39 results on '"Lhommée, Eugénie"'
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2. Axial impairment and falls in Parkinson’s disease: 15 years of subthalamic deep brain stimulation
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Zampogna, Alessandro, Cavallieri, Francesco, Bove, Francesco, Suppa, Antonio, Castrioto, Anna, Meoni, Sara, Pélissier, Pierre, Schmitt, Emmanuelle, Bichon, Amélie, Lhommée, Eugénie, Kistner, Andrea, Chabardès, Stephan, Seigneuret, Eric, Fraix, Valerie, and Moro, Elena
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- 2022
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3. Dysexecutive disorders and their diagnosis: A position paper
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Godefroy, Olivier, Martinaud, Olivier, Narme, Pauline, Joseph, Pierre-Alain, Mosca, Chrystèle, Lhommée, Eugénie, Meulemans, Thierry, Czernecki, Virginie, Bertola, Céline, Labauge, Pierre, Verny, Marc, Bellmann, Anne, Azouvi, Philippe, Bindschaedler, Claire, Bretault, Eric, Boutoleau-Bretonniere, Claire, Robert, Philippe, Lenoir, Hermine, Krier, Marianne, and Roussel, Martine
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- 2018
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4. Hyperdopaminergic behavioral spectrum in Parkinson's disease: A review
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Béreau, Matthieu, Fleury, Vanessa, Bouthour, Walid, Castrioto, Anna, Lhommée, Eugénie, and Krack, Paul
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- 2018
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5. Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial
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Negovanska, Velina, Welter, Marie-Laure, Corvol, Jean-Christophe, Agid, Yves, Navarro, Soledad, Meier, Niklaus, Hartmann, Andreas, Hesekamp, Helke, Cornu, Philippe, Möller, Bettina, Nebel, Adelheid, Raethjen, Jan, Knudsen, Karina, Volkmann, Jens, Falk, Daniela, Paschen, Steffen, Meister, Ingo, Kuhn, Jens, Donner, Kerstin, Kessler, Josef, Barbe, Michael, Fink, Gereon, Maarouf, Mohammad, Kühn, Andrea, Müller, Bianca, Faust, Katharina, Gruber, Doreen, Schneider, Gerd-H., Seigneuret, Eric, Pollak, Pierre, Fraix, Valerie, Kistner, Andrea, Rascol, Olivier, Arbus, Christophe, Danet, Lola, Chaynes, Patrick, Groiss, Stefan J., Hartmann, Christian, Südmeyer, Martin, Partowinia-Peters, Mahnaz, Vesper, Jan, Ledily, Severine, Damier, Philippe, Raoul, Sylvie, Trenkwalder, Claudia, Richter-Dreske, Wenke, Wächter, Tobias, Weiss, Daniel, Eusebio, Alexandro, Azulay, Jean Philippe, Polo, Gustavo, Pinto, Serge, Levin, Johannes, Dornier, Stephanie, Pene, Fredy, Hourton, Delphine, Quintin, Mathieu, Hoffart-Jourdain, Cecile, Brocvielle, Helene, Balthasar, Kerstin, Stein, Meryem, Harnisch, Susanne, Reuss, Alexander, Aminossadati, Behnaz, Nasemann, Christian, Oertel, Wolfgang, Bataille, Benoit, Hellwig, Dieter, Gharabaghi, Alireza, Amtage, Florian, Mertens, Patrick, Kloss, Manja, Post, Bart, Speelman, Hans, Lhommée, Eugénie, Wojtecki, Lars, Czernecki, Virginie, Witt, Karsten, Maier, Franziska, Tonder, Lisa, Timmermann, Lars, Hälbig, Thomas D, Pineau, Fanny, Durif, Franck, Witjas, Tatiana, Pinsker, Marcus, Mehdorn, Maximilian, Sixel-Döring, Friederike, Kupsch, Andreas, Krüger, Rejko, Elben, Saskia, Chabardès, Stephan, Thobois, Stéphane, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Regis, Jean-Marie, Maltête, David, Sauvaget, Anne, Rau, Jörn, Schnitzler, Alfons, Schüpbach, Michael, Schade-Brittinger, Carmen, Deuschl, Gunther, Houeto, Jean-Luc, and Krack, Paul
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- 2018
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6. Dementia and subthalamic deep brain stimulation in Parkinson disease: A long-term overview
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Bove, Francesco, Fraix, Valerie, Cavallieri, Francesco, Schmitt, Emmanuelle, Lhommée, Eugénie, Bichon, Amélie, Meoni, Sara, Pélissier, Pierre, Kistner, Andrea, Chevrier, Eric, Ardouin, Claire, Limousin, Patricia, Krack, Paul, Benabid, Alim Louis, Chabardès, Stephan, Seigneuret, Eric, Castrioto, Anna, and Moro, Elena
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- 2020
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7. Suicide and suicide attempts after subthalamic nucleus stimulation in Parkinson disease
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Giannini, Giulia, Francois, Matthieu, Lhommée, Eugénie, Polosan, Mircea, Schmitt, Emmanuelle, Fraix, Valérie, Castrioto, Anna, Ardouin, Claire, Bichon, Amélie, Pollak, Pierre, Benabid, Alim-Louis, Seigneuret, Eric, Chabardes, Stephan, Wack, Maxime, Krack, Paul, and Moro, Elena
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- 2019
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8. Mood and behavioural effects of subthalamic stimulation in Parkinson's disease
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Castrioto, Anna, Lhommée, Eugénie, Moro, Elena, and Krack, Paul
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- 2014
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9. Psychostimulant effect of dopaminergic treatment and addictions in Parkinsonʼs disease
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Delpont, Benoit, Lhommée, Eugénie, Klinger, Hélène, Schmitt, Emmanuelle, Bichon, Amélie, Fraix, Valérie, Castrioto, Anna, Quesada, Jean‐Louis, Pélissier, Pierre, Kistner, Andrea, Carnicella, Sébastien, Lüscher, Christian, Broussolle, Emmanuel, Pollak, Pierre, Thobois, Stéphane, and Krack, Paul
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- 2017
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10. Postoperative apathy can neutralise benefits in quality of life after subthalamic stimulation for Parkinsonʼs disease
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Martinez-Fernandez, Raul, Pelissier, Pierre, Quesada, Jean-Louis, Klinger, Hélène, Lhommée, Eugénie, Schmitt, Emmanuelle, Fraix, Valerie, Chabardes, Stephan, Mertens, Patrick, Castrioto, Anna, Kistner, Andrea, Broussolle, Emmanuel, Pollak, Pierre, Thobois, Stéphane, and Krack, Paul
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- 2016
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11. Iowa gambling task impairment in Parkinsonʼs disease can be normalised by reduction of dopaminergic medication after subthalamic stimulation
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Castrioto, Anna, Funkiewiez, Aurélie, Debû, Bettina, Cools, Roshan, Lhommée, Eugénie, Ardouin, Claire, Fraix, Valérie, Chabardès, Stephan, Robbins, Trevor W, Pollak, Pierre, and Krack, Paul
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- 2015
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12. Early Parkinson's Disease Phenotypes Tailored by Personality, Behavior, and Motor Symptoms.
