Introduction – Deep Brain Stimulation is an established treatment for movement disorders. Data-driven approaches like probabilistic mapping and predictive modeling are being increasingly used to optimize stimulation parameter selection. However, it remains unclear whether intra-operative test data alone can reliably inform such models. Clarifying the predictive value of intra-operative data is essential, as it may influence data collection strategies and surgical and programming protocols. Objective – This study examined whether post-operative DBS effects can be accurately predicted using intra-operative data alone or if post-operative information is required. Methods – A dataset comprising 1117 intra-operative and 1553 post-operative stimulation tests from 35 patients (14 Essential Tremor, 21 Parkinson’s Disease) was analyzed. Volumes of tissue activated (VTAs) were simulated to generate probabilistic maps, from which mapping and target anatomy-related features were extracted to train predictive classification models (low and high improvement, side effects). Model performance was assessed across scenarios linking intra- and post-operative data. Results – Intra-operative data effectively identified regions associated with optimal stimulation, highlighting their utility in guiding parameter selection (predictive accuracy ~60%). However, the predictive relationship between VTAs, probabilistic maps, and clinical outcomes differed between intra- and post-operative contexts. When trained solely on intra-operative VTAs, the model performed at a near chance level (predictive accuracy ~35%). Discussion – The study demonstrates that while intra-operative data are useful for identifying optimal target regions, they are insufficient for accurately predicting post-operative DBS outcomes. Incorporating post-operative data remains crucial for reliable and clinically meaningful DBS effect prediction.

BACKGROUND:Peripheral neuropathy has been described in Parkinson's disease (PD) patients receiving continuous levodopa delivery. Whether subcutaneous foslevodopa/foscarbidopa (fLD/fCD) infusion carries a similar risk remains unclear. CASES:We report four PD patients treated with continuous subcutaneous fLD/fCD who experienced clinical and electrophysiological worsening of peripheral neuropathy after treatment initiation. At baseline, none reported functional neuropathic symptoms, although electrophysiological evidence of mild subclinical peripheral neuropathy and/or biochemical abnormalities was present. Neuropathic symptoms developed within a few months of fLD/fCD initiation and were associated with vitamin B6 and/or B12 deficiency and persistent hyperhomocysteinemia. In all cases, electrophysiological deterioration accompanied symptoms emergence. CONCLUSIONS:Although causality cannot be established, these cases suggest that fLD/fCD infusion may be associated with aggravation of pre-existing peripheral neuropathy, despite non-enteral administration, supporting a potential systemic metabolic contribution. These findings underscore the importance of baseline assessment and longitudinal monitoring of peripheral nerve function and B-vitamin status in patients receiving fLD/fCD. Optimal vitamin supplementation strategies in this setting remain to be defined.

Rare loss-of-function variants in ITSN1 were recently reported to confer a high risk for Parkinson’s disease (PD). From our local large exome sequencing dataset of PD cases, we identified five carriers from three families. Clinical features of ITSN1-PD are typical and responsive to standard treatments. Additionally, we discuss whether ITSN1 loss-of-function variants should only be considered as a high-risk factor or a Mendelian PD gene.

CONTEXT:Previous studies assessing adapted physical activity (APA) in Parkinson's disease (PD) have been very heterogeneous regarding methodology and intervention, and have generally not addressed the question of combining various types of physical activity with a long-term evaluation. OBJECTIVES:To evaluate the immediate and long-term effect of a 3-month APA program, combining endurance, resistance training and stretching on motor symptoms, body composition, cardiorespiratory function and metabolic profile in PD patients. METHODS:In this controlled trial, we randomly assigned forty-four PD patients in a 1:1 ratio to receive a 3-month APA program (APA + group, n = 22), or freely practice physical activity (APA- group, n = 22). The patients were evaluated for parkinsonian symptoms (UPDRS-III), body composition, cardiorespiratory function and metabolic profile at baseline, immediately after the end of the program (M3) and six months later (M9). RESULTS:Between baseline and M3, the mean UPDRS-III score decreased in PD patients from the APA + group whereas it increased in the APA- group (-1.2 ± 6.6 vs. +1.9 ± 8.9; p = 0.04), regardless of age, sex, disease duration, dopaminergic treatment, UPDRS-III and axial score at baseline, but these between group differences waned at M9. No between group difference was observed regarding the evolution of body composition, metabolic profile or cardiorespiratory function between baseline, M3 and M9. CONCLUSION:A 3-month APA program combining endurance and resistance training plus stretching is more efficient for improving motor symptoms in PD compared to an unstructured engagement in non-specific physical activities. However, the benefits fade away six months after discontinuation of the program. STATISTICAL ANALYSIS CONDUCTED BY:LAMBERT Céline, CHU Clermont-Ferrand, DRCI, Biostatistics Unit, Clermont-Ferrand, FRANCE. REGISTRATION NUMBER:clinicaltrials.gov number NCT02816619.

