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Ischemic Stroke in Emergency Medicine

The terms intracerebral hemorrhage and hemorrhagic stroke are used interchangeably in this article and are regarded as separate entities from hemorrhagic transformation of ischemic stroke. Hemorrhagic stroke is less common than ischemic stroke (ie, stroke caused by thrombosis or embolism); epidemiologic studies indicate that only 8-18% of strokes are hemorrhagic.[1] However, hemorrhagic stroke is associated with higher mortality rates than is ischemic stroke. (See Epidemiology.)[2] Patients with hemorrhagic stroke present with focal neurologic deficits similar to those of ischemic stroke but tend to be more ill than are patients with ischemic stroke. However, though patients with intracerebral bleeds are more likely to have headache, altered mental status, seizures, nausea and vomiting, and/or marked hypertension, none of these findings reliably distinguishes between hemorrhagic and ischemic stroke. (See Presentation.)[3] Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be obtained on an emergent basis (see the image below). Brain imaging aids in excluding ischemic stroke, and it may identify complications of hemorrhagic stroke such as intraventricular hemorrhage, brain edema, and hydrocephalus. Either noncontrast computed tomography (NCCT) scanning or magnetic resonance imaging (MRI) is the modality of choice. For more information, see Ischemic Stroke in Emergency Medicine. (See Workup.)

Axial noncontrast computed tomography scan of the brain of a 60-yearold man with a history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are seen in the right lentiform nucleus, with surrounding edema and effacement of the adjacent cortical sulci and right sylvian fissure. Mass effect is present upon the frontal horn of the right lateral ventricle, with intraventricular extension of the hemorrhage. The treatment of patients with acute stroke depends on the cause and severity of the bleeding. Basic life support, as well as control of bleeding, seizures, blood pressure (BP), and intracranial pressure, are critical. Surgical evacuation of the hematoma is a potential therapeutic option, but it remains controversial. (See Treatment.) For patient education information, see the Stroke Health Center, as well as Stroke.

Anatomy

Knowledge of cerebrovascular arterial anatomy and the brain regions supplied by the arteries is useful in determining which vessels are involved in acute stroke. Atypical patterns that do not conform to a vascular distribution may indicate another diagnosis, such as venous infarction. The cerebral hemispheres are supplied by 3 paired major arteries: the anterior, middle, and posterior cerebral arteries. The anterior and middle cerebral arteries are responsible for the anterior circulation and arise from the supraclinoid internal carotid arteries. The posterior cerebral arteries arise from the basilar artery and form the posterior circulation, which also supplies the thalami, brainstem, and cerebellum. The angiograms in the images below demonstrate some portions of the circulation involved in hemorrhagic strokes.

Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery illustrates the anterior circulation. The anterior cerebral artery consists of the A1 segment proximal to the anterior communicating artery with the A2 segment distal to it. The middle cerebral artery can be divided into 4 segments: the M1 (horizontal segment) extends to the limen insulae and gives off lateral lenticulostriate branches, the M2 (insular segment), M3 (opercular branches), and M4 (distal cortical branches on the lateral hemispheric convexities).

Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery (ACA) and sylvian triangle. The pericallosal artery has been described as arising distal to the anterior communicating artery or distal to the origin of the

callosomarginal branch of the ACA. The segmental anatomy of the ACA has been described as follows: (1) the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior communicating artery, (2) A2 extends to the junction of the rostrum and genu of the corpus callosum, (3) A3 extends into the bend of the genu of the corpus callosum, and (4) A4 and A5 extend posteriorly above the callosal body and superior portion of the splenium. The sylvian triangle overlies the opercular branches of the middle cerebral artery, with the apex

representing the sylvian point. Frontal projection from a right vertebral artery angiogram illustrates the posterior circulation. The vertebral arteries join to form the basilar artery. The posterior inferior cerebellar arteries (PICA) arise from the distal vertebral arteries. The anterior inferior cerebellar arteries (AICA) arise from the proximal basilar artery. The superior cerebellar arteries (SCA) arise distally from the basilar artery before its bifurcation into the posterior cerebral arteries.

Pathophysiology

In intracerebral hemorrhage, bleeding occurs directly into the brain parenchyma. The usual mechanism is thought to be leakage from small intracerebral arteries damaged by chronic hypertension. Other mechanisms include bleeding diatheses, iatrogenic anticoagulation, cerebral amyloidosis, and cocaine abuse. Intracerebral hemorrhage has a predilection for certain sites in the brain, including the thalamus, putamen, cerebellum, and brainstem. In addition to the area of the brain injured by the hemorrhage, the surrounding brain can be damaged by pressure produced by the mass effect of the hematoma. A general increase in intracranial pressure may occur.

Subarachnoid hemorrhage

The pathologic effects of subarachnoid hemorrhage (SAH) on the brain are multifocal. SAH results in elevated intracranial pressure and impairs cerebral autoregulation. These effects can occur in combination with acute vasoconstriction, microvascular platelet aggregation, and loss of microvascular perfusion, resulting in profound reduction in blood flow and cerebral ischemia.[4] See the images below.

Noncontrast computed tomography (CT) scanning was performed emergently in a 71-year-old man who presented with acute onset of severe headache and underwent rapid neurologic deterioration requiring intubation. The noncontrast CT scan (left image) demonstrates diffuse, high-density subarachnoid hemorrhage in the basilar cisterns and both Sylvian fissures. There is diffuse loss of gray-white differentiation. The fluid-attenuated inversion-recovery (FLAIR) image (right) demonstrates high signal throughout the cortical sulci and in the basilar cisterns, as well as in the dependent portions of the ventricles. FLAIR is highly sensitive to acute subarachnoid hemorrhage; the suppression of high cerebrospinal fluid signal aids in making subarachnoid hemorrhage more conspicuous than do conventional magnetic resonance imaging sequences.

Computed tomographic angiography examination and subsequent cerebral angiography were performed in 71-year-old man who presented with acute onset of severe headache and underwent rapid neurologic deterioration. Multiple aneurysms were identified, including a 9-mm aneurysm at the junction of the anterior cerebral and posterior communicating arteries seen on this lateral view of an internal carotid artery injection. Balloon-assisted coil

embolization was performed. Lateral view of a selective injection of the left internal carotid artery demonstrates a microcatheter passing distal to the aneurysm neck. This lateral view from an angiogram performed during balloon-assisted coil embolization demonstrates significantly diminished filling of the aneurysm.

Etiology
The etiologies of stroke are varied, but they can be broadly categorized into ischemic or hemorrhagic. Approximately 80-87% of strokes are from ischemic infarction caused by thrombotic or embolic cerebrovascular occlusion. Intracerebral hemorrhages account for most of the remainder of strokes, with a smaller number resulting from aneurysmal subarachnoid hemorrhage.[5, 6, 7, 8] In 20-40% of patients with ischemic infarction, hemorrhagic transformation may occur within 1 week after ictus.[9, 10] Differentiating between the different types of stroke is an essential part of the initial workup of patients with stroke, as the subsequent management of each disorder will be vastly different.
Risk factors

The risk of hemorrhagic stroke is increased with the following factors:


Advanced age Hypertension (up to 60% of cases) Previous history of stroke Alcohol abuse Use of illicit drugs (eg, cocaine, other sympathomimetic drugs)

Causes of hemorrhagic stroke include the following[8, 9, 11, 12, 13] :


Hypertension Cerebral amyloidosis

Coagulopathies Anticoagulant therapy Thrombolytic therapy for acute myocardial infarction (MI) or acute ischemic stroke (can cause iatrogenic hemorrhagic transformation) Arteriovenous malformation (AVM), aneurysms, and other vascular malformations (venous and cavernous angiomas) Vasculitis Intracranial neoplasm

Amyloidosis Cerebral amyloidosis affects people who are elderly and may cause up to 10% of intracerebral hemorrhages. Rarely, cerebral amyloid angiopathy can be caused by mutations in the amyloid precursor protein and is inherited in an autosomal dominant fashion. Coagulopathies Coagulopathies may be acquired or inherited. Liver disease can result in a bleeding diathesis. Inherited disorders of coagulation such as factor VII, VIII, IX, X, and XIII deficiency can predispose to excessive bleeding, and intracranial hemorrhage has been seen in all of these disorders. Anticoagulant therapy Anticoagulant therapy is especially likely to increase hemorrhage risk in patients who metabolize warfarin inefficiently. Warfarin metabolism is influenced by polymorphism in the CYP2C9 genes. Three known variants have been described. CYP2C9*1 is the normal variant and is associated with typical response to dosage of warfarin. Variations *2 and *3 are relatively common polymorphisms that reduce the efficiency of warfarin metabolism.[14] Atrioventricular malformations Numerous genetic causes may predispose to AVMs in the brain, although AVMs are generally sporadic. Polymorphisms in the IL6 gene increase susceptibility to a number of disorders, including AVM. Hereditary hemorrhagic telangiectasia (HHT), previously known as OslerWeber-Rendu syndrome, is an autosomal dominant disorder that causes dysplasia of the vasculature. HHT is caused by mutations in ENG, ACVRL1, or SMAD4 genes. Mutations in SMAD4 are also associated with juvenile polyposis, so this must be considered when obtaining the patients history. HHT is most frequently diagnosed when patients present with telangiectasias on the skin and mucosa or with chronic epistaxis from AVMs in the nasal mucosa. Additionally, HHT can result

in AVMs in any organ system or vascular bed. AVM in the gastrointestinal tract, lungs, and brain are the most worrisome, and their detection is the mainstay of surveillance for this disease. Hypertension The most common etiology of primary hemorrhagic stroke (intracerebral hemorrhage) is hypertension. At least two thirds of patients with primary intraparenchymal hemorrhage are reported to have preexisting or newly diagnosed hypertension. Hypertensive small-vessel disease results from tiny lipohyalinotic aneurysms that subsequently rupture and result in intraparenchymal hemorrhage. Typical locations include the basal ganglia, thalami, cerebellum, and pons.
Aneurysms and subarachnoid hemorrhage

The most common cause of atraumatic hemorrhage into the subarachnoid space is rupture of an intracranial aneurysm. Aneurysms are focal dilatations of arteries, with the most frequently encountered intracranial type being the berry (saccular) aneurysm. Aneurysms may less commonly be related to altered hemodynamics associated with AVMs, collagen vascular disease, polycystic kidney disease, septic emboli, and neoplasms. Nonaneurysmal perimesencephalic subarachnoid hemorrhage may also be seen. This phenomenon is thought to arise from capillary or venous rupture. It has a less severe clinical course and, in general, a better prognosis. Berry aneurysms are most often isolated lesions whose formation results from a combination of hemodynamic stresses and acquired or congenital weakness in the vessel wall. Saccular aneurysms typically occur at vascular bifurcations, with more than 90% occurring in the anterior circulation. Common sites include the following:

The junction of the anterior communicating arteries and anterior cerebral arteriesmost commonly, the middle cerebral artery (MCA) bifurcation The supraclinoid internal carotid artery at the origin of the posterior communicating artery The bifurcation of the internal carotid artery (ICA)

Genetic causes of aneurysms Intracranial aneurysms may result from genetic disorders. Although rare, several families have been described that have a predispositioninherited in an autosomal dominant fashionto intracranial berry aneurysms. A number of genes, all categorized as ANIB genes, are associated with this predisposition. Presently, ANIB1 through ANIB11 are known. Autosomal dominant polycystic kidney disease (ADPKD) is another cause of intracranial aneurysm. Families with ADPKD tend to show phenotypic similarity with regard to intracranial hemorrhage or asymptomatic berry aneurysms.[15]

