Survival analysis of clinical and genetic factors in an amyotrophic lateral sclerosis cohort from China

Objectives: To investigate the clinical and genetic factors influencing the survival of amyotrophic lateral sclerosis (ALS) patients in China.

Methods: 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.

Results: 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.

Conclusion: 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.