Stimulation du noyau sous-thalamique (DBS-STN) dans la maladie de Parkinson : quelle cible pour la meilleure efficacité ?

National audienceLa stimulation du noyau sous-thalamique est le traitement de référence des complications motrices persistantes, malgré les adaptations thérapeutiques chez le patient parkinsonien. La nature de la cible optimale au niveau de la région sous-thalamique en termes de bénéfice clinique et de tolérance reste discutée. Dans notre expérience, les contacts utilisés de façon chronique sont souvent différents que ceux sélectionnés au cours de la procédure chirurgicale. Nous avons donc réalisé une étude afin d'explorer systématiquement l'efficacité et la tolérance des 4 contacts (numérotés de 0 à 3, le contact 0 étant le plus profond) de chaque électrode chez 30 patients

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

International audienc

Emergence of restless legs syndrome after subthalamic stimulation in Parkinson's disease: a dopaminergic overstimulation?

International audienc

Compulsive eating behaviors in Parkinson’s disease

International audiencePURPOSE: 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

Deep brain stimulation in routine clinical practice: monocentric study of the battery lifetime of different generations of neurostimulators

TalkInternational audienceRoutine clinical practice of Deep Brain Stimulation (DBS) enters a new era where battery-related events are challenging. The important number of primary implantations and replacements pushed industrials to develop new generations of devices. We aimed to analyze the battery lifetime of different kinds of non-rechargeable devices, manufactured by a single company (Medtronic, USA): the first generation of 4-contact neurostimulator for one DBS-lead (1 channel; Soletra®) and 8-contact neurostimulator for two DBS-leads (two channels of 4 contacts; Kinetra®); the second generation of advanced programming neurostimulator (Activa® PC, two channels of 8 contacts, and SC, 1 channel of 8 contacts). We retrospectively reviewed 281 consecutive patients operated on in a single institution (from 1995 to 2016): 584 surgeries for primary implantation or replacement of neurostimulator (infection and traumatic etiologies of battery replacement were excluded). The battery lifetime was defined as the period between the surgical implantation and the removal at battery depletion. Two hundred and eighty eight battery-lifetimes were analyzed in 157 patients suffering of Parkinson disease (n=129), essential tremor (n=19), dystonia (n=9). Exclusion criteria were: battery related, still operational (n=217); patient related, died before battery depletion (n=50); missing follow-up (n=3); and other diseases treated by DBS (n=2). Battery lifetime was analyzed using survival methods (univariate, Log-Rank test; multivariate, marginal cox model; two-sided tests) accounting for the following parameters: gender, neurological disease, age at the primary implantation, the UPDRS-score before DBS surgery, the deep brain target, battery model, mean voltage (low 4V), location of battery (abdominal or sub clavicular) and presence of an adapter for replacement of first generation (Kinetra or Soletra) by second generation model (Activa).Results: The battery lifetime was shorter in male (p=0.03) and young (p<0.001) patients suffering of essential tremor (p<0.001) and dystonia (p<0.001). High voltage reduced battery lifetime (p<0.001). The second generation device, Activa models, had shorter lifetime than first generation, Soletra and Kinetra (p<0.001). Replacement of battery decreased lifetime independently of models (p<0.001). Patient and disease characteristics, high voltage, second generation devices and replacement seem to shorten lifetime of battery

Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial

International audienceIntroduction: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study.Methods: We conducted a double-blind randomized placebo-controlled cross-over trial in PD patients with motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for 14 days. The two co-primary endpoints were the area under curve (AUC) of motor (MDS-UPDRS part III) and dyskinesia (AIMS) scores during an acute levodopa challenge performed at the end of each period. Secondary endpoints were UDysRS and axial symptoms scores during the challenge; AIMS, UDysRS, and time spent with or without dyskinesia the day before the challenge. The primary analysis was performed in the per protocol population.Results: Sixteen patients were included in the analysis. There was no difference between naftazone and placebo for the AUC of MDS-UPDRS III (-89, 95%CI[-1071; 893], p = 0.85), and AIMS (70, 95%CI[-192; 332], p = 0.57). At the end of treatment periods, AIMS score tended to be lower with naftazone than placebo (4.4 ± 3.4 versus 6.7 ± 4.4, p = 0.07), but UDysRS scores and other secondary outcomes were not different. Naftazone was safe and well tolerated.Conclusions: This study did not confirm previous results on the efficacy of naftazone on dyskinesia nor motor fluctuations highlighting the problem of translating results obtained in preclinical models into clinical trials. Further investigation of naftazone may be conducted in PD with longer treatment duration

OpenSIMPLe: A real-world implementation feasibility study of a smartphone-based psychoeducation programme for bipolar disorder

International audienc

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

International audienceBackground 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

Parkinson's disease polygenic risk score is not associated with impulse control disorders: A longitudinal study

International audienceObjective: 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

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs