MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait
BackgroundFreezing of gait (FOG) is a debilitating motor deficit in a subset of Parkinson’s Disease (PD) patients that is poorly responsive to levodopa or deep brain stimulation (DBS) of established PD targets. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN)...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Human Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnhum.2021.676755/full |
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| author | Stephano J. Chang Stephano J. Chang Iahn Cajigas Iahn Cajigas James D. Guest James D. Guest Brian R. Noga Brian R. Noga Eva Widerström-Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Letitia Fisher Corneliu C. Luca Corneliu C. Luca Jonathan R. Jagid Jonathan R. Jagid |
| author_facet | Stephano J. Chang Stephano J. Chang Iahn Cajigas Iahn Cajigas James D. Guest James D. Guest Brian R. Noga Brian R. Noga Eva Widerström-Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Letitia Fisher Corneliu C. Luca Corneliu C. Luca Jonathan R. Jagid Jonathan R. Jagid |
| author_sort | Stephano J. Chang |
| collection | DOAJ |
| description | BackgroundFreezing of gait (FOG) is a debilitating motor deficit in a subset of Parkinson’s Disease (PD) patients that is poorly responsive to levodopa or deep brain stimulation (DBS) of established PD targets. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN), to address FOG was based on its observed neuropathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region (MLR). Initial reports of PPN DBS were met with enthusiasm; however, subsequent studies reported mixed results. A closer review of the MLR basic science literature, suggests that the closely related cuneiform nucleus (CnF), dorsal to the PPN, may be a superior site to promote gait. Although suspected to have a conserved role in the control of gait in humans, deliberate stimulation of a homolog to the CnF in humans using directional DBS electrodes has not been attempted.MethodsAs part of an open-label Phase 1 clinical study, one PD patient with predominantly axial symptoms and severe FOG refractory to levodopa therapy was implanted with directional DBS electrodes (Boston Science Vercise CartesiaTM) targeting the CnF bilaterally. Since the CnF is a poorly defined reticular nucleus, targeting was guided both by diffusion tensor imaging (DTI) tractography and anatomical landmarks. Intraoperative stimulation and microelectrode recordings were performed near the targets with leg EMG surface recordings in the subject.ResultsPost-operative imaging revealed accurate targeting of both leads to the designated CnF. Intraoperative stimulation near the target at low thresholds in the awake patient evoked involuntary electromyography (EMG) oscillations in the legs with a peak power at the stimulation frequency, similar to observations with CnF DBS in animals. Oscillopsia was the primary side effect evoked at higher currents, especially when directed posterolaterally. Directional DBS could mitigate oscillopsia.ConclusionDTI-based targeting and intraoperative stimulation to evoke limb EMG activity may be useful methods to help target the CnF accurately and safely in patients. Long term follow-up and detailed gait testing of patients undergoing CnF stimulation will be necessary to confirm the effects on FOG.Clinical Trial RegistrationClinicaltrials.gov identifier: NCT04218526. |
| first_indexed | 2024-12-21T15:50:09Z |
| format | Article |
| id | doaj.art-d47db3c82221460e93174d0d3949441e |
| institution | Directory Open Access Journal |
| issn | 1662-5161 |
| language | English |
| last_indexed | 2024-12-21T15:50:09Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Human Neuroscience |
| spelling | doaj.art-d47db3c82221460e93174d0d3949441e2022-12-21T18:58:15ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612021-06-011510.3389/fnhum.2021.676755676755MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of GaitStephano J. Chang0Stephano J. Chang1Iahn Cajigas2Iahn Cajigas3James D. Guest4James D. Guest5Brian R. Noga6Brian R. Noga7Eva Widerström-Noga8Eva Widerström-Noga9Ihtsham Haq10Letitia Fisher11Letitia Fisher12Corneliu C. Luca13Corneliu C. Luca14Jonathan R. Jagid15Jonathan R. Jagid16The Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurosurgery, University of British Columbia, Vancouver, BC, CanadaThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL, United StatesThe Miami Project to Cure Paralysis, Miami, FL, United StatesDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesBackgroundFreezing of gait (FOG) is a debilitating motor deficit in a subset of Parkinson’s Disease (PD) patients that is poorly responsive to levodopa or deep brain stimulation (DBS) of established PD targets. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN), to address FOG was based on its observed neuropathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region (MLR). Initial reports of PPN DBS were met with enthusiasm; however, subsequent studies reported mixed results. A closer review of the MLR basic science literature, suggests that the closely related cuneiform nucleus (CnF), dorsal to the PPN, may be a superior site to promote gait. Although suspected to have a conserved role in the control of gait in humans, deliberate stimulation of a homolog to the CnF in humans using directional DBS electrodes has not been attempted.MethodsAs part of an open-label Phase 1 clinical study, one PD patient with predominantly axial symptoms and severe FOG refractory to levodopa therapy was implanted with directional DBS electrodes (Boston Science Vercise CartesiaTM) targeting the CnF bilaterally. Since the CnF is a poorly defined reticular nucleus, targeting was guided both by diffusion tensor imaging (DTI) tractography and anatomical landmarks. Intraoperative stimulation and microelectrode recordings were performed near the targets with leg EMG surface recordings in the subject.ResultsPost-operative imaging revealed accurate targeting of both leads to the designated CnF. Intraoperative stimulation near the target at low thresholds in the awake patient evoked involuntary electromyography (EMG) oscillations in the legs with a peak power at the stimulation frequency, similar to observations with CnF DBS in animals. Oscillopsia was the primary side effect evoked at higher currents, especially when directed posterolaterally. Directional DBS could mitigate oscillopsia.ConclusionDTI-based targeting and intraoperative stimulation to evoke limb EMG activity may be useful methods to help target the CnF accurately and safely in patients. Long term follow-up and detailed gait testing of patients undergoing CnF stimulation will be necessary to confirm the effects on FOG.Clinical Trial RegistrationClinicaltrials.gov identifier: NCT04218526.https://www.frontiersin.org/articles/10.3389/fnhum.2021.676755/fullfreezing of gaitgait dysfunctionParkinson’s Diseasemesencephalic locomotor regioncuneiform nucleuspedunculopontine nucleus |
| spellingShingle | Stephano J. Chang Stephano J. Chang Iahn Cajigas Iahn Cajigas James D. Guest James D. Guest Brian R. Noga Brian R. Noga Eva Widerström-Noga Eva Widerström-Noga Ihtsham Haq Letitia Fisher Letitia Fisher Corneliu C. Luca Corneliu C. Luca Jonathan R. Jagid Jonathan R. Jagid MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait Frontiers in Human Neuroscience freezing of gait gait dysfunction Parkinson’s Disease mesencephalic locomotor region cuneiform nucleus pedunculopontine nucleus |
| title | MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait |
| title_full | MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait |
| title_fullStr | MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait |
| title_full_unstemmed | MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait |
| title_short | MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait |
| title_sort | mr tractography based targeting and physiological identification of the cuneiform nucleus for directional dbs in a parkinson s disease patient with levodopa resistant freezing of gait |
| topic | freezing of gait gait dysfunction Parkinson’s Disease mesencephalic locomotor region cuneiform nucleus pedunculopontine nucleus |
| url | https://www.frontiersin.org/articles/10.3389/fnhum.2021.676755/full |
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