Chapter 2 Clinical-Anatomical Syndromes of Ischemic Infarction

Alejandro A. Rabinstein, Steven J. Resnick

Ischemic stroke can be defined as a sudden focal neurological deficit corresponding to a vascular distribution. Brain imaging techniques allow us to visualize lesions with great anatomical precision. However, optimal interpretation of the information provided by neuroimaging requires having detailed knowledge of the arterial anatomy (Figures 2-1 through 2-4) and the vascular territories of the brain (Figure 2-5).

Figure 2-1 Anterior circulation, frontal view on conventional angiogram (top) and three-dimensional angiogram (bottom). ICA, internal carotid artery; ACA, anterior cerebral artery; MCA, middle cerebral artery.

Figure 2-2 Anterior circulation, lateral view on conventional angiogram (top) and three-dimensional angiogram (bottom). ICA, internal carotid artery; ACA, anterior cerebral artery; MCA, middle cerebral artery.

Figure 2-3 Posterior circulation, frontal view on conventional angiogram (top) and three-dimensional angiogram (bottom). PICA, posterior-inferior cerebellar artery; AICA, anterior-inferior cerebellar artery; SCA, superior cerebellar artery.

Figure 2-4 Posterior circulation, lateral view on conventional angiogram (top) and three-dimensional angiogram (bottom). PICA, posterior-inferior cerebellar artery; AICA, anterior-inferior cerebellar artery; SCA, superior cerebellar artery; PCA, posterior cerebral artery.

Figure 2-5 Arterial territories of the cerebral hemispheres. Coronal image is shown on the left, axial in the middle, and sagittal on the right. A = anterior cerebral artery territory, M = middle cerebral artery territory, P = posterior cerebral artery territory.

Brain imaging has also enhanced our understanding of clinical-anatomical correlations in patients with ischemic infarctions. Before the development of modern neuroimaging modalities, these correlations could only be established by necropsy studies. In fact, clinical research using radiological data has shown that localization based on classical semiological syndromes may often be incorrect. Similar clinical presentations may occur in patients with strokes in different territories and, conversely, infarctions in the same territory may produce dissimilar manifestations in different patients. Nonetheless, accurate diagnosis relies on the recognition of the brain lesion in a defined vascular territory.

This chapter provides illustrations of ischemic infarctions in all major vascular territories and presents the most common clinical correlations. It is conceived as a practical and concise guide to the correct interpretation of brain imaging and not as a comprehensive anatomical or semiological monograph on this important topic. The reader should keep in mind that the variety of distribution of infarctions encountered in practice is enormous. The boundaries of arterial territories are far from invariable across patients, and anatomical variations in the constitution of the cerebral circulation and its interconnections are relatively common.

CAROTID BIFURCATION OCCLUSION

Case Vignette

A 61-year-old man with history of coronary artery disease, previous myocardial infarction, and multiple vascular risk factors presented to the emergency department with global aphasia and right hemiplegia for more than 6 hours. On examination, he was drowsy and exhibited forced left gaze deviation, right hemianopia, right flaccid hemiplegia involving the arm and the leg to similar degree, and absent response to pain on the right side. Diffusion-weighted imagery (DWI) of the brain revealed a large area of ischemia in the left hemisphere, including the territories of the anterior and middle cerebral arteries (Figure 2-6). Fluid-attenuated inversion recovery (FLAIR) sequence showed no parenchymal hyperintensity but disclosed extensive hyperintense signal in the left middle cerebral artery consistent with fresh thrombus (Figure 2-7). Magnetic resonance angiography (MRA) of the intracranial circulation confirmed the presence of a left carotid terminus occlusion (Figure 2-7). The patient was subsequently diagnosed with acute myocardial infarction and a left ventricular mural thrombus. His neurological condition deteriorated over the following 48 hours, and he expired after care was restricted to palliative measures.

