Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A

Heier, Mona Skard; Gautvik, Kaare M.; Wannag, Ebba; Bronder, K.H.; Midtlyng, E.; Kamaleri, Yusman; Storsæter, Jann

doi:10.1016/j.sleep.2013.03.020

Cited by 163 publications

(110 citation statements)

References 27 publications

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“…Recent Norwegian studies have shown a decline in the incidence in vaccinated children aged 4-19 years in the second year after vaccination, falling to levels not significantly different from unvaccinated children during the same period [14]. Further work will be required to examine if that can be replicated in Ireland and elsewhere.…”

Section: Discussionmentioning

confidence: 97%

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010

et al. 2014

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Section: Discussionmentioning

confidence: 97%

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010

et al. 2014

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“…In support of the autoimmune hypothesis underlying narcolepsy, autoantibodies against Tribbles homolog 2 (TRIB2), a protein synthesized in hypocretin neurons, are evident in a proportion of patients with narcolepsy, a finding that has been replicated in three separate studies. [10][11][12] In addition, the surge of cases of narcolepsy following pandemic H1N1 infection and mass vaccination with Pandemrix (GlaxoSmithKline, Brentford, Middlesex, UK) lends further support to an autoimmune etiology, [13][14][15][16] likely due to serum antibodies to H1N1 nucleoprotein in patients with vaccine-associated narcolepsy cross-reacting with the hypocretin receptor 2 (an effect observed following Pandremix, but not Focetria [Novartis, Novartis International AG, Basel, Switzerland] vaccination). 17 However, in the absence of formal identification and detailed understanding of the mechanisms linking autoimmunity with the destruction of hypocretin neurons, no disease-modifying therapies for narcolepsy have yet been developed.…”

mentioning

confidence: 99%

Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

Lecendreux

Berthier

Corny

et al. 2017

Journal of Clinical Sleep Medicine

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Study Objectives: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. Methods: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). Results: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. Conclusions: Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIgtreated patients achieved remission more rapidly than control patients. I NTRO DUCTI O NNarcolepsy is a debilitating and currently an incurable neurological condition with a characteristic constellation of symptoms, including excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep.Until recently, and at the time patients in this study were treated, the disorder was categorized into narcolepsy with cataplexy and narcolepsy without cataplexy according to the revised second edition of the International Classification of Sleep Disorders (ICSD).1 ICSD-2-revised has now been replaced by ICSD-3, which classifies narcolepsy into type 1 and type 2 narcolepsy. 2The majority of patients with type 1 narcolepsy have hypocretin deficiency (cerebrospinal fluid [CSF] hypocretin-1 level ≤ 110 pg/ mL), which is considered to result from an autoimmune-mediated loss of hypocretin-secreting neurons in those who are genetically predisposed (most commonly those with human leucocyte antigen [HLA] DQB1*06:02 haplotype). The...

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“…All children with narcolepsy that were HLA typed were positive for HLA DQB1*0602. An increased risk of narcolepsy was also reported in England and Norway after ASO3 adjuvanted pandemic vaccination in young people [224,225].…”

Section: Narcolepsymentioning

confidence: 74%

Nasal vaccination using novel mucosal adjuvants : with main focus on influenza A virus

Falkeborn¹

2015

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Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A

Cited by 163 publications

References 27 publications

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010

Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

Nasal vaccination using novel mucosal adjuvants : with main focus on influenza A virus

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