The incidence of cerebral cavernous malformation (CM) is approximately 0.02%–0.13%, accounting for 5%–13% of all vascular malformations in the central nervous system. CM can be divided into sporadic and familial types, with the latter typically inherited via Mendelian autosomal dominant patterns. Genetic studies have identified at least three loci (7q11-q22, 7p15-p13, and 3q25.2-q27) linked to the disease. CM affects individuals of all age groups, with similar prevalence rates in males and females. Multiple lesions are observed in 23%–50% of cases, predominantly in familial CM.
Pathology
CMs are located in the brain or spinal cord parenchyma, with rare occurrences in cranial nerves. They range in size from several millimeters to several centimeters and can be associated with venous malformations, arteriovenous malformations, and capillary malformations. Small CMs may also appear in other parts of the body. Grossly, CMs often present as mulberry-like lesions with a black-red or purple appearance. Under light microscopy, von Willebrand factor staining is positive, and smooth muscle is absent. Electron microscopy reveals abnormal slits between endothelial cells, as well as the absence and poor differentiation of subendothelial smooth muscle.
Clinical Manifestations
Intracranial Hemorrhage
The annual risk of hemorrhage is relatively low, ranging from 2.6% to 3.1% (with higher rates reported in females at 4.2% and 0.9% in males). It is unclear whether pregnancy or childbirth increases the risk of hemorrhage. CMs may cause repeated minor bleeding. Although brainstem CMs can result in severe consequences, most CMs do not pose a significant threat to life.
Seizures
Seizures represent the most common symptom, occurring in 35%–55% of CM cases. The annual incidence of newly developing seizures is approximately 2.4%.
Progressive Neurological Impairment
As a CM gradually enlarges, its mass effect can lead to progressive neurological deficits.
Imaging Characteristics
MRI
Lesions often have well-defined borders, with a central area of irregular mixed signals surrounded by a low signal rim. Central or peripheral evidence of hemorrhage at various stages may be visible. On T2-weighted imaging, surrounding brain tissue may exhibit hyperintensity due to edema. Post-contrast imaging may show mild or no enhancement, and in certain cases, associated venous malformations may also be observed.
Cerebral Angiography
Cerebral angiography is primarily used to aid in differential diagnosis.
Surgical Indications
The MRI features of CMs are characteristic, and biopsy or surgical resection is only performed when necessary to confirm the diagnosis.
Asymptomatic CMs discovered incidentally can be monitored through regular follow-up MRI scans. In such cases, an MRI follow-up is typically recommended six months after the initial diagnosis, with annual scans to monitor lesion stability. First-degree relatives of individuals with familial CM should undergo contrast-enhanced MRI and genetic testing.
Decisions regarding surgical versus conservative management depend on patient age, clinical symptoms, available medical resources, and patient preferences. Risks and benefits are carefully weighed when choosing between surgery and observation.
For cases involving repeated hemorrhage, progressive neurological deficits, or refractory epilepsy, minimally invasive neurosurgical techniques may be used to remove the CM. Preoperative functional MRI can map the relationship between the lesion and critical cortical areas involved in motor or language function. Intraoperative electrophysiological monitoring helps preserve motor and language functions.
For patients with epilepsy associated with CMs, surgical resection of the lesion may be combined with cortical cauterization to eliminate the epileptogenic focus. Postoperatively, antiepileptic medications are usually prescribed for three months, with gradual tapering if seizures do not recur.
Preoperative evaluation of potential postoperative neurological deficits is essential, particularly in brainstem CMs. The efficacy of stereotactic radiosurgery for CM remains uncertain, and the procedure is associated with a relatively high complication rate. Currently, this approach is still under clinical investigation.