Acute Ischemic Stroke: Endovascular Management
Rajan K. Gupta
Jennifer R. Simpson
David A. Kumpe
Stroke is the number one cause of severe disability and number four cause of death in the United States with an enormous cost to the medical care system. The ultimate goal of acute stroke treatment is to limit disability and return the patient to functional independent living. This is accomplished by rapid reperfusion of ischemic tissue at risk for progression to infarction. Intravenous (IV) tissue plasminogen activator (tPA) is a proven medical revascularization therapy for acute ischemic stroke indicated in selected patients up to 4.5 hours after symptom onset. Unfortunately, IV tPA is often ineffective in large vessel occlusion (LVO) stroke that carries a high morbidity and mortality. Multiple prospective randomized controlled trials have demonstrated that endovascular thrombectomy is highly effective in reducing disability in selected patients with acute LVO anterior circulation stroke (1,2,3,4,5). The statement that “time is brain” cannot be overemphasized when treating stroke. An estimated 1.9 million neurons are lost per minute in untreated acute LVO strokes (6). Every 30-minute delay is associated with a 10% decrease in function outcome at 90 days (7,8,9). Time can be saved across every level of stroke care from prehospital care to intraprocedural technique. Identification of appropriate patients with noninvasive imaging, an emphasis on rapid and complete revascularization with modern thrombectomy devices, and a multidisciplinary commitment to process improvement are critical factors for improving patient outcomes.
Indications
Patient selection for endovascular therapy is based on the location of the occlusion, time from symptom onset, and imaging findings that estimate the completed core infarct and the ischemic penumbra. Imaging strategies will be discussed in depth in the “Preprocedure Preparation” section. The strongest data for endovascular therapy is in patients who are eligible for and receive full-dose (0.9 mg per kg) IV tPA. Subgroup analysis of randomized trials suggests that the benefit of thrombectomy persists in patients who are not eligible for IV tPA, and endovascular therapy should not be withheld in this population (1,3,4).
1. Acute symptomatic ischemic stroke from documented LVO
a. Anterior circulation
(1) The strongest data for endovascular thrombectomy is in patients with occlusions of the intracranial internal carotid artery and/or proximal middle cerebral artery (M1). Subset analyses of randomized trials demonstrate a benefit when extracranial carotid occlusion is present (1,3). Less data is present for treatment of occlusion of proximal anterior cerebral artery (A1) and proximal middle cerebral artery branches (M2).
(2) The strongest data is for patients who can start endovascular therapy by 6 hours after last seen normal (LSN). The evidence of benefit at time windows beyond 6 hours is less robust but appears promising with strict patient selection (3,10). Selection criteria should be defined at each individual institution.
b. Posterior circulation
(1) Occlusion of the basilar artery is a reasonable target due to the dismal prognosis of large vessel posterior circulation stroke.
(2) Time windows for treatment are often extended up to 24 to 48 hours.
Contraindications
Contraindications to endovascular therapy, particularly now that mechanical thrombectomy can be performed with little or no fibrinolytics, are not uniformly agreed upon and should be institutionally defined or discussed on a case-by-case basis.
Absolute
1. Anaphylactic reaction to contrast
2. Hemorrhagic conversion of stroke or midline shift
3. Large core infarct with expected futile revascularization. These contraindications will depend on the imaging strategy used (see “Preprocedure Preparation” section and discussion on imaging).
a. MRI diffusion-weighted imaging (DWI) core infarct >70 mL
b. Hypodensity >1/3 middle cerebral artery (MCA) territory or Alberta Stroke Program Early Computed Tomography Scan (ASPECTS) <6 on noncontrast computed tomography (CT)
c. Matched defect or <20% penumbra with perfusion imaging
Relative
Lack of appropriate vascular access
1. Although direct carotid and upper extremity access have been described for stroke intervention, the majority of stroke interventions are performed from a femoral approach and lack of appropriate femoral access precludes safe and timely therapy for most operators not skilled with more advanced techniques.
