Dissimilar Changes in Serum Cortisol after Epileptic and Psychogenic Non-Epileptic Seizures: A Promising Biomarker in the Differential Diagnosis of Paroxysmal Events?

The hypothalamic-pituitary-adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.

Post-stroke epilepsy: From clinical predictors to possible mechanisms.

BACKGROUND: Stroke is the most common cause of newly diagnosed epilepsy in the elderly, ahead of degenerative disorders, brain tumors, and head trauma. Stroke accounts for 30-50% of unprovoked seizures in patients aged ≥ 60 years. This review discusses the current understanding of epidemiology, risk factors, mechanisms, prevention, and treatment opportunities for post-stroke epilepsy (PSE). METHODS: We performed a literature search in the PubMed and Cochrane Library databases. The keywords "stroke, epilepsy", "stroke, seizure", "post-stroke seizure", "post-stroke epilepsy" were used to identify the clinical and experimental articles on PSE. All resulting titles and abstracts were evaluated, and any relevant article was considered. The reference lists of all selected papers and reference lists of selected review papers were manually analyzed to find other potentially eligible articles. RESULTS: PSE occurs in about 6% of stroke patients within several years after the event. The main risk factors are cortical lesion, initial stroke severity, young age and seizures in acute stroke period (early seizures, ES). Other risk factors, such as a cardioembolic mechanism or circulation territory involvement, remain debated. The role of ES as a risk factor of PSE could be underestimated especially in young age. Mechanism of epileptogenesis may involve gliosis scarring, alteration in synaptic plasticity, etc.; and ES may enhance these processes. Statins especially in the acute period of stroke are possible agents for PSE prevention presumably due to their anticonvulsant and neuroprotection effects. Antiepileptic drugs (AED) monotherapy is enough for seizure prevention in most cases of PSE; but no evidence was found for its efficiency against epileptic foci formation. The growing interest in PSE has led to a notable increase in the number of published articles each year. To aid in navigating this expanding body of literature, several tables are included in the manuscript. CONCLUSION: Further studies are needed for better understanding of the pathophysiology of PSE and searching the prevention strategies.

Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate.

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.

Post-stroke seizures, epilepsy, and mortality in a prospective hospital-based study.

Background and objectives: Post-stroke epilepsy (PSE) is a significant concern in the elderly population, with stroke being a leading cause of epilepsy in this demographic. Several factors have shown consistent associations with the risk of developing PSE, including cortical lesions, initial stroke severity, younger age, and the occurrence of early seizures. The primary objectives of this study were two-fold: (1) to determine the incidence of PSE and (2) to identify the risk factors associated with PSE in a prospective cohort of post-stroke patients. Methods: A prospective single-hospital study was conducted, involving patients diagnosed with acute ischemic and hemorrhagic stroke. The patients were followed up for 2 years (or until death) from the time of admission. Data about seizure occurrence and recurrent stroke were collected. Kaplan-Meyer curves were used for the assessment of PSE incidence and mortality. Possible predictors of PSE and mortality were selected from between-group analysis and tested in multivariable regressions. Results: Our study enrolled a total of 424 patients diagnosed with acute stroke. Among them, 97 cases (23%) experienced early post-stroke seizures, and 28 patients (6.6%) developed PSE. The cumulative risks of developing PSE were found to be 15.4% after hemorrhagic stroke and 8.7% after ischemic stroke. In multivariable fine and gray regression with competitive risk of death, significant predictors for developing PSE in the ischemic cohort were watershed infarction (HR 6.01, 95% CI 2.29-15.77, p < 0.001) and low Barthel index at discharge (HR 0.98, CI 0.96-0.99, p = 0.04). Furthermore, patients who eventually developed PSE showed slower recovery and presented a worse neurologic status at the time of discharge. The in-hospital dynamics of the National Institutes of Health Stroke Scale (NIHSS) were significantly worse in the PSE group compared to the non-PSE group (p = 0.01). Discussion: A higher proportion of cases experienced early seizures compared to what has been commonly reported in similar studies. Watershed stroke and low Barthel index at discharge were both identified as independent risk factors of PSE in ischemic strokes, which sheds light on the underlying mechanisms that may predispose individuals to post-stroke epilepsy after experiencing an ischemic stroke.

