Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study.

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of "relaxed situations" and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient's unique needs.

Effectiveness of speech therapy in treating vocal blocking tics in children with Tourette syndrome: Two case reports.

Tourette syndrome is characterized by at least two motor tics and one vocal tic, which persist for over a year. Infrequently, tics can manifest as blocking tics in speech when they prevent a person from starting to speak or interrupt their speech flow. Vocal blocking tics (VBTs) resemble stuttering, and they can be difficult to differentiate from each other. A previous report described two patients with severe VBTs who did not benefit from stuttering-therapy-based speech therapy and were treated effectively with cannabis-based medicine. Here, we present the cases of two patients, seven- and nine-year-old boys, who benefited from speech therapy in which stuttering therapy techniques were used. Detailed descriptions of the interventions are included. Further research is needed to test the effectiveness of speech therapy in treating VBTs in a larger group of children with Tourette syndrome.

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.Mit der steigenden Prävalenz des Tourette-Syndroms (TS) ist die Suche nach alternativen Therapien für TS zunehmend zu einer Angelegenheit von öffentlichem Interesse geworden. In den vergangenen Jahren zeigte eine immer größer werdende Zahl randomisierter, kontrollierter Studien den Nutzen der Akupunktur in Kombination mit Heilkräutern; ihre ganzheitliche Wirksamkeit und Sicherheit ist jedoch weiterhin nicht klar. Mit dieser Studie sollten die Wirksamkeit und Sicherheit von Akupunktur in Kombination mit Heilkräutern beurteilt und erste Belege für die klinische Praxis gewonnen werden.Acht (8) Datenbanken wurden ab ihrer Einrichtung bis zum 27. November 2022 nach randomisierten kontrollierten Studien (RCTs) über Akupunktur in Kombination mit Heilkräutern zur Behandlung von TS durchsucht. Das Screening der Studien, die Datenextraktion und die Bewertung des Verzerrungsrisikos wurden von zwei unabhängigen Forschern mit Hilfe von NoteExpress, Excel und dem Cochrane Risk of Bias Tool 2.0 (RoB 2.0) durchgeführt. Die Metaanalyse erfolgte mit der Software Stata 15.0.Insgesamt wurden 1400 Teilnehmer in 18 RCTs eingeschlossen. Im Vergleich zur westlichen Medizin (WM) hatte Akupunktur in Kombination mit Heilkräutern eine bessere kurative Wirkung in Bezug auf die Wirksamkeitsrate (RR = 1,18, 95%-KI [1,12, 1,23], p < 0,05, I2 = 0%), den Gesamtscore der Yale Global Tic Severity Scale (YGTSS) (MD = -3,91, 95%-KI [-5,49, -2,33], p < 0,05, I2 = 96,4%), den TCM-Syndrom-Gesamtscore (MD = -2,42, 95%-KI [-3,71, -1,13], p < 0,05, I2 = 87,1%) und die Serum-IgE-Negativrate (RR = 3,41, 95%-KI [1,69, 6,87], p <0,05, I2 = 0 %). Darüber hinaus verringerte Akupunktur in Kombination mit Heilkräutern die Nebenwirkungsrate (RR = 0,20, 95%-KI [0,14, 0,30], p < 0,05, I2 = 0%) sowie die Rezidivrate (RR = 0,27, 95%-KI [0,13, 0,52], p < 0,05, I2 = 0%).Diese Studie belegt die Wirksamkeit und Sicherheit der Akupunktur in Kombination mit Heilkräutern, die wahrscheinlich eine bessere alternative Therapie für TS darstellt. Unsere Ergebnisse werden allerdings durch die geringe Zahl, die niedrige Qualität und die potenzielle Verzerrung der eingeschlossenen Studien eingeschränkt. Zukünftig sind weitere hochwertige RCTs erforderlich, die zusätzliche Belege liefern.

Protocol description for a randomized controlled trial of fMRI neurofeedback for tics in adolescents with Tourette Syndrome.

This article describes the protocol for a randomized, controlled clinical trial of a neurofeedback (NF) intervention for Tourette Syndrome (TS) and chronic tic disorder. The intervention involves using functional magnetic resonance imaging (fMRI) to provide feedback regarding activity in the supplementary motor area: participants practice controlling this brain area while using the feedback as a training signal. The previous version of this NF protocol was tested in a small study (n = 21) training adolescents with TS that yielded clinically promising results. Therefore, we plan a larger trial. Here we describe the background literature that motivated this work, the design of our original neurofeedback study protocol, and adaptations of the research study protocol for the new trial. We focus on those ideas incorporated into our protocol that may be of interest to others designing and running NF studies. For example, we highlight our approach for defining an unrelated brain region to be trained in the control group that is based on identifying a region with low functional connectivity to the target area. Consistent with a desire for transparency and open science, the new protocol is described in detail here prior to conducting the trial.

[Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment].

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

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.

CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study.

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

Art as relaxation for tic disorders: a pilot randomised control study.

BACKGROUND: Despite the known benefits of art therapy, there are a limited number of studies on art therapy for tic disorders. This pilot randomised controlled study investigated effects of art as a relaxation technique for tic disorders. METHODS: Twenty-two children aged 7-9 years were randomly allocated to art intervention (n= 11) and control (n= 11) groups. Pre- and post-test measurements included the Yale Global Tic Severity Scale (YGTSS), Heart Rate Variability (HRV), and Hassles Scale for Children (HSC). RESULTS: Art as relaxation significantly decreased the YGTSS total score, motor tic frequency, motor tic intensity, motor tic complexity, vocal tic complexity, and total daily stressors compared to the control group. The intervention group showed significantly greater physiological relaxation, as indicated by increases in HRV parameters. CONCLUSIONS: Art appears to be an effective relaxation technique for tic disorders. Extensive research is necessary for rigorous examination of its effectiveness.

From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

Tourette syndrome (TS) is a childhood-onset disorder in which tics are often preceded by premonitory sensory urges. More severe urges correlate with worse tics and can render behavioral therapies less effective. The supplementary motor area (SMA) is a prefrontal region believed to influence tic performance. To determine whether cortical physiological properties correlate with urges and tics, we evaluated, in 8-12-year-old right-handed TS children (n = 17), correlations of urge and tic severity scores and compared both to cortical excitability (CE) and short- and long-interval cortical inhibition (SICI and LICI) in both left and right M1. We also modeled these M1 transcranial magnetic stimulation measures with SMA gamma-amino butyric acid (GABA) levels in TS and typically developing control children (n = 16). Urge intensity correlated strongly with tic scores. More severe urges correlated with lower CE and less LICI in both right and left M1. Unexpectedly, in right M1, lower CE and less LICI correlated with less severe tics. We found that SMA GABA modulation of right, but not left, M1 CE and LICI differed in TS. We conclude that in young children with TS, lower right M1 CE and LICI, modulated by SMA GABA, may reflect compensatory mechanisms to diminish tics in response to premonitory urges.

Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment / 中国中药杂志

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

Efficacy and safety of Jiu-Wei-Xi-Feng granules for treating tic disorders in children: study protocol for a randomized controlled equivalence trial.

BACKGROUND: Tic disorders (TD) is a neuropsychiatric disease with twitch as the main manifestation in childhood. Jiu-Wei-Xi-Feng granules has been marketed in China for treating children with TD. As Long Gu (Os Draconis) in the composition of this Chinese patent medicine is a rare and expensive medicinal material protected by the Chinese government, therefore, we consider replacing it with Mu Li (Concha Ostreae) that has the same effect and is cheaper. This study is designed to evaluate the clinical equivalence between Jiu-Wei-Xi-Feng granules (Os Draconis replaced by Concha Ostreae) (JWXFD) and Jiu-Wei-Xi-Feng granules (original formula) (JWXFO) in children with TD (consumption of renal yin and liver wind stirring up internally syndrome). METHODS/DESIGN: This is a multicenter, randomized, double-blind, equivalence trial comparing the efficacy and safety of JWXFD and JWXFO in treating Children with tic disorders (consumption of renal yin and liver wind stirring up internally syndrome). A total of 288 patients will be recruited and randomly assigned to two groups in a 1:1 ratio. The treatment course is 6 weeks, with a 2 weeks follow-up. The primary outcome is the mean change value from baseline to 6th week by the Yale Global Tic Severity Scale total tic score (YGTSS-TTS). Secondary outcomes include total effective rate of tic, Yale Global Tic Severity Scale (YGTSS) scores and its factor scores (the degree of motor tics, phonic tics and social function damage), Clinical Global Impression-Severity scale, and TCM syndrome efficacy. DISCUSSION: The design of this study refers to a large number of similar research design points, and asked for opinions of peer experts, and finally reached a consensus. This trial will provide high-quality evidence on the clinical equivalence between JWXFD and JWXFO and provide a basis for the marketing of JWXFD. TRIAL REGISTRATION: ChiCTR2000032312 Registered on 25 April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52630.

