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Deep Brain Stimulation–Withdrawal Syndrome in Parkinson’s Disease: Risk Factors and Pathophysiological Hypotheses of a Life-Threatening Emergency

  • Stephan Grimaldi
    Correspondence
    Address correspondence to: Stephan Grimaldi, MD, PhD, Department of Neurology and Movement Disorders, Timone University Hospital, 264 rue Saint-Pierre, 13385 Marseille Cedex 05, France.
    Affiliations
    Department of Neurology and Movement Disorders, Timone University Hospital, Aix-Marseille University, Marseille, France

    Centre national de la recherche scientifique (CNRS), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), Centre d'Exploration Métabolique par Résonance Magnétique (CEMEREM), Aix-Marseille University, Marseille, France
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  • Alexandre Eusebio
    Affiliations
    Department of Neurology and Movement Disorders, Timone University Hospital, Aix-Marseille University, Marseille, France

    Centre national de la recherche scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix-Marseille University, Marseille, France
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  • Romain Carron
    Affiliations
    Department of Functional and Stereotactic Neurosurgery and Gamma Knife Radiosurgery, Timone University Hospital, Aix-Marseille University, Marseille, France

    Institut national de la santé et de la recherche médicale (INSERM), Institut de Neuroscience des Systèmes (INS), Aix-Marseille University, Marseille, France
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  • Jean-Marie Regis
    Affiliations
    Department of Functional and Stereotactic Neurosurgery and Gamma Knife Radiosurgery, Timone University Hospital, Aix-Marseille University, Marseille, France
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  • Lionel Velly
    Affiliations
    Centre national de la recherche scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix-Marseille University, Marseille, France

    Department of Anesthesiology and Critical Care Medicine, Timone University Hospital, Aix-Marseille University, Marseille, France
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  • Jean-Philippe Azulay
    Affiliations
    Department of Neurology and Movement Disorders, Timone University Hospital, Aix-Marseille University, Marseille, France

    Centre national de la recherche scientifique (CNRS), Laboratoire de Neurosciences conginitives (LNC), Aix-Marseille University, Marseille, France
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  • Tatiana Witjas
    Affiliations
    Department of Neurology and Movement Disorders, Timone University Hospital, Aix-Marseille University, Marseille, France

    Centre national de la recherche scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix-Marseille University, Marseille, France
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Published:November 04, 2022DOI:https://doi.org/10.1016/j.neurom.2022.09.008

      Abstract

      Background and Objectives

      Subthalamic nucleus deep brain stimulation (DBS) is the most common therapeutic surgical procedure for patients with Parkinson’s disease with motor fluctuations, dyskinesia, or tremor. Routine follow-up of patients allows clinicians to anticipate replacement of the DBS battery reaching the end of its life. Patients who experience a sudden stop of the DBS battery experience a rapid worsening of symptoms unresponsive to high dose of levodopa, in a life-threatening phenomenon called “DBS-withdrawal syndrome.” In the current context of the COVID-19 pandemic, in which many surgeries are being deprogrammed, it is of utmost importance to determine to what extent DBS battery replacement surgeries should be considered an emergency. In this study, we attempt to identify risk factors of DBS-withdrawal syndrome and provide new insights about pathophysiological hypotheses. We then elaborate on the optimal approach to avoid and manage such a situation.

      Materials and Methods

      We conducted a systematic review of the literature on the subject and reported the cases of 20 patients (including five from our experience) with DBS-withdrawal syndrome, comparing them with 15 undisturbed patients (including three from our experience), all having undergone neurostimulation discontinuation.

      Results

      A long disease duration at battery removal and many years of DBS therapy are the main potential identified risk factors (p < 0.005). In addition, a trend for older age at the event and higher Unified Parkinson’s Disease Rating Scale motor score before initial DBS implantation (evaluated in OFF-drug condition) was found (p < 0.05). We discuss several hypotheses that might explain this phenomenon, including discontinued functioning of the thalamic-basal ganglia loop due to DBS-stimulation cessation in a context in which cortical-basal ganglia loop had lost its cortical input, and possible onset of a severe bradykinesia through the simultaneous occurrence of an alpha and high-beta synchronized state.

      Conclusions

      The patients’ clinical condition may deteriorate rapidly, be unresponsive to high dose of levodopa, and become life-threatening. Hospitalization is suggested for clinical monitoring. In the context of the current COVID-19 pandemic, it is important to widely communicate the replacement of DBS batteries reaching the end of their life. More importantly, in cases in which the battery has stopped, there should be no delay in performing replacement as an emergent surgery.

      Keywords

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