TY - JOUR
T1 - Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease
T2 - study protocol for a prospective, pilot trial
AU - Chang, Stephano J.
AU - Cajigas, Iahn
AU - Guest, James D.
AU - Noga, Brian R.
AU - Widerström-Noga, Eva
AU - Haq, Ihtsham
AU - Fisher, Letitia
AU - Luca, Corneliu C.
AU - Jagid, Jonathan R.
N1 - Funding Information:
This study is supported by the Boston Scientific Investigator Sponsored Research Award ISRNMB0018 (contact person Kaoru Lee Adair – kay.adair@bsci.com) and the University of Miami Scientific Awards Committee Pilot Study Grant ITS 001003 (contact person Coleen Atkins – catkins@miami.edu). The funders had no role in the design of the study and collection, analysis, interpretation of data, nor in writing the manuscript.
Funding Information:
The study is funded in part by Boston Scientific through their Investigator Sponsored Research Award. JJ and CL have consulting agreements with Medtronic Inc., Boston Scientific, Inc., and Abbott Medical. JJ has two funded grants through Medtronic and Boston Scientific. The other authors declare that they have no competing interests.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Cuneiform nucleus (CnF)
KW - Freezing of gait (FOG)
KW - Gait dysfunction
KW - Mesencephalic locomotor region (MLR)
KW - Parkinson’s disease
KW - Pedunculopontine nucleus (PPN)
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UR - http://www.scopus.com/inward/citedby.url?scp=85107199866&partnerID=8YFLogxK
U2 - 10.1186/s40814-021-00855-7
DO - 10.1186/s40814-021-00855-7
M3 - Article
AN - SCOPUS:85107199866
VL - 7
JO - Pilot and Feasibility Studies
JF - Pilot and Feasibility Studies
SN - 2055-5784
IS - 1
M1 - 117
ER -