Stefano Sartori1, Margherita Nosadini2, Elisabetta Cesaroni3, Raffaele Falsaperla4, Giuseppe Capovilla5, Francesca Beccaria6, Maria Margherita Mancardi7, Giuseppe Santangelo8, Leandra Giunta9, Clementina Boniver10, Gaetano Cantalupo11, Alberto Cappellari12, Paola Costa13, Bernardo Dalla Bernardina14, Robertino Dilena15, Maria Grazia Natali Sora16, Maria Federica Pelizza17, Dario Pruna18, Domenico Serino19, Francesca Vanadia20, Federico Vigevano21, Nelia Zamponi22, Caterina Zanus23, Irene Toldo24, Agnese Suppiej25. 1. Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy. Electronic address: stefano.sartori@unipd.it. 2. Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy. Electronic address: margherita.nosadini@gmail.com. 3. Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy. Electronic address: elisabettacesaronix@gmail.com. 4. Paediatric Acute and Emergency Operative Unit and Department, Policlinico Vittorio Emanuele University Hospital, University of Catania, Italy. Electronic address: raffaelefalsaperla@hotmail.com. 5. Department of Child Neuropsychiatry, Epilepsy Center, C. Poma Hospital, Mantua, Italy. Electronic address: giuseppe.capovilla@aopoma.it. 6. Department of Child Neuropsychiatry, Epilepsy Center, C. Poma Hospital, Mantua, Italy. Electronic address: francesca.beccaria@aopoma.it. 7. Unit of Child Neuropsychiatry, Head-Neck and Neuroscience Department, Giannina Gaslini Institute, Genoa, Italy. Electronic address: margheritamancardi@ospedale-gaslini.ge.it. 8. Child and Adolescent Neuropsychiatry Unit, Department of Paediatrics, ARNAS Civico - Di Cristina, Palermo, Italy. Electronic address: giuseppe.santangelo@ospedalecivicopa.org. 9. Paediatric Acute and Emergency Operative Unit and Department, Policlinico Vittorio Emanuele University Hospital, University of Catania, Italy. Electronic address: leandra.giunta@gmail.com. 10. Paediatric Neurophysiology Unit, Department of Paediatrics, University of Padua, Italy. Electronic address: boniver@pediatria.unipd.it. 11. Child Neuropsychiatry, Department of Life and Reproduction Sciences, University of Verona, Italy. Electronic address: gcantalupo@gmail.com. 12. Child Neuropsychiatry, Department of Life and Reproduction Sciences, University of Verona, Italy. Electronic address: albertocapp@yahoo.it. 13. Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy. Electronic address: paola.costa@burlo.trieste.it. 14. Child Neuropsychiatry, Department of Life and Reproduction Sciences, University of Verona, Italy. Electronic address: dallabernardina@univr.it. 15. Unit of Clinical Neurophysiology, Department of Neurological Sciences, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: robertino.dilena@policlinico.mi.it. 16. Department of Neurology, S. Raffaele Hospital, Milan, Italy. Electronic address: natalisora.mariagrazia@hsr.it. 17. Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy. Electronic address: mariafederica.pelizza@gmail.com. 18. Child Neurology and Psychiatry Dept, Pediatric Hospital, Cagliari, Italy. Electronic address: d.pruna@tiscali.it. 19. Neurology Unit, Bambino Gesù Children's Hospital, Rome, Italy. Electronic address: domenico.serino@opbg.net. 20. Child and Adolescent Neuropsychiatry Unit, Department of Paediatrics, ARNAS Civico - Di Cristina, Palermo, Italy. Electronic address: francesca.vanadia@ospedalecivicopa.org. 21. Neurology Unit, Bambino Gesù Children's Hospital, Rome, Italy. Electronic address: federico.vigevano@opbg.net. 22. Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy. Electronic address: n.zamponi@tin.it. 23. Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy. Electronic address: caterina.zanus@burlo.trieste.it. 24. Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy. Electronic address: irene.toldo@unipd.it. 25. Paediatric Neurology Unit, Department of Woman's and Child's Health, University Hospital of Padua, Padua, Italy. Electronic address: suppiej@pediatria.unipd.it.
Abstract
BACKGROUND: Given the rarity of this condition, especially in children, there is a paucity of large reported paediatric case series of anti-N-methyl-d-aspartate receptor encephalitis. METHODS: To contribute to define the features of this condition, we describe retrospectively a new nationwide case series of 20 children (50% females), referred by 13 Italian centres. RESULTS: Mean age at onset was 8 years (range 3-17). Prodromal symptoms were reported in 31.6%; onset was with neurological symptoms in 70%, and with behavioural/psychiatric disturbances in 30%. Most patients developed a severe clinical picture (90%), and 41% experienced medical complications; children 12-18 years old seemed to be more severe and symptomatic than younger patients. All children received first-line immune therapy; second-line treatment was administered to 45%. Relapses occurred in 15%. At last follow-up (mean 23.9 months, range 5-82), 85% patients had mRS 0-1; this rate was higher among older patients, and in those receiving first immune therapy within 1 month. CONCLUSIONS: Our case series confirms a symptomatologic core of paediatric anti-N-methyl-d-aspartate receptor encephalitis, even though displaying some distinctive features that may be explained by a specific genetic background or by the limited number of patients. The growing incidence of this condition, the relative age-dependent variability of its manifestations, the availability of immunotherapy and the possible better outcome with early treatment impose a high index of clinical suspicion be maintained. In the absence of data suggesting other specific etiologies, paediatricians should consider this diagnosis for children presenting with neurological and/or behavioural or psychiatric disturbances, regardless of age and gender.
BACKGROUND: Given the rarity of this condition, especially in children, there is a paucity of large reported paediatric case series of anti-N-methyl-d-aspartate receptor encephalitis. METHODS: To contribute to define the features of this condition, we describe retrospectively a new nationwide case series of 20 children (50% females), referred by 13 Italian centres. RESULTS: Mean age at onset was 8 years (range 3-17). Prodromal symptoms were reported in 31.6%; onset was with neurological symptoms in 70%, and with behavioural/psychiatric disturbances in 30%. Most patients developed a severe clinical picture (90%), and 41% experienced medical complications; children 12-18 years old seemed to be more severe and symptomatic than younger patients. All children received first-line immune therapy; second-line treatment was administered to 45%. Relapses occurred in 15%. At last follow-up (mean 23.9 months, range 5-82), 85% patients had mRS 0-1; this rate was higher among older patients, and in those receiving first immune therapy within 1 month. CONCLUSIONS: Our case series confirms a symptomatologic core of paediatric anti-N-methyl-d-aspartate receptor encephalitis, even though displaying some distinctive features that may be explained by a specific genetic background or by the limited number of patients. The growing incidence of this condition, the relative age-dependent variability of its manifestations, the availability of immunotherapy and the possible better outcome with early treatment impose a high index of clinical suspicion be maintained. In the absence of data suggesting other specific etiologies, paediatricians should consider this diagnosis for children presenting with neurological and/or behavioural or psychiatric disturbances, regardless of age and gender.