Davide Martino1, Anette Schrag2, Zacharias Anastasiou2, Alan Apter2, Noa Benaroya-Milstein2, Maura Buttiglione2, Francesco Cardona2, Roberta Creti2, Androulla Efstratiou2, Tammy Hedderly2, Isobel Heyman2, Chaim Huyser2, Marcos Madruga2, Pablo Mir2, Astrid Morer2, Nanette Mol Debes2, Natalie Moll2, Norbert Müller2, Kirsten Müller-Vahl2, Alexander Munchau2, Peter Nagy2, Kerstin Jessica Plessen2, Cesare Porcelli2, Renata Rizzo2, Veit Roessner2, Jaana Schnell2, Markus Schwarz2, Liselotte Skov2, Tamar Steinberg2, Zsanett Tarnok2, Susanne Walitza2, Andrea Dietrich2, Pieter J Hoekstra2. 1. From the Department of Clinical Neurosciences (D.M.), Cumming School of Medicine & Hotchkiss Brain Institute, University of Calgary, Canada; Department of Clinical Neuroscience (A.S., Z.A.), UCL Institute of Neurology, University College London, UK; Child and Adolescent Psychiatry Department (A.A., N.B.-M., T.S.), Schneider Children's Medical Center of Israel, Petah-Tikva, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel; Department of Biomedical Sciences and Human Oncology (M.B.), University of Bari "Aldo Moro"; Department of Human Neurosciences (F.C.), University La Sapienza of Rome; Department of Infectious Diseases (R.C.), Istituto Superiore di Sanità, Rome, Italy; WHO Global Collaborating Centre for Reference and Research on Diphtheria and Streptococcal Infections (A.E.), Reference Microbiology, Directorate National Infection Service, Public Health England; Evelina London Children's Hospital GSTT (T.H.), Kings Health Partners AHSC; Psychological Medicine (I.H.), Great Ormond Street Hospital NHS Foundation Trust, London, UK; Department of Child and Adolescent Psychiatry (C.H.), De Bascule, Amsterdam UMC, the Netherlands; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (M.M.), Seville; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica (P.M.), Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville; Department of Child and Adolescent Psychiatry and Psychology (A. Morer), Institute of Neurosciences, Hospital Clínic; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A. Morer), Barcelona; Centro de Investigación en Red de Salud Mental (CIBERSAM) (A. Morer), Instituto Carlos III, Madrid; Department of Medicine (A. Morer), University of Barcelona, Spain; Child and Adolescent Mental Health Center (N.M.D., K.J.P., L.S.), Mental Health Services, Capital Region of Denmark and University of Copenhagen, Denmark; Institute of Laboratory Medicine (N. Moll, M.S.) and Department of Psychiatry and Psychotherapy (N. Müller, J.S.), University Hospital LMU Munich; Department of Psychiatry, Social Psychiatry and Psychotherapy (K.M.-V.), Hannover Medical School; Institute of Neurogenetics (A. Munchau), University of Lübeck, Germany; Vadaskert Child and Adolescent Psychiatric Hospital (P.N., Z.T.), Budapest, Hungary; Division of Child and Adolescent Psychiatry, Department of Psychiatry (K.J.P.), Lausanne University Hospital, Switzerland; ASL BA, Mental Health Department (C.P.), Adolescence and Childhood Neuropsychiatry Unit, Bari; Child and Adolescent Neurology and Psychiatry, Department of Clinical and Experimental Medicine (R.R.), University of Catania, Italy; Department of Child and Adolescent Psychiatry (V.R.), Medical Faculty Carl Gustav Carus, TU Dresden, Germany; Clinic of Child and Adolescent Psychiatry and Psychotherapy (S.W.), University of Zurich, Switzerland; and Department of Child and Adolescent Psychiatry (A.D., P.J.H.), University of Groningen, University Medical Center Groningen, the Netherlands. davide.martino@ucalgary.ca. 2. From the Department of Clinical Neurosciences (D.M.), Cumming School of Medicine & Hotchkiss Brain Institute, University of Calgary, Canada; Department of Clinical Neuroscience (A.S., Z.A.), UCL Institute of Neurology, University College London, UK; Child and Adolescent Psychiatry Department (A.A., N.B.-M., T.S.), Schneider Children's Medical Center of Israel, Petah-Tikva, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel; Department of Biomedical Sciences and Human Oncology (M.B.), University of Bari "Aldo Moro"; Department of Human Neurosciences (F.C.), University La Sapienza of Rome; Department of Infectious Diseases (R.C.), Istituto Superiore di Sanità, Rome, Italy; WHO Global Collaborating Centre for Reference and Research on Diphtheria and Streptococcal Infections (A.E.), Reference Microbiology, Directorate National Infection Service, Public Health England; Evelina London Children's Hospital GSTT (T.H.), Kings Health Partners AHSC; Psychological Medicine (I.H.), Great Ormond Street Hospital NHS Foundation Trust, London, UK; Department of Child and Adolescent Psychiatry (C.H.), De Bascule, Amsterdam UMC, the Netherlands; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (M.M.), Seville; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica (P.M.), Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville; Department of Child and Adolescent Psychiatry and Psychology (A. Morer), Institute of Neurosciences, Hospital Clínic; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A. Morer), Barcelona; Centro de Investigación en Red de Salud Mental (CIBERSAM) (A. Morer), Instituto Carlos III, Madrid; Department of Medicine (A. Morer), University of Barcelona, Spain; Child and Adolescent Mental Health Center (N.M.D., K.J.P., L.S.), Mental Health Services, Capital Region of Denmark and University of Copenhagen, Denmark; Institute of Laboratory Medicine (N. Moll, M.S.) and Department of Psychiatry and Psychotherapy (N. Müller, J.S.), University Hospital LMU Munich; Department of Psychiatry, Social Psychiatry and Psychotherapy (K.M.-V.), Hannover Medical School; Institute of Neurogenetics (A. Munchau), University of Lübeck, Germany; Vadaskert Child and Adolescent Psychiatric Hospital (P.N., Z.T.), Budapest, Hungary; Division of Child and Adolescent Psychiatry, Department of Psychiatry (K.J.P.), Lausanne University Hospital, Switzerland; ASL BA, Mental Health Department (C.P.), Adolescence and Childhood Neuropsychiatry Unit, Bari; Child and Adolescent Neurology and Psychiatry, Department of Clinical and Experimental Medicine (R.R.), University of Catania, Italy; Department of Child and Adolescent Psychiatry (V.R.), Medical Faculty Carl Gustav Carus, TU Dresden, Germany; Clinic of Child and Adolescent Psychiatry and Psychotherapy (S.W.), University of Zurich, Switzerland; and Department of Child and Adolescent Psychiatry (A.D., P.J.H.), University of Groningen, University Medical Center Groningen, the Netherlands.
Abstract
OBJECTIVE: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe. METHODS: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression. RESULTS: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition. CONCLUSIONS: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended.
OBJECTIVE: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe. METHODS: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression. RESULTS: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition. CONCLUSIONS: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended.
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