|Classification and external resources|
Kleine–Levin syndrome, KLS, or Sleeping Beauty syndrome is a neurological disorder characterized by recurring periods of excessive amounts of sleeping and eating. At the onset of an episode the patient becomes drowsy and sleeps for most of the day and night (hypersomnolence), waking only to eat or go to the bathroom. When awake, the patient’s whole demeanor is changed, often appearing “spacey” or childlike. They also experience confusion, disorientation, complete lack of energy (lethargy), and lack of emotions (apathy). Individuals are not able to attend school or work or care for themselves. Most are bedridden, tired, and uncommunicative even when awake.
Most patients report that everything seems out of focus, and that they are hypersensitive to noise and light. In some cases, food cravings (compulsive hyperphagia) are exhibited. Affected individuals also tend to lose interest in hobbies and activities that they used to be fond of before. In males, instances of uninhibited hypersexuality during episodes have also been reported. In females, instances of depression have been reported.
Affected individuals may go for a period of weeks, months or even years without experiencing any symptoms, and then they reappear with little warning. In between episodes those diagnosed with KLS appear to be in perfect health with no evidence of behavioral or physical dysfunction.
Presentation and symptoms 
Individual sufferers may often become irritable, lethargic, and/or apathetic. KLS patients may appear disoriented and report hallucinations. Symptoms are cyclical; with days to weeks (even up to months) of suffering interspersed by weeks or months (even up to years) symptom-free. Although resolution of the disorder may occur for some in later life, this is not universal.
Hypersomnia is a primary symptom of KLS, and is present in all subjects. Subjects are often treated initially for a sleeping disorder. During a KLS episode, subjects often spend an average of 16 hours a day asleep, while some patients can sleep for even longer periods. Another defining symptom of KLS is an altered mental state during the episode. Subjects are hard to arouse from this sleep, and are irritable or aggressive when prevented from sleeping. Subjects also frequently show cognitive impairment, and can show confusion, amnesia for the event, hallucinations, delusions, or experience a dream-like state. About 75% of KLS patients experience changes in eating behavior during episodes, with the majority of these exhibiting polyphagia. Reports describe patients who will eat anything placed in front of them with very little discrimination, resulting in consumption of excessive amounts of food. A small number of KLS patients report experiencing some sort of hypersexual behavior during the event, including promiscuity, excessive masturbation, inappropriate sexual advances, and other risqué, atypical behavior. Hypersexual behavior is more common in males than females, and is associated with a much longer disease course. Other unusual compulsions reported during the event are also not uncommon.
While some researchers speculate that there may be a hereditary predisposition, others believe the condition may be the result of an autoimmune disorder. Both proposals need not be mutually exclusive with the result being a malfunction of the portion of the brain that helps to regulate functions such as sleep, appetite, and body temperature (hypothalamus). Recent studies also suggest that there may be a link to a deficiency of dopamine transporter density in the lower striatum.
Kleine–Levin syndrome is named after Willi Kleine and Max Levin, who reviewed the syndrome in 1925 and 1936 respectively. The syndrome was first described by the French physician Edmé Pierre Chauvot de Beauchêne (1748–1824) in 1786. The term Kleine–Levin syndrome was introduced by the British neurologist MacDonald Critchley (1900-1997) in 1942.
A 2008 study of 108 KLS patients found that the majority of cases were present in adolescent males, with a mean sex ratio of 3:1. The average age of onset was 15.7 years, with 81.7% experiencing their first episode between 10 and 20 years of age. Age ranged from 6 to 59 years when patients experienced their first episode. Females tended to be slightly older than males at first onset, even though they tended to experience puberty earlier. In the US population, KLS presents in Caucasians with three times the expected frequency, and it is found six times more frequently amongst those with Jewish (Ashkenazi)heritage.
First onset 
About 90% of KLS patients associate an event with their first KLS episode. This event is most often a type of infection or cold, but may also be associated with stress, sleep deprivation, alcohol, physical exertion, head trauma or even traveling and marijuana use. This causes some to think that there may be some immunological link, but so far there is no clear proof of this. Only a quarter of KLS patients report events triggering subsequent episodes.
