Stroke Workup
Stroke Workup & Neuroimaging
What Do You Need to Know?
- CT early ischemic signs and ASPECTS scoring
- MRI sequences in stroke and DWI-FLAIR mismatch concept
- Perfusion imaging: core vs. penumbra and thrombectomy selection (DAWN/DEFUSE 3)
- Vascular imaging modalities and carotid stenosis measurement (NASCET vs. ECST)
- Cardiac workup: rhythm monitoring, echocardiography, and PFO evaluation
- Standard and young stroke laboratory workup
- Workup timing algorithm (immediate, 24 hours, days–weeks)
🚩 Don’t Miss — Test-Day Priorities
- TOAST classification: LAA (≥50% stenosis), cardioembolic (AF/MI/valve/mural thrombus), small-vessel/lacunar (deep penetrators — LSA, thalamoperforators, basilar perforators), other determined (dissection, vasculitis, hypercoagulable), undetermined/ESUS.
- First imaging = NCCT to rule out hemorrhage; DWI/ADC is most sensitive for early ischemia (bright DWI + dark ADC within minutes); DWI-FLAIR mismatch is an imaging selection marker for unknown-onset / extended-window thrombolysis (WAKE-UP), not an exact stroke clock.
- CTP core/penumbra mismatch drives late-window thrombectomy (DAWN 6–24h, DEFUSE-3 6–16h); ASPECTS ≥6 is the classic early-window pattern, but selected ASPECTS 3–5 / large-core patients also benefit per SELECT2 / ANGEL-ASPECT / RESCUE-Japan LIMIT.
- Carotid duplex for cervical ICA stenosis (poor intracranial); CTA/MRA for LVO + dissection; DSA gold standard for vasculitis/vasculopathy (beading).
- TEE > TTE for LA appendage thrombus, PFO (bubble study), aortic atheroma, endocarditis; RoPE score stratifies PFO causality in young cryptogenic stroke.
- ESUS → prolonged monitoring: 30-day Holter or implantable loop recorder (CRYSTAL-AF, EMBRACE) to detect paroxysmal AF.
- Hypercoagulable workup timing: defer protein C/S, antithrombin III during acute thrombus/anticoag (false positives — depleted); retest ≥3 mo off anticoag. APLS workup (LAC, β2GPI, anticardiolipin) requires confirmation 12 wk apart.
- Young stroke (<55) → add CADASIL (NOTCH3, anterior temporal pole + external capsule), MELAS (m.3243A>G, crosses vascular boundaries), Fabry (α-galactosidase A), moyamoya, RCVS, vasculitis, sickle cell, HIV/syphilis, drug screen (cocaine, amphetamines).
- Dissection → neck pain + Horner (partial, no anhidrosis) ± trauma/chiropractic; CADISS trial → antiplatelet = anticoagulation, treat 3–6 mo.
- PFO closure if cryptogenic + age <60 + high RoPE (CLOSE, REDUCE, RESPECT trials); sickle cell → chronic transfusion to keep HbS <30% for primary stroke prevention.
