Search

The Tourette OCD Alberta Network (TOAN) supports mental health therapists to improve the delivery of care to patients with Tourette syndrome (TS) and OCD in Alberta. We evaluated the professional development needs of health care workers to develop a continuing professional development (CPD) webinar series. Health care workers demonstrated an urgent need to access a CPD program grounded in evidenced based knowledge about TS and OCD. While 80% of health care workers treated children with TS and OCD, 50% had no formal training. A curriculum consisting of a series of twelve live, online webinars was developed and delivered between September 2020 and June 2021, covering a range of clinical topics. The webinars were attended on average by 63 attendees, with the outcome of a positive knowledge gain. In future, the educational program will need to reflect the ongoing developing clinical understanding of TS and OCD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year., Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants., Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume., Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) more...

Background and Purpose: The aim was to test the specificity of phenomenological criteria for functional tic-like behaviours (FTLBs). The European Society for the Study of Tourette Syndrome (ESSTS) criteria for the diagnosis of FTLBs include three major criteria: age at symptom onset ≥12 years, rapid evolution of symptoms and specific phenomenology., Methods: Children and adolescents with primary tic disorders have been included in a Registry in Calgary, Canada, since 2017. Using the Yale Global Tic Severity Scale, the proportion of youth with primary tic disorders who met specific phenomenological criteria for FTLBs at first visit was assessed: (1) having ≥1 specific complex motor tic commonly seen in FTLBs, including complex arm/hand movements, self-injurious behaviour, blocking, copropraxia; (2) having ≥1 specific complex phonic tic commonly seen in FTLBs, including saying words, phrases, disinhibited speech, coprolalia; (3) having a greater number of complex tics than simple tics. Children seen for the first time between 2017 and 2019 and between 2021 and 2023 were analysed separately., Results: Of 156 participants included between 2017 and 2019, high specificity (94.2%) of the age at onset criterion (≥12 years) and of having at least two complex motor behaviours and one complex phonic behaviour at first visit (96.2%) was observed. Some of the complex motor tics had lower specificity. The specificity of the FTLB diagnostic criterion of having more complex tics than simple tics was 89.7%. There was no significant difference in specificity of the criteria for children seen for the first time between 2017 and 2019 and between 2021 and 2023 (n = 149)., Conclusion: This information supports the use of the ESSTS criteria for FTLBs in clinical practice., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.) more...

Despite the growing interest on how Tourette syndrome (TS) affects social cognition skills, this field remains to date relatively under-explored. Here, we aim to advance knowledge on the topic by studying moral decision-making and moral reasoning in a group of adolescents with TS and a group of healthy controls. Overall, we found higher endorsement (i.e. a greater 'yes' response rate) for utilitarian solutions of incidental and instrumental moral dilemmas in TS compared to controls. By contrast, we reported an overall higher tendency of TS individuals to apply principles described in the moral foundation questionnaire to establish whether something is morally right or wrong. Our results document intact moral reasoning in TS and suggest that a deficit in suppressing inappropriate behaviours and/or altered sense of agency might be responsible for their higher utilitarian moral decision-making., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.) more...

Background: Premonitory urges (PU) are well described in primary tics, but their frequency and intensity in functional tic-like behaviors (FTLB) are unclear., Objective: To study the experience of PU in patients with FTLB., Methods: We compared the results of the premonitory urge for tics scale (PUTS) in adults with tics and FTLB in the University of Calgary Adult Tic Registry., Results: We included 83 patients with tics and 40 with FTLB. When comparing patients with tics, FTLB with tics and FTLB only, we did not detect significant differences either in the total PUTS score (P = 0.39), or in any of the individual PUTS item sub-scores (P values ranging between 0.11 and 0.99)., Conclusions: Patients with FTLB report PU at similar frequency and intensity to patients with tics. This finding confirms that PU are not a useful feature to discriminate FTLB from tics., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.) more...

Background and Purpose: Very little is known about the long-term prognosis of patients with functional tic-like behaviours (FTLBs). We sought to characterize the trajectory of symptom severity over a 12-month period., Methods: Patients with FTLBs were included in our prospective longitudinal child and adult clinical tic disorder registries at the University of Calgary. Patients were prospectively evaluated 6 and 12 months after their first clinical visit. Tic inventories and severity were measured with the Yale Global Tic Severity Scale (YGTSS)., Results: Eighty-three youths and adults with FTLBs were evaluated prospectively until April 2023. Mean YGTSS total tic severity scores were high at baseline, with a mean score of 29.8 points (95% confidence interval [CI] = 27.6-32.1). Fifty-eight participants were reevaluated at 6 months, and 32 participants were reevaluated at 12 months. The YGTSS total tic severity score decreased significantly from the first clinical visit to 6 months (raw mean difference = 8.9 points, 95% CI = 5.1-12.7, p < 0.0001), and from 6 to 12 months (raw mean difference = 6.4 points, 95% CI = 0.8-12.0, p = 0.01). Multivariable linear regression demonstrated that tic severity at initial presentation and the presence of other functional neurological symptoms were associated with higher YGTSS total tic scores at 6 months, whereas younger age at baseline, receiving cognitive behavioural therapy for anxiety and/or depression, and prescription of selective serotonin reuptake inhibitors were associated with lower YGTSS total tic scores at 6 months., Conclusions: We observed a meaningful improvement in tic severity scores in youth and adults with FTLBs over a period of 6-12 months., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.) more...

Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling body movements. However, it remains unclear whether movement disorders have a systematic impact on social cognition. To address this question, we conducted a systematic review examining the influence of hyperkinetic movement disorders (including Huntington disease, Tourette syndrome, dystonia, and essential tremor) on social cognition. Following the PRISMA guidelines and registering the protocol in the PROSPERO database (CRD42022327459), we analyzed 50 published studies focusing on theory of mind (ToM), social perception, and empathy. The results from these studies provide evidence of impairments in ToM and social perception in all hyperkinetic movement disorders, particularly during the recognition of negative emotions. Additionally, individuals with Huntington's Disease and Tourette syndrome exhibit empathy disorders. These findings support the functional role of subcortical structures (such as the basal ganglia and cerebellum), which are primarily responsible for movement disorders, in deficits related to social cognition. more...

Background: Reliably applied criteria to differentiate functional from primary tics are lacking. In the absence of biological markers, the development of new diagnostic criteria to assist clinicians is predicated on expert judgement and consensus. This study examines the level of diagnostic agreement of experts in tic disorders using video footage and clinical descriptions., Methods: Using a two-part survey, eight experts in the diagnosis and management of tics were first asked to study 24 case videos of adults with primary tics, functional tics or both and to select a corresponding diagnosis. In the second part of the survey, additional clinical information was provided, and the diagnosis was then reconsidered. Inter-rater agreement was measured using Fleiss' kappa. In both study parts, the factors which influenced diagnostic decision-making and overall diagnostic confidence were reviewed., Results: Based on phenomenology alone, the diagnostic agreement among the expert raters was only fair for the pooled diagnoses (κ=0.21) as well as specifically for functional (κ=0.26) and primary tics (κ=0.24). Additional clinical information increased overall diagnostic agreement to moderate (κ=0.51) for both functional (κ=0.6) and primary tics (κ=0.57). The main factors informing diagnosis were tic semiology, age at tic onset, presence of premonitory urges, tic suppressibility, the temporal latency between tic onset and peak severity, precipitants and tic triggers and changes in the overall phenotypic presentation., Conclusions: This study confirmed that in the absence of clinical information, the diagnostic distinction between primary and functional tics is often difficult, even for expert clinicians., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Background and Purpose: Developmental stuttering and Tourette syndrome (TS) are common neurodevelopmental disorders. Although disfluencies may co-occur in TS, their type and frequency do not always represent pure stuttering. Conversely, core symptoms of stuttering may be accompanied by physical concomitants (PCs) that can be confused for tics. This scoping review aimed to explore the similarities and differences between stuttering and tics in terms of epidemiology, comorbidities, phenomenology, evolution, physiopathology, and treatment. We also described the nature of PCs in stuttering and disfluencies in TS., Methods: A literature search on Medline, Embase and PsycInfo was executed in March 2022. From 426 studies screened, 122 were included in the review (a majority being narrative reviews and case reports)., Results: TS and stuttering have several epidemiological, phenomenological, comorbidity, and management similarities suggesting shared risk factors and physiopathology (involving the basal ganglia and their connections with speech and motor control cortical regions). PCs in stuttering commonly involve the face (eyelids, jaw/mouth/lip movements) and sometimes the head, trunk and limbs. PCs can be present from early stages of stuttering and vary over time and within individuals. The function of PCs is unknown. Some individuals with TS have a distinct disfluency pattern, composed of a majority of typical disfluencies (mostly between-word disfluencies), and a mix of cluttering-like behaviors, complex phonic tics (e.g. speech-blocking tics, echolalia, palilalia), and rarely, atypical disfluencies., Conclusion: Future investigations are warranted to better understand the complex relationships between tics and stuttering and address the management of disfluencies in TS and PCs in stuttering., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...

Introduction: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines., Objectives: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of Tourette Syndrome guidelines, and 2) to identify categories of barriers leading to these clinical care gaps., Methods and Analysis: This article presents the methodology of a planned cross-sectional survey amongst healthcare professionals routinely involved in the clinical care of patients with persistent tic disorders, aimed at 1) identifying how practices diverge from the published guidelines; and 2) identifying categories of barriers leading to these clinical care gaps. Purposeful sampling methods are used to identify and recruit critical persistent tic disorders stakeholders. The analysis will use descriptive statistics., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JMM has no conflicts that affect the content of this manuscript. In the past two years, she has received honoraria from the Tourette Association of America. In addition, she participates in research funded by the Tourette Association of America and the American Board of Psychiatry and Neurology. HS has no conflicts that affect the content of this manuscript. Dr. Sarva has done consulting work for Neuroderm, Bluerock, Novo Nordisk, and CALA Health. In addition, she has received clinical trial support from Neuroderm, Bluerock, Prevail, Covance, and NIH. IAM has no conflicts that affect the content of this manuscript. She has participated in research funded by AbbVie, Boston Scientific, Eli Lilly, Neuroderm, and Revance but has no ownership interest in any pharmaceutical company. In addition, she has received travel compensation or honoraria from the Tourette Association of America, Parkinson Foundation, Medscape, Efficient CME, and Cleveland Clinic, and royalties for writing a book with Robert Rose publishers. DM has no conflicts that affect the content of this manuscript. In the past two years, he has received personal compensation for consultancies by Roche, Sunovion, and Merz Pharmaceuticals but has no ownership interest in any pharmaceutical company. He has also received travel compensation or honoraria from the Dystonia Medical Research Foundation of Canada, Movement Disorders Society, and the American Academy of Neurology, and book royalties from Springer-Verlag and Oxford University Press. In addition, he received research support from Ipsen Corporate, Owerko Foundation, Dystonia Medical Research Foundation Canada, Parkinson Canada, and the Michael P Smith Family. DLG has received compensation for expert testimony for the U.S. National Vaccine Injury Compensation Program through the Department of Health and Human Services. He has received payment for medical expert opinions through Advanced Medical/Teladoc. He has served as a consultant for Applied Therapeutics, Eumentics Therapeutics, and Emalex. He has received research support from the NIH and the DOD. He has received salary compensation through Cincinnati Children’s for work as a clinical trial site investigator from Emalex (clinical trial, Tourette Syndrome) and EryDel (clinical trial, Ataxia Telangiectasia). He has received book/publication royalties from Elsevier, Wolters Kluwer, and the Massachusetts Medical Society. TP has no commercial or financial relationships that could be construed as a potential conflict of interest. TP receives research support from Alberta Health, the Alberta Children’s Hospital Research Institute, and the Public Health Agency of Canada. KJB has no conflicts that affect the content of this manuscript. In the past two years, author KJB consulted for SK Life Science, Inc., served as faculty for CME programs by Medscape and Mededicus, and served as an expert rater for the Huntington Study Group, which had contracted with Neurocrine Biosciences. In addition, his institution received research funding from Emalex Biosciences for treatment studies with ecopipam. CG has no conflicts that affect the content of this manuscript. A Freigeist Fellowship of the Volkswagen Stiftung supports him. He has received honoraria from the Movement Disorder Society and BIAL for educational activities. He received honoraria from Biomarine Pharmaceuticals as Ad Hoc Advisory Board. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Martindale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) more...

Background and Purpose: In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic-like behaviours. We assembled a working group to develop criteria for the clinical diagnosis of functional tic-like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition., Methods: We used a formal consensus development process, using a multiround, web-based Delphi survey. The survey was based on an in-person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting., Results: In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion., Conclusions: Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity., (© 2023 European Academy of Neurology.) more...

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders., (© 2023. The Author(s).) more...

Background and Purpose: Between 2019 and 2022, there was a marked rise in adolescents/young adults seeking urgent help for functional tic-like behaviours (FTLBs). Given the global scale of this phenomenon, we aimed to pool cases from different institutions in an international registry to better characterize this spectrum and facilitate future longitudinal observation., Methods: An international collaborative group from 10 tertiary referral centres for tic disorders collected retrospective data on FTLB patients who sought specialists' attention between the last quarter of 2019 and June 2022. An audit procedure was used for collection of data, which comprised demographics, course of presentation and duration, precipitating and predisposing factors, phenomenology, comorbidities, and pharmacological treatment outcome., Results: During the study period, we collected data on 294 patients with FTLBs, 97% of whom were adolescents and young adults and 87% of whom were female. FTLBs were found to have a peak of severity within 1 month in 70% of patients, with spontaneous remissions in 20%, and a very high frequency of complex movements (85%) and vocalizations (81%). Less than one-fifth of patients had pre-existing primary tic disorder, 66% had comorbid anxiety disorders, 28% comorbid depressive disorders, 24% autism spectrum disorder and 23% attention deficit/hyperactivity disorder. Almost 60% explicitly reported exposure to tic-related social media content. The vast majority of pharmacologically treated patients did not report benefit with tic-suppressing medications., Conclusions: Our data from the largest multicentre registry of FTLBs to date confirm substantial clinical differences from primary tic disorders. Social modelling was the most relevant contributing factor during the pandemic. Future longitudinal analyses from this database may help understand treatment approaches and responsiveness., (© 2022 European Academy of Neurology.) more...

Tics are repetitive, patterned, and nonrhythmic movements or vocalizations/audible sounds that are misplaced in context. Phenomenology and characteristics of tics (e.g., premonitory urge, suppressibility) differentiate them from compulsions, stereotypies, functional tic-like behaviors, and other types of hyperkinetic movement disorders. With a prevalence of approximately 1% in school-aged boys, Tourette syndrome (TS) is considered a common childhood-onset neurodevelopmental disorder, defined by the combination of at least two motor tics and at least one phonic tic lasting more than 1 year. TS is a highly heritable disorder, with a wide spectrum of severity. In some individuals, tics can cause pain, distress, functional impairment, or stigmatization. About 90% of individuals with TS have at least one mental health comorbidity (attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety/depressive disorders). These comorbidities significantly impact patients' quality of life and must therefore be screened and managed accordingly in this population. Treatment of tics is based on behavioral therapies targeting tics (habit reversal training included in the comprehensive behavioral intervention for tics, and exposure and response prevention for tics), in association with medication if needed (e.g., alpha-2-agonists, second-generation antipsychotics). Deep brain stimulation is considered an experimental option in the most severe, treatment-resistant patients. In adulthood, less than 25% of individuals still have moderate or severe tics., (Copyright © 2023 Elsevier B.V. All rights reserved.) more...

Immune-inflammatory mechanisms seem to play a relevant role in neurodegenerative disorders affecting motor systems, particularly Parkinson's disease, where activity changes in inflammatory cells and evidence of neuroinflammation in experimental models and patients is available. Amyotrophic lateral sclerosis is also characterized by neuroinflammatory changes that involve primarily glial cells, both microglia and astrocytes, as well as systemic immune dysregulation associated with more rapid progression. Similarly, the exploration of gut dysbiosis in these two prototypical neurodegenerative motor disorders is advancing rapidly. Altered composition of gut microbial constituents and related metabolic and putative functional pathways is supporting a pathophysiological link that is currently explored in preclinical, germ-free animal models. Less compelling, but still intriguing, evidence suggests that motor neurodevelopmental disorders, e.g., Tourette syndrome, are associated with abnormal trajectories of maturation that include also immune system development. Microglia has a key role also in these disorders, and new therapeutic avenues aiming at its modulation are exciting prospects. Preclinical and clinical research on the role of gut dysbiosis in Tourette syndrome and related behavioral disorders is still in its infancy, but early findings support the rationale to delve deeper into its contribution to neural and immune maturation abnormalities in its spectrum., (Copyright © 2023 Elsevier B.V. All rights reserved.) more...

