Cerebrovascular

Cerebral Cavernomas

A low-flow cluster of abnormal blood vessels — many never cause trouble, and treatment is individualised.

In brief

A cavernoma is a low-pressure cluster of thin-walled vessels with a ‘popcorn’ look on MRI
Many are found incidentally and never cause symptoms
Can cause seizures or small haemorrhages
MRI is the key investigation
Most do not require surgical treatment and are simply observed. Surgery is only
considered for repetitively symptomatic and accessible lesions.

What is a Cavernoma?

A cerebral cavernoma (also known as a “cavernous malformation”, “cavernous angioma” or “cavernous haemangioma”) is an abnormal cluster of small, dilated blood vessels within the brain or spinal cord. Unlike the high-pressure arteries that form aneurysms, cavernomas are low-flow, low-pressure lesions made up of thin-walled, capillary-like channels filled with slowly circulating blood. They have a characteristic “popcorn” or “mulberry-like” appearance on MRI scanning, surrounded by a rim of dark-staining old blood products (haemosiderin). They can occur anywhere in the brain or spinal cord, though approximately 65–80% are found above the level of the tentorium (the supratentorial region)¹. Cavernomas occur in approximately 0.5% of the population and account for approximately 5–10% of all cerebrovascular malformations². They are found equally in males and females and can occur at any age, including in children.

What are the Types of Cavernoma?

There are two main types:

Sporadic cavernomas are by far the most common form (approximately 80% of cases). They are typically solitary lesions and are often found incidentally on imaging performed for another reason. Sporadic cavernomas are frequently associated with an adjacent abnormal vein called a developmental venous anomaly (DVA).

Familial cavernomas account for approximately 20% of cases and are caused by an inherited change (mutation) in one of three genes — KRIT1 (CCM1), CCM2, or PDCD10 (CCM3) — transmitted in an autosomal dominant fashion. This means a parent with the mutation has a 50% chance of passing it on to each child. Familial cases typically present with multiple lesions throughout the brain and spinal cord, and those with CCM3 (PDCD10) mutations tend to have a more aggressive course with earlier onset and a higher risk of haemorrhage².

What are the Symptoms of a Cavernoma?

Many cavernomas produce no symptoms at all and are found incidentally. When symptoms do occur, they depend on the size and location of the lesion and include:

Seizures (epilepsy) — the most common presenting symptom of cavernomas above the tentorium, affecting 40–70% of patients in this region¹
Headaches — often non-specific; may relate to small episodes of bleeding
Focal neurological deficits — weakness, numbness, visual disturbance, double vision, or speech difficulty, depending on location
Haemorrhage — acute bleeding from the cavernoma can cause sudden onset of any of the above symptoms. Unlike aneurysm rupture, this bleeding is typically confined within or immediately around the lesion, and is rarely life-threatening in isolation

Brainstem cavernomas deserve special mention, as even a small haemorrhage in this critical area can cause significant neurological deficits including facial weakness, swallowing difficulty, limb weakness, or unsteadiness.

Cavernoma Risk Factors and Haemorrhage Risk

Not all cavernomas carry the same risk of bleeding. The overall annual symptomatic haemorrhage risk ranges from approximately 0.7% to 7.5% per person per year³, depending on individual circumstances. Averaged across large studies, the risk is around 2.5% per person per year.1 Key factors that influence bleeding risk include:

Prior haemorrhage — the most important risk factor; significantly increases the risk of subsequent bleeding³
Location — brainstem cavernomas carry a substantially higher annual bleed risk of around 4–5% per person per year; after a first haemorrhage the risk of re-bleeding is much higher still — of the order of 30% or more per year in the first one to two years — before declining over time^3,4
Familial disease — particularly CCM3 (PDCD10) mutations, which are associated with more aggressive disease
Multiple lesions — more common in the familial form; increases the overall chance of a symptomatic event
Incidental discovery with no prior bleeding — carries a very low annual risk (approximately 0.08% per year in some studies)³

Importantly, cavernoma haemorrhage risk appears to decrease over time in the absence of a prior bleed, and current evidence does not suggest a clearly increased risk of bleeding during pregnancy².

