Ischemic%20stroke Diagnosis

• Determine if patient’s symptoms are due to stroke, identify other conditions requiring immediate intervention and determine the potential causes of stroke

• Time of symptom onset is the single most important piece of historical information
  • Stroke onset defined as the last time patient was symptom-free
• Obtain circumstances around the development of symptoms and features that may point to other potential causes of symptoms
• Identify risk factors for arteriosclerosis and cardiovascular disease; medications, conditions that may predispose to bleeding complications; history of drug abuse, infection, migraine, seizure, trauma, oral contraceptive use or pregnancy

• Complete physical examination including vital signs, oxygen saturation and body temperature
• Brief but thorough neurologic exam

Clinical Stroke Score

• National Institutes of Health Stroke Scale (NIHSS)
  • Helps quantify the degree or severity of neurological deficit and may identify possible location of lesion/occlusion
  • Facilitates communication between healthcare professionals and may provide prognostic information
  • May identify patients eligible for interventions and potential risk for complications

Diagnostic Tests

• Blood glucose, HbA1c, complete blood count (CBC) with platelet count, renal function tests, serum electrolytes, fasting or nonfasting lipid profile, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen
• Cardiac biomarkers may be done to confirm or rule out acute coronary syndrome if needed
• 12-lead electrocardiogram (ECG) to screen for atrial fibrillation and atrial flutter and to assess for other accompanying cardiac conditions
• Chest X-ray

Perform the following tests, if required:

• Toxicology screen, blood alcohol level
• Arterial blood gas (if hypoxia is suspected)
• Liver function tests
• Pregnancy test
• Lumbar puncture [if subarachnoid hemorrhage is suspected and computed tomography is negative for blood]
• Electroencephalography (EEG) (if seizures are suspected)
• Echocardiogram (if cardioembolism is suspected)

• Should be done on all admitted patients suspected of acute stroke
• Performed within 20 minutes of arrival in the emergency room for patients who may be candidates for IV Alteplase and/or mechanical thrombectomy 

Non-contrast Cranial Computed Tomography (NCCT)

• Differentiates ischemic from hemorrhagic stroke or other structural brain lesions that may mimic stroke
• CT scan may be normal within the 1st 24 hours of ischemia but will show hemorrhages from onset of hemorrhagic stroke
• Mandatory before initiating any specific therapy to treat acute ischemic stroke
• Effective in ruling out intracerebral hemorrhage prior to IV Alteplase administration
• Alberta Stroke Program Early Computed Tomography Score (ASPECTS) helps in the detection of early ischemic changes and should be evaluated in patients who are candidates for intravenous thrombolysis
• Hyperdense middle cerebral artery CT should not be used as criteria to withhold IV Alteplase

Cranial Computed Tomography Angiography (CTA)

• May be used on patients suspected with intracranial large vessel occlusion without renal impairment history and is a candidate for thrombectomy
  • For patients on Metformin, postponement of administration of Metformin should be considered
• Serum creatinine concentration may be deferred if patient does not present with renal impairment 

Magnetic Resonance Imaging (MRI) of the Brain

• MRI is more sensitive and specific for diagnosis of ischemic stroke and determination of the extent of reversible or irreversible cerebral ischemia especially for stroke within 3-8 hours
• Important in patients with unusual presentations, silent cerebrovascular disease especially chronic microbleeds, rare stroke varieties, or in whom stroke mimics are suspected but not clarified on computed tomography
• May be used to rule out intracerebral hemorrhage prior to IV Alteplase administration
• Can be used to identify diffusion-positive fluid-attenuated inversion recovery (FLAIR)-negative lesions that can be a basis in selecting patients who can benefit from rt-PA administration after 4.5 hours of stroke symptom recognition
• It is not recommended to use MRI to exclude cerebral microbleeds before IV Alteplase administration

Cranial MRI with Diffusion-Weighted Imaging (DWI)

• Highly sensitive in detecting early cerebral ischemic changes in acute stroke patients

Vascular Imaging

• CT and MR angiography, transcranial Doppler ultrasonography, carotid duplex sonography and catheter angiography have been used to detect intracranial or extracranial vessel abnormalities and to screen for stenosis

Intravenous recombinant tissue plasminogen activator (rt-PA) should only be administered under the following conditions:

