Updated at: 26-02-2022 - By: Jane Brody

When a person’s circadian clock does not adhere to the standard 24-hour cycle, they suffer from non-24-hour sleep-wake disorder (N24SWD). Bedtimes tend to get later and later for sufferers of N24SWD, resulting in disrupted daily routines.

Non-24-hour sleep-wake disorder is rare, but sufferers might take solace in the fact that they’re not the only ones with the disorder. Circadian rhythm problems are becoming more widely known in the medical community and the general public.

What Challenges Do People With Non-24-Hour Sleep-Wake Disorder Face?

People with non-24-hour sleep-wake disorder sometimes have difficulty meeting their school, work, social, or other commitments due to their inconsistent sleep cycles. Even simple chores like making doctor’s appointments, shopping during regular business hours, and taking public transportation at night may be challenging for them.

Due to N24SWD’s low prevalence in the general population, there is minimal knowledge of it. N24SWD sufferers are sometimes judged by family members, friends, and coworkers who don’t comprehend the difficulties they encounter. They may be viewed as lazy, sluggish or not trying hard enough to sleep at typical times by those with N24SWD.

N24SWD sufferers feel the pressure to sleep at times that are inconsistent with their natural circadian cycle. Insomnia or other sleep disorders can be misdiagnosed as a result of this. Sleep deprivation at night is common in those with N24SWD due to their tendency to depend on naps to get them through the day. Chronic circadian misalignment and sleep deprivation are real risks for those with N24SWD who aren’t properly diagnosed and treated.

Studies of shift workers have indicated that persons are sensitive to concentration, memory, and mood issues in the short term because of circadian misalignment. This has a negative impact on performance in school and the workplace, and it also raises the danger of accidents. Sleep deprivation can lead to obesity, diabetes, cardiovascular disease, depression, anxiety, and a host of other chronic problems in the long run.

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Talking to Your Doctor About Non-24-Hour Sleep-Wake Disorder

Preparing for your doctor’s appointment ahead of time will help you have a productive discussion about your sleep-wake issue. A sleep journal is a great way to get a handle on your sleep patterns before a big event. Other signs to keep an eye out for include:

  • Having a hard time staying awake during the workday
  • Having a hard time falling asleep at night.
  • Even after a full night’s rest, you still feel drained
  • Anxiety or depression are present in your life.
  • An inability to concentrate or recall information

Your doctor will create a treatment plan for you that may include melatonin, bright light therapy, or a combination of the two based on your answers to questions about your sleep habits and results from tests to track your circadian rhythm. Maintaining circadian signals is an important part of treating non-24-hour sleep-wake disorder. Among them are:

  • A cool, dark, and peaceful atmosphere in the bedroom
  • Regular nighttime rituals that include calming activities
  • Taking a moderate amount of caffeine
  • Having a healthy diet and staying hydrated throughout the day is essential.
  • Doing a lot of physical activity
  • The use of blue-light blockers or limiting screen use in the evening can help.

However, if a treatment plan does not work for you and you inform your doctor of this, they can make the necessary alterations to the plan. A sleep specialist who has a better grasp of circadian rhythm issues may be able to help.

Talking to Friends and Family About Non-24-Hour Sleep-Wake Disorder

Your loved ones will have a better understanding of your fatigue, lack of interest, and inability to keep commitments if you explain your non-24-hour sleep-wake problem.

Describe your experience with N24SWD and any previous symptoms you’ve had, such as insomnia or irritability from sleep deprivation, if you have them. If someone has never heard of non-24-hour sleep-wake disorder before, compare it to something they can comprehend, like jetlag. You can also point them in the direction of additional information on the problem.

Online support groups and organisations can be a source of validation for many people. Sharing your thoughts and experiences with others who suffer from non-24-sleep-wake hour disorder will make you feel less alone and provide you new coping strategies.

How To Maintain a Social Life With Non-24-Hour Sleep-Wake Disorder

N24SWD can make it challenging to have a healthy social life. There are, however, a few things you can do to make things go more smoothly.

Make an effort to be more accommodating when it comes to meeting hours, and suggest other activities like taking a walk that can be done at any time.

You may plan your activities around the times when your body is most likely to fall asleep, if you are aware of your sleep patterns. Finding like-minded coworkers or fellow freelancers might lead to more flexible working arrangements.

Keeping in touch with pals outside of “normal” business hours is possible, but some of these methods may not be suitable if you are in therapy and must maintain a 24-hour schedule. Visiting late-night hangouts like pubs and clubs may seem like a fun alternative, but the stimulation and alcohol intake that come with these experiences can make it extra harder to fall asleep the next night. To answer messages from friends or to talk with friends in other time zones, you can use social media at any time of day or night, although using screens at night can interfere with sleep.

Your therapy should be at the forefront of your decision-making process. Be careful not to increase or acquire behaviors that will have a detrimental impact on your N24SWD treatment.

Non-24-Hour Sleep-Wake Disorder in the Workplace

Under the standards of the American Disabilities Act (ADA), a non 24-hour sleep-wake disturbance is a disability since it can significantly impede major living activities such as concentration, socializing, and working. The Americans with Disabilities Act (ADA) requires most businesses to make reasonable accommodations for you if you are qualified for the job in question.

According to the ADA, businesses might refuse to make modifications if doing so would cause “undue hardship” for the business. However, employers must make accommodations in all cases. You may need to engage a lawyer depending on the nature of your profession. Your business may be able to provide you with a choice of options, including working part- or full-time hours, or working from home.

Explain how having N24SWD makes it difficult for you to function in your job and ask for any modifications that might make it easier for you to do so. Consider contacting a lawyer to see if they can help. If you think it will improve your working relationship with your coworkers, you can also discuss the specifics of your case with them.

Career Ideas for People With Non-24-Hour Sleep-Wake Disorder

Those with erratic sleeping patterns are better suited to certain professions. Despite the fact that your N24SWD should not limit your professional path, you may find yourself gravitating toward positions that allow you to work more flexible hours. The following are examples of flexible jobs:

  • A self-employed author
  • Translator
  • programmer for the internet
  • a professional graphic artist
  • Professional masseuse
  • In-home fitness expert
  • a person in charge of delivery
  • Photographer

People who have trouble keeping a 24-hour cycle or those who still feel unwell even when they adhere to a regular “day and night” routine may find these jobs particularly appealing.

Students With Non-24-Hour Sleep-Wake Disorder

A student’s entitlement to an education tailored to his or her specific requirements is described in Section 504 of the 2008 Disabilities Act Amendment Act. This applies to all levels of education, from elementary to post-secondary. Examples of reasonable accommodations for students include online classes, the ability to miss some classes and make up the work, or having a lower course load.

Signs & Symptoms

N24’s most common symptoms include occasional nighttime sleeplessness and excessive daytime sleepiness, as most people are forced to keep a regular job, school, or social schedule. As a result of the disorder’s cyclical nature, some affected individuals may have periods of normalcy lasting from a few days to a few weeks. It is expected that the sleeplessness and excessive daytime sleepiness would return as the individual’s body once again desynchronizes from the rhythms of the light-dark cycles (or day-night cycles) and their duties.

N24 sufferers often sleep between 24.1 and 28.30 hours per night, but this might vary widely from person to person. The frequency of cases with cycles shorter than 24 hours, in which a steadily increasing rhythm is expected, is exceedingly low.

At the risk of being unable to keep a regular work and social schedule, some people with N24 find relief from their symptoms of sleeplessness and exhaustion when they are permitted to sleep on their own cycle. It’s possible that persons with N24’s internal circadian rhythms will continue to be out of sync no matter what schedule they’re on, causing them to feel tired, groggy, sick, and unable to sleep well. Molecular clocks have recently been shown to exist in practically every cell in the human body, and scientists believe that the symptoms of sleep apnea are caused by the several clocks in the body being out of sync with one another.

Symptoms of chronic sleep deprivation, such as excessive daytime slumber, exhaustion, melancholy and difficulties concentrating, will build up if N24 is not discovered and managed. Inability to fulfill social and professional duties is one of the most debilitating effects of N24. As a result of being awake at times when others are sleeping, isolation and loneliness can be a problem.

