Time is brain: early recanalization in acute ischemic stroke

EDITORIALS

Time is brain - early recanalization in acute ischemic stroke

Cláudia J. Chaves^I; Louis R. Caplan^II

^IAssistant Professor of Neurology, Tufts University School of Medicine, Boston, MA

^IIProfessor of Neurology, Harvard Medical School, Boston, MA

Stroke is the third leading cause of death in America and the number one cause of adult disability. Prompt diagnosis and treatment are imperative to increase the odds of a good outcome.

Even though stroke is not a common complication of catheter angiography, when it occurs, it is associated with a high morbidity and mortality (1-2). Several mechanisms have been proposed to account for the neurologic complications of catheter angiography. The most common cause implicated is thromboembolism, due to thrombi formation inside the catheter or disruption of an atherosclerotic plaque by the catheter or guide wire. Catheter-related arterial dissections, platelet activation, and neurotoxicity of contrast agents are other potential etiologies (1-3).

When facing a patient with signs and symptoms suggestive of an acute ischemic stroke, prompt evaluation of the intra and extracranial vessels for determination of the culprit artery involved as well as establishment of the potential mechanism of the stroke should be pursued (4). New techniques of magnetic resonance imaging and computed tomography, can quickly assess the patient, evaluate early ischemic changes, reveal hypoperfusion/ischemic penumbra, and locate the site of vessel occlusion, stratifying and selecting those patients that will benefit most from reperfusion (5-6).

Even though spontaneous recanalization can occur in one-quarter of patients within the first 24 hours and up to 52.7 % of cases up to 1 week after the stroke, only early recanalization within the first 6 hours have positively correlated with a good clinical outcome in patients with acute ischemic stroke (7). Therefore, early recanalization therapy with the use of fibrinolytic agents and/or mechanical thrombolysis should be pursued in an attempt to re-establish the cerebral blood flow and salvage of the threatened tissues.

A National Institute of Neurological Disorders and Stroke compliant strategy (ie, evaluation by emergency physician <10 minutes after arriving at the hospital, interpretation of CT scans <45 minutes, and administration of tPA <1 hour after initial assessment) renders a substantial clinical gain, with the number of patients needed to treat for benefit of pursued in an attempt to re-establish the cerebral blood flow and salvage of the threatened tissues. A National Institute of Neurological Disorders and Stroke compliant strategy (ie, evaluation by emergency physician <10 minutes after arriving at the hospital, interpretation of CT scans <45 minutes, and administration of tPA <1 hour after initial assessment) renders a substantial clinical gain, with the number of patients needed to treat for benefit of ≈ 3.2, that is, for every 1000 patients treated, ≈ 323 will attain a better outcome (6).

In a recent meta-analysis study (7), the recanalization rate with IV fibrinolytic therapy was shown to be approximately twice the spontaneous rate, but still less than fifty percent. Intra-arterial fibrinolysis (IA) had a substantially higher rate of recanalization, with reperfusion in approximately two thirds of patients. The IA route offers additional advantages, including the accurate demonstration of the vascular anatomy and the exact knowledge of the timing recanalization is achieved. IA also has disadvantages, including the inherent delay in initiation of fibrinolysis (that typically occurs 50 to 90 minutes later than start of intravenous lytic infusion) and the requirement of tertiary hospitals capable of carrying out acute endovascular therapy.

Newer pharmacological reperfusion strategies are being developed with the goal of extending the therapeutic window of efficacy including: other fibrinolytic agents, combination of lytics and antithrombotics , and externally applied ultrasound (US) to enhance enzymatic fibrinolysis (6,8,9).

Endovascular mechanical therapies offer the highest rate of recanalization with approximately 80% of patients achieving arterial patency. They offer other advantages over IA fibrinolysis including working more quickly, having a lower hemorrhagic risk and being more effective in the treatment of large clot burden (6).

Mechanical interventions include techniques for the removal of thrombi (endovascular thrombectomy) and mechanical disruption devices. Endovascular thrombectomy devices extract occluding thrombi from the target vessel through a catheter. The Merci Retriever is the first reperfusion therapy device labeled specifically for use in acute ischemic stroke by the FDA. The Merci Retriever is a corkscrew-like device attached to a catheter that is advanced distal to the clot and then pulled back, and gently withdrawn into the guide catheter. Patients who are ineligible for treatment with intravenous tPA or who fail intravenous tPA therapy are candidates for this approach (10).

Mechanical devices, such as angioplasty with or without stent placement, are intended to fragment the thrombi and can also promote stabilization of the atherosclerotic plaque. Repeated passage of a guidewire through a thrombus is another form of mechanical disruption often used during IA fibrinolytic procedures ¹¹.

Concerning reperfusion injury, no significant difference in the risk of hemorrhagic transformation for recanalized versus non-recanalized patients has been documented (7), suggesting that the severity of the ischemic injury to the blood-brain barrier is an equal or greater determinant of hemorrhagic transformation than whether reperfusion occurs orthograde through the recanalized vessel or retrograde via collateral vessels.

