Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study

Background Conventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. Objectives The current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. Methods This pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. Results There was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5–35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8–24.3) at ClinDBS setting and to (16.5 IQR = 12–20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ ² = 16.1, p = 0.006), posture (χ ² = 15.9, p = 0.007) and with action (χ ² = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. Conclusion BiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required.