Eating disorders (EDs) in patients with Parkinson's disease (PD) are mainly described through impulse control disorders but represent one end of the spectrum of food addiction (FA). Although not formally recognized by DSM-5, FA is well described in the literature on animal models and humans, but data on prevalence and risk factors compared with healthy controls (HCs) are lacking. We conducted a cross-sectional study including 200 patients with PD and 200 age- and gender-matched HCs. Characteristics including clinical data (features of PD/current medication) were collected. FA was rated using DSM-5 criteria and the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R). Patients with PD had more EDs compared to HCs (27.0% vs. 13.0%, respectively, p < 0.001). They mainly had FA (24.5% vs. 12.0%, p = 0.001) and night eating syndrome (7.0% vs. 2.5% p = 0.03). In PD patients, FA was associated with female gender (p = 0.04) and impulsivity (higher attentional non-planning factor) but not with the dose or class of dopaminergic therapy. Vigilance is necessary, especially for PD women and in patients with specific impulsive personality traits. Counterintuitively, agonist dopaminergic treatment should not be used as an indication for screening FA in patients with PD.

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. 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.

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. 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. 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. 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. Clinicaltrials.gov number NCT01114321.

•Apomorphine is used for the treatment of advanced Parkinson's disease. •The most frequent adverse event is subcutaneous nodules at the infusion site. •We report the first case of drug induced agranulocytosis to apomorphine.

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.

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. (C) 2018 Elsevier B.V. All rights reserved.

Introduction: 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.

Bien que le traitement dopaminergique continu soit le facteur de risque principal d’apparition de troubles du contrôle des impulsions (TCI) dans la maladie de Parkinson Idiopathique (MPI), d’autres facteurs de risque non pharmacologiques ont été identifiés. Notre objectif est de déterminer si le syndrome des jambes sans repos (SJSR), dont l’association avec des choix plus impulsifs a été rapportée dans la population générale, indépendamment du traitement dopaminergique, pourrait être associé a un profil psycho-comportemental particulier et à des TCI dans la MPI. Quatre-vingt patients parkinsoniens consécutifs ont été inclus et évalués pour la présence de SJSR. Les paramètres du sommeil ont été étudiés au cours d’une vidéo-polysomnographie. Nous avons comparé la fréquence des TCI et d’un large éventail de caractéristiques psycho-comportementales entre les patients avec SJSR (MPI-SJSR, n = 30) et sans SJSR (MPI-nSJSR, n = 50). Les patients MPI-SJSR présentaient plus de TCI que les MPI-nSJSR (50 % versus 26 %, p = 0,03), notamment des compulsions alimentaires, ainsi qu’un profil psycho-comportemental différent avec plus de comportements hyper dopaminergiques. Les analyses multivariées et le score de propension, contrôlant les facteurs de confusion tels que l’âge, le sexe, le temps total de sommeil, la durée et la dose de traitement dopaminergique, ont montré que la présence de SJSR était un prédicteur indépendant de la présence de TCI dans la MPI (OR = 5,79 [1,63 ; 20,5] et OR = 4,89 [2,27 ; 11]). Le SJSR pourrait être per se un facteur de risque supplémentaire de comportements impulsifs dans la MPI.

Routine 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.

BACKGROUND:Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents a well-established treatment in advanced Parkinson's disease (PD) for motor signs, but it is still debated concerning psychiatric effects.OBJECTIVE:Exploration of relation between position of active electrode contacts and neuropsychological and motor change after STN DBS procedure for PD.METHODS:A cohort of 34 patients who underwent STN DBS was followed for 6 months. Preoperative and postoperative assessments included mood evaluation (depression and mania) and motor status. Active contact localisation was identified regarding position into the STN (4 groups: IN meant contacts were IN-IN IN-BORDER; OUT: OUT-OUT or OUT-BORDER; BORDER: BORDER-BORDER; IN-OUT: IN-OUT) and compared with clinical outcomes.RESULTS:STN DBS significantly improved motor scores and reduced dopaminergic medication when compared with baseline and active lead groups: the best result was seen with the IN group. At 3 and 6 months postsurgery, depression and manic scores do not significantly differ compared with baseline and between leads groups. Focusing on symptom domains and compared with baseline, a significant loss of appetite was observed for the IN group at M3 and a significant increase in appetite from baseline was observed at M3 for the OUT group. Graphic representations illustrate that postsurgery evolution parameters at M3 or M6 are very good discriminant variables and well differentiate all leading groups.CONCLUSIONS:Stimulation of zona incerta may influence appetite and weight gain. Our clinical results seem to support a personalised DBS-targeted Parkinson therapy including individual motor and non-motor parameters.

