The incidence of primary brain tumors is increasing worldwide. When assessing the treatment delivered to patients with brain gliomas, their quality of life (QOL) is an essential criterion for consideration. It is necessary to search for and specify the factors, which determine the QOL changes in patients with brain tumors. The QOL indicators for patients with brain gliomas were assessed in terms of the following factors: clinical (presence of epileptic seizures, seizures type and frequency, antiepileptic drug treatment, presence of speech disorders and pareses), demographic (sex), age of diagnosis, social (level of education, employment, marital status), molecular-genetic (presence of IDH1/2 mutation, 1p/19q codeletion), and morphological (malignancy degree, tumor histological characteristics). The QOL of 48 patients with diffuse brain gliomas was tested according to the objectives of the study. The QOLIE-31 questionnaire (version 1.0) indicates that diffuse glioma patients with epilepsy have statistically significant decrease in such QOL spheres as seizures worry (p<0.0001), cognitive functioning (p=0.0043), antiepileptic drug effect (p=0.0002), social functioning (p=0.0029), as well as in the total score (p=0.0053). In addition, such factors as age, gender, tumor malignancy degree, and its histological type have a statistically significant effect on the QOL of patients with diffuse brain gliomas before surgery. Thus, the treatment of patients with diffuse brain gliomas requires a thorough study and a multidisciplinary approach, including such specialists as a neurologist, oncologist, chemotherapist, radiologist, neuropsychologist, and psychiatrist, in addition to a neurosurgeon.
Introduction. With standard treatment of glioblastoma, the vast majority of cases result in relapse of the disease, for which there is no consensus on the effectiveness of repeat resection. The lack of Level 1 evidence on the efficacy of surgical removal of recurrent glioblastomas (GB) indicates that the problem has not been resolved and stimulates interest in finding ways to combat this disease. Purpose. To study the effect of surgical treatment of a recurrent tumor on the overall life expectancy and post-relapse survival time of patients with glioblastomas. Materials and methods. The analysis was performed on data from 116 patients: 43 (37.1 %) women and 73 (62.9 %) men. The mean age at the time of diagnosis (primary surgery) was 52±12 full years. Surgical interventions were performed between 1999 and 2017. The study group included 50 patients who underwent GB resection. The control group consisted of 66 patients who were not operated on for GB. To achieve group homogeneity for all studied variables, the pseudo-randomization method was used. Statistical analysis was performed using the program SPSS Statistics 26.0. Results. The median overall life expectancy after GB resection was 23.6 [95 % CI=18.1–29.1] months, in the control group — 21.0 [95 % CI=12.8–29.2] months. The fatal outcome for the patients in the study group was simultaneously influenced by two characteristics: the duration of the relapse-free period (p=0.003) and the volume of the recurrent tumor (p=0.050). For the patients in the control group, only the duration of the relapse-free period (p <0.001) was impactful. The median post-relapse survival time was higher in those patients who underwent resection of 95 % or more of the GB volume than in those without surgery: 10.33 months [95 % CI 9.67 — NA months] and 6.33 months [95 % CI 5.07–11.2 months] (p<0.05), respectively. The 2‑year survival rate in the group after resection of 95 % or more of the GB volume is more than twice as high as in the non-operated group: 38.5 % and 13.7 %, respectively. Conclusions. Maximum reduction in GB volume appears to be advisable, especially in patients with a long relapse- free period when the formation is localized in the subdominant hemisphere of the brain, without spreading to the corpus callosum. Microsurgical removal of recurrent glioblastomas is an effective method of treating patients in comparison with conservative therapy.
