Acute Ischemic Stroke
Time is brain. Every minute of ischemia = ~1.9 million neurons lost. Know the tPA window, thrombectomy criteria, NIHSS-driven antiplatelet choice, and BP targets cold. You will not have time to look them up mid-code stroke.
🔍 Overview
Time Windows
| Intervention | Window | Key Criteria | Trial |
|---|---|---|---|
| IV alteplase (tPA, Activase) 1ST LINE | ≤ 4.5 hours from last known well (LKW) | 0.9 mg/kg IV (max 90 mg). 10% bolus over 1 min, 90% infusion over 60 min. No anticoagulants or antiplatelets × 24h post. | NINDS, 1995 ECASS III, 2008 |
| IV tenecteplase (TNKase) 1ST LINE CHANGED 2026 | ≤ 4.5 hours | 0.25 mg/kg IV single bolus (max 25 mg; no infusion, push-and-go). Easier, faster, saves ~5 min vs alteplase. | AcT, 2022: non-inferior to alteplase. AHA/ASA, 2026: tenecteplase or alteplase, both Class 1. |
| Mechanical thrombectomy LVO | ≤ 24 hours (CTA required; perfusion imaging adjunctive) | Proximal anterior LVO (ICA, M1) with NIHSS ≥ 6 and prestroke mRS 0–1. ≤ 6h: ASPECTS 3–10, Class 1 MR CLEAN, 2015 ESCAPE, 2015. 6–24h: CHANGED 2026 ASPECTS ≥ 6 on non-contrast CT is Class 1 without mandatory perfusion imaging; CT perfusion or MRI mismatch is adjunctive (Class 2a) when immediately available DAWN, 2018 DEFUSE 3, 2018. Large core NEW 2026: ASPECTS 3–5 is Class 1 up to 24h (beyond 6h only if age < 80 and no significant mass effect) SELECT2, 2023 ANGEL-ASPECT, 2023; ASPECTS 0–2 within 6h is Class 2a in selected patients under 80 LASTE, 2024. Basilar NEW 2026: Class 1 within 24h if NIHSS ≥ 10, baseline mRS 0–1 and PC-ASPECTS ≥ 6 ATTENTION, 2022 BAOCHE, 2022. | Multiple trials, NNT ~3–5 for LVO. Large-core trials bought better function at the cost of more vascular complications and symptomatic hemorrhage, so the benefit is real but the margin is thinner. |
tPA and thrombectomy are NOT mutually exclusive. If LVO suspected → give tPA AND activate thrombectomy team simultaneously. Do not wait for tPA to work before calling interventional.
NIHSS Severity Bands, Drives Antiplatelet Choice
| NIHSS | Severity | Antiplatelet Strategy (24h post-tPA / day 1 if no tPA) |
|---|---|---|
| 0–3 | Minor stroke / TIA (or high-risk TIA, ABCD² ≥ 4) | DAPT × 21 days: ASA 325 mg load → 81 mg + clopidogrel 300–600 mg load → 75 mg daily. Then ASA alone long-term. CHANCE, 2013 POINT, 2018 |
| 4–5 | Mild-moderate (non-cardioembolic) | ASA alone; NEW 2026 clopidogrel + ASA × 21 days if no IV thrombolysis and a presumed atherosclerotic cause (Class 2a, within 24h at NIHSS 4–5) INSPIRES, 2023; or consider ticagrelor 90 mg BID + ASA × 30d (NIHSS ≤ 5) THALES, 2020 |
| ≥ 6 | Moderate-severe / LVO | ASA 325 mg load → 81 mg. No DAPT, unproven benefit + hemorrhagic conversion risk with large infarct. |
Key rule: DAPT is for minor stroke (NIHSS ≤ 3) or high-risk TIA (ABCD² ≥ 4) within 24h. NEW 2026 The 2026 guideline extends 21-day clopidogrel + aspirin to NIHSS ≤ 5 within 24–72h, or NIHSS 4–5 within 24h, when no IV thrombolysis was given and the cause is presumed atherosclerotic (≥ 50% stenosis of the relevant artery), Class 2a, because INSPIRES cut new stroke from 9.2% to 7.3% at the cost of a small rise in moderate-to-severe bleeding. Starting DAPT in moderate-severe stroke does NOT improve outcomes and increases bleeding. Don't reflexively pair ASA + clopidogrel in every stroke admission.
tPA Contraindications
- Active internal bleeding or known bleeding diathesis
- History of ICH (any time), absolute
- Ischemic stroke or head/spine trauma within 3 months
- Intracranial neoplasm, AVM, or aneurysm
- Platelets < 100,000, INR > 1.7, aPTT elevated, PT > 15
- BP > 185/110 despite treatment (must lower before tPA)
- Glucose < 50 (correct first, hypoglycemia is a stroke mimic)
- On DOAC within 48h (or detectable anti-Xa level) or therapeutic LMWH within 24h
- Recent major surgery within 14 days or intracranial/spinal surgery within 3 months
- GI or GU bleed within 21 days
- Arterial puncture at non-compressible site within 7 days
- Suspected infective endocarditis (hemorrhagic transformation + septic embolus risk)
- Suspected aortic dissection
🚨 Management
Acute Stroke Protocol
0 min -Door
Activate stroke code. ABC. Finger stick glucose (correct if < 60). NIHSS score. Two large-bore IVs. Labs: CBC, BMP, coags, troponin, type & screen.
