Stroke

Scott E. Kasner, MD
University of Pennsylvania Medical Center, Philadelphia, PA

Heather E. Moss, MD, PhD
University of Pennsylvania School of Medicine, Philadelphia, PA

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References


Definition/Key Clinical Features

• A sudden neurologic deficit caused by either ischemia (80%) or hemorrhage (20%)
• Acute ischemic stroke produces varied signs and symptoms, depending on the location of the vascular occlusion
  • Anterior cerebral artery (ACA): contralateral leg weakness
  • Middle cerebral artery (MCA): contralateral hemiparesis and hemisensory deficit (face + arm > leg); aphasia (dominant hemisphere) or neglect (nondominant hemisphere); contralateral visual-field defect
  • Posterior cerebral artery (PCA): contralateral visual-field loss
  • Vertebral arteries or basilar artery: any combination of crossed facial and body motor and sensory signs; diplopia; facial numbness and weakness; vertigo; nausea and vomiting; tinnitus; hearing loss; ataxia; gait abnormality; hemiparesis; dysphagia; and dysarthria
  • Penetrating vessels: pure motor hemiparesis, pure sensory stroke, clumsy hand–dysarthria syndrome, ataxic hemiparesis and any of the above syndromes
• Hemorrhagic stroke produces varied signs and symptoms, depending on the location of the hemorrhage
  • Subarachnoid (5%)
    • Sudden severe headache
    • Photophobia
    • Stiff neck
    • Decreased level of consciousness
    • Focal neurologic signs
  • Intracerebral (intraparenchymal) (15%)
    • Severe headache
    • Focal neurologic signs (can resemble an ischemic stroke)
• Transient ischemic attack (TIA): sudden vascular-related focal neurologic deficit that resolves completely and lasts < 24 hr, generally < 1 hr; a herald of ischemic stroke and an opportunity to intervene

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Differential Diagnosis

Sudden Neurological Deficit

• Drugs or other toxins
• Seizure
• Metabolic derangements
• Migraine
• Brain tumor
• Psychiatric disease

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Best Tests

• Noncontrast head CT to diagnose or exclude hemorrhagic stroke
• Brain MRI to localize lesion in ischemic stroke and intraparenchymal hemorrhagic stroke
• Vascular imaging to evaluate extra and intra-cranial blood vessels
• Angiography (CT, MR, catheter) to identify occluded vessel in an ischemic stroke or the source of bleeding in a hemorrhagic stroke
• Carotid duplex ultrasound to identify possible source of ischemic stroke
• Transcranial Doppler ultrasound to identify possible source of ischemic stroke
• Cardiac evaluation of ischemic strokes to identify source
  • Cardiac history and examination
  • Electrocardiogram, cardiac telemetry and cardiac event monitor
  • Transthoracic echocardiogram (TTE) +/- transesophageal echocardiogram (TEE)
• Laboratory tests
  • Fasting lipids within 48 hours of symptom onset
  • Homocysteine level
  • Complete blood count
  • Prothrombin time
  • Partial thromboplastin time
  • Chemistry panel

