1115 PTG ALG EBM Stroke, Acute Ischemic

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Diseases and Disorders

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i BASIC INFORMATION

DEFINITIONIschemic stroke is the sudden onset of a focal neurologic deficit as a result of ischemia. Acute ischemic stroke may be defined as relating to the first few days after onset of neurologic symptoms. However, the purpose of this chapter is to help the provider make decisions regarding the acute stroke patient within the first several hours of symptoms; this is the crucial time for definitive treatment interventions.

SYNONYMSStrokeBrain attackCerebrovascular accident (this is a nonspecific

term and should not be used.)

ICD-9CM CODES494.31 Ischemic stroke436 Acute strokeICD-10CM CODESI63 Cerebral infarctionI63.3 Cerebral infarction due to thrombosis

of cerebral arteriesI63.4 Cerebral infarction due to embolism

of cerebral arteriesI63.5 Cerebral infarction due to unspecified

occlusion or stenosis of cerebral arteries

I63.6 Cerebral infarction due to cerebral venous thrombosis, nonpyogenic

I63.8 Other cerebral infarctionI63.9 Cerebral infarction, unspecifiedI67.89 Other cerebrovascular disease

EPIDEMIOLOGY & DEMOGRAPHICSINCIDENCE: • ~800,000 new or recurrent strokes occur

each year in the U.S. • Stroke is the number three cause of death

and the leading cause of long-term disability in the U.S.

PREVALENCE: There are ~4.5 million stroke survivors in the U.S.RISK FACTORS: Hypertension, dyslipidemia, diabetes mellitus, and smoking are the four major risk factors. Other risk factors include atrial fibrillation, mechanical heart valve, patent foramen ovale, recent myocardial infarction, carotid stenosis, hypercoagulable states, sub-clinical atrial tachyarrhythmias without clinical atrial fibrillation, sickle cell disease, and obesity.GENETICS: Multifactorial

PHYSICAL FINDINGS & CLINICAL PRESENTATIONClinical presentation varies with the artery and region of CNS affected. Following are some com-mon syndromic presentations. Please note that this list is not comprehensive and that all findings for a particular syndrome may not be listed here. • Large- to medium-sized arteries: C Left middle cerebral artery: right face, arm,

and leg weakness and sensory loss with aphasia (expressive, receptive, or both); possible hemianopia

C Right middle cerebral artery: left face, arm, and leg weakness and sensory loss with hemineglect; possible hemianopia

C Basilar artery: typically an acute loss of consciousness preceded by vertigo, nau-sea, vomiting, and diplopia; quadriparesis or quadriplegia may be seen, including “locked-in” syndrome

C Posterior cerebral artery: unilateral hemi-anopia; blindness with anosognosia (Anton syndrome) if bilateral

C Anterior cerebral artery: unilateral leg weakness and sensory loss

C Cerebellum: ataxia (typically of the limbs), often with vertigo, nausea, and vomiting

• Small arteries (common lacunar syndromes) C Lateral medullary (Wallenberg’s) syndrome C Posterior limb internal capsule

ETIOLOGYEtiologies include atherosclerosis, cardioembo-lism, artery-to-artery embolism, small-vessel lipohyalinosis, arteritis, arterial dissection, and vasospasm.

Dx DIAGNOSIS

DIFFERENTIAL DIAGNOSISThe differential diagnosis of acute ischemic stroke includes hemorrhagic stroke (intra-cerebral hemorrhage), seizure with postictal paralysis, migraine with hemiparesis, syncope, hypoglycemia, hypertensive encephalopathy, and conversion disorder.

