Cerebral — the diffusion infiltration of a brain atypical glial cages covering more than two brain shares. Typical clinical symptoms are spastic paresis, the progressing cognitive decrease, epileptic attacks, a tsefalgiya, a cerebellar syndrome, dysfunction of cranial nerves. Necessary diagnostic testings include brain MRT, an electroencephalography and a cerebral biopsy. Treatment is performed by a combination of courses of chemotherapy and diffusion radiation of a brain. Symptomatic therapy is in parallel carried out.
The term "cerebral " was for the first time entered in 1938. According to the WHO classification of 2007, a brain treats astrotsitarny neyroepitelialny tumors, new growths with the III degree of a zlokachestvennost. In new classification of tumors of TsNS (WHO, 2016) cerebral is considered as option of distribution of a diffusion glioma. The neoplasia belongs to rare tumors of a brain. In literature on neurology data on incidence fluctuate within 0,6-8 cases a year. Pathologies are subject all age categories, aged people of 40-60 years most often get sick. Men suffer gliomatozy slightly more often than women, the ratio makes 1,3:1.
Reasons of a cerebral gliomatoz
Genetic changes of tumor cells in comparison with normal gliotsita allowed to find histochemical and genetic studying of tumors which attempts were made since the beginning of the 21st century. The gene mutations of IDH1, IDH2 which are found in 70% of cases are most known. Mutations cause change of biochemical processes in a healthy cell and its transformation in tumoral. Etiofaktora, provocative mutations and starting , are definitely not established. The multifactorial mechanism of emergence of oncological process including the following components is possible:
- Onkogenny factors. Presumably mutagen role is played by the radioactive radiation, onkogenny viruses (a cytomegalovirus, , a herpetic infection), the harmful chemicals which are contained in some food (preservatives, dyes, emulsifiers), the polluted air. The specified influences are capable to cause the changes in the genetic device of cages leading to transformation of the last in an onkokletka.
- Immunosupression. The Immunosupressivny condition of an organism develops against the background of therapy by corticosteroids, cytostatics, the long course of chronic diseases. Results in lack of active operation of the antineoplastic mechanisms responsible for elimination of the cages which underwent an onkotransformation. Free increase in number of tumor cells, progressive development of an onkoprotsess is result.
- Genetic susceptibility. Genetically determined tendency to various oncopathology of TsNS is traced at a number of hereditary diseases (a neurofibromatosis, Gippelya-Lindau's disease, Li-Fraumeni's syndrome). Mechanisms of realization of the predisposition put in a genome are not defined yet.
Genes of IDH1/2 code the enzymes catalyzing reactions of synthesis alpha (pentoza) and its carboxylation in isocitrate. Mutations of these genes lead to blocking of the specified biochemical reactions, transfer of a pentoza in onkometabolit 2-gidroksiglutarat. Intracellular dismetabolichesky processes cause change of parameters of normal gliotsit, acquisition of characteristics peculiar to onkokletka by them: cellular atipizm, tendency to uncontrollable division. In the presence of other mutations of a cellular genome similar pathogenetic mechanisms are implemented.
Cerebral the onkokletok on brain fabrics without formation of tumoral knots differs in diffusion distribution. Defeat takes not less than two shares, extends in both hemispheres. Most often (76%) the big brain, a calloused body infiltrirutsya. In half of cases involvement of the bridge, a midbrain is noted. Gliomatoz of tissues of a thalamus is observed in 43% of cases, subcrustal — in 34%, a cerebellum — in 29%. Defeat of brain bark is noted at 19% of patients. Microscopically the centers of a gliomatoz are presented by the atypical glial cages mainly similar to astrotsita. In some cases onkokletka, fenotipichesk identical to oligodendrogliotsita prevail.
As cerebral it is classified WHO as a form of a diffusion glioma, relevance is acquired by its division according to phenotypical features of morphology. Information on type of the cages making zones of a gliomatoz has paramount predictive value. In this regard allocate three main options:
- Astrotsitarny. Gliomatozny zones are presented by atypical astrotsita. The most widespread type of a gliomatoz, has the II-III degree of a zlokachestvennost. Over time it is capable to be transformed to more malignant glioblastomny option.
- Oligodendroglialny. Gliomatozny sites consist of atypical oligodendrogliotsit. Zlokachestvennost degree — II-III. In the subsequent perhaps glioblastomny regeneration of a tumor.
- Glioblastomny. It is morphologically presented by the low-differentiated atypical cages. Arises initially or owing to transformation of the previous options. The most aggressive cerebral , IV degree of a zlokachestvennost.
Thanks to introduction to medical practice of genetic testing of tumor cells there was a division of gliomas according to existence of an IDH mutation. At detection of defect of genes of IDH1/IDH2 the tumor is classified as IDH having a mutation. At negative result of the genetic analysis the new growth is regarded as IDH wild type. In cases of inaccessibility of IDH testing the tumor is referred to category NOS.
Symptoms of a cerebral gliomatoz
The symptomatology is extremely not specific, does not reflect massiveness of defeat in initial stages of a disease. Pyramidal disorders of the movements, dementia are typical. Prevalence of defeat of one hemisphere leads to development of a hemiparesis of counterlateral extremities, bilateral is shown by tetraparesis of various expressiveness. Muscular weakness is followed by the increase in tendinous reflexes, a spastic hyper tone giving to extremities halfbent situation. Violations of the intellectual sphere demonstrate decrease in memory, attention, delay of thinking. Steadily progressing nature of cognitive dysfunction leads to development of elements of amnesia, an akalkuliya, agnosia, apraxia with the subsequent transition to deep organic dementia. Mental disorders are possible: change of behavior, aggression, psychomotor excitement, euphoria.
