What are the other Names for this Condition? (Also known as/Synonyms)

• Cavernoma of the Brain
• Cavernous Hemangioma of the Brain
• Cerebral Cavernous Malformation (CCM)

What is Cavernous Malformations of the Brain? (Definition/Background Information)

• Cavernous Malformation of the Brain or CCM is a kind of brain malformation that leads to enlarged blood filled spaces in the brain. The cavernous malformations or cavernomas can exist in any part of the brain, as well as in the spinal cord
• Most cases are reported in adults, but children may also be affected. Generally, two types of CCM have been identified:
  • Sporadic CCM, which occurs without any family history of the condition
  • Familial CCM, which is the inherited form and it accounts for 20% of the reported cases
• Having a family history of this disorder is a known risk factor for being diagnosed with the familial form of Cavernous Malformation of the Brain. However, the risk factors for the sporadic form are unknown
• Genetic mutations in CCM1, CCM2, or CCM3 genes have been linked to Cavernous Malformation of the Brain development. These gene mutations are known to cause multiple cavernomas
• When a genetic basis is known, the condition is mostly inherited in an autosomal dominant manner. In this type of inheritance, a single copy of the defective gene in each of an individual’s cells, is enough to cause the disorder
• In the sporadic type of Cavernous Malformation of the Brain, mutations have been reported to occur spontaneously, and the mechanism of disease development is reportedly similar in manner to the inherited form
• Individuals with CCM can be symptomless, or present symptoms with varying degrees of severity. Some common symptoms include headaches, numbness, weakness in arms and legs, double vision, and speech impediment
• A healthcare professional may perform a physical examination, assess symptoms and evaluate personal and family medical history towards establishing a diagnosis of Cavernous Malformations of the Brain. The affected individual is often referred to a specialist, who may conduct imaging studies, such as computed axial tomography (CT) and magnetic resonance imaging (MRI) scans to arrive at a final diagnosis
• Some potential complications from Cavernous Malformations of the Brain include bleeding in the brain, stroke, loss of vision, paralysis, memory problems, difficulties with speech, and damage to the brain
• The treatment for Cavernous Malformations of the Brain is determined by the size and location of the malformations. The affected individual may be prescribed medication for headaches and seizures. The abnormality may also be removed surgically, where possible
• The prognosis of Cavernous Malformations of the Brain depends on the severity of the condition. If no complications are noted, then the outcome is generally positive

Who gets Cavernous Malformations of the Brain? (Age and Sex Distribution)

• The incidence rate of Cavernous Malformation of the Brain is about 1:200 or 0.5%
• The manifestation of this disorder typically occurs in adulthood. However, it can occur at any age, and 25% of the cases are reported in children
• CCM is known to occur globally, in individuals of all races and ethnicities, and both male and female genders. However, Hispanics are more prone to developing the disorder

What are the Risk Factors for Cavernous Malformations of the Brain? (Predisposing Factors)

The risk factors for developing Cavernous Malformation of the Brain may include:

• Having a family history of CCM
• Having a Hispanic heritage

The risk factors for sporadic CCM are not currently known.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cavernous Malformations of the Brain? (Etiology)

In a majority of cases, the cause of Cavernous Malformations of the Brain is not known.

Familial cavernous malformations of the brain are caused by mutations in 3 genes, namely the CCM1, CCM2, and CCM3 genes, which localize on chromosome 7.

• Under normal circumstances, the genes code for proteins that are involved in the formation and maintenance of blood vessels. Additionally, the gene products ensure no leakage between blood vessels, by maintaining the structural integrity of the vessels
• Therefore, a mutation in any of these genes compromises the development, functioning and integrity of blood vessels, leading to the following:
  • Dilated blood vessels
  • Lack of proper cell-cell junctions
  • Absence of structural support by smooth muscles
  • Sluggish blood flow through these vessels
  • Blood leaks in spaces in the brain between tissues
• Of the 3 genetic mutations that cause the condition, mutations in CCM3 gene are known to cause the most serious symptoms
• The condition is inherited in an autosomal dominant manner. In this type of inheritance, a single defective copy of the gene is sufficient for the disease to manifest itself. An affected individual inherits the disorder from an affected parent

Sporadic Cavernous Malformations of the Brain may be caused by spontaneous mutations. The cause of these mutations is not known, and the genetic changes are not passed on to the next generation.

