This article includes discussion of circadian rhythm sleep disorder: non-24-hour sleep-wake rhythm disorder, N24SWD, non-24-hour sleep-wake disorder, free-running disorder, nonentrained disorder, and hypernychthemeral syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
The authors describe the pathophysiology, clinical manifestations, diagnosis, and treatment of non-24-hour sleep-wake rhythm disorder. This rare circadian rhythm disorder, more commonly seen in blind individuals, is characterized by alternating episodes of excessive daytime sleepiness, insomnia, and normal sleep resulting from an endogenous circadian rhythm that is not entrained to a 24-hour light-dark cycle. Diagnosis is made using sleep logs and/or actigraphy to demonstrate a non-24-hour pattern. Other circadian phase markers including dim light melatonin onset and urinary 6-sulfatoxymelatonin may be used to confirm the non-24-hour pattern. Treatment strategies are targeted at entrainment of the circadian pacemaker, including light therapy and melatonin.
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• Non-24-hour sleep-wake rhythm disorder is a rare circadian rhythm disorder resulting from an endogenous circadian rhythm that it not entrained to a 24-hour light-dark cycle.
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• Although non-24-hour sleep-wake rhythm disorder is more commonly seen in blind individuals, it has also been described in sighted individuals.
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• The key clinical features of non-24-hour sleep-wake rhythm disorder include alternating periods of excessive daytime sleepiness, insomnia, and normal sleep.
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• Non-24-hour sleep-wake rhythm disorder is diagnosed by utilizing sleep logs and/or actigraphy to demonstrate a non-24-hour pattern. Other circadian phase markers may be used to confirm the non-24-hour pattern.
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• Treatment strategies for non-24-hour sleep-wake rhythm disorder are targeted at entrainment of the endogenous circadian pacemaker including light therapy and melatonin. The Food and Drug Administration approved tasimelteon, a melatonin receptor antagonist, for treatment in blind individuals with non-24-hour sleep-wake disorder.
Historical note and terminology
Although the human circadian rhythm was initially studied in the absence of time cues by Kleitman in 1938, indication of a possible inherent free-running rhythm was proposed by Halberg, who noted the disturbance in blinded mice (08). Independent observations by Siffre, Aschoff, and Mills in humans isolated from clues for extended periods of time suggested a similar free-running rhythm in humans (19). Yet the first pathological case of non-24-hour sleep-wake rhythm was described in 1971 in a sighted male individual with a 26-hour circadian period (05). The first description of a blind individual with non-24-hour sleep-wake rhythm disorder was in 1977 (18). In this case report, the blind male individual had a 24.9-hour circadian period. Since these initial case reports, there have been additional accounts of both sighted and blind individuals with non-24-hour sleep-wake rhythm disorder.