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New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability.

ABSTRACT: The search for the genetic foundation of multiple sclerosis (MS) severity remains elusive. It is, in fact, controversial whether MS severity is a stable feature that predicts future disability progression. If MS severity is not stable, it is unlikely that genotype decisively determines disability progression. An alternative explanation tested here is that the apparent instability of MS severity is caused by inaccuracies of its current measurement. We applied statistical learning techniques to a 902 patient-years longitudinal cohort of MS patients, divided into training (n?=?133) and validation (n?=?68) sub-cohorts, to test four hypotheses: (1) there is intra-individual stability in the rate of accumulation of MS-related disability, which is also influenced by extrinsic factors. (2) Previous results from observational studies are negatively affected by the insensitive nature of the Expanded Disability Status Scale (EDSS). The EDSS-based MS Severity Score (MSSS) is further disadvantaged by the inability to reliably measure MS onset and, consequently, disease duration (DD). (3) Replacing EDSS with a sensitive scale, i.e., Combinatorial Weight-Adjusted Disability Score (CombiWISE), and substituting age for DD will significantly improve predictions of future accumulation of disability. (4) Adjusting measured disability for the efficacy of administered therapies and other relevant external features will further strengthen predictions of future MS course. The result is a MS disease severity scale (MS-DSS) derived by conceptual advancements of MSSS and a statistical learning method called gradient boosting machines (GBM). MS-DSS greatly outperforms MSSS and the recently developed Age Related MS Severity Score in predicting future disability progression. In an independent validation cohort, MS-DSS measured at the first clinic visit correlated significantly with subsequent therapy-adjusted progression slopes (r?=?0.5448, p?=?1.56e-06) measured by CombiWISE. To facilitate widespread use of MS-DSS, we developed a free, interactive web application that calculates all aspects of MS-DSS and its contributing scales from user-provided raw data. MS-DSS represents a much-needed tool for genotype-phenotype correlations, for identifying biological processes that underlie MS progression, and for aiding therapeutic decisions.

SUBMITTER: Weideman AM

PROVIDER: S-EPMC5686060 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability.

Weideman Ann Marie AM Barbour Christopher C Tapia-Maltos Marco Aurelio MA Tran Tan T Jackson Kayla K Kosa Peter P Komori Mika M Wichman Alison A Johnson Kory K Greenwood Mark M Bielekova Bibiana B

Frontiers in neurology 20171110

The search for the genetic foundation of multiple sclerosis (MS) severity remains elusive. It is, in fact, controversial whether MS severity is a stable feature that predicts future disability progression. If MS severity is not stable, it is unlikely that genotype decisively determines disability progression. An alternative explanation tested here is that the apparent instability of MS severity is caused by inaccuracies of its current measurement. We applied statistical learning techniques to a ...[more]

PMID: 29176958

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Project description:Background and objectivesLarge-scale observational studies have shown that, in patients with multiple sclerosis (MS), the risk of becoming more severely ill from coronavirus disease 2019 (COVID-19) is determined by older age, male sex, cardiovascular comorbidities, African American ethnicity, progressive disease, recent use of corticosteroids, and B cell-depleting disease-modifying treatment. In contrast, the effect of COVID-19 on the disease course of MS has been studied much less extensively. Our main goal was to explore whether COVID-19 is associated with accelerated clinical disability worsening in patients with MS.MethodsSince March 2020, demographics and infectious outcome (categorized as ambulatory, hospitalized, and/or death) of patients with MS who developed COVID-19 have been collected at the Belgian National MS Center in Melsbroek. On February 28, 2022, this database was locked and complemented with clinical disability measures-Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FWT), 9-Hole Peg Test (9HPT), and Symbol Digit Modalities Test (SDMT)-that were available from a larger local database, obtained during routine medical follow-up. For each parameter, the first 2 assessments before COVID-19 diagnosis (T0 and T1; T1 is the closest to COVID-19 diagnosis), and the first thereafter (T2), were retrieved.ResultsWe identified 234 unique cases of COVID-19. Thirty-one patients were hospitalized (13.2%), and 5 died (2.1%) as a result of their infection. Among survivors with complete EDSS results (N = 138), mean annualized T1-to-T2 EDSS worsening was more pronounced, compared with the respective change between T0 and T1 (0.3 ± 0.9 vs 0.1 ± 0.9, p = 0.012). No such differences were found for the T25FWT, 9HPT, and SDMT scores. Severe COVID-19 (hospitalization) was associated with clinically relevant T1-to-T2 EDSS worsening (OR 2.65, p = 0.042). Vaccination coverage in the total cohort was 53.8%. Being unprotected by vaccination at the time of infection was associated with a worse COVID-19 outcome (hospitalization and/or death; OR 3.52, p = 0.002) but not with clinically relevant T1-to-T2 EDSS worsening.DiscussionThe occurrence and severity of COVID-19 are both associated with clinical disability worsening in patients with MS. Vaccination protects against a more severe course of COVID-19 in this specific population.Trial registration informationThe study has been registered at ClinicalTrials.gov (study registration number: NCT05403463).

Dataset Information

New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability.

Publications

New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability.

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