Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial
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 globu...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Pilot and Feasibility Studies |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40814-021-00855-7 |
| _version_ | 1818865027354984448 |
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| author | Stephano J. Chang Iahn Cajigas James D. Guest Brian R. Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Corneliu C. Luca Jonathan R. Jagid |
| author_facet | Stephano J. Chang Iahn Cajigas James D. Guest Brian R. Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Corneliu C. Luca Jonathan R. Jagid |
| author_sort | Stephano J. Chang |
| collection | DOAJ |
| description | 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) |
| first_indexed | 2024-12-19T10:41:01Z |
| format | Article |
| id | doaj.art-e8b04a178551404f86616752154e9bfe |
| institution | Directory Open Access Journal |
| issn | 2055-5784 |
| language | English |
| last_indexed | 2024-12-19T10:41:01Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Pilot and Feasibility Studies |
| spelling | doaj.art-e8b04a178551404f86616752154e9bfe2022-12-21T20:25:27ZengBMCPilot and Feasibility Studies2055-57842021-06-017111010.1186/s40814-021-00855-7Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trialStephano J. Chang0Iahn Cajigas1James D. Guest2Brian R. Noga3Eva Widerström-Noga4Ihtsham Haq5Letitia Fisher6Corneliu C. Luca7Jonathan R. Jagid8The Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisDepartment of Neurology, University of Miami Miller School of MedicineThe Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisThe Miami Project to Cure ParalysisAbstract 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)https://doi.org/10.1186/s40814-021-00855-7Freezing of gait (FOG)Gait dysfunctionParkinson’s diseaseMesencephalic locomotor region (MLR)Cuneiform nucleus (CnF)Pedunculopontine nucleus (PPN) |
| spellingShingle | Stephano J. Chang Iahn Cajigas James D. Guest Brian R. Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Corneliu C. Luca Jonathan R. Jagid Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial Pilot and Feasibility Studies Freezing of gait (FOG) Gait dysfunction Parkinson’s disease Mesencephalic locomotor region (MLR) Cuneiform nucleus (CnF) Pedunculopontine nucleus (PPN) |
| title | Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial |
| title_full | Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial |
| title_fullStr | Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial |
| title_full_unstemmed | Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial |
| title_short | Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson’s disease: study protocol for a prospective, pilot trial |
| title_sort | deep brain stimulation of the cuneiform nucleus for levodopa resistant freezing of gait in parkinson s disease study protocol for a prospective pilot trial |
| topic | Freezing of gait (FOG) Gait dysfunction Parkinson’s disease Mesencephalic locomotor region (MLR) Cuneiform nucleus (CnF) Pedunculopontine nucleus (PPN) |
| url | https://doi.org/10.1186/s40814-021-00855-7 |
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