Kleine-Levin syndrome
Encyclopedia
Kleine-Levin Syndrome or KLS (also known as 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 craving
s (compulsive hyperphagia) are exhibited. In males, instances of uninhibited hypersexuality
during episodes have also been reported. In females, instances of depression
have been reported. Most cases of Kleine-Levin syndrome are seen in teenage boys.
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.
The cause of Kleine-Levin syndrome is not known. Thus, family support and education are the best management currently available.
s. 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 18 hours a day asleep. 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 megaphagia
. Reports describe patients who will eat anything placed in front of them with very little discrimination, resulting in consumption of excessive amounts of food. Almost half of KLS patients also experience 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.
). Recent studies also suggest that there may be a link to a deficiency of dopamine
transporter density in the lower striatum
.
, sleep deprivation
, alcohol or marijuana use, physical exertion, traveling, or head trauma. 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.
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.
. 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.
, 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 re-occurrence of sleepiness during the premenstrual period in teenage girls that may be controlled with hormonal contraception
.
Patients experienced an average of 12 episodes lasting an average of 12 days, although the range of symptoms reported varied from 2-130 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 towards 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.
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.
neurological disorder
Neurological disorder
A neurological disorder is a disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord, or in the nerves leading to or from them, can result in symptoms such as paralysis, muscle weakness, poor coordination, loss of sensation, seizures,...
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
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...
). 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 craving
Food craving
A food craving is an intense desire to consume a specific food, stronger than simply normal hunger. According to Marcia Levin Pelchat "It may be the way in which foods are consumed A food craving is an intense desire to consume a specific food, stronger than simply normal hunger. According to...
s (compulsive hyperphagia) are exhibited. In males, instances of uninhibited hypersexuality
Hypersexuality
Hypersexuality is extremely frequent or suddenly increased sexual urges or sexual activity. Hypersexuality is typically associated with lowered sexual inhibitions. Although hypersexuality can be caused by some medical conditions or medications, in most cases the cause is unknown...
during episodes have also been reported. In females, instances of depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
have been reported. Most cases of Kleine-Levin syndrome are seen in teenage boys.
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.
The cause of Kleine-Levin syndrome is not known. Thus, family support and education are the best management currently available.
Presentation and symptoms
Individual sufferers may often become irritable, lethargic, and/or apathetic. KLS patients may appear disoriented and report hallucinationHallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s. 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
Hypersomnia
Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent 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 18 hours a day asleep. 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
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause 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 megaphagia
Polyphagia
Polyphagia means "eating too much". It derives from the Greek words πολύς which means "very much", and φαγῶ , verb for "I eat"....
. Reports describe patients who will eat anything placed in front of them with very little discrimination, resulting in consumption of excessive amounts of food. Almost half of KLS patients also experience some sort of hypersexual behavior during the event, including promiscuity
Promiscuity
In humans, promiscuity refers to less discriminating casual sex with many sexual partners. The term carries a moral or religious judgement and is viewed in the context of the mainstream social ideal for sexual activity to take place within exclusive committed relationships...
, excessive masturbation
Masturbation
Masturbation refers to sexual stimulation of a person's own genitals, usually to the point of orgasm. The stimulation can be performed manually, by use of objects or tools, or by some combination of these methods. Masturbation is a common form of autoeroticism...
, 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.
Causes
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 (hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
). Recent studies also suggest that there may be a link to a deficiency of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
transporter density in the lower striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
.
Eponyms
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.Demographics
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 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 stressStress (biology)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
, sleep deprivation
Sleep deprivation
Sleep deprivation is the condition of not having enough sleep; it can be either chronic or acute. A chronic sleep-restricted state can cause fatigue, daytime sleepiness, clumsiness and weight loss or weight gain. It adversely affects the brain and cognitive function. Few studies have compared the...
, alcohol or marijuana use, physical exertion, traveling, or head trauma. 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.
Genetics
There are no known genetic markers for KLS. There are no protein or antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
(HLA) typing revealed that the father was identical to two of his children that were both affected by KLS.
Diagnosis
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 hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
. 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
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
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
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, 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
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. There can also be a number of other mood symptoms or perceptual disturbances which mimic primary psychiatric disorders. Narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
and Klüver-Bucy syndrome
Klüver-Bucy syndrome
Klüver-Bucy syndrome is a behavioral disorder that occurs when both the right and left medial temporal lobes of the brain malfunction. The amygdala has been a particularly implicated brain region in the pathogenesis of this syndrome. The syndrome is named for Heinrich Klüver and Paul...
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.
Treatment
There is no definitive treatment for Kleine-Levin syndrome. Stimulants, including amphetamines, methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
, and modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
, 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
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
and carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
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 re-occurrence of sleepiness during the premenstrual period in teenage girls that may be controlled with hormonal contraception
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
.
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 2-130 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 towards 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.
Prognosis
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.
External links
- The KLS Foundation
- KLS Life
- The teenager who sleeps for 10 days BBC News onlineBBC News OnlineBBC News Online is the website of BBC News, the division of the BBC responsible for newsgathering and production. The website is the most popular news website in the United Kingdom and forms a major part of BBC Online ....
with video (2010-12-08) - Sluggish cognitive tempoSluggish cognitive tempoSluggish Cognitive Tempo is an unformalized descriptive term which is used to better identify what appears to be a homogeneous sub-subgroup within the formal subgroup "ADHD predominantly inattentive"...
- Bipolar II