2. Minimal clinical deficit or rapidly improving stroke symptoms after IV tPA
3. Poor baseline functional status All recent randomized trails excluded patients with poor baseline functional status. Clinical judgment should guide decision making because some patients who are high functioning may not be independent at baseline (such as those with lower extremity amputations) and may benefit substantially from reperfusion therapy.
4. Limited life expectancy or other severe medical comorbidities
5. Medical factors that increase bleeding risks and represent contraindications to IV tPA administration (Table 5.1) are also relative contraindications when intraarterial (IA) fibrinolytics are contemplated, although these risks are substantially reduced with mechanical thrombectomy when fibrinolytics can be avoided.
Preprocedure Preparation
1. History, physical examination, National Institutes of Health stroke scale (NIHSS), and consultation with a neurologist
a. Patients with acute ischemic stroke should be rapidly evaluated in the emergency room in consultation with a neurologist. The primary objective is to establish a correct diagnosis of acute ischemic stroke. The NIHSS should be calculated, as it is a standardized method of determining stroke severity and monitoring changes over time. Large vessel anterior or posterior stroke syndromes (Table 5.2) should be differentiated from lacunar stroke syndromes (Table 5.3) and can be utilized to help guide clinical localization of a clot.
Table 5.1 Inclusion/Exclusion Criteria for Intravenous Tissue Plasminogen Activator (13) | |||||||||
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b. Establishing the correct time of onset of symptoms is critical to establish if the patient is in an acceptable time window for therapy. If the exact time of onset is unknown, the last time the patient was seen normal is used as the onset.
c. Review of medications, allergies, and comorbidities should be performed.
d. Pulse exam is important in patient assessment because most stroke interventions are performed from a femoral approach.
2. Laboratory evaluation
a. Evaluation includes complete blood count; international normalized ratio (INR); and serum electrolytes including creatinine, fingerstick glucose, and troponin. These labs should not delay the administration of endovascular therapy but are important for overall care of the acute stroke patient. Correction is tailored to the overall patient condition and anticipated method
of treatment. For example, a mild elevation of INR may not be corrected if thrombectomy is anticipated but corrected when IA tPA is planned.
of treatment. For example, a mild elevation of INR may not be corrected if thrombectomy is anticipated but corrected when IA tPA is planned.
Table 5.2 Large Vessel Stroke Patterns | ||||||||||||||
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b. Electrocardiogram. Cardiac abnormalities often coexist with stroke and have important implications on patient treatment and outcome.
3. Imaging evaluation
Urgent imaging should occur for patient triage. Guidelines suggest that radiologic imaging should begin within 25 minutes and be interpreted within 45 minutes of arrival in at least 80% of cases (11). During acute stroke, perfusion to the brain distal to the clot is dependent on collateral flow. The ideal revascularization candidate has relatively little irreversibly injured brain (core infarct) and a relatively large area of brain at risk for progression to complete infarction (ischemic penumbra). If no revascularization is performed, then the core
infarct will grow over time leading to greater disability. Recent randomized trials have strongly emphasized CT protocols to promote rapid triage of patients to thrombectomy. Multiple imaging techniques have been demonstrated to lead to effective patient selection including CTA alone, multiphase CTA (mCTA), and perfusion imaging with CT or MRI. Use of advanced imaging is likely more important in late time windows (>6 hours). Institutional protocols should be developed based on evidence, local factors, and operator preferences.
infarct will grow over time leading to greater disability. Recent randomized trials have strongly emphasized CT protocols to promote rapid triage of patients to thrombectomy. Multiple imaging techniques have been demonstrated to lead to effective patient selection including CTA alone, multiphase CTA (mCTA), and perfusion imaging with CT or MRI. Use of advanced imaging is likely more important in late time windows (>6 hours). Institutional protocols should be developed based on evidence, local factors, and operator preferences.