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Causes

Day and night (light/dark) cycles have shaped the evolution of all species on Earth. Cellular and metabolic processes have evolved strategies to anticipate this daily rhythm. A biological clock based on a cycle of synthesis of DNA and protein is present in nearly all cells of the human body. White blood cells, as well as those in the heart, brain, liver, and a slew of other organs, have been revealed to be active in the clock gene.

A 24-hour cycle is maintained by the individual cellular clocks. “circadian rhythm” (circa-) means relating to a 24-hour period. Cellular clocks, however, aren’t perfectly accurate, so the clocks of individual cells can drift apart from one other or from the Earth’s 24-hour day/night pattern. There is a master clock in the brain that keeps these clocks in sync. Master clocks keep the body’s cellular clocks synced up with each other in the same manner that an orchestra conductor keeps the performers performing in sync.

The master clock is located in the suprachiasmatic nucleus (SCN), a region of the brain known as the hypothalamus, which regulates many of the body’s most fundamental functions. Cells in the SCN, which make up roughly 20,000 of the cells in the brain, are intimately connected and their rhythms are coordinated so that their firing rate changes in a nearly 24-hour pattern. Many other parts of the brain receive the clock signal from the SCN, which is subsequently communicated to the rest of the body via neurochemical and hormonal mechanisms.

Temperature and melatonin levels are two of the most well-known rhythms that are driven by the clock signal. The SCN communicates with other parts of the hypothalamus to control the body’s temperature. Temperature changes in a wave-like pattern, with a peak during the day and a low (or nadir) at night.

The pineal gland, which produces melatonin, is controlled by the SCN, which transmits a nerve signal via the cervical spinal ganglia along a complex polysynaptic pathway. Melatonin, also known as “the hormone of night,” is created when it is dark. The pineal gland secretes it into the cerebrospinal fluid, which is then transported to the bloodstream and the body’s cells. Direct control of cellular processes is achieved through binding to particular melatonin receptors. By assisting the nighttime decline in body temperature, the temperature cycle is bolstered even further. As well as helping to prepare the body and brain for sleep, a reduction in body temperature has other benefits.

If you want your body clock to sync up with that of your SCN, then you must also sync it up with the 24-hour period of the Earth. When left to its own devices, the SCN maintains a circadian rhythm that is near to, but not quite, 24 hours long. It is estimated that the SCN clock’s intrinsic period is around 24.2 hours in healthy persons. No means to rectify this cycle to equal 24 hours would lead to the SCN clock drifting several minutes a day until it no longer kept accurate time or was “entrained.”

Light-dark exposure is the major method of maintaining a correct SCN clock. This information is sent to the SCN via a neuronal pathway known as the retinohypothalamic tract, which is made up of cells distinct from those utilized for vision in the retina. Light exposure in the early morning hours provides a signal that moves the SCN’s clock forward by an hour, allowing the body’s internal clock to be set for the day. A delay signal is delivered to the SCN when light falls on the eyes late at night. It is possible to estimate the impact of light on our biological clock by plotting a phase-response curve, a graph showing the effect of light at various times of day and night. Longer-term running of the SCN clock causes it to fall out of sync with the natural day-night cycle, but morning light exposure can correct this. SCN clocks that are less than 24 hours old can be delayed a little by exposure to light at night. Using this method, the SCN clock is kept in sync with the day and night cycle. The circadian rhythms of healthy people can be maintained by regular exposure to morning light.

Melanopsin, a pigment found in the retina, serves as a light sensor for circadian processes in the retina. Blue light has a higher impact on circadian rhythms because melanopsin is particularly sensitive to it. The impact of light in the colors red, orange, and yellow is substantially smaller. Rhythms can be affected by green light in specific situations.

The sleep-wake cycle is one of the most critical biological rhythms governed by the SCN. The homeostatic and circadian processes are in charge of regulating this cycle. At night, the body and mind rest and mend, allowing them to better handle the demands they will face during the day. Resources are depleted progressively throughout the day when the person is awake. As one’s energy depletes throughout the day, it becomes increasingly important to get enough sleep in order to replenish it. The homeostatic sleep drive is the name given to this phenomenon. For example, a person might wake up energised and then progressively lose that energy during the day as if they were a battery. An inconsistent daytime alertness level, with dangerously low levels of awareness in the afternoon and evening, would follow. However, the SCN also controls alertness through the circadian mechanism. The SCN sends a higher awareness signal to the brain and body as the day progresses, compensating for dwindling energy levels. In the two hours leading up to bedtime, this alertness signal reaches its pinnacle. The “forbidden zone for sleep” is so named because the alertness signal makes it practically impossible to sleep while in this zone of maximal alertness. The SCN begins to decrease its alertness signal at the normal bedtime in order to assist the body to fall asleep. The circadian alertness signal is lowered more throughout the night in order to prevent early arousal.