Hallucinations have been described in various clinical populations, but they are neither disorder nor disease specific. In schizophrenia patients, hallucinations are hallmark symptoms and auditory ones are described as the more frequent. In Parkinson's disease, the descriptions of hallucination modalities are sparse, but the hallucinations do tend to have less negative consequences. Our study aims to explore the phenomenology of hallucinations in both hallucinating schizophrenia patients and Parkinson's disease patients using the Psycho-Sensory hAllucinations Scale (PSAS). The main objective is to describe the phenomena of these clinical symptoms in those two specific populations. Each hallucinatory sensory modality significantly differed between Parkinson's disease and schizophrenia patients. Auditory, olfactory/gustatory and cœnesthetic hallucinations were more frequent in schizophrenia than visual hallucinations. The guardian angel item, usually not explored in schizophrenia, was described by 46% of these patients. The combination of auditory and visual hallucinations was the most frequent for both Parkinson's disease and schizophrenia. The repercussion index summing characteristics of each hallucination (frequency, duration, negative aspects, conviction, impact, control and sound intensity) was always higher for schizophrenia. A broader view including widespread characteristics and interdisciplinary works must be encouraged to better understand the complexity of the process involved in hallucinations.

Objective: Studies investigating the effects of subthalamic deep-brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) are limited and report conflicting results, with some describing the emergence of RLS after DBS-STN, while others report postoperative improvement of this disorder. Severe decrease in postoperative dopaminergic medications dose, which may unmask RLS symptoms, has been proposed to explain the emergence of RLS after surgery. We aimed to specifically identify factors associated with the risk of developing RLS after DBS-STN in order to enhance our comprehension of the underlying mechanisms contributing to the development of RLS in PD.Patients: In this observational prospective study, we evaluated the occurrence of RLS in 31 patients with PD originally free from RLS symptoms, six months after bilateral chronic DBS-STN, and compared clinical and treatment parameters of patients who developed postoperative RLS with those of patients without postoperative RLS.Results: Six patients out of 31 reported post-operative emergence of RLS. There was no between-group difference in demographic data, pre-operative treatment parameters or clinical improvement measures after DBS-STN. However, PD patients with emergence of RLS after DBS-STN had a higher dose of dopamine agonists at postoperative evaluation compared to PD patients without emergence of RLS (p = 0.040) and a lower percentage of decrease in dopamine agonists (p = 0.043).Conclusion: Overstimulation resulting from cumulative effects of dopamine agonists and STN-DBS may induce changes in excitability of the dopaminergic system, leading to an emergence of RLS. Clinicians should take into account this phenomenon while adjusting pharmacological treatment after surgery. (C) 2014 Elsevier B.V. All rights reserved.

Peu d’études ont évalué les effets de la stimulation cérébrale profonde du noyau subthalamique (SCP-NST) sur le syndrome des jambes sans repos (SJSR) dans la maladie de Parkinson et leurs résultats sont contradictoires. En effet une amélioration du SJSR après SCP-NST est parfois rapportée alors que d’autres études retrouvent au contraire une émergence de SJSR en postopératoire. Il a été suggéré que la forte diminution des traitements dopaminergiques après la chirurgie puisse démasquer les symptômes de SJSR et expliquer l’apparition de SJSR observée après SCP-NST. Nous avons ici voulu identifier spécifiquement les facteurs associés au risque de développer un SJSR après SCP-NST afin de mieux comprendre les mécanismes à l’origine du SJSR dans la maladie de Parkinson. Dans cette étude observationnelle prospective nous avons évalué la survenue de SJSR chez 31 patients présentant une maladie de Parkinson, initialement sans SJSR, avant et 6 mois après SCP-NST bilatérale chronique. Nous avons comparé les paramètres cliniques et le traitement (dose totale, dose uniquement pour les agonistes dopaminergiques et dose sans les agonistes dopaminergiques) entre les patients qui développaient un SJSR et ceux qui n’en développaient pas. Six patients sur 31 se sont plaints d’une apparition de SJSR en postopératoire. Il n’y avait pas de différence entre les deux groupes concernant les données démographiques, le traitement préopératoire et l’amélioration clinique après SCP-NST. En revanche les patients qui développaient un SJSR avaient, par rapport aux patients sans émergence de SJSR, une plus forte dose d’agonistes dopaminergiques lors de l’évaluation postopératoire (p = 0,040) et un pourcentage de diminution des agonistes dopaminergiques moins important (p = 0,043). Les effets cumulés des agonistes dopaminergiques et de la SCP-NST pourraient, par le biais d’une hyperstimulation, entraîner des modifications d’excitabilité du système dopaminergique à l’origine d’une émergence de SJSR en postopératoire. Ce phénomène devrait être pris en compte par les cliniciens lors de l’adaptation du traitement pharmacologique après la chirurgie.