CCS Integrated Cases

CCS case: acute stroke within thrombolytic window

Clinical Overview and When to Suspect Acute Ischemic Stroke

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

— 5th leading cause of death; leading cause of long-term disability

— Time-sensitive: ~1.9 million neurons lost per minute of LVO

— Balance loss (sudden), Eye changes (diplopia, visual field cut)

— Face droop, Arm weakness, Speech slurred/aphasic, Time to call 911

— Adds posterior circulation signs missed by classic FAST (~14% of strokes)

— Sudden onset focal deficit with clear LKW timestamp

— Atrial fibrillation, recent MI, mechanical valve, hypercoagulable state

— Prior TIA, carotid disease, uncontrolled HTN/DM/dyslipidemia

— Age >55, smoking, OCP use in young women, cervical trauma (dissection)

— "Awoke with right-sided weakness" → wake-up stroke; LKW = time went to bed (unless MRI mismatch protocol)

— "Sudden worst headache" → think SAH first, but stroke if focal deficit

— "Numbness and slurred speech 90 minutes ago" → in window, move fast

CCS pearl: On the CCS interface, the very first orders for suspected stroke are: (1) "Stat non-contrast head CT," (2) "Fingerstick glucose," (3) "IV access × 2, large bore," (4) "Vital signs q15min," (5) "NIH Stroke Scale," (6) "Notify stroke team/neurology." Do NOT order aspirin or antihypertensives before CT — this is a common test trap that delays tPA eligibility. Advance the simulated clock in 15-minute increments until imaging results return; door-to-needle target is ≤60 minutes (ideally ≤45).

Definition: Acute ischemic stroke (AIS) is sudden focal neurologic deficit from arterial occlusion causing brain ischemia. The "thrombolytic window" refers to eligibility for IV alteplase/tenecteplase (≤4.5 hours from last known well, LKW) or mechanical thrombectomy (≤24 hours for selected large vessel occlusions, LVO).

Epidemiology and burden:

When to suspect AIS — BE-FAST mnemonic:

High-risk historical features:

CCS trigger phrasing to recognize:

Presentation Patterns and Key History

— MCA (most common): contralateral face/arm > leg weakness, sensory loss, gaze deviation toward lesion, aphasia (dominant) or neglect (non-dominant), homonymous hemianopia

— ACA: contralateral leg > arm weakness, abulia, urinary incontinence

— Lacunar (small vessel): pure motor, pure sensory, ataxic hemiparesis, dysarthria-clumsy hand; no cortical signs

— Vertigo, diplopia, dysarthria, dysphagia, ataxia, crossed signs (ipsilateral CN + contralateral body)

— Basilar occlusion: locked-in syndrome, coma, quadriparesis — high mortality, aggressive thrombectomy indicated even late

— PCA: isolated homonymous hemianopia with macular sparing

— Exact last known well time — not symptom discovery time

— Witnessed onset vs wake-up vs unwitnessed

— Maximal at onset (embolic) vs stuttering/progressive (thrombotic, dissection)

— Associated headache (dissection, hemorrhage), neck pain/trauma

— Recent surgery, bleeding, anticoagulant use, prior stroke

— Pregnancy status, last menstrual period

— Hypoglycemia (always check glucose), seizure with Todd paralysis, complex migraine, conversion disorder, sepsis unmasking old deficit, hypertensive encephalopathy

— Mimic rate ~5–15%; tPA in mimics has very low ICH risk, so do NOT delay if criteria met

Key distinction: "Last known well" ≠ "symptom discovery." A patient who went to bed at 10 PM neurologically intact and awoke at 6 AM with deficits has LKW = 10 PM — outside the standard 4.5-hour window. However, MRI DWI-FLAIR mismatch or perfusion imaging mismatch (DEFUSE-3, DAWN) can extend treatment eligibility. Always document LKW in CCS notes; it drives every downstream decision.

Anterior circulation (carotid/MCA/ACA) syndromes:

Posterior circulation (vertebrobasilar):

Critical history elements (the LKW interrogation):

Stroke mimics to consider but not delay treatment for:

Physical Exam Findings and Hemodynamic Assessment

— 11 items: LOC, gaze, visual fields, facial palsy, motor arm/leg (×2 each), ataxia, sensory, language, dysarthria, extinction/neglect

— 0–4 minor, 5–15 moderate, 16–20 moderate-severe, 21–42 severe

— NIHSS ≥6 with proximal occlusion → consider thrombectomy

— NIHSS <4 → still treat if disabling deficit (aphasia, hemianopia)

— Forced gaze deviation toward lesion = cortical (MCA); away = pontine

— Pure dysarthria + clumsy hand → lacunar (internal capsule/pons)

— Horner syndrome + contralateral pain/temp loss → lateral medullary (Wallenberg, PICA)

— Wide pulse pressure + neck bruit → consider carotid disease/dissection

— BP: Often elevated reactively. Permissive hypertension up to 220/120 in non-tPA candidates; must be <185/110 before tPA and <180/105 for 24h after

— HR and rhythm — irregular suggests AF (cardioembolic source)

— Temperature — fever worsens outcomes; treat aggressively

— Glucose — both hypo (<60) and hyper (>180) worsen outcomes

— Cardiac auscultation for murmurs (endocarditis, valvular AF source)

— Carotid bruits, peripheral pulses, signs of recent trauma/bleeding

— Decreased LOC, dysphagia, gag — NPO until formal swallow eval

— Posterior circulation strokes have highest aspiration risk

Step 3 management: Before giving tPA, BP must be ≤185/110. If above, give labetalol 10–20 mg IV (may repeat × 1) or nicardipine 5 mg/h IV titrated. Avoid sublingual nifedipine (precipitous drops). If BP cannot be safely lowered, tPA is contraindicated. After tPA, maintain BP <180/105 for 24 hours with q15min monitoring for 2h, then q30min for 6h, then q1h for 16h — memorize this cadence.

