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

Cerebrovasc Dis. 2008;26(2):120-5. doi: 10.1159/000139658. Epub 2008 Jun 17.


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 regions anterior and posterior to the central sulcus: 0 = no lesion, 1 = partly involving 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Decision Making
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Infusions, Intravenous
  • Intracranial Hemorrhages / etiology*
  • Leukoaraiosis / complications
  • Leukoaraiosis / diagnostic imaging*
  • Logistic Models
  • Multicenter Studies as Topic
  • Patient Selection
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / administration & dosage
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Stroke / diagnostic imaging
  • Stroke / drug therapy*
  • Thrombolytic Therapy* / adverse effects
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Tomography, X-Ray Computed*
  • Treatment Outcome


  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator