scholarly journals Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson’s disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome

2018 ◽  
Vol 129 (6) ◽  
pp. 1550-1561 ◽  
Author(s):  
Craig G. van Horne ◽  
Jorge E. Quintero ◽  
John T. Slevin ◽  
Amelia Anderson-Mooney ◽  
Julie A. Gurwell ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Clinical Outcome ◽  
Peripheral Nerve ◽  
Sural Nerve ◽  
Outcome Data ◽  
Nerve Grafts ◽  
Peripheral Nerve Grafts ◽  
Deep Brain

OBJECTIVECurrently, there is no treatment that slows or halts the progression of Parkinson’s disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson’s disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinson’s disease at the time of deep brain stimulation (DBS) surgery.METHODSStandard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery.RESULTSAll 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinson’s Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft.CONCLUSIONSPeripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.Clinical trial registration no.: NCT01833364 (clinicaltrials.gov)

scholarly journals Implantation of autologous peripheral nerve grafts into the substantia nigra of subjects with idiopathic Parkinson's disease treated with bilateral STN DBS: a report of safety and feasibility

2017 ◽  
Vol 126 (4) ◽  
pp. 1140-1147 ◽  
Author(s):  
Craig G. van Horne ◽  
Jorge E. Quintero ◽  
Julie A. Gurwell ◽  
Renee P. Wagner ◽  
John T. Slevin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Peripheral Nerve ◽  
Neurotrophic Factors ◽  
Sural Nerve ◽  
Cell Function ◽  
Nerve Graft ◽  
Clinical Trial Registration ◽  
Peripheral Nerve Graft

OBJECTIVE One avenue of intense efforts to treat Parkinson's disease (PD) involves the delivery of neurotrophic factors to restore dopaminergic cell function. A source of neurotrophic factors that could be used is the Schwann cell from the peripheral nervous system. The authors have begun an open-label safety study to examine the safety and feasibility of implanting an autologous peripheral nerve graft into the substantia nigra of PD patients undergoing deep brain stimulation (DBS) surgery. METHODS Multistage DBS surgery targeting the subthalamic nucleus was performed using standard procedures in 8 study participants. After the DBS leads were implanted, a section of sural nerve containing Schwann cells was excised and unilaterally delivered into the area of the substantia nigra. Adverse events were continuously monitored. RESULTS Eight of 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery. Postoperative MR images did not reveal edema, hemorrhage, or significant signal changes in the graft target region. Three participants reported a patch of numbness on the outside of the foot below the sural nerve harvest site. CONCLUSIONS Based on the safety outcome of the procedure, targeted peripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and may provide a means to deliver neurorestorative therapy. Clinical trial registration no.: NCT01833364 (clinicaltrials.gov)

scholarly journals Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson’s Disease

2021 ◽  
Vol 11 (4) ◽  
pp. 500
Author(s):  
Geetanjali Gera ◽  
Zain Guduru ◽  
Tritia Yamasaki ◽  
Julie A. Gurwell ◽  
Monica J. Chau ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Peripheral Nerve ◽  
Brain Stimulation ◽  
Step Length ◽  
Gait Velocity ◽  
Balance Performance ◽  
Improved Performance ◽  
Deep Brain

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results.

scholarly journals Comparison of General and Local Anesthesia for Deep Brain Stimulator Insertion: A Systematic Review

2017 ◽  
Vol 44 (6) ◽  
pp. 697-704 ◽  
Author(s):  
Veena Sheshadri ◽  
Nathan C. Rowland ◽  
Jigesh Mehta ◽  
Marina Englesakis ◽  
Pirjo Manninen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Outcome ◽  
Rating Scale ◽  
Quality Data ◽  
Cochrane Library ◽  
Disease Rating ◽  
Stn Dbs ◽  
Deep Brain

AbstractBackground: Subthalamic nucleus deep brain stimulation (STN–DBS) has become a standard treatment for many patients with Parkinson’s disease (PD). The reported clinical outcome measures for procedures done under general anesthesia (GA) compared to traditional local anesthetic (LA) technique are quite heterogeneous and difficult to compare. The aim of this systematic review and metaanalysis was to determine whether the clinical outcome after STN–DBS insertion under GA is comparable to that under LA in patients with Parkinson’s disease. Methods: The databases of Medline Embase, Cochrane library and Pubmed were searched for eligible studies (human trials, English language, published between 1946 and January of 2016). The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson’s Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement. Results: The literature searches yielded 395 citations and six retrospective cohort studies with a sample size of 455 (194 in GA and 261 in LA) were included in the analysis. Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson’s disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups. Similarly, the adverse events and target accuracy were also comparable between the groups. Conclusions: This systematic review and meta-analysis shows that currently there is no good quality data to suggest equivalence of GA to LA during STN-DBS insertion in patients with PD, with some factors trending towards LA. There is a need for a prospective randomized control trial to validate our results.

