Discussion
post-stroke, physical disability, reduction of motor impairment, chronic post-stroke hemiparesis, post-stroke motor impairment, disability
SECONDARY, PHYSICAL DISABILITY
Data from this phase I trial of 12 individuals with chronic, moderate-to-severe post-stroke motor impairment support the safety and feasibility of chronic stimulation of the ascending cerebellothalamocortical pathway. Furthermore, it provides an in-human demonstration of significant and clinically meaningful effects of DN-DBS combined with rehabilitation on motor impairmentStroke remains the leading cause of physical disability in the industrialized world, with post-acute care costs exceeding those of acute hospital careWe observed significant and meaningful benefits in the form of both a reduction of motor impairment and gains in motor function in this cohort. It is noteworthy that these improvements were achieved: (1) in patients with overall poor function at enrollment, evidenced by a mean FM-UE of 22.9 points, and deemed to have poor natural prognosis and (2) after participants underwent a 3-month period of supervised rehabilitation aimed at minimizing the impact of renewed rehabilitation alone on impairment and function. In line with prior reportsGiven our prior animal model evidence that potentiation of corticomotor excitability and ipsilesional reorganization mediates the therapeutic effects of DN-DBSThe study has limitations inherent to an early stage, Phase 1 investigation. Overall interpretation of the data presented is limited by the open-label nature of the design, the heterogeneity in baseline impairment level across the sample population, and, finally, the limited size of that same sample that are typical of a phase I neurological device trial. The latter two issues likely contributed to the lack of observed effects on several of the additional secondary measures applied, including the Nine-Hole Peg Test, the Bilateral Box and Block Test and the EQ-5D. Next, although we made some effort to overcome confounds related to chronic physical deconditioning before initiating DBS by including a rehabilitation-only phase, we are not able to distinguish, with certainty, the effects of rehabilitation from the effects of DBS. This is particularly the case given that structured rehabilitation has been shown to result in meaningful improvements even in chronic post-stroke stagesIn summary, this phase I study presents the first evidence of safety and feasibility of DN-DBS in individuals with chronic post-stroke hemiparesis with encouraging rehabilitative effects and associated neurophysiological gains observed across the DBS + rehab phase. This emerging intervention has shown translational potential to modulate the magnitude of neuroplastic reorganization toward recovery of function and to extend its time window to late phases of disability.