Ischemic Stroke Treatment & Management
- Author: Edward C Jauch, MD, MS, FAHA, FACEP; Chief Editor: Helmi L Lutsep, MD more...
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 outcomes in ischemic stroke.
Palliative care is an important component of comprehensive stroke care. Some stroke patients will simply not recover, and others will be in a state of debilitation such that their comfort is the most humane and appropriate therapeutic concern. Some patients have advance directives providing instructions for medical providers in the event of severe medical illness or injury.
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.
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.[74, 75]
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.[76, 77]
Stroke should be a priority dispatch with prompt EMS response. EMS responders should provide advance notice to their ED destination in as timely a manner as possible so as to allow preparation and marshaling 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 has the potential to provide timely expert advice to rural and underserved clinics and hospitals.
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. 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.
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.
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 a special interest in stroke is ideal. Stroke care units with specially trained personnel exist and improve outcomes.
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).
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.
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.
The only fibrinolytic agent that has been shown to benefit selected patients with acute ischemic stroke is 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 hemodynamically significant hemorrhage and angioedema or allergic reactions.
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 :
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)
No seizure with residual postictal impairments
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, 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. 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. 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.[82, 83, 84, 85]
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 thrombolysis 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.[86, 87]
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.[88, 89] Patients scoring in the 7-12 range on the NIHSS had better outcomes when thrombolytic 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.
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. 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 thrombolysis 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.
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.
Researchers have studied the use of transcranial ultrasound as a means of assisting rt-PA in fibrinolysis.[92, 93] 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.
There have been no completed human trials comparing intravenous versus intra-arterial administration of fibrinolytics. 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.
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, 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.
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.
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. 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.
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.
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.[97, 98]
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.
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. 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.
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.
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.
A study in 339 patients with ischemic stroke found that oral candesartan reduced combined vascular events but had no effect on disability. 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.
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 thrombolytic therapy. Mean systolic blood pressure was reduced from 166.7 to 144.7 mm Hg within 24 hours in the antihypertensive treatment group.[104, 105]
Among the 2,038 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.[104, 105]
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. The exceptions would be patients who have 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. 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.
Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated.
In 2015, The American Heart Association/American Stroke Association issued updated guidelines for the emergency treatment of patients with acute ischemic stroke, recommending endovascular treatment using stent retrievers. 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. 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.
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. Seventy-three percent of patients who failed intravenous t-PA therapy had recanalization following mechanical embolectomy. 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.
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).
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). Ongoing studies will better define the role of intra-arterial therapies with and without intravenous fibrinolysis.
Long-term results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study confirm the superiority of aggressive medical management alone to aggressive medical management with stenting in patients with a stroke or transient ischemic attack resulting from stenosis of a major intracranial artery.[113, 114, 115] Long-term follow-up results were available for 227 patients in the medical management group and 224 patients in the stenting group.
Occurrence rates for primary endpoint events (stroke or death within 30 days after enrollment or after either a revascularization procedure for the qualifying lesion during follow-up or a stroke in the territory of the qualifying artery beyond 30 days) in the medical group and the stenting group were 14.1% and 20.6%, respectively, at year 2 and 14.9% and 23.9% at year 3. Rates of any stroke and of any major hemorrhage were also significantly lower in the medical group than in the stenting group.
For more information, see Mechanical Thrombolysis in Acute Stroke.
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.[116, 117, 118]
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.
Cerebral Edema Control
Significant cerebral edema after ischemic stroke is thought to be somewhat rare (10-20%). Maximum severity of edema is 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.
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.[120, 121, 122, 123]
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[124, 125] :
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
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.
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.
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.
Anticoagulation and Prophylaxis
Currently, data are inadequate to justify the routine use of heparin or other anticoagulants in the acute management of ischemic stroke. 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. 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. 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.
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 is fast becoming the standard of care 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.
For more information, see Neuroprotective Agents in Stroke.
Primary prevention refers to the treatment of individuals with no history of stroke. Measures may include the use of platelet antiaggregants, statins, 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.
Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include the use of platelet antiaggregants, antihypertensives, statins, 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.
Smoking cessation, blood pressure control, diabetes control, a low-fat 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.
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, 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.
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.
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[133, 134] :
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. 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. 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.
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.
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.
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.