Loeys-Dietz syndrome (LDS) consists of craniofacial abnormalities, craniosynostosis, marked arterial tortuosity, and aneurysms and is inherited in an autosomal dominant manner. Although intracranial aneurysms occur in LDS of all types, saccular intracranial aneurysms are a prominent feature of LDS type IC, which is caused by mutations in the SMAD3 gene.[16] Ehlers-Danlos syndrome is a group of inherited disorders of the connective tissue that feature hyperextensibility of the joints and changes to the skin, including poor wound healing, fragility, and hyperextensibility. However, Ehlers-Danlos vascular type (type IV) also is known to cause spontaneous rupture of hollow viscera and large arteries, including arteries in the intracranial circulation. Patients with Ehlers-Danlos syndrome may also have mild facial findings, including lobeless ears, a thin upper lip, and a thin, sharp nose. The distal fingers may appear prematurely aged (acrogeria). In the absence of a suggestive family history, it is difficult to separate Ehlers-Danlos vascular type from other forms of Ehlers-Danlos. Ehlers-Danlos vascular type is caused by mutations in the COL3A1 gene; it is inherited in an autosomal dominant manner. See Genetic and Inflammatory Mechanisms in Stroke, as well as Blood Dyscrasias and Stroke. Information on metabolic diseases and stroke can be found in the following articles:

Methylmalonic Acidemia Homocystinuria/Homocysteinemia Fabry Disease MELAS Mitochondrial Encephalomyopathy, Lactic Acidosis, Strokelike Episodes Hyperglycemia/Hypoglycemia

Hemorrhagic transformation of ischemic stroke

Hemorrhagic transformation represents the conversion of a bland infarction into an area of hemorrhage. Proposed mechanisms for hemorrhagic transformation include reperfusion of ischemically injured tissue, either from recanalization of an occluded vessel or from collateral blood supply to the ischemic territory or disruption of the blood-brain barrier. With disruption of the blood-brain barrier, red blood cells extravasate from the weakened capillary bed, producing petechial hemorrhage or frank intraparenchymal hematoma.[8, 9, 17] (For more information, see Reperfusion Injury in Stroke.) Hemorrhagic transformation of an ischemic infarct occurs within 2-14 days postictus, usually within the first week. It is more commonly seen following cardioembolic strokes and is more likely with larger infarct size.[8, 10, 18] Hemorrhagic transformation is also more likely following administration of tissue plasminogen activator (tPA) in patients whose noncontrast computed tomography (CT) scans demonstrate areas of hypodensity.[19, 20, 17] See the image below.

Noncontrast computed tomography scan (left) obtained in a 75-year-old man who was admitted for stroke demonstrates a large right middle cerebral artery distribution infarction with linear areas of developing hemorrhage. These become more confluent on day 2 of hospitalization (middle image), with increased mass effect and midline shift. There is massive hemorrhagic transformation by day 6 (right), with increased leftward midline shift and subfalcine herniation. Obstructive hydrocephalus is also noted, with dilatation of the lateral ventricles, likely due to compression of the foramen of Monroe. Intraventricular hemorrhage is also noted layering in the left occipital horn. Larger infarctions are more likely to undergo hemorrhagic transformation and are one contraindication to thrombolytic therapy.

Prognosis
he prognosis in patients with hemorrhagic stroke varies depending on the severity of stroke and the location and the size of the hemorrhage. Lower Glasgow Coma Scale (GCS) scores are associated with poorer prognosis and higher mortality rates. A larger volume of blood at presentation is also associated with a poorer prognosis. Growth of the hematoma volume is associated with a poorer functional outcome and increased mortality rate. The intracerebral hemorrhage score is the most commonly used instrument for predicting outcome in hemorrhagic stroke. The score is calculated as follows:

GCS score 3-4: 2 points GCS score 5-12: 1 point GCS score 13-15: 0 points Age 80 years: Yes, 1 point; no, 0 points Infratentorial origin: Yes, 1 point; no, 0 points Intracerebral hemorrhage volume 30 cm3: 1 point Intracerebral hemorrhage volume < 30 cm3: 0 points Intraventricular hemorrhage: Yes, 1 point; no, 0 points

In a study by Hemphill et al, all patients with an Intracerebral Hemorrhage Score of 0 survived, and all of those with a score of 5 died; 30-day mortality increased steadily with the Score.[27]

Other prognostic factors include the following:


Nonaneurysmal perimesencephalic stroke has a less severe clinical course and, in general, a better prognosis The presence of blood in the ventricles is associated with a higher mortality rate; in one study, the presence of intraventricular blood at presentation was associated with a mortality increase of more than 2-fold Patients with oral anticoagulation-associated intracerebral hemorrhage have higher mortality rates and poorer functional outcomes

In studies, withdrawal of medical support or issuance of Do Not Resuscitate (DNR) orders within the first day of hospitalization predict poor outcome independent of clinical factors. Because limiting care may adversely impact outcome, American Heart Association/American Stroke Association (AHA/ASA) guidelines suggest that new DNR orders should probably be postponed until at least the second full day of hospitalization. Patients with DNRs should be given all other medical and surgical treatment, unless the DNR explicitly says otherwise.[28] For more information, see Motor Recovery in Stroke.

Approach Considerations
The treatment and management of patients with acute intracerebral hemorrhage depends on the cause and severity of the bleeding. Basic life support, as well as control of bleeding, seizures, blood pressure (BP), and intracranial pressure, are critical. Medications used in the treatment of acute stroke include the following:

Anticonvulsants - To prevent seizure recurrence Antihypertensive agents - To reduce BP and other risk factors of heart disease Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space

Management begins with stabilization of vital signs. Perform endotracheal intubation for patients with a decreased level of consciousness and poor airway protection. Intubate and hyperventilate if intracranial pressure is elevated, and initiate administration of mannitol for further control. Rapidly stabilize vital signs, and simultaneously acquire an emergent computed tomography (CT) scan. Glucose levels should be monitored, with normoglycemia recommended.[28] Antacids are used to prevent associated gastric ulcers. Currently, no effective targeted therapy for hemorrhagic stroke exists. Studies of recombinant factor VIIa (rFVIIa) have yielded disappointing results. Evacuation of hematoma, either via open craniotomy or endoscopy, may be a promising ultra-early-stage treatment for intracerebral hemorrhage that may improve long-term prognosis.

