Treatment Of Tourette Syndrome Research Articles

Progress in the Treatment of Tourette Syndrome

Progress in the Treatment of Tourette Syndrome

Exploring the material basis and molecular targets of Changma Xifeng tablet in treating Tourette syndrome: an integrative approach of network pharmacology and miRNA analysis.

This study was to investigate the mechanism of Changma Xifeng tablet, a traditional Chinese medicine in the treatment of Tourette syndrome. Network pharmacology was utilized to pinpoint blood-entering constituents of Changma Xifeng and explore their potential targets. Additionally, differential microRNA expression analysis was conducted to predict Tourette syndrome-associated targets, complemented by molecular docking and dynamics simulations to support the interactions of the active compounds with these targets. The study identified 98 common targets between Changma Xifeng and Tourette syndrome, which may be involved in the treatment process. A protein-protein interaction network and a drug-active ingredient-disease target network highlighted the formulation's multi-component, multi-target therapeutic approach. Eight pivotal targets-AR, GRM5, MET, RORA, HTR2A, CNR1, PDE4B, and TOP1-were identified at the intersection of microRNA and drug targets. Molecular docking revealed 12 complexes with favorable binding energies below - 7kcal/mol, specifically: AR with Alfacalcidol, TOP1 with Albiflorin, GRM5 with Arachidic Acid, GRM5 with Palmitic Acid, AR with Arachidic Acid, AR with 2-Hydroxyoctadecanoic Acid, RORA with Pinellic Acid, RORA with Palmitic Acid, AR with Acoronene, AR with Epiacoronene, AR with 4,4'-Methylenediphenol, and HTR2A with Calycosin. Our molecular docking and molecular dynamics simulations suggest potential stable interactions between the formulation's active components and target proteins. These computational methods provide a preliminary theoretical framework that will guide our future experimental work. The study provides a scientific rationale for the use of traditional Chinese medicine in Tourette syndrome management and offers new insights for drug development.

Efficacy and Safety of Acupuncture for Tourette Syndrome in Children: A Meta-Analysis and Systematic Review.

Despite the widespread use of acupuncture, its effectiveness and safety in treating Tourette syndrome (TS) remain controversial. Our research seeks to further evaluate the safety and effectiveness of acupuncture as a replacement therapy approach for children with TS. We conducted a comprehensive search for studies published from their inception to October 2023. The statistical analysis and subgroup analysis were conducted by software. Conduct a meta-analysis on the extracted data using the appropriate effect models. The meta-analysis was conducted on 26 studies consisting 1862 pediatric patients, which were selected from 976 identified articles. Acupuncture group demonstrated a significantly lower risk with a risk ratio (RR) of 0.29 (95% confidence interval [CI] = 0.19, 0.44, P < .0001), with only 5% of participants experiencing adverse reactions. Acupuncture treatment resulted in an 18% improvement in total effectiveness rates (RR = 1.18, 95% CI = [1.12, 1.25], P < .00001). The pooled data demonstrated that acupuncture therapy had a significant advantage in reducing the total score with the weighted mean difference (WMD) -4.92 (95% CI = [-6.38, -3.45], P < .00001) of the Yale Global Tic Severity Scale (YGTSS), the motor tic scores (WMD = -2.24, 95% CI = [-3.14, -1.35], P < .00001), the vocal tic scores (WMD: -2.34, 95% CI = [-3.31, -1.37], P < .00001), and the Traditional Chinese Medicine Syndrome Scores (TCMSS) (WMD: -2.47, 95% CI = [-2.87, -2.07], P < .0001). This meta-analysis reveals that acupuncture is more effective than most existing treatments in mitigating the symptoms of motor and vocal tics in children with TS, while also reducing the incidence of adverse reactions.