≤ 20 min -CT
Non-contrast CT head -rule out hemorrhage. CTA head and neck -identify LVO for thrombectomy. CT perfusion if 6–24h window.
≤ 45 min -tPA
If eligible: tenecteplase 0.25 mg/kg bolus (max 25 mg) or alteplase 0.9 mg/kg IV (max 90 mg), both Class 1. Treat a disabling deficit at any NIHSS; for a non-disabling deficit give DAPT instead, since lysis has shown no benefit there. Door-to-needle target < 60 min. Lower BP to < 185/110 before tPA (labetalol 10–20 mg IV or nicardipine drip).
Thrombectomy
If LVO on CTA → activate interventional neuroradiology. Do not delay tPA for thrombectomy. Give tPA, then go to angio suite. Door-to-puncture target < 90 min.
BP Targets
| Scenario | Target | Agents |
|---|---|---|
| Pre-tPA | < 185/110 | Labetalol 10–20 mg IV, nicardipine 5–15 mg/hr |
| Post-tPA (24h) | < 180/105 | Same agents. Avoid antiplatelets/anticoagulants × 24h. Intensive SBP < 140 adds nothing (Class 3: No Benefit). |
| No tPA given, not for thrombectomy | Permissive HTN < 220/120 | Only treat if > 220/120, end-organ damage, or aortic dissection, and then lower by about 15% at first (AHA/ASA 2026), because below 220/120 early lowering has not improved outcomes and a steep drop starves the penumbra. |
| Thrombectomy CHANGED 2026 | ≤ 185/110 before (if no tPA); ≤ 180/105 during and 24h after | Class 2a. Do NOT target SBP < 140 after successful recanalization: harmful for the first 72h (Class 3: Harm), even with complete (TICI 3) reperfusion. |
Permissive hypertension in stroke maintains perfusion through collaterals. Dropping BP too aggressively in the penumbra zone worsens ischemia. Only lower BP if giving tPA, > 220/120, or specific indications.
Post-thrombectomy BP, settled in 2026: CHANGED 2026 AHA/ASA, 2026 keeps BP ≤ 180/105 during and for 24h after thrombectomy (Class 2a) and calls an intensive SBP target below 140 for the first 72h after successful recanalization harmful (Class 3: Harm). Why: BP-TARGET, 2021, ENCHANTED2/MT, 2022 and OPTIMAL-BP, 2023 all found worse or no better function with intensive lowering; the reperfused territory still depends on perfusion pressure, so dropping the BP risks the tissue the thrombectomy just saved. The old habit of targeting < 140/90 to prevent reperfusion hemorrhage is retired.
Post-tPA Management (First 24h)
- ICU or stroke unit admission
- Neuro checks q15 min × 2h → q30 min × 6h → q1h × 16h, catches hemorrhagic conversion early
- BP monitoring on same schedule; keep < 180/105
- NO antiplatelets, NO anticoagulants × 24h
- Avoid central line, arterial line, bladder catheter, NGT × 24h unless essential, bleeding risk at puncture sites
- NPO until dysphagia screen passes (formal SLP eval if concerning)
- Head of bed: flat if tolerated early (perfusion); 30° if aspiration risk
- Repeat CT head at 24h before starting antiplatelets/anticoagulants, rule out asymptomatic hemorrhagic conversion
- Dysphagia screen (bedside water swallow) before any PO. Failed → NPO, SLP consult, NGT for meds
Symptomatic ICH After tPA, Reversal
Any acute neuro decline, new HA, vomiting, or BP spike post-tPA = hemorrhagic conversion until proven otherwise. Stop tPA infusion, stat CT head.
- Stop tPA infusion immediately
- Cryoprecipitate 10 units IV (target fibrinogen > 150–200 mg/dL), the primary reversal agent. NOT FFP (too slow)
- Tranexamic acid (TXA) 1 g IV over 10 min as antifibrinolytic adjunct
- Platelets if plt < 100K
- Aggressive BP control, target SBP < 140 with nicardipine drip INTERACT2, 2013
- Stat neurosurgery consult, possible hemicraniectomy (massive MCA + midline shift < 48h, age < 60) or posterior fossa decompression
📋 Clinical Example, Acute Ischemic Stroke: tPA + Thrombectomy Decision
Patient: 72M with a-fib (not on anticoagulation), last known well 2 hours ago, found with right-sided weakness and aphasia. NIHSS 14. BP 196/104, glucose 112, INR 1.1, plts 240K.
Decision tree (door-to-needle ≤ 60 min):
- 0–10 min: Stroke code activated. Fingerstick glucose 112 (mimic excluded). NIHSS 14. Two large-bore IVs. Labs sent.
- 10–20 min: Non-con CT, no hemorrhage. CTA, left M1 occlusion. CT perfusion, ischemic core 18 mL, penumbra 72 mL (large mismatch).
- 20–30 min: BP 196/104 → labetalol 20 mg IV, then nicardipine drip → BP 178/94 (below 185/110 threshold).
- 30–45 min: Alteplase 0.9 mg/kg IV (weight 80 kg → 72 mg; 7.2 mg bolus, 64.8 mg over 60 min). Simultaneously activate thrombectomy team.
- 45–90 min: To angio suite during tPA infusion. Mechanical thrombectomy → TICI 2b recanalization at 75 min from door.