The aim of the study is to assess the effectiveness and safety of stereotactic photodynamic therapy (sPDT) with 5-aminolevulinic acid (5-ALA) in patients with recurrent malignant supratentorial gliomas in functionally relevant brain areas. Materials and Methods:In a retrospective single-center study the results of sPDT with 5-ALA in 10 patients (6 of 10 were male), aged 30 to 62 years (median: 51.5 years; 95% CI: 38-59 years) with recurrent malignant brain gliomas after standard therapy who underwent surgery during the period of 2020-2023 were analyzed. sPDT was conducted during 15 min using 5-ALA at a dosage of 20 mg/kg, a diode laser with a wavelength of 635 nm and power of 1 W, and the LFT-02-BIOSPEC unit (BIOSPEC, Russia). Three patients got repeated sPDT after 3, 7, and 15 months due to a relapse. The number of target points and the optimal position for intervention paths were determined according to the data of preoperative stereotactic MRI of the brain with contrast intensification using the CRW Precision stereotactic navigation system (Integra, USA) and intraoperative registration of the area with the highest intensity of protoporphyrin IX fluorescence along the path (according to fluorescence biospectroscopy). Results:Glioblastoma (grade IV, WHO) was diagnosed in 7 patients, anaplastic astrocytoma (grade III, WHO) - in 3 persons. Genetic studies were performed for 9 patients, 7 of them had tumors without the IDH1 gene mutation. None of the patients had a combined 1p/19q deletion. The median volume of the contrast-enhancing part of the recurrent tumor was 7.95 cm3 (95% CI: 3.3-13.6 cm3). The median time to relapse after sPDT in patients with anaplastic astrocytomas and glioblastomas was 14.5 and 6.5 months, respectively. The median survival time after sPDT in patients with glioblastomas was 15.8 months (95% CI: 0.5-20.1 months), and in patients with anaplastic astrocytomas - 46.3 months (95%, CI not specified). In the early postoperative period, two patients had motor aphasia and hemiparesis, which further regressed. Conclusion:The results of a small group of patients allow to consider sPDT with 5-ALA as a promising technique to treat patients with recurrent high-grade gliomas in functionally relevant brain areas and require further prospective assessment.
The objectives of surgical treatment of patients with diff use brain gliomas include achieving control over epileptic seizures and improving quality of life, in addition to prolonging relapse-free period and life duration. The aim of the research is to study the factors that determine the eff ectiveness of epilepsy surgery in patients with diffuse brain gliomas. Material and methods. The study group comprised 104 patients with diff use brain gliomas, aged 41.21 ± 14.74. Results of author’s research. Clinical, neuroimaging and morphological factors were studied. Of the studied group of 104 patients with diffuse brain gliomas who had been diagnosed with epilepsy prior to surgery, the remission of 6 months after surgery was achieved in 58 (55.77 %) patients and of 12 months in 55 (52.88 %) patients. The development of acute symptomatic epileptic seizures (p = 0.68067) and acute symptomatic status epilepticus (p = 0.41626) in post-operative period do not determine the outcomes of epilepsy surgery. Neither the histological subtype of the diffuse brain gliomas, nor the molecular-genetic factor (IDH1/2 mutation, 1p/19q codeletion) determines the outcomes of epilepsy surgery in this patient category. The group of antiepileptic medications or the medication regimen (monotherapy, two-drug therapy) also does not determine the surgery outcomes. The factors that determine a favorable outcome of surgical treatment for epilepsy in patients with diff use brain gliomas are complete tumor removal and involvement of brain commissures after magnetic resonance imaging before surgery. Conclusion. The effectiveness of epilepsy surgery is determined by the radical removal of the diff use brain glioma, thereby eliminating the glutamate-mediated mechanisms of epileptogenesis.
Study objective. To develop knowledge of the epileptic status (ES) in early post-op period in patients with diffuse brain gliomas. Design. Single-centre retrospective study. Materials and methods. The study group included 280 patients with diffuse brain gliomas: 156 males (55.71%) and 124 females (44.29%). The average age of subjects was 45.81 ± 15.90 years. To identify the diffuse glioma sub-type, 118 patients underwent an examination of frequent mutations of genes IDH1 (exon 4) and IDH2 (exon 4) in tumour tissue using a high-resolution analysis of PCR product melting profile and sequencing. Results. ES in early post-op period developed in 3.57% of cases (n = 10) and manifested predominantly with motor symptoms (paroxysmal, myoclonic, focal motor symptoms). Epilepsy diagnosed before surgery was not a risk factor of ES in early post-op period. Awake surgeries, aiming at determination of the functionally significant (verbal, motor) areas of the brain, as well as the use of intraoperative neurophysiological monitoring (direct cortex stimulation during surgery) did not increase the rate of ESs. It has been demonstrated that ES in patients with diffuse brain gliomas can develop after a longer surgery (p = 0.0129) or longer anaesthesia (p = 0.0251). The association between ES in early post-op period and cerebral complications has been reported: in patients with complications, the rate of ESs was 17.07% vs. 1.26% (p < 0.00001). in patients without complications. The rate of early ESs did not drop with preventive antiepilepsy drugs prescribed to patients with diffuse brain gliomas without pre-op epilepsy, as well as with prolonged sedation with propofol and artificial lung ventilation. Conclusion. ES in early post-op period requires separate diagnostic and treatment algorithms. Keywords: diffuse brain gliomas, post-op period, epilepsy, epileptic status, antiepilepsy drugs.
