Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS­CoV­2 infection: a short-term follow-up assessment.

BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3-1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID. OBJECTIVES: Considering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS. METHODS: We conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children-present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL). RESULTS: Among the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it. CONCLUSIONS: SARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.

Use of Nutritional Supplements Based on L-Theanine and Vitamin B6 in Children with Tourette Syndrome, with Anxiety Disorders: A Pilot Study.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and co-occurring disorders. It has been suggested that anxiety occurs in 2-45% patients affected by Tourette syndrome. Despite dietary and nutritional factors have been found to affect a range of neurological conditions, no more studies have investigated the relationship between nutritional supplements and tics. OBJECTIVE: To evaluate the effectiveness of supplementation of both L-Theanine and Vitamin B6 in reducing tics and co-occurring disorders in a sample of youth with chronic tic disorder (CTD) or Tourette syndrome with anxiety symptoms. DESIGN: A open-label trial. Patients affected by Tourette syndrome were randomized to receive nutritional supplements based on L-Theanine and vitamin B6, or psychoeducation (PE). PARTICIPANTS: 34 children (30 boys and 4 girls) aged between 4 and 17 years affected by Tourette syndrome or chronic tic disorder, associated with anxiety symptoms. RESULTS: Patients in both groups showed a reduction in the severity of tic and anxiety symptoms. Supplementation with L-Theanine and vitamin B6 was significantly more effective than psychoeducation in reducing tics and co-occurring disorders, as measured by neuropsychological findings. CONCLUSIONS: Supplementation of both L-Theanine and Vitamin B6 may help in the treatment of tic disorders associated with anxious symptoms. Between-group differences in clinician-rated severity did reach statistical significance only for tics. Despite this finding, further placebo-controlled trials are needed.

Functional tic-like behaviours during the COVID-19 pandemic: Follow-up over 12 months.

Background: Functional tics are included in the wide spectrum of functional movement disorders (FMDs). Their distinction from organic tics is challenging because they both phenomenologically present common features. During the COVID-19 pandemic, there has been an increase in functional tic-like behaviours in vulnerable children and adolescents after social media exposure. This study explores the phenomenology and course of a cohort of newly diagnosed functional tic-like behaviors. Methods: We analysed clinical data of 243 patients affected by tic disorders collected at outpatient Tourette Clinic, Child and Adolescent Neurology and Psychiatry Unit, Catania University. Among the clinical cohort with functional tic-like behaviors, we evaluated the clinical course of symptoms at follow-up visits after 6 and 12 months. Results: Among the cohort of 243 patients referred for evaluation at our centre, 11 were diagnosed with functional tic-like behaviours. The majority of participants with functional tic-like behaviours were female with a mean age of 15 years old and presented an explosive symptom's onset. At follow-up visit after 12 months, patients with functional tic-like behaviors showed a significant variation in the severity of tics and anxiety symptoms. Conversely, depressive, and obsessive-compulsive symptoms did not significantly differ during the follow-up. Conclusion: Our data suggest that several characteristics in clinical course and their phenomenology can help clinicians to distinguish functional tic-like behaviours from organic tics. Our results also suggest a better outcome for tics and anxiety symptoms respect on other comorbidities. A prompt diagnosis and management not only of tics but also comorbidities are recommended, as generally conventional pharmacotherapy for tics does not have positive effects on these patients.

Diagnostic Approach to Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS): A Narrative Review of Literature Data.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are clinical conditions characterized by the sudden onset of obsessive-compulsive disorder and/or tics, often accompanied by other behavioral symptoms in a group of children with streptococcal infection. PANDAS-related disorders, including pediatric acute-onset neuropsychiatric syndrome (PANS), childhood acute neuropsychiatric symptoms (CANS), and pediatric infection triggered autoimmune neuropsychiatric disorders (PITANDs), have also been described. Since first defined in 1998, PANDAS has been considered a controversial diagnosis. A comprehensive review of the literature was performed on PubMed and Scopus databases, searching for diagnostic criteria and diagnostic procedures of PANDAS and related disorders. We propose a test panel to support clinicians in the workout of PANDAS/PANS patients establishing an appropriate treatment. However, further studies are needed to improve our knowledge on these acute-onset neuropsychiatric conditions.

Incidence of Autism Spectrum Disorder in Youths Affected by Gilles de la Tourette Syndrome Based on Data from a Large Single Italian Clinical Cohort.

Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are etiologically related neurodevelopmental disorders with an onset age before 18 years and a reported comorbidity of 2.9-20%. The aim of the present study was to identify the incidence of ASD in a large clinical sample of individuals affected by GTS and to compare our results with previously reported incidences. We retrospectively analyzed clinical data (n = 1200) from January 2010 to March 2019 obtained from the outpatient Catania Tourette Clinic, part of the Child and Adolescent Neurology and Psychiatry of the Medical and Experimental Department of Catania University. We used internationally validated evaluation tools. The neuropsychological evaluation was carried out by an expert and a certificated team of child and adolescent neurologists, supervised by two expert child neurologists (R.R. and M.G.). We investigated 975 GTS-affected individuals of various socioeconomic levels aged 5-18 years, and 8.9% (n = 87) were affected by ASD. The incidence of GTS with ASD was significantly lower (p < 0.001) in children than in adolescents. No statistically significant differences were found in the sex distribution and age of onset of tics between individuals with GTS alone and those with GTS and ASD. The incidence of GTS and ASD comorbidity in this study was high, and this has several implications in terms of treatment and prognosis.

Disentangling Restrictive and Repetitive Behaviors and Social Impairments in Children and Adolescents with Gilles de la Tourette Syndrome and Autism Spectrum Disorder.

Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with male predominance, frequently comorbid, that share clinical and behavioral features. The incidence of ASD in patients affected by GTS was reported to be between 2.9% and 22.8%. We hypothesized that higher ASD rates among children affected by GTS previously reported may be due to difficulty in discriminating GTS sub-phenotypes from ASD, and the higher scores in the restrictive and repetitive behaviors in particular may represent at least a "false comorbidity". We studied a large population of 720 children and adolescents affected by GTS (n = 400) and ASD (n = 320), recruited from a single center. Patients were all assessed with The Yale Global Tic Severity Rating Scale (YGTSS), The Autism Diagnostic Observation Schedule (ADOS), The Autism Diagnostic Interview Revised (ADI-R), The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), and The Children's Yale-Brown Obsessive-Compulsive Scale for autism spectrum disorder (CY-BOCS ASD). Our results showed statistically significant differences in ADOS scores for social aspects between GTS with comorbid attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) sub-phenotypes and ASD. No differences were present when we compared GTS with comorbid ASD sub-phenotype to ASD, while repetitive and restrictive behavior scores in ASD did not present statistical differences in the comparison with GTS and comorbid OCD and ASD sub-phenotypes. We also showed that CY-BOCS ASD could be a useful instrument to correctly identify OCD from ASD symptoms.