An update on the pharmacological management of Tourette syndrome and emerging treatment paradigms.

INTRODUCTION: Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by tics. Pharmacotherapy is advised for patients whose symptoms affect their quality of life. AREAS COVERED: The authors review the tic phenomenology and TS diagnostic criteria. The bulk of this article focuses on pharmacotherapeutic options for treating tics. They also highlight pharmacotherapies in the research pipeline. EXPERT OPINION: Tic treatment must be tailored to individual needs. Behavioral therapy is the first line of treatment. Most with bothersome tics need pharmacotherapy and rarely, for medication-refractory cases, surgical therapy is indicated. Alpha-2 agonists are considered in patients with mild tics, especially in those with attention deficit with or without hyperactivity. Second-generation antipsychotics like aripiprazole and tiapride may be considered for severe tics. However, prescribers should be mindful of potential side effects, especially drug-induced movement disorders. Botulinum toxin injections may be considered for focal motor tics. Topiramate can be considered when other treatments are ineffective, and its benefits outweigh the risks. The same holds true for vesicular monoamine transporter-2 inhibitors, as they are deemed to be safe and effective in real-world use and open-label trials despite not meeting primary endpoints in placebo-controlled trials. Cannabinoids may be considered in adults if the approaches above do not control tics.

Prevalence of mass social media-induced illness presenting with Tourette-like behavior in Germany between 2019 and 2021.

Starting in 2019, in Germany the first well documented outbreak of mass sociogenic illness induced by social media (mass social media-induced illness; MSMI) occurred presenting with functional Tourette-like behaviors (FTB). This study aimed to provide first data on the prevalence rate of MSMI-FTB in Germany between 2019 and 2021 in the general population. We conducted a large-scale representative population survey in cooperation with the USUMA market and social research institute. Between August and December 2021, n = 2.509 people (mean age: 49.5 years, range: 16-95 years, n = 1.276 females) were randomly selected, visited in their households, interviewed, and asked to answer for themselves, but also for close family members (n = 6.744). Thus, in total, we received answers for n = 9.253 people. Probable MSMI-FTB was found in n = 33 individuals (mean age at onset: 30.5 years, n = 8 females). Based on strict criteria, the diagnosis of MSMI-FTB was considered highly likely in 16/33 individuals (mean age at onset: 25.6 years, n = 2 females) corresponding to prevalence rates of 0.17% (CIlower = 0.10, CIupper = 0.28) and 0.36% (CIlower = 0.25, CIupper = 0.50), respectively. This is the first large-scale, population representative study investigating the prevalence of MSMI-FTB in the general population in Germany between 2019 and 2021. Based on the prevalence rates found, MSMI-FTB is highly relevant for health economy. Accordingly, we suggest educating healthcare professionals and the general public to avoid misdiagnosis and inefficient treatment.

AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Chromatin regulators (CRs) are capable of causing epigenetic alterations, which are significant features of cancer. However, the function of CRs in controlling Clear Cell Renal Cell Carcinoma (ccRCC) is not well understood. This research aims to discover a CRs prognostic signature in ccRCC and to elucidate the roles of CRs-related genes in tumor microenvironment (TME). METHODS: Expression profiles and relevant clinical annotations were retrieved from the Cancer Genome Atlas (TCGA) and UCSC Xena platform for progression-free survival (PFS) data. The R package "limma" was used to identify differentially expressed CRs. A predictive model based on five CRs was developed using LASSO-Cox analysis. The model's predictive power and applicability were validated using K-M curves, ROC curves, nomograms, comparisons with other models, stratified survival analyses, and validation with the ICGC cohort. GO and GSEA analyses were performed to investigate mechanisms differentiating low and high riskScore groups. Immunogenicity was assessed using Tumor Mutational Burden (TMB), immune cell infiltrations were inferred, and immunotherapy was evaluated using immunophenogram analysis and the expression patterns of human leukocyte antigen (HLA) and checkpoint genes. Differentially expressed CRs (DECRs) between low and high riskScore groups were identified using log2|FC|> 1 and FDR < 0.05. AURKB, one of the high-risk DECRs and a component of our prognostic model, was selected for further analysis. RESULTS: We constructed a 5 CRs signature, which demonstrated a strong capacity to predict survival and greater applicability in ccRCC. Elevated immunogenicity and immune infiltration in the high riskScore group were associated with poor prognosis. Immunotherapy was more effective in the high riskScore group, and certain chemotherapy medications, including cisplatin, docetaxel, bleomycin, and axitinib, had lower IC50 values. Our research shows that AURKB is critical for the immunogenicity and immune infiltration of the high riskScore group. CONCLUSION: Our study produced a reliable prognostic prediction model using only 5 CRs. We found that AURKB promotes immunogenicity and immune infiltration. This research provides crucial support for the development of prognostic biomarkers and treatment strategies for ccRCC.

