Journal of neurology · 2024
Prognostic factors affecting ALS progression through disease tollgates.
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Wu Haoran, Erenay F Safa, Özaltın Osman Y, Dalgıç Özden O, Sır Mustafa Y, He Qi-Ming, Crum Brian A, Pasupathy Kalyan S, Pooled Resource Open-Access ALS Clinical Trials Consortium
Аннотация
BACKGROUND AND OBJECTIVES: Understanding factors affecting the timing of critical clinical events in ALS progression.
METHODS: We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients' data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan-Meier analyses. The significant prognostic factors were found using log-rank tests. Decision-tree-based classifications identified significant ALS phenotypes characterized by the list of body segments involved at the first visit.
RESULTS: Standard (e.g., gender and onset type) and tollgate-related (phenotype and initial tollgate level) prognostic factors affect the timing of ALS tollgates. For instance, by the third year after the first visit, 80-100% of bulbar-onset patients vs. 43-48% of limb-onset patients, and 65-73% of females vs. 42-49% of males lost the ability to talk and started using a feeding tube. Compared to the standard factors, tollgate-related factors had a stronger effect on ALS progression. The initial impairment level significantly impacted subsequent ALS progression in a segment while affected segment combinations further characterized progression speed. For instance, patients with normal speech (Tollgate Level 0) at the first visit had less than a 10% likelihood of losing speech within a year, while for patients with Tollgate Level 1 (affected speech), this likelihood varied between 23 and 53% based on additional segment (leg) involvement.
CONCLUSIONS: Tollgate- and phenotype-related factors have a strong effect on the timing of ALS tollgates. All factors should be jointly considered to better characterize patient groups with different progression aggressiveness.
METHODS: We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients' data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan-Meier analyses. The significant prognostic factors were found using log-rank tests. Decision-tree-based classifications identified significant ALS phenotypes characterized by the list of body segments involved at the first visit.
RESULTS: Standard (e.g., gender and onset type) and tollgate-related (phenotype and initial tollgate level) prognostic factors affect the timing of ALS tollgates. For instance, by the third year after the first visit, 80-100% of bulbar-onset patients vs. 43-48% of limb-onset patients, and 65-73% of females vs. 42-49% of males lost the ability to talk and started using a feeding tube. Compared to the standard factors, tollgate-related factors had a stronger effect on ALS progression. The initial impairment level significantly impacted subsequent ALS progression in a segment while affected segment combinations further characterized progression speed. For instance, patients with normal speech (Tollgate Level 0) at the first visit had less than a 10% likelihood of losing speech within a year, while for patients with Tollgate Level 1 (affected speech), this likelihood varied between 23 and 53% based on additional segment (leg) involvement.
CONCLUSIONS: Tollgate- and phenotype-related factors have a strong effect on the timing of ALS tollgates. All factors should be jointly considered to better characterize patient groups with different progression aggressiveness.