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. 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. However, a 2012 meta-analysis found an increased risk for MI or acute coronary syndrome with dabigatran.
For patients with AF after stroke or TIA, the 2010 AHA/ASA secondary stroke prevention guidelines are in accord with the standard recommendation of warfarin, with aspirin as an alternative for patients who cannot take oral anticoagulants. However, clopidogrel should not be used in combination with aspirin for such patients, because the bleeding risk of the combination is comparable to that of warfarin. The guideline states that the benefit of warfarin after stroke or TIA in patients without AF has not been established.
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 Brain Attack Coalition provided recommendations for the establishment of 2 tiers of stroke centers: primary stroke centers (PSCs) and comprehensive stroke centers (CSCs). The Joint Commission for the Accreditation of Hospital Organizations (JCAHO) now provides accreditation for PSCs and CSCs. These centers are characterized as follows:
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)
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.
Additionally, stroke centers should have personnel versed in the monitoring of stroke vital signs, which include the following:
Change in neurologic status
A further tier, acute stroke ready hospitals, is being defined as hospitals in which most of the necessary resources are in place to emergently evaluate patients and potentially treat them with fibrinolytics, with the assistance of remote stroke expertise, typically by telemedicine. Key to the optimal function of these stroke centers is their interactions within a regional stroke system of care.
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.
Hospitals with specialized stroke teams have demonstrated significantly increased rates of fibrinolytic administration 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.
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
Psychiatrist (commonly for depression)
[Guideline] Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007 May. 38(5):1655-711. [Medline].
Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999 Jul 13. 53(1):126-31. [Medline].
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995 Dec 14. 333(24):1581-7. [Medline].
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27. 131 (4):e29-322. [Medline].
Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC, Khavjou OA, et al. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013 Aug. 44 (8):2361-75. [Medline].
Sacco RL, Shi T, Zamanillo MC, Kargman DE. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the Northern Manhattan Stroke Study. Neurology. 1994 Apr. 44(4):626-34. [Medline].
Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008 May 10. 371(9624):1612-23. [Medline].
Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999 Sep. 22(9):391-7. [Medline].
Yuan J, Yankner BA. Apoptosis in the nervous system. Nature. 2000 Oct 12. 407(6805):802-9. [Medline].
Latchaw RE, Yonas H, Hunter GJ, Yuh WT, Ueda T, Sorensen AG, et al. Guidelines and recommendations for perfusion imaging in cerebral ischemia: A scientific statement for healthcare professionals by the writing group on perfusion imaging, from the Council on Cardiovascular Radiology of the American Heart Association. Stroke. 2003 Apr. 34(4):1084-104. [Medline].
Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med. 1997 Nov. 30(5):642-53. [Medline].
Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke. 1985 Jan-Feb. 16(1):101-9. [Medline].
Bell BA, Symon L, Branston NM. CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons. J Neurosurg. 1985 Jan. 62(1):31-41. [Medline].
Mullins ME, Lev MH, Schellingerhout D, Gonzalez RG, Schaefer PW. Intracranial hemorrhage complicating acute stroke: how common is hemorrhagic stroke on initial head CT scan and how often is initial clinical diagnosis of acute stroke eventually confirmed?. AJNR Am J Neuroradiol. 2005 Oct. 26(9):2207-12. [Medline].
Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993 Spring. 5(1):1-16. [Medline].
Nighoghossian N, Hermier M, Adeleine P, Blanc-Lasserre K, Derex L, Honnorat J, et al. Old microbleeds are a potential risk factor for cerebral bleeding after ischemic stroke: a gradient-echo T2*-weighted brain MRI study. Stroke. 2002 Mar. 33(3):735-42. [Medline].
González RG. Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain". AJNR Am J Neuroradiol. 2006 Apr. 27(4):728-35. [Medline].
Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 Suppl):483S-512S. [Medline].
Dubey N, Bakshi R, Wasay M, Dmochowski J. Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke. J Neuroimaging. 2001 Apr. 11(2):184-8. [Medline].
Brooks M. Migraine Linked to Double Risk for Silent Stroke. Medscape Medical News. Available at http://www.medscape.com/viewarticle/825451. Accessed: May 27, 2014.
Anderson P. Migraine with aura 'major' contributor to all stroke types. Medscape Medical News. June 27, 2013. [Full Text].