What are the Signs and Symptoms of Cavernous Malformations of the Brain?

Cavernous Malformations of the Brain can exist without any signs and symptoms. When symptoms are present, they may vary widely even between individuals within the same family.

The signs and symptoms of CCM may include:

• Headaches
• Bleeding in the brain
• Weakness in arms or legs or both
• Vision problems, such as double vision
• Problems with balance
• Impaired memory
• Speech impediment
• Seizures
• Stroke

How is Cavernous Malformations of the Brain Diagnosed?

A diagnosis of Cavernous Malformation of the Brain is made by the following tools:

• A thorough physical examination and an assessment of symptoms
• An evaluation of the affected individual’s personal and family medical history
• Cerebral arteriography:
  • This test provides information on the location and characteristics of the feeding arteries and draining veins, as well as blockages
  • A thin tube is threaded up towards the brain and inserted into an artery in the groin; a dye is injected through this thin tube. The dye provides a contrast for X-ray analysis of the affected organ/area
• Computerized axial tomography (CAT) scans of the brain
• Magnetic resonance imaging (MRI) of the brain; it is the standard form of testing

Note: A cerebral angiogram is typically not used to diagnose a CCM.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cavernous Malformations of the Brain?

The following are some potential complications of Cavernous Malformations of the Brain:

• Hemorrhage or bleeding in the brain
• Damage to the brain: Enlargement of the blood vessels may displace or compress the brain, preventing the free flow of fluids around the brain. Fluid may start to build up, leading to hydrocephalus. This can cause the brain tissue to move against the skull

Damage to the brain, leading to the following:

• Stroke
• Seizures
• Difficulty in speaking
• Loss of vision
• Unsteadiness that may be very severe
• Paralysis on one side of the body
• Scoliosis
• Benign brain tumors
• Lesions on the skin
• Intellectual impairment, problems with memory

How is Cavernous Malformations of the Brain Treated?

The treatment options for Cavernous Malformation of the Brain depend on the age of the affected individual, the size and location of the malformation, and the possibility of a life-threatening hemorrhage.

The following treatment may be considered:

• Anticonvulsant medications for seizures
• Painkiller medicines for headaches
• Surgical removal of the malformation taking into account the possible risk for hemorrhage. The surgical options may include:
  • Traditional surgery
  • Radiosurgery, using a linear accelerator
  • Radiosurgery, using a gamma knife

In some cases, the individuals with CCM may not need any treatment, but may require monitoring of the condition periodically.

How can Cavernous Malformations of the Brain be Prevented?

At the present time, there are no guidelines or methods available to prevent Cavernous Malformation of the Brain from occurring.

• If there is a family history of the condition, then genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy. Genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Cavernous Malformations of the Brain? (Outcomes/Resolutions)

• The prognosis of Cavernous Malformations of the Brain is determined by factors such as age of the affected individual and location of the lesion. Thus, the prognosis may differ from individual to individual
• A significant number of individuals recover within a few weeks following surgical removal of the malformation. In cases where surgery results in neurological problems, the recovery process may be prolonged

Additional and Relevant Useful Information for Cavernous Malformations of the Brain:

• Dandy-Walker malformation (DWM) is a rare, congenital malformation of the brain that includes the cerebellum and the fluid filled spaces around it

The following link may help you find useful additional information on Dandy-Walker malformation:

http://www.dovemed.com/diseases-conditions/dandy-walker-malformation/