Acute Stroke Imaging

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Chapter 3 Acute Stroke Imaging

Alejandro A. Rabinstein, Steven J. Resnick

There was a time, not too long ago, when acute brain imaging in patients with suspected stroke was thought to be useful only to exclude hemorrhage or obvious stroke mimickers, such as tumors. The introduction of effective acute stroke therapies changed this conception completely, however. Today emergency brain imaging is essential for the management of acute stroke patients. We have learned that computed tomography (CT) scans can offer valuable information even when obtained within the first few hours of the ischemic event (dispelling the notion that CT scans are not useful for ischemic strokes until 1 or 2 days after onset). New CT-based protocols, including CT perfusion (CTP) scans and CT angiograms, are rapidly gaining ground in clinical practice. Diffusion-weighted and perfusion-weighted (DWI and PWI) magnetic resonance imaging (MRI) provide the ability to depict the penumbra and promise expansion of the therapeutic window for vessel opening on individual cases based on the subsistence of salvageable tissue. Conventional angiography has been transformed from a purely diagnostic test into a means for therapeutic intervention. Even transcranial Doppler may have an important role in the emergent evaluation and management of acute ischemic stroke, providing proof of large intracranial vessel occlusion and possibly improving the chances of recanalization with thrombolysis when continuous insonation is employed.

The uses of various neuroimaging techniques in acute stroke are multiple and continue to expand. The most common current indications and purposes of acute neuroimaging in stroke patients are listed in Table 3-1.

TABLE 3-1 Indications and purposes of emergency neuroimaging in patients with suspected acute ischemic stroke

Indication/purpose	Imaging modality
Confirmation of diagnosis (TIA vs. stroke vs. stroke mimics)	CT/MRI
Differentiation of ischemia vs. hemorrhage	CT/MRI
Visualization of established infarction (as contraindication for thrombolysis)	CT
Localization of ischemia/stroke pattern (which may guide evaluation of stroke mechanism)	CT/MRI
Evaluation of penumbra (which may extend therapeutic window for acute revascularization)	DWI-PWI/CTP
Identification of early prognostic markers (e.g., HDMCA sign, extensive high ASPECTS score, large volume of DWI restriction)	CT/MRI
Visualization of arterial site of occlusion	MRA/CTA/catheter angiography
Documentation of recanalization	MRA/CTA/catheter angiography/TCD
US-assisted intravenous thrombolysis	TCD
Access and information to make endovascular treatment possible	Catheter angiography

ASPECTS, Alberta Stroke Program Early CT Score; CT, computed tomography; CTA, CT angiography; CTP, CT perfusion; DWI, diffusion-weighted imaging; HDMCA, hyperdense middle cerebral artery; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; PWI, perfusion-weighted imaging; TCD, transcranial Doppler; TIA, transient ischemic attack; US, ultrasound.

This chapter illustrates and summarizes the multiple values of brain imaging in the acute phase of ischemic stroke and concludes with a succinct discussion on the radiological features of subacute and chronic infarctions that allow timing of ischemic strokes.

COMPUTED TOMOGRAPHY

CT Signs of Acute Ischemia

Case Vignette

A 50-year-old man with a history of hypertension and rapid palpitations presented to the emergency department with acute left hemiparesis. Neurological examination showed right gaze preference, left homonymous hemianopia, left hemiparesis, and left hemineglect. Initial CT scan obtained 5 hours and 20 minutes after symptom onset revealed early signs of edema and infarction throughout the territory of the right middle cerebral artery (Figure 3-1, upper row). Because of the presence of these radiological findings, endovascular revascularization treatments were not attempted. On Day 3, he was more somnolent, and a repeat CT scan showed spontaneous hemorrhage in the area of infarction (Figure 3-1, lower row). The patient was diagnosed with atrial fibrillation, and anticoagulation was subsequently started for secondary stroke prevention. He survived his stroke but remained moderately disabled.

Figure 3-1 Top row: Nonenhanced computed tomography (CT) scan of the brain showing early signs of edema (sulcal effacement, loss of differentiation of gray and white matter) and infarction (hypoattenuation) in the territory of the right middle cerebral artery (arrows). Bottom row: Repeat CT scan showing evolution of the extensive ischemic stroke with evidence of hemorrhage within the infarction.

♦ Far from being uninformative, the CT scan of the brain performed in the emergency department can provide valuable diagnostic and prognostic information and may be crucial in the selection of early management options.

♦ CT scan is available in most emergency departments and can be rapidly obtained. It must be performed in all patients suspected of having an acute stroke, and it is the only radiological study needed before deciding the administration of intravenous thrombolysis.¹

♦ Noncontrast CT can readily and reliably exclude hemorrhage, demonstrate the fresh intraluminal thrombus, and display early signs of brain ischemia (Table 3-2 and Figure 3-2).

♦ When carefully reviewed, noncontrast CT scan of the brain can reveal these signs of ischemia in up to 75% of patients with territorial MCA stroke.²

♦ It is important to discriminate signs of brain edema, such as loss of insular ribbon (Figure 3-3), obscuration of lenticular nucleus (Figure 3-4), loss of gray–white matter differentiation, and sulcal effacement (Figure 3-5) from areas of hypoattenuation, because only the latter represents irreversible damage (established infarction).^3,⁴

♦ Interobserver agreement for the recognition of early ischemic changes is only fair when performed without following a formal method and without considering the clinical information.^5,⁶ Thus it is crucial to know the expected location of the ischemic insult on the basis of the information provided by the history and physical examination and to follow a methodical approach to maximize the yield of CT scan interpretation. Modifications of window settings may also increase the sensitivity of CT scanning to detect early ischemic changes (Figure 3-6).⁷

♦ Visual identification of early signs of ischemia (particularly hypoattenuation) involving more than one third of the estimated middle cerebral artery (MCA) territory was considered an exclusion criterion for enrollment in several thrombolysis trials, most notably those conducted by the European Acute Stroke Study (ECASS) investigators,^8,⁹ on the basis of a reasonable but unproved assumption that patients with early signs of extensive ischemia would have higher risk of bleeding after thrombolysis. However, this preconception was not validated by the analysis of the radiological data from the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA study, which did not include this radiological exclusion criterion.¹⁰ In this trial, ischemic changes on baseline CT scan were observed in 31% of patients. They correlated with greater severity of initial clinical deficits and with longer time from symptom onset but were not independently associated with functional outcome after controlling for other baseline variables. Early ischemic changes were not associated with clinical deterioration within the first 24 hours or symptomatic intracranial hemorrhage within the first 36 hours in the adjusted analysis.¹¹

♦ Moreover, although there is some evidence that extensive early ischemic changes may portend higher risk of intracerebral hemorrhage,¹² there is no proof that the extension of early ischemic changes significantly affects the chances of functional recovery after thrombolysis.^12,¹³

♦ Nonetheless, most current acute stroke management guidelines include extensive early signs of ischemia as a contraindication for thrombolysis. The guidelines sponsored by the American Heart Association indicate that thrombolysis should not be used if the baseline CT scan shows multilobar hypodensity involving more than one third of the cerebral hemisphere.¹ This carefully crafted recommendation appears prudent. It is important to notice that it intentionally indicates hypodensity (as opposed to other early signs that may represent only tissue swelling and are more difficult to identify) and eliminates the need to estimate the MCA territory as a parameter to define the extension of the changes. On the basis of current evidence, withholding thrombolysis in patients with early signs of tissue edema but no large hypodensities is not justified.

♦ The extension of ischemic changes in the territory of the middle cerebral artery can be quantified using the Alberta Stroke Program Early CT Score (ASPECTS) (Figures 3-7 and 3-8), a 10-point topographic scoring system that has been shown to be easy to use in real time with moderately good interrater reliability.^2,^14,¹⁵ A cutoff score of less than 7 points is most useful to determine ischemia involving more than one third of the MCA territory.¹⁵ Notice that this score can only be used in cases of middle cerebral artery ischemia.