To maintain a steady state of alertness during daylight hours, the circadian and homeostatic processes work together to maintain a 7-9-hour period of uninterrupted sleep at night, with the occasional exception of a midafternoon nap.

Eyes’ light signals help keep SCN in sync with the 24-hour day/night cycles, and the SCN then coordinates the clocks of pineal gland cells and cells throughout the body. Like the instruments in a well-tuned orchestra, the clocks all run on the same 24-hour cycle. A person who is able to sleep through the night and stay awake during the day is the consequence of the circadian alertness signal interacting with the body’s homeostatic mechanism.

Many things can go wrong with this system and cause a circadian disorder like N24, but this is the most common one.

1. The inability to see. N24 is the most well-understood form of the disease in the blind. As a result, people who are entirely blind (not able to perceive light) will not be able to fine-tune their body clocks to the 24-hour cycle. Without medical intervention, a blind person’s SCN clock cannot be brought back into sync with the 24-hour clock. A blind person’s circadian timing system will gradually shift over time since the SCN’s natural rhythm is not always exactly 24 hours. Periods of nighttime sleep and periods of nocturnal sleep will alternate over time. There are a few rare situations where the sleep rhythm gradually advances and the period is less than 24 hours; in the great majority of cases, the sleep rhythm gradually delays so that the period is over 24 hours. People who have N24 typically have a circadian rhythm of 23.8 to 25 hours.

Changes in the sensitivity to light. In some people, the circadian system may be less sensitive to light than it is in others. A healthy circadian light signal may not be sent through the eye’s and brain’s vision-producing areas. A blind individual’s circadian condition is exactly the same as that of a person who is completely unresponsive to light’s circadian effects. Although light may affect their cycles to some degree if they are light-sensitive, this effect may not be powerful enough to counteract circadian drift in their specific lighting environment.

Delays in sleep onset, a syndrome associated with N24, has been demonstrated to make some patients hyperaware of light. Circadian rhythms may be thrown off if they are awakened in the evening by ambient light. N24 is the result if this delay is compounded.

3. The Situation. The amount of light that a person is exposed to on a daily basis could possibly play an effect. It is not uncommon for healthy people to fall into a non-24-hour rhythm when they are kept in isolation and given the freedom to turn their lights on and off as they see fit. Longer than 24.2-hour cycles of the SCN, the rhythm’s length may be up to 25 hours or more in length. This is due to the delayed effect of late-day self-selected light exposure. If you live in a situation where you’re constantly exposed to bright light, you’re more likely to develop N24. Even in a non-isolated environment with conventional time cues, people with N24 can’t keep a 24-hour schedule.

Factors related to hormones. Melatonin, a sleep-inducing hormone, may play a role in the emergence or persistence of N24. The lack of melatonin in certain people with N24 can be an issue, as melatonin is a key component of the day-night cycle. In addition, too much melatonin can have negative consequences. Fluvoxamine, an antidepressant, has been linked to the development of DSPD, a condition that is closely linked to N24. Melatonin metabolization is aberrant in some people, which can lead to abnormal daytime melatonin levels, which can cause circadian clock dysfunction.

5. Cellular Clock Differences. Studies of circadian rhythm problems have previously focused on the cellular clock. A link between the cellular clock and the entrainment phase has been found in healthy persons. As a general rule, morning people have a shorter time period than night owls. The cellular rhythm may be too far from 24 hours for typical light exposure to fix it, a state described as being “beyond the range of entrainment,” in which case N24 may be an extension of excessive “eveningness.”

There are two techniques to calculate the period of the biological clock in humans. To begin, you can look at the time period when the individual was living in his or her normal surroundings. A regular person’s life span is 24 hours in these circumstances. Their sleep-wake cycle doesn’t shift over time.. By definition, someone with N24 has a period that is longer than 24 hours, and in some cases, up to 25-26 hours.

