A new, exploratory analysis of the Efficacy and Safety of MRI-Based Thrombolysis in Wake-up Stroke (WAKE-UP) trial by Barow and colleagues1 in this issue of JAMA Neurology provides unique and compelling data suggesting that thrombolysis improves clinical outcomes after acute lacunar infarction. The European Union–commissioned, 500-patient, randomized, double-blind, placebo-controlled WAKE-UP trial of alteplase captured the magnetic resonance imaging (MRI) and magnetic resonance angiography of patients with acute ischemic stroke prior to thrombolysis. This allowed categorization of infarcts as lacunar vs nonlacunar, using the authoritative Standards for Reporting Vascular Changes on Neuroimaging criteria (ie, subcortical lesions in the territory of penetrating arteries, with a rounded, ovoid, or tubular shape and a maximum diameter <20 mm on the axial plane).2 Postthrombolysis MRI diagnosis of lacunar infarction is limited by the possibility that thrombolysis, by averting some ischemia, alters the appearance of the ischemic lesions and recanalizes occluded arteries. For this reason, trialists associated with the National Institute of Neurological Disorders and Stroke3 analyzed patients based on suspected causative mechanisms using prerandomization data alone. Their analysis showed no effect modification by presumed causative subtype, but their conclusion was limited by diagnostic uncertainty owing to the absence of modern imaging data, such as MRI or even higher-resolution computed tomographic (CT) scans with vascular imaging, prior to thrombolytic treatment. A post hoc analysis4 of the National Institute of Neurological Disorders and Stroke trials considered final causative mechanisms of stroke assigned by local investigators after the diagnostic workup and also showed no effect modification. However, an argument has been made that lacunar infarcts, or even all infarcts without vascular occlusion visualized on noninvasive imaging, may not be amenable to reperfusion therapy.5
Khatri P. Thrombolysis Works in Lacunar Infarct, Complicating Imaging Selection. JAMA Neurol. Published online March 25, 201976(6):637–638. doi:10.1001/jamaneurol.2019.0214
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