Table 5.3 Lacunar Stroke Syndromes | ||||||||||
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a. Noncontrast computed tomography (NCCT) NCCT is fast, has no contraindications, and has 24/7/365 availability at most institutions, making it perfect for exclusion of hemorrhage and triage to IV tPA. The ASPECTS is a 10-point scale for defining early ischemic changes on NCCT. A normal NCCT scan yields a score of 10 with 1-point deducted for every area of ischemic change in a defined segment. Patients with a large ischemic core (ASPECTS <6) should be excluded from endovascular therapy. Further vascular imaging should be utilized to document an LVO before proceeding to endovascular therapy.
b. Computed tomographic angiography (CTA)
CTA can be rapidly acquired in nearly all patients. It is highly accurate at identification of vascular occlusion, easy to read, and information obtained about the aortic arch and neck vasculature is useful for planning endovascular interventions. Of recent randomized trials, Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) predominantly used NCCT and CTA alone for endovascular triage (1). Use of CTA alone, however, may select some patients with larger core infarcts or minimal penumbra who may not benefit from endovascular therapy.
mCTA utilizes additional venous phases to assess collaterals and exclude patients with a large core infarct who may not benefit from endovascular therapy. A standard CTA is performed in late arterial phase from the aortic arch through the vertex, and then two additional acquisitions are immediately performed in venous and late venous phases through the brain only. This strategy was utilized in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial where collateral filling of <50% of the MCA territory was used to exclude patients with a large core infarct and correlated well with ASPECTS of ≤5 (3). Advantages of this approach include low cost, minimal additional radiation, and fast post-processing times.
CTP involves an additional contrast bolus with continuous scanning of either a segment of brain or more recently whole brain imaging where software can then be used to calculate various parameters such as time to start (TTS), time to peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF). Color-coded maps are generated. Brain at risk is best quantified by areas where TTP is >6 seconds although areas of increased MTT and TTS roughly approximate penumbra as well. Areas where CBV or CBF falls below specified thresholds are used to estimate the core infarct.
Significant controversy exists in the literature about use of CTP for estimation of core infarct and penumbra for endovascular patient selection. Evaluation of the same source data on different vendor software packages leads to differing estimations of core infarct and penumbra potentially making CTP unreliable for patient selection (12). Radiation concerns also exist with use of CTP. Nevertheless, the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-arterial
(EXTEND-IA) trials demonstrated that CTP with automated reconstruction software (RAPID, iSchemaView) led to appropriate patient selection for endovascular therapy (2,5). In these trials, patients with large core infarcts of >50 to 70 mL were excluded, and patients were required to have a penumbra at least 20% to 80% larger than the core. It is possible that use of more strict eligibility criteria with CTP in these trials selected out some patients who would otherwise benefit from therapy as up to 25% of patients excluded from EXTEND-IA would have been eligible in other trials.
(EXTEND-IA) trials demonstrated that CTP with automated reconstruction software (RAPID, iSchemaView) led to appropriate patient selection for endovascular therapy (2,5). In these trials, patients with large core infarcts of >50 to 70 mL were excluded, and patients were required to have a penumbra at least 20% to 80% larger than the core. It is possible that use of more strict eligibility criteria with CTP in these trials selected out some patients who would otherwise benefit from therapy as up to 25% of patients excluded from EXTEND-IA would have been eligible in other trials.
e. Magnetic resonance imaging (MRI)
Diffusion-weighted restriction on MRI is the most sensitive modality for early detection of irreversibly injured brain. MRI alone is also highly sensitive for blood products. The disadvantages of MRI mainly involve lack of 24/7/365 availability, slower acquisition times, additional time required to screen patients for implants and metallic foreign bodies, increased sensitivity to patient motion, and patient claustrophobia. MR perfusion-weighted images can be used to determine the ischemic penumbra of brain at risk similar to CTP. At the authors’ institution, MRI
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