It’s typical for the circadian clock to be influenced by external variables, such as light. In order to find the intrinsic period of a clock, scientists use unique experimental settings (constant routines and forced desynchronization) to cancel out these external influences. If the clock were completely isolated from external influences, this is the time it would keep. The intrinsic period of the clock is around 24.2 hours for healthy individuals. Regular subjects can maintain a 24-hour day by exposing themselves to normal light on a daily basis, which makes up for the 0.2 difference.

The intrinsic period of N24 patients has been studied in three minor investigations. For a total of six patients, two studies revealed a 24.5-hour period; for four patients, a 24.9-hour period was observed. As a result, in order to maintain a 24-hour cycle, these N24 patients require daily adjustments of 0.5 to 0.9 hours. This correction may not be possible with normal light exposure. Entrainment to a 24-hour day may be impossible if these and other causes cause the clock to move later in the day.

Muscle cells (fibroblasts) isolated and cultured have also been the subject of investigations looking at the internal clock. To determine the age of a cell sample, researchers looked at how long it had been in culture. Cells regulate their own internal timekeeping, as evidenced by this finding. This shows that at least some N24 patients have a fundamental failure of the molecular basis of the circadian clock, which results in a longer intrinsic period.

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There are a few severe evening type persons without clinical N24 who have an intrinsic period that is longer than the usual for N24 patients. It is therefore possible that, in addition to the long intrinsic period, other factors play a role in the development of N24, which differentiates between a severe evening chronotype and free-running N24.

6. Dissimilarities in the Control of Sleeping. Homeostatic and circadian regulation may be another probable cause of N24. N24 sufferers, on average, require a little more sleep than the rest of the population. This isn’t always the case. While a healthy individual can sleep for eight hours and be awake for sixteen hours, a person who needs twelve hours of sleep and is awake for the regular sixteen hours will have a day that lasts 28 hours complete in totality. The shift in the sleep cycle will lead to a shift in light exposure, which in turn will lead to a shift in the N24 cycle. Sleep deprivation may result in the same 28-hour workday as a person who lacks the homeostatic drive for a good night’s rest, even if they sleep a typical amount of time.

When it comes to sleep and internal circadian rhythms, the phase angle between sleep and these rhythms is aberrant in many cases of N24. The link between sleep timing and the circadian rhythm of body temperature is described here in terms of phase angle. Before going to sleep, a person’s temperature begins to fall, and it normally reaches its lowest point around two hours before the person wakes. As a result, the “sleep offset”—the amount of time between the lowest temperature and when you first wake up—can be as much as 8 hours longer for people with N24 than for those without it. If a N24 has an improper relationship between sleep cycles and their circadian rhythms, they will not obtain the light they need on a daily basis to reset their clock since their internal rhythms (such as core temperature) are synched with light-dark exposure. Being awake later than their temperature cycle dictates, they are also more vulnerable to exposure to light during the phase response curve’s delayed phase. As a result, their circadian rhythm shifts toward a day that is significantly longer than usual. This increases the impact of N24 patients’ already long intrinsic period.

It’s also crucial that sleepiness is regulated on a 24-hour cycle. An hour or two before regular bedtime, even healthy people have a “forbidden zone for sleep” connected with the highest circadian alertness signal. It is impossible to sleep on a 24-hour cycle in those who have N24 because the banned zone occurs too late in the day and is too powerful.

Certain impacts of sleep and wakefulness on alertness may strengthen this tendency. Sleep inertia is a condition in which people are less aware when they wake up after a long period of sleep. Sluggishness and drowsiness are common symptoms of N24, and they might last for several hours or even days. They get more alert the longer they remain awake. A possible explanation for this may be found in an observation that brain cell circuits grow more excitable as we spend more time awake. Their alertness will have peaked by the time they need to go to bed (in an attempt to maintain a 24-hour cycle), and their brief burst of energy will prevent them from falling asleep at their usual time. Because they finally feel up, attentive, and productive, people with N24 may not want to try to sleep at this time.