Randomized, double-blind, placebo-controlled trial of aripiprazole oral solution in children and adolescents with Tourette's disorder.

BACKGROUND: Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette's disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. METHODS: All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2-20 mg) with a starting dose of 2 mg. The target dose for patients weighing < 50 kg was 2, 5, and 10 mg/day, and that for patients weighing ≥ 50 kg was 5, 10, 15, and 20 mg/day. The primary efficacy endpoint was the mean change in the Yale Global Tic Severity Scale-total tic score (YGTSS-TTS) from baseline to week 8. RESULTS: Of the 121 patients enrolled, 59 patients (96.7%) in the aripiprazole group and 53 patients (88.3%) in the placebo group completed the study. The aripiprazole group showed significantly greater improvement in the YGTSS-TTS from baseline to week 8 than the placebo group (least squares mean difference [95% confidence interval (CI)] -5.5 [95% CI - 8.4 to - 2.6]). At week 8, the response rate (i.e., percentage of patients with a Tourette's Syndrome Clinical Global Impression-Improvement score of 1 or 2) of the aripiprazole group (86.4%) was significantly higher than that of the placebo group (56.6%; odds ratio: 3.6, p < 0.001). The incidence of treatment-emergent adverse events (TEAEs) reported in at least one patient was 86.9% in the aripiprazole group and 65.5% in the placebo group. All TEAEs were mild or moderate in severity. No serious adverse events or deaths occurred during the study. CONCLUSIONS: Our findings suggest that aripiprazole oral solution is an effective, well-tolerated, and safe treatment for children and adolescents with TD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03487783. Registered 4 April 2018.

PROTOCOL: Mindfulness-based interventions for improving tic-related symptoms in children and adults with chronic tic disorder and Tourette's disorder: A systematic review.

This is a protocol for a Cochrane Review (prototype). The objectives are as follows: This systematic review aims to summarize the available scientific literature on the effect of mindfulness-based approaches in children and adults with Chronic Tic Disorder (CTD) or Tourette Disorder (TD). More specifically, the research question is: What is the effectiveness of mindfulness-based interventions in reducing tic severity and improving overall functioning, quality of life, and co-occurring symptoms in children and adults with CTD or TD?

Bedtime Regularity and Sleep Sufficiency in Children With Tourette Syndrome.

BACKGROUND: Despite research demonstrating sleep disturbance in children with Tourette syndrome (TS), few studies have examined bedtime regularity and sleep sufficiency, two important sleep health dimensions. Therefore, this study examined bedtime regularity and sleep sufficiency in children with TS relative to matched healthy control subjects, and its associated demographic, clinical, and behavioral factors. METHODS: Participants were 384 parents or caregivers of children aged three to 17 years, including 192 with current TS and 192 matched healthy control subjects drawn from the 2020-2021 cycle of the National Survey of Children's Health. Parents completed questions assessing demographic (i.e., age, race, sex), clinical (i.e., attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder, anxiety, depression, tic severity, behavioral or conduct problems, ADHD medication, health condition-related impairment), and behavioral (i.e., screen time) characteristics. Mann-Whitney U test and chi-square test of independence were performed to compare groups on bedtime regularity and sleep sufficiency, respectively. Ordinal regression and binary logistic regression without and with backward elimination were performed to evaluate indicators of bedtime regularity and sleep sufficiency, respectively, in children with TS. RESULTS: Children with current TS had significantly poorer bedtime regularity, but not sleep sufficiency, relative to matched healthy control subjects. In children with TS, anxiety and two or more hours of daily screen time were associated with higher likelihood of poor bedtime regularity. Autism was associated with lower likelihood of insufficient sleep, and depression was associated with increased likelihood of insufficient sleep. CONCLUSIONS: Findings put forth screen time, anxiety, and depression as intervention targets to optimize sleep health in children with TS.

