Enrique C. Leira MD
Harold P. Adams Jr. MD
ESSENTIALS OF DIAGNOSIS
Cerebrovascular disease is the third most frequent cause of death and the leading cause of disability in the United States. Stroke primarily affects the elderly. Given that the American population is aging, it is expected that the burden of disability from cerebrovascular diseases will continue to grow considerably. In the United States the majority of strokes result from insufficient blood perfusion in the brain (ischemic stroke), whereas bleeding that destroys and compresses the brain parenchyma or subarachnoid space (intracerebral or subarachnoid hemorrhage) accounts for -20%.
There are 4 general mechanisms of ischemic stroke: arterial diseases, cardioembolism, hematological disorders, and systemic hypoperfusion (Table 18-1). Hemorrhagic stroke results from hypertension, vascular abnormalities, arteriopathies, coagulopathies, hemorrhagic transformation infarction, and brain tumors or metastasis (Table 18-2).
A stroke presents as an acute neurological deficit or an unusually severe, sudden headache. The neurological impairments reflect the area of the brain affected. Ischemic strokes and intracerebral hemorrhages present in a similar manner and are thus difficult to differentiate (Figure 18-1). Subarachnoid hemorrhages, however, often present as a sudden, explosive, very severe, unusual headache without other neurological signs.
Some clinical features suggest either ischemic stroke or hemorrhagic stroke. For example, in cerebral hemorrhages, the onset of the deficit tends to be very abrupt and is associated with a severe headache. The level of consciousness (LOC) on presentation can be a useful indicator: Patients with cerebral hemorrhage tend to have a more depressed LOC compared with those with ischemic stroke (Figure 18-2). Seizures at stroke onset are more common with intracerebral hemorrhage. Prominent nausea and vomiting also point to intracranial bleeding.
The presenting focal neurological symptoms are variable. Usually, a combination of motor, sensory, visual, coordination, cognitive, and language deficits is found. These deficits correlate with the site and size of the lesion. In ischemic stroke, the lesion should follow 1 or several arterial territories. The typical clinical presentation for the major forms of stroke is detailed in Table 18-3.
Subarachnoid hemorrhages typically present with an abrupt, uncharacteristically explosive headache, often during physical exertion (Figure 18-3). Nuchal rigidity may be present and reflects meningeal irritation. Depending on the extent of the hemorrhage, LOC can vary from normal (grade I) to deep coma (grade V). Focal neurological symptoms resulting from intraparenchymal extension of the hemorrhage, mass effect produced by the aneurysm, or early arterial vasospasm may be present. The abrupt central release of catecholamines, which occurs during a subarachnoid hemorrhage, can induce acute cardiac manifestations, including syncope, chest pain, arrhythmias, electrocardiographic (ECG) ischemic changes, cardiac enzyme elevation, and even cardiac arrest. Other confounding or nonspecific symptoms such as vertigo, malaise, diffuse aches, and leg or back pain can be present, adding to the difficulty in diagnosis.
The emergent tests required in the evaluation of every patient with suspected stroke include serum glucose,
prothrombin time, partial thromboplastin time, and electrolytes; complete cell and platelet blood count; ECG; noninvasive blood pressure monitoring; pulse oximeter/arterial blood gas; chest x-ray film; and unenhanced computed tomography (CT) or magnetic resonance imaging (MRI). Additional tests required emergently in selected patients include MRI/magnetic resonance angiography, cerebral angiogram, lumbar puncture, blood cultures (eg, suspected endocarditis), echocardiogram (eg, valve malfunction), electroencephalogram (EEG), pregnancy test, and neuroimaging studies.
Table 18-1. Causes of acute ischemic stroke.
Table 18-2. Causes of hemorrhagic stroke.
The differential diagnosis of acute ischemic stroke and intracerebral hemorrhage includes subarachnoid hemorrhage, subdural/epidural hematoma, hypoglycemia, postictal (Todd's) paralysis, migraine, brain tumor/metastasis, encephalitis (eg, herpes simplex), brain abscess, demyelinating diseases (eg, multiple sclerosis), metabolic/infective/hypoxic encephalopathy (exacerbating latent deficit), and psychogenic paralysis/malingering. Postseizure paralysis can be difficult to differentiate from a stroke, especially if the seizure was not witnessed. The issue is further complicated by the fact that some strokes present with a seizure at onset. A diffusion-weighted MRI and an EEG may be helpful in this setting.