- Post: NICU admission. Neuro checks q15 min × 2h. BP < 180/105. No antiplatelets × 24h. Repeat CT at 24h → no hemorrhagic conversion → start ASA 325 mg load. NIHSS was 14 (> 3) → NO DAPT, ASA alone. Plan: apixaban 5 mg BID starting day 6 for AF secondary prevention.
Teaching point: tPA is a bridge to thrombectomy, give both when LVO is present. Never delay tPA for CTA. Post-stroke antiplatelet choice is driven by NIHSS: DAPT for NIHSS ≤ 3 (CHANCE, POINT), extended in 2026 to NIHSS ≤ 5 when no thrombolysis was given and the cause is presumed atherosclerotic (INSPIRES, Class 2a); never in moderate-severe stroke, where bleeding risk outweighs benefit.
📋 On Rounds
Pimp Questions
What extended the thrombectomy window from 6h to 24h?
DAWN, 2018 and DEFUSE 3, 2018. Both showed that patients with clinical-imaging mismatch (large clinical deficit but small infarct core on perfusion imaging) benefit from thrombectomy up to 24h. DAWN used clinical-core mismatch; DEFUSE 3 used perfusion-core mismatch. The key concept: it's not about time -it's about salvageable penumbra. The 2026 AHA/ASA guideline now makes 6–24h thrombectomy Class 1 with ASPECTS ≥ 6 on plain CT, with perfusion imaging adjunctive, a position DAWN and DEFUSE investigators have formally contested.
Why check glucose before tPA?
Hypoglycemia is a stroke mimic -it can cause focal neurological deficits identical to stroke (hemiparesis, aphasia, altered consciousness). Giving tPA to a hypoglycemic patient exposes them to major bleeding risk for no benefit. A finger stick glucose takes 10 seconds and is the fastest way to rule out this mimic. Correct glucose < 60, then reassess symptoms before proceeding.
What is the extended window for thrombectomy and what imaging do you need?
Standard tPA window: 0-4.5 hours. Thrombectomy for LVO: up to 24 hours with favorable imaging. DAWN, 2018: 6-24h window if clinical deficit is disproportionate to infarct size on perfusion imaging ("mismatch"). DEFUSE-3, 2018: 6-16h window with perfusion mismatch. Imaging in 2026: CTA is required (confirms LVO -M1 MCA, ICA, basilar); with ASPECTS ≥ 6 on non-contrast CT, thrombectomy to 24h is Class 1, and CT perfusion or MRI mismatch is adjunctive (Class 2a) if immediately available. Large cores (ASPECTS 3–5) now qualify too.
What are the absolute contraindications to IV tPA?
Absolute contraindications (within 4.5h window): (1) Active internal bleeding or bleeding diathesis, (2) History of ICH (any time), (3) Ischemic stroke or head/spine trauma within 3 months, (4) Intracranial neoplasm, AVM, or aneurysm, (5) Platelets < 100K / INR > 1.7 / aPTT elevated / DOAC within 48h, (6) SBP > 185 or DBP > 110 not controlled despite treatment, (7) Recent major surgery within 14 days or intracranial/spinal surgery within 3 months, (8) GI/GU bleed within 21 days, (9) Arterial puncture at non-compressible site within 7 days, (10) Suspected infective endocarditis or aortic dissection. Glucose < 50 must be corrected first (stroke mimic).
Does every stroke patient get aspirin + clopidogrel?
No, NIHSS drives the choice. Dual antiplatelet (ASA + clopidogrel × 21 days) is indicated for minor stroke (NIHSS ≤ 3) or high-risk TIA (ABCD² ≥ 4), started within 24h, and since 2026 also for NIHSS ≤ 5 of presumed atherosclerotic cause without thrombolysis (up to 72 h, INSPIRES) CHANCE, 2013 POINT, 2018. For moderate-severe stroke (NIHSS ≥ 6) or LVO, DAPT increases bleeding without benefit, give ASA alone. THALES, 2020 added ticagrelor + ASA × 30d as alternative for NIHSS ≤ 5 non-cardioembolic. Don't reflexively pair ASA + clopidogrel in every stroke admission.
Tenecteplase or alteplase, which is better?
Non-inferior, and tenecteplase is winning on workflow. AcT, 2022 showed tenecteplase 0.25 mg/kg IV single bolus non-inferior to alteplase 0.9 mg/kg infusion for functional outcome, with similar sICH rates. Tenecteplase advantages: single 5-second push (vs 1-hour infusion), easier transfer to thrombectomy suite, saves ~5 min door-to-needle, same cost. Many stroke centers have switched tenecteplase-first. The 2026 AHA/ASA guideline makes both Class 1 (tenecteplase max 25 mg).
Why permissive hypertension in acute stroke?
The penumbra (viable but ischemic brain around the core infarct) survives on collateral flow, which is passive and pressure-dependent. Dropping BP collapses collaterals → penumbra converts to infarct → worse outcome. AHA guideline: don't treat BP unless > 220/120 in ischemic stroke without tPA. Exceptions: tPA given (must be < 185/110 → < 180/105), aortic dissection, active MI, HF, hypertensive encephalopathy.
Patient on apixaban had last dose 36h ago, can they get tPA?
Usually no. Patients with a DOAC dose in the last 48 h were excluded from every pivotal thrombolysis trial, so the 2026 AHA/ASA guideline leaves it to individualized, expert-opinion judgment (its Table 8) rather than a graded rule. Lysis is considered only if a drug-specific level (calibrated anti-Xa) shows no meaningful activity, which is often unavailable in real time; registries have not shown excess bleeding, but that is not trial evidence. Alternative: mechanical thrombectomy if LVO is present (tPA contraindications don't preclude thrombectomy). Reversal agents are not a practical bridge to thrombolysis (andexanet alfa, once proposed for this, was withdrawn from the US market in 2025). Stick to thrombectomy in DOAC patients with LVO.
