Brain cavernoma is a cerebral vascular malformation consisting of blood—filled cavities. It is clinically manifested in less than half of cases. The main symptoms include cephalgia, convulsive paroxysms, hemorrhages in the brain. Diagnosis is carried out using electroencephalography, cerebral MRI, angiography. Conservative treatment is carried out with the appointment of anticonvulsants. The surgical tactic is to completely excise the cavernoma. With the deep location of the malformation, it is possible to use radiosurgery or laser obliteration.
D18.0 Hemangioma of any localization
According to the classification of vascular malformations, cavernoma refers to the cavernous form of hemangiomas. Previously, it was attributed to neoplasms. Currently, it is considered an anomaly of vascular development. Cavernoma of the brain accounts for about 10-15% of all CNS vascular malformations. More than 70% have supratentorial localization. The prevalence of cavities among the population does not exceed 0.5%. Clinically manifested cases of the disease are observed in 40-45% of patients, the rest are asymptomatic carriers of the anomaly. The detection of pathology has significantly improved with the introduction of neuroimaging methods into medical practice.
About 50% of the caverns of the brain are hereditary, which is proved by the detection of pathology during MRI to the closest relatives. In family cases, an autosomal dominant type of inheritance is traced. It was revealed that the formation of cerebral cavernoma is caused by mutations of the CCM1 and CCM2 genes located on the 7th chromosome, and the CCM3 gene localized on the 3rd chromosome. Studies are continuing on the role of the CCM4 gene, presumably also involved in angiogenesis.
The etiology of sporadic cases remains unclear. It is believed that sporadic cavernoma is formed as a result of disorders of cerebral angiogenesis occurring at 3-8 weeks of intrauterine development. The triggers of the anomaly are any mutagenic factors acting on the pregnant woman’s body during this period. The main mutagens are: intoxication, viral diseases, taking medications with a teratogenic effect. The radio-induced mechanism of the cavern occurrence is proved.
The SSM1, SSM2, and SSM3 genes encode the synthesis of a protein complex necessary for the normal morphogenesis of the endothelial layer of the vascular wall. Mutations of these genes lead to disruption of the formation and migration of endotheliocytes with the formation of cavities. Obviously, similar changes in embryogenesis occur under the influence of mutagenic factors. It is believed that the cavernoma of the brain is congenital, but it is rarely detected in children under one year old, which is due to its initially small size.
The mechanism of occurrence of cavernous hemangiomas under the influence of radioactive radiation has not been precisely studied. There are cases of their appearance after radiation therapy for brain neoplasms, especially in children under 10 years of age. It remains an open question whether they are the result of stimulating the growth of an existing anomaly or are formed de novo.
Morphologically, the cavernoma of the brain is a conglomerate of cavities exiled by the endothelium, separated by connective tissue partitions. The cavities contain blood and thrombotic masses in various stages of formation. The size of the formation varies from 1-2 mm to 9 cm. There are no smooth muscle elements and elastic fibers typical for a normal vessel in the cavity wall.
According to the etiology, cavernomas of the brain are classified into familial and sporadic. By localization within the brain, supra- and subtentorial forms are distinguished, by quantitative characteristics — single and multiple. Microscopic examination allowed us to identify 3 basic histological types of cavernous hemangiomas:
- Classical (type I) — makes up 94% of all caverns. The formation consists of cavities separated by connective tissue. The cerebral substance between the cavities is not determined.
- Mixed (type II) — occurs in 5% of patients. It is characterized by the presence of layers of brain matter between the cavities. Weakly differentiated vascular elements are determined in places.
- Proliferative (type III) is the most rare. Along with the typical tissue, the cavernoma contains areas of endothelial proliferation. In its structure, the latter type is similar to the morphology of capillary telangiectasias.
More than half of those identified by the cavern have an asymptomatic course. The manifestation of a symptomatically manifested cavernoma is possible at any age. The clinical picture depends on the localization and size of the vascular anomaly. The most typical manifestation is convulsive syndrome, observed in 63% of cases of supratentorial form. When localized in the neocortex, epiprimes are present in 90% of patients.
Epileptic paroxysms range from generalized to simple partial. Their rather rare occurrence is characteristic. Generalized epiprimes are typical for frontal localization, partial seizures are typical for cavernoma of the temporal lobe of the brain. In 34% of cases, there is a tendency to generalization and increased frequency of epiprimes with the course of the disease, despite the anticonvulsant therapy. Resistance to anticonvulsants is most characteristic of malformations of temporal localization.
In a number of patients, general cerebral symptoms in the form of cephalgia of varying intensity come to the fore. There may be violations of the function of individual cranial nerves. When the cavernoma is localized near the cerebrospinal tract, intense headache is observed, accompanied by symptoms of increased intracranial pressure such as nausea, pressure on the eyeballs, vomiting.
