Background and Purpose: Stem cell–based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell–based therapy in patients with ischemic stroke. Methods: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. Results: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. Conclusions: Stem cell–based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01716481.

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl–Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

Background. Various prognostic biomarkers for upper extremity (UE) motor recovery after stroke have been reported. However, most have relatively low predictive accuracy in severe stroke patients. Objective. This study suggests an imaging biomarker-based model for effectively predicting UE recovery in severe stroke patients. Methods. Of 104 ischemic stroke patients screened, 42 with severe motor impairment were included. All patients underwent structural, diffusion, and functional magnetic resonance imaging at 2 weeks and underwent motor function assessments at 2 weeks and 3 months after stroke onset. According to motor function recovery at 3 months, patients were divided into good and poor subgroups. The value of multimodal imaging biomarkers of lesion load, lesion volume, white matter integrity, and cortical functional connectivity for motor recovery prediction was investigated in each subgroup. Results. Imaging biomarkers varied depending on recovery pattern. The integrity of the cerebellar tract ( P = .005, R 2 = .432) was the primary biomarker in the good recovery group. In contrast, the sensory-related corpus callosum tract ( P = .026, R 2 = .332) and sensory-related functional connectivity ( P = .001, R 2 = .531) were primary biomarkers in the poor recovery group. A prediction model was proposed by applying each biomarker in the subgroup to patients with different motor evoked potential responses ( P < .001, R 2 = .853, root mean square error = 5.28). Conclusions. Our results suggest an optimized imaging biomarker model for predicting UE motor recovery after stroke. This model can contribute to individualized management of severe stroke in a clinical setting.