Search Results (22)

Cannabinoid receptor 1 (CB₁) signalling is critical for weight gain and for milk intake in newborn pups. This is important as in humans, low birth weight increases the risk for attention-deficit hyperactivity disorder (ADHD). Moreover, some children with ADHD also have Tourette syndrome (TS). However, it remains unclear if insufficient CB₁ receptor signalling may promote ADHD/TS-like behaviours. Here, ADHD/TS-like behaviours were studied from postnatal to adulthood by exposing postnatal wild-type CB₁ and Cannabinoid receptor 2 (CB₂) knockout mouse pups to SR141716A (rimonabant), a CB₁ receptor antagonist/inverse agonist. Postnatal disruption of the cannabinoid system by SR141716A induced vocal-like tics and learning deficits in male mice, accompanied by excessive vocalisation, hyperactivity, motor-like tics and/or high-risk behaviour in adults. In CB₁ knockouts, rearing and risky behaviours increased in females. In CB₂ knockouts, vocal-like tics did not develop, and males were hyperactive with learning deficits. Importantly, females were hyperactive but showed no vocal-like tics. The appearance of vocal-like tics depends on disrupted CB₁ receptor signalling and on functional CB₂ receptors after birth. Inhibition of CB₁ receptor signalling together with CB₂ receptor stimulation underlie ADHD/TS-like behaviours in males. This study suggests that the ADHD/TS phenotype may be a single clinical entity resulting from incorrect cannabinoid signalling after birth. Full article

Tourette syndrome (TS) is the most common cause of tics. Tics are classified as motor and phonic tics. The latter (previously also referred to as “vocal tics”) are manifested by simple sounds (simple phonic tics) or complex, often semantically meaningful utterances (complex phonic tics). Methods: We compared the clinical and demographic features of consecutive patients with TS who exhibited simple and complex phonic tics. Results: There were 149 patients, 117 (78.5%) of whom were males; the mean age at evaluation was 19.61 ± 12.97 years. In total, 35 (23.5%) of these manifested complex phonic tics, and 26 (17.4%) had verbalizations. No statistically significant differences were observed between TS patients with simple versus complex phonic tics with respect to sex, age at onset, age at presentation, or comorbid attention-deficit/hyperactivity disorder or obsessive–compulsive disorder. Patients with complex phonic tics more frequently had trunk tics (p = 0.002), complex motor tics (p < 0.001), copropraxia (p = 0.002), a wider variety of phonic tics (p < 0.001) and greater tic severity (p = 0.001). The multivariate regression analysis showed an independent association between trunk tics and complex phonic tics. Conclusions: Complex phonic tics seem to be part of a more widely distributed, severe, and complex presentation of TS, likely representing a continuum within the spectrum of motor and phonic tics. Full article

Background/Objectives: The co-morbidity between neurodevelopmental tics and functional tic-like behaviors (FTBs) in patients with Tourette syndrome (TS) is relatively under-investigated. The demographic and clinical characteristics of a large sample of patients with TS who presented with co-morbid FTBs (functional overlay) were assessed to raise awareness of this complex clinical presentation and to shed light on the differential diagnosis between the two conditions. Methods: We analyzed the clinical data of 63 patients (44 females, mean age 24 years, range 13–40) with pre-existing TS who (sub)acutely developed co-morbid FTBs (TS + FTBs) after the onset of the COVID-19 pandemic and compared them with 63 age- and gender-matched controls with TS (neurodevelopmental tics only). The diagnosis of co-morbid FTBs was validated by the European Society for the Study of Tourette Syndrome (ESSTS) criteria. Results: Complex vocal tics (p < 0.001), including coprolalia (p = 0.002), and self-injurious behaviors (p < 0.001), often as part of tic attacks (p < 0.001), were confirmed to be more commonly reported by the group of patients with TS + FTBs, who were also more likely to present with anxiety (p < 0.001) and other functional neurological symptoms (p < 0.001) compared to patients with TS. Conclusions: Patients with TS and co-morbid FTBs can pose significant diagnostic and treatment challenges. By systematically applying ESSTS criteria, we confirmed specific red flags for the diagnosis of functional overlay in patients with TS. The correct identification of this composite clinical phenotype plays a key role in preventing the misdiagnosis of treatment-resistant TS and implementing tailored treatment interventions. Full article

