Emboli may arise from the heart, the extracranial arteries or, rarely, the right-sided circulation (paradoxical emboli). The sources of cardiogenic emboli include valvular thrombi (e.g.: in mitral stenosis, endocarditis, prosthetic valves), mural thrombi (e.g.: in myocardial infarction [MI], atrial fibrillation, dilated cardiomyopathy, severe congestive heart failure [CHF]), and atrial myxomas. MI is associated with a 2-3% incidence of embolic stroke, of which 85% occur in the first month after MI.

Thrombotic strokes can be divided into large vessel, including the carotid artery system, or small vessel comprising the intracerebral arteries, including the branches of the Circle of Willis and the posterior circulation. The most common sites of thrombotic occlusion are cerebral artery branch points, especially in the distribution of the internal carotid artery. Arterial stenosis (i.e.: turbulent blood flow), atherosclerosis (i.e.: ulcerated plaques), and platelet adherence cause the formation of blood clots that either embolize or occlude the artery. Less common causes of thrombosis include polycythemia, sickle cell anemia, protein C deficiency, fibromuscular dysplasia of the cerebral arteries, and prolonged vasoconstriction from migraine headache disorders. Any process that causes dissection of the cerebral arteries also can cause thrombotic stroke (e.g.: trauma, thoracic aortic dissection, arteritis). Occasionally, hypoperfusion distal to a stenotic or occluded artery or hypoperfusion of a vulnerable watershed region between 2 cerebral arterial territories can cause ischemic stroke.

Stroke symptoms can result from inadequate cerebral blood flow due to decreased blood pressure or due to hematologic hyperviscosity due to sickle cell disease or other hematologic illnesses such as multiple myeloma and polycythemia vera. In these instances, cerebral injury may occur in the presence of damage to other organ systems.

Within seconds to minutes of the loss of perfusion to a portion of the brain, an ischemic cascade is unleashed that, if left unchecked, causes a central area of irreversible infarction surrounded by an area of potentially reversible ischemic tissue. The ischemic cascade offers many points at which such interventions could be attempted. Multiple strategies for blocking this cascade are currently under investigation. The timing of restoring cerebral blood flow appears to be a critical factor. Time also may prove to be a key factor in neuronal protection.

Stroke is the third leading cause of death and the leading cause of disability in the United States. Men are at higher risk for stroke than women. Although stroke often is considered a disease of elderly persons, 25% of strokes occur in persons younger than 65 years.

Strokes can be mimicked by other conditions. The most frequent stroke mimics include seizures (17%); systemic infections (17%); brain tumors (15%); toxic-metabolic causes, such as hyponatremia (13%); and positional vertigo (6%). Miscellaneous disorders mimicking stroke include syncope, trauma, subdural hematoma, herpes encephalitis, transient global amnesia, dementia, demyelinating disease, myasthenia gravis, parkinsonism, hypertensive encephalopathy, and conversion disorders. A critical masquerading metabolic derangement not to be missed by providers is hypoglycemia.

The physical examination always includes a careful head and neck examination for signs of trauma, infection, and meningeal irritation. A careful search for the cardiovascular causes of stroke requires examination of the ocular fundi (retinopathy, emboli, hemorrhage), heart (irregularities, murmurs, gallops), and peripheral vasculature (palpation of carotid, radial, and femoral pulses, auscultation for carotid bruits). Patients with a decreased level of consciousness should be assessed to ensure that they are able to protect their airway.

The goals of the neurologic examination include (1) confirming the presence of a stroke syndrome (to be defined further by cranial CT scanning), (2) distinguishing stroke from stroke mimics, and (3) establishing a neurologic baseline should the patient's condition improve or deteriorate. Essential components of the neurologic exam include evaluation of mental status and the level of consciousness, cranial nerves, motor function, sensory function, cerebellar function, gait, and deep tendon reflexes.

