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

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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.

Clinical trial registration no.: NCT01833364 (clinicaltrials.gov)

ABBREVIATIONS CID = clinically important difference; DBS = deep brain stimulation; DSMB = Data Safety Monitoring Board; GDNF = glial cell–derived neurotrophic factor; LED = levodopa equivalent dose; PD = Parkinson’s disease; ROI = region of interest; STN = subthalamic nucleus; SWI = susceptibility-weighted imaging; UPDRS = Unified Parkinson’s Disease Rating Scale.

Article Information

Correspondence Craig G. van Horne: University of Kentucky, Lexington, KY. craigvanhorne@uky.edu.

INCLUDE WHEN CITING Published online February 16, 2018; DOI: 10.3171/2017.8.JNS163222.

Disclosures This work was supported by gifts from the Brain Restoration Center, Tom Dupree for Parkinson’s Disease Research, and Pro’s Players Fore Parkinson’s.

Dr. Gerhardt: previously received research support from Medtronic. Dr. Slevin: received educational support grants from Medtronic. Dr. van Horne: received educational support grants from Medtronic.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Axial T2-weighted MR images obtained at 12 months in all participants, showing the area targeted for graft implantation (arrows). Asterisks indicate DBS electrode locations. Figure is available in color online only.

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    Individual changes in motor scores (UPDRS part III) while off DBS and off medication therapy from baseline to 12 months after surgery. Minimal (2.5 points), moderate (5.2 points), and large (10.8 points) CIDs are indicated. Each symbol represents a different participant. Figure is available in color online only.

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    For each of the domains of the UPDRS part III test, the total change in points for all participants was combined. The changes in the scores for all participants who performed worse in each domain were combined, and the changes in scores for all participants who showed improvements in each domain were combined.

  • View in gallery

    Lateralized scores on the UPDRS part III test were used to identify differences in motor performance on the side contralateral or ipsilateral to graft placement. The changes in the scores of all participants who performed worse on the lateralized test were combined, and the changes in scores of all participants who showed improvements on the lateralized test were combined. Lateralized scores include tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements, rapid alternating movements of the hand, and leg agility.

  • View in gallery

    Mean and SD (error bars) LEDs were significantly lower at 12 months postoperatively than before surgery. L-DOPA = levodopa.

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