BRAIN CAVERNOMA
Natural History and Treatment Options
Background
A cavernoma (or cavernous malformation) is a cluster of abnormal blood vessels (made up of veins), usually found in the brain and spinal cord. It is not cancerous and does not spread to other parts of the body. Cavernomas are increasingly being detected incidentally in Australia (and worldwide) due to widespread use of MRI investigations addressing symptoms not related to cavernomas. It is estimated that 1 in 200 people, or around 130,000 Australians, may harbour a brain cavernoma. Most cases are sporadic, and do not have known genetic abnormality. However, around 1 in 5 affected people have a familial (inherited) form of the disorder. A diagnosis of the inherited form can be confirmed by genetic testing.
Cavernomas may lead to one of the following situations:
No clinical symptoms – cavernomas may exist without apparent symptoms.
Seizures – more common for supratentorial cavernomas located in the upper part of the brain. For unknown reasons, seizures from cavernoma are generally not well controlled by conventional anti-seizure medications.
Bleed and rebleed - cavernomas may leak blood, leading to bleeding in the brain.
Natural History
Most cavernomas do not cause any symptoms and may go unnoticed for most of the patient’s life. The behaviour of a brain cavernoma depends ultimately on its location in the brain (supratentorial or infratentorial), underlying genetics, and the total number of lesions detected (i.e., the higher the number the greater the cumulative risk of bleeding).
Interestingly, the risk of bleeding from a cavernoma does not seem to relate to the size of the lesion, patients age or association with developmental venous malformation.
For supratentorial cavernomas that are located in the upper part of the brain, the estimated yearly risk of bleeding is around 1 in 100 chance. In familial cases, bleeding rate may vary depending on the underlying genetic profile. To date, there are 3 types of inherited cavernomas that are known , and type 3 (CCM 3) appear to have a higher rate of bleeding compared to type 1 (CCM1) and 2 (CCM2).
For infratentorial cavernomas that are located in the lower part of the brain and brainstem, the estimated yearly risk of bleeding is higher, ranging between 1 in 40 and 1 in 7 chances of bleeding.
Once a cavernoma has bled, the risk of rebleeding tend to increase. This is particularly so for cavernomas located in the brainstem, where rebleeding seem to occur more frequently. It is estimated that the risk of rebleeding for a brainstem cavernoma can range from 1 in 20 to 1 in 2 chance each year once a cavernoma has bled.
Treatment Options
Most cavernomas do not require surgery. In many patients, conservative treatment of cavernomas remains the best management option due to the fairly benign clinical course of the disease. In general, adults with small cavernomas (<5mm) who are asymptomatic, can be safely observed with regular MRI scans.
Symptomatic cavernomas causing seizures may be managed with medication, at least in the initial stages of the disease.
Occasionally, cavernomas may require surgery due to recurrent bleeding or uncontrolled seizures despite appropriate medical treatment. Available literature data has supported the role of surgery in controlling seizures, especially when accompanied by removing the iron staining parts around the cavernoma. When performed by a highly experienced neurosurgeon, surgery to remove the cavernoma is an excellent option. The surgeon can completely remove the cavernoma with no damage to surrounding brain tissue. Relief from symptoms is usually immediate.
Some reports have shown a potential useful role of radiation therapy (stereotactic radiotherapy) in treatment cavernomas. However, its long-term results are unclear and at best controversial, and the side effects of radiation may outweigh the natural history risks.
Some useful references
Del Curling O,Jr, Kelly DL,Jr, Elster AD, Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702-708, 1991
Kondziolka D, Lunsford LD, Kestle JR: The natural history of cerebral cavernous malformations. J Neurosurg 83:820-824, 1995
Horne MA, Flemming KD et al: Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data. Lancet Neurol 15: 166-173, 2016
Kivelev J, Laakso A, Niemela M, Hernesniemi J: A proposed grading system of brain and spinal cavernomas. Neurosurgery 69:807-814, 2011
Kivelev J, Niemela M, Hernesniemi J: Treatment strategies in cavernomas of the brain and spine. J Clin Neurosci 19:491-497, 2012