[Guideline] Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb. 42(2):517-84. [Medline]. [Full Text].
Kurl S, Laukkanen JA, Rauramaa R, Lakka TA, Sivenius J, Salonen JT. Cardiorespiratory fitness and the risk for stroke in men. Arch Intern Med. 2003 Jul 28. 163(14):1682-8. [Medline].
Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, et al. Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 Feb 6. [Medline].
Hughes S. First AHA/ASA Guidelines to Reduce Stroke Risk in Women. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/820277. Accessed: February 11, 2014.
Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15. 268(23):17478-88. [Medline].
Miller DK, Gillard JW, Vickers PJ, Sadowski S, Léveillé C, Mancini JA, et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature. 1990 Jan 18. 343(6255):278-81. [Medline].
Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet. 2007 Feb. 39(2):212-7. [Medline].
Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet. 1985 Jan. 37(1):1-31. [Medline]. [Full Text].
Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol. 2010 Feb. 67(2):148-53. [Medline].
Jensson O, Gudmundsson G, Arnason A, Blöndal H, Petursdottir I, Thorsteinsson L, et al. Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage. Acta Neurol Scand. 1987 Aug. 76(2):102-14. [Medline].
Oberstein SA. Diagnostic strategies in CADASIL. Neurology. 2003 Jun 24. 60(12):2020; author reply 2020. [Medline].
Dichgans M. Cognition in CADASIL. Stroke. 2009 Mar. 40(3 Suppl):S45-7. [Medline].
Cheng YC, O'Connell JR, Cole JW, Stine OC, Dueker N, McArdle PF, et al. Genome-wide association analysis of ischemic stroke in young adults. G3 (Bethesda). 2011 Nov. 1(6):505-14. [Medline]. [Full Text].
The International Stroke Genetics Consortium (ISGC); the Wellcome Trust Case Control Consortium 2 (WTCCC2), Bellenguez C, Bevan S, Gschwendtner A, Spencer CC, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012 Feb 5. 44(3):328-33. [Medline]. [Full Text].
Arregui M, Fisher E, Knüppel S, Buijsse B, di Giuseppe R, Fritsche A, et al. Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke. Gene. 2012 Feb 25. 494(2):190-5. [Medline].
Witt BJ, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J Med. 2006 Apr. 119(4):354.e1-9. [Medline].
Wessels T, Wessels C, Ellsiepen A, Reuter I, Trittmacher S, Stolz E. Contribution of diffusion-weighted imaging in determination of stroke etiology. AJNR Am J Neuroradiol. 2006 Jan. 27(1):35-9. [Medline].
Roh JK, Kang DW, Lee SH, Yoon BW, Chang KH. Significance of acute multiple brain infarction on diffusion-weighted imaging. Stroke. 2000 Mar. 31(3):688-94. [Medline].
Adams H, Adams R, Del Zoppo G, Goldstein LB. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005 Apr. 36(4):916-23. [Medline].
Derdeyn CP, Khosla A, Videen TO, Fritsch SM, Carpenter DL, Grubb RL Jr. Severe hemodynamic impairment and border zone--region infarction. Radiology. 2001 Jul. 220(1):195-201. [Medline].
Pollanen MS, Deck JH. Directed embolization is an alternate cause of cerebral watershed infarction. Arch Pathol Lab Med. 1989 Oct. 113(10):1139-41. [Medline].
Waterston JA, Brown MM, Butler P, Swash M. Small deep cerebral infarcts associated with occlusive internal carotid artery disease. A hemodynamic phenomenon?. Arch Neurol. 1990 Sep. 47(9):953-7. [Medline].
U.S. Centers for Disease Control and Prevention and the Heart Disease and Stroke Statistics - 2007 Update, published by the American Heart Association. Available at http://www.strokecenter.org/patients/stats.htm. Accessed: September 2008.
Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke. 2011 Aug. 42(8):2351-5. [Medline].
MacKay J, Mensah GA. World Health Organization. Global Burden of Stroke. The Atlas of Heart Disease and Stroke. Available at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf.
Schneider AT, Kissela B, Woo D, Kleindorfer D, Alwell K, Miller R, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004 Jul. 35(7):1552-6. [Medline].