The 4 major neuroanatomic stroke syndromes are caused by disruption of their respective cerebrovascular distributions. Correlating the patient's neurologic deficits with the expected sites of arterial compromise may assist the emergency physician in confirming the diagnosis of stroke and interpreting the subsequent cranial CT scan.

Middle cerebral artery (MCA) occlusions commonly produce contralateral hemiparesis, contralateral hypesthesia, ipsilateral hemianopsia (blindness in one half of the visual field), and gaze preference toward the side of the lesion. Agnosia is common, and receptive or expressive aphasia may result if the lesion occurs in the dominant hemisphere. Neglect, inattention, and extinction of double simultaneous stimulation may occur in nondominant hemisphere lesions. Since the MCA supplies the upper extremity motor strip, weakness of the arm and face is usually worse than that of the lower limb.

Anterior cerebral artery occlusions primarily affect frontal lobe function and can result in dis-inhibition and speech perseveration, producing primitive reflexes (e.g.: grasping, sucking reflexes), altered mental status, impaired judgment, contralateral weakness (greater in legs than arms), contralateral cortical sensory deficits gait apraxia, and urinary incontinence. Posterior cerebral artery occlusions affect vision and thought, producing contralateral homonymous hemianopsia, cortical blindness, visual agnosia, altered mental status, and impaired memory.

Vertebrobasilar artery occlusions are notoriously difficult to detect because they cause a wide variety of cranial nerve, cerebellar, and brainstem deficits. These include vertigo, nystagmus, diplopia, visual field deficits, dysphagia, dysarthria, facial hypesthesia, syncope, and ataxia. A hallmark of posterior circulation strokes is that there are crossed findings: ipsilateral cranial nerve deficits and contralateral motor deficits. This is contrasted to anterior strokes, which produce findings on one side of the body only.

Lastly, lacunar strokes are strokes resulting from occlusion of the small, perforating arteries of the deep subcortical areas of the brain. The resulting infarcts are generally from 2-20 mm in diameter. The most common lacunar syndromes include pure motor, pure sensory, and ataxic hemiparetic strokes. Lacunar infarcts are often associated with partial or full occlusion of the parent feeding artery. Lacunar strokes account for 13-20% of all cerebral infarctions. Lacunar infarcts commonly occur in patients with small vessel disease, such as diabetes and hypertension. By virtue of their small size and well-defined subcortical location, lacunar infarcts do not lead to impairments in cognition, memory, speech, or level of consciousness.

Transient ischemic attack has come to be known as a neurologic deficit that resolves within 24 hours. Transient ischemic attacks (TIAs) can result from any of the aforementioned mechanisms of stroke and precede nearly 30% of ischemic strokes. If left untreated, one third of TIAs lead to ischemic stroke: 20% within the first month and 50% within the first year.

Head CT scan is a fundamental branch point in the evaluation of stroke, since patients with acute ischemic stroke may be triaged to receive thrombolytic therapy, while patients with hemorrhagic stroke are taken down a completely different diagnostic and therapeutic pathway. CT scans also may rule out other life-threatening processes, such as hematomas, neoplasms, and abscesses.

The changes in CT scan over the time course of acute cerebral infarction must be understood. The sensitivity of standard noncontrast head CT increases 24 hours post ischemic event. After 6-12 hours, sufficient edema is recruited into the stroke area to produce a regional hypodensity on CT scan. A large hypodense area present on CT scan within the first 3 hours of symptom onset should prompt careful requestioning regarding the time of stroke symptom onset. The presence of CT evidence of infarction early in presentation has also been associated with poor outcome. MRI has been shown to have higher sensitivity than standard noncontrast head CT in demonstrating infarcts early after symptom onset.

Echocardiography is obtained in all patients with acute ischemic stroke in whom cardiogenic embolism is suspected. Transesophageal echocardiography is useful for detecting thoracic aortic dissection and more accurate for identification of thrombi in the left atrial appendage from atrial fibrillation. A certain proportion of patients with strokes may have underlying systolic dysfunction, diastolic dysfunction, or concentric hypertrophy. Echocardiography is also a modality to identify the presence of a patent foramen ovale.