Functional Tic-like Behaviors: From the COVID-19 Pandemic to the Post-Pandemic Era.

During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis.

Gilles de la Tourette syndrome as a rare co-morbidity of Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (47, XXY) is the most common sex chromosome aneuploidy. In addition to male hypergonadotropic hypogonadism, a wide range of neurodevelopmental disorders, anxiety and affective symptoms have been reported in a substantial proportion of cases. CASE DESCRIPTION: We document the rare case of a 43-year-old man diagnosed with Klinefelter syndrome and co-morbid Gilles de la Tourette syndrome. He presented with multiple motor and vocal tics since adolescence, as well as anxiety and affective symptoms as his main tic-exacerbating factors. Tic severity was rated as marked (Yale Global Tic Severity Scale score of 78/100), and recommendations for the treatment of both tics and psychiatric co-morbidities were formulated. DISCUSSION: Neurodevelopmental tics in the context of Klinefelter syndrome have been previously documented in three cases only. Gilles de la Tourette syndrome is 3-4 times more common in males than females and its etiological factors include multiple genetic components (genetic heterogeneity). Our case report widens the spectrum of neurodevelopmental disorders observed in the context of Klinefelter syndrome and contributes to genetic research on the role of the X chromosome in the pathophysiology of tic disorders.

Clonidine Patch for Tourette Syndrome With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). METHODS: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. RESULTS: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. CONCLUSION: Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

Impacts of ADHD Symptomatology on the Response to Cognitive-Behavioural Therapy with Gilles de la Tourette Syndrome Patients.

(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.

Ocular Tics and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).

Little is known about ocular tics in Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections (PANDAS). In this retrospective study, we examined the clinical records of children with motor tics referred to the Ophthalmology Unit, Azienda Ospedaliero-Universitaria di Sassari, Italy, in 2010-2019. The presence of ocular tics was investigated. Data about antistreptolysin O (ASO) and anti-DNase B antibody titers, erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP), and antibiotic use were recorded. Forty children (thirty-four boys and six girls; mean age: 7.65 ± 2.5 years) with motor tics were identified; thirty-three (82.5%) showed ocular tics. Children with ocular tics had significantly higher titers of anti-DNase B antibodies (p = 0.04) and CRP (p = 0.016) than those with extraocular tics. A diagnosis of PANDAS was made in 24 (60%) children. PANDAS children with oculomotor tics had significantly higher titers of anti-DNase B antibodies (p = 0.05) than those with extraocular tics. Oral antibiotics were given to 25/33 (76%) children with ocular tics and 21/24 (87.5%) with PANDAS. All treated patients showed marked improvement/complete resolution of symptoms. Results suggest that higher titers of anti-DNase B antibodies may be implicated in the pathogenesis of ocular tics in PANDAS. Oral antibiotics may be beneficial in improving ocular tics. Further research is necessary to confirm our findings.

