Non-24-hour sleep-wake rhythm disorder which is also referred to as non-24 or N24 is a chronic and rare circadian rhythm sleep disorder. Non-24 is not a specific sleep-wake disorder; however, people with non-24 circadian rhythm disorder sleep and wake abnormally more than typical 24-hour day-night cycle sleep. Circadian rhythm is a biological clock within an organism that controls rhythms of behavior and physiology in relation to environmental conditions, especially light and darkness.

In individuals with non-24, it has been found that the natural biological rhythm of their bodies takes more than 24 hours to complete one cycle getting out of synchronization with the day-night cycle slowly. 

Non-24 is diagnosed in a small number of people in the general population. However, it is present more commonly in people with the disability of blindness. Currently, it is estimated that 50 to 70% of persons who are entirely blind might be affected by non-24. The sleep-wake patterns in non-24 are defined by a progressive shift in the timing of sleep and wake-up time each day. This leads to a circadian rhythm shift; the cycle turns clockwise, leading to a regular change of sleep during the day and wakefulness during the night. 

Non-24 is a type of circadian rhythm disorder where the molecular clock in the body is disrupted and does not work twenty-four hours a day.  Suprachiasmatic nucleus (SCN) is also known to be the master clock for controlling a number of physiological and behavioral processes, including the sleep/wake cycle. Under normal circadian conditions, light information is transmitted to SCN through the retinohypothalamic tract which consists of photosensitive retinal ganglion cells that can detect light. 

Circadian Disruption: Non-24 can develop due to the inability to reset the circadian rhythm to external light/dark cycle in individuals. 

Melatonin Imbalance: Usually, the amount of melatonin is regulated to be low in the day and gradually rise during the night to induce sleep. However, Non-24 is a condition that can interfere with the natural circadian rhythm and cause irregular sleep patterns because of melatonin production. 

Blindness: Non-24 is most seen in the blind people or those with other severe vision loss conditions. Lack of perception of light or the extent of the light signals can affect the entrainment of the biological clock to the light-dark regime. 

Degree of visual impairment: Non-24 is most likely to occur in severe forms of visual damage, and the severity of the impairment affects the probability and intensity of the condition. The people who have no perceiving of light at all or have very poor perceiving of light are those who are vulnerable to the altering of the circadian rhythms. 

Age of onset: Non-24 can manifest at any age, yet, it has been reported to be most prevalent in young adults. The age may determine the exact chronicity of this disorder, for it may remain chronic if the onset is at the early ages. 
Age Group: Non-24 can impact a patient’s age in one way or the other, but the condition is mostly witnessed in adults. The disorder is said to be less frequent in children and the adolescent population. Non-24 in blind persons can start at birth or adolescence, and the condition is considered chronic. 

A thorough health information is helpful in diagnosing the patient’s sleep duration, efficiency and any complaints they may have. This involves reviewing current medical situations, prescribed drugs, and past or present habits that affect sleep in patients. A physical examination is also required to evaluate patient’s temperature, pulse, blood pressure, and oxygen saturation as well as palpate for any physical signs related to sleep disorders or other illnesses. Another parameter of independent evaluation is the presence of various ailments, like blindness or disorders of the circadian system.

Blindness: Non-24 is mainly related to total or near total loss of sight. Lack of conscious awareness of light or the ability to differentiate between day and night further alters the entrainment of the sleep-wake cycle relative to the external world. 

Depression and Mood Disorders: People with Non-24 typically suffer from sleep disorders, and they did not follow a schedule of developing consistent sleep and wake up times. It is a form of chronic sleep disruption that significantly increases the vulnerability of affected patients to mood disorders such as depression and bipolar disorders. 

There is variation in the severity of presentation of N24SWD in people affected by the condition. Although, onset of the disease may be gradual in some patients and abrupt in others the quality and continuity of their sleep wake cycle will be affected. The intensity of the difficulties can also differ significantly and range from negligible to significant impairment of the individual’s functioning. 

• Light Therapy: This is done using artificial bright light, which is best done in the morning as a way of synchronizing the body clock. Light boxes or specially designed light therapy equipment can be employed. 
• Melatonin Supplements: Melatonin is a drug that functions by controlling the sleep-wake cycle. This can be done through the administration of melatonin supplement, which also assists in the resetting of the sleep cycle. This is usually taken in the evening, preferably one to two hours before the targeted sleeping time. The dosage and timing depend on different factors, and it is advisable to consult a healthcare provider. 
• Sleep Schedule Management: Regular and fixed sleep-wake schedule is therefore most important in cases of non-24. Another approach that can be used to develop a sleep-wake schedule is going to bed and waking up at any given time each day. It is also good to avoid taking naps and have a proper bedtime routine as well as organize some exercises. 
• Medications: In some circumstances the use of Melatonin agonist such as tasimelteon (Hetlioz) may be used. tasimelteon is specifically indicated for the management of non-24 in completely blind patients. 

Neurology

• Melatonin supplements: They are used to treat sleep-wake cycle disorders and non-24 is one of these disorders. This is most often found in those who have no sight at all because their biological clocks do not follow a 24-hour day-night rhythm. It also assists in regulating one’s sleep-wake cycle since it acts to make an individual drowsy or sleepy. Thus, for the individuals suffering from non-24, the treatment involves setting normal sleep wake cycles with the help of melatonin supplement. 
• Avoid stimulants: Reduction or elimination of products containing caffeine, nicotine, and alcohol especially before bed. Sleep disturbances can be produced by these substances, and they may exacerbate Non-24-Hour Sleep-Wake Rhythm Disorder. 
• Regular exercise: Engagement in moderate to vigorous-intensity physical activities during a day result in improved sleep quality and helps regulate circadian rhythms. Do not perform the exercises right before the night because it can warm up your body and contribute to waking up in the middle of the night. 

Neurology

Psychiatry/Mental Health

Tasimelteon: It belongs to the group of drugs that work on the melatonin receptors in the brain and is administered orally. Currently, only the U. S. Food and Drug Administration (FDA) has approved the use of non-24 treatment in those without any form of sight. It has been established through clinical trials that tasimelteon has the potential of being effective in the treatment of non-24. In these studies, tasimelteon was found to enhance the rhythmicity of sleep-wake cycle regulation with respect to 24 h cycle hence has more a regular circadian rhythm. It assisted those with non-24 to synchronise their circadian rhythm to conventional hours and thus enhancing their lives. 

Ramelteon: It is a medication for the management of insomnia, a condition characterized by difficulties in going to sleep. However, it is not particularly recommended for the management of non-24-hour sleep-wake rhythm disorder (non-24) but may sometimes be used as an off-label product. 

Behavioral Interventions 

• Light Therapy: The circadian rhythm of waking can be synchronized with exposure to bright light on some days of the week for the benefit of the sighted persons. It is normally done in the morning to enhance the sleep-wake circadian rhythm. 
• Dark Therapy: Minimizing exposure to light during the night, especially from the screens and other electronic gadgets plays an important role when it comes to enhancing the night period. 

Procedural Interventions 

• Chronotherapy: This is a process of slightly shifting the sleep-wake cycle forward or backward by one to two hours per day until the preferred schedule is attained. This can be challenging to maintain and may necessarily have to be strictly followed. 
• Controlled Light Exposure: In the case of the blind, controlled use of specific lighting instruments, mainly to regulate exposure to light, can assist in reconditioning the chronobiological clock. This involves exposure of light at predetermined intervals to simulate the natural rhythms of day and night. 

Neurology

Psychiatry/Mental Health

The first step of treatment aims at utilization of nonpharmacological interventions such as ensuring the child has established bedtime and morning wake up time and the daily activities do involve the same schedule in addition to pharmacological interventions which involve the use of either melatonin or tasimelteon. In cases where a person can still perceive some level of light, light treatment could also be used. In the cases where a more invasive approach is needed, chronotherapy is used to change sleep times gradually, while a proper sleep setting is also provided. 

The maintenance phase includes follow-up visits to a sleep specialist, the use of sleep diaries, and other forms of support such as cognitive behavioral therapy for insomnia and counseling.