Author Response: Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders: A Multinational Prospective Cohort Study

We are grateful to the European Immuno-Neuropsychiatric Association Scientific and Medical Advisory Group for their interest and positive comments on our study. As correctly pointed out, our study exclusively enrolled patients with an established diagnosis of chronic tic disorders, the vast majority of whom had Tourette syndrome.1 Pediatric acute-onset neuropsychiatric syndrome/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANS/PANDAS) represent a clinical spectrum that is substantially different from the clinical course and phenotype of chronic tic disorders.2 There is growing evidence supporting a direct role of immune-mediated mechanisms in the pathogenesis of chronic, neurodevelopmental disorders such as Tourette syndrome, obsessive-compulsive disorder, and ADHD.3 Genetic and early environmental exposures might prompt a very early priming of neural and immune development, which might lead to altered trajectories of maturation and, ultimately, to behavioral abnormalities and hyperactive immune-inflammatory responses.3,4 Our study focused on the role of a specific exogenous trigger (group A streptococcus) in the temporal course of core behavioral features of chronic tic disorders during early adolescence. Our results do not refute a mechanistic link between immune and neural mechanisms during early development in chronic tic disorders. At the same time, we agree that our clinical overall message applies to chronic tic disorders but not to acute-onset behavioral presentations which encompass PANS/PANDAS.

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