Objectives Stereotactic photodynamic therapy (sPDT) using 5-aminolaevulinic acid (5-ALA) as a cytotoxic photosensitizer may be a potentially prospective treatment option for malignant gliomas. Material and Methods We analyzed data from 10 patients with recurrent malignant gliomas of the brain who were treated with sPDT at the Department of Neurosurgery of the Military-Medical Academy S. M. Kirov, from 2020 to November 2021. Three patients were treated with sPDT again after 3, 7, and 15 months due to relapse. Results The median age of the patients was 55.5 years, range was 30–60 years, there were six men and four women. At the time of sPDT, 7 (70%) patients with recurrent tumors were diagnosed with glioblastomas (WHO grade IV), and 3 (30%) with anaplastic astrocytomas (WHO grade III). Tumors were without IDH mutation in 7 (70%) patients; MGMT gene expression status was evaluated in tumors in 9 (90%) patients. A 1p/19q co-deletion was not detected in any of the patients. The median tumor volume was 5.85 cm 3 (min. 3.2 cm 3 , max. 22.5 cm 3 ). We have found that the median recurrence-free period after sPDT in patients with anaplastic astrocytomas and glioblastomas was 435 and 195 days, respectively. Conclusion This result allows to consider sPDT as one of the perspective methods of treatment of patients with recurrent gliomas of high malignancy in cases when repeated open surgical intervention has high risks of new neurological deficit.
Background. Epileptic seizures represent one of the leading clinical manifestations of glial brain tumors that develop on average in 51% of cases. In gliomas, epileptogenesis is quite complex and multifactorial.Objective: to study a role of the expressed glutamine synthetase enzyme, as well as cystine/glutamate transporter (xCT system, SLC7A11) in the pathogenesis of epilepsy developing in patients with cerebral gliomas.Material and methods. The study included 32 patients with supratentorial gliomas. The average age of the disease onset (diagnosis) was 50.69±18.01 years. All patients underwent inpatient examination and treatment at the Neurosurgery and Nervous Diseases Clinics of Kirov Military Medical Academy from 2018 to 2020. In all cases, a biopsy of tumor tissue was collected. Histological and immunohistochemical studies were performed (expression of glutamine synthetase and cystine/ glutamate transporter (SLC7A11, xCT)).Results. Significant (ANOVA p=0.027, Mann–Whitney U-test p=0.033) differences in the expression of cystine/glutamate transporter (xCT system, SLC7A11) were revealed, by showing the following median values (lower quartile; upper quartile): 50% (45; 75) in the group of patients with seizures, 40% (40; 50) in the seizure-free group. The expression level of glutamine synthetase did not significantly differ in the groups with and without seizures.Conclusion. The data obtained confirmed that one of the pathogenetic mechanisms for epilepsy development in patients with gliomas was related to highly expressed cystine/glutamate transporter (xCT system, SLC7A11) and, as a consequence, an increase in the extracellular glutamate level.
An increased amino acid metabolism is characteristic for many brain malignancies. Combined positron emission and computed tomography (PET/CT) with radiolabeled amino acids is often used in recognizing the tumor nature of the structural brain lesion detected on MRI. On 11C-methionine PET/CT a hallmark of a brain tumor is an increased amino acid uptake, topographically coinciding with a structural lesion on MRI. However, high 11C-methionine uptake in the brain lesion is not tumor specific and could be seen in a number of non-tumor diseases. The paper presents three observations of a brain abscess, radiological and metabolic data of which in MRI and 11C-methionine PET/CT simulated a malignant cerebral tumor. The reasons for patients seeking nuclear medicine examination were seizures or focal neurological symptoms, as well as a suspicion of a cerebral tumor based on the contrast-enhanced MRI. Knowledge of the non-tumor disease characterized by high 11C-methionine uptake will help avoid misdiagnosis of a cerebral tumor.