NIH Stroke Scale (NIHSS) — 0 to 42:

Localizing exam clues:

Hemodynamic and general assessment:

Airway and aspiration risk:

Diagnostic Workup — Initial Labs, Imaging, ECG

— Non-contrast head CT (NCHCT) STAT — primary purpose is to rule out hemorrhage before thrombolytics

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

— ASPECTS score (0–10) on NCHCT for MCA territory; <6 suggests large established infarct → poor thrombectomy candidate

— Door-to-CT goal: ≤25 minutes; door-to-CT-read: ≤45 minutes

— Fingerstick glucose — mandatory; hypoglycemia is a top mimic

— CBC, BMP, coags (PT/INR, aPTT), troponin

— Type and screen if hemorrhagic conversion possible

— Pregnancy test in women of childbearing age

— Toxicology if suspected (cocaine, sympathomimetics)

— 12-lead ECG looking for AF, recent MI, LVH

— Continuous telemetry for ≥24 hours (paroxysmal AF detection)

— Troponin — concurrent MI in ~5–17% of strokes

— CT angiography (CTA) head and neck — identifies LVO candidates for thrombectomy

— Perform concurrently or immediately after NCHCT

— Check creatinine if available, but do NOT delay CTA for Cr in suspected LVO

CCS pearl: Order set for CCS at minute 0: "Non-contrast CT head stat," "CTA head/neck stat," "Fingerstick glucose," "CBC, BMP, PT/INR/aPTT, troponin," "Type and screen," "12-lead ECG," "Continuous cardiac monitor," "Pulse oximetry," "Neuro checks q15min," "NPO," "IV NS at 75 mL/h" (avoid hypotonic fluids — worsen edema). Then advance clock — do NOT order aspirin yet.

Imaging — the critical first step:

Bedside labs (do NOT wait for results to give tPA except glucose):

Only platelets <100k, INR >1.7, or aPTT elevation contraindicate tPA — and only platelet count and glucose must return before tPA in most patients; otherwise treat empirically

ECG and cardiac monitoring:

Vascular imaging (if no delay to tPA):

Diagnostic Workup — Advanced and Confirmatory Studies

— Identifies ischemic core (irreversibly damaged, CBF <30%) vs penumbra (salvageable, Tmax >6 sec)

— DAWN trial (6–24h): thrombectomy if clinical-core mismatch

— DEFUSE-3 (6–16h): thrombectomy if core <70 mL and mismatch ratio ≥1.8

— Core/penumbra ratio drives late-window decisions

— DWI restriction within minutes of ischemia — most sensitive early

— DWI-FLAIR mismatch (DWI+/FLAIR-): lesion <4.5h old → tPA eligibility for wake-up strokes (WAKE-UP trial)

— MRA for vascular anatomy without contrast

— Cardioembolic: Echo (TTE first, TEE if cryptogenic or young), telemetry/Holter, extended monitoring (30-day event monitor or implantable loop) for cryptogenic stroke

— Large artery atherosclerosis: carotid duplex or CTA/MRA neck

— Small vessel: lacunar pattern on MRI

— Other: hypercoagulable panel in young/cryptogenic (antiphospholipid Ab, factor V Leiden, prothrombin gene, protein C/S, antithrombin), vasculitis workup if suspected

— TEE with bubble study for PFO

— Lipid panel, HbA1c, homocysteine

— Drug screen

— Cervical artery imaging for dissection (MRA with fat-sat or CTA)

Board pearl: For cryptogenic stroke after standard workup, prolonged cardiac monitoring (≥30 days) detects occult AF in ~16% of patients (CRYSTAL-AF, EMBRACE). This changes secondary prevention from antiplatelet to anticoagulation. Order an outpatient event monitor or implantable loop recorder before discharge — high-yield Step 3 management decision. Also remember: routine thrombophilia testing in older patients with clear vascular risk factors is low yield and not recommended.

