Acute Ischemic Stroke

1. THE 2-MINUTE PHYSIOLOGY (Rapid Pathophysiology)

• Acute Ischemic Stroke (AIS) is a focal vascular injury that abruptly restricts cerebral blood flow (CBF) to a specific region of the brain, retina, or spinal cord, resulting in rapid-onset neurologic impairment.
• Perfusion Thresholds: Normal CBF is 40 to 60 mL/100 g of brain tissue per minute. When CBF drops below 15 to 18 mL/100 g/min, the affected brain tissue undergoes "electrical silence"—cells remain viable but fail to depolarize, manifesting clinically as a focal neurological deficit. If perfusion drops below 10 mL/100 g/min, active membrane failure occurs within minutes, triggering rapid cell death.
• Core vs. Penumbra: The central region of severe hypoperfusion is the ischemic core, where tissue is irreversibly infarcted. Surrounding this core is the ischemic penumbra, a border zone of viable but hypoperfused tissue preserved by collateral blood vessels. The clinical goal of rapid emergency reperfusion is the survival of this penumbral tissue.
• The Ischemic-Neurotoxic Cascade: At the cellular level, the loss of oxygen and glucose substrates halts oxidative phosphorylation, depleting cellular adenosine triphosphate (ATP). The failure of ATP-dependent Na+/K+ ATPase pumps results in intracellular sodium accumulation, drawing water into the cells to cause cytotoxic edema (which peaks within 48 to 72 hours). This is accompanied by a massive presynaptic release of glutamate. Glutamate over-activates postsynaptic NMDA and AMPA receptors, allowing a catastrophic influx of extracellular calcium (Ca2+). Intracellular calcium overload activates neurotoxic calpains, caspases, and nitric oxide synthase, leading to mitochondrial breakdown, free radical generation, membrane lipid peroxidation, and ultimately programmed cell death (apoptosis).

2. THE BEDSIDE ACTION PLAN (Rapid ER Management)

• Initial Resuscitation & ABCs: Immediately assess airway patency, breathing, and circulation. Ensure airway protective reflexes are intact. If the patient is unable to protect their airway or exhibits respiratory compromise, proceed with endotracheal intubation. Avoid hypoxia and target an oxygen saturation (SpO2) of 94% to 98%; routine supplemental oxygen is not indicated if the patient is normoxic (SpO2 ≥94%).
• Patient Positioning: Keep the head of the bed neutral and flat (supine as tolerated). This position increases cerebral perfusion pressure by approximately 20% compared to a 30° head-up incline. Elevation to 15–30° is reserved only for patients at high risk for aspiration, airway compromise, hypoxia, or elevated intracranial pressure.
• The Point-of-Care Glucose Rule: Perform an immediate fingerstick blood glucose check. This is the only laboratory test required prior to starting thrombolytic therapy (unless coagulopathy, thrombocytopenia, or active anticoagulant use is suspected). Correct hypoglycemia (<60 mg/dL) immediately with IV dextrose. Target a blood glucose of 140 to 180 mg/dL.
• Dehydration & Intake: Maintain NPO status. Correct clinical dehydration with IV crystalloid fluids (e.g., normal saline), but avoid overcorrection or routine volume expansion. A formal bedside swallowing evaluation must be completed prior to any oral intake.
• Blood Pressure Titration:
• Thrombolytic Candidates: Lower BP to systolic <185 mm Hg and diastolic <110 mm Hg before administering thrombolytics. Once thrombolytics are started, maintain BP <180/105 mm Hg for the first 24 hours.
• Non-Thrombolytic/Non-Thrombectomy Candidates: Maintain permissive hypertension up to <220/120 mm Hg. If SBP ≥220 or DBP ≥120 mm Hg, lower the BP gradually by approximately 15% over the first 24 hours.
• First-Line Titratable IV Antihypertensive Agents:
• Labetalol: 10–20 mg IV push over 1–2 minutes; may repeat once. Alternatively, follow with a continuous infusion of 2–8 mg/min.
• Nicardipine: Start at 5 mg/h IV infusion; titrate up by 2.5 mg/h every 5 to 15 minutes to a maximum of 15 mg/h. Reduce to a maintenance rate of 3 mg/h once the target BP is achieved.
• Clevidipine: Start at 1–2 mg/h IV infusion; titrate by doubling the dose every 2 to 5 minutes to a maximum of 21 mg/h.
• Systemic Reperfusion Regimens:
• Alteplase (rtPA): 0.9 mg/kg IV total dose (maximum dose 90 mg). Give 10% of the dose as an initial slow bolus over 1 minute, followed by the remaining 90% as a continuous infusion over 60 minutes. Do not administer antiplatelets or anticoagulants for at least 24 hours following thrombolytic therapy.
• Tenecteplase: Administer as a single IV bolus over 5 seconds.
• FDA-Approved Weight-Tiered Dosing: <60 kg = 15 mg; 60 to <70 kg = 17.5 mg; 70 to <80 kg = 20 mg; 80 to <90 kg = 22.5 mg; ≥90 kg = 25 mg (maximum dose 25 mg).
• Traditional Off-Label Dosing: 0.25 mg/kg IV bolus (maximum dose 25 mg).
• Mechanical Thrombectomy: Indicated for patients with confirmed anterior circulation large vessel occlusion (LVO) (ICA or MCA M1/M2 segments) who present within a 24-hour window of symptom onset.

