Management of acute ischemic stroke

Computed tomography

A noncontrast head CT is the initial imaging modality of choice for patients with suspected stroke. The foremost reason is that CT scans can be readily and quickly obtained because of the widespread availability of CT scanners; the second reason is the ability of CT to exclude intracranial hemorrhage. In addition to differentiating ischemic stroke from hemorrhage, CT may demonstrate subtle parenchymal abnormalities indicative of early edema or infarction. Previously, it was believed that these changes did not occur on CT for at least 6 hours after ischemic stroke. More recent studies indicate, however, that early changes of ischemia frequently occur within a few hours of stroke onset and have been seen as soon as 1 hour after stroke. These changes include reduced attenuation in the basal ganglia ; loss of gray-white differentiation, particularly in the insular region ; low density in the cortex and subcortical white matter; and loss of sulcal markings, suggesting early mass effect and edema ( Fig. 46.1 A and B).

A hyperdense middle cerebral artery (MCA) occurs in 20%–37% of cases, indicating acute thrombus within the artery. This condition rarely occurs without at least one other early CT abnormality. Hyperdensity in the basilar artery associated with thrombosis also has been reported. In 100 patients studied within 14 hours (mean 6.4 hours) of stroke onset, multiple early CT abnormalities correlated with the size of the subsequent infarct and poor outcome. In the ECASS I trial of tPA for acute stroke, early CT changes correlated with larger subsequent infarct volume and a greater likelihood of hemorrhagic conversion after tPA. Quantitative assessment of CT changes using the Alberta Stroke Program Early CT Score (ASPECTS) scale in patients treated with intravenous tPA also showed a relationship between early CT hypodensity (ASPECTS <8) and hemorrhage. ^, Thus some experts recommend withholding thrombolytic therapy in patients with extensive early CT changes, particularly in those later in the thrombolytic time window, although this practice is controversial. For example, subsequent analysis of the NINDS rt-PA trial data revealed that early ischemic changes did not predict symptomatic hemorrhage or response to treatment, and more recent evidence reports no association between early ischemic CT changes and outcome.

Computed tomography angiography

CT angiography (CTA) can be performed using spiral CT, allowing for imaging of the intracranial and extracranial circulation. Optimally, CTA of the neck should also include visualization of the aortic arch. The typical single bolus of iodine contrast material is about 70 cc. This injection limits the use of CTA in patients with renal failure or contrast hypersensitivity. In acute stroke, CTA of the head and neck is highly reliable for diagnosis of intracranial occlusions and correlates with other imaging modalities. ^, Three-dimensional reconstruction images can also be created, providing additional views and information about the carotid bifurcation and carotid lesions, revealing eccentric lesions and ulceration (see Fig. 46.1 C and D).

Computed tomography perfusion

In addition to imaging the brain parenchyma with a noncontrast head CT and the cerebral vasculature with CTA, CT perfusion (CTP) adds assessment of cerebral blood volume (CBV) and cerebral blood flow (CBF) ( Fig. 46.2 ). In patients with acute stroke, CTP has been correlated with final infarct size and outcome, particularly after recanalization. CTP maps combining CBV and CBF identify brain tissue that progresses to infarction if not reperfused, consistent with ischemic penumbra. Recent evidence suggests that the inclusion of CTP in a stroke imaging protocol increases diagnostic performance. ^{, ,}

Whereas CTP serves as a qualitative measure of CBF, there have been investigations into using xenon CT to measure CBF quantitatively. Stable xenon is an inert gas inhaled as a mixture of 27% xenon and 73% oxygen. During inhalation over a few minutes, rapid scanning is performed, and pixel-by-pixel blood flow values are calculated at different brain levels ( Fig. 46.3 ). In a series of patients with MCA occlusion studied with xenon CT, areas of penumbra were present in all patients, and the percentage of MCA territory in the penumbral range (CBF 8–20 mL/100 g/min) remained relatively constant across the group. In contrast, the percentage of MCA territory with CBF values representing infarcted tissue (CBF <8 mL/100 g/min) varied greatly. Outcome correlated highly with the area of infarcted MCA territory, not the amount of ischemic penumbra. Thus after the first few hours, the size of the core infarcted tissue, not the amount of penumbral tissue, may be the most important imaging parameter to determine suitability for acute stroke therapy.

