Brain imaging signs may not indicate an increased risk of symptomatic intracranial hemorrhage after treatment with IV t-PA, according to a study in the May Lancet Neurology. Certain early ischemic and pre-existing signs are associated with reduced independence at six months and increased symptomatic intracranial hemorrhage, however. Neurologists should consider these signs when assessing patients with acute ischemic stroke, said the investigators.
An Analysis of IST-3 Data
The results come from a prespecified analysis of data from the third International Stroke Trial (IST-3), which enrolled 3,035 patients with acute ischemic stroke. Eligible participants were 18 or older, and their treating clinicians observed no clear indication for or contraindication to IV t-PA for them. Before randomization, all patients underwent CT or MRI, which was repeated at 24 to 48 hours after stroke. Participants were randomized to 0.9 mg/kg of IV t-PA plus standard care or to standard care alone within six hours of stroke. A group of neuroradiologists and stroke neurologists who were blinded to study information assessed the scans for early signs of ischemia (ie, tissue hypoattenuation, infarct extent, swelling, and hyperattenuated artery) and pre-existing signs (ie, old infarct, leukoaraiosis, and atrophy).
The primary outcome of IST-3 was independence at six months, which the researchers defined as an Oxford Handicap Scale (OHS) score of 0 to 2. For this secondary analysis, the researchers performed logistic regression to identify associations between imaging signs and age, NIH Stroke Scale (NIHSS) score, time to randomization, and outcomes at seven days (ie, symptomatic intracranial hemorrhage) and six months (ie, OHS score of 0–2 and OHS score of 0–1).
Old Infarct Predicted Symptomatic Hemorrhage
Brain scans were available for 1,507 patients randomized to IV t-PA and for 1,510 controls. In all, 1,224 (41%) patients had early ischemic signs and 1,524 (51%) had pre-existing signs but no early ischemic signs. The most common early ischemic sign was tissue hypoattenuation (40% of patients), and the least common was hyperattenuated artery (24% of patients).
All early ischemic signs except severe hypoattenuation individually predicted worse outcomes. Of all pre-existing signs, only old infarct predicted symptomatic hemorrhage. Time to randomization did not change the associations between imaging signs and outcomes.
Increasing NIHSS score, IV t-PA, antiplatelet treatment, and pre-existing old infarcts predicted a significantly higher risk of symptomatic intracranial hemorrhage. With standard stepwise model selection methods, retaining age, NIHSS score, time to randomization, and treatment group, old infarcts and hyperattenuated arteries were potentially significant predictors of symptomatic intracranial hemorrhage.
Increasing age and NIHSS score were the strongest predictors of adverse functional outcomes. Hyperattenuated arteries, large lesion, and leukoaraiosis each individually reduced the chance of a good outcome by 25% to 30%.
The investigators found no interaction between any individual imaging finding or any combination of imaging findings and IV t-PA for functional outcome or symptomatic intracranial hemorrhage. “Despite the absence of definite interactions between imaging signs and alteplase, the absolute increase in symptomatic intracranial hemorrhage after alteplase with combined imaging signs was substantial,” said the researchers. After adjustments for age, NIHSS score, and time to randomization, the combination of old infarcts and hyperattenuated arteries predicted approximately threefold increased odds of symptomatic intracranial hemorrhage, compared with patients with neither sign. The authors saw similar absolute effects on symptomatic intracranial hemorrhage for patients randomized within three hours of stroke.
“Combinations of imaging signs in patients after stroke might provide additional information to decision making when clinical uncertainty exists about the likely benefit of alteplase—eg, in a patient presenting close to the latest time window or for whom the likelihood of benefit was marginal,” said the authors. “Our findings confirm that neither early tissue hypoattenuation nor large infarct extent on [Alberta Stroke Program Early CT score] should exclude patients from alteplase, hopefully improving confidence in use of CT scanning in acute stroke. ”
—Erik Greb