Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson's Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses

Abstract

Objectives: Evidence suggests that nonconventional programming may improve deep brain stimulation (DBS) therapy for movement disorders. The primary objective was to assess feasibility of testing the tolerability of several nonconventional settings in Parkinson's disease (PD) and essential tremor (ET) subjects in a single office visit. Secondary objectives were to explore for potential efficacy signals and to assess the energy demand on the implantable pulse-generators (IPGs).

Materials and methods: A custom firmware (FW) application was developed and acutely uploaded to the IPGs of eight PD and three ET subjects, allowing delivery of several nonconventional DBS settings, including narrow pulse widths, square biphasic pulses, and irregular pulse patterns. Standard clinical rating scales and several objective measures were used to compare motor outcomes with sham, clinically-optimal and nonconventional settings. Blinded and randomized testing was conducted in a traditional office setting.

Results: Overall, the nonconventional settings were well tolerated. Under these conditions it was also possible to detect clinically-relevant differences in DBS responses using clinical rating scales but not objective measures. Compared to the clinically-optimal settings, some nonconventional settings appeared to offer similar benefit (e.g., narrow pulse widths) and others lesser benefit. Moreover, the results suggest that square biphasic pulses may deliver greater benefit. No unexpected IPG efficiency disadvantages were associated with delivering nonconventional settings.

Conclusions: It is feasible to acutely screen nonconventional DBS settings using controlled study designs in traditional office settings. Simple IPG FW upgrades may provide more DBS programming options for optimizing therapy. Potential advantages of narrow and biphasic pulses deserve follow up.

Keywords: Biphasic pulses; Parkinson's disease; deep brain stimulation; essential tremor; irregular patterns; narrow pulse width.

Figure 1

Standard DBS devices deliver change‐balanced pulses with a passive recharge (a, left, arrow). The research programmer system was used to deliver biphasic pulses which were charge balanced with a square‐wave active recharge (a, right). The research system was capable of delivering pulse widths as low as 10 µs. Standard DBS devices deliver change‐balanced pulses with a passive recharge (a, left, arrow) (b), and was used to deliver pulse widths 50% shorter than the clinically‐optimal settings. The research system was also used to deliver irregular patterns of stimulation (c), which were the same average stimulation frequency as the clinically‐optimal settings but exhibited an overall 20% coefficient of variance (CV).

Figure 2

Grouped PD UPDRS‐III (a), Kinesia (b–d), TUG (e), and Gait Rite (f) data expressed as the median delta relative to the median value during clinical DBS. The box represents the inter‐quartile range, the whiskers represent the spread, the line represents the median and the dots represent outliers. Data were analyzed in pairs using the nonparametric Wilcoxon‐Mann‐Whitney U‐test, comparing the median delta during DBS OFF to the median deltas during the nonconventional DBS settings. Sample sizes ranged from n = 5–7 because not all of the PD subjects were tested during each nonconventional setting. Sample sizes and approximated p values are listed at the bottom of each box (n, p).

Figure 3

The estimated amount of battery drain associated with each DBS setting. Data are expressed as the average ± SEM current drain across all 11 PD and ET subjects participating in the study for the entire series of settings tested, including the clinically‐optimal DBS settings (ClinDBS) delivered using the commercial IPG FW (cFW) and also with the research FW (rFW). Data were analyzed using a paired Students t test, comparing the current drain with clinically‐optimal DBS settings delivered using the cFW to the current drain with each nonconventional setting. *p < 0.05, **p < 0.01, ***p < 0.001.