Figure 2-6 Diffusion weighted imaging (left) and apparent diffusion coefficient map (right) of the brain magnetic resonance imaging show extensive areas of restricted diffusion’indicative of cellular edema’in the territories of the left anterior and middle cerebral arteries.

Figure 2-7 Fluid-attenuated inversion recovery magnetic resonance imaging showing hyperintense signal (top row, arrow) in the left middle cerebral artery extending from the top of the intracranial carotid artery caused by acute thromboembolism; regular (left) and enhanced views (right). Hyperintense signal is also seen in the left anterior cerebral artery (lower left panel, arrowhead). Magnetic resonance angiogram of the intracranial circulation confirms the diagnosis of left carotid terminus occlusion (lower right panel).

♦ Occlusion of the carotid bifurcation (carotid terminus or carotid T) typically results in infarction on the anterior cerebral and middle cerebral artery territories, including the deep structures perfused by the lenticulostriate branches (Figure 2-8).

♦ Patients often present with depressed level of consciousness, forced gaze deviation toward the side of the infarction, contralateral homonymous hemianopia, dense contralateral hemiparesis or hemiplegia (face, arm, and leg), and contralateral sensory loss. Aphasia is present when the infarction affects the dominant hemisphere and neglect when the nondominant side is affected.

♦ Decreased alertness and profound leg weakness are the most useful clinical signs to differentiate a carotid T occlusion from the more common middle cerebral artery stroke.

♦ An intravascular hyperdensity at the level of the carotid bifurcation may often be seen on CT scan. Thin-section computed tomography (CT) scans ¹ and T2* gradient echo magnetic resonance (MR) sequence² may reveal intra-arterial thrombus with greater sensitivity.

♦ Early recognition of this massive stroke is essential because mortality is the rule unless prompt recanalization may be achieved (Figure 2-9).

♦ Although intravenous thrombolysis may occasionally be successful, most experts prefer to pursue intra-arterial treatment (pharmacological thrombolysis or mechanical embolectomy) given the large size of the clot responsible for the vascular occlusion.^3,⁴

Figure 2-8 Multiple ascending cuts of a brain magnetic resonance imaging (diffusion-weighted imagery sequence) illustrating the distribution of ischemia in a patient with carotid terminus occlusion.

Figure 2-9 Fifty-eight-year-old man presenting with right carotid T occlusion who expired on the third day after hospitalization. Admission computed tomography scan is shown in the upper row, and magnetic resonance imaging (MRI) obtained a few hours later is displayed in the middle (diffusion weighted imaging on the left and apparent diffusion coefficient map on the right), and lower (T2-weighted MRI) rows.

MIDDLE CEREBRAL ARTERY OCCLUSION

♦ The clinical manifestations of middle cerebral artery (MCA) strokes can vary broadly, depending on the precise location of the vessel occlusion and the strength of the collateral circulation. Proximal occlusion of the horizontal (M1) segment of the MCA typically results in infarction of the lenticular nucleus and internal capsule (Figure 2-10), whereas more distal M1 occlusions spare these deep structures (Figure 2-11).

♦ The MCA supplies most of the cortical convexity, putamen, upper portion of the globus pallidus, posterior head and whole body of the caudate, large parts of the internal capsule (all but the lowest area of the posterior limb, and often the genu and the posterior-superior aspect of the anterior limb), external capsule, capsula extrema, claustrum, and substantia innominata. Figure 2-12 illustrates the topographical patterns of MCA infarction.

♦ The MCA is divided in four segments (see Figures 2-1 and 2-2). The M1 or horizontal segment is a single stem that give rise to the penetrating lenticulostriate branches. It branches into two (or occasionally three) M2 or insular segments as it enters the Sylvian fissure. The M3 or opercular segments ascend following the curvature of the operculum. The M4 or cortical segments travel along the sulci and gyri of the cerebral convexity.

