Objective: To investigate the use of anodic prepulses in essential tremor (ET) patients treated with deep brain stimulation (DBS).

Background: Since the inception of DBS, cathodic pulses have been used¹. Modelling studies suggests that anodic prepulses may influence the therapeutic window².

Method: Anodic prepulses (i.e. pulses preceding the standard cathodic pulse) of variable width (240 and 360 µs) and strength (50% (low), 100% (mid) and 150% (high) of the charge of the standard cathode at efficacy threshold) were tested in a double-blinded and randomized design. The shape of the prepulse was kept fixed, while the cathodic phase (60 µs) was titrated up until the therapeutic window (TW) was found. The TW was calculated as the difference between the minimal amplitude causing stimulation-induced side effects (UpperTW) and the minimal amplitude inducing tremor arrest while performing a finger-to-nose test (LowerTW). A linear model was used to predict the effect of pulse width and amplitude on UpperTW and LowerTW. The difference between pulses of UpperTW, LowerTW and TW, was calculated with a Wilcoxon signed rank test, Bonferroni-corrected.

Results: Eight ET patients participated in this study. All patients performed 3 repetitions of the assessment. In 1 patient, only the prepulses of 240 µsec were tested. A linear increase of the UpperTW was seen with increasing amplitude of the 240 µs prepulses (slope 0.39, R = 0.87, p = 0.04). A similar, although weaker, effect was observed on the LowerTW (slope 0.30, R = 0.90, p = 0.10). The 360 µs prepulses also showed a linear relation to the cathodic phase for the UpperTW (slope 1.04, R = 0.80, p < 0.01) and, to a lesser extent, the LowerTW (slope 0.65, R = 0.86, p = 0.02) (Figure 1). Furthermore, the TW of 240 low was significantly enlarged (p < 0.05) due to an increase in UpperTW (Figure 2).

Conclusion: Anodic prepulses influence the TW, mostly by increasing the UpperTW in a linear fashion. The biophysical basis for this effect needs to be further explored. Further work is needed to determine if these pulses can bring clinical benefit compared to standard cathodic pulses.

References: 1. Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403-406. doi:10.1016/0140-6736(91)91175-T LK – L 2. Grill WM, Mortimer JT. The effect of stimulus pulse duration on selectivity of neural stimulation. IEEE Trans Biomed Eng. Published online 1996. doi:10.1109/10.481985

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