Ischemic Stroke Treatment & Management

Updated: Mar 28, 2019
  • Author: Edward C Jauch, MD, MS, FAHA, FACEP; Chief Editor: Helmi L Lutsep, MD  more...
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Treatment

Approach Considerations

The central goal of therapy in acute ischemic stroke is to preserve tissue in the ischemic penumbra, where perfusion is decreased but sufficient to stave off infarction. Tissue in this area of oligemia can be preserved by restoring blood flow to the compromised area and optimizing collateral flow.

Recanalization strategies, including the administration of intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial approaches, attempt to establish revascularization so that cells in the penumbra can be rescued before irreversible injury occurs. Restoring blood flow can mitigate the effects of ischemia only if performed quickly.

Many surgical and endovascular techniques have been studied in the treatment of acute ischemic stroke. Carotid endarterectomy has been used with some success in the acute management of internal carotid artery occlusions, but no evidence supports its use acutely in ischemic stroke.

In addition to limiting the duration of ischemia, an alternative strategy is to limit the severity of ischemic injury (ie, neuronal protection). Neuroprotective strategies are intended to preserve the penumbral tissues and to extend the time window for revascularization techniques. At the present time, however, no neuroprotective agents have been shown to impact clinical outcomes in ischemic stroke.

Palliative care

Palliative care is an important component of comprehensive stroke care. Some patients with severe strokes die during the initial hospitalization,  others will be severely disabled and palliative care can begin to address the patient's and family's short- and long-term needs. Some patients have advance directives providing instructions for medical providers in the event of severe medical illness or injury.

Clinical education

Prehospital care providers are essential to timely stroke care. Course curricula for prehospital care providers are beginning to include more information on stroke than ever before. Through certification and Acute Cardiac Life Support (ACLS) instruction, as well as continuing medical education classes, prehospital care providers can remain current on stroke warning signs, prehospital stroke tools, and triage protocols in their region, and can promote stroke awareness in their own communities.

Physician and nursing staff involved in the care of stroke patients, in the Emergency Department (ED) and in the hospital, should participate in scheduled stroke education. This will help them to maintain the skills required to treat stroke patients effectively and to remain current on medical advances for all stroke types.

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Emergency Response and Transport

Recognition that a stroke may have occurred, activation of 911, and rapid transport to the appropriate receiving facility are necessary to provide stroke patients with the best chance for acute interventions. Of patients with signs or symptoms of stroke, 29–65% utilize some facet of the emergency medical services (EMS) system. [75, 76]

Most of the patients who call EMS are those who present within 3 hours of symptom onset. Calls to 911 and the use of EMS are associated with shorter time periods from symptom onset to hospital arrival. [77, 78]

Stroke should be a priority dispatch with prompt EMS response. EMS responders should perform a brief H&P, obtain time of symptom onset or last known normal, perform a prehospital stroke assessment, determine blood glucose levels, and provide advance notice to their ED destination in as timely a manner as possible so as to allow preparation and marshalling of personnel and resources. With the development of stroke center designation, which is currently in progress, such centers would then become the preferred destination for patients with acute stroke symptoms who utilize EMS.

Data supporting the use of emergency air transport for patients with acute stroke symptoms are limited. Further evaluation of this transportation modality is necessary to minimize the potentially high number of stroke mimics and to maximize the appropriate use of transport resources. Telemedicine is also a technology that can provide timely expert advice to rural and underserved clinics and hospitals. [1]

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Acute Management of Stroke

The goal for the emergent management of stroke is to assess the patient’s airway, breathing, and circulation (ABCs); stabilize the patient as necessary; and complete initial evaluation and assessment, including imaging and laboratory studies, within 60 minutes of patient arrival. [1] A Finnish study demonstrated that time to treatment with fibrinolytics can be decreased with changes in EMS and ED coordination and in ED procedures for treating acute stroke patients. [79]

A US study in which a multidisciplinary team used value stream analysis to assess the steps required to treat acute ischemic stroke with IV rt-PA found several inefficiencies in the protocol (eg, in patient routing) that were slowing treatment. Use of a revised protocol that targeted those inefficiencies reduced door-to-needle times from 60 to 39 minutes and increased the percentage of patients treated in 60 minutes or less after hospital arrival from 52% to 78%, with no change in symptomatic hemorrhage rate. [80]

Critical decisions focus on the need for airway management, establishment of optimal blood pressure control, and identification of potential reperfusion therapies (IV fibrinolysis with rt-PA or intra-arterial approaches). Involvement of a physician with stroke expertise is ideal. Stroke care units with specially trained personnel exist and improve outcomes.

Comorbidities

Comorbid medical conditions also need to be addressed. Hyperthermia is infrequently associated with stroke but can increase morbidity. Administration of acetaminophen, by mouth or per rectum, is indicated in the presence of fever (temperature > 100.4°F).

