Cavernous Malformations

Cerebral cavernous malformations (CCMs) are clusters of unusual, small blood vessels with thin walls. These vessels, sometimes shaped like tiny mulberries, are found in the brain or spinal cord. Inside these vessels, blood flows slowly and often clots.

These malformations can range in size, usually being less than half an inch across. Most CCMs happen randomly, without a family history. This is called a sporadic CCM. However, about one in five cases (20%) are familial CCMs. Familial CCMs are passed down through families due to a change in a specific gene. People with familial CCMs often have multiple of these malformations in their bodies.

CCMs are one type of blood vessel abnormality in the brain. Other types include:

• Arteriovenous malformations (AVMs): These involve abnormal connections between arteries and veins.
• Dural arteriovenous fistulas: These are abnormal connections between arteries and veins in the membranes covering the brain (dura).
• Developmental venous anomalies (DVAs): These are unusual patterns of veins in the brain.
• Capillary telangiectasias: These are tiny, dilated blood vessels.

People with sporadic CCMs sometimes also have DVAs.

A key concern with CCMs is that they can cause bleeding, known as a hemorrhage, in the brain or spinal cord. This bleeding can lead to a wide range of symptoms.

Bleeding in the brain (a brain hemorrhage) can cause various problems, including seizures. The location of the bleeding can also cause stroke-like symptoms, such as difficulty moving or feeling sensations in the limbs (legs and sometimes arms). In some cases, CCMs can also affect bowel and bladder function.

Cerebral cavernous malformations (CCMs) are clusters of abnormal blood vessels in the brain. Sometimes, these clusters don't cause any noticeable problems. However, if a CCM is located on the surface of the brain, it might trigger seizures. CCMs in other parts of the brain can lead to a range of symptoms. For instance, if a CCM is in the spinal cord, it could cause issues with bowel and bladder control, or problems with movement or sensation in the arms and legs. Problems can also arise in the brainstem (the part of the brain connecting the spinal cord and the rest of the brain) and the basal ganglia (a group of structures deep inside the brain).

The symptoms of CCMs can vary greatly, but some common signs include:

• Seizures: Sudden bursts of uncontrolled electrical activity in the brain.
• Headaches: Pain in the head, sometimes severe.
• Weakness or numbness: Loss of strength or feeling in the arms or legs.
• Speech problems: Difficulty speaking or understanding speech.
• Memory and attention problems: Difficulties with remembering things or concentrating.
• Balance and walking problems: Instability while walking or maintaining balance.
• Vision changes: Problems with vision, including double vision.

These symptoms can worsen over time if bleeding occurs repeatedly within the CCM. A bleed might happen soon after the first one, or it might not happen again for a long time. In some cases, there's no further bleeding.

Important: If you experience any symptoms of a seizure, seek immediate medical attention. Also, if you have symptoms that could suggest a CCM or brain bleeding, get medical help right away. Early diagnosis and treatment are crucial for managing these conditions.

If you have any signs of a seizure, go to the doctor right away. Similarly, if you notice symptoms that might mean you have a brain condition like a cerebral cavernous malformation (a type of abnormal blood vessel in the brain) or a brain bleed, seek immediate medical attention. These are serious conditions that need prompt medical care.

Many cases of cerebral cavernous malformations (CCMs) are what we call "random" or "sporadic." This means the malformation happens on its own, without any history of it in the person's family. Often, a sporadic CCM is linked to a type of abnormal vein called a developmental venous anomaly (DVA). DVAs look like a cluster of tiny veins, sometimes called a "witch's broom" pattern, on imaging scans.

About one in five people with CCMs have a "family" or "genetic" form of the condition. This means the problem is passed down through generations. This genetic form is sometimes called familial cavernous malformation syndrome. People with the genetic form are more likely to have multiple CCMs, and to have family members who are also affected. A blood or saliva test can confirm if a person has the genetic form of the condition. Doctors often suggest genetic testing for people who:

• Have multiple CCMs on an MRI scan that don't have a DVA associated with them.
• Have a family history of CCMs.

In some cases, radiation therapy to the brain or spinal cord can lead to the development of CCMs. This can happen anywhere from two to twenty years after the radiation treatment. There are also some very rare medical syndromes that can be linked to CCMs.

Cerebral cavernous malformations (CCMs) are often unexplained. However, some CCMs run in families. These inherited forms can lead to multiple CCMs developing, both initially and later in life.

Scientists have found three specific gene changes linked to inherited CCMs. These changes are responsible for almost all cases of CCMs that are passed down through families.

These inherited CCMs are caused by a problem in one of these genes:

• KRIT1 (also called CCM1): This gene helps regulate the walls of blood vessels, preventing them from becoming too leaky.
• CCM2: This gene also plays a critical role in keeping blood vessels healthy and strong.
• PDCD10 (also called CCM3): This gene is involved in the structure and function of blood vessel cells, preventing them from separating.

When these genes have these specific problems, the blood vessels become more prone to leaking, which can lead to the development of CCMs. This is because the blood vessels don't have the proper support and structure to remain intact and healthy.

Cerebral cavernous malformations (CCMs) are problems in the brain. The most serious issue with CCMs is when they bleed repeatedly. This repeated bleeding, called hemorrhages, can be very harmful. Think of it like a leaky pipe in your house. If it leaks repeatedly, it can cause damage. In the brain, this repeated bleeding can lead to a hemorrhagic stroke. A stroke happens when blood flow to a part of the brain is blocked or interrupted. A hemorrhagic stroke is when a blood vessel bursts, causing bleeding. This bleeding can damage the brain's delicate tissues and nerves.

People who have already had a brain bleed from a CCM are more likely to bleed again. This is like a wound that keeps reopening. The risk is also higher if the CCM is located in the brainstem, the lower part of the brain that controls vital functions like breathing and heart rate. This is a particularly vulnerable area because the brainstem is a crucial part of the body's central nervous system. Repeated bleeding in this area can cause serious and potentially life-threatening complications.

Cerebral cavernous malformations (CCMs) are often hidden and don't cause any noticeable problems. Sometimes, a doctor might find a CCM during a brain scan for a different health issue. Other times, specific symptoms could lead a doctor to investigate further.

If a doctor suspects a CCM, they may order tests to confirm the diagnosis or to rule out other possibilities. These tests often involve looking at the blood vessels in the brain. Even if you already have a diagnosis of CCM, further tests might be needed if you develop new symptoms. These tests help see if there's any bleeding or if new CCMs have formed.

Here are some common tests:

• Magnetic Resonance Imaging (MRI): This test creates detailed pictures of your brain or spine. Sometimes, a special dye is injected into a vein in your arm to make the images clearer.

• Genetic Testing: If you have a family history of CCMs, genetic counseling and blood or saliva tests can help identify any gene changes that might be linked to the condition.

An MRI is one of the ways to investigate for CCMs.