Structural or post-traumatic epilepsy often develops after brain tissue damage caused by traumatic brain injury, stroke, infectious diseases of the brain, etc. Most often, between the initiating event and epilepsy, there is a period without seizures—a latent period. At this time, the process of restructuring of neural networks begins, leading to the formation of epileptiform activity, called epileptogenesis. The prediction of the development of the epileptogenic process is currently an urgent and difficult task. MicroRNAs are inexpensive and minimally invasive biomarkers of biological and pathological processes. The aim of this study is to evaluate the predictive ability of microRNAs to detect the risk of epileptogenesis. In this study, we conducted a systematic search on the MDPI, PubMed, ScienceDirect, and Web of Science platforms. We analyzed publications that studied the aberrant expression of circulating microRNAs in epilepsy, traumatic brain injury, and ischemic stroke in order to search for microRNAs—potential biomarkers for predicting epileptogenesis. Thus, 31 manuscripts examining biomarkers of epilepsy, 19 manuscripts examining biomarkers of traumatic brain injury, and 48 manuscripts examining biomarkers of ischemic stroke based on circulating miRNAs were analyzed. Three miRNAs were studied: miR-21, miR-181a, and miR-155. The findings showed that miR-21 and miR-155 are associated with cell proliferation and apoptosis, and miR-181a is associated with protein modifications. These miRNAs are not strictly specific, but they are involved in processes that may be indirectly associated with epileptogenesis. Also, these microRNAs may be of interest when they are studied in a cohort with each other and with other microRNAs. To further study the microRNA-based biomarkers of epileptogenesis, many factors must be taken into account: the time of sampling, the type of biological fluid, and other nuances. Currently, there is a need for more in-depth and prolonged studies of epileptogenesis.

In pediatric practice, epilepsy holds one of the leading places among neurological pathologies. Along with seizures, a child's intellectual impairment lowering quality of life plays a crucial role in social disintegration. Cognitive impairments occuring in idiopathic generalized epilepsies (IGE) and self-limited epilepsy with centrotemporal spikes (SeLECTS) considered benign have been widely investigated. However, available data suggest that such disorders result in multiple persistent alterations in the cognitive sphere. In this case, features of the epilepsy etiopathogenesis account for disease early onset and profoundly remodeled structures involved in the implementation of cognitive functions. Current review is aimed to summarizing data regarding developmental mechanisms and range of cognitive impairment in IGE and SeLECTS.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: “proteomic”, “mass-spectrometry”, “protein expression”, “temporal lobe epilepsy”, and “biomarkers”. Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.

Background: Epilepsy is a group of disorders characterized by a cluster of clinical and EEG signs leading to the formation of abnormal synchronous excitation of neurons in the brain. It is one of the most common neurological disorders worldwide; and is characterized by aberrant expression patterns; both at the level of matrix transcripts and at the level of regulatory RNA sequences. Aberrant expression of a number of microRNAs can mark a particular epileptic syndrome; which will improve the quality of differential diagnosis. Materials and Methods: In this work; the expression profile of six microRNAs was analyzed: hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; hsa-miR-132-3p; hsa-miR-155-5p; and hsa-miR-206-5p in the blood plasma of patients suffering from temporal lobe epilepsy (n = 52) and juvenile myoclonic epilepsy (n = 42); n—amount of participants; in comparison with healthy volunteers. The expression analysis was carried out using RT-PCR. Mathematical processing of the data was carried out according to the Livak method. Results: A statistically significant change in the expression of hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; and hsa-miR-132-3p was found. An increase in the expression of hsa-miR-134-5p and hsa-miR-122-5p was registered in the group of patients with temporal lobe epilepsy compared to the control; as well as an increase in the expression of hsa-miR-132-3p and hsa-miR-106b-5p in the juvenile myoclonic epilepsy group compared to the control. hsa-miR-122-5p; 106b-5p; 132-3p are also able to discriminate groups with different syndromes. Additionally; a number of microRNAs are able to discriminate patients with drug-resistant and drug-sensitive forms of epilepsy from the control; as well as patients with hippocampal sclerosis and patients without hippocampal sclerosis from the control. Conclusion. Our data allow us to propose these microRNAs as plasma biomarkers of various epileptic syndromes

Currently, the problem of effective therapy for drug-resistant epilepsy remains vastly relevant. The severity of drug-resistant epilepsy, remarkable negative social sequelae and sudden death in epilepsy pose a heavy burden on healthcare system. Although many innovative antiepileptic drugs have been developed in recent decades, surgical approach remains the only effective way to treat drug-resistant epilepsy which is coupled to significant health risks and does not guarantee freedom from seizures. The stumbling block in managing this pathology is the lack of knowledge on pathogenetic mechanisms, leaving a significant proportion of patients without quality medical care. There are different viewpoints on developing drug resistance in epilepsy, which are characterized by multilayered and overlapping molecular disease bases. The review presents the analysis of the existing hypotheses regarding the mechanisms underlying drug resistance development in epilepsy.

To date, despite the complexity and risks of not removing seizures hippocampal resection is the only effective solution to overcome drug resistance in epilepsy. Recently, a significant amount of data has been accumulated on the mechanisms of drug resistance development, which allows to develop innovative strategies to overcome it. New antiepileptic drugs have been emerging, directly aimed at acting on disease etiological substrate (many of them are at the stage of clinical trials). Targeted therapy have been extensively introduced, and coupled with precision medicine methods can potentially aid in finding a personalized approach to each individual patient. Migraine models also achieve a qualitatively new level, providing researchers an opportunity to develop highly effective systems for identifying previously unknown disease components, as well as assessing an effect of new drugs. The aim of this review was to highlight current approaches to the treatment of epilepsy and overcoming drug resistance.