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Understanding dopaminergic dose reduction following STN-DBS: mediation analysis

Title: Understanding dopaminergic dose reduction following STN-DBS: mediation analysis
Authors: Lynda Djemmane; Alain Duhamel; Emmanuelle Schmitt; Stéphane Kremer; Dominique Deplanque; Marion Houot; Eve Benchetrit; Eric Bardinet; Marie-Laure Welter; Romain Lefaucheur; Christine Tranchant; Elodie Hainque; Aurélie Meneret; Emmanuel Roze; Marie Chupin; Christine Delmaire; Stéphane Lehéricy; Jean-Christophe Ferré; Francois Caire; Cécile Delorme; Virginie Czernecki; Delphine Lopez; Caroline Moreau; Michel Lefranc; Nadine Girard; Sandrine Bioux; Evangeline Bliaux; Maud Loubeyre; Dorothée Pouliquen; Ana Marques; Jean-Christophe Corvol; Cecilia Bonnet; Gregory Kuchcinski; Yulia Worbe; Philippe Cornu; Nicolas Reyns; Romain Carron; Sara Fernandez Vidal; Pascal Derkinderen; Jean Régis; Mathieu Anheim; Lucette Lacomblez; Yves Berthezene; Stephan Grimaldi; Tatiana Witjas; Frederique Fluchere; Jean-Philippe Azulay; Alexandre Eusebio; Olivier Rascol; Denys Fontaine; Nicolas Magné; Franck Durif; Philippe Damier; François Tison; Jean Christophe Corvol; Hélène Klinger; Patrick Mertens; Stéphane Thobois; Philippe Derost; Cécile Hubsch; David Devos; David Maltête; Thavarak Ouk; Pierre Krystkowiak; Luc Defebvre; Kathy Dujardin; Florence Cormier-Dequaire; Sophie Drapier; Marc Vérin; Arnaud Delval; Jean-François Mangin; Carine Karachi; Jean-Philippe Brandel; Stéphane Derrey; Stephanie Bannier; Isabelle Rieu; David Grabli; Nicolas Carriere; WASSILIOS MEISSNER; Bertrand Accart; Tiphaine Rouaud; Philippe Graveleau; Roxana Ameli; Solène Frismand; Sandrine Wannepain; Isabelle Benatru; Béchir Jarraya; Chloé Laurencin; Dominique Guehl; Lucie Hopes; Melissa Tir; Caroline Giordana; Anne-Sophie Rolland; Guillaume Grolez; Gillaume Baille; Jean-Pierre Pruvo Kreisler; Romain Viard; Julien Dumont; M Delliaux; M Brion; Gustavo Touzet; Valerie Santraine; Marie Pleuvret; Nolwen Dautrevaux; Victor Laugeais; Morgane Coeffet; Camille Potey; Celine Leclercq; Hana You; Jonas Ihle; Raquel Guimeraes-Costa; Andréas Hartmann; Louise-Laure Mariani; Fanny Pineau; Frédérique Bozon; Camille Huiban; Soledad Navarro; Arlette Welaratne; Carole Dongmo-Kenfack; Lise Mantisi; Nathalie Jarry; Sophie Aix; Anne-Gaelle Corbille; Elisabeth Calvier-Auffray; Madame Laetitia Rocher; Madame Anne-Laure Deruet; Raoul Sylvie; Roualdes Vincent; Berangere Debilly; Charlotte Beal; Carine Chassain; Laure Delaby; Tiphaine Vidal; Jean Jeacques Lemaire; Marie Delfini; Giorgio Spatola; Ansquer Solène; Colin Olivier; Guillevin Remy; Fradet Anne; Anziza Manssouri; Blondeau Sophie; Richard Philippe; Cam Philippe; Page Philippe; Bataille Benoit; Rabois Emilie; Frédérique Leh; Alexandre Bonnet; Jean François Houvenaghel; Claire Haegelen; Francoise Kestens; Pierre Burbaud; Nathalie Damon-Perriere; Elsa Krim; Sandrine Molinier-Blossier; Morgan Ollivier; Marion Lacoste; Nicolas Auzou; Marie Bonnet; Emmanuel Cuny; Julien Engelhardt; Olivier Branchard; Clotilde Huet; Fabienne Ory Magne; Marion Simonetta Moreau; Christophe Arbus; Jean Albert Lotterie; Marion Sarrail; Patrick Chaynes; Damien Fetter; Linda Vernon; Ouhaid Lagha-Boukbiza; Odile Gebus; Solveig Montaut; Nadine Longato; Clélie Phillips; Jimmy Voirin; Dominique Chaussemy; Claire Marsé; Lydiane Mondot; Bruno Giordana; Robin Kardous; Bernadette Bailet; Héloise Joly; Aurélie Leplus; Amélie Faustini; Jean-Marc Constans; Audrey Seling; Teodor Danaila; Gustavo Polo; Mylène Meyer; Céline Dillier; Sophie Colnat; Patte Karsenti; Marie Lebouteux; Marc Ziegler; Julien Savatowky; Juliette Vrillac; Claire Nakache; Valérie Mesnage; Camille Decrocq; Anne Boulin; Bérénice Gardel; Catherine Ziz; David Gay; Robin Bonicel; Fouzia El Mountassir; Clara Fischer; Yann Cointepas; Patrick Gelé; Florine Fievet; Matthieu Chabel; Virginie Derenaucourt; Loïc Facon; Yanick Tchantchou Njosse; Florence Duflot; Hajar Chouiki; Aymeric Lanore; Aymeric Basset; David Bendetowicz; Poornima J Menon; Jordan Cornillault; Renaud Lopes Leclerc; Elise GersParis Gers; Elodie Hainque Marie-Vidailhet; Carine Lefort Nantes; Le DilySéverine Clermont-Ferrand; Elodie Durand Marseille; Camille Magnaudet Poitiers; Benatru Isabelle; JL Houeto; Guillemain Annie Rennes; Drapier Sophie; Solennory Bordeaux; Julie Blanchard Toulouse; Rascol Olivier; Christine Brefel Courbon; Fabrice Bonneville-et; Estelle Harroch Rouen; Frédéric Ziegler Strasbourg; Marie des Neiges Santin; Amaury Mengin Nice; Caroline Girodana; Vanessa Ferrier Amiens; Béatrice Schuler Lyon; Elise Metereau Nancy; Vincent D’Hardemare; Lhaouas Belamri; Frédérique Bourdain; Vadim Afanassiev; Jarbas Correa Lino Junior; Elodie Dupuy; Inès Barre; Christophe Fruit
Source: BMJ Neurology Open, Vol 8, Iss 1 (2026)
Publisher Information: BMJ Publishing Group
Publication Year: 2026
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571
Description: 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: https://neurologyopen.bmj.com/content/8/1/e001427.full; https://doaj.org/toc/2632-6140; https://doaj.org/article/37bb1cabb2804067810e9148ecec3d50
DOI: 10.1136/bmjno-2025-001427
Availability: https://doi.org/10.1136/bmjno-2025-001427; https://doaj.org/article/37bb1cabb2804067810e9148ecec3d50
Accession Number: edsbas.F943B2B0
Database: BASE