Cerebral Cavernous Malformation

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What is cerebral cavernous malformation?

Cerebral cavernous malformations (CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls that are prone to leak. They also lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, when the capillaries fill with blood, they stretch out and may not return to their normal size when the blood vessels empty. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the central nervous system (the brain and spinal cord).

Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related medical problems. Other people with cerebral cavernous malformations may experience serious symptoms such as headaches, seizures, paralysis, hearing or vision deficiencies, and bleeding in the brain (cerebral hemorrhage). Severe brain hemorrhages can result in death. The location and number of cerebral cavernous malformations determine the severity of this disorder. These malformations can change in size and number over time, but they do not become cancerous.

How common is cerebral cavernous malformation?

Cerebral cavernous malformations affect about 0.5 percent of the population worldwide.

What genes are related to cerebral cavernous malformation?

Mutations in the CCM2, KRIT1, and PDCD10 genes cause cerebral cavernous malformation.

The precise functions of these genes are not fully understood, but they most likely play a role in blood vessel formation (angiogenesis) during embryonic development. They may also play a role in maintaining existing blood vessels. Researchers have not determined how mutations in these genes can lead to the abnormal capillaries characteristic of cerebral cavernous malformations.

Mutations in these three genes account for 70 percent to 80 percent of all cases of familial cerebral cavernous malformations. The remaining 20 percent to 30 percent of cases may be due to unidentified genes or to other unknown causes.

How do people inherit cerebral cavernous malformation?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent.

Most cases of cerebral cavernous malformation result from a new mutation in the KRIT1, CCM2, or PDCD10 gene. These cases are known as sporadic, and they occur in people with no history of the disorder in their family.

Source: National Institutes of Health

Research from Tohoku University, Department of Neurosurgery provides new data on immunology

"Thus we examined the expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM. We performed immunohistochemistry for MMP-2, -9, and TIMP-2 using Paraffin-embedded sections of the surgical specimens obtained from seven patients with CCM. All patients had a history of hemorrhage from CCM. In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent normal brain tissue. We found that CCM showed the increased endothelial expression of MMP-2, -9, and TIMP-2," wrote M. Fujimura and colleagues, Tohoku University, Department of Neurosurgery.

The researchers concluded: "Endothelial expression of MMPs and/or TIMP may affect the vascular matrix stability, and thus can contribute to hemorrhage from CCM."

Fujimura and colleagues published their study in Acta Neurochirurgica (Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2, -9 and TIMP-2. Acta Neurochirurgica, 2007;149(2):179-83; discussion 183).

For more information, contact M. Fujimura, Tohoku University Graduate School of Medicine, Dept. of Neurosurgery, Sendai, Japan.

Publisher contact information for the journal Acta Neurochirurgica is: Springer Wien, Sachsenplatz 4-6, PO Box 89, A-1201 Vienna, Austria.

Keywords: Japan, Sendai, Immunology, Matrix Metalloproteinase, Proteins, Proteomics.

This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2007, Proteomics Weekly via NewsRx.com.