Trial of Botulinum Toxin for Isolated or Essential Head Tremor.

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).

Deep brain stimulation of the subthalamic nucleus in severe Parkinson's disease: relationships between dual-contact topographic setting and 1-year worsening of speech and gait.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) alleviates severe motor fluctuations and dyskinesia in Parkinson's disease, but may result in speech and gait disorders. Among the suspected or demonstrated causes of these adverse effects, we focused on the topography of contact balance (CB; individual, right and left relative dual positions), a scantly studied topic, analyzing the relationships between symmetric or non-symmetric settings, and the worsening of these signs. METHOD: An observational monocentric study was conducted on a series of 92 patients after ethical approval. CB was specified by longitudinal and transversal positions and relation to the STN (CB sub-aspects) and totalized at the patient level (patient CB). CB was deemed symmetric when the two contacts were at the same locations relative to the STN. CB was deemed asymmetric when at least one sub-aspect differed in the patient CB. Baseline and 1-year characteristics were routinely collected: (i) general, namely, Unified Parkinson's Disease Rating Scores (UPDRS), II, III motor and IV, daily levodopa equivalent doses, and Parkinson's Disease Questionnaire of Quality of Life (PDQ39) scores; (ii) specific, namely scores for speech (II-5 and III-18) and axial signs (II-14, III-28, III-29, and III-30). Only significant correlations were considered (p < 0.05). RESULTS: Baseline characteristics were comparable (symmetric versus asymmetric). CB settings were related to deteriorations of speech and axial signs: communication PDQ39 and UPDRS speech and gait scores worsened exclusively with symmetric settings; the most influential CB sub-aspect was symmetric longitudinal position. CONCLUSION: Our findings suggest that avoiding symmetric CB settings, whether by electrode positioning or shaping of electric fields, could reduce worsening of speech and gait.

Compulsive eating behaviors in Parkinson's disease.

PURPOSE: Eating disorders are common in Parkinson's disease (PD) patients and often class in Impulse control disorders, however, little is known about their phenomenology. Specific symptoms and comorbidities were described in a group of PD patients in this preliminary study. METHODS: Over a period of 6 months, 51 PD patients who experienced significant changes in eating habits following diagnosis of PD and were interviewed during regularly scheduled follow-up visits. We assessed each patient's height and weight, impulsivity, psychological distress, current eating disorder symptoms, food addiction, food habits and craving. RESULTS: Among the PD patients who experienced modified dietary habits following diagnosis, few exhibited binge eating disorders (BED) full criteria (3.9%). However, 21.6% of patients experienced episodes of out-of-control eating with a large quantity of food in short time and 39.2% satisfied food addiction (FA) criteria without binge eating disorder. Food cravings more than once a week were experienced in approximately half of the population including all FA patients. Regarding comorbidities, FA PD patients present impulsive features and anxiety. CONCLUSIONS: This study confirms the existence of FA profile in PD patients. Eating disorders even in PD are complex and have a cross-cutting criteria related to out-of-control eating, FA, and BED. The association of anxiety with PD-related food addiction, contrary to L-dopa equivalent daily dose mean score or the presence of dopamine agonists, underline the complex sustainability of the dopaminergic brainstem support. A study on their detailed prevalence in this population could be helpful to better understand unspecified feeding or eating disorder. CLINICAL TRIAL NUMBER: DR-2012-007. NAME OF THE REGISTRY: French Committee for the Protection of Persons (CPP) & French National Commission on Computing and Liberty (CNIL). LEVEL OF EVIDENCE: Level V, descriptive study.

Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: a kinesthetic imagery approach.

Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown. Specifically, the influence of levodopa on the networks involved in motor imagery (MI) of parkinsonian gait has not been directly studied, comparing the off and on medication states in the same patients. We therefore conducted an [H2 (15) 0] Positron emission tomography study in eight advanced parkinsonian patients (mean disease duration: 12.3 ± 3.8 years) presenting with levodopa-responsive gait disorders and FoG, and eight age-matched healthy subjects. All participants performed three tasks (MI of gait, visual imagery and a control task). Patients were tested off, after an overnight withdrawal of all antiparkinsonian treatment, and on medication, during consecutive mornings. The order of conditions was counterbalanced between subjects and sessions. Results showed that imagined gait elicited activations within motor and frontal associative areas, thalamus, basal ganglia and cerebellum in controls. Off medication, patients mainly activated premotor-parietal and pontomesencephalic regions. Levodopa increased activation in motor regions, putamen, thalamus, and cerebellum, and reduced premotor-parietal and brainstem involvement. Areas activated when patients are off medication may represent compensatory mechanisms. The recruitment of these accessory circuits has also been reported for upper-limb movements in Parkinson's disease, suggesting a partly overlapping pathophysiology between imagined levodopa-responsive gait disorders and appendicular signs. Our results also highlight a possible cerebellar contribution in the pathophysiology of parkinsonian gait disorders through kinesthetic imagery.

Prevalence and phenomenology of olfactory hallucinations in Parkinson's disease.

BACKGROUND: Although visual hallucinations in Parkinson's disease (PD) have been described in several major studies, little is known about olfactory hallucinations (OHs). METHODS: The authors performed a detailed analysis of OHs in a cohort of 87 Parkinsonian patients to estimate the prevalence of OHs and describe their phenomenology. They also evaluated smelling abilities in terms of detection and identification. Assessment of both, OHs and olfactory function, was also performed using a control group of 40 normal subjects. RESULTS: Nine patients exhibited OHs compared with none of the controls, giving a prevalence of 10% for OHs in patients. OHs were described as rare, short-lasting, unpleasant odours which are not frightening since clearly identified by the patient as hallucinations. Parkinsonian patients with OHs exhibited olfactory impairment of detection and identification compared with controls, but there was no difference in their olfactory abilities from Parkinsonian patients without OHs. CONCLUSIONS: In conclusion, OHs should be added to the list of non-motor PD symptoms that can occur early or late in the course of PD. The authors' study did not reveal any significant difference in terms of olfactory abilities between patients with or without OHs. However, olfactory impairment is well documented in Parkinsonian patients and cannot be totally ruled out as a risk factor for OHs. The authors recognise that complex mechanisms are probably involved in this phenomenon.

Quality of life in adults with Gilles de la Tourette Syndrome.

BACKGROUND: Few studies have used standardized QOL instruments to assess the quality of life (QOL) in Gilles de la Tourette Syndrome (GTS) patients. This work investigates the QOL of adult GTS patients and examines the relationships between physical and psychological variables and QOL. METHODS: Epidemiological investigation by anonymous national postal survey of QOL of patients of the French Association of Gilles de la Tourette Syndrome (AFGTS) aged 16 years or older. The clinical and QOL measures were collected by four questionnaires: a sociodemographic and GTS-related symptoms questionnaire, the World Health Organization Quality Of Life questionnaire (WHOQOL-26), the Functional Status Questionnaire (FSQ), and a self-rating questionnaire on psychiatric symptoms (SCL-90), all validated in French. We used stepwise regression analysis to explicitly investigate the relationships between physical and psychological variables and QOL domains in GTS. RESULTS: Questionnaires were posted to 303 patients, of whom 167 (55%) completed and returned them. Our results, adjusted for age and gender, show that patients with GTS have a worse QOL than the general healthy population. In particular, the "Depression" psychological variable was a significant predictor of impairment in all WHOQOL-26 domains, psychological but also physical and social. CONCLUSIONS: The present study demonstrates a strong relationship between QOL in GTS and psychiatric symptoms, in particular those of depression.

The French version of the Gilles de la Tourette Syndrome Quality of Life Scale for adolescents (GTS-QOL-French-Ado): Adaptation and psychometric evaluation.

