Objective: Investigate STN local field potential (LFP) changes in a patient with PD during spinal cord stimulation (SCS).

Background: SCS is explored as a possible treatment for PD notably for axial symptoms refractory to dopaminergic drugs and DBS [1,2]. Preclinical studies in parkinsonian primates [3] and mice [4] demonstrated a reduction of beta band (β) neuronal activity during SCS, frequency range related to PD’s bradykinesia in humans [5,6]. No human studies demonstrated this effect which is concerning with recent negative trials [7,8].

Method: A patient implanted with SCS evolved with DBS indication due to refractory tremor. She was selected for LFP of STN recording performed through DBS surgery. SCS was done with a paddle electrode at T2-T4 level, with six 60 seconds stimulation trials. The first four used a pulse width of 300ms and increasing currents at 40%, 90%, 110% paresthesia inducing threshold, and maximum tolerated intensity, while the fifth and sixth used 60ms with 90% of threshold and maximum tolerated intensity. Stimulation frequency was fixed at 300 hz. A pre-stimulation baseline of 60 seconds and 120 seconds washout records were used for comparison. Motor symptoms were assessed at surgery and 2 weeks later through supine MDS-UPDRS III [9]. Statistics of On and Off stimulation periods were performed by paired t tests. Relevance of effect size differences was calculated through paired samples Cohens’d and subjected to Hedges correction due to small sample. This study was approved by the local ethics committee and the patient provided informed consent.

Results: The patient was a 70 years old woman, with 20 years of PD and 2 years of SCS therapy. We observed a change of LFP [figure 1 and 2] comparing the effects on frequency averaging all stimulation and no stimulation recordings [Table 1]. There was an average reduction of -6% low β and 26,15% increase in gamma range during active stimulation, but without statistically significant differences. No clinical change was seen.

Conclusion: This study is the first to analyze LFP effects of SCS in a human. We observed a suppression of LFP β power during SCS stimulations culminating in a 47% relative reduction with 60ms and 10.6mA. Our final conclusion is that we could not replicate the clinical benefit nor the LFP effects from animal studies yet. It is possible that SCS for PD in humans require more specific devices and parameters.

LFP power in STN normalized spectrograms

A.Consecutive baselines. B.First baseline period.

Cohen effect size analysis.

References: 1. Yadav AP, Nicolelis MAL. Electrical stimulation of the dorsal columns of the spinal cord for Parkinson’s disease. Mov Disord. 2017;32(6):820–32.

2. Cury RG, Moro E. New developments for spinal cord stimulation. In: Int Rev Neurobiol. 2021;159:129-151.

3. Santana MB, Halje P, Simplício H, Richter U, Freire MAM, Petersson P, et al. Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease. Neuron. 2014;84(4):716–22.

4. Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson’s disease. Science 2009;323(5921):1578-1582.

5. Tinkhauser G, Pogosyan A, Tan H, Herz DM, Ku€hn AA, & Brown P (2017). Beta burst dynamics in Parkinson’s disease OFF and ON dopaminergic medication. Brain, 140(11), 2968–2981.

6. Neumann WJ, Staub-Bartelt F, Horn A, Schanda J, Schneider GH, Brown P, et al. (2017). Long term correlation of subthalamic beta band activity with motor impairment in patients with Parkinson’s disease. Clinical Neurophysiology, 128(11), 2286–2291.

7. Nicolelis MA, Fuentes R, Petersson P, Thevathasan W, Brown P. Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology. 2010;75(16):1484-1485. doi:10.1212/WNL.0b013e3181f46f10

8. Carra RB, da Costa Capato TT, Menezes JR, et al. Long-term tonic spinal cord stimulation in advanced Parkinson’s disease: No effect from stimulation under placebo-controlled evaluation. Clin Park Relat Disord. 2023;9:100220. Published 2023 Oct 6. doi:10.1016/j.prdoa.2023.100220

9. Kremer NI, Smid A, Lange SF, Mateus Marçal I, Tamasi K, van Dijk JMC, van Laar T, Drost G. Supine MDS-UPDRS-III Assessment: An Explorative Study. J Clin Med. 2023 Apr 25;12(9):3108. doi: 10.3390/jcm12093108. PMID: 37176549; PMCID: PMC10179103.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subthalamic-local-field-potential-monitoring-in-parkinsons-disease-during-epidural-electric-spinal-cord-stimulation/