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Objective: Screening for depression in people with epilepsy (PWE) is highly recommended in order to avoid underdiagnosis, misdiagnosis, or delayed diagnosis of this highly impacting comorbidity. Here we evaluated the impact of reporting and suggesting depression via the Beck Depression Inventory (BDI) on medical decision-making, and thereby the value of a depression screening for good medical practice., Methods: Of 445 BDI data sets, PWE with scores indicating moderate (BDI 19-29) to severe depressive disorder (BDI >29) were extracted and clinical reports were retrospectively reviewed regarding decisions on antidepressants, anti-seizure medications (ASMs), and non-pharmaceutical interventions., Results: Sixty-four PWE (14%; 56% female; mean age 39.7 years) showed elevated BDI scores, with 40 (63%) categorized as moderate depression and 24 (37%) as severe depression. Thirty-nine percent of PWE already had a pre-existing diagnosis of depression and 53% left the clinic with the diagnosis of depression, half of them with antidepressants. High depression scores were associated with any intervention in 53%, interventions with potentially mood affecting ASM in 19%, treatment with antidepressants in 11%, and non-pharmaceutical interventions in 41%. Non-pharmaceutical interventions were related to BDI scores. Changes of potentially mood-affecting ASMs were more frequent in PWE with moderate scores, and introduction of antidepressants appeared as a trend related to higher depression scores., Significance: The finding of an only weak relation between high depression scores, diagnoses of depression, and treatment consequences questions the diagnosis and treatment pathway and the clinical value of the BDI screening in PWE. Prospective standard procedures need to be established for depression diagnosis and treatment including follow-up evaluations of the validity of the diagnosis and effectiveness of the decisions taken., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Epilepsy as a result of stroke is currently the most rapidly increasing form of epilepsy. The risk of post-stroke epileptogenesis is higher after haemorrhagic stroke than after ischemic stroke. We provide here a brief clinical review of the topic to highlight the misinterpretation and undertreatment of focal epileptic seizures in stroke patients. Correct diagnosis and treatment are important because recurrent epileptic seizures can reduce quality of life and hinder rehabilitation.

Objective: Evaluate the long-term efficacy of vagus nerve stimulation (VNS) in patients with developmental and epileptic encephalopathies (DEE) compared with epilepsy patients without intellectual disability (ID)., Methods: Long-term outcomes from a Norwegian VNS quality registry are reported in 105 patients with DEEs (Lennox-Gastaut syndrome [LGS] n = 62; Dravet n = 16; Rett n = 9; other syndromes n = 18) were compared with 212 epilepsy patients without ID, with median follow-up of 88 and 72 months, respectively. Total seizure reduction was evaluated at 6, 12, 24, 36, and 60 months. Effect on different seizure types was evaluated at baseline and last observation carried forward (LOCF)., Results: Median monthly seizure frequency at LOCF was reduced by 42.2% (p < 0.001) in patients with DEE and by 55.8% (p < 0.001) in patients without ID. In DEE patients, ≥50% seizure reduction at 6 and 24 months were 17.1% and 37.1%, respectively, and 33.5% and 48.6% for patients without ID. Seizure reduction ≥75% at 60 months occurred in 14.3% of DEE patients and 23.1% of patients without ID. Highest median reduction was for atonic seizures, most notably 64.6% for LGS patients. A better effect was seen at 2 years among DEE patients with unchanged medication compared with those with changed medication (54.5% vs. 35.6% responders, p = 0.078). More DEE patients were reported to have greater improvement in ictal or postictal severity (43.8% vs. 28.3%, p = 0.006) and alertness (62.9% vs. 31.6%, p < 0.001) than patients without ID. For both groups, use of the magnet reduced seizure severity. Hoarseness was the most common adverse effect in both groups. In addition, DEE patients were frequently reported to have sleep disturbance, general discomfort, or abdominal problems., Significance: Our data indicate that VNS is very effective for atonic seizures. Patients without ID had best overall seizure reduction, however, patients with DEE had higher retention rates probably due to other positive effects., Plain Language Summary: DEE refers to a group of patients with severe epilepsy and intellectual disability. Many of these patients have restricted lifestyles with frequent seizures. VNS is a treatment option for patients who do not respond well to medicines, either because of insufficient effect or serious adverse