There are no known genetic markers for KLS. There are no protein or antibody markers available for a positive diagnosis of KLS. Some researchers have explored hereditable immunity traits that may predispose individuals for KLS. One such trial focused on a family of twelve in which the father and five children were all affected by KLS. Human leukocyte antigen (HLA) typing revealed that the father was identical to two of his children that were both affected by KLS.
Diagnosis of KLS is very difficult since there are no symptoms that allow for a positive diagnosis. KLS is instead a diagnosis of exclusion, where a doctor must first eliminate a long list of other conditions that could mimic the symptoms. Because hypersomnia is the primary symptom, many patients are initially treated for a sleeping disorder. Potential KLS patients are often referred to an endocrinologist early on to check for metabolic problems including diabetes and hypothyroidism. Several other disorders can also mimic KLS symptoms, but many can be positively diagnosed by MRI—including ones caused by a lesion, tumor, or inflammation. Multiple sclerosis also has neurological components that can mimic the symptom profile for KLS.
People with KLS are often mistakenly diagnosed with a psychiatric disorder. The periods of somnolence, hyperphagia, and withdrawal can mimic severe depression, and some people experience a brief period of high energy following these episodes which looks like a manic episode, so that some patients are incorrectly diagnosed with bipolar disorder. There can also be a number of other mood symptoms or perceptual disturbances which mimic primary psychiatric disorders. Narcolepsy and Klüver–Bucy syndrome can also produce similar symptom profiles. Before a final diagnosis can be made, all other possibilities must be carefully excluded, and the cluster of symptoms must fit with those commonly observed in KLS patients.
There is no definitive treatment for Kleine–Levin syndrome. Stimulants, including amphetamines, methylphenidate, and modafinil, administered orally, can be used to treat sleepiness, but do not improve sluggish cognition or other elements of the altered mental state. There are some similarities between Kleine–Levin syndrome and bipolar disorder, and lithium and carbamazepine are reported to be beneficial in some cases in warding off or shortening episodes. Responses to treatment have often been limited. This disorder needs to be differentiated from cyclic recurrence of sleepiness during the premenstrual period in teenage girls that may be controlled with hormonal contraception.
Frequency and duration of episodes 
A 2005 review of the scientific literature reported that the disease had an estimated median duration of 8 years in 186 KLS patients. Among the subset of 65 patients who had reportedly recovered, the average age was 23 and the median duration was 4 years. The duration of the disease did not seem to be influenced by the age of onset or the presence of hypersexuality.
Patients experienced an average of 12 episodes lasting an average of 12 days, although the range of symptoms reported varied from 2 to 130 episodes and lasted between 2.5 and 80 days. Subjects experienced an average duration of 6 months between episodes, but this ranged from .5 to 72 months. Subjects typically experienced less frequent and less intense attacks toward the end of the disease course, and the subject is considered cured if they do not experience an episode for 6 or more years.
A subsequent study by the same authors of 108 patients, however, found that the disease duration, at least in this disease cohort, was longer in men, those suffering hypersexuality and where the age of onset was after 20.
Living with KLS can be difficult. Many patients report depression during one or more episodes. While the major symptoms may seem innocent enough to some (copious amounts of sleeping, eating, and sexual behavior) the effects can be very debilitating. At the very least, KLS makes it difficult to maintain a normal job—and in some cases criminal charges have resulted from unrestrained sexual behavior. Periodic binges associated with the episode can lead to weight gain, and KLS patients often exhibit an above-average BMI, but no mention of obesity is made in the literature. KLS patients may also suffer from psychosocial stigma because their unusual activities during an episode are not understood by others. Many patients report embarrassing episodes from early in their adolescence before KLS was considered a viable diagnosis.
In many cases, the disorder disappears as mysteriously as it appears; often when patients reach their twenties. Of the patients that have been studied, more than 90% will outgrow KLS symptoms and even those who have some degree of it left after ten years, it is usually much, much milder.
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- The KLS Foundation
- KLS Support UK
- KLS Life
- kleine_levin at NINDS
- The teenager who sleeps for 10 days BBC News online with video (2010-12-08)
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