Pretreatment diffusion- and perfusion-MR lesion volumes have a crucial influence on clinical response to stroke thrombolysis

Abstract

We hypothesized that pretreatment magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes may have influenced clinical response to thrombolysis in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). In 98 patients randomized to intravenous (IV) tissue plasminogen activator (tPA) or placebo 3 to 6 h after stroke onset, we examined increasing acute DWI and PWI lesion volumes (Tmax-with 2-sec delay increments), and increasing PWI/DWI mismatch ratios, on the odds of both excellent (modified Rankin Scale (mRS): 0 to 1) and poor (mRS: 5 to 6) clinical outcome. Patients with very large PWI lesions (most had internal carotid artery occlusion) had increased odds ratio (OR) of poor outcome with IV-tPA (58% versus 25% placebo; OR=4.13, P=0.032 for Tmax +2-sec volume >190 mL). Excellent outcome from tPA treatment was substantially increased in patients with DWI lesions <18 mL (77% versus 18% placebo, OR=15.0, P<0.001). Benefit from tPA was also seen with DWI lesions up to 25 mL (69% versus 29% placebo, OR=5.5, P=0.03), but not for DWI lesions >25 mL. In contrast, increasing mismatch ratios did not influence the odds of excellent outcome with tPA. Clinical responsiveness to IV-tPA, and stroke outcome, depends more on baseline DWI and PWI lesion volumes than the extent of perfusion-diffusion mismatch.

Figure 1

Graphic comparison of the modified Rankin Scale for tPA versus placebo patients fulfilling various PWI, DWI, and ICA occlusion criteria for excellent and good outcomes. Below the graphs for each cut point are the odds ratio (OR) for tPA versus placebo for excellent (mRS: 0 to 1) and good (mRS: 0 to 2) outcomes. MM, mismatch ratio. 95% confidence intervals are displayed in brackets beside the odds ratio.

Figure 2

Graphic comparison of the modified Rankin Scale for tPA versus placebo patients fulfilling various PWI, DWI, and ICA occlusion criteria for poor outcomes. Below the graphs for each cut point are the odds ratio (OR) for tPA versus placebo for poor (mRS: 5 to 6) outcomes. MM, mismatch ratio. 95% confidence intervals are displayed in brackets beside the odds ratio.

Figure 3

Proposed imaging-based selection algorithm for a phase III IV-tPA/placebo-controlled trial in an extended time window.