Motor Tics Research Articles

Safety and Efficacy of Long-Term Deutetrabenazine Use in Children and Adolescents with Tics Associated with Tourette Syndrome: An Open-Label Extension Study.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS. Alternatives for Reducing Tics in TS (ARTISTS) open-label extension (OLE) (NCT03567291) was a 54-week, global, phase 3, open-label extension study of deutetrabenazine (6-48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2-week randomized withdrawal period. Participants (6-16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by treatment-emergent adverse events (TEAEs) and clinical laboratory testing. Efficacy was measured by the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS). The intent-to-treat population (228 participants; mean age, 12.0 years; 79.8% male; 86.4% white) had a median (range) duration of exposure of 28.4 (0.3-52.9) weeks. Of 227 participants in the safety analysis, 161 (70.9%) reported ≥1 TEAE (exposure-adjusted incidence rate, 2.77/patient-year), of which 95 (41.9%) were treatment related. The most frequently reported TEAEs were headaches, somnolence, nasopharyngitis, weight increases, and anxiety. No additional safety signals were observed. Worsening of YGTSS-TTS after the 2-week randomized withdrawal was not statistically significant (least squares mean difference, -0.4; P = 0.78). Several exploratory measures showed sustained improvement throughout the treatment periods. In this long-term, open-label trial, deutetrabenazine was well tolerated with low frequency of TEAEs. There was no significant difference in tics between treatment arms during the 2-week randomized withdrawal period, however, descriptive statistics and comparison with baseline showed a numeric improvement in tics, quality of life, and other measures.

The Dysfunctional Mechanisms Throwing Tics: Structural and Functional Changes in Tourette Syndrome.

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.

Clinical correlates, characteristics and comorbidities of paediatric tic disorders

Background: Tic disorders are complex neuropsychiatric disorders of childhood onset. The associated comorbidities in paediatric tic disorders are of vast importance as they account for the major functional impairment in these children, data of which is lacking in our Indian context. Methods: Descriptive Cross-sectional study conducted among children of 3-15 years of age in child psychiatry department of Institute of Child health, Egmore, Chennai Results: In this study 60 patients were studied of whom 47 were male and 13 were females. Comorbid psychiatric disorders were present in 38 (63.3%) children. They were ADHD (48.3%), OCD (6.6%), ASD (6.6%), SLD (20%), Behavioural problems in 16.6%. Motor tics were the most common type of tics. Significant correlation between tic severity and presence of comorbid psychiatric disorders was seen. Conclusions: Tic disorders are not completely benign and simple as it is thought. Tic disorders usually present with associated comorbidities, which cause more impairment than tics themselves. ADHD is the most common comorbidity associated with paediatric tic disorders.

Group-based comprehensive behavioral intervention for tics (CBIT) for adults with Tourette syndrome or chronic tic disorders: A pilot study.

Comprehensive behavioral intervention for tics (CBIT) administered individually is an effective treatment for tics. However, the effectiveness of CBIT administered in groups for adults with Tourette syndrome and chronic tic disorders has not been investigated yet. This pilot study examined the effectiveness of group-based CBIT with respect to reduction of tic severity and tic-related impairment, as well as improvement of tic-related quality of life. Data from 26 patients were included in the intention-to-treat analyses. The Yale Global Tic Severity Scale was used to assess total tic severity and tic-related impairment. The Gilles de la Tourette - Quality of Life Scale was used to assess tic-related quality of life. These measures were administered at three points in time: at pretreatment, posttreatment, and 1-year follow-up. The results showed a significant reduction of total tic severity from pretreatment to 1-year follow-up, with larges effect sizes. Tic-related impairment and tic-related quality of life also improved significantly, although the effect sizes were smaller. Motor tics showed a stronger reduction than vocal tics. Additional analysis revealed that all change was achieved during treatment and that this effect was maintained from posttreatment to 1-year follow-up. The results of this study indicate that group-based CBIT is a promising treatment for tics.