Trastorno por Déficit de Atención/Hiperactividad (TDAH) y Trastorno de Tourette (TT): entre la comorbilidad y el diagnóstico diferencial / Attention deficit/hyperactivity disorder (ADHD) and To urette disorder (TD): between comorbidity and differential diagnosis

Resumen El Trastorno de Tourette (TT) y el Trastorno por déficit de atención / hiperactividad (TDAH) son entidades neu ropsiquiátricas que usualmente inician en la infancia. Esta revisión busca colaborar con los clínicos, quienes suelen confrontarse al dilema de saber si existe una comorbilidad o un diagnóstico diferencial, ya que esta pregunta cobra vital importancia en el momento de decidir el tratamiento. Invitamos al colega a revisar nuestros hallazgos, soportados por bases moleculares, fisiológicas y neuroanatómicas, además de los datos epidemiológicos. Al final, brindamos una propuesta de algoritmo diag nóstico que podrá utilizar cuando se encuentre ante síntomas compartidos entre los dos diagnósticos. El TDAH y el TT deben ser intervenidos tempranamente, para mejorar la calidad de vida y funcionalidad del paciente y prevenir secuelas, no solo en niños, niñas y adolescentes (NNA), también a lo largo de la vida.

Abstract Tourette Disorder (TD) and attention deficit hyperac tivity disorder (ADHD) are both major neuropsychiatric conditions that usually begin during infancy. This revision aims to collaborate with pediatricians, who are often confronted with the question of co-mor bidity or differential diagnosis between ADHD and TD. The question becomes urgent when the clinician must decide if he/she can start ADHD or TD treatment. We encourage our colleagues to revise our findings, based in bimolecular and neuroanatomic shared issues in ad dition to updated epidemiological findings. The clinician will find an original proposed algorithm that they can use when the shared symptoms are pres ent in a little patient. TD and ADHD must be intervened early, so we can get better outcomes. The consequences of letting the symptoms increase can generate sequels and handicaps, that can interfere with the quality of life and functionality not only during infancy and adoles cence but also in adult life.

Comparing the 'When' and the 'Where' of Electrocortical Activity in Patients with Tourette Syndrome, Body-Focused Repetitive Behaviors, and Obsessive Compulsive Disorder.

Background/Objectives: Tourette Syndrome (TS), Obsessive Compulsive Disorder (OCD), and Body-Focused Repetitive Behaviors (BFRB) are three disorders that share many similarities in terms of phenomenology, neuroanatomy, and functionality. However, despite the literature pointing toward a plausible spectrum of these disorders, only a few studies have compared them. Studying the neurocognitive processes using Event-Related Potentials (ERPs) offers the advantage of assessing brain activity with excellent temporal resolution. The ERP components can then reflect specific processes known to be potentially affected by these disorders. Our first goal is to characterize 'when' in the processing stream group differences are the most prominent. The second goal is to identify 'where' in the brain the group discrepancies could be. Methods: Participants with TS (n = 24), OCD (n = 18), and BFRB (n = 16) were matched to a control group (n = 59) and were recorded with 58 EEG electrodes during a visual counting oddball task. Three ERP components were extracted (i.e., P200, N200, and P300), and generating sources were modelized with Standardized Low-Resolution Electromagnetic Tomography. Results: We showed no group differences for the P200 and N200 when controlling for anxiety and depressive symptoms, suggesting that the early cognitive processes reflected by these components are relatively intact in these populations. Our results also showed a decrease in the later anterior P300 oddball effect for the TS and OCD groups, whereas an intact oddball effect was observed for the BFRB group. Source localization analyses with sLORETA revealed activations in the lingual and middle occipital gyrus for the OCD group, distinguishing it from the other two clinical groups and the controls. Conclusions: It seems that both TS and OCD groups share deficits in anterior P300 activation but reflect distinct brain-generating source activations.

French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

Coping with Tourette's syndrome: a meta-ethnography of individual and family perspectives.

OBJECTIVE: This systematic review and meta-ethnography aimed to examine how children, adults and families cope with Tourette's syndrome (TS). METHODS: A systematic search of four databases was completed in October 2022. Sixteen papers met the inclusion criteria and were synthesised using Noblit and Hare's (1988) meta-ethnographic approach. RESULTS: Three themes were constructed: redefining the self and social identity, controlling the visible presentation of Tourette's syndrome, and challenging the narrative. CONCLUSION: Findings indicate that coping involves the need to integrate TS with identity, to exert control over tics and to challenge the misrepresentations of TS in wider society. A supportive environment provided by parents and friends enables individuals to feel proud that they can control their tics, and this allows for the positive integration of TS into identity. Raising awareness at a societal level through educational campaigns is important when aiming to improve coping with a stigmatised condition. Further research is recommended, for example, to understand how common co-occurring conditions, such as attention deficit hyperactivity disorder, impact coping.

