Common stroke syndromes
Stroke is a sudden-onset neurological syndrome caused by infarction or hemorrhage within the CNS. While there is no substitute for a detailed understanding of neuroanatomy, recognizing the following common stroke syndromes is a powerful bedside tool for localizing and diagnosing stroke.
Anterior circulation ischemic strokes
Middle cerebral artery syndromes
The anatomy of the circle of Willis, including the origin of the middle cerebral artery (MCA), is shown in Figure 21.1. The MCA is one of the two main branches of the internal carotid artery. Infarction of the MCA or its branches is one of the most common causes of stroke. The first important branches of the MCA are the lenticulostriate arteries, which arise from the stem of the artery and supply the caudate nucleus, internal capsule, putamen, and lateral globus pallidus. After giving rise to the lenticulostriate arteries, the MCA most commonly divides into superior and inferior divisions. The superior division supplies the frontal lobe, while the inferior division supplies the superior temporal lobe.1 The parietal lobe may be supplied by either the superior or inferior division or by both. Depending on the site of occlusion, MCA strokes lead to the following sensorimotor abnormalities:
• Occlusion at the stem of the MCA produces a severe contralateral hemiplegia, contralateral hemisensory loss, and ipsilateral eye deviation. Stem occlusion may lead to “malignant MCA syndrome” in which swelling of the infarcted territory produces increased intracranial pressure and potentially herniation and death (see below and Chapter 2).
• Infarction of the MCA distal to the takeoff of the medial lenticulostriate arteries produces contralateral weakness of the face and arm, and may be associated with ipsilateral eye deviation. Hemiparesis tends to be milder than when the occlusion takes place at the stem of the artery.
• Superior division infarction typically produces contralateral weakness and numbness that are greatest in the face and hand.
• Inferior division infarction results in mild contralateral face and hand weakness and numbness, and sometimes a contralateral homonymous hemianopia.
In addition to sensorimotor abnormalities, MCA infarction often produces behavioral manifestations that depend on the hemisphere involved:
• Left MCA. The characteristic behavioral manifestation of left MCA infarction is aphasia, the acquired loss of language (see Chapter 3). Complete left MCA infarction in a patient with left hemispheric dominance for language would be expected to produce global aphasia. Broca’s aphasia is associated with superior division infarction, whereas Wernicke’s aphasia is associated with inferior division infarction.
• Right MCA. The classical behavioral manifestation of a right MCA stroke is left-sided hemineglect (see Chapter 1). Stroke involving the inferior division of the right MCA may produce an acute agitated delirium.2
Anterior cerebral artery syndrome
The anterior cerebral artery (ACA) is derived from the internal carotid artery (Figure 21.1). The proximal ACA, or A1 segment, connects the internal carotid artery and the anterior communicating artery (ACOM). The distal ACA (beginning with the A2 segment) arises from the ACOM, and contains most of the branches that supply the medial frontal and parietal lobes. Anterior cerebral artery stroke results in contralateral leg weakness that is greatest in the foot. Sensory deficits in the leg and foot are usually modest. Stroke involving the left anterior cerebral artery may produce transcortical motor aphasia (Chapter 3). In patients with an azygous
Figure 21.1 The circle of Willis. ACA = anterior cerebral artery, AChA = anterior choroidal artery, ACOM = anterior communicating artery, AICA = anterior inferior cerebellar artery, ICA = internal carotid artery, MCA = middle cerebral artery, PCA = posterior cerebral artery, PCOM = posterior communicating artery, PICA = posterior inferior cerebellar artery, SCA = superior cerebellar artery.
ACA in which both distal segments arise from the same A1, unilateral A1 occlusion leads to infarction of both distal ACA territories, and therefore bilateral leg weakness. Anterior cerebral artery infarction is much less common than MCA infarction.
Internal carotid artery
The common carotid artery bifurcates into the internal carotid artery (ICA) and external carotid artery in the neck at approximately the level of the fourth cervical vertebrae. The ICA enters the skull via the carotid canal and crosses the foramen lacerum before entering the cavernous sinus. After emerging from the cavernous sinus, the carotid artery gives rise to the ophthalmic artery and then trifurcates into the ACA, MCA, and posterior communicating artery (PCOM) (Figure 21.1). The anterior choroidal artery (AChA) usually arises from the ICA just distal to the trifurcation. The following are the common ICA stroke syndromes:
• Internal carotid artery occlusion. Occlusion of the ICA results in the combination of MCA and ACA syndromes. Deficits are usually severe and may be life-threatening if the occlusion takes place rapidly. Deficits are milder if the occlusion develops slowly, after collateral circulation via the circle of Willis has been established.
• Distal embolization. Distal emboli from the ICA most commonly lodge in the MCA or the ophthalmic artery, but may involve any of its branches. Stroke involving the ophthalmic artery or its branches causes monocular blindness, which, if transient, leads to the clinical syndrome of amaurosis fugax (Chapter 5).
• Watershed infarction. The ischemic watershed or borderzone refers to an area of the brain perfused by the end distributions of two vascular territories. Because these areas have the most tenuous blood supplies, systemic hypotension, often in the context of cardiac arrest, may lead to preferential infarction in a watershed distribution. The most common watershed syndrome involves the territory that is jointly perfused by the ACA and MCA, leading to weakness with or without sensory disturbance of the proximal arm and leg, the so-called “man in a barrel” syndrome.
• Carotid artery dissection. Headache, ipsilateral eye pain, and Horner’s syndrome are the most common symptoms of carotid artery dissection (Chapter 19).
• Anterior choroidal artery infarction. The AChA is usually a branch of the ICA, but it may also arise from the MCA or the PCOM. The AChA variably supplies blood to the motor and sensory fibers within the posterior limb of the internal capsule, the optic tract, the lateral geniculate body, and the optic radiations. Anterior choroidal artery syndrome, uncommon and usually incomplete, includes components of contralateral weakness, sensory loss, and homonymous hemianopia.
