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)
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 = small infarct core → thrombectomy candidate
- <6 = large infarct core → poor candidate
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
NCCT is the ONLY required imaging before tPA. Dense MCA sign = hyperdense M1 suggesting acute thrombus. ASPECTS ≥6 for thrombectomy candidacy.
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 = stroke likely <4.5–6 hours old
- WAKE-UP trial: Patients with unknown onset + DWI-FLAIR mismatch benefited from IV tPA
- Allows treatment of wake-up strokes when onset is unknown
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
Core = low CBF + low CBV (dead). Penumbra = low CBF + preserved CBV (salvageable). Large mismatch = GOOD thrombectomy candidate even in extended windows. Perfusion imaging is REQUIRED for 6–24h thrombectomy decisions.
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
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
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
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
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 |
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.