Cerebral cavernous malformation

Other Names: CCM; Cerebral cavernous hemangioma; Cavernous angioma; Cavernoma Cerebral cavernous malformations (CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure which lead to altered blood flow. These capillaries have abnormally thin walls, and they lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, the blood vessels are prone to leakage, which can cause the health problems related to this condition. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the brain and spinal cord (which are described as cerebral).

Types

There are two forms of the condition: familial and sporadic. The familial form is passed from parent to child, and affected individuals typically have multiple cerebral cavernous malformations. The sporadic form occurs in people with no family history of the disorder. These individuals typically have only one malformation.

Epidemiology

Cerebral cavernous malformations affect about 16 to 50 per 10,000 people worldwide.

Cause

Mutations in at least three genes, KRIT1 (also known as CCM1), CCM2, and PDCD10 (also known as CCM3), cause familial cerebral cavernous malformations.

The precise functions of these genes are not fully understood. Studies show that the proteins produced from these genes are found in the junctions connecting neighboring blood vessel cells. The proteins interact with each other as part of a complex that strengthens the interactions between cells and limits leakage from the blood vessels. Mutations in any of the three genes impair the function of the protein complex, resulting in weakened cell-to-cell junctions and increased leakage from vessels as seen in cerebral cavernous malformations.

Mutations in these three genes account for 85 to 95 percent of all cases of familial cerebral cavernous malformations. The remaining 5 to 15 percent of cases may be due to mutations in unidentified genes or to other unknown causes. Mutations in the KRIT1, CCM2, and PDCD10 genes are not involved in sporadic cerebral cavernous malformations. The cause of this form of the condition is unknown.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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

Most people with cerebral cavernous malformations have the sporadic form of the disorder. These cases occur in people with no history of the disorder in their family.

Symptoms

Approximately 25 percent of individuals with cerebral cavernous malformations never experience any related health problems. Other people with this condition may experience serious signs and symptoms such as headaches, seizures, paralysis, hearing or vision loss, 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.

Diagnosis

Clinical findings

• Seizure disorder with onset at any age, but most typically between the second and fifth decades
• Focal neurologic deficits
• Nonspecific headaches
• Cerebral hemorrhage
• Vascular skin lesions (capillary malformations, hyperkeratotic cutaneous capillary venous malformations, venous malformations, red macules, and/or nodular venous malformations)
• Retinal cavernomas and rare choroidal hemangiomas

Brain imaging Brain MRI using either gradient echo (GRE) or susceptibility-weighted imaging (SWI) demonstrating one or more cerebral cavernous malformations

On ultrasound, cavernous haemangiomas in liver appeared as homogenous, hyperechoic lesions with posterior acoustic enhancement. On CT or MRI scans, it shows peripheral globular/nodular enhancement in the arterial phase, with portions of attenuation of enhancing areas. In the portal venous phase, it shows progressive centripetal enhancement. In delayed phase, it shows retention of contrast. It shows a high signal on T2 weighted images.

Treatment

Seizures are usually treated with antiepileptic medications. If seizures don't respond to medication, there is recurring bleeding in the brain, or the lesions are in a surgically accessible location, surgical removal of the lesion(s) using microsurgical techniques may be recommended. Headaches are managed symptomatically and/or prophylactically. Other neurological symptoms may be managed through rehabilitation.

Prognosis

Some people with CCMs will never know they have the disorder because they will never experience symptoms. Individuals who have increases in size and number of lesions, or an acute brain hemorrhage, may be directed to consider surgical removal. Symptomatic lesions are likely to remain symptomatic or progress. If treated surgically, many of these individuals will experience remission or reduction of symptoms.Overall, the prognosis for CCMs is variable, as the location, size and number of lesions determine the severity of the disorder. In some cases, CCMs can be fatal, in particular if they cause severe brain hemorrhage.

NIH genetic and rare disease info

• NIH info on Cerebral cavernous malformation

Cerebral cavernous malformation is a rare disease.

Cerebral cavernous malformation Resources
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