Pons metabolite alterations in narcolepsy type 1.

Introduction: Narcolepsy type 1 (NT1) is a rare central sleep disorder characterized by a selective loss of hypocretin/orexin (hcrt)-producing neurons in the postero-lateral hypothalamus that project to widespread areas of the brain and brainstem. The aim of this study was to explore in a group of NT1 patients the metabolic alterations in the pons and their associations with disease features.

Methods: Twenty-one NT1 patients (16 M) and twenty age-matched healthy controls (10 M) underwent a brain ¹H MRS on a 1.5 T GE Medical Systems scanner. Metabolite content of N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) were estimated relative to creatine (Cr), using LCModel 6.3. Clinical data were also collected with validated questionnaires, polysomnography, the Multiple Sleep Latency Test (MSLT), Cerebrospinal fluid hypocretin-1 (CSF hcrt-1) concentration and genetic markers.

Results: NT1 patients compared with healthy controls showed lower NAA/Cr ratio (p = 0.007) and NAA/mI ratio (p = 0.011) in the pons. The Epworth Sleepiness Scale score showed a significant negative correlation with NAA/Cr content (p = 0.023), MSLT sleep latency a negative correlation with the mI/Cr ratio (p = 0.008), and sleep onset REM periods a positive correlation with the mI/Cr ratio (p = 0.027). CSF hcrt-1 levels were positively correlated with the NAA/Cr ratio (p = 0.039) and negatively with the mI/Cr ratio (p = 0.045) and the Cho/Cr ratio (p = 0.026).

Conclusion: The metabolic alterations found in the pons of NT1 patients using the MR Spectroscopy technique were associated with subjective and objective disease severity measures, highlighting the crucial role of this biomarker in the pathophysiology of the disease.