CADASIL

KEY FACTS

TERMINOLOGY

• Cerebral Autosomal Dominant Arteriopathy with

Subcortical Infarcts and Leukoencephalopathy (CADASIL)

• Hereditary small-vessel disease due to mutations in

NOTCH3 gene on chromosome 19, which causes stroke in

young to middle-aged adults

IMAGING

• Diffuse white matter (WM) hyperintensities = leukoaraiosis,

early finding

• Multiple lacunar infarcts

• Anterior temporal pole, external capsule, and paramedian

superior frontal lobe highly sensitive and specific locations

• Diffusion restriction in acute lacunar infarcts

• Protocol advice: MR with T2, FLAIR, and DWI

TOP DIFFERENTIAL DIAGNOSES

• Arteriolosclerosis ("Binswanger"), MELAS, subcortical

arteriosclerotic encephalopathy, primary angiitis of CNS

PATHOLOGY

• Autosomal dominant disease with mutation in NOTCH3

results in arteriopathy affecting penetrating cerebral and

leptomeningeal arteries

CLINICAL ISSUES

• Most frequent hereditary small-vessel disease of brain

• TIA/stroke or migraine with aura often initial presentation

• TIA or stroke most common manifestation of disease (60-

85% of all patients)

○ Often absence of traditional risk factors

• Migraines, if present, often precede other findings

• Average onset of stroke slightly earlier for men, but not

significantly different (M = 50.7, F = 52.5 yr)

• Clinical differential diagnosis includes multiple sclerosis,

dementia, and CNS vasculitis

• No specific therapy, supportive therapy to reduce stroke

and myocardial infarct risk

(Left) Axial FLAIR MR of a

young patient with migraines

shows focal hyperintensity ſt

in the anterior temporal lobes

highly suggestive of CADASIL.

NOTCH3 mutation confirmed

CADASIL. (Right) Axial FLAIR

MR in the same patient shows

additional subcortical

hyperintense foci in the

paramedian superior frontal

lobes ſt, which is a highly

sensitive and specific location

for lesions in patients with

CADASIL, in addition to the

anterior temporal lobes and

external capsule.

(Left) Axial DWI trace in a

young woman with no

vascular risk factors shows an

acute lacunar ﬇ infarct in the

right basal ganglia. CADASIL

was diagnosed by the

presence of a NOTCH3

mutation. (Right) Axial FLAIR

MR shows multiple

hyperintense white matter

lesions with involvement of

the external capsule st.

External capsule disease

location is characteristic for

CADASIL and rarely seen with

the more common

arteriolosclerosis.

Brain: Pathology-Based Diagnoses: Malformations,

Trauma, and Stroke

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