Magnetic resonance imaging

Compared with CT modalities, MRI is advantageous because it is more sensitive to cerebral infarction, especially in the brainstem and deep white matter. Typical sequences included in an MRI stroke protocol include diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) to evaluate for potential acute ischemia, multiplanar gradient-recalled (MPGR) or gradient-recalled echo (GRE) to evaluate for hemorrhage, and fluid-attenuated inversion recovery (FLAIR) to evaluate for important signs in both hyperacute and acute stages of stroke (i.e., assessment for absence of flow void in major cerebral arteries, suggesting occlusion or slow flow in that artery). Perfusion-weighted imaging (PWI) is often used to determine abnormal tissue perfusion based on transit times for contrast material through brain parenchyma ( Fig. 46.4 ).

DWI shows parenchymal abnormalities earlier than conventional T2-weighted images in patients with acute stroke. It detects the diffusion of water in the brain and shows hyperintensity in areas of reduced diffusion (see Fig. 46.4 ). As water moves from the extracellular to the intracellular space, there is less movement of water and loss of signal, resulting in hyperintensity. Early detection of lesions by DWI helps differentiate cerebral ischemia from other conditions that mimic stroke, such as seizures or toxic-metabolic states. Additionally, combining DWI with PWI may identify reversibly ischemic tissue. If there is a large area of PWI abnormality indicating reduced CBF but limited established infarction, as evidenced by DWI abnormality, penumbral tissue is likely present, indicating areas at risk of undergoing infarction.

In stroke patients, the size of the DWI lesion and the growth of these abnormal DWI regions are strong predictors of outcome. In acute stroke, a marker of tissue viability is needed, and some investigators have suggested that the extent of mismatch between lesions on DWI and PWI could serve as this marker. The concept of DWI/PWI mismatch has been used as an inclusion criterion in several studies (DIAS, DIAS-2, among others) assessing thrombolytic agents and is being employed more frequently to select patients who may benefit from reperfusion therapy. Patients with mismatch might be more likely to respond to reperfusion therapy. Patients with large areas of DWI abnormality or large severe PWI abnormalities may be at greater risk for hemorrhage if reperfusion therapy is pursued. ^,

Magnetic resonance angiography

Magnetic resonance angiography (MRA) of the head and neck offers a noninvasive method of imaging the intracranial and extracranial vasculature. MRA typically uses gadolinium contrast in appropriate patients, but important information can be obtained based on time-of-flight techniques not using contrast. ^, Detection of dissection or occlusion in the circle of Willis and the extracranial vertebral and carotid arteries can be examined with MRA, but occlusions of small peripheral branch arteries may not be detected. Artifacts may also obscure proper identification of arterial pathology. Signal dropout may occur at the site of arterial stenosis owing to the effects of turbulent flow. If an artery is tortuous, it may extend out of the imaging section and appear occluded. MRI tends to overestimate the severity of stenosis, and evidence of severe stenosis should be confirmed with another modality. MRA is better for localizing the site of stenotic lesions than determining severity of stenosis. Similarly, differentiation between severe stenosis and occlusion is unreliable with MRI, and apparent occlusions by MRA should also be confirmed with angiography.

Digital subtraction angiography

Catheter-based digital subtraction angiography (DSA) remains the gold standard for determining the degree of vessel stenosis and understanding the collateral circulation. The high quality of anatomic delineation allows for precise determination of carotid stenosis as with CTA, whereas MRA and carotid Dopplers can misclassify stenosis. Historically, the procedure has been associated with a high risk of complications, although more modern experience estimates a much lower risk of stroke (0.3%) at experienced centers. ^, The technique requires specialized personnel and equipment and may not be readily available at all centers.

Intravenous thrombolysis

Acute stroke trials using intravenous thrombolytic agents date back to the early 1960s, with the use of streptokinase, fibrinolysin, and urokinase showing either no benefit or a higher mortality in patients treated with thrombolysis. These studies preceded CT imaging, and thus patients with hemorrhage were not excluded. The discouraging results hindered the development of more acute stroke trials until the 1980s, when several case reports showed favorable outcomes with intraarterial thrombolytic therapy within a few hours of stroke onset. ^, These reports resulted in small randomized trials and feasibility studies of intravenous thrombolytics ^, that ultimately gave rise to the pivotal NINDS rt-PA trial that showed a beneficial effect of thrombolytic therapy for acute stroke treatment when administered within 3 hours of symptom onset.