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

BACKGROUND AND OBJECTIVE: The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. METHODS: In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. RESULTS: From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. CONCLUSIONS: DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

Predictors of Impairment and Self-Concept in Children and Adolescents with Persistent Tic Disorder.

This study examined predictors of, and associations between, self-concept, demographic variables, and clinical measures in fifty-eight children and adolescents with Persistent Tic Disorder (PTD; 44 males, Mage = 11.9 years, SD = 2.74). Participants completed measures that assessed self-concept, tic severity, tic-related impairment, and comorbid psychological symptoms. Results showed that generalized anxiety disorder, major depressive disorder, persistent depressive disorder, total tic severity, number and complexity of tics, and total and social tic-related impairment were associated with self-concept. Tic-related social impairment mediated the relationship between tic severity and self-concept. Exploratory analyses found that total tic severity, motor tic severity, and vocal tic severity, as well as the number, intensity, and interference of tics predicted social tic-related impairment. Results suggest that treatments to reduce the number and complexity of tics, with additional focus on navigating social interactions, may serve to decrease tic severity and impairment, and in turn, improve self-concept.

A Test of the Behavioral Model of Tic Disorders Using a Dynamical Systems Framework.

Tic disorders are a class of neurodevelopmental disorders characterized by involuntary motor and/or vocal tics. It has been hypothesized that tics function to reduce aversive premonitory urges (i.e., negative reinforcement) and that suppression-based behavioral interventions such as habit reversal training (HRT) and exposure and response prevention (ERP) disrupt this process and facilitate urge reduction through habituation. However, previous findings regarding the negative reinforcement hypothesis and the effect of suppression on the urge-tic relationship have been inconsistent. The present study applied a dynamical systems framework and within-subject time-series autoregressive models to examine the temporal dynamics of urges and tics and assess whether their relationship changes over time. Eleven adults with tic disorders provided continuous urge ratings during separate conditions in which they were instructed to tic freely or to suppress tics. During the free-to-tic conditions, there was considerable heterogeneity across participants in whether and how the urge-tic relationship followed a pattern consistent with the automatic negative reinforcement hypothesis. Further, little evidence for within-session habituation was seen; tic suppression did not result in a reduction in premonitory urges for most participants. Analysis of broader urge change metrics did show significant disruption to the urge pattern during suppression, which has implications for the current biobehavioral model of tics.

Evaluation of a psychoeducation group for children presenting with functional tic-like behaviours.

We describe the implementation and evaluation of an online psychoeducation group for young people experiencing functional tic-like behaviours (FTLBs) - a type of functional neurological disorder (FND). Across six groups, 50 participants completed pre- and post-group goal-based outcomes (GBOs) and 36 participants completed service-user feedback, which gathered qualitative and quantitative data about participants experiences of the group. Young people and their parents reported significant improvement in their GBOs following the group and increased knowledge and confidence in managing FTLBs. The findings highlight that virtual psychoeducation group intervention is an acceptable and effective first step in treatment of young people with FTLBs. We discuss implications for future intervention development.

We describe an online psychoeducation group for young people experiencing functional tic-like behaviours (FTLBs) ­ a type of functional neurological disorder (FND). Across six groups, 50 participants completed goal-based outcomes (GBOs) before and after the intervention. A total of 36 participants completed service-user feedback, which gathered data about participants experiences of the group. Young people and their parents reported significant improvement in their GBOs following the group and increased knowledge and confidence in managing FTLBs. The findings highlight that virtual psychoeducation group intervention is an acceptable and effective first step in treatment of young people with FTLBs. We discuss implications for future intervention development.