Lack of Association of Group A Streptococcal Infections and Onset of Tics
European Multicenter Tics in Children Study
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Abstract
Background and Objectives The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs).
Methods In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti–streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses.
Results A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2–0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037–2.590; definition 2: HR 0.561, 95% CI 0.219–1.436; definition 3: HR 0.853, 95% CI 0.466–1.561; definition 4: HR 0.725, 95% CI 0.384–1.370).
Discussion These results do not suggest an association between GAS exposure and development of tics.
Classification of Evidence This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder.
Glossary
- ADB=
- anti–DNAse B;
- ASOT=
- anti–streptolysin O titer;
- CTD=
- chronic tic disorder;
- DSM-IV-TR=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision;
- EMTICS=
- European Multicentre Tics in Children Studies;
- GAS=
- group A streptococcal;
- TS=
- Tourette syndrome
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
European Multicentre Tics in Children Study (EMTICS) coinvestigators are listed at links.lww.com/WNL/B751.
Infographic: links.lww.com/WNL/B858
Class of Evidence: NPub.org/coe
CME Course: NPub.org/cmelist
- Received April 1, 2021.
- Accepted in final form December 21, 2021.
- © 2022 American Academy of Neurology
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Letters: Rapid online correspondence
- Author Response: Lack of Association of Group A Streptococcal Infections and Onset of Tics
- Anette Schrag, Physician, University College London
Submitted April 28, 2022 - Reader Response: Lack of Association of Group A Streptococcal Infections and Onset of Tics
- Rajat Gupta, Consultant Paediatric Neurologist, Birmingham Children's Hospital, Birmingham, UK
- Dritan Agalliu, Associate Professor, Departments of Neurology, Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
- Alberto Spalice, Professor and Paediatric Neurology, Department of Maternal Sciences, Paediatric Neurology, Sapienza University of Rome, Italy
- Herbert M Lachman, Professor of Medicine (Hematology), Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine. Bronx, New York, U.S.A.
- Tim Ubhi, Consultant Paediatrician, The Children’s e-Hospital, United Kingdom & Consultant Paediatrician, County Durham & Darlington NHS Foundation Trust, UK
- Kiki Chang, Adjunct Professor of Psychiatry, McGovern Medical School University of Texas Health Science Center at Houston, Palo Alto, CA, USA
- Jennifer Frankovich, Clinical Professor of Pediatric Rheumatology, Stanford Children’s Hospital, Stanford University, Palo Alto, CA, USA
- Anders Fasth, Professor of Pediatric Immunology, Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden
- Mats Johnson, Associate Professor of Child and Adolescent Psychiatry, Gillbergcentrum/Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
- Elisabeth Fernell, Professor of Child and Adolescent Psychiatry, Gillbergcentrum/Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
- Ida Walles, Consultant Child and Adolescent Psychiatrist,, Uppsala University Hospital, Uppsala, Sweden
- Susanne Bejerot, Professor of Psychiatry, School of Medical Sciences, Örebro University, Örebro University, Örebro, Sweden
- Peter J van der Spek, Professor of Clinical Bioinformatics, Department of Pathology and Clinical Bioinformatics, Erasmus MC, Rotterdam, Netherlands
- Janet L Cunningham, Associate Professor of Psychiatry, Department. of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
Submitted April 10, 2022
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