To determine the structural basis of Susac’s syndrome (SS)

SS is characterized by the clinical triad of encephalopathy, hearing loss and branch retinal artery occlusion. This condition commonly affects young women and is thought to be the result of an autoimmune microangiopathic process based on the presence of circulating anti-endothelial cell antibodies (AECAs) and endothelial staining for complement components (C3d and C4d).  No brain autopsies have yet been described.

There were no relevant findings on the general autopsy. The brain showed generalized atrophy and thinning of the corpus callosum. Microscopy revealed widespread proliferation of the capillaries accompanied by endothelial cell loss and thickened hyalinized vessel walls. There was patchy labeling of blood vessels by antibodies to membrane attack complex (MAC). Innumerable small patches of demyelination largely sparing axons accompanied by loss of cellular elements without cavitation were scattered in the white and gray matter throughout the brain and spinal cord. Calcifications involving the capillaries, neuron cell bodies and neurites were noted along with large solid calcified foci predominantly in the pons. Immunostains for SV40, tau, beta amyloid, alpha synuclein, P62 and TDP-43 were negative. Whole-exome sequencing did not reveal any genetic abnormalities.

In this first brain autopsy report in SS, autoimmune damage to microvessels is accompanied by innumerable microareas of demyelination with cell loss, and calcifications.