Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Context: The existing literature on the treatment of pediatric chronic tic disorder (CTD) and Tourette syndrome (TS) indicates that both behavioral therapy (BT) and pharmacotherapy (PT) are effective for reducing symptoms. Objective: To evaluate the efficacy of BT compared to psychoeducation (PE) or PT for reducing tics and co-occurring symptoms and for improving quality of life (QoL) in a sample of youths with CTD and TS. Design: A 10 weeks, 2 sites (Catania, Rome) randomized controlled trial. Participants were randomized to receive one of the following treatments: BT, PE, or PT. Participants: 110 outpatients aged between 8 and 17 years affected by CTD or TS. Results: Patients in the BT and PT groups showed a significant reduction in the severity of tic symptoms, while the PE group did not show any improvement. PT was more effective for reducing obsessive compulsive symptoms than BT, while PE group did not show any improvement. Both BT and PT groups showed an improvement in most QoL domains, whereas no differences were found in the PE group. Conclusions: BT is as effective as pharmacological therapy in the treatment of tic disorders in children and adolescents, thus offering an alternative to medications for CTD and TS.

The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen-dependent induction of autoantibodies in susceptible individuals may be involved the occurrence of tic disorders.

The authors report a kindred in which GTP-CH deficiency resulted in a myoclonus–dystonia syndrome. The proband, a 17-year-old boy, presented with early-onset myoclonus and later, dystonia and bradykinesia. Blood prolactin was increased and CSF homovanillic acid, 5-hydroxyindoleacetic acid, and biopterin were all reduced. l-Dopa/carbidopa administration resulted in clinical improvement. In the paternal branch, the grandfather and three relatives had myoclonus–dystonia and resting or postural tremor of limbs. The authors found a missense mutation in the exon 6 of GCH-1 gene (K224R).