The location of the cavernoma in the deep parts of the cerebral hemispheres is manifested by focal symptoms: paresis, sensory deficiency, global aphasia. Cerebellar syndrome in the form of dysarthria, gross coordination disorders, gait is characteristic of cavernous cerebellar hemangioma. The most severe is the cavernoma of the brain stem. It is manifested by alternating syndrome, oculomotor disorders, bulbar symptoms.
The most common cavernoma of the brain is complicated by hemorrhage. Possible subarachnoid bleeding, formation of intracerebral hematoma. Hemorrhage manifests itself by the sudden appearance and rapid progression of focal symptoms. In some cases, a series of epiprimes is observed, turning into an epileptic status. Repeated hemorrhages lead to the formation of persistent neurological disorders. Brain stem hemorrhages can be fatal due to paralysis of the vascular or respiratory center.
An asymptomatic cavernoma of the brain is diagnosed by a neurologist when undergoing an MRI for another disease or due to the presence of a diagnosis from a relative. With a symptomatic course in the neurological status, it is possible to identify focal disorders, speech and coordination disorders. Among the instrumental research methods for the diagnosis of cavities in modern neurology are used:
- Electroencephalography (EEG). It is mandatory for patients with epileptic paroxysms. It is possible to identify typical forms of epiactivity, high-amplitude flashes, hypersynchrony of alpha and beta rhythms.
- CT scan of the brain. Diagnoses the presence of a voluminous rounded formation with clear boundaries. The heterogeneity of the structure indicates the presence of petrificates in the walls of the caverns. Allows you to diagnose a hematoma, subarachnoid hemorrhage. It is not informative about the cavern of medium and small size.
- MRI of the brain. The most informative method of diagnosis of cavernoma. Visualizes malformation with 98% specificity. The images show the presence of a heterogeneous formation with clear contours with a typical low-intensity signal rim in the T2 mode due to hemosiderin deposits.
- Angiography. In most cases, it does not record pathological changes. Sometimes visualizes the cavernous as a non-vascular area. Angiography is used to exclude arteriovenous malformation, vascular tumor, aneurysm.
- Histological examination. It is carried out on the material obtained during the operation. It reveals the presence of characteristic cavities, in some cases — calcification, hemorrhages. Allows accurate verification of the morphological type of malformation.
The cavernous brain must be differentiated from an intracranial tumor, aneurysm, arteriovenous malformation (AVM). Cerebral neoplasm is characterized by a steady increase in clinical symptoms, when germinating into surrounding tissues ‒ by fuzzy boundaries of formation, according to MRI data. Unlike cavernomas, aneurysms and AVMs remain included in the bloodstream, so they are visualized during angiographic examination.
Medical treatment is aimed at relieving the main manifestations of the disease. It is performed when the malformation is located in a functionally significant area of the brain, in the absence of focal deficiency, in patients with rare epileptic paroxysms. Conservative therapy is indicated after primary hemorrhage from a cavernoma of a functionally important area, provided that neurological functions are fully restored.
The basis of pharmacotherapy in patients with convulsive seizures are anticonvulsants. The drug is selected individually, its dosage is adjusted depending on the frequency of the attack. Treatment is carried out for a long time, since its termination leads to the resumption or increase in paroxysms.
Indications for surgery are cerebral cavernomas manifested by hemorrhage, localized outside of functionally significant areas. When the cavernoma is located in a significant area, surgical intervention is recommended in case of severe episyndrome, repeated hemorrhages, progression of neurological deficit, increasing signs of trunk damage. The main methods of surgical treatment are:
- Surgical resection. It is the gold standard of treatment. The operation is performed using microsurgical techniques to completely remove the conglomerate of cavities. With incomplete removal, the remaining pathological tissues serve as a source of hemorrhages and trigger of epileptic activity.
- Stereotactic radiosurgery. It is indicated with a deep location of the cavernoma with the risk of damage to functional zones. The operation can significantly reduce the frequency of hemorrhages.
- Stereotactic laser ablation. A relatively new method of treatment with a small number of clinical observations. The effectiveness of this technique is reported in relation to cavities located in surgically inaccessible areas.
Prognosis and prevention
In general, there is a benign course of cavernoma of the brain. The focal deficiency that occurs during primary hemorrhage usually tends to complete regression. Repeated bleeding from the cavernoma leads to disability of the patient. Complete excision of the malformation during the operation is guaranteed to prevent the occurrence of hemorrhages, in 60% of cases leads to the complete cessation of epiprimes, in 20% ‒ to a decrease in their frequency.
Specific measures for the prevention of cavernoma of the brain have not been developed. To prevent sporadic mutations, it is necessary to observe a protective regime during pregnancy.