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 non-conventional programming may improve deep brain stimulation (DBS) therapy for movement disorders. The primary objective was to assess feasibility of testing the tolerability of several non-conventional 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 (IPG). Materials and Methods A custom firmware (FW) application was developed and acutely uploaded to the IPGs of 8 PD and 3 ET subjects, allowing delivery of several non-conventional 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 non-conventional settings. Blinded and randomized testing was conducted in a traditional office setting. Results Overall, the non-conventional 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 non-conventional 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 non-conventional settings. Conclusions It is feasible to acutely screen non-conventional 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.

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

“…While there are some irregular patterns that seem to be as effective as—or more effective than—regular HFS, evidence for human testing remains limited. A recent randomized, blinded pilot study of nonconventional DBS patterns and pulses—the first reported study of its kind—tested 3 essential tremor and 8 PD clinically-optimized patients in a clinic setting (Akbar et al, 2016). Of the settings tested, the nonconventional biphasic pulse (equal and opposite, active recharge phase) was shown to be more effective than the clinically optimized settings.…”

A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study

“…DBS was delivered utilizing a custom temporary downloadable firmware compatible with Medtronic Activa neurostimulators (Medtronic Neuromodulation), using the previously published protocol by Akbar and colleagues . The parameters were based on chronic settings, and the stimulation mode was modified from the standard passive‐recharge biphasic to the sqBIP pulse shape, except for dual‐channel devices with different settings for each of the leads (i.e., attributed to technical limitations from the software the investigator adopted the lowest of the 2 settings to ensure patient safety).…”

“…In a recent study, Akbar and colleagues investigated several novel stimulation parameters in essential tremor (ET) and Parkinson's disease (PD) patients using a blinded, randomized design. The researchers reported that square biphasic (sqBIP) pulses (with active rather than passive charge‐balancing phase) were well tolerated and provided a greater clinical benefit when compared to continuous commercially available DBS.…”

An update on adaptive deep brain stimulation in Parkinson's disease

“…Also, pulse‐width modulation might provide clinical benefit in certain situations. By exciting thin axon bundles belonging to the direct cortico‐subthalamic pathway more selectively, therapeutic windows may increase using shorter pulse widths, while using less energy …”