Clinical characteristics of comorbid tic disorders in autism spectrum disorder: exploratory analysis

BackgroundThe frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear.MethodsWe included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4–18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive–Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26.ResultsTic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70).ConclusionsThe IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD.Trial registration This study retrospectively registered participants

Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome

BackgroundTourette syndrome is characterized by chronic motor and vocal tics. There is preliminary evidence of benefit from cannabis products containing Δ9-tetrahydrocannabinol (THC) and that coadministration of cannabidiol (CBD) improves the side-effect profile and safety.MethodsIn this double-blind, crossover trial, participants with severe Tourette syndrome were randomly assigned to a 6-week treatment period with escalating doses of an oral oil containing 5 mg/ml of THC and 5 mg/ml of CBD, followed by a 6-week course of placebo, or vice versa, separated by a 4-week washout period. The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0 to 50 [higher scores indicate greater severity of symptoms]). Secondary outcomes included video-based assessment of tics, global impairment, anxiety, depression, and obsessive-compulsive symptoms. Outcomes were correlated with plasma levels of cannabinoid metabolites. A computerized cognitive battery was administered at the beginning and the end of each treatment period.ResultsOverall, 22 participants (eight female participants) were enrolled. Reduction in total tic score (at week 6 relative to baseline) as measured by the YGTSS was 8.9 (±7.6) in the active group and 2.5 (±8.5) in the placebo group. In a linear mixed-effects model, there was a significant interaction of treatment (active/placebo) and visit number on tic score (coefficient = −2.28; 95% confidence interval, −3.96 to −0.60; P=0.008), indicating a greater decrease (improvement) in tics under active treatment. There was a correlation between plasma 11-carboxy-tetrahydrocannabinol levels and the primary outcome, which was attenuated after exclusion of an outlier. The most common adverse effect in the placebo period was headache (n=7); in the active treatment period, it was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration (n=8).ConclusionsIn severe Tourette syndrome, treatment with THC and CBD reduced tics and may reduce impairment due to tics, anxiety, and obsessive-compulsive disorder; although in some participants this was associated with slowed mentation, memory lapses, and poor concentration. (Funded by the Wesley Medical Research Institute, Brisbane, and the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically-funded research organization at the University of Sydney, Australia; Australian and New Zealand Clinical Trials Registry number, ACTRN12618000545268.)

How brain networks tic: Predicting tic severity through rs-fMRI dynamics in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and phonic tics, which several different theories, such as basal ganglia-thalamo-cortical loop dysfunction and amygdala hypersensitivity, have sought to explain. Previous research has shown dynamic changes in the brain prior to tic onset leading to tics, and this study aims to investigate the contribution of network dynamics to them. For this, we have employed three methods of functional connectivity to resting-state fMRI data - namely the static, the sliding window dynamic and the ICA based estimated dynamic; followed by an examination of the static and dynamic network topological properties. A leave-one-out (LOO-) validated regression model with LASSO regularization was used to identify the key predictors. The relevant predictors pointed to dysfunction of the primary motor cortex, the prefrontal-basal ganglia loop and amygdala-mediated visual social processing network. This is in line with a recently proposed social decision-making dysfunction hypothesis, opening new horizons in understanding tic pathophysiology.

Applying an Established Exposure Response Prevention Protocol for Young People With Tourette Syndrome in an Intensive, Group Format: A Feasibility Study.

The motor and vocal tics that characterise Tourette syndrome are stigmatizing and impact on quality of life. Behavioural interventions such as Exposure Response Prevention or Comprehensive Behavioural Interventions for Tics are first line treatment for Tourette syndrome, but availability is limited. This study is the first to explore the impact of an established manualised Exposure Response Prevention treatment protocol, developed for individual therapy, but here uniquely delivered intensively, to a group. A naturalistic study comprised of a consecutive series of children (N = 20), aged 8-16years (M = 12, SD = 2.17) were offered Exposure Response Prevention in one of two groups, delivered in series within a specialist clinic. Young people received the equivalent of 12 sessions (matching the manualised individual protocol). The YGTSS and Giles de la Tourette Syndrome Quality of Life Scale for Children and Adolescents (Satisfaction Scale) showed significant improvement following treatment with moderate to large effect sizes. Thirty-five percent of children demonstrated a reliable improvement on the YGTSS Global Tic Severity score. These data suggest an established Exposure Response Prevention protocol can be delivered in an intensive, group setting with a positive clinical outcome. Replication in a randomized controlled trial is an important next step.

Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission.

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behaviour, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments and behavioural measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette syndrome. We employed this model under light anaesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behaviour. The improvement in tic behaviour was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.

Contrasting features between Tourette syndrome and secondary tic disorders.