A serum glucose determination can be used to rule out hypoglycemia, which can be clinically indistinguishable from an ischemic stroke. Neuroimaging studies are necessary to differentiate between ischemic and hemorrhagic stroke. A lumbar puncture is mandatory for diagnosis when subarachnoid hemorrhage is suspected and the CT scan of the head is normal.
It is also necessary to differentiate strokes from subdural or epidural hematomas, tumors, and brain abscesses. Certain infections, such as herpes simplex encephalitis or cerebral abscesses, can mimic ischemic stroke.
Subarachnoid hemorrhage can imitate ischemic stroke if focal findings are present. Attacks of multiple sclerosis may also present like a stroke, but usually these exacerbations are more gradual in their presentation. Psychogenic paralysis can be difficult to diagnose but
should be suspected in patients with unusual emotional attitudes and who present with deficits that do not follow the laws of neuroanatomy.
Figure 18-1. A. Computed tomography scan of a dense right hemiparesis and aphasia that started 2 h prior appears normal initially. B. Follow-up scan 24 h later shows a large infarction in the left middle artery distribution.
Early complications include extension of the infarction or hemorrhage and recurrent ischemic stroke. Hemorrhagic transformation of the infarction results from late reperfusion over a brain parenchyma with impaired vascular autoregulation. It is more commonly seen after large cardioembolic strokes and with the use of anticoagulants or thrombolytic agents. Brain edema is commonly noticeable after large infarctions. It usually reaches its maximum after 3-5 days in supratentorial lesions. However, in infratentorial strokes, brain edema can become symptomatic in the first 48 h as a result of compression of the brainstem and fourth ventricle, leading to obstructive hydrocephalus.
These complications share similar clinical manifestations: exacerbation of the previous neurological deficit, appearance of a new deficit, or a decrease in LOC.
Seizures and poststroke depression are neurological complications typically seen later in the course of the stroke.
Figure 18-2. Computed tomography scan of a patient with lethargy and an abrupt left hemiparesis 1 h prior shows a large parenchymal hemorrhage that has ruptured into the lateral ventricle.
Aspiration pneumonia can occur whenever there is impaired swallowing function or decreased LOC. It usually manifests initially as a fever spike. Severe cases can lead to sepsis, respiratory failure, or acute respiratory distress syndrome. Urinary tract infection may occur, particularly in patients who require urinary catheterization. Deep venous thrombosis and pulmonary embolism often occur in immobilized patients.
Cardiac arrhythmias and myocardial infarction can follow a stroke. These events might be triggered by a central release of catecholamines. In addition, coronary artery disease and stroke share common risk factors. Falls are common in stroke patients who have gait abnormalities or who are confused or unaware of their neurological limitations. Constipation may also occur. Contractures in paralyzed limbs or pressure sores can occur as a late complication in patients who are not adequately mobilized. Early complications in stroke patients can be reduced by the implementation of the measures described in Table 18-4.
Rebleeding is a feared early complication of subarachnoid hemorrhage that justifies early identification and treatment of the aneurysm. Vasospasm typically occurs in the first week after the hemorrhage and can result in focal ischemic neurological deficits or decreased LOC. An increase in mean arterial velocities usually precedes the clinical symptoms of vasospasm. Therefore, a useful strategy in monitoring this complication is to perform repeated transcranial Doppler measurements. Communicating hydrocephalus results when blood interferes with the reabsorption of cerebrospinal fluid. It is usually manifested by a progressive deterioration in mental status. Hyponatremia and other electrolyte abnormalities can develop, leading to a worsening of the mental status and a lower seizure threshold. In addition, atelectasis, aspiration pneumonia, and gastric stress ulcers can also occur.
Table 18-5 summarizes the initial steps in the evaluation of patients with suspected stroke. The goal of any specific treatment for acute ischemic stroke is to save the area of brain tissue around the core of the infarction known as the ischemic penumbra, which is malfunctioning because of insufficient blood flow and is contributing to the total neurological deficit.
