Acute Stroke Intervention
Ryan M. Hebert, MD
Fouad Chouairi, BS
Branden Cord, MD, PhD
Samuel Sommaruga, MD
Michael Mercier, BA
Anna Lynn, BS
Andrew Koo, BS
Stacy Chu, MD
Charles Matouk, MD, FRCS(C)
Key Points
An occlusion in major blood vessels at the base of the skull supplying the brain (paired internal and vertebral arteries) as well as their proximal intracranial branches (anterior cerebral artery, middle cerebral artery, and basilar artery) is referred to as an LVO (large vessel occlusion).
It is estimated that LVOs account for at least 10%-15% of all acute ischemic strokes.
Mechanical thrombectomy for anterior circulation LVOs is now standard of care for patients presenting within 6 hours of stroke onset but in select cases can be of value up to 24 hours since the event.
I. Introduction
In 2015, five clinical trials were published that established mechanical thrombectomy as a new standard of care in the management of large vessel occlusions (LVOs) of the brain.1,2,3,4,5 These studies and those that followed forever changed the paradigm of acute stoke management from solely focused on the timely administration of intravenous (IV) thrombolytics to emergent interventional revascularization.6,7,8,9 This is a watershed moment in acute stroke care. The stroke community is currently reorganizing triage protocols so that as many people as possible can benefit from this lifesaving intervention.
This chapter will provide a brief review of stroke epidemiology and pathophysiology, clinical trials data, and mechanical revascularization strategies for the nonexpert interventionist. The focus will be on the subset of acute ischemic strokes potentially amenable to mechanical revascularization, ie, LVOs.
II. Acute Stroke 101
A. Stroke Epidemiology
1. The definition of stroke is an acute-onset loss of neurological function (typically focal) that results from a vascular etiology. There are two main types of strokes: (1) ischemic (resulting from an obstruction within a brain blood vessel) and (2) hemorrhagic (resulting from vessel rupture). Ischemic stroke is far more common (accounting for 87% of all stroke cases) and is the topic of this review.10
2. Stroke is a common disease. Every year in the United States, approximately 800,000 people will have a stroke. More than three-fourth of these cases will be first presentations, and nearly 20% will suffer a second stroke within 4 years.11,12
3. Stroke is a leading cause of death and disability. It is the 5th leading cause of death behind heart disease, cancer, chronic lower respiratory disease, and accidents (unintentional injuries). Every 4 minutes, someone in the United States dies of a stroke, accounting for 130,000 deaths per year (or 1 in 20 deaths overall). Because stroke
often takes people out of the workforce, it represents a tremendous societal cost estimated at 34 billion dollars per year.13
4. Often, the largest stroke syndromes with the worst clinical outcomes result from a major blood vessel in the brain being occluded. These major blood vessels are the vessels at the base of the skull supplying the brain (paired internal and vertebral arteries) as well as their proximal intracranial branches (anterior cerebral artery, middle cerebral artery, and basilar artery). A blockage in any of these vessels is referred to as an LVO. It is estimated that LVOs account for 10%-15% of all acute ischemic strokes.14,15 It is these ischemic stroke patients who are potentially candidates for mechanical revascularization.
B. Stroke Pathophysiology
1. In acute ischemic stroke, if a territory of the brain is solely supplied by a single-end vessel, then occlusion of the vessel will result in brain infarction within a very short period of time. This most-at-risk brain territory is referred to as the ischemic core. Just outside of this core area is an area of the brain that experiences decreased, but somewhat maintained, cerebral blood flow (CBF) because of arterial collaterals. This area is referred to as the penumbra. Average CBF in a healthy adult is around 50 mL/100 g/min. Cellular function is perturbed in areas where CBF drops to 15-20 mL/100 g/min. Cells in this penumbral region may survive for several hours before irreversible cell death, ie, cerebral infarction, ensues. CBF <10 mL/100 g/min produces failure of cellular ionic gradients. If flow is not improved, cell death occurs in less than 60 minutes.16 An important clinical correlate of this basic stroke pathophysiology is that a clinician at the bedside cannot determine whether a patient with an acute ischemic stroke, eg, acute-onset hemiplegia, has a penumbral (reversible) or core (irreversible) neurological deficit.