Embedded Human Closed-Loop Deep Brain Stimulation for Tourette Syndrome: A Nonrandomized Controlled Trial.

Importance: Because Tourette syndrome (TS) is a paroxysmal disorder, symptomatic relief in individuals with TS may be possible through the application of stimulation only during the manifestation of human tic neural signatures. This technique could be capable of suppressing both motor and vocal tics and would have similar effectiveness to conventional continuous deep brain stimulation (DBS). Objective: To evaluate the feasibility, safety, and clinical effectiveness of bilateral centromedian-parafascicular complex thalamic closed-loop DBS as a treatment for medication-refractory TS. Design, Setting, and Participants: This single-center double-blinded safety and feasibility trial was conducted between February 2014 and June 2020. Six individuals with TS were screened and recruited from the Norman Fixel Institute at the University of Florida. The primary outcome was measured at 6 months, and participants were followed up for the duration of the neurostimulator battery life. Independent ratings that compared closed-loop and conventional DBS were videotaped. The first 2 of 6 individuals with TS were excluded from the study because the technology for embedded closed-loop capability was not yet available. The date of analysis was August 2020. Interventions: DBS therapy controlled by an embedded closed-loop stimulation system. Main Outcomes and Measures: The primary clinical outcome measure was a minimum of a 40% reduction in the YGTSS score at 6 months following DBS. There was also a comparison of conventional DBS with closed-loop DBS using the Modified Rush Videotape Rating Scale for Tic. Results: The mean (SD) age at TS diagnosis for the cohort was 8.5 (2.9), and the mean (SD) disease duration was 23.7 (5.8) years. Four individuals with TS were analyzed (2 male, 2 female; mean [SD] age, 23.7 [5.8] years). The study showed the closed-loop approach was both feasible and safe. One of the novelties of this study was that a patient-specific closed-loop paradigm was created for each participant. The features and stimulation transition speed were customized based on the signal quality and the tolerance to adverse reactions. The mean (SD) therapeutic outcome with conventional DBS was 33.3% (35.7%) improvement on the YGTSS and 52.8% (21.9%) improvement on the Modified Rush Videotape Rating Scale. Two of 4 participants had a primary outcome variable improvement of 40% meeting the primary efficacy target. When comparing closed-loop DBS with conventional DBS using a Wilcoxon sign-rank test, there was no statistical difference between tic severity score and both approaches revealed a lower tic severity score compared with baseline. The study was feasible in all 4 participants, and there were 25 total reported adverse events with 3 study-related events (12%). The most common adverse events were headache and anxiety. Conclusions and Relevance: Embedded closed-loop deep DBS was feasible, safe, and had a comparable outcome to conventional TS DBS for the treatment of tics. Trial Registration: ClinicalTrials.gov Identifier: NCT02056873.

Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature.

PURPOSE OF REVIEW: This study aims to examine the treatments currently available for Tourette syndrome (TS) and to discuss evolving therapies, spanning behavioral, pharmacologic, complementary and alternative medicine, and neuromodulation approaches. RECENT FINDINGS: Behavioral therapies have undergone several modifications to improve accessibility, including transitioning to a virtual format which is particularly important in the current pandemic. There are several recent or ongoing pharmacologic studies that have shown promise including the selective D1 receptor antagonist ecopipam and various cannabinoid compounds. Adaptive DBS may enable the physiologic markers of tics to determine stimulation parameters and improve tic outcomes related to neuromodulation. In recent years, there has been a wealth of research across multiple treatment domains in the TS field. This review highlights exciting and new potential options for the future treatment of patients with TS.

