Importance of leukoaraiosis on CT for tissue plasminogen activator decision making: Evaluation of the NINDS rt-PA stroke study

Background: Leukoaraiosis is associated with microhemorrhages on T ₂*-weighted magnetic resonance imaging of the brain. Such hemorrhages have been postulated to be responsible for symptomatic intracerebral hemorrhage (ICH) after thrombolytic treatment. We examined the relationship between small-vessel ischemic disease and symptomatic ICH within the NINDS rt-PA Stroke Study. Methods: Baseline CT scans from the NINDS rt-PA Stroke Study were re-evaluated retrospectively by blinded expert CT readers using the van Swieten Score (vSS) for leukoaraiosis. The scale examined the severity of white-matter changes on 3 serial CT slices and graded separately for the 2 distinct regionsanterior and posterior to the central sulcus: 0 = no lesion, 1 = partlyinvolving the white matter, and 2 = extending up to the cortex. Results: 603 CT scans were interpreted. The risk of symptomatic ICH increased with higher vSS in both the placebo and treatment groups. The absolute risk of symptomatic hemorrhage was 7.9% in the rt-PA-treated cohort among patients with severe white-matter disease (vSS = 3-4) versus 2.9% receiving placebo. Among severe leukoaraiosis patients (vSS = 3-4), no differential treatment effect was seen with rt-PA patients achieving better outcomes than placebo, modified Rankin score 0-1 in 31.6% of rt-PA-treated versus 14.7% of placebo-treated patients. Conclusion: The results from the present study do not support the concept that leukoaraiosis present on baseline noncontrast CT scanning is critical to thrombolysis decision making in the first 3 h from symptom onset. No clear leukoaraiosis threshold was identified below which no benefit or harm could be seen from intravenous rt-PA therapy.