effects. Our study shows that VNS is well tolerated in this patient group and leads to a reduction in all seizure types, most notably for seizures leading to fall. Many patients experience other positive effects like shorter and milder seizures, as well as improvement in alertness., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Stroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post-stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high-risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post-stroke epilepsy. Using advanced MR-imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood-brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post-stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high-risk patients for post-stroke epilepsy trials. PLAIN LANGUAGE SUMMARY: Stroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain's waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post-stroke epilepsy., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Guidelines suggest considering antiseizure medication (ASM) discontinuation in seizure-free patients with epilepsy. Past work has poorly explored how discontinuation effects vary between patients. We evaluated (1) what factors modify the influence of discontinuation on seizure risk; and (2) the range of seizure risk increase due to discontinuation across low- versus high-risk patients., Methods: We pooled three datasets including seizure-free patients who did and did not discontinue ASMs. We conducted time-to-first-seizure analyses. First, we evaluated what individual patient factors modified the relative effect of ASM discontinuation on seizure risk via interaction terms. Then, we assessed the distribution of 2-year risk increase as predicted by our adjusted logistic regressions., Results: We included 1626 patients, of whom 678 (42%) planned to discontinue all ASMs. The mean predicted 2-year seizure risk was 43% [95% confidence interval (CI) 39%-46%] for discontinuation versus 21% (95% CI 19%-24%) for continuation. The mean 2-year absolute seizure risk increase was 21% (95% CI 18%-26%). No individual interaction term was significant after correcting for multiple comparisons. The median [interquartile range (IQR)] risk increase across patients was 19% (IQR 14%-24%; range 7%-37%). Results were unchanged when restricting analyses to only the two RCTs., Significance: No single patient factor significantly modified the influence of discontinuation on seizure risk, although we captured how absolute risk increases change for patients that are at low versus high risk. Patients should likely continue ASMs if even a 7% 2-year increase in the chance of any more seizures would be too much and should likely discontinue ASMs if even a 37% risk increase would be too little. In between these extremes, individualized risk calculation and a careful understanding of patient preferences are critical. Future work will further develop a two-armed individualized seizure risk calculator and contextualize seizure risk thresholds below which to consider discontinuation., Plain Language Summary: Understanding how much antiseizure medications (ASMs) decrease seizure risk is an important part of determining which patients with epilepsy should be treated, especially for patients who have not had a seizure in a while. We found that there was a wide range in the amount that ASM discontinuation increases seizure risk-between 7% and 37%. We found that no single patient factor modified that amount. Understanding what a patient's seizure risk might be if they discontinued versus continued ASM treatment is critical to making informed decisions about whether the benefit of treatment outweighs the downsides., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts patients' health-related quality of life (HRQOL). In a randomized controlled design, we compared the change in self-reported HRQOL among adults with difficult-to-treat epilepsy after a 12-week diet intervention. Thirty-nine patients with drug-resistant focal epilepsy (age = 16-65 years) were randomized to eat a modified Atkins diet with maximum 16 g of carbohydrate per day (diet group, n = 19) or to continue eating habitual diet (control group, n = 20). No changes to the other epilepsy treatments were allowed. Patient-reported HRQOL was assessed with the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). The diet group experienced a statistically significant improvement in mean total score of QOLIE-89 of 10 points compared to controls (p = .002). Moreover, although not statistically significant when using a cutoff of 50% seizure reduction, our data suggest an association between diet-induced reduction in seizure frequency and improvement in HRQOL. The improvement in HRQOL was not associated with diet-induced weight reduction., (© 2023 International League Against Epilepsy.)