7. The advancement of the project. Another factor is the growth of the brain’s circadian and sleep centers. N24 and other circadian rhythm and sleep problems have been found to be prevalent in autism and other widespread developmental disorders. If the circadian and sleep areas of the brain were not correctly developed or were damaged by other neurochemical or physical deficiencies, it is assumed. Non-pervasive developmental problems, such as sleep and circadian brain regions, may affect other N24s, as well.

Trauma, in this case. N24 has been linked to brain damage, such as that caused by a head injury, in previously healthy individuals. The hypothalamus and pineal gland are thought to have been harmed by the head injury, which has been linked to sleep and circadian dysfunction. N24 has also been linked to brain cancers, according to research. Survivors of tumors on the pons and hypothalamus have been found to suffer from circadian sleep abnormalities. Those with cranopharyngiomas are more likely to suffer from sleep problems. Toxicology can be a factor in some circumstances while radiation treatment can be a factor in others. An aneurysm near the SCN caused a temporary N24 in one patient. Following chemotherapy for Hodgkin’s lymphoma, N24 has also been reported.

In terms of physical defects, any factor that causes total blindness, whether genetic, disease, or injury, might result in secondary N24.

Iatrogenic, to be precise. The more frequent disease, delayed sleep phase disorder, can also lead to the development of N24 (DSPD). As a common treatment for DSPD, patients are taught to gradually postpone their bedtime and wake up time by up to three hours each day until they achieve a more socially acceptable sleep-wake schedule that is based on a 24-hour cycle. Essentially, this implies switching to a N24 schedule for the time being. Unfortunately, a N24 schedule can be almost tough to break in certain patients once it has been established. One circadian rhythm disorder has been replaced by another that is considerably more debilitating, N24. Once established, the N24 pattern is difficult to break for a variety of reasons. Other factors include the timing of sleep in relation to the temperature cycle. The other is referred to as circadian system plasticity. To put it another way, the circadian clock recalls the cycles that an organism has been set on, even if those cycles are not 24 hours long. Chronotherapy has been linked to a rise in the risk of N24 since the 1990s, although many clinicians are still unaware of this danger while prescribing it.

Inheritance N24 may have a genetic basis, as evidence for this finding grows. Most of the time, it’s not a simple genetic disorder (Medelian inheritance). The majority of N24 individuals do not have any close relatives or parents who also have the illness. N24 appears to be caused by a combination of hereditary and environmental factors.

SNPs (single nucleotide polymorphisms) in the gene BHLHE40 were detected in four patients with N24 in one investigation. It is possible that the abnormalities observed in N24 are caused by mutations in this gene, which encodes components of the cell’s circadian clock.

Polymorphisms in the PER3 gene were shown to be associated with 67 N24 patients in a separate investigation. The circadian clock is encoded by PER3 as well. Researchers found that these polymorphisms were related with extreme evening chronotypes, a hereditary inclination to perform better late in the day that is also found in people under the age of 24. Both SNPs and repeat number variations in the PER3 gene are thought to alter the free-running period (in animals), the homeostatic desire for sleep (in humans), and the response to light (in humans). N24 has been theorized to have abnormalities in all of these components.

A mutation in the CRY1 gene, which regulates the circadian clock, has been linked to DSPD, a disorder associated with N24, in a study of one family.

A number of genome-wide association studies (GWAS) – genetic screenings of more than 100,000 people – have found genetic links to human chronotypes. Even though N24 patients were not specifically studied in these investigations, the fact that N24 is strongly associated with an extreme evening chronotype suggests that some of the same genetic variables may be important.

N24 may be genetically predisposed in some individuals, according to both particular investigations of N24 genes and more general genetic studies of circadian rhythms.

Affected Populations

This disease has yet to be identified, but researchers believe it is more prevalent among the blind than the sighted. N24 is thought to be present in between 55% and 70% of those who are completely blind. People who have had their eyes enucleated (for example) are more likely to be affected than those who still have some degree of light sensitivity. The prevalence of N24 in the sighted is unknown, but there are approximately 100 case studies of sighted people with N24 in the medical literature around the world. A single Japanese research documented fifty-seven of these instances. An organization called the Circadian Sleep Disorders Network has 98 members who say they or a member of their family suffer from N24. The Facebook group N24 has more than 500 members, but it’s not clear how many of them are patients. There may be a large number of undiagnosed cases due to the condition’s lack of awareness.

In documented cases of sighted patients, approximately 75 percent are male, although it is not known if this is a true reflection of the broader patient population’s gender distribution. According to studies on healthy adults, men tend to have longer circadian rhythms than women. There are almost the same amount of men and women in support groups. The most common time for the development of N24 is in late adolescence or early adolescence, however it can also appear much earlier or later in life. It appears that the condition is a lifelong one. There is not enough evidence to tell whether or not N24 is advancing. According to long-term sufferers’ accounts, the condition worsens as they grow older, and this may be owing to the interaction between N24 and age-related sleep disturbances. There is currently no clinical study on how N24 manifests itself across the lifespan.

In 1970, Eliott, Mills, and Waterhouse described N24 in the medical literature.

Related Disorders

Some of the following conditions have symptoms that are very similar to N24. Using comparisons can aid in determining the cause of a patient’s illness.

Although less frequent than N24, delayed sleep-wake phase disorder (DSPD) alters the body’s sleep-wake cycle so that it occurs several hours later than in healthy people.

As opposed to people who suffer from N24, those with DSPD have a consistent delay in their sleep phase while their sleep time shifts back and forth throughout the day. A person with DSPD, for example, may often retire to bed about 4 a.m. on a regular basis. Although the exact hour may vary (e.g. 3am one day and 5am the next), there is no cumulative delay. If you’ve had N24, you’ll wake up at 4 a.m. one day, 5 a.m. the next, 6 a.m. the next, 7 a.m. the next, etc.

People with DSPD may have biological clocks set to a significantly longer circadian rhythm than normal, similar to people with N24, although the former can still entrain to 24 hours of daylight. This is the theory that researchers have come up with. According to this notion, the individual with DSPD’s biological clock shifts entrainment to a later time because of the prolonged circadian rhythm. Some people with DSPD may later develop N24, either as a result of their disorder’s progression or as a result of chronotherapy (see “causes”), which supports the hypothesis that the underlying biology is the same in some instances.

Disruption in the circadian rhythm of sleep and wakefulness (ISWRD) is one of the symptoms of this condition. Insomniacs tend to sleep at random times during the day and night, with no clear pattern. Over the course of a 24-hour period, the average person has three or more phases of varying lengths of sleep. While N24 and ISWRD both share a 24-hour sleep cycle, ISWRD sufferers have a distinct rhythm to their sleep that extends beyond the 24-hour mark. Patients with ISWRD have no discernible rhythmic pattern at all. Disorganized sleep patterns have been seen in patients with a lengthy history of N24. However, they usually preserve some rhythmic pattern that distinguishes them from patients with ISWRD. Developmental impairments and dementia are the two most common causes of ISWRD. It can also be brought on by a traumatic brain injury or a tumor in the brain. It’s also known as irregular sleep, circadian rhythm sleep disorder, or just ISWRD.

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A common sleep problem, sleep apnea is characterized by repeated, brief pauses in breathing while sleeping. Snoring, impatience, lack of attention, and/or cognitive impairment are all symptoms of obstructive sleep apnea. Having a big neck, thin or packed airways, and obesity are all linked to snoring. Airway collapse is the most common cause of obstructive sleep apneic syndrome, which is the most common form of sleep apnea. Afterward, the person may gasp for air as they begin to wake up a little bit. This condition can cause high blood pressure, irregular heartbeats, and an increased risk of cardiovascular disease such as heart attack, stroke and diabetes if it is not addressed. Because obstructive sleep apnea affects 24% of men and 9% of women, it’s not uncommon for someone with N24 to also have this condition.

N24 may be mistaken for idiopathic hypersleep, which is an uncommon illness that may be co-morbid with N24. An individual may have a sleep onset time that shifts later each day as a result of chronic, persistent hypersomnia if he or she remains awake for a normal length of time while sleeping for an abnormally long duration of time; this is known as N24. The hallmark of idiopathic hypersomnia is a tendency to oversleep for no apparent reason (idiopathic). Symptoms might be long-lasting or recurring. It is possible for some people with idiopathic hypersomnia to sleep for lengthy amounts of time (up to 10 hours), while others sleep for shorter lengths of time (e.g. fewer than 10 hours). Idiopathic hypersleep can have a negative impact on a person’s daily routine. The illness is treated with a combination of counseling and medication.

