{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, CIC Neurosciences, Pitié-Salpêtrière University Hospital, Paris, France"
      ],
      "name": "Aymeric Lanore"
    },
    {
      "affiliations": [
        "Department of Neurology, CIC Neurosciences, Pitié-Salpêtrière University Hospital, Paris, Île-de-France, France"
      ],
      "name": "Marion Houot"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Aymeric Basset"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "David Bendetowicz"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Poornima J Menon"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Eric Bardinet"
    },
    {
      "affiliations": [
        "Paris Brain Institute, Paris, Île-de-France, France"
      ],
      "name": "Sara Fernandez Vidal"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Jordan Cornillault"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Carine Karachi"
    },
    {
      "affiliations": [
        "Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Paris, France"
      ],
      "name": "Soledad Navarro"
    },
    {
      "affiliations": [
        "Institut du Cerveau-Paris Brain Institute-ICM, Sorbonne Université, Paris, France"
      ],
      "name": "Jonas Ihle"
    },
    {
      "affiliations": [
        "APHM, Marseille, France"
      ],
      "name": "Alexandre Eusebio"
    },
    {
      "affiliations": [
        "Department of Neurology, Centre Hospitalier Universitaire de Nice, Nice, Provence-Alpes-Côte d’Azu, France"
      ],
      "name": "Caroline Giordana"
    },
    {
      "affiliations": [
        "Department of Neurology, Nantes University Hospital, Nantes, France"
      ],
      "name": "Tiphaine Rouaud"
    },
    {
      "affiliations": [
        "Neurologie, CHU Pontchaillou, Rennes, France"
      ],
      "name": "Sophie Drapier"
    },
    {
      "affiliations": [
        "Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France",
        "CNRS UMR 5293, Institut des Maladies Neurodegeneratives, Bordeaux, France"
      ],
      "name": "Dominique Guehl"
    },
    {
      "affiliations": [
        "EA7280, Université Clermont Auvergne, Clermont-Ferrand, France",
        "Neurology, University Hospital Centre Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Ana Marques"
    },
    {
      "affiliations": [
        "Neurology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France"
      ],
      "name": "Cécile Hubsch"
    },
    {
      "affiliations": [
        "Neuroscience, Hospital Foch, Suresnes, Île-de-France, France"
      ],
      "name": "Béchir Jarraya"
    },
    {
      "affiliations": [
        "Centre Hospitalier Universitaire de Poitiers, Poitiers, France"
      ],
      "name": "Isabelle Benatru"
    },
    {
      "affiliations": [
        "Neurology C, Hopital Neurologique Pierre Wertheimer, Lyon, France"
      ],
      "name": "Stephane Thobois"
    },
    {
      "affiliations": [
        "Neurology, Centre Hospitalier Universitaire de Nancy, Nancy, Lorraine, France"
      ],
      "name": "Lucie Hopes"
    },
    {
      "affiliations": [
        "Neurology, Rouen University Hospital, Rouen, France"
      ],
      "name": "David Maltete"
    },
    {
      "affiliations": [
        "Pharmacology, Toulouse University, Toulouse, France"
      ],
      "name": "Olivier Rascol"
    },
    {
      "affiliations": [
        "Amiens University Hospital, Amiens, France"
      ],
      "name": "Melissa Tir"
    },
    {
      "affiliations": [
        "Department of Medical Pharmacology, University Hospital Lille, Lille, France"
      ],
      "name": "Caroline Moreau"
    },
    {
      "affiliations": [
        "Neurologie, Hopital de Hautepierre, Strasbourg, France"
      ],
      "name": "Christine Tranchant"
    },
    {
      "affiliations": [
        "Department of Medical Pharmacology, Neurology and Movement Disorders Department, Referent center of Parkinson’s disease, CHU of Lille, Univ. Lille Neuroscience & Cognition, Inserm, UMR-S1172, Lille, France"
      ],
      "name": "Anne-Sophie Rolland"
    },
    {
      "affiliations": [
        "Medical Pharmacology, Lille University Medical Center, Lille, France"
      ],
      "name": "David Devos"
    },
    {
      "affiliations": [
        "Department of Neurology, CIC Neurosciences, Pitié-Salpêtrière University Hospital, Paris, France"
      ],
      "name": "Jean Christophe Corvol"
    },
    {
      "affiliations": [
        "Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France"
      ],
      "name": "David Grabli"
    },
    {
      "affiliations": [
        "Department of Neurology, Pitié-Salpêtrière University Hospital, Paris, France"
      ],
      "name": "Elodie Hainque"
    },
    {
      "affiliations": [],
      "name": "PREDISTIM study group"
    }
  ],
  "title": "Understanding dopaminergic dose reduction following STN-DBS: mediation analysis",
  "uid": "c8b1aece-b968-5dae-8d99-c7926ff6013d"
}