Some have also recommended continuous cardiac monitoring for all patients, since 4% of patients have a life-threatening arrhythmia during the course of their illness and 3% have concurrent MI. Acute ischemic stroke has been associated with acute cardiac dysfunction and arrhythmia, which are then associated with worse functional outcome and morbidity at 3 months.

Angiography continues to play an important role in the preoperative evaluation of carotid artery disease.

Patients presenting with Glasgow Coma Scale scores less than or equal to 8, rapidly decreasing Glasgow Coma Scale scores, or inadequate airway protection reflexes require emergent airway control via rapid sequence intubation.

The goal of mechanical ventilation is hyperventilation, which decreases intracranial pressure by decreasing cerebral blood flow. The recommended endpoint of hyperventilation is an arterial pCO2 of 32-36 mm Hg. Supplemental oxygen requirements should be guided by pulse oximetry. Patients should only receive supplemental oxygen if their pulse oximetry or arterial blood gas reveals that they are hypoxic.

Blood glucose control: Recent data suggest that severe hyperglycemia is independently associated with poor outcome and reduced reperfusion in thrombolysis. Additionally, normoglycemic patients should not be given excessive glucose- containing intravenous fluids, as glucose may exacerbate ischemic cerebral injury.

Head positioning: Studies have shown that cerebral perfusion pressure is maximized when patients are maintained in a supine position. However, lying flat may serve to increase ICP and thus is not recommended in cases of subarachnoid or other intracranial hemorrhage. Because prolonged immobilization may lead to its own complications including deep venous thrombosis, pressure ulcer aspiration, and pneumonia patients should not be kept flat for longer than 24 hours.

Blood pressure control: In poor flow states as occurs with thrombotic and embolic ischemic strokes, the cerebral vasculature is without vasoregulatory capability and thus relies directly on MAP (mean arterial pressure) and cardiac output for maintenance of cerebral blood flow. Therefore, aggressive efforts to lower blood pressure may decrease perfusion pressure and may prolong or worsen ischemia. Monitoring of blood pressure is crucial, and, for the first 2 hours, blood pressure should be checked every 15 minutes, then every 30 minutes for 6 hours, and finally every hour for 16 hours. The management of blood pressure in patients with acute ischemic stroke is divided into those who are candidates for thrombolytics (rt-PA) and those who are not.

For patients who are not rt-PA candidates and whose systolic blood pressure is less than 200 mm Hg and whose diastolic blood pressure is less than 120 mm Hg in the absence of evidence of end-organ involvement (i.e.: pulmonary edema, aortic dissection, hypertensive encephalopathy), blood pressure should be monitored and stroke symptoms and complications should be treated (increased ICP, seizures). For patients with elevated diastolic blood pressures between 120 and 140 mm Hg labetalol (10-20 mg IV for 1-2 min) should be the initial drug of choice, unless a contraindication to its use exists. Dosing may be repeated or doubled every 10 minutes to a maximum dose of 300 mg. Alternatively, nitroprusside at 0.5 mcg/kg/min IV infusion may be used in the setting of continuous blood pressure monitoring. The goal of intervention being a reduction of 10-15% of blood pressure.

For patients who will be receiving rt-PA, systolic blood pressure greater than 185 mm Hg and diastolic blood pressure greater than 110 mm Hg require intervention. The initial drug of choice is labetalol (10-20 mg IV for 1-2 min). One to two inches of nitropaste may also be used. For diastolic blood pressures greater than 140 mm Hg, sodium nitroprusside 0.5 mcg/kg/min initial IV dose titrated to effect.

