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The purpose of this mini-review is to provide the latest information on epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome (TS). The authors conducted a literature search of available sources describing the issue of tic disorders with special focus on TS and made a comparison and evaluation of relevant findings. The results of this mini-review indicate that TS is a complex disorder, which has a significant impact on the quality of life of both the patients and his/her family. Therefore, early and proper diagnosis and treatment are necessary in order to reduce or even eliminate both symptoms and social burden of the patient. This requires a multidisciplinary management approach in order to meet the patients' special needs. Future research should focus on neuroimaging, new neurotransmitter targets, in functional neurosurgery, as well as the effect of non-pharmacological psychotherapies for these people.
We present selected highlights from research that appeared during 2015 on Tourette syndrome and other tic disorders. Topics include phenomenology, comorbidities, developmental course, genetics, animal models, neuroimaging, electrophysiology, pharmacology, and treatment. We briefly summarize articles whose results we believe may lead to new treatments, additional research or modifications in current models of TS.
This is the fifth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2018 relevant to Tourette syndrome and other tic disorders. The authors briefly summarize reports they consider most important or interesting. The highlights from 2019 article is being drafted on the Authorea online authoring platform, and readers are encouraged to add references or give feedback on our selections using the comments feature on that page. After the calendar year ends, the article is submitted as the annual update for the Tics collection on F1000Research.
This is the sixth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2019 relevant to Tourette syndrome and other tic disorders. The highlights from 2020 is being drafted on the Authorea online authoring platform; readers are encouraged to add references or give feedback on our selections comments feature on this page. After the calendar year ends, this article is submitted as the annual update for the Tics collection F1000Research.
This is the fourth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2017 relevant to Tourette syndrome and other tic disorders. The authors briefly summarize reports they consider most important or interesting. The highlights from 2018 article is being drafted on the Authorea online authoring platform, and readers are encouraged to add references or give feedback on our selections using the comments feature on that page. After the calendar year ends, the article is submitted as the annual update for the Tics collection on F1000Research.
It is a common phenomenon that somatosensory sensations can trigger actions to alleviate experienced tension. Such "urges" are particularly relevant in patients with Gilles de la Tourette (GTS) syndrome since they often precede tics, the cardinal feature of this common neurodevelopmental disorder. Altered sensorimotor integration processes in GTS as well as evidence for increased binding of stimulus- and response-related features ("hyper-binding") in the visual domain suggest enhanced perception-action binding also in the somatosensory modality. In the current study, the Theory of Event Coding (TEC) was used as an overarching cognitive framework to examine somatosensory-motor binding. For this purpose, a somatosensory-motor version of a task measuring stimulus-response binding (S-R task) was tested using electro-tactile stimuli. Contrary to the main hypothesis, there were no group differences in binding effects between GTS patients and healthy controls in the somatosensory-motor paradigm. Behavioral data did not indicate differences in binding between examined groups. These data can be interpreted such that a compensatory "downregulation" of increased somatosensory stimulus saliency, e.g., due to the occurrence of somatosensory urges and hypersensitivity to external stimuli, results in reduced binding with associated motor output, which brings binding to a "normal" level. Therefore, "hyper-binding" in GTS seems to be modality-specific.
Tourette syndrome (TS) is a neuropsychiatric disorder that affects both children and adults. We searched for randomised controlled trials (RCTs) using acupuncture to treat TS written in English or Chinese without restrictions on publication status. Study selection, data extraction, and assessment of study quality were conducted independently by two reviewers. Meta-analyses were performed using Review Manager (RevMan) 5.3 software from the Cochrane Collaboration. Data were combined with the fixed-effect model based on a heterogeneity test. Results were presented as risk ratios for dichotomous data and mean differences (MDs) for continuous data. This review included 7 RCTs with a total of 564 participants. The combined results showed that acupuncture may have better short-term effect than Western medicine for TS and that acupuncture may be an effective adjuvant therapy in improving the effect of Western medicine on TS, but the evidence is limited because of existing biases. Rigorous high-quality RCTs are needed to verify these findings.
Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder and its impact on cognitive development needs further study. Evidence from neuropsychological, neuroimaging and electrophysiological studies suggests that the decline in tic severity and the ability to suppress tics relate to the development of self-regulatory functions in late childhood and adolescence. Hence, tasks measuring performance monitoring might provide insight into the regulation of tics in children with TS.
Tourette Syndrome (TS) appears to be an inherited disorder, although genetic abnormalities have been identified in less than 1% of patients, and the mode of inheritance is uncertain. Many studies have investigated environmental factors that might contribute to the onset and severity of tics and associated comorbidities such as obsessive compulsive disorder (OCD) and attention deficit hyperactive disorder (ADHD). A systematic review and qualitative analysis were performed to provide a broad view of the association between pre- and perinatal factors and TS.
Tourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study.
Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.
Deep brain stimulation (DBS) has emerged as a novel therapy for the treatment of several movement and neuropsychiatric disorders, and may also be suitable for the treatment of Tourette syndrome (TS). The main DBS targets used to date in patients with TS are located within the basal ganglia-thalamo-cortical circuit involved in the pathophysiology of this syndrome. They include the ventralis oralis/centromedian-parafascicular (Vo/CM-Pf) nucleus of the thalamus and the nucleus accumbens. Current DBS treatments deliver continuous electrical stimulation and are not designed to adapt to the patient's symptoms, thereby contributing to unwanted side effects. Moreover, continuous DBS can lead to rapid battery depletion, which necessitates frequent battery replacement surgeries. Adaptive deep brain stimulation (aDBS), which is controlled based on neurophysiological biomarkers, is considered one of the most promising approaches to optimize clinical benefits and to limit the side effects of DBS. aDBS consists of a closed-loop system designed to measure and analyse a control variable reflecting the patient's clinical condition and to modify on-line stimulation settings to improve treatment efficacy. Local field potentials (LFPs), which are sums of pre- and post-synaptic activity arising from large neuronal populations, directly recorded from electrodes implanted for DBS can theoretically represent a reliable correlate of clinical status in patients with TS. The well-established LFP-clinical correlations in patients with Parkinson's disease reported in the last few years provide the rationale for developing and implementing new aDBS devices whose efficacies are under evaluation in humans. Only a few studies have investigated LFP activity recorded from DBS target structures and the relationship of this activity to clinical symptoms in TS. Here, we review the available literature supporting the feasibility of an LFP-based aDBS approach in patients with TS. In addition, to increase such knowledge, we report explorative findings regarding LFP data recently acquired and analysed in patients with TS after DBS electrode implantation at rest, during voluntary and involuntary movements (tics), and during ongoing DBS. Data available up to now suggest that patients with TS have oscillatory patterns specifically associated with the part of the brain they are recorded from, and thereby with clinical manifestations. The Vo/CM-Pf nucleus of the thalamus is involved in movement execution and the pathophysiology of TS. Moreover, the oscillatory patterns in TS are specifically modulated by DBS treatment, as reflected by improvements in TS symptoms. These findings suggest that LFPs recorded from DBS targets may be used to control new aDBS devices capable of adaptive stimulation responsive to the symptoms of TS.
Tourette syndrome is a neurodevelopmental disorder associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. In this study, we examine whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference for smaller-but-sooner over larger-but-later rewards. We assessed intertemporal choice in two studies including nineteen adolescents (age: mean[sd] = 14.21[±2.37], 13 male subjects) and twenty-five adult patients (age: mean[sd] = 29.88 [±9.03]; 19 male subjects) with Tourette syndrome and healthy age- and education matched controls. Computational modeling using exponential and hyperbolic discounting models via hierarchical Bayesian parameter estimation revealed reduced temporal discounting in adolescent patients, and no evidence for differences in adult patients. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. Specifically, adolescents might show attenuated discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. Future studies would benefit from a longitudinal approach to further elucidate the developmental trajectory of these effects.
Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric condition in which motor manifestations are often accompanied by comorbid conditions that impact the patient's quality of life. In the DSM-5, TS belongs to the "neurodevelopmental disorders" group, together with other neurodevelopmental conditions, frequently co-occurring. In this study, we searched the PubMed database using a combination of keywords associating TS and all neurodevelopmental diagnoses. From 1009 original reports, we identified 36 studies addressing TS and neurodevelopmental comorbidities. The available evidence suggests the following: (1) neurodevelopmental comorbidities in TS are the rule, rather than the exception; (2) attention deficit/hyperactivity disorder (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD or/and learning disorder) to a more complex phenotype (TS + autism spectrum disorder). We conclude that a prompt diagnosis and a detailed description of TS comorbidities are necessary not only to understand the aetiological basis of neurodevelopmental disorders but also to address specific rehabilitative and therapeutic approaches.
Considerable prior work suggests basal ganglia dysfunction in Tourette syndrome (TS). Analysis of a small number of postmortem specimens suggests deficits of some striatal interneuron populations, including striatal cholinergic interneurons. To assess the integrity of striatal cholinergic interneurons in TS, we used [18F]FEOBV positron emission tomography (PET) to quantify striatal vesicular acetylcholine transporter (VAChT) expression, a measure of cholinergic terminal density, in human TS and control subjects. We found no evidence of striatal cholinergic deficits. Discrepant imaging and postmortem analysis results may reflect agonal or postmortem changes, medication effects, or significant disease heterogeneity.
Deep 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.
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