Background: Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics. Although Tourette syndrome is known to have various comorbidities, comprehensive data on its prevalence and associated conditions in a large, diverse population are limited. This study aimed to examine the prevalence of Tourette syndrome and its comorbidities in children aged 3 to 17 years using data from the 2021 National Survey of Children’s Health (NSCH). Methods: Data from 79,236 children aged 3–17 years were analyzed. The prevalence of Tourette syndrome was assessed, and its association with socio-demographic factors and comorbid conditions, including prematurity and low birth weight, was examined using univariate and multivariate logistic regression models. Results: The prevalence of Tourette syndrome was 0.3% among children aged 3–17 years, with higher rates in males (74%) and adolescents aged 11–17 years (74%). Prematurity and low birth weight were associated with higher rates of Tourette syndrome and its comorbidities. Neurodevelopmental conditions such as ADHD (49% in Tourette syndrome vs. 10.2% in non-Tourette syndrome), autism spectrum disorder (21% vs. 3.2%), and learning disabilities were significantly more prevalent among children with Tourette syndrome. Similarly, psychiatric disorders such as anxiety (60% vs. 11.3%) and depression (25% vs. 5%) were more common in the Tourette syndrome group. Immune-based conditions, including asthma and allergies, and physical health conditions such as diabetes and vision or hearing problems, were also significantly associated with TS. Conclusions: The study highlights the significant burden of comorbidities in children with Tourette syndrome, emphasizing the need for early diagnosis and comprehensive management strategies to address the multifaceted challenges faced by these children. Full article

Tic disorders (TDs) are neurodevelopmental conditions which affect 0.3–0.9% of individuals aged < 18 years. Although tics often improve or resolve spontaneously over time, treatment is often recommended. Pharmacological approaches are widely used as primary interventions. However, their side effects encouraged the development and the interest in nonpharmacological approaches, whose efficacy in pediatric populations remains poorly understood. This systematic review aimed to evaluate the efficacy of nonpharmacological treatments for children and adolescents with TDs. A literature review was performed using PubMed, EBSCOhost, and JABA databases up to 16 May 2024. Eligible articles were randomized controlled trials, written in English and published in peer-reviewed journals, investigating the efficacy of nonpharmacological treatments in pediatric populations diagnosed with TDs. Significant evidence supported the efficacy of behavioral interventions such as the Comprehensive Behavioral Intervention for Tics (CBIT), its reduced version the Habit Reversal Therapy (HRT), and the Exposure and Relapse Prevention (ERP) in reducing tics and tic-related impairment among young people, as assessed through the Yale Global Tic Severity Scale. Behavioral interventions were generally effective in reducing tics, although some studies reported higher effects on motor tics when compared to vocal tics. High level of efficacy was observed for both face-to-face and online treatments. While future studies are needed to improve treatment effects, especially on vocal tics, as well as to have a better understanding of treatment components and modalities, taken together, the present findings support the use of nonpharmacological intervention for TDs in youth. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) include a wide range of conditions that develop during the formation of the central nervous system, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Tourette syndrome (TS) is another neurodevelopmental disorder characterised by motor and vocal tics, which often co-occurs with ASD and ADHD. This study explores the feasibility of assessing joint hypermobility in children with specific neurodevelopmental conditions by measuring both ankles’ passive range of motion (pROM). Methods: This study involved children diagnosed with ASD, ADHD, and TS, aged 5 to 15 years, who were compared with a control group of healthy children. The Beighton and Brighton scores and the pROM of the left and right ankles were measured. Data were analysed using SPSS version 22.0 for Windows (IBM SPSS Statistics, Chicago, IL, USA). A total of 102 subjects participated in this study (72.52% male, with a mean age of 10.7 ± 2.2 years). The sample included 24 children with ASD, 27 with ADHD, 26 with TS, and 25 healthy controls. Results: The pROM of the right and left ankles showed a significant positive correlation with the Beighton and Brighton scores in children with NDDs (ASD, ADHD, and TS combined). A trend towards higher Beighton scores (≥6) was observed in the ADHD and TS groups, with significance found in the TS group (p = 0.013). The pROM of the right ankle was significantly higher in the ADHD (p = 0.021) and TS (p = 0.013) groups compared to the controls. Although the left ankle followed a similar trend in the TS group, the difference was not statistically significant (p = 0.066). Controlling for age, the diagnosis of ASD, ADHD, and TS does not appear to impact any of the variables examined. Conclusions: There is a trend towards a higher prevalence of individuals with elevated Beighton scores in the ADHD and TS groups, suggesting greater general flexibility or hypermobility in these patients. However, the pROM of the right ankle is significantly higher in the ADHD and TS groups, with solid evidence in the TS group. These findings were not observed in children with ASD. However, it is necessary to consider the measurements obtained in relation to the patients’ age. Finally, given that the pROM of the ankles correlates with the Beighton and Brighton scores, it could be utilised for the initial screening, monitoring, and follow-up of JH in some children with NDDs. Further investigations are required. Full article