♦ CT scan may allow visualization of intraluminal thrombi in the terminal carotid, middle cerebral trunk, middle cerebral branches, and basilar arteries (Figure 3-9).

♦ The hyperdense MCA sign has good specificity for thrombotic MCA occlusion (it can be mimicked by a calcified plaque or high hematocrit, but in these cases the hyperdensity is typically bilateral), but its sensitivity is poor (approximately 30%).¹⁶

♦ The hyperdense MCA sign on baseline CT scan has been found to be associated with poor prognosis ^17,¹⁸ and a higher risk of hemorrhage after thrombolysis.¹⁹ The combination of hyperdense MCA sign and extensive sulcal effacement predicts massive swelling and brain herniation.²⁰ Conversely, early resolution of the hyperdensity in the MCA indicates successful reperfusion and is associated with favorable outcome after thrombolysis.

♦ Intravenous thrombolysis can be beneficial in patients presenting with the hyperdense MCA sign.¹⁸ However, when the hyperdense signal appears to involve the carotid terminus in a patient with signs suspicious for carotid bifurcation occlusion (depressed arousal, severe leg weakness), it may be more effective to pursue intra-arterial therapy directly if this is a pragmatically feasible option.²¹

♦ Distal thrombi can sometimes be visualized generating the Sylvian fissure “dot” sign (Figure 3-9, C).²² Its sensitivity is modest (close to 40%), but when identified, it is very specific in predicting M2 or M3 branch occlusion.²³ The dot sign is associated with better outcome than more proximal hyperdense vessel signals.²²

♦ Rarely, air or fat emboli can produce hypodense vessel signs.²⁴

TABLE 3-2 Early signs of ischemic stroke on brain CT scan.

Sign	Significance
Hyperdense vessel sign	Intraluminal thrombus
Loss of insular ribbon	Focal tissue edema
Obscuration of the lenticular nucleus	Focal tissue edema
Loss of gray–white matter distinction	Focal tissue edema
Sulcal effacement	Focal tissue edema
Areas of hypoattenuation	Tissue infarction

Figure 3-2 Nonenhanced computed tomography scan of the brain revealing a hyperdense vessel sign in the Sylvian fissure (arrowhead) and early hypoattenuation involving the right lenticular nucleus and insular region (open arrows). Notice loss of differentiation of the insular ribbon and margins of the lenticular nucleus, as well as partial effacement of the Sylvian fissure (solid arrow).

Figure 3-3 Example of early brain ischemia in the anterior division of the right middle cerebral artery causing loss of visualization of the insular cortex (insular ribbon sign).

Figure 3-4 Example of early ischemia in the territory of the right middle cerebral artery causing loss of differentiation of the boundaries of the lenticular nucleus (arrows). Notice gaze deviation to the right, a clinical sign pointing to the side of the stroke (arrowheads).

Figure 3-5 Prominent sulcal effacement and loss of gray–white matter differentiation (arrows) in a patient with early right middle cerebral artery ischemia.

Figure 3-6 Computed tomography scan of the brain of a patient who presented with symptoms suspicious for right middle cerebral artery stroke. (A) Brain window barely reveals subtle loss of differentiation of gray and white matter in a portion of the posterior right frontal cortex (arrows). (B) The early changes become much more noticeable (arrows) after modifying the window settings to increase the contrast.

Figure 3-7 Illustration of the Alberta Stroke Program Early CT Score (ASPECTS) scoring system to classify the extension of early ischemic changes in the middle cerebral artery territory on computed tomography scan. The entire middle cerebral artery territory is allotted 10 points; 1 point is subtracted for each of the defined regions affected with early ischemic changes. Thus lower scores indicate larger areas of ischemia.

Figure 3-8 Extensive right middle cerebral artery territory stroke on early computed tomography scan shown to exemplify the use of the Alberta Stroke Program Early CT Score (ASPECTS) score. The ASPECTS score in this case is 5 because of changes in the regions M1, I, M4, M5, and M6.

Figure 3-9 Examples of hyperdense vessel sign on the middle cerebral artery (A), Sylvian branch of the middle cerebral artery (linear hyperdensity shown in B and dot sign shown in C), and basilar artery (D).

CT Perfusion

♦ There is growing interest in the application of CT protocols using multimodal CT scanning (CT scan, CT perfusion, and CT angiogram) for the emergency diagnosis and management of ischemic stroke.^3,²⁵ The most attractive features of CT perfusion imaging are its potential for widespread availability (it can be performed on any standard helical CT scanner) and the short time required for the acquisition of data (with adequate training, CT perfusion and CT angiogram can be acquired in 15–20 minutes, and images can be processed and interpreted in 10 minutes or less).^26,²⁷

♦ Dynamic contrast-enhanced CT perfusion imaging (bolus tracking CT perfusion) generates maps of mean transit time (MTT; reflecting the time difference between arterial inflow and venous outflow), time to peak (TTP; representing the time to maximal concentration of contrast enhancement in a region of interest), cerebral blood flow (CBF), and cerebral blood volume (CBV) (Figure 3-10). These physiological measures can be precisely quantified, which represents an advantage over PWI MRI (Table 3-3).

♦ However, CT perfusion has limited spatial resolution, because most multidetector scanners at present only allow coverage of four brain slices (20 mm) and do not directly depict acute cellular damage. CT perfusion imaging requires exposure to iodine contrast (50–80 ml of contrast medium containing 300 mg of iodine/ml infused over approximately 10 sec), but complications related to contrast exposure are extremely infrequent.

♦ Prolonged relative MTT and delayed relative TTP are the most sensitive physiological parameters to detect hypoperfusion.²⁸ These measures correlate well with MRI abnormalities on PWI and accurately predict final infarct volume in patients who have persistent arterial occlusions (Figure 3-10).^29,³⁰ Meanwhile, reduced absolute CBV (or reduced relative CBV by visual inspection) is the best indicator of established infarction; it correlates well with DWI lesions on MRI and with final infarct size in patients who recanalize.²⁸^–³⁰ The product CBF × CBV may have greater diagnostic accuracy than CBV alone, but this requires the use of quantitative measures.³¹

♦ As with PWI, the main value of the CBF map on CT perfusion is the distinction between areas of hypoperfusion that may survive despite persistent vascular occlusion thanks to collateral circulation (although commonly included within the radiologically defined penumbra, these areas of oligemia are not at high risk of infarction unless there is a drop in cerebral perfusion pressure) from those destined to evolve to infarction unless prompt recanalization occurs. Although no definitive CBF thresholds have been defined for this distinction, the lower the CBF within an area of prolonged MTT, the higher the likelihood that the tissue will become infarcted unless rapidly reperfused.³¹

♦ When quantitative measures are used, the optimal threshold to detect tissue at risk for infarction is a relative MTT of 145% (i.e., 45% longer than in the contralateral side) and the optimal threshold to define the infarction core is an absolute CBV of 2.0 ml × 100 g^−1.32 The postprocessing technique that affords these quantitative measurements has been shown to be solidly reproducible.³³ Nonetheless, qualitative visual interpretation of the MTT and CBV maps yield fast and reliable information to estimate the penumbra.²⁸

♦ Hence, the mismatch between the areas of prolonged MTT (hypoperfusion) and reduced CBV (ischemic core) constitutes the best indicator of the penumbra on CT perfusion imaging (Figure 3-11).^28,^31,³²

Figure 3-10 A 58-year-old patient with history of hypertension and hypercholesterolemia who presented to the emergency department with aphasia, right superior quadrantanopsia, mild right hemiparesis, and right hemisensory loss. Computed tomography (CT) scan (shown with contrast) 4.5 hours after symptom onset did not depict the infarction (A) but CT perfusion clearly delineated the area of ischemia. Mean transit time map (B) showed delayed perfusion in the territory of the posterior division of the left middle cerebral artery (arrows). Cerebral blood flow map (C) confirmed hypoperfusion in that brain region (arrows). However, cerebral blood volume was relatively preserved (D). CT angiogram (E) (three-dimensional reconstruction shown) revealed lack of filling of the branches of the posterior division of the left middle cerebral artery (arrow). One day later, diffusion-weighted magnetic resonance imaging (F) disclosed an acute infarction in the area previously characterized as penumbra by the CT perfusion scan.

