Treatment Of Tourette Syndrome Research Articles

FV 1 Segregating the prefrontal cortex by means of deep brain stimulation

Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto- cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To map the functional organization of the the frontal cortex (FC), we employ optimal connectivity profiles from successful deep brain stimulation (DBS) electrodes to the same target, which receives input from the entire FC, in four different disorders. Specifically, we identify cortical projection sites that, on a group level, associate with maximal improvements following subthalamic nucleus (STN) DBS in dystonia (DYT), Parkinson's disease (PD), Tourette syndrome (TS) or obsessive-compulsive disorder (OCD). Patients and Methods: Using Lead-DBS (2), stimulation volumes were estimated for six patient cohorts from six centers, each implanted with DBS to the STN for treatment of either DYT (N = 62), PD (N = 51), TS (N = 14), or OCD (N = 19). Via DBS Network Mapping (3) we derived disease-specific structural connections between cortex and STN from a normative connectome (4) that relate to optimal clinical outcomes. Results: Functional organization in the STN and FC was reflected along a caudo-rostral gradient (Fig. 1). Beneficial DBS networks for DYT predominantly projected to the primary motor cortex, while in PD, electrode connectivity to pre- and supplementary motor areas, in TS to the dorsomedial preFC, and in OCD to ventromedial, dorsal anterior cingulate and dorsolateral preFC emerged. Conclusion: Our findings demonstrate the usefulness of DBS to investigate the organizational gradient of frontal network (dys)function. As such, they bear both interest for cognitive neurosciences as well as clinical-translational value for circuit-guided DBS.

Is Traditional Chinese Medicine Effective in Treating Tic Disorders (Tourette Syndrome)? A Meta-Analysis of Randomized Controlled Trials

Introduction: Traditional Chinese medicine (TCM) is a type of alternative medicine that has been widely utilized in the prevention and treatment of neuropsychiatric diseases such as schizophrenia, ADHD, Alzheimer disease, and Tourette syndrome (TS) in many countries. However, the results regarding TCM’s effectiveness and safety in treating TS are conflicting. Therefore, the goal of the present study is to analyze and summarize the available literature related to the efficacy of TCM in the treatment of tic disorders, especially TS. Methods: Relevant articles for the meta-analysis were searched using appropriate keywords from PubMed, MEDLINE, and CENTRAL databases. Event data for TCM for the treatment of TS in the control and intervention arms were determined from the randomized controlled trials, and diagnostic odds ratio (DOR) and risk of bias analysis were performed. Meta-analysis was performed using MedCalc software, and suitable parameters to assess heterogeneity were computed. Results: Twelve randomized clinical trials with a total of 1,681 TS patients were included as per the inclusion criteria. The patients’ clinical symptoms were improved to a greater extent, and the pooled DOR of 1.311 with a 95% confidence interval (CI) value ranging from 0.804 to 2.139 and I² value of 72.04% were obtained. The pooled relative risk was 1.09, with a 95% CI value ranging from 0.97 to 1.268. The data heterogeneity was assessed, and we achieved a Q value of 33.54, a p value of 0.0004, and I² value of 67.21% with a 95% CI value of 32.91–82.10. All these values are statistically significant, with p < 0.005, and confirmed the effectiveness of TCM for TS patients. Conclusion: The present meta-analysis on account of these statistically significant results highly recommends using TCM to treat TS.

Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.

Background: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota–gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.Methods: TS mice model (TSMO) (n = 80) were established with 3,3′-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.Results: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.Conclusions: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

Efficacy of Behavioural Intervention, Antipsychotics, and Alpha Agonists in the Treatment of Tics Disorder in Tourette's Syndrome.

