Cavernous malformations

Cerebral cavernous malformations (CCMs) are groups of tightly packed, abnormal small blood vessels with thin walls. They may be present in the brain or spinal cord. The vessels contain slow-moving blood that's usually clotted. CCMs, which look like a small mulberry, can create problems in the brain or spinal cord due to leaking of blood in some people.

The clusters can vary in size from less than a quarter of an inch (0.6 centimeter) to 3 to 4 inches (7.6 to 10.2 centimeters). CCMs can run in families, but most often they occur on their own.

CCMs are one of several types of brain vascular malformations, which contain abnormal blood vessels. Other types of vascular malformations include:

• Arteriovenous malformations (AVMs)
• Dural arteriovenous fistulas
• Developmental venous anomaly (DVA)
• Capillary telangiectasias.

It's common to have both a DVA and a CCM.

CCMs may leak blood and lead to bleeding in the brain or spinal cord (hemorrhage). Brain hemorrhages can cause many signs and symptoms, such as seizures.

Depending on the location of the cavernous malformation in a person's nervous system, CCMs can also cause stroke-like symptoms. Bleeding in the spinal cord can cause difficulty with movement or feeling in the legs and sometimes arms, as well as bowel and bladder symptoms.

Symptoms

CCMs may exist without apparent symptoms. Seizures may occur when there is a CCM on the outer surface of the brain.

A wide variety of signs and symptoms may occur when CCMs are found in the brainstem, basal ganglia and spinal cord. For example, bleeding in the spinal cord may cause bowel and bladder symptoms or trouble with movement or feeling in the legs or arms.

Generally, signs and symptoms of CCMs may include:

• Seizures
• Severe headaches
• Weakness in the arms or legs
• Numbness
• Difficulty speaking
• Problems with memory and attention
• Problems with balance and walking
• Vision changes, such as double vision

Neurological issues can progressively worsen over time with recurrent bleeding. Repeat bleeding can happen soon after an initial bleed or much later. In other cases, a repeat bleed may never occur.

When to see a doctor

Seek medical help immediately if you experience any symptoms of seizure, or signs and symptoms that suggest a CCM or brain bleeding.

Causes

Most CCMs are known as "sporadic form." They occur as a single formation without an apparent cause and without any family history. The sporadic form often has an associated developmental venous anomaly (DVA), which is an irregular vein with a witch's broom appearance.

However, roughly 20% of affected people have a genetic (inherited) form of the disorder (familial cavernous malformation syndrome). In many cases, such people can identify similarly affected family members, most often with multiple malformations. A diagnosis of the inherited form can be confirmed by genetic testing. Genetic testing is often recommended for people who have:

• MRI evidence of multiple CCMs without a DVA
• A family history of CCMs

Radiation to the brain or spinal cord may also result in CCMs 2 to 20 years afterward. Other rare syndromes may be associated with CCM.

Risk factors

While most CCMs occur with no clear cause, the inherited form of the condition can cause multiple cavernous malformations, both initially and over time.

To date, research has identified three genetic variants responsible for inherited cavernous malformations, to which almost all familial cases of cavernous malformations have been traced.

Familial CCMs are inherited through a mutation in one of these genes:

• KRIT1, also called CCM1
• CCM2
• PDCD10, also called CCM3

It isn't fully understood why these mutations lead to CCM. These genes are thought to work together to communicate between cells and reduce leaking from blood vessels.

Complications

The most concerning complications of CCMs stem from recurrent bleeding, which may cause a hemorrhagic stroke and lead to progressive neurological damage.

Bleeding is more likely to recur in people with prior diagnosed hemorrhages. They're also more likely to happen again with malformations located in the brainstem.

Diagnosis

Often, people with cerebral cavernous malformations (CCMs) don't show any signs or symptoms. Your diagnosis may result from brain imaging for other neurological conditions. In some cases, specific symptoms may prompt your health care provider to pursue more extensive testing.

Tests

Depending on why the condition is suspected, your health care provider may order tests to confirm CCMs or to identify or rule out other related conditions. You may have diagnostic imaging tests (radiology) to identify changes in the blood vessels. Your health care provider may also order tests if you've experienced new symptoms. The tests can determine if there's bleeding or new CCMs.

