Tomi Sarkanen1,2, Anniina Alakuijala2,3, Ilkka Julkunen4, Markku Partinen5,6. 1. Department of Neurology, Tampere University Hospital, Tampere, Finland. 2. Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland. 3. HUS Medical Imaging Center, Department of Clinical Neurophysiology, Helsinki University Central Hospital, Helsinki, Finland. 4. Institute of Biomedicine, University of Turku, Turku, Finland. 5. Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland. markpart@me.com. 6. Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland. markpart@me.com.
Abstract
PURPOSE OF REVIEW: After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix and narcolepsy was recognized in 2010, research on narcolepsy has been more intensive than ever before. The purpose of this review is to provide the reader with current concepts and recent findings on the Pandemrix-associated narcolepsy. RECENT FINDINGS: After the Pandemrix vaccination campaign in 2009-2010, the risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults. According to observational studies, the risk of narcolepsy was elevated for 2 years after the Pandemrix vaccination. Some confounding factors and potential diagnostic biases may influence the observed narcolepsy risk in some studies, but it is unlikely that they would explain the clearly increased incidence in all the countries where Pandemrix was used. An increased risk of narcolepsy after natural H1N1 infection was reported from China, where pandemic influenza vaccination was not used. There is more and more evidence that narcolepsy is an autoimmune disease. All Pandemrix-associated narcolepsy cases have been positive for HLA class II DQB1*06:02 and novel predisposing genetic factors directly linking to the immune system have been identified. Even though recent studies have identified autoantibodies against multiple neuronal structures and other host proteins and peptides, no specific autoantigens that would explain the disease mechanism in narcolepsy have been identified thus far. There was a marked increase in the incidence of narcolepsy after Pandemrix vaccination, especially in adolescents, but also in young adults and younger children. All vaccine-related cases were of narcolepsy type 1 characterized by hypocretin deficiency in the central nervous system. The disease phenotype and the severity of symptoms varied considerably in children and adolescents suffering from Pandemrix-associated narcolepsy, but they were indistinguishable from the symptoms of idiopathic narcolepsy. Narcolepsy type 1 is most likely an autoimmune disease, but the mechanisms have remained elusive.
PURPOSE OF REVIEW: After the connection between AS03-adjuvanted pandemic H1N1 vaccine Pandemrix and narcolepsy was recognized in 2010, research on narcolepsy has been more intensive than ever before. The purpose of this review is to provide the reader with current concepts and recent findings on the Pandemrix-associated narcolepsy. RECENT FINDINGS: After the Pandemrix vaccination campaign in 2009-2010, the risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults. According to observational studies, the risk of narcolepsy was elevated for 2 years after the Pandemrix vaccination. Some confounding factors and potential diagnostic biases may influence the observed narcolepsy risk in some studies, but it is unlikely that they would explain the clearly increased incidence in all the countries where Pandemrix was used. An increased risk of narcolepsy after natural H1N1 infection was reported from China, where pandemic influenza vaccination was not used. There is more and more evidence that narcolepsy is an autoimmune disease. All Pandemrix-associated narcolepsy cases have been positive for HLA class II DQB1*06:02 and novel predisposing genetic factors directly linking to the immune system have been identified. Even though recent studies have identified autoantibodies against multiple neuronal structures and other host proteins and peptides, no specific autoantigens that would explain the disease mechanism in narcolepsy have been identified thus far. There was a marked increase in the incidence of narcolepsy after Pandemrix vaccination, especially in adolescents, but also in young adults and younger children. All vaccine-related cases were of narcolepsy type 1 characterized by hypocretin deficiency in the central nervous system. The disease phenotype and the severity of symptoms varied considerably in children and adolescents suffering from Pandemrix-associated narcolepsy, but they were indistinguishable from the symptoms of idiopathic narcolepsy. Narcolepsy type 1 is most likely an autoimmune disease, but the mechanisms have remained elusive.
Authors: Arash Zandian; Björn Forsström; Anna Häggmark-Månberg; Jochen M Schwenk; Mathias Uhlén; Peter Nilsson; Burcu Ayoglu Journal: J Proteome Res Date: 2017-02-09 Impact factor: 4.466
Authors: Syed Sohail Ahmed; Wayne Volkmuth; José Duca; Lorenzo Corti; Michele Pallaoro; Alfredo Pezzicoli; Anette Karle; Fabio Rigat; Rino Rappuoli; Vas Narasimhan; Ilkka Julkunen; Arja Vuorela; Outi Vaarala; Hanna Nohynek; Franco Laghi Pasini; Emanuele Montomoli; Claudia Trombetta; Christopher M Adams; Jonathan Rothbard; Lawrence Steinman Journal: Sci Transl Med Date: 2015-07-01 Impact factor: 17.956
Authors: Julia Stowe; Nicholas Andrews; Christopher Kosky; Gary Dennis; Sofia Eriksson; Andrew Hall; Guy Leschziner; Paul Reading; John M Shneerson; Katherine Donegan; Elizabeth Miller Journal: Sleep Date: 2016-05-01 Impact factor: 5.849
Authors: Guillermo Domínguez-Cherit; Stephen E Lapinsky; Alejandro E Macias; Ruxandra Pinto; Lourdes Espinosa-Perez; Alethse de la Torre; Manuel Poblano-Morales; Jose A Baltazar-Torres; Edgar Bautista; Abril Martinez; Marco A Martinez; Eduardo Rivero; Rafael Valdez; Guillermo Ruiz-Palacios; Martín Hernández; Thomas E Stewart; Robert A Fowler Journal: JAMA Date: 2009-10-12 Impact factor: 56.272
Authors: Federico Martinón-Torres; Adolfo García-Sastre; Andrew J Pollard; Carlos Martín; Albert Osterhaus; Shamez N Ladhani; Octavio Ramilo; Jose Gómez Rial; Antonio Salas; F Xavier Bosch; María Martinón-Torres; Michael J Mina; James Cherry Journal: Hum Vaccin Immunother Date: 2021-11-11 Impact factor: 3.452
Authors: Julia Stowe; Nick Andrews; Paul Gringras; Timothy Quinnell; Zenobia Zaiwalla; John Shneerson; Elizabeth Miller Journal: PLoS Med Date: 2020-09-14 Impact factor: 11.069