Special Vascular Topics

What You'll Learn

Young stroke etiologies and the expanded workup approach
Primary CNS vasculitis (PACNS) vs. RCVS — critical board distinction
Moyamoya disease vs. syndrome: pathology, imaging, and surgical management
RCVS triggers, complications, and why steroids are harmful
CADASIL genetics, clinical progression, and pathognomonic MRI findings
Antiphospholipid syndrome criteria, Sneddon syndrome, and why DOACs are inferior to warfarin
Stroke in pregnancy: unique etiologies, imaging, and treatment considerations
Sickle cell stroke prevention (STOP trial), Fabry disease, and drug-induced stroke

HighYield Pearls

CADASIL: NOTCH3 (chr 19) AD — mid-life migraine with aura → recurrent lacunar strokes → vascular dementia + mood disorder; MRI hallmark is bilateral symmetric WMH in the anterior temporal pole and external capsule; GOM on skin biopsy; antiplatelet is standard — avoid anticoagulation when possible due to microbleed/ICH risk, but CADASIL alone is not an absolute contraindication to IV thrombolysis.
Fabry disease: X-linked α-galactosidase A deficiency — angiokeratomas + corneal verticillata + acroparesthesias + cardiomyopathy + renal failure + early stroke; screen young cryptogenic stroke; treat with agalsidase ERT ± migalastat (chaperone).
MELAS: m.3243A>G in MT-TL1 — stroke-like episodes crossing vascular territories + lactic acidosis + ragged-red fibers + seizures + sensorineural hearing loss; acute SLE → IV arginine.
Moyamoya: bilateral progressive ICA narrowing with basal collaterals (“puff of smoke”); RNF213 in East Asian; ischemic in children, hemorrhagic in adults; treat with EDAS / STA-MCA bypass + antiplatelet; avoid hypotension, hyperventilation, dehydration.
Sickle cell stroke prevention: children — TCD screening with abnormal time-averaged mean maximum velocity (TAMMV ≥200 cm/sec in MCA/distal ICA) = high risk → chronic transfusion to keep HbS <30% (STOP trial); hydroxyurea adjunct; voxelotor + crizanlizumab supportive; adults get both ischemic and hemorrhagic strokes + moyamoya-like vasculopathy.
APS: lupus anticoagulant + anticardiolipin + anti-β2GPI (Sapporo criteria); arterial thrombosis → standard-intensity warfarin INR 2–3 is common; consider higher intensity or added antiplatelet for recurrent arterial events / high-risk (e.g., triple-positive) APS; DOACs inferior in triple-positive APS (TRAPS); catastrophic APS → anticoag + IVIG + steroids + PLEX.
Cervical artery dissection: minor trauma, chiropractic, cough; ipsilateral neck/face pain + Horner ± TIA/stroke; CTA shows long tapered “string sign,” intramural hematoma, pseudoaneurysm; anticoagulation and antiplatelet equivalent (CADISS) for 3–6 mo.
RCVS vs PRES vs PACNS: RCVS — recurrent thunderclap headaches + segmental vasoconstriction that resolves ≤12 wk, treat with nimodipine and avoid triptans/ergots/steroids; PRES — HTN/eclampsia/calcineurin inhibitor with vasogenic parieto-occipital edema; PACNS — recurrent ICH/WMH/infarcts, beading on DSA, definitive on brain biopsy → steroids + cyclophosphamide.
FMD: “string of beads” on cervical ICA imaging in young women — cause of dissection and aneurysm; antiplatelet; consider in cryptogenic young stroke.
CARASIL & RVCL-S: CARASIL — HTRA1 AR with alopecia + spondylosis + lacunar strokes/WMH; RVCL-S — TREX1 AD with retinal vasculopathy + leukoencephalopathy + ICH + nephropathy + Raynaud.

🔍 Quick ReferenceClinical · Imaging · Genetics / treatment

Clinical phenotype

Mid-life migraine with aura + recurrent lacunar strokes + vascular dementia + mood disorder → CADASIL
Angiokeratomas + corneal verticillata + acroparesthesias + cardiomyopathy + renal failure + young stroke → Fabry disease
Stroke-like episodes crossing vascular territories + lactic acidosis + ragged-red fibers + sensorineural hearing loss + short stature → MELAS
Recurrent thunderclap headaches over days–weeks (postpartum, SSRI, cannabis, cocaine) → RCVS
Headache + cortical visual loss + seizures + altered mental status in HTN/eclampsia/calcineurin inhibitor → PRES
Ipsilateral neck/face pain + Horner syndrome ± TIA after minor trauma or chiropractic → carotid/vertebral dissection
Alopecia + spondylosis deformans + small-vessel disease in young adult → CARASIL (HTRA1)
Retinal vasculopathy + leukoencephalopathy + ICH + nephropathy + Raynaud in adult → RVCL-S (TREX1)

Imaging signs

Anterior temporal pole + external capsule WMH → CADASIL
“Puff of smoke” basal collaterals on DSA with bilateral terminal ICA narrowing → moyamoya
“String of beads” on cervical ICA in young woman → FMD
“String of beads” on CTA/MRA that resolves within 12 wk → RCVS
Long tapered narrowing / “string sign” + intramural hematoma + pseudoaneurysm on CTA → arterial dissection
Symmetric parieto-occipital vasogenic edema on FLAIR → PRES
Beading of small/medium intracranial vessels (DSA may be normal) → primary CNS vasculitis (PACNS)
Stroke not respecting vascular territory, often occipital/parietal cortex → MELAS

