Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Neurol Res. 2022 Jul;44(7):651-658. doi: 10.1080/01616412.2022.2029292. Epub 2022 Feb 23.
To investigate the clinical and genetic factors influencing the survival of amyotrophic lateral sclerosis (ALS) patients in China.
Patients were enrolled in the study between December 2013 and December 2018. Clinical variables were recorded upon patient diagnosis. Causative genes related to ALS were screened by whole-exome sequencing and validated by Sanger sequencing. Each patient was followed up every 3-6 months until the endpoint (death or tracheotomy) or the last connection time on 31 December 2020. Propensity score matching analysis was performed to match the genetic and non-genetic ALS patients. The Kaplan-Meier method and multivariable Cox regression were performed for survival analysis.
A total of 337 patients, including 32 with genetic ALS and 305 with non-genetic ALS, were enrolled in the study. Before matching, in univariate analysis, age of onset (P < 0.001), site of onset (P = 0.036), diagnostic delay (P < 0.001), ALSFRS-R score at diagnosis (P < 0.001), ΔALSFRS-R (P < 0.001), and causative mutations (P = 0.020) were significant prognostic factors. These factors remained statistically significant after multivariate analysis. After matching, in the multivariate analysis, age of onset (P = 0.003), site of onset (P = 0.014), diagnostic delay (P = 0.007), ALSFRS-R score at diagnosis (P = 0.010), ΔALSFRS-R (P = 0.007), and causative mutations (P = 0.003) were found to be significant prognostic factors.
Both clinical factors and genetic factors influenced survival in our ALS cohort. Clarifying of the underlying mechanisms is crucial for the development of future therapies.
研究影响中国肌萎缩侧索硬化（ALS）患者生存的临床和遗传因素。
患者于 2013 年 12 月至 2018 年 12 月期间入组本研究。在患者确诊时记录临床变量。通过全外显子组测序筛选与 ALS 相关的致病基因，并通过 Sanger 测序进行验证。每位患者每 3-6 个月随访一次，直至终点（死亡或气管切开术）或 2020 年 12 月 31 日最后一次联系时间。采用倾向评分匹配分析匹配遗传和非遗传 ALS 患者。采用 Kaplan-Meier 法和多变量 Cox 回归进行生存分析。
共纳入 337 例患者，其中 32 例为遗传 ALS，305 例为非遗传 ALS。在匹配前，单因素分析中，发病年龄（P<0.001）、发病部位（P=0.036）、诊断延迟（P<0.001）、诊断时 ALSFRS-R 评分（P<0.001）、ΔALSFRS-R（P<0.001）和致病突变（P=0.020）是显著的预后因素。多因素分析后这些因素仍具有统计学意义。匹配后，多因素分析中，发病年龄（P=0.003）、发病部位（P=0.014）、诊断延迟（P=0.007）、诊断时 ALSFRS-R 评分（P=0.010）、ΔALSFRS-R（P=0.007）和致病突变（P=0.003）是显著的预后因素。
临床因素和遗传因素均影响本 ALS 队列患者的生存。阐明潜在机制对于未来治疗方法的发展至关重要。
