The term “Gilles de la Tourette syndrome”, or the more commonly used term “Tourette syndrome” (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

Les tics de l’enfant sont fréquents et touchent, à un moment ou un autre du développement, jusqu’à 20 % de la population. Dans environ 1 % des cas, ces tics deviennent chroniques et, s’il y a association de tics moteurs et vocaux, on parle du syndrome Gilles de la Tourette (SGT). Ce dernier est souvent léger, voire frustre, et ne correspond donc pas aux représentations dramatiques, voire caricaturale que l’on retrouve dans les médias et sur les réseaux sociaux. En particulier, la coprolalie est plutôt rare et n’est pas un symptôme obligatoire pour poser le diagnostic de SGT. Si les tics sont gênants, alors plusieurs modalités de traitements existent en passant par la psychoéducation, les thérapies comportementales, les médicaments, la toxine botulique et, dans les cas les plus sévères, la stimulation cérébrale profonde. Hormis les tics, il faut aussi s’intéresser aux possibles comorbidités des tics/du SGT qui s’inscrivent dans les troubles du neurodéveloppement (trouble déficit de l’attention avec ou sans hyperactivité [TDA/H], troubles obsessionnels compulsifs, anxiété, crises de rage, automutilations, troubles de l’apprentissage ou troubles du spectre autistique) et faire appel à des spécialistes si besoin, en premier lieu les pédopsychiatres. Enfin, il est important d’insister sur le bon pronostic des tics à l’âge adulte et, en conséquence, une insertion socioprofessionnelle qui est généralement normale.

Les tics chroniques/le syndrome Gilles de la Tourette (SGT) font partie des troubles du neurodéveloppement, dont le trouble déficitaire de l’attention avec hyperactivité (TDAH), les troubles des apprentissages, et les troubles du spectre autistique. Parmi ceux-ci, le TDAH est de loin le plus fréquemment associé, présent chez plus de 50 % des personnes atteintes du SGT. Ainsi, il semblerait utile, si le TDAH est jugé suffisamment invalidant, de proposer un traitement par méthylphénidate aux patients souffrant de SGT. Malheureusement, cette prescription se fait de manière bien trop rare, de peur que le méthylphénidate puisse augmenter la sévérité des tics. Or, même si cette possibilité existe, il s’agit d’un effet indésirable rare et facile à corriger si besoin. La formule galénique du méthylphénidate peut jouer un rôle déterminant dans sa tolérance par rapport aux tics et plusieurs tentatives de traitement sont parfois nécessaires.

Background: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. Methods: Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. Results: At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Omega) and TEED (33.7/69.0/84.4/93.0 V2*mu s*Hz/Omega) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 mu s), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. Conclusion: In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study.

INTRODUCTION:In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders. METHODS:The PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients' examinations and to assess patients' satisfaction with the setup. RESULTS:Both study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients' satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC. DISCUSSION/CONCLUSION:This study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.

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.

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. (C) 2016 Published by Elsevier Masson SAS.

Background: Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMTHH), intermediate (Val/Met, COMTHL) and low metabolizers (Met/Met, COMTLL). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype.Methods: Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was defined by the ratio of tracerbinding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan (R) SNP genotyping assay. We used a regression model to evaluate the effect of COMT genotype on the BP in the striatum and its sub-regions.Results: Genotype distribution was: 11 (27.5%) COMTHH, 26 (65%) COMTHL and 3 (7.5%) COMTLL. There were no significant differences in disease severity, treatments, or motor scores between genotypes. When adjusted to clinical severity, gender and age, low and intermediate metabolizers showed significantly higher rates of striatal denervation (COMTHL+LL BP = 1.32 +/- 0.04) than high metabolizers (COMTHH, BP = 1.6 +/- 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender genotype interaction.Conclusions: Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms. (C) 2015 Elsevier Ltd. All rights reserved.

Motion is a behavior involving a motor act programmed and executed in a particular cognitive and emotional context. Deep structures of the brain, including the basal ganglia, appear to play a crucial role in the integration of these three kinds of cortex information (motion, cognition, emotion). Through its organization, the basal ganglia system enables learning and memorization of behavioral sequences, which can then be executed as routines. Their dysfunctions seem to be associated with many psychopathological situations. Thus, tics in Tourette's syndrome (TS) can be seen as a control routines defect that may result from wiring anomaly between the cortex and the basal ganglia. By precisely targeting deep brain circuits implicated in psychiatric disorders, deep brain stimulation (DBS) offers hope for the alleviation of severe illnesses resistant to drug therapies and provides a novel tool to investigate the neuroanatomic and physiological bases of certain disorders, including Obsessive-Compulsive Disorder (OCD) and TS, for which early results indicate positive therapeutic outcomes, even during the long-term follow-up. The pathophysiologies of OCD and of TS share dysfunctions of the associative and limbic circuits running between cortical and sub-cortical structures. Recent pathophysiological hypotheses suggest that TS symptoms result from a dysfunction of the basal ganglia circuitry, notably of the ventral striatum. These data are consistent with the supposed function of cortico-basal ganglia circuits in habit learning and routine performance of habits. Based on early reports indicating that high-frequency stimulation of structures along the cortico-basal ganglia axis might be effective in alleviating TS symptoms, DBS is being tested across the world at several nodes of this circuit, including the pallidum, and thalamus. Increasing our knowledge of the functional organization of the cortico-basal ganglia circuits and of their dysfunction in pathological repetitive behaviors would certainly contribute to better define the surgical therapeutic targets, thereby improving available treatments.

ObjectifsÉtudier la qualité de vie liée à la santé (QVS) et ses déterminants chez des adolescents consultant pour syndrome de Gilles de la Tourette (SGT).MéthodeAprès hétéro-évaluation par la YGTSS et la CY-BOCS, la QVS des adolescents était mesurée à l’aide de 3 questionnaires d’autoévaluation (SF-36, VSP-A, CHAQ). Des contrôles appariés sur l’âge et le sexe ont rempli les mêmes questionnaires. Les parents des patients et des contrôles ont renseigné les questionnaires sociodémographique et médical, la CBCL et deux hétéroévaluations de la QVS des adolescents (VSP P et CHAQ parents). Tous les participants avaient donné leur consentement éclairé.RésultatsPour les 75 adolescents (14,8 ans, DS = 1,8 ; 80 % de garçons) inclus, le score YGTSS moyen était de 33,9 (DS = 20). Pour la CBCL, le score total, les scores symptômes internalisés et symptômes externalisés étaient limites/pathologiques pour 39,4 %, 52,1 % et 33,3 % des adolescents respectivement. La QVS des adolescents SGT était significativement altérée comparée aux contrôles pour toutes les dimensions de la SF-36, pour les dimensions vitalité, relations avec les pairs et loisirs de la VSP A et pour le score total de la CHAQ. On retrouvait des corrélations négatives significatives entre les scores Tics moteurs et sévérité globale de la YGTSS et les dimensions psychologiques et sociales du SF-36, une corrélation positive entre le score Tics vocaux de la YGTSS et le score total à la CHAQ. Les adolescents avec des scores CBCL total et symptômes internalisés limites/pathologiques avaient des scores significativement plus bas sur plusieurs dimensions de QVS.ConclusionLes dimensions physiques, psychologiques et sociales de la QVS sont altérées chez les adolescents SGT. La sévérité des tics, les difficultés émotionnelles et comportementales ont un impact négatif sensible sur les dimensions physiques, psychologiques et sociales de la QVS chez les adolescents SGT.

Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS.