Objective:
To highlight unusual brain MRI findings suggestive of familial cavernous malformation in CADASIL.
Background:
CADASIL is an adult-onset autosomal dominant disorder characterized by MRI findings of bilateral diffuse white matter hyperintensities with predilection for anterior temporal lobe, lacunar infarcts and microbleeds. We report a case with MRI findings of diffuse cavernoma-like lesions on brain MRI in CADASIL.
Results:
A 47-year-old male patient was evaluated for severe migraines since childhood, chronic right-sided numbness in his 30s and progressive cognitive decline causing early retirement. There is history of dementia in both parents. Exam showed right-sided sensory loss, generalized brisk reflexes and shuffling gait. Neuropsychological evaluation showed impairment in speed of processing and flexibility of thinking with intact attention, working memory, language and visuospatial abilities. MRI revealed numerous diffuse multifocal microhemorrhages within bilateral temporal lobes, insulae, basal ganglia, thalami, midbrain, pons, medulla and cerebellum with moderate confluent bilateral subcortical and periventricular T2 hyperintensities and bilateral centrum semiovale lacunar infarct. Subtle minimal temporal pole involvement prompted CADASIL testing which was positive for a pathogenic cysteine-involving NOTCH3 mutation (c.1630c>T (p.Arg544Cys)).
Conclusions:
Brain MRI was remarkable with extensive microbleeds in a posterior distribution raising concern for familial forms of cavernous malformation (FFCM), also an autosomal dominant condition presenting with seizures and focal deficits. Although microbleeds are described in CADASIL, they are not as copious and lacunar infarcts are more common. Cognitive decline in CADASIL is known to be associated with lacunar lesion load rather than the white matter lesion volume. Our patient had minimal lacunar load and cognitive decline was relatively early and progressive without overt stroke-like episodes. This supports that microbleeds and lacunar stroke have a similar microvascular abnormality and that microbleed load may also contribute to cognitive decline in CADASIL. CADASIL testing is recommended in the presence of anterior temporal lobe involvement, however subtle.