2. Although time plays a significant role in stroke pathophysiology, it is not the only factor. The brain is supplied by a robust network of arterial collaterals, primarily arising from the circle of Willis (COW). The COW is supplied anteriorly by the internal carotid arteries (anterior circulation) and posteriorly by the vertebrobasilar system (posterior circulation). A complete COW is found in less than 50% of people. An incomplete COW has been associated with increased stroke risk.17 COW facilitates leptomeningeal collateralization between the middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA) territories. Some patients have good collateral circulations, others do not. It is the strength of these collaterals that helps define, in large part, the size of the ischemic core and penumbra. A second important clinical correlate is that the penumbral area is dynamic in space and time. For example, blood pressure augmentation may better support brain tissue supplied by a collateral network for a longer period of time, effectively increasing the size of the penumbra. Collateral status can be assessed noninvasively and has been correlated to stroke outcome.18,19
3. Noninvasive Imaging of “At-Risk Brain”—Clinical Assessment of Ischemic Core, Penumbra, and Collateral Circulation
Patients being evaluated for stroke universally undergo noncontrast computed tomography (NCCT) of the brain. This is primarily used to identify hemorrhagic stroke for intravenous tissue plasminogen activator (IV tPA) exclusion. NCCT is also useful in identifying early ischemic parenchymal changes. The Alberta Stroke Program Early CT (ASPECT) Score is a popular method to quantify anterior circulation early ischemic change (EIC) on computed tomography (CT) to predict the outcome after IV thrombolysis. In this scoring system, 7 points are assigned to the MCA territory and 3 to subcortical structures. The scoring system starts at 10. Each region showing EIC accounts for a 1-point deduction. Lower ASPECT Scores were associated with poor outcomes after IV tPA.20
CT angiography (CTA) is an extremely useful diagnostic tool and establishes the diagnosis of LVO. In addition, it provides the interventionist with valuable technical information about the aortic arch, vessel tortuosity, and carotid bifurcation disease. CTA of the head also provides important information about collateral blood flow to the territory at risk. Several studies have shown that good collaterals on CTA are predictors of good outcome after mechanical thrombectomy.18,21
CT perfusion is performed by intravenously administering a bolus of contrast and using serial CT scans to follow the contrast bolus through the intracranial circulation. This imaging technique provides estimates of CBF, mean transit time (MTT), time-to-peak (TTP), and cerebral blood volume (CBV). Decreased CBF and CBV reflect the ischemic core, ie, irreversibly injured (nonsalvageable) brain. The penumbra is demonstrated as a region of brain with preserved CBV and increased MTT (or TTP).22,23,24,25,26,27
MRI (magnetic resonance imaging) is more sensitive than CT for detecting cerebral ischemia and infarction. Diffusion-weighted imaging (DWI) can detect ischemic changes within 5-10 minutes of symptom onset. T2-weighted sequences identify subacute infarction 6-24 hours after ictus. Hyperintensity on DWI is the best imaging correlate of the ischemic core.28,29
There is vigorous debate regarding utilization of CT perfusion and MRI in the evaluation and triage of acute ischemic stroke. Both have been shown to increase time to puncture and are not associated with improved outcomes. However, in certain scenarios, both provide invaluable data that aid in complex clinical decision-making.30
III. Intravenous Tissue Plasminogen Activator—Long-Time Standard of Care and Important Limitations
A. NINDS and ECASS In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) published a paper in the New England Journal of Medicine supporting the efficacy of IV recombinant tissue plasminogen activator (tPA) in the setting of acute stroke.31 Their results failed to show a statistically significant, clinical improvement or resolution of stroke symptoms at 24 hours. However, at 3 months, there was a statistical,
clinical improvement in the IV tPA group compared with placebo. This clinical improvement was realized despite an increase in the rate of symptomatic intracerebral hemorrhage (6% vs 0.6%). These results were confirmed by the European Cooperative Acute Stroke Study (ECASS) that also extended the time window in which IV tPA could be administered (4.5 hours after stroke onset).32 These studies established the first effective treatment for acute ischemic stroke and defined a new standard of care.
B. Intravenous Tissue Plasminogen Activator for Ischemic Stroke Limitations
1. A narrow therapeutic window. The narrow window from stroke onset to administration of IV tPA means that most patients arrive in hospital too late to receive the medication. Approximately one-fourth of patients have so-called “wake up” strokes of uncertain time of onset and are therefore ineligible to receive IV tPA. On average, only 7% of patients presenting with acute ischemic stroke receive IV tPA.33,34,35,36,37
2. Limited efficacy for LVOs and large stroke syndromes. In 2006, Smith et al. reported on a consecutive series of patients with large stroke syndromes and LVOs.38 They divided their study population into two groups: one group in which IV tPA achieved recanalization and another with persistent vessel occlusion. The group in which recanalization was achieved, albeit much smaller than the group with persistent occlusion, realized much better clinical outcomes. These data are consistent with other reports demonstrating poor recanalization rates for internal carotid artery (ICA) terminus and basilar artery occlusions.39
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