What Are Cerebral Cavernous Malformations?

Cerebral cavernous malformations (CCMs) are vascular lesions comprised of clusters of tightly packed, abnormally thin-walled small blood vessels (capillaries) that displace normal neurological tissue in the brain or spinal cord. The vessels are filled with slow-moving or stagnant blood that is usually clotted or in a state of decomposition.

Cavernous malformations can occur in the brain, spinal cord, and some other body regions.

In the brain and spinal cord these cavernous lesions are quite fragile and are prone to bleeding, causing hemorrhagic strokes (bleeding into the brain), seizures, and neurological deficits. CCMs can range in size from a few fractions of an inch to several inches in diameter, depending on the number of blood vessels involved.

Some people develop multiple lesions while others never experience related medical problems. Hereditary forms of CCM are caused by mutations in one of three CCM disease genes: CCM1, CCM2, and CCM3.

A large population with hereditary CCM disease is found in New Mexico and the Southwestern United States, in which the disease is caused by mutations in the gene CCM1 (or KRIT1).

Treatment Of Cerebral Cavernous Malformations

The primary treatment option for a CCM is surgical removal. Radiation therapy has not been shown to be effective.

The decision to operate is made based upon the risk of approaching the lesion. For example, symptomatic lesions close to the brain surface in “non eloquent” brain (areas for example, those areas not involved with motor function, speech, vision, hearing, memory, and learning) are very likely to be candidates for removal.

On the other hand, lesions located in deep brain areas are associated with higher surgical risk and are often not candidates for surgery until the lesion has bled multiple times. Medications can often lessen general symptoms such as headache, back pain, and seizures.

Prognosis

Rebleeding from a cavernous angioma is common, it is not predictable, and individuals frequently have multiple CCMs found via magnetic resonance imaging. Individuals with CCM are faced with a diagnosis that imparts risk of multiple future hemorrhages that occur seemingly at random and without any preventative therapy except surgical removal.

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.

The condition is also known as central nervous system cavernous hemangioma, cerebral cavernous hemangioma, familial cavernous hemangioma, familial cavernous malformation, familial cerebral cavernous angioma, familial cerebral cavernous malformation, and intracerebral cavernous hemangioma.

Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacquet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E; Société Française de Neurochirurgie
Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations
Am J Hum Genet. 2005 Jan;76(1):42-51

Gault J, Sarin H, Awadallah NA, Shenkar R, Awad IA.
Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance
Neurosurgery. 2004 Jul;55(1):1-16; discussion 16-7