Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double‐Blind Primary Endpoint

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.

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Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease

Neurology ◽

10.1212/wnl.51.3.850 ◽

1998 ◽

Vol 51 (3) ◽

pp. 850-855 ◽

Cited By ~ 391

Author(s):

R. Kumar ◽

A. M. Lozano ◽

Y. J. Kim ◽

W. D. Hutchison ◽

E. Sime ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Double Blind ◽

Advanced Parkinson’S Disease ◽

Deep Brain

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Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson’s disease

BMJ Open ◽

10.1136/bmjopen-2021-049955 ◽

2022 ◽

Vol 12 (1) ◽

pp. e049955

Author(s):

Sara Marceglia ◽

Costanza Conti ◽

Oleg Svanidze ◽

Guglielmo Foffani ◽

Andres M Lozano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Pilot Trial ◽

Clinical State ◽

Double Blind ◽

Deep Brain

IntroductionAfter several years of brain-sensing technology development and proof-of-concept studies, adaptive deep brain stimulation (aDBS) is ready to better treat Parkinson’s disease (PD) using aDBS-capable implantable pulse generators (IPGs). New aDBS devices are capable of continuous sensing of neuronal activity from the subthalamic nucleus (STN) and contemporaneous stimulation automatically adapted to match the patient’s clinical state estimated from the analysis of STN activity using proprietary algorithms. Specific studies are necessary to assess superiority of aDBS vs conventional DBS (cDBS) therapy. This protocol describes an original innovative multicentre international study aimed to assess safety and efficacy of aDBS vs cDBS using a new generation of DBS IPG in PD (AlphaDBS system by Newronika SpA, Milan, Italy).MethodsThe study involves six investigational sites (in Italy, Poland and The Netherlands). The primary objective will be to evaluate the safety and tolerability of the AlphaDBS System, when used in cDBS and aDBS mode. Secondary objective will be to evaluate the potential efficacy of aDBS. After eligibility screening, 15 patients with PD already implanted with DBS systems and in need of battery replacement will be randomised to enter a two-phase protocol, including a ‘short-term follow-up’ (2 days experimental sessions during hospitalisation, 1 day per each mode) and a ‘long-term follow-up’ (1 month at home, 15 days per each mode).Ethics and disseminationThe trial was approved as premarket study by the Italian, Polish, and Dutch Competent Authorities: Bioethics Committee at National Oncology Institute of Maria Skłodowska-Curie—National Research Institute in Warsaw; Comitato Etico Milano Area 2; Comitato Etico IRCCS Istituto Neurologico C. Besta; Comitato Etico interaziendale AOUC Città della Salute e della Scienza—AO Ordine Mauriziano di Torino—ASL Città di Torino; De Medisch Ethisch Toetsingscommissie van Maastricht UMC. The study started enrolling patients in January 2021.Trial registration numberNCT04681534.

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