Competency in the management of women of childbearing age with epilepsy among primary care and specialist doctors in Estonia.

Objective: Although abundant new information has emerged in the last decade(s) on the management of women with epilepsy (WWE), whether said knowledge has reached clinical practice remains largely unknown. We assessed knowledge of this matter among primary care and specialist doctors in Estonia. Methods: This study was conducted via an online questionnaire, which was used to explore healthcare specialists' awareness in five domains: pre-pregnancy counseling, contraception, side effects of antiseizure medications (ASMs), and the management of epilepsy during pregnancy and in the peri- and postpartum periods. Results: The survey response rate was low - 8.14%. Knowledge of epilepsy management in WWE was inconsistent among different medical specialists. The median numbers of correctly answered questions among gynecologists, neurologists, and general practitioners were 7, 6.5, and 3 of 10, respectively. Gynecologists were more informed about appropriate contraceptive methods. Neurologists were more familiar with ASM side effects. General practitioners' knowledge level for this topic was low. Surprisingly, only 30.8% of general practitioners were aware of the high teratogenic potential of valproate. Conclusions: We observed significant knowledge gaps regarding the optimal treatment of WWE of reproductive age. To improve epilepsy management, doctors' awareness of treatment considerations for this patient group needs to be increased.

Pre-pregnancy counseling for women with epilepsy: Can we do better?

OBJECTIVE: For many women with epilepsy (WWE), decision making about pregnancy is difficult, due mainly to the potential teratogenic risks of anti-seizure medications (ASMs). Pre-pregnancy counseling is essential to minimize these risks. This study was conducted to assess the rate and effectiveness of pre-pregnancy counseling for women treated with valproate (VPA) in Estonia. METHODS: We used outpatient prescription data from the national health insurance provider to identify all women treated with VPA during 2011-2018 in Estonia. The personal medical documentation of women who became pregnant while on VPA treatment was reviewed. Pre-pregnancy counseling history and VPA-treatment indications were analyzed. RESULTS: Data from 141 women who became pregnant while on VPA treatment during 2011-2018 time period were analyzed. Of these patients, 77% had epilepsy and 19% psychiatric diagnoses. Pre-pregnancy counseling was recorded for 13% (n = 19) of women who later became pregnant. VPA monotherapy and the lack of VPA treatment indication were associated with the lack of counseling before pregnancy. CONCLUSIONS: This study revealed a significant deficit in pre-pregnancy counseling for WWE treated with VPA in Estonia. Awareness of the need for such counseling should be increased among medical specialists.

Valproic acid prescription trends among females of childbearing age in Estonia: A 14-year nationwide prescription database study.

PURPOSE: Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age. METHODS: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex- and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated. RESULTS: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged <15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period. CONCLUSIONS: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community.

Creutzfeldt-Jakob Disease Presenting as Nonconvulsive Status Epilepticus.

Creutzfeldt-Jakob disease is a rare, rapidly progressive spongiform encephalopathy in humans. EEG plays an important role in diagnosing this disease. In some patients, epileptic activity and encephalopathy from various aetiologies may share morphological features on EEG. This similarity could create difficulties in EEG interpretation, especially if the patient presents with disturbed consciousness. In this case report, a 74-year-old female with Creutzfeldt-Jakob disease presented initially with rapidly progressive impairment of consciousness and focal epileptiform activity on EEG. An EEG performed 25 days later showed periodic sharp-wave complexes with triphasic morphology at a rate of 0.5 Hz, compatible with a diagnosis of Creutzfeldt-Jakob disease. Based on these results, we recommend that a diagnosis of Creutzfeldt-Jakob disease be considered in patients presenting with a rapid deterioration of consciousness and a clinical presentation of nonconvulsive status epilepticus. Monitoring these patients with serial EEGs could be useful to establish an accurate diagnosis.

3D Cinema and Headache: The First Evidential Relation and Analysis of Involved Factors.

BACKGROUND: A possible link between 3D movies and headache (HA) has never been a target of specific and systematic investigations. The aim of this study was to investigate the relationship between 3D cinema and HA and to evaluate possible risk factors of developing HA during or after watching a 3D movie. METHODS: This was a prospective, non-randomized, observational study. Six thousand specifically designed questionnaires were distributed to consecutive cinema visitors. Relative HA risks for 2D- vs. 3D-movie visitors and the effects of background variables were analyzed. RESULTS: The questionnaire was filled and returned by 1293 persons. The mean age of responders was 33.0 ± 11.3 years. Individuals who viewed 3D movies reported HA during or after the movie 1.61 times more often than 2D-movie viewers (11.1% in 3D vs. 7.2% in 2D movies, p = 0.017). The risk was higher in women: 2.65 times for 2D (p = 0.019) and 1.85 times for 3D movies (p = 0.06), and decreased with age by 4.6% with each year for 2D (p = 0.0035) and by 3.2% for 3D movies (p = 0.0098). Among 3D-movie visitors, those with previous HAs were 4.17 times more prone to get a cinema-induced HA (p = 0.02). The risk was the highest for persons with migraine (OR = 3.37, p = 0.001). CONCLUSION: For the first time, it was evidentially shown that 3D movies can provoke HA. Persons at risk are mostly younger women and/or migraineurs. Based on our results, for those belonging to the aforementioned risk groups, it can be mainly recommended to choose passive 3D technology and to view movies from the farthest possible distance.

Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

PURPOSE: The aim of this study was to compare the risk of metabolic syndrome (MS) and evaluate related factors for MS among people with epilepsy treated with valproate (VPA) or carbamazepine (CBZ). METHODS: A total of 213 adult patients with epilepsy treated with VPA (n=118) or CBZ (n=95) monotherapy were included in the study. Participants were evaluated for the presence of MS, diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: In the multiple logistic regression analysis, the risk of MS in CBZ- and VPA-treated patients was similar (odds ratio [OR]=0.99; 95% confidence interval [CI], 0.43-2.26; P=0.979). A lower proportion of CBZ-treated patients had abnormally low levels of high-density lipoprotein cholesterol (OR=0.10; 95% CI, 0.02-0.42; P=0.002), whereas a lower proportion of VPA-treated patients had abnormally high concentrations of fasting blood glucose (OR=0.30; 95% CI, 0.13-0.69; P=0.004). Females treated with VPA tended to have a higher risk of MS (OR=1.48; 95% CI, 0.50-4.41; P=0.485) compared to males (OR=0.74; 95% CI, 0.28-1.96; P=0.551), although this difference was not statistically significant. CONCLUSION: Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males.

Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy.

Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy. As a well-known histone deacetylase (HDAC) inhibitor, VPA regulates epigenetic programming by altering the expression of many genes. The aim of study was to analyze differences in gene expression profiles before and after the start of VPA treatment in patients with newly diagnosed epilepsy. RNA sequencing was used to compare whole-genome gene expression patterns of peripheral blood from nine patients with epilepsy before and 3 months after the start of treatment with VPA. Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1. Functional annotation and network analyses showed activation of only one genetic network (enrichment score = 30), which included genes for cardiovascular system development and function, cell morphology, and hematological system development and function. The finding of such a small number of differently expressed genes between before and after the start of treatment suggests a lack of HDAC inhibition in these patients, which could be explained by the relatively low doses of VPA that were used. In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes. Therefore, to minimize the potential side effects of HDAC inhibition, it is recommended that the lowest effective dose of VPA be used for treating epilepsy.

Valproate modulates glucose metabolism in patients with epilepsy after first exposure.

Valproate (VPA) treatment has been reported to be associated with weight gain and metabolic changes, such as hyperinsulinemia. The question of whether hyperinsulinemia and other metabolic changes are consequences of increased weight, or are instead direct results of VPA treatment, remains a matter of debate. The aim of the current study was to explore the influence of VPA treatment on glucose and insulin levels during the oral glucose tolerance test (OGTT) directly following the first intravenous (IV) administration. Sixteen patients (18-46 years old) with newly diagnosed epilepsy underwent an OGTT with 75 g glucose prior to the start of VPA treatment, as well as directly following the first IV VPA administration. We observed that plasma glucose levels during the 120 min of OGTT session following infusion of VPA were significantly lower than those measured during OGTT without VPA treatment (mean ± standard deviation [SD] 4.28 ± 0.94 mmol/l vs. 4.75 ± 1.09 mmol/l respectively, p = 0.038). However, blood concentrations of insulin and C-peptide did not differ significantly between the two measurements. This is the first study to show a potential acute glucose-lowering effect of VPA during OGTT in patients with newly diagnosed epilepsy.

Comparison of the metabolic syndrome risk in valproate-treated patients with epilepsy and the general population in Estonia.

BACKGROUND: No study has explored the risk of metabolic syndrome (MS) in patients with epilepsy treated with valproate (VPA) at the population level. The aim of this study was to compare the risk of MS in VPA-treated patients in Estonia to the risk in the general population. METHODS: This study involved 118 patients with epilepsy (63 men, 55 women) who received VPA monotherapy. MS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Data were compared with the results of a population-based study of the prevalence of MS in the same geographic region (N = 493; 213 men, 280 women). RESULTS: In the multiple logistic regression analysis, after adjustment for age and sex, the risk of MS in VPA-treated patients was not increased compared to the control subjects (odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.59-1.68). VPA-treated patients had higher serum insulin concentrations than control subjects, independent of body mass index (BMI). A positive association was found between MS development and BMI (OR = 1.47; 95% CI, 1.25-1.73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. In control subjects, BMI and HOMA-IR had similar predictive abilities for MS occurrence. In VPA-treated patients, the predictive ability of the HOMA-IR index was significantly lower than that of BMI, with areas under the receiver operating characteristic curves of 0.808 and 0.897 (P = 0.05), respectively. CONCLUSIONS: The risk of MS is not increased among VPA-treated patients with epilepsy in Estonia compared to the general population. The HOMA-IR index likely has a lower predictive ability for MS in VPA-treated patients compared to its predictive ability in the general population.