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

Abstract

Objective: To measure CSF biomarkers of hypothalamic dysfunction in patients with typical Kleine-Levin syndrome (KLS) during symptomatic and asymptomatic periods.

Patients/methods: Two 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.

Results: CSF 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.

Conclusion: We 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.

Keywords: Histamine; Hypocretin; Hypothalamus; Kleine–Levin syndrome; Telemethyl histamin.