Manifold learning for amyotrophic lateral sclerosis functional loss assessment
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ORIGINAL COMMUNICATION
Manifold learning for amyotrophic lateral sclerosis functional loss assessment Development and validation of a prognosis model Vincent Grollemund1,2 · Gaétan Le Chat2 · Marie‑Sonia Secchi‑Buhour2 · François Delbot1,3 · Jean‑François Pradat‑Peyre1,3 · Peter Bede4,5,6 · Pierre‑François Pradat4,5,7 Received: 22 June 2020 / Revised: 5 August 2020 / Accepted: 6 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords ALS · Prognosis · UMAP · Manifold learning · Non-linear dimension reduction
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00415-020-10181-2) contains supplementary material, which is available to authorized users. * Vincent Grollemund [email protected] 1
LIP6, Sorbonne Université, Paris, France
2
FRS Consulting, Paris, France
3
Modal’X, Nanterre Université, Nanterre, France
4
Laboratoire d’Imagerie Biomédicale, Sorbonne Université, Paris, France
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative condition involving both the upper and lower motor neurons, leading to progressive limb weakness and bulbar dysfunction. Mean survival from 5
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