CT perfusion (CTP) — extends treatment window:

MRI brain with DWI/FLAIR:

Etiologic workup (within 24–48h of admission, TOAST classification):

Young stroke (<50) additional studies:

Risk Stratification and First-Line Management Logic

— Step 1: Is hemorrhage present on NCHCT? Yes → stop, manage as ICH

— Step 2: Is LKW ≤4.5 hours? Yes → assess tPA eligibility

— Step 3: Is there LVO on CTA? Yes → thrombectomy candidate up to 24h

— Step 4: Outside windows? → supportive care, antiplatelet, secondary prevention

— Inclusion: Age ≥18, measurable deficit, LKW ≤4.5h, BP controllable <185/110

— Absolute contraindications:

— Active hemorrhage or hemorrhage on CT

— Recent ICH ever; ischemic stroke <3 months

— Severe head trauma <3 months

— Recent intracranial/spinal surgery <3 months

— GI malignancy or GI bleed <21 days

— Aortic dissection

— Platelets <100k, INR >1.7, therapeutic LMWH <24h, DOAC <48h (unless reversed)

— Endocarditis (septic emboli)

— Age >80, NIHSS >25, prior stroke + diabetes, anticoagulant use even with normal INR

— Recent MI, major surgery <14 days, GU/GI bleed <21 days, pregnancy (relative)

— ICA, M1, basilar, occasionally M2 occlusions

— NIHSS ≥6 typical threshold (lower for disabling deficits)

— ASPECTS ≥6 for early window; perfusion mismatch for late window

Step 3 management: Tenecteplase (single 0.25 mg/kg IV bolus, max 25 mg) is now preferred over alteplase at many centers — same/better outcomes, easier dosing, especially before transfer for thrombectomy. After lytic, transfer to comprehensive stroke center if LVO present. Document the risk-benefit conversation with family (1% symptomatic ICH risk with tPA vs disability benefit NNT ~7 for mRS 0–1) — this is testable as informed consent.

The fundamental decision tree (time + imaging + eligibility):

IV thrombolytic eligibility (alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg):

Relative contraindications (3–4.5h window stricter):

LVO and thrombectomy decision:

Pharmacotherapy — First-Line Drug Regimen

— 0.9 mg/kg, maximum 90 mg total

— 10% as bolus over 1 minute, remaining 90% over 60 minutes

— Calculate weight carefully — dosing errors are a safety event

— Hold all antiplatelets/anticoagulants for 24 hours post-lytic

— 0.25 mg/kg IV bolus over 5 seconds, max 25 mg

— Single dose, no infusion — operationally simpler

— Equivalent or superior to alteplase (AcT, EXTEND-IA TNK)

— Pre-lytic: <185/110 (labetalol 10–20 mg IV, nicardipine 5 mg/h titrate to 15 mg/h, or clevidipine)

— Post-lytic for 24h: <180/105

— Monitoring: q15min × 2h, q30min × 6h, q1h × 16h

— Aspirin 325 mg PO/PR within 24–48h if not getting tPA

— If tPA given, hold aspirin for 24h, then start after repeat CT shows no hemorrhage

— Minor stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4): start dual antiplatelet (DAPT) with aspirin + clopidogrel for 21 days (CHANCE, POINT trials), then aspirin monotherapy

— Alternative: aspirin + ticagrelor (THALES) for 30 days

— Statin: high-intensity atorvastatin 80 mg within 24h (improves outcomes)

— DVT prophylaxis: intermittent pneumatic compression immediately; pharmacologic (enoxaparin 40 mg SQ daily) after 24h if no hemorrhage

— Glycemic control: target 140–180 mg/dL; avoid hypoglycemia

— Antipyretics: acetaminophen 650 mg q6h for T >38°C

CCS pearl: Common CCS trap — ordering aspirin within 24h of tPA causes hemorrhagic transformation and is a scored safety error. The correct sequence: tPA → q15min neuro/BP checks → repeat NCHCT at 24h → if no bleed, then aspirin 81–325 mg. Also order "Avoid NG tube, foley, arterial puncture × 24h" post-lytic to minimize bleeding sites.

IV alteplase dosing:

IV tenecteplase (TNK) dosing:

BP management during/after lytic:

Non-lytic candidates — antiplatelet therapy:

Supportive medications:

Procedures — Mechanical Thrombectomy and Endovascular Care

— Anterior circulation LVO (ICA, M1; selected M2): up to 24h from LKW with favorable imaging

— Basilar artery occlusion: up to 24h (ATTENTION, BAOCHE trials) — often higher mortality without MT

— NIHSS ≥6, ASPECTS ≥6 (early window) or perfusion mismatch (late window)

— Pre-stroke mRS 0–1 ideal; consider in mRS 2 case-by-case

— Stent retriever ± aspiration catheter via femoral or radial access

— TICI 2b/3 reperfusion is the goal (≥50% or complete reperfusion)

— Door-to-puncture: ≤90 min (direct arrival), ≤60 min (transfer)

— Don't delay MT for IV lytic — give lytic concurrently if eligible (bridging therapy is standard)

— Neuro ICU monitoring × 24h minimum

— BP goal post-successful recanalization: <180/105 (some <140 systolic if complete reperfusion) to reduce reperfusion hemorrhage

— Groin/access site checks q15min × 2h, q1h × 6h

— Repeat NCHCT at 24h before starting antiplatelet

— Symptomatic ICH ~4–6%

— Embolization to new territory

— Vessel perforation, dissection

— Groin hematoma, retroperitoneal bleed, pseudoaneurysm

— Contrast nephropathy (less concerning than missing MT)

— Symptomatic carotid stenosis 70–99% → CEA or CAS within 2 weeks of index event

— 50–69% stenosis: CEA in selected men, especially if recent symptoms

— <50% stenosis: medical management

Step 3 management: A patient with NIHSS 18, M1 occlusion on CTA, LKW 5 hours ago is OUTSIDE the IV lytic window but INSIDE the thrombectomy window. Order: "Transfer to comprehensive stroke center for mechanical thrombectomy," "Continue BP <185/110," "Maintain NPO," "Continuous neuro monitoring." Don't withhold MT because tPA is too late — these are independent decisions.

Mechanical thrombectomy (MT) — indications:

Procedural workflow:

Post-procedure management:

Complications of MT:

Carotid revascularization (later, not acute):

Special Populations — Elderly and Renal/Hepatic Impairment

— tPA still indicated within 4.5h despite older trial exclusions; IST-3 supports benefit

— Higher absolute ICH risk (~5–7% vs 3% in younger) but net benefit preserved

— In 3–4.5h window: age >80 was an exclusion in ECASS-III but US guidelines allow it

— Higher comorbidity burden — review all anticoagulants, antiplatelets, bleeding history carefully

— Higher fall risk post-stroke; falls + anticoagulation = ICH risk in long-term planning

— No upper age limit; benefit shown into 90s if pre-stroke mRS 0–2

— Functional status, frailty, and goals of care drive decision, not chronologic age

— tPA not renally dosed — full dose regardless of eGFR

— Contrast for CTA: shared decision; don't delay CTA in suspected LVO even with elevated Cr — benefit far exceeds CIN risk

— DOACs for secondary prevention require renal dose adjustment:

— Apixaban: 2.5 mg BID if any 2 of: age ≥80, weight ≤60 kg, Cr ≥1.5

— Dabigatran: avoid if CrCl <30

— Rivaroxaban: 15 mg daily if CrCl 15–50

— Warfarin preferred if CrCl <15 or dialysis

— Severe liver disease with coagulopathy (INR >1.7) → tPA contraindicated

— Statins generally safe in mild-moderate; avoid in active hepatitis

— DOAC caution in Child-Pugh B (apixaban/edoxaban preferred); avoid in Child-Pugh C

— Reconcile all meds — antiplatelets, anticoagulants, NSAIDs, SSRIs (bleeding)

— Deprescribe anticholinergics that worsen post-stroke cognition

Board pearl: Age alone is never an exclusion for tPA or thrombectomy. Pre-stroke functional status (mRS) and patient goals matter more than age. A spry 88-year-old with mRS 0 deserves full reperfusion therapy; a 65-year-old bed-bound with mRS 5 typically does not. Document the functional baseline conversation.

Elderly (≥80 years):

Mechanical thrombectomy in elderly:

Renal impairment:

Hepatic impairment:

Polypharmacy in elderly:

Special Populations — Pregnancy, Pediatrics, Young Stroke

— Pregnancy is a relative, not absolute contraindication to tPA

— Risk of placental abruption, postpartum hemorrhage discussed; tPA does not cross placenta in significant amounts

— Causes to consider: preeclampsia/eclampsia, RCVS, cerebral venous thrombosis (CVT), peripartum cardiomyopathy with embolism, paradoxical embolus via PFO, amniotic fluid embolism

— CVT presents with headache, seizure, focal deficit; diagnose with MRV; treat with anticoagulation even if hemorrhagic infarct present

— Imaging: NCHCT safe; MRI without gadolinium preferred in pregnancy

— Rare (~2–13/100,000/year); causes differ — sickle cell disease, congenital heart disease, moyamoya, arteriopathy, dissection

— Sickle cell: exchange transfusion to reduce HbS <30% is first-line acute therapy

— tPA pediatric data limited; TIPS protocol guidelines for ≥2 years case-by-case

— Always check for child abuse in unexplained pediatric stroke (abusive head trauma)

— Consider dissection (especially with neck pain, trauma, chiropractic manipulation, connective tissue disease)

— PFO with paradoxical embolism — TEE with bubble; closure if RoPE score high and recurrent

— Substance use: cocaine, methamphetamine, cannabis

— OCPs + smoking + migraine with aura = potent triad

— Hypercoagulable workup: antiphospholipid syndrome (lupus anticoagulant, anti-cardiolipin, anti-β2 GP1), factor V Leiden, prothrombin gene mutation

— Acute: exchange transfusion + standard stroke care

— Long-term: chronic transfusions, hydroxyurea, consider HSCT

Key distinction: Cerebral venous sinus thrombosis (CVT) ≠ arterial stroke. CVT presents with headache (most common), papilledema, seizures, and bilateral or atypical infarcts (often hemorrhagic). Treatment is anticoagulation with heparin — even in the presence of hemorrhagic transformation. Don't withhold heparin for CVT just because there's blood on imaging.

