Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor.

BACKGROUND: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET). OBJECTIVE: To compare the DBS effect of shorter pulse width at 40 µs (DBS-40 µs) to conventional pulse width at 60 µs (DBS-60 µs) on the therapeutic window in ET patients. METHODS: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 µs and DBS-60 µs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width. RESULTS: DBS-40 µs showed a significantly larger therapeutic window than DBS-60 µs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 µs and DBS-60 µs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 µs compared to DBS-60 µs. CONCLUSIONS: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window.