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Meira, Bruna, Lhommée, Eugénie, Schmitt, Emmanuelle, Klinger, Hélène, Bichon, Amélie, Pélissier, Pierre, Anheim, Mathieu, Tranchant, Christine, Fraix, Valérie, Meoni, Sara, Durif, Franck, Houeto, Jean-Luc, Azulay, Jean Philippe, Moro, Elena, Thobois, Stéphane, Krack, Paul, and Castrioto, Anna
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APATHY , *PARKINSON'S disease , *REWARD (Psychology) , *PERSONALITY , *PHENOTYPES , *SYMPTOMS , *MOVEMENT disorders - Abstract
Background: Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson's disease (PD) patients and their relationships with motor and neuropsychiatric symptoms. Objective: To investigate personality in de novo PD and explore its relationship with PD symptoms. Methods: Using Cloninger's biosocial model, we assessed personality in 193 de novo PD patients. Motor and non-motor symptoms were measured using several validated scales. Cluster analysis was conducted to investigate the interrelationship of personality traits, motor, and non-motor symptoms. Results: PD patients showed low novelty seeking, high harm avoidance, and normal reward dependence and persistence scores. Harm avoidance was positively correlated with the severity of depression, anxiety, and apathy (rs = [0.435, 0.676], p < 0.001) and negatively correlated with quality of life (rs = –0.492, p < 0.001). Novelty seeking, reward dependence, and persistence were negatively correlated with apathy (rs = [–0.274, –0.375], p < 0.001). Classification of patients according to personality and PD symptoms revealed 3 distinct clusters: i) neuropsychiatric phenotype (with high harm avoidance and low novelty seeking, hypodopaminergic neuropsychiatric symptoms and higher impulsivity), ii) motor phenotype (with low novelty seeking and higher motor severity), iii) benign phenotype (with low harm avoidance and high novelty seeking, reward dependence, and persistence traits clustered with lower symptoms severity and low impulsivity). Conclusion: Personality in early PD patients allows us to recognize 3 patients' phenotypes. Identification of such subgroups may help to better understand their natural history. Their longitudinal follow-up will allow confirming whether some personality features might influence disease evolution and treatment. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Fatigue in de novo Parkinson's Disease: Expanding the Neuropsychiatric Triad?
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Béreau, Matthieu, Castrioto, Anna, Lhommée, Eugénie, Maillet, Audrey, Gérazime, Aurélie, Bichon, Amélie, Pélissier, Pierre, Schmitt, Emmanuelle, Klinger, Hélène, Longato, Nadine, Fraix, Valérie, Benatru, Isabelle, Durif, Franck, Azulay, Jean-Philippe, Moro, Elena, Broussolle, Emmanuel, Tranchant, Christine, Anheim, Mathieu, Thobois, Stéphane, and Krack, Paul
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APATHY ,PARKINSON'S disease ,CANCER fatigue ,FATIGUE (Physiology) ,UNIVARIATE analysis - Abstract
Background: Fatigue is a frequent and troublesome symptom present from the early stages of Parkinson's disease (PD). Objective: To examine the relationship between fatigue and the neuropsychiatric triad, which includes apathy, depression, and anxiety, in de novo PD. Methods: We performed a cross-sectional study including 197 patients with de novo PD and assessed fatigue using the Parkinson's Disease Fatigue Scale (PDFS-16). We evaluated motor status using the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and evaluated neuropsychiatric status using the Ardouin Scale of Behavior in Parkinson's Disease (ASBPD). We carried out univariate and multivariate analyses to model association between motor signs, non-motor signs, and fatigue risk. Results: Frequency of fatigue (28.9%) was of the same order of magnitude as that of apathy. PD patients with fatigue reported a lower quality of life than patients without fatigue (p < 0.0001). The ASBPD showed that patients with fatigue had higher scores for depressed mood (p < 0.0001), anxiety (p < 0.0001), and apathy (p < 0.0001). In the univariate analysis, fatigue score was positively correlated with apathy, depression, anxiety, and the neuropsychiatric triad as a whole, and to a lesser extent with female sex, hyperemotivity, and the UPDRS part III score. In the multivariate analysis, after adjusting for sex and motor status, the fatigue score remained significantly correlated with apathy (OR = 11.17 [4.33–28.78], p < 0.0001) and depression (OR = 4.28 [1.39–13.12], p = 0.01), but not with anxiety (OR = 0.94 [0.34–2.58], p = 0.9). Conclusion: We propose that the neuropsychiatric triad could be expanded to include fatigue. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil
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Thobois, Stéphane, Lhommée, Eugénie, Klinger, Hélène, Ardouin, Claire, Schmitt, Emmanuelle, Bichon, Amélie, Kistner, Andrea, Castrioto, Anna, Xie, Jing, Fraix, Valerie, Pelissier, Pierre, Chabardes, Stephan, Mertens, Patrick, Quesada, Jean-Louis, Bosson, Jean-Luc, Pollak, Pierre, Broussolle, Emmanuel, and Krack, Paul
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- 2013
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15. Long‐term independence and quality of life after subthalamic stimulation in Parkinson disease.
