Intracerebral hemorrhage (ICH) is the most dangerous and dreaded complication of thrombolytic therapy for acute ischemic stroke (AIS). The risk for symptomatic ICH (SICH) after AIS was increased from 0.6 to 6.4% after treatment with recombinant tissue plasminogen activator (rt-PA) compared with placebo in the National Institute of Neurological Disorders and Stroke (NINDS) trial.1 Despite this increased risk for ICH, treatment with rt-PA was associated with significantly better clinical outcomes at three months and one year after stroke.1,2 These results led to approval of rt-PA by the US Food and Drug Administration (FDA) for the treatment of AIS in 1996. Almost two decades after the NINDS trial reported the benefit of thrombolytic therapy, fewer than 5% of stroke patients receive rt-PA despite aggressive community and physician education.3 While there are several factors limiting its utility, fear surrounding hemorrhagic complications has undoubtedly played a significant role in limiting the clinical use of rt-PA.
Definitions of Post-thrombolysis Intracerebral Hemorrhage
Post-thrombolysis ICH can be classified based on radiographic criteria alone or on the combination of a clinical change in a patient’s neurological status in conjunction with evidence of ICH on brain imaging studies. Both approaches have strengths and weaknesses. Use of a classification scheme incorporating clinical changes (i.e. symptomatic versus asymptomatic ICH) is subject to imprecision given the fact that observed neurological changes may or may not be causally related to visualized ICH, and the criteria used to establish a change in neurological status may be variable. On the other hand, ICH associated with neurological deterioration (SICH) may be most relevant to patients and physicians as this is directly related to an observable clinical change. Radiographic criteria for defining ICH may be more objective and reliable, but may have less direct clinical relevance.
At present, the most common radiographic classification scheme divides post-thrombolysis ICH into hemorrhagic infarction (HI) and parenchymal hemorrhage (PH).4 In the NINDS trial, HI was defined as punctuate or patchy hyperdensity with an indistinct border, and PH was described as a hyperdensity with a sharply demarcated border with or without edema or mass effect.1 The European Cooperative Acute Stroke Study (ECASS) further expanded this scheme, with the subclasses of HI1 for small petechiae at the borders of an infarct, HI2 for confluent petechiae without mass effect within an infarct, PH1 for hematomas occupying <30% of the infarct with mass effect, and PH2 for hemorrhages occupying >30% of the infarcted territory with mass effect.5,6 PH, and in particular PH2, has been shown to worsen clinical outcomes.7–9