Vaccination against swine flu caused narcolepsy in several european countries
I. Boström1, O. Lindberger2,3, M. Partinen4,5, A.M. Landtblom1,2
1Departments of Neurology and Clinical and Experimental Medicine, Linköping University, SE-581 83, Linköping, Sweden
2Department of Neurosciences, Uppsala University, 3 Husargatan, Uppsala, SE-752 36, Sweden
3Uppsala Innovative Wellness Center Ekeby Hälsocenter, 21 Ekebi Bruk, Uppsala, SE-752 63, Sweden
4Department of Neurological Sciences, University of Helsinki, 4 Haartmaninkatu, Helsinki, 00014, Finland
5Helsinki Sleep Clinic, Vitalmed Research Centre, 3 Sitratori, Helsinki, 00420, Finland
Narcolepsy is a rare sleeping disorder that gives sleep onset rapid eye movement periods and excessive daytime sleepiness. It is divided into two subgroups, narcolepsy type 1 where there also is orexin deficiency and cataplexy and narcolepsy type 2 that lack these features. Narcolepsy type 1 is assumed to be an autoimmune disease with destruction of orexinproducing cells. The pathology behind is unclear. There is a strong association to a class II HLA allele, HLADQB1*06:02 and the H1N1-virus and streptococcal infections has also been associated with narcolepsy. The severity of narcolepsy differs between patients from those who can manage their disease without medication to those who has a severe impact on their everyday life. There is a diagnostic delay between the onset of symptoms and time for diagnosis that in some cases can be more than a decade. The global mean prevalence is 30 per 100 000 inhabitants. The incidence in children in northern Europe has risen since 2010. An early study of the 2009 H1N1 influenza A pandemic indicated a high mortality and prompted efforts to rapidly come up with a vaccine. One of these was Pandemrix that was the most widely used in Europe and 61 % of the inhabitants in Sweden was vaccinated. Studies have shown an increased incidence of narcolepsy type 1 in European countries that had used Pandemrix, but no increased risk was seen in countries that had used other vaccines than Pandemrix.
- Partinen M., Kornum B.R., Plazzi G., Jennum P., Julkunen I., Vaarala O. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Current Neurology and Neuroscience reports, 2018, vol. 13, no. 6, pp. 600–613. DOI: 10.1016/S1474-4422(14)70075-4
- Nordstrand S.E.H., Hansen B.H., Rootwelt T., Karlsen T.-I., Swanson D., Nilsen K.B., Knudsen S. Psychiatric symptoms in patients with post-H1N1 narcolepsy type 1 in Norway. SLEEPJ, 2019, vol. 42, no. 4, pp. 1–9. DOI: 10.1093/sleep/zsz008
- Sarkanen T., Alakuijala A., Partinen M. Clinical course of H1N1-vaccine-related narcolepsy. T. Sleep Medicine, 2016, vol. 19, pp. 17–22. DOI: 10.1016/j.sleep.2015.11.005
- Sarkanen T., Alakuijala A., Julkunen I., Partinen M. Narcolepsy associated with Pandemrix Vaccine. Current Neurology and Neuroscience reports, 2018, vol. 18, pp. 43. DOI: 10.1007/s11910-018-0851-5
- Witt S.T., Drissi N.M., Tapper S., Wretman A., Szakács A., Hallböök T., Landtblom A.-M., Karlsson T. [et al.]. Evidence for cognitive resource imbalance in adolescents with narcolepsy. Brain Imaging and Behavior, 2018, vol. 12, no. 2, pp. 411–424. DOI: 10.1007/s11682-017-9706-y
- Thorpy M.J., Krieger A.C. Delayed diagnosis of narcolepsy: characterization and impact. Sleep Med, 2014, vol. 15, no. 5, pp. 502–507. DOI: 10.1016/j.sleep.2014.01.015
- Ingravallo F., Gnucci V., Pizza F., Vignatelli L., Govi A., Dormi A., Cicognani A., Dauvilliers Y., Plazzi G. The burden of narcolepsy with cataplexy: How disease history and clinical features influence socio-economic outcomes. Sleep. Med., 2012, vol. 13, no. 10, pp. 1293–1300. DOI: 10.1016/j.sleep.2012.08.002
- BaHammam A.S., Alenezi A.M. Narcolepsy in Saudi Arabia. Demographic and clinical perspective of an underrecognized disorder. Saudi. Med. J., 2006, vol. 27, no. 9, pp. 1352–1357.
