Stroke, a cerebrovascular accident, is prevalent across patient populations and can be a significant cause of morbidity and mortality. Stroke can be categorized as ischemic, hemorrhagic, or subarachnoid. Among ischemic strokes, the Trial Org 10172 in Acute Stroke Treatment (TOAST) classification is used to subdivide the categories that include cardioembolism, small-vessel occlusion, large-artery atherosclerosis, a stroke of other undetermined etiology, and stroke of undetermined etiology.
The etiology of ischemic strokes is due to either a thrombotic or embolic event that causes a decrease in blood flow to the brain. In a thrombotic event, blood flow to the brain is obstructed within the blood vessel due to dysfunction within the vessel itself, usually secondary to atherosclerotic disease, arterial dissection, fibromuscular dysplasia, or inflammatory condition. In an embolic event, debris from elsewhere in the body blocks blood flow through the affected vessel. Stroke etiology effects both prognosis and outcomes.
Stroke is the fifth cause of death if considered separately from other cardiovascular diseases. In the United States, an estimated 795,000 strokes occur annually, and the prevalence of stroke increases with age. The lifetime risk of all strokes is higher in women; however, this is attributed to longer life-expectancy.
According to the Framingham Heart Study, the stroke incidence is declining over time. However, the cohort was predominantly a white population.
In thrombosis, there is an obstructive process that prevents blood flow to areas of the brain. Risk factors include atherosclerotic disease, vasculitis, or an arterial dissection.
Embolic events occur when there is a clot that originated from another location in the body. Most commonly, the source of the clot is the valve or chambers of the heart, for example, when a clot forms within the atria in atrial fibrillation and dislodges into the arterial vascular supply.
Other less frequent causes include venous, septic, air, or fat emboli. Lacunar infarcts are usually seen in the subcortical areas of the brain and occur due to small vessel disease. The proposed mechanism is a perforating artery in the subcortical region that causes the blood vessel occlusion.
Ischemic Stroke Syndromes
Ischemic strokes can present in pre-determined syndromes due to the effect of decreased blood flow to particular areas of the brain that correlate to exam findings. This allows clinicians to be able to predict the area of the brain vasculature that can be affected.
Middle Cerebral Artery (MCA) Infarction
The middle cerebral artery (MCA) is the most common artery involved in stroke. It supplies a large area of the lateral surface of the brain and part of the basal ganglia and the internal capsule via four segments (M1, M2, M3, and M4). The M1 (horizontal) segment supplies the basal ganglia, which is involved in motor control, motor learning, executive function, and emotions. The M2 (Sylvian) segment supplies the insula, superior temporal lobe, parietal lobe, and the inferolateral frontal lobe.
The MCA distribution involves the lateral cerebral cortex. MCA syndrome is best explained by the understanding of the somatosensory cortex, in which the lateral portion contains motor and sensory functions that involve the face and upper extremity. This correlates to the classical presentation of contralateral hemiparesis, facial paralysis, and sensory loss in the face and upper extremity. Lower extremity may be involved, but upper extremity symptoms usually predominate. Gaze preferences towards affected lesion may be seen. Additional symptoms include:
Anterior Cerebral Artery (ACA) Infarction
The anterior cerebral artery (ACA) provides blood supply to the frontal, pre-frontal, primary motor, primary sensory, and supplemental motor cortices. Pure ACA infarcts are uncommon because of significant collateral blood supply provided by the anterior circulating artery. The sensory and motor cortices receive sensory information and control movement of the contralateral lower extremity. The supplemental motor area contains Broca’s area, which is involved in the initiation of speech. The pre-frontal cortex is used to organize and plan complex behavior and is thought to influence the personality.
The ACA distribution involves the medial cerebral cortex. The somatosensory cortex in that area comprises a motor and sensory functions of the leg and foot. The clinical presentation of an ACA infarction includes contralateral sensory and motor deficits in the lower extremity. The upper extremity and face are spared. Kumral et al. examined clinical spectrums of ACA with correlation to MRI/MRA and demonstrated left-sided lesions presented with more transcortical motor aphasia, in which patients have difficulty responding spontaneously with speech but repetition is preserved. Right-sided lesions presented with more acute confusion state and motor hemineglect (unilateral motor function is lost).