Clinical Examples
📋 Case 1, Large Vessel Occlusion within tPA Window
Patient: 73F with Afib (not on anticoagulation), found by husband with left-sided weakness and slurred speech. Last known well 2 hours ago.
Key findings: BP 178/96, HR 88 (irregular), NIHSS 18 (R gaze preference, left hemiplegia, left hemineglect, dysarthria). CT head: no hemorrhage. CTA: right MCA M1 occlusion. CT perfusion: large penumbra with small core (< 30 mL).
Management:
- IV alteplase 0.9 mg/kg (10% bolus, 90% over 60 min). Door-to-needle target ≤ 60 min NINDS, 1995
- BP must be < 185/110 BEFORE tPA. Use IV labetalol or nicardipine drip. After tPA: maintain < 180/105 x 24h
- Thrombectomy: M1 LVO + NIHSS ≥ 6 at 2h = Class 1 on CTA (ASPECTS 3–10 all qualify within 6h); perfusion imaging is not needed to decide DAWN, 2018
- tPA is a bridge to thrombectomy. Do NOT delay tPA for CTA
Teaching point: tPA is a bridge, not a destination. If LVO is identified, proceed to thrombectomy regardless of tPA response. Never delay tPA to obtain CTA.
📋 Case 2, Minor Stroke, DAPT Candidate
Patient: 62M with HTN, presents with 30 min of mild right facial droop and word-finding difficulty. Symptoms now resolved. NIHSS 1 (mild dysarthria only). LKW 90 min ago. BP 158/92. Glucose 104.
Key findings: CT head: no hemorrhage. CTA: 60% left MCA stenosis, no occlusion. MRI DWI: punctate left M2 infarct. Within tPA window but NIHSS = 1 → marginal tPA benefit vs bleeding risk. Rapid resolution suggests TIA-like physiology.
Management:
- Hold tPA: NIHSS 1 with a non-disabling deficit. The 2026 guideline recommends DAPT rather than thrombolysis here, because lysis showed no benefit for non-disabling deficits ARAMIS, 2023. A disabling deficit would be lysed at any NIHSS.
- Start DAPT: ASA 325 mg load → 81 mg daily + clopidogrel 300 mg load → 75 mg daily × 21 days, then ASA alone CHANCE, 2013 POINT, 2018
- High-intensity statin: atorvastatin 80 mg daily SPARCL, 2006
- BP goal: add lisinopril, target < 130/80 long-term
- Etiology workup: carotid Doppler, echo, AF monitoring (Holter or Reveal LINQ if cryptogenic)
Teaching point: Minor stroke / high-risk TIA is the DAPT niche. NIHSS ≤ 3 within 24h → ASA + clopidogrel × 21 days. This is CHANCE, 2013 / POINT, 2018 territory. Don't extend DAPT beyond 21 days (bleeding rises).
📋 Case 3, Wake-Up Stroke with Unknown Onset
Patient: 65M found by wife at 6 AM with right-sided weakness and aphasia. Was normal at bedtime (11 PM). Last known well ~7 hours ago.
Key findings: NIHSS 14 (global aphasia, right hemiplegia). CT head: no hemorrhage. MRI DWI: acute left MCA infarct. FLAIR: no corresponding signal change (DWI-FLAIR mismatch = stroke likely < 4.5h). CTA: left M1 occlusion.
Management:
- DWI-FLAIR mismatch suggests onset < 4.5h despite unknown last known well WAKE-UP Trial, 2018
- IV alteplase can be given based on WAKE-UP trial criteria (DWI positive, FLAIR negative)
- M1 LVO with NIHSS ≥ 6: thrombectomy is Class 1 up to 24h if ASPECTS ≥ 6 (and for ASPECTS 3–5 if age < 80 without mass effect); perfusion imaging adds information if immediately available but is no longer required
- If MRI not rapidly available, automated CT perfusion showing salvageable penumbra within 9h of the midpoint of sleep makes IV thrombolysis reasonable (Class 2a) EXTEND, 2019
Teaching point: Wake-up strokes are no longer excluded from thrombolysis. DWI-FLAIR mismatch on MRI can extend the treatment window. Perfusion imaging selects patients based on tissue status, not time alone.
📋 Case 4, Hemorrhagic Conversion After tPA
Patient: 70M received tPA 4 hours ago for acute ischemic stroke (NIHSS 12). Nurse calls: new vomiting, declining consciousness (GCS 14 to 9), new hypertension 210/115.
Key findings: GCS 9, left pupil dilating, right hemiplegia worsening. Consistent with symptomatic intracerebral hemorrhage (sICH) -- most feared tPA complication (~6% incidence).
Management:
- Stop tPA infusion immediately. Stat CT head without contrast
- Reversal: cryoprecipitate 10 units IV (target fibrinogen > 200 mg/dL). Tranexamic acid 1g IV as adjunct
- Aggressive BP control: target SBP < 140 with nicardipine drip INTERACT2, 2013
- Stat neurosurgery consult for possible EVD or hemicraniectomy. Reverse coagulopathy before any procedure
Teaching point: Any neurological decline after tPA = hemorrhagic conversion until proven otherwise. Stop tPA, get immediate CT, and give cryoprecipitate (NOT FFP -- too slow). Fibrinogen is the critical target in tPA-related ICH.
📣 Sample Presentation
One-Liner
"Mrs. Taylor is a 73-year-old with Afib (not on anticoagulation) presenting with acute left-sided weakness and aphasia, NIHSS 18, last known well 2 hours ago. CT head negative for hemorrhage. CTA shows right MCA M1 occlusion."
Key Points to Cover on Rounds
Acute ischemic stroke, right MCA LVO, NIHSS 18. CT negative for hemorrhage. Alteplase 0.9 mg/kg administered at 2.5h. Thrombectomy team activated → TICI 2b recanalization. Post-procedure NIHSS 8 (improving). BP target < 180/105 × 24h post-tPA. Repeat CT at 24h: no hemorrhagic conversion. Antiplatelet: ASA 325 mg load → 81 mg (NIHSS 18 → no DAPT per CHANCE/POINT, which require NIHSS ≤ 3). Dysphagia screen: failed → NPO, NGT. Etiology: AF, never anticoagulated. Plan: apixaban 5 mg BID starting day 6 (moderate infarct per 1-3-6-12 rule). Atorvastatin 80 mg. PT/OT/SLP. Secondary prevention (BP < 130/80, lipids, AF).
Monitoring (Post-tPA / Post-Thrombectomy)
| Parameter | Frequency | Target / Action |
|---|---|---|
| Neuro checks (NIHSS-guided) | q15 min × 2h → q30 min × 6h → q1h × 16h (then q4h × 24h) | Any decline = stat CT to rule out hemorrhagic conversion |
| Blood pressure | Same schedule as neuro checks × 24h | < 180/105 post-tPA. < 185/110 pre-tPA. ≤ 180/105 after thrombectomy, never a target below 140 (harmful). Treat with labetalol or nicardipine. |
| Fingerstick glucose | q1–4h initially | Target 140–180 mg/dL. Avoid hypoglycemia (mimic) and severe hyperglycemia (worsens infarct). Do not drive it to 80–130 with IV insulin: no benefit, more severe hypoglycemia (SHINE, 2019). |
| Temperature | q4h | Fever > 38°C worsens outcome, acetaminophen PRN, find source, treat aggressively. |
| Telemetry | Continuous × 24h minimum | Catch occult AF (major etiology). Prolonged monitoring (Holter, Reveal LINQ) if cryptogenic. |
| Dysphagia screen | Before ANY PO intake | Failed → NPO, SLP eval, NGT for meds/nutrition. Aspiration pneumonia is a top post-stroke killer. |
| Repeat CT head | At 24h post-tPA (before antiplatelets) | Rule out asymptomatic hemorrhagic conversion before starting ASA ± clopidogrel |
| DVT prophylaxis | From admission | Mechanical immediately; LMWH (enoxaparin 40 mg SC daily) after 24h if repeat CT clear |
🧪 Workup
Rapid Workup, Everything Happens in Parallel
Stroke code = parallel processing. Labs, CT, NIHSS, and IV access happen simultaneously. Nobody waits for anyone. Door-to-needle ≤ 60 min.
Focused History (from patient, family, EMS, bystanders)
- Last known well (LKW), NOT symptom-discovery time. "When was the patient definitely at their neurologic baseline?" This drives the tPA window.
- Wake-up stroke? LKW = bedtime. Consider MRI DWI-FLAIR mismatch for thrombolysis WAKE-UP, 2018.
- Anticoagulants or antiplatelets: warfarin (check INR), DOACs (last dose < 48h = contraindication), LMWH, DAPT
- Prior stroke / TIA, ICH, head trauma, seizures, migraines (mimics)
- Recent surgery (within 14 days major; 3 months intracranial/spinal), recent GI/GU bleed (within 21 days), recent arterial puncture (within 7 days)
- Medical history: AF, HTN, DM, HLD, CAD, PFO, hypercoagulable states, pregnancy, recent illness (endocarditis risk)
- Red flags: Thunderclap HA (SAH), neck pain after trauma (dissection), cocaine/sympathomimetic use, recent febrile illness (endocarditis)
NIHSS, Score Every Patient
NIHSS drives thrombectomy eligibility (≥ 6), antiplatelet choice (≤ 3 = DAPT), prognosis, and transfer decisions. Score BEFORE tPA, after tPA, and daily. 11 items, 0–42 scale. → Open interactive NIHSS calculator
NIHSS underscores posterior circulation strokes. A basilar occlusion may score 2–4 despite catastrophic disease. Don't let a low NIHSS talk you out of thrombectomy for a vertebrobasilar LVO, use clinical judgment + CTA.