• Magnetic resonance imaging (MRI). In this test, a detailed picture is made of your brain or spine. The blood vessels in the brain may be imaged as well. Sometimes a contrast dye injected into a vein in the arm provides images of brain tissue in a slightly different way or provides images of the blood vessels in the brain (magnetic resonance angiography or magnetic resonance venography).
• Genetic testing. If you have a family history of the condition, genetic counseling and tests are helpful to identify changes associated with CCMs in genes or chromosomes.

Treatment

Doctors trained in brain and nervous system conditions (neurologists and cerebrovascular neurologists), brain and nervous system surgery (neurosurgeons), brain imaging (neuroradiologists), and other specialties work with you to treat CCMs as well as other neurological conditions.

Your treatment may include:

• Observation. If you're not experiencing symptoms, your doctor may initially decide to monitor your cavernous malformation, especially since risk is generally lower for those who are non-symptomatic. Sometimes regular testing with an MRI is recommended to watch for any changes in the malformation. Let your doctor know right away about any changes in your symptoms.
• Medications. If you have seizures related to a cavernous malformation, you may be prescribed medications to stop the seizures.
• Counseling. Your doctor will review with you how other medical problems may impact a CCM. Also, talk to your doctor about how lifestyle factors and medications may affect a CCM.
• Surgery. If you're experiencing symptoms related to a cavernous malformation that can be reached surgically, your doctor may recommend surgery to remove the malformation.

Potential future treatments

Several imaging technology areas hold promise for improving predictions of the course of disease in some cases and for enhancing the level of information available about a particular individual's disease state. They include imaging through quantitative susceptibility mapping (QSM) and permeability imaging using dynamic contrast-enhanced MRI.

There are several medications being tested in clinical trials to see if a medication — rather than surgery — could reduce the chance of further bleeding. Talk to your doctor about which clinical trials may be available to you.

Preparing for an appointment

See your health care provider if you have any signs or symptoms that worry you. If a cerebral cavernous malformation is suspected, a referral to an experienced specialist can provide the best outcome.

Here's some information to help you get ready for the appointment, and what to expect from your health care provider.

What you can do

• Keep a detailed symptoms calendar. Each time a symptom occurs, write down the time, what you experienced and how long it lasted.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medications, vitamins or supplements you're taking.
• Take a family member or friend along. Sometimes it can be difficult to remember all the information provided to you during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Bring any recent brain scans in a CD to your appointment.

Also, if you've experienced seizures, your doctor may want to ask questions of someone who has witnessed them. It's common not to be aware of everything that happens when you experience one.

Write down questions to ask your doctor

Preparing a list of questions will help you make the most of your time with your doctor. List your questions from most important to least important in case time runs out. Most of these should be covered during your visit. Here are some examples of good questions to ask your doctor.

General questions

• How many cavernous malformations do I have?
• Where is it, or where are they located?
• What functions do the area or areas of the brain perform?
• Should I have genetic tests for hereditary CCMs?
• Should my children or anyone else in my family be tested?

Management and observation

• How often will I need follow-up tests?
• How often will I follow up with you?

Surgery (to remove a malformation)

• How long would you estimate I'd be in surgery?
• How long does surgery recovery usually take?
• How long should I plan to be in the hospital?

Surgical background

• How many CCMs have you seen, and how many have you treated?
• Does your institution have a cerebrovascular specialty practice?

Other questions may be useful for your needs. The Angioma Alliance offers an extensive set of suggested questions.

In addition to the questions you've prepared to ask your doctor, don't hesitate to ask questions during your appointment at any time if you don't understand something.

What to expect from your doctor

Your doctor is also likely to ask you a number of questions:

• When did you first begin experiencing symptoms (seizures, hemorrhage or bleeding, weakness in arms or legs, vision problems, balance problems, speech problems, difficulty with memory and attention, headaches, and so on)?
• Do your symptoms come and go (intermittent) or are they persistent (present all the time)?
• Do your symptoms seem to be triggered by certain events or conditions?

What you can do in the meantime

Certain conditions and activities can trigger seizures, so it may be helpful to:

• Avoid excessive alcohol consumption
• Avoid nicotine usage
• Get enough sleep
• Reduce stress

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