Genetics / treatment

NOTCH3 mutation (chr 19) AD + granular osmiophilic material on skin biopsy → CADASIL
HTRA1 AR (CARASIL) / HTRA1 AD (CSVD2) → CARASIL / HTRA1-related SVD
X-linked α-galactosidase A deficiency → agalsidase ERT + migalastat chaperone → Fabry disease
m.3243A>G in MT-TL1 → IV arginine for acute stroke-like episodes → MELAS
RNF213 (East Asian) + EDAS / STA-MCA bypass → moyamoya
TCD TAMMV ≥200 cm/sec in MCA/distal ICA → chronic transfusion to keep HbS <30% (STOP trial) → sickle cell stroke prevention
Triple-positive APS → warfarin (standard INR 2–3 common; higher intensity or added antiplatelet considered for recurrent arterial events); DOACs inferior (TRAPS) → APS
Nimodipine + avoid triptans/ergots/steroids → RCVS
Steroids + cyclophosphamide; definitive dx on brain biopsy (granulomatous angiitis) → PACNS
TREX1 AD → RVCL-S

Young Stroke (Age <50)

Overview

~10–15% of all ischemic strokes occur in patients aged 18–50
Etiologies differ significantly from older patients — atherosclerosis is less common; dissection, cardioembolism, and rare vasculopathies are more prevalent
Cryptogenic stroke is more common in young adults (~30–40%) compared to the elderly (~25%)
Higher proportion of women (OCPs, pregnancy, migraine with aura)

Etiologies by Mechanism

Mechanism	Key Causes
Arterial dissection	One of the leading causes of young-adult ischemic stroke (and a key cause after minor neck trauma); ICA or vertebral; chiropractic manipulation, connective tissue disorders (Ehlers-Danlos type IV, Marfan, FMD)
Cardioembolism	PFO (especially with atrial septal aneurysm), valvular disease (rheumatic, endocarditis, prosthetic), cardiomyopathy, atrial myxoma, Libman-Sacks (lupus)
Hypercoagulable states	APS (#1 acquired), Factor V Leiden, prothrombin G20210A, protein C/S/AT III deficiency, malignancy, OCP use, pregnancy/postpartum
Vasculopathy	Moyamoya, RCVS, PACNS, FMD, radiation vasculopathy
Genetic/metabolic	CADASIL, Fabry disease, sickle cell disease, homocystinuria, mitochondrial (MELAS)
Drug-related	Cocaine (#1 drug cause), amphetamines, cannabis, heroin, anabolic steroids
Infectious	VZV vasculopathy, HIV, syphilis, TB, infective endocarditis, COVID-19
Hematologic	Sickle cell, polycythemia vera, thrombotic thrombocytopenic purpura (TTP), PNH

Expanded Workup for Young Stroke

Standard stroke workup (CT/CTA, MRI/DWI, echo, telemetry, lipids, A1c) PLUS:
Vessel wall imaging (MRI): Dissection, vasculitis, RCVS, intracranial atherosclerosis
Hypercoagulable panel: APS antibodies (lupus anticoagulant, anticardiolipin, anti-β2GP1), protein C/S/AT III, Factor V Leiden, prothrombin mutation, homocysteine
TEE with bubble study: PFO, atrial septal aneurysm, valvular vegetations
Prolonged cardiac monitoring: 30-day event monitor or implantable loop recorder (CRYSTAL AF: 12.4% occult AF at 12 months)
ESR/CRP, ANA, ANCA: Vasculitis screen
HIV, RPR/VDRL, VZV IgG: Infectious causes
Toxicology screen: Cocaine, amphetamines
Genetic testing: NOTCH3 (CADASIL), alpha-galactosidase A (Fabry), hemoglobin electrophoresis (sickle cell) when clinically suspected
CSF analysis: If vasculitis or infection suspected

💎 Board Pearl

Cervical artery dissection is one of the leading causes of young-adult ischemic stroke and a key cause after minor neck trauma. Always get CTA head/neck or vessel wall MRI. The expanded workup includes TEE with bubble study (PFO), hypercoagulable panel, ESR/CRP, and prolonged cardiac monitoring. ~30–40% of young strokes remain cryptogenic despite extensive workup.

Fat Embolism Syndrome (FES)

Setting: 24–72 hours after long-bone fracture (femur > tibia), pelvic fracture, intramedullary orthopedic instrumentation, sickle-cell vaso-occlusive crisis, or pancreatitis.
Triad (Gurd): (1) hypoxemic respiratory failure (ARDS pattern), (2) petechial rash (axilla, conjunctiva, oral mucosa, retina), (3) encephalopathy / multifocal neurologic deficits.
MRI: “starfield” pattern — innumerable punctate DWI-bright lesions scattered diffusely throughout both hemispheres (especially in the watershed white matter).
Diagnosis: clinical — Gurd's criteria (≥2 major or 1 major + 4 minor); fat globules in urine/sputum nonspecific.
Treatment: supportive (oxygen, mechanical ventilation, hemodynamic support); early fracture stabilization reduces incidence; steroids debated (prophylactic only in select cohorts).

💎 Board Pearl — Fat Embolism

Long-bone fracture 24–72 h ago + hypoxia + petechiae + encephalopathy + starfield DWI pattern = fat embolism syndrome.

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