Incidence, severity and outcomes of COVID-19 in age and gender matched adults with and without epilepsy in Moscow: A historical cohort study.

OBJECTIVE: We hypothesized that PWE have an increased risk to acquire COVID-19. This was a historical cohort study to determine COVID-19 incidence, severity, mortality and risk factors in adults with active epilepsy (PWE) compared to residents of Moscow without epilepsy matched by age, gender, and region of residence - Moscow Community Comparisons (MCC). METHODS: Subjects were derived from a cohort of adult PWE and a cohort of age- and gender-matched population-based MCC without epilepsy identified in 2018. Incidence of COVID-19 was compared in each cohort from 01.03.2020 through 28.02.21. Influence of age, gender, comorbidities, and for the PWE cohort, epilepsy type, seizure frequency, and number/class of antiseizure medications was evaluated using Pearson's chi-squared test and logistic regression analysis. RESULTS: We found 887 COVID-19 positive people in the two cohorts: 156 in PWE (51.8 ± 19.7 years) and 731 in MCC (52.0 ± 17.3 years,). COVID-19 incidence was lower in PWE: 13.8 % versus 18.7 % in MCC (p = 0.0002). In PWE no specific epilepsy related variables influenced incidence. Despite no difference in severity distribution in PWE versus MCC, hospitalization rate (37.6 % versus 25.5 %, p = 0.002), disease duration (57.1 % versus 47.1, p = 0.023), and mortality (10.9% versus 4.2 %, p = 0.0009) were significantly higher in PWE. Age and number of comorbidities significantly influenced COVID-19 incidence, severity, duration, and outcomes in both cohorts. SIGNIFICANCE: Incidence of COVID-19 in PWE in Moscow was significantly lower compared to MCC. Age and comorbidities were strongly associated with severity, duration and outcomes of COVID-19 for all infected persons. Higher mortality in PWE may be explained by a higher number of comorbidities.

Self-injurious thoughts and behaviors in Russian patients with epilepsy: A prospective observational study.

OBJECTIVE: A two-stage study aimed to estimate the prevalence of different types of self-injurious behaviors (suicidal ideation (SI), suicide attempts (SA), and nonsuicidal self-injury (NSSI)) in Russian patients with epilepsy (PWE), to identify factors associated with such behaviors, and to assess their impact on 3-year mortality. METHODS: We enrolled 459 consecutive adult PWE from two level 2 outpatient epilepsy centers in Moscow. The study consisted of two phases - first, we assessed all demographic and clinical characteristics and patients' history of SI, SA, and NSSI. In the second phase, three years after the initial screening, we analyzed patients' medical records to assess how self-injurious thoughts and behaviors were related to actual mortality. RESULTS: In our sample, the total lifetime and 12-month prevalence of SI was 20% and 5.7%, of SA was 8.3% and 0.7%, and of NSSI was 15.3% and 2.8%, respectively. We found no differences between deceased and alive PWE regarding lifetime and 12-month prevalence of SI, SA, and NSSI. Higher seizure frequency, lifetime NSSI and lifetime diagnosis of mental disorder were associated with SI, whereas traumatic brain injury (TBI), substance abuse, and NSSI were associated with SA in PWE. SIGNIFICANCE: Our study adds to the existing data on the prevalence of different types of suicidal behaviors in PWE and advances research on NSSI in this population. However, more research is needed on the long-term consequences of different types of self-injurious behaviors.

Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression.

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.

Not always that EASI: Validating the Russian version of the epilepsy anxiety survey instrument and its brief counterpart.

