1
7. Adverse Effects Peripheral nerve graft implants into the substantia nigra of subjects with Parkinson’s disease undergoing deep brain stimulation surgery: a safety study Jorge E. Quintero 1* , Wissam S.Z. Asfahani 2 , Fariha Zaheer 3 , Julie A. Gurwell 3 , Greg A. Gerhardt 1,2,3 , John T. Slevin 3 , Craig G. van Horne 1,2 1 Department of Anatomy & Neurobiology, 2 Department of Neurosurgery, 3 Department of Neurology University of Kentucky, Lexington, KY USA 1. Introduction In Parkinson’s disease (PD), the substantia nigra undergoes a loss of dopaminergic cells and cellular function. Previous studies have shown that neurotrophic factors including GDNF, BDNF, and NT-3 can promote dopaminergic function. We have begun a Phase I clinical trial 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. The Schwann cells in the graft may serve as an alternative source of the growth factors GDNF, NGF, BDNF, and NT-3. 3. Methods Participant profile: • Average age = 59.5 • 4 males, 1 female. • Progressive Idiopathic PD >5 yrs • Medication responsive with motor fluctuations • Cognitively intact • Met criteria for DBS surgery 2. Goal • Examine safety and side effect profile from implanting peripheral nerve tissue into the substantia nigra during DBS surgery. • Test potential clinical response. P527.07 8. Summary • Peripheral nerve graft surgery successfully completed in 5 of 5 participants. • Adverse events comparable to reported effects with DBS surgery. • Average medication levels decreased after 3 months. • Motor scores OFF medication and OFF stimulation improved after 3 months. 9. Future Work •Examine safety and feasibility of bilateral nerve graft implants to the substantia nigra. •Examine efficacy of nerve graft implant on motor and non-motor symptoms. 4. DBS surgery provides an avenue for delivering peripheral nerve graft to substantia nigra 5. Off-treatment motor scores improving three months after graft implant Motor scores were compared Off stimulation/Off medication and On stimulation and On medication. Additionally, lateralized scores on UPDRS Part III were compared. Baseline evaluations: • Unified Parkinson Disease Rating Scale (UPDRS) on and off medication, • Quality of life rating (PDQ-8), • Formal neuropsychological evaluation • Treat to best patient response 1, 3, 6, 9, 12 months: • UPDRS evaluations on/off stimulation 10. Acknowledgements Support provided by University of Kentucky start-up funds (CVH) and CTSA-UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosure: CVH receives educational support grant through Medtronic. 6. Imaging results Subject No. Adverse Event Status Relatedness 1 Urinary retention Resolved procedure 2 hypomania Resolved Stimulation 3 none N/A N/A 4 Superficial cellulitis Resolved procedure 5 Cough headache Resolved Resolved Not related DBS surgery UPDRS scores show improvement 3 months after graft implantation. N=4, paired-t-test Stage II A) Awake, CRW Frame based surgery B) Microelectrode recordings C) Test stimulations D) Implantation of stimulating electrodes. DBS electrode and graft placement evaluated with 1.5T MRI. Reversed two stage procedure to implant DBS system Stage I Implantation of DBS hardware and sural nerve preparation. Graft harvesting, loading and implantation of graft during Stage II Harvesting of sural nerve tissue Implantation of graft Target: substantia nigra, 1-6mm below base of subthalamic nucleus Trajectory: 3mm posterolateral to DBS based on visual targeting Motor Exam On and Off Medication and Stimulation UPDRS III -- Off/Off Baseline 3 Months 0 10 20 30 40 50 60 p = 0.02 Individual motor scores Part I UPDRS Score 0 2 4 6 p = 0.03 Part II UPDRS Score 0 5 10 15 20 25 p = 0.02 Baseline 3 Months Part IV UPDRS Score 0 2 4 6 8 10 p = 0.02 Daily L-Dopa Equivalents L-Dopa equivalents (mg) Baseline 3 months 0 500 1000 1500 2000 N.S.
![7 0 4 . T h e R i c k T h o m p s o n R e p o r t : B r e x i t U p ......[ 0 0 : 0 0 : 5 9 ] H e l l o [ 0 0 : 0 1 : 0 0 ] e ve r yo n e . I h o p e yo u ' r e d o i n g w e l l t](https://static.documents.pub/doc/80x56/61391ab9a4cdb41a985b7daf/7-0-4-t-h-e-r-i-c-k-t-h-o-m-p-s-o-n-r-e-p-o-r-t-b-r-e-x-i-t-u-p-0.jpg)
