A systematic review of all published cases of Kleine-Levin syndrome (KLS) described in 195 articles since 1962 is presented from Stanford University Center for Narcolepsy, Palo Alto, CA; the Kleine-Levin Syndrome Foundation, Boston, MA; and Hopital Pitie-Salpetriere, Paris, France. KLS is primary or infrequently, secondary to stroke, brain trauma and other disorders. Of 168 primary cases, 68% occurred in males, and the median age of onset was 15 years (range 4-82 years). Onset was preceded by infection in 43% of cases, commonly a nonspecific fever or flu-like illness, upper respiratory tract infection or tonsillitis, and less often, gastroenteritis, Epstein-Barr virus, varicella-zoster virus, Asian influenza, and streptococcus. Hypersomnia is the characteristic symptom, occurring in 100% cases. Other common symptoms include mental disorders (confusion, amnesia, derealization, hallucinations) in 98%, eating disorders (80%), hypersexuality (masturbation, inappropriate sexual advances) (43%), compulsions (29%), and depression (48%). Episodes of hypersomnia lasted 10 days, recurred every 3.5 months, and recovery followed in 8 years. Women had a longer disease course than males (9+/-8.7 years vs 5.4+/-5.6 years, p=0.01). Treatment with stimulants (mainly amphetamines) relieved somnolence in 40%. Lithium prevented relapses in 41% cases cf to 19% with no relapse in untreated cases (p=0.02). CSF was normal. EEG showed only nonspecific diffuse slowing in 70% patients. Brain CT and MRI were normal. Hormonal tests showed no consistent abnormality. In 18 patients with secondary KLS, 5 had stroke or brain trauma, and the remainder had various diseases, including genetic, infectious encephalitis, and multiple sclerosis. Symptoms in secondary cases began later than in primary KLS, and the disease course was longer and more severe. [1]

COMMENT. First named KLS by Critchley et al (1942), these authors emphasized the male preponderance, adolescent onset of episodic hypersomnia, compulsive eating, and spontaneous recovery. The infectious factor in causation of KLS requires further study, especially in relation to viral or post-infectious autoimmune encephalitis, with involvement of the hypothalamus. Neuropathology in 2 primary KLS cases showed inflammatory changes in the thalamus, hypothalamus, and basal ganglia. A genetic factor is suggested, since one-sixth of patients were Jewish. Epilepsy and depressive causes have been ruled out.