Kleine–Levin syndrome: A systematic study of 108 patients

• Published in: Annals of neurology Vol. 63; no. 4; pp. 482 - 493
• Main Authors: Arnulf, Isabelle, Lin, Ling, Gadoth, Nathan, File, Jennifer, Lecendreux, Michel, Franco, Patricia, Zeitzer, Jamie, Lo, Betty, Faraco, Juliette H., Mignot, Emmanuel
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2008; Willey-Liss
• Subjects: Adolescent; Adult; Biological and medical sciences; Biomarkers - analysis; Child; Disorders of Excessive Somnolence - complications; Disorders of Excessive Somnolence - epidemiology; Disorders of Excessive Somnolence - genetics; Female; Genetic Predisposition to Disease; Humans; Hyperphagia - complications; Hyperphagia - epidemiology; Hyperphagia - genetics; Internationality; Kleine-Levin Syndrome - complications; Kleine-Levin Syndrome - epidemiology; Kleine-Levin Syndrome - genetics; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Retrospective Studies; Sexual Dysfunction, Physiological - complications; Sexual Dysfunction, Physiological - epidemiology; Sexual Dysfunction, Physiological - genetics; Sleep Wake Disorders - complications; Sleep Wake Disorders - epidemiology; Sleep Wake Disorders - genetics; Surveys and Questionnaires; Human; Sleep disorder; Nervous system diseases; Kleine-Levin syndrome; Neurological disorder; Behavioral disorder
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.21333

Objective Kleine–Levin syndrome is a rare disorder characterized by relapsing‐remitting episodes of hypersomnia, cognitive disturbances, and behavioral disturbances, such as hyperphagia and hypersexuality. Methods We collected detailed clinical data and blood samples on 108 patients, 79 parent pairs, and 108 matched control subjects. We measured biological markers and typed human leukocyte antigen genes DR and DQ. Results Novel predisposing factors were identified including increased birth and developmental problems (odds ratio, 6.5). Jewish heritage was overrepresented, and five multiplex families were identified. Human leukocyte antigen typing was unremarkable. Patients were 78% male (mean age at onset, 15.7 ± 6.0 years), averaged 19 episodes of 13 days, and were incapacitated 8 months over 14 years. The disease course was longer in men, in patients with hypersexuality, and when onset was after age 20. During episodes, all patients had hypersomnia, cognitive impairment, and derealization; 66% had megaphagia; 53% reported hypersexuality (principally men); and 53% reported a depressed mood (predominantly women). Patients were remarkably similar to control subjects between episodes regarding sleep, mood, and eating attitude, but had increased body mass index. We found marginal efficacy for amantadine and mood stabilizers, but found no increased family history for neuropsychiatric disorders. Interpretation The similarity of the clinical and demographic features across studies strongly suggests that Kleine–Levin syndrome is a genuine disease entity. Familial clustering and increased prevalence in the Jewish population support a role for a major genetic susceptibility factor. Considering the inefficacy of available treatments, we propose that disease management should primarily be supportive and educational. Ann Neurol 2008;63:482–492