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve muscles in the cranial-cervical area more often and have greater severity and complexity than those in patients with STD. Similar findings were observed when contrasting patients with TS with patients with functional tics only. Simple phonic tics showed the greatest diagnostic accuracy for TS, compared with STD, but marked overlap in the types of tics and comorbidities was observed between patients with TS and STD. Patients with TS were more likely males, had a younger age at onset, phonic tics and motor tics affecting predominantly the head and neck area, and had a greater complexity and severity of tics than those with STD. When these features are absent a consideration should be given to the possibility of a tic disorder other than TS.

Increasing Ecopipam Exposure Improves Yale Global Tic Severity Scale-Total Tic Scores (YGTSS-TTS) in Children and Adolescents with Tourette Syndrome (TS): Results from a Population Pharmacokinetic (popPK) Model-Based Simulation Using D1AMOND Trial Data (P5-9.007)

<h3>Objective:</h3> To develop popPK and exposure-response (E-R) models to characterize the relationship between ecopipam concentrations and efficacy as well as safety in children and adolescents (ages 6 to &lt;18 years) with TS. <h3>Background:</h3> Ecopipam is a first-in-class selective dopamine-1 receptor antagonist in development for TS. Results from the 12-week randomized, double-blind placebo-controlled phase 2b D1AMOND trial demonstrated 2 mg/kg/day ecopipam significantly reduced motor and phonic tics (YGTSS-TTS) and was well-tolerated. Understanding the PK of ecopipam and its active metabolite, the intrinsic/extrinsic factors affecting variability, and the relationships between exposure and efficacy/safety in TS are key to perform model-based simulations to ensure the optimal dose in TS. <h3>Design/Methods:</h3> In D1AMOND, a responder was defined as a ≥25% improvement in YGTSS-TTS. Logistic regression modeling was used to determine the relationship between responder status and exposure (area-under-the-curve, AUC) of ecopipam and its active metabolite (E+M) in children and adolescents with TS. <h3>Results:</h3> The steady-state (E+M) AUC exposure predicted clinical YGTSS-TTS responders at week 12. A 2-compartment model with first-order absorption and elimination described plasma concentration-time data for ecopipam and a 1-compartment model with first order elimination described the active metabolite concentration-time data. The final logistic regression model was based on the combined steady-state AUC for E+M as a univariate predictor for a clinical responder. The odds of ≥25% improvement in YGTSS-TTS increased near linearly by 6.8% for each 100 unit increase in E+M steady-state AUC. E-R modeling of safety parameters was not performed as there were not enough adverse events in the study to model. <h3>Conclusions:</h3> These data demonstrate a positive relationship between ecopipam exposure and efficacy in pediatric patients with TS. This study validates the D1AMOND trial ecopipam dosing and informed the posology for a confirmatory Phase 3 trial, currently recruiting patients. <b>Disclosure:</b> Dr. Freidy has received personal compensation for serving as an employee of Allucent. Dr. Pene Dumitrescu has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Allucent. Dr. Pene Dumitrescu has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for TEVA Pharmaceutics. Dr. Pene Dumitrescu has stock in GlaxoSmithkline. Dr. Schmith has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Emalex Biosciences. Dr. Schmith has received research support from Emalex BIosciences. The institution of Dr. Gilbert has received research support from NIMH. The institution of Dr. Gilbert has received research support from Emalex. The institution of Dr. Gilbert has received research support from Erydel. The institution of Dr. Gilbert has received research support from PTC Therapeutics. Dr. Gilbert has received publishing royalties from a publication relating to health care. Dr. Gilbert has received publishing royalties from a publication relating to health care. Dr. Gilbert has received personal compensation in the range of $500-$4,999 for serving as a Medical Second Opinion Expert with Teldoc/Advanced Medical. Dr. Gilbert has received personal compensation in the range of $5,000-$9,999 for serving as a Medical Expert with Department of Health and Human Services/Vaccine Injury Compensation Program. Atul Mahableshwarkar has received personal compensation for serving as an employee of Emalex Biosciences. Atul Mahableshwarkar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ecor1 Capital. Atul Mahableshwarkar has stock in Johnson &amp; Johnson. Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Paragon Biosciences. Dr. Dubow has stock in Avadel Pharmaceuticals. Dr. Cunniff has received personal compensation for serving as an employee of Paragon Biosciences. Dr. Cunniff has stock in Harmony Biosciences. Dr. Cunniff has stock in Emalex Biosciences. Mr. Kim has received personal compensation for serving as an employee of Emalex Biosciences. Mrs. Miller has received personal compensation for serving as an employee of Emalex Biosciences. Mrs. Miller has stock in Emalex Biosciences. Dr. Wanaski has received personal compensation for serving as an employee of Paragon Biosciences. Dr. Wanaski has stock in Paragon Biosciences.

