Introduction

What is cavernous malformation?

Let’s understand cavernous malformation using a raspberry analogy. A cavernous malformation (CM) is similar in appearance to a cluster of raspberries. It consists of a cluster of entangled thin-walled capillaries and abnormally dilated blood vessels that are prone to rupture. These vessels have low blood pressure and slow blood flow, increasing the risk of clot formation. 

Cavernous malformations are mainly found in neural tissues, such as the brain and spinal cord. Their size can vary from a few millimetres to several centimetres.¹

Cavernous malformation is also known as:

• Cavernoma
• Cavernous angioma
• Cavernous hemangioma
• Cerebral cavernous malformation
• Intracranial vascular formation

The most common location of cavernous malformations is the supratentorial region, which includes the upper part of the brain, such as the cerebrum, hypothalamus, pineal gland, and the lateral and third ventricles.²

Types of cavernous malformation

Cavernous malformations (CM) are broadly classified as:

Sporadic 

Sporadic lesions usually present as single or solitary lesions and are less likely to have a family history. There is no clear cause for the sporadic type of cavernous malformation. 

Familial/hereditary 

Familial lesions are inherited through genetic mutations (changes) in the KRIT1 (CCM1), CCM2, and PDCD10 (CCM3) genes.² They typically present as multiple lesions.

Cavernous malformations (CMs) are inherited in an autosomal dominant pattern, meaning they appear in every generation of the family, and each child has a 50% chance of inheriting the condition.

According to a study, about 85% of familial cases present with multiple lesions, whereas only 25% of sporadic cases show multiple lesions.³

Brain vascular malformations refer to abnormal formations of blood vessels in the brain. These malformations can cause various symptoms depending on their size, location, and tendency to bleed. The main types include:

• Cerebral cavernous malformation
• Arteriovenous malformation (AVM)
• Dural arteriovenous fistula 
• Developmental venous anomaly (DVA)
• Vein of Galen malformations
• Capillary telangiectasias
• Brain aneurysm

Prevalence and epidemiology

Cavernous malformations are relatively common in the general population. The incidence rate is 0.4 to 0.8%, meaning about 4 to 8 people out of every 1,000 experience cavernous malformations.⁴ Despite being so common, they are usually found incidentally due to a lack of characteristic symptoms. However, they may be diagnosed during the evaluation of headaches, seizures, neurological issues, or haemorrhage (bleeding). 

Cavernous malformations are most commonly seen in adults aged 20 to 50, with people in their 40s being the most commonly affected, though they can occur at any age. 

Males (people assigned male at birth) and females (people assigned female at birth) are equally affected. 

Cavernous malformations are 50% more frequent in Hispanic-American populations.⁵

Symptoms

Neurological symptoms

Headaches

Headache is a common symptom of cavernous malformations. The type of headache depends on the location of the lesion. It may last for a short period (acute) or a long period (chronic). 

Seizures

Cavernous malformations can irritate surrounding neural tissue, disrupt normal brain activity, and cause bleeding. This may lead to sudden, abnormal, and uncontrolled electrical activity in the brain, resulting in altered sensations and intense, jerky limb movements called seizures (or epilepsy). Seizures are one of the most frequent manifestations of cerebral cavernous malformations (CMs). 

Focal neurological deficits

Focal neurological deficits refer to symptoms caused by problems in neural tissues such as the nerves, brain, or spinal cord. The specific symptoms depend on the area of neural tissue involved:

• Cerebrum: Paralysis or loss of sensation on one side of the body, which may be accompanied by difficulty speaking or slurred speech
• Cerebellum: Poor balance and uncoordinated limb movements. Spinal Cord: Paralysis in both legs or all four limbs
• Brainstem: Weakness on one side of the body with loss of sensation on the other side
• Occipital lobe: Changes in vision, such as blurry vision, double vision, or vision loss

Other symptoms

• Fatigue 
• Dizziness
• Weakness 
• Numbness
• Tremors

Haemorrhages

CMs are prone to haemorrhage (bleeding) due to the fragility of their thin-walled blood vessels. Small, slow bleeding can lead to various neurological symptoms, such as headaches, muscle spasms, muscle weakness, and, most importantly, stroke. 

More often than not, bleeding may be silent or misdiagnosed. Headaches and seizures may occur with or without new bleeding.²

Recurrent bleeding increases the risk of more severe symptoms and complications, such as stroke or coma. It can be fatal at times.

Asymptomatic cases

Cavernous malformations that present without any symptoms are referred to as asymptomatic cases of CM. They are often detected incidentally via MRI, meaning they are found during imaging conducted for another condition. 

