Sensory phenomena in children with Tourette syndrome or autism spectrum disorder.

Background: Tourette syndrome (TS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with an onset before the age of 18 years. TS patients frequently reported atypical sensory phenomena (SP). Sensory processing abnormalities are also particularly frequent in ASD individuals. Objectives: Considering the higher rate of atypical sensory behaviours in both neurodevelopmental disorders, in the present study we analysed sensory experiences in patients with ASD and in patients with TS. Methods: We enrolled patients with a primary diagnosis of TS or ASD. All participants were assessed for primary diagnosis and associated comorbidities. The presence of sensory behaviours was investigated using the University of Sao Paulo's Sensory Phenomena Scale (USP-SPS). Results: SP were significantly more represented in the ASD-group versus TS-group, except for sound just-right perceptions and energy to released. ASD participants presented higher mean scores in all fields of USP-SPS severity scale respect on TS patients and healthy controls. The USP-SPS total score had significant positive correlations with the CYBOCS and MASC total scores in the TS cohort. In the ASD group, the USP-SPS total score was significantly negative correlated with the total IQ and marginally positive correlated with ADOS total score. Conclusion: SP are a frequently reported characteristic both of ASD and TS. Future studies are needed to better evaluate the differences on their phenomenology in patients with TS and ASD.

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.

Copy Number Variations in Children with Tourette Syndrome: Systematic Investigation in a Clinical Setting.

Tourette syndrome (TS) is a neurodevelopmental disturbance with heterogeneous and not completely known etiology. Clinical and molecular appraisal of affected patients is mandatory for outcome amelioration. The current study aimed to understand the molecular bases underpinning TS in a vast cohort of pediatric patients with TS. Molecular analyses included array-CGH analyses. The primary goal was to define the neurobehavioral phenotype of patients with or without pathogenic copy number variations (CNVs). Moreover, we compared the CNVs with CNVs described in the literature in neuropsychiatric disorders, including TS, to describe an effective clinical and molecular characterization of patients for prognostic purposes and for correctly taking charge. Moreover, this study showed that rare deletions and duplications focusing attention on significant genes for neurodevelopment had a statistically higher occurrence in children with tics and additional comorbidities. In our cohort, we determined an incidence of potentially causative CNVs of about 12%, in line with other literature studies. Clearly, further studies are needed to delineate the genetic background of patients with tic disorders in a superior way to elucidate the complex genetic architecture of these disorders, to describe the outcome, and to identify new possible therapeutic targets.

Novel malformations: Chiari type 1 and hydrocephalus in Zhu-Tokita-Takenouchi-Kim syndrome and novel SON variants.

Zhu-Tokita-Tachenouchi-Kim syndrome (ZTTK) is a recently recognized malformation syndrome presenting with craniofacial dysmorphism, developmental delay/intellectual disability, seizures, anomalies involving brain white matter, and other body-organs. In humans, the disorder is linked to the loss-of-function variants in the SON gene (MIM# 617140). Herewith, a new case of this syndrome is reported in a 2-year-old Caucasian child who presented the classical clinical features of the ZTTK syndrome in association with hydrocephalus and Chiari malformations type 1 an anomaly previously unreported. Exome analysis showed a de novo heterozygous variant in SON gene. Literature review of similar cases is reported.

Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration.

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

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.

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.

Self- and Parent-Reported Psychological Symptoms in Young Cancer Survivors and Control Peers: Results from a Clinical Center.

Pediatric cancer survivors are at increased risk for psychological distress. We sought to understand the severity and symptoms' co-occurrence among pediatric survivors compared to controls by rating both self- and parent-reported symptomatology. Forty survivors (22 males; mean age at study time: 12.9 years) participated in the study. Most survivors (85%) had a diagnosis of acute lymphoblastic leukemia. Seventy-nine healthy controls with the same age and gender distribution as the patients were included. A standardized assessment of psychological functioning was conducted by self- and parent-reported symptoms evaluations. The self-reported anxious symptom severity was significantly higher in survivors. A significantly higher proportion of survivors compared to controls had clinically significant anxiety, depression, and combined anxiety symptoms (i.e., social anxiety, separation anxiety, or physical symptoms). In both study groups, the self-reported emotional and somatic symptoms were significantly associated. The multi-informant assessments of the psychological symptoms revealed distinct associations between the child- and parent-reported symptoms in the survivors' group: the survivors' self-reports of depressive symptoms, somatic symptoms, and functional impairment were significantly correlated with the parent reports of child behavioral concerns, somatic complaints, and functional impairment, respectively. Conclusion: Self-reported symptoms showed similar comorbidity profiles in survivors and control peers. The multi-informant assessments detected differences in the association of self- and parent-reported symptoms between the survivor and control groups. The present study showed that multi-informant assessment is critical to understanding symptom profiles and to informing intervention with particular regard to parental participation and support.