TABLE 3-3 Relative advantages of CT perfusion and DWI-PWI MRI for the assessment of ischemic penumbra.

CT perfusion

Easier access

Rapid acquisition of images

Robust quantitative physiological measurements

Feasible in patients with contraindication for MRI

DWI-PWI MRI

May be easier to visualize the penumbra

Depiction of cellular edema

Greater spatial resolution (whole brain imaging)

Does not require iodine contrast

CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; PWI, perfusion-weighted imaging.

Figure 3-11 Definitions of ischemic penumbra by magnetic resonance imaging and computed tomography perfusion criteria.

CT Angiogram

♦ CT angiography is also widely available, because it can also be performed with any helical scanner, and should be part of a comprehensive, multimodal CT protocol for evaluation of acute brain ischemia. After a bolus of iodine contrast is injected to enhance the vessels (100–120 ml of contrast), high-speed, timed scanning is performed typically covering from the aortic arch to the circle of Willis. After acquisition, the data are digitally reformatted to generate multiplanar, three-dimensional, and maximum intensity projection images.

♦ Although CT angiography has not been formally tested against catheter angiography to determine its precise positive and negative predictive values, in practice it allows rapid and reliable demonstration of intracranial or extracranial vessel occlusion.³⁴ Thus this technique may be valuable to guide timely therapeutic decisions, as illustrated by the case in Figure 3-12.

♦ CT angiography has been shown to be safe.²⁷ Renal complications related to contrast administration are exceptional and almost uniformly reversible.

♦ The source images of CT angiography have been used to estimate perfusion deficits (Figure 3-12 serves as example).³⁵ The advantages of this method over dynamic CT perfusion imaging include visualization of the whole brain and use of a single bolus of contrast material.³ However, this application has not been validated, and its sensitivity is likely to be poorer than those of CT perfusion or DWI-PWI.

Figure 3-12 A 58-year-old woman who presented with acute aphasia and right hemiparesis after a witnessed first generalized seizure. Computed tomography (CT) scan was negative. CT angiogram showed occlusion of the left M1 segment (arrow). The vascular occlusion recanalized with mechanical embolectomy and the patient recovered well.

MAGNETIC RESONANCE IMAGING

Although MRI scans provide better anatomical definition for the recognition of ischemic lesions than CT (particularly for small infarctions and strokes in the brainstem and posterior fossa), the added expense of MRI was deemed unjustified in the acute stroke setting until the introduction of physiological sequences: diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). These new sequences are extremely valuable tools for the acute diagnosis of ischemic stroke and offer promise to expand the therapeutic window for recanalization. Equally important are the advances in our understanding of stroke pathophysiology facilitated by the information afforded by these imaging techniques.

Furthermore, MRI (with DWI and susceptibility weighted sequence) has been proved superior to CT scanning for the detection of acute ischemia and chronic hemorrhage and at least comparable to CT for the diagnosis of acute hemorrhage.³⁶ Thus solid arguments support the use of MRI as the primary imaging modality for the emergency evaluation of acute stroke patients if the study can be performed without delay.

Diffusion-Weighted and Perfusion-Weighted Imaging

♦ DWI depicts the degree of diffusion of water molecules. Severe ischemia causes failure of ionic pumps at the cellular membrane and trapping of water molecules in the intracellular compartment (cellular edema) where water motion becomes limited (restricted diffusion).

♦ Evidence of restricted diffusion on DWI constitutes the most sensitive indicator of hyperacute and acute cerebral ischemia, greatly exceeding the sensitivity of CT scan ^37,³⁸ and conventional MRI sequences.³⁹

♦ DWI is obtained within 2 minutes by applying ultrafast echo-planar MRI scanning. Hence, DWI is considerably less susceptible to motion artifacts than conventional MRI sequences.

♦ Areas with restricted diffusion due to cellular edema are hyperintense on the DWI sequence and hypointense on the apparent diffusion coefficient (ADC) map (Figure 3-13). The ADC value quantifies diffusion; the lower the value, the greater the restriction of motion of water molecules. Conversely, high ADC values are observed in areas of vasogenic edema and chronic infarction in which water molecules have freedom of motion.

♦ When interpreting the MRI of a patient with acute stroke, it is essential to read the DWI images, ADC map, and T2-weighted sequence in combination. A bright signal on DWI matching with a dark signal on the ADC map will be indicative of restrictive diffusion (i.e., cellular edema consistent with acute ischemia). Bright signals appearing both on DWI and ADC map are caused by the “T2 shine through” phenomenon (Figure 3-14).⁴⁰ Hence isolated review of the DWI sequence may be misleading and should always be avoided.

♦ Decreased diffusion becomes apparent within 30 minutes of stroke onset and the reduction reaches its nadir 2 to 4 days later. ADC values then begin to increase until they return to baseline between 7 and 14 days later (pseudo-normalization) before increasing in the chronic phase.^41,⁴² After pseudo-normalization of the ADC value, DWI may continue to show a mildly hyperintense signal generated by T2 shine through.

♦ DWI is extremely sensitive for the detection of acute ischemia. In fact, DWI lesions are often seen in patients with reversible neurological deficits classified clinically as transient ischemic attacks (Figure 3-15).⁴³^–⁴⁶ The sensitivity of DWI only decreases slightly in cases of small medullary infarctions.

♦ Although highly indicative of acute ischemia in the right clinical setting, other mechanisms that produce intracellular edema may exhibit restricted diffusion on DWI. Examples include herpes encephalitis, Creutzfeldt-Jakob disease, diffuse axonal injury after brain trauma, and some acute demyelinating plaques among others.⁴⁷

♦ Table 3-4 lists the practical values of DWI in the evaluation of acute stroke patients.

Figure 3-13 Example of acute right middle cerebral artery territory stroke on a magnetic resonance imaging scan performed 2 days after symptom onset. (A) Diffusion-weighted imaging (DWI) showing bright signal in the right insular cortex and anterior temporal lobe (arrows). (B) Corresponding low signal on apparent diffusion coefficient map (arrows) confirms that the area of hyperintense signal on DWI represented restricted diffusion, thus indicating cellular edema. (C) Magnetic resonance angiogram shows marked reduction of flow starting at the distal end of the horizontal segment of the right middle cerebral artery (arrow).

Figure 3-14 Example of subacute right middle cerebral artery territory stroke on an magnetic resonance imaging scan performed 9 days after symptom onset. (A) Diffusion-weighted imaging showing heterogeneously bright signal in the right frontal lobe (arrows). (B) Apparent diffusion coefficient map shows a predominantly high signal in that region (i.e., diffusion is no longer restricted) from T2 shine through (arrows), thus indicating the subacute nature of the infarction. (C) Fluid-attenuated inversion recovery sequence already shows a well-delineated area of infarction.

Figure 3-15 A 69-year-old man evaluated at an outside emergency department for acute right hemiparesis. Symptoms resolved in less than 2 hours, and the patient was discharged home on aspirin to be evaluated as an outpatient. He was seen in our clinic 4 days later. He had remained asymptomatic. Magnetic resonance imaging performed at that time showed two small foci of faint hypersensitivity on diffusion-weighted imaging (arrows) with matching low apparent diffusion coefficient (not shown) indicative of ischemic strokes. Prolonged Holter monitoring revealed paroxysmal atrial fibrillation, and transesophageal echocardiogram disclosed an enlarged left atrium with spontaneous echo contrast. He was anticoagulated with warfarin and has not had any stroke recurrence over the subsequent 2 years.

