Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders: A Multinational Prospective Cohort Study

Davide Martino, Anette Schrag, Zacharias Anastasiou, Alan Apter, Noa Benaroya-Milstein, Maura Buttiglione, Francesco Cardona, Roberta Creti, Androulla Efstratiou, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Marcos Madruga, Pablo Mir, Astrid Morer, Nanette Mol Debes, Natalie Moll, Norbert Müller, Kirsten Müller-Vahl, Alexander MunchauPeter Nagy, Kerstin Jessica Plessen, Cesare Porcelli, Renata Rizzo, Veit Roessner, Jaana Schnell, Markus Schwarz, Liselotte Skov, Tamar Steinberg, Zsanett Tarnok, Susanne Walitza, Andrea Dietrich, Pieter J. Hoekstra

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27 Scopus citations

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. Conclusion: sThis 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.

Original languageEnglish
Pages (from-to)E1680-E1693
JournalNeurology
Volume96
Issue number12
DOIs
StatePublished - 23 Mar 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 American Academy of Neurology.

Funding

D. Martino has received honoraria for lecturing from the Movement Disorders Society, Tourette Syndrome Association of America, and Dystonia Medical Research Foundation Canada; research funding support from Dystonia Medical Research Foundation Canada, the University of Calgary, the Michael P. Smith Family, the Owerko Foundation, Ipsen Corporate, the Parkinson Association of Alberta, and the Canadian Institutes for Health Research; and royalties from Springer-Verlag. A. Münchau is supported by the Deutsche Forschungsgemeinschaft (DFG; FOR 2698). A. Schrag is supported by the UCL/H NIHR Biomedical Research Centre. V. Roessner has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals; lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma; and support for research from Shire and Novartis. He has carried out (and is currently carrying out) clinical trials in cooperation with Novartis, Shire, and Otsuka. S. Walitza has received in the last 5 years royalties from Thieme Hogrefe, Kohlhammer, Springer, and Beltz. Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, and Gertrud Thalmann Fonds. Outside professional activities and interests are declared under the link of the University of Zurich ( uzh.ch/prof/ssl-dir/interessenbindungen/client/web/ ). A. Schrag, Z. Anastasiou, A. Apter, N. Benaroya-Milstein, M. Buttiglione, F. Cardona, R. Creti, A. Efstratiou, T. Hedderly, I. Heyman, C. Huyser, M. Madruga, P. Mir, A. Morer, N. Mol Debes, N. Moll, N. Müller, K. Müller-Vahl, P. Nagy, K.J. Plessen, C. Porcelli, R. Rizzo, J. Schnell, M. Schwarz, L. Skov, T. Steinberg, Z. Tarnok, A. Dietrich, and P.J. Hoekstra do not have financial disclosures. Go to Neurology.org/N for full disclosures. This project has received funding from the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreement 278367. This project has received funding from the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement 278367.

FundersFunder number
European Union's Seventh Framework Program for research, technological development and demonstration
European Union’s Seventh Framework Program for research, technological development and demonstration278367
Ipsen Corporate
Michael P. Smith Family
Owerko Foundation
Tourette Syndrome Association of America
International Parkinson and Movement Disorder Society
University of Calgary
Canadian Institutes of Health Research
University College London
Deutsche ForschungsgemeinschaftFOR 2698
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Dystonia Medical Research Foundation Canada
NIHR Great Ormond Street Hospital Biomedical Research Centre
Parkinson Association of Alberta

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