Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine–Levin syndrome

Abstract

ObjectiveTo measure CSF biomarkers of hypothalamic dysfunction in patients with typical Kleine–Levin syndrome (KLS) during symptomatic and asymptomatic periods. Patients/methodsTwo patients with typical KLS were admitted during symptomatic and asymptomatic periods to a research Sleep Disorders Center. Cerebrospinalfluid (CSF) hypocretin-1, histamine (HA), and its major metabolite tele-methylhistamine (t-MHA) levels were measured in two KLS patients in and out of episode. ResultsCSF biomarkers of hypothalamic dysfunction measured in two KLS patients in and out of episode revealed low hypocretin levels (within the narcolepsy–cataplexy range) during a hypersomnia episode in the more severe patient, and a 42% decrease (although within normal range) in the second patient. CSF HA and t-MHA measurements in and out of episode revealed a two-fold in-episode decrease in HA in the more severe patient, with no significant change for the second patient, nor for t-MHA levels. ConclusionWe reported reversible changes in CSF hypothalamic biomarkers in a typical patient with KLS that reinforces the hypothesis that in some patients KLS episodes may be caused by recurrent functional alterations of the hypothalamus.