Fonarow GC, Saver JL, Smith EE, Broderick JP, Kleindorfer DO, Sacco RL, et al. Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke. J Am Heart Assoc. 2012 Feb. 1(1):42-50. [Medline]. [Full Text].
von Kummer R, Allen KL, Holle R, Bozzao L, Bastianello S, Manelfe C, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology. 1997 Nov. 205(2):327-33. [Medline].
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995 Oct 4. 274(13):1017-25. [Medline].
Bruno A, Levine SR, Frankel MR, Brott TG, Lin Y, Tilley BC, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002 Sep 10. 59(5):669-74. [Medline].
Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, et al. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology. 1999 Jan 15. 52(2):280-4. [Medline].
Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, et al. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003 Sep. 34(9):2208-14. [Medline].
Mandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke. 2006 May. 37(5):1248-53. [Medline].
National Institutes of Health Stroke Scale. Available at http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf. Accessed: October 2008.
Huff JS. Stroke mimics and chameleons. Emerg Med Clin North Am. 2002 Aug. 20(3):583-95. [Medline].
Libman RB, Wirkowski E, Alvir J, Rao TH. Conditions that mimic stroke in the emergency department. Implications for acute stroke trials. Arch Neurol. 1995 Nov. 52(11):1119-22. [Medline].
Runchey S, McGee S. Does this patient have a hemorrhagic stroke?: clinical findings distinguishing hemorrhagic stroke from ischemic stroke. JAMA. 2010 Jun 9. 303(22):2280-6. [Medline].
Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurolo... Stroke. 2009 Jun. 40(6):2276-93. [Medline].
Tintinalli J, Kellen G, Stapczynski J. American College of Emergency Physicians. Emergency Medicine: A Comprehensive Study Guide. 6th. New York: McGraw Hill; 2004. 1382-1390.
Leira EC, Chang KC, Davis PH, Clarke WR, Woolson RF, Hansen MD, et al. Can we predict early recurrence in acute stroke?. Cerebrovasc Dis. 2004. 18(2):139-44. [Medline].
Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005 Sep 3-9. 366(9488):809-17. [Medline].
Byrne JV. The aneurysm "clip or coil" debate. Acta Neurochir (Wien). 2006 Feb. 148(2):115-20. [Medline].
Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev MH, Huang-Hellinger FR, et al. Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. Radiology. 1996 May. 199(2):391-401. [Medline].
González RG, Schaefer PW, Buonanno FS, Schwamm LH, Budzik RF, Rordorf G, et al. Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset. Radiology. 1999 Jan. 210(1):155-62. [Medline].
Marks MP, Olivot JM, Kemp S, Lansberg MG, Bammer R, Wechsler LR, et al. Patients with acute stroke treated with intravenous tPA 3-6 hours after stroke onset: correlations between MR angiography findings and perfusion- and diffusion-weighted imaging in the DEFUSE study. Radiology. 2008 Nov. 249(2):614-23. [Medline]. [Full Text].
Schellinger PD, Bryan RN, Caplan LR, Detre JA, Edelman RR, Jaigobin C, et al. Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010 Jul 13. 75(2):177-85. [Medline].
Sorensen AG, Copen WA, Ostergaard L, Buonanno FS, Gonzalez RG, Rordorf G, et al. Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time. Radiology. 1999 Feb. 210(2):519-27. [Medline].
Camerlingo M, Casto L, Censori B, Ferraro B, Gazzaniga GC, Mamoli A. Transcranial Doppler in acute ischemic stroke of the middle cerebral artery territories. Acta Neurol Scand. 1993 Aug. 88(2):108-11. [Medline].
Sagar G, Riley P, Vohrah A. Is admission chest radiography of any clinical value in acute stroke patients?. Clin Radiol. 1996 Jul. 51(7):499-502. [Medline].
Meerwaldt R, Slart RH, van Dam GM, Luijckx GJ, Tio RA, Zeebregts CJ. PET/SPECT imaging: from carotid vulnerability to brain viability. Eur J Radiol. 2010 Apr. 74(1):104-9. [Medline].
Handschu R, Poppe R, Rauss J, Neundörfer B, Erbguth F. Emergency calls in acute stroke. Stroke. 2003 Apr. 34(4):1005-9. [Medline].
Williams JE, Rosamond WD, Morris DL. Stroke symptom attribution and time to emergency department arrival: the delay in accessing stroke healthcare study. Acad Emerg Med. 2000 Jan. 7(1):93-6. [Medline].
