Irregular sleep-wake rhythm disorder: From the pathophysiologic perspective to the treatment

Irregular sleep-wake rhythm disorder (ISWRD) is an intrinsic circadian rhythm disorder caused by loss of the brain's circadian regulation, through changes of the input and/or output to the suprachiasmatic nucleus (SCN), or of the SCN itself. Although there are limited prevalence data for this rare disease, ISWRD is associated with neurodegenerative disorders, including the Alzheimer disease (AD) and the Parkinson disease (PD), which will become increasingly prevalent in an aging population. It additionally presents in childhood developmental disorders, psychiatric disorders, and traumatic brain injury (TBI). Patients present with unpredictable, short sleep periods over a 24-h period, with significant day-to-day and weekly variability. Symptoms manifest as insomnia and excessive daytime sleepiness. Sleep logs and actigraphy monitoring capture rest-activity patterns required for diagnosis. Treatment aims to enhance external circadian cues through timed light therapy, behavioral activity regimens, and melatonin, but efficacy remains quite limited. Pathophysiology of ISWRD in association with various diseases and their specific management are discussed. There is a need for further investigation of disease pathophysiology, development of widely applicable tools for diagnosis, and development of treatments.