EPV027 - DEEP BRAIN STIMULATION OF THE CEREBELLAR DENTATE NUCLEUS TO ENHANCE CHRONIC, POST-STROKE MOTOR REHABILITATION: PRELIMINARY OUTCOMES AND ELECTROPHYSIOLOGICAL CORRELATES OF THERAPEUTIC PARAMETER SELECTION (ID 461)
- Kenneth B. Baker, United States of America
- Kenneth B. Baker, United States of America
- Raghavan Goplalakrishnan, United States of America
- Andre G. Machado, United States of America
Abstract
Introduction
Cerebellar pathways are increasingly being targeted using both non-invasive and invasive neurostimulation-based approaches for the treatment of neurologic disease. Our on-going clinical trial is investigating deep brain stimulation (DBS) of the cerebello-thalamo-cortical (CTC) pathway as an approach to enhance post-injury rehabilitation by means of perilesional facilitation and promotion of cerebral cortical plasticity. In addition to the safety and efficacy of that work to date, we will present electrophysiological features of the cerebellar dentate nucleus (DN) in relation to motor behavior as well as the scalp EEG correlates of DN DBS that hold promise for guiding therapeutic programming for this novel treatment approach.
Methods/Materials
Patients with chronic (>1yr) post-MCA-stroke, moderate-to-severe upper extremity motor deficits underwent implantation of an 8-channel DBS lead targeting the contralesional DN. The Fugl-Meyer Assessment for upper extremity (FMA-UE) was recorded monthly over the 14–18-month trial, within which participants received up to eight months of DN DBS. Electrophysiological data were recorded at specific trial stages, including combined local field potential (LFP), scalp EEG, and electromyography (EMG) recordings made during 1) intra-operative lead placement, 2) peri-operative DBS lead externalization, and 3) DBS programming. During the latter two session types, electrophysiological data were recorded 1) at rest, 2) in relation to motor task performance, and 3) in response to low-frequency activation of the CTC pathway.
Results
Twelve patients have undergone device implantation. Of those, 10 have completed the treatment phase, with 7 achieving a >4.5-point improvement in FMA-UE scores (i.e., therapeutic responder). Moreover, five of seven participants with minimally-preserved hand function at study entry showed a mean FMA-UE improvement of 10.5 points. DN LFPs have revealed DBS contact-specific changes in alpha- and beta-band power during visuomotor task performance with the affected upper extremity. DBS-evoked activation of the DTC pathway, observed by time-lock averaging the EEG/EMG recordings to stimulus delivery, elicited multi-phasic responses maximal over contralateral frontal cortex, including peaks discernible as early as 8ms post-stimulation.
Discussion
Our preliminary, open-label results support DN DBS as a promising emerging therapy for patients with post-stroke hemiparesis, while electrophysiology-based metrics show promise for guiding lead placement and therapeutic stimulation parameters.
Conclusions
Novel, neuromodulation-based treatment approaches continue to hold potential to mitigate persistent post-injury deficits associated with acquired brain injuries. Our electrophysiology data support the potential development of novel biomarkers that may facilitate DBS programming in applications where acute, readily-appreciable behavioral changes are not seen.
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