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Best Therapy*

• Aspirin (325 mg daily) administered within 48 hr of stroke onset; aspirin should be withheld for at least 24 hr after administration of thrombolytics
• Intravenous recombinant tissue plasminogen activator (rt-PA) as soon as possible after onset of symptoms
  • Indications
    • Firm clinical diagnosis of potentially disabling stroke
    • Onset of symptoms or last time seen normal < 4.5 hr ago
  • Absolute contraindications
    • Onset > 4.5 hr ago or patient not seen normal within previous 4.5 hr
    • Intracranial mass lesion or hemorrhage on noncontrast head CT
    • Previous stroke or serious head trauma within previous 3 mo
    • Any history of intracranial hemorrhage
    • Current use of anticoagulants with PT > 15 sec or use of heparin within the past 48 hr
    • Platelets < 100,000/mm³
    • Presenting symptoms suggestive of subarachnoid hemorrhage (worst headache of patient's life)
    • Blood pressure > 185/110 mm Hg unless minimal doses of a smooth-acting I.V. agent such as labetalol are sufficient to lower below this range
    • Previously known cerebral aneurysm or arteriovenous malformation
  • Relative contraindications
    • Glucose < 50 or > 400 mg/dl
    • Seizure at stroke onset
    • Major surgery within 14 days
    • Arterial puncture at a noncompressible site or lumbar puncture within 1 wk
    • Rapidly improving symptoms suggestive of TIA
    • GI or GU hemorrhage within 21 days
  • Dose: 0.9 mg/kg (maximum dose, 90 mg) infused over 1 hour, with 10% of the total dose infused over the first minute; if treatment with rt-PA is suspected of inducing intracranial hemorrhage, the infusion should be suspended
• Intra-arterial catheter based therapy for severely affected patients not eligible for IV tpa therapy; this is only available at select medical centers
• Close neurological monitoring during the first 72 hours following the event
• Supportive medical management
  • Maintain respiratory function, using intubation and mechanical ventilation if necessary; maintain oxygen saturation above 95%
  • Maintain adequate blood pressure; avoid rapid lowering of blood pressure; antihypertensive therapy is indicated before and during thrombolysis with rt-PA, when infarction converts to hemorrhage, and in patients with myocardial ischemia, aortic dissection, or hypertensive encephalopathy
  • Maintain normal fluid volume
  • Maintain normal body temperature with antipyretics or cooling blankets
  • Maintain normal blood glucose levels
  • Surgical decompression to relieve intracranial pressure in acute cerebellar stroke with signs of brainstem compression (e.g. lethargy, brainstem signs)
  • Begin early prophylaxis for deep vein thrombosis with heparin (5,000 units S.C. q. 12 hr) or low-molecular-weight heparin; if these are contraindicated, use pneumatic compression stockings
  • Prevent aspiration pneumonia
  • Early physical therapy, occupational therapy, and speech therapy
• Reduce risk factors for ischemic stroke prevention: control hypertension, tobacco use, hyperlipidemia, diabetes, excessive alcohol consumption, elevated homocysteine levels, infection, and inflammation; encourage exercise
• Management of risk of cardioembolism implicated in ischemic stroke or TIA etiology
  • Oral anticoagulation for patients at high risk for cardioembolism, including those with atrial fibrillation, mechanical prosthetic valves, severe dilated cardiomyopathy, intracardiac thrombus, and/or akinetic ventricular segments
    • Warfarin: contraindicated in pregnancy, poor compliance, alcohol abuse, and risk of falling; dose: adjusted to international normalized ratio (INR) between 2.0 and 3.0 for most patients
    • Ximelagatran: efficacy similar to that of warfarin in patients with atrial fibrillation and deep vein thromboembolism
  • Aspirin or other antiplatelet agents for patients at lower risk of cardioembolism or with contraindication to warfarin
  • Antibiotics for treatment of endocarditis
• Manage carotid artery disease implicated in ischemic stroke or TIA etiology by carotid endarterectomy or carotid angioplasty and stenting
• Antiplatelet treatment to prevent ischemic stroke for non-cardioembolic etiologies
  • Clopidogrel: reduces risk of major vascular events by 7.3%, compared with aspirin, though not specifically stroke; equivalent efficacy to dipyridamole and aspirin; can cause rash, diarrhea, and, rarely, thrombotic thrombocytopenic purpura
    • Dose: 75 mg daily
  • Aspirin: can cause gastritis, peptic ulcer disease
    • Dose: 81 mg daily
  • Dipyridamole (extended-release) + aspirin: reduces risk of stroke by 23%, compared with aspirin alone; equivalent efficacy to clopidogrel; side effect: headache
    • Dose: 25 mg aspirin + 200 mg extended-release dipyridamole b.i.d.
  • Statin therapy to prevent recurrent ischemic stroke for non-cardioembolic etiologies

