Larger hypothalamic volume in narcolepsy type 1

doi:10.1093/sleep/zsad173

. 2023 Nov 8;46(11):zsad173.

doi: 10.1093/sleep/zsad173.

Larger hypothalamic volume in narcolepsy type 1

Hilde T Juvodden¹, Dag Alnæs^{2

3}, Martina J Lund^{2

4}, Ingrid Agartz^{4

5

6}, OIe A Andreassen^{2

6}, Andres Server⁷, Per M Thorsby^{8

9}, Lars T Westlye^{2

6

10}, Stine Knudsen Heier^{1

9}

Affiliations

¹ Department of Rare Disorders, Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Oslo University Hospital, Ullevål, Oslo, Norway.
² Division of Mental Health and Addiction, NORMENT Centre, University of Oslo and Oslo University Hospital, Oslo, Norway.
³ Departement of Psychology, Pedagogy and Law, Kristiania University College, Oslo, Norway.
⁴ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁶ K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁷ Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁸ Hormone Laboratory, Department of Medical Biochemistry, Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway.
⁹ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁰ Department of Psychology, University of Oslo, Oslo, Norway.

PMID: 37463428
PMCID: PMC10636249
DOI: 10.1093/sleep/zsad173

Larger hypothalamic volume in narcolepsy type 1

Hilde T Juvodden et al. Sleep. 2023.

. 2023 Nov 8;46(11):zsad173.

doi: 10.1093/sleep/zsad173.

Authors

Affiliations

¹ Department of Rare Disorders, Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Oslo University Hospital, Ullevål, Oslo, Norway.
² Division of Mental Health and Addiction, NORMENT Centre, University of Oslo and Oslo University Hospital, Oslo, Norway.
³ Departement of Psychology, Pedagogy and Law, Kristiania University College, Oslo, Norway.
⁴ Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁶ K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
⁷ Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁸ Hormone Laboratory, Department of Medical Biochemistry, Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway.
⁹ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁰ Department of Psychology, University of Oslo, Oslo, Norway.

PMID: 37463428
PMCID: PMC10636249
DOI: 10.1093/sleep/zsad173

Abstract

Study objectives: Narcolepsy type 1 (NT1) is a neurological sleep disorder. Postmortem studies have shown 75%-90% loss of the 50 000-70 000 hypocretin-producing neurons and 64%-94% increase in the 64 000-120 000 histaminergic neurons and conflicting indications of gliosis in the hypothalamus of NT1 patients. The aim of this study was to compare MRI-based volumes of the hypothalamus in patients with NT1 and controls in vivo.

Methods: We used a segmentation tool based on deep learning included in Freesurfer and computed the volume of the whole hypothalamus, left/right part of the hypothalamus, and 10 hypothalamic subregions. We included 54 patients with post-H1N1 NT1 (39 females, mean age 21.8 ± 11.0 years) and 114 controls (77 females, mean age 23.2 ± 9.0 years). Group differences were tested with general linear models using permutation testing in Permutation Analysis of Linear Models and evaluated after 10 000 permutations, yielding two-tailed P-values. Furthermore, a stepwise Bonferroni correction was performed after dividing hypothalamus into smaller regions.

Results: The analysis revealed larger volume for patients compared to controls for the whole hypothalamus (Cohen's d = 0.71, p = 0.0028) and for the left (d = 0.70, p = 0.0037) and right part of the hypothalamus (d = 0.65, p = 0.0075) and left (d = 0.72, p = 0.0036) and right tubular-inferior (d = 0.71, p = 0.0037) hypothalamic subregions.

Conclusions: In conclusion, patients with post-H1N1 NT1 showed significantly larger hypothalamic volume than controls, in particular in the tubular-inferior subregions which could reflect several processes as previous studies have indicated neuroinflammation, gliosis, and changes in the numbers of different cell types.

Keywords: MRI; T1; hypothalamus; narcolepsy.

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Figures

**Figure 1.**
Example of the hypothalamic segmentation as included in Freesurfer v 7.2.0 [58] for one participant. (A) Light blue: anterior–superior; purple: anterior–inferior; (B) green: tubular-superior; blue: tubular-inferior; (C) yellow, posterior.

See this image and copyright information in PMC

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References

1. Bassetti CLA, Adamantidis A, Burdakov D, et al. . Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519–539. doi: 10.1038/s41582-019-0226-9 - DOI - PubMed
1. Heier MS, Gautvik KM, Wannag E, et al. . Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med. 2013;14(9):867–871. doi: 10.1016/j.sleep.2013.03.020 - DOI - PubMed
1. Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM.. Incidence of narcolepsy after H1N1 influenza and vaccinations: systematic review and meta-analysis. Sleep Med Rev. 2018;38:177–186. doi: 10.1016/j.smrv.2017.06.006 - DOI - PubMed
1. Kornum BR, Knudsen S, Ollila HM, et al. . Narcolepsy. Nat Rev Dis Primers. 2017;3:16100. doi: 10.1038/nrdp.2016.100 - DOI - PubMed
1. Thannickal TC, Moore RY, Nienhuis R, et al. . Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469–474. doi: 10.1016/s0896-6273(00)00058-1 - DOI - PMC - PubMed

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[1] Bassetti CLA, Adamantidis A, Burdakov D, et al. . Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519–539. doi: 10.1038/s41582-019-0226-9 - DOI - PubMed

[2] Bassetti CLA, Adamantidis A, Burdakov D, et al. . Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519–539. doi: 10.1038/s41582-019-0226-9 - DOI - PubMed

[3] Heier MS, Gautvik KM, Wannag E, et al. . Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med. 2013;14(9):867–871. doi: 10.1016/j.sleep.2013.03.020 - DOI - PubMed

[4] Heier MS, Gautvik KM, Wannag E, et al. . Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med. 2013;14(9):867–871. doi: 10.1016/j.sleep.2013.03.020 - DOI - PubMed

[5] Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM.. Incidence of narcolepsy after H1N1 influenza and vaccinations: systematic review and meta-analysis. Sleep Med Rev. 2018;38:177–186. doi: 10.1016/j.smrv.2017.06.006 - DOI - PubMed

[6] Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM.. Incidence of narcolepsy after H1N1 influenza and vaccinations: systematic review and meta-analysis. Sleep Med Rev. 2018;38:177–186. doi: 10.1016/j.smrv.2017.06.006 - DOI - PubMed

[7] Kornum BR, Knudsen S, Ollila HM, et al. . Narcolepsy. Nat Rev Dis Primers. 2017;3:16100. doi: 10.1038/nrdp.2016.100 - DOI - PubMed

[8] Kornum BR, Knudsen S, Ollila HM, et al. . Narcolepsy. Nat Rev Dis Primers. 2017;3:16100. doi: 10.1038/nrdp.2016.100 - DOI - PubMed

[9] Thannickal TC, Moore RY, Nienhuis R, et al. . Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469–474. doi: 10.1016/s0896-6273(00)00058-1 - DOI - PMC - PubMed

[10] Thannickal TC, Moore RY, Nienhuis R, et al. . Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469–474. doi: 10.1016/s0896-6273(00)00058-1 - DOI - PMC - PubMed

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Larger hypothalamic volume in narcolepsy type 1

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Larger hypothalamic volume in narcolepsy type 1

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