Thrombotic or embolic occlusion of a major vessel leads to cerebral infarction. Causes are identical to the disorders predisposing to TIAs. The resulting deficit depends on the particular vessel involved and the extent of any collateral circulation. Cerebral ischemia leads to release of excitatory and other neuropeptides that may augment calcium flux into neurons, thereby leading to cell death and increasing the neurologic deficit.
Onset is usually abrupt, and there may then be very little progression except that due to brain swelling. Clinical evaluation should always include examination of the heart for murmurs and rhythm irregularities. Auscultating over the carotid or subclavian vessels may reveal a bruit but is not sensitive enough to substitute for vascular imaging.
1. Obstruction of carotid circulation
Occlusion of the anterior cerebral artery distal to its junction with the anterior communicating artery causes weakness and cortical sensory loss in the contralateral leg and sometimes mild weakness of the arm, especially proximally. There may be a contralateral grasp reflex, paratonic rigidity, abulia (lack of initiative), or frank confusion. Urinary incontinence is not uncommon, particularly if behavioral disturbances are conspicuous. Bilateral anterior cerebral infarction is especially likely to cause marked behavioral changes and memory disturbances. Unilateral anterior cerebral artery occlusion proximal to the junction with the anterior communicating artery is generally well tolerated because of the collateral supply from the other side.
Middle cerebral artery occlusion leads to contralateral hemiplegia, hemisensory loss, and homonymous hemianopia (ie, bilaterally symmetric loss of vision in half of the visual fields), with the eyes deviated to the side of the lesion. If the dominant hemisphere is involved, global aphasia is also present. It may be impossible to distinguish this clinically from occlusion of the internal carotid artery. With occlusion of either of these arteries, there may also be considerable swelling of the hemisphere during the first 72 hours. For example, an infarct involving one cerebral hemisphere may lead to such swelling that the function of the other hemisphere or the rostral brainstem is disturbed and coma results. Occlusions of different branches of the middle cerebral artery cause more limited findings. For example, involvement of the superior division in the dominant hemisphere leads to a predominantly expressive (Broca) aphasia and to contralateral paralysis and loss of sensations in the arm, the face and, to a lesser extent, the leg. Inferior branch occlusion in the dominant hemisphere produces a receptive (Wernicke) aphasia and a homonymous visual field defect. With involvement of the nondominant hemisphere, speech and comprehension are preserved, but there may be a left hemispatial neglect syndrome or constructional and visuospatial deficits.
Occlusion of the ophthalmic or central retinal artery leads to sudden painless visual loss with retinal pallor and a macular cherry red spot on fundoscopic examination. Sudden, transient vision loss in one eye (amaurosis fugax) is a TIA in this arterial territory. Patients with a cilioretinal artery (approximately 25%) may have macular sparing due to collateral blood supply.
2. Obstruction of vertebrobasilar circulation
Occlusion of the posterior cerebral artery may lead to a thalamic syndrome in which contralateral hemisensory disturbance occurs, followed by the development of spontaneous pain and hyperpathia. There is often a macular-sparing homonymous hemianopia and sometimes a mild, usually temporary, hemiparesis. Depending on the site of the lesion and the collateral circulation, the severity of these deficits varies and other deficits may also occur, including involuntary movements and alexia. Occlusion of the main artery beyond the origin of its penetrating branches may lead solely to a macular-sparing hemianopia.
Vertebral artery occlusion below the origin of the anterior spinal and posterior inferior cerebellar arteries may be clinically silent because the circulation is maintained by the other vertebral artery. If the remaining vertebral artery is congenitally small or severely atherosclerotic, however, a deficit similar to that of basilar artery occlusion is seen unless there is good collateral circulation from the anterior circulation through the circle of Willis. An obstruction of the posterior inferior cerebellar artery or an obstruction of the vertebral artery just before it branches to this vessel leads to the lateral medullary syndrome, characterized by vertigo and nystagmus (vestibular nucleus), ipsilateral spinothalamic sensory loss involving the face (trigeminal nucleus and tract), dysphagia (nucleus ambiguus), limb ataxia (inferior cerebellar peduncle), and Horner syndrome (descending sympathetic fibers), combined with contralateral spinothalamic sensory loss involving the limbs.
Occlusion of both vertebral arteries or the basilar artery leads to coma with pinpoint pupils, flaccid quadriplegia and sensory loss, and variable cranial nerve abnormalities. With partial basilar artery occlusion, there may be diplopia, visual loss, vertigo, dysarthria, ataxia, weakness or sensory disturbances in some or all of the limbs, and discrete cranial nerve palsies. In patients with hemiplegia of pontine origin, the eyes are often deviated to the paralyzed side, whereas in patients with a hemispheric lesion, the eyes commonly deviate from the hemiplegic side. When the small paramedian arteries arising from the basilar artery are occluded, contralateral hemiplegia and sensory deficit occur in association with an ipsilateral cranial nerve palsy at the level of the lesion.
