Episodic hypersomnia, hyperphagia, and hypersexual behavior has been referred to as the classical symptom triad but is presented by only half of KLS patients. In the majority of patients, cognitive dysfunction, hallucinations, and déjà vu-like experiences accompany hypersomnia [4].

In detail, the following symptoms have been related to the disease [5]:

• Sleep disorders- Besides hypersomnia (100%), intense dreaming (59%), sleep paralysis (14%) and post-episode insomnia (72%) have been described in affected individuals.
• Eating disorders comprise hyperphagia (66%) and excessive drinking (16%), but a loss of appetite (34%) may also be claimed.
• An excess sexual drive (59%) is much more common than decreased sexuality (6%) and is more often observed in male patients [6].
• Cognitive impairment may manifest in form of impaired speech (94%), concentration problems (91%), temporal and spatial disorientation (87 and 43%, respectively).
• Visual, hearing, olfactory and gustatory impairment as well as an altered perception of tactile stimuli and pain have been reported (in total, 100%).
• An altered mental state may lead to irritability (65%), anxiety (45%) and depression (53%). The latter mainly affects females [6].
• Constitutive symptoms described in KLS patients include fever (68%), hot flashes (24%) and sweating (46%), migraine-like headaches (48%), photophobia (59%) and nausea (18%).

During early stages of the disease, KLS episodes may be experienced several times a year, but frequency declines over time. Similarly, the severity of symptoms gradually decreases with disease progression. A single episode typically lasts about ten days [3], but may also extend over more than a month [7]. Between episodes, affected individuals may present unaltered sleep, eating and sexual patterns, but a trend towards fatigue and higher incidence rates of anxiety and depression has been registered [8].

Patients may or may not be able to recall a KLS episode.

• Hypersomnia

  PATIENTS: 26 narcoleptic patients with cataplexy, 9 narcoleptic patients without cataplexy, 2 patients with abnormal REM-sleep-associated hypersomnia, 7 patients with idiopathic hypersomnia, 2 patients with post-traumatic hypersomnia, 4 patients with [ncbi.nlm.nih.gov]

• Asymptomatic

  The longer the duration of the syndrome, the more extended the hypoperfusion regions during the asymptomatic period. [ncbi.nlm.nih.gov]

• Epilepsy

  This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants. [ncbi.nlm.nih.gov]

• Fever

  Immediately preceding to it the child had been an episode of enteric fever confirmed by the serological tests. [ncbi.nlm.nih.gov]

  [3] In this Indian review, the most frequent precipitating factor was a brief episode of fever or a probable viral infection, with the symptoms of the KLS occurring shortly after (between 2 and 6 days) the onset of fever. [4], [5], [6] Other precipitating [neurologyindia.com]

  No. of patients Frequency at KLS onset (%) Frequency before KLS reoccurrences (%) None reported 66 39 84 Infection or fever 72 42.8 8.9 Unspecific fever, flu-like fever 42 25 Upper respiratory tract infection: Tonsillitis, sore throat, cough 20 12 Gastro [doi.org]

  Constitutive symptoms described in KLS patients include fever (68%), hot flashes (24%) and sweating (46%), migraine-like headaches (48%), photophobia (59%) and nausea (18%). [symptoma.com]

• Fatigue

  Acute illness or fatigue may precede an episode which may occur as often as several times a year. Between attacks the person recovers completely and the sleep periods usually disappear in adult age. [psychnet-uk.com]

  Between episodes, affected individuals may present unaltered sleep, eating and sexual patterns, but a trend towards fatigue and higher incidence rates of anxiety and depression has been registered. [symptoma.com]

  Fatigue can be so severe that people with KLS are bedridden until an episode passes. This takes time and energy away from family, friends, and personal obligations. [healthline.com]

  Additional characteristic symptoms of Kleine-Levin syndrome may include: Childlike or “spacey” demeanor Confusion and disorientation Lethargy and fatigue Lack of emotions and focus Photosensitivity and photosensitivity Compulsive hyperphagia (food cravings [news-medical.net]

  Kleine-Levin syndrome: a unique cause of fatigue in an athlete C M J Conklin 1, J E Taunton 1 University of British Columbia, Vancouver, BC, Canada Correspondence to: Mr Conklin Faculty of Medicine, University of British Columbia, 317–2194 Health Sciences [bjsm.bmj.com]

