Citation

Chang SJ, Cajigas I, Guest JD, Noga BR, Widerström-Noga E, Haq I, Fisher L, Luca CC, Jagid JR. Pilot Feasibility Stud. 2021; 7(1).

Copyright

(Copyright © 2021, Holtzbrinck Springer Nature Publishing Group - BMC)

DOI

10.1186/s40814-021-00855-7

PMID

unavailable

Abstract

BACKGROUND: Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of Parkinson's disease (PD) patients that is poorly responsive to standard levodopa therapy or deep brain stimulation (DBS) of established PD targets such as the subthalamic nucleus and the globus pallidus interna. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN) to address FOG, was based on its observed pathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region, a functionally defined area of the midbrain that elicits locomotion in both intact animals and decerebrate animal preparations with electrical stimulation. Initial reports of PPN DBS were met with much enthusiasm; however, subsequent studies produced mixed results, and recent meta-analysis results have been far less convincing than initially expected. A closer review of the extensive mesencephalic locomotor region (MLR) preclinical literature, including recent optogenetics studies, strongly suggests that the closely related cuneiform nucleus (CnF), just dorsal to the PPN, may be a superior target to promote gait initiation.

METHODS: We will conduct a prospective, open-label, single-arm pilot study to assess safety and feasibility of CnF DBS in PD patients with levodopa-refractory FOG. Four patients will receive CnF DBS and have gait assessments with and without DBS during a 6-month follow-up.

DISCUSSION: This paper presents the study design and rationale for a pilot study investigating a novel DBS target for gait dysfunction, including targeting considerations. This pilot study is intended to support future larger scale clinical trials investigating this target. Trial registration: ClinicalTrials.gov identifier: NCT04218526 (registered January 6, 2020). © 2021, The Author(s).

Language: en

Keywords

adult; human; safety; pilot study; screening; pathophysiology; physical examination; nuclear magnetic resonance imaging; computer assisted tomography; prospective study; clinical observation; pain assessment; levodopa; electrocardiogram; Parkinson disease; preoperative evaluation; Beck Depression Inventory; laboratory test; thorax radiography; brain depth stimulation; neurologic examination; Article; velocity; medical history; clinical assessment; gait disorder; electromyogram; blood pressure measurement; Columbia Suicide Severity Rating Scale; Parkinson Disease Questionnaire; mental disease assessment; Parkinson’s disease; cuneiform nucleus; Cuneiform nucleus (CnF); freezing of gait; Freezing of gait (FOG); Gait dysfunction; Mattis Dementia Rating Scale; MDS-Unified Parkinson Disease Rating Scale; Mesencephalic locomotor region (MLR); Parkinson Disease Quality of Life Questionnaire; Pedunculopontine nucleus (PPN); pedunculopontine tegmental nucleus; stride length; timed up and go test