Narcolepsy: clinical picture, diagnostics, and association with H1N1 vaccination

Tutkimustuotos: OpinnäyteVäitöskirjaArtikkelikokoelma

Abstrakti

After the 2009-2010 pandemic H1N1 vaccination campaign the incidence of narcolepsy increased sharply in countries where the Pandemrix vaccination was used. An increased incidence was observed also in China, where vaccine coverage was very low. Moreover, epidemiological studies are prone to biases, and animal studies suggest that H1N1 virus infection per se might be able to manifest a narcolepsy-like phenotype. Therefore, some controversy exists in the association between vaccination and narcolepsy. pNC cases had severe onset and common psychiatric comorbidity, which warranted thorough analysis of the pNC phenotype. Tools to measure narcolepsy symptoms or to help in diagnostics remain scarce. Our first aim was to systematically analyze the magnitude of the risk of H1N-vaccine-associated narcolepsy (pNC) and to examine whether an increased association emerged with any other vaccine or H1N1 virus infection. In Studies II and III, we aimed to determine whether differences were present in clinical, polysomnographic (PSG), or actigraphic (ACT) characteristics between pNC and sporadic narcolepsy (sNC). In study IV we aimed to validate the Ullanlinna Narcolepsy Scale (UNS), a population screening tool for narcolepsy published in 1994, in clinical population. Based on the meta-analysis in Study I, the relative risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults in the countries where Pandemrix vaccine was used widely (Finland, Sweden, Norway, France, England, Ireland). The vaccine-attributable risk in children and adolescents was 1 per 18,400 vaccines. The risk seems to have increased for two years and was not associated with any other vaccine. In study II we analyzed PSG and ACT characteristics of 69 pNC and 57 sNC subjects and in study III sleep questionnaires of 26 pNC and 25 sNC subjects. We found that pNC patients had shorter diagnostic delays, were diagnosed younger, had less periodic limb movements in sleep, and had earlier sleep-wake rhythm than sNC patients. The clinical course was highly variable in a two-year follow-up. There were no significant differences between pNC and sNC questionnaire scores. In study IV we analyzed questionnaire scores of patients with narcolepsy type 1 (n = 89), narcolepsy type 2 (n = 10), sleep apnea (n = 37), restless legs syndrome or periodic limb movement disorder (n = 56), other sleep-related disorders (n = 56), or other hypersomnias (n = 24). Sensitivity and specificity of the UNS in separating NT1 from other disorders were 83.5-85.4% and 84.1-87.6%, respectively. The UNS had a strong negative correlation with hypocretin-1 levels and mean sleep latency in MSLT.
Alkuperäiskielienglanti
Valvoja/neuvonantaja
  • Partinen, Markku, Valvoja
  • Alakuijala, Anniina, Valvoja
JulkaisupaikkaHelsinki
Kustantaja
Painoksen ISBN978-951-51-4622-9
Sähköinen ISBN978-951-51-4623-6
TilaJulkaistu - 2019
OKM-julkaisutyyppiG5 Tohtorinväitöskirja (artikkeli)

Tieteenalat

  • 3112 Neurotieteet
  • 3124 Neurologia ja psykiatria

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