Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr;46(4):1905-1909.
doi: 10.1007/s10072-025-08009-w. Epub 2025 Feb 14.

Pons metabolite alterations in narcolepsy type 1

Micaela Mitolo  1   2 , Fabio Pizza  3   4 , David Neil Manners  2   5 , Lucia Guidi  2 , Annalena Venneri  1   6 , Luca Morandi  2   3 , Caterina Tonon  7   8 , Giuseppe Plazzi  4   9 , Raffaele Lodi  3   4
Affiliations

Pons metabolite alterations in narcolepsy type 1

Micaela Mitolo et al. Neurol Sci. 2025 Apr.

Abstract

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.

Keywords: Metabolic alterations; Narcolepsy type 1; Pons; Proton MR spectroscopy.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: The study protocol was approved by the local AVEC Ethics Committee (17009-EM1-OSS-AUSLBO − 17009) and informed written consent was obtained from all participants. Conflict of interest: The authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Localization of the pons MRS voxel (volume = 1.78 ± 1.11 ml; PRESS localization sequence, PROBE, TR = 1500 ms, TE = 40 ms, 512 FIDs) on the sagittal view of a partecipant’s T1-w image and two representative spectra, showing reduced NAA content in an NT1 patient (on the left) compared with ahealthy control (on the right). NAA: N-acetyl-aspartate; ppm = parts per million
See this image and copyright information in PMC

References

    1. Peyron C, Tighe DK, Van Den Pol AN, De Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18(23):9996–10015. 10.1523/JNEUROSCI.18-23-09996.1998 - PMC - PubMed
    1. Plazzi G, Montagna P, Provini F, Bizzi A, Cohen M, Lugaresi E (1996) Pontine lesions in idiopathic narcolepsy. Neurology 46(5):1250–1250. 10.1212/wnl.46.5.1250 - PubMed
    1. Öz G, Alger JR, Barker PB, Bartha R, Bizzi A, Boesch C, MRS Consensus Group (2014) Clinical proton MR spectroscopy in central nervous system disorders. Radiology 270(3):658–679. 10.1148/radiol.13130531 - PMC - PubMed
    1. Ellis CM, Simmons A, Lemmens G, Williams SCR, Parkes JD (1998) Proton spectroscopy in the narcoleptic syndrome: is there evidence of a brainstem lesion? Neurology 50(2suppl1):S23–S26. 10.1212/wnl.50.2_suppl_1.s23 - PubMed
    1. Bican A, Bora I, Algin O, Hakyemez B, Ozkol V, Alper E (2009) Neuroimaging in narcolepsy. Sleep Med 11(2):225–226. 10.1016/j.sleep.2009.05.011 - PubMed

Supplementary concepts

LinkOut - more resources