June 2012
Non-24-Hour Sleep-Wake Syndrome (780.55-2)
Synonyms and Key Words: Free-running pattern, incremental asynchrony relative to typical
environmental pattern, periodic insomnia, periodic excessive sleepiness, blindness,
hypernycthemeral syndrome.
Essential Features:
Non-24-hour sleep-wake syndrome consists of a chronic steady pattern comprising one- to
two-hour daily delays in sleep onset and wake times in an individual living in society.
Patients with non-24-hour sleep-wake syndrome exhibit a sleep-wake pattern that is
reminiscent of that found in normal individuals living without environ- mental time cues (i.e.,
sleep-onset and wake times occur at a period of about every 25 hours). At times, one or more
noncircadian (longer than 27 hours) sleep-wake cycles may occur in the patient with the non24-hour syndrome, similar to the phenomenon of internal desynchrony observed in some timeisolation experiments. Such individuals are literally sleeping “around the (24-hour) clock,”
despite the presence of 24-hour social and environmental time cues. In the long run, their sleep
phase periodically travels in and out of phase with the conventional social hours for sleep. When
“in phase,” the patient may have no sleep com- plaint, and daytime alertness is normal. As
incremental phase delays in sleep occur, the complaint will consist of difficulty initiating sleep
at night coupled with oversleeping into the daytime hours or inability to remain awake in the
daytime. Therefore, over long periods of time, patients alternate between being symptomatic
and asymptomatic, depending on the degree of synchrony between their internal biologic
rhythm and the 24-hour world.
Some individuals with this condition intermittently or permanently give up attempting to
synchronize their sleep with conventional hours. In these patients, a sleep-wake diary or log will
appear similar to that of the free-running pattern of time-isolated normals. Most patients,
however, attempt to sleep and wake at conventional social times. These attempts produce
progressively less sleep, with secondary daytime sleepiness interfering with functioning at work
or school. In addition, sleep may be skipped for 24 to 40 hours, followed by sleeping for 14 to
24 hours without awakening. Unlike patients with the delayed sleep-phase syndrome, who share
some of the above symptoms, the patient with a non-24-hour disorder does not achieve a
stable pattern of normal sleep at a delayed phase during vacations from work or school.
Associated Features: Typically, individuals with this condition are partially or totally unable to
function in scheduled social activities on a daily basis, and most are unable to work at
conventional jobs. Most of the patients described in the medical literature have been blind,
either congenitally or on an acquired basis, and some have been mentally retarded as well. Less
commonly, a severely schizoid or avoidant personality disorder may accompany the condition.
One patient who was initially described as having this disorder was later discovered to have a
large pituitary adenoma that involved the optic chiasma.
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Efforts to induce sleep at conventional times in these patients often include the use of, and
dependency on, hypnotic and analeptic medication, at times in very large doses. A history that
such medications alternate between apparent efficacy and progressive loss of efficacy with no
change in dose suggests that the non24-hour syndrome may be the underlying cause of the patient’s sleep-wake symptoms.
Course: Depending mostly on associated conditions, the non-24-hour syndrome may be chronic
and intractable or may respond well to the institution of strict and regular 24-hour time cues.
Some blind individuals, mostly in institutionalized set- tings, have responded to strict 24-hour
scheduling, consisting of strong social time cues.
Predisposing Factors: See Associated Features.
Prevalence: This disorder is apparently rare in the general population. Although the prevalence
in the blind is unknown, one survey of blind individuals revealed a high incidence of sleep-wake
complaints, with 40% of the respondents having recognized that their symptoms occurred in a
cyclic pattern.
Age of Onset: The syndrome has been described in congenitally blind infants as well as in blind
middle-aged and elderly individuals. Onset in normal-sighted individuals appears variable.
Sex Ratio: Not known.
Familial Pattern: None known.
Pathology: Various causes of blindness involving the optic chiasma or prechiasmatic visual
structures have been present in blind patients with the non-24-hour syndrome, suggesting that
the blindness itself underlies the syndrome, rather than being the cause of the syndrome. This
theory is in keeping with the likelihood that the environmental light-dark cycle, acting through
the retinohypothalamic tract on the suprachiasmatic nucleus of the hypothalamus, is a major
source of 24- hour time information for humans as well as lower animals. Blindness deprives the
endogenous circadian timing system of this crucial information, and, particularly when other
brain abnormalities are present, social zeitgebers may be ineffective. In sighted individuals, a
suprachiasmatic tumor may have been the cause of the syndrome in one case, but personality
factors appear to be paramount. In such cases, the conscious or unconscious disregard of
entraining cues may serve an adaptive, albeit a pathologic, function for the patient.
