James Gebel, MD, MSc
Gabor Toth, MD
DESCRIPTION 
Ischemic stroke is defined as a partially irreversible focal ischemic injury (or injuries) to the brain, retina, or spinal cord that produces clinical symptoms lasting at least 10 minutes. Cerebral infarction is defined as an area of focal brain ischemia sufficient to produce radiologically or pathologically evident infarction. Not all cerebral infarctions produce clinical symptoms.
EPIDEMIOLOGY
There are approximately 731,000 new or recurrent strokes every year in the US; 80–85% of these are ischemic.
- Age: 75% of strokes occur in persons ≥65
- Sex: Lifetime risk females 1 in 5, males 1 in 6
- Race/ethnicity: More common in African Americans, Asians, and Hispanics.
RISK FACTORS
Risk factors include hypertension, diabetes mellitus, elevated C-reactive protein, hyperlipidemia, tobacco, sedentary life, obesity, family history of stroke, and prior history of stroke or TIA, and known coronary artery or peripheral vascular disease.
Pregnancy Considerations
Pregnancy increases the risk of ischemic stroke. Conditions peculiar to pregnancy that lead to stroke include paradoxical emboli from the legs or pelvic veins, cardiomyopathy of pregnancy, cervical arterial dissection during labor and delivery, hypercoagulable state, amniotic fluid embolism, and vasoconstrictive medications like ergotamines.
Genetics
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, prothrombin variant, and infrequently (in young patients) Leiden factor V mutation, are all genetic conditions that can present with stroke.
ETIOLOGY
- Cardiac emboli: Conditions that predispose to the formation of cardiac emboli include persistent or paroxysmal atrial fibrillation/flutter, mitral valve stenosis, sick sinus syndrome, prosthetic heart valve, infective or marantic endocarditis,congestive heart failure with EF of 35% or less, dilated cardiomyopathy, myxomas, left atrial enlargement, and spontaneous echo contrast.
- Large artery disease: Stenosis of the extracranial internal carotid and vertebral arteries, and large intracranial vessels of the Circle of Willis and posterior circulation (intracranial vertebral and basilar arteries, usually due to atherosclerosis). Other diseases include dissection, vasculitis, moyamoya, and fibromuscular dysplasia.
- Small vessel disease: Lacunar infarction.
- Hypercoagulable states, both inherited such as prothrombin II variant mutation; and acquired such as antiphospholipid antibody syndrome, lupus anticoagulant, sickle cell anemia, and paraneoplastic (especially mucin-secreting carcinomas with elevated CA-125 levels).
- Cerebral vasculitis, moyamoya disease, vasospasm, fibromuscular dysplasia, carotid or vertebral artery dissection, and reversible cerebral vasoconstrictive syndrome (uncommon).
COMMONLY ASSOCIATED CONDITIONS
The commonly associated conditions comprise TIA, coronary artery disease, and peripheral arterial disease.
[Outline]
The clinical features depend on the brain area affected. Common symptoms include hemiparesis, hemisensory loss, visual field defects, ataxia, aphasia, dysarthria, dysphagia, diplopia, and vertigo.
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
- All patients with stroke should have blood drawn for fasting lipid profile, BUN, creatinine, CBC and platelets, PT with international normalized ratio (INR), and PTT.
- Hypercoagulable profile including factor V mutation, factor II mutation, lupus anticoagulant, antiphospholipid antibodies, and homocysteine should be requested in young patients. Protein S, C, and antithrombin II deficiencies rarely cause TIA or stroke and much more often cause venous, not arterial, thromboembolic events.
- Serial blood cultures for endocarditis prn.
Imaging
- CT scan of the brain non-contrast must be performed in all patients with suspected stroke because it is very sensitive in detecting intracerebral hemorrhage or subdural hematoma, which can mimic ischemic stroke clinically. CT angiography of the neck and brain can also be simultaneously or subsequently performed to detect stenosis or occlusion of the large neck or brain vessels.
- MRI of brain is much more sensitive than CT scan in detecting small or early cerebral infarction. MR angiography of the neck and brain is another noninvasive testing option for assessing the major extracranial and intracranial arteries for stenosis, though it may overestimate the degree of stenosis.