Oxygen supplementation

Supplemental oxygen is recommended when the patient has a documented oxygen requirement (ie, oxygen saturation < 95%). In the small proportion of patients with stroke who are relatively hypotensive, administration of IV fluid, vasopressor therapy, or both may improve flow through critical stenoses.

Hypoglycemia and hyperglycemia

Hypoglycemia needs to be identified and treated early in the evaluation. In contrast, the management of hyperglycemia in acute stroke remains an area of uncertainty. [81]  Extreme hyperglycemia is detrimental in the setting of acute stroke.

Hyperglycemia is common after acute ischemic stroke, even in patients without diabetes. A Cochrane review found that the use of IV insulin to maintain serum glucose in the range of 4–7.5 mmol/L (72-135 mg/dL) in the first 24 hours of ischemic stroke did not improve functional outcome, death rates, or final neurologic deficit and significantly increased the risk of hypoglycemia. [82]

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Fibrinolytic Therapy

The only fibrinolytic agent that has been shown to benefit selected patients with acute ischemic stroke is alteplase (rt-PA). While streptokinase may benefit patients with acute MI, in patients with acute ischemic stroke it has been shown to increase the risk of intracranial hemorrhage and death.

Fibrinolytics (ie, rt-PA) restore cerebral blood flow in some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits. Unfortunately, fibrinolytics may also cause symptomatic intracranial hemorrhage. Other complications include potentially extracranial hemorrhage and angioedema or allergic reactions. [1]

Inclusion/exclusion criteria

Therefore, if the patient is a candidate for fibrinolytic therapy, a thorough review of the inclusion and exclusion criteria must be performed. The exclusion criteria largely focus on identifying risk of hemorrhagic complications associated with fibrinolytic use. The American Heart Association/American Stroke Association (AHA/ASA) inclusion guidelines for the administration of rt-PA are as follows: [1]

  • Diagnosis of ischemic stroke causing measurable neurologic deficit

  • Neurologic signs not clearing spontaneously to baseline

  • Neurologic signs not minor and isolated

  • Symptoms not suggestive of subarachnoid hemorrhage

  • No head trauma or prior stroke in past 3 months

  • No myocardial infarction (MI) in past 3 months

  • No gastrointestinal/genitourinary hemorrhage in previous 21 days

  • No arterial puncture in a noncompressible site during the past 7 days

  • No major surgery in past 14 days

  • No history of prior intracranial bleeding

  • Systolic blood pressure under 185 mm Hg, diastolic blood pressure under 110 mm Hg

  • No evidence of acute trauma or bleeding

  • Not taking an oral anticoagulant, or if so, international normalized ratio (INR) under 1.7

  • If taking heparin within 48 hours, a normal activated prothrombin time (aPT)

  • Platelet count of more than 100,000/μL

  • Blood glucose greater than 50 mg/dL (2.7 mmol)

  • CT scan does not show evidence of multilobar infarction (hypodensity over one third hemisphere) or intracerebral hemorrhage

  • The patient and family understand the potential risks and benefits of therapy

Whereas these inclusion/exclusion criteria are from the original FDA approval, a more recent revision by the FDA of the product insert has reclassified many prevous absolute contraindications to now relative contraindications. Furthermore, subsequent data and experience have allowed some patients with what were previously considered relative contraindications to be safely treated. Involvement of a physician with stroke expertise is critical for assessing the risk/benefit consideration for these groups of patients.

Time to therapy

An rt-PA stroke study group from the National Institute of Neurologic Disorders and Stroke (NINDS) first reported that the early administration of rt-PA benefited carefully selected patients with acute ischemic stroke. [3] The FDA subsequently approved the use of rt-PA in patients who met NINDS criteria. In particular, rt-PA had to be given within 3 hours of stroke onset and only after CT scanning had ruled out hemorrhagic stroke.

Subsequently, fibrinolytic therapy administered 3–4.5 hours after symptom onset was found to improve neurologic outcomes in the European Cooperative Acute Stroke Study III (ECASS III), suggesting a wider time window for fibrinolysis in carefully selected patients. [83] On the basis of these and other data, in May 2009 the AHA/ASA revised the guidelines for the administration of rt-PA after acute stroke, expanding the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to benefit from this therapy. [83, 84, 85, 86]

Eligibility criteria for treatment during this later period are similar to those for earlier treatment but are more stringent, with any 1 of the following serving as an additional exclusion criterion:

  • Age older than 80 years

  • Use of oral anticoagulants, regardless of the INR

  • Baseline score on the National Institutes of Health Stroke Scale (NIHSS) greater than 25

