Narcolepsy with intermediate cerebrospinal level of hypocretin-1

Study objectives: To describe the phenotype of narcolepsy with intermediate cerebrospinal hypocretin-1 levels (CSF hcrt-1). Methods: From 1600 consecutive patients with narcolepsy from Bologna and Montpellier sleep centers we selected patients with intermediate CSF hcrt-1 levels (110-200 pg/ml). Clinical, neurophysiological and biological data were contrasted for the presence of cataplexy, HLA-DQB1*06:02, and median CSF hcrt-1 levels (149.34 pg/mL). Results: Forty-five (55% males, aged 35 ± 17 years) patients (2.8% of all cases) were included. Thirty-three (73%) were HLA-DQB1*06:02, 29 (64%) reported cataplexy (21, 72.4% with typical features), and 5 (11%) had presumed secondary etiology. Cataplexy was associated with other core narcolepsy symptoms, increased sleep onset REM periods, and nocturnal sleep disruption. Cataplexy and irrepressible daytime sleep were more frequent in HLA DQB1*06:02 positive patients. Lower CSF hcrt-1 levels were associated with hallucinations. Conclusion: Narcolepsy with intermediate CSF hcrt-1 level is a rare condition with heterogeneous phenotype. HLA DQB1*06:02 and lower CSF hcrt-1 were associated with typical narcolepsy features, calling for future research to distinguish incomplete from secondary narcolepsy forms.