• Physician and staff with expertise in acute stroke management, in delivering thrombolysis and in monitoring for complications
• Immediate access to high-resolution imaging (eg noncontrast CT scan) facilities which are available 24 hours/day and staff trained and experienced in interpreting the results
• Facility has the means to treat potential complications (eg intracerebral hemorrhage)
• Intravenous rt-PA is given only to patients satisfying specific inclusion and exclusion criteria

Patient Inclusion Criteria

• Patients within 3-4.5 hours of acute ischemic stroke symptom onset or last known well or baseline state
• Ischemic stroke with measurable neurological deficit by clinical assessment confirmed through neuroimaging and shows no signs of hemorrhage
• Medically eligible patients ≥18 years of age 
• In the 3- to 4.5-hour window, patients ≤80 years old with no known history of both diabetes mellitus and stroke, NIHSS score ≤25, not taking any oral anticoagulants and no evidence of ischemic injury involving >⅓ of the middle cerebral artery territory on imaging
  • May be given with caution in patients >80 years of age presenting in the 3- to 4.5-hour window from stroke onset
• Mild with disabling stroke symptoms to severe stroke symptoms
• Known case of sickle cell disease presenting with acute ischemic stroke
• Patients with blood pressures that can be lowered safely to <185/110 mmHg with antihypertensive agents
• Patients with history of small number (1-10) of cerebral microbleeds demonstrated on MRI
• Initial glucose levels >50 mg/dL

Patient Exclusion Criteria

Clinical Contraindications

• Onset of stroke >4.5 hours prior to planned start of treatment
• Neurologic deficit is minor or spontaneously and rapidly improving
• Symptoms of stroke suggestive of subarachnoid hemorrhage, regardless of a computed tomography result
• Hypertension: Systolic blood pressure (SBP) >185 mmHg and diastolic blood pressure (DBP) >110 mmHg on repeated measurements despite aggressive treatment to lower blood pressure
• In the setting of middle cerebral artery stroke, an obtunded or comatose state may be a relative contraindication
• Signs of active internal bleeding or acute trauma (ie fracture) on examination
• Mild nondisabling stroke symptoms (NIHSS score 0-5) that can be treated within 3 and 4.5 hours of ischemic stroke symptom onset or last known well or baseline state

History Contraindications

• Major surgery (eg recent intracranial or spinal surgery) or serious trauma within the last 2 weeks
• History of or current intracranial hemorrhage
• Prior stroke or serious head injury in the preceding 3 months
• Gastrointestinal or urinary tract hemorrhage within 21 days
• Structural gastrointestinal malignancy
• Infective endocarditis
• Arterial puncture at a noncompressible site within the preceding 7 days or lumbar puncture within the last 3 days
• Untreated cerebral aneurysm, arteriovenous malformation (AVM) or brain tumor
• Clinical presentation suggestive of post-myocardial infarction pericarditis
• Patient is taking oral anticoagulants (eg Warfarin) and with INR >1.7 or prothrombin time >15 seconds
• Direct thrombin inhibitors or direct factor Xa inhibitors
  • May be re-evaluated if lab tests (eg aPTT, INR, platelet count) are normal or if last dose of these agents was taken >48 hours in patients with normal renal function
• Patient has received heparin within the last 48 hours and has an elevated activated partial thromboplastin time greater than the upper limit of normal
• Patient has received low-molecular-weight heparin within the last 24 hours
• Known hereditary or acquired hemorrhagic diathesis or unsupported coagulation factor deficiency
• Known case or suspected case of aortic arch dissection

Laboratory Contraindications

• Platelet count <100,000 mm³
• INR >1.7 and elevated activated partial thromboplastin time (>1.5x normal)
• Positive pregnancy test

Radiology Contraindications

• Intracranial hemorrhage
• Large area of low attenuation consistent with an infarcted brain (time of symptom onset may have been earlier)
• Intracranial tumor, aneurysm, AVM or other space-occupying lesion

Relative Exclusion Criteria

• Seizure at stroke onset
• Pregnancy or possible pregnancy
• >10 cerebral microbleeds on MRI
• Acute myocardial infarction occurred in the past 3 months is a ST-elevation myocardial infarction (STEMI) involving the left anterior myocardium
• History of gastrointestinal or genitourinary bleeding