As in any other emergency, the management of acute stroke starts with assessment of the “ABC's”:Airway,Breathing,Circulation. Most stroke patients do not require intubation or ventilatory support; however, those with intracerebral hemorrhage, large hemispheric infarctions, or severe brainstem lesions do. The decision to intubate is largely based on the assessment of LOC rather than respiratory parameters. Although some strokes require intubation for respiratory failure, in most instances, a decision to protect the airway is made based on the clinical likelihood of aspiration or obstruction. Acute assessment of the circulatory status includes ECG, blood pressure monitoring, and cardiac enzyme determination.
Table 18-6 summarizes the basic steps required in the general management of an acute stroke patient. Most patients with acute ischemic stroke have an elevated
blood pressure. This elevation is usually transient and helps maintain perfusion in the ischemic penumbra. The ischemic penumbra has lost cerebral autoregulation, rendering the blood flow to that area of the brain perfusion dependent. A rapid reduction of blood pressure in a patient with moderate blood pressure elevation can result in an acute exacerbation of the neurological deficit and should be avoided. No treatment is recommended unless the mean arterial pressure is >130 mm Hg or systolic pressure is >220 mm Hg. Exceptions to this rule may involve cases of concomitant myocardial infarction, aortic dissection, or hypertensive end-organ damage. Another exception involves thrombolytic therapy, which requires a blood pressure <185/110 mm Hg. If the elevated blood pressure needs to be treated, intravenous βblocking agents are preferred because of their predictable response and minimal vasodilatory effect, a factor that could potentially worsen intracranial pressure. Labetalol should be avoided in stroke patients who are cocaine abusers. Other alternatives are sodium nitroprusside and hydralazine.
Table 18-3. Symptoms of acute stroke depending on the site of the lesion.
Acute stroke patients should not take food or liquid by mouth until the competency of the swallowing function is formally assessed, and intravenous fluids should be started. Peripheral intravenous access is preferred initially because central catheters constitute a relative contraindication for subsequent thrombolytic therapy. The patient should be kept flat in bed to avoid worsening of ischemia in potentially perfusion-dependent areas. Although oxygen supplementation is routinely used in the emergency setting, its usefulness is unproven.
The immediate assessment includes a rapid general and neurological exam (eg, National Institutes of Health Stroke Scale [NIHSS]) tailored to the stroke victim. The NIHSS is the standard method to evaluate stroke patients for thrombolytic therapy. The patient's NIHSS score ranges from 0 (normal) to 42, and the total score correlates with the size of the lesion and outcome at 3 mo.
Reperfusion therapy with intravenous recombinant tissue-type plasminogen activator (rt-PA) is the only approved treatment for ischemic stroke in the United States. Treatment with intravenous rt-PA increases the chances of a good outcome after an ischemic stroke if it is administered within a 3-h window. Not every case is eligible for this therapy. Patients who are candidates need to have a time of onset <3 h, significant measurable neurological deficit, and symptoms attributed to cerebral ischemia. Table 18-7 summarizes the protocol for intravenous rt-PA treatment. Contraindications for TPA are summarized in Table 18-8.
Advanced age is not a contraindication for the use of rt-PA. However, the risk of intracerebral hemorrhage after rt-PA may increase with age. Therefore, one must use caution when administering rt-PA to elderly patients. Patients and families should be given a thorough explanation of the risks and benefits of rt-PA.
Figure 18-3. Computed tomography scan of a patient with an explosive headache and lethargy shows a subarachnoid hemorrhage that seems to originate in the left sylvian fissure.
Intra-arterial thrombolysis has the advantage of concentrating the agent at the occlusion site, which minimizes systemic bleeding. However, it is more complicated to perform because it requires the availability of emergent neurointerventional capabilities. Intra-arterial thrombolysis is an option for patients with angiographically proven major vessel occlusion and has a promising future either as an isolated therapy or in combination with intravenous thrombolysis (“bridging therapy”).
