Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.
The results mean that if pre-teens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, Department of Clinical Neuroscience, Institute of Neurology, University College London, United Kingdom, told Medscape Medical News.
Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Schrag.
The study was published online February 2 in Neurology.
Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.
There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.
This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess the development of streptococcal infections and tics, said Schrag.
The study included 259 children aged 3–10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.
The average age at TS onset is 7 years, peaking in prevalence and severity at about 9–12 years. GAS throat infections are common in this age group.
Although study participants did not have tics themselves, they represented “an enriched group,” said Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”
Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.
The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1944 assessments, including 939 telephone interviews and 1005 clinical visits.
More Common in Boys
Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.
The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.
They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Schrag. She explained a definite strep infection is not always clear-cut.
At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.
During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.
Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.
However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2–0.7; P < .01).
This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Schrag.
Results from sensitivity analyzes confirmed the results. This was also the case with analyzes that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Schrag.
“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”
Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Schrag.
It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.
Commenting for Medscape Medical News, Tamara Pringsheim, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary, Alberta, Canada, praised the research.
“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”
The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”
The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Pringsheim reports no relevant financial relationships.
Neurology. Published online February 2, 2022. Abstract
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