Assessment of cardiac autonomic nervous system during sleep and sleep stability in patients affected by Amyotrofic Lateral Sclerosis

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease, associated with an almost exclusive involvement of upper and lower motor neurons, although autonomic impairment has also been described. Often patients affected by ALS complain of disturbed sleep and sudden death during sleep has been reported. To date, few overnight polysomnographic studies have been performed and a complete evaluation of autonomic nervous system (ANS) during sleep has never been performed before in ALS subjects. The aim of our study was to assess macro- and microstructure of sleep, detect any sleep disorders and evaluate cardiac ANS in a cohort of ALS patients, in order to better characterize the disease and identify novel strategies to improve quality of life and possibly prolong life expectancy. Methods: 23 patients affected by ALS (16M/7 F, age 26-79, mean 61) were compared to 15 healthy controls matched for age and sex. Each subject underwent a full-night videopolysomnography. Sleep staging was performed according to AASM criteria, assessment of sleep stability was made by means of both CAP detection and CPC (cardiopulmonary coupling), evaluation of ANS was made with assessment of HRV. Results: Compared to controls, ALS patients showed a significant reduction of sleep efficiency and of total sleep time, longer sleep latency than controls, together with an increased number of WASO, increased N1 sleep and decreased N2, N3 and REM sleep. Moreover patients showed a significant reduction of CAP rate mainly due to a significant reduction in phase A1 and A2. Compared to controls, patients showed significant reductions in: total HRV power during non-REM (p=0.005), LF in non-REM (p=0.01) and REM (p=0.003) sleep, and wake after sleep onset (WASO) (p=0.06) and also in HF during non-REM (p=0.04) and REM (p=0.05) sleep and WASO (p=0.03). CPC analysis showed the patients with the most advanced pathology, i.e. those with ALS-FRS<30, had the most unstable sleep patterns, with high percentage of LFC and low percentage of HFC (<4%). Interpretation: Our results confirm that sleep structure and stability of ALS patients is altered, and that there is a subclinical alteration of cardiac autonomic control in both sleep and wakefulness, with an impairment of both vagal and sympathetic systems. Moreover reduction of CAP rate, analogously to the reduction of HRV, may reflect an alteration of cortical circuits wich underlie to the organization of sleep and autonomic functions, which are strongly interconnected, that in these patients seem to be characterized by a marked rigidity, with poor reactivity and reduced adaptability to external or internal stimuli. These findings suggest the potential importance of assessment of autonomic nervous system and sleep in ALS, in conjunction with standard motor system evaluations.