Importance of leukoaraiosis on CT for tissue plasminogen activator decision making: evaluation of the NINDS rt-PA...

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.

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 regions anterior and posterior to the central sulcus: 0 = no lesion, 1 = partly involving the white matter, and 2 = extending up to the cortex.

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.

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.