🔍 Buzzwords & Pathognomonic FindingsTOAST mechanism · Imaging / workup · Young stroke / mimics
TOAST mechanism / clues
- Cortical infarct + carotid bruit + ≥50% ipsilateral ICA stenosis → Large-artery atherothrombosis (LAA)
- Multiple territories / wedge-shaped cortical + AF on telemetry → Cardioembolic
- Pure motor / pure sensory / ataxic hemiparesis / dysarthria–clumsy hand → Small-vessel/lacunar (deep penetrator)
- Lacune in posterior limb of internal capsule → Lenticulostriate (MCA-LSA) infarct
- No source after standard workup + nonlacunar infarct → ESUS (embolic stroke of undetermined source)
- Young patient + neck pain + Horner syndrome → Carotid dissection
Imaging / workup
- Hyperdense MCA / dot sign on NCCT → Acute M1/M2 thrombus
- Loss of insular ribbon / lentiform obscuration → Early MCA ischemia
- Bright DWI + dark ADC → True cytotoxic restriction (acute infarct)
- DWI-positive + FLAIR-negative mismatch → Onset <4.5h (WAKE-UP → tPA)
- CTP: low CBF + preserved CBV (mismatch) → Salvageable penumbra (DAWN/DEFUSE-3)
- Positive bubble study on TEE → Right-to-left shunt / PFO
- String sign / intimal flap on CTA neck → Cervical artery dissection
- Beading / sausage-on-a-string on DSA → CNS vasculitis or RCVS
Young stroke / special
- Lacunes + leukoencephalopathy + anterior temporal pole + external capsule (NOTCH3) → CADASIL
- Stroke-like episodes crossing vascular territories + lactic acidosis (m.3243A>G) → MELAS
- Cornea verticillata + small-fiber neuropathy + LVH + renal failure (X-linked) → Fabry disease
- Puff of smoke collaterals + bilateral supraclinoid ICA stenosis → Moyamoya
- Thunderclap headache + postpartum/SSRI + reversible string-of-beads → RCVS
- Alopecia + spondylosis + lacunar strokes (HTRA1) → CARASIL
- Recurrent fetal loss + APLS antibodies + livedo → Antiphospholipid syndrome
- Black patient <50 + HbS >30% → Sickle cell vasculopathy
CT & CT Angiography
Non-Contrast CT Head (NCCT)
- FIRST study in acute stroke — primary purpose is to rule out hemorrhage
- Sensitivity for acute ischemic stroke is LOW in first 6–12 hours
Early Ischemic Signs on CT
- Loss of gray-white differentiation — insular ribbon sign (loss of insular cortex definition)
- Sulcal effacement — early cytotoxic edema
- Hyperdense vessel sign — dense MCA sign = thrombus visible in M1
- Obscuration of lentiform nucleus
ASPECTS Score
- 10-point scale for MCA territory; subtract 1 point per region with early ischemic changes
- ≥6 = classic early-window EVT pattern (HERMES)
- 3–5 = large core, but selected patients still benefit from EVT out to 24 h per SELECT2 / ANGEL-ASPECT / RESCUE-Japan LIMIT
CT Angiography (CTA)
- Identifies large vessel occlusion (LVO) — essential for thrombectomy decisions
- Evaluates ICA, vertebral, basilar, MCA, ACA, PCA
- Also evaluates carotid stenosis, dissection, and aneurysm
- Should be obtained simultaneously with NCCT but should NOT delay tPA
💎 Board Pearl
NCCT is the ONLY required imaging before tPA. Dense MCA sign = hyperdense M1 suggesting acute thrombus. ASPECTS ≥6 is the classic early-window EVT pattern; selected ASPECTS 3–5 also benefit (SELECT2 / ANGEL-ASPECT / RESCUE-Japan LIMIT).
MRI & Diffusion-Weighted Imaging
MRI Sequences in Stroke
| Sequence | What It Shows | Timing |
|---|---|---|
| DWI | Acute cytotoxic edema = BRIGHT | Positive within MINUTES; most sensitive |
| ADC map | Confirms true restriction = DARK | Dark in acute stroke (vs. T2 shine-through) |
| FLAIR | Vasogenic edema, chronic changes | Positive 6–12 hours after onset |
| GRE/SWI | Hemorrhage, microbleeds | More sensitive than CT for microbleeds |
| MRA | Vessel patency, stenosis | No contrast needed for TOF-MRA |
DWI-FLAIR Mismatch
- DWI positive + FLAIR negative is an imaging selection marker for unknown-onset / extended-window thrombolysis — not a precise stroke clock
- WAKE-UP trial: Patients with unknown onset + DWI-FLAIR mismatch benefited from IV tPA
- Allows treatment of wake-up strokes when onset is unknown
💎 Board Pearl
DWI is the MOST SENSITIVE sequence for acute stroke (positive within minutes). DWI bright + ADC dark = true restricted diffusion = acute infarct. DWI-FLAIR mismatch = stroke <6h old (WAKE-UP trial). DWI-positive = stroke by definition, even if symptoms resolved.
