Search Results (118)

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: The potential therapeutic role of fecal microbiota transplantation (FMT) in various diseases has been thoroughly studied over the last few decades. However, the majority of studies focus on the adult population, therefore, conclusions regarding the application of FMT in the pediatric population are much less clear. This systematic review aims to summarize the research conducted so far on the efficacy and safety of FMT in the pediatric population, assess the quality of the evidence of its effectiveness, and outline the most promising areas for future research. Methods: We performed a systematic literature search from the index date to 8 June 2024 on the Embase, PubMed, and Web of Science databases. One author screened the resulting 121 articles. Eventually, 35 eligible studies that reported FMT use in seven different diseases were identified. Results: All of the studies assessed FMT as a safe procedure without many serious adverse effects. The best-documented application, which is the only one recommended in official guidelines, is recurrent Clostridioides difficile infection. Other disease entities in which the use of FMT has been studied with good clinical effects are inflammatory bowel disease, allergic colitis, autism, Tourette syndrome, and colonization with multi-drug-resistant organisms. However, it should be noted that the majority of studies are cohort and case-control studies, without randomization, which translates into low evidence quality. In one randomized, controlled trial focusing on the effect of FMT on weight loss in obese individuals, a lack of effect was found. Conclusions: While FMT and subsequent iterations of gut microbiota-targeted interventions hold promising therapeutic potential for various disease entities in the pediatric population, the current evidence behind this conclusion is of low quality. Based on current studies, these methods appear to be both effective and safe. However, further randomized clinical trials are necessary, especially within the pediatric population, for which such studies remain scarce. Full article

The intestine is an important segment of the gastrointestinal tract, which is involved in complex processes that maintain the body’s normal homeostasis. It hosts a vast, diverse, and dynamic microbial community called the gut microbiota, which develops from birth. It has been observed that the gut microbiota is involved in essential physiological processes, including the development of the central nervous system via the gut microbiota–brain axis. An alteration of the gut microbiota can lead to serious health problems, including defective neurodevelopment. Thus, this paper aims to highlight the most recent advances in studies that focus on the link between the gut microbiota and the evolution of neurodevelopmental diseases in children. Currently, studies show that the use of drugs that stimulate and restore the gut microbiota (e.g., probiotics and prebiotics) have the potential to alleviate some of the symptoms associated with conditions such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Tic Disorder, Tourette Syndrome, epilepsy, and Down Syndrome. In addition, due to the challenges associated with drug administration in children, as well as the widespread shortage of medications intended for pediatric use, researchers are working on the development of new delivery systems. Liposome-based systems or solid lipid nanoparticles have been safely used for drug delivery in various pediatric conditions, which may also indicate their potential for use in the administration of microbiota-modulating therapies. 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/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies. Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms “Tourette syndrome”, “tics”, “tic disorders”, “epidemiology”, “prevalence”, and “incidence”. Results: The prevalence of TS is estimated to be about 1% in children and adolescents and approximately 0.01% in adults, with a male-to-female (M:F) ratio of about 4:1. The prevalence of tic disorders is higher in all studies performed in special education populations. Conclusions: Despite substantial methodological variability, our review of the literature indicates that TS is a relatively common neurobehavioral disorder, affecting nearly 1% of children, especially boys. Raising global awareness and expanding training in TS should lead to better identification of undiagnosed patients. Full article

Background/Objectives: Asthma is one of the most common chronic diseases in children, and montelukast is widely prescribed to manage symptoms. However, concerns have emerged regarding its potential association with neuropsychiatric disorders. This study aims to investigate the impact of montelukast duration on neuropsychiatric risks in children with asthma. Methods: A cohort study was conducted using Taiwan’s National Health Insurance Research Database (NHIRD), including children diagnosed with asthma between 2004 and 2007. A total of 14,606 children in the montelukast cohort and 8432 in the non-montelukast cohort were analyzed, with propensity score matching applied to reduce confounding bias. Neuropsychiatric outcomes, including Tics/Tourette’s syndrome, were evaluated using Cox proportional hazard models. Results: Overall, montelukast use did not increase the risk of neuropsychiatric disorders. However, among children aged 6–15 years, prolonged use beyond 63 days was associated with a significantly elevated risk of Tics/Tourette’s syndrome, with a 2.6-fold increase observed in girls and a 1.8-fold increase in boys. Conversely, shorter montelukast use in children aged 0–6 years was linked to a lower risk of neuropsychiatric disorders. Conclusions: Although montelukast generally does not elevate neuropsychiatric risks, extended use in older children may increase the likelihood of developing Tics/Tourette’s syndrome. These findings highlight the importance of cautious prescribing in pediatric asthma management. Further research is necessary to validate these associations and inform clinical decision making. Full article

