CADASIL, Moyamoya and Uncommon Stroke Causes
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Direct answer
CADASIL is an autosomal dominant NOTCH3 small vessel arteriopathy that causes recurrent subcortical infarcts, migraine with aura and dementia. Moyamoya is progressive bilateral stenosis of the terminal internal carotid arteries with a network of collateral vessels, seen as a puff of smoke on angiography. Both are important causes of stroke in young adults, alongside arterial dissection and Fabry disease.
What you must remember
- CADASIL genetics: an autosomal dominant mutation of NOTCH3 on chromosome 19, causing a small vessel arteriopathy throughout the brain.
- CADASIL features: migraine with aura, recurrent subcortical infarcts, mood disturbance and progressive cognitive decline, with anterior temporal pole white matter change on MRI.
- CADASIL diagnosis: skin biopsy showing granular osmiophilic material on electron microscopy, supported by NOTCH3 genetic testing.
- Moyamoya meaning: the Japanese term for a puff of smoke, describing the basal collateral network seen on angiography.
- Moyamoya associations: Down syndrome, neurofibromatosis type 1, sickle cell disease and previous cranial irradiation.
- Moyamoya treatment: revascularisation surgery is the mainstay in symptomatic patients, since the disease progresses.
- Arterial dissection: neck pain or headache with a partial Horner syndrome, usually managed with antithrombotic therapy for several months.
- Fabry disease: X-linked alpha-galactosidase A deficiency causing stroke in young men, with angiokeratoma and acroparaesthesia.
Stroke in the young: a diagnostic map
A 31-year-old woman has migraine with aura, two subcortical infarcts on MRI and a father who developed early dementia. A stroke in a young adult needs a targeted search, because the common vascular risk factors are often absent.
| Condition | Underlying basis | Key test | Key clue |
|---|---|---|---|
| CADASIL | NOTCH3 mutation, small vessels | MRI, skin biopsy, genetics | Migraine with aura, family history |
| Moyamoya | Terminal ICA stenosis | Cerebral angiography | Puff of smoke collaterals |
| Arterial dissection | Intimal tear in neck arteries | MRI or CT angiography | Neck pain, Horner syndrome |
| Fabry disease | Alpha-galactosidase A deficiency | Enzyme assay, GLA gene | Angiokeratoma, acroparaesthesia |
Other causes include fibromuscular dysplasia, which gives a string-of-beads appearance on angiography in young women, and MELAS, which causes stroke-like episodes with lactic acidosis. Arterial dissection is among the commonest causes of stroke in young adults, so imaging of the neck belongs in every young-stroke work-up. Taking the family history and the migraine history first often narrows the search before any test is ordered.
Where the exam tries to catch you
Most lost marks come from missing a young-stroke clue that is printed in the stem.
- Trap: Dismissing migraine with aura as irrelevant in a stroke patient. Correct: Migraine with aura in a young stroke patient is a classic CADASIL clue, especially with temporal pole white matter change.
- Trap: Calling bilateral terminal carotid stenosis with collaterals atherosclerotic. Correct: This angiographic pattern is moyamoya, which differs from bifurcation plaque in an older patient.
- Trap: Assuming neck pain plus stroke always needs surgery. Correct: Cervical dissection is usually managed with antithrombotic therapy for several months, with surgery kept for specific complications.
- Trap: Looking only for hypertension and diabetes in a young stroke. Correct: Dissection, fibromuscular dysplasia, Fabry disease and MELAS must be considered in the young.
Frequently asked questions
What is the genetic basis of CADASIL?
CADASIL is caused by an autosomal dominant mutation in the NOTCH3 gene on chromosome 19. It produces a small vessel arteriopathy with migraine with aura, recurrent subcortical infarcts and dementia as its typical features.
Which test confirms the diagnosis of CADASIL?
Skin biopsy showing granular osmiophilic material on electron microscopy, together with NOTCH3 genetic testing, confirms CADASIL. MRI showing anterior temporal pole white matter change supports the diagnosis but does not confirm it alone.
What does the angiogram show in moyamoya disease?
Moyamoya disease shows progressive bilateral stenosis of the terminal internal carotid arteries with a network of fine collateral vessels. This gives the puff of smoke appearance, which is the diagnostic angiographic feature.
Which conditions cause stroke in young adults besides CADASIL and moyamoya?
Arterial dissection, Fabry disease, fibromuscular dysplasia, MELAS and antiphospholipid syndrome are important causes of stroke in young adults. Cervical dissection typically presents with neck pain and Horner syndrome, while Fabry disease causes angiokeratoma and acroparaesthesia.
How is cervical artery dissection treated?
Cervical artery dissection is usually treated with antithrombotic therapy for several months, while surgery is reserved for specific complications. The choice of antithrombotic agent depends on the patient and the clinical situation, per current guidance.