CT & MR Perfusion Imaging
Core vs. Penumbra
| Parameter | Core | Penumbra |
|---|---|---|
| CBF | Decreased | Decreased |
| CBV | Decreased | MAINTAINED (autoregulation) |
| MTT/Tmax | Prolonged | Prolonged |
- Core = low CBF + low CBV → irreversible injury (dead tissue)
- Penumbra = low CBF + preserved CBV → salvageable tissue
- Mismatch = penumbra − core = tissue at risk (target of reperfusion)
Thrombectomy Selection Parameters (DAWN/DEFUSE 3)
- Infarct core (CBF <30%): should be small (<70 mL in DEFUSE 3)
- Mismatch ratio ≥1.8 and mismatch volume ≥15 mL
- Tmax >6 seconds defines critically hypoperfused tissue
- RAPID software: Automated processing, generates core/penumbra volumes in minutes
💎 Board Pearl
Core = low CBF + low CBV (dead). Penumbra = low CBF + preserved CBV (salvageable). Large mismatch = GOOD thrombectomy candidate even in extended windows. Perfusion imaging supports DAWN/DEFUSE-3 style selection in the 6–24 h window, but advanced imaging, collateral imaging, or large-core trial criteria may be used depending on protocol.
Vascular Imaging
- CTA (head & neck): Gold standard for LVO detection in the acute setting; also evaluates carotid stenosis
- MRA: No radiation; can overestimate stenosis (flow artifact); useful for follow-up
- Carotid duplex ultrasound: Screening for extracranial carotid stenosis. PSV >125 cm/s = ≥50%; PSV >230 cm/s = ≥70%
- Transcranial Doppler (TCD): Detects MCA stenosis, vasospasm in SAH, microembolic signals, PFO (bubble study); sickle cell monitoring (keep mean velocity <200 cm/s)
- Conventional angiography (DSA): Gold standard for cerebral vasculature; invasive, 0.5–1% complication rate; reserved for inconclusive non-invasive imaging
Carotid Stenosis Measurement
- NASCET: % stenosis at narrowest point relative to distal ICA — North American standard
- ECST: Relative to estimated original bulb diameter — European method
💎 Board Pearl
CTA = initial vascular study in acute stroke. Carotid duplex = screening for extracranial stenosis. TCD uses: (1) SAH vasospasm monitoring, (2) sickle cell stroke screening, (3) PFO detection, (4) microembolic signals. DSA = gold standard but reserved for inconclusive cases.
Cardiac Workup
Standard Cardiac Evaluation
- 12-lead ECG: All patients — AF detection, MI, LVH
- Continuous telemetry (≥24h): Standard of care for all ischemic stroke
- Extended cardiac monitoring (14–30 day Holter/event monitor): For cryptogenic stroke — CRYSTAL-AF and EMBRACE trials showed longer monitoring detects more AF
- Implantable loop recorder (ILR): CRYSTAL-AF: detected AF in 12.4% at 12 months vs. 2% with standard monitoring
- TTE: Initial screening for LV thrombus, wall motion abnormalities, valvular disease, EF
- TEE: Superior to TTE for PFO, LAA thrombus, and aortic arch atheroma — recommended in young/cryptogenic stroke
- Bubble study: PFO/right-to-left shunt detection; Valsalva increases sensitivity
PFO and Stroke
- PFO in ~25% of general population, ~40–50% of cryptogenic stroke patients <60 years
- CLOSE, RESPECT, GORE-REDUCE trials: PFO closure + antiplatelet superior to medical therapy alone in select patients (age <60, cryptogenic stroke, high-risk PFO features)
- High-risk PFO features: Large shunt, atrial septal aneurysm, septal hypermobility
💎 Board Pearl
All stroke patients need ECG + telemetry (≥24h). Cryptogenic → extended monitoring or ILR for AF. TEE > TTE for PFO and LAA thrombus. PFO closure indicated in young (<60) cryptogenic stroke with high-risk features (CLOSE/RESPECT/REDUCE).
