Hemorrhagic progression of cavernous angiomas: a review

Abstract

Cerebral cavernous malformations, also known as cerebral cavernous angiomas or cavernomas, are low-pressure berrylike vascular lesions with minimal to no intervening brain parenchyma. They occur with an incidence of 0.5% in the population, putting them at risk for epilepsy, neurological deficits, or hemorrhage. Genetic and inflammatory factors seem to be implicated in the development and rupture of cavernomas. Two forms of cavernomas have been described in the literature: the sporadic form, associated with single isolated lesions and the familial form that tends to result in multiple lesions. Both forms express loss of function mutations of endothelial genes that encode for proteins that play crucial roles in the proper formation of vascular lumen and maintenance of the vascular barrier, namely CCM1, CCM2 and CCM3. Therefore, cavernomas have been theorized to form due to vascular stabilization failure in angiogenesis which promotes the development of capillary dysplasia, weak intercellular junctions, and defective smooth muscle recruitment. These are also highly inflamed lesions laden with monocytes, macrophages, T cells, B cells, plasma cells and inflammatory cytokines. Further complicating this multi-factorial process is a new observation that chronic hypertension may be involved in the development or rupture of certain types of cerebral cavernous angioma lesions. We previously reported on a patient with new onset hypertension treated with medication that developed symptomatic sequential supra- and infratentorial cavernoma hemorrhages that caused hydrocephalus and cranial nerve deficits.One must theorize that this observation either represents an anomaly without causation in the process of cerebral cavernous malformation hemorrhage or possibly part of a multifactorial process in the physiology of certain cavernoma hemorrhage types. Studies of capillary physiology and successful treatment of cavernoma with beta blockers may suggest the latter in certain circumstances. Here we present a review of the literature in the development and treatment of hemorrhagic cavernous angiomas.