LABORATORY TESTS • Immediate (Box 1-82): CBC, metabolic panel

that includes blood glucose and renal func-tion, PT/INR, aPTT, troponin I, and urinalysis

• National Institutes of Health Stroke Scale: a brief, focused neurologic examination aimed at providing a numeric estimate of the sever-ity of stroke; can be performed by any health care provider trained in its use; may increase the likelihood of the correct assessment of stroke

• ECG and telemetry monitoring

All Patients Noncontrast brain computed tomographic

scan (magnetic resonance imaging, if available)

Blood glucose levelSerum electrolyte and renal function testsElectrocardiographyMarkers of cardiac ischemiaComplete blood count, including platelet

count*Prothrombin time/international normalized

ratio*Activated partial thromboplastin time*Oxygen saturation

Selected Patients Hepatic function testsToxicology screenBlood alcohol levelPregnancy testArterial blood gas tests (if hypoxia is

suspected)Chest radiography (if lung disease is

suspected)Lumbar puncture (if subarachnoid hemor-

rhage is suspected and computed to-mography scan is negative for blood)

Electroencephalogram (if seizures are suspected)

BOX 1-82 Immediate Diagnostic Studies: Evaluation of a Patient with Suspected Acute Ischemic Stroke

* Although it is desirable to know the results of these tests before giving a patient tissue plasminogen activator, thrombolytic therapy should not be delayed while awaiting the results unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia; (2) the patient has received heparin or warfarin; or (3) the patient’s use of anticoagulants is not known.

From Christensen H et al: Abnormalities on ECG and telemetry predict stroke outcome at 3 months, J Neu-rol Sci 234:99-103, 2005.

A B

FIGURE 1-892 Large right middle cerebral artery infarct on an unenhanced computed tomographic scan (A) and a diffusion-weighted magnetic resonance image (B). There is a mass effect, and this patient is at risk for cerebral herniation syndromes.

1116 Stroke, Acute Ischemic PTG ALG EBM

IMAGING STUDIES • Immediate (Fig. 1-892): computed tomog-

raphy (CT) of the head without contrast or MRI of the brain with stroke protocol to rule out hemorrhage and, if possible, to assess the extent of stroke. (Because CT typically will not show an ischemic stroke for several hours, it may also be useful to estimate how long ischemia has been present for cases in which the time of onset is unclear.)

• Several other neuroimaging studies are use-ful during the early stages of acute stroke to assess whether there is a thrombus that is amenable to intervention (Table 1-460).

Cross reference: see “Transient Ischemic Attack” for general workup, which is identical to that for ischemic stroke.

Rx TREATMENT

NONPHARMACOLOGIC THERAPYGENERAL CONSIDERATIONS: • Airway and breathing should be maintained. • Supplemental oxygen should be provided to

keep the oxygen saturation at ≥92%. • Fever is harmful during acute stroke.

Ascertaining and addressing the cause while lowering an elevated temperature is strongly advised.

• Pneumatic compression devices or phar-macologic means should be applied to help prevent deep venous thromboses.

• Avoid any and all oral intake until swallow-ing is clearly unimpaired; this helps to avoid aspiration pneumonia.

• Early mobilization for rehabilitation is desirable. • Consider neurosurgical intervention for

craniectomy in select cases. Typical cases in which craniectomy may be performed include cerebellar ischemia with compres-sion of the brain stem and/or the fourth ventricle as well as large right middle cere-bral artery ischemia. Available evidence sug-gests that it may be better to perform early hemicraniectomy (<48 hr) to achieve better outcomes. Decompressive hemicraniectomy has shown good benefit in terms of mortality but not much benefit in terms of disability and functional outcomes.

IMMEDIATE CATHETER CEREBRAL ANGIO-GRAPHY FOR ENDOVASCULAR INTERVENTION(Figs. 1-893 and 1-894): Methods available: 1. The Merci clot retrieval system is approved

by the U.S. FDA for use up to 8 hr after the onset of symptoms.

2. The Penumbra System is also available at some centers. More recently, 2 other me-chanical revascularization devices, namely the Solitaire FR (flow restoration) and Trevo, have been approved by the FDA. These de-vices showed better recanalization rates with fewer complications compared to the Merci device, based on SWIFT and TREVO 2 trials.

3. Intraarterial tissue plasminogen activator (TPA) is used routinely for up to 6 hr af-ter the onset of symptoms, although it is not approved by the U.S. FDA for this purpose.

Pearls and caveats: • Multimodal therapy (i.e., thrombectomy and

intraarterial TPA) is sometimes performed. • Endovascular treatment may be performed

for select cases in which intravenous (IV) TPA has failed to recanalize an occluded artery.

