Abstract：
OBJECTIVE: Clarification of propagation patterns in amyotrophic lateral sclerosis (ALS) is challenging, but understanding these has implications for individual prognostication and clinical trial design. However, systematic knowledge in this area is lacking. The aim of this study was to characterize the spatial and temporal features of propagation patterns in ALS, and to evaluate the association between propagation patterns and survival.
METHODS: A cohort of 833 patients with ALS, diagnosed between January 2018 and December 2019 and followed to August 2021, was analysed. Spatial and temporal features of propagation patterns were determined based on the involved functional regions (bulbar, cervical, thoracic/respiratory and lumbar) in time order. The final propagation pattern was identified in patients with at least three functional regions involved. Kaplan-Meier analysis and Cox regression analysis were performed.
RESULTS: During a median follow-up of 21.2 months, 19 final propagation patterns were identified in 657 patients (78.9%). In survival analysis, we found that the earlier the respiratory functional region becomes involved, the higher the risk of death (time order: 1st: hazard ratio [HR], 3.35, 95% confidence interval [CI] 1.23-9.15; 2nd: HR 2.45, 95% CI 1.55-3.87; 3rd: HR 1.94, 95% CI 1.52-2.49), adjusting for age, sex, diagnostic delay, revised ALS Functional Rating Scale score, cognitive impairment and riluzole. Shorter interval time between involved regions was an independent adverse prognostic factor.
CONCLUSIONS: The propagation patterns of ALS are varied. The order in which the respiratory region becomes involved and the interval time between involvement of functional regions are predictors for prognosis.
METHODS: A cohort of 833 patients with ALS, diagnosed between January 2018 and December 2019 and followed to August 2021, was analysed. Spatial and temporal features of propagation patterns were determined based on the involved functional regions (bulbar, cervical, thoracic/respiratory and lumbar) in time order. The final propagation pattern was identified in patients with at least three functional regions involved. Kaplan-Meier analysis and Cox regression analysis were performed.
RESULTS: During a median follow-up of 21.2 months, 19 final propagation patterns were identified in 657 patients (78.9%). In survival analysis, we found that the earlier the respiratory functional region becomes involved, the higher the risk of death (time order: 1st: hazard ratio [HR], 3.35, 95% confidence interval [CI] 1.23-9.15; 2nd: HR 2.45, 95% CI 1.55-3.87; 3rd: HR 1.94, 95% CI 1.52-2.49), adjusting for age, sex, diagnostic delay, revised ALS Functional Rating Scale score, cognitive impairment and riluzole. Shorter interval time between involved regions was an independent adverse prognostic factor.
CONCLUSIONS: The propagation patterns of ALS are varied. The order in which the respiratory region becomes involved and the interval time between involvement of functional regions are predictors for prognosis.
摘要：
目的：明确肌萎缩侧索硬化症（ALS）的传播模式具有挑战性，但了解这些对个体预测和临床试验设计有意义.然而,缺乏这方面的系统知识。这项研究的目的是表征ALS中传播模式的时空特征，并评估传播模式与生存之间的关联。
方法：833名ALS患者的队列，分析了在2018年1月至2019年12月之间诊断并随访至2021年8月。传播模式的空间和时间特征是根据所涉及的功能区域(Bulbar，子宫颈,胸/呼吸和腰部)按时间顺序。在涉及至少三个功能区的患者中鉴定了最终的传播模式。进行Kaplan-Meier分析和Cox回归分析。
结果：在21.2个月的中位随访期间，在657例患者中确定了19种最终的传播模式（78.9％）。在生存分析中,我们发现呼吸功能区参与得越早，死亡风险越高(时间顺序：第1：危险比[HR]，3.35，95%置信区间[CI]1.23-9.15；第二：HR2.45，95%CI1.55-3.87；第三：HR1.94，95%CI1.52-2.49），调整年龄，性别,诊断延迟,修订后的ALS功能评定量表评分，认知障碍和利鲁唑。受累区域间隔时间越短是一个独立的不良预后因素。
结论：ALS的传播模式各不相同。呼吸区域参与的顺序以及功能区参与之间的间隔时间是预后的预测因子。
方法：833名ALS患者的队列，分析了在2018年1月至2019年12月之间诊断并随访至2021年8月。传播模式的空间和时间特征是根据所涉及的功能区域(Bulbar，子宫颈,胸/呼吸和腰部)按时间顺序。在涉及至少三个功能区的患者中鉴定了最终的传播模式。进行Kaplan-Meier分析和Cox回归分析。
结果：在21.2个月的中位随访期间，在657例患者中确定了19种最终的传播模式（78.9％）。在生存分析中,我们发现呼吸功能区参与得越早，死亡风险越高(时间顺序：第1：危险比[HR]，3.35，95%置信区间[CI]1.23-9.15；第二：HR2.45，95%CI1.55-3.87；第三：HR1.94，95%CI1.52-2.49），调整年龄，性别,诊断延迟,修订后的ALS功能评定量表评分，认知障碍和利鲁唑。受累区域间隔时间越短是一个独立的不良预后因素。
结论：ALS的传播模式各不相同。呼吸区域参与的顺序以及功能区参与之间的间隔时间是预后的预测因子。
