Non-24-hour sleep–wake disorder

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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Non-24-hour sleep–wake disorder
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Insomnia, excessive daytime sleepiness
Complications	N/A
Onset	Typically in blind individuals
Duration	Chronic
Types	N/A
Causes	Circadian rhythm disruption
Risks	Blindness, shift work
Diagnosis	Actigraphy, sleep diary, polysomnography
Differential diagnosis	Delayed sleep phase disorder, advanced sleep phase disorder
Prevention	N/A
Treatment	Melatonin, light therapy, chronotherapy
Medication	N/A
Prognosis	N/A
Frequency	Rare in the general population, more common in blind individuals
Deaths	N/A

Non-24-hour sleep-wake disorder (non-24 or N24SWD) is a type of chronic circadian rhythm sleep disorder (CRSD) characterized by a persistent pattern of daily delays in sleep onset and wake times for individuals living in society. The disorder occurs when the endogenous circadian rhythm is not entrained (free-running) and becomes misaligned with the natural light/dark cycle. While it is more prevalent in blind individuals, affecting up to 70% of those who are completely blind, it can also impact sighted individuals. Non-24 may be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) has provided guidelines for CRSD since 2007, with the most recent update in 2015.

Sighted Individuals

In those with non-24, the body resists adapting to the 24-hour light-dark cycle, insisting on a day and night duration that is noticeably longer (or, very rarely, shorter). This makes it difficult to sleep at conventional times and causes daily shifts in other aspects of the circadian rhythm, such as peak alertness, body temperature minimum, metabolism, and hormone secretion. Non-24 causes the sleep-wake cycle to shift around the clock each day, eventually returning to "normal" before drifting again. This phenomenon is known as free-running sleep. Individuals with non-24 may struggle to adjust to changes in typical sleep-wake cycles due to factors like vacations, stress, evening activities, daylight saving time, time zone travel, illness, medications (particularly stimulants or sedatives), seasonal daylight hour changes, and growth spurts that can cause fatigue. They also exhibit lower sleep propensity following total sleep deprivation compared to normal sleepers. Non-24 can begin at any age, often during childhood, and may be preceded by delayed sleep phase disorder. The disorder can severely impair functioning in school, work, and social situations. Attempts to adhere to conventional schedules typically result in insomnia and excessive sleepiness. Sighted individuals with non-24 who force themselves to maintain a regular work schedule often experience difficulties and may develop physical and psychological complaints, such as sleepiness, fatigue, headache, decreased appetite, or depressed mood. These individuals may also struggle to maintain ordinary social lives and may lose their jobs or fail to attend school.

Blind Individuals

It is estimated that non-24 affects more than half of all totally blind individuals. The disorder can occur at any age and often develops shortly after the loss or removal of a person's eyes, as the retina's photosensitive ganglion cells are also removed. In the absence of light reaching the retina, the suprachiasmatic nucleus (SCN) in the hypothalamus is not signaled daily to synchronize the circadian rhythm to the 24-hour social day. This results in non-24 for many completely blind individuals. Non-24 is rare among visually impaired patients who retain some light perception. Even minimal light exposure at night can influence the body clock.

Symptoms

Individuals with non-24 may find it challenging to follow a regular schedule, as their biological clock can shift significantly, causing sleepiness during the day and insomnia at night. Another diagnostic feature of non-24 is its cyclical nature, with periods of daytime sleeping (symptomatic periods) alternating with periods of sleeping during normal nighttime hours (asymptomatic periods). When forced into a 24-hour schedule, patients may experience symptoms similar to sleep deprivation, including:

• Apraxia (ideational, ideomotor, kinetic, limb, verbal)
• Cognitive dysfunction
• Concentration difficulties
• Confusion
• Depressed mood
• Diarrhea
• Extreme nausea
• Extreme fatigue
• Hair loss
• Headaches
• Impaired balance
• Photosensitivity
• Joint pain
• Loss of muscle coordination (ataxia)
• Menstrual irregularities
• Muscle pain
• Suicidal thoughts
• Weight gain
• Hallucinations

Causes

Sighted

Sighted individuals with non-24 are less common than blind individuals with the disorder, and the etiology of their circadian disorder is less well understood. In some cases, non-24 in sighted individuals has been preceded by a head injury or the discovery of a large pituitary adenoma affecting the optic chiasma. The problem appears to be neurological, specifically involving abnormal functioning of the suprachiasmatic nucleus (SCN) in the hypothalamus. Other cases have been preceded by chronotherapy, a prescribed treatment for delayed sleep phase disorder.

Blind

In blind individuals, non-24 is primarily caused by the absence of light perception, which prevents the proper entrainment of the circadian rhythm. The retina's photosensitive ganglion cells, responsible for transmitting light information to the SCN, are unable to receive light signals, leading to a free-running sleep pattern that does not align with the 24-hour day.

PRC light and Melatonin

Treatment

Treatment for non-24 typically involves regulating the sleep-wake cycle to help patients synchronize their circadian rhythms with the 24-hour day. Common treatment options include:

• Melatonin: Melatonin supplements may be prescribed to help regulate the sleep-wake cycle. This hormone is naturally produced by the body and helps to signal when it's time to sleep.
• Light therapy: Exposure to bright light at specific times during the day can help entrain the circadian rhythm. For blind individuals, light therapy may not be effective due to the lack of light perception.
• Tasimelteon: A melatonin receptor agonist, tasimelteon is specifically approved for the treatment of non-24 in totally blind individuals. It works by mimicking the effects of melatonin to help regulate the sleep-wake cycle.
• Sleep hygiene: Maintaining good sleep habits, such as creating a consistent bedtime routine, avoiding caffeine and alcohol close to bedtime, and creating a comfortable sleep environment, can help improve overall sleep quality.
• Chronotherapy: In some cases, gradually shifting sleep times to align with the desired schedule may help entrain the circadian rhythm. This approach should be undertaken with caution and under the guidance of a healthcare professional, as it may worsen the disorder in some individuals.

Due to the complexity of non-24, treatment should be tailored to the individual's specific needs and circumstances. Consulting with a healthcare professional experienced in circadian rhythm sleep disorders is essential for obtaining an accurate diagnosis and developing an appropriate treatment plan.

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