• Endovascular intervention may be an option for cases in which there are systemic contra-indications to IV TPA.

• Endovascular intervention is useful only for large, accessible thrombi. Therefore, if a

stroke patient is a candidate for IV TPA, then he or she should probably receive IV TPA.

• One can reasonably expect an endovascu-lar recanalization rate of 60% in appropri-ate patients when used alone. Combining the Solitaire device with other endovascular approaches has shown recanalization rates close to 88% in recent studies (Solitaire).

• Complications can ensue from the endovas-cular procedure itself, including an intrace-rebral hemorrhage rate that is similar to that associated with IV TPA.

TABLE 1-460 Imaging Modalities for Stroke

Imaging Modality Advantage Disadvantage

Cerebral catheter angiography

• Allows for the definitive assessment of cerebral circulation (gold standard)

• Allows for the deployment of intra arterial thrombolysis and thrombectomy devices if a thrombus is found

• Allows for the assessment of collateral circulation

• Invasive (significant risks) • High cost • Not available at all facilities

Doppler studies • Noninvasive • May be performed at the patient’s bed-

side

• Can be limited by the patient’s body habitus

• Operator dependentMagnetic resonance

angiography • Excellent view of the large arteries of the

neck and brain • No contrast material needed

• Cannot be performed in patients who are critically ill, who are un-able to tolerate supine position-ing, who have a pacemaker or other ferromagnetic hardware, or who are claustrophobic

Magnetic resonance perfusion

• Assesses cerebral hemodynamics • May show ischemic penumbra (i.e., the

area of the brain that may be saved by timely intervention)

• Not commonly available • Not well standardized

CT angiography • Excellent view of the large arteries of the neck and brain

• Similar to magnetic resonance angiogra-phy with regard to resolution

• Requires intravenous contrast

CT perfusion • Assesses cerebral hemodynamics • May show ischemic penumbra (i.e., the

area of the brain that may be saved by timely intervention)

• Challenging to interpret in some cases

• Not routinely available at many facilities

• Requires intravenous contrast

A B

FIGURE 1-893 A, A catheter angiogram showing left middle cerebral artery occlusion, which caused severe stroke symptoms for several hours. B, The artery was opened with the Merci clot retrieval system, and this resulted in normal flow.

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1117PTG ALG EBM Stroke, Acute Ischemic

• Endovascular intervention is typically avail-able only at select large stroke centers.

• Some practitioners are making use of perfu-sion imaging (i.e., CT perfusion and magnetic resonance perfusion) to assess whether there is salvageable brain tissue before performing the procedure. In some cases, this may lead to a dramatic expansion of traditional time windows; this practice is currently being studied in clinical trials.

ACUTE GENERAL RxINTRAVENOUS THROMBOLYSIS: • IV TPA is the only medical therapy approved

by the U.S. FDA for the treatment of acute ischemic stroke. Recent trials involving tenecteplase, a genetically engineered mutant TPA, have shown significantly better reperfu-sion and clinical outcomes than alteplase in patients with stroke who were selected on the basis of CT perfusion imaging.

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Diseases and Disorders

A B

FIGURE 1-894 A, A diffusion-weighted magnetic resonance image of the same patient as shown in previous figure, this time showing only mild left cerebral ischemia after intervention. The patient was clinically normal. B, Thrombi removed from the middle cerebral artery with the use of the Merci clot retrieval system.

Criteria for considering TPA as a treat-ment option: • Noncontrast CT head without evi-

dence of hemorrhage • Time since onset of symptoms

clearly <3 hr (3-4.5 hr with additional exclusion criteria) before TPA ad-ministration would begin

Criteria for excluding TPA as a treatment option: • Historic and clinical findings: C Clinical presentation suggestive

of subarachnoid hemorrhage, even if CT scan is normal

C Sudden, severe headache, often with a loss of consciousness at onset

C Vomiting • Active internal bleeding, increased

risk of bleeding, or known bleeding diathesis, including those resulting from:

