Penumbral Imaging-Based Thrombolysis with Tenecteplase Is Feasible up to 24 Hours after Symptom Onset

Mahesh Kate, Robert Wannamaker, Harsha Kamble, Parnian Riaz, Laura C Gioia, Brian Buck, Thomas Jeerakathil, Penelope Smyth, Ashfaq Shuaib, Derek Emery, Kenneth Butcher, Mahesh Kate, Robert Wannamaker, Harsha Kamble, Parnian Riaz, Laura C Gioia, Brian Buck, Thomas Jeerakathil, Penelope Smyth, Ashfaq Shuaib, Derek Emery, Kenneth Butcher

Abstract

Background and purpose: Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset.

Methods: Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators.

Results: The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; P=0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (-90.8 mL [range, -197 to -20]; P<0.0001) patients.

Conclusions: This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.

Keywords: Stroke; Tenecteplase.

Figures

Figure 1.
Figure 1.
Acute computed tomography perfusion (CTP) maps and 24 hours follow-up perfusion weighted imaging (PWI) in a 74-year-old man presenting 18 hours after onset. The CTP demonstrated a penumbral pattern (infarct core 15 mL, mismatch >1.8). Tenecteplase was associated with recanalization (vertical arrows) and reperfusion, as well as minimal infarct growth on the magnetic resonance image at 24 hours after treatment (horizontal arrows). NCCT, non-contrast computed tomography; ASPECTS, Alberta Stroke Program Early CT Scores; MCA, middle cerebral artery; MTT, mean transit time; GRE, gradient recalled echo; MRA, magnetic resonance angiography; FLAIR, fluid attenuated inversion recovery; TTP, time to peak.
Figure 2.
Figure 2.
Study screening and enrollment profile. IA, intra-arterial; NIHSS, National Institutes of Health Stroke Scale.

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