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Journal Articles Journal of Neurology Year : 2021

Manifold learning for amyotrophic lateral sclerosis functional loss assessment


Amyotrophic lateral sclerosis (ALS) is an inexorably progressive neurodegenerative condition with no effective diseasemodifying therapy at present. Given the striking clinical heterogeneity of the condition, the development and validation of reliable prognostic models is a recognised research priority. We present a prognostic model for functional decline in ALS where outcome uncertainty is taken into account. Patient data were reduced and projected onto a 2D space using Uniform Manifold Approximation and Projection (UMAP), a novel non-linear dimension reduction technique. Information from 3756 patients was included. Development data were sourced from past clinical trials. Real-world population data were used as validation data. Predictors included age, gender, region of onset, symptom duration, weight at baseline, functional impairment, and estimated rate of functional loss. UMAP projection of patients showed an informative 2D data distribution. As limited data availability precluded complex model designs, the projection was divided into three zones defined by a functional impairment range probability. Zone membership allowed individual patient prediction. Patients belonging to the first zone had a probability of 83% (± 3%) to have an ALSFRS score over 20 at 1-year follow-up. Patients within the second zone had a probability of 89% (± 4%) to have an ALSFRS score between 10 and 30 at 1 year follow-up. Finally, patients within the third zone had a probability of 88% (± 7%) to have an ALSFRS score lower than 20 at 1 year follow-up. This approach requires a limited set of features, is easily updated, improves with additional patient data, and accounts for results uncertainty. This method could therefore be used in a clinical setting for patient stratification and outcome projection.
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hal-03401779 , version 1 (25-10-2021)



Vincent Grollemund, Gaétan Le Chat, Marie-Sonia Secchi-Buhour, François Delbot, Jean-François Pradat-Peyre, et al.. Manifold learning for amyotrophic lateral sclerosis functional loss assessment. Journal of Neurology, 2021, 268 (3), pp.825 - 850. ⟨10.1007/s00415-020-10181-2⟩. ⟨hal-03401779⟩
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