Figure 2-10 Ischemic infarction of the middle cerebral artery territory from proximal occlusion of the horizontal (M1) segment of the vessel. Note that the infarction involves the basal ganglia and internal capsule because the occlusion is proximal to the takeoff of the lenticulostriate braches.

Figure 2-11 Ischemic infarction of the middle cerebral artery territory from distal occlusion of the horizontal (M1) segment of the vessel. Note that the infarction spares the basal ganglia and internal capsule because the occlusion is distal to the takeoff of the lenticulostriate braches.

Figure 2-12 Topographical patterns of middle cerebral artery infarction.

Case Vignette

A 65-year-old man with history of hypertension presented with acute global aphasia and right flaccid hemiplegia involving the lower face, the arm, and, to a lesser degree, the leg. He also had a dense right visual field deficit and profound right sensory loss. Magnetic resonance imaging (MRI) with DWI revealed extensive ischemia in the territory of the left MCA (Figure 2-13). T2* sequence disclosed a hypointense signal in the left MCA indicative of acute vessel thrombosis and MRA confirmed the left M1 occlusion (Figure 2-14). Atrial fibrillation was noted on cardiac telemetry. Over the following 48 hours, the patient developed fatal brain swelling (see Figure 2-14).

Figure 2-13 Brain magnetic resonance imaging showing acute infarction of the left middle cerebral artery territory (diffusion-weighted imaging on the left and matching apparent diffusion coefficient on the right). Note sparing of the deep territory indicating distal M1 occlusion.

Figure 2-14 T2* sequence demonstrates acute thrombus in the distal part of the M1 segment of the left middle cerebral artery (MCA) (upper left, arrow). Fluid-attenuated inversion recovery sequence depicts the extension of the infarction (upper right); notice hyperintense vessel signal in sulcal braches (arrowhead). Intracranial magnetic resonance angiography confirmed the distal MCA occlusion (lower left). Computed tomography scan 2 days later shows massive progression of ischemic brain swelling (lower right).

Territorial MCA Infarction

♦ The largest MCA infarctions (territorial infarctions) result from proximal occlusion of the proximal M1 segment and absence of enough collateral flow to limit the extent of the infarction.

♦ Patients characteristically present with preserved level of consciousness, gaze deviation or strong preference toward the side of the infarction, contralateral homonymous visual field deficit, and contralateral hemiparesis/hemiplegia (leg weakness is caused by involvement of deep capsular fibers) and hemi-hypoesthesia/anesthesia. Aphasia and hemineglect occur in dominant and nondominant infarctions, respectively (see later discussion for more details on deficits of cortical function).

♦ Hyperdense MCA sign may be seen on the initial CT scan. Its presence is associated with less chances of recanalization after thrombolysis ^5,⁶ and worse likelihood of favorable recovery.⁵^–⁷ Still, intravenous thrombolysis remains the standard of care for patients with MCA stroke presenting within 3 hours of symptom onset regardless of the presence of this radiological sign.⁶ Although preferential use of intra-arterial interventions has been advocated by some groups, the benefits of this approach are thus far unproved.⁸

♦ Occlusions of the distal M1 (horizontal) segment of the MCA produce large infarctions involving the cortex and subcortical white matter but sparing the striatocapsular structures perfused by the lenticulostriate branches (Figure 2-11).

♦ Patients present with facial-brachial weakness (relative leg sparing), which tends to be less severe and recover better than in cases of proximal M1 occlusion. Hemisensory loss usually follows a similar distribution. Contralateral homonymous hemianopsia and transient deviation of the eyes and head toward the side of the infarction are also characteristically present.

♦ Complete cortical infarctions of the MCA on the dominant hemisphere cause global aphasia and ideomotor apraxia (Figure 2-13).

♦ Extensive cortical infarctions of the MCA on the nondominant hemisphere manifest with a combination of contralateral visuospatial neglect, anosognosia, motor impersistence, dressing and constructional apraxia, and occasionally sensory aprosodia. Acute confusion, often with pronounced agitation, may predominate upon presentation (Figure 2-15).