  • History of stroke and diabetes

In a meta-analysis of nine major trials of fibrinolysis treatment involving a total of 6756 patients with acute ischemic stroke, researchers found that administration of alteplase within 4.5 hours of stroke onset significantly improved outcomes, irrespective of age or stroke severity, with earlier treatment providing the greatest benefit. Good outcome was defined as modified Rankin score of 0 or 1, which indicates little or no residual disability at 3–6 months. The odds of a good stroke outcome were 75% higher for patients who received alteplase within 3 hours of symptom onset compared with those who did not. Patients given alteplase 3 to 4.5 hours after symptom onset had a 26% increased chance of a good outcome, and patients with a delay of more than 4.5 hours in receiving alteplase treatment had a nonsignificant 15% increase in the chance of a good recovery. [87, 88]

A 10-center European study of nearly 6900 patients found IV rt-PA to be most effective when given within 90 minutes of the onset of stroke symptoms. [89, 90] Patients scoring in the 7–12 range on the NIHSS had better outcomes when fibrinolytic therapy was provided within 90 minutes of symptom onset than when it was provided 90–270 minutes after onset. For patients with minor stroke or moderate-to-severe stroke, however, treatment within the initial 90-minute window provided no additional advantage.

Hemorrhage risk

Although antiplatelet therapy may increase the risk for symptomatic intracerebral hemorrhage with fibrinolysis, a study by Diedler et al that included 3782 patients who had received 1 or 2 antiplatelet drugs found that the risk of intracerebral hemorrhage was small compared with the documented benefit of fibrinolysis. [91] These researchers concluded that antiplatelet treatment should not be considered a contraindication to fibrinolysis, although caution is warranted in patients receiving the combination of aspirin and clopidogrel.

A 2015 study, the largest of its kind, provides data supporting the use of fibrinolysis for stroke in patients taking antiplatelet therapy. Researchers analyzed a cohort of more than 85,000 stroke patients who had received tPA, approximately half of whom were taking antiplatelet medication at the time of their stroke. Results show that among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for hemorrhage but better functional outcomes than those who were not receiving antiplatelet therapy. [92]

Data regarding the safety of fibrinolytic therapy in patients taking dabigatran, rivaroxaban, or apixaban are not available. Extreme caution should be used when considering fibrinolytic therapy in such patients.

Caution should also be exercised in the administration of rt-PA to patients with evidence of low attenuation (edema or ischemia) involving more than a third of the distribution of the middle cerebral artery (MCA) on their initial noncontrast CT scan; such patients are less likely to have a favorable outcome after fibrinolytic therapy and are at higher risk for hemorrhagic transformation of their ischemic stroke. [52]

Ultrasound therapy

Researchers have studied the use of transcranial ultrasound as a means of assisting rt-PA in fibrinolysis. [93, 94] By delivering mechanical pressure waves to the thrombus, ultrasound can theoretically expose more of the thrombus’s surface to the circulating fibrinolytic agent. Further research is necessary to determine the exact role of transcranial Doppler ultrasound in assisting fibrinolytics in acute ischemic stroke.

For more information, see Thrombolytic Therapy in Stroke and Reperfusion Injury in Stroke.

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Intra-arterial Reperfusion

Theoretically, intra-arterial delivery may produce higher local concentrations of the fibrinolytic agent at lower total doses (and thus possibly lower the risk of a systemic bleed) and allow a longer therapeutic window. However, the longer time for initiating intra-arterial administration may mitigate some of this advantage and earlier phase II studies did not show a statistically significant difference in clinical outcomes. [1]

The Interventional Management of Acute Stroke Study (IMS-III) was halted for futility after showing no additional benefit from intra-arterial therapies (rt-PA, mechanical thrombectomy with mostly first-generation devices, or both) compared with intravenous rt-PA in patients with large-vessel occlusions. Additional analyses of the IMS III data are under way to better understand the results and potentially identity subsets of patients who may benefit from the combined approach. [95]

Intra-arterial fibrinolysis has been the traditional approach for patients with stroke from basilar artery occlusion. However, results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry study in 592 patients, did not support unequivocal superiority of intra-arterial fibrinolysis over intravenous fibrinolysis. [96]

A meta-analysis of case studies involving a total of 420 patients with basilar artery occlusion did indicate that recanalization was achieved more frequently with intra-arterial fibrinolysis than with intravenous fibrinolysis (65% vs 53%), but the report also found that death and long-term disability were equally common with the 2 techniques. [97] These researchers concluded that intravenous fibrinolysis represents probably the best treatment that can be offered to these patients in hospitals without a 24-hour interventional neuroradiologic service. [97]

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Antiplatelet Agents

AHA/ASA guidelines recommend giving aspirin, 325 mg orally, within 24–48 hours of ischemic stroke onset. The benefit of aspirin is modest but statistically significant and appears principally to involve the reduction of recurrent stroke. [86]

