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Schrag, Anette-Eleonore; Martino, Davide; Wang, Hanyuying; Ambler, Gareth; Benaroya-Milstein, Noa; Buttiglione, Maura; Cardona, Francesco; Creti, Roberta; Efstratiou, Androulla; Hedderly, Tammy; Heyman, Isobel; Huyser, Chaim; Mir, Pablo; Morer, Astrid; Moll, Natalie; Müller, Norbert E.; Müller-Vahl, Kirsten R.; Plessen, Kerstin J.; Porcelli, Cesare; Rizzo, Renata; Roessner, Veit; Schwarz, Markus; Tarnok, Zsanett; Walitza, Susanne; Dietrich, Andrea und Hoekstra, Pieter J. (2022): Lack of Association of Group A Streptococcal Infections and Onset of Tics European Multicenter Tics in Children Study. In: Neurology, Bd. 98, Nr. 11, E1175-E1183

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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 approximate to 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.

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