Fever control: Antipyretics are indicated for febrile stroke patients, since hyperthermia accelerates ischemic neuronal injury. Substantial experimental evidence suggests that mild brain hypothermia is neuroprotective. The use of induced hypothermia is currently being evaluated in phase I clinical trials.

Cerebral edema control: Cerebral edema occurs in up to 15% of patients with ischemic stroke, reaching maximum severity 72-96 hours after the onset of stroke. Hyperventilation and mannitol are used routinely to decrease intracranial pressure quickly and temporarily. No evidence exists supporting the use of corticosteroids to decrease cerebral edema in acute ischemic stroke. Prompt neurosurgical assistance should be sought when indicated.

Seizure control: Seizures occur in 5-7% of patients within the first 24 hours after stroke. Although seizure prophylaxis is not indicated, prevention of subsequent seizures with standard antiepileptic therapy is recommended.

Although heparin prevents recurrent cardioembolic strokes and may help inhibit ongoing cerebrovascular thrombosis, current guidelines do not recommend anticoagulation for any subsets of patients with stroke because of insufficient data. Both randomized prospective trials evaluating t-PA for acute ischemic stroke (ECASS and NINDS) excluded patients who were receiving anticoagulants. Heparin is known to prolong the lytic state caused by t-PA. Immobilized stroke patients who are not receiving anticoagulants, such as IV heparin or an oral anticoagulant, may benefit from low-dose subcutaneous unfractionated or low molecular weight heparin, which reduces the risk of deep vein thrombosis.

The use of low molecular weight heparin as treatment for acute ischemic stroke has not yet been studied adequately. However, multiple past studies have failed to show any beneficial effect of anticoagulation in acute ischemic stroke. Although trials of anticoagulants in the treatment of acute ischemic stroke are ongoing no current data exist to support their use in acute ischemic stroke.

Thrombolytics: Thrombolytics restore cerebral blood flow in acute ischemic stroke, leading to improvement or resolution of neurologic deficits. Unfortunately, thrombolytics can also cause symptomatic intracranial hemorrhage.

Major clinical trials evaluating the use of intravenous thrombolysis have included the MASK-E, MASK-I, ASK, ECASS I and II, NINDS trial, and ATLANTIS A and B. While both streptokinase and rt-PA have been shown to benefit patients with acute MI, only alteplase (rt-PA, Activase) has been shown to benefit selected patients with acute ischemic stroke.

Current AHA/ASA inclusion guidelines for the administration of rt-PA are as follows: Diagnosis of ischemic stroke causing measurable neurologic deficit;Neurologic signs should not be clearing spontaneously; Neurologic signs should not be minor and isolated; Onset of symptoms <3 hours before beginning treatment; No head trauma or prior stroke in past 3 months; No MI in prior 3 months; No GI/GU hemorrhage in previous 21 days; No arterial puncture in noncompressible site during prior 7 days; No major surgery in prior 14 days; No history of prior intracranial bleed; SBP <185, DBP <110; No evidence of acute trauma or bleeding; Not taking an oral anticoagulant, or if so INR <1.7; If taking Heparin within 48 hours must have a normal activated prothrombin time (apt);Platelet count >100,000.

The clinical diagnosis of stroke must be as accurate as possible, and special care must be taken to avoid the misdiagnosis of stroke mimics. Missing the diagnosis can result in substantial harm to the patient.

Regarding diagnosis, hospital protocols must be in place to ensure that patients with undifferentiated stroke have prioritized access CT imaging within 10 minutes of arrival. Regarding therapeutic recommendations the benefit of early aspirin administration is modest and systemic anticoagulation is not recommended. If the administration of t-PA is considered, care must be given to follow the current inclusion and exclusion criteria guidelines derived from the NINDS study. Protocol violations can result in higher rates of cerebral hemorrhage.

Lastly, there is some controversy regarding how to handle patient's presenting with a TIA (transient ischemic attack). Discharging these patients prematurely without thorough evaluation, treatment and follow-up can have catastrophic consequences, and can lead to litigation.