Wu Haoran, Erenay F Safa, Özaltın Osman Y, Dalgıç Özden O, Sır Mustafa Y, He Qi-Ming, Crum Brian A, Pasupathy Kalyan S
School of Business, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Department of Management Sciences and Engineering, University of Waterloo, Waterloo, ON, Canada.
J Neurol. 2024 Dec 16;272(1):69. doi: 10.1007/s00415-024-12819-x.
Understanding factors affecting the timing of critical clinical events in ALS progression.
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.
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.
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.
了解影响肌萎缩侧索硬化症（ALS）进展过程中关键临床事件发生时间的因素。
我们通过使用分类法，将来自PRO-ACT数据库的6366名患者的数据与通过关卡的信息相结合，根据关键事件（关卡）的发生时间来记录ALS的进展情况。首次就诊后通过ALS关卡的时间轨迹采用Kaplan-Meier分析得出。使用对数秩检验找出显著的预后因素。基于决策树的分类确定了以首次就诊时受累身体节段列表为特征的显著ALS表型。
标准预后因素（如性别和起病类型）以及与关卡相关的预后因素（表型和初始关卡水平）会影响ALS关卡的发生时间。例如，在首次就诊后的第三年，80%-100%的延髓起病患者与43%-48%的肢体起病患者，以及65%-73%的女性与42%-49%的男性失去了说话能力并开始使用饲管。与标准因素相比，与关卡相关的因素对ALS进展的影响更强。初始损伤水平在一个节段中对随后的ALS进展有显著影响，而受累节段组合进一步表征了进展速度。例如，首次就诊时言语正常（关卡水平0）的患者在一年内失去言语能力的可能性小于10%，而对于关卡水平1（言语受累）的患者，根据其他节段（腿部）受累情况，这种可能性在23%至53%之间变化。
与关卡和表型相关的因素对ALS关卡的发生时间有很大影响。应综合考虑所有因素，以更好地表征具有不同进展侵袭性的患者群体。