Tourette's Syndrome (TS), in which patients have sudden, repeated, involuntary twitches and movements, called tics, is a condition of the nervous system. They can be motor, vocal, simple, or complex tics. It can be physically, emotionally, mentally, and socially distressing and challenging for those suffering from it. Usually, it is accompanied by various comorbidities like attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and sleep disorders. A variety of environmental and genetic factors are also associated with tics in TS like the first-degree relatives are more at risk of developing TS.TS is heterogeneous with complicated patterns of inheritance and phenotypic manifestations. There is a strong association between common single nucleotide polymorphisms (SNP, s) in the SLITRK1 gene and TS. Environmental factors like prenatal, postnatal, and perinatal factors directly influence tics in TS. These factors are low birth weight, intrauterine growth retardation (IGR), and various infections. The treatment of TS can be broadly classified into non-pharmacological and pharmacological treatment. Non-pharmacological therapy includes various behavioural interventions that can be helpful in situations when patients are tolerant of medical treatments. Psychoeducation and counselling play an essential role in the treatment of TS. It is vital to give a proper understanding to the patient and their family about the disease. Cognitive-behavioral intervention for tics, cognitive-behavioral therapy, exposure and response prevention, relaxation techniques, deep brain stimulation, and habit reversal training are the commonly used therapies for tics. These therapies have shown good efficacy because it improves the Yale Global Tic Severity Scale score (YGTSS) significantly. And they show effectiveness in patients who are irresponsive to medical treatment. The main lines of medical treatment are antipsychotics and alpha agonists. Typical (haloperidol, pimozide) or atypical (aripiprazole, risperidone, olanzapine) Antipsychotics differ in their side effects, efficacy, and tolerance in different age groups of children. Haloperidol was the first drug approved by the Food and Drug Administration for tics, but later on, new developments and improvements were made as far as drug therapy is concerned. The alpha-agonist most commonly used is clonidine which is also available in the form of adhesive patches. Another alpha agonist which is also widely used is guanfacine. Botulinum toxin and baclofen have also shown efficacy in dealing with tics in TS with other comorbidities. We will review in this article all the main lines of treatment and their effectiveness in TS.

Assessing the educational needs of physicians in the management of patients with Tourette syndrome: results of a United States survey on practicing clinicians and caregivers.

To better understand current practices of U.S.-based physicians in the management of Tourette syndrome (TS) and identify gaps that may be addressed by future education. Two survey instruments were developed to gather data on management of TS and perceptions from physicians and caregivers of children with TS. The clinician survey was developed in consultation with a TS physician expert and utilized clinical vignettes to assess and quantify practice patterns. The caregiver survey was adapted from the clinician survey and other published studies and gathered details on diagnosis, treatment, and perceptions regarding management. Data included responses from 138 neurologists (including 57 pediatric neurologists), 162 psychiatrists (including 42 pediatric psychiatrists), and 67 caregivers. Most (65%) pediatric neurologists rely solely on clinical findings to make a diagnosis, whereas the majority of other specialists utilize additional testing (eg, neuroimaging, lab testing, and genetics). Most psychiatrists (96%) utilize standardized criteria to make a diagnosis, whereas 22% of neurologists do not. Many physicians (44% of psychiatrists and 20% of neurologists) use pharmacotherapy to treat a patient with "slightly bothersome" tics and no functional impairment, whereas caregivers favored behavioral therapy. Most (76%) caregivers preferred to make the final treatment decision, whereas 80% of physicians preferred equal or physician-directed decision-making. This study provides insight into practice patterns and perceptions of U.S.-based neurologists and psychiatrists in managing TS. Results highlight the potential value of physician education, including diagnostic approach, tic management and monitoring, involvement of caregivers in decision-making, and updates on TS management.

Effectiveness of Low-Frequency Pallidal Deep Brain Stimulation at 65 Hz in Tourette Syndrome

