Nervous System & Special Senses

Ischemic stroke: acute management and thrombolysis decisions

Clinical Overview and When to Suspect Ischemic Stroke

— Distinguished from TIA by tissue-based definition: infarct on MRI = stroke regardless of symptom duration.

— ~800,000 strokes/year in US; 87% ischemic, 13% hemorrhagic.

— 5th leading cause of death, #1 cause of adult long-term disability.

— Risk factors: HTN (strongest modifiable), atrial fibrillation, DM, smoking, hyperlipidemia, prior stroke/TIA, age, sickle cell, OSA.

— Balance loss, Eye changes (diplopia/visual field cut), Face droop, Arm weakness, Speech change, Time to call 911.

— Sudden onset is the hallmark — gradual or "marching" symptoms favor migraine, seizure, or mass.

— Activate stroke code → goal door-to-CT ≤25 min, door-to-needle ≤45–60 min, door-to-groin (LVO) ≤90 min.

— Establish last known well (LKW) time — anchors every treatment decision.

— NIHSS score within first 10 min.

— Fingerstick glucose is mandatory before any treatment decision.

— Large-artery atherosclerosis (carotid/intracranial)

— Cardioembolic (AFib, LV thrombus, endocarditis, PFO)

— Small-vessel/lacunar (chronic HTN, DM)

— Other determined (dissection, vasculitis, hypercoagulable)

— Cryptogenic

Board pearl: A patient who "woke up with deficits" has LKW = time they went to bed, not time they awoke — this often excludes IV tPA by the standard 4.5-hr window, but MRI-based wake-up stroke protocols (DWI-FLAIR mismatch) may still permit thrombolysis.

Definition: Acute neurologic deficit from focal brain ischemia due to arterial occlusion (thrombotic, embolic, or lacunar/small-vessel), lasting >24 hours or with infarction on imaging.

Epidemiology and burden:

When to suspect (BE-FAST):

Acute setting priorities (ED door):

Stroke mimics (15–20% of codes): hypoglycemia, seizure with Todd paralysis, complex migraine, conversion disorder, sepsis-unmasked old deficit, hypertensive encephalopathy, Bell palsy.

Etiologic subtypes (TOAST):

Presentation Patterns and Key History

— MCA (most common): contralateral face/arm > leg weakness, sensory loss, homonymous hemianopia, gaze deviation toward lesion.

— Dominant (usually left) hemisphere: aphasia (Broca expressive, Wernicke receptive, global).

— Non-dominant (right): hemineglect, anosognosia, constructional apraxia, dysprosody.

— ACA: contralateral leg > arm weakness, urinary incontinence, abulia, transcortical motor aphasia.

— ICA: combined MCA/ACA features, ipsilateral monocular blindness (amaurosis fugax if transient).

— Vertigo, diplopia, dysarthria, dysphagia, ataxia, crossed deficits (ipsilateral cranial nerve + contralateral body).

— Wallenberg (lateral medullary, PICA): ipsilateral Horner, facial sensory loss, ataxia; contralateral body pain/temp loss; vertigo, hoarseness, dysphagia.

— Basilar artery occlusion: locked-in syndrome, coma, quadriparesis, "top of the basilar" with bilateral occipital + thalamic strokes — often missed, devastating.

— PCA: isolated homonymous hemianopia (macular sparing), alexia without agraphia (dominant), memory deficits if thalamic.

— Pure motor (internal capsule), pure sensory (thalamus), ataxic hemiparesis, dysarthria–clumsy hand, sensorimotor.

— No cortical signs (no aphasia, neglect, hemianopia).

— LKW time and witnessed onset

— Anticoagulant use (DOAC last dose, warfarin INR), recent surgery, trauma, GI bleed

— Prior stroke, AFib, recent MI, valve disease, IV drug use (endocarditis), sickle cell, pregnancy/postpartum, hormone use

— Headache (suggests hemorrhage, dissection, venous sinus thrombosis), neck pain/trauma (dissection)

Key distinction: Gaze deviation toward the lesion in a cortical stroke; away from the lesion in a pontine stroke or seizure. Use this to localize at the bedside before imaging.

Anterior circulation (ICA/MCA/ACA) — ~80% of strokes:

Posterior circulation (vertebrobasilar) — ~20%:

Lacunar syndromes (small-vessel, deep penetrators):

History essentials:

Physical Exam Findings and Hemodynamic Assessment

— Domains: LOC, orientation, commands, gaze, visual fields, facial palsy, motor arms/legs, ataxia, sensory, language, dysarthria, extinction/neglect.

— Score ≥6 suggests large-vessel occlusion (LVO); ≥10 strong LVO predictor.

— Score <4 = "minor" but disabling deficits (aphasia, hemianopia, hand weakness in a surgeon) still qualify for tPA.

— Cranial nerves: facial asymmetry (forehead-sparing = central), tongue deviation, dysarthria, gag.

— Motor: pronator drift is sensitive for subtle hemiparesis.

— Cerebellar: finger-nose, heel-shin, gait if safe.

— Cortical: aphasia screen ("no ifs, ands, or buts"), neglect (double simultaneous stimulation), visual fields by confrontation.

— Cardiac: irregularly irregular pulse (AFib), murmurs (endocarditis, valve), S3/S4.

— Vascular: carotid bruits, BP differential between arms (>20 mmHg → aortic dissection/subclavian disease), absent pulses.

— Skin: splinter hemorrhages, Janeway lesions, Osler nodes; livedo reticularis (antiphospholipid).

— Fundoscopy: Hollenhorst plaques (carotid emboli), papilledema (mass/venous thrombosis).

— BP paradox: Permissive hypertension is therapeutic in acute ischemic stroke — autoregulation is impaired and the penumbra depends on collateral perfusion.

— Treat BP only if: >185/110 before tPA; >180/105 during/after tPA (×24 h); >220/120 if not getting tPA.

— First-line: IV labetalol 10–20 mg or nicardipine drip 5 mg/h titrated.

— Avoid sublingual nifedipine and rapid drops — risk of penumbral infarction extension.

— Hypotension: rare; aggressively correct (often reveals dehydration or sepsis-mimic).

Step 3 management: A patient with NIHSS 12 and BP 198/108 is not yet tPA-eligible — lower BP with IV labetalol to <185/110, then proceed. If BP cannot be controlled with 2 doses, withhold tPA.

NIHSS (0–42) — must be documented before tPA:

Targeted neuro exam:

General exam (clues to etiology):

Hemodynamic assessment:

Diagnostic Workup — Initial Labs, Imaging, ECG

— Fingerstick glucose — must precede tPA; hypoglycemia is the #1 mimic.

— Non-contrast head CT (NCCT) — primary purpose is to rule out hemorrhage; ischemia often invisible <6 h.

— Early ischemic signs: hyperdense MCA sign, loss of gray-white differentiation, sulcal effacement, insular ribbon sign.

— ASPECTS score (0–10) on NCCT for MCA territory — score ≤6 traditionally argued against thrombectomy but expanded with DAWN/DEFUSE-3.

— ECG — detect AFib, recent MI (LV thrombus source), QT for medications.

— CT angiography (CTA) head and neck — performed concurrently to identify LVO (ICA, M1, M2, basilar, vertebral) and guide thrombectomy decision; also detects dissection, stenosis.

— CBC, BMP, troponin, coags (PT/INR, PTT) — only INR strictly required before tPA if anticoagulant use suspected.

— Lipid panel, HbA1c (for secondary prevention, not acute decision).

— Pregnancy test in women of childbearing age.

— Type and screen if hemorrhagic concern.

— Carotid duplex (if CTA not done) within 24 h for anterior circulation stroke.

— Transthoracic echo (TTE) within 24–48 h; consider TEE if cryptogenic and TTE non-revealing.

CCS pearl: On a CCS case, the correct opening orders for a suspected stroke are: "Stat NCCT head, fingerstick glucose, ECG, IV access ×2, NIHSS, labs (CBC, BMP, coags, troponin), continuous telemetry, CTA head/neck." Advancing the clock before checking the CT result is a frequent error — wait for NCCT to exclude hemorrhage before ordering tPA.

Immediate (parallel, not sequential) — within first 25 min:

Labs (do not delay tPA waiting for results unless suspicion of coagulopathy):

Telemetry: Continuous cardiac monitoring × ≥24 h to detect paroxysmal AFib.

Other early workup:

Diagnostic Workup — Advanced and Confirmatory Studies

— Gold standard for tissue diagnosis; DWI positive within minutes, sensitivity >95% for ischemia.

— DWI-FLAIR mismatch: DWI bright + FLAIR negative implies infarct <4.5 h old — used to qualify wake-up strokes or unknown LKW patients for tPA (WAKE-UP trial).

— Identifies brainstem/cerebellar strokes that CT misses.

— Identifies penumbra (salvageable tissue) vs core (already infarcted).

— Used to extend thrombectomy window to 6–24 h in LVO (DAWN, DEFUSE-3).

— DAWN criteria (6–24 h): clinical-core mismatch (e.g., NIHSS ≥10 with core <31 mL in older patients).

— DEFUSE-3 (6–16 h): perfusion-core mismatch ratio ≥1.8, core <70 mL, mismatch volume ≥15 mL.

— MRA head/neck (no contrast option in CKD).

— Digital subtraction angiography (DSA) — used during thrombectomy; gold standard for dissection, vasculitis.

— TTE first; TEE if young patient, cryptogenic, or PFO/atrial septal aneurysm suspected.

— Prolonged cardiac monitoring (mobile telemetry/loop recorder) 14–30 days if cryptogenic — detects occult AFib in 10–20%.

— Hypercoagulable: antiphospholipid antibodies, factor V Leiden, prothrombin gene mutation, protein C/S, antithrombin (drawn off anticoagulation).

— Vasculitis: ESR, CRP, ANA, ANCA; LP if CNS vasculitis suspected.

— Toxicology screen (cocaine, amphetamines).

— Homocysteine, lipoprotein(a).

— HIV, syphilis if risk factors.

Board pearl: A 35-year-old with neck pain after chiropractic manipulation and a posterior circulation stroke → suspect vertebral artery dissection. Best test is MRA neck with fat-saturated T1 showing crescent-shaped intramural hematoma. Treat with antiplatelet or anticoagulation × 3–6 months (CADISS: equivalent outcomes).

MRI brain with DWI:

CT or MR perfusion:

Vessel imaging beyond CTA:

Cardiac source evaluation:

Young/cryptogenic stroke workup (<55 y or no clear cause):

Risk Stratification and First-Line Management Logic

— (1) Hemorrhage on NCCT? → If yes, stop ischemia pathway, manage as hemorrhagic stroke.

— (2) Is patient within tPA window and eligible? → If yes, give IV thrombolytic.

— (3) Is there an LVO amenable to thrombectomy? → If yes, mobilize endovascular team regardless of tPA status.

— IV alteplase/tenecteplase: ≤4.5 h from LKW (standard); ≤9 h or wake-up with imaging mismatch (extended, select centers).

— Mechanical thrombectomy: ≤6 h standard, 6–24 h with perfusion mismatch (DAWN/DEFUSE-3).

— NIHSS ≥6 + LVO on CTA → transfer to thrombectomy-capable center if at primary stroke center ("drip and ship" — give tPA, then transfer).

— NIHSS <6 without disabling deficit → individualized; tPA benefit less clear, weigh risk.

— Pre-tPA: <185/110

— Post-tPA (×24 h): <180/105

— No tPA, no thrombectomy: treat only if >220/120 or end-organ dysfunction (MI, dissection, encephalopathy, eclampsia).

— After successful thrombectomy with full recanalization: more aggressive control (<140–160 systolic) to prevent reperfusion injury.

Step 3 management: A patient at a community ED has LKW 3 h ago, NIHSS 16, NCCT negative, CTA shows M1 occlusion. Correct sequence: give IV tenecteplase now, then arrange immediate transfer to comprehensive stroke center for thrombectomy. Do not delay tPA waiting for transfer.

The acute ischemic stroke decision tree rests on three sequential questions:

Time windows:

NIHSS-based triage:

Permissive hypertension targets (recap):

Glucose: Target 140–180 mg/dL; treat hypoglycemia (<60) immediately and hyperglycemia (>180) with insulin.

Temperature: Treat fever >38°C with acetaminophen; fever worsens outcomes.

Head of bed: Flat (0°) if LVO and tolerating, to maximize collateral flow; elevate 30° if airway/aspiration concern or post-thrombectomy.

NPO: Until formal bedside dysphagia screen passed — aspiration pneumonia is the most common early complication.

Pharmacotherapy — IV Thrombolysis

— Alteplase (IV tPA): 0.9 mg/kg (max 90 mg); 10% bolus over 1 min, remainder over 60 min.

— Tenecteplase (TNK): 0.25 mg/kg single IV bolus (max 25 mg) — increasingly preferred (AHA 2019/2024): equivalent or superior recanalization, simpler dosing, especially before thrombectomy.

— Age ≥18, clinical diagnosis of ischemic stroke with measurable disabling deficit.

— Onset (LKW) ≤4.5 h.

— Hemorrhage on CT, or history of ICH ever.

— Active internal bleeding; suspected SAH.

— BP >185/110 despite treatment.

— Platelets <100k, INR >1.7, PTT elevated, therapeutic LMWH within 24 h.

— DOAC within 48 h (unless reversal documented or specific assays normal).

— Recent ischemic stroke <3 mo, head trauma <3 mo, intracranial/spinal surgery <3 mo.

— Known intracranial neoplasm (intra-axial), AVM, aneurysm.

— Suspected aortic dissection or infective endocarditis.

— Glucose <50 (correct first and reassess).

— Age >80, NIHSS >25, prior stroke + diabetes, anticoagulant use even if INR normal — these were exclusions in ECASS III but AHA 2019 allows tPA 3–4.5 h with these.

— Pregnancy, recent MI <3 mo, recent GI/GU bleed <21 d, major surgery <14 d, recent arterial puncture at noncompressible site.

— Neuro checks + BP q15 min × 2 h, q30 min × 6 h, q1 h × 16 h.

— Maintain BP <180/105 × 24 h.

— No antiplatelet/anticoagulant × 24 h.

— Repeat NCCT at 24 h before starting antithrombotics.

Board pearl: Orolingual angioedema occurs in ~5% of tPA recipients, especially those on ACE inhibitors — stop infusion, secure airway, give antihistamines, steroids, epinephrine if severe. Always ask about ACEi use pre-tPA.

Agents:

Inclusion criteria:

Absolute exclusions:

Relative cautions (3–4.5 h window stricter):

Post-tPA monitoring (ICU/stroke unit):

Symptomatic ICH (sICH) rate: ~6%; if suspected (sudden ↓LOC, headache, BP surge, worsening exam), stop infusion, stat NCCT, send fibrinogen/CBC/PT/PTT, give cryoprecipitate (10 U) ± platelets, neurosurgery consult.

Endovascular Thrombectomy and Antithrombotic Therapy

— Devices: stent retrievers (Solitaire, Trevo), aspiration catheters; often combined.

— Eligible vessels: ICA, M1, proximal M2, basilar; emerging data for distal M2, vertebral.

— Outcome: NNT ~2.6 for reduced disability when given ≤6 h with LVO (HERMES meta-analysis).

— Age ≥18, pre-stroke mRS 0–1, NIHSS ≥6, ASPECTS ≥6, LVO confirmed, treatment ≤6 h from LKW.

— Extended window (6–24 h): DAWN/DEFUSE-3 criteria using perfusion imaging mismatch.

— Recent data (SELECT2, RESCUE-Japan LIMIT): benefit extends to large core infarcts (ASPECTS 3–5) — selected patients still benefit.

— Give IV tPA first if eligible; do not delay MT to "see if tPA works."

— In LVO patients presenting directly to thrombectomy center within 4.5 h, tPA still indicated (SKIP and MR CLEAN-NO IV trials inconclusive; AHA still recommends).

— Aspirin 325 mg within 24–48 h of stroke onset → secondary prevention.

— Dual antiplatelet (DAPT) with aspirin + clopidogrel × 21 days then aspirin alone — for minor stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4) (CHANCE, POINT trials).

— DAPT for 30–90 days in symptomatic intracranial atherosclerotic stenosis (SAMMPRIS protocol).

— Ticagrelor + aspirin alternative (THALES) — particularly if CYP2C19 loss-of-function and clopidogrel resistance.

— Acute anticoagulation not routinely indicated in acute stroke (no benefit, ↑ bleed risk).

