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      Recent Advances in Understanding and Managing Tourette Syndrome

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      F1000Research
      F1000Research
      Tourette syndrome, neurology, behaviour

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          Abstract

          Tourette syndrome (TS) is a neurologic and behavioral disorder consisting of motor and phonic tics with onset in childhood or adolescence. The severity of tics can range from barely perceptible to severely impairing due to social embarrassment, discomfort, self-injury, and interference with daily functioning and school or work performance. In addition to tics, most patients with TS have a variety of behavioral comorbidities, including attention deficit hyperactivity disorder and obsessive-compulsive disorder. Studies evaluating the pathophysiology of tics have pointed towards dysfunction of the cortico-striato-thalamo-cortical circuit, but the mechanism of this hyperkinetic movement disorder is not well understood. Treatment of TS is multidisciplinary, typically involving behavioral therapy, oral medications, and botulinum toxin injections. Deep brain stimulation may be considered for “malignant” TS that is refractory to conventional therapy. In this review, we will highlight recent developments in the understanding and management strategies of TS.

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          Most cited references39

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          Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome.

          Corticobasal ganglia neuronal ensembles bring automatic motor skills into voluntary control and integrate them into ongoing motor behavior. A 5% decrease in caudate (Cd) nucleus volume is the most consistent structural finding in the brain of patients with Tourette syndrome (TS), but the cellular abnormalities that underlie this decrease in volume are unclear. In this study the density of different types of interneurons and medium spiny neurons (MSNs) in the striatum was assessed in the postmortem brains of 5 TS subjects as compared with normal controls (NC) by unbiased stereological analyses. TS patients demonstrated a 50%-60% decrease of both parvalbumin (PV)+ and choline acetyltransferase (ChAT)+ cholinergic interneurons in the Cd and the putamen (Pt). Cholinergic interneurons were decreased in TS patients in the associative and sensorimotor regions but not in the limbic regions of the striatum, such that the normal gradient in density of cholinergic cells (highest in associative regions, intermediate in sensorimotor and lowest in limbic regions) was abolished. No significant difference was present in the densities of medium-sized calretinin (CR)+ interneurons, MSNs, and total neurons. The selective deficit of PV+ and cholinergic striatal interneurons in TS subjects may result in an impaired cortico/thalamic control of striatal neuron firing in TS.
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            Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome

            See Jackson (doi:10.1093/brain/awu338) for a scientific commentary on this article. The neural substrate of Gilles de la Tourette syndrome is unknown. Worbe et al. use probabilistic tractography to demonstrate widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways—likely arising from abnormal brain development—in patients with this syndrome.
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              Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome.

              Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [(11)C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABA(A) receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABA(A) receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABA(A) receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics.
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                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                9 February 2016
                2016
                : 5
                : F1000 Faculty Rev-152
                Affiliations
                [1 ]Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
                Author notes

                Competing interests: Dr. Thenganatt has no relevant disclosures. Dr. Jankovic has served as a consultant or as an advisory committee member for Allergan, Inc; Auspex Pharmaceuticals, Inc; Teva Pharmaceutical Industries Ltd.

                Article
                10.12688/f1000research.7424.1
                4755417
                26918185
                3362793b-8ab5-4f6a-9356-0108e5d3bc98
                Copyright: © 2016 Thenganatt MA and Jankovic J

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 February 2016
                Funding
                Dr. Jankovic has received research grants from Allergan, Inc; Auspex Pharmaceuticals, Inc; Lundbeck Inc; Medtronic; Merz Pharma; Psyadon Pharmaceuticals, Inc; St. Jude Medical; Teva Pharmaceutical Industries Ltd.
                I confirm that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles
                Anxiety Disorders
                Child & Adolescent Psychiatry
                Mood Disorders
                Movement Disorders
                Neurobiology of Disease & Regeneration
                Neuroimaging
                Neuropharmacology & Psychopharmacology
                Schizophrenia & Other Psychoses

                tourette syndrome,neurology,behaviour
                tourette syndrome, neurology, behaviour

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