The International Stroke Trial and the Chinese Acute Stroke Trial (CAST) demonstrated modest benefit from the use of aspirin in the setting of acute ischemic stroke. The International Stroke Trial randomized 19,435 patients within 48 hours of stroke onset to treatment with aspirin 325 mg, subcutaneous heparin in 2 different dose regimens, aspirin with heparin, and a placebo. The study found that aspirin therapy reduced the risk of stroke recurrence within 14 days (2.8% vs 3.9%), with no significant excess of hemorrhagic strokes. [98, 99]

In CAST, which included 21,106 patients, aspirin treatment (160 mg/day) that was started within 48 hours of the onset of suspected acute ischemic stroke and was continued in hospital for up to 4 weeks reduced mortality to 3.3%, compared with 3.9% with placebo. A separate study also found that the combination of aspirin and low–molecular-weight heparin did not significantly improve outcomes. [98]

Other antiplatelet agents have also been under evaluation for use in the acute presentation of ischemic stroke. In a preliminary pilot study, abciximab given within 6 hours showed a trend toward improved outcome at 3 months. [100] However, the phase 3 Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II) was terminated prematurely after 808 patients because of lack of efficacy and an increased rate of symptomatic or fatal intracranial hemorrhage in patients receiving abciximab. [101]

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Blood Pressure Control

Although hypertension is common in acute ischemic stroke and is associated with poor outcome, studies of antihypertensive treatment in this setting have produced conflicting results. A theoretical drawback of blood pressure reduction is that elevated blood pressure may counteract dysfunctional cerebral autoregulation from stroke, but limited evidence suggests that antihypertensive treatment in acute stroke does not change cerebral perfusion. [102]

Calcium channel blockers did not alter outcome after ischemic stroke in some trials. Possible adverse effects of antihypertensive treatment have been reported in certain trials, especially those using intravenous calcium channel blockers or oral beta blockers. In the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) trial, early lowering of blood pressure with labetalol and lisinopril slightly improved outcome and did not increase serious adverse events. However, CHHIPS had a small sample size. [103]

A study in 339 patients with ischemic stroke found that oral candesartan reduced combined vascular events but had no effect on disability. [102] However, the Scandinavian Candesartan Acute Stroke Trial (SCAST), a randomized, placebo-controlled, double-blind study involving 2029 patients, found no indication of benefit from candesartan but did find some suggestion of harm. [104]

In the single-blind, randomized China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) study, which included 4,071 patients with acute ischemic stroke and elevated blood pressure, immediate blood pressure reduction with antihypertensive medication within 48 hours of symptom onset did not reduce the risk for death or major disability. CATIS excluded patients who received fibrinolytic therapy. Mean systolic blood pressure was reduced from 166.7 to 144.7 mm Hg within 24 hours in the antihypertensive treatment group. [105, 106]

Among the 2038 patients who received antihypertensive treatment, 683 reached the primary endpoint of death or major disability at 14 days or hospital discharge, compared with 681 of the 2,033 patients who received no antihypertensive treatment. At 3-month follow-up, 500 patients in the antihypertensive treatment group and 502 patients in the control group reached the secondary endpoint of death or major disability. [105, 106]

For patients who are not candidates for fibrinolytic therapy, current guidelines recommend permitting moderate hypertension in most patients with acute ischemic stroke. Most patients will experience spontaneous reduction in blood pressure over the first 24 hours without treatment. [86] The exceptions would be patients who have active comorbidities (eg, aortic dissection, acute myocardial infarction [MI], decompensated heart failure, hypertensive emergency) that require emergent blood pressure management.

Thresholds for antihypertensive treatment in acute ischemic stroke patients who are not fibrinolysis candidates, according to the 2013 ASA guidelines, are systolic blood pressure higher than 220 mm Hg or diastolic blood pressure above 120 mm Hg. [86] In those patients, a reasonable goal is to lower blood pressure by 15% during the first 24 hours after onset of stroke. Care must be taken to not lower blood pressure too quickly or aggressively, since this could worsen perfusion in the penumbra.

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Mechanical Thrombectomy

Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated.

The 2018 American Heart Association/American Stroke Association guidelines for the emergency treatment of patients with acute ischemic stroke extend the time limit on mechanical clot removal from 6 hours to up to 24 hours in select patients. The new guidelines recommend thrombectomy in eligible patients 6 to 16 hours after a stroke. [107] They also broaden the eligibility criteria for IV tPA.

Currently, 4 devices are approved by the FDA for the endovascular treatment of acute ischemic stroke, as follows:

  • Merci Retriever (Concentric Medical, Mountain View, CA): Corkscrew-shaped device that captures and engages clots

  • Penumbra System (Penumbra, Alameda, CA): Employs both aspiration and extraction

  • Solitaire FR Revascularization Device (Covidien, Dublin, Ireland): Stent-retriever system; combines the ability to restore blood flow and retrieve clot

  • Trevo (Concentric Medical, Mountain View, CA): Stent-retriever system

Successful recanalization occurred in 12 of 28 patients in the Mechanical Embolus Retrieval in Cerebral Ischemia (MERCI) 1 pilot trial, a study of the Merci Retrieval System. [108] In a second MERCI study, recanalization was achieved in 48% of patients in whom the device was deployed. Clot was successfully retrieved from all major cerebral arteries; however, the recanalization rate for the MCA was lowest. [109]

The Multi MERCI trial used the newer-generation Concentric retrieval device (L5). Recanalization was demonstrated in approximately 55% of patients who did not receive t-PA and in 68% of those to whom t-PA was given. Of patients who failed intravenous t-PA therapy, 73% had recanalization following mechanical embolectomy. [110] On the basis of these results, the FDA cleared the use of the MERCI device in patients who are either ineligible for or who have failed intravenous fibrinolytics.