- Morrish E., King M.A., Smith I.E., Shneerson J.M. Factors associated with a delay in the diagnosis of narcolepsy. Sleep. Med., 2004, vol. 5, no. 1, pp. 37–41. DOI: 10.1016/j.sleep.2003.06.002
- Luca G., Haba-Rubio J., Dauvilliers Y., Lammers G.J., Overeem S., Donjacour C.E., Mayer G., Javidi S. [et al.]. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J. Sleep. Res., 2013, vol. 22, no. 5, pp. 482–495. DOI: 10.1111/jsr.12044
- Broughton R.J., Fleming J.A., George C.F., Hill J.D., Kryger M.H., Moldofsky H., Montplaisir J.Y., Morehouse R.L. [et al.]. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology, 1997, vol. 49, no. 2, pp. 444–451. DOI: 10.1212/wnl.49.2.444
- Frauscher B., Ehrmann L., Mitterling T., Gabelia D., Gschliesser V., Brandauer E., Poewe W., Högl B. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the Innsbruck narcolepsy cohort. J. Clin. Sleep. Med., 2013, vol. 9, no. 8, pp. 805–812. DOI: 10.5664/jcsm.2926
- Taddei R.N., Werth E., Poryazova R., Baumann C.R., Valko P.O. Diagnostic delay in narcolepsy type 1: combining the patients’ and the doctors’ perspectives. J. Sleep. Res., 2016, vol. 25, no. 6, pp. 709–715. DOI: 10.1111/jsr.12420
- Lindberger O. Characterizing the diagnostic delay in Narcolepsy: A literature review. Uppsala, Uppsala University Publ., 2019, 63 p.
- Läkemedelsbehandling av narkolepsi – ett kunskapsdokument. Läkemedelsverket. Farmaceutical treatment of narcolepsy from Swedish medical products agency, 2013, vol. 24, no. 4, pp. 21–27.
- Dauvilliers Y., Arnulf I., Szakacs Z., Leu-Semenescu S., Lecomte I., Scart-Gres C., Lecomte J.-M., Schwartz J.-Ch. [et al.]. Long-term use of pitolisant to treat patients with narcolepsy: Harmony III Study. SLEEPJ, 2019, vol. 42, no. 11, pp. 1–11. DOI: 10.1093/sleep/zsz174
- Bolin K., Niska P.-Å., Pirhonen L., Wasling P., Landtblom A-M. The cost utility of pitolisant as narcolepsy treatment. Acta. Neurol. Scand., 2020, vol. 141, no. 4, pp. 301–310. DOI: 10.1111/ane.13202
- Hallberg P., Smedje H., Eriksson N., H Kohnke., Daniilidou M., Öhman I., Yue Q.-Y., Cavalli M. [et al.]. Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival. EBioMedicine, 2019, vol. 40, pp. 595–604. DOI: 10.1016/j.ebiom.2019.01.041
- Feltelius N., Persson I., Ahlqvist-Rastad J., Andersson M., Arnheim-Dahlström L., Berman P., Granath F., Adori C. [et al.]. A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009–2010 Pandemrix vaccination programme in Sweden. J. Intern. Med., 2015, vol. 278, pp. 335–353. DOI: 10.1111/joim.12391
- Sarkanen T.O., Alakuijala A.P.E., Dauvilliers Y.A., Partinen M.M. Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis. Sleep Medicine Reviews, 2018, vol. 38, pp. 177–186.
- Qasrawi S.O., Albarrak A.M., Alharbi A.S., Nashwan S., Almeneessier A.S., Pandi-Perumal S.R., Alsaadi M.M., BaHammam A.S. Narcolepsy in Saudi patients before and after the 2009 H1N1 vaccination. The experience of 2 referral centers. Saudi. Med. J., 2017, vol. 38, no. 12, pp. 1196–1200. DOI: 10.15537/smj.2017.12.21046
- Persson I., Granath F., Askling J., Ludvigsson J.F., Olsson T., Feltelius N. Risks of neurological and immunerelated diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up. J. Intern. Med., 2014, vol. 275, no. 2, pp. 172–190. DOI: 10.1111/joim.12150
- Trogstad L., Bakken I.J., Gunnes N., Ghaderi S., Stoltenberg C., Magnus P., Håberg S.E. Narcolepsy and hypersomnia in Norwegian children and young adults following the influenza A(H1N1) 2009 pandemic. Vaccine, 2017, vol. 35, pp. 1879–1885. DOI: 10.1016/j.vaccine.2017.02.053