AngiCerebral Cavernous Angioma (Cerebral Cavernous Malformation, CCM)
Cerebral cavernous angioma, also known as cerebral cavernous malformation (CCM), is a vascular pathology of the central nervous system characterized by the presence of tangled, abnormal, and dilated capillaries, called cavernomas. These structures have thin, fragile walls that predispose them to rupture, causing cerebral hemorrhages. Cavernomas can be located in different areas of the central nervous system (brain and spinal cord) and can remain asymptomatic or cause neurological symptoms. The most common manifestations include epileptic seizures, headache, focal neurological deficits, and small cerebral hemorrhages due to the rupture of the malformed vessels.
The disease can present in a sporadic form, with a single lesion, or in a familial form, of genetic origin, characterized by the presence of multiple lesions. Diagnosis is mainly carried out via magnetic resonance imaging (MRI), which allows for the identification and monitoring of cavernomas.
In the familial form, three main genes associated with the disease have been identified:
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CCM1 (KRIT1)
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CCM2 (MGC4607 or malcavernin)
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CCM3 (PDCD10)
Mutations in one of these genes alter the mechanisms regulating endothelial cell stability and vascular wall formation, promoting the development of cavernomas. The familial form is transmitted in an autosomal dominant manner, meaning a single mutated copy of the gene is sufficient to increase the risk of developing the disease. However, penetrance is variable, meaning not all carriers of the mutation develop the same symptoms or the same number of lesions. From a clinical perspective, the genetic form is often characterized by multiple lesions and the possible appearance of new cavernomas over time. For this reason, genetic testing and genetic counseling for family members can be useful in suspected cases.
The clinical manifestations of cerebral cavernous angioma are variable and depend on the size, number, and location of the cavernomas. In many cases, the disease can remain asymptomatic and be discovered incidentally during an MRI.
The most common symptoms include:
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Epileptic seizures, especially when the lesion is located in the cerebral cortex
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Headache
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Focal neurological deficits (for example, limb weakness, sensory disturbances, language or coordination difficulties)
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Cerebral hemorrhages, generally minor but sometimes responsible for sudden symptoms
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Visual or balance disturbances, if specific areas of the brain are involved
The severity of the symptoms can vary greatly: some patients present mild or episodic manifestations, while others may develop more significant neurological deficits, especially in the event of bleeding from the lesion.
The diagnosis of cerebral cavernous angioma is mainly based on neuroimaging techniques, integrated with clinical evaluation and, in some cases, genetic investigations.
The primary diagnostic test is a brain magnetic resonance imaging (MRI), which represents the most sensitive method for identifying cavernomas. On MRI, the lesions show a characteristic appearance, often described as “popcorn-like” or “mulberry-like”, due to the presence of blood in different stages of degradation. Specific sequences, such as T2* or SWI (Susceptibility Weighted Imaging), are particularly useful for detecting even very small or multiple lesions.
Computed tomography (CT) can be used especially in acute situations, for example to highlight an intracranial hemorrhage, but it is less sensitive than MRI in detecting cavernomas.
When a familial form is suspected, genetic testing may be indicated to identify mutations in the CCM1, CCM2, or CCM3 genes, along with genetic counseling for family members.
Available therapies
Treatment depends on the symptoms and the location of the lesions and can include clinical monitoring, pharmacological therapy (for example, for epilepsy), or neurosurgical intervention in more complex or symptomatic cases.
The main therapeutic options include:
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Observation and follow-up: periodic MRIs to monitor the evolution of lesions in patients without significant symptoms.
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Pharmacological therapy: used primarily for the control of epileptic seizures with antiepileptic drugs and for the management of associated symptoms.
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Neurosurgical surgery: indicated in selected cases, for example, when the cavernoma causes epileptic seizures uncontrolled by medication, repeated hemorrhages, or progressive neurological deficits, and when the lesion is in an accessible location.
The choice of treatment is therefore personalized and requires evaluation by a multidisciplinary team, which may include neurologists, neurosurgeons, and neurorandiologists.
Research in progress
- Costruzione di un registro italiano per pazienti affetti da angiomatosi cavernosa cerebrale.
- Follow-up clinico e neuroradiologico nei pazienti naive o precedentemente arruolati in trial clinici per questa patologia.
- Studio di biomarcatori associati alla condizione e loro correlazione con dati molecolari.
- Analisi avanzate dei dati di neuroimaging e loro correlazione con dati molecolari.
- Approfondimento patogenetico su tessuto o mediante la creazione di modelli cellulari pazienti specifici.
Reference laboratory
Contacts and informations
Dott.ssa Sara Bonato
Responsabile Stroke Unit
Links to scientific publications or useful resources:
Pubblicazione scientifiche del neurologo ricercatore del Centro (Dott. G. Costamagna)
Linee guida società europea di stroke (ESO)
Linee guida società italiana di stroke (ISA-AII)