Children with chronic tic disorders, mainly Tourette syndrome, did not have tic exacerbations when exposed to group A Streptococcus, a longitudinal study suggested.
No significant association with tic exacerbations emerged across four definitions of pharyngeal strep exposure over mean follow-up of 16 months, although trends suggested a possible weak link (OR 1.006-1.235, all P>0.3), reported Davide Martino, MD, PhD, of the University of Calgary in Canada, and co-authors.
However, strep was significantly associated with longitudinal changes of hyperactivity-impulsivity symptom severity that ranged from 17% to 21% depending on how exposure was defined, the team wrote in Neurology.
“The link between Streptococcus and tics in children is still a matter of intense debate,” Martino said in a statement. “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.”
“While our findings suggest that strep is not likely to be one of the main triggers for making tics worse, more research is needed into other possible explanations,” he added. “For example, the social stress of having this disorder could be implicated in making tics worse more than infections. It’s also possible another pathogen might be triggering an immune response associated with tic worsening.”
Group A Streptococcus has been studied as a possible environmental agent associated with tic disorders for the past 2 decades, observed Andrea Cavanna, MD, PhD, of the University of Birmingham in England, and Keith Coffman, MD, of Children’s Mercy Hospital in Kansas City, Missouri, in an invited editorial.
Isolated clinical observations have suggested that tic disorders be included as a collateral feature in conditions known as pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS) infections, the editorialists noted. But “a few longitudinal clinical studies including mixed populations of PANDAS and chronic tic disorders found that tic exacerbations were unrelated to group A Streptococcus infection in the majority of cases. Interestingly, the results of a case-control study of a large primary care database also led to arguing against this association.”
In their analysis, Martino and co-authors pulled data from EMTICS, a large multicenter epidemiological study in Europe and Israel. One arm of the study prospectively examined associations between new group A Streptococcus throat exposures and exacerbations of tics, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD) symptoms in children with chronic tic disorders.
Patients were recruited between 2013 and 2016, had an established diagnosis of Tourette syndrome or chronic motor or vocal tic disorders, and had four monthly face-to-face visits over 16-18 months and phone interviews between visits. In addition, parents kept a weekly diary to record tic worsening.
Serum evaluations included anti-streptolysin O (ASOT) and anti-DNAseB (ADB) antibody titers. To minimize the risk of false-negative findings, the researchers looked at four definitions of strep exposure: new definite (newly positive throat swab regardless of serological results), new possible (elevated ASOT or ADB titers with negative or no throat swab), ongoing definite, and ongoing possible.
Tic exacerbations were defined by an increase of at least six points on the Yale Global Tic Severity Scale from the previous assessment. OCD and ADHD were monitored using the Children’s Yale-Brown Obsessive-Compulsive Scale and the parent-reported Swanson, Nolan, and Pelham-IV questionnaire.
The study included 715 patients with an average age of 11; 77% were boys. Most (91%) had a diagnosis of Tourette syndrome. ADHD was diagnosed in 258 children and OCD in 227.
At baseline, 59 children had a positive throat swab; over the course of the study, 103 children had new definite strep exposure. During follow-up, 308 children (43%) had tic exacerbations. The proportion of exacerbations temporally associated with strep exposure ranged from 5.5% to 12.9%, depending on how exposure was defined. There was no association between strep exposure and OCD symptoms.
“Our study of the largest prospective cohort of youth with chronic tic disorders ever documented to date provides evidence against a temporal association between group A Streptococcus exposure and clinically relevant tic exacerbations,” Martino and co-authors wrote.
“This result indicates that specific diagnostic work-up or active management of group A Streptococcus infections in the context of worsening of tic severity in patients with chronic tic disorders is not warranted,” the researchers added.
Study limitations, the team noted, included that data were collected in specialty clinics in several countries, which could have different clinical and microbiological assessment procedures, and that some cases of strep may have been missed since elevated ASOT and ADB titers might not always occur.
Last Updated February 11, 2021
The study was supported by the European Union’s Seventh Framework Program.
Researchers reported relationships with the Movement Disorders Society, Tourette Syndrome Association of America, Dystonia Medical Research Foundation Canada, Dystonia Medical Research Foundation Canada, Michael P Smith Family, Owerko Foundation, Ipsen Corporate, Parkinson Association of Alberta, Canadian Institutes for Health Research, Springer-Verlag, Deutsche Forschungsgemeinschaft, Eli Lilly, Novartis, Shire Pharmaceuticals, Medice Pharma, Otsuka, Thieme Hogrefe, Kohlhammer, Springer, Beltz, Swiss National Science Foundation, Hochspezialisierte Medizin of the Kanton Zurich, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, and Gertrud Thalmann Fonds.
Cavanna and Coffman had no disclosures.