Posterior circulation ischemic strokes
The vertebral arteries are derived from the subclavian arteries in the chest and ascend through the foramen transversarium of the C2–6 vertebrae. They then pass through the foramen magnum to enter the skull. The vertebral arteries give rise to the posterior inferior cerebellar arteries at the inferior medullary level and send branches to the anterior spinal artery at the mid-medullary level (Figure 21.1). The vertebral arteries then fuse at the pontomedullary junction to form the basilar artery. The anterior inferior cerebellar arteries are the first branches of the basilar artery. Penetrating
Figure 21.2 Cross section of the medulla showing the structures involved in a lateral medullary infarction (Wallenberg’s syndrome). Although there is considerable variety among patients with this syndrome, typical features include vertigo and ipsilateral limb ataxia (inferior cerebellar peduncle), ipsilateral facial sensory loss (spinal trigeminal tract and nucleus), contralateral hemibody sensory loss (spinothalamic tract), ipsilateral Horner’s syndrome (Horner’s tract), and dysphagia (nucleus ambiguus and vagus nerve).
branches arise from the basilar artery as it runs along the ventral surface of the pons. The superior cerebellar arteries and the posterior cerebral arteries are the next branches. Finally, the basilar artery gives rise to the paired posterior communicating arteries, which anastomose with the anterior circulation. Posterior circulation infarction is often patchy, producing a variety of deficits such as diplopia, dysarthria, facial and body numbness, vertigo, and nausea and vomiting. Nonetheless, there are several well-defined posterior circulation syndromes, described below.
Occlusion of the vertebral or (less commonly) the posterior inferior cerebellar artery results in infarction of the lateral medulla, leading to Wallenberg’s syndrome (Figure 21.2). Common symptoms of Wallenberg’s syndrome include vertigo, nausea, vomiting, facial pain, dysarthria, dysphagia, and ipsilateral limb ataxia. Examination findings include nystagmus, loss of pinprick sensation in the ipsilateral face and contralateral body, ipsilateral Horner’s syndrome, and ipsilateral limb ataxia.
Mid-basilar artery occlusion
The basilar artery runs along the midline of the ventral pons. Complete occlusion of the basilar artery deprives the descending bilateral corticospinal and corticobulbar tracts of their blood supplies, leading to locked-in syndrome in which the patient is completely paralyzed with the exception of preserved vertical eye
Table 21.1 Cerebellar stroke syndromes
movements and blinking. Although the patient may appear uncommunicative, consciousness is actually preserved because the midbrain and thalamus are spared.
Mid-basilar penetrating branch occlusion
Occlusion of one of the smaller penetrating branches of the mid-basilar artery most commonly produces contralateral hemiparesis. If the abducens or facial nerve fascicles are involved, ipsilateral eye abduction (Chapter 6) and ipsilateral facial movement (Chapter 8) may be impaired.
Rostral basilar (top of the basilar) occlusion
Occlusion of the rostral basilar artery produces a variety of ocular motor and behavioral manifestations, most commonly vertical gaze and convergence impairments.3 In many cases, the distal basilar branches (the superior cerebellar artery and posterior cerebral artery) are also involved. There is, however, no single unifying clinical feature of rostral basilar occlusion that allows it to be instantly recognized.
Posterior cerebral artery infarction
The posterior cerebral artery (PCA) supplies the visual cortex in the occipital lobes. Visual abnormalities are therefore the most consistent manifestations of PCA infarction (Chapter 5):
• Unilateral PCA infarction leads to macular-sparing contralateral homonymous hemianopia. The patient often does not recognize this problem until their visual fields are tested at the bedside.
• Bilateral PCA infarction results in complete visual loss. In some cases, a patient with bilateral PCA infarction may deny that they are blind and confabulate a detailed visual scene (Anton’s syndrome).
• Infarction of the left PCA may produce alexia without agraphia.
• Occasionally, PCA infarction may lead to a state of agitated confusion (Chapter 1).4
Thalamic strokes produce a heterogeneous group of clinical deficits. The arteries that supply the thalamus are derived from the posterior cerebral and posterior communicating arteries, and are often quite variable in their origins. The common vascular syndromes of the thalamus involve the following four arteries5:
• Thalamogeniculate artery. This artery supplies the lateral thalamus and leads to contralateral hemibody numbness (see “pure sensory lacune”, below).
• Paramedian thalamic–subthalamic artery. Medial thalamic infarction leads to problems with consciousness, behavior, and vertical gaze. These patients often present in coma, and when they awaken, appear confused or apathetic (Chapter 2).
• Polar artery. Infarction of the anterior thalamus leads to a variety of behavioral manifestations including amnesia, aphasia, and confusion, in some cases causing “sudden-onset dementia” (Chapter 4).
• Posterior choroidal artery. This artery supplies the lateral geniculate body and leads to contralateral homonymous field deficits, most characteristically the loss of a central wedge of vision (Chapter 5).
The three arteries that supply blood to the cerebellum are the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), and the posterior inferior cerebellar artery (PICA). Typical features of cerebellar strokes include occipital–nuchal headache, nausea and vomiting, ataxia, and dysarthria. In some cases, isolated cerebellar infarctions may produce only vertigo and thus resemble a more benign condition such as labyrinthitis (Chapter 9). Unless the adjacent brainstem is involved, it may be difficult to distinguish among infarctions in the three arterial territories (Table 21.1). Although the majority of cerebellar infarcts produce mild, temporary deficits, larger strokes may lead to hydrocephalus or life-threatening brainstem compression if untreated.
Lacunar strokes are small-vessel occlusions that usually occur in the context of hypertension.6 The following are the most common lacunar syndromes:
• Pure motor lacune. Infarction anywhere in the pyramidal tract may produce contralateral hemiparesis affecting the face, arm, and leg without sensory or behavioral manifestations. Most commonly, the infarction is in the posterior limb of the contralateral internal capsule, although infarction in the contralateral corona radiata, base of the pons, or cerebral peduncle may also result in a pure motor syndrome.