Network analysis of Tourette syndrome and attention-deficit/hyperactivity disorder symptoms in children and adolescents

BackgroundWhile Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD) often co-occur, the nature of the relationship between their symptoms is not well understood. Network analysis of psychopathology allow for detailed examinations of symptom interactions, providing an effective approach to explore the patterns of comorbidity between TS and ADHD symptoms.MethodsThis study included 3,958 participants (male/female = 3,004/954, age mean ± SD = 8.60 ± 2.25 years). We collected data on TS symptoms using the Motor Tic, Obsessions and Compulsions, Vocal Tic Evaluation Survey (MOVES), and ADHD symptoms using the Swanson, Nolan, and Pelham Rating Scale-IV (SNAP-IV). Network analysis was employed to construct a combined network of TS and ADHD symptoms at the symptom level. We utilized the expected influence (EI) and bridge EI metrics to explore the core and bridge symptoms within the network.ResultsThe network structure demonstrated a moderate number of non-zero connections between TS and ADHD symptoms, constituting 23.06% of all potential connections. Core symptoms in the comorbidity network included “Often has difficulty sustaining attention in tasks or play activities,” “Certain bad words or thoughts keep going through my mind,” and “Words come out that I can’t stop or control.” Bridging symptoms identified were “Words come out that I can’t stop or control,” “I do certain things like jumping or clapping over and over,” “I can’t control all my movements,” and “Often talks excessively.”ConclusionThe core and bridging symptoms identified in this study serve as potential therapeutic targets for the treatment of TS and ADHD comorbidity in clinical children and adolescents.

Efficacy of cognitive-behavioral therapy combined with habit reversal training on anxiety disorders in children with Tourette's syndrome.

Cognitive-behavioral therapy (CBT) and habit reversal training (HRT) have shown application potential in addressing tic symptoms and comorbid psychiatric conditions. Despite their theoretical potential, empirical evidence on their combined efficacy remains limited. To evaluate the efficacy of CBT combined with HRT on anxiety disorders in children with Tourette's syndrome (TS). Clinical data of children with TS admitted to our hospital from January 2022 to June 2023 were collected, and the patients were grouped into the conventional therapy (control) group and the CBT combined with HRT group. Baseline characteristics, anxiety scores, tic severity scores, treatment adherence, and parental satisfaction were assessed. Statistical analysis was performed using t-tests, chi-square tests, and correlation analysis. A total of 136 patients, including 65 patients in the control group and 71 patients in the CBT combined with HRT group, were included. The CBT combined with HRT group showed remarkable improvements compared with the control group. Post-intervention assessment revealed a decrease in anxiety scores from 63.52 ± 1.81 to 40.53 ± 1.64 (t = 2.022, P = 0.045), and the Yale Global Tic Severity Scale total score decreased from 22.14 ± 5.67 to 16.28 ± 4.91 (t = 2.288, P = 0.024). Treatment adherence was significantly higher in the CBT combined with HRT group (85.47 ± 7.62%) compared with the control group (82.32 ± 6.54%; t = 2.596, P = 0.010). Parental satisfaction scores were also higher in the CBT combined with HRT group (8.69 ± 1.77) compared with the control group (7.87 ± 1.92; t = 2.592, P = 0.011). This study demonstrates that CBT combined with HRT significantly reduces anxiety symptoms and tic severity in children with TS, with higher treatment adherence and parental satisfaction. These findings support the potential application of this comprehensive therapeutic approach for TS treatment.

THE EFFECTIVENESS OF COGNITIVE-BEHAVIORAL THERAPY IN THE TREATMENT OF TOURETTE SYNDROME: A systematic review

This work addressed Tourette Syndrome (TS) as a complex challenge that affects not only the physical but also the psychological aspects of individuals. The history of the syndrome, the course of the disease, associated pathologies, and treatment options were explored. The objective of this review was established: to map studies addressing the importance of Cognitive-Behavioral Therapy (CBT) in the treatment of TS. Thus, the research was conducted in the database: Biblioteca Virtual de Saúde - BVS, where the descriptors used were: “Tourette Syndrome” AND “Cognitive-Behavioral Therapy”. This research resulted in a total of 76 articles, 74 of which were in English, from the periods 1985 to 2023. CBT was highlighted as a relevant therapeutic approach for TS, and its contributions and challenges were emphasized. The importance of addressing these issues to improve care and well-being of patients with TS was underscored. Topics such as symptom variation, long-term outcome assessment, contextual influences, and the integration of CBT with other therapeutic approaches were discussed. The study concluded by pointing out the scarcity of Brazilian research in the area and proposed a future direction for research, aiming to improve the quality of life of patients with TS through adapted CBT and greater contribution from psychology.