• Overeating

  Seven subjects with Kleine-Levin Syndrome accumulated over time had systematic SPECT studies during (n=5) and out (n=7) of the symptomatic period. [ncbi.nlm.nih.gov]

  • Menstruation-associated periodic hypersomnia is a rare condition in which episodes of hypersomnia, with or without overeating, and mental disturbances are linked with menses. [medlink.com]

• Increased Appetite

  Kleine-Levin syndrome is a rare self-limited disorder which usually affects adolescent males and is characterized by episodic hypersomnia, increased appetite, and behavioral/psychiatric disturbances. Individuals are normal between the attacks. [ncbi.nlm.nih.gov]

  Symptoms of Kleine-Levin syndrome include excessive daytime sleepiness and sleeping for long stretches (patients sometimes wake only to eat and use the bathroom), sometimes accompanied by increased appetite and hypersexuality, for a period of 2 to 31 [tuck.com]

  Episodes can also trigger other symptoms, such as: hallucinations disorientation irritability childish behavior increased appetite excessive sex drive This may result from reduced blood flow to parts of the brain during an episode. [healthline.com]

• Nausea

  Constitutive symptoms described in KLS patients include fever (68%), hot flashes (24%) and sweating (46%), migraine-like headaches (48%), photophobia (59%) and nausea (18%). [symptoma.com]

  She typically had headache, nausea, and vomiting at episode onset. [aasmnet.org]

  The most common side effects are nausea and weight loss [ 60 ]. [doi.org]

• Loss of Appetite

  Eating disorders comprise hyperphagia (66%) and excessive drinking (16%), but a loss of appetite (34%) may also be claimed. An excess sexual drive (59%) is much more common than decreased sexuality (6%) and is more often observed in male patients. [symptoma.com]

• Acne Vulgaris

  The synthetic retinoid isotretinoin is an effective treatment option for severe forms of acne vulgaris. However, several reports indicate that some patients experience altered central nervous system functions in association with treatment. [ncbi.nlm.nih.gov]

• Photophobia

  Constitutive symptoms described in KLS patients include fever (68%), hot flashes (24%) and sweating (46%), migraine-like headaches (48%), photophobia (59%) and nausea (18%). [symptoma.com]

  […] in the presence of meningeal inflammation due to high molecular mass and affinity for P-glycoprotein. 6 Viral and autoimmune causative factors have been suggested in KLS, based on the frequent report of flu-like meningeal symptoms such as headache, photophobia [aasmnet.org]

  […] hypersexuality (43%–53%) Neuropsychiatric symptoms: Eating disturbances - 80% Depressed mood - 48% Hallucinations/illusions - 33% Mild psychotic symptoms (grandiosity, delusions, hyperreligiosity, paranoia) - lasts hours to days Anxiety Common symptoms: Headache Photophobia [emedicine.medscape.com]

• Blurred Vision

  Clomipramine, imipramine, desipramine, or protriptyline may all be used, although these compounds not only inhibit monoamine reuptake, they also have anticholinergic properties responsible for additional side effects (increased constipation, blurred vision [doi.org]

• Delusion

  Some psychiatric symptoms (megaphagia, hypersexuality, anxiety, depressed mood, hallucinations, delusions) arise during episodes, albeit less frequently, while patients are normal between episodes. [ncbi.nlm.nih.gov]

  Common mental symptoms are confusion, irritability, restlessness, euphoria, hallucinations, delusions, and schizophreniform states. Attacks may occur every 3 to 6 months and last from 2 to 3 days. [whonamedit.com]

  Aside from this feeling of unreality, some patients experienced visual or auditory hallucinations and paranoid or paranoiac delusions. [doi.org]

  In addition, some of them may feel they live in dream world, have hallucinations and delusions. [medigoo.com]

  Some experienced hallucinations, paranoia and delusions. One patient’s own voice appeared “strange to himself.” [vanwinkles.com]

• Abnormal Behavior

  Abstract Since 1962, when Critchley and Hoffman coined the term Kleine-Levin Syndrome (KLS) for the triad of hypersomnia, excessive eating and "often abnormal behavior" which they have observed in 11 adolescent boys, the number of patients recognized [ncbi.nlm.nih.gov]

• Behavior Disorder

  The same haplotype has been associated with sleepwalking and with rapid eye movement (REM) sleep behavior disorder. [ncbi.nlm.nih.gov]