OBJECTIVES To estimate the incidence of epileptic seizures in patients with glial and metastatic brain tumors and to identify clinical and morphological risk factors for epileptic seizures in patients with glial and metastatic brain tumors. MATERIAL AND METHODS The study included 225 (88.6%) patients with glial brain tumors and 29 patients (11.4%) with metastatic tumors. RESULTS Statistically significant differences in the incidence of epileptic seizures depending on age, histological characteristics of the tumor, degree of malignancy, tumor localization, involvement of the cerebral cortex, the presence of the midline shift were obtained. CONCLUSIONS Epilepsy and epileptic seizures was found to develop in 51.11% and 24.14% of cases in glial and metastatic brain tumors, respectively. Risk factors for developing epileptic seizures include younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytomas, anaplastic astrocytomas, oligodendrogliomas, oligoastrocytomas, grade I-III malignancy, lesion of the temporal lobe, involvement of the cerebral cortex. Factors that reduce the risk for attacks include age over 57, histological characteristics corresponding to glioblastomas and metastatic tumors, grade IV malignancy, subcortical localization of the tumor, damage to the occipital lobe, involvement of the commissural pathways, subtentorial localization of the tumor, the absence of lesions of the temporal and frontal lobes of the brain, the involvement of both brain hemispheres, damage to two or more brain lobes, the presence of a midline shift.
The aim of the study was to compare the level of accumulation of protoporphyrin IX (ППIX) in the brain of rats in normal conditions and in experimental C6 glioma. Materials and methods. In an experiment on 15 rats, one group of animals (n=5) was intracranially implanted with rat glioma of the C6 line. 14 days after tumor implantation, the animals were injected into the lateral vein of the tail with a photosensitizer — a preparation of 5-aminolevulinic acid (5-ALA) Alasens at a dose of 100 mg / kg. Another group consisted of 5 intact rats, which were also injected with Alasens. The rats were euthanized 4–5 hours after the injection of the photosensitizer, and fluorescent metabolic navigation was performed with illumination of the brain with light with wavelengths of 417 and 435 nm. For objectification, fluorescence biospectroscopy was performed. Similar manipulations were performed with animals of another group (n=5) — intact rats that did not receive Alasens. Results. In contrast to humans, in rats, the 5-ALA metabolite — PPIX accumulates in healthy brain tissue, while the fluorescence intensity does not differ from that visualized in the tumor area. It was also noted that the light of the blue spectrum promotes weak fluorescence of the white matter of the rat brain in the absence of exogenous 5-ALA, which can potentially be explained by the activation of endogenous PPIX or other fluorophores. Conclusion. After the administration of Alasens (5-ALA preparation), the accumulation of PPIX by the rat brain tissue occurs not only by malignant cells, but also by normal brain tissue without signs of malignancy or other pathological changes. A more thorough study of this phenomenon is required, since significant differences in the metabolism of 5-ALA in humans and laboratory animals will call into question the correctness of translation of experimental results into clinical practice.
The immune status of 58 patients with gliomaswas evaluated. Prior to surgical treatment in patients with low-grade gliomas was observed higher (p ˂0.05) the absolute number of total T-lymphocytes, Thelper cells and NK-cells compared to patients with high grade glioma. Postoperatively group grade II was observed explicit reduction in the number of CD3 + , CD3 + CD4 + , CD3 – CD56 + and increase in the population CD3 + CD8 + cytotoxic T-lymphocytes. Reducing of the number of CD3 – CD56 + lymphocytes in patients with diffuse astrocytomas and anaplastic gliomas after surgical treatment, maybe, related to the migration of these cells into the area of surgical intervention. At the same time in patients with grade III, IV gliomas was revealed an increase of the absolute number of killer T-cells. In the group of grade IV also was recorded increase in the percentage of T-reg, having a suppressor function, which may indicate a breach of anti-tumor immune response and cause suppression of the cytotoxic response in patients with highgrade gliomas.