A Case Series on Complexities in Recognition and Management of Tourette Syndrome with Variable Behavioral Presentations: Comorbidity Versus Umbrella Construct

In Tourette syndrome (TS), apart from multiple motor and vocal tics, there are often myriads of associated conditions apparently similar to attention-deficit-hyperactivity-disorder (ADHD), obsessive-compulsive-disorder (OCD), mood-and-conduct disorder, learning difficulties, etc. On the other hand, tic disorders often occur as co-morbidity with many neurodevelopmental disorders such as ADHD, OCD and mood disorders, and pharmacotherapy of these behavioral conditions may worsen the tics. So, the confusion lies whether to separately code and manage the different neurodevelopmental disorders or assume an umbrella construct of “TS-plus,” as suggested by some researchers. In this background, we share three cases of children and adolescents having multiple tics with mixed behavioral presentations of ADHD/OCD/mood disorders that created a lot of diagnostic dilemma and treatment-related complications in prior psychiatric consultations. They were finally diagnosed as “TS-plus” and managed with low-dose-risperidone-mono-pharmaco-therapy and psychological interventions. In conclusion, psychiatrists should be vigilant for Tourette-syndrome while handling children with repetitive motor behaviors along with hyperactivity, obsession-compulsion, mood-conduct, etc. Assumption of an umbrella-construct approach of “TS-plus” may be beneficial in limiting the number of diagnosis and their separate pharmacotherapy, which may worsen the clinical scenario.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

Guanfacine in the Treatment of a Child Diagnosed with Tourette Syndrome: A Case Report

Introduction Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the development of persistent and changing motor and phonic tics over time. The presence of at least two motor tics and one vocal tic that have persisted for at least a period of 1 year is required, and which developed before the age of 18. The most commonly used pharmacological treatment are antipsychotics, with a preference for atypical antipsychotics such as aripiprazole or risperidone. Clonidine and guanfacine have shown effectiveness in suppressing tics, and although generally less effective than antipsychotics, some authors are considering them as first-line treatments. The treatment is also influenced by any comorbidities the patient may present.ObjectivesTo enumerate in a clinical case the pharmacological alternatives for TS, which vary according to the patient’s comorbidities and the intensity of the tic symptoms.MethodsCase study. Anamnesis of the patient and their family.Results A 12-year-old boy presenting simple motor and vocal tics for over a year. At the same time that a valuation is requested by child psychiatry, the mother also requests follow-up by neuropediatrics. Other causes are ruled out, an EEG is performed, and a TS diagnosis is made. The initial treatment was low-dose aripiprazole with partial effectiveness. After 3 months, he presents an exacerbation of the tics, interfering with his social and academic life, making it impossible to attend classes. The mother takes him to emergency services, and he is admitted to pediatrics. During the stay in pediatrics, he is diagnosed with Attention Deficit Hyperactivity Disorder, in addition to confirming the TS diagnosis. Extended-release methylphenidate is initiated (neuropediatrics). After starting methylphenidate, the patient’s tics worsen, also presenting insomnia and hyporexia. Due to the diagnosis of ADHD, school failure, and affective symptoms (hypothymia), atomoxetine is initiated. The tics become constant and incapacitating. As the dose of aripiprazole is increased, the child presents extrapyramidal effects. As a therapeutic alternative, guanfacine is initiated, progressively discontinuing aripiprazole. Currently, the child is stable from motor and vocal tics, allowing him to lead a normalized life.ConclusionsAlthough guanfacine is not as effective in reducing tics as antipsychotics, since the latter produce more side effects, it is justifiable to use it. This drug is capable of enhancing the therapeutic effect and reducing the adverse effects that antipsychotics could produce. Guanfacine may be a good alternative as a first line in the treatment of Tourette Syndrome with or without attention deficit disorder and hyperactivity .Disclosure of InterestNone Declared

A meta-analysis of transcranial magnetic stimulation in Tourette syndrome

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity—the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = −0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

