Circadian Factors in Stroke: A Clinician's Perspective

Stroke remains one of the leading causes of mortality and long-term and permanent disability worldwide despite technological innovations and developments in pharmacotherapy. In the last few decades, the growing data have evidenced the role of the circadian system in brain vulnerability to damage, the development and evolution of stroke, and short-term and long-term recovery. On the other hand, the stroke itself can affect the circadian system via direct injury of specific brain structures involved in circadian regulation (i.e., hypothalamus, retinohypothalamic tracts, etc.) and impairment of endogenous regulatory mechanisms, metabolic derangement, and a neurogenic inflammatory response in acute stroke. Moreover, the disruption of circadian rhythms can occur or exacerbate as a result of exogenous factors related to hospitalization itself, the conditions in the intensive care unit and the ward (light, noise, etc.), medication (sedatives and hypnotics), and loss of external factors entraining the circadian rhythms. In the acute phase of stroke, patients demonstrate abnormal circadian variations in circadian biomarkers (melatonin, cortisol), core body temperature, and rest-activity patterns. The approaches aimed at the restoration of disrupted circadian patterns include pharmacological (melatonin supplementation) and non-medication (bright light therapy, shifting feeding schedules, etc.) interventions; however, their effects on short- and long-term recovery after stroke are not well understood.