Treatment Of Tourette Syndrome Research Articles

Review: Physical exercise in Tourette syndrome - a systematic review.

Tourette syndrome (TS) is a common neuropsychiatric disorder which, in addition to the core symptoms of motor and vocal tics, includes a high association with co-existing mental health disorders. Physical exercise is increasingly being recommended as part of management for children and young people with mental health problems. However, there is a lack of guidance regarding the role of physical exercise in the management of TS in children. EMBASE, MEDLINE, PsycINFO, SportDiscus, Google scholar and Cochrane register of controlled trials (CENTRAL) databases were searched. Studies investigating interventions aimed at reducing core symptoms of TS and comorbidities and exploring the relationship between physical exercise and tic severity were included. Seven studies were identified. Five focused on physical exercise interventions and two were observational studies investigating the relationship between tic severity and physical activity. There was some evidence indicating that physical exercise reduces tic severity in the short term and some evidence regarding the benefit of physical exercise on associated co-occurring symptoms, such as anxiety. However, none of the intervention studies involved randomisation and interventions varied in terms of content and duration. There was some evidence of a short-term improvement in tic expression as a result of physical exercise interventions, but there is a lack of methodologically robust studies. Thus, conclusions about the impact of exercise on TS symptoms or comorbidities cannot be drawn at this stage. There is a clear need for well-designed methodologically robust studies, including prospective observational studies and randomised controlled designs.

Review of the evidence for the management of co-morbid Tic disorders in children and adolescents with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders (TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis (meta-analysis) was deemed appropriate. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors (Atomoxetine) and stimulants (Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette’s syndrome (TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.

Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3–1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

Global network modulation during thalamic stimulation for Tourette syndrome.

Background and objectivesDeep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood.MethodsFive participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions.ResultsOur results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS.ConclusionsOverall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms.

The Implementation of Parent–Child Interaction Therapy for the Treatment of Tourette Syndrome and Disruptive Behavior

A diagnosis of Tourette syndrome (TS) can confer a plethora of negative outcomes including impaired psychosocial functioning, academic difficulties, disruptive behavior, and mood dysregulation. Further, children diagnosed with TS can engender immense amounts of burden and stress experienced by their caregivers which can put strain and tension on the parent–child relationship. Uncovering efficacious treatments for improving the quality of life for children diagnosed with TS and their families represents both a great challenge as well as a chief concern for professionals working with this population. The present case study describes the provision of parent–child interaction therapy for addressing behavioral problems in a 5-year-old boy diagnosed with TS. Results suggest improvements in child compliance, decreases in disruptive behaviors, and decreases in certain symptomatology associated with TS. Treatment implications for working with youth with TS are described in detail.

The Role of Transcranial Direct Current Stimulation (tDCS) in Tourette Syndrome: A Review and Preliminary Findings.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is being investigated for a variety of neurological and psychiatric conditions. Preliminary evidence suggests that tDCS may be useful in the treatment of Tourette Syndrome (TS). This paper reviews the literature on the use of tDCS in commonly occurring comorbid conditions that are relevant to its proposed use in TS. We describe the protocol for a double-blind, crossover, sham-controlled trial of tDCS (Trial ID: ACTRN12615000592549, registered at www.anzctr.org.au) investigating the efficacy, feasibility, safety, and tolerability of tDCS in patients with TS aged 12 years and over. The intervention consists of cathodal tDCS positioned over the Supplementary Motor Area. Patients receive either sham tDCS for three weeks followed by six weeks of active tDCS (1.4 mA, 18 sessions over six weeks), or six weeks of active sessions followed by three weeks of sham sessions, with follow-up at three and six months. Pilot findings from two patients are presented. There was a reduction in the frequency and intensity of patients’ tics and premonitory urges, as well as evidence of improvements in inhibitory function, over the course of treatment. Larger scale studies are indicated to ascertain the maintenance of symptom improvement over time, as well as the long-term consequences of the repetitions of sessions.

13 Underprovision of behavioural therapies for tourette syndrome

Objective To assess the unmet need for comprehensive behavioural intervention for tics (CBIT) and habit reversal therapy (HRT) in adults and children with Tourette Syndrome. Method Patients with Tourette Syndrome who attended the St George’s clinic between 2004 and 2015 were selected for the study (Total 388). Basic clinical characteristics and the status of CBIT/HRT was assessed for each case. It was classified as being: (1) recommended by the clinician, (2) directly referred for therapy, (3) actually received therapy, (4) stated not suitable as not indicated for reasons such as significant learning difficulty or implied lack of availability of therapists or (5) explicitly stated to be inaccessible for the patient or (6) not mentioned at all in the notes. Results Of the 388 patients 24% were female and 76% male. 41% were adults and 56% were children of 17 years and under. In total only 111 (29%) had behavioural therapy mentioned in their clinical notes. This has increased over the years with an increase from 6% in adults in 2005 to 43% in 2015 and from 11% in children in 2005 to 78% in 2015. 23 patients (6%) were categorised as not suitable. Behavioural therapy was recommended but not eventually provided to 31 of these patients (8%). In a further 35 patients (9%), behavioural therapy was deemed inaccessible by the clinician to begin with, before any attempt was even made for a referral. Only 18 (5%) patients were actually referred for behavioural therapy and 4 (1%) patients out the total 388 received behavioural therapy (2 children and 2 adults) although missing notes may have reduced this number. Conclusion Behavioural therapies are an evidence-based treatment for Tourette syndrome. The data presented here were extracted from clinical notes and were not collected prospectively for this purpose so it was often difficult to know if clinicians omitted explicit mention of CBIT/HRT because of lack of availability or on the basis of patient selection. Increasing interest over the years is however demonstrated here by an increasing focus in the patient notes, but there is still very little access to this form of treatment, a national problem. Anecdotally, many more referrals have been made for children from this clinic to another centre in the last 12 months. Under provision in the NHS of specialised psychological services for Tourette syndrome needs to be urgently addressed.

Behavioural therapy in the treatment of Tourette syndrome

Behavioural therapy in the treatment of Tourette syndrome

The Case of "Hiro": Treating Tourette Syndrome by Comprehensive Behavioral Intervention for Tics (CBIT)

Cognitive-behavioral therapy (CBT) with Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment for Tourette Syndrome (TS), with a manualized version available for guiding practitioners through treatment. However, CBIT is still a fairly new treatment for TS and rigorous training in its application is sparse. Additionally, potential treatment considerations are not thoroughly described in the manual. This dissertation presents a systematic case study that specifically analyzes the use of the manual with 10-year-old "Hiro," a South Asian Indian boy with TS who also had attention deficit hyperactivity disorder (ADHD), which is a confounding factor in the treatment of TS. To do this meant applying flexibility and an "hypothesizing-then-testing" mentality. The creation of an individualized case formulation and an associated treatment plan for Hiro were very valuable components in his treatment. The case study chronicles Hiro's successful treatment and explores how and when adherence to the manual was effective as well as how and when greater flexibility was required. Furthermore, the case study explores factors in the clinician/client relationship and how that relationship can prove a powerful tool in treatment. Options for how to maintain treatment goals after termination are also examined.

Mechanical/Algorithmic Versus Flexible/Creative Clinical Practice: How Underlying Principles Bridge the Gap

In the case of "Hiro" (Lichtman, 2017) I described the successful use of Comprehensive Behavioral Intervention for Tics (CBIT) in a young boy with Tourette Syndrome (TS). In three different commentaries on this case, authors noted important concepts regarding the use of manuals in treating TS; how an understanding of underlying principles is important in flexible use of manuals; and how training impacts the treatment of TS. In my response to these commentaries, I hope to continue the conversation of how to use manuals in psychotherapy in general as well as in the treatment of TS in particular. Specifically, I hope to address the seeming dichotomy between a mechanical, algorithmic approach to treatment versus a flexible, creative approach, and to ultimately show that an understanding of the underlying principles guiding manualized treatment provides room for ingenuity that proves this dichotomy false.

Topiramate in the Adjunctıve Treatment of Tourette Syndrome: A Case Report

ABSTRACTTourette Syndrome (TS) is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple motor tics and at least one vocal tic. In many of the cases, Attention Deficit Hyperactivity Disorder (ADHD) is a frequent comorbid disorder. Many treatment options have been suggested for TS and ADHD comorbidity. In this article, we present a case diagnosed with TS and ADHD whose tics were refractory to many other suggested treatment options for Tic Disorders (TD) and worsened during the use of recommended first-line treatment agents for ADHD, that were significantly reduced by using topiramate. New therapeutic options that would be easily used and with less side effects are needed in the treatment of TD. Topiramate treatment seems like an appropriate option raising hope for the future to be used as monotherapy or in adjuvant treatment for TD. Larger trials with longer follow up are required in this field.

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.

A Family's Guide to Tourette Syndrome

This well-written and easy-to-read text is designed for patients, parents, educators, and medical professionals who are impacted by Tourette syndrome (TS). The book provides not only a historical perspective but also a summary of current knowledge, available resources, and future directions for research and study in nontechnical language that is accessible to all readers. This book was released by the National Tourette Syndrome Association, Inc. (TSA) which describes itself as “the most notable advocate for people touched by this disorder and is perhaps the leading supporter of Tourette syndrome research and education around the world.” The opening chapter provides an overview for the contents of the book, including the definition, diagnosis, and treatment of TS, as well as the genetic basis and possible environmental triggers of the syndrome. One particularly memorable chapter is written by a physician who has spent her life working with patients with TS, and she illustrates how the psychosocial aspects of TS can impact the individual's perception of his or her disorder. Another chapter is written by a mother of three children with TS who, herself, also suffers from TS. This chapter provides an intimate and personal description of living with TS and parenting children with TS. The authors of each chapter represent a diverse array of experience with the disorder and each lends a unique perspective based on their role as a clinician, researcher, or parent. The final chapter contains 50 “Frequently Asked Questions” with brief responses and is an excellent resource for people looking for a quick answer. Throughout the book, multiple figures, graphs, and illustrative case examples help to make more of the complex concepts or multiple treatment strategies easier to understand and interpret. Several chapters address treatment. One section is devoted to drug treatments used to target the symptoms of TS and the multiple disorders known to be comorbid with TS, including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and depression. The chapter begins by defining how scientific studies into drug efficacy are conducted, followed by a description and chart of medications which includes the generic drug names, brand drug names, mechanism of action, FDA approval status, and side effects. Later chapters discuss behavioral therapies including Comprehensive Behavioral Intervention for Tics (CBIT), a form of cognitive behavioral therapy that is focused on first “awareness training” of when a tic is about to occur, followed by “competing response training” where the patient then identifies a physical response that he or she can use when feeling the urge to tic. This form of therapy emphasizes the importance of social support and encouragement for the person practicing the CBIT techniques. In addition to discussing the history and well-defined knowledge related to TS, the book also explores more controversial areas including pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), complementary and alternative medicine (CAM) therapies, medication use during pregnancy and breastfeeding, and deep brain stimulation (DBS) as a treatment for some with TS. However, an updated version reflecting more recent discussions regarding these topics and using the language of the Diagnostic and Statistical Manual–Fifth Edition would make this section more practical and applicable. While the language of this text is aimed toward parents and caregivers, interested clinicians may find this an accurate and easy-to-read resource to refresh their knowledge of this disorder. However, this book is not meant to be a clinical reference, and interested parties seeking peer-reviewed material would need to look elsewhere. Overall, A Family's Guide to Tourette Syndrome offers concise and easily understandable information in a manner that is accessible to all readers. This book will be of special interest to parents, teachers, patients, or any person interested in an overview of how TS is defined, what treatments are available, and what research is ongoing.

EP 68. Identification of electrophysiological biomarkers in a novel animal model of Tourette Syndrome

Introduction Treating Tourette syndrome (TS) remains challenging as therapies fail to take temporal presentation of symptoms into account. Therefore, to optimize therapies the investigation of biomarkers predicting repetitive behavior is required. Objectives We are currently studying repetitive behavior and associated electrophysiological changes in a new animal model of Tourette syndrome – the dopamine transporter (DAT) over-expressing rat model. The DAT rat resembles TS pathology in various aspects, including marked up-regulation of D2/D1 receptors, brain site-specific dopamine alterations and decrease in parvalbumin expressing interneurons in the caudate putamen. In line with clinical findings, the DAT rats display time-locked increase in tic-like behavior following amphetamine application. Math/meth To study stereotypic behavior, extracellular bipolar in vivo recordings were conducted under urethane anesthesia in different areas of the basal-ganglia thalamo-cortical loop for 4 h (2 h before (baseline) and 2 h after amphetamine). Signals were amplified, filtered (0.05–250 Hz) and sampled at 1 kHz. Power Spectral Densities were calculated using Spike 2 software (FFT size 1024/0.0256 s, Hanning Window) for baseline and post amphetamine time-windows, where behavioral analysis revealed stereotypy or not. Power-spectra were normalized to the mean s. d. of power between 103–147 Hz and 153–197 Hz power. Results Results show that DAT rats at the time-point of tic induction, exhibit time-locked abnormalities in alpha and beta bands, especially in the dorsomedial thalamus. This indicates characteristic electrophysiological modulation temporally related to distinct repetitive behavior. Conclusion The time-locked manifestation allows us to further investigate biomarkers of repetitive behavior and to employ this in constructing a close-loop stimulation device treating repetitive behavior in a controlled fashion.

Deep Brain Stimulation of the Globus Pallidus Internus in Patients with Intractable Tourette Syndrome: A 1-year Follow-up Study.

Background:Deep brain stimulation (DBS) has been a promising treatment for patients with refractory Tourette syndrome (TS) for more than a decade. Despite successful DBS treatment of TS in more than 100 patients worldwide, studies with a large patient sample and long-term follow-up assessments are still scarce. Accordingly, we investigated the clinical efficacy and safety of globus pallidus internus (GPi) DBS in the treatment of intractable TS in 24 patients with a 1-year follow-up assessment.Methods:Bilateral/unilateral GPi-DBS was performed in 24 patients with TS. We evaluated symptoms of tics and obsessive-compulsive disorder (OCD) through the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive-compulsive Scale (Y-BOCS). We used the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) to evaluate the safety of the treatment. We conducted follow-up assessments of all patients for at least 12 months (12–99 months).Results:Symptoms of tics and OCD were significantly relieved at a 12-month follow-up assessment. The mean YGTSS score was 74.04 ± 11.52, 49.83 ± 10.91, 32.58 ± 7.97, and 31.21 ± 8.87 at baseline, 3, 6, and 12 months, respectively. The mean YGTSS scores obtained at the follow-up assessments were significantly different from the baseline (P < 0.05). The improvement in motor tics was superior to that in phonic tics. The mean Y-BOCS scores were 21.61 ± 4.97, 18 ± 4.58, 14.39 ± 3.99, and 13.78 ± 4.56 at baseline, 3, 6, and 12 months, respectively (P < 0.05). We observed a remarkable improvement in psychiatric comorbidities, such as OCD and attention-deficit hyperactivity disorder, after the procedure. WAIS-RC scores were comparable before and after the operation. There were no severe postoperative complications.Conclusion:GPi-DBS appears to comprehensively alleviate tic symptoms and psychiatric comorbidities in patients with TS, thus significantly improving patients’ quality of life.

Practitioner Review: Treatments for Tourette syndrome in children and young people - a systematic review.

Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1-2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we conducted a systematic review of interventions for children and young people. Databases were searched from inception to 1 October 2014 for placebo-controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach. Forty trials were included [pharmacological (32), behavioural (5), physical (2), dietary (1)]. For tics/global score there was evidence favouring the intervention from four trials of α2-adrenergic receptor agonists [clonidine and guanfacine, standardised mean difference (SMD)=-0.71; 95% CI -1.03, -0.40; N=164] and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD=-0.64; 95% CI -0.99, -0.29; N=133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD=-0.54; 95% CI -0.92, -0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD=-0.74; 95% CI -1.08, -0.40; N=76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit. When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours α2-adrenergic receptor agonists (clonidine and guanfacine) as first-line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when α2-adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments.

N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial.

Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

Habit reversal training and educational group treatments for children with tourette syndrome: A preliminary randomised controlled trial

Quality of life of children with Tourette Syndrome (TS) is impacted greatly by its symptoms and their social consequences. Habit Reversal Training (HRT) is effective but has not, until now, been empirically evaluated in groups.This randomised controlled trial evaluated feasibility and preliminary efficacy of eight HRT group sessions compared to eight Education group sessions. Thirty-three children aged 9–13 years with TS or Chronic Tic Disorder took part. Outcomes evaluated were tic severity and quality of life (QoL).Tic severity improvements were found in both groups. Motor tic severity (Yale Global Tic Severity Scale) showed greatest improvements in the HRT group. Both groups showed a strong tendency toward improvements in patient reported QoL.In conclusion, group-based treatments for TS are feasible and exposure to other children with tics did not increase tic expression. HRT led to greater reductions in tic severity than Education. Implications, such as cost-effectiveness of treatment delivery, are discussed.

A Review and Update on Tourette Syndrome: Where Is the Field Headed?

Tourette syndrome (TS) is a childhood onset neurologic disorder with manifestations including multiple motor and phonic tics, and in most cases a variety of behavioral comorbidities such as attention deficit hyperactivity disorder, obsessive compulsive disorder, and other impulse control disorders. Although it is considered a hereditary disorder, likely modified by environmental factors, genetic studies have yet to uncover relevant causative genes and there is no animal model that mimics the broad clinical phenomenology of TS. There has been a marked increase in the number of neurophysiological, neuroimaging, and other studies on TS. The findings from these studies, however, have been difficult to interpret because of small sample sizes, variability of symptoms across patients, and comorbidities. Although anti-dopaminergic drugs are the most widely used medications in the treatment of TS, there has been increasing interest in other drugs, behavioral therapies, and surgical approaches including deep brain stimulation. Herein, we review the current literature and discuss the complexities of TS and the challenges in understanding its pathophysiology and in selecting the most appropriate treatment. We also offer an expert's view of where the field of TS may be headed.

Effect of mesenchymal stem cell transplantation on brain-derived neurotrophic factor expression in rats with Tourette syndrome.

The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell (MSC) transplantation on brain-derived neurotrophic factor (BDNF) expression in the striatum of Tourette syndrome (TS) rats. In addition, the possible mechanism of MSC transplantation in the treatment of TS was investigated. A total of 72 Wistar rats were randomly allocated into the control (sham surgery) group and the two experimental groups, including the TS+vehicle and TS+MSC. MSCs were co-cultured with 5-bromodeoxyuridine for 24 h for labeling prior to grafting. An autoimmune TS rat model was successfully established in the present study. Rat MSCs were cultured and expanded using density gradient centrifugation in vitro, identified by flow cytometry and then transplanted into the striata of the TS+MSC group rats. The mRNA and protein expression levels of BDNF were detected by RT-qPCR and ELISA, respectively. The results indicated that the stereotypic behavior of TS rats was reduced 7 days after MSC transplantation, while the mRNA and protein BDNF levels in the striatum increased, compared with the sham surgery group (P<0.05). In addition, the BDNF mRNA and protein expression level was lower in the striatum of TS+MSC transplantation, compared with that in TS+vehicle rats. In conclusion, intrastriatal transplantation of MSCs may provide relief from stereotypic TS behavior, since the BDNF level was reduced in TS rats after MSC transplantation.