Posterior Cerebral Artery (PCA) Infarction
The superficial posterior cerebral artery (PCA) supplies the occipital lobe and the inferior portion of the temporal lobe, while the deep PCA supplies the thalamus, and the posterior limb of the internal capsule, as well as other deep structures of the brain. The occipital lobe is the location of the primary and secondary visual areas, where sensory input from the eyes is interpreted. The thalamus relays information between the ascending and descending neurons, while the internal capsule contains the descending fibers of the lateral and ventral corticospinal tracts.
PCA infarctions can be divided into deep and superficial categories, based on the PCA supply. If the deep segments of the PCA are involved, symptoms may include hypersomnolence, cognitive deficits, ocular findings, hypesthesia, and ataxia. Ocular findings may include homonymous hemianopsia, in which patients experience visual field deficits in one half of their visual field. Larger infarcts that involve the deep structures can lead to hemisensory loss and hemiparesis due to the involvement of the thalamus and the internal capsule. Superficial infarcts present with visual and somatosensory deficits, which can include stereognosis, tactile sensation, and proprioception. Rarely, bilateral PCA infarcts present with amnesia and cortical blindness. Cortical blindness is due to lesions in the optic radiation that causes vision loss. A unilateral headache is a common finding, which can be confused with a complicated migraine.
The vertebrobasilar region of the brain is supplied by the vertebral arteries and the basilar arteries that originate within the spinal column and terminate at the Circle of Willis. These areas supply the cerebellum and brainstem.
The clinical presentation includes ataxia, vertigo, headache, vomiting, oropharyngeal dysfunction, visual-field deficits, and abnormal oculomotor findings. Patterns of clinical presentation vary depending on the location and the infarction pattern of embolism or atherosclerosis.
Patients may present with ataxia, nausea, vomiting, headache, dysarthria, and vertigo symptoms. Edema and rapid clinical deterioration can complicate cerebellar infarction.
Lacunar infarcts result from occlusion of a small perforating artery. The exact mechanism is under debate, as the nature of the infarct can result from intrinsic vessel occlusion or an embolism. Infarction in this territory can present with pure motor or sensory, sensorimotor, or ataxia with hemiparesis.
Ischemic strokes present acutely and establishing the time of symptom onset is critical. If the time of symptom onset is unknown, the time the patient was last known to be normal without new neurological symptoms is used. The time that is established is utilized to decide whether to give intravenous thrombolytics.
A neurological exam should be performed for all patients suspected of stroke. The National Institutes of Health Stroke Scale (NIHSS) is most commonly used to measure the severity of the stroke and has 11 categories and a score that ranges from 0 to 42. The 11 categories include the level of consciousness (LOC) which incorporate LOC questions and LOC command: best gaze, visual, facial palsy, motor arm, motor leg, limb ataxia, sensory, best language, dysarthria, and extinction and inattention. The stroke scale should be performed in the order listed. Each score is based on the patient’s action on the exam, not a prediction of what the patient can do.
An organized stroke protocol is highly recommended to expedite evaluation. The door-to-needle time within 60 minutes is recommended for acute ischemic strokes for patients who qualify for thrombolytics.
The initial evaluation of any patient is airway, breathing, circulation, and vital signs. Patients may present with respiratory abnormalities from either elevated intracranial pressure or a physical obstruction such as vomiting and are at risk for aspiration and asphyxiation. Endotracheal intubation may be necessary to ensure adequate oxygenation and ventilation.
A finger stick glucose check should be performed, as it is an easy way of rule out hypoglycemia as a cause of neurological abnormalities.
A noncontrast CT head or brain MRI is recommended for patients within 20 minutes of presentation to rule out hemorrhage. In hospitals that are stroke centers or able to provide emergency care, vascular imaging should be considered for possible endovascular intervention. However, this should not delay administration of thrombolytics if vascular imaging was not performed.
