Sleep, behavioral rhythms, and neurological disease

Abstract

Humans are creatures of habit, and behavioral rhythms both consciously and/or unconsciously govern our waking, sleeping, and working lives. Sleep is one of the most commonly studied behavioral rhythms and in animals is governed by a highly conserved genetic transcriptiontranslation network controlled by the genes PER1-3, CRY1-2, BMAL1, and CLOCK. Circadian traits influenced by these genes may, therefore, be heritable, however, the behavioral rhythm of sleep is less well understood in humans and complicated further by the fact that objective assessment, particularly in clinical settings, can be extremely difficult. However, behavioral rhythms are clearly of considerable relevance to aspects of human disease so that disruption of the circadian rhythm of sleep, for example, has been shown to influence disease onset, play a role in the timing and treatment of some neurological disorders, and even influence the time of death. Symptoms associated with abnormalities of sleep architecture are a frequent cause of referral to neurology services and a working knowledge of sleep rhythms and physiology is of considerable value to practicing clinicians. Presentations may constitute an isolated sleep disorder such as night terrors or parasomnias, a sleep-related presentation of a common neurological disorder such as nocturnal or frontal lobe epilepsy, or as an early manifesting feature of specific neurodegenerative disorders. In addition, patients with established neurological disease may also present with symptoms relating to abnormalities of sleep such as daytime fatigue or somnolence as a result of central and obstructive sleep apnea, central demyelinating diseases, or nocturnal breathlessness and wearing-off in Parkinson’s disease. Finally, sleep disruption may present alongside respiratory muscle weakness and bulbar dysfunction in patients with neuromuscular disease. The study of behavioral rhythms such as sleep together with the investigation of disorders of sleep as a risk factor or symptom of neurological disease may, therefore, provide insights into the understanding of pathophysiology of neurological disease and even the mechanisms of disease initiation, as illustrated by one of the studies reported below. In addition, information gathered in this specialist area may also provide an opportunity to study early disease traits, help identify potential disease biomarkers, target areas for neuroprotection, and illustrate opportunities for symptomatic sleep therapy in those with established disease. In this month’s Journal Club, we review three papers addressing three different aspects of clinical and scientific research in sleep. The first of these is a candidate gene association study evaluating associations between polymorphisms of evolutionally conserved clock genes and the timing of behavioral rhythms measured by actigraphy. The second paper is a prospective study of the clinical features and quantitative motor measures in patients with idiopathic REM sleep behavior disorder in prodromal pre-motor Parkinsonism, and the final paper is a retrospective study of sleep-disordered breathing in multiple sclerosis.