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The mystery hidden in the brain: How does CCM, a cerebrovascular malformation, form?
Cerebral cavernous malformation (CCM) is a cavernous hemangioma that forms within the central nervous system and is considered a variant of hemangioma. This disease is characterized by dilation of the vascular lumen with larger vascular channels that are less obvious in appearance and more involved in the deeper tissues. Patients' blood vessels range in size from a few millimeters to several centimeters, and although most lesions occur in the brain, any organ can be affected.
Clinical symptoms include recurring headaches, focal neurological deficits, hemorrhagic strokes, and epilepsy, but CCM may be asymptomatic in some cases, making its diagnosis more complicated.
Association between CCM and venous vascular malformations
In a proportion of CCM cases, 30% co-exist with venous angioma, which are lesions that appear as enhanced linear vessels or small vessel radiation characterized by "Medusa's hair" arranged like. These lesions are considered developmental abnormalities of normal venous drainage. Due to the risk of venous infarction, these lesions should generally not be removed, especially if discovered concurrently with CCM requiring resection, and should be approached with caution.
Genetic discovery
Three genetic loci are currently known to be involved in the development of familial CCM. The CCM1 gene encodes KRIT1, which interacts with other proteins; and the CCM2 and CCM3 genes have also been found to be associated with this disorder. Most interestingly, a study of specific mutations, such as the Q455X mutation, showed that these mutations are associated with clusters of cases in certain regions. This was particularly observed among early Spanish immigrant communities in northern New Mexico.
Mutations in three genes, CCM1, CCM2 and CCM3, account for 70% to 80% of all CCM cases, and the remaining 20% to 30% of cases may be caused by as yet unidentified genes.
Pathological mechanism
Multiple studies have confirmed the molecular pathological mechanisms of CCM. It has been reported that the endothelial cells of these cerebral vascular malformations undergo an endothelial-to-mesenchymal transition and, under certain conditions, can recruit non-mutated cells into the lesion. Recent evidence suggests that CCM-related immune thrombosis and hypoxic responses are also dysregulated.
Diagnostic methods
Current diagnostic methods mainly rely on magnetic resonance imaging (MRI), especially the use of gradient echo sequence MRI to detect small or punctate lesions. FLAIR imaging also has advantages over standard T2-weighted imaging in showing certain lesions. Many times, quiescent CCM is discovered accidentally while searching for other pathologies, and in the setting of bleeding, CT scans are more effective at showing new bleeding.
When MRI results do not conclusively identify the lesion, the surgeon may order a cerebral angiogram to further confirm the diagnosis; however, because CCMs are low-flow lesions, they are often not visible on angiography.
Treatment methods
The only current treatment for symptomatic CCM is surgery, depending on the location of the disease. To date, there are no drug options to treat CCM, leaving patients dependent on surgery to manage the condition.
Incidence rate
In the general population, the incidence of CCM is approximately 0.5%, with clinical symptoms usually appearing between the ages of 20 and 30 years. The formation of this kind of vascular disease is no longer simply regarded as congenital, and some cases can also occur newly.
The formation of cerebral vascular malformation CCM is still an area full of mystery. As more research continues, can we find more effective treatments?
