Preclinical and Clinical Evidence on Ipsilateral Corticospinal Projections: Implication for Motor Recovery

Abstract

Motor impairment is the most common complication after stroke, and recovery of motor function has been shown to be dependent on the extent of lesion in the ipsilesional corticospinal tract (iCST) and activity within ipsilesional primary and secondary motor cortices. However, work from neuroimaging research has suggested a role of the contralesional hemisphere in promoting recovery after stroke potentially through the ipsilateral uncrossed CST fibers descending to ipsilateral spinal segments. These ipsilateral fibers, sometimes referred to as “latent” projections, are thought to contribute to motor recovery independent of the crossed CST. The aim of this paper is to evaluate using cumulative evidence from animal models and human patients on whether an uncrossed CST component is present in mammals and conserved through primates and humans, and whether iCST fibers have a functional role in hemiparetic/hemiplegic human conditions. This review highlights that an ipsilateral uncrossed CST exists in human during development, but the evidence on a functionally relevant iCST component in adult humans is still elusive. In addition, this review argues that whereas activity within the ipsilesional cortex is essential for enhancing motor recovery after stroke, the role of iCST projections specifically is still controversial. Finally, conclusions from current literature emphasize the importance of activity in the ipsilesional cortex and the integrity of crossed CST fibers as major determinants of motor recovery after brain injury.

Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke

“…This neurophysiological deficit was significantly ameliorated by the combined cell/ CTZ therapy, suggesting a novel cell-based rehabilitation strategy, particularly for restoration of damaged neuronal connectivity. Overall, the present investigation supports and successfully demonstrates the importance of activity in the integrity and functional repair of neuronal connections in sensorimotor recovery after brain injury (Alawieh et al, 2017).…”

The unsolved role of heightened connectivity from the unaffected hemisphere to paretic arm muscles in chronic stroke

“…Instead, arm function is closely related to the integrity of contralateral projections. This therefore suggests that control of these proximal arm muscles after stroke is similar to that of distal muscles in which many reports have shown that functional recovery is tightly linked to the integrity of the crossed corticospinal tract (Alawieh et al, 2017;Byblow et al, 2015;Ward et al, 2006). It differs from what has been reported in axial muscles, in which the presence of ipsilateral responses after stroke is related to increased trunk control (Bradnam et al, 2011;Turton et al, 1996;Misawa et al, 2008;Tsao et al, 2008;Matthews et al, 2013).…”

“…Recovery from motor stroke depends upon the presence of functional connections between the cortex and the spinal cord (Byblow et al, 2015;Ward et al, 2006;Netz et al, 1997;Lemon, 2008b). However, the relative role and importance of connections from the lesioned hemisphere versus those from the non-lesioned hemisphere is still unclear (Buetefisch, 2015;Bradnam et al, 2013;Alawieh et al, 2017;Dodd et al, 2017). In rodent models a large body of evidence has shown that recovery following a cortico-subcortical lesion on one side is accompanied by intraspinal sprouting of connections from pathways originating from the non-lesioned hemisphere (Rouiller et al, 1991;Krakauer et al, 2012;Biernaskie et al, 2005).…”

Outcome in Stroke Patients Is Associated with Age and Fractional Anisotropy in the Cerebral Peduncles: A Multivariate Regression Study

“…Accordingly, in terms of clinical significance, the role of ipsilateral (contralesional) corticospinal projections in motor recovery remains unclear. 35) Clinical severity in the initial phase of stroke is another important determinant of long-term outcome. 3,36,37) We previously reported that the National Institutes of Health Stroke Scale score 38) during the acute phase can predict the extent of FIM-motor recovery.…”