Update on genetic small vessel diseases, CADASIL and CARASIL (from bed to bench and converse)

Abstract

Genetic ischemic cerebral subcortical small vessel diseases (SSVD) are rare, usually autosomal dominant conditions related to impairment of proteins mainly involved in small vessel functions. Symptoms are characterized by combinations of migraine with aura, ischemic events (transient ischemic attacks, lacunar strokes) and progressively worsening ischemic lesion load in brain imaging, vascular cognitive impairment (usually of the frontal-subcortical type) with behavioral-psychiatric symptoms and bilateral pyramidal and pseudobulbar signs leading to severe disability and premature death. In some patients, microbleeds and hemorrhagic strokes may be evident. A large clinical heterogeneity is usually present. Between the different forms the most frequent is CADASIL, due to mutations of the NOTCH3 gene, followed by COL4A1/A2-related disease, autosomal dominant forms of HTRA1-related disease and leucoencephalopathies with calcifications and cysts. CARASIL, with an autosomal recessive HTRA1 mutation, is less frequent. A new form has been recently described, named CARASAL. In this presentation we will report our experience with these patients describing recent data on their pathogenesis and some guideline on the diagnosis and therapeutic options.