GBA-related diseases and the application in Tourette syndrome treatment

This paper discusses the gut-brain axis (GBA) and how it takes part in various neurological diseases, including Alzheimers disease (AD), Attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome. The gut microbiota, inducing vital communications with the brain through the GBA, is not to be neglected in maintaining physiological balance, with the potential to become a source of new therapeutic opportunities for treating these diseases. Current studies show that methods such as personalized diets, oral bacteriotherapy, and multi-strain probiotics like SLAB51 and DEX have promising results in treating AD and ADHD through manipulation of the biotas. Based on the analysis of previous research, this paper finds how changes in gut microbiota amount in feces between healthy and TS mice, in particular the decrease in Firmicutes and Actinobacteria, and the increase in Bacteroidetes and Proteobacteria. However, future studies and experiments are required to evaluate potential side effects of microbiome alterations in humans, and potential treatments for Tourettes syndrome based on gut microbiota analysis. The GBA is a promising area for developing new therapeutic approaches for neurological diseases, and future research in this field holds great potential for advancements in the treatment of these disorders currently with no verified cures.

Exploring the Mechanism of Action of Spleen-Tonifying Medication in Treating Tourette Syndrome Based on Network Pharmacology and Mitochondrial Metabolism Experiment

Exploring the Mechanism of Action of Spleen-Tonifying Medication in Treating Tourette Syndrome Based on Network Pharmacology and Mitochondrial Metabolism Experiment

Automated Quantification of Eye Tics Using Computer Vision and Deep Learning Techniques.

Tourette syndrome (TS) tics are typically quantified using "paper and pencil" rating scales that are susceptible to factors that adversely impact validity. Video-based methods to more objectively quantify tics have been developed but are challenged by reliance on human raters and procedures that are resource intensive. Computer vision approaches that automate detection of atypical movements may be useful to apply to tic quantification. The current proof-of-concept study applied a computer vision approach to train a supervised deep learning algorithm to detect eye tics in video, the most common tic type in patients with TS. Videos (N = 54) of 11 adolescent patients with TS were rigorously coded by trained human raters to identify 1.5-second clips depicting "eye tic events" (N = 1775) and "non-tic events" (N = 3680). Clips were encoded into three-dimensional facial landmarks. Supervised deep learning was applied to processed data using random split and disjoint split regimens to simulate model validity under different conditions. Area under receiver operating characteristic curve was 0.89 for the random split regimen, indicating high accuracy in the algorithm's ability to properly classify eye tic vs. non-eye tic movements. Area under receiver operating characteristic curve was 0.74 for the disjoint split regimen, suggesting that algorithm generalizability is more limited when trained on a small patient sample. The algorithm was successful in detecting eye tics in unseen validation sets. Automated tic detection from video is a promising approach for tic quantification that may have future utility in TS screening, diagnostics, and treatment outcome measurement. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Working Mechanisms of Exposure and Response Prevention in the Treatment of Tourette Syndrome and Tic Disorders Revisited: No Evidence for within-Session Habituation to Premonitory Urges.

Exposure and response prevention (ERP) has been shown to be an effective treatment for Tourette syndrome (TS) and chronic tic disorders (CTD). ERP is based on voluntary tic suppression in combination with prolonged exposure to premonitory urges preceding tics. A prevailing hypothesis of the working mechanism underlying ERP in tics is habituation to the premonitory urges as a result of prolonged exposure. However, results so far are equivocal. This study aims to further explore the relation between urges and ERP in tics, by investigating the course of premonitory urges during ERP sessions. Using a data-driven approach, within-session habituation to premonitory urge intensity was investigated. In total, 29 TS patients rated urge intensity at seven timepoints during ten 1 h ERP sessions. Latent growth modeling showed an increase in urge intensity during the first 15 min of each session followed by a plateau in the remaining 45 min of the session. This does not support the idea of within-session habituation to premonitory urges as a working mechanism of ERP. Other potential underlying working mechanisms are discussed and should be tested in future research.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder

BackgroundThis study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. MethodsConsecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. ResultsFamily-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. ConclusionFamily, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine for Children and Adolescents with Tourette Syndrome: A Systematic Review and Meta-Analysis

