A meaningful prediction of functional decline in amyotrophic lateral sclerosis based on multi-event survival analysis

• URL: http://arxiv.org/abs/2506.02076v1
• Date: Mon, 02 Jun 2025 09:04:59 GMT
• Title: A meaningful prediction of functional decline in amyotrophic lateral sclerosis based on multi-event survival analysis
• Authors: Christian Marius Lillelund, Sanjay Kalra, Russell Greiner,
• Abstract summary: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons that causes progressive paralysis in patients.<n>We propose a novel method to predict the time until a patient with ALS experiences significant functional impairment.
• Score: 4.3399653291481215
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons that causes progressive paralysis in patients. Current treatment options aim to prolong survival and improve quality of life; however, due to the heterogeneity of the disease, it is often difficult to determine the optimal time for potential therapies or medical interventions. In this study, we propose a novel method to predict the time until a patient with ALS experiences significant functional impairment (ALSFRS-R<=2) with respect to five common functions: speaking, swallowing, handwriting, walking and breathing. We formulate this task as a multi-event survival problem and validate our approach in the PRO-ACT dataset by training five covariate-based survival models to estimate the probability of an event over a 500-day period after a baseline visit. We then predict five event-specific individual survival distributions (ISDs) for each patient, each providing an interpretable and meaningful estimate of when that event will likely take place in the future. The results show that covariate-based models are superior to the Kaplan-Meier estimator at predicting time-to-event outcomes. Additionally, our method enables practitioners to make individual counterfactual predictions, where certain features (covariates) can be changed to see their effect on the predicted outcome. In this regard, we find that Riluzole has little to no impact on predicted functional decline. However, for patients with bulbar-onset ALS, our method predicts considerably shorter counterfactual time-to-event estimates for tasks related to speech and swallowing compared to limb-onset ALS. The proposed method can be applied to current clinical examination data to assess the risk of functional decline and thus allow more personalized treatment planning.

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