Characterizing Functional Tics (P11-11.014)

<h3>Objective:</h3> To assess the characteristics of patients presenting with functional tics (FT) at two different pediatric neurology sites. A subaim was to assess for differences in presentations of FT between cisgender versus non-binary or transgender youth. <h3>Background:</h3> In the years between 2020 and 2022, coinciding with the COVID-19 pandemic, we have seen a large increase in the incidence of functional tics in adolescents (ages 12–18 years). Understanding how FT differs from tic disorders and whether FT presents differently among gender identity groups may help to better identify FT in individuals. <h3>Design/Methods:</h3> We conducted a systematic chart review at two different sites using the Epic Electronic Medical Record System of the Pediatric Neurology Departments at Strong Memorial Hospital in Rochester, NY (UR) and at Atrium Health Wake Forest Baptist in Winston-Salem, NC (WF). <h3>Results:</h3> There were 83 subjects, 37 of whom were patients at UR and 46 at WF. The average age of onset of FT was 13.6 years old with 5% male, 70% female, 12% transgender female-to-male, 13% nonbinary or gender fluid. At onset, 76% of patients had complex tics, 45% had abusive behavior, 73% had motor tics which localized below the neck, and 55% had contextual or specific triggers to tics. 37% endorsed exposure to tics by social media or peers. The two most common co-occurring conditions were anxiety (69%) and depression (51%). There was no significant difference in phenomenology of FT in cisgender versus non-binary or transgender youth. <h3>Conclusions:</h3> Functional tics were more common in adolescent females and were associated with more complex presentation at onset than tic disorders. There was no significant difference in age of onset, symptomatology, and treatment of FT in cisgender versus non-binary or transgender youth. <b>Disclosure:</b> Miss Nguyen has nothing to disclose. Mr. Wang has nothing to disclose. Dr. Vermilion has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. The institution of Dr. Vermilion has received research support from Tourette Association of America, American Academy of Neurology and American Brain Foundation. Dr. Martindale has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Tourette Association of America. The institution of Dr. Martindale has received research support from Tourette Association of America.

Gender Identity and Treatment Response in Patients with Functional Tic-Like Behavior (P12-11.013)

<h3>Objective:</h3> To add to the limited existing reports on the demographics, clinical history, phenomenology, and treatment response of patients with functional tic-like behavior (FTLB), with the addition of gender-identity associations. <h3>Background:</h3> Reported numbers of young adults presenting with FTLB has increased recently, partly related to the COVID-19 pandemic and social media. Patients with FTLB are predominantly young females with rapid symptom onset. Gender identity has not been assessed. Response to therapy and medications has been variable. <h3>Design/Methods:</h3> This single-center case series included patients that presented to the Northwestern University Parkinson’s Disease and Movement Disorders Center with FTLB between February and September 2021. <h3>Results:</h3> The mean age of onset and diagnosis were 22 and 22.4 years old (n=8), respectively. All patients were female sex at birth, and 5 (62.5%) identified their gender as non-binary. Three patients (37.5%) had comorbid functional neurological disorders. The majority (n=7, 87.5%) had depression and anxiety, 2 (25%) had ADHD, and 2 (25%) had OCD. Three-quarters (n=6, 75%) of patients were on psychiatric medications. Half (n=4, 50%) of the patients used substances, including alcohol, nicotine, marijuana, or drugs. One patient had isolated motor tics and the rest (n=7, 87.5%) had complex motor and verbal tic-like movements with frequent self-injurious behavior. All patients were recommended to start comprehensive behavioral intervention for tics with habit reversal therapy (CBIT/HRT), guanfacine, and gingko biloba. One year follow up was available for 5 patients. Tics improved in 2 patients (25%) following CBIT/HRT and in 1 patient (12.5%) using guanfacine and gingko biloba. Tics were stable in 2 patients (25%) without intervention. <h3>Conclusions:</h3> All patients were young adults of female sex, with abrupt onset of FTLB during the COVID-19 pandemic. Interestingly, the majority identified their gender as non-binary. Several patients experienced tic reduction after using CBIT/HRT, alpha-agonists, and/or gingko biloba, suggesting that these may be beneficial treatments. <b>Disclosure:</b> Dr. Kola has nothing to disclose. Dr. Larson has received personal compensation in the range of $0-$499 for serving as a Consultant for Acadia Pharmaceuticals.