Background: With the increasing prevalence of Tourette syndrome (TS), the search for alternative therapy for TS is a growing public concern. In recent years, a growing number of randomized controlled trials (RCTs) have revealed the value of acupuncture combined with herbal medicine for the treatment of TS; however, its holistic efficacy and safety remains unclear. This study aimed to evaluate the efficacy and safety of acupuncture combined with herbal medicine and to provide preliminary evidence for clinical practice. Methods: Eight databases were searched from their establishment to November 27, 2022, to collect RCTs of acupuncture combined with herbal medicine for TS treatment. Two researchers independently completed the study screening, data extraction, and risk of bias assessment by using NoteExpress, Excel, and Cochrane Risk of Bias Tool 2.0 (RoB 2.0). Stata 15.0 software was applied to conduct meta-analysis. Results: A total of 1,400 participants in 18 RCTs were included. Compared with the Western medicine, acupuncture combined with herbal medicine had better curative effect in the field of effective rate (risk ratio [RR] = 1.18, 95% CI: [1.12, 1.23], p < 0.05, I2 = 0%), Yale Global Tic Severity Scale (YGTSS) total score (mean difference [MD] = −3.91, 95% CI: [−5.49, −2.33], p < 0.05, I2 = 96.4%), TCM syndrome total score (MD = −2.42, 95% CI: [−3.71, −1.13], p < 0.05, I2 = 87.1%), and serum IgE negative rate (RR = 3.41, 95% CI: [1.69, 6.87], p < 0.05, I2 = 0%). Furthermore, acupuncture combined with herbal medicine reduced the adverse reaction rate (RR = 0.20, 95% CI: [0.14, 0.30], p < 0.05, I2 = 0%) and the recurrence rate (RR = 0.27, 95% CI: [0.13, 0.52], p < 0.05, I2 = 0%). Conclusion: This study demonstrated the efficacy and safety of acupuncture combined with herbal medicine, which is probably a better alternative therapy for TS. However, the small number, low quality, and potential bias of the included studies caused the limitations of our results. More high-quality RCTs are required to provide supplementary evidence in the future.

Present situation on the causes and treatments of tourette syndrome

Tourette Syndrome (TS), a neurological disorder classified as the most complex form of tic disorder in the DSM-5, has remained a prominent concern for the adolescent population. Owing to its complexity and the unknowability of its physiology, it currently has no cure. Through the review of two family studies, two twin studies, one Genome-Wide Association Study, and two other reviews, firm evidence for additive genetic influences and non-shared environmental influences was found, suggesting TSs high heritability. Specific genetic factor (SNP-rs2504235), environmental (pre-and peri-natal) factors, and the interaction between these factors were evident from the studies as well. Through the analysis of these findings, one coping strategy was emphasized over the two existing classes, pharmacological and non-pharmacological, of typical treatments: preventative approaches under the assistance of advanced technology like genetic testing. The inability of the now available treatments to cure TS and their respective side effects cause them to be less desirable than prevention as early actions were shown to be effective in hindering the disorders deterioration and persistence.

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.

Median Nerve Stimulation for Treatment of Tics: A 4-Week Open Trial with Ecological Momentary Assessment.

Median nerve stimulation (MNS) at 10-12 Hz was recently proposed as a treatment for Tourette syndrome and other chronic tic disorders (TS/CTD). We report on 31 participants ages 15-64 with TS/CTD in an open-label, comparative (within-group, several time points) study of MNS (ClinicalTrials.gov registration number NCT05016765). Participants were recruited from completers of a randomized controlled trial (RCT) of MNS and were given a transcutaneous electrical nerve stimulation (TENS) unit to use as desired for 12 Hz MNS for 4 weeks. Participants were instructed to complete surveys regarding tic symptoms and stimulation discomfort before and after stimulation, as well as twice daily when randomly prompted by text message. Participants also completed an extensive final survey. Twenty-seven participants completed the study. Median device use was 1.5 days per week and 50 min per day used. Tic frequency improved during MNS (mean improvement: 1.0 on a 0-5 scale, p < 0.001), as did tic intensity (mean improvement: 0.9, p < 0.001). Mean discomfort was mild (1.2 on a 3-point scale). In total, 21 participants (78%) planned to continue using the device. Participants' results in this study did not correlate significantly with their results in the blinded RCT. We found MNS to improve tic frequency and intensity with minimal side effects.