Increased childhood incidence of narcolepsy in western Sweden after H1NI influenza vaccination

and Department of Pediatrics (A.S., N.D., T.H.), Institute of Clinical Sciences, University of Gothenburg, The Queen Silvia Children's Hospital, Göteborg, Sweden.
Neurology (Impact Factor: 8.29). 03/2013; 80(14). DOI: 10.1212/WNL.0b013e31828ab26f
Source: PubMed


To assess the incidence of narcolepsy between January 2000 and December 2010 in children in western Sweden and its relationship to the Pandemrix vaccination, and to compare the clinical and laboratory features of these children.

The children were identified from all local and regional pediatric hospitals, child rehabilitation centers, outpatient pediatric clinics, and regional departments of neurophysiology. Data collection was performed with the aid of a standardized data collection form, from medical records and telephone interviews with patients and parents. The laboratory and investigational data were carefully scrutinized.

We identified 37 children with narcolepsy. Nine of them had onset of symptoms before the H1N1 vaccination and 28 had onset of symptoms in relationship to the vaccination. The median age at onset was 10 years. All patients in the postvaccination group were positive for human leukocyte antigen (HLA)-DQB1*0602. Nineteen patients in the postvaccination group, compared with one in the prevaccination group, had a clinical onset that could be dated within 12 weeks.

Pandemrix vaccination is a precipitating factor for narcolepsy, especially in combination with HLA-DQB1*0602. The incidence of narcolepsy was 25 times higher after the vaccination compared with the time period before. The children in the postvaccination group had a lower age at onset and a more sudden onset than that generally seen.

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Available from: Attila Szakacs, Oct 08, 2014
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    • "RR: 6·6 (23·1–14·5) Persson [18] 2014 Skane, Vastra Gotaland, Kalmar, Ostergotland, Stockholm, Varmland and Norrbotten All Cohort 31-12-2011 Diagnosis (registry) Presence diagnosis code (non- validated) Diagnosis included period after awareness, no validation HR: 2·92 (1·78–4·79) VAESCO [3] 2012 National all Case control 30-6-2010 MSLT referrals (clinics) BC definition level 1–4 Multiple, primary ref. to specialist 3.5 (0.4- infinity) 1.8–12.9 Bardage [42] 2011 Stockholm county All Cohort 31-8-2010 Diagnosis (registry) Non- validated Diagnosis No validation, small sample size, 3.53 (0.31–40) Szakacs [19] 2013 Western Sweden Children Cohort 31-12-2010 Diagnosis (registry) International Classification of Sleep disorder EDS onset Validation not blinded, no personal level vaccination data, include period of awareness 25 France Dauvilliers 2013 France Children Case control 30-4-2011 Diagnosis (special- ists) International Classification of Sleep disorder Diagnosis Modified analyses from primary VAESCO analysis plan, interview data on exposure, selection bias possible also in controls, period of awareness included OR 6.5 (2.1–19.9) 6.1–27 M.C. "
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    ABSTRACT: A safety signal around Pandemrix, an AS03 adjuvanted influenza A(H1N1) pdm09 vaccine potentially causing narcolepsy in children and adolescents became public in August 2010, long after cessation of the influenza A(H1N1) pdm09 campaigns in Europe. The signal originated from Finland and Sweden, two countries with school based pandemic vaccination campaigns, with high vaccine coverage, and vaccinations being provided at the peak of the circulating wild virus. Since the announcement awareness grew in Europe, with extensive public media dissemination and regulatory actions. This resulted in a steep increase in the spontaneous reports of exposed cases, a decrease in diagnostic lag times of this rare, underdiagnosed disease and finally victim compensation. The signaling countries conducted rapid risk assessment studies to quantify the signal to the best of their abilities, in the midst of the public awareness, most of which could not distinguish between a vaccine and an awareness effect. Due to the strong but variable associations from the epidemiological studies, the search for biological mechanisms started. Currently it is not yet understood how Pandemrix might cause narcolepsy, and whether it would be specific to Pandemrix. The paper describes the current evidence and puts forward the questions that remain to be answered, which are relevant for future pandemic preparedness when adjuvants may be used for dose sparing. Copyright © 2015. Published by Elsevier Ltd.
    Preview · Article · Jun 2015 · Vaccine
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    • "Animal narcolepsy models and optogenetic device studies have shown that hypocretin maintains wakefulness, increases arousal, and suppresses REM and non-REM sleep [8] [9]. The observed association of narcolepsy with streptococcal [10] and H1N1 [11] infections and with H1N1 vaccination [12] [13] [14] [15] further supports the concept that narcolepsy is an immune-mediated disease. "
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    ABSTRACT: Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (i.e., alcohol, nicotine, caffeine, cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (e.g., Epworth Sleepiness Scale, Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance effective management of patients with narcolepsy.
    Full-text · Article · Oct 2014 · Sleep Medicine
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    • "Other diseases that can cause fatigue and start in young ages are for example rheumatoid arthritis, allergy, Mb Crohn, and ulcerative colitis. The increase in narcolepsy incidence during 2010 and 2011 after the Pandemrix vaccination against the H1N1 virus seen in children and young people in many countries motivates specific focus on this disease (10, 11). New cases with mild pathology are still diagnosed in Sweden, supporting the importance of keeping this disease in mind. "
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    ABSTRACT: The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area.
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