Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

Socioeconomic differences in use of antiseizure medication in pregnancies with maternal epilepsy: A population-based study from Nordic universal health care systems.

OBJECTIVE: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. METHODS: We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. RESULTS: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). SIGNIFICANCE: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.

The epidemiology and societal costs of myasthenia gravis in Norway: A non-interventional study using national registry data.

BACKGROUND AND PURPOSE: With the emergence of new treatment options for myasthenia gravis (MG), there is a need for information regarding epidemiology, healthcare utilization, and societal costs to support economic evaluation and identify eligible patients. We aimed to enhance the understanding of these factors using nationwide systematic registry data in Norway. METHODS: We received comprehensive national registry data from five Norwegian health- and work-related registries. The annual incidence and prevalence were estimated for the period 2013-2021 using nationwide hospital and prescription data. The direct, indirect (productivity losses) and intangible costs (value of lost life-years [LLY] and health-related quality of life [HRQoL]) related to MG were estimated over a period of 1 year. RESULTS: In 2021, the incidence of MG ranged from 15 to 16 cases per year per million population depending on the registry used, while the prevalence varied between 208.9 and 210.3 per million population. The total annual societal costs of MG amounted to EUR 24,743 per patient, of which EUR 3592 (14.5%) were direct costs, EUR 8666 (35.0%) were productivity loss, and EUR 12,485 (50.5%) were lost value from LLY and reduced HRQoL. CONCLUSION: The incidence and prevalence of MG are higher than previously estimated, and the total societal costs of MG are substantial. Our findings demonstrate that productivity losses, and the value of LLY and HRQoL constitute a considerable proportion of the total societal costs.

Generalized myasthenia gravis with acetylcholine receptor antibodies: A guidance for treatment.

BACKGROUND: Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. METHODS: MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. RESULTS: Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. CONCLUSIONS: Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.

Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG. METHODS: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials. RESULTS: In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity. CONCLUSIONS: This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires. TRIAL REGISTRATION: The protocol for this systematic review was registered in PROSPERO: CRD42022328444.

Adverse Childhood Experiences and the Risk of Multiple Sclerosis Development: A Review of Potential Mechanisms.

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, contribute to long-term systemic toxic stress and inflammation that may last well into adulthood. Such early-life stressors have been associated with increased susceptibility to multiple sclerosis (MS) in observational studies and with the development of experimental autoimmune encephalomyelitis in animal models. In this review, we summarize the evidence for an ACE-mediated increase in MS risk, as well as the potential mechanisms for this association. ACEs dysregulate neurodevelopment, stress responses, and immune reactivity; they also alter the interplay between the immune system and neural networks. All of this may be relevant for MS risk. We further discuss how ACEs induce epigenetic changes and how the toxic stress caused by ACEs may reactivate the Epstein-Barr Virus (EBV), a key risk factor for MS. We conclude by suggesting new initiatives to obtain further insights into this topic.

High-dose folic acid and cancer risk; unjustified concerns by von Wrede and colleagues regarding our paper.

Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.

Association of adverse childhood experiences with the development of multiple sclerosis.

OBJECTIVE: To study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development. METHODS: A nationwide, prospective cohort study based on participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999-2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators. RESULTS: In this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67). INTERPRETATION: Childhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose-response relationship. Further studies are needed to identify underlying mechanisms.

Prevalence of self-reported emotional, physical, and sexual abuse and association with fear of childbirth in pregnant women with epilepsy: The Norwegian Mother, Father, and Child Cohort Study.

OBJECTIVE: This study was undertaken to examine the prevalence of self-reported experiences with abuse in pregnant women with epilepsy and the association between having experienced abuse and childbirth expectations, particularly the fear of childbirth. METHODS: We performed a cross-sectional study of women with and without epilepsy enrolled in the Norwegian Mother, Father, and Child Cohort Study 1999-2008. Data on epilepsy diagnosis; antiseizure medication (ASM) use; emotional, physical, and sexual abuse; and childbirth expectations were collected from questionnaires completed during gestational Weeks 17-19 and 30. RESULTS: Our study population included 295 women with ASM-treated epilepsy, 318 women with ASM-untreated epilepsy, and 93 949 women without epilepsy. A total of 115 women (47%) with ASM-treated and 132 women (57%) with ASM-untreated epilepsy reported any emotional, physical, or sexual abuse, compared to 25 100 women (32%) without epilepsy. The adjusted odds ratios (aORs) for having experienced any abuse were 1.8 (95% confidence interval [CI] = 1.4-2.3) and 1.8 (95% CI = 1.4-2.2) for ASM-treated and ASM-untreated epilepsy, respectively. A total of 29 women (11%) with ASM-treated and 34 women (11%) with ASM-untreated epilepsy reported having been raped, compared to 3088 women (4%) without epilepsy (aORs = 2.8 [95% CI = 1.8-4.1] and 2.9 [95% CI = 2.0-4.2], respectively). In nulliparous women with ASM-untreated epilepsy, having experienced abuse was associated with fear of childbirth; 22 women (31%) with abuse experiences reported fear of childbirth compared to five women (7%) with no experience of abuse (aOR = 5.4 [95% CI = 1.7-17.2]). This association was not seen in multiparous women or in women with ASM-treated epilepsy. SIGNIFICANCE: More women with epilepsy reported emotional, physical, and sexual abuse than women without epilepsy. Such experiences may be associated with childbirth expectations.