• Pure sensory lacune. Lacunar infarction of the contralateral ventroposterior thalamus (ventroposterolateral and ventroposteromedial nuclei) leads to the sudden onset of contralateral numbness of the face, arm, and leg.
• Ataxic hemiparesis. Small-vessel infarction involving the base of the pons may produce contralateral limb weakness and ataxia. The foot tends to be weaker than the hand, which in turn tends to be weaker than the face.
• Clumsy hand–dysarthria. Lacunes involving the base of the pons or the genu of the internal capsule may produce severe dysarthria with contralateral face and hand weakness.
Intracranial hemorrhage (ICH) accounts for approximately 20% of strokes. It presents in a very similar or identical manner to ischemic stroke, but is more likely to progress over minutes to hours. It is often difficult to distinguish between hemorrhage and infarction by history and physical examination alone. Although headache makes ICH slightly more likely than ischemic stroke, neuroimaging studies are much more reliable in distinguishing between the two stroke types. Evaluation and treatment of ICH is discussed in greater detail below.
Cerebral venous thrombosis
Venous strokes are much less common than arterial ones. Susceptible populations include women in the puerperium, patients with hereditary coagulation defects, and patients with systemic inflammatory diseases. Because headache is the most common presentation of venous sinus thrombosis, it is discussed in more detail in Chapter 19.
The rapidity of symptom onset that characterizes stroke is not unique, and in approximately one-third of cases, sudden-onset neurological deficits are produced by other medical, neurological, or psychiatric conditions.7
Acute confusional state
While acute confusional states may occasionally be secondary to stroke in the distribution of the left posterior cerebral or right middle cerebral arteries, they are more commonly secondary to toxic or metabolic disturbances.4,8Evaluation of confusion is discussed further in Chapter 1.
Deep sleep, usually secondary to heavy intoxication or surgery, may lead to a sudden-onset, painless focal neuropathy that mimics stroke. The best-known focal neuropathy of this type is “Saturday night palsy,” which occurs when a patient awakens with a radial neuropathy after sleeping with their arm draped over a chair or bed. Other nerves that are susceptible to focal injuries mimicking stroke include the ulnar, sciatic, and common peroneal nerves. The techniques to distinguish between stroke and focal neuropathy are discussed in further detail in Chapter 11. Although physical examination may help to differentiate focal neuropathies from stroke in most cases, neuroimaging studies or electromyography are often required to solidify the diagnosis. Exercise caution in diagnosing a focal neuropathy rather than a stroke, as infarction of the “hand knob” area of the cerebral cortex may resemble a radial or ulnar neuropathy quite closely.9
Metabolic insult causing re-expression of old stroke
The frequently observed, although not formally studied, phenomenon of metabolic insult causing re-expression of old stroke (MICROS) is characterized by the apparent return of prior stroke deficits when patients are subjected to metabolic insults, most commonly urinary tract infections, pneumonia, or medication toxicity. The pathophysiology of MICROS is not well understood, but it is likely that compensatory synaptogenesis, which occurs in the process of stroke recovery, is susceptible to relatively small metabolic perturbations that do not affect otherwise healthy brain tissue. The phenomenon of MICROS should be considered only after thorough evaluation excludes the presence of an actual stroke. Treat MICROS by correcting the responsible medical condition: deficits will improve, sometimes in a few hours but more often over the course of several days.
Migraine aura may resemble stroke when it is not followed by headache (Chapter 19). Usually, however, the tempo and progression of deficits help to distinguish between migraine aura and stroke. Focal deficits in migraine aura are typically followed by symptoms that develop over several minutes when adjacent cortical areas become involved by a wave of spreading depression. Stroke deficits, in contrast, are maximal at onset and progress very little, if at all. Younger patients with a history of migraine do not require further evaluation for stroke. Older patients and those without any prior history of aura, however, require neuroimaging studies before the diagnosis may be made comfortably.
A combination of neuronal exhaustion and inhibition following a seizure may produce a variety of clinical deficits including focal numbness, visual field cuts, and aphasia (Chapter 20). The most well-known postictal deficit is Todd’s paralysis, characterized by focal weakness following a motor seizure. Todd’s paralysis and related postictal phenomena are most likely to be misdiagnosed as stroke when the preceding seizure is not witnessed.
Transient global amnesia
Transient global amnesia (TGA) is an acute-onset amnestic state in which a patient loses the ability to encode new memories (Chapter 1).10 The patient with TGA characteristically repeats the same questions every 2–5 minutes, but is otherwise capable of performing cognitive tasks at a very high level. An episode typically lasts for several hours and resolves spontaneously. The exact pathophysiology of TGA is unclear: it may be related to migraine, seizure, or stroke.
The protean manifestations of subdural hematoma (SDH) include hemiparesis, seizures, and confusion,
Figure 21.3 Noncontrast head CT showing right subdural hematoma (arrow). Note the presence of a midline shift.
and even the best neurologist may miss the diagnosis by failing to consider it. In the presence of a typical history of head trauma with headache and focal neurological signs, the diagnosis of SDH is fairly straightforward. Head trauma, however, is often occult or not remembered, and the diagnosis may thus be delayed by several days or weeks. Noncontrast head CT is the diagnostic study of choice (Figure 21.3). The first step in treating SDH is to prevent further hematoma expansion by reversing anticoagulation (see below). Indications for neurosurgical intervention include significant midline shift, progression of neurological deficits, and expansion of hematoma size on serial CT scans.
Hypoglycemia and hyperglycemia
Both high and low blood sugar levels may result in focal neurological deficits that closely resemble acute ischemic stroke. Restoring normoglycemia usually resolves any deficits in a few hours, but improvement may sometimes take several days.
Psychogenic disorders, especially malingering and conversion disorders, may mimic stroke. While these conditions are often quite transparent, mimicry of true neurological deficits may be precise enough to require detailed neuroimaging to secure the diagnosis.
Figure 21.4 Noncontrast head CT showing an intracranial hemorrhage.