The case related by Sánchez et al.12, published in this issue of the RBCI, illustrates that in patients with an angiography related stroke, mechanical thrombolysis or intra-arterial fibrinolysis makes sense and can be accomplished quickly, leading to a rapid restoration of the cerebral blood flow with salvage of ischemic brain and a subsequent good outcome.

REFERENCES:

1- Robert A. Willinsky, MD, FRCPC, Steve M. Taylor, BA, Karel terBrugge, MD, FRCPC, Richard I. Farb, MD, FRCPC, George Tomlinson, PhD and Walter Montanera, MD, FRCPC. Neurologic Complications of Cerebral Angiography: Prospective Analysis of 2,899 Procedures and Review of the Literature. Radiology 2003;227:522-528.

2- Dawkins AA, Evans AL, Wattam J, Romanowski CA, Connolly DJ, Hodgson TJ, Coley SC. Complications of cerebral angiography: a prospective analysis of 2,924 consecutive procedures. Neuroradiology 2007 Sep; 49(9):753-9.

3- Cloft HJ, Jensen ME, Kallmes DF, Dion JE. Arterial dissections complicating cerebral angiography and cerebrovascular interventions. AJNR Am J Neuroradiol 2000 Mar; 21(3):541-5.

4- Kumar S, Caplan LR. Why identification of stroke syndromes is still important. Curr Opin Neurol 2007 Feb; 20(1):78-82.

5- Kidwell CS, Hsia AW. Imaging of the brain and cerebral vasculature in patients with suspected stroke: advantages and disadvantages of CT and MRI. Curr Neurol Neurosci Rep 2006 Jan;6(1):9-16.

6- Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005 Oct; 36(100:2311-20.

7- Joung-Ho Rha, MD; Jeffrey L. Saver, MD. The Impact of Recanalization on Ischemic Stroke Outcome. A Meta-Analysis. Stroke. 2007;38:967-973

8- Mehdiratta M, Caplan LR. Acute stroke thrombolysis: an update. Prog Cardiovasc Dis. 2007 May-Jun;49(6):430-8.

9- Mikulik R, Alexandrov AV. Acute stroke: therapeutic transcranial Doppler sonography. Front Neurol Neurosci. 2006;21:150-61.

10- Flint AC, Duckwiler GR, Budzik RF,Liebeskind DS, Smith WS for the MERCI and Multi MERCI Writing Committee. Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. Stroke. 2007 Apr;38(4):1274-80.

11- Fussel D, Schumacher HC, Meyers PM, Higashida RT. Mechanical interventions to treat acute stroke. Curr Neurol Neurosci Rep 2007 Jan;7(1):21-7.

• 1. Willinsky RA, Taylor SM, TerBrugge K, Farb RI, Tomlinson G, Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Radiology 2003;227(2):522-8.
• 2. Dawkins AA, Evans AL, Wattam J, Romanowski CA, Connolly DJ, Hodgson TJ, et al. Complications of cerebral angiography: a prospective analysis of 2,924 consecutive procedures. Neuroradiology. 2007;49(9):753-9.
• 3. Cloft HJ, Jensen ME, Kallmes DF, Dion JE. Arterial dissections complicating cerebral angiography and cerebrovascular interventions. AJNR Am J Neuroradiol. 2000;21(3):541-5.
• 4. Kumar S, Caplan LR. Why identification of stroke syndromes is still important. Curr Opin Neurol. 2007;20(1):78-82.
• 5. Kidwell CS, Hsia AW. Imaging of the brain and cerebral vasculature in patients with suspected stroke: advantages and disadvantages of CT and MRI. Curr Neurol Neurosci Rep. 2006;6(1):9-16.
• 6. Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke. 2005;36(10):2311-20.
• 7. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;383:967-73.
• 8. Mehdiratta M, Caplan LR. Acute stroke thrombolysis: an update. Prog Cardiovasc Dis. 2007;49(6):430-8.
• 9. Mikulik R, Alexandrov AV. Acute stroke: therapeutic transcranial Doppler sonography. Front Neurol Neurosci. 2006;21:150-61.
• 10. Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS. Mechanical thrombectomy of intracranial internal carotid occlusion: pooled results of the MERCI and Multi MERCI Part I trials. MERCI and Multi MERCI Writing Committee. Stroke. 2007;38(4):1274-80.
• 11. Fussel D, Schumacher HC, Meyers PM, Higashida RT. Mechanical interventions to treat acute stroke. Curr Neurol Neurosci Rep. 2007;7(1):21-7.
• 12. Sánchez AG, Kambara AM, Moreira SM, Chaves AJ, Cano MN, Mattos LA, et al. Terapia de recanalização endovascular de oclusão da artéria carótida em paciente com acidente vascular cerebral agudo. Rev Bras Cardiol Invas. 2008;16(1):102-5.

Publication Dates

• Publication in this collection
  15 Aug 2012
• Date of issue
  2008