Chronic embedded cortico-thalamic closed-loop deep brain stimulation for the treatment of essential tremor

Effective tremor suppression in ET with half the energy requirements was achieved by on-demand DBS based on real-time cortical sensing. Reducing tremor on-demand Deep brain stimulation (DBS) has been shown to be effective for treating movement disorders, including essential tremor (ET). Most stimulators work in open-loop mode, applying continuous stimulation with no consideration of patients’ symptoms. Now, Opri et al. developed a closed-loop system for thalamic DBS (CL-DBS) and tested in three patients with ET. CL-DBS delivered the therapeutic stimuli based on upper limb motor activity detected with a cortical electrode. The system was as effective as the open-loop stimulation while preserving energy. The results suggest that CL-DBS could save energy and possibly reduce side effects associated with continuous DBS. Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal (6 months) within-subject crossover protocol (DBS OFF, OL-DBS, and CL-DBS). Most patients with ET experience involuntary limb tremor during goal-directed movements, but not during rest. Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulation amplitude based on patient-specific motor behavior, suppressing the pathological tremor on-demand based on a cortical electrode detecting upper limb motor activity. Here, we demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal and distal posture, water pouring, and writing) while having a consistent reduction in energy delivery. The proposed paradigm is an important step toward a behaviorally modulated fully embedded DBS system, capable of delivering stimulation only when needed, and potentially mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device replacement.