(1) Background: Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Attention deficit and hyperactivity disorder (ADHD) is a common comorbidity of TS that adds further impairment. Cognitive-behavioural therapy (CBT) has shown efficacy in treating tics, yet its effectiveness in individuals with TS and comorbid ADHD remains unclear. Also, it is suggested that ADHD characteristics like executive dysfunction and inattention could hinder the response to CBT. This study aims to compare the response to CBT for tics and its maintenance six months post-therapy among TS individuals with and without ADHD symptoms. (2) Methods: In this study, 55 TS participants who completed 14-week CBT for tics were split into high (TS+) or low (TS−) ADHD symptomatology groups. Outcomes were evaluated using the Yale Global Tic Severity Scale (YGTSS) regarding global tic severity and motor and vocal tic frequency post-CBT and at a 6-month follow-up. (3) Results: No significant group difference was found regarding improvements post-CBT (n = 55), nor the maintenance six months later (n = 45). (4) Conclusions: ADHD symptoms may not hinder the response to CBT or its maintenance, suggesting that TS individuals with ADHD symptoms may not require specialized CBT interventions. Full article

Background. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is a rare pediatric disorder consisting of a sudden onset of obsessive–compulsive disorder (OCD) and/or tics after a group A Streptococcus (GAS) infection. Methods. In the period between 2013 and 2023, 61 children presented to our Pediatric Rheumatology unit with a suspicion of PANDAS syndrome. Among these, a retrospective analysis was conducted, and 19 fulfilled the current classification criteria and were included in this study. Results. The male-to-female ratio was 14:5, the median age at onset was 7.0 (2.0–9.5) years, and the median age at diagnosis was 8.0 (3.0–10.4) years. The median follow-up period was 16.0 (6.0–72.0) months. Family and personal history were relevant in 7/19 and 6/19 patients. Tics were present in all patients. Details for motor tics were retrospectively available in 18/19 patients, with the eyes (11/18) and neck/head (10/18) being most often involved. Vocal tics were documented in 8/19, behavioral changes in 10/19, and OCD in 2/19. Regarding the therapeutic response, all patients responded to amoxicillin, 12/13 to benzathine benzylpenicillin, and 7/9 to azithromycin. Conclusions. Our findings partially overlap with previous reports. Larger prospective studies are needed to improve treatment strategies and classification criteria. Full article

Aim: To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. Method: In 226 male GTS patients (5–14 years), we followed vocal and motor tics and obsessive–compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. Results: At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. Discussion: Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia–thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS. Full article

Tourette Syndrome (TS) is a high-incidence multifactorial neuropsychiatric disorder characterized by motor and vocal tics co-occurring with several diverse comorbidities, including obsessive-compulsive disorder and attention-deficit hyperactivity disorder. The origin of TS is multifactorial, with strong genetic, perinatal, and immunological influences. Although almost all neurotransmettitorial systems have been implicated in TS pathophysiology, a comprehensive neurophysiological model explaining the dynamics of expression and inhibition of tics is still lacking. The genesis and maintenance of motor and non-motor aspects of TS are thought to arise from functional and/or structural modifications of the basal ganglia and related circuitry. This complex wiring involves several cortical and subcortical structures whose concerted activity controls the selection of the most appropriate reflexive and habitual motor, cognitive and emotional actions. Importantly, striatal circuits exhibit bidirectional forms of synaptic plasticity that differ in many respects from hippocampal and neocortical plasticity, including sensitivity to metaplastic molecules such as dopamine. Here, we review the available evidence about structural and functional anomalies in neural circuits which have been found in TS patients. Finally, considering what is known in the field of striatal plasticity, we discuss the role of exuberant plasticity in TS, including the prospect of future pharmacological and neuromodulation avenues. Full article