How are Cavernomas Diagnosed?

Magnetic Resonance Imaging (MRI)

MRI is the gold standard for diagnosing cavernomas². Specialised sequences — particularly susceptibility-weighted imaging (SWI) and gradient-echo (GRE) sequences — are highly sensitive to blood products and are essential for detecting cavernomas, especially small or multiple lesions. MRI can characterise the location, size, surrounding haemosiderin rim and any associated DVA. CT scanning is less sensitive and may be used in emergencies to identify acute haemorrhage, but is not appropriate for definitive diagnosis or follow-up.

Genetic Testing

Genetic testing for mutations in KRIT1, CCM2, and PDCD10 is recommended for patients with multiple cavernomas, a family history of cavernoma, or a suspected familial form. Identifying the responsible mutation allows for family screening and informs prognosis.

Angiography

Digital subtraction angiography (DSA) is not routinely required for cavernoma diagnosis, as these are low-flow lesions that are typically angiographically “occult” (invisible). It may occasionally be requested if an associated DVA needs further characterisation or to exclude an underlying arteriovenous malformation.

Should a Cavernoma be Treated?

The majority of cavernomas do not require any form of active treatment. For most patients, a cavernoma that is found incidentally or has caused only a single episode of bleeding is best managed without surgery. This is because the natural annual risk of a clinically significant haemorrhage is low for most lesions, and — critically — surgical morbidity can sometimes equal or exceed the risk posed by the untreated lesion itself.⁵ A large prospective study found that patients managed conservatively had a lower incidence of repeat haemorrhage than those managed surgically.⁵ The decision about management should always be made on an individual basis, in discussion with your neurosurgeon, and should take into account the size and location of the cavernoma, any symptoms it has caused, your overall health, and your personal wishes. The most important guiding principle is that the risk of any proposed treatment must be clearly less than the risk of doing nothing. Conservative (non-surgical) management is the preferred approach for the majority of patients, including:

Incidentally discovered, asymptomatic cavernomas — in which the risk of a clinically significant event is very low³
Cavernomas that have caused only a single haemorrhage, particularly if neurological recovery has been good
Lesions in deep, brainstem, or other eloquent (function-critical) locations, where surgical risk is high
Multiple cavernomas in the familial form, where operating on each lesion individually is neither practical nor appropriate
Patients in whom the overall risks of a general anaesthetic or major surgery are elevated

Conservative management involves regular clinical review and interval MRI monitoring. For stable, asymptomatic lesions, MRI follow-up is typically performed every 3–5 years, with prompt imaging if any new symptoms develop. Anti-seizure medications are used if seizures occur. The CARE pilot randomised trial (Lancet Neurology, 2024) — the first randomised comparison of surgery versus medical management alone for symptomatic cavernomas — found that the majority of eligible patients preferred non-invasive treatment, and that medical management alone is a clinically reasonable and patient-preferred strategy for symptomatic disease.⁶ A definitive large-scale randomised trial comparing surgery with medical management is now being planned.⁶ Surgical treatment is reserved for a small, carefully selected group of patients and should only be considered when the potential benefit of surgery clearly outweighs its risks. It may be considered in the following specific circumstances:

Recurrent, disabling haemorrhages from a lesion in an accessible location
Drug-resistant epilepsy clearly attributable to a superficial, surgically accessible cavernoma⁷
Progressive and disabling neurological deficit from a lesion that is surgically accessible

Surgery is rarely, if ever, indicated for an asymptomatic cavernoma, regardless of its size, and should not be offered on the basis of imaging appearances alone.

How are Cavernomas Treated?

Microsurgical Resection

For the carefully selected patient in whom surgery is appropriate, microsurgical removal of the cavernoma is the primary surgical technique. The goal is complete removal of the cavernoma itself, while carefully preserving the associated developmental venous anomaly (DVA), which provides important venous drainage to the surrounding brain². Removing the surrounding haemosiderin-stained rim of brain is generally reserved for operations aimed at controlling epilepsy, where its benefit is debated; in deep or eloquent locations such as the brainstem it is left undisturbed to avoid injuring functioning brain⁷. This requires a general anaesthetic, an opening in the skull (craniotomy), and the use of a surgical microscope. It is important to understand that whilst surgery can be highly effective in selected cases, it is a serious procedure. Surgical morbidity can sometimes be significant, particularly for lesions in or near critical brain structures, and may on occasion exceed the risk of the untreated lesion itself.⁵ This type of surgery should only be performed by an experienced cerebrovascular neurosurgeon in a centre with appropriate expertise.

Stereotactic Radiosurgery

Stereotactic radiosurgery (such as Gamma Knife or CyberKnife) delivers focused radiation to the cavernoma without opening the skull. Its role in cavernoma management is controversial and its effectiveness in reducing haemorrhage risk remains unproven². It is not recommended for asymptomatic lesions, familial cavernomas, or as a routine treatment. In familial cases specifically, radiosurgery may promote the formation of new lesions and should generally be avoided. It is occasionally considered as a last resort for patients with repeatedly symptomatic lesions in surgically inaccessible locations, with the understanding that any benefit, if present, is unlikely to be realised for at least two years following treatment.

Are There Any Medications for Cavernomas?

At present, there is no medication approved for the treatment of cavernomas, and drug therapy does not form part of routine management. However, this is an active and exciting area of research, and several medications have been investigated in clinical trials. It is important that patients understand that these treatments remain investigational and should not be commenced outside of a formal clinical trial.

Beta-blockers (e.g., propranolol, metoprolol)

Beta-blockers are a class of medication most commonly used to treat high blood pressure and heart conditions. Laboratory studies have shown they may reduce the growth and leakage of cavernomas. A clinical trial (the Treat_CCM trial) investigated propranolol in patients with familial cavernomas and found it was safe and well tolerated, though it did not demonstrate a significant reduction in bleeding events⁸. Larger trials are being planned, and interest has also shifted toward more selective agents such as metoprolol.

Statins (e.g., atorvastatin, simvastatin)

Statins are medications widely used to lower cholesterol. They also have effects on a cellular signalling pathway (the RhoA/ROCK pathway) that is disrupted in cavernoma disease, which has led to interest in their potential to reduce lesion activity and haemorrhage risk. Observational studies have shown a possible trend toward reduced bleeding in patients who take statins. A randomised clinical trial of high-dose atorvastatin (the AT CASH EPOC trial) has now been completed; it did not reduce bleeding or the iron deposits that mark cavernoma activity.⁹

ROCK inhibitors (e.g., fasudil)

ROCK inhibitors act directly on the same cellular pathway disrupted in cavernoma disease and have shown promising results in laboratory and animal studies¹⁰. They have not yet been tested in human clinical trials for cavernomas, but represent an important area of future research.

Antithrombotic agents (aspirin and blood thinners)

Patients and their treating doctors are often concerned about whether aspirin or blood-thinning medications are safe to take when a cavernoma is present. For antiplatelet medicines such as low-dose aspirin, the available evidence is reassuring — their use has not been shown to increase cavernoma bleeding and may even be associated with a lower risk¹¹. The position for full anticoagulation (such as warfarin or a direct oral anticoagulant) is less certain: some studies show no added risk, but a recent large study found a higher rate of bleeding, mainly with anticoagulants¹². There is very little evidence on dual antiplatelet therapy. The decision to start, continue or stop any of these medicines should be individualised and made together with your treating doctors — weighing why the medication is needed against your particular cavernoma, with extra caution for anticoagulation, dual antiplatelet therapy, brainstem lesions, or a recent haemorrhage. None of these medicines is used as a treatment for the cavernoma itself.

Cavernoma Screening

Screening is recommended for first-degree relatives (parents, siblings, children) of patients with a confirmed familial cavernoma (i.e., a known CCM gene mutation)². Screening involves MRI of the brain (with susceptibility-weighted sequences) and consideration of genetic testing. The identification of a gene mutation in a family member allows at-risk relatives to be counselled and monitored appropriately.

References

Helpful links

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Cerebral Cavernomas — patient information sheet PDF · prepared by Mr Jeremy Russell

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Content on this page is for education and information only and is not a substitute for advice from your doctor. Medically reviewed by Mr Jeremy Russell.