Anticoagulant agents are a proven intervention in preventing recurrent cardioembolic strokes and pulmonary embolism in immobilized patients. However, they cannot be recommended to treat acute stroke in nonselected patients.
Treatment of early complications includes the use of antibiotics for aspiration pneumonia or sepsis, anticoagulants and pneumatic stocking devices, stool-bulking agents, early physical therapy, and early mobilization.
Table 18-4. Measures to reduce complications after acute stroke.
controversial and is left to the preference of the treating physicians.
Table 18-5. Emergent evaluation of a patient with suspected stroke.
Table 18-6. General management of patients with stroke.
Complications of subarachnoid hemorrhage must be managed. Vasospasm can be treated with calcium channel antagonists (eg, nimodipine), hypervolemia-hemodilution-hypertensive therapy (triple H therapy), or cerebral angioplasty. Hydrocephalus may require frequent daily lumbar punctures for cerebrospinal fluid drainage or a lumboperitoneal shunt. Medical treatment of complications includes the correction of electrolyte abnormalities (eg, hyponatremia), antibiotics for pulmonary infections and sepsis, anticonvulsants for seizures, and mannitol infusions for cerebral edema.
Table 18-7. Protocol for use of intravenous rt-PA in acute ischemic stroke.
Table 18-8. Contraindications for intravenous rt-PA in acute ischemic stroke.
Secondary prevention strategies in ischemic stroke should be initiated as soon as possible. The choice of strategy depends on the stroke subtype: large artery atherosclerosis (atherothrombotic), small vessel atherosclerosis (lacunar), cardioembolic, other cause, or undetermined cause. Table 18-9 lists common tests used to determine stroke subtype. Cardioembolic strokes, such as those secondary to atrial fibrillation and high-risk cardiac lesions, are better prevented by the use of oral anticoagulants. The benefit of anticoagulants for medium-risk or uncertain risk cardiac lesions, such as patent foramen ovale or atrial septal aneurysm, is not clear.
Antiplatelet agents are the first choice to prevent recurrent strokes in patients with noncardioembolic strokes. Available alternatives are aspirin, aspirin and dipyridamole, ticlopidine, and clopidogrel. Newer antiplatelet agents show a modest benefit over aspirin but
are more expensive or have side effects. Warfarin cannot be recommended as the first-line secondary prevention agent for patients whose strokes are not due to cardioembolism because it does not provide additional benefits compared with aspirin and has the potential for serious hemorrhagic complications. It is common practice to change the secondary prevention strategy after one agent fails, resulting in switching among different antiplatelet agents and anticoagulants after each recurrent vascular event despite the absence of supporting evidence.
Table 18-9. Common investigations used to determine stroke subtype.
A subgroup of patients with large artery arteriosclerosis may benefit from preventive surgical measures in addition to antiplatelet medical therapy. Large artery arteriosclerosis is subdivided into extracranial and intracranial disease. Patients with extracranial stenosis in the carotid artery have the option of endarterectomy. This strategy is proven for those patients with >50% stenosis of the ipsilateral carotid artery. However, this strategy is effective only if the procedural complications (including surgery and angiogram) of death and disabling stroke can be kept at <2%. Therefore, this approach may not be effective for high-risk medical patients or institutions without adequate experience. Age by itself is not an exclusion criterion for endarterectomy.
The technique of carotid angioplasty and stenting is an alternative to endarterectomy for patients with symptomatic carotid disease. Patients with intracranial stenosis may benefit from endovascular therapy with angioplasty and stenting.
Additional secondary prevention measures include adequate control of modifiable risk factors (in particular blood pressure), treatment of hypercholesterolemia, adequate control of diabetes, and avoidance of smoking. These measures can lower the risk of recurrent ischemic events.
Advanced age increases the risk of mortality after a stroke and is also a risk factor for recurrence. Disability is a more common outcome after ischemic stroke than death. The admission NIHSS score strongly predicts the outcome at 3 mo. For example, patients with an NIHSS score ranging from 0-3 have a 90% chance of a good or excellent outcome at 3 mo, whereas for those with scores ranging from 16-22 the percentage decreases to 12%.
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American Stroke Association: http://www.strokeassociation.org
National Stroke Association: http://www.stroke.org
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