Vitamin B status and association with antiseizure medication in pregnant women with epilepsy.

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.

Prenatal exposure to valproate and risk of congenital malformations-Could we have known earlier?-A population-based cohort study.

OBJECTIVE: Prenatal exposure to the antiseizure medication (ASM) valproate is associated with an increased risk of congenital malformations, but warnings against the use of valproate in pregnancy were not issued until 2009. The objective was to study how early administrative health registers could have identified the teratogenic risk associated with valproate. METHODS: This was a population-based cohort study of individual-linked data from Danish health care and socioeconomic registers including children born in Denmark between January 1, 1997 and December 31, 2014. Information on ASM use, including valproate, in pregnancy was obtained from the Danish National Prescription Registry. Children identified with major congenital malformations from the Danish National Patient Register and the Danish Register of Causes of Death were included. Using logistic regression models, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for major congenital malformations during the first year of life in children with and without prenatal exposure to ASMs adjusted for potential confounders. RESULTS: Among the 895 507 children (males, 51.3%), 31 790 (3.6%) were diagnosed with a major congenital malformation in the first year of life. In the analyses including children born in 1997, the risk of major congenital malformations among children prenatally exposed to valproate compared with children not exposed to ASMs was increased by a fully adjusted OR (aOR) of 3.95 (95% CI = 1.65-9.47). With the addition of data from the following years, the teratogenic effect of valproate was further substantiated, as the precision of the estimate improved (1997-2014: aOR = 2.44, 95% CI = 1.80-3.30). SIGNIFICANCE: Using Danish health care data, we were able to identify a teratogenic risk associated with prenatal valproate exposure in children born in 1997, which is much earlier than prospective clinical cohorts. Health registry data represent an important tool for early identification of risk associated with drugs in pregnancy.

Complications and mortality after acute traumatic spinal cord injury in Saint Petersburg, Russia.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: We studied complications during early rehabilitation and their relation to length of stay (LOS) in the hospital as well as to survival in people with traumatic spinal cord injury (TSCI). SETTING: All specialized hospitals of Saint Petersburg. METHODS: We analysed all charts of patients admitted with acute TSCI to the city hospitals, 2012-2016. Patient characteristics, complications, time and cause of death, and LOS were recorded. Mean values with standard deviations and t-tests were used. We analysed mortality rate using the Kaplan-Meier method and calculated relative risks (RRs). RESULTS: A total of 311 patients with TSCI were included. Complications occurred in 34% of patients; most were respiratory complications and pressure ulcers. Complications occurred more often in those with concomitant traumatic brain injury (TBI) (RR = 1.4, 95% CI: 1.2-1.8). All complications prolonged LOS (median, 11 days) and increased mortality in the acute phase (p < 0.001). In the early phase, 15% died, with a median time to death of 13 days. Respiratory complications markedly increased the death rate (RR = 18, 95% CI: 15-22). Mortality rate correlated also with age, TSCI severity and level, and concomitant TBI. Alcohol/drug consumption before TSCI increased the likelihood for complications (RR = 1.7, 95% CI: 1.3-2.1) and mortality (RR = 2.2, 95% CI: 1.6-3.1). CONCLUSION: Focus on prevention as well as early and optimal treatment of complications, together with no or low alcohol/drug consumption may reduce mortality in the early phase after TSCI and at the same time shorten LOS.

Incidence of adult traumatic spinal cord injury in Saint Petersburg, Russia.

