Fluoxetine May Enhance Visual Recovery After Acute Ischemic Stroke By Cortical Remapping Of The Blind Visual Field.

Post-stroke homonymous hemianopia is disabling and complete spontaneous recovery is rare (12.5%). Other than acute revascularization, no proven treatments are available to enhance recovery. Compensatory training may lead to modest functional improvements, but does not restore native function. As such, therapies effective beyond the acute stage are desperately needed. In this phase IIa single-center, double-blinded, randomized, placebo-controlled pilot clinical trial, we tested whether fluoxetine (FLX) enhances visual recovery after an ischemic stroke by facilitating cortical remapping as measured by fMRI. We randomized 10 consecutive adults in a 1:1 ratio to 90 days of FLX 20 mg daily vs placebo within 5 days of a stroke in the PCA ( n = 9) or MCA ( n = 1) territory causing an isolated homonymous field defect. Only one subject was treated with tPA. The primary outcome measure was percent improvement in perimetric mean deviation (PMD) as measured by automated Humphrey perimetry at 6 months. Eight subjects completed the study. Intention-to-treat analysis of the primary outcome measure showed a non-significant benefit of FLX ( n = 4) over placebo (70.5 ± 21.1% vs 30.1 ± 23.5%; one-tailed t -test, p = 0.12). Complete recovery occurred more frequently than expected in both groups (75% vs 25%), but was significantly greater than 12.5% only in the FLX group ( p = 0.007 vs p = 0.41). Percent improvement in PMD significantly correlated with scores on the 25-item Visual Functioning Questionnaire, a vision-targeted measure of health-related quality of life ( r 2 = 0.74; p = 0.012). Subjects in both groups who fully recovered showed fMRI evidence of cortical remapping by expansion and shifting of the center of their ipsilesional V1 receptive fields. In those with partial recovery, fMRI showed no cortical remapping, but a return of function in normal retinotopic locations, possibly due to recovery of “stunned” tissue. In conclusion, these results illustrate the feasibility of our approach, suggest a trend in favor of FLX, and have the potential to inform the design of a multi-center trial. Our fMRI analysis raises testable hypotheses about post-stroke recovery and suggests that FLX may improve outcomes by enabling the same kind of plasticity that underlies spontaneous recovery.