ObjectivesPallidal deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is often applied using a high frequency. The effectiveness of low-frequency long-term stimulation is unknown. We aimed to evaluate the clinical efficacy of low-frequency DBS applied to the globus pallidus pars internus (GPi) at 65 Hz for the treatment of TS, with long-term follow-up, to provide data for the optimization of stimulation parameters. Materials and MethodsA total of six patients with refractory TS were implanted with electrodes in the GPi and were assigned to receive low-frequency (65 Hz) DBS programming. Assessments were performed pre-DBS and at 3, 12, and a median of 34 (range 26–48) months post-DBS. The primary outcome was tic severity, as assessed by the Yale Global Tic Severity Scale (YGTSS), and the secondary outcomes were comorbid behavioral disorders, mood, functioning, and quality of life. ResultsWe noted significant differences in the YGTSS scores between the baseline and the post-DBS follow-ups (p = 0.01). At the final follow-up, four of six (66.6%) patients had a greater than 50% reduction in the YGTSS score, whereas the remaining two patients showed a mild worsening of tic severity. The secondary outcome measures also showed remarkable improvements in associated behavioral disorders, mood, functioning, and quality of life. Stimulation-induced adverse effects were not reported, although a device-related complication (an uncomfortable feeling in the neck) occurred in one patient. ConclusionsThe results of this study indicated that low-frequency DBS represents an effective and practical treatment for refractory TS with comparable efficacy to high-frequency DBS.

Long-term Outcome of Deep Brain Stimulation in Intralaminar Thalamus for Refractory Tourette Syndrome: A Case Report

BACKGROUND: Tourette syndrome (TS) is a neurobehavioral disease that has onset at an early age around 5–7 years old. This disease affects 0.3–0.8% of young age population. With criteria diagnosis at least one vocal and two motor tics beginning before 18 years old. The symptoms of tics remain unusual from a social point of view, thus making it difficult for patients to evolve their professional life and education level. We present a case report of a young male patient with refractory TS with a Yale Global Tic Severity Scale (YGTSS) score of 88 out of 100; he has experienced remarkable improvement after undergoing a deep brain stimulation (DBS) procedure. CASE REPORT: A 23-year-old male came to our neurosurgery outpatient clinic who had had a history of TS since 8 years ago. He had facial and jumping-type tics. Lately, his jumping movements cannot be controlled, with increasing frequency and intensity. The maximum tic-free interval is only 30 min. On 1st-time evaluation in the neurosurgery outpatient clinic, he scored 88 out 0f 100 on the YGTSS even after medication treatment, repetitive transcranial magnetic stimulation, and behavioral therapies. The DBS procedure was carried out in November 2018 with targets on the bilateral intralaminar nuclei of thalamus (centromedian nucleus). The result is convincing, with decrease of YGTSS score until 14 after 3 years evaluation postsurgery. CONCLUSION: After performing DBS targeting the bilateral thalamus (central thalamus nucleus), the severity of tic was dramatically reduced. The result is pleasing to the patient as they can resume activity in public and return to college. Case reports regarding the treatment of refractory TS with DBS are still rare in Indonesia. To the best of our knowledge, this is the first such report with long-term follow-up in South East Asia.

Neurosurgical management of Tourette syndrome: A literature review and analysis of a case series treated with deep brain stimulation.

Tourette syndrome (TS) is a heterogeneous disorder, which clinical presentation includes both multiple motor and vocal tics and commonly associated psychiatric conditions (obsessive-compulsive disorder, attention deficit hyperactivity disorder, depression, anxiety, etc.). Treatment options primarily consist of non-pharmacological interventions (habit reversal training, relaxation techniques, cognitive behavioral therapy, and social rehabilitation) and pharmacotherapy. In case of the intractable forms, neurosurgical treatment may be considered, primarily deep brain stimulation (DBS). DBS appear to be effective in medically intractable TS patients, although, the preferential brain target is still not defined. The majority of studies describe small number of cases and the issues of appropriate patient selection and ethics remain to be clarified. In this article, we review the main points in management of TS, discuss possible indications and contraindications for neurosurgical treatment, and analyze our experience of DBS in a case series of refractory TS patients with the focus on target selection and individual outcomes.

Establishment and evaluation of a compound fear behavior model of Tourette's syndrome in rats.

