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

• Cerebral Vascular Malformations
• Occult Intracranial Vascular Malformations
• VMB (Vascular Malformations of the Brain)

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

• Vascular Malformations of the Brain (VMB) is a collective term designated to describe abnormalities in the formation and structure of the blood vessels, and their subsequent malfunction in the brain
• It may affect individuals of a wide age range including infants, young children, and adults. The symptoms, in most cases, begin appearing in early adulthood, although these brain malformations can occur at any age
• Vascular Malformations of the Brain encompasses 6 different conditions, namely:
  • Arteriovenous malformation (AVM): A condition is which abnormal arteries and veins that are enlarged and twisted. This is the most common of the malformations, and is believed to begin forming in early developmental stages, when capillaries that connect arteries and veins are missing in parts of the brain, resulting in abnormal connections. The size of the tangled structures are variable, and can often reach several centimeters in diameter
  • Cavernous malformations (CM); enlarged blood filled spaces are observed in the brain
  • Venous malformations or venous angiomas, in which abnormally-enlarged veins are observed
  • Telangiectasia causing enlarged capillaries
  • Vein of Galen malformation (VGM): The vein of Galen is a large vein that carries deoxygenated blood to the heart from the brain. The supporting fibrous wall to the vein is absent in VGM, making the vein vulnerable to blood pressure changes
  • Mixed malformations (MM): As the name suggests, it is a condition when any combination of the above 5 abnormalities is found together. Most often, arteriovenous malformations and telangiectasia are the conditions that coexist together
• The risk factors have not been clearly identified for these disorders. However, having a family history of Vascular Malformations of the Brain may pose some risk for developing the condition
• 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
• The signs and symptoms of Vascular Malformations of the Brain may include headaches, numbness, weakness, and seizures. An audible whooshing sound may be heard from the skull with a stethoscope
• A healthcare professional may perform a physical examination, assess symptoms and evaluate personal and family medical history towards establishing a diagnosis of Vascular Malformations of the Brain. The affected individual is often referred to a specialist, who may conduct imaging studies, such as computed tomography (CT), magnetic resonance imaging (MRI) scans, and cerebral arteriography, to arrive at a final diagnosis
• Some potential complications from Vascular Malformations of the Brain include bleeding in the brain, stroke, loss of vision, memory problems, difficulties with speech, and severe damage to the brain
• The treatment for Vascular 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 Vascular Malformations of the Brain depends on the severity of the condition. If no complications arise, the outcome is generally positive

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

• Vascular Malformations of the Brain are reported to occur in less than 1% of the population.
• All individuals, irrespective of age and race, are susceptible to the disorder
• However, in many cases, the manifestation of the condition occurs between the ages 10 and 40 years (predominantly in young adults.
• Generally, cavernous malformations are more prevalent in Mexican-American populations. And, arteriovenous malformations are more common in males than females.

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

The risk factors for Vascular Malformations of the Brain are not clearly known.

• In rare cases, having a family history of cavernous malformation, telangiectasia, and possibly arteriovenous malformations may pose a risk for VMB
• Males are more at risk for arteriovenous malformations

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones 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 Vascular Malformations of the Brain? (Etiology)

In most cases, Vascular Malformations of the Brain arise without any precedent family history. However, there are reports of inherited genetic mutations leading to VMBs the following cases:

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

Venous malformations of the brain owing to TIE-2 gene mutations.

• Under normal circumstances, the TIE-2 gene codes for a receptor. This receptor is regulated by factors known as angiopoietins, which play a role in the development of blood vessels during gestation and after birth
• The binding of angiopoietin 1 to the receptor sets forth a signaling mechanism that promotes the formation and stabilization of blood vessels
• The binding of angiopoietin 2 to the TIE-2 receptor has the opposite effect, and results in the destabilization of cell-cell connections and blood vessels
• A mutated or deficient TIE-2 receptor most likely leads to disruption in the formation of blood vessels causing venous malformations

If capillary telangiectasia is associated with Osler-Rendu Syndrome, then:

• Mutation(s) in the ACVRL1, ENG, and SMAD4 genes are known to cause the brain malformations
• These genes code for proteins that interact with growth factors and play a role in the formation of blood vessels

A gene mutation is also suspected in arteriovenous malformations, although there are no reports of strong evidence for the same.

Where the condition is heritable, it is generally passed on from the parents to offspring in an autosomal dominant manner. In this type of inheritance, a single copy of the causative defective gene in every cell of an individual is sufficient to cause symptoms.

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

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

Following are the general signs and symptoms manifested in Vascular Malformations of the Brain:

• Headaches
• Hemorrhage or bleeding in the brain
• Seizures
• A whooshing sound inside the skull that can be heard with the help of a stethoscope
• Vascular overload, leading to abnormally increased blood flow to the heart, resulting in symptoms of heart failure, such as
  • Chest pain
  • Dizziness
  • Tiredness
• Shortness of breath during exercise and/or while resting or sleeping
• Vision defects
  • Double vision
  • Blurred vision
  • Loss of sight
• Problems with short-term memory, such as an inability to concentrate
• Problems with articulating thoughts
• Speech problems
• Weakness; numbness

How is Vascular Malformations of the Brain Diagnosed?

A healthcare professional and/or a specialist may need information from the following in order to diagnose Vascular Malformations of the Brain:

• 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 tomography (CT) scans of the brain; it may include CT angiogram that may be performed with a dye injection
• Magnetic resonance imaging (MRI) of the brain; it may include MRI angiogram with an injected dye

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 Vascular Malformations of the Brain?

Potential complications that can arise from Vascular Malformations of the Brain may include:

• Hemorrhage or bleeding in the brain
• Reduced oxygen supply to the brain tissues that may result in the following: (in the developing child)
  • Stroke
  • Difficulty in speaking
  • Weakness; numbness
  • 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
• Thin or weak blood vessels which may lead to the following:
  • Bulges in the blood vessel wall (aneurysm)
  • Rupturing of the blood vessels
• 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 may cause brain tissue to move up against the skull
• Congestive heart failure

How is Vascular Malformations of the Brain Treated?

Treatment options for Vascular Malformations of the Brain are determined by the size and location of the malformation. The following treatments may be recommended:

• Anticonvulsant medications for seizures
• Painkillers for headaches
• Surgical removal of the malformation
• Endovascular embolization: Introduction of small particles to block the flow of blood, with the help of a catheter introduced in a leg artery
• Stereotactic radio surgery: Use of radiation to destroy tangled vessels, which makes the vessels clot gradually over a period of time

The following may be prescribed for symptoms of heart failure:

• Beta blockers and calcium channel blockers
• Angiotensin converting enzyme (ACE) inhibitors; angiotensin II receptor blockers
• Diuretics
• Anticoagulants or blood thinners, which prevent blood clot formation
• Anti-inflammatory medicines

How can Vascular Malformations of the Brain be Prevented?

Currently, there are no preventive methods or guidelines available for Vascular Malformations of the Brain.

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

• The prognosis of Vascular Malformations of the Brain is good, if the condition is diagnosed early, accurately, and treated promptly
• However, there is a likelihood for this condition to become chronic. Also, complications due to the condition itself or due to the treatment provided, may lead to an overall reduced quality of life
• In rare cases, complications arising from the disorder can be fatal as well

Additional and Relevant Useful Information for Vascular 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/