Imaging (Target ≤ 20 min)
| Study | Purpose | Key Findings |
|---|---|---|
| Non-contrast CT head FIRST | Rule out hemorrhage, tPA contraindicated if ICH | Early ischemic changes (loss of gray-white differentiation, insular ribbon sign, hyperdense MCA sign). ASPECTS ≥ 6 alone qualifies for thrombectomy up to 24h (2026, Class 1). CHANGED 2026 A large core no longer excludes it: ASPECTS 3–5 is Class 1 up to 24h (beyond 6h if age < 80 and no mass effect). |
| CTA head & neck ESSENTIAL FOR LVO | Identify LVO (ICA, M1, M1-equivalent, basilar) for thrombectomy triage | Clot visualization. Collateral scoring. Carotid stenosis / dissection. Tandem occlusions. Do NOT delay tPA waiting for CTA. |
| CT perfusion | Adjunctive for 6–24h thrombectomy (Class 2a, if immediately available; no longer required when ASPECTS ≥ 6). Selects extended-window thrombolysis (4.5–9h or wake-up) | Mismatch: large hypoperfused region + small core = penumbra. RAPID / Olea software auto-quantifies Tmax and CBF. |
| MRI DWI + FLAIR | Confirm infarct. Wake-up stroke selection. | DWI+/FLAIR− = stroke < 4.5h (even if LKW unknown) → tPA-eligible per WAKE-UP. |
| Echo (TTE ± TEE) | Etiology workup (post-acute) | LV thrombus, PFO, atrial myxoma, endocarditis. TEE better for LA appendage, aortic arch atheroma, vegetation. |
| Carotid duplex / CTA neck | Etiology, carotid stenosis | > 70% symptomatic stenosis → CEA (within 2 weeks) or CAS. |
Labs
- Fingerstick glucose FIRST (10 seconds, hypoglycemia is the #1 stroke mimic). Target > 60 before tPA; 140–180 on admission.
- CBC, platelets > 100K required for tPA
- BMP, glucose, electrolytes, renal function, but never delay CTA or CT perfusion waiting for the creatinine (Class 1): the contrast risk is small next to the cost of missing an LVO
- PT/INR, aPTT, INR > 1.7 contraindicates tPA
- Troponin, co-existing MI is common; may change dispo
- Type & screen, in case of hemorrhagic conversion
- Pregnancy test (if reproductive age), tPA is not absolutely contraindicated but needs MFM discussion
- DOAC level / anti-Xa if on apixaban/rivaroxaban within 48h (often unavailable in real time, default to thrombectomy)
- EKG, AF, STEMI, LVH
- Tox screen if AMS (sympathomimetic-induced stroke, cocaine)
Stroke Mimics, Rule Out Before tPA
- Hypoglycemia, fingerstick glucose. Single most important mimic. Correct and reassess.
- Seizure / Todd paralysis, post-ictal focal weakness. History of seizure, tongue-biting, incontinence, confusion clearing.
- Migraine with aura, gradual onset, positive phenomena (scintillations), HA follows.
- Conversion disorder, non-anatomic distribution, give-way weakness, psych context.
- Complex migraine / hemiplegic migraine
- Sepsis, toxic-metabolic encephalopathy, hypertensive encephalopathy
- Bell's palsy, forehead-sparing is UMN (stroke); no forehead sparing is LMN (Bell's).
- Peripheral vertigo, BPPV, vestibular neuritis. HINTS exam to differentiate from central (posterior stroke).
💊 Medications
Thrombolytics
| Drug | Dose | Administration | Key Points |
|---|---|---|---|
| Alteplase (tPA, Activase) STANDARD | 0.9 mg/kg IV (max 90 mg) | 10% as bolus over 1 min, 90% infused over 60 min | Binds fibrin → plasmin → clot lysis. sICH ~6%. Monitor for orolingual angioedema (esp. on ACEi), stop infusion, IV steroid + H1/H2 blockers. |
| Tenecteplase (TNKase) 1ST LINE CHANGED 2026 | 0.25 mg/kg IV bolus (max 25 mg) | Single push, no infusion. Done in 5 seconds. | Genetically modified alteplase, higher fibrin specificity, longer half-life. AcT, 2022 showed non-inferiority; the 2026 AHA/ASA guideline makes it Class 1 alongside alteplase. Faster workflow, same safety. Do not add argatroban or eptifibatide: MOST, 2024 found more deaths and no benefit. |
tPA Reversal (Symptomatic ICH)
| Agent | Dose | Purpose |
|---|---|---|
| Cryoprecipitate 1ST LINE | 10 units IV | Fibrinogen replacement, target > 150–200 mg/dL. Works within 30 min. NOT FFP (too slow). |
| Tranexamic acid (TXA, Cyklokapron) | 1 g IV over 10 min | Antifibrinolytic adjunct. Alternative: aminocaproic acid. |
| Platelets | 1 unit apheresis (if plt < 100K) | Replacement if thrombocytopenic. |
Blood Pressure (Pre/Post-tPA)
| Drug | Dose | Notes |
|---|---|---|
| Labetalol (generic) | 10–20 mg IV q10 min, max 300 mg | β1/β2/α blocker. First-line. Avoid in severe asthma/COPD, decompensated HF, bradycardia < 50. |
| Nicardipine (Cardene) | Start 5 mg/hr IV, titrate 2.5 mg/hr q5–15 min, max 15 mg/hr | Dihydropyridine CCB. Smooth titratable infusion. Preferred in reactive airway disease. |
| Clevidipine (Cleviprex) | Start 1–2 mg/hr IV, double q90 sec, max 32 mg/hr | Ultra-short half-life (~1 min). Lipid emulsion, avoid in egg/soy allergy, severe HLD. |
| Hydralazine (generic) | 10–20 mg IV q4–6h PRN | Rescue option. Unpredictable response + reflex tachycardia. Not first-line in stroke. |
Antiplatelets, NIHSS Drives the Choice
Wait 24h post-tPA before starting any antiplatelet. Check repeat CT first, rule out asymptomatic hemorrhagic conversion.