- Transthoracic echocardiogram (TTE) is indicated in most patients with stroke. If the TTE is negative and a cardiac source of embolism is still suspected, the transesophageal echocardiogram (TEE) should be performed. TEE is also indicated in almost all young stroke patients (unless an explanation for the stroke is found on TTE), in whom half of all ischemic strokes are of cardioembolic origin.
- TEE is more accurate than TTE in showing atrial and ventricular thrombi, vegetations, and left atrial enlargement, detecting shunts, and aortic arch atheroma.
- Angiography is the gold standard for an accurate assessment of both the extra- and intracranial vasculature. However, it is an invasive expensive procedure with greater risk than CTA, MRA, or ultrasound, and should be reserved for patients in whom noninvasive testing has not definitely shown the source of stroke or gives conflicting estimation of degree of stenosis of the large neck or brain vessels.
- Ultrasound is a safe, portable, and inexpensive. It includes transcranial Doppler to look for intracranial disease and carotid duplex to assess for extracranial carotid disease. Carotid duplex insensitive in extracranial vertebral disease.
Diagnostic Procedures/Other
ECG and cardiac monitoring, either inpatient telemetry or 24-hour Holter monitoring to evaluate for arrhythmias.
DIFFERENTIAL DIAGNOSIS
Differential diagnosis includes migraine aura/status, migrainosus, multiple sclerosis, seizures (Todd's paralysis), vertigo, syncope, metabolic disorders, intracerebral hemorrhage, subdural hematoma, conversion disorder, and cerebral venous sinus thrombosis.
[Outline]
MEDICATION
- Recombinant tissue plasminogen activator (rt-PA) is the only FDA-approved medication for acute ischemic stroke and must be given within 3–4.5 hours from the onset of symptoms. Dose 0.9 mg/kg to maximum of 90 mg; 10% of the dose given IV bolus over 1 minute and the rest as an IV drip over 1 hour. Only alteplase is FDA approved for use in ischemic stroke patients. Retevase and other (non-alteplase) thrombolytic medications should NOT be administered for acute ischemic stroke treatment under any circumstances.
- Antiplatelet agents: Indicated for stroke prevention in small vessel disease, intracranial large artery disease, mild (<50%) extracranial carotid artery disease, extracranial vertebral artery disease, aortic arch disease without mobile plaque, irregular nonstenotic valve surfaces, and in patients who are not Coumadin candidates.
- Anticoagulants
- Warfarin (Coumadin): Indicated in hypercoagulable states; cardiac sources like atrial fibrillation, intracardiac thrombi, and intracranial large artery stenosis
- Dabigatran (Pradaxa): Indicated in patients with persistent or paroxysmal nonvalvular atrial fibrillation and is preferred over warfarin due to superior efficacy and at least comparable safety
- Contraindications
- IV rTPA given within 3 hours: Suspicion of subarachnoid hemorrhage; recent (within 3 months) intracerebral or intraspinal surgery; recent head trauma; recent major (abdominal or thoracic) surgery; previous stroke within 3 months; history of intracerebral hemorrhage; history of uncontrolled hypertension; uncontrolled hypertension at time of treatment (SBP >185 mm Hg or DBP >110 mm Hg); seizure at the onset of stroke; active internal bleeding; GI bleeding within 30 days; known or suspected intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis including but not limited to current use of oral anticoagulants (e.g., warfarin sodium), or an INR >1.7; administration of heparin in the preceding 48 hours and an elevated aPTT at presentation; platelet count <100,000/mm3; blood glucose <70 or >400; presence of low attenuation on head CT in >
rd of the middle cerebral artery; presence of any blood on head CT - IV rTPA given within 4.5 hours: In addition to all of the above; age >80, history of BOTH previous stroke AND diabetes mellitus, warfarin use no matter what the PT INR is, NIH Stroke Scale Score >25
- Aspirin/Aggrenox: Mainly known allergic reaction to salicylic acid, active systemic bleeding, or active gastric ulcer
- Clopidogrel: Mainly active systemic bleeding
- Warfarin: Mainly active bleeding, bleeding tendency, noncompliance, drug interactions and dietary (vitamin K containing foods) interactions. Rarely warfarin skin necrosis
- Dabigatran: Known history of active/recent GI bleeding; other active bleeding
- Precautions