Chronic, excessive daytime sleepiness is one of the hallmarks of narcolepsy, a neurological sleep disorder that also goes by the name of excessive daytime sleepiness (EDS) (EDS). The duration of sleepiness attacks varies from a few seconds to a few minutes, depending on the severity. The frequency of these instances ranges from a few per day to several in a single day. Sleep patterns at night (nocturnal) may also be interrupted. Cataplexy, a form of hallucination that occurs before or after sleep, and momentary paralysis upon waking up are three additional symptoms that are frequently connected with narcolepsy. Another symptom of narcolepsy is what’s known as “automatic behavior,” which is when you do something without thinking about it beforehand. To learn more about narcolepsy, type “Narcolepsy” into the Rare Disease Database search box.

Hypersomnolence (i.e., sleeping up to 20 hours a day), excessive food intake (compulsive hyperphagia), and behavioral abnormalities, such as an excessively unconstrained sexual drive, are all hallmarks of Kleine-Levin syndrome. Patients may be irritable, lethargic, or emotionally flat when they first wake up (apathy). While hallucinations may also occur, they may also appear disoriented (confused). Kleine-Levin syndrome is characterized by a recurrence of symptoms. Symptoms may be absent for weeks or months in certain cases. As long as symptoms are present, they can last for days to weeks. The signs and symptoms of Kleine-Levin syndrome may fade away with time in some people. However, it is possible that relapses will occur in the future. Kleine-Levin syndrome has no recognized cause. To learn more about Kleine-Levin, type “Kleine-Levin” into the Rare Disease Database.)

Other disorders such as hypothyroidism, periodic limb movement disorder (PLMD), depression, hypoglycemia, and others can also induce excessive daytime sleepiness. Excessive daytime sleepiness can be a symptom of a variety of medical illnesses, including those that are connected to excessive nocturia, such as heart disease, diabetes, prostate disorders, congestive heart failure, interstitial cystitis, cystoceles, and other bladder problems.

Diagnosis

Based on the patient’s home sleep logs, which demonstrate a non-24-hour sleep pattern, an initial diagnosis is made. If a patient’s sleep schedule isn’t restricted by social or professional obligations, it’s easier to spot this.

An actigraph, a wrist-worn device that records movement and is used to assess sleep timing, can help confirm a diagnosis. For the sleep cycle to complete at least one full cycle around the clock, the actigraph should be worn for several weeks.

Documenting melatonin secretion patterns that aren’t 24 hours a day can help establish a diagnosis, however this approach is more widely employed in research than clinical practice.

Preliminary and Final Clinical Examinations

Treatment

Hetlioz (tasimelteon), a melatonin receptor agonist, was authorized by the FDA in 2014 to treat N24. The first FDA-approved medication for the disease is Hetlioz, developed by Vanda Pharmaceuticals Inc. Hetlioz’s effectiveness was tested in two clinical trials with N24-blind patients.

Phototherapy and dark exposure (dark therapy) are two of the most commonly prescribed treatments for sighted people (scototherapy).

Lightboxes are commonly used in phototherapy. In order to maintain a regular sleep cycle, the lightbox is utilized in the early morning for a period of two hours at a time. When the patient’s circadian rhythm has them waking up at the desired hour, light therapy can be started. The retinohypothalamic tract, which connects the retina to the brain, is responsible for registering light and transmitting that information to the brain. This signal reduces melatonin production and alters the time of day when people go to sleep. The ideal moment to expose yourself to light is determined by a phase-response curve.

In order to achieve dark therapy (scototherapy), it is necessary to avoid light exposure at night. Patients should stay in dim light or use special dark goggles that minimize light exposure at night and in the evening. Even typical room light may have a phase-delaying impact.

Both light and darkness therapy are thought to be more effective when used in conjunction. Patients who successfully synchronize to a 24-hour cycle with light and dark therapy are need to keep up the regimen or the synchronization will be lost.

Use of the hormone melatonin can help to maintain a regular sleep-wake cycle. Sleep aids such as melatonin can be taken up to four hours before to bedtime. With the exception of patients who are blind and suffering from N24, it is rare to see good results when melatonin is utilized only as treatment.

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