Effects of Yi-Gan-san on the psychiatric behavior of children and adolescents with Tourette's Syndrome: A randomized, double-blind, controlled preliminary study.

ETHNOPHARMACOLOGICAL RELEVANCE: Gilles de la Tourette's Syndrome (TS) is a childhood-onset disease with clinical features of motor and phonic tics. Yi-Gan-san (YGS) is a traditional Chinese medicine formula that can reduce aggressiveness and agitation and inhibit dopamine function. This study investigated the effects of YGS on the psychiatric behavior of children and adolescents with TS. METHODS: A double-blind, randomized, controlled preliminary study was conducted. A total of 38 patients with TS were assigned to the control group (CG, 19 patients) who received the oral administration of YGS placebo (90% starch and 10% YGS; 2.5 g thrice daily) or to a treatment group (TG, 19 patients) who received YGS for 4 weeks. The primary outcome measure was the change in Yale Global Tic Severity Scale (YGTSS) overall and subscale scores. RESULTS: The intensity score for phonic tics before oral administration of YGS, and after 2 weeks, 3 weeks and 4 weeks was not significantly different between CG and TG groups (2.94 ± 1.14 vs 2.79 ± 1.08, p = .686; 2.29 ± 1.21 vs 1.95 ± 1.08, p = .370; 2.41 ± 1.18 vs 2.05 ± 1.51, p = .435; and 2.29 ± 1.26 vs 1.84 ± 1.42, p = .323, respectively), while the intensity score for phonic tics after 1-week oral administration of YGS in the TG was 1.89 ± 1.10 lower than 3.06 ± 1.39 in the CG (p = .008). CONCLUSION: Oral administration of YGS for 1 week only reduced the intensity of phonic tics compared with oral administration of YGS placebo, suggesting that YGS can reduce their intensity for a short period, and the compliance of oral administration of YGS for 4 weeks can be accepted in children and adolescents with Tourette's Syndrome. However, because this study was preliminary, the selection of an appropriate placebo and dosage and long-term observations are crucial areas for future studies.

Frequency and Intensity of Premonitory Urges-to-Tic in Tourette Syndrome Is Associated With Supplementary Motor Area GABA+ Levels.

BACKGROUND: Individuals with Tourette syndrome (TS) often report that they express tics as a means of alleviating the experience of unpleasant sensations. These sensations are perceived as an urge to act and are referred to as premonitory urges. Premonitory urges have been the focus of recent efforts to develop interventions to reduce tic expression in those with TS. OBJECTIVE: The aim of this study was to examine the contribution of brain γ-aminobutyric acid (GABA) and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS. METHODS: Edited magnetic resonance spectroscopy was used to assess GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) of the right SM1, SMA, and insula in 68 children with TS (MAge = 10.59, SDAge = 1.33) and 41 typically developing control subjects (MAge = 10.26, SDAge = 2.21). We first compared GABA+ and Glx levels of these brain regions between groups. We then explored the association between regional GABA+ and Glx levels with urge and tic severity. RESULTS: GABA+ and Glx of the right SM1, SMA, and insula were comparable between the children with TS and typically developing control subjects. In children with TS, lower levels of SMA GABA+ were associated with more severe and more frequent premonitory urges. Neither GABA+ nor Glx levels were associated with tic severity. CONCLUSIONS: These results broadly support the role of GABAergic neurotransmission within the SMA in the experience of premonitory urges in children with TS. © 2021 International Parkinson and Movement Disorder Society.

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome.

INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients. MATERIAL AND METHODS: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: ('Tourette syndrome' [MeSH Terms] OR 'Gilles de la Tourette syndrome' [MeSH Terms] OR 'tic disorders' [MeSH Terms] OR 'tics' [MeSH Terms] OR 'tic disorders'[Title/Abstract]) AND ('cannabis-based medicine' [Title/Abstract] OR 'cannabis' [Title/Abstract] OR 'dronabinol' [Title/Abstract] OR 'nabiximols' [Title/Abstract] OR 'tetrahydrocannabinol' [Title/Abstract] OR 'THC' [Title/Abstract] OR 'cannabidiol' [Title/Abstract], limit: 'humans'. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV). RESULTS: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant. CONCLUSIONS: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS.

[Efficacy and safety of body-insulated acupuncture needle for electrical stimulation at rabbit scia-tic nerve trunk].

OBJECTIVE: To evaluate the efficacy and safety of electrical stimulation at the rabbit sciatic nerve trunk with the body-insulated acupuncture needle whose body is painted with insulating material. METHODS: Eighteen male New Zealand rabbits were randomized into the body-insulated acupuncture needle (BIAN), the general acupuncture needle (GAN), and the blank control groups，with 6 rabbits in each group. The rats'sciatic nerve trunks in BIAN and GAN groups were stimulated by electroacupuncture with the body-insulated acupuncture needle (only allowing the uncoated needle handle and tip to conduct electricity) and the general acupuncture needle, separately. The current intensity was recorded when regular plantarflexion reflexes (sciatic nerve effector reflexes) were observed in the rabbit's foot. The pathological changes of the sciatic nerve at the acupuncture site were observed by H.E. staining, and the ultrastructural changes of the sciatic nerve trunk were observed by transmission electron microscope. RESULTS: The intensity of the current causing the regular plantar flexion reflection in BIAN group (ï¼»0.29±0.07ï¼½ mA) was significantly lower than that in the GAN group(ï¼»0.86±0.08ï¼½ mA, P<0.01). H.E. staining revealed nerve axon degeneration, forming eosinophilic bodies, nerve fiber edema, and focal loss of myelin sheath in the GAN group. While the nerve fiber damage was not obvious, and axons were only degenerated in a few areas in the BIAN group. Transmission electron microscopy observations showed that the nerve myelin sheath structure was separated, the layers were arranged disorderly and bubbled in the GAN group. while the nerve myelin sheath structure of the BIAN group was normal, and it presents a concentric circle-like light and dark lamellar structure, with fewer myelin vacuoles and fissures, only a small part of the mitochondria, microfilaments, and microtubules of the nerve axons were abnormal, and the overall vacuole-like degeneration was significantly reduced, with few of the myelinated fibers were slightly degenerated, and axonal disease was not obvious. CONCLUSION: Insulated acupuncture needle is more accurate and safer than ordinary acupuncture needle for electrical stimulation of rabbit sciatic nerve trunk, and the required electric current intensity is smaller.

Evidence for the role of the dorsal ventral lateral posterior thalamic nucleus connectivity in deep brain stimulation for Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) can manifest as debilitating, medically-refractory tics for which deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM) can provide effective treatment. However, patients have reported benefit with activation of contacts dorsal to the CM and likely in the ventro-lateral thalamus (VL). At our institution, a case of a robust and durable response in a GTS patient required stimulation in the CM and more dorsally. We explore the structural connectivity of thalamic subregions associated with GTS using diffusion MRI tractography. Diffusion weighted images from 40 healthy Human Connectome Project (HCP) subjects and our GTS patient were analyzed. The VL posterior nucleus (VLp) and the CM were used as seeds for whole-brain probabilistic tractography. Leads were localized via linear registration of pre-/post-operative imaging and cross-referenced with the DBS Intrinsic Template Atlas. Tractography revealed high streamline probability from the CM and VLp to the superior frontal gyrus, rostral middle frontal gyrus, brainstem, and ventral diencephalon. Given reported variable responses to DBS along the thalamus, we segmented the VLp based on its connectivity profile. Ventral and dorsal subdivisions emerged, with streamline probability patterns differing between the dorsal VLp and CM. The CM, the most reported DBS target for GTS, and the dorsal VLp have different but seemingly complimentary connectivity profiles as evidenced by our patient who, at 1-year post-operatively, had significant therapeutic benefit. Stimulation of both regions may better target reward and motor circuits, resulting in enhanced symptom control for GTS.