Zweifler RM, Mendizabal JE, Cunningham S, Shah AK, Rothrock JF. Hospital presentation after stroke in a community sample: the Mobile Stroke Project. South Med J. 2002 Nov. 95(11):1263-8. [Medline].
Lacy CR, Suh DC, Bueno M, Kostis JB. Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E.). Stroke. 2001 Jan. 32(1):63-9. [Medline].
Puolakka T, Väyrynen T, Häppölä O, Soinne L, Kuisma M, Lindsberg PJ. Sequential analysis of pretreatment delays in stroke thrombolysis. Acad Emerg Med. 2010 Sep. 17(9):965-9. [Medline].
Ford AL, Williams JA, Spencer M, McCammon C, Khoury N, Sampson TR, et al. Reducing door-to-needle times using Toyota's lean manufacturing principles and value stream analysis. Stroke. 2012 Dec. 43(12):3395-8. [Medline]. [Full Text].
Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008 Feb. 39(2):384-9. [Medline].
Bellolio MF, Gilmore RM, Stead LG. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 2011 Sep 7. 9:CD005346. [Medline].
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25. 359(13):1317-29. [Medline].
[Guideline] Del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009 Aug. 40(8):2945-8. [Medline]. [Full Text].
Wahlgren N, Ahmed N, Dávalos A, Hacke W, Millán M, Muir K, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Oct 11. 372(9646):1303-9. [Medline].
Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2013 Jan 31. [Medline].
Brooks M. Stroke a Race Against the Clock, Review Confirms. Medscape Medical News. Available at http://www.medscape.com/viewarticle/830611. Accessed: September 2, 2014.
Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Aug 5. [Medline].
Strbian D, Ringleb P, Michel P,et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?. Stroke. 2013 Aug 22. [Medline].
Brooks M. Ultra-Early' Thrombolysis Cuts Disability in Mild Stroke. Medscape Medical News. Aug 28 2013. [Full Text].
Diedler J, Ahmed N, Sykora M, Uyttenboogaart M, Overgaard K, Luijckx GJ, et al. Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke. 2010 Feb. 41(2):288-94. [Medline].
Xian Y, Federspiel JJ, Grau-Sepulveda M, Hernandez AF, Schwamm LH, Bhatt DL, et al. Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator. JAMA Neurol. 2015 Nov 9. 1-10. [Medline].
Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004 Nov 18. 351(21):2170-8. [Medline].
Tsivgoulis G, Eggers J, Ribo M, Perren F, Saqqur M, Rubiera M, et al. Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke. 2010 Feb. 41(2):280-7. [Medline].
Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7. 368(10):893-903. [Medline]. [Full Text].
Schonewille WJ, Wijman CA, Michel P, Rueckert CM, Weimar C, Mattle HP, et al. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol. 2009 Aug. 8(8):724-30. [Medline].
Lindsberg PJ, Mattle HP. Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke. 2006 Mar. 37(3):922-8. [Medline].
CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7. 349(9066):1641-9. [Medline].
The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997 May 31. 349(9065):1569-81. [Medline].
Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, dose-escalation study. The Abciximab in Ischemic Stroke Investigators. Stroke. 2000 Mar. 31(3):601-9. [Medline].
Adams HP Jr, Effron MB, Torner J, Dávalos A, Frayne J, Teal P, et al. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke. 2008 Jan. 39(1):87-99. [Medline].
Sare GM, Geeganage C, Bath PM. High blood pressure in acute ischaemic stroke--broadening therapeutic horizons. Cerebrovasc Dis. 2009. 27 Suppl 1:156-61. [Medline].
Potter JF, Robinson TG, Ford GA, Mistri A, James M, Chernova J, et al. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurol. 2009 Jan. 8(1):48-56. [Medline].
Sandset EC, Bath PM, Boysen G, Jatuzis D, Kõrv J, Lüders S, et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011 Feb 26. 377(9767):741-50. [Medline].
Jeffrey S. CATIS: No Benefit of BP Reduction in Acute Phase of Stroke. Medscape Medical News. Available at http://www.medscape.com/viewarticle/814531. Accessed: November 24, 2013.
He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS, et al. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial. JAMA. 2013 Nov 17. [Medline].
[Guideline] Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jun 29. [Medline].
