Illustrated overview of dentatothalamocortical pathway depicting a single deep brain stimulation lead implanted in the left dentate nucleus (brown).
stroke, upper-extremity motor impairment, impaired post-stroke, disability, upper-extremity impairment
ADVERSE EVENTS, STROKE, EVENT, CEREBRAL ISCHEMIA, SECONDARY, CORTEX
The crossed dentatothalamic projections (blue in upper-left illustration) terminate across multiple contralateral thalamic (green) nuclei that, in turn, project (orange), to broad regions of cerebral cortex. The dentatothalamocortical pathway represents the ascending component of a robust, reciprocal loop interconnecting the cerebral cortex with the contralateral cerebellar hemisphere. DN is shown in brown. RN, red nucleus; PN, pontine nuclei.Here we report a first-in-human translation of this research in a group of 12 stroke survivors with persistent, moderate-to-severe upper-extremity impairment. In this open-label, phase I clinical trial, we evaluated the safety and feasibility of surgical implantation and chronic DBS of the cerebellar DN. Overall, we found that our surgical approach and chronic stimulation was feasible and well tolerated in the target population, with no study-related serious adverse events encountered across the trial. Additionally, participants underwent a battery of secondary assessments to begin to characterize and understand the effect of therapy on upper-extremity motor impairment and function. We report significant improvements in motor function across all individuals who, at the time of enrollment, had even minimal residual distal motor function in the affected upper extremity and correlated effects on cortical metabolism. Of particular interest to stroke survivors, the magnitude of benefit was not found to depend on time after stroke, with robust improvements observed in participants who enrolled as late as 3 years after their index event. These early findings support that this new neuromodulation-based approach is safe and feasible in a moderately-to-severely impaired post-stroke population and shows promise for promoting recovery of function and influencing neuroplastic processes after cerebral ischemia, even in the later stages of disability.