Laboratory Workup
Standard Stroke Labs (All Patients)
- CBC with platelets — thrombocytopenia (tPA contraindication if <100K)
- BMP (glucose, electrolytes, creatinine) — hypoglycemia is a stroke mimic
- PT/INR, aPTT — coagulopathy assessment
- Lipid panel (fasting) — statin decision
- HbA1c — diabetes screening
- TSH — hyperthyroidism-related AF
- Troponin — cardiac ischemia (stroke can elevate troponin via sympathetic surge)
- Urine drug screen — cocaine (vasospasm), amphetamines
💎 Board Pearl
The ONLY lab needed before tPA is blood glucose (rule out hypoglycemia). Do NOT delay tPA for coags UNLESS clinical suspicion of coagulopathy. Glucose <50 mg/dL is an exclusion criterion.
Young Stroke Workup (Age <50)
Young stroke has a broader differential requiring additional workup:
| Category | Tests |
|---|---|
| Hypercoagulable | Factor V Leiden, prothrombin G20210A, protein C/S, antithrombin III, homocysteine, antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein I) |
| Cardiac | TEE with bubble study (PFO), extended monitoring, consider ILR |
| Vascular | CTA/MRA head and neck (dissection), vessel wall MRI (vasculitis), consider DSA |
| Infectious | RPR/VDRL (neurosyphilis), HIV, VZV CSF PCR (varicella vasculopathy) |
| Inflammatory | ESR, CRP, ANA, ANCA; if PACNS suspected → brain biopsy + CSF |
| Genetic | CADASIL (NOTCH3), Fabry disease (alpha-galactosidase A), MELAS, sickle cell |
- Hypercoagulable labs: draw acutely but do NOT delay treatment. Protein C/S and antithrombin III may be falsely low acutely — retest at 3–6 months
- Antiphospholipid antibodies require POSITIVE results on 2 occasions at least 12 weeks apart
💎 Board Pearl
Young stroke = broader workup: hypercoagulable panel, TEE with bubble, extended cardiac monitoring, vessel wall imaging. Fabry disease: X-linked, alpha-galactosidase A deficiency, strokes + painful neuropathy + cardiac disease, pulvinar T1 hyperintensity. CADASIL: NOTCH3, chromosome 19, migraines → strokes → dementia, anterior temporal pole white matter hyperintensities.
Stroke Workup Algorithm
| Timing | Studies | Purpose |
|---|---|---|
| Immediate (ED) | NCCT + CTA + glucose + CBC + BMP + coags + ECG | tPA/thrombectomy decision; rule out hemorrhage and mimics |
| Within 24 hours | MRI with DWI, lipids, HbA1c, TSH, troponin, TTE, telemetry, carotid duplex | Define infarct, identify risk factors, initial cardiac eval |
| Days–weeks | Extended cardiac monitoring (if cryptogenic), TEE (if cryptogenic/young), hypercoagulable workup (if young), follow-up vascular imaging | Determine etiology for secondary prevention |
💎 Board Pearl
NEVER delay acute treatment for additional workup. NCCT + glucose first. Everything else after treatment is initiated. The etiologic workup determines secondary prevention (antiplatelets vs. anticoagulation vs. carotid intervention vs. PFO closure).
References
- Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 2019;50(12):e344-e418.
- Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN). N Engl J Med. 2018;378(1):11-21.
- Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (DEFUSE 3). N Engl J Med. 2018;378(8):708-718.
- Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset (WAKE-UP). N Engl J Med. 2018;379(7):611-622.
- Saver JL, Carroll JD, Thaler DE, et al. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke (RESPECT). N Engl J Med. 2017;377(11):1022-1032.
- Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke (EMBRACE). N Engl J Med. 2014;370(26):2467-2477.
- Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation (CRYSTAL-AF). N Engl J Med. 2014;370(26):2478-2486.
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