- rtPA: Noncompressible arterial or venous punctures must be avoided. Blood pressure must be monitored closely during administration of the medicine and treated if elevated. If serious bleeding is suspected, then it must be stopped immediately. Watch for allergic reaction
- Clopidogrel: Monitor for TTP
- Warfarin: Watch for compliance, bleeding events, and falling events
- Dabigatran: Watch for bleeding events (especially GI bleeding)
ADDITIONAL TREATMENT
General Measures
General treatment of stroke includes acute supportive care and stroke, e.g., screening for dysphagia prior to administering any diet or medication by mouth, oxygen administration, DVT risk assessment and prophylaxis, fall risk and pressure sore risk assessment and prevention, evaluation for rehabilitation, administration of statins to atherosclerosis-related stroke patients with LDL >70, Stroke education, management of coexisting medical illnesses, secondary stroke prevention. Physical, occupational, speech, and cognitive therapy may be needed.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
- Symptomatic treatment
- Rx hyperglycemia, fever, and infection; aspiration precautions when indicated; adequate hydration and nutrition; judicious control of blood pressure with avoidance of excessive reduction in the acute setting and adequate control (SBP <120 and DBP <80) in the long run, and avoidance of prolonged use of indwelling catheter to prevent urinary tract infection.
- Amitriptyline or gabapentin for pain related to thalamic strokes; antidepressants for the depression that may accompany some cortical strokes; muscle relaxants such as Lioresal for residual spasticity; and stool softeners for constipation.
SURGERY/OTHER PROCEDURES
- Carotid endarterectomy (CEA) or carotid artery stenting (CAS) is indicated for most patients with significant (>50%) symptomatic extracranial carotid artery stenosis and for almost all patients with >70% symptomatic extracranial carotid stenosis. Patients with known concomitant coronary artery disease are generally better CAS candidates, and patients over the age of 72 are generally better CEA candidates. CAS associated with higher rate of periprocedural stroke than CEA but lower incidence of periprocedural MI and minimal risk of cranial nerve palsies (5% of CEA cases). Recent preliminary clinical trial data suggests that angioplasty and stenting of symptomatic large intracranial stenosis may be inferior to maximal medical management with antiplatelet medication + aggressive modifiable risk factor management. Angioplasty and stenting of symptomatic large intracranial stenosis at this time is reserved only for patients in clinical trials, or last resort for recurrent strokes on maximal medical therapy.
- Neurointerventional therapies: These are utilized mostly for patients with large vessel occlusions presenting within 6–8 hours of symptoms onset. They may be considered for patients ineligible for IV tPA, with contraindications to IV tPA, or refractory to conventional medical therapy. Further randomized trials are needed to establish improved efficacy compared to medical therapy
- Intra-arterial therapies:
- Chemical thrombolysis: tPA, pro-urokinase, glycoprotein IIb/IIIa inhibitors, etc.
- Mechanical clot disruption
- Thrombectomy and clot retrieval: Merci and Penumbra device
- Angioplasty and stenting
- Retrievable stents: Trevo, Solitaire, Revasc, etc.
- Multimodal therapy: Combination of the above
IN-PATIENT CONSIDERATIONS
Admission Criteria
In general, any patient presenting with acute ischemic stroke should be admitted to the hospital for the evaluation of etiology and appropriate prevention measures; prevention and management of stroke complications; early initiation of physical, occupational, and speech therapy; evaluation for eligibility for inpatient rehabilitation; assistance with appropriate placement; and patient and caregiver education.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Frequent follow-up visits are important to assess patients for recurrent events, compliance with treatment and recommendations, and adverse reactions from the treatment medications.
- Monitor INR for treatment with Coumadin.
PATIENT EDUCATION
American Stroke Association, National Center, 7272 Greenville Avenue, Dallas, TX, 75231, 1-888-478-7653. www.strokeassociation.org
PROGNOSIS
Appropriate preventive secondary measures significantly decrease the risk of recurrent stroke. However, despite these measures patients continue to be at increased risk.
[Outline]
