Increased muscle activity during sleep and more RBD symptoms in H1N1-(Pandemrix)-vaccinated narcolepsy type 1 patients compared with their non-narcoleptic siblings

Rannveig Viste; Louise F Follin; Birgitte R Kornum; Benedicte A Lie; Marte K Viken; Per M Thorsby; Terje Rootwelt; Julie A E Christensen; Stine Knudsen-Heier

doi:10.1093/sleep/zsac316

Increased muscle activity during sleep and more RBD symptoms in H1N1-(Pandemrix)-vaccinated narcolepsy type 1 patients compared with their non-narcoleptic siblings

Sleep. 2023 Mar 9;46(3):zsac316. doi: 10.1093/sleep/zsac316.

Authors

Rannveig Viste^{1

2}, Louise F Follin^{1

2}, Birgitte R Kornum³, Benedicte A Lie^{4

5}, Marte K Viken^{4

5}, Per M Thorsby^{2

6

7}, Terje Rootwelt^{2

8}, Julie A E Christensen^{1

9}, Stine Knudsen-Heier¹

Affiliations

¹ Department of Rare Disorders, Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Kornum Laboratory, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
⁵ Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
⁶ Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
⁷ Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Oslo, Norway.
⁸ Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
⁹ T&W Engineering A/S, Copenhagen, Denmark.

Abstract

Study objectives: Narcolepsy type 1 (NT1) is characterized by unstable sleep-wake and muscle tonus regulation during sleep. We characterized dream enactment and muscle activity during sleep in a cohort of post-H1N1 NT1 patients and their siblings, and analyzed whether clinical phenotypic characteristics and major risk factors are associated with increased muscle activity.

Methods: RBD symptoms and polysomnography m. tibialis anterior electromyographical signals [long (0.5-15 s); short (0.1-0.49 s)] were compared between 114 post-H1N1 NT1 patients and 89 non-narcoleptic siblings. Association sub-analyses with RBD symptoms, narcoleptic symptoms, CSF hypocretin-1 levels, and major risk factors [H1N1-(Pandemrix)-vaccination, HLA-DQB1*06:02-positivity] were performed.

Results: RBD symptoms, REM and NREM long muscle activity indices and REM short muscle activity index were significantly higher in NT1 patients than siblings (all p < 0.001). Patients with undetectable CSF hypocretin-1 levels (<40 pg/ml) had significantly more NREM periodic long muscle activity than patients with low but detectable levels (40-150 pg/ml) (p = 0.047). In siblings, REM and NREM sleep muscle activity indices were not associated with RBD symptoms, other narcolepsy symptoms, or HLA-DQB1*06:02-positivity. H1N1-(Pandemrix)-vaccination status did not predict muscle activity indices in patients or siblings.

Conclusion: Increased REM and NREM muscle activity and more RBD symptoms is characteristic of NT1, and muscle activity severity is predicted by hypocretin deficiency severity but not by H1N1-(Pandemrix)-vaccination status. In the patients' non-narcoleptic siblings, neither RBD symptoms, core narcoleptic symptoms, nor the major NT1 risk factors is associated with muscle activity during sleep, hence not indicative of a phenotypic continuum.

Keywords: CSF hypocretin-1 deficiency; NT1; Narcolepsy type 1; REM sleep behavior disorder; disease continuum in first-degree relatives; dream enactment; leg movements in sleep; muscle activity in sleep; periodic leg movements; post Pandemrix NT1; post-H1N1 NT1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Influenza A Virus, H1N1 Subtype*
Muscle, Skeletal
Narcolepsy* / diagnosis
Narcolepsy* / etiology
Orexins
Siblings
Sleep

Substances

Orexins
pandemrix