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BACKGROUND Different deep brain stimulation (DBS) targets have been suggested as treatment for patients with pharmacologically refractory Holmes tremor (HT). We report the clinical and quality of life (QoL) long-term (up to nine years) outcome in four patients with HT treated with DBS (in thalamic ventral intermediate nucleus-VIM or in dentato-rubro-thalamic tract-DRTT). MATERIALS AND METHODS The patients underwent routine clinical evaluations before and after DBS (typically annually). Tremor severity and activities of daily living (ADL) were quantified by the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTMTRS). QoL was assessed using the RAND SF-36-item Health Survey (RAND SF-36). In addition, we computed, in all four patients, the VTA based on the best stimulation settings using heuristic approaches included in the open source toolbox LEAD-DBS. RESULTS In all patients, tremor and ADL improved significantly at one-year post-DBS follow-up (34-61% improvement in FTMTRS total score compared to baseline). In three out of four patients, the improvement of tremor was sustained no longer than two to three years and only in one patient was sustained up to nine years. In this patient, the largest intersection between VTA and DBS target has been observed. Scores for ADL deteriorated over the course of time, reaching worse levels compared to baseline already during the three-year post-DBS follow-up, in three out of four patients. Physical and mental health component scores of RAND SF-36 had very different outcome between patients and follow-ups and were not associated with tremor-related outcomes. CONCLUSIONS The benefits of DBS in HT might not be always long lasting. Although QoL slightly improved, this change seemed to be independent of the motor outcome following DBS. The estimation of DBS target and VTA proximity could be a useful tool for DBS clinicians in order to facilitate the DBS programming process and optimize DBS treatment.

Background Impulse control disorders (ICDs) are a frequent side effect of dopamine replacement therapy (DRT) in Parkinson's disease (PD). Reckless generosity might expand the spectrum of known ICDs. Cases Over 18 months, we encountered three PD patients exhibiting reckless generosity under DRT, leading to disastrous financial and social consequences. Literature Review Except for another case series describing reckless generosity in three PD patients, only one study has examined generosity in PD patients; with findings suggesting that PD patients with ICDs are less sensitive to the aversive aspects of the lack of reciprocation in social settings. Studies with healthy individuals suggest that increased availability of dopamine might reduce social discounting and promote egalitarian behavior, and thereby increase generous behavior towards strangers. Genetic studies show that polymorphisms in dopamine D4 receptors influence generous behavior. Conclusions Reckless generosity in PD patients with DRT might be underreported and should therefore be carefully be screened for by clinicians. A potential mechanism underlying this ICD‐related behavior might be a sensitization of the mesolimbic and mesocortical dopaminergic system, leading to reduced social discounting and maladaptive reward‐learning. Further research is needed to investigate the prevalence and underlying mechanisms of reckless generosity in PD patients.

International audience; Objective: To examine the relationship between a Parkinson's disease (PD) polygenic risk score (PRS) and impulse control disorders (ICDs) in PD. Background: Genome wide association studies (GWAS) have brought forth a PRS associated with increased risk of PD and younger disease onset. ICDs are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. It is unknown whether ICDs and PD share genetic susceptibility. Methods: We used data from a multicenter longitudinal cohort of PD patients with annual visits up to 6 years (DIG-PD). At each visit ICDs, defined as compulsive gambling, buying, eating, or sexual behavior were evaluated by movement disorders specialists. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted PRS based on 90 SNPs associated with PD. We estimated the association between PRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for dopaminergic treatment and other known risk factors for ICDs. Results: Of 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p < 0.001) as well as higher PRS values (p = 0.06). At baseline, there was no association between the PRS and ICDs (overall, p = 0.84). The prevalence of ICDs increased over time similarly across the quartiles of the PRS (overall, p = 0.88; DA users, p = 0.99). Conclusion: Despite younger disease onset being associated with both higher PRS and ICD prevalence, our findings are not in favor of common susceptibility genes for PD and ICDs.

Background Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. Methods Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). Results The results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. Conclusions The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the ‘off’-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5–6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS.

INTRODUCTION The Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES) is a self-report scale suggested as a severity scale for tics and related sensory phenomena observed in Gilles de la Tourette syndrome (GTS) and recommended as a screening instrument by the Committee on Rating Scale Development of the International Parkinson's Disease and Movement Disorder Society. OBJECTIVES To cross-culturally adapt a French version of the MOVES and to evaluate its psychometric properties. METHODS After the cross-cultural adaptation of the MOVES, we assessed its psychometric properties in 53 patients aged 12-16 years and in 54 patients aged 16 years and above: reliability and construct validity (relationships between items and scales), internal consistency and concurrent validity with the Yale Global Tic Severity Scale (YGTSS) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) or the auto-Yale-Brown scale. RESULTS The results showed very good acceptability with response rates greater than 92%, good internal consistency (Cronbach's alpha ranging from 0.62 and 0.89) and good test-retest reliability (ICCs ranging from 0.59 to 0.91). Concurrent validity with the YGTSS, CY-BOCS and auto-Yale-Brown scales showed strong expected correlations. The cut-off points tested for diagnostic performance gave satisfactory values of sensitivity, specificity, and positive and negative predictive values. DISCUSSION Our study provides evidence of the good psychometric properties of the French version of the MOVES. The cross-cultural adaptation of this specific instrument will allow investigators to include French-speaking persons with GTS aged 12 years and over in national and international collaboration research projects.

International audience; 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 tracer-binding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan® 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

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS.

Impulse control disorders (ICD) have been recognised in Parkinson's disease (PD) as adverse effects of dopamine replacement therapy, particularly with dopamine agonists. Although virtually all PD patients are treated with dopaminergic drugs, only a minority will develop hyperdopaminergic states, suggesting predisposing and/or protecting factors. The age at onset, the sex and the dose or type of dopaminergic drugs have been identified as clinical predictive factors. Recent genetic studies have investigated associations between ICD and polymorphisms of genes involved in the dopamine metabolism pathway (COMT, DAT), dopamine receptors (DRD1, DRD2, DRD3, DRD4), serotonin receptors and its transporter (HTR2A, 5HTT), and glutamate receptors (GRIN2B). Although validation in larger and independent cohorts is needed, the results from these studies give us some insights into the pathophysiology of hyperdopaminergic states and may be useful, at term, in personalising antiparkinsonian treatment in clinical practice.

BACKGROUND Neurogenic thoracic outlet syndrome is an underestimated cause of brachial weakness and pain. The subclavius posticus muscle (SPM) is an aberrant muscle originating from the medial aspect of the first rib reaching to superior border of the scapula, which may cause, depending on its activation, dynamic compression of the brachial plexus. CASE PRESENTATION In the present study, we report about a 32-year-old male caucasian patient with weakness in radial deviation of his left hand. An isolated macrodactyly of his left middle finger had been operated twice. Electroneurography showed a carpal-tunnel-syndrome (CTS) on the left side. MRI of the brachial plexus revealed an additional muscle in the costoclavicular space, identified as SPM. To our knowledge, this is the second case report of a neurogenic thoracic outlet syndrome due to SPM, and the first case described with isolated macrodactyly and CTS in the same patient. CONCLUSION If complaints about hand weakness are only reported in cases of distinct hand positions, a dynamic compression of the brachial plexus by SPM may be the cause. A neurogenic thoracic outlet syndrome may facilitate the development of CTS.