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed 'lesion network mapping' to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain. We probed this using a normative functional connectome acquired in 1000 healthy participants. We then examined the specificity of the identified network by contrasting tic-lesion connectivity maps to those seeding from 717 lesions associated with a wide array of neurological and/or psychiatric symptoms within the Harvard Lesion Repository. Finally, we determined the predictive utility of the tic-inducing lesion network as a therapeutic target for neuromodulation. Specifically, we collected retrospective data of 30 individuals with Tourette disorder, who underwent either thalamic (n = 15; centromedian/ventrooralis internus) or pallidal (n = 15; anterior segment of globus pallidus internus) deep brain stimulation and calculated whether connectivity between deep brain stimulation sites and the lesion network map could predict clinical improvements. Despite spatial heterogeneity, tic-inducing lesions mapped to a common network map, which comprised the insular cortices, cingulate gyrus, striatum, globus pallidus internus, thalami and cerebellum. Connectivity to a region within the anterior striatum (putamen) was specific to tic-inducing lesions when compared with control lesions. Connectivity between deep brain stimulation electrodes and the lesion network map was predictive of tic improvement, regardless of the deep brain stimulation target. Taken together, our results reveal a common brain network involved in tic generation, which shows potential as a therapeutic target for neuromodulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...

Background and Purpose: The prognosis of rapid onset functional tic-like behaviors (FTLBs) is unknown. This prospective cohort study describes the course and treatment of rapid onset FTLBs in adolescents (n = 20) and adults (n = 9) previously reported in two case series., Methods: Yale Global Tic Severity Scale (YGTSS) scores were compared between first clinical presentation and 6-month follow-up assessment. All treatments used for FTLBs and any psychiatric comorbidities were recorded., Results: In adolescents with FTLBs, motor tics, vocal tics, total tics, impairment, and global scores on the YGTSS significantly improved at 6 months, with a mean decrease in the YGTSS global score of 31.9 points, 95% confidence interval (CI) 15.4, 48.4, p = .0005. In adults with FTLBs, only impairment and global scores significantly improved, with a mean decrease in the YGTSS global score of 19.6 points, 95% CI -3.2, 42.3, p = .04. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) for anxiety and depression were the most used treatment in both age groups., Conclusions: This prospective study suggests that adolescents have a better prognosis than adults with FTLBs. Management of comorbidities with SSRIs and CBT seems effective., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.) more...

Aim: To investigate sex-related differences in tic severity, tic-related impairments, and psychiatric comorbidities in childhood., Method: In this cross-sectional study, tic severity/impairment and demographic factors were collected from 270 children and young people (aged 5-17y, mean 10y 6mo, SD 3y 4mo; 212 males and 58 females) with a tic disorder diagnosis at a specialty clinic. Psychiatric diagnoses and corresponding screening questionnaire scores were collected for attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), major depressive disorder, and anxiety disorders. Logistic regression was used to compare the effect of sex and age on psychiatric comorbid diagnoses. The Mann-Whitney U test and t-tests were used to assess differences in questionnaire score distribution between sexes., Results: Females had more severe motor tics (12.55 vs 10.81, p=0.01) and higher global severity scores (38.79 vs 32.66, p=0.03) on the Yale Global Tic Severity Scale. Females were less likely to be diagnosed with ADHD (odds ratio=0.48, 95% confidence interval=0.26-0.89). No significant sex difference was observed in diagnosis rates or symptom severity scores for anxiety or OCD. Females had significantly higher scores than males on the Children's Depression Inventory, Second Edition., Interpretation: The higher level of motor tic severity and global severity in females further supports the differential natural history of tic disorders in females. Females with tic disorders may be underdiagnosed for ADHD., (© 2021 Mac Keith Press.) more...

Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics., Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample., Results: Children with tic onset were more frequently male (β = -0.36), had higher baseline severity of conduct problems (β = 0.23), autism spectrum disorder symptoms (ASD; β = 0.08), compulsions (β = 0.02) and emotional problems (β = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (β = 0.39) and emotional problems were female-specific predictors., Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.) more...

In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills., (© 2021. The Author(s).) more...

Infectious pathogens may represent an environmental risk factor for chronic tic disorders (CTD). This cross-sectional study aimed to determine whether Mycoplasma pneumoniae (M. pneumoniae) IgG positivity is associated with the presence or severity of tics. We compared M. pneumoniae IgG positivity across three groups: children and adolescents (3-16 years) with CTD (CTD group; n = 302); siblings (3-10 years) of people with CTD who developed tics within a seven-year follow-up period (tic onset group; n = 51); siblings (4-10 years) who did not develop tics within the study period and were ≥10-years-old at their last assessment (unaffected group; n = 88). The relationship between M. pneumoniae IgG positivity and the presence and severity of tics was analysed using multilevel models controlling for site, family relatedness, sex, age, presence of comorbid obsessive-compulsive and/or attention-deficit/hyperactivity disorder and use of psychotropic medication. M. pneumoniae IgG positivity was not associated with the presence of CTD, or the first onset of tics as compared to siblings who remained unaffected. M. pneumoniae IgG positivity was associated with a higher tic severity score within the CTD group (β = 2.64, s.e. = 1.15, p = 0.02). It is possible that M. pneumoniae infection influences tic severity in CTD or, that having more severe tics, increases the risk of infection. However, it is more likely that the association observed in this study reflects a propensity toward enhanced immune responses in people with CTD and that, rather than a causal relationship, infection and greater tic severity are indirectly linked via shared underlying immune mechanisms., (Copyright © 2021. Published by Elsevier Inc.) more...

Background and Purpose: Clinicians have reported an increase in functional tic-like behaviours in children and youth during the COVID-19 pandemic. We describe adults developing rapid onset of functional tic-like behaviours between May 2020 and June 2021., Methods: Data were analysed from the Adult Tic Disorders Registry, a single-site,12-month prospective cohort study that began enrolment in January 2021. We compared clinical features of participants with Tourette syndrome or persistent motor/vocal tic disorder to participants with rapid onset tic-like behaviours., Results: Thirty-three participants registered between January and June of 2021; nine had rapid onset tic-like behaviours, and 24 had Tourette syndrome or persistent motor tic disorder. Participants with rapid onset tic-like behaviours were younger (19.9 vs. 38.6 years, p = 0.003), had older age at onset (15.3 vs. 10.1, p = 0.0009), and were more likely female (p < 0.0001). They had higher motor and vocal tic severity and impairment scores (all p < 0.01) and were more likely to have complex arm/hand motor tics (p < 0.0001), complex vocal tics (p < 0.0001), and coprolalia (p = 0.004). They had significantly higher scores on all mental health symptom self-report measures (all p < 0.05) and were significantly more likely to be diagnosed with depression (p = 0.03)., Conclusions: The clinical features that help differentiate rapid onset tic-like behaviours from Tourette syndrome or persistent motor tic disorder include their phenomenology, onset age, and clinical course. Rapid onset tic-like behaviours are a distinct subtype of functional neurological disorder that has emerged during the COVID-19 pandemic in young people and appears to be strongly socially influenced., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.) more...

Background: Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood., Objectives: To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders., Methods: A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders., Results: Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention., Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).) more...

Background: Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural-immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen-presenting cells; changes in their frequency have been observed in several autoimmune conditions., Methods: In 18 TS patients (15 on stable pharmacological treatment, three unmedicated) and 18 age-matched healthy volunteers (HVs), we explored circulating blood-derived DCs and their relationship with clinical variables and brain metabolites, measured via proton magnetic resonance spectroscopy (1H-MRS). DC subsets, including plasmacytoid and myeloid type 1 and 2 dendritic cells (MDC1, MDC2), were studied with flow cytometry. 1H-MRS was used to measure total choline, glutamate plus glutamine, total creatine (tCr), and total N-acetylaspartate and N-acetylaspartyl-glutamate levels in frontal white matter (FWM) and the putamen., Results: We did not observe differences in absolute concentrations of DC subsets or brain inflammatory metabolites between patients and HVs. However, TS patients manifesting anxiety showed a significant increase in MDC1s compared to TS patients without anxiety (p = 0.01). We also found a strong negative correlation between MDC1 frequency and tCr in the FWM of patients with TS (p = 0.0015), but not of HVs., Conclusion: Elevated frequencies of the MDC1 subset in TS patients manifesting anxiety may reflect a proinflammatory status, potentially facilitating altered neuro-immune crosstalk. Furthermore, the strong inverse correlation between brain tCr levels and MDC1 subset frequency in TS patients suggests a potential association between proinflammatory status and metabolic changes in sensitive brain regions., (© 2021 European Academy of Neurology.) more...

The purpose of this study was to examine associations between physical activity, sleep and symptom severity in children with tic disorders. Children with tic disorders wore the GeneActiv device, a wrist-worn accelerometer that measures physical activity intensity and sleep/wake parameters continuously for seven days, and completed questionnaires on sleep quality, exercise and severity of tics, ADHD, obsessive-compulsive behaviours, anxiety and depression. 110 children participated in the study. Children with more severe tics had significantly more frequent comorbid diagnoses, greater impairment in subjective sleep measures, greater sedentary activity time and less light, moderate and vigorous activity time (all p < 0.05). There was a significant negative correlation between light, moderate and vigorous physical activity and the severity of tics (- 0.22, p = 0.04), obsessive compulsive behaviours (- 0.22, p = 0.03), anxiety (- 0.35, p = 0.0005) and depression (- 0.23, p = 0.03). There was no correlation between objective sleep time, sleep efficiency and symptom severity. Subjective sleep quality was positively correlated with all symptom severity measures, with the strongest correlation with ADHD severity (0.42, p < 0.00001). The results of this observational study indicate a small, but significant relationship between activity and sleep measures and the severity of the main symptom domains present in tic disorders. more...

The selection of patients with Tourette syndrome (TS) for deep brain stimulation (DBS) surgery rests on 5 fundamental pillars. However, the operationalization of the multidisciplinary screening process to evaluate these pillars remains highly diverse, especially across sites. High tic severity and tic-related impact on quality of life (first 2 pillars) require confirmation from objective, validated measures, but malignant features of TS should per se suffice to fulfill this pillar. Failure of behavioral and pharmacologic therapies (third pillar) should be assessed taking into account refractoriness through objective and subjective measures supporting lack of efficacy of all interventions of proven efficacy, as well as true lack of tolerability, adherence, or access. Educational interventions and use of remote delivery formats (for behavioral therapies) play a role in preventing misjudgment of treatment failure. Stability of comorbid psychiatric disorders for 6 months (fourth pillar) is needed to confirm the predominant impact of tics on quality of life, to prevent pseudo-refractoriness, and to maximize the future DBS response. The 18-year age limit (fifth pillar) is currently under reappraisal, considering the potential impact of severe tics in adolescence and the predictive effect of tic severity in childhood on tic severity when transitioning into adulthood. Future advances should aim at a consensus-based definition of failure of specific, noninvasive treatment strategies for tics and of the minimum clinical observation period before considering DBS treatment, the stability of behavioral comorbidities, and the use of a prospective international registry data to identify predictors of positive response to DBS, especially in younger patients., (© 2021 American Academy of Neurology.) more...

