Larger hypothalamic volume in narcolepsy type 1

Author:

Juvodden Hilde T1ORCID,Alnæs Dag23ORCID,Lund Martina J24,Agartz Ingrid456,Andreassen OIe A26,Server Andres7ORCID,Thorsby Per M89ORCID,Westlye Lars T2610ORCID,Knudsen Heier Stine19ORCID

Affiliation:

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

Abstract

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.

Funder

Norwegian Ministry of Health and Care Services

Research Council of Norway

European Union’s Horizon 2020 Research and Innovation

South–Eastern Norway Regional Health Authority

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Neurology (clinical)

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