Diagnosis

Physical examination

While CMs may not present with characteristic physical signs, changes in vision, movement, and speech can help diagnose the condition. The patient may complain of headaches, double vision, difficulty speaking, balancing, or walking. 

Imaging

Magnetic resonance imaging (MRI)

MRI is the most definitive tool for identifying cavernous malformations, especially multiple lesions in familial cases. MRIs are 100% sensitive for detecting cavernous malformations, meaning that if a person has the condition, an MRI will reliably identify it. 

Susceptibility-weighted imaging MRI is the most effective for detecting cavernous malformations and other vascular lesions.⁷ The characteristic imaging provides a straightforward diagnosis of the types of CMs. The type of CM is determined using Zabramski's classification of cavernous malformations.

Computed tomography (CT) scan 

A CT scan may provide a well-demarcated appearance of CMs but it isn’t the preferred imaging method. It lacks sensitivity and specificity, meaning it may not correctly identify the presence or absence of the condition. However, it can help detect acute (sudden or severe) bleeding. 

Genetic testing

Genetic Testing is a method of examining genetic material for any changes or conditions. It is recommended in familial cases to identify specific mutations.

Treatment options

Observation 

For asymptomatic or mildly symptomatic cases that do not pose risks or problems, an MRI should be performed annually for the first 2 years and then once every 5 years to check for any new lesions, changes in lesion size, or new bleeding.⁶ For deep-seated CM lesions, observation is the most preferable treatment strategy.¹⁰

Medications 

• Antiepileptic drugs (AEDs) such as carbamazepine, valproic acid, and phenytoin are used to manage seizures
• Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are used to manage pain

Surgical intervention 

For symptomatic cases, especially those with repeated bleeding, surgery is the only cure for treating cavernous malformations. The goal is to remove the malformation and prevent further bleeding and other symptoms. Depending on the location of the CM, the surgeon will make a small hole in the skull (craniotomy) under general anaesthesia and remove the lesion. 

Surgical intervention poses several risks, such as stroke, paralysis, coma, or even death due to its complicated nature. Your surgeon will carefully analyse the risks versus benefits before planning the treatment. However, modern procedures such as microsurgery, stereotactic radiosurgery, and gamma knife surgery have reduced these complications.

Radiotherapy

Gamma knife surgery is a non-invasive form of radiotherapy that uses gamma rays to target a specific lesion. It is performed for inoperable or deep-seated CM lesions that are difficult to access with traditional surgery. 

Prognosis

Cavernous malformations form before birth or shortly after birth; however, they can develop at any age. About 40% of affected individuals are undiagnosed due to the absence of symptoms.⁸ Sometimes, these lesions may regress on their own. The prognosis of cavernous malformations depends on various factors, such as: 

Lesion size

Large lesions are prone to bleeding.

Number of lesions 

Familial cases with multiple lesions may increase risk. 

Location of the lesion

Brainstem lesions are riskier due to the critical functions in that area.

Frequency and amount of bleeding

Repeated bleeding can severely affect neurological functions.

Proximity to other vital structures

Nearby large blood vessels and cranial nerves increase the risk of complications.

Age of the patient

Recovery is generally better in younger patients.

Presence of other anomalies

The presence of Developmental Venous Abnormality (DVA) and Cerebral Cavernous Malformation (CCM) in the same individual increases the risk of bleeding.⁹

Prevention

There is no way to prevent the development of cavernous malformations. However, some lifestyle adjustments can help manage symptoms and lead to a better quality of life:

• Avoiding stress as much as possible
• Avoiding triggers that may provoke seizures
• Avoiding blood-thinning medications such as aspirin
• Avoiding unhealthy foods that can clog blood vessels with fat
• Exercising, meditating, and practising an active lifestyle
• Following up with a healthcare provider at regular intervals
• Joining support groups and seeking counselling

Summary

A cavernous malformation (CM) is a cluster of entangled blood vessels that can vary from a harmless to a life-altering condition. It manifests as severe headaches, seizures, postural imbalance, dizziness, and bleeding. Therefore, early diagnosis and regular monitoring are crucial for symptom management. Susceptibility-weighted imaging MRIs are the preferred method for detecting CMs. 

Treatment is based on individual symptoms, lesion location, and risk factors. Asymptomatic lesions require regular monitoring and observation, while symptomatic lesions with bleeding necessitate surgical intervention. With advances in MRI techniques, gene therapies, and clinical trials on drugs such as propranolol, we hope for improved treatment outcomes.