Management of Seizures

Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage; these seizures are often nonconvulsive.[30, 31] According to American Heart Association/American Stroke Association (AHA/ASA) 2010 guidelines for the management of spontaneous intracerebral hemorrhage, patients with clinical seizures or electroencephalographic (EEG) seizure activity accompanied by a change in mental status should be treated with antiepileptic drugs.[28] Patients for whom treatment is indicated should immediately receive a benzodiazepine, such as lorazepam or diazepam, for rapid seizure control. This should be accompanied by phenytoin or fosphenytoin loading for longer-term control.
Prophylaxis

The utility of prophylactic anticonvulsant medication remains uncertain. In prospective and population-based studies, clinical seizures have not been associated with worse neurologic outcome or mortality. Indeed, 2 studies have reported worse outcomes in patients who did not have a documented seizure but who received antiepileptic drugs (primarily phenytoin).[28] The 2010 AHA/ASA guidelines do not offer recommendations on prophylactic anticonvulsants, but suggest that continuous EEG monitoring is probably indicated in patients with intracranial hemorrhage whose mental status is depressed out of proportion to the degree of brain injury Prophylactic anticonvulsant therapy has been recommended in patients with lobar hemorrhages to reduce the risk of early seizures. One large, single-center study showed that prophylactic antiepileptic drugs significantly reduced the number of clinical seizures in these patients.[30] In addition, AHA/ASA guidelines from 2012 suggest that prophylactic anticonvulsants may be considered for patients with aneurysmal subarachnoid hemorrhage. In such cases, however, anticonvulsant use should generally be limited to the immediate post-hemorrhagic period. Routine long-term use is not recommended, but it may be considered in patients with a prior seizure history, intracerebral hematoma, intractable hypertension, or infarction or aneurysm at the middle cerebral artery.[32]

Blood Pressure Control


No controlled studies have defined optimum BP levels for patients with acute hemorrhagic stroke, but greatly elevated BP is thought to lead to rebleeding and hematoma expansion. Stroke may result in loss of cerebral autoregulation of cerebral perfusion pressure. Suggested agents for use in the acute setting are beta blockers (eg, labetalol) and angiotensinconverting enzyme inhibitors (ACEIs) (eg, enalapril). For more refractory hypertension, agents such as nicardipine and hydralazine are used. Avoid nitroprusside because it may raise intracranial pressure. The 2010 AHA/ASA guidelines acknowledge that evidence for the efficacy of managing BP in hemorrhagic stroke is currently incomplete. With that caveat, the AHA/ASA recommendations for treating elevated BP are as follows[28] :

If systolic BP is over 200 mm Hg or mean arterial pressure (MAP) is over 150 mm Hg, then consider aggressive reduction of BP with continuous IV infusion; check BP every 5 minutes If systolic BP is over 180 mm Hg or MAP is over 130 mm Hg and intracranial pressure may be elevated, then consider monitoring intracranial pressure and reducing BP using intermittent or continuous intravenous medications, while maintaining a cerebral perfusion pressure of 60 mm Hg or higher If systolic BP is over 180 or MAP is over 130 mm Hg and there is no evidence of elevated intracranial pressure, then consider modest reduction of BP (target MAP of 110 mm Hg or target BP of 160/90 mm Hg) using intermittent or continuous intravenous medications to control it, and perform clinical reexamination of the patient every 15 minutes In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe

For patients with aneurysmal subarachnoid hemorrhage, the 2012 AHA/ASA guidelines recommend lowering BP below 160 mmHg acutely to reduce rebleeding.[32] The ongoing Antihypertensive Treatment in Acute Cerebral Hemorrhage-II (ATACH-II) phase 3 randomized clinical trial is designed to determine whether the likelihood of death or disability at 3 months after spontaneous supratentorial intracerebral hemorrhage is lower when systolic BP has been reduced to 180 mm Hg or below or to 140 mm Hg or below. In ATACH-II, intravenous nicardipine is started within 3 hours of stroke onset and continued for the next 24 hours.

Intracranial Pressure Control


Elevated intracranial pressure may result from the hematoma itself, from surrounding edema, or from both. The frequency of increased intracranial pressure in patients with intracerebral hemorrhage is not known. Elevate the head of the bed to 30. This improves jugular venous outflow and lowers intracranial pressure. The head should be midline and not turned to the side. Provide analgesia and sedation as needed. Antacids are used to prevent gastric ulcers associated with intracerebral hemorrhage. More aggressive therapies, such as osmotic therapy (ie, mannitol, hypertonic saline), barbiturate anesthesia, and neuromuscular blockage, generally require concomitant monitoring of intracranial pressure and BP with an intracranial pressure monitor to maintain adequate cerebral perfusion pressure of greater than 70 mm Hg. A randomized, controlled study of mannitol in intracerebral hemorrhage failed to demonstrate any difference in disability or death at 3 months.
[33]

Hyperventilation (partial pressure of carbon dioxide [PaCO2] of 25 to 30-35 mm Hg) is not recommended, because its effect is transient, it decreases cerebral blood flow, and it may result

in rebound elevated intracranial pressure.[2] Glucocorticoids are not effective and result in higher rates of complications with poorer outcomes

Treatment of Anticoagulation-associated Intracranial Hemorrhage


Patients on warfarin have an increased incidence of hemorrhagic stroke. Morbidity and mortality for warfarin-associated bleeding is high, with over one half of patients dying within 30 days. Most episodes occur with a therapeutic international normalized ratio (INR), but overanticoagulation is associated with an even greater risk of bleeding. The need to reverse warfarin anticoagulation is a true medical emergency, and reversal must be accomplished as quickly as possible to prevent further hematoma expansion. Options for reversal therapy include the following:

Intravenous vitamin K Fresh frozen plasma (FFP) Prothrombin complex concentrates (PCC) rFVIIa