OBJECTIVE: To develop a Russian version of The Epilepsy Anxiety Survey Instrument (EASI) and assess its psychometric properties in a Russian sample of patients with epilepsy (PWE). To compare the brief version of EASI with the General Anxiety Disorder-7 (GAD-7) - the most common tool for a rapid anxiety screening. METHODS: The study sample consisted of 181 consecutive Russian-speaking PWE. The Mini-International Neuropsychiatric Interview was used as a gold standard for diagnosing anxiety disorders. All patients completed the set of questionnaires - the Russian version of the GAD-7, The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and the EASI. Internal reliability of the EASI and brEASI, convergent and divergent validity of the brEASI with the GAD-7 and the NDDI-E, and factor structure assessment were performed. RESULTS: Among 33.7% of patients with epilepsy diagnosed with any anxiety disorder, 16% had panic disorder, 10.5% had agoraphobia, 8.3% had social anxiety disorder, 21.0% had generalized anxiety disorder, and 13.3% had several comorbid anxiety disorders. The EASI factor structure differed from the original, revealing an additional factor with two items. Nevertheless, the brief version (brEASI) showed excellent screening properties - the AUC to detect any anxiety disorder was 0.916 with the optimal cutoff point > 7 points. CONCLUSION: The brEASI performed better than the GAD-7 in our sample and, therefore, may be considered a first-line screening tool for anxiety disorders in PWE.

Increased ciliary neurotrophic factor in blood serum and lacrimal fluid as a potential biomarkers of focal epilepsy.

PURPOSE: To evaluate ciliary neurotrophic factor (CNTF) level in blood serum (BS) and lacrimal fluid (LF) of people with epilepsy (PWE). METHODS: A case-control study of 72 consecutive patients with focal epilepsy (cases, epilepsy group) and 60 age- and gender-matched healthy volunteers (controls) was performed. Based on comorbid depression, two subgroups of PWE were formed. CNTF level was measured by an enzyme-linked immunosorbent assay (ELISA) in the BS and LF. For measurements of low CNTF levels in the BS, the methodology previously improved by the authors was applied. RESULTS: As compared to controls, CNTF level (pg/mL) in PWE was increased both in the BS (7.0±2.9 vs. 3.7±2.0, P<0.000) and in LF (34.0±8.0 vs. 30.6±4.8, P=0.005). No significant correlation was found between CNTF level in the BS and LF either in PWE or in controls. No impact of comorbid depression or any demographic or clinical parameters studied on CNTF level in the BS or LF of PWE could be detected. CONCLUSIONS: In patients with focal epilepsy, CNTF level is increased both in the BS and LF, though without correlation between them. No association of CNTF levels with age, gender, or clinical parameters, as well as depression occurrence, was found. High CNTF levels in the BS and LF could be considered as non-invasive biomarkers of focal epilepsy.

Differential diagnosis between epileptic and psychogenic nonepileptic seizures through conversational analysis: A blinded prospective study in the Russian language.

The current study examined the validity of conversational analysis (CA) in Russian patients with seizures, using a scoring table for the Simplified Linguistic Evaluation (SLE). The study sample was composed of 12 adult participants suffering either from epilepsy (ES) or psychogenic nonepileptic seizures (PNES) recruited in the Moscow Research and Clinical Center for Neuropsychiatry. Definitive diagnosis was established only after a habitual event was captured onvEEG. All participants with PNES or ES and at least one mental disorder underwent a 20-minute-long interview recorded on video. The interview then was evaluated by the external blinded physician already experienced in CA. Finally, that physician filled the SLE, consisting of 5 items analyzing the main characteristics of patient narrations. A score of ≥12 suggested a diagnosis of ES, while a score of <12 suggested a diagnosis of PNES. The blinded evaluator correctly identified 11 out of 12 cases. The concordance between the vEEG diagnosis and the CA diagnostic hypothesis was 91.67%. The sensitivity of the scoring table was 100%, while the specificity was 80%. The positive and the negative predictive values were, respectively, 87.5% and 100%. Our results suggested that the differences in seizure descriptions between patients with PNES and patients with ES are similar across Indo-European language family and are independent of psychiatric comorbidity.

Validation of the Generalized Anxiety Disorder-7 (GAD-7) in Russian people with epilepsy.