INTRODUCTION: The aim of this study was to create a new version of the French GTS-QOL adapted to adolescents with GTS aged 12-16 years (GTS-QOL-French-Ado) and to evaluate its psychometric properties. METHODS: We assessed the psychometric properties of the GTS-QOL-French-Ado in 84 adolescents (mean age 13.6 years, standard deviation 1.2) in terms of factor structure, internal consistency, reliability and convergent validity with the Child Depression Inventory (CDI), the Multidimensional Anxiety Scale for Children (MASC), the Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES) and the French "Vécu et Santé Perçue de l'Adolescent" (VSP-A), a generic self-administered measure of health-related quality of life (HRQoL) in adolescents. RESULTS: Exploratory factor analysis of the GTS-QOL-French-Ado resulted in a 5-factor solution. The GTS-QOL-French-Ado demonstrated good acceptability with missing values per subscale ranging from 0% to 1.2%, good internal consistency for four of the five subscales with Cronbach's alpha ranging from 0.56 to 0.87 and good test-retest reliability with intraclass correlation coefficients ranging from 0.74 (95% CI: 0.52-0.86) to 0.82 (95% CI: 0.66-0.91). Convergent validity was supported by correlations with CDI, MASC, MOVES, VSP-A and clinical variables. DISCUSSION: The GTS-QOL-French-Ado is the first disease-specific HRQoL tool for French-speaking adolescents with GTS aged 12-16 years, and shows good psychometric properties. Further psychometric testing on responsiveness to change would be of great interest.

Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.

BACKGROUND: Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS: In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS: After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS: These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

Contact dependent reproducible hypomania induced by deep brain stimulation in Parkinson's disease: clinical, anatomical and functional imaging study.

Hypomanic symptoms depending on anatomical location of contacts are reported in patients with Parkinson's disease (PD) treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, the underlying cortical and subcortical dysfunction is debated. In this study, five PD patients implanted with DBS-STN who presented with reversible and reproducible hypomanic symptoms after stimulation of specific 'manic' contacts were investigated. Hypomanic symptoms were assessed using the Bech and Rafaelsen Mania Scale (MAS). Three dimensional anatomical location of 'euthymic' and 'manic' contacts, after matching the postoperative CT scan with the preoperative stereotactic MRI, and a H(2)(15)O positron emission tomography (PET) study testing 'euthymic' and 'manic' contacts, were performed. Under 'euthymic' conditions, MAS score (mean±SD) was 0.6±0.5 compared with 7.8±3.1 under 'manic' conditions. Nine of 10 'manic' contacts were located in the substantia nigra, mainly in its ventral part. PET showed that hypomania was associated with strong asymmetrical cerebral activation involving preferentially the right hemisphere and was mediated by activation of the anterior cingulate and medial prefrontal cortex. The present study demonstrates the role of the subcortical structures in the genesis of hypomania in PD patients treated with DBS and stresses the involvement of the substantia nigra.

Hypersexuality and pathological gambling in Parkinson's disease: A cross-sectional case-control study.

BACKGROUND: Substance and behavioral addictions have already been described separately or in combination in Parkinson's disease. However, no comparisons of the prevalence of addictive behaviors in patients with Parkinson's disease and the general population have been published. The objective of this study was to compare the prevalence and characteristics of addictions (gambling, hypersexuality, tobacco, and alcohol) in patients with Parkinson's disease and in a matched, paired sample from the general population. METHODS: After matching for age, sex, and complete field questionnaires on addictions, we had 115 data sets. RESULTS: No difference was observed between Parkinson's disease and control populations concerning pathological gambling (0.87% vs 0.87%, P = .99), tobacco addiction (1.7% vs 1.7%, P = .99), and alcohol dependence (2.6% vs 3.5%, P = .71). The Parkinson's disease group showed 2 cases of sexual addiction (1.7% vs 0, P = .15). CONCLUSIONS: Our results indicate that patients with Parkinson's disease do not have specific profiles for tobacco or alcohol addiction and pathological gambling compared with the general population.

Preoperative REM Sleep Behavior Disorder and Subthalamic Nucleus Deep Brain Stimulation Outcome in Parkinson Disease 1 Year After Surgery.

BACKGROUND AND OBJECTIVES: To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD. METHODS: We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD-) probable RBD preoperatively. RESULTS: At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] III "off": 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire-39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD- patients. Both pre-opRBD+ and pre-opRBD- patients had significant MDS-UPDRS IV score decrease (-37% and -33%, respectively), MDS-UPDRS III "med 'off'/stim 'on'" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes. CONCLUSIONS: In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery. TRIAL REGISTRATION INFORMATION: NCT02360683. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery.