— Exceptions: mechanical valve, LV thrombus, cerebral venous sinus thrombosis, extracranial arterial dissection (case-by-case).

— Timing for AFib-related stroke: "1-3-6-12 day rule" — start DOAC based on infarct size (1 d for TIA, 3 d small, 6 d moderate, 12 d large) to balance hemorrhagic transformation risk.

Key distinction: tPA dissolves clot; thrombectomy removes clot. They are complementary, not competing. The biggest sin is delaying transfer for thrombectomy because "we already gave tPA."

Mechanical thrombectomy (MT) — standard of care for LVO:

Selection criteria (AHA Class I):

tPA + MT:

Antiplatelet therapy (when tPA NOT given):

Anticoagulation:

Statin: High-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg) started during admission — improves outcomes even acutely.

Special Populations — Elderly, Renal, Hepatic

— No upper age limit for IV tPA in 0–3 h window.

— In 3–4.5 h window, age >80 was an ECASS III exclusion, but AHA 2019 recommends tPA is reasonable.

— Thrombectomy benefit demonstrated up to age 90+ (no age cutoff); pre-stroke functional status (mRS) matters more than chronological age.

— Higher sICH risk (~7–10%); informed discussion with family/proxy on risk-benefit.

— Polypharmacy: check for warfarin (INR), DOAC last dose, antiplatelets, NSAIDs.

— Fall risk post-stroke; PT/OT early.

— tPA dosing not renally adjusted.

— Avoid iodinated contrast (CTA) if eGFR <30 — but in acute LVO, benefit of imaging outweighs risk; hydrate post-procedure.

— Gadolinium contraindicated if eGFR <30 (NSF risk) — use non-contrast MRA.

— DOAC selection for AFib post-stroke: apixaban preferred in CKD; avoid dabigatran if CrCl <30; rivaroxaban requires dose adjustment.

— Severe liver disease with coagulopathy (INR >1.7) is a tPA contraindication.

— Cirrhotics have variable bleeding risk — individualize; mild–moderate disease not absolute contraindication if INR normal.

— Statin caution if AST/ALT >3× ULN; otherwise statins safe in stable chronic liver disease.

— Heparin during dialysis ≠ contraindication to tPA if last dose >12 h and PTT normal.

— Higher hemorrhagic transformation risk; uremic platelet dysfunction.

— Warfarin: INR ≤1.7 permits tPA.

— DOAC: tPA contraindicated if last dose <48 h unless idarucizumab (dabigatran) or andexanet alfa (factor Xa inhibitors) given, or specific drug-level assays normal.

— Thrombectomy can still be performed regardless of anticoagulation status.

Step 3 management: An 84-year-old on apixaban (last dose 36 h ago) presents with NIHSS 18 and M1 occlusion 2 h after LKW. Skip tPA (DOAC <48 h), proceed directly to mechanical thrombectomy — anticoagulation is not a contraindication to MT.

Elderly (≥80 y):

Renal impairment:

Hepatic impairment:

Dialysis patients:

Anticoagulated patients:

Special Populations — Pregnancy, Pediatrics, Sickle Cell

— Stroke risk elevated, especially postpartum (eclampsia, PRES, RCVS, cerebral venous sinus thrombosis, peripartum cardiomyopathy, amniotic fluid embolism, paradoxical embolism via PFO).

— IV tPA is not absolutely contraindicated in pregnancy — case series support use; risk of placental abruption and uterine bleeding. Decision shared with OB and patient.

— Thrombectomy preferred when possible (no systemic lytic exposure).

— Imaging: NCCT acceptable (shielded); MRI without gadolinium preferred for follow-up.

— Postpartum: standard tPA eligibility usually applies after >10 d.

— Workup: rule out preeclampsia/eclampsia, CVST (D-dimer, MRV), peripartum cardiomyopathy (echo, BNP).

— Causes differ: congenital heart disease, sickle cell, moyamoya, arteriopathy (post-VZV), dissection, prothrombotic states.

— tPA: not FDA-approved; used off-label at experienced centers, age ≥2; TIPS trial guidance.

— Thrombectomy: increasingly performed for LVO; SAVE ChildS registry supports safety.

— Immediate: hydration, normoglycemia, normothermia, antiplatelet/anticoagulation based on etiology.

— Acute ischemic stroke = medical emergency.

— Exchange transfusion to reduce HbS <30% is first-line; simple transfusion if exchange unavailable.

— tPA generally avoided unless concurrent thrombotic mechanism — exchange transfusion is the priority.

— Primary prevention: annual transcranial Doppler in kids 2–16 y; chronic transfusion if TCD >200 cm/s.

— Secondary prevention: chronic transfusion or hydroxyurea (TWiTCH trial).

— Workup expanded: dissection, PFO with paradoxical embolism (close PFO if cryptogenic stroke + RoPE score high, per RESPECT/CLOSE trials), hypercoagulable disorders, vasculitis, illicit drug use.

— PFO closure: superior to medical therapy alone for prevention in selected patients age 18–60.

Board pearl: A 25-year-old with sudden left hemiparesis 2 weeks postpartum and a normal CT — order MRV to evaluate for cerebral venous sinus thrombosis, especially if headache and seizures present. Treat with heparin even if hemorrhagic infarct present.

Pregnancy and postpartum:

Pediatric stroke:

Sickle cell disease:

Young adults (<55 y):

Complications and Adverse Outcomes

— Spontaneous in 10–40% of large strokes; symptomatic ICH in 2–6% (higher post-tPA).

— Risk factors: large infarct, hyperglycemia, uncontrolled HTN, late reperfusion, anticoagulation.

