*Article* **Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy**

**I. Daria Bogdan 1,2, Teus van Laar 1,\*, D.L. Marinus Oterdoom 2, Gea Drost 1,2, J. Marc C. van Dijk 2 and Martijn Beudel 3**


Received: 21 May 2020; Accepted: 9 June 2020; Published: 14 June 2020

**Abstract:** The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive e fforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters' voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO's), including the occurrence of side-e ffects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer *p* = 0.02, PRO *p* = 0.02) and sustained (*p* = 0.01) tremor suppression compared to baseline was achieved. Less side-e ffects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial e ffect on stimulation-related complications.

**Keywords:** DBS; tremor; stimulation parameters; DBS programming algorithm; DBS side e ffects; thalamic nucleus; zona incerta
