A Unifying Pathophysiological Account for Post-stroke Spasticity and Disordered Motor Control.

Cortical and subcortical plastic reorganization occurs in the course of motor recovery after stroke. It is largely accepted that plasticity of ipsilesional motor cortex primarily contributes to recovery of motor function, while the contributions of contralesional motor cortex are not completely understood. As a result of damages to motor cortex and its descending pathways and subsequent unmasking of inhibition, there is evidence of upregulation of reticulospinal tract (RST) excitability in the contralesional side. Both animal studies and human studies with stroke survivors suggest and support the role of RST hyperexcitability in post-stroke spasticity. Findings from animal studies demonstrate the compensatory role of RST hyperexcitability in recovery of motor function. In contrast, RST hyperexcitability appears to be related more to abnormal motor synergy and disordered motor control in stroke survivors. It does not contribute to recovery of normal motor function. Recent animal studies highlight laterality dominance of corticoreticular projections. In particular, there exists upregulation of ipsilateral corticoreticular projections from contralesional premotor cortex (PM) and supplementary motor area (SMA) to medial reticular nuclei. We revisit and revise the previous theoretical framework and propose a unifying account. This account highlights the importance of ipsilateral PM/SMA-cortico-reticulospinal tract hyperexcitability from the contralesional motor cortex as a result of disinhibition after stroke. This account provides a pathophysiological basis for post-stroke spasticity and related movement impairments, such as abnormal motor synergy and disordered motor control. However, further research is needed to examine this pathway in stroke survivors to better understand its potential roles, especially in muscle strength and motor recovery. This account could provide a pathophysiological target for developing neuromodulatory interventions to manage spasticity and thus possibly to facilitate motor recovery.