— Management of post-tPA sICH: stop tPA, stat CT, cryoprecipitate (target fibrinogen >150), platelets, neurosurgery consult.

— Peak day 2–5; large MCA stroke (>50% territory), young patients at risk because no atrophy = less room for swelling.

— Signs: declining LOC, anisocoria, Cushing triad.

— Management: head of bed 30°, hyperosmolar therapy (mannitol 1 g/kg or 3% hypertonic saline), avoid hypotonic fluids.

— Decompressive hemicraniectomy within 48 h reduces mortality from 70% to ~30% in patients ≤60 y (DESTINY, DECIMAL, HAMLET pooled); benefit also in >60 y but with more disability.

— Risk of brainstem compression, obstructive hydrocephalus.

— Suboccipital craniectomy ± EVD if mass effect, declining exam.

Step 3 management: A 45-year-old with day-3 large left MCA stroke, declining LOC, midline shift on CT. Order: mannitol bolus, hypertonic saline, neurosurgery consult for hemicraniectomy, intubate for airway protection. Hemicraniectomy within 48 h is life-saving in this age group.

Hemorrhagic transformation (HT):

Malignant MCA edema:

Cerebellar stroke with edema:

Seizures: ~5–10% post-stroke; treat acute seizures with levetiracetam; no prophylaxis.

Aspiration pneumonia: Leading early complication; dysphagia screen before any PO, including meds.

DVT/PE: Mechanical prophylaxis (IPC — CLOTS-3 trial) immediately; pharmacologic prophylaxis (LMWH/UFH) after 24 h if no hemorrhage and stable.

Cardiac complications: Stress cardiomyopathy (Takotsubo), arrhythmia (especially insular strokes), demand ischemia — check troponin, telemetry.

Depression and post-stroke cognitive impairment: Screen at follow-up; SSRIs effective (FLAME trial suggested motor benefit but FOCUS/EFFECTS did not replicate — use for depression only).

Central post-stroke pain (thalamic): gabapentin, pregabalin, amitriptyline.

Shoulder subluxation / spasticity: PT, slings, botulinum toxin for focal spasticity.

When to Escalate Care — ICU, Consults, Triage

— Post-tPA × 24 h (intensive BP and neuro monitoring) — many centers admit to step-down/stroke unit.

— Post-thrombectomy × 24 h.

— NIHSS ≥10–15 or large MCA, basilar, or cerebellar territory infarct.

— Hemodynamic instability, requiring IV vasoactive drips.

— Airway compromise (decreased LOC, bulbar dysfunction, aspiration).

— Symptomatic ICH or evolving mass effect.

— All ischemic strokes that don't meet ICU criteria — meta-analyses show stroke unit care reduces death/dependency vs general ward (NNT ~20).

— Multidisciplinary: neurology, nursing, PT/OT/SLP, social work, pharmacy.

— Neurology — all strokes; vascular neurology if available.

— Neurosurgery — hemorrhagic transformation, large MCA edema, cerebellar stroke, hydrocephalus.

— Neuro-interventional — LVO confirmed.

— Cardiology — AFib management, LV thrombus, endocarditis, PFO closure decision.

— Vascular surgery — symptomatic carotid stenosis 70–99% for CEA within 2 weeks.

— PT/OT/SLP — within 24–48 h for early mobilization and dysphagia evaluation.

— Palliative care — devastating stroke, family meeting, goals of care.

— LVO on CTA at non-thrombectomy center.

— Post-tPA needing ICU monitoring not available locally.

— Hemorrhagic transformation requiring neurosurgery.

— Cerebellar stroke at risk for edema.

— Suspected basilar occlusion (always transfer).

CCS pearl: On a CCS stroke case, early consults (neurology immediately, neurosurgery if any hemorrhage or large MCA, PT/OT/SLP within 24 h) and stroke unit admission are routinely tested orders. Forgetting the dysphagia screen before allowing PO is a common deduction.

ICU / neuro-ICU admission criteria:

Stroke unit (step-down) admission:

Consults:

Transfer triggers (primary → comprehensive stroke center):

Telestroke: When in-person vascular neurology unavailable, telestroke consultation increases tPA delivery and is evidence-based (AHA Class I).

Key Differentials — Same-Category Causes (Stroke Mimics & Subtypes)

— Brief focal deficit without infarction on imaging; tissue-based definition.

— Same workup as stroke; same secondary prevention.

— ABCD² score stratifies short-term risk (age, BP, clinical features, duration, diabetes).

— High-risk TIA (ABCD² ≥4) gets DAPT × 21 d (CHANCE/POINT).

— Intracerebral hemorrhage (ICH): hypertensive deep bleeds (basal ganglia, thalamus, pons, cerebellum); lobar bleeds in amyloid angiopathy.

— Subarachnoid hemorrhage (SAH): "thunderclap" headache, meningismus, ruptured aneurysm.

— Management: BP control (target SBP 130–140 in ICH per INTERACT-2/ATACH-2), reverse anticoagulation, neurosurgery consult, never give tPA.

— Headache, seizures, focal deficits, papilledema; risk factors: OCPs, pregnancy/postpartum, thrombophilia, dehydration, mastoiditis.

— Diagnose with MRV or CTV; "empty delta sign" on contrast CT.

— Treat with heparin then warfarin/DOAC even if hemorrhagic infarct.

— Cardioembolic — abrupt, multiple territories, AFib, valve disease.

— Large-artery atherosclerosis — stuttering onset, carotid bruit, watershed pattern.

— Small-vessel/lacunar — chronic HTN, DM, deep small infarcts, no cortical signs.

— Cryptogenic — workup negative; extended monitoring may reveal AFib.