Complications: The complications relate to impaired psychosocial functioning.
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Polysomnographic Features: Little specific information is available. Recordings done at
fixed times over several successive days would be expected to show progressively longer sleep
latencies and progressively less total sleep, but normal age-related sleep-stage architecture
across the period of study. Electroencephalographic abnormalities, such as reduced sleep
spindles and K- complexes, may be present in brain-damaged or retarded patients.
Other Laboratory Test Features: Sighted individuals, as well as those with blindness of
unknown etiology, should undergo a neurologic evaluation that includes imaging of the
suprasellar region (computed tomographic scan or magnetic resonance imaging scan)
Differential Diagnosis: A carefully kept sleep-wake log that is recorded for a lengthy period
of time is essential to making this diagnosis. Non-24-hour sleep- wake syndrome should be
differentiated from delayed sleep-phase syndrome and irregular sleep-wake pattern. In the
delayed sleep-phase syndrome, stable entrainment to a 24-hour schedule with sleep at a
delayed phase from conventional hours is present during vacations. Patients with the non-24hour sleep-wake syndrome continue in a pattern of progressive delays of sleep. The diagnosis
should be suspected in any blind individual with sleep or somnolence complaints.
Diagnostic Criteria: Non-24-Hour Sleep-Wake Syndrome (780.55-2)
A. The patient has a primary complaint of either difficulty initiating sleep or difficulty in
awakening.
B. Sleep onset and offset are progressively delayed, with the patient unable to maintain
stable entrainment to a 24-hour sleep-wake pattern.
C. The sleep pattern has been present for at least six weeks.
D. Progressive sequential delay of the sleep period is demonstrated by one of the following
methods:
1. Polysomnography performed over several consecutive days on a fixed
24-hour bedtime and waketime schedule
2. Continuous 24-hour temperature monitoring over at least five days that shows a
progressive delay of the temperature nadir
E. The symptoms do not meet the criteria for any other sleep disorder causing inability to
initiate sleep or excessive sleepiness.
Note: If the sleep disorder is believed to be socially or environmentally induced, state and
code as non-24-hour sleep-wake syndrome (extrinsic type). If there is evidence that the sleep
disorder is due to an abnormal circadian pacemaker or its entrainment mechanism, state and
code as non-24-hour sleep- wake syndrome (intrinsic type).
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Minimal Criteria: A plus B plus C.
Severity Criteria:
Mild: Mild insomnia or mild excessive sleepiness, as defined on page 23; usually associated
with a mild impairment of social or occupational functioning.
Moderate: Moderate insomnia or moderate excessive sleepiness, as defined on page 23;
usually associated with a moderate impairment of social or occupational functioning.
Severe: Severe insomnia or severe excessive sleepiness, as defined on page 23; usually
associated with a severe impairment of social or occupational functioning.
Duration Criteria:
Acute: 6 months or less.
Subacute: More than 6 months but less than 1 year.
Chronic: 1 year or longer.
Bibliography:
Kokkoris CP, Weitzman ED, Pollak CP, et al. Long-term ambulatory monitoring in a subject with a hypernychthemeral sleepwake cycle disturbance. Sleep 1977;1:177–190.
Miles LE, Raynal DM, Wilson MA. Blind man living in normal society has circadian rhythms of 24.9 hours. Science 1973;
198: 421–423.
Miles LE, Wilson MA. High incidence of cyclic sleep-wake disorders in the blind. Sleep Res 1977; 6: 192. Okawa M. Sleepwaking rhythm and its central mechanism in humans: Studies of biological rhythm, computed tomography and autopsy of severely brain-damaged children. Adv Neurol 1985; 29: 346–365. Okawa M, Nanami
T, Wada S, et al. Four congenitally blind children with circadian sleep-wake rhythm
disorder. Sleep 1987; 10: 101–110.
Weber AL, Cary MS, Conner N, Keyes P. Human non-24-hour sleep-wake cycles in an everyday environment. Sleep 1980;
2: 347–354.
Adapted from: www.aasmnet.org
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