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Our previous studies showed that in patients with brain diseases, neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in the control of neuronal networks in an epileptic brain, we aimed to assess the GDNF levels in LF and BS as well as the BDNF and the hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (FE) and epilepsy and comorbid depression (FE + MDD) and to compare them with those of patients with major depressive disorder (MDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in FE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. GDNF concentrations in LF and BS positively correlated in HC, but not in patient groups. BDNF level was lower in BS of patients compared with HC and higher in FE + MDD taking valproates. A reduction in the GDNF level in LF might be an important biomarker of FE. Logistic regression models demonstrated that the probability of FE can be evaluated using GDNF in LF and BDNF in BS; that of MDD using GDNF in LF and cortisol and TNF-α in BS; and that of epilepsy with MDD using GDNF in LF and TNF-α and BDNF in BS.

Objective: To assess the morphological features of the brain structures in patients with temporal lobe epilepsy and comorbid depression., Material and Methods: From 1 January 2017 to 31 December 2020, we studied 80 patients with temporal lobe epilepsy (aged 18-60 years, 38 of whom had comorbid depression) and 48 healthy subjects of comparable age. Magnetic resonance imaging (MRI) of the brain was performed using the epilepsy protocol in a scanner with a magnetic field strength of 1.5 T. Focal temporal lobe epilepsy was diagnosed by neurologists (epileptologists) specialising in epilepsy according to the International League Against Epilepsy (ILAE) classification of epilepsy. Psychiatrists assessed the presence and severity of depressive disorders by clinical interview and by participants' scores on the Beck Depression Inventory (BDI-II). MRI data were processed using FreeSurfer 6.0 software to determine volumes of subcortical structures and thicknesses of cortical structures. At the group level, analysis of covariance with Holm-Bonferroni correction was used as the statistical method., Results: Morphometric analysis revealed a significant decrease in the volume of the thalamus bilaterally and the brain stem and an increase in the volume of the choroid plexus in the left hemisphere, as well as a significant decrease in the thickness of the entorhinal cortex, temporal pole and isthmus of the cingulate gyrus in the left hemisphere and middle temporal gyrus and inferior temporal gyrus in the right hemisphere in patients with epilepsy compared to healthy controls. No association was found between the presence of depression and significant structural changes on MRI., Conclusion: The data obtained suggest an effect of temporal lobe epilepsy, but not comorbid depression, on the morphology of brain structures.

Psychogenic non-epileptic seizures (PNES) are paroxysmal conditions that resemble epileptic seizures, but are not accompanied by epileptiform activity on the electroencephalogram and are not associated with other neurological or somatic disorders. Unrecognized PNES places a heavy burden on the patient and family, and on the health care system. Among many possible combinations of PNES with psychiatric disorders, autistic spectrum disorders are the least studied. This article presents a case of a 19-year-old female patient with autistic spectrum disorder and paroxysmal events and the presence of potentially epileptogenic changes in the brain. A multidisciplinary approach made it possible to diagnose PNEP in the patient.

Background: The hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes and neurotrophic factor systems are involved in pathogenesis of both epilepsy and depressive disorders. The study aimed to explore these systems in patients with focal epilepsy (PWE, n = 76), epilepsy and comorbid depression (PWCED n = 48), and major depressive disorder (PWMDD, n = 62) compared with healthy controls (HC, n = 78)., Methods: Parameters of the HPA axis, neurotrophic factors, and TNF-α were measured in blood serum along with the hemogram., Results: Serum cortisol level was augmented in PWE, PWCED, and PWMDD compared with HC and was higher in PWMDD than in PWE. Serum cortisol negatively correlated with Mini-Mental State Examination (MMSE) score in PWE, and positively with depression inventory-II (BDI-II) score in PWMDD. Only PWMDD demonstrated elevated plasma ACTH. Serum TNF-α, lymphocytes, and eosinophils were augmented in PWMDD; monocytes elevated in PWE and PWCED, while neutrophils were reduced in PWE and PWMDD. Serum BDNF was decreased in PWE and PWCED, CNTF was elevated in all groups of patients. In PWE, none of above indices depended on epilepsy etiology., Conclusions: The results confirm the involvement of HPA axis and inflammatory processes in pathogenesis of epilepsy and depression and provide new insights in mechanisms of epilepsy and depression comorbidity.