In a trial of the Penumbra System in 23 patients who presented within 8 hours of symptom onset, revascularization to a Thrombolysis in Myocardial Infarction (TIMI) grade of 2 or 3 was accomplished in all 21 treated vessels. Vessel tortuosity prevented access by the device in 3 patients. [111]

More recent trials of the stent-retriever systems demonstrated superiority in reperfusion over the original Merci systems. In the Solitaire Flow Restoration Device Versus the Merci Retriever in Patients with Acute Ischaemic Stroke (SWIFT) study, which enrolled 113 subjects with moderate or severe strokes within 8 hours after symptom onset, the Solitaire FR system demonstrated successful revascularization (TIMI 2-3 flow) in 61% of patients, compared with 24% of patients treated with the Merci system. Patients in the Solitaire FR group also had a higher rate of good 90-day clinical outcomes than did those in the Merci group (58% versus 33%, respectively). [112]

A similar study, the Trevo Versus Merci Retrievers for Thrombectomy Revascularisation of Large Vessel Occlusions in Acute Ischaemic Stroke (TREVO 2) trial, reported successful reperfusion (TIMI 2-3 flow) in 86% of patients using the Trevor stent retriever, compared with 60% in the Merci group. The rate of good clinical outcomes at 90 days was also higher in the Trevo group than in the Merci group (40% vs 22%, respectively). [113] Ongoing studies will better define the role of intra-arterial therapies with and without intravenous fibrinolysis.

For more information, see Mechanical Thrombolysis in Acute Stroke.

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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 II clinical trials. [114, 115, 116]

High body temperature in the first 12–24 hours after stroke onset has been associated with poor functional outcome. However, results from the Paracetamol (Acetaminophen) in Stroke (PAIS) trial did not support the routine use of high-dose acetaminophen (6 g daily) in patients with acute stroke, although post-hoc analysis suggested a possible beneficial effect on functional outcome in patients admitted with a body temperature of 37–39° C. [117]

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Cerebral Edema Control

Significant cerebral edema after ischemic stroke is thought to be somewhat rare (10–20%). Maximum severity of edema is typically reached 72–96 hours after the onset of stroke.

Early indicators of ischemia on presentation and on noncontrast CT (NCCT) scans are independent indicators of potential swelling and deterioration (see the image below). Mannitol and other therapies to reduce intracranial pressure (ICP) may be used in emergency situations, although their usefulness in swelling secondary to ischemic stroke is unknown. No evidence exists supporting the use of corticosteroids to decrease cerebral edema in acute ischemic stroke. Prompt neurosurgical assistance should be sought when indicated. [1]

Axial noncontrast computed tomography (NCCT) scan Axial noncontrast computed tomography (NCCT) scan demonstrates diffuse hypodensity in the right lentiform nucleus with mass effect upon the frontal horn of the right lateral ventricle in a 70-year-old woman with a history of left-sided weakness for several hours.

Patient position, hyperventilation, hyperosmolar therapy, and, rarely, barbiturate coma may be used, as in patients with increased ICP secondary to closed head injury. Hemicraniectomy has been shown to decrease mortality and disability among patients with large hemispheric infarctions associated with life-threatening edema. [118, 119, 120, 121]

The American Heart Association and the American Stroke Association have released a guideline for the management of cerebral and cerebellar infarction with brain swelling; recommendations include the following: [122, 123]

  • Selected patients, including those able to handle an aggressive rehabilitation program, may benefit from decompressive craniectomy; younger patients may benefit most, and surgery is not recommended for patients older than 60 years

  • Clinical evidence of deterioration in swollen supratentorial hemispheric ischemic stroke includes new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size

  • In patients with swollen cerebellar infarction, level of consciousness decreases because of brainstem compression; this decrease may include early loss of corneal reflexes and the development of miosis

  • Standardized definitions are needed to facilitate studies of incidence, prevalence, risk factors, and outcomes

  • Identification of high-risk patients should include both clinical and neuroimaging data

  • Complex medical care of these patients includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control

  • In patients with swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but in patients who continue to deteriorate neurologically, decompressive craniectomy with dural expansion should be considered

  • In patients with swollen cerebellar stroke who deteriorate neurologically, suboccipital craniectomy with dural expansion should be performed

