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Circadian Rhythm Abnormalities

Zee, Phyllis C. MD, PhD; Attarian, Hrayr MD, FAASM, FCCP; Videnovic, Aleksandar MD, MSc

doi: 10.1212/01.CON.0000427209.21177.aa
Review Articles

Purpose: This article reviews the recent advances in understanding of the fundamental properties of circadian rhythms and discusses the clinical features, diagnosis, and treatment of circadian rhythm sleep disorders (CRSDs).

Recent Findings: Recent evidence strongly points to the ubiquitous influence of circadian timing in nearly all physiologic functions. Thus, in addition to the prominent sleep and wake disturbances, circadian rhythm disorders are associated with cognitive impairment, mood disturbances, and increased risk of cardiometabolic disorders. The recent availability of biomarkers of circadian timing in clinical practice has improved our ability to identify and treat these CRSDs.

Summary: Circadian rhythms are endogenous rhythms with a periodicity of approximately 24 hours. These rhythms are synchronized to the physical environment by social and work schedules by various photic and nonphotic stimuli. CRSDs result from a misalignment between the timing of the circadian rhythm and the external environment (eg, jet lag and shift work) or a dysfunction of the circadian clock or its afferent and efferent pathways (eg, delayed sleep-phase, advanced sleep-phase, non–24-hour, and irregular sleep-wake rhythm disorders). The most common symptoms of these disorders are difficulties with sleep onset and/or sleep maintenance and excessive sleepiness that are associated with impaired social and occupational functioning. Effective treatment for most of the CRSDs requires a multimodal approach to accelerate circadian realignment with timed exposure to light, avoidance of bright light at inappropriate times, and adherence to scheduled sleep and wake times. In addition, pharmacologic agents are recommended for some of the CRSDs. For delayed sleep-phase, non–24-hour, and shift work disorders, timed low-dose melatonin can help advance or entrain circadian rhythms; and for shift work disorder, wake-enhancing agents such as caffeine, modafinil, and armodafinil are options for the management of excessive sleepiness.

Address correspondence to Dr Phyllis C. Zee, Northwestern University, 710 North Lake Shore Dr, Chicago, IL 60611,

Relationship Disclosure: Dr Zee has received personal compensation for activities with Jazz Pharmaceuticals; Merck & Co, Inc; Perdue Pharma; Philips Respironics; Sanofi-Aventis; Takeda Pharmaceutical Company Limited; UCB; and Zeo, Inc. Dr Zee receives research support from Philips Respironics. Dr Attarian receives personal compensation for activities with American Physicians Institute. Dr Videnovic reports no disclosure.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Zee discusses the unlabeled use of melatonin for the treatment of circadian disorders. Dr Attarian discusses the unlabeled use of melatonin and light boxes to advance or delay circadian rhythms. Dr Videnovic discusses the unlabeled use of melatonin, ramelteon, and supplemental light exposure to advance circadian rhythms and treat jet-lag disorder.

© 2013 American Academy of Neurology
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