Affiliation:
1. Department of Neurosurgery, College of Medicine, University of Florida, Florida 32013, United States
Abstract
Abstract:
Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the
brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernoma
takes on a mulberry-like shape contributed by the shape and relation to vascular and capillary
elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays
a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most
invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas can be
guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas
present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is
recommended. For asymptomatic and non-multilobal lesions, medical and symptom management
is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations
in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1,
CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can
cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and
KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and
cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease
endothelial to mesenchymal transition and CCM lesion development in mice models. All in
all, understanding the research behind the molecular genetics in CCMs can foster personalized
medicine and potentially create new neurosurgical and medicative treatments.
Publisher
Bentham Science Publishers Ltd.
Cited by
2 articles.
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