Non-24-Hour Sleep–Wake Disorder (N24) is a rare disorder that affects the circadian rhythms of 55%–70% of the totally blind population and a small proportion of the sighted population (the exact figure is unknown) [1, 2]. It is an extremely debilitating disorder, as it prevents affected individuals from adhering to the standard cycle of day and night, creating both social and occupational difficulties . Attempts to maintain the standard 24-hour cycle often result in severe sleep deprivation and consequent health complications such as depression and memory deficiencies . To help raise awareness for N24, this article explains the mechanism by which the disorder affects its sufferers, the extent to which it affects their lives, the difficulties in diagnosis and some of the treatments that are available.
How our sleep–wake pattern is controlled
Our circadian rhythm acts as an internal biological clock, which maintains our sleep–wake pattern around the 24-hour cycle of day and night. The circadian rhythm is controlled by the suprachiasmatic nucleus (SCN) in the brain via a hormone called melatonin, and its main function is to effectively boot up and shut down biological systems as required . Without regulation, the cycle of the SCN lasts slightly longer than 24 hours, leaving it marginally out of sync with the 24-hour day . Although this may not seem like a severe issue, if an individual’s circadian rhythm is regularly unsynchronised by an hour or more, this can have a cumulative effect and be extremely detrimental to day-to-day functioning. Usually, light and dark signals from the environment are crucial in helping to synchronise the internal biological clock to the external day–night cycle by controlling the release of melatonin from the SCN. Issues with any of the components involved in this system can cause our internal biological clock to be out of kilter and consequently cause circadian rhythm sleep–wake disorders, such as N24 [4,5].
How N24 arises
N24 occurs mainly in completely blind individuals because of their inability to consciously perceive light, which is the main regulator of the SCN (as discussed above) . N24 can also develop in sighted individuals, but this is a rare occurrence and the cause has not been established. There are a variety of different factors that can adversely affect the circadian rhythm, including, but not limited to, hormonal changes, prolonged periods of sleep inertia (the state of grogginess upon waking), differences in sensitivity to light and complications as a result of physical abnormalities (for example, head trauma) [2, 6]. If the SCN is unregulated, the circadian rhythm reverts to its natural length, lasting longer, or, in extremely rare cases, shorter, than the standard 24-hour day . As a result, the affected individual’s sleep and wake times gradually progress around the clock, leading to a persistent pattern of excessive daytime somnolence and nighttime insomnia . Because of the cyclic tendency of the condition, there are a few weeks where the affected person’s circadian rhythm will fall back into sync with the 24-hour clock; however, in general they will find they are unable to keep to the conventional sleep and wake times defined by occupational and social norms . Besides the strain this puts on the individual’s ability to maintain a career and participate in society, it can have a serious impact on their mental health, in some cases causing depression and feelings of loneliness .
Difficulties with diagnosis
Because N24 is such a rare disorder in sighted people, it is often challenging to diagnose and treat . Diagnosis usually takes the form of sleep pattern assessments over a suitable time period (often one week, although some patients may require longer). However, as symptoms are often initially seen in young adults, and because of the limited knowledge surrounding N24, the inability to adhere to standard sleep–wake times can sometimes be perceived as indolence .
Treatment in blind and sighted individuals
Various interventions can be used to promote sleeping and waking at conventional times, including a designated time for exercise, use of sleeping pills, and scheduled exposure to and avoidance of light . Blue light has one of the shortest wavelengths of visible light, which has a high impact on the SCN and melatonin release; because of this, it is the predominant type of light used in bright light therapy . In blind individuals, administering melatonin at strategically planned intervals is one of the most common treatments for N24 and is particularly effective when combined with light therapy . However, melatonin treatment is not recommended for sighted individuals with N24 – in fact, treatment guidelines for this group of patients are often vague and varied because of the difficulties and limitations of diagnosis .
Thanks to organisations such as the National Sleep Foundation, awareness of rare circadian rhythm sleep–wake disorders, such as N24, is being spread across the globe, contributing towards a drive to explore new treatments and improve diagnostic methods. For more information on N24, please visit their website: National Sleep Foundation.
- Emens JS and Eastman CI. Diagnosis and treatment of non-24-h sleep-wake disorder in the blind. Drugs 2017; 77 (6): 637–650.
- National Organization for Rare Disorders. Rare disease database: Non-24-hour sleep-wake disorder. Available at: https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder/. Accessed November 2019.
- Richards J and Gumz ML. Mechanism of the circadian clock in physiology. Am J Physiol Regul Integr Comp Physiol 2013; 304 (12): R1053–R1064.
- Auger RR, Burgess HJ, Emens JS et al. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: Advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), and irregular sleep-wake rhythm disorder (ISWRD). An update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med 2015; 11 (10): 1199–1236.
- Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol 2018; 175 (16): 3190–3199.
- Malkani RG, Abbott SM, Reid KJ et al. Diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder. J Clin Sleep Med 2018; 14 (4): 603–613.