Gobin YP, Starkman S, Duckwiler GR, Grobelny T, Kidwell CS, Jahan R, et al. MERCI 1: a phase 1 study of Mechanical Embolus Removal in Cerebral Ischemia. Stroke. 2004 Dec. 35(12):2848-54. [Medline].
Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005 Jul. 36(7):1432-8. [Medline].
Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008 Apr. 39(4):1205-12. [Medline].
Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A. The Penumbra System: a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008 Aug. 29(7):1409-13. [Medline].
Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012 Oct 6. 380(9849):1241-9. [Medline].
Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6. 380(9849):1231-40. [Medline].
Anderson P. Medical management still bests intracranial stenting. Medscape Medical News. October 31, 2013. [Full Text].
Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2013 Oct 25. [Medline].
Rothwell PM, Markus HS. Improved medical treatment in secondary prevention of stroke. Lancet. 2013 Oct 25. [Medline].
Marion DW. Controlled normothermia in neurologic intensive care. Crit Care Med. 2004 Feb. 32(2 Suppl):S43-5. [Medline].
Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke. Lancet Neurol. 2003 Jul. 2(7):410-6. [Medline].
Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010 Oct. 41(10):2265-70. [Medline].
den Hertog HM, van der Worp HB, van Gemert HM, Algra A, Kappelle LJ, van Gijn J, et al. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial. Lancet Neurol. 2009 May. 8(5):434-40. [Medline].
Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol. 2009 Apr. 8(4):326-33. [Medline].
Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007 Sep. 38(9):2518-25. [Medline].
Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007 Mar. 6(3):215-22. [Medline].
Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke. 2007 Sep. 38(9):2506-17. [Medline].
Wijdicks EF, Sheth KN, Carter BS, Greer DM, Kasner SE, Kimberly WT, et al. Recommendations for the Management of Cerebral and Cerebellar Infarction With Swelling: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 Jan 30. [Medline].
Hughes S. AHA/ASA Guideline on Stroke With Brain Swelling. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/820481. Accessed: February 25, 2014.
Padma V, Fisher M, Moonis M. Role of heparin and low-molecular-weight heparins in the management of acute ischemic stroke. Expert Rev Cardiovasc Ther. 2006 May. 4(3):405-15. [Medline].
CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 2013 Aug 10. 382(9891):516-24. [Medline].
Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 Jan 8. 308(6921):81-106. [Medline]. [Full Text].
Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10. 355(6):549-59. [Medline].
Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31. 352(13):1305-16. [Medline].
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30. 373(9678):1849-60. [Medline]. [Full Text].
Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31. 352(13):1293-304. [Medline].
[Guideline] Hughes S. New AHA/ASA Stroke Secondary Prevention Guidelines. Medscape Medical News. May 2 2014. [Full Text].
[Guideline] Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 May 1. [Medline]. [Full Text].
Geeganage CM, Diener HC, Algra A, Chen C, Topol EJ, Dengler R, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012 Apr. 43(4):1058-66. [Medline].
Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20. 367(9523):1665-73. [Medline].
Dengler R, Diener HC, Schwartz A, Grond M, Schumacher H, Machnig T, et al. Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2010 Feb. 9(2):159-66. [Medline].
Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004 Jul 24-30. 364(9431):331-7. [Medline].
Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10. 367(9526):1903-12. [Medline].
[Guideline] Wann LS, Curtis AB, Ellenbogen KA, Estes NA 3rd, Ezekowitz MD, Jackman WM, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on Dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Mar 15. 123(10):1144-50. [Medline]. [Full Text].
Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012 Mar 12. 172(5):397-402. [Medline].
[Guideline] Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Jan. 42(1):227-76. [Medline]. [Full Text].
Hughes S. Endovascular Stroke Therapy Proven at Last: MR CLEAN Published. Medscape Medical News. Dec 17 2014. [Full Text].
Berkhemer OA, Fransen PS, Beumer D, et al. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med. 2014 Dec 17. [Medline].
Anderson P. Wait on elective surgery after stroke. Medscape Medical News. July 17, 2014. [Full Text].
Chiong W, Kim AS, Huang IA, Farahany NA, Josephson SA. Testing the presumption of consent to emergency treatment for acute ischemic stroke. JAMA. 2014 Apr 23-30. 311(16):1689-91. [Medline].