Pregnancy and postpartum:

Pediatric stroke:

Young adults (<50):

Sickle cell disease adults:

Complications and Adverse Outcomes

— Symptomatic ICH after tPA: ~6%; after MT: ~4–6%; spontaneous in untreated large infarcts: ~5%

— Risk factors: large infarct, late treatment, uncontrolled HTN, hyperglycemia, antiplatelet use

— Management of post-lytic ICH:

— Stop tPA infusion immediately

— Stat NCHCT, CBC, fibrinogen, PT/PTT, type and cross

— Cryoprecipitate 10 units (replaces fibrinogen, goal >150)

— Tranexamic acid 1 g IV or aminocaproic acid

— Platelets if antiplatelet exposure

— Neurosurgery consult

— BP <140 systolic

— Peak edema days 3–5 post-stroke

— Large MCA ("malignant MCA") in young patients → consider decompressive hemicraniectomy within 48h if NIHSS >15, age <60 (DESTINY/HAMLET; cautiously up to 80)

— Cerebellar stroke with mass effect → suboccipital craniectomy

— Osmotherapy bridge: mannitol 1 g/kg or hypertonic saline 3% bolus

— ~5–10% acute, higher in cortical strokes

— Treat clinical seizures; do not give prophylactic AEDs

— Continuous EEG if unexplained altered mental status

— Leading cause of post-stroke mortality

— Mandatory bedside swallow screen before any PO intake

— NPO until passed; SLP formal eval if failed screen

— DVT/PE (use IPC immediately, chemoprophylaxis after 24h post-tPA)

— UTI (avoid unnecessary Foley)

— Pressure ulcers (turn q2h)

— Depression (~30%; screen with PHQ-9 at follow-up)

— Shoulder subluxation, spasticity, central post-stroke pain

CCS pearl: Sudden neurologic worsening post-tPA → order: "Stop tPA," "Stat non-contrast head CT," "CBC, fibrinogen, type and cross," "Cryoprecipitate 10 units IV," "Tranexamic acid 1 g IV," "Neurosurgery consult," "BP <140 systolic with nicardipine drip." Cluster these together to avoid CCS clock penalties.

Hemorrhagic transformation:

Cerebral edema and herniation:

Seizures:

Aspiration pneumonia:

Other complications:

When to Escalate Care — ICU, Consult, Transfer

— Confirmed or suspected LVO needing thrombectomy

— Need for neuro-ICU

— Malignant edema candidates for hemicraniectomy

— Subarachnoid hemorrhage or complex ICH

— Carotid revascularization not available locally

— Post-tPA in first 24h (per institution; many use stroke unit instead)

— Post-thrombectomy 24h minimum

— NIHSS >15, decreased LOC, intubated

— Malignant MCA edema risk (young, large infarct)

— Cerebellar/brainstem stroke (herniation risk)

— Blood pressure needing IV titratable drip

— Hemorrhagic transformation

— Dedicated nursing, telemetry, q1–2h neuro checks day 1, q4h thereafter

— Reduces mortality and disability vs general ward (NNT ~20)

— Neurology / vascular neurology — primary management

— Neurointerventional radiology — for MT decisions

— Neurosurgery — for hemorrhagic conversion, hemicraniectomy, EVD

— Cardiology — AF, cardioembolic source, concurrent ACS

— PT/OT/SLP within 24–48h — early mobilization improves outcomes (but not in first 24h after large stroke — AVERT trial cautioned against very early aggressive mobilization)

— Dietitian — for swallow-safe diet planning

— Social work / case management — disposition planning starts on day 1

— Home with services: mild deficit, good support

— Acute inpatient rehab: tolerates ≥3h therapy/day, needs ≥2 disciplines

— Skilled nursing facility: lower-intensity rehab needs

— Long-term acute care: vent-dependent, complex medical needs

— Hospice: catastrophic stroke with goals of care aligned

Step 3 management: Mobilize early but not too early — out of bed within 24–48 hours is the sweet spot for most patients. Very early aggressive mobilization (<24h) in large strokes worsened outcomes (AVERT). Order PT/OT/SLP consults day 1, but specify "evaluate for mobilization after 24 hours" in CCS notes.

Comprehensive stroke center transfer indications:

Neuro-ICU admission criteria:

Stroke unit admission (most patients):

Consultations to order early:

Disposition decisions:

Key Differentials — Other Stroke Subtypes and Vascular Mimics

— Same presentation but NCHCT shows blood

— Treat: BP <140 systolic (INTERACT-2, ATACH-2), reverse anticoagulants

— Andexanet alfa for factor Xa inhibitors; idarucizumab for dabigatran; PCC for warfarin

— Neurosurgery for cerebellar hemorrhage >3 cm or with mass effect

— Thunderclap headache, meningismus, often without focal deficit initially

— NCHCT then LP if CT negative and suspicion high (xanthochromia)

— CT angiography for aneurysm; neurosurgery/IR for coil/clip

— Nimodipine 60 mg q4h × 21 days for vasospasm prevention

— Focal deficit resolving within 24h (now tissue-based: no DWI lesion)

— ABCD² score stratifies risk; high-risk TIA = DAPT for 21 days (CHANCE/POINT)

— Full stroke workup — TIA is a warning, not a benign event

— ~10% recurrent stroke risk at 90 days, half within 48h

— Young patient, neck pain, Horner, recent trauma/manipulation

— Vessel imaging shows intimal flap or pseudolumen

— Treat: antiplatelet OR anticoagulation × 3–6 months (CADISS — equivalent)

— Headache + seizure + focal deficit ± papilledema

— MRV/CTV; treat with heparin even if hemorrhagic

— Hypotension or severe stenosis; bilateral parasagittal weakness

— Treat underlying hemodynamic cause; revascularize stenosis if symptomatic

Key distinction: ICH and ischemic stroke can look identical clinically — never give tPA without imaging. The first 60 seconds of CT viewing is exclusively "is there blood?" Only after that question is answered "no" does the ischemic stroke pathway proceed.

