Objective: Evaluate clinical and biomarker changes from spinal cord stimulation (SCS) in Parkinsons Disease (PD) under sham controlled randomized evaluation.

Background: SCS has been proposed as a promising treatment for PD motor and gait impairment [1], but so far only two blinded sham-controlled trials have been published both negative albeit small and heterogeneous [2,3]. Moreover, no study so far demonstrated changes in biomarkers from SCS. Considering functional magnetic imaging (FMRI) changes in PD and freezing of gait [4] we devised a study comparing clinical and imaging changes from SCS.

Method: Patients with PD diagnosis were selected for refractory gait disorders. A paddle electrode at T3-T4 level was used for stimulation. After a 6-month period of parameter optimization, patients were subjected to randomized double blinded cross over evaluations comparing three weeks of continuous active or sham stimulation. All evaluations included off and on medication status and used timed up and go, Movement Disorder Society Unified PD Rating Scale part III, Mini Balance Evaluation Systems Test, New Freezing of Gait Questionnaire, Fall Efficacy Scale International and PD Questionnaire 39. Resting state FMRI and connectivity analyses [5] were performed using 1.5 T imaging on both stimulation phases. Wilcoxon signed-rank test was used for clinical effects significance while tract based functional statistics and corrected for multiple comparisons [6].

Results: 8 patients were successfully implanted. Demographics and final stimulation parameters are exposed in table 1. All patients completed FMRI comparisons but due to health complications unrelated to SCS patient 8 was excluded from clinical evaluations. No significant effect was observed from SCS in either off or on medication status [table 2]. No significant difference was observed in corrected FMRI between stimulation settings. No notable alteration was detected in the fractional anisotropy of participants across sessions.

Conclusion: Direct randomized sham controlled and blinded comparison of subthreshold SCS led to no improvement in any outcomes or FMRI changes. With the paucity of controlled and blinded evaluations and no documented biomarker change from SCS this negative result should greatly heighten the need for further robust evidence for clinical use of SCS in PD.

Table 1

Table 2

References: [1] Opova K, Limousin P, Akram H. Spinal Cord Stimulation for Gait Disorders in Parkinson’s Disease. J Parkinsons Dis. 2023;13(1):57–70.
[2] Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, et al. Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology. 20 de abril de 2010;74(16):1325–7.
[3] Carra RB, da Costa Capato TT, Menezes JR, Barbosa ER, Duarte KP, Teixeira MJ, 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. 6 de outubro de 2023;9:100220.
[4] Filippi M, Sarasso E, Agosta F. Resting-state Functional MRI in Parkinsonian Syndromes. Mov Disord Clin Pract. 2019 Feb 8;6(2):104-117. doi: 10.1002/mdc3.12730. PMID: 30838308; PMCID: PMC6384182.
[5] Nieto-Castanon A. (2020). Handbook of functional connectivity magnetic resonance imaging methods in CONN. Boston, MA: Hilbert Press. doi: 10.56441/hilbertpress.2207.6598
[6] Smith SM, Jenkinson M, Johansen-Berg H, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006;31(4):1487-1505. doi:10.1016/j.neuroimage.2006.02.024

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-imaging-changes-in-parkinsons-disease-patients-under-spinal-cord-stimulation-a-double-blinded-analysis/