♦ Cortical infarctions may have a patchy appearance when some cortical regions are saved by collateral circulation (Figure 2-16).

Figure 2-15 A 54-year-old woman presented to the emergency department with mild confusion, left visual field impairment, left hemiparesis, and left-sided neglect. Computed tomography scan of the brain (upper row) shows early low attenuation changes in the right middle cerebral artery (MCA) distribution, sparing the deep structures. The acute right MCA infarction was subsequently confirmed by magnetic resonance imaging (diffusion-weighted imaging sequence shown, lower left). Intracranial magnetic resonance angiography displayed the occlusion of the right MCA responsible for the ischemic stroke (lower right).

Figure 2-16 Patchy infarction of the right middle cerebral artery territory shown on diffusion-weighted imaging. Although the patient had an occluded right M1 segment, the infarction is discontinuous likely because of preservation of part of the cortex of the arterial territory by perfusion through collateral flow.

Deep Middle Cerebral Artery Infarction

♦ Deep infarctions in the territory of the MCA are caused by occlusion of lenticulostriate branches.

♦ These vessels perfuse the anterior limb, genu, and anterior segment of the posterior limb of the internal capsule (especially its rostral portion); the corona radiata adjacent to the body of the lateral ventricle; the body and upper half of the head of the caudate nucleus, lentiform nucleus, and external capsule.

♦ The anatomical pattern of lenticulostriate arteries is highly variable. Most often, there are two medial and four or five lateral main lenticulostriate branches, all of which arise most commonly from the dorsal aspect of the MCA horizontal trunk.⁹ Lateral branches are generally larger and longer than the medial. Ramifications of these arteries generate an average of more than 20 penetrating vessels.⁹ Often multiple small branches originate from a single common stem.

♦ Deep infarctions are classified as lacunar, when they measure less than 15 mm in maximal diameter on axial cuts, or striatocapsular when they are larger (usually >20 mm in greatest diameter) (Figure 2-17).^10,¹¹

♦ Lacunar infarctions are typically produced by occlusion of a single penetrating artery, whereas striatocapsular infarctions characteristically occur when multiple penetrating branches are occluded. However, this is far from a rule, because infarctions clearly larger than lacunes may originate from occlusion of a common lenticulostriate stem that gives rise to two or more smaller penetrating branches.^10,¹²

♦ Deep infarctions in the MCA territory often present with lacunar syndromes (pure motor, sensorimotor, dysarthria-clumsy hand). Deficits may be more restricted and result in brachiocrural or brachiofacial syndromes. Manifestations traditionally associated with cortical lesions may occur in larger infarctions of the upper internal capsule or even the external capsule, including aphasia, hemineglect, and apraxia. Similarly, subinsular infarctions may present with signs indistinguishable from the anterior opercular syndrome (loss of voluntary control of facial, lingual, pharyngeal, and masticatory muscles, resulting in severe dysarthria and dysphagia). Also, extrapyramidal signs have been noted in patients with putaminal ischemia,¹³ and abulia, akinesia, and, more rarely, chorea have been reported in association with caudate infarctions.¹⁴

Figure 2-17 Examples of deep infarctions in the middle cerebral artery (MCA) territory. The case displayed in the top row is unusual because of concomitant involvement of the head of the caudate’typically perfused by the recurrent artery of Heubner, most often a branch of the anterior cerebral artery’and the lenticular nucleus (diffusion-weighted imaging [DWI] on upper left and matching apparent diffusion coefficient map on the upper right). The case portrayed in the lower row illustrates extension of the infarction into the paraventricular corona radiata (DWI is shown). These cases serve to highlight the various anatomical presentations that can be seen with deep infarctions in the MCA territory.

Superficial Divisional Middle Cerebral Artery Infarction

♦ Occlusions of the superior (or anterior) M2 branch most commonly cause infarctions involving the extensive cortical and subcortical regions of the frontal lobe convexity and the anterior parietal lobe (Figure 2-18). Both the precentral and postcentral gyri are usually affected.