TABLE 3-4 Main practical uses of DWI in patients with acute stroke presentation.

Hyperacute and acute diagnostic confirmation of ischemic stroke

Differentiation of acute vs. subacute vs. chronic ischemic lesions

Assessment of ischemic penumbra (in combination with PWI)

Acute differential diagnosis between TIA and minor stroke with reversible neurological deficits

Distinction of cytotoxic and vasogenic edema (in conditions such as eclampsia or hyperperfusion syndrome)

Identification of patients at risk of severe reperfusion hemorrhage

DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; PWI, perfusion-weighted imaging; TIA, transient ischemic attack.

PWI-DWI Mismatch

♦ PWI techniques rely on measuring the concentration of contrast (typically gadolinium) as it passes through the cerebral microcirculation. Dynamic susceptibility-weighted (T2*-weighted) imaging is most commonly used to track the bolus of gadolinium, which produces a transient loss of T2* signal and allows the creation of a hemodynamic curve of signal intensity over time. Noninvasive techniques of PWI using endogenous contrast agents (deoxyhemoglobin in blood oxygen level dependent [BOLD] or hydrogen proton in arterial spin labeling [ASL]) are much less commonly employed in acute stroke protocols.

♦ PWI produces maps of MTT, TTP, CBF, and CBV. However, measurements are relative to the contralateral side as opposed to the absolute hemodynamic values provided by CTP.

♦ A TTP delay greater than 4 seconds relative to the contralateral hemisphere appears to be the best marker of the penumbra.⁴⁸ Nonetheless, this measure may overestimate the size of penumbra in some cases.⁴⁸ CBF maps most closely identify the final infarct volume.^49,⁵⁰

♦ The ischemic penumbra is represented on MRI by the perfusion-diffusion (PWI-DWI) mismatch (Figures 3-11, 3-16, and 3-17). The PWI lesion corresponds to the area of hypoperfusion and the DWI lesion to the ischemic core.

♦ PWI-DWI mismatch is seen in approximately 70% of patients with proximal occlusion of the middle cerebral artery (MCA).⁵¹

♦ Unfortunately, there is no validated definition of PWI-DWI mismatch.⁵² Different definitions have been used in published studies, and visual estimates are most commonly used in practice for acute decision making.

♦ In theory, the DWI lesion can expand to reach the size of the initial PWI deficit unless reperfusion occurs. However, confirmation of this hypothesis has proved elusive at times. In fact, some studies have shown that mismatch volume may fail to correlate with DWI lesion expansion.^50,⁵³ Possible explanations for this lack of correlation are that areas of ischemia are highly heterogeneous,⁵⁴ DWI lesions may be reversible (normalization of ADC values has been noted in some patients after thrombolysis),⁵⁵ and PWI lesions actually incorporate regions of true penumbra and regions of reversible oligemia.⁵⁶

♦ Determining whether PWI-DWI mismatch can be reliably used to identify salvageable tissue is of major practical importance. Because DWI expansion can be prevented by early reperfusion regardless of the presence of PWI-DWI mismatch,⁵³ there is no indication for MRI before administering intravenous thrombolysis within 3 hours of symptom onset (there are some data suggesting greater safety for thrombolysis within 3 hours in patients selected with MRI vs. those only evaluated with CT scan,⁵⁷ but not enough solid evidence to change current practice guidelines). However, all other acute revascularization treatments are not the standard of care, and there is considerable interest in developing imaging protocols to guide their application (penumbra-based protocols). MRI protocols have been used in research trials to select candidates for intravenous thrombolysis beyond the currently accepted therapeutic window.^58,⁵⁹

♦ In a recent prospective, multicenter study of ischemic stroke patients treated with intravenous thrombolysis between 3 and 6 hours after symptom onset, those patients with larger PWI-DWI mismatch had greater likelihood of favorable clinical outcome after reperfusion.⁶⁰ In this same study, patients with very large DWI or PWI lesion volumes had very high risk of fatal hemorrhagic conversion after reperfusion.⁶⁰ Thus MRI profiles may help identify the best and worst candidates for revascularization therapy beyond 3 hours.⁵²

♦ In fact, the EPITHET trial has shown that penumbra defined by DWI-PWI mismatch is common (86% in this study) in patients evaluated between 3 and 6 hours after symptom onset. Treating these patients with intravenous thrombolysis was found to increase the chances of reperfusion, which in turn improves clinical outcomes.⁶¹

♦ In centers in which PWI has not been standardized, clinicians may rely on the clinical-radiological mismatch, understood as the discrepancy between relatively small DWI lesions and severe clinical deficits (Figure 3-18).⁶² These patients are likely to have large areas of penumbra in which brain tissue is dysfunctional (hence the severe clinical deficits) but salvageable (hence the relatively small DWI lesion). This clinical-radiological mismatch has been found to predict the presence of PWI-DWI mismatch with high specificity, although low sensitivity.⁶³

Figure 3-16 A 64-year-old man presenting with fluent aphasia. Diffusion-weighted imaging (A) and apparent diffusion coefficient (B) showed a small area of restricted diffusion, indicating cellular edema from infarction (open arrows). This infarct core was surrounded by a larger region of hypoperfusion well delineated by the perfusion-weighted imaging scan (C, solid arrow). Notice the curves of signal intensity over time (D), showing the delayed perfusion peak in the affected region compared with the contralateral side.

Figure 3-17 A 79-year-old woman with left internal carotid occlusion near its origin who presented with severe symptoms of anterior circulation stroke. However, symptoms reversed almost completely with hemodynamic augmentation (crystalloids, colloids, and vasopressors to increase perfusion pressure). On the first day, diffusion-weighted imaging (DWI) (A) barely revealed a few punctuate areas of restricted diffusion (matching apparent diffusion coefficient map not shown) despite a very large region of compromised perfusion on perfusion-weighted imaging in the territory of the left middle cerebral artery (B). The patient remained stable over the subsequent 36 hours, and a repeat magnetic resonance imaging at that point showed some additional areas of restricted diffusion on DWI following the internal watershed distribution (C) and persistent hypoperfusion in the entire left middle cerebral artery territory (D); this large mismatch indicated the persistence of an extensive area of ischemic penumbra. Unfortunately, the patient developed pulmonary edema and myocardial ischemia on the fourth hospital day, requiring diuretic therapy and discontinuation of the vasopressors. Shortly after these therapeutic decisions were forced by the cardiopulmonary complications, the patient’s neurological status worsened considerably, and a repeat computed tomography scan then showed the expected large middle cerebral artery infarction (E).

Figure 3-18 A 54-year-old woman presented to the emergency department with global aphasia, right visual field impairment, and dense right facial and brachial paresis with associated sensory loss. National Institutes of Health Stroke Scale score (NIHSS) was 12. Computed tomography scan obtained nearly 4 hours after symptom onset was negative for signs of acute ischemia. Diffusion-weighted imaging only displayed scattered small areas of restricted diffusion in the left middle cerebral artery and internal watershed distribution (arrowheads), indicating a large clinical-diffusion mismatch. Perfusion-weighted imaging was not performed, but magnetic resonance angiography revealed distal occlusion of the M1 segment of the left middle cerebral artery (arrow). Successful recanalization was achieved with a combination of mechanical embolectomy and adjuvant intra-arterial thrombolysis. The patient improved substantially, and the following morning, her NIHSS had diminished to 4. She was discharged to rehabilitation in good functional status and recovered well with therapy.

Direct Thrombus Visualization

♦ The intravascular occluding thrombus can be seen on T1-weighted sequence, and especially on fluid-attenuated inversion recovery (FLAIR)⁶⁴ and T2* sequences (Figure 3-19).

