Non 24 hour sleep wake disorder

Other Names: Circadian rhythm sleep disorder, free-running type; Hypernychthemeral syndrome

Non 24 hour sleep wake disorder refers to a steady pattern of one- to two-hour delays in sleep onset and wake times in people with normal living conditions. This occurs because the period of the person's sleep-wake cycle is longer than 24 hours. The condition most commonly affects people who are blind, due to an impaired sense of light-dark cycles.Non 24 hour sleep wake disorder can also affect sighted people.

Causes

The possible causes of non-24-hour sleep-wake disorder are 2-fold: (1), extrinsic: isolation from daily light cycles (such as working in an environment completely devoid of natural lighting); and,intrinsic: where some condition, such as blindness or malfunctioning biochemical response to light in the subject - prevent normal levels of light-activated melatonin release.Melatonin is responsible for sleep regulation, and its release is controlled by the amount of light entering the eyes.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Abnormal pineal melatonin secretion
• Asthenia
• Blindness
• Depressivity(Depression)
• Excessive daytime sleepiness
• Excessive daytime somnolence(More than typical sleepiness during day).

Diagnosis

Non-24-hour sleep–wake disorder is diagnosed when the patient fails to follow (entrain to) a 24-hour light-dark cycle and clock times. As such, the entrainment status (defined as whether the hypothalamic circadian clock is synchronized to a 24-hour day) physiologically defines this disorder and can thus be used as the sole outcome measure. This is similar to elevated blood pressure characterizing essential hypertension. In contrast to other circadian rhythm sleep disorders (CRSD), a diagnosis of non-24-hour sleep-wake disorder requires the documentation of progressive shifting of the sleep-wake times over at least 14 days using sleep diaries and/or actigraphy. In sighted people, the diagnosis is typically made based on a history of persistently delayed sleep onset that follows a non-24-hour pattern. In their large series, Hayakawa reported the average day length was 24.9 ± 0.4 hours (with the range of 24.4–26.5).There may be evidence of "relative coordination" with the sleep schedule becoming more normal as it coincides with the conventional timing for sleep. Most reported cases have documented a non-24-hour sleep schedule with a sleep diary (see below) or actigraphy.In addition to the sleep diary, the timing of melatonin secretion or core body temperature rhythm has been measured in a few patients who were enrolled in research studies, confirming the endogenous generation of the non-24-hour circadian rhythm.

In the research setting, the diagnosis can be confirmed, and the length of the free-running circadian cycle can be ascertained, by periodic assessment of circadian marker rhythms, such as the core body temperature rhythm,the timing of melatonin secretion,or by analyzing the pattern of the sleep–wake schedule using actigraphy. Most recent research has used serial measurements of melatonin metabolites in urine or melatonin concentrations in saliva. These assays are not currently available for routine clinical use.

Treatment

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• tasimelteon (Brand name: Hetlioz)Treatment of non-24-hour sleep-wake disorder.

Melatonin administration 1 hour before bedtime is considered another treatment for those suffering from non-24. However, it is important to note that melatonin may only treat the inability to sleep and may not help to improve the daytime sleepiness.

Light therapy, which involves a bright light exposure of thousands of lux of white light or about 400 lux of blue light on awakening to counteract the tendency for circadian rhythms to delay (similar to treatment for delayed sleep phase disorder and seasonal affective disorder), is not currently recommended until more studies appear, although it has been found to be effective in some cases. This can be combined with dark therapy (or scototherapy), which involves filtering blue light (using software, screen filters or (amber-color)glasses) and preferring red-colored lights with a low amount of lux in the few hours before bedtime to avoid melatonin suppression. Both melatonin administration and light therapy work by shifting circadian rhythms according to a phase response curve (PRC), with the melatonin PRC being essentially the inverse of the light PRC. Furthermore, light can suppress melatonin secretion. In addition to natural fluctuations within the circadian rhythm, seasonal changes including temperature, hours of daylight, light intensity and diet are likely to affect the efficacy of melatonin and light therapies since these exogenous zeitgebers would compete for hormonal homeostasis. Further to this, there are unforeseen disruptions to contend with even when a stabilized cycle is achieved, such as travel, exercise, stress, alcohol, or even the use of light-emitting technology close to a subjective evening/night.