3. THE DIAGNOSTIC GRID (Differential Diagnosis & Workup)

Top Stroke Mimics

1. Hypoglycemia: Instantly ruled in or out by bedside fingerstick blood glucose.
2. Seizure with Todd's Paralysis: Postictal focal deficits (often unilateral) that typically resolve within an average of 15 hours (up to 36 hours).
3. Complicated or Hemiplegic Migraine: Often presents with preceding aura or "positive" (irritative) neurological phenomena (e.g., paresthesias) rather than purely "negative" (ablative) deficits.
4. Intracranial Mass (Tumor, Abscess, or Subdural/Epidural Hematoma): Slowly progressive focal signs, often with constitutional symptoms or trauma history, identified on neuroimaging.
5. CNS Infection (Meningitis, Encephalitis) or Sepsis: Presents with fever, altered mental status, and meningismus, but may cause focal deficits.

Prioritized Diagnostic Workup Strategy

• Fingerstick Blood Glucose: Checked immediately at triage to rule out hypoglycemia.
• Non-Contrast Head CT: The primary initial imaging modality. Must be acquired within 20 minutes of arrival to rapidly exclude hemorrhage, which is the key contraindication to thrombolysis.
• CT Angiography (CTA) of the Head and Neck: Obtained concurrently with or immediately following the non-contrast CT to visualize intra- and extracranial cervicocephalic vessels. It is utilized to detect an LVO or evaluate for cervical artery dissection.
• CT Perfusion (CTP) / MRI Perfusion: Performed in patients presenting in the 6–24 hour extended window or with an unknown time of onset (e.g., wake-up stroke) to quantify the mismatch between the ischemic core and salvageable penumbra.
• MRI Brain with Diffusion-Weighted Imaging (DWI): The diagnostic gold standard for acute ischemic stroke. It identifies small infarcts early (within minutes of onset) that are missed on CT.
• Standard Stroke Lab Panel: Complete blood count (to check platelet count), basic metabolic panel, coagulation studies (PT/INR, aPTT), cardiac troponin, and a 12-lead ECG.

4. THE VISUAL BOARD (ECG / POCUS / Imaging)

Standard ECG Visual Checklist

• Atrial Fibrillation: Look for an irregularly irregular rhythm with absent P-waves, representing a major source of cardioembolic stroke.
• Acute Coronary Syndrome / Myocardial Infarction: Check for hyperacute T-waves, ST-segment elevations, or depressions, as concomitant MI occurs in 2.3% of stroke patients.
• Stroke-Induced ECG Changes: Look for QT prolongation, U-waves, and deep, symmetric T-wave inversions caused by autonomic disruption or catecholamine surges.

Point-of-Care Ultrasound (POCUS) Findings

• Focused Echo: Assess for left ventricular mural thrombus, severe apical hypokinesis, valvular vegetations, or patent foramen ovale (PFO) to identify embolic origins.
• Carotid/Vertebral Assessment: Examine the neck vessels for an intimal flap, double lumen, or occlusive thrombus suggesting cervical artery dissection.

Non-Contrast Head CT Checklist (Signs of Infarction & Mimics)

• Hemorrhage Exclusion: Rule out hyperdense (white) blood in the parenchyma, ventricles, or subarachnoid space.
• Hyperdense Vessel Sign: Look for a hyperdense segment of the MCA or basilar artery, indicating an acute, occlusive thrombus.
• Early Ischemic Changes (Within 3 Hours):
• Loss of grey-white matter differentiation.
• Sulcal effacement in the affected vascular territory.
• Loss of the insular ribbon sign.
• Focal areas of hypoattenuation (mild hypodensity).

MRI Sequence visual Checklist

• Diffusion-Weighted Imaging (DWI): Look for hyperintense (bright white) lesions reflecting restricted water diffusion in cytotoxic edema.
• Apparent Diffusion Coefficient (ADC) Map: Confirm true restricted diffusion with hypointense (dark/black) signaling corresponding exactly to the DWI bright spot.
• FLAIR Sequence (DWI-FLAIR Mismatch): Since ischemia takes roughly 4.5 hours to show hyperintensity on FLAIR, a DWI-positive / FLAIR-negative mismatch confirms a fresh ischemic stroke within the 4.5-hour thrombolytic window, allowing safe treatment in wake-up strokes.