Aripiprazole (ARZ) is an atypical antipsychotic drug used to treat a variety of mood and psychotic disorders, such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette’s syndrome. Although ARZ offers significant therapeutic benefits, its poor solubility in water requires the development of delivery systems aimed at improving the solubility and bioavailability of the drug. In this work, cryogels based on two natural products—agar and β-cyclodextrin (CD)—were developed and evaluated as a drug delivery system for ARZ. The cryogels were prepared by cryogenic treatment of aqueous solutions of agar and the β-CD/ARZ complex, followed by thawing. The main characteristics of the material, including gel fraction yield, swelling degree, pore volume, elastic properties, and morphology were studied in detail. The release of ARZ from composite cryogels was assessed in two media resembling the pH in stomach and intestine. The system exhibited a pH-dependent release of ARZ, with a slower rate in acidic media (pH 1.2) than in the neutral phosphate buffer (pH 6.8). Under in vitro conditions, the amount of released ARZ over 48 h reached 33%. 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

SLITRK1 is a critical protein involved in neural development and is associated with various neurological disorders, including Tourette Syndrome. This study investigates the structural dynamics, intrinsic disorder propensity, and pharmacological interactions of SLITRK1, with a particular focus on amino acid substitutions and their pathological implications. A comprehensive computational framework was employed, including intrinsic disorder region analysis, transmembrane topology predictions, and stability assessments of SLITRK1 variants. Integrated with reinforcement learning (RL), molecular docking and dynamics simulations were used to evaluate the pharmacotherapeutic potential of drugs commonly prescribed for Tourette Syndrome, such as Pimozide, Aripiprazole, Risperidone, and Haloperidol. Structural analyses revealed that the S656M mutation significantly alters SLITRK1’s 3D conformation, biological functions, and drug binding profiles. Among the tested drugs, Aripiprazole exhibited the highest binding affinity across various SLITRK1 variants, with reinforcement learning highlighting a notable interaction with the S659K mutation. These findings were supported by Ramachandran plot and molecular dynamics analyses, which identified mutation-induced structural and dynamic changes. This study provides an integrative analysis of SLITRK1, offering insights into its role in Tourette Syndrome and laying a foundation for targeted therapeutic strategies to mitigate SLITRK1-related neurological disorders. Full article

Background/Objectives: Prosopagnosia is the inability to recognize people by their faces. Developmental prosopagnosia is the hereditary or congenital variant of the condition. The aim of this study was to demonstrate the assessment of developmental prosopagnosia in a clinical context, using a combination of commercially available clinical assessment tools and experimental tools described in the research literature. Methods: We conducted a comprehensive neuropsychological assessment of a man with Tourette syndrome and attention deficit hyperactivity disorder (ADHD). The patient (ON) had experienced difficulties with face identity recognition throughout his life but believed they were caused by a lack of interest in others. Results: The neuropsychological assessment revealed varying degrees of difficulties primarily related to executive functions, attention, reaction time, and memory processes, as expected in a person with Tourette’s syndrome and ADHD. In addition, ON reported severe problems with face recognition on a prosopagnosia questionnaire and demonstrated severely impaired performance on tests of face memory and face perception commonly used to diagnose prosopagnosia. Interestingly, he reported familial face recognition problems on the maternal side of the family, while tics and ADHD symptoms occurred on the paternal side. This suggests that, in this case, the conditions were likely inherited through different genetic pathways. Conclusions: Proper assessment of face recognition problems, which includes a broad spectrum of clinical assessment tools, could help patients develop awareness and acceptance of themselves and their difficulties, and could serve as a basis for the development of clinical interventions. While ON’s DP, Tourette syndrome, and ADHD may have distinct genetic origins, impairment in face identity recognition has been observed across several neurodevelopmental conditions and is likely more common than currently thought. Full article