♦ The susceptibility vessel sign on T2* sequence may actually identify fibrin-rich emboli (more likely to be originated by a cardiac source).⁶⁵ It is unclear whether this sign may predict greater likelihood of recanalization, a notion supported by some studies⁶⁵ but not by others.⁶⁶ Disappearance of the sign on follow-up MRI after thrombolysis correlates with recanalization but does not necessarily portend favorable clinical outcome.⁶⁷

Figure 3-19 Images illustrating visualization of acute intravascular thrombus on various magnetic resonance imaging/angiography sequences.

MAGNETIC RESONANCE ANGIOGRAPHY

♦ Magnetic resonance angiography (MRA) can be valuable in the acute setting to determine the actual site of the vascular occlusion (see Figure 3-18) and to assess whether the vessel was successfully opened after noninvasive revascularization treatments (Figure 3-20).

♦ Stroke protocols typically include two-dimensional and three-dimensional time-of-flight (2D and 3D TOF) and contrast-enhanced MRA images of the neck and 3D TOF MRA images of the intracranial circulation. For acute evaluations, often only intracranial MRA is obtained.

♦ It is important to be aware that saturation artifact may produce loss of signal, which may be misinterpreted as occlusion. This type of artifact occurs because whereas blood flow perpendicular to the plane of application of radiofrequency pulses is exposed briefly to these pulses and can be well imaged, blood flowing in the same plane as the angle of imaging is exposed to an excessive amount of radiofrequency pulses, leading to saturation and signal loss.⁶⁸ Saturation artifact is commonly encountered at the levels of the horizontal turns of the vertebral arteries and in the knees of the petrous carotid arteries, but it can also be found in distal branches of the circle of Willis, where it can be more deceiving. Contrast-enhanced images may improve accuracy in the assessment of patency of distal arterial branches.⁶⁹

♦ In addition, slow or turbulent flow may also generate loss of signal, a phenomenon known as flow-related artifact.⁶⁸

♦ Despite these pitfalls, MRA remains an accurate noninvasive technique to assess vessel pathology in acute ischemic stroke.

♦ Nonetheless, CT angiography has the advantage of providing confirmation of large vessel occlusion faster than MRA and may therefore be preferable for the emergency evaluation. Transcranial Doppler (TCD) can be performed in the emergency department and may also be used for this purpose, although its value is limited to proximal M1 occlusions.⁶⁴

♦ When administration of gadolinium is considered, the small risk of inducing nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) in patients with renal failure should be kept in mind.⁷⁰^–⁷²

Figure 3-20 Magnetic resonance imaging of the brain showing small areas of acute infarction (arrows) on diffusion-weighted imaging involving the right lateral thalamus/dorsal end of the posterior limb of the internal capsule (A) and the posterior aspect of the right medial temporal lobe (B), corresponding to the distribution of the right posterior cerebral artery. Magnetic resonance angiography of the intracranial circulation disclosed a distal occlusion of this vessel (arrowhead).

IMAGING IN STROKE EMERGENCIES

Intravenous Thrombolysis

Case Vignette

A 72-year-old man presented to the emergency department with sudden onset of visual disturbance and behavioral changes. On neurological examination, he was mildly confused and had a dense left homonymous hemianopia. He also had slight weakness in the left upper extremity and possible mild hypoesthesia on the left hemibody. CT scan obtained 90 minutes after symptom onset demonstrated no acute changes. He underwent intravenous thrombolysis starting 115 minutes after symptom onset. Over the following 12 hours, his symptoms gradually improved and 24 hours later, he had no residual deficits. Brain MRI at that point revealed an acute infarction involving the posterior aspect of the right medial temporal lobe and a small area of the posterior limb of the right internal capsule (see Figure 3-20). MRA of intracranial circulation demonstrated distal occlusion of the terminal segment of the posterior cerebral artery (see Figure 3-20). Because the patient’s clinical syndrome at presentation had been consistent with a proximal occlusion of the posterior cerebral artery, these radiological findings were most likely caused by fragmentation of the initially larger clot due to successful thrombolysis that subsequently led to a more distal (and asymptomatic) vessel occlusion.

♦ As noted in our previous discussion, CT scan is indicated before infusing intravenous thrombolytic agents.

♦ The main goals of CT scanning are excluding hemorrhage or a large hypodensity. These are the only radiological contraindications for the use of intravenous thrombolysis within 3 hours of symptom onset.

♦ A repeat CT scan must be obtained 24 hours after thrombolysis to exclude hemorrhagic conversion before starting any antithrombotic therapy for secondary stroke prevention. The risk of symptomatic intracranial hemorrhage after intravenous thrombolysis was 6.4% in the landmark NINDS trial,¹⁰ and similar or even lower rates have been reported in subsequent studies and from community registries.⁷³

♦ MRI protocols are being evaluated to expand the therapeutic window of intravenous thrombolysis. Initial results indicate that patients with persistent penumbra defined by PWI-DWI mismatch beyond 3 hours from symptom onset may significantly benefit from recanalization.⁶⁰

♦ CT protocols may offer similar information on the penumbra and should be evaluated as alternatives to identify candidates for delayed revascularization because CT imaging is more widely accessible and information can be quickly acquired.

♦ The likelihood of recanalization with intravenous thrombolysis may be increased by combining it with continuous insonation of the site of the occlusion using TCD.⁷⁴ A Phase II trial evaluating this approach showed promising results. However, correct application of this combined therapeutic modality is labor intensive and requires TCD expertise. TCD may also be used to diagnose early reocclusion after initially successful recanalization; this finding is strongly predictive of clinical decline and poor functional outcome.⁷⁵

Intra-Arterial Revascularization Therapies

Case Vignette

A 52-year-old woman presented to a local hospital with acute aphasia and right hemiplegia. CT scan was negative for hemorrhage, and she was referred to our academic hospital for acute management. Upon arrival to our emergency department 3 hours and 30 minutes after symptom onset, her examination revealed global aphasia, left gaze preference, right homonymous hemianopia, paralysis of the lower right face and the right arm, comparatively milder weakness of the right leg, and right hemihypoesthesia. Her initial National Institutes of Health Stroke Scale score (NIHSS) was 20. Because she was outside of the accepted therapeutic window for intravenous thrombolysis, she was immediately taken to the angiographic suite. Digital subtraction angiography demonstrated a proximal occlusion of the M1 segment of the left middle cerebral artery. Intra-arterial infusion of the rt-PA (22 mg) combined with mechanical disruption of the clot and subsequent angioplasty of the previously occluded segment resulted in successful vessel recanalization (Figure 3-21). Over the following 24 hours, the patient recovered substantially from her initially severe deficits. Repeat brain imaging only showed a small left periopercular infarction. Her NIHSS at discharge was 4, and after a few weeks of outpatient rehabilitation, she was able to return to work with no functional restrictions.

Figure 3-21 DSA after left carotid injection showing proximal occlusion of the M1 segment of the middle cerebral artery on anteroposterior (A) and lateral (B) views (arrows). Initial infusion of intra-arterial rt-PA only achieved minimal opening of the vessel (C). Therefore, additional administration of the thrombolytic agent was combined with gentle acute angioplasty (arrows) (D, E). Postintervention DSA shows successful recanalization of the M1 segment and distal branches of the middle cerebral artery (F, anteroposterior view; G, lateral view). Notice residual irregularity of the previously occluded segment indicated by the arrowhead.

(Images courtesy of Dr. Ajay Wakhloo.)

♦ Intra-arterial revascularization can be achieved using intra-arterial infusion of thrombolytic agents, mechanical disruption of the clot, mechanical embolectomy, or, less commonly, angioplasty. These interventions are often combined or used sequentially after one of them fails.