Peripheral vestibulopathy is often difficult to separate from central causes of vertigo such as brainstem or cerebellar infarction (Chapter 9).
Bell’s palsy is acute facial weakness caused by a peripheral lesion of the facial nerve, and is discussed further in Chapter 8.
Obviously, every patient with a suspected stroke requires comprehensive neurological examination to define the clinical effects of the stroke. Cardiovascular and funduscopic examinations are the most important components of the general physical examination. Auscultation of a heart murmur or atrial fibrillation points to a potential cardioembolic source of stroke. A carotid bruit is often a nonspecific finding of systemic atherosclerosis. A long, high-pitched bruit located high within the neck at the carotid bifurcation, however, suggests the possibility of carotid artery stenosis.11 Funduscopic examination may disclose Hollenhorst plaques, which are bright white particles that appear at retinal vascular bifurcations and usually suggest an embolic stroke source from the ipsilateral carotid artery or heart. In patients with central retinal artery occlusion, funduscopy shows macular pallor and a cherry-red spot in the fovea (Chapter 5).
Table 21.2 CT changes in early ischemic stroke
All patients evaluated for suspected acute stroke require a routine set of laboratory tests, including a complete blood count, basic metabolic profile, coagulation studies, urinalysis, toxicology screen, and chest X-ray. While these tests may have only limited utility in defining the etiology of stroke, they help to diagnose stroke mimics, screen for conditions that may worsen stroke outcome, and determine whether patients are eligible for intravenous thrombolysis.
Neuroimaging studies are essential in differentiating between ischemic and hemorrhagic strokes, help to establish the diagnosis when the history or physical examination are unreliable, point to alternative diagnoses such as brain tumor or subdural hematoma, and help to define stroke pathophysiology. Remember that neuroimaging studies are complementary to the history and examination, and that all radiographic abnormalities must be placed in the appropriate clinical context.
Noncontrast head CT
Noncontrast head CT is usually the first and often the only neuroimaging study performed because it is widely available and can be obtained rapidly. In many cases, patients with suspected stroke have already had a head CT before neurological consultation is requested. The main use of a CT scan is to detect intracranial hemorrhage (Figure 21.4). The changes suggestive of acute stroke have only modest sensitivity and interobserver reliability (Table 21.2).12,13
Diffusion-weighted MRI (DWI) is the imaging study of choice for acute ischemic stroke. A bright DWI signal reflecting cytotoxic edema appears within 15–30 minutes of ischemic stroke onset, and its high sensitivity for
Figure 21.5 An acute occipital–temporal infarction (arrow) as captured by (A) diffusion-weighted imaging and (B) the apparent diffusion coefficient map.
acute stroke makes it ideal for evaluating patients with confusing or atypical presentations (Figure 21.5A).14 There are two minor limitations of DWI. First, it may be insensitive to very small strokes, particularly those involving the brainstem. Secondly, old T2 lesions may “shine through” and appear bright on DWI, falsely suggesting an acute infarction. The way to differentiate between newly infarcted tissue and an old T2 lesion is by looking at the apparent diffusion coefficient (ADC) map. Acute infarction is bright on DWI, dark on the ADC map, and remains dark on the ADC map for fewer than 10 days (Figure 21.5B).15 Older T2 hyperintensities are bright on both DWI and the ADC map.
Although the sensitivity of DWI for acute ischemia makes MRI the modality of choice for evaluating patients with suspected stroke, compared with CT, routine MRI sequences are less sensitive in detecting hemorrhage. Some patients undergo CT scanning first before they proceed to MRI. Patients who do not have a CT scan before MRI should undergo gradient echo susceptibility-weighted MR imaging (also referred to as T2*) to firmly exclude the possibility of hemorrhage (Figure 21.6). Susceptibility images are as sensitive as noncontrast head CT scan in detecting acute blood.16
Perfusion-weighted imaging (PWI) provides information about relative cerebral blood flow. Areas that
Figure 21.6 Susceptibility imaging showing left temporal– parietal hemorrhage. Note the presence of two cerebral microbleeds in the right temporal lobe (arrows), likely reflective of amyloid angiopathy.
are infarcted or are acutely vulnerable to infarction (the “ischemic penumbra”) show decreased perfusion. Mismatch between the infarcted tissue on DWI and the infarcted-plus-vulnerable tissue on PWI therefore theoretically indicates the area that is potentially salvageable by reperfusion therapy.17 The value of this diffusion–perfusion mismatch, however, is not clear in clinical practice, and PWI remains largely a research tool.
Figure 21.7 Magnetic resonance angiography of the cerebral vasculature. Note the dominance of the right vertebral artery over the left vertebral artery (*) in this patient (normal variant). ACA = anterior cerebral artery, ICA = internal carotid artery, MCA = middle cerebral artery, PCA = posterior cerebral artery.
Vascular imaging studies
Vascular imaging studies such as magnetic resonance angiography (MRA, Figure 21.7) and computed tomographic angiography (CTA) are useful in defining the specific vessel responsible for a stroke. Such information is not essential, however, in the hyperacute stage of stroke management when rapid determination of eligibility for intravenous thrombolysis is essential. Vascular imaging is useful, however, when planning intra-arterial thrombolysis. Other vascular imaging studies that may help in the acute setting include CT or MR angiogram of the neck vessels, which helps to establish the presence of carotid or vertebral artery dissection, and magnetic resonance venography (MRV), which is useful when evaluating possible cerebral venous sinus thrombosis.18
Selecting imaging studies
Each stroke center has specific protocols for neuroimaging, which are based largely on the preferences of the stroke specialists and the availability of interventional techniques. If rapid results to exclude hemorrhage are required to determine whether a patient is eligible for intravenous thrombolysis, then treatment should not be delayed, and a noncontrast head CT to exclude hemorrhage is necessary and sufficient. However, if a high-sensitivity study is required to establish the diagnosis of stroke, MRI including DWI, ADC map, and susceptibility images may be required. Vascular imaging studies help to define the pathophysiology of stroke, and may be necessary if an intervention is planned, but in most cases should not delay acute therapy.
Hyperacute ischemic stroke treatment
Intravenous recombinant tissue plasminogen activator
Intravenous recombinant tissue plasminogen activator (IV rt-PA) is a thrombolytic agent used to treat acute ischemic stroke.19 Details on the administration of IV rt-PA are found in the protocol in Box 21.1. The randomized, double-blind, placebo-controlled study sponsored by the National Institute of Neurological Disorders and Stroke provides the following data on its safety and efficacy20:
• Although IV rt-PA is a “clot-busting” agent, it provides no benefit compared with placebo within minutes or even 24 hours after administration.
• Patients who receive IV rt-PA have a probability of a good neurological outcome (as defined by the modified Rankin scale) of 39% at 3 months compared with 26% for those who do not receive it.
• The most important side effect of IV rt-PA is symptomatic brain hemorrhage, which occurs in approximately 6% of patients.
Intravenous rt-PA is effective when it is given within 3 hours of ischemic stroke onset. Although this may seem like a generous amount of time, few patients undergo thrombolysis because of delays in recognizing stroke, in getting to the emergency room in a timely fashion, in undergoing a directed history and noncontrast head CT, and in excluding contraindications to IV rt-PA. Thus, each minute spent in patient evaluation is critical, and it becomes essential to focus on the four “big picture” questions in order to maximize the chance that a patient receives treatment:
1. When did the problem begin? Intravenous rt-PA is only approved for stroke treatment within 3 hours of symptom onset. It is, therefore, imperative to establish the exact time at which deficits developed. Although initial investigations into IV rt-PA for patients who awaken with stroke seem promising, awakening with stroke is currently an exclusion from undergoing thrombolysis.21
2. Is the deficit disabling? It is also necessary to establish that the deficit from the suspected ischemic stroke is disabling. Mild dysarthria or subtle nondominant hand weakness probably does not warrant treatment with IV rtPA, but hemiparesis, aphasia, or neglect do.
3. Is there an explanation for the neurological deficit other than acute ischemic stroke? Hemorrhagic stroke is the most important condition that must be differentiated from acute ischemic stroke. All patients should therefore undergo a noncontrast head CT prior to intravenous thrombolysis. This test will also help to exclude mass lesions, which may mimic an ischemic stroke. Other important stroke mimics, including hypoglycemia, hyperglycemia, and postictal paralysis, are discussed in greater detail above and summarized in Box 21.1.
4. Are there any factors that would exclude the patient from receiving rt-PA? Contraindications to rt-PA administration are listed in Box 21.1.
Intravenous rt-PA is indicated for patients with suspected ischemic stroke within 3 hours of stroke onset. The dose of IV rt-PA is 0.9 mg/kg, with 10% given as a bolus and the remaining 90% infused over 1 hour.
For IV rt-PA candidates with systolic blood pressure >185 or diastolic blood pressure >110 mmHg, use antihypertensive medications such as labetalol (10–20 mg IV prn) to lower the blood pressure. Patients who receive rt-PA should be admitted to an intensive care unit for close vital sign monitoring and serial neurological examinations for at least 24 hours. Anticoagulants and invasive procedures such as intravenous catheter and nasogastric tube placement should be avoided for 24 hours. Should the patient develop any change in neurological status, perform a CT scan immediately to exclude the possibility of hemorrhage and treat as discussed in the text.
Intra-arterial tPA and clot retrieval devices
Despite public education campaigns and community outreach programs, most patients with acute ischemic stroke will not reach a stroke center within the approved 3-hour window to receive IV rt-PA. Intra-arterial (IA) tPA is an option for ischemic stroke patients who are not otherwise candidates for IV rt-PA, and may be given up to 6 hours after stroke onset.22 Risks of IA rt-PA include intracranial hemorrhage and the possibility of stroke or other complications from the angiography itself.23 Investigational techniques such as mechanical clot retrieval devices may also be considered for patients who are not IV rt-PA candidates.24
The rationale for acutely anticoagulating a patient with acute ischemic stroke is that it may reduce the chance of early stroke recurrence, limit the extent of an existing stroke, and improve neurological outcome. There is no clear evidence, however, that heparin or low-molecular-weight heparin is effective in doing any of these things. In addition, these anticoagulants increase the risk for hemorrhagic stroke transformation or bleeding in other parts of the body. Until clear evidence is available that anticoagulation provides more benefit than risk, it is best to avoid heparin in patients with acute ischemic stroke. Exceptions to this general statement including arterial dissection, intracardiac thrombi, and venous sinus thrombosis are discussed below.22
Blood pressure management
Blood pressure is almost always elevated in patients with acute ischemic stroke. Based on their experience with cardiac patients, emergency room physicians often administer antihypertensive agents to stroke patients prior to neurological consultation. This approach is often deleterious, as rapid blood pressure lowering may lead to hypoperfusion of the vulnerable ischemic penumbra and worsen both acute clinical signs and long-term outcome.25 The indications for treating elevated blood pressure include:22
• intravenous thrombolysis
• excessive hypertension, arbitrarily defined as systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg
• signs of malignant hypertension such as retinal hemorrhages and exudates, acute renal failure, and hypertensive encephalopathy
• evidence of compromise of other organ systems including cardiac ischemia or pulmonary edema
Labetalol (10–20 mg IV) is the most commonly employed antihypertensive agent for patients with acute ischemic stroke. In most cases, patients actually benefit from a slightly elevated cerebral perfusion pressure, which may be achieved by lowering the head of the bed. Hold outpatient antihypertensive medications for 24 hours unless there is a compelling reason to continue them in the acute phase.
Surgical treatment of ischemic stroke
Ischemic stroke is rarely treated surgically. The two exceptions are malignant MCA syndrome and cerebellar infarction.