C Recent use of warfarin with an INR of ≥1.7

C Use of heparin within 48 hr with a prolonged aPTT

C Platelet count of <100,000/mm3

C History of intracranial hemor-rhage

C Known arteriovenous malforma-tion or aneurysm

C GI or GU bleeding within the past C 21 days C Arterial puncture within the past

7 days • Recent lumbar puncture • Stroke, intracranial surgery, or head

trauma within the previous 3 mo • Major surgery or serious trauma

within the preceding 14 days • Systolic blood pressure >185 mm

Hg or diastolic blood pressure >110 mm Hg that does not decrease below that range with treatment

• Seizure at stroke onset • Rapidly improving neurologic signs • Isolated mild neurologic deficits • Acute myocardial infarction • Post–myocardial infarction pericarditis • Blood glucose <50 mg/dl or >400

mg/dl • Patient who is pregnant or lactating • CT findings: C Evidence of intracranial hemor-

rhage C Hypodensity or effacement of the

sulci in one third of the territory of the middle cerebral artery

BOX 1-83 Three-Hour Criteria for Tissue Plasminogen Activator (Alteplase [Activase]) Use in Patients with Thromboembolic Stroke

From Rakel RE [ed]: Principles of family practice, ed 6, Philadelphia, 2002, Saunders.

aPTT, Activated partial thromboplastin time; CT, computed tomography; GI, gastrointestinal; GU, genitourinary; INR, international normalized ratio; TPA, tissue plasminogen activator.

• The time window for administration is within 3 hr of symptom onset.

• There are strict criteria for the administration of IV TPA (see Box 1-83).

• The protocol is weight based, with 90 mg being the maximum allowable dose.

• The risk of brain hemorrhage with IV TPA is about 5% in stroke patients.

• Recent data suggest that IV TPA can be administered safely and with benefit in select patients up to 4.5 hours after symp-tom onset. There are additional exclusion criteria if IV TPA is given beyond the 3-hr window.

HYPERTENSION: Elevated blood pressure is common during acute stroke, and it often subsides without specific therapy. In general, hypertension is not treated acutely unless it is extremely high (e.g., >220 mm Hg sys-tolic blood pressure); there is evidence of organ damage caused by the hypertension; or throm-bolysis is being considered, in which case the blood pressure needs to come down (if it can be safely accomplished) to <185/110 mm Hg. It is risky to severely decrease blood pressure in the presence of acute ischemic stroke as it can cause an extension of the stroke into the ischemic penumbra. A 15% to 25% decrease over the first 24 hours is recommended.HYPOGLYCEMIA: Hypoglycemia can mimic stroke. Prompt assessment of serum glucose level and replacement as necessary are impor-tant.HYPERGLYCEMIA: The presence of hyper-glycemia worsens ischemic stroke outcome. Hyperglycemia should be managed aggressively.HYPOTENSION: The presence of systemic hypotension in acute ischemic stroke portends a poor outcome. The cause should be sought, and volume depletion should be corrected with normal saline. Cardiac arrhythmias should be treated. Induced hypertension with vasopressor agents may be useful for select cases with an ischemic penumbra that is at risk, but caution is strongly advised.ANTIPLATELET THERAPY: Oral or feeding tube administration of aspirin (325 mg/day) within 48 hours of stroke onset is advised to decrease the likelihood of a repeat ischemic stroke. Other oral antiplatelet regimens approved for secondary stroke prophylaxis (e.g., clopidogrel, aspirin plus extended-release dipyridamole) will also suffice and may be superior in the long term. In patients with acute ischemic stroke and atrial fibrillation, full dose anticoag-ulation with heparin infusion or low molecular weight heparin should be avoided in the acute setting, as this could potentially harm the patient by causing symptomatic intracranial hemorrhage and there is very little evidence to suggest any benefit.

DISPOSITIONPatients with acute ischemic stroke should be cared for in a stroke unit or an intensive care unit. Nurses with skills in stroke care and telemetry monitoring should be routine. Once the patient is stable and the workup is complete, rehabilitation should be arranged.

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REFERRALPatients with acute ischemic stroke should be transported to a hospital in which providers are skilled in stroke care. Depending on the sever-ity and duration of symptoms, the patient may qualify for immediate endovascular intervention at a comprehensive stroke center, even if he or she is not a candidate for IV TPA. If complica-tions from brain edema develop, further evalu-ation by a neurosurgeon may be helpful during the acute phase.

! PEARLS & CONSIDERATIONS

PREVENTIONThe prevention of acute ischemic stroke depends on the aggressive management of risk factors in individual patients.

Cross reference: stroke, secondary prevention

PATIENT & FAMILY EDUCATIONPatients and families need to be taught about ways to reduce the risk for recurrent stroke, including lifestyle modifications. Education about rehabilitation goals, when appropriate, should also be accomplished.

SUGGESTED READINGSavailable at www.expertconsult.com

RELATED CONTENTFig. E3-183 Algorithm for the emergency evalu-

ation of a patient with suspected stroke (Algorithm)

Stroke (Patient Information)

AUTHORS: PRASHANTH KRISHNAMOHAN, M.B.B.S., M.D., and MICHAEL R. DOBBS, M.D.

EVIDENCEavailable at www.expertconsult.com

1118.e1Stroke, Acute Ischemic

EVIDENCEAbstract[1]

Background and Purpose:In ischemic stroke, MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch represents tissue at risk for infarc-tion. Infarct growth should only take place in the presence of mismatch, although there have been reports of this occurring. We hypothesized that this observation may be attributable to the presence of undetected “hid-den mismatch,” which may become obvious when coregistration tech-niques are used.Methods:MR PWI/DWI was performed within 48 hours of stroke onset and a fi-nal T2-weighted image at ≈3 months. Volumetric-subtraction mismatch volume was defined as PWI minus DWI volume and infarct growth was defined as T2 minus DWI volume. Coregistration mismatch volume was PWI not overlapped by DWI. Mismatch salvage was the proportion of coregistered mismatch tissue that had not progressed to infarction.Results:Thirty-four patients were studied with MR at a median of 4.9 hours (in-terquartile range, 2.9–21.1 hours). With the volumetric-subtraction tech-nique, 5 patients (14.7%; 95% CI, 0.05%–0.31%) had infarct growth exceeding mismatch volume, 11 patients (32.0%) had no mismatch and, among these, 3 (27.3%) had infarct growth (median volume, 2.2 mL; interquartile range, 1.0–6.5 mL). All patients had mismatch volume identified by coregistration method that was greater than infarct growth volume. The proportion of this volume salvaged was 77.7% (interquartile range, 63.0%–98.9%).Conclusions:The illogical finding of infarct growth volume being greater than the pres-ence of mismatch volume can be explained by the presence of “hidden mismatch,” which may be detected by coregistration methods. A

Evidence-Based Reference1. Ma HK et al: The hidden mismatch: an explanation for infarct growth without

perfusion-weighted imaging/diffusion-weighted imaging mismatch in patients with acute ischemic stroke, Stroke 42:662-668, 2011. A

SUGGESTED READINGSAdams HP Jr et al: Guidelines for the early management of adults with ischemic

stroke, Stroke 38(5):1655-1711, 2007.Baker WL et al: Neurothrombectomy devices for the treatment of acute ischemic

stroke: state of the evidence, Ann Intern Med 154:243-252, 2011.Broderick JP et al: Endovascular therapy after intravenous t-PA versus t-PA alone

for stroke, N Engl J Med 368:893-903, 2013.Ciccone A et al: Endovascular treatment for acute ischemic stroke, N Engl J Med

368:904-913, 2013.Healey JS et al: Subclinical atrial fibrillation and the risk of stroke, N Engl J Med

366:120-129, 2012.Juttler G et al: Hemicraniotomy in older patients with extensive middle-cerebral-

artery stroke, N Engl J Med 370:1091-1100, 2014.Parsons M et al: A randomized trial of tenecteplase vs. alteplase for acute isch-

emic stroke, N Engl J Med 366:1099, 2012.Solitaire FR: Thrombectomy for acute ischemic stroke: retrospective multicenter

analysis of early postmarket experience after FDA approvalWechsler LR: Intravenous thrombolytic therapy for acute ischemic stroke, N Engl

J Med 364:2138-2146, 2011.