Neuroimaging Identifies Patients Most Likely to Respond to a Restorative Stroke Therapy

Abstract

Background and purpose: Patient heterogeneity reduces statistical power in clinical trials of restorative therapies. Valid predictors of treatment responsiveness are needed, and several have been studied with a focus on corticospinal tract (CST) injury. We studied performance of 4 such measures for predicting behavioral gains in response to motor training therapy.

Methods: Patients with subacute-chronic hemiparetic stroke (n=47) received standardized arm motor therapy, and change in arm Fugl-Meyer score was calculated from baseline to 1 month post-therapy. Injury measures calculated from baseline magnetic resonance imaging included (1) percent CST overlap with stroke, (2) CST-related atrophy (cerebral peduncle area), (3) CST integrity (fractional anisotropy) in the cerebral peduncle, and (4) CST integrity in the posterior limb of internal capsule.

Results: Percent CST overlap with stroke, CST-related atrophy, and CST integrity did not correlate with one another, indicating that these 3 measures captured independent features of CST injury. Percent injury to CST significantly predicted treatment-related behavioral gains (r=-0.41; P=0.004). The other CST injury measures did not, neither did total infarct volume nor baseline behavioral deficits. When directly comparing patients with mild versus severe injury using the percent CST injury measure, the odds ratio was 15.0 (95% confidence interval, 1.54-147; P<0.005) for deriving clinically important treatment-related gains.

Conclusions: Percent CST injury is useful for predicting motor gains in response to therapy in the setting of subacute-chronic stroke. This measure can be used as an entry criterion or a stratifying variable in restorative stroke trials to increase statistical power, reduce sample size, and reduce the cost of such trials.

Keywords: clinical trial; humans; pyramidal tracts; rehabilitation; stroke.

Figure 1

Greater percent injury to CST significantly predicted poorer treatment-induced gains in arm motor status (n=47).

Figure 2

Percent CST injury in two representative patients. Lesions are denoted in blue, the CST in red, and CST injury by the lesion in purple. [A] Severe CST injury: Two views of Patient 1, who had lesion volume of 7.0 cc and 93.7% CST injury. [B] Mild CST injury: Two views of Patient 2, who had lesion volume of 10.3 cc but only 18.7% CST injury. Despite similar lesion volumes, Patient 1 sustained greater percent injury to CST and had lower treatment-related gains in arm Fugl-Meyer score (1.5 points) as compared to Patient 2 (7.5 points).