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Dear Editor

Since the National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) studies, intravenous alteplase has been used for acute stroke patients who present within 4·5 h from symptom onset [1, 2]. While those studies showed clear benefit from treatment over placebo, there remain a large proportion of patients who do not improve or get worse and patients who present later than 4·5 h are being excluded from treatment. In addition, recent studies demonstrated the safety of intravenous thrombolysis in wake-up strokes that are outside the therapeutic window [3]. Another study showed the safety of interventional treatment based on Magnetic Resonance (MR) perfusion scans [4].

The time of conversion of brain tissue from ischemia to infarction varies depending on multiple factors such as the degree of collateral flow, vascular anatomy, and lesion location; some patients may convert their ischemic brain tissue into infarction on perfusion scans as early as two-hours, while others may have a significant penumbra even up to six-hours from symptom onset. Thus, if a tissue-based decision for thrombolysis is utilized, then we may potentially exclude patients who may not benefit from treatment and include patients outside the time window who could potentially benefit from treatment.

Thus, selecting patients based on advanced neuroimaging may potentially increase the use of intravenous thrombolysis in acute stroke extending its use to patients outside the therapeutic time window who may still benefit from reperfusion.

Although this approach may seem appealing, it may delay time to treatment and may not be available in small hospitals. A prospective multicenter trial may be warranted to evaluate the benefit of intravenous alteplase in stroke patients with favorable advanced neuroimaging who are between 4·5 and 6 h from last known well time.

References

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  2. References
  • 1
    Hacke W, Kaste M, Bhumki E et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:13171329.
  • 2
    Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333:15811587.
  • 3
    Barreto AD, Martin-Schild S, Hallevi H et al. Thrombolytic therapy for patients who wake-up with stroke. Stroke 2009; 40:827832.
  • 4
    Han MK, Kim SH, Ko SB et al. 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; 8:353359.