Disease activity predicts worse prognosis


Yet more evidence that lesion accumulation utilmately is detrimental in the future in terms of disability. So again further emphasizing that one needs to do want one can to limit damage accumulation. Sorry its so brief but not near a computer

Spinal cord lesions and brain grey matter atrophy independently predict clinical worsening in definite multiple sclerosis: a 5-year, multicentre study.

Rocca MA, Valsasina P, Meani A, Gobbi C, Zecca C, Barkhof F, Schoonheim MM, Strijbis EM, Vrenken H, Gallo A, Bisecco A, Ciccarelli O, Yiannakas M, Rovira A, Sastre-Garriga J, Palace J, Matthews L, Gass A, Eisele P, Lukas C, Bellenberg B, Margoni M, Preziosa P, Filippi M; MAGNIMS Study Group.J Neurol Neurosurg Psychiatry. 2022 Sep 28:jnnp-2022-329854. doi: 10.1136/jnnp-2022-329854. Online ahead of print.

Objectives: To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients.

Methods: Baseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8-5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years.

Results: At follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing-remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (β)=0.97), higher EDSS (β=0.41), higher cord lesion number (β=0.41), lower normalised cortical volume (β=-0.15) and lower cord area (β=-0.28) (C-index=0.81). Older age (β=0.86), higher EDSS (β=1.40) and cord lesion number (β=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (β=1.49), cord lesion number (β=1.02) and lower normalised cortical volume (β=-0.56) (C-index=0.88). Baseline age (β=0.30), higher EDSS (β=2.03), higher cord lesion number (β=0.66) and lower cord area (β=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (β=1.87) and cord lesion number (β=0.54) predicted EDSS=6.0 (C-index=0.91).

Conclusions: Spinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.

This one below is open sourse so have a read. It groups people and finds slow and fast progressors. Trials fail when people do not progress fast enough.

Signori A, Lorscheider J, Vukusic S, Trojano M, Iaffaldano P, Hillert J, Hyde R, Pellegrini F, Magyari M, Koch-Henriksen N, Sørensen PS, Spelman T, van der Walt A, Horakova D, Havrdova E, Girard M, Eichau S, Grand’Maison F, Gerlach O, Terzi M, Ozakbas S, Skibina O, Van Pesch V, Sa MJ, Prevost J, Alroughani R, McCombe PA, Gouider R, Mrabet S, Castillo-Trivino T, Zhu C, de Gans K, Sánchez-Menoyo JL, Yamout B, Khoury S, Sormani MP, Kalincik T, Butzkueven H; Big MS Data Network. Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network. J Neurol Neurosurg Psychiatry. 2022 Sep 28:jnnp-2022-329987. doi: 10.1136/jnnp-2022-329987

Background: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.

Methods: All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2.. Click. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis.) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled.

Results: A total of 3613 patients with SPMS were included in the cohort 1. Modelling detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.

Conclusions: Contrary to previous interpretations, patients with SPMS (between EDSS 3-4. I think the previous stuff was EDSS 4-6 being at a similar rate) progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression

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  • My consultant actually had the nerve, no pun intended, to tell me that relapses can be good in relation to disease progression, whilst I was in the middle of a horrible brainstem relapse last year. I have this in writing from him.
    When I questioned him at length about how this could be possible, at a face to face appointment, he did answer me, and I still do not understand. I kept on thinking of Prof G’s comments re relapses.
    After putting up with several years of such replies & comments to my many questions, I have requested a change of neurologist – fingers crossed we will be on the same wavelength.

    • Sorry to hear that. Relapses are never beneficial, unless in the WON (world of NHS), where a certain n relapses is required to make you eligible for specific DMTs.

  • Were the people with MS in this study on any DMTs? The summary does not inform about this. I would expect DMTs to have some sort of effect on the progression of MS.

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