Acute Ischemic Stroke: Thrombolysis and Thrombectomy
CVA · EP 02 · THROMBECTOMY
Before You Listen
- Prerequisites: CVA-01 vascular anatomy and stroke syndromes (Circle of Willis, MCA face-and-arm pattern, lacunar localization); the basic difference between ischemic and hemorrhagic stroke; familiarity with the Glasgow Coma Scale (GCS) and basic ICU pharmacology of intravenous (IV) antihypertensives (labetalol, nicardipine).
- Runtime: 1 hour 2 minutes 31 seconds.
- Topic in one line: the five-subtype Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and how it drives secondary prevention, the National Institutes of Health Stroke Scale (NIHSS) zero-to-42 severity tool with its 17%-per-point prognostic gradient and posterior-circulation blind spots, the modified Rankin Scale (mRS) with functional independence defined as 0-2, the alteplase 0.9 mg/kg / 90 mg cap / 10% bolus / 60-minute infusion protocol with the NINDS 0-3 hour and ECASS III 3-4.5 hour windows and the corresponding numbers needed to treat (NNT) of 10 and 20, the 6.8% symptomatic intracerebral hemorrhage (sICH) rate, the 185/110 pre-treatment and 180/105 post-treatment blood-pressure thresholds, the glucose-only mandatory pre-treatment lab and the ≤45-minute door-to-needle target, the ECASS III combined diabetes-plus-prior-stroke exclusion, tenecteplase (TNK) 0.25 mg/kg / 25 mg cap as a single bolus, the WAKE-UP DWI-FLAIR mismatch and EXTEND perfusion mismatch trials, and the Class of 2015 thrombectomy trials with DAWN clinical-core mismatch out to 24 hours and DEFUSE 3 perfusion mismatch out to 16 hours, plus the ASPECTS ≥6 cutpoint. Memorize them cold.
Vignette. A 74-year-old right-handed woman with atrial fibrillation (not on anticoagulation), diabetes, and well-controlled hypertension is brought to a primary stroke center 95 minutes after the sudden onset of right facial droop, dense right-arm flaccidity, and global aphasia witnessed by her husband. Her blood pressure on arrival is 192/108. Initial fingerstick glucose is 118 mg/dL. Non-contrast head computed tomography (CT) is unremarkable for hemorrhage with an Alberta Stroke Program Early CT Score (ASPECTS) of 9; CT angiography (CTA) shows occlusion of the proximal left middle cerebral artery (MCA) at the M1 segment. National Institutes of Health Stroke Scale (NIHSS) is 18. The comprehensive stroke center is 35 minutes away by helicopter.
What is the next pharmacologic step and the exact dose, what blood-pressure target must be achieved before that drug is given and maintained after, what is the only mandatory pre-treatment laboratory test, and what is the rationale for proceeding to mechanical thrombectomy in parallel rather than waiting to see if the drug works?
(Answer at the end of this chapter)
Section 1: TOAST Classification, NIHSS, and the Modified Rankin Scale
Bottom line: the TOAST classification sorts ischemic stroke into five etiologic subtypes that drive secondary prevention; the National Institutes of Health Stroke Scale (NIHSS) is a 0-42 acute-severity tool that under-weights posterior strokes and loses 17% odds of an excellent outcome per point; the modified Rankin Scale (mRS) is the trial-defining global disability scale, with functional independence = mRS 0-2.
Before treatment, every acute ischemic stroke must be sorted by mechanism because the secondary prevention regimen depends on it. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification organizes ischemic strokes into five etiologic subtypes. Large artery atherosclerosis captures strokes from atheromatous plaques in the internal carotid artery, vertebral artery, or major intracranial vessels. The plaque either causes hemodynamic narrowing or seeds an artery-to-artery embolus; vascular imaging typically reveals greater than 50% stenosis. Secondary prevention combines a high-intensity statin, antiplatelet therapy, and carotid endarterectomy or stenting when stenosis exceeds 70%. Cardioembolism is the second subtype; the heart harbors the clot and the brain catches the embolus. The most common cardiac source is atrial fibrillation, with mechanical valves, recent myocardial infarction with left ventricular thrombus, dilated cardiomyopathy, endocarditis, and patent foramen ovale rounding out the list. The clinical clue is a sudden maximal deficit at onset (no stuttering progression), and secondary prevention requires anticoagulation rather than antiplatelet therapy alone.
