Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Background: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. Methodology/Principal Findings: To this end, we conducted 18 FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucos

Parkinson's disease and iatrogenic impulsive-compulsive behaviors: A case/non-case study to build a complete model of individual vulnerability

Background and aims: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual’s vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability. Methods: The PARKADD study was a case/non-case study. A total of 225 patients were enrolled (“ICB” group, N 5 75; “no ICB” group, N 5 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed. Results: Factors associated with “ICBs” were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance. Discussion and conclusions: The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients

Efficacité, tolérance et impact sur la qualité de vie de la pompe à apomorphine dans la maladie de Parkinson, à court et moyen terme

Au stade des fluctuations (motrices et non-motrices) et des dyskinésies, les traitements pharmacologiques classiques de la maladie de Parkinson idiopathique ne suffisent plus à assurer aux patients un état moteur stable sur le nycthémère. La perfusion sous-cutanée continue d'apomorphine a prouvé son efficacité dans cette indication en cas de contre-indications pour la chirurgie de stimulation cérébrale profonde, ou dans l'attente de celle-ci. Elle apparaît cependant sous-utilisée, notamment chez le sujet âgé, par crainte d'une mauvaise tolérabilité générale ou cognitivo-comportementale.Nous avons donc évalué l'efficacité, la tolérance et l'impact sur la qualité de vie de la pompe à apomorphine à court et moyen terme grâce au suivi prospectif d'un an de 16 patients parkinsoniens suite à la pose de la pompe en continue sur le nycthémère. Conformément aux données de la littérature, notre étude a montré que la mise en place de la pompe permet une diminution de plus de 35 % en moyenne du traitement per-os en équivalent dopamine à 6 mois de la pose. Le score moteur de l'UPDRS s'améliore de façon significative dès le troisième mois. L'amélioration la plus significative est celle des sous-scores de fluctuations et de dyskinésies (diminution respective de 45% et de 35%). L'évaluation de la qualité de vie par la PDQ39 a permis de mettre en évidence une amélioration significative du score mental mais pas du score physique. Ces résultats sont en partie discordants avec l'évaluation subjective des patients et des médecins, notamment par la CGI-I (où 80% des patients se déclarent fortement améliorés à un an de la pose et 90% selon les médecins). La tolérabilité générale est très bonne. Il n'y a pas de dégradation des tests neuropsychologiques et la pompe permettrait même la diminution des hallucinations visuelles préalables. Les seuls effets indésirables significatifs sont l'apparition de nodules sous-cutanés, d'une somnolence diurne et d'une addiction à la dopamine. D'après les résultats de notre étude la pompe à apomorphine est une thérapeutique efficace et bien tolérée sur le plan général, neuro-psychologique et psychiatrique chez les patients parkinsoniens fluctuants, notamment en cas de contre-indications pour la neurostimulation du NST du fait de signes axiaux ou d'un déclin cognitif, y compris chez la personne agée.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Critères prédictifs cliniques et radiologiques des résultats de la stimulation du noyau sous-thalamique dans la maladie de Parkinson

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Efficacité et tolérabilité de la neurostimulation bipallidale dans les syndromes tardifs provoqués par les neuroleptiques (étude prospective multicentrique sur 20 patients suivis pendant 1 an)

Objectif. Les syndromes tardifs sont des mouvements anormaux involontaires chroniques provoqués par les neuroleptiques. Ils peuvent être invalidants et retentir sur la qualité de vie. Leur prise en charge médicale est souvent décevante. Les premiers résultats du groupe français d'étude de la neurostimulation dans les dyskinésies tardives (STARDYS) suggèrent l'efficacité de la stimulation cérébrale profonde sur 10 patients suivis pendant 6 mois. Notre objectif est de confirmer l'efficacité et la bonne tolérabilité de la stimulation bipallidale dans les syndromes tardifs, en complétant cette série par 10 patients supplémentaires. Méthodes. Vingt patients présentant un syndrome tardif sévère, ont participé à cet essai multicentrique thérapeutique de phase II. Avant stimulation bipallidale, puis à 3, 6 et 12 mois, des évaluations motrices (scores ESRS et AIMS), cognitives, psychiatriques, et de qualité de vie ont été réalisées. A 6 mois, une évaluation en double aveugle stimulation éteinte et allumée a été faite. Les évènements indésirables étaient recensés à chaque visite. Résultats. Une diminution significative de 51% de l'ESRS (p < 0,0001) et de 44% de l'AIMS (p <0,0001) était constatée dès 3 mois et persistait à 12 mois. Tous les sous-scores de l'ESRS étaient concernés. L'évaluation en double aveugle confirmait cette amélioration motrice, avec une diminution moyenne de l'ESRS de 46% (p < 0,0001). Malgré les comorbidités psychiatriques, aucune dégradation cognitive n'a été retrouvée. Il existe même une amélioration cognitive sur le score total de la MATTIS et une tendance à l'amélioration de l'humeur est constatée. Trois patients ont présenté des évènements indésirables graves liés à l'intervention, non spécifiques des syndromes tardifs. Conclusion. Cette étude confirme l'efficacité de la stimulation bipallidale dans les syndromes tardifs, sur les composantes dystonique, choréique et parkinsonienne, avec une bonne tolérabilité cognitive et psychiatrique. Il s'agit de la plus grande cohorte de patients traités par cette procédure.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

The subthalamic nucleus is a key-structure of limbic basal ganglia functions

International audienc

Apomorphine infusion in advanced Parkinson's patients with subthalamic stimulation contraindications.

International audienceThe efficacy of continuous subcutaneous apomorphine infusion (APO) has been evaluated in advanced Parkinson's disease in several open-label studies but never in a population of patients for whom subthalamic nucleus deep brain stimulation (STN-DBS) was contraindicated. The aim of this study was to evaluate the efficacy and cognitive safety of APO at 12-month follow-up in 23 advanced parkinsonian patients (mean age: 62.3 years; mean disease duration: 13.9 years) whose dopa-resistant axial motor symptoms and/or cognitive decline constituted contraindications for STN-DBS. Their motor and cognitive status were evaluated before APO and 12 months afterwards. After one year, patients expressed high levels of satisfaction, with a mean rating on the Visual Analog Scale of 52.8% under APO. Daily OFF time, recorded in a 24-h diary, was reduced by 36% and ON time improved by 48%. There was a significant reduction (-26%) in mean oral levodopa equivalent dose. Dopa-resistant axial symptoms and neuropsychological performance remained stable. No adverse event was noted and none of the patients needed to take clozapine at any time. APO is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN-DBS is contraindicated due to dopa-resistant axial motor symptoms and/or cognitive decline. As such, it should be regarded as a viable alternative for these patients

Pallidal stimulation in advanced Parkinson's patients with contraindications for subthalamic stimulation.

International audienceThe aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa-resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45-70), mean disease duration of 12.5 ± 4.3 years (range, 7-20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off-dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off-dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6-month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa-resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients

Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease

To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson’s disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n 5 32) or GPi (n 5 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi–DBS group. Food intake did not change in the two groups,either quantitatively or qualitatively. Frequent weight gain,inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement

Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease.

International audienceThe recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD). These changes have been linked to a disturbance in the STN's limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody. An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly. These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody