Cavernous angiomas: deconstructing a neurosurgical disease

J Neurosurg. 2019 Jul 1;131(1):1-13. doi: 10.3171/2019.3.JNS181724.


Cavernous angioma (CA) is also known as cavernoma, cavernous hemangioma, and cerebral cavernous malformation (CCM) (National Library of Medicine Medical Subject heading unique ID D006392). In its sporadic form, CA occurs as a solitary hemorrhagic vascular lesion or as clustered lesions associated with a developmental venous anomaly. In its autosomal dominant familial form (Online Mendelian Inheritance in Man #116860), CA is caused by a heterozygous germline loss-of-function mutation in one of three genes-CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10-causing multifocal lesions throughout the brain and spinal cord.In this paper, the authors review the cardinal features of CA's disease pathology and clinical radiological features. They summarize key aspects of CA's natural history and broad elements of evidence-based management guidelines, including surgery. The authors also discuss evidence of similar genetic defects in sporadic and familial lesions, consequences of CCM gene loss in different tissues at various stages of development, and implications regarding the pathobiology of CAs.The concept of CA with symptomatic hemorrhage (CASH) is presented as well as its relevance to clinical care and research in the field. Pathobiological mechanisms related to CA include inflammation and immune-mediated processes, angiogenesis and vascular permeability, microbiome driven factors, and lesional anticoagulant domains. These mechanisms have motivated the development of imaging and plasma biomarkers of relevant disease behavior and promising therapeutic targets.The spectrum of discoveries about CA and their implications endorse CA as a paradigm for deconstructing a neurosurgical disease.

Keywords: CA = cavernous angioma; CASH = CA with symptomatic hemorrhage; CCM = cerebral cavernous malformation; CD14 = cluster of differentiation 14; DCEQP = dynamic contrast enhanced quantitative perfusion; DVA = developmental venous anomaly; FDR = false discovery rate; MEKK = mitogen-activated protein kinase kinase; QSM = quantitative susceptibility mapping; SRS = stereotactic radiosurgery; SWI/VenBold = susceptibility weighted imaging/BOLD venographic imaging; T2*/GRE = gradient recalled echo acquired; TLR4 = toll-like receptor 4; VEGF = vascular endothelial growth factor; angioma; cavernoma; cavernous; epilepsy; hemangioma; hemorrhagic stroke; sCD14 = soluble form of CD14; sROBO4 = soluble form of Roundabout 4; vascular disorders; vascular malformation.

Publication types

  • Review