Cross-cultural adaptation and psychometric evaluation of the French version of the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL).

INTRODUCTION: The Gilles de la Tourette Syndrome-Quality of Life Scale (GTS-QOL) is a self-rated disease-specific questionnaire to assess health-related quality of life of subjects with GTS. Our aim was to perform the cross-cultural adaptation of the GTS-QOL into French and to assess its psychometric properties. METHODS: The GTS-QOL was cross-culturally adapted by conducting forward and backward translations, following international guidelines. The psychometric properties of the GTS-QOL-French were assessed in 109 participants aged 16 years and above with regard to factor structure, internal consistency, reliability and convergent validity with the MOVES (Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey) and the WHOQOL-BREF (World Health Organization Quality of Life Brief). RESULTS: Exploratory factor analysis of the GTS-QOL-French resulted in a 6-factor solution and did not replicate the original structure in four subscales. The results showed good acceptability (missing values per subscale ranging from 0% to 0.9%), good internal consistency (Cronbach's alpha ranging from 0.68 to 0.94) and good test-retest reliability (intraclass correlation coefficients ranging from 0.70 to 0.81). Convergent validity with the MOVES and WHOQOL-BREF scales showed high correlations. DISCUSSION: Our study provides evidence of the good psychometric properties of the GTS-QOL-French. The cross-cultural adaptation and validation of this specific instrument will make it possible to assess health-related quality of life in French-speaking subjects with GTS. The GTS-QOL-French could be recommended for use in future research.

Visual hallucinations and illusions in Parkinson's disease: the role of ocular pathology.

INTRODUCTION: Whether different mechanisms, particularly ocular pathology, could lead to the emergence of visual hallucinations (VH) (defined as false perceptions with no external stimulus) versus visual illusions (VI) (defined as a misperception of a real stimulus) in Parkinson's disease (PD) remains debated. We assessed retinal, clinical and structural brain characteristics depending on the presence of VH or VI in PD. METHODS: In this case-control study, we compared retinal thickness using optical coherence tomography (OCT), between PD patients with: VI (PD-I; n = 26), VH (PD-H; n = 28), and without VI or VH (PD-C; n = 28), and assessed demographic data, disease severity, treatment, anatomical and functional visual complaints, cognitive and visuo-perceptive functions and MRI brain volumetry for each group of PD patients. RESULTS: Parafoveal retina was thinner in PD-H compared to PD-C (p = 0.005) and PD-I (p = 0.009) but did not differ between PD-I and PD-C (p = 0.85). Multivariate analysis showed that 1/retinal parafoveal thinning and total brain gray matter atrophy were independently associated with the presence of VH compared to PD-I; 2/retinal parafoveal thickness, PD duration, sleep quality impairment and total brain gray matter volume were independent factors associated with the presence of VH compared to PD-C; 3/anterior ocular abnormalities were the only factor independently associated with the presence of illusions compared to PD-C. CONCLUSION: These findings reinforce the hypothesis that there may be different mechanisms contributing to VH and VI in PD, suggesting that these two entities may also have a different prognosis rather than simply lying along a continuous spectrum. REGISTRATION NUMBER: Clinicaltrials.gov number NCT01114321.

Subthalamic nucleus location: relationships between stereotactic AC-PC-based diagrams and MRI anatomy-based contours.

Subthalamic nucleus (STN) targeting is classically performed based on AC-PC probabilistic position. Nevertheless, MRI allows direct visualization and targeting. We aimed to compare the position localized on MR images with standard stereotactic diagrams. The STN was manually contoured on MR images (22 Parkinson's disease patients); boundaries were simplified in a schematic polygonal form. Front and lateral stereotactic diagrams were constructed according to Talairach and Benabid. We compared x, y and z coordinates of the geometrical center of MRI-based polygons and stereotactic diagrams (Wilcoxon matched-pairs tests). There was significant discordance between MRI-based polygons and AC-PC-based images. MRI shows the STN as more posterior, medial and slightly inferior.

Contact position analysis of deep brain stimulation electrodes on post-operative CT images.

PURPOSE: Groups performing deep brain stimulation advocate post-operative imaging [magnetic resonance imaging (MRI) or computer tomography (CT)] to analyse the position of each electrode contact. The artefact of the Activa 3389 electrode had been described for MRI but not for CT. We undertook an electrode artefact analysis for CT imaging to obtain information on the artefact dimensions and related electrode contact positions. METHODS: The electrode was fixed on a phantom in a set position and six acquisitions were run (in-vitro study). The artefacts were compared with the real electrode position. Ten post-operative acquisitions were analysed (in-vivo analysis). We measured: H (height of the lateral black artefact), D (distance between the beginning of the white and the lateral black artefacts) and W (maximal artefact width), representing respectively the lengths of the four contacts and the electrode tip and width of the contact zone. A Student t-test compared the results: in vivo vs in vitro and coronal vs sagittal reconstructions along the electrode. RESULTS: The limits of the lateral black artefact around the electrode contacts corresponded to the final electrode position. There was no significant difference for D (in vivo, 1.1 +/- 0.1 mm; in vitro, 1.2 +/- 0.2 mm; p = 0.213), while W and H differed slightly (in vivo, W = 3.3 +/- 0.2 mm, H = 7.7 +/- 0.2 mm; in vitro, W = 3.1 +/- 0.1 mm, H = 7.5 +/- 0.2 mm). Results obtained with sagittal and coronal reconstructions were similar (p > 0.6). CONCLUSIONS: Precise three-dimensional (3D) localisation of the four-contact zone of the electrode can be obtained by CT identification of the limits of the lateral black artefact. The relative position of the four contacts is deduced from the size of the contacts and the inter-contact distance. Sagittal and coronal reconstructions along the electrode direction should be considered for the identification of the four electrode contacts. CT offers a useful alternative to post-operative MRI.

Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia.

Tardive dystonia (TD) is a disabling disorder induced by neuroleptics. Internal globus pallidus (GPi) stimulation can dramatically improve TD. The present positron emission tomography and H(2)(15)O study aimed to characterize the abnormalities of brain activation of TD and the impact of GPi stimulation on these abnormalities in five TD patients treated with GPi stimulation and eight controls. Changes of regional cerebral blood flow (rCBF) were determined: (i) at rest; (ii) when moving a joystick with the right hand in three freely chosen directions in on and off bilateral GPi stimulation. A significant increase of rCBF was found in TD patients in off-stimulation condition compared to controls: (1) during motor execution in the prefrontal, premotor lateral, and anterior cingulate cortex; (2) at rest, in the prefrontal and anterior cingulate cortex and the cerebellum. Internal globus pallidus stimulation led to a reduction of rCBF (1) during motor execution, in the primary motor and prefrontal cortex and the cerebellum; (2) at rest, in the primary motor and anterior cingulate cortex and supplementary motor area. The results are as follows: (1) TD is related to an excess of brain activity notably in the prefrontal and premotor areas; (2) GPi stimulation reduces the activation of motor, premotor, and prefrontal cortex as well as cerebellum.

Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia.

CONTEXT: Tardive dyskinesia (TD) is a common and potentially disabling disorder induced by use of antipsychotic drugs for which medical treatment often gives disappointing results. OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal part of the globus pallidus to treat severe TD. DESIGN: Prospective phase 2 multicenter study. SETTING: Six French university hospitals. Patients Patients with severe TD refractory to medical treatment were studied to evaluate the severity of abnormal involuntary movements before and after 6 months of bilateral globus pallidus deep brain stimulation. A 2-step open Fleming procedure was used to avoid unnecessary accrual of patients. A successful outcome was defined as a decrease of more than 40% in the main outcome measure at 6 months. The early stopping rule was invoked if the number of successful outcomes in 10 patients was fewer than 2, or 5 or more. A double-blind evaluation in the presence and absence of stimulation was performed at 6 months after surgery. Main Outcome Measure Change in score on the Extrapyramidal Symptoms Rating Scale. RESULTS: At 6 months after surgery, the Extrapyramidal Symptoms Rating Scale score had decreased compared with baseline by more than 40% (mean improvement, 61%; range, 44%-75%) in the first 10 patients included. In accord with the 2-step open Fleming procedure, we ended the trial at the first step and concluded that pallidal stimulation is an effective treatment for TD. The efficacy of the treatment was confirmed by a double-blind evaluation, with a mean decrease of 50% (range, 30%-66%) (P = .002) in the Extrapyramidal Symptoms Rating Scale score when stimulation was applied compared with the absence of stimulation. There were no marked changes in the patients' psychiatric status. CONCLUSION: Although these results need to be confirmed in a larger group of patients with a longer follow-up, bilateral globus pallidus deep brain stimulation seems to offer a much-needed new treatment option for disabling TD.

