Motor tract integrity predicts walking recovery: A diffusion MRI study in subacute stroke.

OBJECTIVE: To identify candidate biomarkers of walking recovery with motor tract integrity measurements using fractional anisotropy (FA) from the corticospinal tract (CST) and alternative motor pathways in patients with moderate to severe subacute stroke. METHODS: Walking recovery was first assessed with generalized linear mixed model (GLMM) with repeated measures of walking scores (WS) over 2 years of follow-up in a longitudinal study of 29 patients with subacute ischemic stroke. Baseline FA measures from the ipsilesional and contralesional CST (i-CST and c-CST), cortico-reticulospinal pathway (i-CRP and c-CRP), and cerebellar peduncles were derived from a 60-direction diffusion MRI sequence on a 3T scanner. We performed correlation tests between WS and FA measures. Third, we investigated using GLMM whether motor tract integrity contributes to predict walking recovery. RESULTS: We observed significant improvements of WS over time with a plateau reached at ≈6 months after stroke. WS significantly correlated with FA measures from i-CST, c-CST, i-CRP, and bilateral cerebellar peduncles. Walking recovery was predicted by FA measures from 3 tracts: i-CST, i-CRP, and contralesional superior cerebellar peduncle (c-SCP). Diffusion tensor imaging (DTI) predictors captured 80.5% of the unexplained variance of the model without DTI. CONCLUSIONS: We identified i-CST and alternative motor-related tracts (namely i-CRP and c-SCP) as candidate biomarkers of walking recovery. The role of the SCP in walk recovery may rely on cerebellar nuclei projections to the thalamus, red nucleus, and reticular formation. Our findings suggest that a set of white matter tracts, part of subcortical motor networks, contribute to walking recovery in patients with moderate to severe stroke.

Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke.

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p < 0.001). Baseline motor-FMS alone predicted only 54% of the variance. When baseline motor-FMS was removed, the combination of increased activity in ipsilesional MI-BA4a, ipsilesional thalamus, contralesional mid-cingulum, contralesional OP4 and decreased activity in ipsilesional OP1, predicted better motor outcome (djusted-R2 = 0.96; bootstrap p < 0.001). In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a) and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.