Hypothalamic volume reduction in adult patients with narcolepsy type 1

Study Objectives Narcolepsy-type 1 (NT1) is a neurological sleep disorder, characterized by a loss of orexin-producing cells in the posterior hypothalamus. These neurons are approximately 70 000 but have large orexin-containing projections within the hypothalamus and other brain areas. Several evidences suggest an autoimmune origin, while pathological studies in postmortem samples collected decades after onset have found variable gliosis. In this study, we studied MRI-based volumes in the hypothalamus in a large cohort of patients with NT1 versus healthy controls. Methods A consecutive cohort of 75 adult NT1 patients (36 females 33.1 +/- 12.8 years old) and 85 age- and sex-matched healthy controls (42 females, 32.5 +/- 8.2 years old) underwent neuroimaging, including T1-weighted MPRAGE MRI at 3Tesla. The hypothalamus and its subregions (anterior-inferior, anterior-superior, posterior, tuberal-inferior, and tuberal-superior) were segmented from T1 images using an automated tool. Hypothalamic volumes were compared between groups and correlated with clinical features and orexin levels in the cerebrospinal fluid. Results Adjusted for whole brain-volume, patients showed reductions in hypothalamic volume compared to healthy controls (p=.01). These reductions were found across most hypothalamic subregions, anterior-inferior (p<.001), anterior-superior (p=.003), posterior (p=.03), and tuberal-superior (p=.04), but not in the tuberal-inferior subregion. No significant correlations were found with clinical or laboratory variables. Conclusions Automated volumetric analysis of brain MRI showed hypothalamic atrophy in NT1 patients compared to healthy controls. Future pathological studies are needed to address the diagnostic and mechanistic relevance of this finding.