Acute Ischemic Stroke

by Fatih Büyükcam

Introduction

Patients with stroke present with sudden onset of paresis, sensory deficits, visual loss or visual field defects, diplopia, dysarthria, facial droop, ataxia, vertigo, aphasia and altered mental status. These symptoms and signs may be seen alone or in combination.

Acute ischemic stroke is a type of brain ischemia due to thrombosis, embolism or systemic hypoperfusion. Atherosclerosis, dissection, fibromuscular dysplasia, arteritis, vasculitis, non-inflammatory vasculopathy, and vasoconstriction may cause thrombosis . The most common source of emboli is cardiac or aortic diseases.

Management principles include stabilization, diagnosing and reversing the cause and decreasing harm to the patient. All patients with acute ischemic stroke have to be evaluated for suitability to thrombolytic therapy or invasive procedures (see Table 2).

Differential Diagnosis

Syncope, hypoglycemia, drug toxicity, seizure, intracranial hemorrhagic conditions can be misdiagnosed as acute ischemic stroke.

History and Physical Examination Hints

Most important data of the history is the time onset of symptoms because this is the main data that determine the eligibility for thrombolytic therapy. If the symptom onset time is not known, the time the patient was last awake and free of stroke symptoms is accepted as symptom onset time. Also, other important data have to be asked like co-morbidities, medications, head trauma and prior stroke.

Stabilization is a priority in every critically ill patient. Once the patient is stable, a focused neurologic examination should be performed. Level of consciousness (LOC), speech, cranial nerve (CN) function, motor and sensory function, and cerebellar function are the main abilities to assess. The physician may assess LOC and speech in a dialogue with the patient. The physician should also check pupillary size, reactivity, and eye movements to assess CN III through CN VI. Additionally, eyebrow elevation and squinting, smiling, gag reflex, shoulder elevation and tongue protrusion are parts of CN evaluation.

As we are still in differential diagnosis process, we have to do full systemic examination including especially cardiopulmonary and neurological examination. Whole body skin should be controlled for suspicion of trauma. Neurological examination findings give us some clues about the affected or obstructed vascular region.

Next step is to test motor and sensory function. Muscle strength is assessed against resistance. Pronator drift can be tested by having the patient sit with eyes closed and arms outstretched, with palms toward the ceiling, for 10 seconds. Double simultaneous stimulation may be performed by simultaneously touching the right and left limbs. The patient with sensory neglect may feel the right and left sides individually but may ignore one side when both are touched simultaneously.

The last step is to assess cerebellar function, reflexes, and gait. Finger-to-nose and heel-to-shin evaluations, asymmetry of the deep tendon reflexes or unilateral Babinski’s sign and observing routine ambulation are al informative parts of the neurologic examination.

Emergency Tests and Imaging Studies

Hypoglycemia may mimic a stroke. Therefore, fingertip blood glucose measurement is one of the initial essential steps. In case of hypoglycemia (blood glucose level <60 mg/dL), immediate intravenous glucose administration (slow intravenous push of 25 mL of 50% dextrose) is indicated. Whether the patient is hypoglycemic or not, stroke probability should be kept in mind until exclusion.

The basic workup should include an electrocardiogram, complete blood count, plasma urea nitrogen, creatinine, electrolytes, cardiac enzymes, coagulation parameters like prothrombin time, activated partial thromboplastin time and an international normalized ratio (INR). If there is a suspicion for other specific diseases liver function tests, toxicology tests, urinalysis, blood culture, β-HCG, arterial blood gases, lumbar puncture, etc. could be evaluated.

The physician should send the patient to imaging without waiting for the laboratory results.

The evaluation of a suspected stroke patient starts with non-contrast brain computed tomography (CT). A non-contrast brain CT is the fundamental imaging to differentiate hemorrhagic or ischemic stroke. This information determines subsequent treatment.

In the acute ischemic stroke, the sensitivity of standard non-contrast CT increases after 24 hours. However, there may be some early signs of infarction in the first six hours (Table 1) .

Table 1: Early signs of acute ischemic stroke

Hypodensity of the lentiform nucleus obscuration Hypoattenuation of 1/3 or more of the middle cerebral artery region Hyperdensity of large vessels Sulcal effacement Hypoattenuation of a focal parenchymal region Obscuration of the silvian fissure and insular ribbon The gray-white matter differentiation defect of basal ganglia

 

 

 

 

The prevalence of these signs is 61% (±21 standard deviation). The mean sensitivity and specificity of early CT signs are 66% (range 20-97) and 87% (range 56-100) respectively. If the diagnosis is unclear, a diffusion-weighted magnetic resonance imaging (DW-MRI) may visualize the affected area. DW-MRI can show ischemic changes within 3 to 30 minutes of onset. The apparent diffusion coefficient (ADC) view of DW-MRI gives a quantitative measure of the water diffusion. The decreased water diffusion in cytotoxic edema of acute ischemic stroke causes a hyperintense DW-MRI signal and a hypointense ADC signal. Please see couple examples below.

 

79-year-old female with left parieto-occipital cortex subcortical white matter infarct. CT imagining of at admission.

 

CT imagining of at 48th hour

 

DW-MRI imagining of the patient

 

ADC view of the patient

Table 2: Eligibility criteria for treatment of acute ischemic stroke with recombinant tissue plasminogen activator (alteplase)

INCLUSION CRITERIA
Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal Age ≥18 years
EXCLUSION CRITERIA
Historical Significant stroke or head trauma in the previous three months Previous intracranial hemorrhage Intracranial neoplasm, arteriovenous malformation, or aneurysm Recent intracranial or intraspinal surgery Arterial puncture at a noncompressible site in the previous seven days Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg) Serum glucose <50 mg/dL (<2.8 mmol/L) Active internal bleeding Acute bleeding diathesis, including but not limited to conditions defined in Hematologic' Hematologic Platelet count <100,000/mm3 * Current anticoagulant use with an INR >1.7 or PT >15 seconds* Heparin use within 48 hours and an abnormally elevated aPTT* Current use of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT scan Evidence of hemorrhage Evidence of a multilobar infarction with hypodensity involving >33 percent of the cerebral Hemisphere
RELATIVE EXCLUSION CRITERIA
Only minor and isolated neurologic signs Rapidly improving stroke symptoms Major surgery or serious trauma in the previous 14 days Gastrointestinal or urinary tract bleeding in the previous 21 days Myocardial infarction in the previous three months Seizure at the onset of stroke with postictal neurologic impairments Pregnancy
ADDITIONAL RELATIVE EXCLUSION CRITERIA FOR TREATMENT FROM 3 TO 4.5 HOURS FROM SYMPTOM ONSET
Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus
aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; TT: thrombin time. * Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), (3) use of anticoagulants is not known. For patients without recent use of oral anticoagulants or heparin, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table. ¶ The available data suggest that under some circumstances – with careful consideration and weighting of risk-to-benefit – patients may receive fibrinolytic therapy despite one or more relative contraindications. In particular, there is now consensus that patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: o Complete hemianopsia: ≥2 on NIHSS question 3, or o Severe aphasia: ≥2 on NIHSS question 9, or o Visual or sensory extinction: ≥1 on NIHSS question 11, or o Any weakness limiting sustained effort against gravity: ≥2 on NIHSS question 5 or 6, or o Any deficits that lead to a total NIHSS >5, or

 

Emergency Department Management

Oxygen is not recommended for all patients. If the pulse saturation is below 94%, supplemental oxygen should be given.

Fluids should be individualized according to patients’ cardiovascular status, plasma glucose, and electrolyte levels. Isotonic fluid is the best choice because hypotonic fluids may aggravate cerebral edema. Both hypoglycemia and hyperglycemia worsen the prognosis; normoglycemia (60–126 mg/dL) is the best target point. American Diabetes Association suggests achieving glucose targets of 140 to 180 mg/dL in acute ischemic stroke.

Thrombolysis is done in patients eligible for thrombolytic therapy by alteplase, (Figure 10) which is a tissue plasminogen activator (explained in Table 2). Within 4.5 hours of symptom onset, thrombolytic therapy may be applied.

Apart from brain injury of acute stroke, central nervous system infection, subdural empyema, brain abscess and any concomitant infection may cause fever. Fever is associated with the increased mortality rate, disability, and extended hospital stays. The physician should find and treat the source of fever. Additionally, antipyretics may be used for febrile patients, but its effect on prognosis is still unclear.

Drug of choice for fever:

• Acetaminophen
  • <50 kg: 12.5 mg/kg IV q4hr OR 15 mg/kg IV q6hr; not to exceed 750 mg/dose or 3.75 g/day
  • ≥50 kg: 650 mg IV q4hr OR 1000 mg IV q6hr; not to exceed 4 g/day Infuse IV over at least 15 minutes

Reducing the blood pressure does not affect the early and long-term outcome. However, systolic blood pressure should be kept under 185 mmHg and diastolic pressure under 110 mmHg to administer thrombolytic treatment. If thrombolytic therapy is contraindicated, the physician should not interfere unless systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg or the patient has active coronary artery disease, aortic dissection, hypertensive encephalopathy, acute renal failure, pre-eclampsia, and eclampsia.

The first-line antihypertensive agents are labetalol and nicardipine, and the second-line choice is nitroprusside.

• Labetalol
  • 20 mg IV over 2 minutes initially, then 40-80 mg IV q10min; total dose not to exceed 300 mg
  • Alternative: 1-2 mg/min by continuous IV infusion; total dose of 300 mg has been used
• Nicardipine
  • Start with 5 mg/hr
  • If necessary, increase infusion rate 2.5 mg/hr every 5 minutes to a maximum dose of 15 mg/hr.
• Nitroprusside sodium
  • Initial: 0.25-0.3 mcg/kg/min IV infusion; may increase by 0.5 mcg/kg/min every few minutes to achieve desired results
  • Usual range: 3-4 mcg/kg/min IV infusion, not to exceed 10 mcg/kg/min

Aspirin reduces the 14-day recurrence of ischemic stroke and total mortality. Clopidogrel and aspirin-extended-release dipyridamole can be used alone or with aspirin. Aspirin is the only medication that is effective for the very early treatment of acute ischemic stroke.

• Aspirin (acetylsalicylic acid)
  • 160 to 325 mg/day PO
  • Aspirin may be given rectally for patients with acute stroke who cannot take by the oral route.
  • To the Asian patients with high-risk TIA (i.e., ABCD2 score of ≥4) or minor stroke (NIHSS score ≤3) clopidogrel and aspirin as dual antiplatelet therapy could be given for 21 days 35

Anticoagulation with heparin or low molecular weight heparin is not recommended. It is associated with higher mortality and poor outcomes compared to aspirin alone in 48 hours. However, secondary stroke prevention is recommended for patients with atrial fibrillation and in case of risk for cardiogenic embolism. For this treatment, warfarin may be given in the first 24 hours and continue for two weeks.

Prognosis

Presence of facial paresis, arm weakness or drift and abnormal speech are the main predictors of outcome. The NIHSS (National Institutes of Health Stroke Scale) score on admission gives a clue about stroke outcome. The use of NIHSS score is recommended for all patients with stroke.

References and Further Reading

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