scholarly journals Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Rene Molina ◽  
Chris J. Hass ◽  
Stephanie Cernera ◽  
Kristen Sowalsky ◽  
Abigail C. Schmitt ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Clinical Outcome ◽  
Brain Stimulation ◽  
Closed Loop ◽  
Group Analysis ◽  
Freezing Of Gait ◽  
Deep Brain

Background: Treating medication-refractory freezing of gait (FoG) in Parkinson’s disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS).Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

scholarly journals Combination Targeting of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Deep Brain Stimulation for Tremor-Dominant Parkinson's Disease: Experience and Outcomes

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Islam Fayed ◽  
Kelsey Diva Cobourn ◽  
Gnel Pivazyan ◽  
Fernando Pagan ◽  
Steven Lo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Thalamic Nucleus ◽  
Rating Scale ◽  
Case Reports ◽  
Outcome Data ◽  
Deep Brain

Abstract INTRODUCTION Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat the bradykinesia and rigidity of Parkinson's disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory to treat patients with tremor-dominant PD; yet, outcome data for this procedure remain sparse. METHODS We conducted a single-center retrospective review of all patients who underwent combined STN-VIM DBS. Demographic and outcome data, including Unified Parkinson Disease Rating Scale (UPDRS), changes in symptom severity, and levodopa equivalent daily dose (LEDD), were collected and analyzed. RESULTS Nineteen patients underwent combined STN-VIM trajectory DBS between January 2013 and April 2019. Patients were 90% male and 10% female, with an average age of 63.6 ± 12 yr. Average preoperative UPDRS was 24.2 and LEDD was 807.8. At an average follow-up of 23.9 mo, UPDRS and LEDD decreased by an average of 9.25 and 404.8, respectively. A total of 95% of our patients reported an improvement in tremor symptoms, and 58% were able to decrease the total medication burden. CONCLUSION Combined targeting of STN and VIM thalamus for tremor-dominant PD results in an excellent control of tremor symptoms, as well as a decrease in UPDRS and LEDD. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.

Preoperative Magnetic Resonance Image Quality in Motion Disorder Patients Scheduled for Deep Brain Stimulation Surgery

2020 ◽  
Vol 98 (6) ◽  
pp. 363-370
Author(s):  
Elsa M. Ronde ◽  
Marja Silvasti-Lundell ◽  
Johanna Pekkola ◽  
Minna Tallgren ◽  
Riku Kivisaari
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Magnetic Resonance ◽  
Image Quality ◽  
Clinical Outcome ◽  
Brain Stimulation ◽  
Mr Images ◽  
Mri Sequences ◽  
Deep Brain

<b><i>Background:</i></b> To obtain magnetic resonance (MR) images of good quality for accurate target localization in deep brain stimulation (DBS) surgery, sedation or anesthesia may be used, although their usefulness has not been proven. <b><i>Objective:</i></b> To assess whether sedation or general anesthesia (GA) improve the quality of MR imaging (MRI). <b><i>Methods:</i></b> The records of DBS procedures for Parkinson’s disease (PD), dystonia, and essential tremor in our tertiary neurosurgical unit between January 2011 and June 2016 were reviewed. Adult patients with preoperative MR images were included. Patient records concerning MRI, surgery, adverse events, and clinical outcome were retrospectively scrutinized and analyzed. MR image quality was assessed by two independent radiologists. <b><i>Results:</i></b> A total of 215 preoperative MR images for 177 DBS procedures were analyzed. The MRI sequences performed under GA were superior to those performed without anesthesia or under sedation (<i>p</i> &#x3c; 0.01). Virtually all images captured under GA were of good quality, while the proportions among those captured with sedation or without anesthesia were &#x3c;65%. Good image quality was not associated with better clinical outcome (&#x3e;50% improvement in the Unified Parkinson’s Disease Rating Scale III score) among patients with PD. <b><i>Conclusion:</i></b> GA was associated with better MRI sequences than intravenous sedation or no anesthesia.

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