  • After a cerebellar infarct, performance of ventriculostomy to relieve obstructive hydrocephalus should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement

  • As many as one third of patients with swollen hemispheric supratentorial infarcts will be severely disabled and fully dependent on care even after decompressive craniectomy, whereas most patients with cerebellar infarct will have acceptable functional outcomes after surgery

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Seizure Control

Seizures occur in 2–23% of patients within the first days after ischemic stroke. These seizures are usually focal, but they may be generalized. Although primary prophylaxis for poststroke seizures is not indicated, secondary prevention of subsequent seizures with standard antiepileptic therapy is recommended. [1]

A fraction of patients who have experienced stroke develop chronic seizure disorders. Seizure disorders secondary to ischemic stroke should be managed in the same manner as other seizure disorders that arise as a result of neurologic injury. [1]

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Acute Decompensation

In the case of the rapidly decompensating patient or the patient with deteriorating neurologic status, reassessment of the ABCs as well as hemodynamics and reimaging are indicated. Many patients who develop hemorrhagic transformation or progressive cerebral edema will demonstrate acute clinical decline. Rarely, a patient may have escalation of symptoms secondary to increased size of the ischemic penumbra. Careful observation for hemorrhagic transformation (especially in the first 24 hours postreperfusion) and cerebral edema in patients with hemispheric or posterior fossa strokes in the first 24–36 hours is warranted.

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Anticoagulation and Prophylaxis

Currently, data are inadequate to justify the routine use of heparin or other anticoagulants in the acute management of ischemic stroke. [124] Patients with embolic stroke who have another indication for anticoagulation (eg, atrial fibrillation) may be placed on anticoagulation therapy nonemergently, with the goal of preventing further embolic disease; however, the potential benefits of that intervention must be weighed against the risk of hemorrhagic transformation. [1] For more information, see Stroke Anticoagulation and Prophylaxis.

Immobilized stroke patients in particular are at increased risk of developing deep venous thrombosis (DVT) and should receive early efforts to reduce the occurrence of DVT. The use of low-dose, subcutaneous unfractionated or low–molecular-weight heparin may be appropriate in these cases. [1] The CLOTS (Clots in Legs Or sTockings after Stroke) trial demonstrated that intermittent pneumatic compression of the lower extremities, started in the first 3 hospital days, reduced the risk of DVT in immobile patients with acute stroke. [125]

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Neuroprotective Agents

The rationale for the use of neuroprotective agents is that reducing the release of excitatory neurotransmitters by neurons in the ischemic penumbra may enhance the survival or these neurons. Despite very promising results in several animal studies, however, no single neuroprotective agent in ischemic stroke has as yet been supported by randomized, placebo-controlled human studies. Nevertheless, substantial research is under way evaluating different neuroprotective strategies.

Hypothermia was very promising for the ongoing treatment of patients surviving cardiac arrest from ventricular tachycardia or ventricular fibrillation. However, no major clinical study has demonstrated a role for hypothermia in the early treatment of ischemic stroke. [1]  

For more information, see Neuroprotective Agents in Stroke.

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Stroke Prevention

Primary prevention refers to the management of individuals with no history of stroke. Preventative measures may include the use of antiplatelet agents, statins, smoking cessation and exercise. The 2011 AHA/ASA guidelines for the primary prevention of stroke emphasize the importance of lifestyle changes to reduce well-documented modifiable risk factors, citing an 80% lower risk of a first stroke in people who follow a healthy lifestyle compared with those who do not. [22]

Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include the use of anitplatelet agents, [126] anticoagulants (warfarin or newer novel oral anticoagulants) antihypertensives, statins, [127] and lifestyle interventions. A study by the Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators concluded that in stroke patients who have significant intracranial arterial stenosis, aspirin should be used in preference to warfarin for secondary prevention. [128]

Smoking cessation, blood pressure control, diabetes control, a low-fat low-salt diet, weight loss, and regular exercise should be encouraged as strongly as the medications described above. The 2011 AHA/ASA guidelines recommend ED-based smoking cessation interventions, and consider it reasonable for EDs to screen patients for hypertension and drug abuse. [22]

Written prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions. In addition, the 2011 AHA/ASA guidelines for primary stroke prevention indicate that it is reasonable to avoid exposure to environmental tobacco smoke, despite a lack of stroke-specific data.

