Impaired executive functioning in children of women with epilepsy.

OBJECTIVE: While neurodevelopmental symptoms are often seen in children of mothers with epilepsy, research specifically addressing executive function (EF) in this population is limited. This study aims to investigate EF in children of mothers with epilepsy, both with and without fetal exposure to anti-seizure medications, compared to typically developing children whose mothers do not have epilepsy. METHODS: We evaluated EF in children aged 8 to 17 years born to mothers with clinically validated diagnoses of epilepsy, using the Behavior Rating Inventory of Executive Function completed by the mothers. The results were then compared to a typically developing control group at the same age living in the same geographic area. RESULTS: The results showed significantly higher levels of EF problems in children of mothers with epilepsy who were exposed (p = 0.005, d = 0.63), and unexposed (p = 0.001, d = 0.74) to anti-seizure medications during pregnancy, compared to typically developing children. There was no significant difference in EF problems between the exposed and unexposed groups. These findings remained statistically significant after adjusting for mothers' education levels, and when excluding participants exposed to valproate during pregnancy. SIGNIFICANCE: This study highlights the increased risk of EF problems in children of mothers with epilepsy, independent of exposure to anti-seizure medications. Findings underscore the importance of continuous monitoring of EF in these children and highlights the need for further research into the diverse factors affecting EF development in this group.

Sexual function in people with epilepsy: Similarities and differences with the general population.

OBJECTIVE: The potential impact of epilepsy on sexual function is important for patient welfare, but often neglected. This study explored the occurrences of different sexual problems in patients with both well-controlled and mostly refractory epilepsy, and compared these with equivalent information from the general population. METHODS: Between 2015 and 2017, a total of 221 adult inpatients and outpatients, mostly with intractable epilepsy, at the National Centre for Epilepsy in Norway, and 78 outpatients with well-controlled epilepsy at Lillehammer hospital participated in a questionnaire survey on sexual function. Information on the individual patient's epilepsy was collected. The results were compared with equivalent data on sexual function from 1671 adult Norwegians in the general population. RESULTS: Patients with epilepsy reported a significantly higher frequency of problems with orgasm, dyspareunia, erectile dysfunction, and feelings of sexual deviance. However, reduced sexual desire, premature ejaculation/climax, and vaginal dryness occurred at similar frequencies in the general population. After controlling for gender, we found no significant association between sexual problems and seizure control or use of enzyme-inducing antiepileptic drugs. In both genders, feelings of sexual deviance were associated with lower quality of life. Fewer patients with epilepsy were satisfied with their sex lives. The perception of sex as an important part of daily life was similar among women with epilepsy and women from the general population, whereas significantly fewer men with epilepsy than men in the general population reported that sex was an important part of their daily lives. Women with mostly refractory epilepsy reported asking for help with their sexual problems significantly more often than women in the other groups. SIGNIFICANCE: Some sexual problems occur significantly more often in patients with epilepsy than in the general population and feelings of sexual deviancy occur more frequently. No epilepsy-related factors could be identified as specific predictors.

A man in his fifties with variable weakness and difficulty in walking. / En mann i 50-årene med varierende kraftsvikt og gangvansker.

BACKGROUND: An active man in his fifties was treated for atrial fibrillation with ablation. One week later he noticed variable weakness in his lower extremities. In the days that followed, his symptoms improved but could vary from day to day. CASE PRESENTATION: On admission 3 months after the initial symptoms, he had spasticity and weakness in both lower extremities, with hyperreflexia and positive Babinski. Spinal fluid contained slightly elevated protein levels. Spinal MRI showed cord oedema and gadolinium enhancement over multiple spinal levels. Autoimmune myelitis was suspected, and he was treated with high dose steroids and rituximab. Due to lack of effect, repeated examinations were initiated. Information from his patient history regarding symptom exacerbation by walking or bending forward was emphasised. Repeated MRI showed unchanged spinal oedema and dilated peri- and intramedullary vessels. MRA and spinal digital DSA revealed a dural fistula at third lumbar level, with the left L3 radiculomedullary artery as the feed artery. The fistula was successfully ligated by the neurosurgeon. INTERPRETATION: Spinal vascular lesions are rare and the diagnosis may be challenging due to atypical presentation. The case shows that detailed information from the patient history and thorough clinical investigation is of paramount importance to disclose this probably underreported condition.