The present review discusses the comorbidity of psychogenic non-epileptic seizures (PNES) with other mental disorders. Data on the prevalence of mood, anxiety, psychotic and personality disorders are presented. The role of traumatic experience in the development of PNES is described. Special attention is given to PNES as an independent nosological entity and its place in the modern classifications of mental disorders.

Objective: To evaluate brain-derived neurotrophic factor (BDNF) level in blood serum (BS) and lacrimal fluid (LF) of people with epilepsy (PWE)., Methods: It was a case-control study of 72 consecutive patients with focal epilepsy (cases, Epilepsy group) and 60 age- and gender-matched healthy volunteers (controls). Based on comorbid depression, two subgroups of PWE were formed. BDNF level was measured by enzyme-linked immunosorbent assay (ELISA) in BS and LF., Results: Compared to controls, BDNF level (pg/mL) in PWE was lower both in BS (22,520 ± 3810 vs. 26,360 ± 3090, P < 0.000) and in LF (100.8 ± 23.3 vs. 113.4 ± 19.3, P = 0.001). However, no significant correlation was found between BDNF level in BS and LF either in the Epilepsy group or in controls. No impact of comorbid depression on BDNF level was found either in BS or LF of PWE. We revealed a higher BDNF level in LF of men as compared to women in controls and a similar non-significant trend in PWE. Higher BDNF level in BS of PWE receiving valproates versus other AEDs was found, however, a relatively small number of observations and use of polytherapy in most cases should be taken into account., Significance: In patients with focal epilepsy, BDNF level is decreased both in BS and LF, though with no correlation between them. No association of BDNF levels with age and epilepsy characteristics, as well as the occurrence of depression, was found. Low BDNF level in LF could be considered as a non-invasive biomarker of focal epilepsy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epilepsy surgery is effective in 30-82% of patients with drug-resistant epilepsy. However, risk factors of unfavorable outcomes after epilepsy surgery require further study., Objective: To evaluate risk factors of favorable and unfavorable long-term postoperative outcomes in patients with drug-resistant epilepsy., Material and Methods: Postoperative outcomes in a large cohort of patients with epilepsy are reported for the first time in the Russian Federation. There were 271 patients with drug-resistant scheduled for surgery. Preoperative examination and surgical treatment were carried out between January 1, 2014 and December 12, 2019 at the Evdokimov Moscow State University of Medicine and Dentistry and Sklifosovsky Research Institute for Emergency Care. We used Engel grading system to assess postoperative outcomes after 12, 24, 48 and 60 months. We distinguished favorable (Engel I-II) and unfavorable (Engel III-IV) outcomes and analyzed the factors influencing postoperative results in these patients., Results: There were 319 surgical procedures in 271 patients (217 primary resections, implantation of vagus nerve stimulator in 31 patients, 9 redo resections and 8 radiosurgical procedures). Focal cortical dysplasia (FCD) was found in 162 (60%) patients, «dual pathology» - in 118 (44%) cases. In 12 months after surgery, favorable outcomes (Engel l-II) were observed in 69% of patients ( n =148), after 24 months - in 71% ( n =127) of patients. Postoperative complications occurred in 6 (1.9%) patients. There was no mortality. The earlier onset of epilepsy ( p =0.01), multifocal ( p =0.002) and bilateral lesions ( p =0.0038) were the most significant risk factors of unfavorable postoperative outcomes., Conclusion: Surgical resection is effective approach for drug-resistant epilepsy.

The review provides epidemiological data and discuss the associated burden of non-epileptic seizures (PNES). Data on the prevalence, socio-demographic and clinical risk factors for the development of PNES are presented. The hypotheses of the PNES origin, including the contribution of psychological trauma, are considered. We also describe contemporary methods for differential diagnosis of epileptic seizures and PNES, including biomarkers and the use of diagnostic questionnaires. Special attention is given to the issues of the psychiatric comorbidity of PNES.

There are as yet no data pointing to any increase in the incidence of the novel coronavirus infection (COVID-19) or a more severe course of illness in patients with epilepsy. However, considering the high prevalence of epilepsy in patients over 60 years of age, the high comorbidity of epilepsy and a whole series of somatic diseases, and the need to maintain the opportunity for constant access to antiepileptic medications and follow-up of epilepsy patients, we can expect a whole set of difficulties in the management of these patients in the conditions imposed by the COVID-19 pandemic. This article addresses the main principles of the management of epilepsy patients in the conditions of the COVID-19 pandemic: the need to follow regimes; preservation of regular and continuous taking of antiepileptic drugs, including consideration of interdrug interactions; and switching patients to i.v. forms of antiepileptic drugs where necessary., (© Springer Science+Business Media, LLC, part of Springer Nature 2021.)

There is currently no data on the increased incidence of new coronavirus infection (COVID-19) or on the more severe course of the disease in patients with epilepsy. However, given the high prevalence of epilepsy among patients after age 60, an increased burden of somatic comorbidities among people with epilepsy, as well as the need of continuous access to antiepileptic drugs (AED) and care for patients with epilepsy, there are a number of important concerns in time of regarding the management of epilepsy during COVID-19 pandemic. The article discusses the main principles of epilepsy management during the COVID-19 pandemic: the need to comply with the regime; the importance of AED adherence, taking into account drug-drug interactions; switching patients to intravenous AED forms if necessary.

Aim: To assess the psychometric properties of the Stigma Scale of Epilepsy, a short simple to complete questionnaire to quickly and reliably determine the presence and the level of perceived stigma in a particular patient, as well as to assess the prevalence, socio-demographic, clinical and socio-psychological factors associated with this phenomenon., Material and Methods: The study included 398 patients with epilepsy. Exploratory (EFA) and confirmatory factor analysis (CFA) were used to assess the psychometric characteristics of the scale., Results and Conclusion: The EFA showed a two-factor scale structure explaining 57.25% of the variance. Values of GFI 0.948, CFI 0.927 and RMSEA 0.057 after the data correction show a good conformity of the model to the empirical data. Cronbach's alpha coefficient was 0.862 for the scale, 0.815 for factor 1, 0.809 for factor 2, which indicates a high consistency of both the entire scale and its subscales. The Russian-language variant of the Stigma Scale of Epilepsy is a short, economical to use tool with good psychometric properties for assessing perceived stigma in patients with epilepsy.

Aim: To examine alterations of functional connectivity (FC) of the brain in patients with frontal and temporal lobe epilepsies., Material and Methods: Forty-three patients, aged 18-55 years, including 32 with temporal lobe epilepsy (TLE) and 11 with frontal lobe epilepsy (FLE), and 32 age/gender-matched healthy controls (HC) underwent structural and functional MRI on 1,5 T scanner. Imaging data were further analysed for functional connectivity characteristics by seed-based and ICA analyses., Results: Most prominent in the TLE group, was a decrease in FC of insula and peri-insular cortical regions compared to HC. These alterations of FC in left-side TLE were significant on the left. An increase of FC between dorsal part of attention resting network and regions of temporal and parietal cortices characterized right-side TLE. In addition, TLE group had decreased FC between anterior cingulate and basal ganglia. All the significant alterations of FC in FLE related to increased FC in patients compared to HC. FC of temporal regions was altered to a greater extent., Conclusion: Localization and lateralization of seizure focus determines the alterations of brain FC in patients with focal epilepsy.

This review focuses on the role of mental and cognitive disorders in the prognosis for surgical treatment of pharmacoresistant epilepsy. The authors analyze historical aspects of the surgical treatment of epilepsy and present current data on the prognosis of operative intervention with respect to seizure control, cognitive functioning, and psychiatric disorders. The psychiatrist's role in the structure of preoperative and postoperative management of patients is considered.

The results of studies on the prevalence of suicidal behavior in patients with epilepsy are discussed in the article. The reasons for the high incidence of suicides among patients with epilepsy are given, with special attention paid to social, demographic, clinical and pathopsychological risk factors. Existing gaps in our knowledge about suicidal behavior in patients with epilepsy are analyzed.

The article considers the problem of social restrictions caused by epilepsy. Information on historical aspects and discrimination of patients with epilepsy is presented. The authors consider factors influencing marital status of patients in different countries and present information on the differences in medical restrictions to driving in different countries and in the Russian Federation. Employment status of patients with epilepsy, restrictions related to objective reasons and attitudes of patients and others toward epilepsy are elucidated.

Aim: To compare neuronet restructuring in focal and generalized epilepsy., Material and Methods: Seventy-seven patients, aged from 18 to 65 years, with the diagnosis of epilepsy, including 63 patients with focal epilepsy and 14 with generalized epilepsy, were examined. A control group included 23 healthy people. Neuronet restructuring was studied using fMRI., Results and Conclusion: According to resting state fMRI, there were between-group differences in spatial organization (activity map) of the brain structures as well as in the results of cross-correlation analysis of interaction maps of resting-state networks. It has been concluded that functional restructuring in connectomes in focal and generalized epilepsy have the opposite patterns of disorganization (toward increase or decrease) in most structures studied though there are structures with the same direction of connectivity changes.

Development of new antiepileptic drugs (AED) does not stop due to the fact that the number of patients with pharmacoresistant epilepsy remains at about 30%. One of the newest AEDs is perampanel (PER), a selective, non-competitive AMPA receptor antagonist to target post-synaptic glutamate transmission. PER is approved in the Russian Federation as adjunctive treatment for focal seizures with or without secondarily generalized seizures and for primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE) in patients with epilepsy aged ≥12 years. The drug is effective and well-tolerated in the dose of 4-8 mg/day, and most side effects are dose-dependent. The high efficacy of PER combined with the good tolerability, absence of life-threatening adverse reactions and convenient intake allow us to recommend PER as the first choice additional drug in treatment of patients with epilepsy.

Numerous trials of last years confirm the bilateral link between depression and epilepsy with mutual complication of both diseases. Depression increases the risk of the first unprovoked paroxysm, worsens the compliance of epileptic patients, leads to decrease of the response both to therapeutic and surgical treatment and to increase of side effects of antiepileptic drugs. Depression is associated with high risk of suicidal behavior and reduces the quality of life level. Depression in epileptic patients is characterized by atypical clinical course in most cases what makes its diagnostics difficult and becomes the reason of the absence of the necessary pharmacologic and psychotherapeutic treatment. All of the above creates significant economical burden for the community because the epileptic patient with comorbid depression visits the physicians 2-4 times more often.

We studied changes in the levels of inhibitory and excitatory neurotransmitters in female rat brain structures during different phases of the estrous cycle in health and after creation of a cobalt epileptogenic focus at stage I of epileptogenic system development. The most pronounced shifts were found in the contralateral cortex, where the levels of GABA and glycine decreased significantly during the diestrus-2 phase (corresponding to menstruation), which attests to a convulsive threshold decrease during this period.

An association between a polymorphism of the SCN1 gene, a therapeutical target of lamotrigine, and an effective dose (a blood plasma concentration) of the drug in patients with epilepsy has been studied. Fifty patients with different forms of epilepsy have been genotyped for the SCN1 IVS5N+5 G>A polymorphism using polymerase chain reaction. The distribution of allelic variants was as follows: 23 patients had the mutant homozygous genotype (V/V), 20 - the heterozygous genotype Wt/V and 7 were homozygous for the wild allele (Wt/Wt). Mean lamotrigine doses were 85,7+/-7,4 mg/day for carriers of the Wt/Wt genotype, 113,75+/-7,13 mg/day for the Wt/V genotype and 142,4+/-15,43 mg/day for the V/V genotype. Peak plasma concentrations corresponded to effective doses were 0,6+/-0,065 mg/ml for Wt/Wt, 0,96+/-0,1 mg/ml for V/V and 0,72+/-0,1 mg/ml for Wt/V. The hypothesis on the association between the SCN1 IVS5N+5 G>A polymorphism and the effective dose (concentration) of lamotrigine was confirmed. The significantly higher frequency of the SCN1A mutation in the group of patients with epilepsy compared to the control group of Caucasians (45,5 and 21,3%, respectively) implies that this polymorphism may contribute to the pathogenesis of epilepsy.