European clinical guidelines recommend the use of Exposure and Response Prevention (ERP) and Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatments for tic disorders. Although ongoing efforts in research are being made to understand the mechanisms underlying these behavioral approaches, as of yet, the neurophysiological mechanisms behind behavioral interventions are poorly understood. However, this is essential to tailor interventions to individual patients in order to increase compliance and efficacy. The Theory of Event Coding (TEC) and its derivative BRAC (Binding and Retrieval in Action Control) provide a theoretical framework to investigate cognitive and neural processes in the context of tic disorders. In this context, tics are conceptualized as a phenomenon of enhanced perception–action binding, with premonitory urges constituting the perceptual and the motor or vocal expression constituting the action part of an event file. Based on this, CBIT is assumed to strongly affect stimulus–response binding in the context of response selection, whereas the effects of ERP presumably unfold during stimulus–response binding in the response inhibition context. Further studies are needed to clarify the neurophysiological processes underlying behavioral interventions to enable the individualization and further development of therapeutic approaches for tic disorders. Full article

Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children’s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. Methods: We collected 94 samples of plasma and 69 samples of urine from 3–12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. Results: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8–12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD. Full article

Tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by involuntary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders (e.g., attention deficit hyperactivity disorder and obsessive–compulsive disorder), which indeed aggravate clinical symptoms and complicate diagnosis and treatment. Micro-RNAs (miRNAs) derived from small extracellular vesicles (sEVs) have been recognized as novel circulating biomarkers of disease. To identify specific miRNAs derived from plasma sEVs for TDs’ diagnosis and prognosis, we used official EV isolation and purification methods to characterize the plasma-derived EV miRNAs from children with different types of TDs. Nanoparticle tracking analysis, transmission electron microscopy, and immunoblot analysis of EV surface markers were applied to confirm the features and quality of sEVs. The RNA sequencing (RNA-seq) approach was adapted to identify novel circulating sEVs-derived miRNAs with altered expression levels in paired comparisons of TDs versus healthy controls (HCs), transient tic disorder (TTD) versus chronic motor or vocal tic disorder (CTD), and TTD versus Tourette Syndrome (TS). GO term and KEGG pathway were performed for functional analysis and the receiver operator curve analysis was followed to test the diagnosis efficacy of differentially expressed miRNAs (DEMs) derived from plasma sEVs among paired groups, namely, TDs versus HCs, TTD versus CTD, and TTD versus TS. As a result, 10 miRNAs (hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7e, hsa-let-7f, hsa-miR-25-3p, hsa-miR-29a-3p, hsa-miR-30b-5p, hsa-miR-125b-5p, and hsa-miR-1469) have demonstrated a significantly different expression signature in the TDs group compared to HCs with excellent area under curve (AUC) values of 0.99, 0.973, 0.997, 1, 0.99, 0.997, 0.987, 0.993, 0.977, and 0.997, respectively, and the diagnostic efficacy of miRNAs was also estimated for discriminating TTD from CTD or TS. In our research, we finally obtained several potential sEVs-derived miRNA biomarkers to assess the diagnosis and prognosis of TDs. Full article

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by motor and vocal tics and strong association with autistic deficits, obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). The genetic overlap between TS and autism spectrum disorder (ASD) includes those genes that encode the neurexin trans-synaptic connexus (NTSC) inclusive of the presynaptic neurexins (NRXNs) and postsynaptic neuroligins (NLGNs), cerebellin precursors (CBLNs in complex with the glutamate ionotropic receptor deltas (GRIDs)) and the leucine-rich repeat transmembrane proteins (LRRTMs). In this study, we report the first evidence of a TS and ASD association with yet another NTSC gene family member, namely LRRTM4. Duplication of the terminal exon of LRRTM4 was found in two females with TS from the same family (mother and daughter) in association with autistic traits and ASD. Full article

Coprolalia and echophenomena repeated in the patients’ mind (CTPh—cognitive tic-like phenomena) have been rarely recognized as part of Gilles de la Tourette syndrome (GTS) symptomatology and their assignment to tics, OCD or other psychopathologies has not been settled. The aim of the paper was to assess the incidence and clinical associations of CTPh in GTS, and to establish if CTPh belong to the tic spectrum. We performed a prospective, one-registration study on a cohort of 227 consecutive patients with GTS. CTPh were diagnosed during the interview and defined as brief, sudden, involuntary thoughts that had corresponding complex vocal tics. CTPh occurred at some point in the lives of 34 (15.0%) patients. The median age at onset of CTPh was 14.5 years (IQR: 10.5–17.5). CTPh were found more frequently in adults, with the most frequent onset in adolescence (44.1%). Four mental phenomena resembling tics were recognized: echolalia (n = 17), coprolalia (n = 16), palilalia (n = 13) and repeating of words in the mind (n = 7). The older the age of patients, the more severe tics, and anxiety disorder significantly correlated with CTPh. CTPh may be considered as a part of tic spectrum with a substantial impact of anxiety disorder. CTPh are a late and age-related symptom of GTS. Full article