Intracerebral hemorrhage (ICH):

Subarachnoid hemorrhage (SAH):

Transient ischemic attack (TIA):

Cervical artery dissection:

Cerebral venous sinus thrombosis (CVT):

Watershed (border-zone) infarcts:

Key Differentials — Non-Vascular Stroke Mimics

— Focal deficits possible, especially in diabetics

— Always check fingerstick glucose first — reversible cause

— Treat: D50 25–50 mL IV or glucagon 1 mg IM

— Postictal focal weakness, usually resolves within hours

— History of witnessed seizure, tongue bite, incontinence

— EEG, consider AEDs; imaging still indicated to rule out structural lesion

— Younger patient, prior similar episodes, headache prominent

— Slow march of symptoms (vs sudden onset stroke)

— Diagnosis of exclusion; still image and consider tPA if criteria met

— Inconsistent exam (give-way weakness, Hoover sign positive)

— Often follows psychological stressor

— Imaging negative; reassurance and PT

— Hyponatremia, hyperammonemia, uremia, hepatic encephalopathy

— Usually diffuse, not focal — but can unmask old deficit

— Recrudescence of old stroke symptoms with fever, UTI, pneumonia

— Treat underlying infection; deficit resolves

— Usually subacute; imaging shows mass with edema

— Ring-enhancing on MRI with contrast

— Severe HTN, headache, seizure, vision changes

— Posterior white matter edema on MRI

— Treat with gradual BP lowering

— Confusion, ataxia, ophthalmoplegia in alcohol use disorder

— Treat empirically: thiamine 500 mg IV TID × 3 days

Board pearl: The "5% rule" — about 5–15% of suspected strokes are mimics. Giving tPA to a mimic has very low bleed risk (<1% symptomatic ICH). It is safer to treat a mimic than to miss a true stroke. Document the LKW, NIHSS, glucose, and CT findings; if criteria are met, treat. This is a high-yield Step 3 risk-benefit point.

Hypoglycemia:

Seizure with Todd paralysis:

Complicated/hemiplegic migraine:

Conversion/functional neurologic disorder:

Toxic-metabolic:

Infection unmasking deficit:

Brain tumor or abscess:

Hypertensive encephalopathy / PRES:

Wernicke encephalopathy:

Secondary Prevention and Discharge Medications

— Non-cardioembolic (atherosclerotic, lacunar, cryptogenic):

— Aspirin 81 mg daily lifelong, OR clopidogrel 75 mg daily, OR aspirin + dipyridamole

— Minor stroke/high-risk TIA: DAPT (ASA + clopidogrel) × 21 days then monotherapy

— Intracranial stenosis 70–99%: DAPT × 90 days (SAMMPRIS), then aspirin

— Cardioembolic (AF, mechanical valve, LV thrombus):

— DOAC preferred for nonvalvular AF: apixaban 5 mg BID (or 2.5 if criteria), rivaroxaban 20 mg daily, dabigatran 150 mg BID, edoxaban 60 mg daily

— Warfarin INR 2–3 for mechanical valve, moderate-severe mitral stenosis, antiphospholipid syndrome (triple positive)

— Timing of anticoagulation start: "1-3-6-12 day rule" — TIA day 1, small stroke day 3, moderate day 6, large day 12

— <130/80 mmHg for most stroke patients (SPS3, SPRINT)

— Thiazide + ACEi/ARB combination preferred (PROGRESS trial)

— Don't drop BP too quickly in first 24–48h post-stroke

— High-intensity statin: atorvastatin 80 mg or rosuvastatin 20–40 mg

— LDL goal <70 mg/dL (some guidelines <55 for very high risk)

— Add ezetimibe, then PCSK9 inhibitor if not at goal

— HbA1c <7% generally; <8% in older/frail

— Prefer GLP-1 RA (semaglutide) or pioglitazone (IRIS trial) for stroke patients with insulin resistance

— Smoking cessation (varenicline, bupropion, NRT)

— Mediterranean or DASH diet

— Moderate exercise 150 min/week as tolerated

— Alcohol ≤2 drinks/day men, ≤1 women

— OSA screening — STOP-BANG, treat with CPAP if positive

Step 3 management: For cryptogenic embolic stroke (ESUS), do NOT empirically anticoagulate — NAVIGATE-ESUS and RE-SPECT ESUS showed no benefit over aspirin. Order extended cardiac monitoring (30-day event monitor or implantable loop) before discharge; if AF detected, switch to DOAC.