STUDY DESIGN: Retrospective population-based cohort study. OBJECTIVES: To characterise the epidemiology of traumatic spinal cord injury (TSCI) among the inhabitants of Saint Petersburg, Russia. SETTING: All hospitals in Saint Petersburg. METHODS: Charts for all individuals admitted to city hospitals from 1st January 1 2012 to 31st December 2016 with acute TSCI were reviewed. Incidence rates were calculated for the whole period and for each year separately. Gender-specific and age-specific incidence rates were calculated, and epidemiological characteristics and possible risk factors were analysed. RESULTS: A total of 361 people were identified. The average annual incidence rate was 17.6 per million, varying from 21.2 (2013) to 13.6 (2016), and 70.9% were men. Mean age at injury was 42.1 years. Injuries from falls represented 49.8% of cases, and motor vehicle accidents 18.9%. The male:female ratio in the low-falls group was 1.2:1, and among the elderly patients, it was 0.5:1. Lesions at the cervical level were involved in 49.3%, thoracic in 24.7%, and lumbar/sacral in 23.5%. TSCI was complete in 16.9%. Concomitant injuries occurred in 47.2% of cases, and traumatic brain injuries in 37.7%. CONCLUSION: TSCI incidence decreased during the observation period and was 2.4 times more common among men than women. In half of the cases, injuries involved the cervical level, and a fall was the most frequent injury cause. Elderly women more often had falls from a low height than men. Multiple injuries-most frequently traumatic brain injuries-were common.

Antiepileptic and psychiatric medication in a nationwide cohort of patients with glioma WHO grade II-IV.

INTRODUCTION: Glioma is the most common intracranial primary brain tumor. Patients with glioma often suffer from epilepsy, anxiety and depression. Aims of this study were to identify risk factors for drug-treated anxiety and depression, and to determine the use of psychiatric medication in a national glioma cohort. METHODS: Data from the Cancer Registry of Norway on all persons diagnosed with glioma WHO grade II-IV 2004-2010 were linked with data from the Norwegian Prescription Database. Cox regression analysis was used to assess risk factors for drug-treated anxiety and depression. Standardized incidence ratios were calculated for psychiatric medication dispensed to glioma patients and compared to the general population. RESULTS: The glioma cohort consisted of 1056 males and 772 females. Of the 1828 patients, 565 had glioma grade II-III, and 1263 had grade IV. The patients with glioma grade II-III who were treated with levetiracetam had an increased risk for drug-treated anxiety compared to patients without levetiracetam; hazard ratio 2.8 (95% confidence interval 1.7-4.9). Female gender increased the risk for drug-treated anxiety compared to males in patients with glioma grade IV; hazard ratio 1.5 (95% confidence interval 1.2-2.0). Antidepressants were less frequently dispensed to patients with glioma grade II-III and epilepsy than to the general population. CONCLUSIONS: Patients with glioma grade II-III on levetiracetam had an increased risk for drug-treated anxiety. The subgroup of patients with glioma grade II-III and epilepsy received less antidepressants than the general population.

Overweight in epilepsy as a risk factor for pregnancy and delivery complications.

OBJECTIVE: To investigate whether prepregnancy overweight in women with epilepsy increases their risk for complications during pregnancy and delivery. METHODS: This study is based on The Norwegian Mother and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway. A diagnosis of epilepsy was reported in 706 pregnancies. Overweight was defined as body mass index ≥ 25 prepregnancy. Overweight women with epilepsy (n = 259) were compared to normal-weight women with epilepsy (n = 416), and to women without epilepsy with and without overweight (n = 30,516 and n = 67,977, respectively). The risks of pregnancy and delivery complications were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for adverse socioeconomic factors, age, parity, and smoking. RESULTS: Women with epilepsy were more often overweight than women without epilepsy (38.4% vs. 31.3%, p < 0.001). The majority of pregnancy and delivery complications were more frequent in overweight women with epilepsy. Compared to overweight women without epilepsy, the risk was increased for cesarean section (OR 1.6, CI 1.2-2.2, p < 0.001), excessive bleeding (OR 1.4, CI 1.0-1.8, p = 0.04), peripartum anxiety and depressive symptoms (OR 1.9, CI 1.3-2.8, p < 0.001), small for gestational age children (OR 2.4, CI 1.2-4.8, p = 0.02), and transfer of the infant to a neonatal ward (OR 1.5, CI 1.1-2.2, p = 0.02). Compared to normal-weight women with epilepsy, the risk of cesarean section (OR 1.6, CI 1.1-2.3, p < 0.05), gestational hypertension (OR 2.0, CI 1.1-3.5, p < 0.05), preeclampsia (OR 2.3, CI 1.2-4.5, p < 0.05), and transfer of the infant to a neonatal ward (OR 2.2, CI 1.3-3.6, p < 0.01) was increased. SIGNIFICANCE: Prepregnancy overweight in combination with epilepsy entails a strong negative effect on risk of complications during pregnancy and delivery. In women with epilepsy and overweight referral to a nutritionist should be considered when an antiepileptic drug is started as well as when pregnancy is planned. These women should be regarded as a high-risk group.

