Cavernous Malformation (Cavernoma)

Cavernous Malformations or Cavernomas are lesions comprising of abnormal blood vessels which lack the usual muscle and elastic tissue in their walls. They can occur anywhere in the nervous system and may be multiple. Although a cause of epilepsy and disability many remain clinically silent or behave in a relatively benign manner. The menu on the right of the page provides more information about subtypes of cavernomas and their particular challenges

cavernomaThe blood contained within cavernous malformations is under very little pressure and they do not attract a very large blood supply themselves. In life their appearence is frequently compared with that of rasberries, blackberries or mulberries. They range in size from millimetres to several centimetres. It is estimated that about 1 in 600 persons harbour a cavernoma although many have no symptoms as a result.

They are occasionally associated with malformations of the veins in the brain where they are located. These malformations are called Deep Venous Anomalies (DVA). DVAs are considered normal variants and they drain blood from the brain to the normal circulation. DVAs are carefully preserved when removing a cavernoma to prevent stroke in the surrounding brain. With the increased availability of MR scanning it has been recognised that cavernomas are relatively common being found in between 1 in 200 and 1 in 600 MR scans. It has also been recognised that cavernomas may develop de-novo and that they become visible on MR images when blood leaks from them staining the brain or spinal cord.

Cavernoma are best seen on MR scans. Certain specialised MR scan sequences (Gradient echo imaging, T2*-Susceptibility weighted imaging) which are particularly sensitive for blood-breakdown products in the brain increase the chances of detecting small cavernomas. Cavernomas which have not bled overtly may appear as relatively high density lesions on CT scan. Sometimes calcification can be detected within them. They are not visible on angiography although assosciated deep venous anomalies may be demonstrated.

What is the Risk of Bleeding from a Cavernoma

This is a more complicated question than it first appears. Firstly one must be clear what one means by "bleeding". The egress of small amounts of blood from a cavernoma is characteristic of their development and does not alway result in symptoms. Furthermore symptoms that are difficult to otherwise explain are sometimes attributed to the leakage of such small volumes of blood that it may not be evident on imaging. Such "microhaemorrhage" is a plausible explanation for brainstem symtoms occurring int he presence of a brainstem cavernoma but it is more difficult to relate to less-specific symptoms (e.g. a bitemporal headache). Occasionally there will be overt bleeding from a cavernoma which damages the surrounding nervous tissue and resulting in stroke. When reading the medical literature on the topic it is not always clear what authors mean by "bleeding" and it is not clear that these different tyoes of bleeding should be regarded as equivalent in terms of the danger to a patient.

Genetic Influences on Cavernous Malformations

The majority of cavernomas are isolated lesions without a known genetic cause. On occasion the cavernoma is the result of a gene mutation. In these cases multiple cavernomas are usually present. Three gene mutations have been identified: CCM1(KRT1), CCM2 and CCM3(PDCD10) but there are cases of inherited cavernoma within families where none of these mutations can be identified suggesting that other mutations remain to be discovered. If only a single lesion is visible on imaging it is improbable that it is linked to the gene mutations described above. Whether any given mutation confers particular characteristics to the cavernoma is still being explored e.g. are some gene mutations assosciated with a higher risk of haemorhage?

The currently recognised genetic forms of cavernoma exhibit an autosomal dominant pattern of inheritence; that is to say that a child with one parent carring the gene mutation has 50% chance of inheriting it. An individual with the faulty gene may not have a detectable cavernoma themselves but has the same chance as an affected individual of passing the gene mutation on.

Cavernoma has been described in the wake of radiotherapy to the brain although there is no evidence these malformations behave in a more aggressive way. Cavernomas that develop after radiation therapy may do so many years, even decades after the treatment was originally given.

Treatment of Cavernous Malformations

Treatment may be undertaken if it is determined that leaving the cavernoma alone carries more risk than the procedure to remove it. If determined that a cavernous malformation should be treated microsucrgical removal is the best established treatment and will be preferred in most cases. Stereotactic radiosurgery has been used to treatment cavernous malformations judged to be inoperable. There remains uncertainty as to the degree that radiosurgery alters the natural history of a cavernous malformation and like surgical removal there are risks assosciated with treatment. The risks of any treatment must be assessed on a case-by-case basis and will largely be determined by the location of the malformation within the nervous system.

Investigational Therapies

At present there is no proven medical therapy that definitely and positively alters the behaviour of a symptomatic cavernoma.

Statins are widley used to lower certain types of cholesterol in the blood but has other effects demonstrable in a laboratory setting. A clinical trial is currently assessing whether a statin medication reduces the deposition of iron in nervous tissue. If that proves to be the case however it is not given that patients will derive benefit from taking statins. Presently statins should not be prescribed solely because an individual harbours a cavernous malformation.