Impulse control disorders in Parkinson's disease patients with RLS: a cross sectional-study.

BACKGROUND: Although dopamine replacement therapy is the main risk factor for the occurrence of Impulse Control Disorders (ICDs) in Parkinson's disease (PD), non-pharmacological risk factors for have also been identified in that population and sleep disorders could be part of them. Our objective is to determine whether Restless Legs Syndrome (RLS), that has been associated with more impulsive choices in general population regardless of dopaminergic therapy, could be associated with a specific psycho-behavioral profile and ICDs in PD. METHODS: Eighty consecutive PD patients were screened for the presence of RLS in a cross-sectional study. Sleep features were evaluated during one video-polysomnography. The frequency of ICDs, according to standard criteria, together with a broad range of psycho-behavioral features using the Ardouin Scale of Behavior in PD, were compared in patients with RLS (PD-RLS, n = 30) versus without RLS (PD-nRLS, n = 50). RESULTS: PD patients with RLS reported significantly more ICDs than those without RLS (50% versus 26%, p = 0.03), especially compulsive eating disorders, and a different psycho-behavioral profile with more hyperdopaminergic behaviors. There was no between group difference for total and dopamine agonists levodopa equivalent doses. However, age and durations of both disease and dopaminergic treatment were greater in the RLS group. Multivariate and propensity score analyses controlling for age, gender, total sleep time, disease severity, dose and duration of treatment, anxiety and depression showed that RLS was an independent predictor of ICDs in PD (OR = 5.91 [1.63; 22.1] and OR = 2.89 [1.63; 6.67] respectively). CONCLUSION: RLS per se could be a risk factor for impulsive behaviors in PD.

The MOVES (Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey): cross-cultural evaluation of the French version and additional psychometric assessment.

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.

Anatomical predictors of cognitive decline after subthalamic stimulation in Parkinson's disease.

We investigated whether pre-operative MRI measures of focal brain atrophy could predict cognitive decline occurring after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). For that purpose, we prospectively collected data of 42 consecutive patients with PD who underwent bilateral STN-DBS. Normalized brain structure volumes and cortical thicknesses were measured on pre-operative T1-weighted MRI. Patients were tested for their cognitive performances before surgery and 1 year after. After controlling for age, gender, pre-operative disease severity, change in dopaminomimetic dose after surgery and contact location, we found correlations: (1) between the variation of the total Mattis dementia rating scale (MDRS) score and left lateral ventricle volume (p = 0.032), (2) between the variation of the initiation/perseveration subscore of the MDRS and the left nucleus accumbens volume (p = 0.042) and the left lateral ventricle volume (p = 0.017) and (3) between the variation of the backward digit-span task and the right and left superior frontal gyrus thickness (p = 0.004 and p = 0.007, respectively). Left nucleus accumbens atrophy was associated with decline in the initiation/perseveration subscore with the largest effect size (d = - 1.64). Pre-operative left nucleus accumbens volume strongly predicted postoperative decline in the initiation/attention subscore (AUC = 0.92, p < 0.001, 96.3% sensitivity, 80.0% specificity, 92.9% PPV and 92.9% NPV). We conclude that the morphometric measures of brain atrophy usually associated with cognitive impairment in PD can also explain or predict a part of cognitive decline after bilateral STN-DBS. In particular, the left accumbens nucleus volume could be considered as a promising marker for guiding surgical decisions.