BackgroundTourette syndrome (TS) is a common childhood disorder characterized by unwanted movements or vocal sounds called tics. It is often accompanied by other psychobehavioral disorders, including fearful behavior. The establishment and evaluation of rat models of TS and comorbid fear can provide an experimental basis for the treatment of TS and its comorbid fear disorder.MethodsSixteen rats were randomly divided into a model group (n=8) and control group (n=8). In the model group, rats were injected intraperitoneally with iminodipropionitrile (IDPN) for 1 week to establish the TS model, which was followed by acoustic and electrical stimulation for 3 weeks to establish the rat models of TS and comorbid fear. The control group received intraperitoneal injection of saline for 1 week, and no further intervention was given in the last 3 weeks. The behavioral changes of the rats were observed and analyzed by the open field test (OFT). Protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA), and tyrosine hydroxylase (TH) and microRNA-134 (miRNA-134) in the brain tissue were detected by using polymerase chain reaction (PCR).ResultsOne rat in the model group died on the 24th day. Compared with the control group, the model group had significantly higher scores of locomotor activity, stereotyped behavior, and motor behavior, along with prolonged freezing time and significantly lower expression of miRNA-134. The differences in the expressions of PKA, cAMP, DA, and TH in brain tissue were not statistically significant.ConclusionsThe rat models of TS and comorbid fear have similar changes in behaviors and miRNA-134 level to those in clinical settings and therefore can be used as a reliable animal model to study the mechanism of action of TS and comorbid fear.

European clinical guidelines for Tourette Syndrome and other tic disorders: patients' perspectives on research and treatment.

The formation of a new umbrella organisation called Tics and Tourette Across the Globe (TTAG) representing Tic and Tourette Syndrome (TS) patient associations around the world has led to a clearer voice for patients with Tourette Syndrome (TS). An opportunity has been created for this group to bridge research, clinical work and shared decision-making between researchers, clinicians and patients across Europe, with the result of improving the treatment and management of TS. A survey was sent out to capture the patients' perspective on research and treatment, and 2269 participants responded. 71% of participants reported they would prefer research into how to treat TS and/or make symptoms better. The inclusion of patients' perspectives on research and treatment in the updated European clinical guidelines for TS and other tic disorders highlights the new opportunities that have been created for the participation of patients in the discussion of TS research.

Aripiprazole for the treatment of Tourette syndrome

ABSTRACT Introduction: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple tics which often persisting in forms of different severity throughout adult life. The prevalence of neuropsychiatric co-morbidity in patients with TS is high. Treatment of TS can involve pharmacological, behavioral, or, in rare cases, surgical therapies. Over the last two decades there has been growing interest in the use of aripiprazole, a novel partial dopamine receptor agonist, as a promising anti-tic agent. Areas covered: The authors reviewed the available literature evaluating the role of aripiprazole in the treatment of TS and other tic disorders in both children and adults. This includes data from five randomized controlled trials (RCTs) and eleven open-label studies. Expert opinion: There is moderate quality evidence supporting the use of aripiprazole in reducing tic severity in children and adolescents, however there is a lack of robust evidence evaluating its use in adults, despite expert consensus. Overall, it appears that aripiprazole is a safe and effective treatment for tics. Further large scale RCTs assessing the long-term efficacy and safety of aripiprazole in the treatment of tics are warranted, especially in adult populations with TS.

Thalamic Local Field Potentials Are Related to Long-Term DBS Effects in Tourette Syndrome.

Background: Local field potential (LFP) recordings helped to clarify the pathophysiology of Tourette syndrome (TS) and to define new strategies for deep brain stimulation (DBS) treatment for refractory TS, based on the delivery of stimulation in accordance with changes in the electrical activity of the DBS target area. However, there is little evidence on the relationship between LFP pattern and DBS outcomes in TS.Objective: To investigate the relationship between LFP oscillations and DBS effects on tics and on obsessive compulsive behavior (OCB) comorbidities.Methods: We retrospectively analyzed clinical data and LFP recordings from 17 patients treated with DBS of the centromedian-parafascicular/ventralis oralis (CM-Pf/VO) complex, and followed for more several years after DBS in the treating center. In these patients, LFPs were recorded either in the acute setting (3–5 days after DBS electrode implant) or in the chronic setting (during impulse generator replacement surgery). LFP oscillations were correlated with the Yale Global Tic Severity Scale (YGTSS) and the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) collected at baseline (before DBS surgery), 1 year after DBS, and at the last follow-up available.Results: We found that, at baseline, in the acute setting, the power of the oscillations included in the 5–15-Hz band, previously identified as TS biomarker, is correlated with the pathophysiology of tics, being significantly correlated with total YGTSS before DBS (Spearman's ρ = 0.701, p = 0.011). The power in the 5–15-Hz band was also correlated with the improvement in Y-BOCS after 1 year of DBS (Spearman's ρ = −0.587, p = 0.045), thus suggesting a relationship with the DBS effects on OCB comorbidities.Conclusions: Our observations confirm that the low-frequency (5–15-Hz) band is a significant biomarker of TS, being related to the severity of tics and, also to the long-term response on OCBs. This represents a step toward both the understanding of the mechanisms underlying DBS effects in TS and the development of adaptive DBS strategies.

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome.

Background: Traditional medical treatments are not effective for some patients with Tourette syndrome (TS). According to the literature, repetitive transcranial magnetic stimulation (rTMS) may be effective for the treatment of TS; however, different targets show different results.Objective: To assess the efficacy and safety of low-frequency rTMS in patients with TS, with the bilateral parietal cortex as the target.Methods: Thirty patients with TS were divided into two groups: active and sham groups. The active group was subjected to 0.5-Hz rTMS at 90% of resting motor threshold (RMT) with 1,200 stimuli/day/side, whereas the sham group was subjected to 0.5-Hz rTMS at 10% of RMT with 1,200 stimuli/day/side with changes in the coil direction. Both groups were bilaterally stimulated over the parietal cortex (P3 and P4 electrode sites) for 10 consecutive days. The symptoms of tics and premonitory urges were evaluated using the Yale Global Tic Severity Scale (YGTSS), Modified Scoring Method for the Rush Video-based Tic Rating Scale (MRVBTS), and Premonitory Urge for Tics Scale (PUTS) scores at baseline, the end of the 10-day treatment, 1 week after treatment, and 1 month after treatment.Results: At the end of the 10-day treatment, the YGTSS total, YGTSS motor tic, YGTSS phonic tic, MRVBTS, and PUTS scores in the active group significantly improved and improvements were maintained for at least 1 month.Conclusions: Low-frequency bilateral rTMS of the parietal cortex can markedly alleviate motor tics, phonic tics, and premonitory urges in patients with TS.

The α6 GABAA Receptor Positive Allosteric Modulator DK-I-56-1 Reduces Tic-Related Behaviors in Mouse Models of Tourette Syndrome.

Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists.

Multidisciplinary Telemedicine Care for Tourette Syndrome: Minireview.

Tourette syndrome (TS) is a childhood-onset, chronic neuropsychiatric disorder characterized by multiple motor and vocal tics. TS poses a considerable burden on both patients and health care providers, leading to a major detriment of educational success, occupation, and interpersonal relationships. A multidisciplinary, specialist-driven management approach is required due to the complexity of TS. However, access to such specialty care is often dramatically limited by the patients' locations and the specialists' geographic clustering in large urban centers. Telemedicine uses electronic information and communication technology to provide and support health care when distance separates participants. Therefore, we conducted this mini-review to describe the latest information on telemedicine in the assessment and management of TS and discuss the potential contributions to care for TS patients with a multidisciplinary approach. We believe that telemedicine could be a revolutionary method in improving medical access to patients with TS.

Investigation on the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children

Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

Utilizing network pharmacology to explore the underlying mechanism of Qiangzhi decoction in treating Tourette's syndrome.

Tourette's syndrome (TS) is a neurodevelopmental condition characterized by multiple motor and vocal tics. Qiangzhi decoction (QD), a well-known herbal decoction, has been used in treating TS in China for decades. We have found relevance between the indications of QD and the classic symptoms of TS. The pharmacological mechanisms of QD in treating TS are still unclear. The active compounds of QD were extracted from multi-database, including TCMSP (the Traditional Chinese Medicine Systems Pharmacology database), and potential targets of the compounds were compiled by target fishing. The TS target database was established, and then the protein-protein interaction (PPI) network was constructed to analyze the interactions between the potential targets of compounds in QD and targets associated with TS and screened the core targets by topology. The DAVID bioinformatics database was used to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. 59 active molecules and 585 potential targets of QD were selected. The consequences of the DAVID enrichment analysis show that 36 cellular biological processes (FDR <0.01) and 65 pathways (FDR <0.01) of QD chiefly took part in the convoluted treating effects relevant to the dopamine system, inflammation, and infection, and miRNA pathway. Fourteen core targets of QD were found as potential targets of the treatment of TS. QD could relieve the symptoms of TS through the molecular mechanisms predicted by network pharmacology. This study supplies insight into how network pharmacology can predict traditional Chinese herbal medicine's possible molecular mechanisms (TCHM).

Treatment of Tourette Syndrome With Attention Training Technique-A Case Series.

The existing therapeutic strategies of Tourette syndrome (TS) do not lead to sufficient improvement in a significant number of patients. Recently published studies show that paying attention to tics increases whereas directing attention away decreases tic frequency. The aim of the present case series in three patients with TS was to investigate the effect of attention training technique (ATT) on TS symptoms. ATT is a technique derived from metacognitive therapy that aims on training patients to consciously (re-)focus their attention away from themselves. Friedman’s chi-square test indicated a trend regarding the reduction of tic frequency and tic severity and a significant reduction of positive metacognitions from pre-baseline to follow-up. Reliable Change Indices (RCIs) are given for each measure and patient. Given the small number of patients, further studies including randomized controlled trials appear warranted.

Treatment use among children with Tourette syndrome living in the United States, 2014

Treatment of Tourette syndrome (TS) can be complicated by changes over time in tic expression, severity, and co-occurring disorders. Using the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome, this study provides descriptive estimates of the use of behavioral interventions and medication among children living with TS. Parent-reported data on 115 children aged 5–17 years ever diagnosed with TS were analyzed to provide descriptive, unweighted results. Overall, 77.4% of children had current or past use of any TS treatment; 59.1% ever used behavioral interventions and 56.1% had ever taken TS medication. Children with "moderate” or “severe” versus “mild” TS, ≥1 co-occurring disorders, and tics that interfered with functioning were significantly more likely to have used one or more TS treatments. Side effects were reported for 84.4% of children who took TS medication. Most parents of children with current TS (87.2%) were satisfied with the management of their child's TS. However, parents of children with “moderate” or “severe” current TS were significantly more dissatisfied compared to parents of children with “mild” TS. Findings from this study could be used to inform efforts to support children living with TS and their families.

Regulatory effects of Ningdong granule on microglia-mediated neuroinflammation in a rat model of Tourette's syndrome.

Tourette's syndrome (TS) is an inherited neurologic disorder characterized by involuntary stereotyped motor and vocal tics. Its pathogenesis is still unclear and its treatment remains limited. Recent research has suggested the involvement of immune mechanisms in the pathophysiology of TS. Microglia are the brain's resident innate immune cells. They can mediate neuroinflammation and regulate brain development and homeostasis. A traditional Chinese medicine (TCM), Ningdong granule (NDG), has been found to be efficacious in the treatment of TS while causing few adverse reactions. In the current study, a rat model of 3,3'-iminodipropionitrile (IDPN)-induced TS was used to explore the regulating effects and mechanisms of NDG on microglia-mediated neuroinflammation. IDNP led to robust pathological changes and neurobehavioral complications, with activation of microglia in the striatum of rats with TS. After activation by IDNP, microglia strongly responded to this specific injury, and TNF-α, IL-6, and MCP-1 were released in the striatum and/or serum of rats with TS. Interestingly, NDG inhibited the activation of microglia and decreased the abnormal expression of TNF-α, IL-6, and MCP-1 in the striatum and/or serum of rats with TS, thus controlling tics. However, there were no significant changes in the striatum and/or serum of rats with TS after treatment with haloperidol. The anti-TS action of haloperidol might occur not through microglial activation and neuroinflammation but through the DAT system, thus controlling tics. In conclusion, microglia might play key roles in mediating neuroinflammatory responses in TS, triggering the release of TNF-α, IL-6, and MCP-1.NDG inhibited tics in rats with TS, and this mechanism may be associated with a reduction in the increased number of activated microglia and a decrease in the expression of pro-inflammatory cytokines and chemokines in the striatum and/or serum.