♦ Intra-arterial thrombolysis (without mechanical disruption of the clot) may achieve recanalization in two thirds of patients with proximal MCA occlusions when infusion of the drug is started within 6 hours of symptom onset.⁷⁶ The rate of symptomatic intracranial hemorrhage in these cases is approximately 10%.⁷⁶

♦ Mechanical embolectomy using an embolus retrieving device (MERCI Retriever Concentric Medical, Mountain View, CA) has been reported to achieve recanalization in more than half of patients with large intracranial artery occlusions treated between 3 and 8 hours from stroke onset (Figure 3-22).⁷⁷^–⁷⁹ Use of adjuvant intra-arterial rt-PA can increase the rate of recanalization up to 57%.⁷⁹

♦ This recanalization rate is obviously far greater than the rate of spontaneous recanalization in the placebo arm of the largest intra-arterial thrombolysis trial (PROACT II) but does not compare favorably against the rate of recanalization of MCA occlusions in the treatment arm (i.e., patients who were actually treated with intra-arterial thrombolysis) of the same trial (57% with embolectomy vs 66% with intra-arterial thrombolysis). The functional outcomes of patients treated with mechanical embolectomy are similar to those observed in the PROACT II trial (36% with embolectomy regained functional independence vs 40% with intra-arterial thrombolysis), and mortality rate was slightly higher in the studies evaluating the MERCI device (34% vs. 25% in the treatment arm of PROACT II).^76,⁷⁹

♦ However, because failure of the Merci Retriever can be followed by intra-arterial thrombolysis, it has become a common practice in many centers to attempt embolectomy first.

♦ Mechanical embolectomy, with or without intra-arterial thrombolysis, can be safely attempted and may achieve recanalization in patients initially treated unsuccessfully with intravenous thrombolysis.^78,⁷⁹

♦ The rate of symptomatic complications in the MERCI trial has been acceptable (7.8%–9.8% rate of symptomatic ICH).⁷⁷^–⁷⁹ The possibility of vessel wall perforation was a major concern with the first generation of the device,⁷⁷ but the newer generation (L5 Retriever) has proved substantially safer.^78,⁷⁹ Nonetheless, procedural complications still occur in more than 5% of cases.⁷⁹

♦ The Merci Retriever should be used in patients with large intracranial vessel occlusions, such as M1 segment of the middle cerebral artery, and particularly the terminal carotid, vertebral, and basilar arteries. Occlusive thrombi in more distal or smaller branches should not be treated with mechanical embolectomy, but intra-arterial thrombolysis may be useful in selected cases.

♦ Advances in technology are constantly improving these new intravascular devices. The latest generation of the Merci device includes the possibility of using the EKOS (EKOS Corporation, Bothell, WA) microcatheter, which allows insonation of the clot with ultrasound delivered intravascularly at the site of occlusion.⁷⁸

♦ Multiple new devices are being tested. A promising example is the Penumbra (Penumbra, Inc., Alameda, CA) aspiration catheter, which enables the operator to combine aspiration and grasping to remove the occlusive thrombus. Initial reports of the experience with this device claim partial or complete recanalization rates exceeding 80% with acceptable rates of hemorrhage and procedural complications.

♦ Interventionalists employing new recanalization devices should report their results in the literature to better define the true efficacy and safety of this treatment modality.

♦ There is considerable interest in exploring the therapeutic option of pursuing intra-arterial thrombolysis in patients who fail to recanalize after receiving a bridging dose (0.6 mg/kg as opposed to the full dose of 0.9 mg/kg) of intravenous rt-PA within the first 3 hours of deficits.⁸⁰ This approach has been proven feasible and relatively safe in a Phase II trial that showed promising clinical results in patients with severe strokes at presentation;⁸¹ a Phase III trial is underway.

♦ Aggressive mechanical clot disruption, often attempted in practice along with intra-arterial thrombolysis, may increase the rate of recanalization in patients with large intracranial vessel occlusion.⁸² The most commonly used technique consists of trying to macerate the clot by repeat passes of the microwire or microcatheter. Acute angioplasty (with or without stenting) of the vessel may be successful in selected patients with resistant occlusions,⁸³ as illustrated by our case (Figure 3-21).

♦ Intra-arterial (or intravenous) IIb–IIIa antagonists may be used as part of a multimodality approach.⁸⁴ Perhaps the most valuable role of these agents is preventing reocclusion of a partially recanalized vessel. Excellent results with the use of these agents for the treatment of acute thromboembolic complications during neuroendovascular procedures have been reported.⁸⁵

Figure 3-22 A 56-year-old woman with history of hypertension, atrial fibrillation on chronic anticoagulation, and hysterectomy 5 days before was found by her sister confused and dragging her left leg. She deteriorated en route to the hospital. On evaluation in the emergency department, she had right gaze deviation, left homonymous hemianopia, left hemiplegia, and left-sided neglect. National Institutes of Health Stroke Scale score (NIHSS) was 16. INR was 2.3 but had been 1.6 the previous day. Computed tomography scan of the brain was unremarkable (not shown), but Digital substraction angiography (DSA) showed a carotid T occlusion (A). She was treated with mechanical embolectomy using the Merci Retriever, with the procedure starting 3.5 hours after symptom onset. The intervention was successful, and she achieved excellent recanalization (B). Her deficits improved substantially over the following 24 hours (NIHSS decreased to 4), and repeat brain imaging showed only a relatively small insular infarction. Six weeks later, she had returned to work with minimal residual symptoms.

Massive Hemispheric Infarction

Case Vignette

A 44-year-old woman was found collapsed in her apartment by her neighbor and brought emergently to the hospital. On examination, she was awake but incoherent. She had left hemianopia, hemiplegia, hyperreflexia, Babinski sign, and hemineglect. CT scan of the brain confirmed the presence of extensive infarction in the right middle cerebral artery territory (Figure 3-23, A). The patient was carefully monitored in the stroke unit, and 36 hours later, she was noticed to have difficulty opening her eyes despite being awake and able to follow other commands (cerebral ptosis). She had also developed Babinski sign on the right side (i.e., ipsilateral to the infarcted hemisphere). Repeat CT scan showed progression of mass effect and midline shift (Figure 3-23, B). Forty-two hours after admission, she became less arousable, and a new CT scan disclosed a 15-mm displacement of the septum pellucidum (Figure 3-23, C). Her pupils remained isocoric and reactive to light. She was intubated, hyperventilated, treated with 1 g/kg of 20% mannitol, and taken to the operating room. Decompressive hemicraniectomy and duroplasty were performed without complications. Repeat CT scan 18 hours after surgery demonstrated outward brain herniation through the site of craniectomy with partial improvement in the midline shift (Figure 3-23, D). The patient’s level of consciousness improved after surgery and did not decline again. Six months after the stroke, she had achieved meaningful functional recovery, with moderate residual disability. She underwent replacement of the bone flap with no complications.

Figure 3-23 Serial computed tomography (CT) scans of the brain in a patient with massive right middle cerebral artery stroke requiring decompressive hemicraniectomy. (A) Initial CT scan with early ischemic changes throughout the right middle cerebral artery territory. (B) Evolution of low attenuation changes in the large area of infarction with incipient mass effect and mild midline shift. (C) Marked increased in mass effect causing a 10-mm shift of the septum pellucidum. (D) Improvement in hemispheric mass effect and midline shift after decompressive hemicraniectomy. Notice outward herniation of the brain tissue through the bone defect.

♦ Baseline and serial CT scans are useful prognosticators for the development of massive brain swelling and herniation after a large hemispheric stroke (terminal carotid artery or proximal MCA occlusion).⁸⁶

♦ Radiological markers of poor outcome on CT scan include:

♦ Involvement of more than one vascular territory ^87,⁸⁸

♦ Shift of the septum pellucidum 9 mm or more or the pineal gland 4 mm or more at 48 hours ⁸⁹

♦ Hypodensity exceeding 50% of the MCA territory (with associated occlusion of the MCA on CTA)⁹⁰

♦ Hyperdense MCA sign (especially when combined with extensive sulcal effacement on baseline CT scan)^91,⁹²

♦ Still, radiological findings should never be interpreted in isolation. Stroke severity (measured by the NIHSS)⁹³ and level of responsiveness⁸⁹ remain the strongest predictors of outcome.