Other diagnostic tests include an electrocardiogram (ECG), troponin, complete blood count, electrolytes, blood urea nitrogen (BUN), creatinine (Cr), and coagulation factors. An ECG and troponin are suggested because stroke is often associated with coronary artery disease. A complete blood count can look for anemia or suggest infection. Electrolyte abnormalities should be corrected. BUN and Cr should be monitored as a further intervention with contrast studies may worsen kidney function. Coagulation factors include PTT, PT, and INR. Elevated levels can suggest a cause of hemorrhagic stroke.
For institutions without expert imaging interpretation, the US Food and Drug Administration highly recommends teleradiology system for image interpretation for suspected stroke patients. This helps with the decision to administer IV alteplase. A discussion and agreement between telestroke neurologists and radiologists are highly recommended.
In areas that do not have an in-house stroke team or telestroke protocol, a telephone consult may be considered for the administration of thrombolytics. The level of evidence is limited for this recommendation.
The AHA/ASA recommends intravenous (IV) alteplase for patients who satisfy inclusion criteria and have symptom onset or last known baseline within 3 hours. IV alteplase is 0.9 mg/kg, with a maximum dose of 90 mg. The first 10% of the dose is given over the first minute as a bolus, and the remainder of the dose is given over the next 60 minutes. The time has been extended to 4.5 hours for selected candidates.
Inclusion criteria are a diagnosis of ischemic stroke with “measurable neurological deficit,” symptom onset within 3 hours before treatment, and age 18 years or older.
A review of the exclusion criteria for thrombolytics should be performed before administering alteplase. According to the Food and Drug Administration, the contraindications to intravenous thrombolysis include active internal bleeding, recent intracranial surgery or serious head trauma, intracranial conditions that may increase the risk of bleeding, bleeding diathesis, severe uncontrolled hypertension, current intracranial hemorrhage, subarachnoid hemorrhage, and a history of recent stroke.
For patients that present between 3 and 4.5 hours from symptoms onset, the treatment benefits and risks must be considered. Additional relative exclusion criteria for this patient category include age >80 years, NIHSS greater 25, oral anticoagulant use, and a history of both diabetes and prior ischemic stroke.
Orolingual angioedema is a potential side effect of IV alteplase. If angioedema should occur, management of the airway is a priority. Endotracheal intubation or awake fiberoptic intubation may be necessary to secure the airway. If there is suspected angioedema, hold IV alteplase and ACE inhibitors. Administer methylprednisolone, diphenhydramine, and ranitidine or famotidine. Epinephrine may be considered if the previous therapies do not alleviate signs and symptoms. Icatibant or C1 esterase inhibitor may be considered for the treatment of hereditary angioedema and ACE inhibitor angioedema.
Other fibrinolytic agents such as tenecteplase may be considered as an alternative to alteplase. In one study, tenecteplase appears to have similar efficacy and safety profiles in a mild stroke but did not demonstrate superiority when compared to alteplase.
The use of mechanical thrombectomy should be considered in all patients, even in those who received fibrinolytic therapy. The AHA/ASA guidelines do not recommend observation for a response after IV alteplase in patients who are being considered for mechanical thrombectomy.
The current recommendation in selected patients with large vessel occlusion with acute ischemic stroke in the anterior circulation and meet other DAWN and DEFUSE 3 criteria, mechanical thrombectomy is recommended within the time frame of 6 to 16 hours of last known normal. In selected patients who meet the DAWN criteria, mechanical thrombectomy is reasonable within 24 hours of last known normal.
The guidelines suggest blood pressure management of less than 180/105 mm Hg for the first 24 hours after IV alteplase. A new recommendation is lowering BP initially by 15% in patients with comorbid conditions such as acute heart failure or aortic dissection. There is no benefit to antihypertensive management to prevent death or dependency in patients with BP less than 220/120 mm Hg who did not receive IV alteplase and have no comorbid conditions requiring blood pressure reduction. This applies to the first 48 to 72 hours after an acute ischemic stroke. For patients with greater than or equal 220/120 mm Hg who did not receive IV alteplase, the guideline suggests it may be reasonable to reduce BP by 15% in the first 24 hours, although the benefit is uncertain.
Antihypertensive options include:
Hypotension and hypovolemia should be avoided because the cerebral perfusion pressure is dependent on maintenance of elevated MAP as ICP increases due to an ischemic event.