— Other — dissection, vasculitis, hypercoagulability, drug-induced.

— Between MCA-ACA or MCA-PCA territories; from systemic hypotension or critical carotid stenosis.

— "Man-in-the-barrel" — proximal arm weakness.

Key distinction: A stroke with abrupt maximal deficit + AFib → cardioembolic; stuttering progression + carotid bruit → large-artery atherosclerosis; isolated lacunar syndrome without cortical signs → small-vessel. Mechanism drives prevention strategy.

TIA (transient ischemic attack):

Hemorrhagic stroke:

Cerebral venous sinus thrombosis (CVST):

Stroke subtypes by mechanism (TOAST):

Watershed (borderzone) infarcts:

Key Differentials — Other-Category Causes (True Mimics)

— Can produce hemiparesis, aphasia indistinguishable from stroke.

— Always check fingerstick first; resolves with glucose.

— Postictal focal weakness lasting minutes to 36 h.

— Look for tongue bite, incontinence, witnessed convulsion; EEG if uncertain.

— Aura with weakness, sensory, visual, language symptoms; gradual march, headache, history of similar episodes.

— Diagnosis of exclusion.

— Hoover sign (involuntary contralateral hip extension when lifting "weak" leg), give-way weakness, non-anatomic patterns.

— Stroke workup still warranted; manage compassionately.

— Peripheral CN VII = entire hemiface including forehead; cortical stroke spares forehead.

— Posterior white matter edema, often vision changes, seizures, headache.

— MRI shows symmetric posterior vasogenic edema; treat BP, remove triggers (immunosuppressants, eclampsia).

— Old stroke deficits reappear with fever, infection, metabolic derangement; treat underlying cause.

— Encephalopathy patterns; usually global, not focal.

— Subacute progression; imaging reveals it.

— Younger patients, subacute onset, MRI lesions; LP shows oligoclonal bands.

— HINTS exam (Head Impulse, Nystagmus, Test of Skew) — central features (skew deviation, direction-changing nystagmus, normal head impulse) → posterior stroke; peripheral vestibulopathy is benign.

— Neck pain/headache + Horner ± stroke; young patient, trauma history.

Board pearl: The HINTS exam outperforms early MRI for posterior circulation stroke in acute vestibular syndrome — a central pattern mandates stroke workup even if CT/MRI are initially negative.

Hypoglycemia:

Seizure with Todd paralysis:

Complex (hemiplegic) migraine:

Conversion disorder / functional neurologic disorder:

Bell palsy:

Hypertensive encephalopathy / PRES:

Sepsis-unmasking ("recrudescence"):

Hyponatremia, hyperammonemia, uremia, Wernicke encephalopathy:

Mass lesion (tumor, abscess, subdural hematoma):

MS exacerbation, transverse myelitis:

Vertigo causes (peripheral vs central):

Carotid/vertebral dissection:

Secondary Prevention and Discharge Medications

— Aspirin 81 mg daily lifelong, OR clopidogrel 75 mg, OR aspirin + extended-release dipyridamole.

— Short-term DAPT (aspirin + clopidogrel) × 21 days then aspirin alone for minor stroke (NIHSS ≤3) or high-risk TIA (CHANCE/POINT); 90 days for symptomatic intracranial atherosclerosis (SAMMPRIS).

— DOAC (apixaban, rivaroxaban, dabigatran, edoxaban) preferred over warfarin for non-valvular AFib.

— Warfarin (INR 2–3) for mechanical valves and moderate-severe mitral stenosis.

— Start timing per "1-3-6-12 day rule" based on stroke size.

— Left atrial appendage occlusion (Watchman) if anticoagulation contraindicated.

— Target <130/80 for most (SPRINT, AHA 2017).

— Start/intensify after 24 h if stable; thiazide + ACEi (PROGRESS trial: perindopril + indapamide).

— Atorvastatin 80 mg or rosuvastatin 40 mg for all ischemic stroke (SPARCL); target LDL <70 mg/dL (or <55 mg/dL in very high-risk per recent ESC/AHA).

— Add ezetimibe or PCSK9 inhibitor if not at goal.

— Smoking cessation (varenicline, nicotine replacement, counseling).

— Mediterranean diet (PREDIMED).

— Exercise 150 min/week moderate intensity.

— Weight reduction; OSA screening and CPAP if indicated.

— Moderate alcohol use; no illicit drugs.

— CEA within 2 weeks for symptomatic stenosis 70–99% (NNT ~6); 50–69% benefits selected patients (men, older, NASCET).

— Carotid stenting if surgical risk high or anatomy unfavorable.

Step 3 management: At discharge for an ischemic stroke patient with new AFib: apixaban 5 mg BID (or per renal dose), atorvastatin 80 mg, lisinopril titrated to BP <130/80, smoking cessation counseling, follow-up with neurology in 1–2 weeks, primary care in 1 week. Avoid concomitant aspirin unless coronary indication.

Antiplatelet therapy (non-cardioembolic):

Anticoagulation (cardioembolic — AFib, LV thrombus, mechanical valve):

BP control:

Statin (high-intensity):

Diabetes: HbA1c <7%; consider GLP-1 agonist or SGLT2 inhibitor for cardiovascular benefit and weight.

Lifestyle:

Carotid revascularization:

PFO closure if cryptogenic stroke, age 18–60, high-risk PFO features (atrial septal aneurysm, large shunt).

Follow-Up, Monitoring Parameters, and Rehabilitation

— Stroke etiology documented (TOAST); secondary prevention regimen reconciled.

— Dysphagia status and diet textures specified.

— Functional status (mRS, Barthel) and disposition (home, inpatient rehab, SNF).

