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.


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.

MeSH terms

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


  • Orexins
  • pandemrix