Normal Appearing Ischaemic Brain Tissue on CT and Outcome After Intravenous Alteplase.

Background and aims: The visibility of ischaemic brain lesions on non-enhanced CT increases with time. Obviously hypoattenuating lesions likely represent infarction. Conversely, viable ischaemic brain lesions may be non-visible on CT. We tested whether patients with normal appearing ischaemic brain tissue (NAIBT) on their initial CT are identifiable, and if NAIBT yields better outcomes with alteplase.

Methods: With data from the Third International Stroke Trial (IST-3, a large randomized-controlled trial of intravenous alteplase for ischaemic stroke) we used receiver-operating characteristic analysis to find a baseline National Institutes of Health Stroke Scale (NIHSS) threshold for identifying patients who developed medium-large ischaemic lesions within 48 h. From patients with baseline CT (acquired <6 h from stroke onset), we used this NIHSS threshold for selection and tested whether favorable outcome after alteplase (6-month Oxford Handicap Score 0-2) differed between patients with NAIBT vs. with those with visible lesions on baseline CT using binary logistic regression (controlled for age, NIHSS, time from stroke onset to CT).

Results: From 2,961 patients (median age 81 years, median 2.6 h from stroke onset, 1,534 [51.8%] female, 1,484 [50.1%] allocated alteplase), NIHSS>11 best identified those with medium-large ischaemic lesions (area under curve = 0.79, sensitivity = 72.3%, specificity = 71.9%). In IST-3, 1,404/2,961 (47.4%) patients had baseline CT and NIHSS>11. Of these, 745/1,404 (53.1%) had visible baseline ischaemic lesions, 659/1,404 (46.9%) did not (NAIBT). Adjusted odds ratio for favorable outcome after alteplase was 1.54 (95% confidence interval, 1.01-2.36), p = 0.045 among patients with NAIBT vs. 1.61 (0.97-2.67), p = 0.066 for patients with visible lesions, with no evidence of an alteplase-NAIBT interaction (p-value = 0.895).

Conclusions: Patients with ischaemic stroke and NIHSS >11 commonly develop sizeable ischaemic brain lesions by 48 h that may not be visible within 6 h of stroke onset. Invisible ischaemic lesions may indicate tissue viability. In IST-3, patients with this clinical-radiological mismatch allocated to alteplase achieved more favorable outcome than those allocated to control.