Although rarely observed, Kleine-Levin syndrome is an interesting disorder affecting 1 to 2 patients per million inhabitants worldwide and is associated with recurrent cognitive behavioral and emotional problems. It may severely affect quality of life and social adaptation. Increasing evidence points to a diencephalic dysregulation as the main source of symptoms. Some functional neuroimaging results, as well as reports of 2 affected couples of monozygotic twins, provide new insights to better understanding the physiopathology of this disorder. Clinical and cognitive follow-up of affected patients has, in several cases, demonstrated persistence of memory impairments long after resolution of episodes of the disorder itself, especially in patients with longstanding disease. A Cochrane review of drug trials for the management of Kleine-Levin syndrome symptoms did not find eligible studies to recommend any of the different treatments so far employed, even if therapeutic. Lithium seems to hold the best prospective benefits.
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• In Kleine-Levin syndrome (KLS), recurrent episodes of excessive sleepiness are variable in duration and occur at least once per year, whereas alertness, cognition, and behavior appear normal between the attacks.
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• An autoimmune basis for Kleine-Levin syndrome supported by HLA data has been clinically suggested.
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• Despite prolonged total sleep time during the attack, polysomnography shows reduced sleep efficiency and increased wakefulness after sleep onset during episodes or recurrent hypersomnia.
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• Both preventive and symptomatic drugs are scarcely efficacious in the management of Kleine-Levin syndrome.
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• Menstruation-associated periodic hypersomnia is a rare condition in which episodes of hypersomnia, with or without overeating, and mental disturbances are linked with menses.
Historical note and terminology
Except for the report by Anfimoff (53; 54), Kleine, Lewis, and Levin were the first to describe cases of adolescent boys with recurrent episodes of excessive sleep, abnormal behavior including overeating and sexual disinhibition, and mental disturbances (56; 63; 61). In 1936 Levin collected several reports and published them as examples of "a new syndrome of periodic somnolence and morbid hunger" (62). Critchley and Hoffman gave this condition the eponym "Kleine-Levin syndrome" (27). Critchley subsequently published 11 personal cases and 15 cases from literature (26). 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. Billiard substituted the term "recurrent hypersomnia" for "periodic hypersomnia," a true periodicity of the hypersomnic episodes being exceptional (14). In the International Classification of Sleep Disorders (03), the Kleine-Levin syndrome is classified under “Hypersomnias of Central Origin not due to a Circadian Rhythm Sleep Disorder, Sleep Related Breathing Disorder, or other cause of disturbed nocturnal sleep.”