Study on sleep-wake disorders in patients with genetic and non-genetic amyotrophic lateral sclerosis

Objective To study the frequency and clinical features of sleep disturbances in amyotrophic lateral sclerosis (ALS) patients and compare sleep disorders between ALS with and without mutations. Methods In this case–control study, 204 ALS patients and 206 controls were included. We evaluated sleep quality using Pittsburgh Sleep Quality Index (PSQI). Excessive daytime sleepiness (EDS) was diagnosed according to Epworth Sleepiness Scale (ESS). Other characteristics, including rapid eye movement sleep behaviour disorder, restless legs syndrome (RLS), cognitive and psychological impairments, were also evaluated. All ALS patients underwent whole exome sequencing analysis to screen for ALS mutations and were divided into genetic ALS and non-genetic ALS subgroups based on the genetic testing results. Results A total of 114 men and 90 women ALS patients, with a mean onset age of 53.5±9.9 years, were included in this study. There were 21 mutations detected, contributing to 46.6% of familial amyotrophic lateral sclerosis (FALS) and 7.4% of sporadic amyotrophic lateral sclerosis (SALS). The PQSI and ESS scores were higher in ALS patients than in controls (PSQI 6.0 (3.0,10.0) vs 3.5 (2.0,5.0) (p<0.01); ESS 6.0 (3.0,10.0) vs 4.0 (3.0,8.0) (p<0.01), respectively). RLS was more frequent in ALS patients than in controls (p<0.01). Genetic ALS patients were more likely to show EDS than non-genetic ALS patients (adjusted OR 5.2, p<0.01). Genetic ALS scored lower on Revised ALS Functional Rating Scale, and higher on PSQI and ESS than non-genetic ALS (p<0.01). Conclusions In the current study, ALS patients with mutations were more likely to have sleep-wake disturbances than were those without mutations. The former group may benefit more from sleep management.