  All healthcare centers recommend caring for the person who has KLS at home, don’t leave this individual alone and manage anxieties and other behavioral disorders during awake. [medigoo.com]

  The association between narcolepsy and REM behavior disorder (RBD). Sleep Med. 2005; 6(3) 253-258 32 Dauvilliers Y, Rompré S, Gagnon J F, Vendette M, Petit D, Montplaisir J. REM sleep characteristics in narcolepsy and REM sleep behavior disorder. [doi.org]

  Sleep paralysis, rapid eye movement (REM) behavior disorder, and cataplexy are not features of Kleine-Levin syndrome and, if present, should prompt the clinician to consider an alternative diagnosis of narcolepsy. [dovepress.com]

• Compulsive Behavior

  Repetitive or compulsive behaviors are also common. Patients may become aggressive, especially if they are prevented from eating. Verbal outbursts may take the form of rude, offensive, and sexually charged language. [dovepress.com]

• Onset in Adolescence

  STUDY OBJECTIVES: The objectives of this study were to investigate possible neuropathology behind the Kleine-Levin Syndrome (KLS), a severe form of hypersomnia with onset during adolescence. [ncbi.nlm.nih.gov]

  He emphasized 4 clinical features: males principally affected, onset during adolescence, eventual spontaneous disappearance, and the possibility that overeating is of the compulsive rather than the bulimic type. [medlink.com]

  Critchley 1962 : Predominance in adolescent males; Onset in adolescence; Periodic hypersomnia; Hyper/mega/polyphagia; Associated behavioural and psychological changes; Benign clinical course with spontaneous disappearance of clinical symptoms; Lack of [doi.org]

• Confusion

  This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants. [ncbi.nlm.nih.gov]

  Kleine-Levin syndrome: a cause of diagnostic confusion. Abstract The case is described of a boy with the Kleine-Levin syndrome in whom prominent behavioural disturbances and the initial absence of a clear cyclical pattern obscured the diagnosis. [adc.bmj.com]

• Irritability

  Stimulant pills, including amphetamines, methylphenidate, and modafinil, are used to treat sleepiness but may increase irritability and will not improve cognitive abnormalities. [ninds.nih.gov]

  This explains the withdrawn behavior and irritability present in our case, thereby ruling out Major Depressive Disorder. KLS is a clinical diagnosis. [doi.org]

  Psychiatric manifestations are common to both and include irritability, depression, apathy, inattention and poor concentration. Both disorders are diagnosed clinically and no specific laboratory investigation is available to confirm the diagnosis. [ncbi.nlm.nih.gov]

• Somnolence

  Levin M: Periodic somnolence and morbid hunger: a new syndrome. Brain 1936;59:494–504. Critchley M, Hoffman H: The syndrome of periodic somnolence and morbid hunger (Kleine–Levin syndrome). BMJ 1942;1:137–139. [doi.org]

  KLS should be considered in young patients, who present with episodes of undue somnolence. [ncbi.nlm.nih.gov]

• Apathy

  Defects in the dorsomedial prefrontal cortex may cause apathy. [ncbi.nlm.nih.gov]

• Amnesia

  During episodes, patients suddenly present hypersomnia (with sleep lasting 15-21 h/d), cognitive impairment (major apathy, confusion, slowness, amnesia), and a specific feeling of derealization (dreamy state, altered perception). [ncbi.nlm.nih.gov]

  During episodes, all patients have hypersomnia (with sleep periods lasting 15-21 hours per day), cognitive impairment (apathy, confusion, slowness and amnesia) and a specific feeling of derealization (a dream-like state with altered perception). [orpha.net]

  On recovery, total or partial loss of memory (amnesia) of what has happened is usual. There may be a short period of depression, or sometimes euphoria and sleeplessness. [southerncross.co.nz]

According to The International Classification of Sleep Disorders [9], KLS falls into the categories "hypersomnias of central origin" and "recurrent hypersomnia." Diagnostic criteria are defined as follows:

• A minimum of two episodes of hypersomnia each lasting more than two days and less than five weeks.
• A month to one and a half years lie between single episodes.
• Episodes are further characterized by at least one of the following symptoms: eating disorder, disinhibited behavior, cognitive impairment, altered perception.
• Between episodes, consciousness, cognitive function, mood, and behavior remain unaltered.
• Symptoms cannot be explained by other pathologies, e.g., epilepsy, narcolepsy, bipolar disorder, or medication.

