Abstract TP290: Glyburide Reduces Cytotoxic Edema within the Cerebral Peduncles in Acute Ischemic Stroke

Abstract

Introduction: Diffusion tensor imaging (DTI) measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within the cerebral peduncle (CP) and corticospinal tract (CST) correlate with functional outcomes in ischemic stroke. We evaluated the utility of FA and ADC as quantitative biomarkers of cytotoxic edema in acute stroke subjects treated with intravenous glyburide (RP-1127), which may prevent brain swelling after ischemia. Methods: Nine acute hemispheric stroke subjects enrolled in the Glyburide Advantage in Malignant Edema and Stroke (GAMES) Pilot study were compared to a cohort of seven stroke patients not treated with RP-1127. GAMES subjects received an intravenous bolus of RP-1127 within 10 hours of symptom onset, followed by an intravenous drip for 72 hours. The cohorts were matched for admission NIHSS score, infarct volume, and time from infarct to DTI data acquisition. CPs were manually traced on color FA maps and used as seed regions to identify CST fiber tracts using deterministic, streamline tractography. Ipsilesional FA and ADC values were normalized to contralesional values, yielding four quantitative metrics: CP FA ratio, CP ADC ratio, CST FA ratio, and CST ADC ratio. Results: Median NIHSS score was 19 in both cohorts. Mean time to DTI data acquisition was 2.5 ± 0.4 and 2.4 ± 0.6 days, and mean infarct volume was 170 ± 49 and 188 ± 13 cc in the GAMES and control cohorts, respectively. CP ADC ratios were significantly higher in patients treated with RP-1127 compared to the control cohort (1.05 vs. 0.98, p=0.045). No difference between the GAMES and control cohorts was observed for the CP FA ratio (1.02 vs. 0.98, p=0.30), CST FA ratio (1.0 vs. 0.99, p=0.78), or CST ADC ratio (0.92 vs. 0.93, p=0.75). Conclusions: CP ADC ratio may provide a quantitative imaging biomarker of response to RP-1127 in acute stroke. Higher CP ADC ratios reflect a reduction of cytotoxic edema within CST axons at the level of the CP, consistent with RP-1127’s proposed mechanism of preventing cellular edema.