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Kleine-Levin syndrome

Orpha number ORPHA33543
Synonym(s) -
Prevalence 1-9 / 1 000 000
Inheritance -
Age of onset Childhood
Adolescent
Adult
ICD-10
  • G47.8
ICD-O -
OMIM
UMLS
  • C0206085
MeSH
  • D017593
MedDRA
  • 10053712
SNOMED CT
  • 111488004

Summary

Kleine-Levin syndrome (KLS) is a rare neurological disorder of unknown origin characterised by relapsing-remitting episodes of hypersomnia in association with cognitive and behavioural disturbances. It affects around 1-2/million 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). The first episode is triggered by an infection in 72% of patients. Patients experience 7-19 neurological episodes with a duration of 10-13 days/episode and relapses every 3.5 months. Episodes recur more quickly in patients with childhood onset. 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). Less frequently, patients experience hyperphagia (66% of patients), hypersexuality (53% of patients, principally men), anxiety, compulsive or mood disorders and depression (53% of patients, predominantly women). Sleep, vigilance, mood, and eating habits are remarkably similar to those of controls between episodes, but patients with KLS have an increased body mass index. The median disease course is 8-14 years, but is longer in men, in patients with hypersexuality, and when onset occurs after 20 years of age. Newly identified susceptibility factors include perinatal and developmental problems. Familial clustering (5% of cases involve multiplex families, suggesting autosomal recessive transmission) and a potential Jewish founder effect support a role for genetic susceptibility factors. An association of KLS with HLA-DQ2 positivity was found in a small series but was not replicated in a larger independent sample group. There is no family history of neuropsychiatric disorders. In 10% of cases, KLS arises secondary to various genetic, inflammatory, vascular or paraneoplastic conditions. In these cases the patients are older and have more frequent and longer episodes, but clinical symptoms, disease course and treatment response are similar to those in primary cases. Structural brain imaging, cerebrospinal fluid and serological inflammatory markers are unremarkable. EEG slowing is noted in 70% of cases during episodes, without epileptic activity. Sleep structure varies from harmonious hypersomnia to hypoarousal with low sleep efficiency. Brain scintigraphy may show hypoperfusion, mainly focused in the thalamic, hypothalamic and frontotemporal areas, especially when compared to images obtained between episodes. Patients generally show a poor response to medical treatment. Some stimulants (amantadine and, more rarely, modafinil or amphetamines) and mood stabilisers (lithium, valproate, but not carbamazepine) have marginal efficacy. KLS is a puzzling and disabling disease. Until its cause is identified, disease management should be primarily supportive and educational.

Expert reviewer(s)

  • Pr Isabelle ARNULF

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Detailed information

Review article
  • FR (2008,pdf)
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