Peripheral Artery Disease as a Manifestation of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Practical Implications

Abstract

48-year-old white man was seen in November in the emergency room of a county hospital in Houston with cold blue toes on both feet after exposure to temperatures that were above freezing, and with no snow on the ground. Besides the blue toes, the foot pulses were diminished. The skin over the feet was intact. An arteriogram revealed the absence of flow in multiple digital arteries (Figure 1). Subsequently over the following 2 months, the worst affected toes developed dry gangrene (Figure 2).One month earlier, in October, the patient had been admitted to the same hospital with migranous headaches and memory loss. He had severe dementia on cognitive testing, ataxia, and resting tremors. He had mildly impaired renal function that reversed with hydration. We noted transient, easy to control hypertension and asymptomatic bradycardia. A 12-lead ECG showed sinus bradycardia with no evidence of conduction pathway abnormalities or ongoing acute ischemia (Figure 3). A pharmacological stress test suggested nonreversible single vessel disease in the right coronary artery territory. MRI of the brain showed chronic ischemic changes involving the watershed areas of the frontal and the parietal lobes (Figure 4). On direct questioning, the patient recalled a half-brother who volunteered that they shared the same father, also with severe dementia.With this history of a familial dementia, and ruling out other commoner causes of dementia, a skin biopsy was performed. Electron microscopy showed granular osmiophilic material, confirming the diagnosis of cerebral autosomal dominant arte-riopathy with subcortical infarcts and leukoencephalopathy (CADASIL; Figure 5).At 3 months follow-up after the first encounter, the patient was still severely demented and with dry gangrene of the right 1st through 3rd toes. Unfortunately, he left unannounced from a personal care home before completion of the process of making him a ward of state.