Aspirin for primary prevention

Overall, the value of aspirin in primary prevention appears uncertain, [129] and its use for this purpose is not recommended for patients at low risk. Aspirin is recommended for primary prevention only in persons with at least a 6–10% risk of cardiovascular events over 10 years. [22]

On the other hand, low-dose aspirin may be beneficial for primary prevention of stroke in women. A randomized, placebo-controlled trial in 39,876 initially healthy women aged 45 years or older demonstrated that 100 mg of aspirin on alternate days resulted in a 24% reduction in the risk of ischemic stroke, with a nonsignificant increase in the risk of hemorrhagic stroke. [130]

Secondary prevention guidelines

Guidelines issued in 2014 by the American Heart Association (AHA)/American Stroke Association (ASA) on the secondary prevention of stroke emphasize nutrition and lifestyle and include a new section on aortic atherosclerosis. New recommendations include the following: [131, 132]

  • Patients who have had a stroke or transient ischemic attack (TIA) should be screened for diabetes and obesity

  • Patients should possibly be screened for sleep apnea

  • Patients should possibly undergo a nutritional assessment and be advised to follow a Mediterranean-type diet

  • Patients who have had a stroke of unknown cause should undergo long-term monitoring for atrial fibrillation (AF)

  • The new oral anticoagulants dabigatran (class I, level of evidence [LOE] A), apixaban (class I, LOE B), and rivaroxaban (class IIa, LOE B) are among the drugs recommended for patients with nonvalvular AF

Based on research results, the guidelines also recommend that, in patients without deep venous thrombosis (DVT), a patent foramen ovale not be closed. In addition, because there is little data to suggest that niacin or fibrate drugs, as a means to raise high-density lipoprotein (HDL) cholesterol, reduce secondary stroke risk, the guidelines no longer recommend their use.

Dual antiplatelet therapy for secondary prevention

A systematic review and meta-analysis of 12 randomized trials involving 3766 patients concluded that, compared with aspirin alone, dual antiplatelet therapy with aspirin plus either dipyridamole or clopidogrel appears to be safe and effective in reducing stroke recurrence and other vascular events (ie, transient ischemic attack [TIA], acute coronary syndrome, MI), in patients with acute ischemic stroke or TIA. [133] Dual therapy was also associated with a nonsignificant trend toward increased major bleeding.

The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) showed that the combination of aspirin and dipyridamole was preferable to aspirin alone as antithrombotic therapy for cerebral ischemia of arterial origin. [134] In ESPRIT, secondary prevention was started within 6 months of a TIA or minor stroke of presumed arterial origin.

The addition of extended-release dipyridamole to aspirin therapy appears to be equally safe and effective whether started early or late after stroke. A German study in 543 patients found no significant difference in disability at 90 days, regardless of whether dipyridamole was started within 24 hours of stroke or TIA onset or after 7 days of aspirin monotherapy. [135]

In contrast, the Management of AtheroThrombosis with Clopidogrel in High-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH) trial, which included 7599 patients, found that adding aspirin to clopidogrel did not significantly reduce major vascular events. However, the risk of life-threatening or major bleeding was increased by the addition of aspirin. [136]

Research shows that aspirin combined with rivaroxaban cuts the ischemic stroke rate by almost half without significantly increasing the risk for intracerebral hemorrhage (ICH) compared with aspirin alone. The COMPASS trial studied 27,395 patients with stable atherosclerotic vascular disease divided into three treatment groups: aspirin 100 mg a day, rivaroxaban 5 mg twice daily, and a combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg per day. The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction and occurred in 379 patients in the combination group compared to 496 patients taking aspirin alone. However, bleeding events occurred in more patients in the combination group (3.1% vs 1.9%; HR, 1.70; 95% CI, 1.40 - 2.05; P< .001). [51]

Carotid artery stenosis

For patients at risk for stroke from asymptomatic carotid artery stenosis, the 2011 AHA/ASA primary prevention guidelines state that older studies that showed revascularization surgery as more beneficial than medical treatment may now be obsolete because of improvements in medical therapies. Therefore, individual patient comorbidities, life expectancy, and preferences should determine whether medical treatment alone or carotid revascularization is selected. [22]

Atrial fibrillation

Atrial fibrillation (AF) is a major risk factor for stroke. The 2011 AHA/ASA primary stroke prevention guideline recommends that EDs screen for AF and assess patients for anticoagulation therapy if AF is found. [22]

In the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W), oral anticoagulation with warfarin proved superior to clopidogrel plus aspirin for prevention of vascular events in patients with AF who were at high risk of stroke. [137] The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy.

Interestingly, in ACTIVE W, the rate of vascular events was significantly higher in patients who switched from warfarin to clopidogrel plus aspirin as a result of randomization than in patients who had been on warfarin before study enrollment and remained on warfarin during the study. The benefit of anticoagulation therapy over dual antiplatelet therapy was much more modest in patients who had not been on warfarin before study initiation and were then randomized to warfarin.

