Combined intravenous and intraarterial revascularization therapy using MRI perfusion/diffusion mismatch selection for acute ischemic stroke at 3-6 h after symptom onset

Neurocrit Care. 2008;8(3):353-9. doi: 10.1007/s12028-007-9046-7.


Background and purpose: Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) has demonstrated favorable clinical outcomes in a 3-6 h window in patients selected with perfusion/diffusion mismatch. However, the advantages of combined IV and intraarterial (IA) thrombolysis after 3 h of stroke onset are unexplored.

Methods: Acute ischemic stroke patients with persistent occlusion of intracranial large arteries were screened prospectively for thrombolysis by evaluating perfusion/diffusion mismatch on MRI. The IV rt-PA was initiated within 3-6 h, and additional urokinase (UK) was then administered via the IA route after angiography.

Results: Four patients had middle cerebral artery occlusion and one patient had an internal carotid artery occlusion. The median time from the symptom onset to the initiation of IV therapy and to the initiation of IA treatment was 215 +/- 30 min and 292 +/- 41 min, respectively. The median National Institutes of Health Stroke Scale (NIHSS) scores were as follows: initial, 13; immediately after IA treatment, 8; at 24 h, 5; and at 7 days, 3. The Thrombolysis in Myocardial Infarction (TIMI) score after the completion of thrombolysis was 2-3. Four patients without intracerebral hemorrhage recovered completely or exhibited mild disability and one patient with hemorrhage also demonstrated a favorable outcome.

Conclusion: This preliminary result suggests that if a significant perfusion/diffusion mismatch on MRI is identified, a sequential combination thrombolysis of IV rt-PA and IA UK is potentially beneficial in moderate to severe acute ischemic stroke patients who are treated within 3-6 h after symptom onset.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Brain Ischemia / diagnostic imaging
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology*
  • Cerebral Angiography
  • Cerebral Revascularization
  • Diffusion Magnetic Resonance Imaging*
  • Drug Therapy, Combination
  • Feasibility Studies
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Humans
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Prospective Studies
  • Stroke / diagnostic imaging
  • Stroke / drug therapy*
  • Stroke / pathology*
  • Thrombolytic Therapy / methods*
  • Tissue Plasminogen Activator / administration & dosage
  • Treatment Outcome
  • Urokinase-Type Plasminogen Activator / administration & dosage


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator