Cavernous Malformation (Cavernoma)
What is a Cavernous Malformation?
A cavernous malformation is an abnormal cluster of tiny blood vessels (capillaries and venules) that creates a “mulberry-like” lesion in the brain or spinal cord. Cavernous malformations are also referred to as cavernomas, cavernous angiomas, cavernous hemangiomas or intracranial vascular malformations. The clusters are filled with blood of different ages, and due to the especially thin walls of these capillaries, and the abnormal gapping of the tight junctions between endothelial cells, they are prone to leaking. These blood vessel malformations can occur anywhere in the body but generally only produce symptoms when they are found in the spinal cord, the brain, the covering of the brain (dura), or the nerves of the skull. Unlike an AVM, there is no large feeding artery and no large draining vein in a cavernous angioma.
Cavernous malformations are usually 1-5cm in size. 48-86% of cavernous malformations are found in the larger parts of the brain hemispheres, 4-35% of cavernous malformations are found in the brainstem, and 5-10% of cavernous malformations are found in the basal ganglia. Cavernous malformations rarely may occur in the spinal cord, although 42% of patients with spinal cavernous malformations also harbor one or more intracranial cavernous malformation.
How do they develop?
Less than one percent of people are born with a brain or spinal cord lesion that eventually becomes a cavernous malformation. The two types of cavernous malformation include hereditary and sporadic.
The hereditary form of cavernous malformation occurs when genes associated with cavernous malformations are passed from parents to their children. Researchers have discovered three different genes associated with cavernous malformations. On chromosome 7, the specific two genes involved are referred to as CCM1 and CCM 2. A third gene referred to as CCM 3 (on chromosome 3q) has also been identified. Studies are currently underway to investigate these genes further, so as to understand the relationship between the mutations of each of these genes and their corresponding symptoms.
Sporadic cases of cavernous malformations are thought to occur for no clear reason.
Incidence and Prevalence
- Their prevalence in the population is estimated to be somewhere between 0.02-0.13%
- Cavernous malformations account for an estimated 5-13% of Central Nervous System vascular malformations.
- Experts estimate around 25% of people with cavernous malformation will never experience any related medical problems.
- 60% of patients with cavernous malformations develop seizures, 50% develop progressive neurologic deficits, 20% hemorrhage, and over 50% of patients develop hydrocephalus.
- Cavernous malformations hemorrhage at an estimated rate of approximately 2.6-3.1%/yr; appearing higher in females (4.2%/yr) than males (0.9%/yr)
- At least 20% of those with cavernous malformation have the hereditary form of the illness (referred to as cavernous angioma).
- The hereditary form is associated with Hispanic heritage, multiplicity of lesions and a demonstrated propensity for growth of lesions. The latter two features are less characteristic of the sporadic form of the illness.
- If a parent has cavernous angioma, his or her child may have a 50% chance of developing this condition.
- As high as 40% of solitary cavernous malformations may have an associated venous malformation.
Diagnosis by age:
40 and Older: 10-15%
Symptoms and Complications
A person with a cavernous malformation may experience no symptoms. When symptoms occur, they often are related to the location of the malformation and the strength of the malformation walls. The type of neurological deficit is associated with the size and location of the cavernous malformation and the extent and multiplicity of the hemorrhages. Unlike a patient who experiences a subarachnoid hemorrhage, the hemorrhage occurring with a cavernous malformation is rarely a large devastating hemorrhage, although the progressive brain (or spinal cord) injury associated with vascular lesion may be severely disabling as time goes on. Different cavities of the cavernous malformation have different ages of blood product. The walls of the cavernous malformation are fragile and the growth of micro blood vessels into these lesions causes blood to drain out and settle around the cavernous malformation. This results in the cycle of cavernous malformation growth through hemorrhage and rehemorrhage.
Any of the following symptoms may occur:
- Progressive neurological impairment or “deficits”
- Hydrocephalus or raised intracranial pressure causing the following (depending on their size and location):
- Visual disturbance
- Weakness in arms or legs
- Balance problems
- Memory and attention problems
The rehemorrhage rate varies in the literature, but is probably somewhere between 4-10% per year (some reports indicate an even higher rate in the first year or two following the first diagnosed hemorrhage).
Cavernous malformations are part of a group of lesions known as “angiographically occult vascular malformations.” This means that they are not visible on an angiogram. Angiograms cannot visualize cavernous malformations because blood flows through these types of lesions slowly. Angiography may be needed to rule out other diagnoses in questionable cases. Magnetic resonance imaging (MRI), with and without contrast and with gradient echo sequences (GRE) remains the best means of diagnosing cavernous malformations. MRI scans may need to be repeated in order to analyze a change in the size of a cavernous malformation, recent bleeding, or the appearance of new lesions. A contrast CT scan can also illustrate a cavernous malformation, but the resolution is better with an MRI.
In hereditary cases where a patient has multiple cavernous malformations, it can be worthwhile to screen the cervicothoracic spinal cord via MRI to exclude the presence of an occult cavernous malformation there.
Asymptomatic, incidentally discovered cavernous malformations should be managed expectantly with serial imaging studies for about 2-3 years, to rule out frequent subclinical bleeds, then every five years thereafter. An MRI should be performed sooner if there is any clinical indication of hemorrhage or new symptoms appear. Some patients may be prescribed anti-convulsant medications.
However, some experts would recommend removal for single, easily accessible incidental cavernous malformations in non-eloquent brain.
A cavernous malformation that is enlarging radiologically and/or causing progressive neurological deficits should be given consideration for surgery. Even less accessible lesions that repeatedly bleed with progressive neurologic deterioration may be considered for excision, even in delicate regions such as the brain stem or spinal cord. Lesions in the brainstem and spinal cord, and other highly “eloquent” regions, require a highly experienced neurosurgeon for safe and effective treatment. Although brain or spine surgery may carry substantial risk, so may hemorrhage into nervous tissue. The risk of surgery must be balanced against the risk of no surgery, on an individualized, case-by-case basis and discussed comprehensively between the doctor, patient and his/her family.
In general, although seizures may be cured by successful microsurgical removal, the primary goal of surgery is to prevent future bleeding and problems such as seizures that may be associated with it. If there is low risk of bleeding and seizures are controlled through medication management, there may not be any compelling reason to perform surgery. Seizure control by itself is not enough justification for performing microsurgery on a cavernous malformation.
When Cavernous Malformations can be completely removed, the risk of further growth or hemorrhage is essentially permanently eliminated. However, recurrence of symptoms has been noted in cases of only partial cavernous malformation removal. It is important for patients to understand that with cavernous malformations treated surgically, post-op neurologic worsening is very common, especially with brain stem cavernous malformations. These deficits may be temporary, but they may take months to resolve.
All patients are taken to the neurocritical care unit after surgery where they are closely monitored by highly trained staff. Most patients are able to leave the hospital a few days following and are able to resume normal life within a few weeks of surgery. Many patients can be cured without any neurological deficits. Many patients with neurological deficits are able to regain their neurological baseline (condition at time of surgery) with therapy, and may even show further improvements. Patients with neurological deficits may require a prolonged period of treatment and are sent to rehabilitation centers for varied amounts of time following their discharge from the hospital.
A follow-up MRI 3 months post-op is recommended. The MRI never looks norm.