disability in patients with EDSS < 4.0 at treatment start which calls for effective prevention of relapses.
Today we may as well have a 2 for 1
Sotiropoulos MG, Lokhande H, Healy BC, Polgar-Turcsanyi M, Glanz BI, Bakshi R, Weiner HL, Chitnis T. Relapse recovery in multiple sclerosis: Effect of treatment and contribution to long-term disability. Mult Scler J Exp Transl Clin. 2021 May 28;7(2):20552173211015503. doi: 10.1177/20552173211015503.
Background: Although recovery from relapses in MS appears to contribute to disability, it has largely been ignored as a treatment endpoint and disability predictor.
Objective: To identify demographic and clinical predictors of relapse recovery in the first 3 years and examine its contribution to 10-year disability and MRI outcomes.
Methods: Relapse recovery was retrospectively assessed in 360 patients with MS using the return of the Expanded Disability Status Scale (EDSS), Functional System Scale and neurologic signs to baseline at least 6 months after onset. Univariate and multivariable models were used to associate recovery with demographic and clinical factors and predict 10-year outcomes.
Results: Recovery from relapses in the first 3 years was better in patients who were younger, on disease-modifying treatment, with a longer disease duration and without bowel or bladder symptoms. For every incomplete recovery (meaning damage accumulated match struck and fire smouldering away) and , 10-year EDSS increased by 0.6 and 10-year timed 25-foot walk increased by 0.5 s. These outcomes were also higher with older age and higher baseline BMI. Ten-year MRI brain atrophy was associated only with older age, and MRI lesion volume was only associated with smoking.
Conclusions: Early initiation of disease-modifying treatment in MS was associated with improved relapse recovery, which in turn prevented long-term disability.
General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.