Premonitory Urge and Tic Severity, Comorbidities, and Quality of Life in Chronic Tic Disorders.

Tics are intimately associated with premonitory urges (PU) but knowledge about urges is still limited, with small sample sizes often limiting the generalizability of findings. This study addressed the following open questions: (1) is tic severity associated with urge severity, (2) how common is relief, (3) which comorbidities are associated with urges, (4) are urges, tics, and comorbidities associated with lower quality of life, and (5) can complex and simple, motor and vocal tics be differentiated based on PU? N = 291 patients who reported a confirmed diagnosis of chronic primary tic disorder (age = 18-65, 24% female) filled out an online survey assessing demographic data, comorbid conditions, location, quality and intensity of PU, as well as quality of life. Every tic was recorded, and whether the patient experienced a PU, the frequency, intensity, and quality of that urge. PU and tic severity were significantly associated, and 85% of urge-related tics were followed by relief. A diagnosis of attention deficit/hyperactivity disorder (ADHD) or depression, female gender, and older age increased the likelihood of experiencing PU, while more obsessive compulsive (OCD) symptoms and younger age were associated with higher urge intensities. PU, complex vocal tics, ADHD, OCD, anxiety, and depression were related to lower quality of life. Motor and vocal, complex and simple tics did not differ regarding PU intensity, frequency, and quality, or relief. The results shed light on the relationship between PU, tics, comorbidities, age, gender, and quality of life in tic disorders.

Integrated UPLC-MS, network pharmacology, and intestinal flora analysis to determine the treatment effect of Qiangzhi decoction on comorbid Tourette syndrome and RRTI.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.

Brief Youth Self-Report Screener for Tics: Can a Subscale of the Motor Tic, Obsession and Compulsion, and Vocal Tic Evaluation Survey (MOVES) Identify Tic Disorders in Youth?

ABSTRACT Tics are unwanted, repetitive movements and sounds that frequently present during childhood. They are typically brief and purposeless, but can create significant distress for individuals, and often co-occur with other neuropsychiatric conditions. Thus, early identification of tics is warranted. Unfortunately, tics are often misdiagnosed, and because tics may wax and wane, identification can be difficult, especially in the context of routine clinical visits. There are limited tools that can be used to reliably identify tics in clinical practice, especially in non-specialty settings. The purpose of the current study was to evaluate the performance of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES), a self-report scale with some support as a screening tool. In addition, the performance of a subset of questions (the MOVES-6) was evaluated for rapid screening. Participants were recruited across two study sites and included children and adolescents diagnosed with Tourette syndrome (n = 151) or another persistent tic disorder (n = 10) and community controls (n = 74). Results suggest that both MOVES and the MOVES-6 have high sensitivity (90% and 88%, respectively) and at least acceptable specificity (77% and 86%, respectively) compared with expert assessment of tic disorders, suggesting that both versions can identify tic disorders without high proportions of false negatives. Both versions were highly sensitive with acceptable specificity regardless of sex, race/ethnicity, and age. The MOVES and MOVES-6 show promise as a screener for tics or tic disorders, but additional research is needed, particularly in a general population setting.

Volkameria inermis: An overview of its chemical constituents and pharmacological properties, notably the amelioration of motor tics

This overview on Volkameria inermis (Lamiaceae) is the first in updating information on the chemical constituents and pharmacological properties of the species, notably on its unique ability in ameliorating motor tics. The information was procured from Google, Google Scholar, PubMed, PubMed Central, Science Direct, J-Stage, and PubChem. Previously named Clerodendrum inerme (Verbenaceae), V. inermis is a scrambling or scandent coastal shrub in the tropics and sub-tropics. From different parts of the plant, compounds such as flavonoids, diterpenes/diterpenoids, sterols, triterpenes/triterpenoids, iridoid glycosides, phenolic glycosides, phenylethanoid glycosides (PEGs), phenylpropanoid glycosides (PPGs), chalcones, and sesquiterpenes have been reported. Major pharmacological properties of V. inermis include anti-cancer, anti-inflammatory, antioxidant, hepatoprotective, analgesic, and antibacterial activities. Other properties include anti-tyrosinase, antifungal, neuroprotective, hypotensive, hypoglycemic, amyloid-β aggregation, wound healing, antipyretic, and larvicidal activities. A unique pharmacological property of V. inermis leaf extract, discovered by scientists from Taiwan, is the amelioration of motor tic disorders, a spectrum of Tourette syndrome. This property included a case report, three in vivo studies, and one patent. Areas of further research of V. inermis are suggested.

