EDITORIAL ARTICLES
Currently, the number of antiepileptic drugs (AEDs) has been growing. While choosing the most optimal AEDs by criteria of their efficacy, tolerability and retention time on therapy, many clinical factors, individual biological characteristics of any certain patient, as well as socio-economic aspects should be taken into account, including those associated with the burden on the health care system. In practice, a doctor is primarily focused on the best clinical result while health care is obliged to take costs into account. Calculating the ratio of benefits and costs associated with pharmacotherapy is not complete without comparing the cost of original and reproduced AEDs. For many, sometimes very weighty, reasons, an idea that the original AEDs are preferable in terms of clinical expectations from their use with a significant economic disadvantage (cost) has been established. In this paradigm, reproduced AEDs are always perceived as a compromise in which an acceptable result can be obtained at moderate cost, which is true for the generalized group of reproduced AEDs. However, there are many examples when AEDs do not differ from the reference agents. In particular, Seizar from the Alkaloid company (Republic of North Macedonia) has been recently in wide use in Russia as an alternative to the original lamotrigine. On October 5–6, 2021, the II International Conference “Epilepsy and Women” was held in Belgrade, wherein the leading experts from Serbia and Russia presented reports on the effectiveness and quality of care for epilepsy at the symposiums “Childhood with Seizar”, “Preparing for adulthood with Seizar”, “Assessment of the benefits and prospects of using Seizar at all stages of women’s life with epilepsy”, “Epilepsy and comorbidity – universal opportunities”. Here, we summarize selected messages presented during the conference.
ORIGINAL ARTICLES
Background. Detected temporal lobe focal cortical dysplasia (FCD) often results in developing drug-resistant epilepsy requiring surgical treatment. In turn, temporal lobectomy, despite its high efficiency, can cause a certain deficit associated with direct or indirect damage to the brain pathways.
Objective: to describe the main anatomical features of temporal lobe brain pathways and clinical outcomes of surgical treatment of drug-resistant epilepsy that developed in temporal lobe FCD.
Material and methods. A retrospective analysis of the treatment of 14 patients with drug-resistant structural focal epilepsy (temporal lobe FCD) who underwent surgery (anterior temporal lobectomy) was carried out. To localize the epileptogenic zone, specialists of the multidisciplinary group performed a comprehensive presurgical examination in all participants. The surgical material was examined by a neuromorphologist, the diagnosis was verified. In the postoperative period, patients underwent a series of control examinations at standard time points (after 3, 6, 12, 36 months). The minimum follow-up period was 12 months. As a part of the anatomical study, 6 brain hemispheres were investigated prepared for the white matter fibers dissection using Klingler technique. The main pathways that run within or near the temporal lobe were selectively examined: the lower longitudinal, medial longitudinal, lower fronto-occipital and uncinate fasciculi.
Results. In the postoperative period, no complications were observed in 14.3% of patients after 4 cm resection of the temporal lobe subdominant hemisphere. Speech disorders (mostly transient) were detected in 35.7% of the subjects, visual field disorders (mainly transient) – in 21.4%, neuropsychiatric disorders – in 43.9%. Overall seizure control: 93% of patients achieved class I according to Engel Epilepsy Surgery Outcome Scale.
Conclusion. Anterior temporal lobectomy can be considered as a highly effective method of surgical treatment of drug-resistant structural focal epilepsy with a high rate of achieving control over epileptic seizures in the postoperative period. However, the mandatory conditions for maintaining the quality of life for patients after such a surgical intervention include preoperative analysis of the risk of adverse effects performed by a multidisciplinary team as well as postoperative management and rehabilitation.
Background. Juvenile myoclonic epilepsy (JME) is the most common type of idiopathic generalized epilepsy with onset in adolescence and adulthood. During medical genetic counseling in probands with JME, aggravated epilepsy-related heredity is often detected. However, specific genetic variants of JME predisposition remain inconclusive. The use of contemporary methods of genetic analysis, particularly whole-exome and whole-genome sequencing, allows to detect, confirm and strengthen an association of any certain pathological phenotype with one or another pathogenic variant in a number of genes.
Objective: to analyze the results of whole exome sequencing in patients with JME and seek for JME associations.
Material and methods. The study included 7 patients with established JME diagnosis and 1 proband child without clinical signs of epilepsy. Whole exome sequencing was carried out by using MiSeq (Illumina, USA), bioinformatics analysis was performed on the Genomenal platform (Novel Software Systems, Russia).
Results. Heterozygous carriage of pathogenic variants in the genes of recessive diseases was revealed: SACS, AHI1, CEP164, ANO10, RMND1, POMGNT1, FLG, ACTB. The analysis of the identified genetic variants in the patients examined showed no association with the clinical picture of the disease. Heterozygous missense mutations in CLCN2, EFHC1, JRK, ME2 genes and frameshift mutation in the CACNB4 gene were detected.