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Castrioto, Anna, Debû, Bettina, Cousin, Emilie, Pelissier, Pierre, Lhommée, Eugénie, Bichon, Amélie, Schmitt, Emmanuelle, Kistner, Andrea, Meoni, Sara, Seigneuret, Eric, Chabardes, Stephan, Krack, Paul, Moro, Elena, and Fraix, Valérie
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PARKINSON'S disease ,QUALITY of life ,SUBTHALAMIC nucleus ,BECK Depression Inventory ,NEUROPSYCHOLOGICAL tests ,ACTIVITIES of daily living ,THALAMIC nuclei - Abstract
Background and purpose: Studies on long‐term nonmotor outcomes of subthalamic nucleus stimulation in Parkinson disease (PD) are scarce. This study reports on very long‐term non‐motor and motor outcomes in one of the largest cohorts of people with advanced PD, treated for >10 years with subthalamic nucleus stimulation. The main outcome was to document the evolution of independence in activities of daily living. The secondary outcomes were to measure the change in quality of life, as well as non‐motor and motor outcomes. Methods: Patients were studied preoperatively, at 1 year, and beyond 10 years after subthalamic stimulation with an established protocol including motor, non‐motor, and neuropsychological assessments. Results: Eighty‐five people with PD were included. Independence scores in the off‐medication condition (measured with the Schwab & England Activities of Daily Living Scale) as well as quality of life (measured with the Parkinson's Disease Questionnaire [PDQ]‐37) remained improved at longest follow‐up compared to preoperatively (respectively, p < 0.001, p = 0.015). Cognitive scores, measured with the Mattis Dementia Rating Scale, significantly worsened compared to before and 1 year after surgery (p < 0.001), without significant change in depression, measured with the Beck Depression Inventory. Motor fluctuations, dyskinesias, and off dystonia remained improved at longest follow‐up (p < 0.001), with a significant reduction in dopaminergic treatment (45%, p < 0.001). Conclusions: This study highlights the long‐term improvement of subthalamic stimulation on independence and quality of life, despite the progression of disease and the occurrence of levodopa‐resistant symptoms. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Psychostimulant effect of levodopa: reversing sensitisation is possible
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Castrioto, Anna, Kistner, Andrea, Klinger, Hélène, Lhommée, Eugénie, Schmitt, Emmanuelle, Fraix, Valérie, Chabardès, Stephan, Mertens, Patrick, Quesada, Jean-Louis, Broussolle, Emmanuel, Pollak, Pierre, Thobois, Stéphane C, and Krack, Paul
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- 2013
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17. Subthalamic stimulation in Parkinson’s disease: restoring the balance of motivated behaviours
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Lhommée, Eugénie, Klinger, Hélène, Thobois, Stéphane, Schmitt, Emmanuelle, Ardouin, Claire, Bichon, Amélie, Kistner, Andrea, Fraix, Valérie, Xie, Jing, Aya Kombo, Magaly, Chabardès, Stephan, Seigneuret, Eric, Benabid, Alim-Louis, Mertens, Patrick, Polo, Gustavo, Carnicella, Sebastien, Quesada, Jean-Louis, Bosson, Jean-Luc, Broussolle, Emmanuel, Pollak, Pierre, and Krack, Paul
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- 2012
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18. Non-motor dopamine withdrawal syndrome after surgery for Parkinson’s disease: predictors and underlying mesolimbic denervation
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Thobois, Stéphane, Ardouin, Claire, Lhommée, Eugénie, Klinger, Hélène, Lagrange, Christelle, Xie, Jing, Fraix, Valérie, Coelho Braga, Maria Clara, Hassani, Rachid, Kistner, Andrea, Juphard, Alexandra, Seigneuret, Eric, Chabardes, Stephan, Mertens, Patrick, Polo, Gustavo, Reilhac, Anthonin, Costes, Nicolas, LeBars, Didier, Savasta, Marc, Tremblay, Léon, Quesada, Jean-Louis, Bosson, Jean-Luc, Benabid, Alim-Louis, Broussolle, Emmanuel, Pollak, Pierre, and Krack, Paul
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- 2010
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19. Does Motor Symptoms Asymmetry Predict Motor Outcome of Subthalamic Deep Brain Stimulation in Parkinson's Disease Patients?
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Bove, Francesco, Cavallieri, Francesco, Castrioto, Anna, Meoni, Sara, Schmitt, Emmanuelle, Bichon, Amélie, Lhommée, Eugénie, Pélissier, Pierre, Kistner, Andrea, Chevrier, Eric, Seigneuret, Eric, Chabardès, Stephan, Valzania, Franco, Fraix, Valerie, and Moro, Elena
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DEEP brain stimulation ,SUBTHALAMIC nucleus ,PARKINSON'S disease ,MOVEMENT disorders ,REGRESSION analysis ,SYMPTOMS ,LINEAR statistical models - Abstract
Background: In Parkinson's disease (PD), the side of motor symptoms onset may influence disease progression, with a faster motor symptom progression in patients with left side lateralization. Moreover, worse neuropsychological outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) have been described in patients with predominantly left-sided motor symptoms. The objective of this study was to evaluate if the body side of motor symptoms onset may predict motor outcome of bilateral STN-DBS. Methods: This retrospective study included all consecutive PD patients treated with bilateral STN-DBS at Grenoble University Hospital from 1993 to 2015. Demographic, clinical and neuroimaging data were collected before (baseline condition) and 1 year after surgery (follow-up condition). The predictive factors of motor outcome at one-year follow-up, measured by the percentage change in the MDS-UPDRS-III score, were evaluated through univariate and multivariate linear regression analysis. Results: A total of 233 patients were included with one-year follow-up after surgery [143 males (61.40%); 121 (51.90 %) right body onset; 112 (48.10%) left body onset; mean age at surgery, 55.31 ± 8.44 years; mean disease duration, 11.61 ± 3.87]. Multivariate linear regression analysis showed that the left side of motor symptoms onset did not predict motor outcome (β = 0.093, 95% CI = −1.967 to 11.497, p = 0.164). Conclusions: In this retrospective study, the body side of motor symptoms onset did not significantly influence the one-year motor outcome in a large cohort of PD patients treated with bilateral STN-DBS. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Limbic Serotonergic Plasticity Contributes to the Compensation of Apathy in Early Parkinson's Disease.
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Prange, Stéphane, Metereau, Elise, Maillet, Audrey, Klinger, Hélène, Schmitt, Emmanuelle, Lhommée, Eugénie, Bichon, Amélie, Lancelot, Sophie, Meoni, Sara, Broussolle, Emmanuel, Castrioto, Anna, Tremblay, Léon, Krack, Paul, and Thobois, Stéphane
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Background: De novo Parkinson's disease (PD) patients with apathy exhibit prominent limbic serotonergic dysfunction and microstructural disarray. Whether this distinctive lesion profile at diagnosis entails different prognosis remains unknown. Objectives: To investigate the progression of dopaminergic and serotonergic dysfunction and their relation to motor and nonmotor impairment in PD patients with or without apathy at diagnosis. Methods: Thirteen de novo apathetic and 13 nonapathetic PD patients were recruited in a longitudinal double‐tracer positron emission tomography cohort study. We quantified the progression of presynaptic dopaminergic and serotonergic pathology using [11C]PE2I for dopamine transporter and [11C]DASB for serotonin transporter at baseline and 3 to 5 years later, using linear mixed‐effect models and mediation analysis to compare the longitudinal evolution between groups for clinical impairment and region‐of‐interest‐based analysis. Results: After the initiation of dopamine replacement therapy, apathy, depression, and anxiety improved at follow‐up in patients with apathy at diagnosis (n = 10) to the level of patients without apathy (n = 11). Patients had similar progression of motor impairment, whereas mild impulsive behaviors developed in both groups. Striato‐pallidal and mesocorticolimbic presynaptic dopaminergic loss progressed similarly in both groups, as did serotonergic pathology in the putamen, caudate nucleus, and pallidum. Contrastingly, serotonergic innervation selectively increased in the ventral striatum and anterior cingulate cortex in apathetic patients, contributing to the reversal of apathy besides dopamine replacement therapy. Conclusion: Patients suffering from apathy at diagnosis exhibit compensatory changes in limbic serotonergic innervation within 5 years of diagnosis, with promising evidence that serotonergic plasticity contributes to the reversal of apathy. The relationship between serotonergic plasticity and dopaminergic treatments warrants further longitudinal investigations. © 2022 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]
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- 2022
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21. Pathological Gambling in Parkinsonʼs Disease Improves on Chronic Subthalamic Nucleus Stimulation
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Ardouin, Claire, Voon, Valerie, Worbe, Yulia, Abouazar, Nehman, Czernecki, Virginie, Hosseini, Hassan, Pelissolo, Antoine, Moro, Elena, Lhommée, Eugénie, Lang, Anthony E., Agid, Yves, Benabid, Alim-Louis, Pollak, Pierre, Mallet, Luc, and Krack, Paul
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- 2006
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22. Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs.
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Maillet, Audrey, Météreau, Elise, Tremblay, Léon, Favre, Emilie, Klinger, Hélène, Lhommée, Eugénie, Le Bars, Didier, Castrioto, Anna, Prange, Stéphane, Sgambato, Véronique, Broussolle, Emmanuel, Krack, Paul, and Thobois, Stéphane
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Background: Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far. Methods: To fill this gap, we conducted a cross‐sectional study combining clinical and dual‐tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([11C]‐N‐(3‐iodoprop‐2E‐enyl)‐2‐beta‐carbomethoxy‐3‐beta‐(4‐methylphenyl)‐nortropane) ([11C]PE2I) and serotonin ([11C]‐N,N‐dimethyl‐2‐(‐2‐amino‐4‐cyanophenylthio)‐benzylamine) ([11C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short‐disease duration drug‐naive de novo (n = 27, 0–2 years‐duration), suffering from apathy (n = 14) or not (n = 13); intermediate‐disease duration (n = 15, 4–7 years‐duration) and long‐disease duration, non‐demented (n = 15, 8–10 years‐duration) patients). Fifteen age‐matched healthy subjects were also enrolled. Results: The main findings are threefold: (1) both dopaminergic and serotonergic lesions worsen with the duration of Parkinson's disease, spreading from midbrain/subcortical to cortical regions; (2) the presence of apathy at PD onset is associated with more severe cortical and subcortical serotonergic and dopaminergic disruption, similar to the denervation pattern observed in intermediate‐disease duration patients; and (3) the severity of parkinsonian apathy, depression, and trait‐anxiety appears primarily related to serotonergic alteration within corticostriatal limbic areas. Conclusions: Altogether, these findings highlight the prominent role of serotonergic degeneration in the expression of several neuropsychiatric symptoms occurring after different durations of Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]
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- 2021
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23. Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease
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Cormier-Dequaire, Florence, Bekadar, Samir, Anheim, Mathieu, Lebbah, Saïd, Pelissolo, Antoine, Krack, Paul, Lacomblez, Lucette, Lhommée, Eugénie, Castrioto, Anna, Azulay, Jean-Philippe, Defebvre, Luc, Kreisler, Alexandre, Durif, Franck, Marques-Raquel, Ana, Brefel-Courbon, Christine, Grabli, David, Roze, Emmanuel, Llorca, Pierre-Michel, Ory-Magne, Fabienne, Benatru, Isabelle, Ansquer, Solène, Maltête, David, Tir, Fazia Mélissa, Krystkowiak, Pierre, Tranchant, Christine, Lagha-Boukbiza, Ouhaid, Lebrun-Vignes, Bénédicte, Mangone, Graziella, Vidailhet, Marie, Charbonnier-Beaupel, Fanny, Rascol, Olivier, Lesage, Suzanne, Brice, Alexis, Tezenas Du Montcel, Pierre, Corvol, Jean-Christophe, Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Neurologie [Hôpitaux Universitaires de Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANTE-INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Unité de Désordres du Mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Unité Médicale des Troubles du Mouvement, CHU Grenoble-Clinique de Neurologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Pharmacologie, PRES Université Lille Nord de France, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de pharmacologie clinique, CHU Toulouse [Toulouse], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Amiens-Picardie, Service de neurologie [Amiens], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse]
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Adult ,Male ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Receptors, Opioid, mu ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Parkinson Disease ,Middle Aged ,Disruptive, Impulse Control, and Conduct Disorders ,Levodopa ,Risk Factors ,Dopamine Agonists ,Gambling ,Humans ,Female ,ComputingMilieux_MISCELLANEOUS ,Aged - Abstract
Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD.We performed a multicenter case-control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of300 mg levodopa-equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset.The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P 0.001) and had a higher family history of pathological gambling (12% vs 5%, P = 0.03). No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32-0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40-base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24-2.68; P = 0.0021; Bonferroni adjusted P = 0.105).Our results are suggestive of a novel association of the opioid receptor gene OPRM1 with impulse control disorders and related behaviors in PD and confirm a previous association with DAT1. Although replication in independent studies is needed, our results bring potential new insights to the understanding of molecular mechanisms of impulse control disorders. © 2018 International Parkinson and Movement Disorder Society.
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- 2018
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24. The Neuropsychiatric Fluctuations Scale for Parkinson's Disease: A Pilot Study
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Schmitt, Emmanuelle, Krack, Paul, Castrioto, Anna, Klinger, Helene, Bichon, Amelie, Lhommée, Eugénie, Pelissier, Pierre, Fraix, Valerie, Thobois, Stephane, Moro, Elena, and Martinez‐Martin, Pablo
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Research Articles - Abstract
BACKGROUND: Non‐motor fluctuations represent a main source of disability in Parkinson's disease (PD). Among them, neuropsychiatric fluctuations are the most frequent and are often under‐recognized by patients and physicians, partly because specific tools for assessment of neuropsychiatric fluctuations are lacking. OBJECTIVE: To develop a scale for detecting and evaluating the presence and the severity of neuropsychological symptoms during the ON and OFF phases of non‐motor fluctuations. METHODS: Neuropsychiatric symptoms reported by PD patients in the OFF‐ and the ON‐medication conditions were collected using different neuropsychiatric scales (BDI‐II, BAI, Young, VAS, etc.). Subsequently, tree phases of a pilot study was performed for cognitive pretesting, identification of ambiguous or redundant items (item reduction), and to obtain preliminary data of acceptability of the new scale. In all the three phases, the scale was applied in both the OFF and ON condition during a levodopa challenge. RESULTS: Twenty items were selected for the final version of the neuropsychiatric fluctuation scale (NFS): ten items measured the ON neuropsychological symptoms and ten items the OFF neuropsychological manifestations. Each item rated from 0‐3, providing respective subscores from 0 to 30. CONCLUSIONS: Once validated, our NFS can be used to identify and quantify neuropsychiatric fluctuations during motor fluctuations. The main novelty is that it could be used in acute settings. As such, the NFS can assess the neuropsychiatric state of the patient at the time of examination. The next step will be to validate the NFS to be used in current practice.
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- 2018
25. Predictors of Long-Term Outcome of Subthalamic Stimulation in Parkinson Disease.
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Cavallieri, Francesco, Fraix, Valérie, Bove, Francesco, Mulas, Delia, Tondelli, Manuela, Castrioto, Anna, Krack, Paul, Meoni, Sara, Schmitt, Emmanuelle, Lhommée, Eugénie, Bichon, Amélie, Pélissier, Pierre, Chevrier, Eric, Kistner, Andrea, Seigneuret, Eric, Chabardès, Stephan, and Moro, Elena
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PARKINSON'S disease ,DEEP brain stimulation ,SUBTHALAMIC nucleus ,FRONTAL lobe ,MOVEMENT disorders - Abstract
Objective: This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS).Methods: All consecutive PD patients who underwent bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short-term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long-term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores compared to the baseline off-medication scores. As a secondary objective, potential predictors of short-term motor outcome after STN-DBS were assessed by performing univariate and multivariate linear regression analyses.Results: In the long-term analyses (mean follow-up = 8.4 ± 6.26 years, median = 10 years, range = 1-17 years), 138 patients were included. Preoperative higher frontal score and off-medication MDS-UPDRS part III scores predicted a better long-term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1-year follow-up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off-medication MDS-UPDRS part III scores predicted the short-term motor outcome.Interpretation: Frontal lobe dysfunction, disease severity in the off-medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long-term motor STN-DBS effects. ANN NEUROL 2021;89:587-597. [ABSTRACT FROM AUTHOR]- Published
- 2021
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26. Personality, dopamine, and Parkinson's disease: Insights from subthalamic stimulation
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Lhommée, Eugénie, Boyer, François, Wack, Maxime, Pélissier, Pierre, Klinger, Hélène, Schmitt, Emmanuelle, Bichon, Amélie, Fraix, Valérie, Chabardès, Stéphan, Mertens, Patrick, Castrioto, Anna, Kistner, Andrea, Broussolle, Emmanuel, Thobois, Stéphane, and Krack, Paul
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ddc:616.8 - Published
- 2017
27. Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease.
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Prange, Stéphane, Metereau, Elise, Maillet, Audrey, Lhommée, Eugénie, Klinger, Hélène, Pelissier, Pierre, Ibarrola, Danielle, Heckemann, Rolf A., Castrioto, Anna, Tremblay, Léon, Sgambato, Véronique, Broussolle, Emmanuel, Krack, Paul, and Thobois, Stéphane
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Background: Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.Methods: We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems.Results: De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long-range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right-sided limbic subnetwork involving limbic and frontal association tracts.Conclusions: Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]- Published
- 2019
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28. Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease.
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Martínez‐Fernández, Raul, Kibleur, Astrid, Chabardès, Stéphan, Fraix, Valérie, Castrioto, Anna, Lhommée, Eugénie, Moro, Elena, Lescoules, Lucas, Pelissier, Pierre, David, Olivier, and Krack, Paul
- Abstract
Parkinson's disease impairs the decoding of emotional stimuli reflecting alterations of the limbic cortico‐subcortical network. The objective of this study was to assess and compare the behavioral and electrophysiological effects of both levodopa and subthalamic stimulation on emotional processing in Parkinson's disease. Operated patients (n =16) and matched healthy subjects performed an emotional Stroop task, in which the emotion expressed by a face must be recognized while ignoring an emotional distractive word and that includes a neutral control sub‐task. Patients were tested in the four possible treatment conditions (off stim/off med; on stim/off med; off stim/on med; and on stim/on med). High‐resolution electroencephalography was recorded while performing the task. Patients made significantly more mistakes in facial emotion recognition than healthy subjects (p < .005). Untreated patients performed worse in the emotional trials than in the control sub‐task (p < .05). Fearful faces induced significantly slower reaction times than happy faces in patients (p = .0002), but not in the healthy subjects. The emotional Stroop effect with levodopa was significantly higher than with subthalamic stimulation when fearful faces were assessed (p = .0243). Conversely, treatments did not modulate the Stroop effect of the control sub‐task. EEG demonstrated that, compared with the untreated state, levodopa but not subthalamic stimulation significantly increases the amplitude of the event‐related potential N170 (p = .002 vs. p = .1, respectively), an electrophysiological biomarker of early aspects of facial processing. The activity of the N170 cortical sources within the right fusiform gyrus was increased by levodopa (p < .05) but not by stimulation. While levodopa normalizes the recognition of emotional facial expression and early EEG markers of emotional processing, subthalamic stimulation does not. Thus, operated patients require dopaminergic medication in addition to stimulation to treat emotional symptoms of Parkinson's disease. [ABSTRACT FROM AUTHOR]
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- 2018
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29. Subthalamic stimulation and neuropsychiatric symptoms in Parkinson's disease: results from a long-term follow-up cohort study.
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Abbes, Marie, Lhommée, Eugénie, Thobois, Stéphane, Klinger, Hélène, Schmitt, Emmanuelle, Bichon, Amélie, Castrioto, Anna, Jing Xie, Fraix, Valérie, Kistner, Andrea, Pélissier, Pierre, Seigneuret, Éric, Chabardès, Stéphan, Mertens, Patrick, Broussolle, Emmanuel, Moro, Elena, Krack, Paul, and Xie, Jing
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PARKINSON'S disease ,NEUROBEHAVIORAL disorders ,BRAIN stimulation ,DOPAMINERGIC neurons ,IMPULSE control disorders - Abstract
Background: Reports on behavioural outcomes after subthalamic nucleus deep brain stimulation in Parkinson's disease are controversial and limited to short-term data. Long-term observation in a large cohort allows a better counselling and management.Methods: To determine whether a long-term treatment with subthalamic stimulation induces or reduces impulse control behaviours, neuropsychiatric fluctuations and apathy, 69 patients treated with subthalamic stimulation are prospectively and retrospectively assessed using Ardouin Scale of Behavior in Parkinson's Disease before and after 3-10 years of stimulation.Results: At a mean follow-up of 6 years, all impulse control disorders and dopaminergic addiction were significantly decreased, apart from eating behaviour and hypersexuality. Neuropsychiatric fluctuations also significantly improved (ON euphoria: 38% of the patients before surgery and 1% after surgery, P<0.01; OFF dysphoria: 39% of the patients before surgery and 10% after surgery, P<0.01). However, apathy increased (25% of the patients after surgery and 3% before, P<0.01). With the retrospective analysis, several transient episodes of depression, apathy, anxiety and impulse control disorders occurred.Conclusions: Bilateral subthalamic nucleus stimulation was overall very effective in improving impulse control disorders and neuropsychiatric fluctuations in parkinsonian patients in the long term despite a counteracting frequent apathy. Transient episodes of impulse control disorders still occurred within the follow-up. These findings recommend a close follow-up in parkinsonian patients presenting with neuropsychiatric symptoms before deep brain stimulation surgery.Clinical Trial Registration: NCT01705418;Post-results. [ABSTRACT FROM AUTHOR]- Published
- 2018
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30. Dysexecutive syndrome in Parkinson’s disease: the GREFEX study.
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Roussel, Martine, Lhommée, Eugénie, Narme, Pauline, Czernecki, Virginie, Gall, Didier Le, Krystkowiak, Pierre, Diouf, Momar, and Godefroy, Olivier
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SYNDROMES , *PARKINSON'S disease , *COGNITION , *DIAGNOSIS , *HYPERACTIVITY - Abstract
The objectives of this study were to characterize the frequencies and profiles of behavioral and cognitive dysexecutive syndromes in PD (based on validated battery and diagnostic criteria) and to develop a shortened diagnostic battery. Eighty-eight non-demented patients with a diagnosis of PD were examined with an executive validated battery. Using a validated framework, the patients’ test results were interpreted with respect to normative data from 780 controls. A dysexecutive syndrome was observed in 80.6% of the patients [95% confidence interval: 71.1–90.1]. The dysexecutive profile was characterized by prominent impairments in deduction, flexibility, inhibition and initiation in the cognitive domain, and by global hypoactivity with apathy and hyperactivity in the behavioral domain. This finding implies that patients with PD should be assessed with cognitive tests and a validated inventory for behavioral dysexecutive syndromes. A shortened battery (based on three cognitive tests and three behavioral domains) provided high diagnostic accuracy. [ABSTRACT FROM PUBLISHER]
- Published
- 2017
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31. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease.
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Maillet, Audrey, Krack, Paul, Lhommée, Eugénie, Météreau, Elise, Klinger, Hélène, Favre, Emilie, Le Bars, Didier, Schmitt, Emmanuelle, Bichon, Amélie, Pelissier, Pierre, Fraix, Valérie, Castrioto, Anna, Sgambato-Faure, Véronique, Broussolle, Emmanuel, Tremblay, Léon, and Thobois, Stéphane
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SEROTONINERGIC mechanisms ,PARKINSON'S disease ,ANXIETY ,DOPAMINERGIC neurons ,POSITRON emission tomography ,APATHY ,MENTAL depression ,PSYCHOLOGICAL tests ,SEROTONIN ,STATE-Trait Anxiety Inventory ,DISEASE complications - Abstract
SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(11)C-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane (PE2I)] (n = 29) and serotonergic [(11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine (DASB)] (n = 27) presynaptic transporter radioligands. Apathetic parkinsonian patients presented higher depression (P = 0.0004) and anxiety (P = 0.004) scores - as assessed using the Beck Depression Inventory and the part B of the State-Trait Anxiety Inventory, respectively - compared to the non-apathetic ones - who were not different from the age-matched healthy subjects (n = 15). Relative to the controls, the non-apathetic parkinsonian patients mainly showed dopaminergic denervation (n = 14) within the right caudate nucleus, bilateral putamen, thalamus and pallidum, while serotonergic innervation (n = 15) was fairly preserved. Apathetic parkinsonian patients exhibited, compared to controls, combined and widespread dopaminergic (n = 15) and serotonergic (n = 12) degeneration within the bilateral caudate nuclei, putamen, ventral striatum, pallidum and thalamus, but also a specific bilateral dopaminergic disruption within the substantia nigra-ventral tegmental area complex, as well as a specific serotonergic alteration within the insula, the orbitofrontal and the subgenual anterior cingulate cortices. When comparing the two parkinsonian groups, the apathetic patients mainly displayed greater serotonergic alteration in the ventral striatum, the dorsal and the subgenual parts of the anterior cingulate cortices, bilaterally, as well as in the right-sided caudate nucleus and the right-sided orbitofrontal cortex. Regression analyses also revealed that the severity of apathy was moreover mainly related to specific serotonergic lesions within the right-sided anterior caudate nucleus and the orbitofrontal cortex, while the degree of both depression and anxiety was primarily linked to serotonergic disruption within the bilateral subgenual parts and/or the right dorsal part of the anterior cingulate cortex, without prominent role of the dopaminergic degeneration in the pathogenesis of these three non-motor signs. Altogether, these findings highlight a prominent role of the serotonergic degeneration in the expression of the neuropsychiatric symptoms occurring at the onset of Parkinson's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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32. Dysexecutive syndrome in Parkinson's disease: the GREFEX study.