• Emergent treatment of any bleeding diathesis (i.e., thrombocytopenia or coagulopathy)
• Close neurological monitoring, including consideration of invasive intracranial pressure monitoring if patient is obtunded
• Consideration of surgical hemorrhage evacuation if there is evidence for elevated ICP, brain herniation or brain stem compression
  • Maintenance of mean arterial pressure under 140 mm Hg
  • Further supportive care as for ischemic stroke including early initiation of deep venous thrombosis prophylaxis with compression boots

• Rapid identification and surgical clipping or endovascular coiling of causative aneurysm within 72 hr of onset; before clipping or coiling, patients are kept mildly sedated in a quiet room and given stool softeners to reduce the risk of rebleeding
• Therapy with nimodipine and simvastation
• Anticonvulsants at first sign of seizure
• Blood pressure should be gently, not drastically, controlled
• Close monitoring of neurological status with emergent head CT if there is any change
• After aneurysm has been secured, daily transcranial Doppler examinations to monitor for vasospasm
• Treatment of vasospasm with hypertension, hypervolemia and perhaps angioplasty

• Dissection of the internal carotid artery or vertebral artery: may follow head and neck trauma or occur spontaneously
  • Clinical features: neck pain, headache, Horner's syndrome, TIA or ischemic stroke, and tinnitus or audible bruits
  • Diagnosis: conventional angiography (gold standard) shows string sign, tapered stenosis or occlusion, dissecting aneurysm, intimal flap, distal pouch formation, and an underlying arteriopathy; CT-A, MRI, or MRA show similar findings
  • Treatment: antithrombotic therapy with anticoagulation or antiplatelet therapy
• Vasculitis: may be primary or secondary to infections (syphilis, tuberculosis, or varicella-zoster virus), toxins (cocaine, amphetamines, or LSD), neoplasms, or systemic inflammatory disorders (polyarteritis nodosa, Churg-Strauss angiitis, Wegener granulomatosis, giant cell arteritis, systemic lupus erythematosus, or rheumatoid arthritis)
  • Clinical features: headache, seizures, TIA or ischemic stroke, and multifocal encephalopathy
  • Diagnosis: angiography shows segmental narrowing and dilatation ("beading")
  • Treatment: appropriate for any underlying systemic disorder; immunosuppressive regimens with corticosteroids and other agents are often used empirically
• Prothrombotic states: may be hereditary or acquired, including abnormalities of red cell or platelet function, coagulation factors, or endogenous fibrinolysis; should be considered in young patients when no alternative etiology is identified
• Cerebral venous thrombosis: a rare cause of stroke; most commonly caused by infection in children and by pregnancy in adults
  • Clinical features: severe headache, nausea, vomiting, papilledema, fluctuating focal neurologic deficits such as unilateral weakness, numbness, or seizures
  • Diagnosis: cerebral angiography (gold standard), MRI, or MR venogram (MRV); lumbar puncture may show elevated protein levels, red blood cells, or xanthochromia; noncontrast CT may reveal acute hemorrhage or mass effect; contrast CT may show empty delta sign in the sagittal sinus
  • Treatment: I.V. heparin during acute period even if there is hemmorhage, then oral anticoagulation for several months until MRI or MRV shows sinus patency

  *To obtain additional drug information, click on the DrugInfo tab in the left, or click on the following link: http://search.medscape.com/drug-reference-search?queryText=

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Best References

Adams HP, et al: Stroke 38:1655, 2007 [PMID 17431204]

Adams RJ, et al: Stroke 39: 1647, 2008 [PMID 18322260]

Broderick JP, et al: Stroke 38:1072, 2007 [PMID 17290026]

Bederson JB, et al: Stroke 40: 994, 2009 [PMID 19164800]

March 2010