Antithrombotic strategy by stroke mechanism:

Blood pressure target:

Lipid management:

Diabetes:

Lifestyle:

Follow-Up, Monitoring, Rehab, and Counseling

— Antithrombotic on discharge ✓

— Anticoagulation for AF ✓

— Statin if LDL ≥70 or atherosclerotic ✓

— Smoking cessation counseling ✓

— Stroke education to patient/family ✓

— Rehab assessment completed ✓

— DVT prophylaxis during hospitalization ✓

— PCP visit within 7–14 days — med reconciliation, BP check, function assessment

— Vascular neurology within 4–6 weeks — review etiologic workup, adjust prevention

— Cardiology within 2–4 weeks if AF or cardioembolic source

— Carotid surgery within 2 weeks if symptomatic stenosis 70–99%

— Repeat lipid panel at 4–12 weeks to assess statin response

— HbA1c every 3 months until at goal

— BP log review at each visit; home BP monitoring encouraged

— Acute inpatient rehab: 2–4 weeks for moderate-severe deficits

— Subacute/SNF: lower-intensity needs

— Home health PT/OT/SLP: mild deficits, mobile

— Outpatient therapy: ongoing functional gains can occur 6–12 months

— Constraint-induced movement therapy, mirror therapy, robotics for selected patients

— Depression screening (PHQ-9) at 1 month and periodically — 30% post-stroke depression; treat with SSRI (sertraline preferred)

— Cognitive screening (MoCA) — vascular cognitive impairment common

— Driving evaluation — most states require deficit-free + physician clearance; formal driving eval if any concern

— Return to work assessment

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

— Caregiver support and respite

— Recognize stroke recurrence — call 911, don't drive to ER

— Medication adherence (especially anticoagulants)

— Fall prevention

— Advance directives discussion

CCS pearl: On the CCS discharge order set, include: "Follow up with PCP in 7 days," "Vascular neurology in 4 weeks," "Outpatient cardiac event monitor × 30 days" (if cryptogenic), "Home BP monitoring log," "PHQ-9 at 1 month," "Stroke education provided," "Medic alert bracelet if on anticoagulation." Missing follow-up cadence loses points.

Discharge checklist (the AHA "Get With The Guidelines" measures):

Follow-up cadence post-discharge:

Rehabilitation continuum:

Counseling and psychosocial:

Patient education priorities:

Ethical, Legal, and Patient Safety Considerations

— Standard of care is to attempt consent from patient or surrogate

— If patient lacks capacity (aphasia, decreased LOC) and no surrogate immediately available, emergency exception applies — treat under implied consent given the disabling/life-threatening nature

— Document attempts to reach family and the clinical reasoning

— Two-physician documentation strengthens the medical-legal position

— Court-appointed guardian → durable POA for healthcare → spouse → adult children → parents → siblings

— Always check for advance directive / POLST in chart

— Some patients have documented preferences against thrombolytics or aggressive care

— Aphasia ≠ incapacity — use yes/no questions, writing, AAC

— Reassess capacity for major decisions (PEG tube, DNR, rehab placement)

— Involve speech therapy for augmentative communication

— Most states require physicians to report new seizures, loss of consciousness, or significant neurologic impairment affecting driving — know your state law

— California, Pennsylvania, New Jersey, Oregon, Nevada, Delaware have mandatory physician reporting

— Stroke patients are at high readmission risk (~12% at 30 days)

— Medication reconciliation at every transition — anticoagulants, antiplatelets, antihypertensives

— Warm handoff to PCP with specific follow-up timing

— Patient/family teach-back on stroke recurrence signs

— Avoid "anticoagulation + antiplatelet" combinations unless clearly indicated (e.g., recent PCI) — major bleeding risk

— Falls (high risk post-stroke; orthostatic, hemiparetic gait)

— Aspiration (mandatory swallow screen)

— Pressure injury (turn q2h)

— Medication errors at discharge (use teach-back)

— Anticoagulation dosing errors in elderly/renal impairment

— Family meetings within 72h for severe stroke (NIHSS >20, comatose, dominant hemisphere with herniation)

— Avoid early withdrawal-of-care decisions (<72h) — prognosis is most uncertain then

— Palliative care consultation for symptom management even if pursuing aggressive treatment

Board pearl: A common Step 3 vignette: aphasic patient with stroke needing tPA, family unavailable. You proceed under emergency consent, document attempts to reach surrogate, and treat. Withholding tPA "because we can't consent" is the wrong answer.

Informed consent for tPA in time pressure:

Surrogate decision-making hierarchy (varies by state):

Capacity assessment post-stroke:

Mandatory reporting and DMV:

Transition-of-care safety:

Patient safety events to anticipate:

Goals of care for catastrophic stroke:

High-Yield Associations and Rapid-Fire Clinical Facts

— MCA superior division: Broca aphasia, contralateral face/arm weakness (leg spared)

— MCA inferior division: Wernicke aphasia, contralateral hemianopia, no major motor

— ACA: contralateral leg weakness, abulia

— PCA: homonymous hemianopia with macular sparing, alexia without agraphia

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

— AICA: lateral pontine — like Wallenberg + ipsilateral facial weakness + deafness

— Basilar tip: bilateral PCA territory, "top of the basilar" — visual, behavioral, eye movement abnormalities

— Lenticulostriate (lacunar): pure motor (internal capsule), pure sensory (thalamus), ataxic hemiparesis, dysarthria-clumsy hand

— tPA window: ≤4.5h

— Thrombectomy window: ≤24h selected

— tPA dose: 0.9 mg/kg, max 90 mg

— TNK dose: 0.25 mg/kg, max 25 mg

— Pre-tPA BP: <185/110

— Post-tPA BP: <180/105 × 24h

— Door-to-needle: ≤60 min (goal ≤45)