| NIHSS | Regimen | Evidence |
|---|---|---|
| 0–3 (minor stroke) OR high-risk TIA (ABCD² ≥ 4) | DAPT × 21 days: • ASA 325 mg load → 81 mg daily • Clopidogrel 300–600 mg load → 75 mg daily • Then ASA alone long-term | CHANCE, 2013 POINT, 2018 |
| ≤ 5 within 24–72h, or 4–5 within 24h (no IV thrombolysis, presumed atherosclerotic, ≥ 50% stenosis) NEW 2026 | Same clopidogrel + ASA regimen × 21 days, then single agent (Class 2a) | INSPIRES, 2023: new stroke 7.3% vs 9.2%; moderate-to-severe bleeding 0.9% vs 0.4% |
| ≤ 5 (non-cardioembolic) | Alternative: Ticagrelor 180 mg load → 90 mg BID + ASA × 30 days | THALES, 2020 |
| ≥ 6 or LVO | ASA alone, 325 mg load → 81 mg daily. No DAPT. | DAPT increases bleeding without proven benefit in moderate-severe stroke. Large infarct core + DAPT = hemorrhagic conversion risk. |
Clopidogrel CYP2C19 non-responders (~30% of East Asians, ~15% of others): consider ticagrelor instead. Genotyping is done at some stroke centers after DAPT failure.
Statin
| Drug | Dose | Notes |
|---|---|---|
| Atorvastatin (Lipitor) HIGH INTENSITY | 80 mg PO daily | Start on admission. SPARCL, 2006. LDL goal < 70 mg/dL. |
| Rosuvastatin (Crestor) HIGH INTENSITY | 20–40 mg PO daily | Alternative if atorvastatin intolerance. In Asian patients lower doses may suffice. |
Anticoagulation (Cardioembolic Stroke, AF)
Timing rule of thumb ("1-3-6-12 day rule"): start DOAC based on infarct size, TIA (day 1), small stroke (day 3), moderate (day 6), large (day 12). ELAN, 2023 supports earlier start than the traditional rule. CHANGED 2026 AHA/ASA, 2026: in carefully selected (e.g., milder) strokes, early anticoagulation is low risk and reasonable compared with delaying it (Class 2a), although its efficacy for preventing early recurrence is not established.
| Drug | Dose | When to Start (post-stroke) |
|---|---|---|
| Apixaban (Eliquis) PREFERRED | 5 mg BID (2.5 mg BID if ≥ 2 of: age ≥ 80, weight ≤ 60 kg, Cr ≥ 1.5) | Typical: day 1–3 for small, day 6–12 for large infarct. ELAN 2023 supports earlier. |
| Rivaroxaban (Xarelto) | 20 mg daily (15 mg if CrCl 15–50) | Take with food for bioavailability. |
| Dabigatran (Pradaxa) | 150 mg BID (110 mg BID if high bleed risk) | Avoid CrCl < 30. Idarucizumab for reversal. |
| Edoxaban (Savaysa) | 60 mg daily (30 mg if CrCl 15–50 or weight ≤ 60 kg) | Avoid if CrCl > 95 (reduced efficacy). |
| Warfarin (Coumadin) | Goal INR 2–3 | Use if mechanical valve, significant mitral stenosis, antiphospholipid syndrome. Bridge with heparin if INR < 2. |
Adjuncts & Supportive
- Glucose control: target 140–180 mg/dL. Avoid hypoglycemia (mimic) and severe hyperglycemia (worsens infarct). IV insulin to 80–130 mg/dL is not recommended (Class 3: No Benefit): SHINE, 2019 found no functional gain and 2.6% severe hypoglycemia.
- Fever: acetaminophen PRN. Fever > 38°C worsens outcome, find source, treat aggressively.
- DVT prophylaxis: mechanical compression from admission. Enoxaparin 40 mg SC daily after 24h post-tPA (if no ICH on repeat scan). Avoid heparin gtt in cardioembolic stroke, increases hemorrhagic conversion.
- Orolingual angioedema on tPA: stop infusion, IV methylprednisolone 125 mg + diphenhydramine 50 mg + famotidine 20 mg. Epinephrine if airway compromise. Higher risk in ACEi users.
⚡ Summary
Summary
Time Is Brain
Roughly 1.9 million neurons are lost per minute of ischemia. Target door-to-needle under 60 minutes and door-to-CT under 20. Establish the last known well time, not the time symptoms were noticed: everything downstream depends on that single piece of history, and it usually comes from a family member or EMS rather than the patient.
Know the Two Windows
Thrombolysis: within 4.5 hours of last known well. Thrombectomy: up to 24 hours for a large vessel occlusion, and the 2026 guideline broadened it: ASPECTS 6 or more on plain CT is enough in the late window, large cores (ASPECTS 3 to 5) now qualify, and basilar occlusion with NIHSS 10 or more is Class 1. Wake-up strokes may still qualify for thrombolysis using MRI diffusion-FLAIR mismatch or automated perfusion imaging, so an unwitnessed onset is not automatically excluded.
Non-Contrast CT First, to Exclude Hemorrhage
Its job is to rule out bleeding, not to confirm infarction, which is often invisible in the first hours. Then CT angiography for large vessel occlusion, and perfusion imaging for the extended thrombectomy window. Check a glucose immediately, since hypoglycemia is the great stroke mimic and is instantly correctable.