OBJECTIVE: To assess the capacity of Generalized Anxiety Disorder-7 (GAD-7) to detect anxiety disorders in a Russian sample of patients with epilepsy and to validate this instrument for rapid screening of anxiety in these patients. METHODS: Study included 233 patients with epilepsy, both inpatients and outpatients. For all patients Mini-International Neuropsychiatric Interview was conducted as a gold standard for diagnosis of mental disorders. All patients also completed the questionnaires - the Russian version of GAD-7 and Hospital Anxiety and Depression Scale (HADS) to assess convergent validity. Chi-square and Fisher's exact tests were used to compare categorical variables, and the Mann-Whitney test was used for the quantitative ones. Internal consistency was assessed using Cronbach's alpha, Cronbach's alpha at point deletion, and corrected point-to-point correlation. ROC analysis was used to evaluate the properties of the GAD-7 to determine anxiety disorders. RESULTS: Among 97 (41.6%) patients with epilepsy diagnosed with any anxiety disorders, 42 (18%) had panic disorder, 37 (15.9%) had agoraphobia, 17 (7.3%) had social anxiety disorder, and 64 (27.5%) had generalized anxiety disorder; 42 patients (18%) showed a combination of several anxiety disorders. The overall GAD-7 score was similar to other epilepsy studies, but higher cutoff scores characterize our sample. The scale performed well in detecting any anxiety disorder with the AUC of 0.866 and the optimal cutoff point > 8 points, and in detecting GAD with AUC = 0.922 and the optimal cutoff point > 9 points, showing overall acceptable sensitivity. CONCLUSION: Russian version of the GAD-7 could be used as a screening tool for any anxiety disorders in PWE with the optimal cutoff score > 8 points.

Brain-derived neurotrophic factor in blood serum and lacrimal fluid of patients with focal epilepsy.

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.

Interictal dysphoric disorder in people with and without epilepsy.

OBJECTIVE: Interictal dysphoric disorder (IDD) has been regarded as an affective disorder occurring only in people with epilepsy (PWE). Data showing similar characteristics and similar prevalence of IDD in patients with migraine and with psychogenic nonepileptic seizures question the epilepsy-specific nature of IDD. The aim of the study was to investigate the nature of IDD in people with prevalent epilepsy with mood disorders and people with mood disorders who are free of neurological disease. METHODS: This is a case-control study, with 142 patients with a confirmed diagnosis of epilepsy and major depressive disorder (MDD; cases) and 222 patients with MDD only (controls). MDD diagnosis was confirmed by a structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID-I-RV). We used the Beck Depression Inventory and the Beck Anxiety Inventory to estimate anxiety and depression levels and the Interictal Dysphoric Disorder Inventory (IDDI) to confirm the presence of IDD. Mann-Whitney U test, Pearson chi-squared, Spearman correlation, and logistic regression were used. RESULTS: No differences were found in the prevalence of IDD between PWE with MDD and people with MDD alone (88.73% vs. 85.13%, χ2 = .96, p = .32). There were no differences between the groups overall or for any IDDI subscales (all p > .05). In both groups, IDD symptoms were grouped with the same incidence and had the same duration and periodicity. IDD was not associated with epilepsy (odds ratio = .84, 95% confidence interval = .40-1.98, p = .72). No significant correlation was found between epilepsy, demographic characteristics, and all IDDI subscales (all p > .05). Notably, patients with IDD suffered from affective disorders longer (6.68 ± 6.82 years vs. 3.7 ± 3.97 years, p = .001) and also received higher scores on all psychometric scales (all p < .05). SIGNIFICANCE: This study does not confirm the specificity of IDD for epilepsy. The presence of IDD symptoms may be associated with a more severe course of MDD and significant anxiety distress.

Validation of the Russian version of neurological disorders depression inventory for epilepsy (NDDI-E).