The Clinical Characterization of Blocking Tics in Patients With Tourette Syndrome

Objective Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. Blocking phenomena, characterized by arrests in motor activity causing interruptions in movements or speech, have also been described in patients with TS. In this study, we aimed to characterize the frequency and features of blocking tics in patients with TS. Methods We studied a cohort of 201 patients with TS evaluated at our movement disorders clinic. Results We identified 12 (6%) patients with blocking phenomena. Phonic tic intrusion causing speech arrest was the most common (n = 8, 4%), followed by sustained isometric muscle contractions arresting body movements (n = 4, 2%). The following variables were statistically related to blocking phenomena: shoulder tics, leg tics, copropraxia, dystonic tics, simple phonic tics, and number of phonic tics per patient (all p < 0.050). In the multivariate regression, the presence of dystonic tics (p = 0.014) and a higher number of phonic tics (p = 0.022) were associated with blocking phenomena. Conclusion Blocking phenomena are present in approximately 6% of patients with TS, and the presence of dystonic tics and a higher frequency and number of phonic tics increase the risk for these phenomena.

Pre-movement gating of somatosensory evoked potentials in Tourette syndrome

ObjectiveTourette syndrome (TS) is a neurobehavioral disorder characterized by motor and vocal tics. Simple tics are purposeless involuntary movements that spontaneously resolve during middle adolescence. Complex tics appear to be semi-voluntary movements that may become intractable when associated with obsessive–compulsive disorder (OCD). Sensory tics or urges preceded by tics suggest sensorimotor processing impairment in TS. We aimed to clarify its pathophysiology by exploring the pre-movement gating (attenuation) of somatosensory evoked potentials (SEPs). MethodsWe examined 42 patients (aged 9–48 years), 4 of whom underwent follow-up assessment, along with 19 healthy controls. We defined patients with only simple tics as TS-S and patients with complex tics as TS-C. Pre-movement gating of SEPs was assessed using a previously described method. Frontal N30 (FrN30) amplitudes were compared between pre-movement and resting states. The gating ratio of pre-movement/resting amplitude of the FrN30 component was assessed: the larger the ratio, the less the gating. ResultsThe gating ratio for TS-C patients was larger than that of TS-S patients and healthy controls, but a statistical difference between TS-S and TS-C appeared after 15 years and over (p < 0.001). There were no significant differences in the gating ratio between TS-S patients and healthy controls. The gating ratio was related to the severity of OCD (p < 0.05). ConclusionSensorimotor processing was preserved for simple tics but impaired in complex tics, specifically after middle adolescence. Our study supports an age-dependent dysfunction of both motor and non-motor cortico-striato-thalamo-cortical circuits in complex tics. SEP gating seems promising as a tool for assessing age-dependent sensorimotor disintegration in TS.

Have We Forgotten What Tics Are? A Re-Exploration of Tic Phenomenology in Youth with Primary Tics.

The first systematic description of tics in a large sample was in 1978. To assess the phenomenology of tics in youth and investigate how age and sex influence tic phenomenology. Children and adolescents with primary tic disorders have been prospectively included in our Registry in Calgary, Canada, since 2017. We examined tic frequency and distribution using the Yale Global Tic Severity Scale, differences between sexes, and changes in tic severity with age and with mental health comorbidities. A total of 203 children and adolescents with primary tic disorders were included (76.4% males; mean age=10.7 years, 95% CI=10.3-11.1). At first assessment, the most common simple motor tics were eye blinking (57%), head jerks/movements (51%), eye movements (48%) and mouth movements (46%); 86% had at least one simple facial tic. The most frequent complex motor tics were tic-related compulsive behaviors (19%). Throat clearing was the most common simple phonic tic (42%); 5% only had coprolalia. Females had higher frequency and intensity of motor tics than males (P= 0.032 and P= 0.006, respectively), associated with greater tic-related impairment (P= 0.045). Age was positively correlated with the Total Tic Severity Score (coefficient 0.54, P= 0.005), along with the number, frequency and intensity of motor tics but not with their complexity. Psychiatric comorbidities were associated with greater tic severity. Our study suggests that age and sex affect clinical presentation in youth with tics. The phenomenology of tics in our sample was similar to the 1978 description of tics, and contrasts with functional tic-like behaviors.