Get the Blood Pressure Rules the Right Way Round
If giving thrombolysis: below 185/110 before, and below 180/105 for 24 hours after. If not giving thrombolysis: permissive hypertension, treating only above 220/120, because the ischemic penumbra depends on collateral perfusion and lowering the pressure extends the infarct. These two targets are opposite, and confusing them causes harm in both directions. After thrombectomy, stay at or below 180/105 and never target a systolic below 140, which the 2026 guideline classifies as harmful.
Antiplatelet Choice Depends on the NIHSS
Minor stroke with NIHSS 3 or below, or high-risk TIA with ABCD2 4 or above: dual antiplatelet with aspirin plus clopidogrel for 21 days, then single agent (CHANCE, POINT), extended in 2026 to NIHSS 5 or below within 72 hours when the cause is atherosclerotic and no thrombolysis was given (INSPIRES). A non-disabling deficit gets DAPT instead of thrombolysis. Larger strokes: single antiplatelet, because prolonged dual therapy increases hemorrhage without benefit. Start aspirin at 24 to 48 h, and wait 24 h after thrombolysis.
Manage the First 24 Hours After Thrombolysis Deliberately
No antiplatelets or anticoagulants for 24 hours, no central lines or arterial punctures at non-compressible sites, and frequent neurologic checks. Any sudden deterioration, headache, vomiting or a rise in blood pressure means stop the infusion and get an urgent CT, and treat symptomatic hemorrhage with cryoprecipitate and tranexamic acid.
Time Anticoagulation for Atrial Fibrillation by Infarct Size
Timing depends on infarct size and hemorrhagic risk: the 2026 guideline calls early anticoagulation reasonable in carefully selected, milder strokes (ELAN), while a large infarct still waits, because early anticoagulation there risks hemorrhagic transformation. Treat fever, glucose and hypoxia, all of which worsen outcome, and screen swallowing before anything goes by mouth, since aspiration pneumonia is a leading complication.
Finish the Workup and the Secondary Prevention
Vessel imaging, echocardiography, prolonged rhythm monitoring for occult atrial fibrillation, lipids and A1c. High-intensity statin, blood pressure control, antithrombotic matched to the mechanism, and carotid revascularization for symptomatic stenosis of 70% or more, ideally within 2 weeks. Add early rehabilitation and mobilization, which independently improve functional outcome.
📄 One Pager
Text version
Neurology · One Pager
Acute Ischemic Stroke
tPA within 4.5h. Thrombectomy for LVO up to 24h with mismatch. Door-to-needle ≤ 60 min. NIHSS drives antiplatelet choice. Dysphagia screen before PO.
Diagnosis
Acute focal neurologic deficit. Fingerstick glucose FIRST (#1 mimic). Non-con CT (rule out ICH). CTA (identify LVO). CT perfusion (mismatch for extended window). NIHSS, drives severity, thrombectomy (≥ 6), antiplatelet (≤ 3 = DAPT).
Acute Treatment
≤ 4.5h: alteplase 0.9 mg/kg (max 90) OR tenecteplase 0.25 mg/kg bolus. Tenecteplase and alteplase both Class 1 (2026). LVO: thrombectomy up to 24h, ASPECTS ≥ 3, perfusion imaging optional. BP < 185/110 pre-tPA, < 180/105 post × 24h; after thrombectomy ≤ 180/105, never target SBP < 140. No antiplatelet/anticoag × 24h post-tPA.
Secondary Prevention (by NIHSS)
NIHSS ≤ 3: DAPT × 21d (ASA + clopidogrel) [CHANCE, 2013, POINT, 2018]. NIHSS ≤ 5, atherosclerotic, no tPA, ≤ 72h: DAPT × 21d (2026). NIHSS ≥ 6: ASA alone. AF → DOAC (apixaban preferred, timing by infarct size, 1-3-6-12 rule). Atorvastatin 80 mg. BP < 130/80. Carotid stenosis > 70% → CEA/CAS.
Key Drugs
Alteplase0.9 mg/kg IV (max 90 mg)
Tenecteplase0.25 mg/kg IV bolus
Labetalol10–20 mg IV q10 min
Nicardipine5–15 mg/hr infusion
ASA325 mg load → 81 mg (after 24h)
Clopidogrel300–600 mg load → 75 mg × 21d (NIHSS ≤ 3, or ≤ 5 if atherosclerotic)
Atorvastatin80 mg PO daily
Apixaban5 mg BID (AF, timing by infarct size)
Pitfalls
- Delaying tPA for detailed neuro exam (time is brain)
- Not checking fingerstick glucose first (hypoglycemia mimic)
- Reflexively starting DAPT in moderate-severe stroke, NIHSS ≥ 6 (bleeding risk, no benefit)
- Targeting SBP < 140 after thrombectomy (harmful per 2026 guideline)
- Lysing a non-disabling deficit (DAPT instead)
- Dropping BP too aggressively in untreated stroke (collapses penumbra)
- Skipping dysphagia screen before PO (aspiration pneumonia)
- FFP instead of cryoprecipitate for tPA-related ICH (too slow)
- Missing posterior circulation stroke (NIHSS underscores basilar LVO)
- Lysing after a DOAC dose in the last 48 h without a drug level (go to thrombectomy if LVO)
Present on Rounds
One-liner: "[Age, sex] with [risk factors] presenting with [deficit], NIHSS [#], LKW [time]. CT no hemorrhage. [CTA findings]. tPA [given/held]. [Thrombectomy]. Post-procedure NIHSS [#]. Plan: [antiplatelet/anticoag by NIHSS], dysphagia screen, [statin/BP/etiology workup]."