Pharmacokinetic variability of valproate in women of childbearing age.

The purpose was to investigate pharmacokinetic variability of valproic acid (VPA) in women of childbearing age by therapeutic drug monitoring (TDM) data to elucidate the variable relationship between dose and serum concentrations with the ultimate aim of facilitating safer use of VPA. Anonymized retrospective data from the TDM database (2006-2015) at the National Center for Epilepsy in Norway were used. Trough total concentrations of VPA at assumed steady state in women aged 14-46 years were analyzed. Data from 643 nonpregnant women of childbearing age (mean age = 27 years) were included. Mean dose and serum concentration of VPA were 968 (standard deviation [SD] = 453) mg/day and 411 (SD = 138) µmol/L, respectively, and 59% used polytherapy. The pharmacokinetic variability in serum concentration/dose (C/D) ratios between women was extensive. For doses <700 mg/day (n = 202; 32%; 150-625 mg/day), mean serum concentration was 336 µmol/L and variability in C/D ratio was 10-fold. The variability decreased with increasing dose to eightfold (≥700 to <1,500 mg/day, n = 358) and fourfold (≥1,500 mg/day, n = 96). This study demonstrates the extensive pharmacokinetic variability of VPA among women of childbearing age, which is most pronounced at low doses. In future studies, serum concentrations of VPA, rather than dosage, should be used as a guide for exposure of VPA and possible risks of teratogenicity to evaluate safety aspects of VPA in women.

[Idiopathic intracranial hypertension as a cause of headache]. / Idiopatisk intrakranial hypertensjon.

Idiopathic intracranial hypertension (IIH) is characterised by increased intracranial pressure with normal cerebrospinal fluid, and no evidence of space occupying process, meningeal pathology or venous thrombosis. The condition is associated with obesity, especially in women of childbearing age. IIH is a rare but serious cause of headache, and constitutes a differential diagnosis for sudden-onset headache, particularly if the patient has visual disturbances not related to migraine and reports pulsatile tinnitus, cranial nerve palsy or radiculopathy.

[Polyunsaturated fatty acids and epilepsy]. / Flerumettede fettsyrer og epilepsi.

BACKGROUND: 30 % of patients with epilepsy have recurrent drug-resistent seizures. Some children with catastrophic epilepsy have responded well to a ketogenic diet. Polyunsaturated fatty acids are at least partly responsible for the anticonvulsive effect of this diet and could perhaps be used to treat epilepsy. MATERIAL AND METHODS: The paper is based on literature (published before June 2008) retrieved through a non-systematic search of the Cochrane and PubMed databases. The following search words were used: epilepsy, polyunsaturated fatty acids, clinical trials, ketogen diet, and treatment. Articles focusing on clinical aspects were selected. RESULTS AND INTERPRETATION: Articles on clinical studies and laboratory research were retrieved from Pubmed, while studies on ketogen diet were retrieved from Cochrane. Animal studies show that increased intake of polyunsaturated fatty acids can reduce the likelihood of epileptic seizures through various biochemical mechanisms. However, there is not sufficient evidence to conclude that polyunsaturated fatty acids have antiepileptic effects in people with epilepsy. More research is needed before polyunsaturated fatty acids can be presented as a treatment option for epilepsy.

Pharmacokinetic variability of valproate during pregnancy - Implications for the use of therapeutic drug monitoring.

