ReviewState-of-the-art reperfusion strategies for acute ischemic stroke
Introduction
With an annual incidence of 795,000 and mortality of about 140,000, stroke is the third leading cause of death and the leading cause of adult disability in the USA.1 A recent report on the lifetime risk of stroke from the Framingham Study found that one in five middle-aged women and one in six men are expected to suffer a stroke in their lifetimes.2 Worldwide, there were an estimated 5.54 million deaths from stroke in 1999, making it the second most common cause of death.3
Most patients presenting with acute ischemic stroke (AIS) have arterial thrombi that occlude extracranial and/or intracranial arteries. Fast dissolution of the thrombi and arterial recanalization in AIS often lead to dramatic clinical recovery.4 Intravenously administered tissue plasminogen activator (IV tPA) is intended to induce thrombolysis. IV tPA, administered within 3 hours of symptom onset, remains the only United States Food and Drug Administration (FDA)-approved thrombolytic agent for AIS.5
While IV tPA improved outcomes in ischemic stroke, most patients with stroke present more than 3 hours after stroke onset, and thus efforts are constantly made to identify subpopulations in which the IV tPA window for therapy can be extended.6 The last decade has been a period of rapid advance in physiopathology and neuroimaging of cerebral ischemia. These advances I have directly improved the management of patients with AIS. Treatment in the acute phase is largely aimed at partially or completely restoring blood flow in the affected artery. Since “time is brain,” timely recanalization of the occluded cerebral artery may restore cerebral perfusion, thereby salvaging threatened ischemic tissue and improving clinical outcome.7 Therefore, the true success of recanalization therapy depends on timing as well as the degree of reperfusion. However, as with myocardial infarction, recanalization and reperfusion of ischemic tissue may occasionally exacerbate tissue damage by reperfusion injury, cerebral edema, and hemorrhagic transformation.7 Additional pharmaceutical agents, as well as an increasing variety of devices tailored to neuroendovascular applications, used alone and in combination, have been used to achieve recanalization and reperfusion in AIS. We aimed to review these approaches and the current understanding of recanalization in stroke patients.
Section snippets
Intravenous thrombolysis
IV tPA, the only FDA-approved treatment for stroke, is of demonstrated and substantial benefit for select patients with acute cerebral ischemia when administered in the first 3 hours after stroke onset. Treatment with IV tPA is supported by two phase 3 National Institute of Neurological Disorders and Stroke (NINDS) trials.5 The NINDS Trials 1 and 2 together randomized 624 participants to receive 0.9 mg/kg of IV tPA or placebo within 3 hours of stroke onset. The proportion of patients with
Intra-arterial thrombolysis
Intra-arterial (IA) administration of thrombolytics can reduce the overall quantity of drug used and increase the efficiency of drug delivery into the clot, thus increasing the chances for recanalization. PROACT II is the only randomized study to date that has examined the safety and efficacy of IA thrombolysis in patients with AIS.26 Outcomes in 121 patients treated with IA prourokinase + heparin in 3-to-6 hours from stroke onset were compared with those in 59 patients treated with heparin
Mechanical clot retrieval
Several devices aiming to aspirate or retrieve the occluding clot in patients who are ineligible for IA thrombolysis have been devised, with the snare and basket Mechanical Embolus Removal in Cerebral Ischemia (MERCI) devices (Concentric Medical, Mountain View, CA, USA) gaining most attention.[35], [36] The MERCI approach entails deploying a corkscrew-like retrieval device into the clot. The balloon of the guiding catheter is inflated proximally to the clot, to achieve flow arrest and prevent
Initial low-dose IV tPA with late IA tPA and IA ultrasound
The Interventional Management of Stroke (IMS) I and II studies examined the effects of initial low dose IV tPA treatment (0.6 mg/kg) combined with late IA tPA in patients whose vessel failed to recanalize after the IV bolus in 80 and 81 patients respectively.44 Some patients also received IA ultrasound administered with a specialized device, the EKOS EkoSonic Endovascular System (EKOS Corporation, Bothell, WA, USA) after evidence showed that ultrasound energy hastens clot breakdown.[45], [46]
Endovascular angioplasty and stenting
Balloon angioplasty with or without stent placement represents a different approach to the recanalization of arterial occlusion. This strategy, which is similar to the approach commonly taken in patients with acute myocardial infarction, was hampered for a long time by the absence of dedicated catheters for the cerebral vasculature. The cerebral blood vessels are suspended in cerebrospinal fluid, without the firm muscular support of the myocardium, thus they are more prone to dissections and
Stent-based thrombectomy
The Solitaire AB stent (ev3, Irvine, CA, USA) is a self-expanding microstent especially designed for neurointerventional use that offers the unique capability of being able to be fully deployed and then completely retrieved, if it has not been detached. It was originally designed for the treatment of cerebral aneurysms. Castaño et al. tested whether the Solitaire AB stent could be used as a novel mechanical embolectomy device for large artery occlusions of the anterior circulation in patients
Multimodal reperfusion therapy
Because the results of the previously discussed interventions are similar and because reperfusion significantly improves outcome, attempts were made to use more than one endovascular modality to achieve quick reperfusion. This approach, termed multimodal reperfusion therapy (MMRT), is the mainstay of endovascular therapy of stroke in our Center, in both the posterior55 and anterior circulation.56
The MMRT approach is particularly promising for patients with anterior circulation infarcts. MMRT,
Discussion
Reperfusion is associated with better outcome after stroke, and vessel recanalization is crucial to increasing the possibility of meaningful tissue reperfusion. These attempts should be carried out as early if possible, since it is plausible that earlier recanalization will result in increased tissue salvage and a better functional outcome. Therefore, in patients who fail to reperfuse the ischemic tissue after IV thrombolysis, and in those who are ineligible or inadequate candidates for such
References (62)
- et al.
Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study
Lancet Neurol
(2007) - et al.
Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century
Lancet Neurol
(2003) - et al.
Efficacy and safety of different doses of intravenous tissue plasminogen activator in Chinese patients with ischemic stroke
J Clin Neurosci
(2010) - et al.
Ultrasound-enhanced thrombolysis in acute ischemic stroke: potential, failures, and safety
Neurotherapeutics
(2007) - et al.
Stent for temporary endovascular bypass and thrombectomy device in major ischemic stroke
J Clin Neuroscience
(2011) - et al.
The use of abciximab in the treatment of acute cerebral thromboembolic events during neuroendovascular procedures
Surg Neurol
(2006) - et al.
Deaths: final data for 2006
Natl Vital Stat Rep
(2009) Number needed to treat estimates incorporating effects over the entire range of clinical outcomes: novel derivation method and application to thrombolytic therapy for acute stroke
Arch Neurol
(2004)The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group
N Engl J Med
(1995)- et al.
Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials
Stroke
(2006)
The impact of recanalization on ischemic stroke outcome: a meta-analysis
Stroke
Hemorrhage after thrombolytic therapy for stroke: the clinically relevant number needed to harm
Stroke
Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials
Lancet
Commentary: thrombolysis in stroke: it works!
BMJ Br Med J
Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data
Stroke
Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study
Ann Neurol
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
N Engl J Med
Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association
Stroke
Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT)
Stroke
Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists
Stroke
Routine use of intravenous low-dose recombinant tissue plasminogen activator in Japanese patients: general outcomes and prognostic factors from the SAMURAI register
Stroke
Clinical and radiological predictors of recanalisation and outcome of 40 patients with acute basilar artery occlusion treated with intra-arterial thrombolysis
J Neurol Neurosurg Psychiatry
Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome
Stroke
Intra-arterial thrombolysis is the treatment of choice for basilar thrombosis: pro
Stroke
Intra-arterial thrombolytic therapy for acute basilar occlusion: pro
Stroke
Intravenous tissue plasminogen activator and flow improvement in acute ischemic stroke patients with internal carotid artery occlusion
J Neuroimaging
Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke
Ann Neurol
Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator
Stroke
Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism
JAMA
Intra-arterial thrombolysis in 24 consecutive patients with internal carotid artery T occlusions
J Neurol Neurosurg Psychiatry
Intra-arterial thrombolysis in 100 patients with acute stroke due to middle cerebral artery occlusion
Stroke
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Excellent rates of recanalization and good functional outcome after stent-based thrombectomy for acute middle cerebral artery occlusion. Is it time for a paradigm shift?
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Thrombolytic Therapy
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