title: Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait.
abstract: Gait and akinesia deterioration in PD patients during the immediate postoperative period of DBS has been directly related to stimulation in the subthalamic region. The underlying mechanisms remain poorly understood. The aim of the present study was to clinically and anatomically describe this side effect.
  
  
  
  PD patients presenting with a worsening of gait and/or akinesia following STN-DBS, that was reversible on stimulation arrest were included. The evaluation included (1) a Stand Walk Sit Test during a monopolar survey of each electrode in the on-drug condition; (2) a 5-condition test with the following conditions: off-drug/off-DBS, off-drug/on-best-compromise-DBS, on-drug/off-DBS, on-drug/on-best-compromise-DBS, and on-drug/on-worsening-DBS, which utilized the contact inducing the most prominent gait deterioration. The following scales were performed: UPDRSIII subscores, Stand Walk Sit Test, and dyskinesia and freezing of gait scales. Localization of contacts was performed using a coregistration method.
  
  
  
  Twelve of 17 patients underwent the complete evaluation. Stimulation of the most proximal contacts significantly slowed down the Stand Walk Sit Test. The on-drug/on-worsening-DBS condition compared with the on-drug/off-DBS condition worsened akinesia (P = 0.02), Stand Walk Sit Test (P = 0.001), freezing of gait (P = 0.02), and improved dyskinesias (P = 0.003). Compared with the off-drug/off-DBS condition, the on-drug/on-worsening-DBS condition improved rigidity (P = 0.007) and tremor (P = 0.007). Worsening contact sites were predominantly dorsal and anterior to the STN in the anterior zona incerta and Forel fields H2.
  
  
  
  A paradoxical deterioration of gait and akinesia is a rare side effect following STN-DBS. We propose that this may be related to misplaced contacts, and we discuss the pathophysiology and strategies to identify and manage this complication. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, Geneva University Hospital, Geneva, Switzerland. Vanessa.FleuryNissen@hcuge.ch.|Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France. Vanessa.FleuryNissen@hcuge.ch.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fleury
authors.affiliation: Department of Neurology, Geneva University Hospital, Geneva, Switzerland.|Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France.|Department of Neurology, Savoie Hospital, Chambery, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Gere
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France.|Department of Neurology, University Hospital of Verona, Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tommasi
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France.|Department of Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Romito
authors.affiliation: Department of Health and Community Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.affiliation: Sorbonne Université, UPMC Univ Paris, Inserm U975, CNRS UMR 7225, Centre de Neuroimagerie de Recherche, Institut du Cerveau et de la Moelle Épinière, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bardinet
authors.affiliation: Department of Neurosurgery, Grenoble University Hospital, Grenoble, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Chabardes
authors.affiliation: Department of Neurosurgery, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Shahan
authors.initials: S
authors.lastname: Momjian
authors.affiliation: US 017, INSERM, UMS 3552, CNRS, Grenoble University Hospital, Neuroradiology and MRI, Grenoble, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krainik
authors.affiliation: Department of Neurology, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Burkhard
authors.affiliation: Sorbonne Université, UPMC Univ Paris, Inserm U975, CNRS UMR 7225, Centre de Neuroimagerie de Recherche, Institut du Cerveau et de la Moelle Épinière, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Yelnik
authors.affiliation: Movement Disorder Unit, Department of Psychiatry and Neurology, Grenoble University Hospital, Grenoble, France.|INSERM U836, University Grenoble Alpes, Grenoble Neuroscience Institute, Grenoble, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020820:Dyskinesias / Q000209:etiology*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000628:therapy*; D020531:Subthalamic Nucleus
chemical_list: D015259:Dopamine Agents; D007980:Levodopa