— Door-to-puncture: ≤90 min direct

— DAPT duration in minor stroke: 21 days

— Anticoagulation start in AF stroke: 1-3-6-12 day rule

— Symptomatic carotid revascularization: within 2 weeks

— Symptomatic ICH after tPA: ~6%

— NNT for tPA mRS 0-1 within 3h: ~7

— Statin: atorvastatin 80 mg

— NINDS, ECASS-III — tPA windows

— DAWN, DEFUSE-3 — late thrombectomy

— CHANCE, POINT, THALES — DAPT in minor stroke

— SAMMPRIS — intracranial stenosis

— CRYSTAL-AF — occult AF detection

— WAKE-UP — MRI mismatch

— RESPECT, CLOSE — PFO closure

Board pearl: "Cortical signs" (aphasia, neglect, gaze deviation, hemianopia) distinguish large-artery from lacunar stroke. Lacunar strokes never cause cortical signs — they're pure motor, pure sensory, or sensorimotor.

Vessel → syndrome shortcuts:

Numbers to memorize:

Trial names to recognize:

Board Question Stem Patterns

— 68 y/o with right-sided weakness, NIHSS 12, LKW 3 hours ago, BP 178/95, glucose 110, CT negative for bleed → Give tPA after confirming no contraindications

— Variant: BP 198/115 → labetalol first, recheck, then tPA

— Variant: warfarin user, INR 2.3 → tPA contraindicated

— Variant: DOAC last dose 30h ago → contraindicated (<48h)

— Patient outside 4.5h window with NIHSS 18, M1 occlusion on CTA, ASPECTS 8 → transfer for thrombectomy even at 8h LKW

— Wake-up stroke with DWI-FLAIR mismatch → tPA eligible

— Sudden headache, vomiting, decreased LOC 1h after tPA → stop infusion, stat CT, cryoprecipitate, TXA, neurosurgery

— Stroke + AF newly diagnosed → DOAC (apixaban preferred in elderly/renal)

— Stroke + carotid stenosis 80% symptomatic → CEA within 2 weeks + DAPT + statin

— Cryptogenic stroke, age 35, PFO on TEE with bubble → PFO closure + antiplatelet (RESPECT, CLOSE)

— Lacunar stroke → aspirin + BP control + statin

— Minor stroke NIHSS 2, ABCD² 5 → DAPT (ASA + clopidogrel) × 21 days then aspirin

— Standard workup negative → 30-day event monitor or implantable loop recorder to detect occult AF

— Confused diabetic with hemiparesis, glucose 38 → D50, not tPA

— Aphasic with prior stroke and new UTI → treat infection, deficit recrudescence

— Pregnant patient with stroke at 3h → tPA still indicated; pregnancy is relative

— Young patient + neck pain + Horner → dissection; antiplatelet or anticoagulation × 3–6 months

— Pediatric SCD patient with stroke → exchange transfusion

Step 3 management: When the stem gives you a number — LKW time, BP, INR, NIHSS, ASPECTS, time since last DOAC — that number is the answer's trigger. Always extract those numerical anchors first; they decide treatment eligibility more than narrative cues.

Pattern 1 — The tPA decision under time pressure:

Pattern 2 — The thrombectomy stem:

Pattern 3 — The post-tPA complication:

Pattern 4 — Secondary prevention selection:

Pattern 5 — Workup of cryptogenic stroke:

Pattern 6 — The mimic:

Pattern 7 — Special populations:

One-Line Recap

Acute ischemic stroke is a time-critical emergency where rapid imaging-driven decisions — IV thrombolytics within 4.5 hours, mechanical thrombectomy for large vessel occlusion within 24 hours, and immediate secondary prevention — determine lifelong disability and recurrence risk.

Board pearl: The single most testable concept across Step 3 stroke vignettes is time and imaging drive every decision — extract LKW, NIHSS, BP, glucose, INR, and CT/CTA findings before considering treatment, and remember that age alone never excludes reperfusion therapy in a previously functional patient.

Door-to-needle ≤60 minutes: CT first (rule out bleed), glucose, BP <185/110, then alteplase 0.9 mg/kg (max 90 mg) or tenecteplase 0.25 mg/kg bolus. Keep BP <180/105 for 24h with q15min checks initially. No aspirin or anticoagulant for 24h post-lytic.

Thrombectomy for LVO up to 24 hours: ICA, M1, basilar occlusions with NIHSS ≥6 and favorable imaging (ASPECTS ≥6 early; DAWN/DEFUSE-3 perfusion mismatch late). Don't withhold MT just because tPA window has closed — they are independent decisions.

Secondary prevention pillars: Antiplatelet (aspirin or clopidogrel; DAPT × 21d for minor stroke/high-risk TIA) or anticoagulation (DOAC for AF using 1-3-6-12 day rule), high-intensity statin (atorvastatin 80 mg, LDL <70), BP <130/80, smoking cessation, OSA screening, prolonged cardiac monitoring for cryptogenic stroke.

Follow-up cadence: PCP within 7–14 days, vascular neurology within 4–6 weeks, carotid surgery within 2 weeks if symptomatic 70–99% stenosis, PHQ-9 depression screen at 1 month, repeat lipids 4–12 weeks, lifelong stroke recurrence education with 911 activation for any new deficit.