Introduction: Converging evidence from both clinical and experimental studies has shown that Tourette syndrome (TS) is not a unitary condition, but a cluster of multiple phenotypes, which encompass both tics and specific behavioural and cognitive symptoms (mainly attention-deficit and hyperactivity disorder and obsessive-compulsive disorder). Methods: We conducted a narrative review of the recent literature on the cognitive neuropsychiatry of TS. Results: Although clinical research has shown that TS is not associated with cognitive deficits per se, the findings of recent studies have suggested the presence of subtle alterations in specific cognitive functions. A promising line of research on imitative behaviour could provide a common background for the alterations in executive control and social cognition observed in TS. Two different (but not mutually exclusive) neurocognitive theories have recently suggested that TS could originate from altered perception-action binding and social decision-making dysfunction, respectively. Conclusions: Since the presence of behavioural comorbidities influences individualised treatment approaches, it is likely that a more precise characterisation of TS phenotypes, including cognitive aspects, will result in improved levels of care for patients with tic disorders. more...

Gilles de la Tourette syndrome (GTS) is a neurological condition characterized by motor and vocal tics. Previous studies suggested that this syndrome is associated with abnormal sensorimotor cortex activity at rest, as well as during the execution of voluntary movements. It has been hypothesized that this abnormality might be interpreted as a form of increased tonic inhibition, probably to suppress tics; however, this hypothesis has not been tested so far. The present study was designed to formally test how voluntary tic suppression in GTS influences the activity of the sensorimotor cortex during the execution of a motor task. We used EEG to record neural activity over the contralateral sensorimotor cortex during a finger movement task in adult GTS patients, in both free ticcing and tic suppression conditions; these data were then compared with those collected during the same task in age-matched healthy subjects. We focused on the levels of activity in the beta frequency band, which is typically associated with the activation of the motor system, during three different phases: a pre-movement, a movement, and a post-movement phase. GTS patients showed decreased levels of beta modulation with respect to the healthy controls, during the execution of the task; however, this abnormal pattern returned to be normal when they were explicitly asked to suppress their tics while moving. This is the first demonstration that voluntary tic suppression in GTS operates through the normalization of the EEG rhythm in the beta frequency range during the execution of a voluntary finger movement., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.) more...

Background: Trends in the use of antipsychotics and alpha agonists for the treatment of tic disorders in Canadian children, and how closely these trends align with evidence-based guidelines on the pharmacotherapy of tic disorders, have not been explored., Methods: IQVIA's Canadian Disease and Therapeutic Index, a survey-based data set, was used to identify prescription patterns by physicians. Respondents recorded all patient visits during a 48-hour period in each quarter of the year, including patient age, gender, drug recommendation and therapeutic indication. Recommendations for alpha agonists and antipsychotics from 2012 to 2016 were analysed for children and adolescents with tic disorders., Results: Risperidone and clonidine were the most commonly recommended medications for tic disorders over the study period, with 36,868 and 35,500 recommendations in 2016, respectively. Recommendations for clonidine increased over the study period, whereas those for risperidone decreased. Guanfacine (approved in Canada in 2013) was used less frequently than clonidine. Clonidine was more frequently recommended than antipsychotics in children younger than 6, in whom antipsychotic recommendations were uncommon. Aripiprazole was the second most commonly recommended antipsychotic for tic disorders, with 22,892 recommendations in 2016. Of the first-generation antipsychotics, pimozide was most commonly recommended (11,334 recommendations in 2016); haloperidol was infrequently recommended., Discussion: The trends observed are in line with guideline recommendations reflected in the decreasing use of risperidone, and the growing use of clonidine and guanfacine. The growing use of aripiprazole is likely due to emerging evidence from clinical trials supporting its efficacy for tics. Recommendations for pimozide and haloperidol were limited, likely due to the greater adverse effects associated with these medications., Competing Interests: Funding: None. Conflicts of Interest: The authors report no conflict of interest. David Stewart and Ali Tehrani are employees of IQVIA Canada. Ethics Statement: The data used for this study were drawn from IQVIA’s Canadian Disease and Therapeutic Index (CDTI). This is a proprietary source of data belonging to IQVIA and therefore not publicly available. IQVIA is a multinational company offering consultative and analytical services pertaining to their data products, focusing chiefly on clinical research and health information technologies. As noted in the Methods section, participating physicians completed an anonymised record of all patient visits during a 48-hour period in each quarter of the year. Informed consent was not required as no personal identifying information was collected. No institutional review board was required, as the research did not entail experimental investigation of human participants. more...

Introduction: Tourette syndrome is a common childhood-onset neuropsychiatric disorder, with tics that wax and wane in frequency and severity over time. The purpose of the proposed scoping review is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tic severity and identify key concepts and gaps in research., Methods: Our scoping review will use the six-step framework recommended by Arksey and O'Malley, with enhancements from Levac et al and Joanna Briggs Institute. We will attempt to identify all the relevant literature regardless of study design. We will search six electronic databases, the reference lists of all selected studies and the grey literature for studies examining an association between dietary factors, sleep or physical exercise and tics, or studies of interventions targeting diet, sleep or exercise to reduce tics. Our analysis plan includes description of the reported associations among dietary factors, sleep and physical exercise and tics, the effects of interventions, the research methodologies and how outcomes are measured., Ethics and Dissemination: An approval from a recognised committee is not required to conduct the proposed review, as the study entails secondary analysis of the literature available publicly. For dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Objective: To systematically evaluate the efficacy of treatments for tics and the risks associated with their use., Methods: This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics., Results: There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs., Conclusions: There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations., (© 2019 American Academy of Neurology.) more...

Objective: To make recommendations on the assessment and management of tics in people with Tourette syndrome and chronic tic disorders., Methods: A multidisciplinary panel consisting of 9 physicians, 2 psychologists, and 2 patient representatives developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence., Results: Forty-six recommendations were made regarding the assessment and management of tics in individuals with Tourette syndrome and chronic tic disorders. These include counseling recommendations on the natural history of tic disorders, psychoeducation for teachers and peers, assessment for comorbid disorders, and periodic reassessment of the need for ongoing therapy. Treatment options should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered. Treatment options include watchful waiting, the Comprehensive Behavioral Intervention for Tics, and medication; recommendations are provided on how to offer and monitor these therapies. Recommendations on the assessment for and use of deep brain stimulation in adults with severe, treatment-refractory tics are provided as well as suggestions for future research., (© 2019 American Academy of Neurology.) more...

