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

Schrag et al. reported that Group A streptococcal (GAS) exposure is unrelated to tics in children at risk for tic disorders.1 The critical limitations of this study are that only children with genetic risks for tics were studied and information about risk for autoimmunity, infection susceptibility, and antibiotics use are absent.1 The EMTICS home page states that many patients refused to participate when told that antibiotic use would be limited. This would introduce a negative selection bias against families who perceive themselves as high risk and patients procuring antibiotics outside the trial.2

GAS infections trigger autoimmune disorders through mechanisms mediated by superantigens and adaptive immunity.3 Studies in rodent models for GAS-induced neuropsychiatric symptoms showed that Th17 lymphocytes and autoantibodies, generated in response to multiple infections, targeted the brain and triggered neuroinflammation. They also caused blood-brain barrier damage and neuronal circuitry dysfunction, which elicited behavioral abnormalities.4

We have witnessed the transformative effect of antibiotic treatment in a small group of patients with OCD and/or movement disorders secondary to GAS infections.5 Consequently, we are concerned that results from the EMTICS study may be incorrectly extrapolated to children and adolescents with acute onset of tics, resulting in effective treatment being withheld.

Disclosure

The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures. 

References

  1. Schrag AE, Martino D, Wang H, et al. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study. Neurology. 2022;98(11):e1175-e1183. doi:10.1212/WNL.0000000000013298
  2. Community Research and Development Information Service (CORDIS). European Multicentre Tics in Children Studies - Reporting. Updated November 26, 2018. Accessed April 18, 2022. https://cordis.europa.eu/project/id/278367/reporting
  3. Castro SA, Dorfmueller HC. A brief review on Group A Streptococcus pathogenesis and vaccine development. R Soc Open Sci. 2021;8(3):201991. Published 2021 Mar 10. doi:10.1098/rsos.201991
  4. Platt MP, Agalliu D, Cutforth T. Hello from the Other Side: How Autoantibodies Circumvent the Blood-Brain Barrier in Autoimmune Encephalitis. Front Immunol. 2017;8:442. Published 2017 Apr 21. doi:10.3389/fimmu.2017.00442
  5. Endres D, Pollak TA, Bechter K, et al. Immunological causes of obsessive-compulsive disorder: is it time for the concept of an "autoimmune OCD" subtype?. Transl Psychiatry. 2022;12(1):5. Published 2022 Jan 10. doi:10.1038/s41398-021-01700-4

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