Acute Ischemic Stroke Management & Thrombolysis

Acute Ischemic Stroke Management & Thrombolysis

Acute ischemic stroke ($AIS$) is a hyperacute medical emergency where rapid recanalization directly determines neurological salvage and long-term functional independence. Neurocritical care management requires rapid triage, rigorous physiological optimization, and the prompt deployment of intravenous thrombolysis and endovascular therapies.

Emergency Evaluation & Hyperacute Triage

The Neurovascular Clock: Time Is Brain

In acute large vessel occlusion ($LVO$), interruption of cerebral arterial blood flow triggers a core of immediate, irreversible necrotic infarction surrounded by an ischemic penumbra—hypoperfused tissue ($CBF\text{ between }10\text{ and }20\text{ mL}/100\text{ g}/\text{min}$) that remains electrically silent but metabolically viable. Quantitatively, the typical patient with an untreated anterior circulation large vessel occlusion loses:

• $1.9\text{ million}$ neurons every minute
• $14\text{ billion}$ synapses every minute
• $12\text{ km}$ ($7.5\text{ miles}$) of myelinated axonal fibers every minute
• An estimated 3.1 weeks of healthy brain life lost for every hour of delayed reperfusion

National Institutes of Health Stroke Scale (NIHSS)

The NIHSS is a validated 15-item neurological impairment scale ranging from 0 to 42. It evaluates level of consciousness, horizontal gaze, visual fields, facial palsy, motor drift, limb ataxia, sensory loss, language/aphasia, dysarthria, and inattention/extinction:

• Minor stroke: $1\text{--}4$
• Moderate stroke: $5\text{--}14$
• Severe stroke: $15\text{--}20$
• Very severe stroke: $> 20$

Clinical Pitfall: The NIHSS is heavily weighted toward left hemispheric anterior circulation deficits (aphasia yields up to 7 points), whereas severe right hemisphere non-dominant strokes (profound neglect, anosognosia) or posterior circulation strokes (vertigo, diplopia, dysmetria, bulbar palsy, isolated hemiataxia) may score deceitfully low (e.g., NIHSS 2–4) despite carrying catastrophic disability or impending basilar thrombosis.

Emergency Neuroimaging & ASPECTS Scoring

Emergent non-contrast head CT ($NCCT$) is mandatory to rule out acute intraparenchymal hemorrhage ($IPH$), subdural hematoma, or extensive established infarction. Early ischemic changes ($EIC$) include loss of gray-white matter differentiation at the insular ribbon, lentiform nucleus obscuration, and cortical sulcal effacement.

The Alberta Stroke Program Early CT Score (ASPECTS) is a 10-point quantitative topographic CT assessment of the middle cerebral artery ($MCA$) territory across two axial slices (ganglionic and supraganglionic levels):

• Subcortical structures (3 points): Caudate ($C$), Lentiform ($L$), Internal Capsule posterior limb ($IC$)
• Cortical regions (7 points): Insular cortex ($I$), $M1$ (anterior inferior MCA), $M2$ (anterior lateral MCA), $M3$ (posterior temporal MCA), $M4$ (anterior superior MCA), $M5$ (lateral MCA above M2), $M6$ (posterior superior MCA above M3)
• Normal CT receives $10/10$; each defined area demonstrating early hypodensity subtracts 1 point. An ASPECTS $\le 7$ indicates extensive ischemic core, while ASPECTS $\le 5$ historically carried higher hemorrhage risk.

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Intravenous Thrombolysis: Pharmacology & Evidence

Intravenous thrombolysis converts plasminogen to active plasmin, which lyses cross-linked fibrin polymers within the thromboembolism. The 2026 AHA/ASA Stroke Guidelines recognize two primary thrombolytic agents.

Tenecteplase Advantages

Tenecteplase's enhanced fibrin specificity preserves circulating fibrinogen and alpha-2-antiplasmin, producing less systemic lytic coagulopathy. In the AcT trial (randomized non-inferiority trial of 1,600 patients), tenecteplase $0.25\text{ mg/kg}$ demonstrated non-inferiority to alteplase with identical rates of 90-day functional independence (mRS 0–1: $36.9\%$ vs $34.8\%$) and symptomatic intracranial hemorrhage ($3.4\%$ vs $3.2\%$). In EXTEND-IA TNK, tenecteplase prior to endovascular thrombectomy achieved substantially higher rates of substantial early recanalization than alteplase ($22\%$ vs $10\%$) and superior 90-day functional recovery. Furthermore, single-bolus administration streamlines inter-facility transfer without requiring infusion pump maintenance.

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Eligibility Criteria, Hemodynamics, and Absolute Contraindications

Blood Pressure Thresholds

Hypertension dramatically increases the risk of reperfusion-induced intracranial hemorrhage.

• Pre-treatment threshold: Blood pressure must be lowered to $SBP < 185\text{ mmHg}$ and $DBP < 110\text{ mmHg}$ before initiating thrombolysis.
• Post-treatment maintenance: Blood pressure must remain strictly $< 180/105\text{ mmHg}$ for at least 24 hours post-thrombolysis.

First-line intravenous antihypertensives include:

• Nicardipine: Continuous IV infusion at $5\text{ mg/h}$, titrated by $2.5\text{ mg/h}$ every 5–15 minutes (maximum $15\text{ mg/h}$).
• Clevidipine: Rapidly cleared dihydropyridine calcium channel blocker; start at $1\text{--}2\text{ mg/h}$, titrate by doubling every 2–5 minutes until goal achieved (follow the current dosing protocol and lipid-load limits).
• Labetalol: $10\text{--}20\text{ mg}$ IV push over 1–2 minutes, repeatable once or followed by continuous infusion ($2\text{--}8\text{ mg/min}$).

Eligibility Is a Structured Risk Decision

Use the complete current stroke protocol rather than a short memorized absolute-contraindication table. Acute intracranial bleeding, active major bleeding, severe relevant coagulopathy, uncontrolled pressure despite treatment, suspected aortic dissection, and suspected infective endocarditis can make IV thrombolysis unsafe. Recent surgery, trauma, anticoagulant exposure, prior hemorrhage, and structural lesions require attention to their specific characteristics and the current guideline.

An incidental unruptured aneurysm or extra-axial neoplasm does not automatically prohibit IVT. An intra-axial tumor has different bleeding considerations. Recent DOAC exposure requires timing, kidney function, drug-specific activity testing when available, and specialist interpretation; a normal INR does not exclude significant DOAC activity. No single universal concentration cutoff or administration of a reversal agent guarantees eligibility. Do not delay an eligible treatment while obtaining laboratory tests that are not clinically required, but investigate suspected coagulopathy promptly.

Within 4.5 hours, treat eligible adults with disabling deficits rapidly regardless of a low NIHSS. For nondisabling deficits, the 2026 guideline favors appropriate dual antiplatelet therapy rather than IVT. Disability is patient-specific: hand weakness or aphasia may prevent a patient's usual work despite few NIHSS points. Selected unknown-onset or 4.5–9-hour patients may qualify through DWI-FLAIR or perfusion mismatch criteria. These pathways require their own imaging and clinical criteria and do not make every late presentation eligible.

Unknown Time of Onset & Wake-Up Strokes (The WAKE-UP Protocol)

1. T2-FLAIR: Visible signal changes evolve over a variable interval. Absence of marked FLAIR signal can support an established imaging-selection pathway but is not a precise clock for an individual lesion.

In WAKE-UP, administering alteplase to patients with DWI-FLAIR mismatch resulted in a significantly higher proportion of patients with favorable functional outcomes at 90 days ($53.3\%$ vs $41.8\%$, $p = 0.02$) with an acceptable sICH rate ($2.0\%$ vs $0.4\%$).

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Suspected Hemorrhage After IVT

A new headache, vomiting, abrupt hypertension, reduced consciousness, or worsening deficit requires urgent assessment. Stop an alteplase infusion if still running, obtain emergency noncontrast CT and blood tests including CBC, coagulation studies, fibrinogen, and blood bank testing, and involve the stroke, neurocritical, neurosurgical, and transfusion teams. Different studies use different sICH definitions; do not wait for a four-point NIHSS change or a particular hematoma category before investigating deterioration.

The 2026 guidance includes cryoprecipitate 10 units over 10–30 minutes with repeat fibrinogen assessment and replacement to maintain at least 150 mg/dL. Antifibrinolytics such as tranexamic acid or aminocaproic acid may be useful, particularly when blood products are contraindicated or cryoprecipitate is not available promptly. This is not a mandatory identical cryoprecipitate-plus-TXA bundle for every patient. Address any additional coagulopathy separately. PCC is not a specific antidote to fibrinolysis.

Individualize pressure management to bleeding severity, perfusion, intracranial pressure, and the patient's trajectory rather than applying a universal SBP-below-140 rule after all reperfusion complications. Treat hydrocephalus, herniation, airway failure, and systemic instability in parallel. Document serial examinations and imaging, reassess hemostasis, and communicate uncertainty to the family.

Source: 2026 AHA/ASA ischemic stroke guideline.