Small vessel occlusion (lacunar stroke) is the third subtype, covered fully in CVA-01: lipohyalinosis of small penetrators from chronic hypertension produces a less than 15 mm subcortical infarct in the basal ganglia, thalamus, internal capsule, or pons, with no cortical signs; secondary prevention focuses on aggressive blood pressure control. Stroke of other determined etiology is the wildcard subtype: arterial dissection, hypercoagulable states, sickle cell disease, vasculitis, moyamoya. Stroke of undetermined etiology (cryptogenic) applies when the workup fails to identify a definitive cause, when multiple causes are found simultaneously, or when the workup is incomplete, and accounts for approximately 25-30% of all ischemic strokes. Prolonged cardiac monitoring with implantable loop recorders has revealed occult atrial fibrillation in a substantial proportion of cryptogenic patients, shifting many into the cardioembolic category and from antiplatelet therapy to anticoagulation.
The National Institutes of Health Stroke Scale (NIHSS) is the standardized 15-item acute-severity tool, scored 0-42. Items cover level of consciousness, orientation questions, response to commands, horizontal eye movements, visual fields, facial symmetry, motor function in each limb, limb coordination, sensation, language (naming, reading, describing), dysarthria, and extinction/inattention. Severity cutpoints: less than 5 mild, 5-9 moderate, 10 or above severe, above 20 very severe with high probability of large vessel occlusion (LVO), above 25 very severe with high probability of death or major disability. Each additional point on the NIHSS decreases the odds of an excellent functional outcome by approximately 17%; every point matters.
The most critical board-tested limitation of the NIHSS is that it under-represents posterior circulation strokes. The scale is heavily weighted toward anterior-circulation deficits (language, neglect, gaze, facial strength, limb motor function are all prominent in MCA strokes). A patient with a devastating basilar occlusion causing vertigo, severe dysphagia, bilateral unsteadiness, and cranial nerve deficits can score deceptively low because those posterior-fossa deficits are poorly captured. The NIHSS also does not test memory, executive function, emotional state, or swallowing. A patient with a thalamic stroke causing severe amnesia may score 0 despite a devastating cognitive deficit; a patient with a lateral medullary stroke and severe dysphagia at high risk for aspiration may score 3 or 4. The NIHSS measures acute severity, not total functional burden.
The modified Rankin Scale (mRS) is the primary outcome measure used in stroke clinical trials. It rates global disability on a 7-point scale: 0 = no symptoms; 1 = no significant disability (some symptoms but all usual activities preserved); 2 = slight disability (cannot do all previous activities but independent in self-care); 3 = moderate disability (requires some help, can walk without assistance); 4 = moderately severe (cannot walk and cannot attend to bodily needs without assistance); 5 = severe (bedridden, incontinent, constant nursing care); 6 = death. Functional independence = mRS 0, 1, or 2 at 90 days. Every landmark thrombolysis and thrombectomy trial defines benefit by the proportion of patients reaching mRS 0-2; when a board question references functional independence in the context of a stroke trial, it means a 90-day mRS of 2 or below.
High Yield — TOAST, NIHSS, and mRS
- TOAST subtypes: large artery atherosclerosis, cardioembolism, small vessel (lacunar), other determined etiology, undetermined (cryptogenic ≈ 25-30%).
- Cardioembolism clue: sudden maximal deficit at onset; secondary prevention = anticoagulation (NOT antiplatelet alone).
- NIHSS = 15 items, 0-42; <5 mild, 5-9 moderate, ≥10 severe, >20 very severe (LVO probable), >25 portends death/major disability.
- 17% drop in odds of excellent outcome per NIHSS point.
- NIHSS under-represents posterior circulation strokes: a basilar/Wallenberg patient may score deceptively low.
- mRS 0-6: 0 = no symptoms; 6 = death.
- Functional independence = mRS 0-2 at 90 days (the trial-defining endpoint).
- Cryptogenic stroke: implantable loop recorder reveals occult AF in a substantial fraction; reclassification shifts secondary prevention to anticoagulation.
Clinical Pearl — 75% of cardiogenic emboli go to the brain
Three-quarters of clots launched from the heart end up in cerebral circulation rather than peripheral vessels. The cerebral arterial bed is a low-resistance high-flow target, and emboli that travel up the carotid take the path of least resistance into the proximal MCA. That tropism is what makes atrial fibrillation the dominant cause of cardioembolic stroke and what makes anticoagulation, not antiplatelet therapy, the correct secondary prevention for any TOAST-cardioembolic patient.
In a Type II cardioembolic stroke, a massive clot shoots out of the heart, travels up the healthy carotid artery at high speed, and instantly lodges in a normal, unnarrowed proximal middle cerebral artery. The brain has had zero time to prepare. It goes from 100% flow to 0% flow in a fraction of a second.
— CVA-02 podcast, ~12:00