Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson’s Disease: Interim Results from a Randomized Double-Blind Clinical Trial

Article type: Research Article

Authors: Bourilhon, Julie^{a; b} | Olivier, Claire^{b; c} | You, Hana^{b; d} | Collomb-Clerc, Antoine^b | Grabli, David^{b; e} | Belaid, Hayat^f | Mullie, Yannick^b | François, Chantal^b | Czernecki, Virginie^e | Lau, Brian^b | Pérez-García, Fernando^{b; g} | Bardinet, Eric^{b; g} | Fernandez-Vidal, Sara^{b; h} | Karachi, Carine^{b; f} | Welter, Marie-Laure^{a; b; *}

Affiliations: [a] Department of Neurophysiology, Rouen University Hospital and University of Rouen, France | [b] Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Institut du Cerveau (ICM), Paris, France | [c] PANAM platform, Institut du Cerveau (ICM), Paris, France | [d] Clinical Investigation Center, Pitié-Salpêtrière, Charles Foix University Hospital, Assistance Publique–Hôpitaux de Paris, Institut du Cerveau (ICM), Paris, France | [e] Fédération des Maladies du Système Nerveux, Pitié-Salpêtrière, Charles Foix University Hospital, Assistance Publique–Hôpitaux de Paris Paris, Paris, France | [f] Department of Neurosurgery, Pitié-Salpêtrière, Charles Foix University Hospital, Assistance Publique–Hôpitaux Paris, Paris, France | [g] CENIR Platform, Institut du Cerveau (ICM), Paris, France | [h] STIM Platform, Institut du Cerveau (ICM), Paris, France

Correspondence: [*] Correspondence to: Marie-Laure Welter, MD, PhD, Neurophysiology Department, Rouen University Hospital, 1 rue de Germont, 76031 Rouen Cedex, France. Tel.: +33232888047; Fax: +33232883046; E-mail: marielaure.welter@icm-institute.org.

Abstract: Background:Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective:We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods:Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results:The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion:Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.

Keywords: Mesencephalic locomotor region, Parkinson’s disease patients, freezing of gait, postural instability, deep brain stimulation

DOI: 10.3233/JPD-212793

Journal: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 639-653, 2022