Introduction: The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation. more...

Tics are neurodevelopmental hyperkinetic symptoms typically associated with unpleasant sensory experiences called premonitory urges. Tourette syndrome (TS) is the primary chronic tic disorder for which medical surveillance is most frequently required, and is associated with a complex phenotypical spectrum encompassing different types of abnormal behaviors. Animal models of tics support their link to phasic activity changes throughout the sensorimotor loop of the cortico-basal ganglia-thalamo-cortical network. Event-related functional magnetic resonance imaging (fMRI) studies on patients with TS showed that the supplementary motor area relays preparatory signals related to tics to the primary motor area and other cortical regions relevant to action monitoring, following which cortico-basal ganglia-thalamo-cortical activation leads to the manifestation of tics. Despite their methodological heterogeneity, structural MRI studies highlighted the existence of anatomical markers of distinct sub-phenotypes of the TS spectrum. Initial evidence suggests that combining MRI structural methods and functional intrinsic connectivity assessed during resting state could even discriminate between TS patients and control groups. MR-spectroscopy and positron emission tomography studies suggest that TS may be related to a complex interplay between different neurotransmitters (particularly dopamine, GABA and glutamate), but discrepancy across studies prevents firm conclusions. Recent volumetric, cortical thickness and fMRI studies results showed an association between premonitory urges and somatosensory and insular cortical regions, involved in the processing of interoceptive and enteroceptive stimuli and motor output modulation. Finally, both structural and functional MRI studies have provided important support to the subtyping of the TS spectrum with respect to behavioral co-morbidities, in line with a "dimensional approach" to the classification of neuropsychiatric disorders, which is based on the identification of neurocognitive endophenotypes and of their anatomical substrate., (© 2018 Elsevier Inc. All rights reserved.) more...

Youth with Tourette syndrome (TS) exhibit, compared to healthy, abnormal ability to lateralize digital sequential tasks. It is unknown whether this trait is related to inter-hemispheric connections, and whether it is preserved or lost in patients with TS persisting through adult life. We studied 13 adult TS patients and 15 age-matched healthy volunteers. All participants undertook: 1) a finger opposition task, performed with the right hand (RH) only or with both hands, using a sensor-engineered glove in synchrony with a metronome at 2 Hz; we calculated a lateralization index [(single RH-bimanual RH)/single RH X 100) for percentage of correct movements (%CORR); 2) MRI-based diffusion tensor imaging and probabilistic tractography of inter-hemispheric corpus callosum (CC) connections between supplementary motor areas (SMA) and primary motor cortices (M1). We confirmed a significant increase in the %CORR in RH in the bimanual vs. single task in TS patients (p<0.001), coupled to an abnormal ability to lateralize finger movements (significantly lower lateralization index for %CORR in TS patients, p = 0.04). The %CORR lateralization index correlated positively with tic severity measured with the Yale Global Tic Severity Scale (R = 0.55;p = 0.04). We detected a significantly higher fractional anisotropy (FA) in both the M1-M1 (p = 0.036) and the SMA-SMA (p = 0.018) callosal fibre tracts in TS patients. In healthy subjects, the %CORR lateralization index correlated positively with fractional anisotropy of SMA-SMA fibre tracts (R = 0.63, p = 0.02); this correlation was not significant in TS patients. TS patients exhibited an abnormal ability to lateralize finger movements in sequential tasks, which increased in accuracy when the task was performed bimanually. This abnormality persists throughout different age periods and appears dissociated from the transcallosal connectivity of motor cortical regions. The altered interhemispheric transfer of motor abilities in TS may be the result of compensatory processes linked to self-regulation of motor control. more...

Objective: Gilles de la Tourette syndrome (GTS) and depression are both common disorders. It has been suggested that depression occurs in 13%-76% GTS patients. Despite this, there are few studies into the specific relationships and correlates between the two disorders. There is only some consensus as to the precise relationship between the two disorders., Materials and Methods: We undertook the study to investigate the relationship between depressive symptomatology and the core clinical features of GTS in a well-characterized clinical population of youth with this disorder. Our aim was to verify the association between depression and comorbid obsessive-compulsive disorder and explore further other potential associations highlighted in some, but not all, of the studies focused on this topic., Results: Our results demonstrated that (1) the GTS patients were significantly older than the controls, (2) the GTS patients were significantly more depressed than controls, (3) depression was associated with tic severity, (4) the Diagnostic Confidence Index scores were higher in GTS patients without depression, (5) anxiety, attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and behavioral problems were significantly associated with depression, and (6) finally, patients with GTS and depression have a positive family history of depression. However, obsessionality (CY-BOCS) did not differentiate between depressed and not depressed GTS patients., Conclusions: Depression is common in patients with GTS and occurs significantly more in GTS than in controls. Depression is significantly associated with GTS factors such as tic severity, comorbidity with ADHD, and the presence of coexistent anxiety, CDs, and behavior problems. Depression is importantly significantly associated with a positive family history of depression. Intriguingly, depression in our sample was not related to obsessionality. more...