The 2011 ACC Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) AF guideline update states that the new anticoagulant dabigatran is useful as an alternative to warfarin in patients with AF who do not have a prosthetic heart valve or hemodynamically significant valve disease. [138] However, a 2012 meta-analysis found an increased risk for MI or acute coronary syndrome with dabigatran. [139]  With the advent of other novel anticoagulants, the American Academy of Neurology (AAN) produced guidelines for the prevention of stroke in nonvalvuar atrial fibrillation in 2014. [140] The guidelines recommend that clinicians should administer dabigatran, rivaroxaban, or apixaban to patients who have nonvalvular atrial fibrillation requiring anticoagulant medication and are at higher risk of intracranial bleeding; they also suggest that clinicians might offer apixaban to patients with nonvalvular atrial fibrillation and GI bleeding risk who require anticoagulant medication. The AAN guidelines recommend that where oral anticoagulants are unavailable, clinicians might offer a combination of aspirin and clopidogrel. This combination was found to be more effective than aspirin for reducting strokes in atrial fibrillation in the ACTIVE trial although it did increase major hemorrhage risk. [141]

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Specialized Stroke Centers

The concept of the specialized stroke center has evolved in response to the multitude of factors involved in the care of patients with acute stroke. The American Heart Association and the Brain Attack Coalition provided recommendations for the establishment of 3 tiers of stroke centers: acute stroke ready hospitals (ASRHs), primary stroke centers (PSCs), and comprehensive stroke centers (CSCs). [1] The Joint Commission for the Accreditation of Hospital Organizations (JC) and others now provide accreditation for ASRH, PSCs and CSCs. These centers are characterized as follows:

  • ASRH: Designed to address the lack of hospitals typically in rural areas that have the resources to achieve PSC or CSC certification and yet serve as a critical access point for healthcare. Typically they have all the elements of a PSC but lack a physician with stroke expertise and often a dedicated stroke unit. Through the use of telemedicine and teleradiology these centers can evaluate patients for the potential use of fibrinloytics. Key to the optimal function of these stroke centers is their interactions within a regional stroke system of care.

  • PSC: Designed to maximize the timely provision of stroke-specific therapy, including the administration of rt-PA; the center is also capable of providing care to patients with uncomplicated stroke

  • CSC: Shares the commitment that the PSC has to acute delivery of rt-PA and also provides care to patients with hemorrhagic stroke and intracranial hemorrhage, as well as to all patients with stroke who require emergent advanced imaging, intra-arterial therapies, neurosurgical interventions, and management in a neurosurgical intensive care unit (NSICU)

ASRHs, PSCs, and CSCs work most effectively when integrated into a regional stroke system of care so that patients are treated at the most appropriate hospital based on factors such as severity, comorbidities, and timing. Integrating regional prehospital services (911 and EMS) into this system of care ensures the most appropriate triage from the field.

Coordination of care

Once patients have been identified as potential stroke patients, their ED evaluation must be fast-tracked to allow for the completion of required laboratory tests and requisite noncontrast head CT scanning, as well as for the notification and involvement of neurologic consultants. These requirements have led to the development of "code stroke" protocols for the ED. In addition, EMS personnel are trained to identify possible stroke patients and arrange for their speedy, preferential transport to a PSC or CSC. [80]

Hospitals with specialized stroke teams have demonstrated significantly increased rates of fibrinolytic administration, decreased door-to-needle (DTN) times, and decreased mortality. Cumulatively, the center should identify performance measures and include mechanisms for evaluating the effectiveness of the system, as well as its component parts. The acute care of the stroke patient is more than anything a systems-based team approach requiring the cooperation of the ED, radiology, pharmacy, neurology, and intensive care unit (ICU) staff.

A stroke system should ensure effective interaction and collaboration among the agencies, services, and people involved in providing prevention and the timely identification, triage to the most appropriate hospital, rapid transport, treatment, and rehabilitation of stroke patients. For more information, see Stroke Team Creation and Primary Stroke Center Certification.

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Consultations

A stroke team or an experienced professional who is sufficiently familiar with stroke should be available within 15 minutes of the patient's arrival in the ED. Other consultations are tailored to individual patient needs. Often, occupational therapy, physical therapy, speech therapy, and physical medicine and rehabilitation experts are consulted within the first day of hospitalization.

Consultation of cardiology, vascular surgery, or neurosurgery may be warranted based on the results of carotid duplex scanning , neuroimaging, transthoracic and transesophageal echocardiography, and clinical course. During hospitalization, additional useful consultations include the following:

  • Home health care coordinator

  • Rehabilitation coordinator

  • Social worker

  • Psychiatrist (commonly for depression)

  • Dietitian

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Diet

Ischemic stroke is associated with vascular dementia; stroke survivors have almost double the rate of dementia than the general population. Patients may be helped by following the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, according to a 2018 study. [142] The diet may help prevent dementia as well. [143]

The MIND diet recommends at least three servings of whole grains a day and six servings of green leafy vegetables and two servings of berries a week, and it encourages regular consumption of other vegetables, fish, poultry, beans, and nuts. As well, it recommends olive oil as the primary oil and alcohol once per day. The diet restricts intake of red meats, fast foods, cheese, desserts, and butter.

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