FFP versus PCC

Because vitamin K requires more than 6 hours to normalize the INR, it should be administered with either FFP or PCC. FFP is the standard of care in the United States[39] ; however, FFP needs to be given in a dose of 15-20 mL/kg and therefore requires a large-volume infusion. PCC contains high levels of vitamin K-dependent cofactors and thus involves a smaller-volume infusion than FFP and more rapid administration.[40, 41] However, PCC is associated with high rates of thrombotic complications. No randomized, controlled trial has studied the safety and efficacy of FFP versus PCC for reversing the effects of warfarin in patients with intracranial hemorrhage. The International Normalised ratio normalisation in patients with Coumarin-related intracranial Haemorrhages (INCH) trial, a prospective, randomized, controlled, multicenter trial comparing the 2 agents, began recruiting subjects in 2009.[42]
FVIIa

Based upon the available medical evidence, the use of FVIIa is currently not recommended over other agents. The PCC available in the United States contains only low levels of FVII, however, and Sarode et al have described successful, rapid reversal of vitamin K antagonistrelated coagulopathy using a combination of low-dose FVIIa with PCC, although they note the need for caution in patients at high risk for thrombosis.[39]

Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who develop a hemorrhagic stroke should immediately have anticoagulation reversed with protamine. [2] The dose of protamine is dependent upon the dose of heparin that was given and the time elapsed since that dose. Patients with severe deficiency of a specific coagulation factor who develop spontaneous intracerebral hemorrhage should receive factor replacement therapy.[28]
Reversal of antiplatelet therapy and platelet dysfunction

There is controversy about whether patients on antiplatelet medications (eg, aspirin, aspirin/dipyridamole [Aggrenox], clopidogrel) should be given desmopressin (DDAVP) and/or platelet transfusions. Patients with renal failure and platelet dysfunction may also benefit from the administration of desmopressin (DDAVP). The 2010 AHA/ASA guideline for management of spontaneous intracerebral hemorrhage recommends platelet transfusions only when such hemorrhaging complicates severe thrombocytopenia.[28]

Prevention of Hemorrhagic Stroke


Antihypertensives

The 2010 AHA/ASA guidelines for spontaneous ICH recommend that after acute intracerebral hemorrhage, patients without medical contraindications should have BP well controlled, especially for hemorrhage in typical hypertensive vasculopathy locations.[28] In addition, the guidelines strongly recommend maintenance of BP below 140/90 mm Hg to prevent a first stroke. In patients with hypertension plus either diabetes or renal disease, the treatment goal is BP below 130/80 mm Hg.[53] BP-lowering medications include thiazide diuretics, calcium channel blockers, angiotensinconverting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). For patients with diabetes, the use of ACEIs and ARBs to treat hypertension is a class I-A recommendation (strongest and best-documented), according to the 2011 AHA/ASA primary prevention guidelines.[28] Beta blockers are considered second-line agents given their inferiority in preventing vascular events, despite producing similar reductions in BP. (Adverse effects of ACEIs include cough [10%], which is less common with ARBs.) Although statin therapy is recommended for primary prevention of ischemic stroke (class I-A recommendation),[53] especially if other risk factors are present, some studies have found an increased risk of intracerebral hemorrhage with statin use. However, a meta-analysis of 31 randomized, controlled trials of statin therapy found that active statin therapy was not associated with a significant increase in intracerebral hemorrhage.[54] In the Heart Outcomes Prevention Evaluation (HOPE) study, the addition of the ACEI ramipril to all other medical therapy, including antiplatelet agents, reduced the relative risk of stroke, death, and myocardial infarction by 32% compared with placebo.[55] Only 40% of the efficacy of

ramipril could be attributed to its BP-lowering effects. Other postulated mechanisms included endothelial protection. Whether the beneficial effect of ramipril represents a class effect of ACEIs or whether it is a property unique to ramipril is unclear. In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a regimen based on perindopril, an ACEI, was superior to placebo.[56] Although this drug alone was not superior to placebo, the combination of perindopril with indapamide (a thiazide diuretic) substantially reduced the recurrence of stroke.[56] Much of the effect in reducing stroke recurrence was attributable to the lowering of BP, in contrast to findings for ramipril from the HOPE study. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed slight superiority of chlorthalidone (a thiazide diuretic) over lisinopril (an ACEI) in terms of stroke occurrence.[57] The Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE) demonstrated that an ARB (losartan) was superior to a beta blocker (atenolol) in reducing the occurrence of stroke.[58] The Morbidity and Mortality after Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study found that the ARB eprosartan was superior to the calcium channel blocker nitrendipine in the secondary prevention of stroke and transient ischemic attack (TIA).[59] This was true despite comparable BP reductions. The absolute annual difference in stroke and TIA risk was approximately 4%. The study was relatively small, and most events were TIAs.
Lifestyle interventions

Smoking cessation, a low-fat diet (eg, Dietary Approaches to Stop Hypertension [DASH] or Mediterranean diets), weight loss, and regular exercise should be encouraged as strongly as pharmacologic treatment. Written prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions. Reducing sodium intake and increasing consumption of foods high in potassium to reduce BP may also help in primary prevention.[53] High alcohol intake should be reduced, as drinking more than 30 drinks per month has been tied to increased risk of intracerebral hemorrhage. Exercise A Finnish study showed that the likelihood of stroke in men with the lowest degree of physical fitness (maximal oxygen uptake [VO2max] < 25.2 mL/kg/min) was more than 3 times greater than in men with the highest degree of physical fitness (VO2max >35.3 mL/kg/min).[60] level of physical fitness was a more powerful risk factor than low-density lipoprotein cholesterol level, body mass index, and smoking, and it was nearly comparable to hypertension as a risk factor.