Tourette Syndrome (TS) is a childhood onset neuropsychiatric disorder. The objective of this study was to compare self-perceived health status, health-related behaviours, and chronic health conditions in individuals with and without TS using population-based data. Data were derived from Canadian Community Health Survey (CCHS) 2010 and 2011 cycles. The CCHS is a national population-based cross-sectional survey that collects information related to health status for Canadians. We evaluated the association between TS and self-perceived health, health related behaviours and chronic health conditions. 122,884 Canadians participated with 122 participants diagnosed with TS. After controlling for age and sex, the TS population was significantly less likely to have good self-perceived physical health and significantly more likely to need help with instrumental activities of daily living. More individuals with TS were diagnosed with an anxiety disorder, a mood disorder, or asthma. We observed no significant differences in health related behaviours between individuals with TS and the general population other than a higher odds of consultation for mental health. Individuals with TS experience a higher frequency of anxiety and mood disorders, and require more assistance with activities of daily living than the general population., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.) more...

Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions. more...

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care., (© 2017 Elsevier Inc. All rights reserved.) more...

Objective: The objective of this study was to examine: (1) the prevalence of diagnosed Tourette syndrome in Canada by sex in youth (aged 12-17) and adults and (2) socioeconomic factors in this population., Background: The majority of epidemiological studies of tics have focused on children and youth, with few studies describing the prevalence of tics in adult populations., Methods: Canadian data on Tourette syndrome prevalence were derived from the Canadian Community Health Survey 2010 and 2011 cycles, a Statistics Canada population-based cross-sectional survey that collects information related to health status. We determined the prevalence of diagnosed Tourette syndrome and examined sociodemographic factors, including age, sex, education, income, employment, and birthplace., Results: Overall, 122,884 Canadians participated in the surveys, with 122 participants diagnosed with Tourette syndrome. The prevalence of Tourette syndrome was higher in males in youth: 6.03 per 1000 (95% confidence interval: 3.24-8.81) in males versus 0.48 per 1,000 (95% confidence interval: 0.05-0.91) in females, with a prevalence risk ratio of 5.31 (95% confidence interval: 2.38-11.81). In adults, the prevalence of Tourette syndrome was 0.89 per 1,000 (95% confidence interval: 0.48-1.29) in males versus 0.44 (95% confidence interval: 0.16.0-0.71) in females, with a prevalence risk ratio of 1.93 (95% confidence interval: 1.21-3.08). After adjusting for age and sex, adults with Tourette syndrome had lower odds of receiving postsecondary education or being employed and higher odds of having income lower than the median and receiving governmental support., Conclusion: Data on the prevalence of Tourette syndrome in adults are scarce because most studies focus on children. Our data demonstrate a decreasing prevalence risk ratio for sex in adults compared to children. A diagnosis of Tourette syndrome is associated with lower education, income, and employment in adulthood. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.) more...

In this study, we have tested the effects of the dopamine D2 receptor blocker pimozide on timing performance in patients with Tourette syndrome (TS). Nine children with TS were tested off-medication and following 3 months of daily treatment with pimozide. Subjects completed a time reproduction and a time production task using supra-second temporal intervals. We show that pimozide improves motor timing performance by reducing the patients' variability in reproducing the duration of visual stimuli. On the other hand, this medication has no effect on the reproduction accuracy and on both variability and accuracy of the performance on the time production task. Our results suggest that pimozide might have improved motor timing variability as a result of its beneficial side effect on endogenous dopamine levels (i.e., normalization)., (© 2015 The British Psychological Society.) more...

Introduction: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Psychiatric comorbidity is frequent but does not enter into the official classification of the syndrome. In the present article, we will focus on treatment options for tics., Methods: We have reviewed the relevant literature on treatment of tics and GTS, especially in the period from 2011-2016 since the publication of the European Society for the Study of Tourette Syndrome (ESSTS) treatment guidelines in 2011., Results: We present current and up-to-date approaches in psychotherapy, pharmacotherapy and neurosurgery for GTS with an outlook for the upcoming years., Conclusions: Although many patients and health-care professionals seem to view tics and/or GTS as difficult to treat, or believe that treatment requires severe side effects with reduction in quality of life, we wish to convey that there is cause for optimism, both with regard to available treatment modalities and future therapeutic developments., (Copyright © 2016. Published by Elsevier Masson SAS.) more...

Tourette syndrome (TS) frequently involves complex tics with social significance, including imitation or socially inappropriate behaviour. This study explored every-day perspective taking and empathic tendencies in 95 patients with TS and 60 healthy controls. Analyses indicated that both males and females with TS exhibited a different interpersonal reactivity profile to controls, characterised by a reduced tendency to take other people's perspectives, and elevated personal distress in response to intense emotional situations (e.g. people experiencing crises)., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.) more...

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease., (Copyright © 2014 Elsevier B.V. All rights reserved.) more...

Background: Tics are the hallmark feature of Tourette syndrome. The basic phenomenological and neurophysiological characteristics of tics have been widely investigated. Interestingly, the spatial distribution of tics across different body parts has received little attention. No previous study has investigated whether the capacity for voluntary tic inhibition also varies across body parts., Methods: We analyzed video sequences of 26 adolescents with Tourette syndrome in a "tic freely" condition, and in a "voluntary tic inhibition" condition, to obtain absolute tic counts for different body parts. Two measures of the spatial distribution of tics were then analyzed. Linear regression analyses were employed to investigate the relation between the contribution of each body part to overall tic behavior and the ability to inhibit tics in that body part, averaged over our patient group., Results: Tic distribution across patients showed a characteristic somatotopic pattern, with the face most strongly represented. A significant negative relation was found between the ability to inhibit tics and pooled tic frequency across body parts. The body parts that exhibited the fewest tics were the ones for which tic inhibition was most effective., Conclusions: Our data are consistent with the idea that tic recruitment order reflects a "tic generator" spreading across a somatotopic map in the brain. Voluntary tic inhibition did not simply cause a proportional reduction of tics in each body part. Rather, the least affected body parts showed most effective voluntary tic inhibition. The results are discussed in terms of signal and noise within cortical-subcortical motor loops., (© 2015 International Parkinson and Movement Disorder Society.) more...