♦ Clinical manifestations are contralateral hemiparesis and hemisensory loss, predominantly faciobrachial. Conjugate eye deviation or gaze preference toward the side of the infarction occurs often, but visual fields tend to be spared. Nonfluent aphasia with oral apraxia and severe dysarthria are frequently disabling deficits in patients with dominant infarctions. Depression is also a common feature in these patients. Acute confusional state, contralateral hemi-inattention, visual perceptual impairment, aprosodia, and anosognosia are prevailing neuropsychological disturbances in infarctions of the nondominant hemisphere.

♦ Superior division MCA infarctions may be caused by large artery atherothrombosis or cardiac embolism; the former mechanism probably predominates.¹⁵

♦ Occlusion of the inferior (or posterior) M2 branch produces infarction involving the parietal and temporal lobes (Figure 2-19).

♦ The most common clinical manifestations include contralateral sensory and visual field deficits. Variable degrees of hypoesthesia with tactile extinction upon double simultaneous stimulation and homonymous hemianopia or superior quadrantanopia are the most characteristic features. Weakness, when present, is usually mild and transient. Fluent (Wernicke’s) aphasia occurs with infarctions of the dominant hemisphere. Hemineglect, constructional dyspraxia and other visual-perceptual difficulties, and sensory aprosody are encountered in patients with nondominant infarctions.

♦ Acute confusional state, often associated with agitated delirium, may predominate in right-sided infarctions of the inferior M2 division.¹⁶ It is important to keep this diagnosis in mind when evaluating any patient presenting with acute confusion and agitation, because detailed neurological examination may be difficult in these cases, and sensory, visual, and perceptual deficits may be easily missed.

♦ Infarctions of the inferior division of the MCA are predominantly caused by cardiac embolism.^15,¹⁶ Carotid artery disease is rarely a cause of infarctions in this vascular distribution.

Figure 2-18 Superior division middle cerebral artery stroke. Diffusion-weighted imaging and apparent diffusion coefficient map shown in the upper row. Fluid-attenuated inversion recovery sequence displayed on the lower left. Conventional angiogram (lateral view, lower right) demonstrates the absence of filling of the occluded superior M2 branch.

Figure 2-19 Inferior division left middle cerebral artery infarction. Diffusion-weighted imaging sequence is shown.

Superficial Cortical Infarctions

♦ Insular infarctions rarely occur in isolation, but insular involvement is seen in close to half of patients with nonlacunar infarctions of the MCA territory (Figure 2-20). Damage to the insular cortex is most frequently found with large MCA infarctions and proximal M1 occlusions.¹⁷

♦ Insular infarctions have received considerable attention because they have been consistently associated with increased likelihood of cardiac arrhythmias, myocardial injury, and adverse outcome including sudden cardiac death.¹⁸^–²⁰

♦ Left ²⁰ and right-sided^18,¹⁹ infarctions have been associated with worse cardiac outcomes in different studies. Hence, the degree of lateralization in the control of autonomic cardiac function in humans remains to be fully elucidated.

♦ It has been reported that MCA infarctions involving the insular territory may be more prone to growth.²¹ The nature of this phenomenon deserves further exploration.

♦ Other cortical branch infarctions may be caused by occlusion of M3 branches (Figure 2-12) and may present with distinctive clinical syndromes. Some common examples of localizing clinical features encountered in practice are shown in Table 2-1.

♦ These cortical infarctions are typically caused by embolism (from arterial or, probably most often, cardiac sources).

♦ Occasionally cortical branch infarctions represent the only sequelae in patients who present with severe hemispheric deficits but later improve dramatically. These cases of “spectacular shrinking deficits” are thought to result from fragmentation of a large embolus that initially occludes the ICA bifurcation or proximal M1 segment.^22,²³