Conclusion. In recent years, significant efforts were made to identify genes which predispose to JME. During our study, monogenic and/or polygenic pathogenic variants in patients with JME and a child of proband with JME were not identified. The high genetic heterogeneity of JME can explain numerous unsuccessful attempts to find genes predisposing to JME. Further research is necessary to confirm variants associated with potential JME. Advances in genomic technology can expand our understanding of the genetics of this pathology.
Objective: to determine the indigenous practices that are used to manage epilepsy in South Africa rural communities.
Material and methods. A qualitative, ethnographic technique that was exploratory and descriptive was used. Purposive and snowball sampling were used to select a group of 17 traditional healers for in-depth interviews at their homes. The data were analysed through the open coding data analysis method.
Results. The traditional healers had different perspectives on the origins and treatment plans of epilepsy based on their knowledge of the disease and their training. They used plants and alternative measures, even though western medicine was still used. The traditional healers’ status in rural communities was acceptable and their treatment modalities were preferred.
Conclusion. Traditional healers and primary health care providers must work collaboratively to educate communities on the importance of integrating biomedicine and indigenous practices, as traditional healers had strong inspirations from the communities.
SCIENTIFIC SURVEYS
Lennox–Gastaut syndrome is an epileptic encephalopathy with onset in childhood. The classical triad of diagnostic criteria is well known: 1) presence of various types of refractory epileptic seizures (tonic, atypical absences, myoclonic, tonic/atonic drop attacks, generalized tonic-clonic, focal); 2) cognitive disorders with frequent behavioral disorders (not always evident by the beginning of epileptic seizures); 3) generalized, slow (≤2.5 Hz) spike-wave activity of wakefulness and generalized paroxysmal fast activity on sleep electroencephalogram. Despite the seizure onset usually occurring before the age of 8 (peak at 3–5) years old, the Lennox–Gastaut syndrome is often featured with a lifelong course. Many patients with this syndrome suffer from refractory epilepsy in adulthood, however, not always being provided a proper syndromological diagnosis. Expanding the criteria to diagnose the Lennox–Gastaut syndrome discussed here would allow to choose a proper treatment algorithm. Rufinamide is the drug of the second choice in the adjunctive therapy of epileptic seizures associated with Lennox–Gastaut syndrome. However, a pediatric-to-adult clinic transition of patients with Lennox–Gastaut syndrome may pose some obstacles. Herein, an effective patient management requires not only seizure control, but also improvement of patient's quality of life by influencing cognitive and behavioral issues, sleep disorders, disability (both physical and social), educational problems and employment.
The high prevalence of pharmacoresistant epilepsy requires the use of nonpharmacological, including surgical approaches to the treatment of this disease. The surgical methods currently used to treat epilepsy (resection, stimulation, and disconnection) carry certain risks of developing intra- and postoperative complications. The technique of magnetic resonance-guided focused ultrasound (MRgFUS) may be an alternative to traditional neurosurgical interventions. Currently, MRgFUS is successfully used in the treatment of essential tremor and Parkinson’s tremor. As the literature data show, the use of focused ultrasound is a promising method in the treatment of epilepsy. It has been reported about successful FUS application for neuromodulation in animal epilepsy models. Studies related to FUS ablation of epileptogenic foci, neuromodulation in humans with epilepsy are currently underway. The technique of locally increased permeability of the blood-brain barrier after FUS, used for the treatment of brain oncological diseases and neurodegenerative disorders is also of interest in the targeted delivery of antiepileptic drugs. However, some experimental works are contradictory, and the lack of large-scale studies of MRgFUS in patients with epilepsy requires further investigation of this technique and its effectiveness.
Background. Epilepsy is a common disease in children and adults, requiring long-term or lifelong use of antiepileptic drugs (AEDs) in 60% of cases. Enzyme-inducing and enzyme-inhibiting AEDs may have a negative effect on vitamin D metabolism. However, at present, standard treatment protocols for patients with epilepsy include no nutrients and vitamin-mineral vitamin D containing complexes.
Objective: to analyze studies on the prevalence of vitamin D deficiency induced by AEDs intake in patients with epilepsy.
Material and methods. The search for full-text publications in Russian and English was carried out in еLibrary, PubMed/ MEDLINE, ClinicalKey, Google Scholar databases, covering the last five years. The analysis included 9 domestic and 54 foreign epidemiological studies assessing prevalence of AED-induced vitamin D deficiency and, consequently, altered bone mineralization and osteomalacia/osteoporosis.
Results. Both in children and adults, the prevalence of AED-induced vitamin D deficiency reaches 40% and even higher. The region of residence of patients with epilepsy does not significantly affect this indicator. Impaired bone mineralization is associated with AED-induced vitamin D deficiency and requires the inclusion of vitamin D in the protocols of disease-modifying epilepsy therapy in children and adults.
Conclusion. The results of the review showed high relevance of the discussed interdisciplinary problem and need to introduce laboratory screening of vitamin D deficiency among pediatric and adult patients with epilepsy.

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