♦ For instance, although the presence of extensive areas of restricted diffusion on baseline DWI usually portend poor outcome, it has been shown that DWI should not replace clinical evaluation of stroke severity in the prognostication of acute ischemic stroke.^93,⁹⁴

♦ Vascular studies indicating persisting large vessel occlusion or poor collateral flow also predict poor outcome.⁹⁵

♦ Ischemic edema most often peaks around Day 3 after the stroke; however, large infarctions may swell as early as during the first 24 hours (malignant edema), whereas in other cases, the edema may be maximal 5 or more days after the stroke. Also, hemorrhagic conversion may rapidly accelerate the progression of mass effect. Thus temporal evolution of ischemic brain edema is not truly predictable, and close clinical and radiological monitoring is indispensable.

♦ Recognizing the clinical and radiological signs that predict high risk of malignant brain edema and monitoring for imminent signs of brain herniation and progression of mass effect on brain imaging are crucial in young patients with large MCA strokes because timely decompressive hemicraniectomy (with duroplasty) is effective in improving not only survival but also functional outcome in these patients.⁹⁶

♦ Some clinical signs, such as the development of cerebral ptosis ⁹⁷ or ipsilateral Babinski sign, and serial CT scans to monitor the progression of midline shift may be helpful to guide the timing of hemicraniectomy. However, other neuroimaging techniques may allow earlier prediction of malignant edema formation. Deficit of ligand uptake throughout the whole MCA territory on 99^m ethylcysteinate-single photon emission CT (SPECT) within 6 hours of stroke onset⁹⁸ and 99^m diethylenetriaminepentaacetic-SPECT imaging at 36 hours demonstrating extensive disruption of blood brain barrier permeability⁹⁹ have been reported to predict malignant infarction with high reliability. Unfortunately, these techniques are not widely available at present.

♦ It is important to identify multiterritorial infarction (anterior cerebral artery [ACA]-MCA or MCA-posterior cerebral artery [PCA]) because their presence is almost invariably associated with poor prognosis even if hemicraniectomy is performed.¹⁰⁰

Acute Internal Carotid Artery Occlusion

Case Vignette

A 49-year-old woman with history of hypertension and hyperlipidemia presented to our emergency department with fluctuating depression in her level of consciousness; forced right gaze deviation; dense left hemianopia; left hemiplegia involving face, arm, and leg; and left hemineglect. At her worst, her NIHSS was 22. Initial CT scan of the brain was unremarkable except for possible slight effacement of the insular ribbon. CT angiogram revealed occlusion of the right cervical internal carotid artery near its origin (Figure 3-24, A). The patient was aggressively treated with intravenous fluids and phenylephrine to elevate her blood pressure and started to respond within minutes to this treatment. A few hours later, her examination had essentially normalized. Her mean arterial pressure was maintained above 120 mm Hg over the following 24 hours, and then fluids and vasopressor were gradually tapered. Her deficits did not recur, and she was discharged home 2 days later with normal neurological function and CT scan of the brain (Figure 3-24, B).

Figure 3-24 (A) Computed tomography (CT) angiogram showing tapering and occlusion of the flow in the right internal carotid artery near its origin (arrow). (B) Normal CT scan of the brain upon hospital discharge despite severe neurological deficits on admission.

♦ The case illustrates a situation we have often encountered in practice. Prompt recognition of a discrepancy between the clinical deficits on examination and the baseline radiological findings may streamline the diagnostic evaluation and facilitate successful treatment.

♦ In patients with internal carotid artery occlusion, the penumbra is often extensive and manifests as a large clinical-radiological mismatch. Thus patients with symptoms and signs of ACA/MCA ischemia but a relatively normal brain parenchyma on CT scan and no evidence of a hyperdense vessel sign (which is often seen in cases of carotid terminus occlusion) should be emergently studied with noninvasive angiograms of the neck and brain and, if available, perfusion scans. When these tests are not available, carotid duplex may suffice to make the diagnosis and guide therapy.

♦ Occlusions of the cervical internal carotid artery are generally not amenable to revascularization procedures (the clot is too large to be dissolved with thrombolytic agents, and the risk of reperfusion injury is too high to consider endovascular interventions), but hemodynamic augmentation may effectively salvage the hypoperfused tissue when collateral pathways are anatomically favorable.

Basilar Artery Occlusion

Case Vignette

A 52-year-old man with history of uncontrolled hypertension, diabetes, hyperlipidemia, and smoking was admitted with bilateral acute cerebellar infarctions. Brain MRI (Figure 3-25, A-D) confirmed the areas of cerebellar ischemia and also showed changes consistent with acute basilar trunk occlusion (hyperintense vessel signal on FLAIR and absent basilar flow on MRA, which allowed visualization of bilaterally patent posterior communicating arteries). During the first day, the patient remained stable on intravenous crystalloids, colloids, and heparin. The following morning, however, he became more difficult to arouse, and he developed diplopia with disconjugate gaze and worsening bilateral weakness. Dopamine infusion was initiated to elevate his blood pressure resulting in partial improvement of his new deficits. He then underwent emergent catheter angiography, which demonstrated a proximal occlusion of the basilar artery (Figure 3-25, E). The patient was treated with mechanical clot disruption and angioplasty of the basilar artery with excellent radiographic results (Figure 3-25, F and G). After the procedure, his deficits improved, and he was discharged home 10 days later with residual ataxia. His residual deficits continued to improve steadily over the following year. Three years later, the patient remained free of recurrent ischemic neurological symptoms, and his basilar artery remained widely patent on follow-up noninvasive angiography.

Figure 3-25 (A) Diffusion-weighted imaging showing bilateral cerebellar and left occipital acute infarction. (B) Magnetic resonance angiography reveals no flow in the basilar artery but allows visualization of both posterior communicating arteries (arrowheads). This noninvasive angiogram suggests that the right posterior cerebral artery could have fetal origin (i.e., filling exclusively from the anterior circulation due to a lack of P1 segment connecting the vessel with the basilar artery). (C) Fluid-attenuated inversion recovery displaying the early changes of infarction in the left posterior cerebral artery territory but also showing a hyperintense signal in the basilar artery, indicative of acute thrombosis. This finding is better seen on panel D (arrow). (E) DSA demonstrating occlusion of the basilar artery between its proximal and middle thirds (arrow). (F) Successful recanalization of the basilar artery; notice good filling of the superior cerebellar arteries and the left posterior cerebral artery. The right posterior cerebral artery had fetal origin. (G) Final DSA confirming excellent angiographic results.

♦ The clinical suspicion of basilar artery occlusion represents a neurological emergency that requires immediate angiographic evaluation.

♦ When a noninvasive angiogram (MRA or CTA) can be performed expeditiously, it may have a role in confirming the diagnosis. MRI has the advantage of disclosing the extent of ischemia on DWI, as seen in the case presented. If extensive brainstem infarction is seen on MRI, recanalization efforts will be futile (Figure 3-26). However, we often prefer to proceed directly with catheter angiography because this modality provides access for treatment and time is invaluable in these cases.

♦ In the absence of revascularization, 80% of patients with basilar artery occlusion have poor prognosis.¹⁰¹

♦ In patients with basilar thrombosis, revascularization may be compatible with favorable functional outcomes even if achieved after 12 hours or more from the onset of deficits.¹⁰² This is the case because midbasilar thrombotic occlusions often present with progressive symptoms (indicative of worsening compromise of perfusion) before irreversible ischemia ensues.¹⁰³

♦ Intra-arterial thrombolysis, mechanical embolectomy, and acute angioplasty and stenting are the best treatment options in these situations.^83,^102,^104,¹⁰⁵ However, intravenous thrombolysis can be successful in patients presenting within 3 hours of symptom onset^106,¹⁰⁷ and probably represents the treatment of choice in cases of top-of-the-basilar syndrome evaluated within this time window.

Figure 3-26 A 64-year-old woman with history of hypertension and smoking presented with progressive loss of brainstem function over 72 hours. Over the 18 hours before transfer to our hospital, she had become locked in. Magnetic resonance imaging scan on arrival confirmed the clinical diagnosis of basilar artery thrombosis: diffusion-weighted imaging (A) and apparent diffusion coefficient (B) showed extensive acute infarction of the pons. The area of infarction was already visible on fluid-attenuated inversion recovery (C), indicating that the ischemia was no longer hyperacute. Magnetic resonance angiogram of the neck (D) and intracranial circulation (E) displayed the occlusion of the basilar artery beyond its proximal portion (arrows).

Massive Cerebellar Infarction

Case Vignette

A 42-year-old woman with history of hypertension and diabetes presented with sudden onset of acute ataxia. Brain imaging (CT scan and MRI) disclosed patchy cerebellar infarctions, mostly involving the right posterior inferior cerebellar artery territory (Figure 3-27, A and B). MRA of the intracranial circulation revealed occlusion of the right vertebral artery (Figure 3-27, C). The following day, the patient was clinically stable, but swelling of the infarction was already evident on repeat CT scan (Figure 3-27, D). Early on the third hospital day, she became drowsy and developed new right facial and abducens palsies. A new CT scan revealed further progression of mass effect (Figure 3-27, E). She underwent emergency suboccipital craniectomy. After surgery, her level of consciousness improved, but her right esotropia persisted. Postsurgical imaging confirmed adequate decompression (Figure 3-27, F). Although no additional complications occurred during the rest of the hospitalization, her functional recovery was limited.

Figure 3-27 Initial computed tomography (CT) scan (A) and diffusion-weighted magnetic resonance imaging (B) showing areas of bilateral cerebellar infarction, predominantly affecting the right posterior-cerebral artery territory (arrows). On magnetic resonance angiogram of the intracranial circulation (C), the right vertebral artery was not visualized. Repeat CT scans of the brain on the second (D) and third (E) hospital days revealed progressive worsening of cerebellar edema with regional mass effect, causing effacement of the peripontine cistern, deformity of the fourth ventricle, and compression of the pons (small arrows). Delayed CT scan after decompressive suboccipital craniectomy (F) shows resolution of the swelling and full reopening of the fourth ventricle without additional areas of ischemic damage.

♦ Cerebellar infarctions can be complicated with massive and potentially fatal swelling.^108,¹⁰⁹

♦ The causes of deterioration from progression of mass effect in patients with cerebellar infarctions are similar to those observed in cases of cerebellar hematomas’namely, direct brainstem compression (Figure 3-27), obstructive hydrocephalus from compression of the fourth ventricle (Figure 3-28, A and B), and aqueductal occlusion from upward herniation of the vermis through the tentorial notch (Figure 3-28, C and D). Apart from edema, sudden increment in mass effect can be produced by hemorrhagic conversion of the ischemic infarction. All of these mechanisms may be reliably diagnosed and differentiated by brain imaging, allowing timely surgical intervention when necessary.¹⁰⁹

♦ The risk of herniation is only significant after infarctions of the posterior-inferior cerebellar artery (PICA) territory. Although patients with strokes in the anterior-inferior or superior cerebellar artery distributions may develop clinical worsening during their acute phase, mass effect is typically not life-threatening in these cases.

♦ As illustrated by our case, the initial size of the infarction may be deceivingly reassuring. After PICA occlusion, cerebellar infarctions of relatively small initial size (especially when bilateral) may progress to produce massive edema in the posterior fossa. Thus serial neurological examinations and brain scans are indicated in all these cases (nonenhanced CT scans are sufficient for this purpose).

♦ Our case also illustrates that surgical management with suboccipital craniectomy may preserve life and function in deteriorating patients.^108,¹¹⁰ External ventricular drainage should probably be avoided in patients with radiological signs of upward herniation because it may exacerbate the tissue displacement in these cases.

Figure 3-28 Possible causes of deterioration in patients with massive cerebellar infarction. Obstructive hydrocephalus (arrows) from compressive occlusion of the fourth ventricle (A and B) and upward herniation with compromise of the aqueduct (C and D, arrows).

Subacute and Chronic Infarctions

♦ DWI (in conjunction with the ADC map) is unrivaled in its ability to diagnose acute ischemic lesions and distinguish them from late subacute or chronic infarctions (Figure 3-29).

♦ Subacute lesions are more hypodense on CT scan, hypointense on T1, hyperintense on T2 and FLAIR, less bright on DWI, and less dark on ADC (as diffusion increases in the infarcted tissue, the ADC map appears to normalize after 7–10 days, before the diffusion coefficient becomes elevated and the signal becomes bright) (Figure 3-30).

♦ Some degree of hemorrhagic transformation is seen in nearly one third of MCA infarctions within the first 72 hours of evolution (and in up to three quarters of patients with fatal hemispheric infarctions).¹¹¹ Gradient-recalled echo (T2*) is particularly sensitive for the detection of small hemorrhagic components within the infarction.

♦ On contrast scans, patchy or gyral enhancement begins to appear 2 to 3 days after the stroke (Figure 3-31), peaks after 2 to 3 weeks (Figure 3-32), and may persist for up to 10 weeks. Recognizing these areas of enhancement is important to avoid confusing a subacute ischemic lesion with tumors or cerebritis (the distribution of the ischemic infarction in a specific vascular distribution is pivotal in making this distinction).

♦ In the early subacute phase (2–7 days), edema may also be observed surrounding the infarction and grossly sharing the signal characteristics of the infarcted tissue. Hence, edema appears as hypodense signal on CT scan (although less dark and less well delineated than the area of infarction), hypointense signal on T1, and hyperintense signal on T2 and FLAIR. This edema is predominantly vasogenic, and therefore it appears bright on DWI and bright on the ADC map.

♦ During the late subacute phase, areas of infarction may appear deceivingly normal in noncontrast scans because of a phenomenon known as “fogging effect.” This phenomenon, ascribed to the development of new capillaries, influx of lipid-laden macrophages, and relative decrease of water content in the evolved infarction, has been reported 2 to 3 weeks after a stroke on CT scans ¹¹² and 10 to 14 days after on T2-weighted imaging¹¹³ (and to a lesser degree on FLAIR).¹¹⁴ The fogging effect is more likely to compromise diagnostic sensitivity in cases of small cortical infarctions and cerebellar infarctions. Strong enhancement after contrast administration reliably discloses the subacute infarction in these cases.

♦ Chronic infarctions are hypodense on CT scan, hypointense on T1, and hyperintense on T2. FLAIR is particularly useful to differentiate chronic from subacute lesions: in chronic infarctions, FLAIR demonstrates a hypointense cystic core (filled with fluid) with hyperintense borders (from gliosis) (Figure 3-29, E and F, arrows), whereas in subacute strokes, core and borders are hyperintense. DWI may be normal or show a bright signal related to the T2 shine-through phenomenon, but the signal is always bright on the ADC map (high diffusion coefficient because water molecules can move freely in the cystic old infarction).

♦ Infarct borders are much better delineated in chronic ischemic infarctions because they have become gliotic. Edema, hemorrhage, and contrast enhancement are no longer present. Because of tissue loss, adjacent sulci become more prominent, and the ipsilateral ventricle enlarges losing its natural shape. Dystrophic calcifications occasionally occur and are best recognized by CT scan. Previous hemorrhage within the infarction can be inferred by the presence of hemosiderin recognized on gradient-recalled echo (or T2*).