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Roussel, Martine, Lhommée, Eugénie, Narme, Pauline, Czernecki, Virginie, Gall, Didier Le, Krystkowiak, Pierre, Diouf, Momar, Godefroy, Olivier, and GREFEX study group
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COGNITION disorders diagnosis ,DRUG therapy for Parkinson's disease ,PARKINSON'S disease diagnosis ,ANTIPARASITIC agents ,COGNITION disorders ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,PARKINSON'S disease ,PSYCHOLOGICAL tests ,RESEARCH ,EVALUATION research ,SEVERITY of illness index ,EXECUTIVE function ,DISEASE complications ,THERAPEUTICS ,PSYCHOLOGY - Abstract
The objectives of this study were to characterize the frequencies and profiles of behavioral and cognitive dysexecutive syndromes in PD (based on validated battery and diagnostic criteria) and to develop a shortened diagnostic battery. Eighty-eight non-demented patients with a diagnosis of PD were examined with an executive validated battery. Using a validated framework, the patients' test results were interpreted with respect to normative data from 780 controls. A dysexecutive syndrome was observed in 80.6% of the patients [95% confidence interval: 71.1-90.1]. The dysexecutive profile was characterized by prominent impairments in deduction, flexibility, inhibition and initiation in the cognitive domain, and by global hypoactivity with apathy and hyperactivity in the behavioral domain. This finding implies that patients with PD should be assessed with cognitive tests and a validated inventory for behavioral dysexecutive syndromes. A shortened battery (based on three cognitive tests and three behavioral domains) provided high diagnostic accuracy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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33. Profile of Neuropsychiatric Symptoms in Parkinson's Disease: Surgical Candidates Compared to Controls.
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Lamberti, Valérie M. J., Pereira, Bruno, Lhommée, Eugénie, Bichon, Amélie, Schmitt, Emmanuelle, Pelissier, Pierre, Kistner, Andrea, Fraix, Valérie, Castrioto, Anna, Esselink, Rianne A. J., Durif, Frank, and Krack, Paul
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NEUROBEHAVIORAL disorders ,SUBTHALAMIC nucleus ,DEEP brain stimulation ,DOPAMINE antagonists ,THERAPEUTICS - Abstract
Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson's disease (PD) and motor complications of dopaminergic treatment. Whether STN-DBS should be considered when PD patients experience neuropsychiatric symptoms is controversial. Lack of systematic behavioral evaluation at baseline hampers the understanding of postoperative neuropsychiatric outcomes. Objective: This study compares the behavioral profile of a surgical population to that in general PD. Methods: Single center data from 234PDsurgical candidates were compared to data from 260 non-dementedPDpatients consulting in 13 PD expert centers at different stages of disease. The latter were considered representative of the general PD population. Neuropsychiatric symptoms were assessed using the Ardouin Scale of Behavior in PD, a guided interview quantifying changes in severity of 21 neuropsychiatric symptoms, classified into psychic non-motor fluctuations, hypo- and hyperdopaminergic behaviors. Multivariate analyses were performed to study differences in behavioral items between the two groups. Results: Surgical candidates were younger, had longer disease duration and used significantly higher doses of dopaminergic drugs. After adjustment for covariates, dopaminergic addiction (OR 10.83; p = 0.002), nocturnal hyperactivity (OR 1.87; p = 0.04), excessive hobbyism(OR2.37; p = 0.008), "excess in motivation"(OR4.02; p < 0.001), psychicOFF(2.87; p < 0.001) and psychic ON (2.10; p = 0.001) fluctuations were more frequent in the surgical candidates. Depressed mood prevailed in the general PD population (OR 0.53; p = 0.045). Conclusion: Behavioral complications of dopaminergic treatment are frequent in PD patients candidates for STN-DBS. They cannot be considered as contraindications for STN-DBS but must be taken into account in postoperative management. [ABSTRACT FROM AUTHOR]
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- 2016
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34. Apathy and Impulse Control Disorders: Yin & Yang of Dopamine Dependent Behaviors.
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Sierra, María, Carnicella, Sébastien, Strafella, Antonio P., Bichon, Amélie, Lhommée, Eugénie, Castrioto, Anna, Chabardes, Stephan, Thobois, Stéphane, and Krack, Paul
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APATHY ,IMPULSE control disorders ,YIN-yang ,DOPAMINE ,PARKINSON'S disease - Abstract
Neuropsychiatric symptoms are common non-motor symptoms in Parkinson's disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states. Apathy belongs to the spectrum of hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy is a key symptom of PD which worsens with disease progression. Animal models, imaging and pharmacological studies concur in pointing out dopaminergic denervation in the aetiology of parkinsonian apathy with a cardinal role of decreased tonic D2/D3 receptor stimulation. ICDs are part of the hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine dysregulation syndrome (DDS), which are all related to non-physiological dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical observations in drug addiction and PD as well as data from studies in dopamine depleted rodents provide hints allowing to argue that both pulsatile D1 and D2 receptor stimulation and the severity of dopaminergic denervation are risk factors to develop punding behavior and DDS. Imaging studies have shown that the brain structures involved in drug addiction are also involved in hyperdopaminergic behaviours with increase of bottom-up appetitive drive and decrease in prefrontal top down behavioural control. [ABSTRACT FROM AUTHOR]
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- 2015
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35. Dopaminergic modulation of emotional conflict in Parkinson's disease.
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Fleury, Vanessa, Cousin, Emilie, Czernecki, Virginie, Schmitt, Emmanuelle, Lhommée, Eugénie, Poncet, Antoine, Fraix, Valérie, Troprès, Irène, Pollak, Pierre, Krainik, Alexandre, and Krack, Paul
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PARKINSON'S disease ,DRUG administration ,DOPA ,DOPAMINERGIC mechanisms ,NEUROPSYCHOLOGICAL tests ,VISUAL analog scale ,PSYCHOLOGY - Abstract
Neuropsychiatric fluctuations in Parkinson's disease (PD) are frequent and disabling. One way to investigate them is to assess the ability to inhibit distractive emotional information by a modified emotional Stroop (ES) task. We compared non-depressed, non-demented PD patients with healthy controls. During an acute levodopa challenge, patients performed a modified ES task during functional MRI and a neuropsychological assessment including Visual Analog Mood (VAMS) and Apathy scales. Ten patients and 12 controls completed the study. The VAMS scores were significantly improved by the acute intake of levodopa (p = 0.02), as was the apathy score (p = 0.03). Negative ES task (i.e. fearful facial expressions with the words "happy" or "fear" written across them), induced a lengthening of the mean reaction time during the incongruent trials compared with the congruent trials in controls (relative difference = 2.7%, p < 0.001) and in ON patients (relative difference = 5.9%, p < 0.001), but not in OFF patients (relative difference = 1.7%, p = 0.28). Controls and ON patients displayed greater activation than OFF patients within the right pregenual anterior cingulate cortex (pACC), an area specifically involved in emotional conflict resolution (p < 0.001 and p < 0.008 respectively, k > 5 uncorrected). No difference in the activation of the pACC was found between controls and ON patients, suggesting a normalization of the activation following levodopa administration. These results suggest that emotional conflict processes could be dopamine-dependent. Pregenual ACC hypoactivation could be directly due to the degeneration of dopaminergic mesocorticolimbic pathway. Our results propose that neuropsychiatric fluctuations in PD patients could be partially explained by pACC hypoactivation and that adjustments of dopaminergic medication might be helpful for their treatment. [ABSTRACT FROM AUTHOR]
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- 2014
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36. Mechanisms of body weight fluctuations in Parkinson's disease.
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Kistner, Andrea, Lhommée, Eugénie, and Krack, Paul
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BODY weight ,WEIGHT gain ,WEIGHT loss ,BRAIN disease research - Abstract
Typical bodyweight changes are known to occur in Parkinson's disease (PD).Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand, an increasing number of patients show weight gain under dopamine replacement therapy or after surgery. These weight changes are multifactorial and involve changes in energy expenditure, perturbation of homeostatic control, and eating behavior modulated by dopaminergic treatment. Comprehension of the different mechanisms contributing to body weight is a prerequisite for the management of body weight and nutritional state of an individual PD patient. This review summarizes the present knowledge and highlights the necessity of evaluation of body weight and related factors, as eating behavior, energy intake, and expenditure in PD. [ABSTRACT FROM AUTHOR]
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- 2014
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37. Is Motor Side Onset of Parkinson's Disease a Risk Factor for Developing Impulsive-Compulsive Behavior? A Cross-Sectional Study.
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Phillipps, Clélie, Longato, Nadine, Béreau, Matthieu, Carrière, Nicolas, Lagha‐Boukbiza, Ouhaid, Mengin, Amaury C., Monga, Ben, Defebvre, Luc, Ory‐Magne, Fabienne, Castrioto, Anna, Lhommée, Eugénie, Rascol, Olivier, Krack, Paul, Tranchant, Christine, Corvol, Jean‐Christophe, Anheim, Mathieu, Lagha-Boukbiza, Ouhaid, Ory-Magne, Fabienne, and Corvol, Jean-Christophe
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- 2020
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38. Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial
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Lhommée, Eugénie, Wojtecki, Lars, Czernecki, Virginie, Witt, Karsten, Maier, Franziska, Tonder, Lisa, Timmermann, Lars, Hälbig, Thomas D, Pineau, Fanny, Durif, Franck, Witjas, Tatiana, Pinsker, Marcus, Mehdorn, Maximilian, Sixel-Döring, Friederike, Kupsch, Andreas, Krüger, Rejko, Elben, Saskia, Chabardès, Stephan, Thobois, Stéphane, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Regis, Jean-Marie, Maltête, David, Sauvaget, Anne, Rau, Jörn, Schnitzler, Alfons, Schüpbach, Michael, Schade-Brittinger, Carmen, Deuschl, Gunther, Houeto, Jean-Luc, and Krack, Paul
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610 Medicine & health ,3. Good health - Abstract
BACKGROUND Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. METHODS We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. FINDINGS Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p
39. Dopamine and the biology of creativity: lessons from Parkinson's disease.
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Lhommée E, Batir A, Quesada JL, Ardouin C, Fraix V, Seigneuret E, Chabardès S, Benabid AL, Pollak P, and Krack P
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Background: Parkinson's disease (PD) is characterized by reduced flexibility, conceptualization, and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists., Methods: Eleven consecutive creative PD patients were selected from candidates for subthalamic nucleus deep brain stimulation (STN DBS) surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III), cognition (Frontal score, Mattis scale), and behavior (Ardouin scale) were assessed before surgery and 1 year after., Results: Before surgery, whereas cognitive and motor assessments were similar between groups, dopamine agonist (but not levodopa) dosages were higher in creative patients (p = 0.01). The Ardouin scale revealed also a specific psycho-behavioral profile of creative patients which had higher scores for mania (p < 0.001), hobbyism (p = 0.001), nocturnal hyperactivity (p = 0.041), appetitive functioning (p = 0.003), and ON euphoria (p = 0.007) and lower scores for apathy and OFF dysphoria (p = 0.04 for each). Post-operative motor, cognitive, and behavioral scores as dopaminergic treatment dosages were equivalent between groups. Motor improvement allowed for a 68.6% decrease in dopaminergic treatment. Only 1 of the 11 patients remained creative after surgery. Reduction of dopamine agonist was significantly correlated to the decrease in creativity in the whole population of study (Spearman correlation coefficient ρ = 0.47 with confidence index of 95% = 0.16; 0.70, p = 0.0053)., Conclusion: Creativity in PD is linked to dopamine agonist therapy, and tends to disappear after STN DBS in parallel to reduction of dopamine agonists, which are relatively selective for the mesolimbic D3 dopamine receptors.
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- 2014
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