5. THE SCORING MATRIX (Risk Stratification & Guidelines)

National Institutes of Health Stroke Scale (NIHSS)

• A standardized, 11-item clinical scale scoring from 0 to 42. High scores correlate with larger infarct size and worse outcomes.
• Critical Board Exam Limitation: The NIHSS is heavily weighted toward the anterior circulation and undervalues posterior circulation findings. Cerebellar or brainstem strokes can present with an NIHSS score of 0 despite disabling symptoms (e.g., severe truncal ataxia).

ROSIER Score (Rule Out Stroke in the Emergency Room)

• A validated tool used in the ED to differentiate stroke from common mimics.

\[\text{ROSIER Score} = \text{Facial Weakness (1)} + \text{Arm Weakness (1)} + \text{Leg Weakness (1)} + \text{Speech Disturbance (1)} + \text{Visual Field Defect (1)} - \text{Loss of Consciousness (-1)} - \text{Seizure (-1)}\]

• Interpretation: A score of \(\le 0\) makes an acute stroke highly unlikely.

ASPECTS (Alberta Stroke Program Early CT Score)

• A 10-point quantitative scale grading early ischemic hypodensity across 10 defined regions of the MCA territory on non-contrast CT. One point is subtracted for each region demonstrating hypoattenuation.
• Inclusion Criteria: An ASPECTS score \(\ge 6\) (combined with an NIHSS score \(>6\)) is required to support mechanical thrombectomy within the 24-hour window.

ABCD2 Score (Post-TIA Stroke Risk Stratification)

• Used to predict the 48-hour risk of stroke following a TIA.
• Criteria:
• Age \(\ge 60\) years (1 point).
• Blood pressure \(>140/90\) mm Hg (1 point).
• Clinical features: Unilateral weakness (2 points) OR Speech impairment without weakness (1 point).
• Duration of symptoms: \(\ge 60\) minutes (2 points) OR 10–59 minutes (1 point).
• Diabetes history (1 point).
• Risk Stratification & 48-Hour Stroke Risk:
• 0–3 points: Low risk (1% risk).
• 4–5 points: Moderate risk (4.1% risk).
• \(\ge 6\) points: High risk (8% risk).
• Board Warning: Do not rely solely on the ABCD2 score to dictate ED disposition. Current guidelines recommend that almost all TIA patients undergo a front-loaded workup, including urgent vascular imaging, regardless of their score.

6. THE DANGER ZONE (Pitfalls & Critical Actions)

Deadly Cognitive Traps & Trainee Pitfalls

• Premature Closure on the "Dizzy" Patient: Labeling cerebellar strokes as benign peripheral vestibulopathy. Because the NIHSS undervalues the posterior circulation, cerebellar infarcts can present with an NIHSS of 0. Missing these can lead to fatal cerebellar edema, hydrocephalus, or brainstem compression.
• The "Time of Discovery" Error: Miscalculating the time of onset in a patient who awoke with symptoms. The onset must always be clocked from the "last known well" time when the patient was at their baseline.
• Thrombolysis Delay Awaiting Labs: Delaying the administration of alteplase/tenecteplase while waiting for laboratory panels (e.g., platelet count or coagulation times) in a patient with no history of bleeding disorders, thrombocytopenia, or active anticoagulant use.
• Overly Aggressive BP Reduction in Non-Candidates: Lowering blood pressure aggressively below 220/120 mm Hg in patients with acute stroke who are not candidates for reperfusion therapy. This reduces cerebral perfusion pressure, converting the salvageable penumbra into an irreversible infarct.
• Administering Thrombolytics with Uncontrolled Blood Pressure: Commencing alteplase or tenecteplase when SBP remains \(>185\) mm Hg or DBP remains \(>110\) mm Hg. This dramatically increases the risk of catastrophic symptomatic intracerebral hemorrhage.

Mandatory Critical Actions

• Obtain and review a bedside fingerstick blood glucose immediately on arrival for every suspected stroke patient.
• Clearly establish and document the "last known well" time utilizing bystander or family confirmation.
• Perform a strict review of absolute and relative contraindications before administering thrombolytics.
• Stop the thrombolytic infusion immediately if the patient develops signs of hemorrhagic transformation (acute neurological decline, severe headache, sudden hypertension, vomiting, or seizure) and obtain an emergency non-contrast head CT.
• Withhold all antiplatelet and anticoagulant agents for a strict 24 hours following thrombolytic administration; a repeat CT must show no hemorrhage before these are initiated.