— Inpatient rehab if can tolerate ≥3 h/day therapy; SNF if less.

— Driving restrictions: typically no driving × 1 month minimum; longer if hemianopia, neglect, seizures.

— Return precautions: any new deficit → call 911.

— PCP within 7–14 days post-discharge for medication reconciliation, BP check, mood screen.

— Neurology/stroke clinic 1–3 months, then 6 and 12 months.

— Cardiology if AFib, LV thrombus, PFO.

— Vascular surgery post-CEA at 1 month.

— BP log at home; target <130/80.

— Lipid panel at 4–12 weeks after starting statin; LDL target <70.

— HbA1c every 3 months until controlled.

— If on warfarin: INR weekly until stable, then monthly; goal 2–3.

— If on DOAC: annual CBC, renal/hepatic function; dose-adjust as renal function changes.

— Prolonged cardiac monitoring (14–30 d event monitor or implantable loop) if cryptogenic.

— Early mobilization within 24–48 h reduces complications; AVERT trial cautioned against very-early high-dose mobilization.

— PT for gait, balance, strength; OT for ADLs; SLP for aphasia, dysarthria, dysphagia.

— Constraint-induced movement therapy for unilateral arm weakness.

— Cognitive rehab for neglect, executive dysfunction.

— Recognize stroke (BE-FAST) — recurrence risk ~5–10%/yr without prevention.

— Sexual activity safe when can climb 2 flights of stairs.

— Air travel: typically OK after 2 weeks for uncomplicated stroke.

— Vaccinations: annual flu, pneumococcal, COVID — reduce vascular events.

— Mood: post-stroke depression in ~30%; screen PHQ-9 at each visit.

CCS pearl: Document the dysphagia screen before allowing PO at any point in the case, schedule PT/OT/SLP within 24–48 h, and write the outpatient follow-up plan with neurology in 1–4 weeks plus PCP in 1 week before "ending" the case — these are commonly tested transitions-of-care items.

Discharge planning checklist:

Follow-up cadence:

Monitoring parameters:

Rehabilitation:

Counseling topics:

Ethical, Legal, and Patient Safety Considerations

— Time-pressured discussion; explain ~30% chance of meaningful recovery improvement and ~6% sICH risk (1% fatal).

— Implied/emergency consent is appropriate when patient is aphasic or impaired and no surrogate is immediately available — documented as emergency exception.

— If the patient retains capacity and refuses tPA, that refusal must be respected and documented.

— Surrogate decision-makers: spouse, adult child, parent, sibling per state hierarchy.

— Aphasic patients may retain capacity — use written choices, yes/no questions, communication boards.

— Document understanding, appreciation, reasoning, expression of choice.

— Check for DNR/DNI, POLST, healthcare proxy on arrival.

— A DNR is not a "do not treat" — tPA, thrombectomy, and supportive care are still indicated unless explicitly refused.

— Day 1–3 prognostic discussions are unreliable; avoid premature withdrawal of life-sustaining therapy (self-fulfilling prophecy).

— AHA recommends waiting at least 24–72 h before DNR decisions in severe stroke.

— Palliative care involvement early for complex decisions.

— Driving restrictions reportable to DMV in some states (CA, others) — physician must inform patient and document.

— Suspected elder abuse if neglect contributed (e.g., missed AFib anticoagulation).

— Medication reconciliation errors at discharge are the #1 readmission driver — re-verify anticoagulant, antiplatelet, statin, antihypertensives.

— Ensure outpatient INR or follow-up monitoring arranged; do not discharge on warfarin without scheduled INR.

— Avoid "dual antiplatelet + anticoagulant" unless specific indication (e.g., recent PCI) — bleeding risk multiplied.

— Verify follow-up appointments made before discharge, not "to be scheduled."

— Door-to-needle <60 min is the Get With The Guidelines target; tracked publicly.

— Hospitals certified as primary vs comprehensive stroke centers — affects EMS routing.

Board pearl: A patient with aphasia and clear capacity who shakes their head "no" to tPA must have that refusal honored — document the decisional capacity assessment, attempt alternative communication, and involve family/proxy without coercing. Autonomy supersedes urgency.

Informed consent for tPA:

Capacity assessment:

Advance directives:

Goals of care for devastating strokes:

Mandatory reporting:

Transition-of-care risks (Step 3 favorite):

Telestroke and quality:

High-Yield Associations and Rapid-Fire Facts

Key distinction: LVO = clot in big vessel = thrombectomy; small distal clot = tPA only. CTA at presentation makes this distinction in <5 minutes.

Hyperdense MCA sign on NCCT → thrombus in MCA → suspect LVO, get CTA stat.

Insular ribbon sign / loss of gray-white → early MCA infarct, ASPECTS-relevant.

Pure motor hemiparesis → lacunar stroke in posterior limb of internal capsule.

Wallenberg syndrome → lateral medulla, PICA territory.

Locked-in syndrome → ventral pons, basilar artery occlusion.

"Top of the basilar" → bilateral thalami + occipital → coma, vision loss, memory.

Amaurosis fugax ("curtain coming down") → ipsilateral carotid disease, retinal embolus.

Subclavian steal syndrome → arm exertion → vertebrobasilar symptoms; check inter-arm BP differential.

Crossed deficits (ipsilateral face + contralateral body) → brainstem stroke.

Forehead-sparing facial weakness → cortical (UMN); forehead involved → peripheral (Bell).

HINTS exam > MRI in first 24 h for posterior stroke (acute vestibular syndrome).

Hollenhorst plaque (cholesterol crystal in retinal artery) → carotid source.

