As the name suggests, vascular malformations of the brain is an umbrella term for at least six conditions in which blood vessels of the brain are affected. Such malformations are classified into several types in which the symptoms, severity, and causes vary. These types of VMB are: (1) arteriovenous malformations (AVM), abnormal arteries and veins; (2) cavernous malformations (CM), enlarged blood-filled spaces; (3) venous angiomas (VA), abnormal veins; (4) telangiectasias (TA), enlarged capillary-sized vessels; (5) vein of Galen malformations (VGM); and (6) mixed malformations (MM).
Vascular malformations of the brain may cause headaches, seizures, strokes, or bleeding in the brain (cerebral hemorrhage). Some researchers believe that the type of malformation determines the symptoms and progression of the disease. Other researchers believe that only the severity rather than the type of malformation is important.
Arteriovenous malformations or AVMs affect arteries, veins, and middle- sized vessels but not capillaries. These blood vessels are enlarged, twisted, and tangled. Arteries and veins may be connected directly instead of being connected through fine capillaries for which reason they are often referred to as “shunt lesions” since the capillaries are by-passed. These abnormal “feeding” arteries progressively enlarge and as a result the “draining” veins dilate as well. The brain tissue between these vessels may be hardened or rigid (atrophied), full of a network of fine small fibers (fibrils) interspersed with flattened cells (gliotic), and sometimes may be calcified. Such malformations may, by drawing blood away from the brain, cause brain cell atrophy. Hemorrhages or seizures are commonly experienced with AVMs. (For more information on this disorder choose “Arteriovenous” for your search term in the Rare Disease Database.)
Cavernous malformations, CMs (also called cavernous angiomas, or cavernous hemangiomas, or cavernomas) present as abnormally enlarged collections of blood-filled spaces. A cavernous hemangioma acts like a “blood sponge” soaking up blood that has found its way between capillaries, in the spaces between tissues (sinusoids) and “larger cavernous spaces.” These are “slow-flow lesions.” There is not usually any brain tissue in these spaces in contrast with symptoms of AVMs. Hemorrhages or seizures are also common with CMs. (For more information on this disorder choose “cavernous hemangioma” for your search term in the Rare Disease Database.)
Venous angiomas (VAs) involve enlarged, tangled, and twisted veins that vary in size but do not involve the arteries. The site of these “growths” is most often just after the capillary stage of the vessel (post-capillary malformation). They may be isolated defects or associated with cavernous malformations. The defect shows itself as a “crown” of small veins (venules) that meet to form part of a larger vein (trunk).
Telangiectasias are the malformations that arise as a result of the enlarging (dilation) of the tiny capillaries. These dilated capillaries make themselves known as small pink-red spots in various parts of the body such as the face, eyes, membranes that cover the brain (dura) and spinal cord (meninges), and mucous membranes (the thin moist layer lining the body’s internal surfaces). (For more information on a disorder involving telangiectasias choose “hemorrhagic telangiectasia, hereditary” for your search term in the Rare Disease Database.)
Vein of Galen malformations (VGMs begin while the embryo is developing. The vein of Galen is located under the cerebral hemispheres and drains the forward (anterior) and central regions of the brain into the proper sinuses. The malformations occur when the vein of Galen is not supported within the head by surrounding tissue and lacks the normal fibrous wall. Thus, the vein of Galen appears free-floating within the fluids of the cerebral spaces (sinuses). Should the pressure increase within the vein of Galen, its shape changes from a cylinder to that of a sphere. Such changes are accompanied by abnormal fetal blood circulation. In extreme cases, there may be cardiac failure or swelling of the brain (hydrocephalus).
Mixed malformation is a phrase used to include any of several multiple-mixed malformations. Frequently, these malformations appear to be mixes of arteriovenous malformations with telangiectasias.
Three types or forms of VMB have a genetic component. The evidence for a genetic cause is strong in the case of cavernous hemangiomas and telangiectasias. The case is much weaker for arteriovenous malformation of the brain (AVM). In each of these cases, the condition is transmitted as an autosomal dominant trait. The malfunctioning gene in the case of cavernous malformations has been tracked to gene map locus 7q11.2-q21, and in the case of telangiectasia to gene map locus 9q34.1.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 9q34.1″ refers to band 34.1 on the long arm of chromosome 7. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
To say that the abnormal gene is located at 7q11.2-q21 means that the gene in question is located in a region on the long arm of chromosome 7 between bands 11.2 and 21.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
Vascular malformations of the brain affect males and females in equal numbers. A hereditary form of cavernous malformations tends to occur more frequently in Mexican-Americans. Arteriovenous malformations occur more frequently in males.
Imaging apparatus, such as magnetic resonance imaging (MRI), computed tomography (CT) scans, venograms and/or digital intravenous or common angiography can take pictures of the brain's blood vessels to see if vascular malformations are present.
Current treatment options vary according to the severity and location of the malformation. Surgical removal (resection), multiple embolization (an operation in which pellets are put into the circulatory system in order to block blood flow to and/or from the abnormal blood vessels), and irradiation are the treatments currently in use. In some cases, treatment may not be necessary. Recently introduced techniques involve particle beam and stereotaxic radio-surgery. Genetic counseling may be of benefit for patients and their families if they have a hereditary form of this disorder. Other treatment is symptomatic and supportive.
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