Ebinger M, Winter B, Wendt M, Weber JE, Waldschmidt C, Rozanski M, et al. Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke: a randomized clinical trial. JAMA. 2014 Apr 23-30. 311(16):1622-31. [Medline].
Fonarow GC, Zhao X, Smith EE, Saver JL, Reeves MJ, Bhatt DL, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA. 2014 Apr 23-30. 311(16):1632-40. [Medline].
Hughes S. DESTINY II: benefit of surgery for stroke with swelling. Medscape Medical News. March 24, 2014. [Full Text].
Jeffrey S. TARGET: STROKE Cuts Door-to-Needle Time, Improves Outcomes. Medscape Medical News. Available at http://www.medscape.com/viewarticle/824008. Accessed: April 29, 2014.
Jørgensen ME, Torp-Pedersen C, Gislason GH, Jensen PF, Berger SM, Christiansen CB, et al. Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery. JAMA. 2014 Jul 16. 312(3):269-77. [Medline].
Jüttler E, Unterberg A, Woitzik J, Bösel J, Amiri H, Sakowitz OW, et al. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014 Mar 20. 370(12):1091-100. [Medline].
Ropper AH. Hemicraniectomy--to halve or halve not. N Engl J Med. 2014 Mar 20. 370(12):1159-60. [Medline].
Shiber JR, Fontane E, Adewale A. Stroke registry: hemorrhagic vs ischemic strokes. Am J Emerg Med. 2010 Mar. 28(3):331-3. [Medline].
|VASCULAR TERRITORY||Structures Supplied|
|Anterior Circulation (Carotid)|
|Anterior Cerebral Artery||Cortical branches: medial frontal and parietal lobe
Medial lenticulostriate branches: caudate head, globus pallidus, anterior limb of internal capsule
|Middle Cerebral Artery||Cortical branches: lateral frontal and parietal lobes lateral and anterior temporal lobe
Lateral lenticulostriate branches: globus pallidus and putamen, internal capsule
|Anterior Choroidal Artery||Optic tracts, medial temporal lobe, ventrolateral thalamus, corona radiata, posterior limb of the internal capsule|
|Posterior Circulation (Vertebrobasilar)|
|Posterior Cerebral Artery||Cortical branches: occipital lobes, medial and posterior temporal and parietal lobes
Perforating branches: brainstem, posterior thalamus and midbrain
|Posterior Inferior Cerebellar Artery||Inferior vermis; posterior and inferior cerebellar hemispheres|
|Anterior Inferior Cerebellar Artery||Anterolateral cerebellum|
|Superior Cerebellar Artery||Superior vermis; superior cerebellum|
|1a||level of consciousness (LOC)||Alert
|1b||LOC questions (month, age)||Answers both correctly
Answers 1 correctly
Incorrect on both
|1c||LOC commands (open and close eyes,
grip and release nonparetic hand)
|Obeys both correctly
Obeys 1 correctly
Incorrect on both
|2||Best gaze (follow finger)||Normal
Partial gaze palsy
|3||Best visual (visual fields)||No visual loss
|4||Facial palsy (show teeth, raise brows,
squeeze eyes shut)
|5||Motor arm left* (raise 90°, hold 10 seconds)||No drift
Cannot resist gravity
No effort against gravity
|6||Motor arm right* (raise 90°, hold 10 seconds)||No drift
Cannot resist gravity
No effort against gravity
|7||Motor leg left* (raise 30°, hold 5 seconds)||No drift
Cannot resist gravity
No effort against gravity
|8||Motor leg right* (raise 30°, hold 5 seconds)||No drift
Cannot resist gravity
No effort against gravity
|9||Limb ataxia (finger-nose, heel-shin)||Absent
Present in 1 limb
Present in 2 limbs
|10||Sensory (pinprick to face, arm, leg)||Normal
|11||Extinction/neglect (double simultaneous testing)||No neglect
|12||Dysarthria (speech clarity to "mama,
baseball, huckleberry, tip-top, fifty-fifty")
Mild to moderate dysarthria
Near to unintelligible or worse
|13||Best language** (name items,
Mild to moderate aphasia
|* For limbs with amputation, joint fusion, etc, score 9 and explain.
** For intubation or other physical barriers to speech, score 9 and explain. Do not add 9 to the total score. NIH Stroke Scale (PDF)