40% of patients show complaints to the tsefalgiya having diffusion character. Symptoms of intra cranial hypertensia (nausea without communication with food, vomiting at tsefalgiya height, feeling of pressure upon eyeballs) arise at 34% of patients. In 38% of cases epileptic paroxysms are observed. With the same frequency dysfunction of various craniocereberal nerves is noted. In 33% of cases cerebral proceeds with a cerebellar syndrome. Signs of a cerebellar ataxy include krupnorazmashisty , instability of the walking which is followed by body deviations in the parties, a diskoordination, a gipermetriya of movements, the chanted speech, a makrografiya. Touch violations are noted in 18% of cases, are presented by a superficial and deep gipesteziya, paresteziya.
Damage of cranial nerves of bulbarny group is followed by swallowing violations. Popyorkhivaniye can be complicated by hit of food/liquid in respiratory system with development of aspiration pneumonia. The expressed pyramidal, cerebellar frustration do the patient to bed patients. Restriction of physical activity without the corresponding leaving is fraught with developing of decubituses, stagnant pneumonia. Spastic paresis leads to formation of contractures of joints. The heaviest zhizneugrozhayushchy complications are possible at defeat of a cerebral trunk where the vascular and respiratory centers are located.
Diagnostic difficulties are connected with not specificity of a clinical picture. In the neurologic status the various neurologic deficiency testifying to the diffusion nature of defeat of brain fabrics is defined. Till a neurovisualization era cerebral it was diagnosed only by pathologists. Modern lifetime diagnosis of a disease is possible only by results of MRT of a brain and a biopsy. The list of the inspections appointed by the neurologist during diagnostics includes:
- Electroencephalography. EEG is carried out at an initial diagnostic stage. Registers diffusion changes of bioelectric activity. Paroksizmalny epileptogenny solderings are observed in case of a convulsive syndrome.
- Magnetic and resonant tomography. In the T1 mode a tumor from - or a gipodensivna that complicates assessment of its prevalence. The gold standard of diagnostics is MRT in the T2 mode which gives giperdensivny visualization of gliomatozny zones. KT of a brain can not reveal tumoral process as at this research it is izodensivny in relation to normal brain fabrics.
- Stereotaksichesky biopsy. Despite heterogeneity of a structure of various gliomatozny sites, most of clinical physicians incline to need of a biopsy. The received cerebral material is subject to a histologic research that allows to establish morphological accessory of a tumor, to estimate zlokachestvennost degree.
- IDH typing. The new diagnostic method which is gradually introduced in neurooncological practice. It is carried out on technology of genetic PTsR-diagnostics. Results of typing are considered at the choice of medical tactics, allow to do more exact predictive assumptions.
Cerebral it is necessary to differentiate from multiple lymphoma of TsNS, a multifocal glioblastoma, encephalitis, the progressing leykoentsefalopatiya. For encephalitis the corresponding epidemiological anamnesis, is characteristic of a leykoentsefalopatiya — development against the background of HIV, JC virus DNA identification at a research of tserebrospinalny liquid. Allows to distinguish from multifocal defeats (lymphoma, glioblasty) MRT.
Treatment of a cerebral gliomatoz
The diffusion nature of tumoral process does not allow to make radical surgical treatment. Operation is possible at a combination of a gliomatoz to single great focal defeat. In similar cases neurosurgical intervention is directed to removal of the center. The main methods of conservative therapy are:
- Radiological treatment. A series of sessions of radiation therapy with total cerebral radiation is made. The best results are yielded by IMRT use — radiations by means of the computerized x-ray accelerators. The method allows to regulate intensity of influence in various sites of a brain: to send radiation to large zones of a gliomatoz, to minimize a dose of radiation of crucial cerebral structures.
- Chemotherapy. It is combined with radiotheraphy. It is carried out by stage-by-stage course treatment by cytostatics: temozolomidy, karmustiny, karboplatiny. Use of several medicines with the different mechanism of action is the most productive. The break between courses of chemotherapy is caused by the expressed side effect of himiopreparat, need of restoration of an organism.
- Symptomatic treatment. It is directed to knocking over of the main symptoms of a disease, side effects of cytostatic and radiation therapy. Antiemetic, analgeziruyushchy, antiedematous, psychotropic, antiepileptic pharmaceuticals are applied.
Attempts of development of new effective ways of treatment are continuously made. The most perspective two directions – genetics and biochemistry look. Researches in the field of genetic engineering are sent to search for the methods of change of a genome of a tumor cell capable to cause its apoptosis. Studying of biochemical features an onkokletok means search of cardinally new ways of pharmacological impact on tumoral process.
Forecast and prevention
Cerebral — a serious illness with a lethal outcome. Longevity of patients after establishment of the diagnosis averages 2-3 years, in some cases exceeds 10 years. The forecast depends on morphological option, prevalence of a tumor. Researches show essential increase in life expectancy of the patients having gliomas with IDH1/IDH2 mutations in comparison with patients whose tumors are free from IDH defects. Measures of the prevention of a gliomatoz are the exception of onkogenny influences, correct treatment of viral infections, inclined to a persistention, maintenance of due level of immunity.