OBJECTIVE: To translate and validate the English version of the Neurologic Depression Disorders Inventory in Epilepsy (NDDI-E) into the Russian language as an instrument for rapid detection of major depressive episodes (MDE) for patients with epilepsy (PWE) from Russian Federation. METHODS: One hundred and 75 consecutive PWE were included in the study. All patients were assessed with Mini-International Neuropsychiatric Interview (MINI 6.0.0), Hospital Anxiety and Depression Scale (HADS) and the Russian version of NDDI-E. Chi-square, Fisher's exact and Mann-Whitney tests were used to compare PWE with and without MDE. We analyzed internal structural validity, external validity, and receiver operator characteristics. RESULTS: None of the participants had any difficulties in understanding the questions of NDDI-E. The internal consistency of the inventory was satisfactory (Cronbach's ά = 0.856). Correlation between the NDDI-E and the HADS scores was moderate (r = 0.64, P < 0.001), indicating acceptable external validity. NDDI showed good capacity to detect MDE, with area under the curve of 0.919 (95% CI = 0.868-0.955; standard error: 0.019; P < 0.001). An optimal cut-off point with the highest Yuden's index (J = 0.699) was  > 12. At this point NDDI-E showed sensitivity of 88.16% (95% CI = 78.7%-94.4%), specificity of 81.82% (95% CI = 72.8%-88.9%), positive predictive value of 59.3% (95% CI = 48.8%-69.0%), negative predictive value of 95.8% (95% CI = 92.5%-97.7%). CONCLUSION: Russian version of NDDI-E is an affordable and fast screening tool with a good combination of sensitivity and specificity.

How to understand and address the cultural aspects and consequences of diagnosis of epilepsy, including stigma.

Epilepsy is one of the most prevalent serious neurological diseases. It is unique, being the only severe and disabling neurological disease that is fully treatable in the majority of cases, but on the other hand, associated with stigma, prejudice and discriminatory practices, which negatively impact people's everyday life in important areas, such as access to education, employment, marriage and social integration. For centuries, people with epilepsy (PWE) were stigmatized in all societies, with the consequences of prejudice and discrimination adding to the medical burden of the disease. Myths and misconceptions about this disease still occur, mostly in low-resources settings, however, in many industrialized countries, the knowledge regarding epilepsy is still limited in the population. The stigma is perceived as a negative attribute that is undesirable for the community to which the individual belongs. PWE are intrinsically undervalued, both by themselves ("felt stigma") and by the others. Actual discrimination by peers and institutions generates what is referred to as "enacted stigma". Misconceptions, stigma and negative attitudes towards PWE dramatically decrease quality of life, affecting the most sensitive areas, such as marriage, employment and driving. The Resolution 68.28 of the World Health Assembly (2015), the WHO-ILAE-IBE Global Report "Epilepsy: a public health imperative", advocates for strengthening and implementing national policies and legislation to promote and protect the rights of PWE, reducing misconceptions about epilepsy and improving access to care. Consolidated efforts are required from different organizations, public health managers, healthcare providers, PWE and their families to work together to improve socialization and quality of life of PWE. Educational programs and awareness to support activities among the general population, health service providers and PWE are the best way to reduce all types of stigma and discrimination.

Prevalence of valproate prescriptions in women of childbearing age in certain regions of Russia.

AIM: The goal of this retrospective study was to analyze the proportion of women with epilepsy who had received valproate (VPA) prescriptions in certain regions of Russia in 2018. METHODS: This retrospective cross-sectional study was based on the IQVIA Russia longitudinal prescriptions (LRx) database and included all individuals with a documented epilepsy code (International Classification of Diseases, Tenth Revision [ICD-10]: G.40) from 13 regions in Russia who had received at least one prescription of an antiepileptic drug (AED). The prevalence of VPA prescriptions in female patients with epilepsy aged 16-45 years was analyzed by age group and epilepsy diagnosis code. A multivariate logistic regression model was used to study the association between predefined variables and the probability of having received a VPA prescription. RESULTS: We found a total of 15,412 patients with epilepsy aged 16-45 who had received AED prescriptions in 2018 in the LRx database; 4488 (29.1%) of those patients were women. Of those, 64% had received at least one VPA prescription in 2018. The highest prevalence of VPA prescriptions was found in the age group 16-20 years (69%). This prevalence decreased with age. When compared with women aged 41-45 years, the 16-20-year-old age group was associated with a 1.6-fold increased probability of having receiving a VPA prescription (odds ratio [OR]: 1.60; p < 0.001), followed by the 21-25-year-old age group (OR: 1.46; p < 0.001). Nevertheless, the majority of women received VPA in low dosages (below 700 MG per day). CONCLUSIONS: The prevalence of VPA prescriptions in women of childbearing age was quite high in Russia. The therapeutic doses were in line with international guidelines and had low teratogenic potential. Further research is needed to gain a better understanding of the reasons for prescribing VPA to women with epilepsy who are of childbearing age.