Thus, thorough anamnesis, general and neurological examinations are the mainstays of KLS diagnosis. Additional measures may be carried out to rule out psychiatric disorders.

In this context, polysomnography [10], brain imaging, laboratory analyses of blood or cerebrospinal fluid, and neuropsychological tests may be performed [4].

• HLA-DQ2

  An association of KLS with HLA-DQ2 positivity was found in a small series but not replicated in larger independent sample groups. There is no family history of neuropsychiatric disorders. [orpha.net]

  En un grupo pequeño, se encontró una asociación del SKL con el genotipo HLA-DQ2 positivo, pero no se confirmó en un grupo más grande. No hay historial familiar de alteraciones neuropsiquiátricas. [femexer.org]

This provides scope for offering established and effective migraine treatment options to patients who with a potential misdiagnosis of Kleine-Levin syndrome, providing scope for offering established and effective migraine treatment to some patients originally [ncbi.nlm.nih.gov]

Types of interventions We included all drugs used for the treatment of KLS. [doi.org]

Lithium therapy stops episodes in 37% patients (vs. 3.4% if no treatment is given) and reduces the frequency/duration of episodes in 46% of other patients. The treatment is usually given to patients with frequent, prolonged or very severe episodes. [orpha.net]

The prognosis is generally benign, with normal cognitive and social functions after the episodes. [ncbi.nlm.nih.gov]

Prognosis The prognosis is generally good, with most patients presenting less frequent and less severe episodes with advancing age and disappearance of the syndrome around 30-35 y old. [orpha.net]

Read More Read Less Prognosis Prognosis Episodes eventually decrease in frequency and intensity over the course of eight to 12 years. Clinical Trials Clinical Trials [ninds.nih.gov]

Kleine-Levin syndrome is a rare sleep disorder of unknown etiology. It is characterized by intermittent periods of excessive sleepiness, cognitive disturbances and behavioral abnormalities. [ncbi.nlm.nih.gov]

Summary Epidemiology It affects around 1/500 000 individuals. Patients are mostly male (68-78% of cases) and adolescents (81% of patients), with a mean age of onset of 15 years (range 4-82 years). [orpha.net]

This rare disorder has been studied more closely in the last few years with abundant epidemiologic data assembled through literature and worldwide case reviews. [doi.org]

Cancer epidemiology biomarkers and prevention. 20: 2222-2231 A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. [uefconnect.uef.fi]

Epidemiology [ edit ] Population-based studies of KLS have not been performed. Its prevalence is about 1 case per million people. In France, KLS has a prevalence of 1.5 per million people. It occurs most frequently among Jews in the US and Israel. [en.wikipedia.org]

(See Epidemiology.) KLS may be precipitated by infections (72%), alcohol consumption (23%), sleep deprivation (22%), unusual stress (20%), physical exertion (19%), traveling (10%), head trauma (9%), and marijuana use (6%). [emedicine.medscape.com]

Kleine-Levin syndrome (KLS) is a rare disorder whose pathophysiological mechanisms remain unknown. [ncbi.nlm.nih.gov]

Here, we report a case of recurrent hypersomnia in which gabapentin was effective for the prevention of attacks. [ncbi.nlm.nih.gov]

Prevention of Sleeping Beauty Syndrome or Kleine-Levin Syndrome Lithium is the only element or drug that has a preventive effect on Sleeping Beauty Syndrome or Kleine-Levin Syndrome. [epainassist.com]

Because of similarities between Kleine-Levin syndrome and certain mood disorders, lithium and carbamazepine may be prescribed and, in some cases, have been shown to prevent further episodes. [ninds.nih.gov]

Kleine-Levin syndrome (KLS) is a rare disease with as-of-yet unknown etiology. Affected individuals suffer from episodic hypersomnia, cognitive impairment, and an altered mental state. It has been speculated that these symptoms indicate hypothalamic lesions, although scientific evidence regarding this hypothesis is scarce. Disease onset has been related to encephalitis [1], though, single episodes may be triggered by infection, head trauma, alcohol or drug abuse. Familial KLS has also been described [2].

To date, symptomatic treatment is not available. Spontaneous remission is likely, though, particularly in patients who experience first episodes of hypersomnia during adolescence. However, years may pass until resolution occurs [3].

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