Introduction. Mutations in the isocytrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are considered driver genetic events in gliomas. Their frequency reaches 7080 % in low-grade gliomas and in secondary glioblastomas, and their oncogenic effect is realized by accumulation of the metabolite 2-hydroxyglutarate, which disrupts DNA and protein methylation processes. The aim of the study was to analyze the associations between the presence of IDH1/2 mutations and clinical and morphological parameters of glial tumors. Material and Methods. The study included 147 patients with glial brain tumors. Associations between IDH1/2 status and tumor histological type, age of disease onset, tumor localization, and clinical manifestations were investigated. Results. Gliomas containing IDH1/2 mutations were characterized by a younger age at diagnosis (mean: 39.5 years) compared to IDH-negative cases (47.2 years) (p<0.01). IDH1/2-mutated tumors were more often localized in the frontal (53.4 %) and parietal lobes (61.3 %) than in the other areas of the brain (p<0.05). It was demonstrated that the incidence of epilepsy was significantly higher among patients with IDH1/2 genetic defects (69.2 % vs. 48.2 %, p<0.05). Patients with IDH1/2 mutations had more favorable course of the disease. Among individuals with a combination of these factors (localization of the tumor in the frontal or parietal lobe, presence of epilepsy, age younger than 39 years), the frequency of IDH1/2 mutations reached 21/27 (77.8 %), which was significantly higher than that in all other patients (44/119 (37.0 %), OR = 5.97, 95 % CI: 2.2415.91, p<0.001). Conclusion. The presence of IDH1/2 genetic defects is associated with localization of glial tumors in the frontal and parietal lobes of the brain, earlier age at disease onset and the presence of epileptic syndrome.
We report a patient with recurrent glioblastoma in eloquent brain area. Stereotactic fluorescence biospectroscopy and stereotactic photodynamic therapy of tumor in opercular area of the left frontal lobe under neurophysiological monitoring were carried out. Literature data on this issue were analyzed.
МР-сПЕКТРОсКОПиЯ ПРи ГЛиОМАХ ГОЛОВнОГО МОЗГАПрокудин М.ю
Results of own investigations and literature review on clinical symptomatology of temporal epilepsy seizures are represented in the article. Analysis of 63 seizures in 32 patients showed that often during temporal epilepsy initial implications of seizures like aura, oral alimentary and hand automatisms, discontinuation of activities are present. High prognostic value for determination of epileptiform site lateralization in temporal epilepsy has combination of following clinical symptoms: automatism of hand at side of epileptogenic site and dystonic hand placement at the opposite side. Although, none of the clinical symptom alone can reflect epileptogenic site localization with absolute accuracy.
The effectiveness of the surgical removal of glial tumors of the brain largely depends on the visualization of the malignant growth loci. The amino acid 5-aminolevulinic acid, which induces the accumulation of protoporphyrin IX in tumor cells, is used for these purposes. It is detected by the red fluorescence that characterizes porphyrins. Various methods are used for fluorescence visualization. This paper compares them, using test solutions with various concentrations of coproporphyrin III. The results showed that methods in which the exciting radiation is completely blocked are more sensitive by a factor of 4.3-4.7 by comparison with the traditional method, in which part of the exciting radiation is used to visualize the entire operating field in reflected blue light. Either coherent or incoherent light sources can be used to implement the new approach, with the former being preferable. The advantages are illustrated with examples of clinical studies. (C) 2017 Optical Society of America
Cryosurgical method is used in treatment of patients with glial tumors which localized in depth and functionally meaningful brain areas. These patients are generally considered as inoperable and receive conservative treatment. Their prognosis has become worse as compared to the patients whose brain tumor is available for surgical removal. The authors used a multiway stereotactic destruction of tumors by cryosurgical cannula, which is inserted in bone cutter opening using manipulator. MR-imaging and PET/CT of brain were applied for stereotactic guidance. The majority of patients who underwent this operation didn’t noticed any loss of quality of life. The rates of survival were higher than corresponding indicators for patients who were treated only by chemo- or radiation therapy and the rates were equal to the patients underwent the radical operations. Thus, the multiway stereotactic cryodestruction is a new, safe and effective method of surgical treatment for the patients with tumor localization in such areas, that their location blocked an application of traditional surgical removal by open method.
Cryosurgical method is used in treatment of patients with glial tumors which localized in depth and functionally meaningful brain areas. These patients are generally considered as inoperable and receive conservative treatment. Their prognosis has become worse as compared to the patients whose brain tumor is available for surgical removal. The authors used a multiway stereotactic destruction of tumors by cryosurgical cannula, which is inserted in bone cutter opening using manipulator. MR-imaging and PET/CT of brain were applied for stereotactic guidance. The majority of patients who underwent this operation didn’t noticed any loss of quality of life. The rates of survival were higher than corresponding indicators for patients who were treated only by chemo- or radiation therapy and the rates were equal to the patients underwent the radical operations. Thus, the multiway stereotactic cryodestruction is a new, safe and effective method of surgical treatment for the patients with tumor localization in such areas, that their location blocked an application of traditional surgical removal by open method.