In the medical field, there are several very different movement disorders, such as tremors, Parkinson’s disease, or Huntington’s disease. A wide range of motor and non-motor symptoms characterizes them. It is evident that in the modern era, the use of smart wrist devices, such as smartwatches, wristbands, and smart bracelets is spreading among all categories of people. This diffusion is justified by the limited costs, ease of use, and less invasiveness (and consequently greater acceptability) than other types of sensors used for health status monitoring. This systematic review aims to synthesize research studies using smart wrist devices for a specific class of movement disorders. Following PRISMA-S guidelines, 130 studies were selected and analyzed. For each selected study, information is provided relating to the smartwatch/wristband/bracelet model used (whether it is commercial or not), the number of end-users involved in the experimentation stage, and finally the characteristics of the benchmark dataset possibly used for testing. Moreover, some articles also reported the type of raw data extracted from the smart wrist device, the implemented designed algorithmic pipeline, and the data classification methodology. It turned out that most of the studies have been published in the last ten years, showing a growing interest in the scientific community. The selected articles mainly investigate the relationship between smart wrist devices and Parkinson’s disease. Epilepsy and seizure detection are also research topics of interest, while there are few papers analyzing gait disorders, Huntington’s Disease, ataxia, or Tourette Syndrome. However, the results of this review highlight the difficulties still present in the use of the smartwatch/wristband/bracelet for the identified categories of movement disorders, despite the advantages these technologies could bring in the dissemination of low-cost solutions usable directly within living environments and without the need for caregivers or medical personnel. Full article

Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies. Full article

Background: Pimozide is a conventional antipsychotic drug of the diphenylbutylpiperidine class, widely used for treating schizophrenia and delusional disorders and for managing motor and phonic tics in Tourette’s syndrome. Pimozide is known to block dopaminergic D2 receptors and various types of voltage-gated ion channels. Among its side effects, dizziness and imbalance are the most frequently observed, which may imply an effect of the drug on the vestibular sensory receptors, the hair cells. Amniotes possess two classes of vestibular hair cells, named type I and type II hair cells, which differ in terms of signal processing and transmission. We previously reported that Pimozide [3 μM] significantly increased a delayed outward rectifying K⁺ current (I_K,V). Methods and Results: In the present study, using the whole-cell patch-clamp technique we additionally show that Pimozide decreases the inward rectifying K⁺ current (I_K,1) and the mixed Na⁺/K⁺ current (I_h) of chicken embryo type II hair cells, whereas it does not affect type I hair cells’ ionic currents. Since ion channels’ expression can vary depending on age and animal species, in the present study, we also tested Pimozide in adult mouse vestibular hair cells. We found that, like in the chicken embryo, Pimozide significantly increases I_K,V and decreases I_K,1 and I_h in type II hair cells. However, in the adult mouse, Pimozide also slightly increased the outward rectifying K⁺ current in type I hair cells. Conclusions: While providing a possible explanation for the vestibular side effects of Pimozide in humans, its inhibitory action on mammalian hair cells might be of interest for the local treatment of vestibular disorders characterized by altered vestibular input, like Ménière’s disease. Full article

Background/Objectives: The treatment of tics and psychiatric comorbidities is crucial when they affect the patient’s well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient’s phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment received for tics and psychiatric comorbidities in our cohort of children and adult patients with tic disorders. Additionally, a further aim was to quantify the severity of tics, comorbidities and overall severity, and the overall clinical changes observed during the follow-up. Methods: Retrospective descriptive study of patients with tic disorders under follow-up at our Tic Functional Unit from January 2022 to March 2024. Two independent neurologists retrospectively applied the Clinical Global Impression of Change (CGI-C) and the Clinical Global Impression of Severity (CGI-S) scales at baseline and at last assessment. Results: A total of 36 individuals were included (63.8% males, median age = 18 years, IQR 19): 94.4% with Tourette syndrome (TS), 2.8% with chronic tic disorder (CTD), and 2.8% with provisional tic disorder (PTD). A total of 86% had at least one psychiatric comorbidity, the most common being obsessive–compulsive symptomatology (OCS) (52%), anxiety (52%), and attention deficit hyperactivity disorder (ADHD) (35%). At last assessment, 26 patients (72.2%) were on undergoing PT for tics and 3 were receiving additional botulinum toxin. The most used medication for tics were aripiprazole (46.2%) and clonazepam (46.2%), and for psychiatric comorbidities, SSRIs (42.9%), methylphenidate (19%), and benzodiazepines (57.1%). Overall improvement according to the CGI-C scale was mild (CGI-C 3). Children and adolescents showed greater improvement than adults (CGI-C 2 vs. 3; p = 0.005). Aripiprazole and clonazepam produced similar outcomes in reducing CGI-C. Conclusions: We observed a favorable clinical course in patients treated with aripiprazole and clonazepam, which appear to be better than that obtained with other treatments. We consider that clonazepam may be useful as a first-line monotherapy and as an adjuvant for both tics and comorbidities in selected cases. Full article