Hyperthermia of greater than 38 C should be avoided and treated appropriately. Antipyretics such as acetaminophen may be used. Common sources of infection should be ruled out, such as pneumonia and urinary tract infections. There is insufficient data to support therapeutic hypothermia in acute ischemic strokes currently. A retrospective study recently demonstrated an association between a peak temperature in the first 24 hours of greater than 39 C and increased risk of in-hospital mortality.
Maintain glucose in the range of 140 to 180 in the first 24 hours. Hypoglycemic patients less than 60 mg/dL should be treated to achieve normoglycemia. The brain is dependent on oxidative pathways that require glucose for metabolism, and the metabolic demand of the brain is high; therefore, episodes of hypoglycemia can decrease repair of the brain. However, hyperglycemia is hypothesized to decrease reperfusion due to oxidation of nitric oxide-dependent mechanisms and subsequent loss of vascular tone, and increase acidosis, possible due to injury to lactic acid-sensing channels. Capes et al. showed that hyperglycemia in ischemic stroke patients increase 30-day mortality and is an independent risk factor for hemorrhagic stroke conversion.
Early enteric feeding should be encouraged. For patients with dysphagia, use a nasogastric tube to promote enteric feeding. If there is concern that the patient may have swallowing difficulties for a prolonged period (more than 2 to 3 weeks), placing a percutaneous gastrostomy tube is recommended. Early feeding has been demonstrated to have an absolute reduction in risk of death.
Intermittent pneumatic compression is recommended for all immobile patients unless there are contraindications. Although prophylactic heparin is often used for immobile patients, the benefit is not clear in stroke patients.
Screening for depression should be considered; however, the optimal timing is unclear.
Cerebellar edema complicates cerebellar infarctions, and clinicians must be aware that these patients can rapidly decompensate. Cerebellar swelling is thought to be due to cytotoxic and vasogenic edema. The increased intracranial pressure can cause obstructing hydrocephalus on the fourth ventricle, or cause transtentorial herniation of the superior vermis and downward cerebellar tonsillar herniation. Signs include change or worsening mental status, decreased level of consciousness, respiratory abnormalities, change in pupillary size, posturing, and death.
Obtain neurosurgical consult early. A ventriculostomy is indicated in the setting of obstructive hydrocephalus after cerebellar infarct. In cases of cerebral edema with mass effect, a decompressive suboccipital craniectomy is highly recommended.
If patients experience recurrent seizures, anti-epileptic drugs are recommended. However, the routine prophylactic use of anti-epileptic drugs is not recommended.
Cardiac monitoring for atrial fibrillation or other arrhythmias is recommended in the first 24 hours. The benefit of further monitoring is unclear.
An initial troponin is recommended because there is an association between stroke and coronary artery disease.
Aspirin is recommended within 24 to 48 hours of symptom onset. A Cochrane review concluded that aspirin given within 48 hours of symptom onset for ischemic strokes prevented recurrence of ischemic strokes and improved long-term outcomes such as being independent. The was no major risk of early intracranial hemorrhage with aspirin.
The use of warfarin in secondary stroke prevention is not recommended.
In patients with atrial fibrillation, the guidelines state it is reasonable to initiate oral anticoagulation within 4 to 14 days after neurological symptoms onset.
High-intensity statins (atorvastatin 80 mg daily or rosuvastatin 20 mg daily) is recommended for patients 75 or younger years old who have clinical atherosclerotic cardiovascular disease. In addition, patients may be continued on statins if they were on them prior to ischemic stroke.
Prognosis for CVA is highly dependent on the degree, involved structures, area involved, time to identification and diagnosis, time to treatment, length and intensity of physical and occupational therapy, and prior baseline functioning, among criteria.
In many posterior CVAs, symptomatology can be subtle and therefore clinicians should have a low index of suspicion and obtain imaging and neurology consultation early.
Early rehabilitation for stroke patients is beneficial and should be performed. Very early rehabilitation, within 24 hours, should not be performed. The AVERT trial randomized patients to receive very early rehabilitation within 24 hours of stroke compared to usual stroke-unit care and early mobilization demonstrated less favorable outcomes using the modified Rankin’s score.