Malignant middle cerebral artery syndrome
Large MCA infarctions, defined as those that involve >50% of the territory of the MCA, are associated with massive edema 24–48 hours after stroke onset and a high likelihood of death or poor neurological outcome.26 Medical interventions targeted towards reducing swelling and lowering intracranial pressure are generally ineffective in changing the course of malignant MCA syndrome (Chapter 2). Hemicraniectomy and duraplasty, however, allow room for the swollen brain to expand, thereby reducing the probability of herniation and death. Although surgical intervention reduces the likelihood of poor outcomes, most surviving patients still need assistance with all their activities of daily living and will be unable to walk.27 Decisions about surgical intervention should therefore be made carefully in conjunction with the patient’s family.
Many patients with isolated cerebellar infarctions recover spontaneously and have no lasting stroke deficits. Other patients, particularly those with large PICA infarctions, develop massive edema 24–48 hours after stroke onset, leading to brainstem compression and obstructive hydrocephalus. A patient with a cerebellar infarction should be monitored frequently, and any change in their level of consciousness should prompt neurosurgical consultation. Suboccipital decompressive craniectomy may reduce the likelihood of death and poor neurological outcome, and many patients who undergo surgery survive with only modest deficits. Because surgical intervention is widely considered the standard of care in rapidly progressing cerebellar infarction, a randomized controlled trial to better define the benefit of surgery is unlikely.
Atrial fibrillation (AF) and intracardiac thrombi are important sources of embolic strokes. Evaluation for AF and thrombi begins with careful cardiac examination to screen for irregular rhythms or murmurs. While inpatient cardiac telemetry is routinely ordered in an attempt to capture paroxysmal AF, it is generally of low yield, leading to a change in management in fewer than 2% of patients.28 The best tool to evaluate structural abnormalities of the heart and intracardiac thrombi is transesophageal echocardiography (TEE). Although it is somewhat more invasive and less readily available than transthoracic echocardiography (TTE), TEE is superior to TTE for detecting abnormalities such as left atrial appendage thrombi, aortic atheromatous disease, patent foramen ovale (PFO), and atrial septal aneurysms.29
Assessment of the intracranial circulation using MRA or CTA is typically performed at initial presentation. With the exception of patients who are being evaluated for cervical carotid or vertebral artery dissections, evaluation of the extracranial circulation usually begins when stroke deficits are stable, generally 24 hours or more into the patient’s hospital course. Imaging of the extracranial carotid arteries is generally of greatest interest:
• Conventional angiography. While conventional angiography is the gold standard for the assessment of carotid artery stenosis, it is an invasive procedure associated with a 1% risk for serious side effects including death and disabling stroke.30 Many surgeons, however, still prefer to perform conventional angiography to accurately define vascular anatomy in the planning stages of carotid endarterectomy.
• Carotid duplex ultrasound. This study is noninvasive and readily available, and is generally the first test performed to evaluate carotid artery stenosis.
• CTA and MRA. Because ultrasound may overestimate the degree of carotid artery stenosis, MRA or CTA of the neck vessels often plays a confirmatory role. For patients with posterior circulation strokes, MRA with fat suppression or CTA of the cervical portion of the vertebral arteries is used to evaluate suspected vertebral artery dissection.
Because hyperlipidemia and diabetes are common modifiable risk factors for stroke recurrence, measure lipid levels and hemoglobin A1c percentages in all patients with ischemic stroke. Blood tests for hypercoagulable states are ordered excessively and often incorrectly in stroke patients. The “hypercoagulable panel” includes tests for deficiencies of protein C, protein S, antithrombin III, plasminogen, activated protein C resistance/factor V Leiden mutation, anticardiolipin antibodies, and lupus anticoagulant, and is generally of low yield.31 Factors that may increase the probability of an abnormal test result include age <50, prior venous thrombosis, multiple family members with venous thrombosis, and personal history of miscarriages.
Blood pressure control
In the acute setting, lowering blood pressure is often deleterious to a patient with an ischemic stroke as it may decrease perfusion to vulnerable areas of the brain. For the purposes of secondary prevention, however, hypertension is the most commonly identified treatable stroke risk factor, and must be treated aggressively. Although specific target blood pressure levels are not defined, a common goal is 120/80, with blood pressure reductions by even as little as 10/5 decreasing the likelihood of stroke recurrence.32 There is no set time after a stroke at which antihypertensive therapy should be initiated or restored, but 1 week poststroke is a reasonable target.
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce the risk for stroke recurrence by approximately 20%.33 Even patients with normal low-density lipoprotein (LDL) and total cholesterol levels benefit from statin therapy.34 Although the majority of risk reduction is likely secondary to lowering of LDL levels, other important effects of statins include plaque stabilization and anti-inflammatory actions. Diet and other agents capable of lowering cholesterol are not as effective as statins in secondary stroke prevention.35 Thus, all patients with ischemic stroke should be treated with atorvastatin 80 mg qd, lovastatin 40 mg qd, pravastatin 40 mg qd, or simvastatin 40 mg qd. Side effects of these medications include myotoxicity (Chapter 10), diarrhea, and transaminitis.
Diabetes mellitus is an independent risk factor for ischemic stroke. Strict glucose control (hemoglobin A1c percentage <7%), whether achieved by diet, oral hypoglycemic medications, or aggressive insulin therapy, decreases the risk for stroke recurrence.32
General lifestyle recommendations
While official target weights for stroke patients are not available, it is important to recommend weight loss, as overweight patients (BMI >25 kg/m2) are at increased risk of stroke recurrence. It is also important to encourage smoking cessation and regular exercise.
Table 21.3 Antiplatelet agents used in stroke prevention
A small number of stroke etiologies require oral anticoagulation for secondary stroke prophylaxis:
• Unless there is a clear contraindication (e.g. a bleeding diathesis or high risk of falls), treat all patients with stroke secondary to atrial fibrillation with warfarin, aiming for a goal INR of 2.0–3.0.32
• In general, consider treating patients with hypercoagulable states, carotid artery or vertebral dissection, or cerebral venous sinus thrombosis with warfarin for 3–6 months.
