Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome

Background Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). Method A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10±4 years old) and 11 HC (all females, 11±4 years old; p=0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0V% (sympathetic), 2UV%, and 2LV% (vagal). Results The 0V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p<0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p<0.01). However, the 0V% increased similarly from the wake to the REM stage in both RTT and HC groups. Conclusions Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.