Anatomy and physiology predict response to motor cortex stimulation after stroke

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.