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Understanding dopaminergic dose reduction following STN-DBS: mediation analysis

Title: Understanding dopaminergic dose reduction following STN-DBS: mediation analysis
Authors: Lanore, Aymeric; Houot, Marion; Basset, Aymeric; Bendetowicz, David; Menon, Poornima; Bardinet, Eric; Fernandez Vidal, Sara; Cornillault, Jordan; Karachi, Carine; Navarro, Soledad; Ihle, Jonas; Eusebio, Alexandre; Giordana, Caroline; Rouaud, Tiphaine; Drapier, Sophie; Guehl, Dominique; Marques, Ana; Hubsch, Cécile; Jarraya, Béchir; Benatru, Isabelle; Thobois, Stephane; Hopes, Lucie; Maltete, David; Rascol, Olivier; Tir, Melissa; Moreau, Caroline; Tranchant, Christine; Rolland, Anne-Sophie; Devos, David; Corvol, Jean Christophe; Grabli, David; Hainque, Elodie
Contributors: Centre d'investigation clinique Neurosciences CHU Pitié Salpêtrière (CIC Neurosciences); 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); Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Plateforme de neuroimagerie CENIR = Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research ICM Paris (CENIR); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Assistance Publique - Hôpitaux de Marseille (APHM); Centre Hospitalier Universitaire de Nice (CHU Nice); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux); Institut des Maladies Neurodégénératives Bordeaux (IMN); Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS); CHU Clermont-Ferrand; Neuro-Psycho Pharmacologie des Systèmes Dopaminergiques sous-corticaux (NPsy-Sydo); CHU Clermont-Ferrand-Université Clermont Auvergne 2017-2020 (UCA 2017-2020 ); Fondation Ophtalmologique Adolphe de Rothschild Paris; Hôpital Foch Suresnes; Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ); Hôpital neurologique et neurochirurgical Pierre Wertheimer CHU - HCL; Hospices Civils de Lyon (HCL); Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy); CHU Rouen; Normandie Université (NU); Université de Toulouse (EPE UT); Communauté d'universités et établissements de Toulouse (Comue de Toulouse); CHU Amiens-Picardie; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Hôpital de Hautepierre Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS); Lille Neurosciences & Cognition - U 1172 (LilNCog); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); PREDISTIM study group: Caroline Moreau, Luc Defebvre, Nicolas Carriere, Guillaume Grolez, Gillaume Baille, Jean-Pierre Pruvo Kreisler, Renaud Lopes Leclerc, Romain Viard, Gregory Kuchcinski, Julien Dumont, Kathy Dujardin, M Delliaux, M Brion, Gustavo Touzet, Nicolas Reyns, Arnaud Delval, Valerie Santraine, Marie Pleuvret, Nolwen Dautrevaux, Victor Laugeais, Morgane Coeffet, Thavarak Ouk, Camille Potey, Celine Leclercq, Elise GersParis Gers, Jean-Christophe Corvol, Elodie Hainque Marie-Vidailhet, Marie-Laure Welter, Lucette Lacomblez, David Grabli, Emmanuel Roze, Yulia Worbe, Cécile Delorme, Hana You, Jonas Ihle, Raquel Guimeraes-Costa, Florence Cormier-Dequaire, Aurélie Méneret, Andréas Hartmann, Louise-Laure Mariani, Stéphane Lehericy, Virginie Czernecki, Fanny Pineau, Frédérique Bozon, Camille Huiban, Eve Benchetrit, Carine Karachi, Soledad Navarro, Philippe Cornu, Arlette Welaratne, Carole Dongmo-Kenfack, Lise Mantisi, Nathalie Jarry, Sophie Aix, Carine Lefort Nantes, Tiphaine Rouaud, Philippe Damier, Pascal Derkinderen, Anne-Gaelle Corbille, Elisabeth Calvier-Auffray, Madame Laetitia Rocher, Madame Anne-Laure Deruet, Raoul Sylvie, Roualdes Vincent, Le DilySéverine Clermont-Ferrand, Ana Marques, Berangere Debilly, Franck Durif, Philippe Derost, Charlotte Beal, Carine Chassain, Laure Delaby, Tiphaine Vidal, Jean Jeacques Lemaire, Isabelle Rieu, Elodie Durand Marseille, Alexandre Eusebio, Jean-Philippe Azulay, Tatiana Witjas, Frédérique Fluchère, Stephan Grimaldi, Nadine Girard, Eve Benchetrit, Marie Delfini, Romain Carron, Jean Regis, Giorgio Spatola, Camille Magnaudet Poitiers, Ansquer Solène, Benatru Isabelle, Colin Olivier, J L Houeto, Guillevin Remy, Fradet Anne, Anziza Manssouri, Blondeau Sophie, Richard Philippe, Cam Philippe, Page Philippe, Bataille Benoit, Rabois Emilie, Guillemain Annie Rennes, Drapier Sophie, Frédérique Leh, Alexandre Bonnet, Marc Vérin, Jean-Christophe Ferré, Jean François Houvenaghel, Claire Haegelen, Francoise Kestens, Solennory Bordeaux, Pierre Burbaud, Nathalie Damon-Perriere, Wassilios Meissner, Francois Tison, Stéphanie Bannier, Elsa Krim, Dominique Guehl, Sandrine Molinier-Blossier, Morgan Ollivier, Marion Lacoste, Nicolas Auzou, Marie Bonnet, Emmanuel Cuny, Julien Engelhardt, Olivier Branchard, Clotilde Huet, Julie Blanchard Toulouse, Rascol Olivier, Christine Brefel Courbon, Fabienne Ory Magne, Marion Simonetta Moreau, Christophe Arbus, Fabrice Bonneville-Et, Jean Albert Lotterie, Marion Sarrail, Patrick Chaynes, François Caire, Estelle Harroch Rouen, David Maltete, Romain Lefaucheur, Damien Fetter, Nicolas Magne, Sandrine Bioux, Maud Loubeyre, Evangéline Bliaux, Dorothée Pouliquen, Stéphane Derrey, Linda Vernon, Frédéric Ziegler Strasbourg, Mathieu Anheim, Ouhaid Lagha-Boukbiza, Christine Tranchant, Odile Gebus, Solveig Montaut, Stéphane Kremer, Nadine Longato, Clélie Phillips, Jimmy Voirin, Marie des Neiges Santin, Dominique Chaussemy, Amaury Mengin Nice, Caroline Girodana, Claire Marsé, Lydiane Mondot, Bruno Giordana, Robin Kardous, Bernadette Bailet, Héloise Joly, Denys Fontaine, Aurélie Leplus, Amélie Faustini, Vanessa Ferrier Amiens, Pierre Krystkowiak, Mélissa Tir, Jean-Marc Constans, Sandrine Wannepain, Audrey Seling, Michel Lefranc, Béatrice Schuler Lyon, Stephane Thobois, Teodor Danaila, Chloe Laurencin, Yves Berthezene, Roxana Ameli, Helene Klinger, Gustavo Polo, Patrick Mertens, Elise Metereau Nancy, Lucie Hopes, Solène Frismand, Emmanuelle Schmitt, Mylène Meyer, Céline Dillier, Sophie Colnat, Jean-Philippe Brandel, Cécile Hubsch, Patte Karsenti, Marie Lebouteux, Marc Ziegler, Christine Delmaire, Julien Savatowky, Juliette Vrillac, Claire Nakache, Vincent D'Hardemare, Lhaouas Belamri, Frédérique Bourdain, Vadim Afanassiev, Philippe Graveleau, Cécilia Bonnet, Valérie Mesnage, Jarbas Correa Lino Junior, Camille Decrocq, Anne Boulin, Elodie Dupuy, Inès Barre, Bérénice Gardel, Béchir Jarraya, Delphine Lopez, Christophe Fruit, Catherine Ziz, David Gay, Robin Bonicel, Fouzia El Mountassir, Clara Fischer, Jean-François Mangin, Marie Chupin, Yann Cointepas, Bertrand Accart, Patrick Gelé, Florine Fievet, Matthieu Chabel, Virginie Derenaucourt, Loïc Facon, Yanick Tchantchou Njosse, Dominique Deplanque, Alain Duhamel, Lynda Djemmane, Florence Duflot, Hajar Chouiki
Source: ISSN: 2632-6140 ; BMJ Neurology Open ; https://u-picardie.hal.science/hal-05472217 ; BMJ Neurology Open, 2026, 8 (1), pp.e001427. ⟨10.1136/bmjno-2025-001427⟩.
Publisher Information: CCSD
Publication Year: 2026
Collection: Université Toulouse III - Paul Sabatier: HAL-UPS
Subject Terms: NEUROSURGERY; PARKINSON'S DISEASE; PHARMACOLOGY; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Description: International audience ; Background Levodopa equivalent dopaminergic dose (LEDD) reduction after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease varies widely. Identifying predictors may guide patient selection and programming. Our objectives were to identify predictors of LEDD reduction and to test whether motor improvement mediates this association. Methods Data from 144 patients treated by STN-DBS were analysed. Predictors of LEDD reduction were selected using the Boruta algorithm, a machine-learning method comparing variable importance to randomised features and then tested in a structural equation model for direct and motor-mediated effects. Results Mean LEDD reduction was 41.7% (±38.2%) and motor improvement was 48.6% (±26.7%) at 1 year. Among the four predictors identified by Boruta, lower baseline LEDD (β=0.39, p=0.001), greater axial impairment (β=−0.25, p=0.003) and higher total volume of tissue activated (β=−0.17, p=0.031) were directly associated with lower LEDD reduction, independent of motor improvement. Sensorimotor STN overlap was not directly linked to LEDD reduction but was positively associated with motor improvement (β=0.34, p=0.001), which showed a trend-level effect on LEDD reduction (β=0.16, p=0.065). The total effect of sensorimotor STN overlap on LEDD reduction was not significant. Discussion Dopaminergic dose reduction after STN-DBS is constrained by preoperative axial symptoms and stimulation spread, independently of motor improvement, while sensorimotor STN overlap improves motor symptoms but not dose reduction. Integrating motor phenotype with anatomical guidance may enhance medication management post DBS.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41561678; PUBMED: 41561678; PUBMEDCENTRAL: PMC12815016
DOI: 10.1136/bmjno-2025-001427
Availability: https://u-picardie.hal.science/hal-05472217; https://u-picardie.hal.science/hal-05472217v1/document; https://u-picardie.hal.science/hal-05472217v1/file/e001427.full.pdf; https://doi.org/10.1136/bmjno-2025-001427
Rights: https://creativecommons.org/licenses/by-nc/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.7380BCA5
Database: BASE