Strep A and Tic Worsening: Final Word?

Batya Swift Yasgur, MA, LSW

February 12, 2021

Exposure to Group A streptococcus (GAS) does not appear to worsen symptoms of Tourette syndrome and other chronic tic disorders (CTDs) in children and adolescents, new research suggests.

Investigators studied over 700 children and teenagers with CTDs, one third of whom also had attention deficit hyperactivity disorder (ADHD) and one third who had obsessive-compulsive disorder (OCD).

The youngsters were followed for an average of 16 months and evaluated at 4-month intervals to see if they were infected with GAS. Tic severity was monitored through telephone interviews, in-person visits, and parental reports.

A little less than half the children experienced worsening of tics during the study period, but the researchers found no association between these exacerbations and GAS exposure.

There was also no link between GAS and worsening OCD. However, researchers did find an association between GAS exposure and an increase in hyperactivity and impulsivity in patients with ADHD.

"This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD," the authors note.

"Specific work-up or active management of GAS infections is unlikely to help modifying the course of tics in CTD and is therefore not recommended," they conclude.

The study was published online February 10 in Neurology.

"Intense Debate"

The association between GAS and CTD stems from the description of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) — a condition that is now incorporated in the pediatric acute neuropsychiatric syndromes (PANS), the authors note. Tics constitute an "accompanying feature" of this condition.

However, neither population-based nor longitudinal clinical studies "could definitely establish if tic exacerbations in CTD are associated with GAS infections," they note.  

"The link between streptococcus and tics in children is still a matter of intense debate," said study author Davide Martino, MD, PhD, director of the Movement Disorders Program at the University of Calgary, Calgary, Canada, in a press release.

"We wanted to look at that question, as well as a possible link between strep and behavioral symptoms like obsessive-compulsive disorder and attention deficit hyperactivity disorder," he said.

The researchers followed 715 children with CTD (mean age 10.7 years, 76.8% male) who were drawn from 16 specialist clinics in nine countries. Almost all (90.8%) had a diagnosis of Tourette syndrome (TS); 31.7% had OCD and 36.1% had ADHD.

Participants received a throat swab at baseline, and of these, 8.4% tested positive for GAS.

Participants were evaluated over a 16- to 18-month period, consisting of:

  • Face-to-face interviews and collection of throat swabs and serum at 4-month intervals

  • Telephone interviews at 4-month intervals, which took place at 2 months between study visit

  • Weekly diaries; parents were asked to indicate in the diary worsening of tics and focus on detecting the earliest possible tic exacerbation.

Beyond the regularly scheduled visits, parents were instructed to report by phone or email any noticeable increase in tic severity and then attend an in-person visit.

Tic exacerbations were defined as an increase of ≥ 6 points on the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTS), compared with the previous assessment.

OCD and ADHD symptoms were assessed according to the Yale-Brown Obsessive-Compulsive Scale and the parent-reported Swanson, Nolan, and Pelham-IV (SNAP-IV) questionnaire.

The researchers divided GAS exposures into 4 categories: new definite exposure; new possible exposure; ongoing definite exposure; and ongoing possible exposure

Unlikely Trigger

During the follow-up period, 43.1% (n = 308) of participants experienced tic exacerbations. Of these, 218 participants experienced one exacerbation, while 90 participants experienced two, three, or four exacerbations.

The researchers did not find a significant association between GAS exposure status and tic exacerbation.

Participants who did develop a GAS-associated exacerbation (n = 49) were younger at study exit (9.63 vs. 11.4 years, P < .0001) and were more likely to be male (46/49 vs 210/259, Fisher's = .035), compared with participants who developed a non-GAS-associated tic exacerbation (n = 259).

Additional analyses were adjusted for sex, age at onset, exposure to psychotropic medications, exposures to antibiotics, geographical regions, and number of visits in the time interval of interest. These analyses continued to yield no significant association between new or ongoing concurrent GAS exposure episodes and tic exacerbation events.

Of the children in the study, 103 had a positive throat swab, indicating a new definite GAS exposure, whereas 46 had a positive throat swab indicating an ongoing definite exposure (n = 149 visits). Of these visits, only 20 corresponded to tic exacerbations.

There was also no association between GAS exposure and OCD symptom severity. However, it was associated with longitudinal changes (between 17% and 21%, depending on GAS exposure definition) in the severity of hyperactivity-impulsivity symptoms in children with ADHD.

"It is known that immune activation may concur with tic severity in youth with CTDs, and that psychosocial stress levels may predict short-term future tic severity in these patients," the authors write.

"Our findings suggest that GAS is unlikely to be the main trigger for immune activation in these patients," they add.

Brick or Cornerstone?

Commenting on the study for Medscape Medical News, Margo Thienemann, MD, clinical professor of psychiatry, Stanford University School of Health, Stanford, California, said that in the clinic population they treat, GAS, other pathogens, and other stresses can "each be associated with PANS symptom exacerbations."

However, these "would not be likely to cause PANS symptoms exacerbations in the vast majority of individuals, only individuals with genetic backgrounds and immunologic dysfunctions creating susceptibility," said Thienemann, who also directs the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) Clinic at Stanford Children’s Health. She was not involved with the study.

In an accompanying editorial, Andrea Cavanna, MD, PhD, honorary reader in neuropsychiatry, Birmingham Medical School, UK, and Keith Coffman, MD, director, Tourette Syndrome Center of Excellence, Children’s Mercy Hospital, Kansas City, Missouri, suggest that perhaps the "interaction of psychosocial stress and GAS infections contributes more to tic exacerbation than psychosocial stress alone."

"Time will tell whether this study stands as another brick — a cornerstone?— in the wall that separates streptococcus from tics," they write.

The study was supported by the European Union's Seventh Framework Program. 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. The other authors' disclosures are listed in the original article. Cavanna, Coffman, and Thienemann have disclosed no relevant financial relationships.

Neurology. Published online February 10, 2021. Abstract, Editorial

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