Occlusion of any of the major cerebellar arteries produces vertigo, nausea, vomiting, nystagmus, and ipsilateral limb ataxia. Contralateral spinothalamic sensory loss in the limbs may also be present. Deafness due to cochlear infarction may follow occlusion of the anterior inferior cerebellar artery, which may also cause ipsilateral facial spinothalamic sensory loss and weakness. Massive cerebellar infarction may lead to obstructive hydrocephalus, coma, tonsillar herniation, and death.
A CT scan of the head (without contrast) should be performed immediately, before the administration of aspirin or other antithrombotic agents, to exclude cerebral hemorrhage (Table 24–3) (eFigure 24–3). CT is relatively insensitive to acute ischemic stroke within the first 6–12 hours, and subsequent MRI with diffusion-weighted sequences helps define the distribution and extent of infarction as well as exclude tumor or other differential considerations (eFigure 24–4, eFigure 24–5). CT angiography of the head and neck should be performed to identify large vessel occlusions amenable to endovascular therapy in patients presenting within 6 hours of stroke onset (eFigure 24–6) and should be considered in those presenting between 6 and 24 hours, together with CT perfusion studies. Regardless of timing of presentation, imaging of the cervical vasculature is indicated as part of a search to identify the source of the stroke. In patients with a PFO and otherwise cryptogenic stroke, the intracranial vasculature must be imaged to rule out large vessel atherosclerosis before PFO closure can be considered.
CT scan in hypertensive intracerebral hemorrhage. Blood is seen as a high-density signal at the site of hemorrhage in the thalamus (left arrow) and its extension into the third ventricle (top arrow) and the occipital horns of the ipsilateral (bottom arrow) and contralateral (right arrow) lateral ventricles. (Reproduced, with permission, from Simon RP, Aminoff MJ, Greenberg DA. Clinical Neurology, 4th ed. Originally published by Appleton & Lange. Copyright © 1999 by The McGraw-Hill Companies, Inc.)
Acute left MCA infarct on MRI of a 65-year-old hypertensive man. The MRI demonstrates increased signal intensity (arrows). Abnormalities in MRI occur before those seen on CT during ischemic strokes. (Used, with permission, from Chen MY, Pope TL Jr, Ott DJ. Basic Radiology. McGraw-Hill, 2004.)
Noncontrast CT image of a subacute left middle cerebral artery infarct (arrows). This was done 2 weeks after the stroke in the same patient as previous figure. CT findings occur later than MRI findings in ischemic strokes. (Used, with permission, from Chen MY, Pope TL Jr, Ott DJ. Basic Radiology. McGraw-Hill, 2004.)
CT angiogram demonstrating right middle cerebral artery occlusion (arrow). This patient subsequently underwent embolectomy with restoration of blood flow through the occluded vessel.
C. Laboratory and Other Studies
Investigations should include a complete blood count, blood glucose determination, and fasting lipid panel. Serologic tests for syphilis and HIV infection may be included depending on the circumstances. Screening for antiphospholipid antibodies (lupus anticoagulants, anticardiolipin, and anti-beta2-glycoprotein antibodies); the factor V Leiden mutation; abnormalities of protein C, protein S, or antithrombin; or a prothrombin gene mutation is indicated only if a hypercoagulable disorder is suspected (eg, a young patient without apparent risk factors for stroke) or needs to be ruled out if PFO closure is under consideration. While elevated serum homocysteine is a risk factor for stroke, lowering homocysteine levels with vitamin supplementation has not been shown to decrease stroke risk, and therefore, routinely checking homocysteine is not recommended. Electrocardiography or continuous cardiac monitoring for at least 24 hours will help exclude a recent myocardial infarction or a cardiac arrhythmia that might be a source of embolization. While atrial fibrillation will be discovered in approximately 10% of patients with ischemic stroke during their hospitalization, it is estimated that an arrhythmia will be found in an additional 10% with prolonged ambulatory ECG monitoring after discharge; this testing is indicated in cases where atrial fibrillation is suspected (eg, nonlacunar stroke and left atrial enlargement on echocardiography or lack of intracranial or carotid atherosclerosis) but has not been demonstrated. Echocardiography (with agitated saline contrast) should be performed in cases of nonlacunar stroke to exclude valvular disease, right-to-left shunting, and cardiac thrombus. Blood cultures should be performed if endocarditis is suspected but are not required routinely. Examination of the cerebrospinal fluid is not always necessary but may be helpful if cerebral vasculitis or another inflammatory or infectious cause of stroke is suspected, but it should be delayed until after CT or MRI to exclude any risk for herniation due to mass effect.
Management is divided into acute and chronic phases: the first is aimed at minimizing disability and the second at preventing recurrent stroke. A combination of thrombolysis and endovascular therapies is available to patients who present within 24 hours of stroke onset, determined by when the patient was last normal.
Intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA; 0.9 mg/kg to a maximum of 90 mg, with 10% given as a bolus over 1 minute and the remainder over 1 hour) improves the chance of recovery without significant disability at 90 days from 26% to 39% if given within 3 hours from stroke onset; it is still effective up to 4.5 hours from stroke onset. Treatment should be initiated as soon as possible; outcome is directly related to the time from stroke onset to treatment. Intravenous thrombolysis is approved in Europe for use up to 4.5 hours from stroke onset but only for up to 3 hours in the United States, although off-label use during the 3- to 4.5-hour window is standard. In patients with systolic pressure greater than 185 mm Hg or diastolic pressure greater than 110 mm Hg, the blood pressure should be lowered to less than 185/110 mm Hg with intravenous labetalol or nicardipine to enable rtPA administration. Due to the risk of hemorrhage, rtPA should not be used beyond 4.5 hours, or in other situations where it is medically contraindicated, although some evidence suggests patients with ischemic but not infarcted tissue identified by automated perfusion imaging or MRI may be treated up to 9 hours after onset or upon awakening with stroke symptoms.
Several randomized trials have demonstrated an increased likelihood of achieving functional independence after endovascular mechanical embolectomy by stent retrievers as an adjunct to intravenous rtPA. Patients with large vessel occlusion (about 20% of patients with acute ischemic stroke) in whom treatment can be initiated within 6 hours of stroke onset are eligible for embolectomy, as are patients who present between 6 hours and 24 hours and also have a large ischemic penumbra identified by perfusion CT, perfusion MRI, or diffusion-weighted MRI.
Early management of a completed stroke otherwise requires general supportive measures. Management in a stroke care unit has been shown to improve outcomes, likely due to early rehabilitation and prevention of medical complications. During the acute stage, there may be marked brain swelling and edema, with symptoms and signs of increasing intracranial pressure, an increasing neurologic deficit, or herniation syndrome. Elevated intracranial pressure is managed by head elevation and osmotic agents such as mannitol. Maintenance of an adequate cerebral perfusion pressure helps prevent further ischemia. Early decompressive hemicraniectomy (within 48 hours of stroke onset) for malignant middle cerebral artery infarctions reduces mortality and improves functional outcome. Attempts to lower the blood pressure of hypertensive patients during the acute phase (ie, within 72 hours) of a stroke should generally be avoided unless the purpose is to enable the safe administration of rtPA, as there is loss of cerebral autoregulation, and lowering the blood pressure may further compromise ischemic areas. However, if the systolic pressure exceeds 220 mm Hg, it can be lowered using intravenous labetalol or nicardipine with continuous monitoring to 170–200 mm Hg, and then after 72 hours, it can be reduced further to less than 140/90 mm Hg. Blood pressure augmentation is usually not necessary in patients with relative hypotension but maintenance of intravenous hydration is important.
Prophylactic and medical measures are discussed in the section on TIAs and should guide management. Once hemorrhage has been excluded by CT, aspirin (325 mg orally daily) is started immediately unless the patient received thrombolysis, in which case aspirin is initiated after a follow-up CT has ruled out thrombolytic-associated hemorrhage at 24 hours. Dual antiplatelet therapy should be used for 21 days in patients with minor stroke (National Institutes of Health Stroke Scale of 3 or less). Anticoagulant medications are started when indicated, as discussed in the section on TIAs. There is generally no advantage in delay, and the common fear of causing hemorrhage into a previously infarcted area is misplaced, since there is a far greater risk of further embolism to the cerebral circulation if treatment is withheld.
Physical therapy has an important role in the management of patients with impaired motor function. Passive movements at an early stage will help prevent contractures. As cooperation increases and some recovery begins, active movements will improve strength and coordination. In all cases, early mobilization and active rehabilitation are important. Occupational therapy may improve morale and motor skills, while speech therapy may help expressive aphasia or dysarthria. Because of the risk for dysphagia following stroke, access to food and drink is typically restricted until an appropriate swallowing evaluation; the head of the bed should be kept elevated to prevent aspiration. Urinary catheters should not be placed and, if placed, removed within 24–48 hours.
The prognosis for survival after cerebral infarction is better than after cerebral or subarachnoid hemorrhage. Patients receiving treatment with rtPA are at least 30% more likely to have minimal or no disability at 3 months than those not treated by this means. Those treated with mechanical embolectomy are also at least 30% more likely to achieve functional independence. Loss of consciousness after a cerebral infarct implies a poorer prognosis than otherwise. The extent of the infarct governs the potential for rehabilitation. Patients who have had a cerebral infarct are at risk for additional strokes and for myocardial infarcts. The prophylactic measures discussed earlier reduce this risk. Antiplatelet therapy reduces the recurrence rate by 30% among patients without a cardiac cause for the stroke who are not candidates for carotid endarterectomy. Nevertheless, the cumulative risk of recurrence of noncardioembolic stroke is still 3–7% annually.
In patients with massive strokes from which meaningful recovery is unlikely, management is focused on palliative care (see Chapter 5).
All patients should be referred.
All patients should be hospitalized, preferably in a stroke care unit.
et al; DEFUSE 3 Investigators. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018 Feb 2;378(8):708–18.
CC. JAMA patient page. Recovery after stroke. JAMA. 2016 Dec13;316(22):2440.
et al; DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018 Jan 4;378(1):11–21.
et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–418.