Abstract

Introduction: Many cell-based therapies attenuate secondary degeneration after initial ischemic injury and enhance repair. We serially compared over time the integrity of the corticospinal tract (CST) in ischemic stroke (IS) patients treated with autologous bone marrow cells versus a prospectively collected, comparable stroke patient population not treated with cells (controls). Methods: We imaged 37 IS patients (17=treated, 20=control) at 1, 3, and 12 mo after stroke on a 3T MRI. A maximum of 10 million cells/kg were administered IV within 72 hrs of stroke. 3D anatomical and DTI images were obtained. CST integrity was assessed by relative (ipsilesional/contralesional) rFA in the rostral pons (RP). A mixed model was used for statistical analysis. Results: Infarct size of controls was 26.4 ±27 mL and the treated group was 64.7 ± 40.3 mL. The rFA in the rostral pons (RP) of controls decreased from 0.91 ± 0.1 to 0.86 ± 0.1 over 12 months. In the cell treated group, rFA in the RP decreased initially from 0.73 ±0.1 to 0.69 ±0.1 between 1 and 3 months but then increased to 0.76 ± 0.1 at 12 months. Qualitative and quantitative results are summarized (fig). The rFA in the RP was significantly correlated (p <0.05) to the mRS in the treated group. Conclusion: Despite smaller infarct size in controls, CST integrity continued to degenerate and showed no improvement by 12 months after stroke. In contrast, the cell treated patients with initial larger infarcts showed initial degeneration of the CST but then had improved CST integrity by 12 months after stroke. The temporal decrease in rFA in controls and increase in rFA in treated patients suggest a potential treatment effect from the cells. Although the results are generated from a non-randomized trial, the significant correlation between mRS and rFA suggests rFA could be used as a surrogate marker of treatment effect.

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