Factors affecting outcome in myasthenia gravis.

INTRODUCTION AND METHODS: Information from myasthenia gravis (MG) patients treated and evaluated for at least 2 years between 1980 and 2014 was reviewed to assess the effect of demographics, antibody status and titer, thymus histology, and clinical severity on outcome after 2, 5, and 10 years of treatment. RESULTS: Among 268 patients, 74% had acetylcholine receptor antibodies, 5% had muscle specific tyrosine kinase-antibodies, and 22% had neither. Optimal outcome was achieved by 64% of patients at 2 years of follow-up, 73% at 5 years, and 75% after 10 years. Optimal outcome was achieved more often in patients with late onset, in those who had thymectomy, and in those with ocular-only disease at maximum severity. The only consistent independent predictor of optimal outcome was onset after age 50 years on multivariate analysis. CONCLUSIONS: Prognosis is favorable for the majority of MG patients, regardless of age, maximum disease severity, or antibody status. Muscle Nerve, 2016 Muscle Nerve 54: 1041-1049, 2016.

Does the choice of antiepileptic drug affect survival in glioblastoma patients?

Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004-2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004-2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs.

Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors.

Patients with the autoimmune polyendocrine syndrome type I (APS-I), caused by mutations in the autoimmune regulator (AIRE) gene, and myasthenia gravis (MG) with thymoma, show intriguing but unexplained parallels. They include uncommon manifestations like autoimmune adrenal insufficiency (AI), hypoparathyroidism, and chronic mucocutaneous candidiasis plus autoantibodies neutralizing IL-17, IL-22, and type I IFNs. Thymopoiesis in the absence of AIRE is implicated in both syndromes. To test whether these parallels extend further, we screened 247 patients with MG, thymoma, or both for clinical features and organ-specific autoantibodies characteristic of APS-I patients, and we assayed 26 thymoma samples for transcripts for AIRE and 16 peripheral tissue-specific autoantigens (TSAgs) by quantitative PCR. We found APS-I-typical autoantibodies and clinical manifestations, including chronic mucocutaneous candidiasis, AI, and asplenia, respectively, in 49 of 121 (40%) and 10 of 121 (8%) thymoma patients, but clinical features seldom occurred together with the corresponding autoantibodies. Both were rare in other MG subgroups (n = 126). In 38 patients with APS-I, by contrast, we observed neither autoantibodies against muscle Ags nor any neuromuscular disorders. Whereas relative transcript levels for AIRE and 7 of 16 TSAgs showed the expected underexpression in thymomas, levels were increased for four of the five TSAgs most frequently targeted by these patients' autoantibodies. Therefore, the clinical and serologic parallels to APS-I in patients with thymomas are not explained purely by deficient TSAg transcription in these aberrant AIRE-deficient tumors. We therefore propose additional explanations for the unusual autoimmune biases they provoke. Thymoma patients should be monitored for potentially life-threatening APS-I manifestations such as AI and hypoparathyroidism.

Life satisfaction in women with epilepsy during and after pregnancy.

OBJECTIVE: The aim of this study was to investigate life satisfaction in women with epilepsy during and after pregnancy. METHODS: The study was based on the Norwegian Mother and Child Cohort Study, including 102,265 women with and without epilepsy from the general population. Investigation took place at pregnancy weeks 15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a reference group without epilepsy. RESULTS: The proportion of women with epilepsy was 0.6-0.7% at all three time points. Women with epilepsy reported lower life satisfaction and self-esteem both during and after pregnancy compared with the references. Single parenting correlated negatively with life satisfaction in epilepsy during the whole study period. Epilepsy was associated with lower levels of relationship satisfaction and higher levels of work strain during pregnancy and lower levels of self-efficacy and satisfactory somatic health 18months postpartum. Adverse life events, such as divorce, were more common in women with epilepsy compared with the references, and fewer women with epilepsy had a paid job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with epilepsy during and after pregnancy showed that, even in a highly developed welfare society, women with epilepsy struggle. Mothers with epilepsy and their partners should be examined for emotional complaints and partnership satisfaction during and after pregnancy. Validated screening tools are available for such measures.

[Myasthenia gravis - optimal treatment and accurate diagnosis]. / Myasthenia gravis - diagnostikk og behandling.

Around 700 people in Norway have myasthenia gravis, an autoimmune disease that affects neuromuscular transmission and results in fluctuating weakness in some muscles as its sole symptom. The diagnosis is based on typical symptoms and findings, detection of antibodies and neurophysiological examination. Symptomatic treatment with acetylcholinesterase inhibitors is generally effective, but most patients also require immunosuppressive drug treatment. Antigen-specific therapy is being tested in experimental disease models.