Spinal Cord Stimulation for Very Advanced Parkinson's Disease: A 1‐Year Prospective Trial

Lately, there has been increasing interest in spinal cord stimulation (SCS) for Parkinson’s disease (PD) based on initial observations in patients who underwent SCS for pain and more recent 6-month studies in pain-free PD patients with or without deep brain stimulation. This open-label pilot study assessed the safety and efficacy of SCS in 6 pain-free patients (3 men aged 31–76 years; PD duration: 12–18 years) with significant axial symptoms (Hoehn and Yahr stage: 4.1 1.1); see Supplemental Table 1. Patients underwent the implantation of 2 cylindrical 8-contact electrodes at the T10 level and were prospectively followed for 1 year. Study procedures are detailed in the Supplementary Material online. In contrast with previous studies, patients were stimulated with an amplitude subthreshold for paresthesia to partly avoid a placebo response. However, after we learned about the positive effect by Samotus et al, we also tried high settings causing paresthesia during the last month of the trial. No adverse events except for transient postoperative delirium in 1 patient was reported. Figure 1 shows the individual outcomes in terms of total motor score and axial subscore of the Unified Parkingson’s Disease Rating Scale (UPDRS) as well as the freezing of gait (FOG) questionnaire (see Supplementary Material online for details). No effect of SCS was noted, particularly for the medication on condition, that is, no synergistic effect of SCS and L-dopa was detected. Group-level effects on medication off scores are depicted in Supplementary Figure 1. No other acute or chronic significant differences were observed in terms of UPDRS I–IV, Push and Release test, Tinetti Balance Assessment Tool, Parkinson’s Disease Questionnaire 39, Schwab and England Scale, Hoehn and Yahr stage or gait analysis parameters (Supplementary Tables 2 and 3). Despite the remarkable improvement reported in the rat and primate model treated with SCS and promising outcomes reported in short, small, and open-label PD studies, our study confirms safety but shows no clinically meaningful effect on patients’ mobility, particularly while on L-dopa, thus failing to improve the motor signs resistant to dopaminergic treatment (videos 1–3). Taking all published SCS studies together, a variety of inclusion criteria, stimulating parameters, and hardware were chosen, without a clear association between these features and the outcome. Noteworthy, most positive studies enrolled pain patients, whereas the effects seen in pain-free patients mainly involved parameters known to be sensitive to placebo, such as balance confidence, gait velocity, and FOG. In fact, these studies were not blinded and used stimulating parameters causing paresthesia. Of note, preclinical studies did not detect the best combination of stimulating parameters because any type would improve locomotion, even in control animals. In contrast with the existing literature, we decided to operate on advanced cases. Our study has other limitations, particularly the unblinded assessment and the small sample size. Nevertheless, ours is the largest and longest prospective trial in pain-free PD patients.