CADASIL in a patient with bilateral internal carotid artery agenesis

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a well-recognised cause of stroke in the young. Bilateral internal carotid artery (ICA) agenesis is a rare congenital malformation, with few previous reported cases in the literature. CADASIL is not reported to be associated with ICA agenesis. We report the case of a 41 year old man who presented with recurrent orthostatic symptoms associated with increasingly frequent falls. Initial investigation with CT angiography revealed absent bilateral ICAs with an ectatic vertebrobasilar arterial tree supplying the intracranial circulation. Skull base CT revealed simultaneous absence of ICAs and bilateral carotid canals, confirming agenesis of bilateral ICAs. MRI of the brain revealed extensive areas of confluent high T2 signal intensity in the subcortical and periventricular zones of both hemispheres. The patient subsequently developed episodic and progressive headache, dysarthria, ataxia, cognitive impairment and personality changes. Radiological progression of cerebral subcortical and periventricular abnormalities was demonstrated with established lacunar infarcts and generalised atrophic changes. Genetic testing confirmed the diagnosis of CADASIL with the presence of a heterozygous c.994C > T (p.Arg332Cys) mutation in exon 6 of the NOTCH 3 gene. We report the first case of coexistent bilateral ICA agenesis and CADASIL. This case highlights the need to consider CADASIL in patients with cerebral subcortical and periventricular imaging abnormalities, even with coexistent large vessel pathology.