TY - JOUR
T1 - Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery
T2 - 1-year follow-up study of safety, feasibility, and clinical outcome
AU - Van Horne, Craig G.
AU - Quintero, Jorge E.
AU - Slevin, John T.
AU - Anderson-Mooney, Amelia
AU - Gurwell, Julie A.
AU - Welleford, Andrew S.
AU - Lamm, John R.
AU - Wagner, Renee P.
AU - Gerhardt, Greg A.
N1 - Publisher Copyright:
© AANS 2018 except where prohibited by US copyright law
PY - 2018
Y1 - 2018
N2 - OBJECTIVE Currently, 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. METHODS Standard 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. RESULTS All 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. CONCLUSIONS Peripheral 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.
AB - OBJECTIVE Currently, 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. METHODS Standard 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. RESULTS All 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. CONCLUSIONS Peripheral 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.
KW - Cell therapy
KW - Deep brain stimulation
KW - Functional neurosurgery
KW - Multimodal DBS
KW - Neurotrophic factor
UR - http://www.scopus.com/inward/record.url?scp=85059496434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059496434&partnerID=8YFLogxK
U2 - 10.3171/2017.8.JNS163222
DO - 10.3171/2017.8.JNS163222
M3 - Article
C2 - 29451447
AN - SCOPUS:85059496434
SN - 0022-3085
VL - 129
SP - 1550
EP - 1561
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
IS - 6
ER -