The 2011 AHA/ASA guidelines for the primary prevention of stroke, which address hemorrhagic and ischemic stroke, emphasize exercise and other lifestyle modifications. The guidelines endorse the 2008 Physical Activity Guidelines for Americans, which include a recommendation of at least 150 minutes per week of moderate-intensity aerobic physical activity.[53]

ischemic stroke
Practice Essentials
Stroke is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Strokes are classified as either hemorrhagic or ischemic. Acute ischemic stroke refers to stroke caused by thrombosis or embolism and is more common than hemorrhagic stroke.
Essential update: Certain antipsychotics associated with greater risk of stroke

An analysis of 14,584 stroke patients who had at least 1 antipsychotic prescription during the year before their first hospitalization for stroke indicates that antipsychotics with a high binding affinity for alpha-2-adrenergic and M1-muscarinic receptors are associated with a greater risk for stroke than other types of antipsychotics. Overall, use of any antipsychotic in the 2 weeks before the stroke occurred was associated with a 1.6-fold increased risk. This association was observed only in the initial 28 days of antipsychotic use, was dose related, and was noted in patients who were older and/or had dementia.[1]
Signs and symptoms

Although signs and symptoms of stroke can occur alone, they are more likely to occur in combination. Common stroke signs and symptoms include the following:

Abrupt onset of hemiparesis, monoparesis, or quadriparesis Acute hemisensory loss Complete or partial hemianopia, monocular or binocular visual loss, or diplopia Visual field deficits Diplopia Dysarthria Ataxia

Vertigo Nystagmus Aphasia Sudden decrease in the level of consciousness

In younger patients, a history of recent trauma, coagulopathies, illicit drug use (especially cocaine), migraines, or use of oral contraceptives should be elicited. See Clinical Presentation for more detail.
Diagnosis

With the availability of thrombolytic therapy for acute ischemic stroke in selected patients, the physician must be able to perform a brief, but accurate, neurologic examination on patients with suspected stroke syndromes. Essential components of the neurologic examination include evaluations of the following:

Cranial nerves Motor function Sensory function Cerebellar function Gait Deep tendon reflexes Mental status level of consciousness

The patients skull and spine also should be examined, and signs of meningismus should be sought. Laboratory studies Laboratory tests performed in the diagnosis and evaluation of ischemic stroke include the following:

Complete blood cell count: The CBC count serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia, thrombocytosis, thrombocytopenia, leukemia) or provide evidence of concurrent illness (eg, anemia) Basic chemistry panel: The chemistry panel serves as a baseline study and may reveal a stroke mimic (eg, hypoglycemia, hyponatremia) or provide evidence of concurrent illness (eg, diabetes, renal insufficiency)

Coagulation studies: Coagulation studies may reveal a coagulopathy and are useful when thrombolytics or anticoagulants are to be used Cardiac biomarkers: Cardiac biomarkers are important because of the association of cerebral vascular disease and coronary artery disease Toxicology screening: Toxicology screening may assist in identifying intoxicated patients with symptoms/behavior mimicking stroke syndromes Pregnancy testing: A urine pregnancy test should be obtained for all women of childbearing age with stroke symptoms; recombinant tissue-type plasminogen activator (rt-PA) is a pregnancy class C agent Arterial blood gas analysis: Although infrequent in patients with suspected hypoxemia, arterial blood gas defines the severity of hypoxemia and may be used to detect acid-base disturbances

Imaging studies Imaging in ischemic stroke can involve the following modalities:

Several types of magnetic resonance imaging Several types of computed tomography scanning Angiography Ultrasonography Radiology Echocardiography Nuclear imaging

Lumbar puncture A lumbar puncture is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is negative but the clinical suspicion remains high See Workup for more detail.
Management

Ischemic stroke therapies include the following:

Thrombolytic therapy: Thrombolytics restore cerebral blood flow among some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits

Antiplatelet agents: 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[2, 3] Mechanical thrombolysis: Involves the endovascular treatment of acute ischemic stroke

Stroke prevention Primary stroke prevention refers to the treatment of individuals with no previous history of stroke. Measures may include use of the following:

Platelet antiaggregants 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (ie, statins) Exercise

Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include use of the following:

Platelet antiaggregants Antihypertensives HMG-CoA reductase inhibitors (statins) Lifestyle interventions

See Treatment and Medication for more detail.


Image library

Vascular distributions: ACA infarction. Diffusion-weighted image on the left demonstrates high signal in the paramedian frontal and high parietal regions. The opposite diffusion-weighted image in a different patient demonstrates restricted diffusion in a larger ACA infarction involving the left paramedian frontal and posterior parietal regions. There is also infarction of the lateral temporoparietal regions bilaterally (both MCA distributions), greater on the left indicating multivessel involvement suggesting emboli.

Prognosis

The prognosis after acute ischemic stroke varies greatly, depending on the stroke severity and on the patients premorbid condition, age, and poststroke complications.[5] Some patients experience hemorrhagic transformation of their infarct (See Pathophysiology). This is estimated to occur in 5% of uncomplicated ischemic strokes, in the absence of thrombolytics. Hemorrhagic transformation is not always associated with neurologic decline and ranges from small petechial hemorrhages to hematomas requiring evacuation. In the Framingham and Rochester stroke studies, the overall mortality rate at 30 days after stroke was 28%, the mortality rate at 30 days after ischemic stroke was 19%, and the 1-year survival rate for patients with ischemic stroke was 77%. In the United States, 20% of individuals die within the first year after a first-time stroke, as previously mentioned. Cardiogenic emboli are associated with the highest 1-month mortality in patients with acute stroke. In stroke survivors from the Framingham Heart Study, 31% needed help caring for themselves, 20% needed help when walking, and 71% had impaired vocational capacity in long-term followup. The presence of CT scan evidence of infarction early in presentation has been associated with poor outcome and with an increased propensity for hemorrhagic transformation after thrombolytics.[6, 35, 36] Acute ischemic stroke has been associated with acute cardiac dysfunction and arrhythmia, which then correlate with worse functional outcome and morbidity at 3 months. Data suggest that severe hyperglycemia is independently associated with poor outcome and reduced reperfusion in thrombolysis, as well as extension of the infarcted territory.[37, 38, 39] To see complete information on Motor Recovery in Stroke, please go to the main

Patient Education
Public education must involve all age groups. Incorporating stroke into basic life support (BLS) and cardiopulmonary resuscitation (CPR) curricula is just one way to reach a younger audience. Avenues to reach an audience with a higher stroke risk include using local churches, employers, and senior organizations to promote stroke awareness. The American Stroke Association advises the public to be aware of the symptoms of stroke that are easily recognized and to call 911 immediately. These symptoms include the following:

Sudden numbness or weakness of face, arm, or leg, especially on 1 side of the body Sudden confusion

Sudden difficulty in speaking or understanding Sudden deterioration of vision in 1 or both eyes Sudden difficulty in walking, dizziness, and loss of balance or coordination Sudden, severe headache with no known cause

Physical Examination
The goals of the physical examination include detecting extracranial causes of stroke symptoms, distinguishing stroke from stroke mimics, determining and documenting for future comparison the degree of deficit, and localizing the lesion. The physical examination always includes a careful head and neck examination for signs of trauma, infection, and meningeal irritation. Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or global) or altered level of consciousness. No historical feature distinguishes ischemic from hemorrhagic stroke, although nausea, vomiting, headache, and change in level of consciousness are more common in hemorrhagic strokes. Common symptoms of stroke include the following:

Abrupt onset of hemiparesis, monoparesis, or quadriparesis Hemisensory deficits Monocular or binocular visual loss Visual field deficits Diplopia Dysarthria Ataxia Vertigo Aphasia Sudden decrease in the level of consciousness

Although such symptoms can occur alone, they are more likely to occur in combination. A careful search for the cardiovascular causes of stroke requires examination of the ocular fundi (retinopathy, emboli, hemorrhage), heart (irregular rhythm, murmur, gallop), and peripheral vasculature (palpation of carotid, radial, and femoral pulses, auscultation for carotid bruit).

Patients with a decreased level of consciousness should be assessed to ensure that they are able to protect their airway. The physical examination must encompass all of the major organ systems, starting with the airway, breathing, and circulation (ABC) and the vital signs. Patients with stroke, especially hemorrhagic stroke, can clinically deteriorate quickly; therefore, constant reassessment is critical. Ischemic strokes, unless large or involving the brainstem, do not tend to cause immediate problems with airway patency, breathing, or circulation compromise. On the other hand, patients with intracerebral or subarachnoid hemorrhage frequently require intervention for airway protection and ventilation. Vital signs, while nonspecific, can point to impending clinical deterioration and may assist in narrowing the differential diagnosis. Many patients with stroke are hypertensive at baseline, and their blood pressure may become more elevated after stroke. While hypertension at presentation is common, blood pressure decreases spontaneously over time in most patients. Acutely lowering blood pressure has not proven to be beneficial in these stroke patients in the absence of signs and symptoms of associated malignant hypertension, acute myocardial infarction, CHF, or aortic dissection.
Head and neck examination

A careful examination of the head and neck is essential. Contusions, lacerations, and deformities may suggest trauma as the etiology for the patient's symptoms. Auscultation of the neck may elicit a bruit, suggesting carotid disease as the cause of the stroke.
Cardiac examination

Cardiac arrhythmias, such as atrial fibrillation, are found commonly in patients with stroke. Similarly, strokes may occur concurrently with other acute cardiac conditions, such as acute myocardial infarction and acute CHF; thus, auscultation for murmurs and gallops is recommended.
Examination of the extremities

Carotid or vertebrobasilar dissections and, less commonly, thoracic aortic dissections may cause ischemic stroke. Unequal pulses or blood pressures in the extremities may reflect the presence of aortic dissections.
Neurologic examination

With the availability of thrombolytic therapy for acute ischemic stroke in selected patients, the physician must be able to perform a brief, but accurate, neurologic examination on patients with suspected stroke syndromes. The goals of the neurologic examination include the following:

Confirming the presence of a stroke syndrome (to be defined further by cranial computed tomography [CT] scanning)

Distinguishing stroke from stroke mimics Establishing a neurologic baseline should the patient's condition improve or deteriorate

Essential components of the neurologic examination include the evaluation of cranial nerves, motor function, sensory function, cerebellar function, gait, and deep tendon reflexes, as well as of mental status and level of consciousness. The skull and spine also should be examined, and signs of meningismus should be sought. Central facial weakness from a stroke should be differentiated from the peripheral weakness of Bell palsy. With peripheral lesions (Bell palsy), the patient is unable to lift the eyebrows, wrinkle the forehead, or or close the eye on the affected side. A useful tool in quantifying neurological impairment is the National Institutes of Health Stroke Scale (NIHSS). The NIHSS (see Table 2, below and the NIH Stroke Score calculator) is used mostly by stroke teams. It enables the consultant to rapidly determine the severity and possible location of the stroke. A patient's score on the NIHSS is strongly associated with outcome, and it can help to identify those patients who are likely to benefit from thrombolytic therapy and those who are at higher risk of developing hemorrhagic complications of thrombolytic use. This scale is easily used and focuses on the following 6 major areas of the neurologic examination:

level of consciousness Visual function Motor function Sensation and neglect Cerebellar function Language

Middle cerebral artery stroke

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

ACA occlusions primarily affect frontal lobe function and can result in disinhibition and speech perseveration, producing primitive reflexes (eg, grasping, sucking reflexes), altered mental

status, impaired judgment, contralateral weakness (greater in legs than arms), contralateral cortical sensory deficits gait apraxia, and urinary incontinence.
Posterior cerebral artery stroke

PCA occlusions affect vision and thought, producing contralateral homonymous hemianopsia, cortical blindness, visual agnosia, altered mental status, and impaired memory. Vertebrobasilar artery occlusions are notoriously difficult to detect because they cause a wide variety of cranial nerve, cerebellar, and brainstem deficits. These include the following:

Vertigo Nystagmus Diplopia Visual field deficits Dysphagia Dysarthria Facial hypesthesia Syncope Ataxia

A hallmark of posterior circulation stroke is that there are crossed findings: ipsilateral cranial nerve deficits and contralateral motor deficits. This is contrasted to anterior stroke, which produces only unilateral findings.
Lacunar stroke

Lacunar strokes result from occlusion of the small, perforating arteries of the deep subcortical areas of the brain. The infarcts are generally from 2-20 mm in diameter. The most common lacunar syndromes include pure motor, pure sensory, and ataxic hemiparetic strokes. By virtue of their small size and well-defined subcortical location, lacunar infarcts do not lead to impairments in cognition, memory, speech, or level of consciousness.

Diagnostic Considerations
Stroke mimics commonly confound the clinical diagnosis of stroke. One study reported that 19% of patients diagnosed with acute ischemic stroke by neurologists before cranial CT scanning actually had noncerebrovascular causes for their symptoms. The most frequent stroke mimics include the following:

Seizure (17%) Systemic infection (17%) Brain tumor (15%) Toxic-metabolic cause, such as hyponatremia and hypoglycemia (13%) Positional vertigo (6%).

A critical masquerading metabolic derangement not to be missed by providers is hypoglycemia.


[41, 42]

For more information, see Metabolic Disease and Stroke Hyperglycemia/Hypoglycemia. Diagnosis and management of a rare form of stroke, cerebral venous thrombosis (CVT), was the subject of a 2011 AHA/ASA statement for healthcare professionals. According to the statement, diagnosing CVT requires a high degree of clinical suspicion. Most people diagnosed with CVT present with headache, often of increasing severity, usually but not always accompanied by focal neurological signs.[43]

Differential Diagnoses

Acute Coronary Syndrome Atrial Fibrillation Bell Palsy Benign Positional Vertigo Brain Abscess Epidural Hematoma Hemorrhagic Stroke in Emergency Medicine Inner Ear Labyrinthitis Myocardial Infarction Neoplasms, Brain Subarachnoid Hemorrhage Syncope Transient Ischemic Attack

Approach Considerations

Multiple factors contribute to delays in seeking care for symptoms of stroke. Many strokes occur while patients are sleeping (also known as "wake-up" stroke) and are not discovered until the patient wakes. Stroke can leave some patients too incapacitated to call for help. Occasionally, a stroke goes unrecognized by the patient or their caregivers. (See Diagnostic Considerations).[33, 53] The median time from symptom onset to ED presentation ranges from 4-24 hours in the United States.[21] 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 ACLS instruction, as well as continuing medical education classes, prehospital care providers can remain current on stroke and promote stroke awareness in their own communities. Physician and nursing staff involved in the care of patients who have had a stroke, in the 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. Establishing the time at which stroke symptoms first occurred is of paramount importance when considering patients for possible thrombolytic therapy. An essential question is, "When was the patient last seen to be normal?" It is advisable for emergency clinicians to rapidly enlist the assistance of family members or relatives to establish time of symptom onset and to identify other pertinent components of the patient's presentation history. The central goal of therapy in acute ischemic stroke is to preserve the area of oligemia in the ischemic penumbra. The area of oligemia can be preserved by limiting the severity of ischemic injury (ie, neuronal protection) or by reducing the duration of ischemia (ie, restoring blood flow to the compromised area). Recanalization strategies, including 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. Neuroprotective strategies are intended to preserve the penumbral tissues and to extend the time window for revascularization techniques; however, at the present time, no neuroprotective agents are available and approved for use in ischemic stroke. The ischemic cascade offers many points at which such interventions could be attempted. Multiple strategies and interventions for blocking this cascade are currently under investigation. The timing of the restoration of cerebral blood flow appears to be a critical factor. Time may also prove to be a key factor in neuronal protection. It is expected that neuroprotective agents, which block the earliest stages of the ischemic cascade (eg, glutamate receptor antagonists, calcium channel blockers), will be effective only in the proximal phases of presentation. The American Heart Association (AHA) and American Stroke Association (ASA) released new guidelines for the early management of acute ischemic stroke in January

2013. New features of the guidelines include a focus on the importance of stroke systems of care, a recommendation for the use of tissue plasminogen activator (t-PA) in selected patients presenting within 3 to 4.5 hours of symptom onset, and a recommendation for door-to-needle times within 60 minutes of hospital arrival in patients eligible for thrombolysis.[1, 2]

Emergency Response and Transport


Recognition that a stroke may have occurred and rapid transport to the appropriate receiving facility are necessary after addressing the ABCs. Of patients with signs or symptoms of stroke, 29-65% utilize some facet of the emergency medical services (EMS) system.[56, 57] Furthermore, most patients who call EMS are those who present within 3 hours of symptom onset. EMS use is associated with shorter time periods from symptom onset to hospital arrival.[58, 59] Stroke should be a priority dispatch with prompt EMS response. EMS responders should provide in as timely a manner as possible advance notice to their emergency department destination so as to allow preparation and marshaling of personnel and resources. There is now ongoing development of stroke center designation that would then become the preferred destination for patients with acute stroke symptoms utilizing 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.[21]

Acute Management of Stroke


The goal for the acute management of patients with stroke is to stabilize the patient and to complete initial evaluation and assessment, including imaging and laboratory studies within 60 minutes of patient arrival.[21] A Finnish study demonstrated that time to treatment with thrombolytics can be decreased with changes in EMS and ED coordination and in ED procedures for treating acute stroke patients.[60] Critical decisions focus on blood pressure control, the need for intubation, and determination of risk-tobenefit profile for thrombolytic intervention. Referral to a physician with a special interest in stroke is ideal. Stroke care units exist and improve outcomes with specially trained personnel. Comorbid medical problems need to be addressed. Hypoglycemia and hyperglycemia need to be identified and treated early in the evaluation. 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 >100.4F). Supplemental oxygen is recommended when the patient has a documented oxygen requirement. In the small proportion of patients with stroke who are relatively hypotensive, pharmacologically increasing blood pressure may improve flow through critical stenoses.

An area of continued interest in acute stroke is glucose management. A Cochrane review found that the use of intravenous insulin to maintain serum glucose within the first few hours of ischemic stroke did not improve functional outcome, death, or final neurological deficit and significantly increased the risk of hypoglycemia.[61] The 2011 AHA/ASA statement on CVT notes that appropriate acute therapy should focus on preventing complications and anticoagulation therapy. The recommended tests were MRI and MR venography (MRV) because they are the most sensitive. Blood workup should be performed later based on the underlying causes.[43]