• There is no clear evidence supporting anticoagulation for patients with PFO, atrial septal aneurysm (ASA), or the combination of PFO and ASA.36
• Anticoagulation is not recommended for patients with ischemic stroke of undefined etiology (cryptogenic strokes).37
Most ischemic stroke patients are not candidates for anticoagulants and are treated instead with antiplatelet agents. The four most commonly used antiplatelet agents are aspirin, aspirin plus extended-release dipyridamole, clopidogrel, and ticlopidine. Selecting the appropriate agent depends largely on the individual patient and is often the most time-consuming and passionately debated decision in secondary stroke prevention. Table 21.3 provides guidance in choosing an antiplatelet agent. For most patients, aspirin plus extended-release dipyridamole is the agent of first choice. The most common side effect of this medication is headache, which usually resolves on its own without treatment. If the headache is particularly severe and does not improve, clopidogrel is usually the preferred agent. Clopidogrel is also the first-choice medication in patients who do not tolerate aspirin.
Carotid endarterectomy and stenting
As discussed above, carotid artery stenosis is an important cause of stroke and transient ischemic attacks. Carotid endarterectomy (CEA) is the standard surgical approach to prevent ipsilateral stroke or transient ischemic attack from this process, but, because of the risks of surgery, must be considered carefully. The most important variable in determining who should undergo CEA is the degree of carotid stenosis (see also Box 21.2):
• Patients with stenosis between 70 and 99% derive the greatest benefit from CEA, and should undergo surgery, preferably within 2 weeks of their stroke or transient ischemic attack.43–45
• Patients with 50–69% stenosis may or may not benefit from surgery. Men with this degree of stenosis tend to benefit more than women.46 To improve the chances of a good outcome, CEA for 50–69% stenosis should only be performed by surgeons with low complication rates.
• Patients with stenosis <50% or complete occlusion of the carotid artery should be managed with antiplatelet agents and statins.
Carotid artery stenting is a less invasive interventional approach to carotid artery stenosis, which may be used for patients with stenosis between 70 and 99% who have multiple medical comorbidities, extensive or poorly accessible lesions, radiation-induced carotid stenosis, and restenosis after previous CEA.47
Box 21.2 Asymptomatic carotid artery stenosis
Carotid bruits are detected frequently on routine physical examination. Primary care physicians often refer these patients to neurologists, or do so after an ultrasound discloses carotid artery stenosis. In some cases, vascular surgeons seek guidance in managing these patients. Because asymptomatic carotid artery stenosis is such a common problem, it is important to understand the data in order to recommend the appropriate course of treatment. Meta-analysis of the three major studies that addressed surgical treatment showed that carotid endarterectomy for patients with moderate-to-severe stenosis (defined as 60–99% in two of the studies and 50–99% in the third) reduced the absolute risk of stroke by approximately 1% for each year of subsequent survival.48 The benefit of carotid endarterectomy was counterbalanced by a perioperative risk for stroke or death of approximately 3%. Benefits of intervention appeared to be greater for men than for women. Thus, in centers with low complication rates, it seems prudent to consider (although it is not absolutely indicated) carotid endarterectomy for asymptomatic carotid stenosis, especially for men.
Stenting of the vertebral or basilar arteries may be an option for patients with continued symptomatic posterior circulation ischemia despite maximal medical treatment.32 Surgical or percutaneous closure of a PFO may be employed on a research basis, but should not be used as part of routine clinical care.32
Although they often take a back seat to decisions about thrombolysis and antiplatelet agent selection, supportive measures are critical in reducing disability and death from stroke. The pillars of supportive care for stroke patients are:
Treating hyperthermia and infection
Hyperthermia worsens stroke outcome, independent of the presence of underlying infection.49 Evaluate for sources of fever by performing a complete blood count, blood cultures, chest X-ray, urinalysis, and urine cultures, and treat with antibiotics as appropriate. For patients with unexplained fevers, consider lower-extremity duplex ultrasound studies to investigate for deep venous thrombosis (DVT), echocardiography to evaluate for endocarditis, and infectious disease consultation. Treat mild hyperthermia with antipyretics such as acetaminophen and more severe hyperthermia with antipyretics and cooling blankets.
Because hyperglycemia, like fever, worsens stroke outcome, it is important to maintain strict glucose control.50
Maintaining adequate nutrition
Dysphagia, weakness, and cognitive impairments all lead to inadequate nutrition and impede recovery from stroke. If necessary, prescribe parenteral nutrition or tube feedings. Do not use hypotonic fluids, as they may worsen brain edema.
Assessing aspiration risk and preventing aspiration
Patients with strokes involving large hemispheric territories or the brainstem are at increased risk of aspiration, which may lead to both acute airway compromise and aspiration pneumonia. Assess aspiration risk at the bedside by asking the patient to swallow three ounces of water and then observing for coughing or a wet, hoarse voice.51 A patient who fails this simple swallow test is at risk for aspiration, and should be placed on precautions, which may include monitored eating or restrictions on oral intake. Because difficulties may be subtle (e.g. silent aspiration), patients often require a formal swallowing study to determine whether dysphagia is present.
Deep venous thrombosis prophylaxis
Because patients with severe stroke deficits are generally bed bound for at least several days, DVT prophylaxis is essential to prevent life-threatening pulmonary emboli. Options for DVT prophylaxis include compression stockings, sequential compression devices, unfractionated heparin, and low-molecular-weight heparin. Unless there is a clear contraindication (such as heparin-induced thrombocytopenia or a bleeding diathesis), DVT prophylaxis should consist of unfractionated heparin (5000 units sc tid) or a low-molecular-weight heparin.22 Treat patients who cannot receive heparin with a sequential compression device.
Weakness, ataxia, sensory impairments, and cognitive dysfunction are all factors that increase the risk of falls following stroke. Activating bed alarms, employing patient sitters, and even using physical restraints may be necessary to prevent falls and additional injuries.
Initiating a rehabilitation program
Recovery from stroke is a complex process that results from a combination of brain adaptation to injury by new synapse formation and by patient-driven efforts to compensate for irreparable deficits. Improvement is usually maximal 6 weeks after a stroke, and is almost always complete within 3–6 months.52 Early rehabilitation tends to be more effective than delayed rehabilitation, and for this reason, it is important to involve physical therapists, occupational therapists, speech and swallowing specialists, and cognitive rehabilitation experts as soon as possible.53
Evaluation and treatment of intracranial hemorrhage
Intracranial hemorrhage (ICH) is a life-threatening emergency associated with high morbidity and mortality. It may be difficult to differentiate ICH from ischemic stroke on clinical grounds alone. As noted above, possible clues to ICH include headache and the presence of deficits that progress over minutes to hours. Emergency room physicians or other doctors usually make the diagnosis of ICH by noncontrast head CT, well before a neurologist is involved.
Acute life support
Because a patient with ICH may present in extremis, the first priority is to assure that they have a patent airway, adequate cardiopulmonary function, and intravenous access for medication administration. A patient with ICH may initially be conscious and then deteriorate rapidly. Thus, it is essential to monitor the patient carefully and transfer them to an intensive care unit should their clinical condition decline.
After ensuring basic life support measures, the next step in managing ICH is to discontinue any anticoagulants and reverse their effects if applicable. Review the patient’s medication list and check their prothrombin time, PTT, and platelet count.
The three options available for reversing anticoagulation secondary to warfarin are:
• Prothrombin complex concentrate (factor IX complex) 25–50 IU/kg. Factor IX complex reverses the blood-thinning effects of warfarin within several hours, but because of its short half-life, it must be administered with vitamin K. Unfortunately, factor IX complex is quite expensive and may not be available at all medical centers.
• Fresh frozen plasma (FFP) 15–20 ml/kg. This is readily available, but administration may be delayed by thawing and preparation times. In addition, FFP takes several hours to administer and represents a substantial volume load.
• Vitamin K 10 mg IV. Treat all patients with ICH who are taking warfarin with vitamin K. Because vitamin K requires at least 24 hours to work, it is not appropriate monotherapy for reversing ICH in the hyperacute setting.
Reverse heparin using protamine sulfate. In general, the dose of protamine is 1 mg per 100 units of heparin if the heparin is being actively infused and between 0.25–0.5 mg per 100 units if the heparin was discontinued >30 minutes prior to beginning protamine infusion. It is good practice to review each case with the pharmacy in order to optimize treatment.
Blood pressure treatment
Blood pressure management in acute ICH is an area of great controversy. Lowering blood pressure reduces the likelihood of hemorrhagic expansion but may also lower perfusion pressure and increase the risk of perilesional ischemia. Similar to ischemic stroke, there is no clearly defined ideal blood pressure, although guidelines suggest a goal blood pressure of no greater than 160/90 for ICH patients.54 The agents used most commonly to lower blood pressure in ICH are labetalol (10–20 mg IV) or hydralazine (5–10 mg IV) by intravenous push.
Managing increased intracranial pressure
Intraparenchymal hemorrhage may result in increased intracranial pressure, a potentially life-threatening emergency, which is discussed in further detail in Chapter 2.
Surgical hematoma evacuation
Surgical hematoma evacuation has the theoretical potential to rescue vulnerable adjacent brain tissue from ischemia and to reduce the likelihood that ICH will increase intracranial pressure and lead to herniation. Despite these possible benefits, decompressive craniectomy does not appear to improve neurological outcomes or reduce the chance of death in most patients with ICH.54 Large cerebellar hemorrhages (>3 cm), however, may lead to brainstem compression and obstructive hydrocephalus, and should be evacuated as soon as possible to prevent further neurological deterioration.55
Defining the etiology
Defining the etiology of ICH helps to prevent hemorrhage recurrence and points to underlying disease processes that may need specific therapies. Common causes of ICH include:
• Hypertension. This is the most common cause of ICH. Typical locations of hypertensive hemorrhages include the caudate nucleus, thalamus, pons, and cerebellum.
• Amyloid angiopathy. Hemorrhages secondary to amyloid angiopathy tend to involve the parietal and occipital lobes. Other than location, finding cerebral microbleeds with susceptibility imaging studies may help to identify amyloid angiopathy as the source of ICH (Figure 21.6).
• Anticoagulant and thrombolytic agents.
• Bleeding diatheses such as hemophilia and von Willebrand disease. In most cases, these conditions are identified long before ICH occurs.
• Metastatic tumors. Tumors that have a propensity to bleed include renal cell carcinoma, melanoma, thyroid carcinoma, and choriocarcinoma. In patients with a known primary cancer, defining metastasis as the etiology is often straightforward. In patients with no known primary tumor, a careful screening examination must be conducted, as discussed in Chapter 23.
• Arteriovenous malformations. These should be considered as an etiology of ICH in younger patients. Although these masses have a fairly characteristic appearance, they may be masked by the overlying hemorrhage. Arteriovenous malformations are discussed further in Chapter 23.
Table 21.4 Glasgow Coma Scale scores58
The GCS score is derived by adding the best eye movement, verbal response, and motor response.
Prognosis of intracranial hemorrhage
Approximately half of patients with ICH will die within 30 days.56,57 Among the most important prognostic factors are the initial level of consciousness (as summarized by the Glasgow Coma Scale (GCS) score; Table 21.4) and volume of the hemorrhage, which can be estimated from the CT scan using the formula57:
Volume = (A × B × C)/2,
where A is the largest diameter of the bleed, B is the diameter perpendicular to the bleed, and C is the number of slices on the CT scan multiplied by the slice thickness. Patients with ICH volumes >60 cm3and GCS scores 8 had a 30-day mortality of 91%, while those with a volume <30 cm3 and GCS scores >8 had a 30-day mortality of 19% in one study.57 Other risk factors for poor prognosis from ICH include older age, intraventricular blood, and early clinical deterioration.59
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