BACKGROUND AND PURPOSE: Use of valproate (VPA) in women of childbearing age is restricted due to dose-dependent risk of teratogenicity. The purpose of this study was to characterise pharmacokinetic variability of VPA in pregnancy, and discuss use of therapeutic drug monitoring (TDM) as guidance to exposure in women. METHOD: Measurements of trough total and unbound VPA concentrations before, during and after pregnancy, at assumed steady-state were collected from the TDM-database (2006-2016) at the National Center for Epilepsy in Norway. Additional clinical data were obtained from the Oppland county Perinatal Database (1994-2011). RESULTS: Data from 51 pregnancies in 33 women aged 19-40 years were included. Each woman underwent 1-4 pregnancies, and 1-7 measurements per pregnancy were performed. The variability in total concentration/dose (C/D)-ratios between women was 13-fold, and intra-patient variability extensive. Total C/D-ratios were reduced by 46% from before pregnancy to third trimester (0.48-0.29 µmol/L/mg). Unbound concentrations of VPA were only requested in 10% of the pregnancies. Repeated measurements from two pregnancies in one women revealed increased unbound concentration of VPA during pregnancy. There were 19 with idiopathic generalized epilepsy and two focal based on clinical data from 21 women and 38 pregnancies; 1 major congenital malformation was noted. CONCLUSION: There is pronounced pharmacokinetic variability of VPA during pregnancy. Unbound concentrations are rarely requested. TDM should be used by measurements of both total and unbound concentrations since total concentrations may be misleading for efficacy and fetal exposure of VPA.

Age-specific birth rates in women with epilepsy: a population-based study.

OBJECTIVE: The aim of this study was to investigate birth rates and use of hormonal contraception in different age groups among women with epilepsy (WWE) in comparison to women without epilepsy. MATERIALS AND METHODS: Demographic data and medical information on more than 25,000 pregnant women (40,000 births), representing 95% of all pregnancies in Oppland County, Norway, were registered in the Oppland Perinatal Database in the period 1989-2011. Data were analyzed with respect to epilepsy diagnoses, and 176 women with a validated epilepsy diagnosis (303 pregnancies) were identified. Age-specific birth rates in these women were estimated and compared with age-specific birth rates in women without epilepsy in the same county. RESULTS: In WWE over 25 years of age, birth rates were significantly lower than in those of the same age group without epilepsy. In women below 20 years of age, birth rates were similar in those with and without epilepsy. The use of hormonal contraceptives prior to pregnancy was lower among WWE under 25 years than in the corresponding age group without epilepsy. CONCLUSIONS: Health professionals who counsel WWE who are of fertile age should be aware of the strongly reduced birth rates in WWE over 25 years of age, and the lower rates of use of contraceptives among young WWE.

Intrauterine growth retardation in foetuses of women with epilepsy.

PURPOSE: Various factors may affect intrauterine foetal growth, amongst which conditions such as epilepsy and the use of anti-epileptic drugs (AED) may play a role. This study investigated intrauterine growth of foetuses in women with epilepsy, as compared with controls, and explored whether intrauterine growth was affected by prenatal exposure to AED. METHOD: Data were obtained from prospectively registered data regarding pregnancy and prenatal and perinatal factors in women in Oppland County in Norway. The final analysis included information from 166 mothers with epilepsy and 287 children. The control group consisted of 40,553 pregnancies in women without epilepsy registered in the same database. RESULTS: There was a significantly higher risk of the ponderal index being below the 10th percentile and infants being small for gestational age (SGA) in the epilepsy group; exposure to AED increased the risk. The frequency of SGA and low ponderal index was highest in Lamotrigine exposed infants. In the AED group, head circumference was significantly smaller among Carbamazepine exposed. CONCLUSION: Impaired intrauterine growth of foetuses in women with epilepsy was identified. The frequency of SGA and low ponderal index was highest in Lamotrigine exposed infants. The epilepsy group had a higher risk profile for having smaller babies, in being younger at age, lower in body weight and more frequent smokers. However despite these differences, the effects of epilepsy and AED exposure were significant. The ponderal index may be a useful supplement to more established measures assessing intrauterine growth in epilepsy.