Janeway lesions, Osler nodes, splinter hemorrhages → endocarditis → septic emboli.

DWI-FLAIR mismatch → infarct <4.5 h old → wake-up stroke tPA eligibility.

ABCD² score ≥4 → high-risk TIA → DAPT × 21 d.

CHA₂DS₂-VASc ≥2 (men) or ≥3 (women) → anticoagulate AFib.

HAS-BLED → bleed risk assessment, not a reason to withhold anticoagulation alone.

NIHSS ≥6 → likely LVO → get CTA, mobilize thrombectomy team.

ASPECTS ≤6 → larger core; historically discouraged thrombectomy, but recent trials (SELECT2) show benefit even in large cores.

1-3-6-12 day rule → DOAC start timing post-stroke for AFib (TIA, small, moderate, large).

Door-to-needle ≤45–60 min, door-to-groin ≤90 min — quality metrics.

CEA within 2 weeks of symptomatic 70–99% carotid stenosis.

PFO closure for cryptogenic stroke age 18–60 with high-risk features.

Sickle cell stroke → exchange transfusion, not tPA.

CVST → anticoagulate even if hemorrhagic.

Orolingual angioedema with tPA + ACEi.

Statin acutely (atorvastatin 80) — start in hospital.

Hemicraniectomy ≤48 h, age ≤60, malignant MCA → mortality 70% → 30%.

Board Question Stem Patterns

— Answer: Give IV tPA (BP <185/110 OK), then CTA — if LVO, mobilize thrombectomy.

— Answer: LKW is 11 PM; outside standard 4.5-h window. Order MRI with DWI-FLAIR — if mismatch present, tPA may be given (WAKE-UP protocol). Always pursue CTA for LVO regardless of time.

— Answer: Skip tPA (DOAC <48 h, no reversal); proceed directly to thrombectomy.

— Answer: MRV → cerebral venous sinus thrombosis → heparin.

— Answer: Vertebral artery dissection → MRA neck with fat-sat T1; antiplatelet or anticoagulation × 3–6 months.

— Answer: Stop infusion, stat NCCT, cryoprecipitate + platelets, neurosurgery consult.

— Answer: Orolingual angioedema (ACEi association); stop infusion, secure airway, antihistamines/steroids/epi.

— Answer: Exchange transfusion to HbS <30%, not tPA.

— Answer: Decompressive hemicraniectomy for malignant MCA edema.

— Answer: TEE confirms, RoPE score high → PFO closure + antiplatelet.

— Answer: Aspirin + clopidogrel × 21 d, then aspirin; statin; BP control; carotid imaging.

— Answer: Treat BP (target ~15% reduction in 24 h; permissive otherwise unless >220/120).

Board pearl: When the stem mentions a specific time and specific NIHSS, write them down. Step 3 questions weaponize the 4.5-h tPA, 6-h thrombectomy, and 24-h extended thrombectomy windows — knowing which clock applies wins the question.

Stem: "65 y/o with AFib presents with right hemiparesis and aphasia 90 min ago, NIHSS 14, NCCT negative, BP 178/96."

Stem: "Woke up with left hemiparesis at 7 AM, last seen well at 11 PM."

Stem: "75 y/o on apixaban (last dose 30 h ago) with NIHSS 18, M1 occlusion on CTA."

Stem: "30 y/o postpartum woman, severe headache, seizure, left hemiparesis, CT negative."

Stem: "55 y/o with right-sided weakness, neck pain after chiropractic adjustment, posterior circulation symptoms."

Stem: "Patient given tPA, 45 min into infusion develops headache, BP surge, declining LOC."

Stem: "tPA infusing, patient develops tongue swelling."

Stem: "8-year-old with sickle cell and acute hemiparesis."

Stem: "Day 3 post-stroke, declining LOC, midline shift on CT, 45 y/o."

Stem: "Cryptogenic stroke, 35 y/o, TTE shows PFO."

Stem: "TIA with right arm weakness × 30 min, ABCD² = 5, NCCT/MRI negative."

Stem: "Acute MCA stroke, BP 240/130, no tPA candidate."

One-Line Recap

Acute ischemic stroke management is a time-locked algorithm: confirm no hemorrhage on NCCT, give IV thrombolysis (tPA or tenecteplase) within 4.5 h of last known well, identify large-vessel occlusion on CTA and mobilize mechanical thrombectomy within 6–24 h with perfusion mismatch — then start aspirin, high-intensity statin, BP control, and etiology-specific secondary prevention.

— 4.5 h → IV thrombolysis from LKW.

— 6 h → standard thrombectomy.

— 24 h → extended thrombectomy with DAWN/DEFUSE-3 perfusion mismatch.

— <185/110 pre-tPA, <180/105 post-tPA × 24 h, <220/120 if no reperfusion therapy, <130/80 chronic secondary prevention.

— Antiplatelet (aspirin ± short-term DAPT for minor stroke/TIA), high-intensity statin (LDL <70), BP control + lifestyle. Add anticoagulation if AFib (using 1-3-6-12 day rule) and CEA for symptomatic carotid 70–99% within 2 weeks.

— Treating permissive hypertension aggressively (worsens penumbra).

— Delaying thrombectomy transfer because tPA was given (they are complementary).

— Discharging without dysphagia screen, mood screen, follow-up appointments, and medication reconciliation — transitions of care are where Step 3 questions live.

Step 3 management: Master the time-window decision tree, the BP targets at each phase, and the discharge bundle — these three layers cover the vast majority of stroke testable content from ED through follow-up.

Three clocks to memorize:

Three blood pressure targets:

Three secondary prevention pillars (non-cardioembolic):

Three management traps to avoid: