Editors' Note: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial

Abstract

Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis. Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis.