Anatomy and physiology predict response to motor cortex stimulation after stroke.

Abstract

Preclinical studies found that epidural motor cortex stimulation improved motor deficits after stroke, but a phase III trial in humans did not corroborate these results. The current retrospective analysis examined subjects randomized to stimulation in order to identify features distinguishing responders from nonresponders. Anatomic (MRI measures of gray matter thickness and of white matter tract injury) and physiologic methods (motor evoked responses) were examined as predictors of treatment response. Among 60 subjects randomized to cortical stimulation, both anatomic and physiologic measures at baseline predicted behavioral response to therapy. Anatomically, those achieving the primary efficacy endpoint had a smaller fraction of the corticospinal tract injured by stroke compared to those who did not (44% vs 72%, p < 0.04), and rarely had severe tract injury. Physiologically, the primary efficacy endpoint was reached more often (67%) by those with preserved motor evoked responses (MER) upon cortical stimulation compared to those lacking MER (27%, p < 0.05). Those with an elicitable MER also had a lower rate of precentral gyrus injury (0% vs 33%, p < 0.05) by stroke, as compared to those lacking MER, and had higher gray matter volume compared to those lacking MER in regions including ipsilesional precentral gyrus. In this clinical stroke trial, the more that the physiologic integrity of the motor system was preserved, the more likely that a patient was to derive gains from subsequent therapy, consistent with preclinical models. Functional and structural preservation of key brain substrates are important to deriving gain from a restorative therapy.