7. MCQ MASTERCLASS (Written Exam Tips)

High-Yield Exam "Buzzwords" and Landmarks

• "Crossed Deficits": Ipsilateral cranial nerve deficits paired with contralateral extremity motor or sensory deficits. This always localizes the lesion to the brainstem (pons/medulla) where motor tracts decussate, rather than the cerebral cortex.
• Wallenberg Syndrome (Lateral Medullary Syndrome): Look for vertigo, Horner syndrome, ipsilateral facial numbness, loss of corneal reflex, and contralateral loss of pain and temperature. This is caused by occlusion of the vertebral artery or the posterior inferior cerebellar artery (PICA).
• "Amaurosis Fugax": Painless, transient monocular blindness. This identifies the ischemia as involving the anterior circulation (ipsilateral internal carotid/ophthalmic artery).
• Horner Syndrome + Unilateral Headache/Neck Pain: In a young patient (<45 years old), this is cervical artery dissection until proven otherwise.
• Cerebral Venous Thrombosis (CVST): Classically tested as a young female on oral contraceptives, pregnant, or postpartum, presenting with atypical headache, seizures, and focal deficits crossing typical arterial territories.
• Most Common Cause of Cardioembolic Stroke: Embolization of a mural thrombus in the setting of atrial fibrillation.
• Most Common Vascular Territory in AIS: The Middle Cerebral Artery (MCA).

Differentiation of Common Distractors

• Distractor: Initiating heparin or a direct oral anticoagulant (DOAC) in the ED for an acute ischemic stroke patient with atrial fibrillation.
• Correction: Do not anticoagulate stroke patients in the ED. The risk of hemorrhagic transformation is greatest in the first 48 hours; anticoagulation is always initiated in the inpatient setting.
• Distractor: Forehead-sparing facial weakness as a sign of Bell Palsy.
• Correction: Forehead sparing indicates a central upper motor neuron lesion (stroke) due to bilateral cortical innervation of the upper face. Facial weakness that includes the forehead indicates a peripheral lower motor neuron lesion (Bell Palsy).
• Distractor: Excluding a patient from thrombolysis solely because they had a lumbar puncture or a TIA clinic visit in the past week.
• Correction: Lumbar puncture within 7 days is a relative contraindication, and current guidelines state IV thrombolysis may still be considered on a case-by-case basis.

8. THE BOARDROOM SCRIPT (OSCE & Oral Board Tips)

Communication Pearls & Initial Script

• "As soon as this patient arrives, I am activating a Stroke Code to immediately mobilize our multidisciplinary stroke team, charge nurse, and CT technicians."
• "I will state clearly to my team: 'My immediate clinical priorities are to establish the patient's exact last known well time, obtain a bedside point-of-care glucose, secure the airway, and position the head in a midline, neutral, flat position'."

Mandatory Physical Exam Phrasing

• "I am performing a focused neurological examination to calculate the baseline National Institutes of Health Stroke Scale (NIHSS) score."
• "I am specifically examining the cranial nerves, assessing pupillary reactivity and extraocular movements, testing for facial asymmetry and speech fluency, and evaluating the motor system for pronator drift."
• "If a posterior circulation stroke is suspected due to dizziness, I will perform a formal assessment of gait and truncal stability at the bedside, keeping in mind that cerebellar infarcts can present with an NIHSS of 0."

Smooth Articulation of Management Steps

• "I will transport the patient directly to the CT scanner. If the non-contrast head CT shows no evidence of hemorrhage or other contraindications, and the patient is within the 4.5-hour treatment window, I will recommend weight-based IV Alteplase at 0.9 mg/kg up to a maximum of 90 mg, with 10% given as an initial IV bolus over 1 minute and the remaining 90% infused over 60 minutes."
• "While administering Alteplase, if the CT angiogram identifies a proximal large vessel occlusion in the anterior circulation, I will immediately consult neuro-interventional radiology for emergency mechanical thrombectomy within the 24-hour window, without delaying my thrombolytic infusion."
• "To ensure a safe infusion, I will strictly manage the patient's blood pressure to <185/110 mm Hg before starting Alteplase, and <180/105 mm Hg for the next 24 hours. I will achieve this by initiating a titratable IV infusion of Nicardipine at 5 mg/h, titrating up by 2.5 mg/h every 5–15 minutes, or using Labetalol 10–20 mg IV slow push."
• "If the patient develops a sudden headache, vomiting, acute hypertension, or neurological decline during the infusion, I will stop the thrombolytic infusion immediately, order an emergency non-contrast head CT, send a coagulation panel and fibrinogen level, and empirically administer 10 units of cryoprecipitate while consulting neurosurgery."