Purpose: As comorbidities can affect treatment decisions, quality of life, and prognosis in epilepsy, it is important that they are detected and addressed as soon as possible. Screening tools can help by rapidly assessing various additional challenges in epilepsy., Methods: To map the use and perceived benefit of different screening instruments for quality of life, psychiatric comorbidity, and cognition, along with side effects from anti-seizure medication in Europe, we sent an online questionnaire to dedicated epilepsy centres departments within the European Reference Network for Rare and Complex Epilepsies (EpiCARE)., Results: Among the 40 hospitals in the EpiCARE network, we received responses from 25 (63%), with 28 individual respondents. Most respondents reported using screening for quality of life (86%) and psychiatric comorbidity (82%), but relatively few (14%) screen for sexual problems. Many (47) different tools were used for evaluation of cognitive dysfunction, but just a few (5) different tools were used to screen for adverse events. The optimization of individual patient care was one main reason given for using screening tools (58%-100% - depending on purpose of tool), another was research (50% - 88% - depending on purpose of tool). A major benefit of using screening tools perceived by the respondents is the detection of "hidden" comorbidity (67% - 90% - depending on purpose of tool)., Conclusion: In the absence of a broad consensus regarding use of screening tools, practices vary considerably among epilepsy centres. Greater emphasis should be directed towards harmonizing use of screening tools. Future research should address how screening results influence treatment choices, and how these might affect clinical care., Competing Interests: Declaration of Competing Interests O.H. reports personal fees from Roche, Eisai, UCB, Novartis, and LivaNova, outside the submitted work. M.I.L. reports personal fees from Eisai, UCB, and Arvelle, outside the submitted work. C.J.L. reports personal fees from Eisai, GW/Jazz, Angelini and UCB Pharma, outside the submitted work. C.H. reports personal fees from UCB, Eisai, Precisis, GW Pharma. A.H.S. reports personal fees from Eisai outside the submitted work. K.Å.A. reports no disclosures., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Insecure and fearful attachment styles have been reported in psychogenic nonepileptic seizures (PNES). We have investigated associations between long-term clinical outcome in PNES, parenting and attachment styles and demographic, clinical, and neuropsychiatric factors., Material and Methods: Patients aged at least 16 years and with documented PNES, according to criteria from the International League Against Epilepsy, were prospectively recruited to this study. They were assessed at baseline to determine clinical characteristics, experience of attachment and perceptions of experienced parenting styles, trauma history, dissociation, and health-related quality of life. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were contacted by telephone and asked about their current medical status and psychiatric/psychological interventions., Results: Of 53 patients included in the study, 51 (96 %) provided follow-up data. Most (84.9 %) patients were female, and the mean age of PNES onset was 25.6 years. At follow-up, 20 patients (39 %) were free of PNES. Those patients that had achieved PNES freedom at follow-up had lower levels of attachment anxiety (p = 0.01) and reported to have experienced their fathers as less controlling (p = 0.02) and their mothers as more caring (p = 0.04) at baseline compared with those patients still suffering from PNES. Seizure freedom at follow-up was predicted by male gender, younger age at PNES onset, and less attachment anxiety., Conclusion: In our cohort from a tertiary epilepsy center the long-term prognosis of PNES is poor. Attachment anxiety is a risk factor for persistent PNES. It may be of therapeutic relevance to assess attachment patterns in patients with PNES., Competing Interests: Declaration of Competing Interest Author AV has served as a paid consultant for Eisai and Arvelle Therapeutics, unrelated to this study Author RD receives royalties from UpToDate. Author MIL has served as a paid consultant for Eisai, UCB and Arvelle Therapeutics, unrelated to this study. Author CL has no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Brivaracetam (BRV) is one of our latest antiseizure medications (ASMs). It is an analogue of levetiracetam with limited real-life experience. The purpose of this study was to evaluate clinical experience with BRV with focus on efficacy, tolerability and pharmacokinetic variability among adult patients with difficult-to-treat epilepsy., Methods: We retrospectively collected clinical and laboratory data from patients aged > 18 years who initiated treatment with BRV during 2016-2019 and were followed for > one year or cessation of BRV., Results: The study cohort consisted of 120 adults with drug-resistant epilepsy. Serum concentrations of BRV were available in 72 patients. After one-year follow-up, the retention rate of BRV was 52%. Fifty-seven patients (48%) were responders (>50 reduction of seizure frequency), of whom six became seizure free. Adverse effects were reported in 78 patients (65%); 37 (31%) experienced psychiatric problems like increased irritability, anxiety and depressive symptoms. The mean daily BRV dose was 159 mg (SD 80 mg) and the mean serum concentration 5.4 μmol/L (SD 4.1 μmol/L). In 24 patients, BRV replaced levetiracetam. Pharmacokinetic variability between patients was considerable; 14-fold variation in concentration/dose (C/D)-ratios. Concomitant use of enzyme-inducing ASMs decreased the C/D-ratio by 48%. There were no significant differences in serum concentrations between responders vs. non-responders, or those who experienced adverse effects or not., Conclusion: After > 1 year of treatment with BRV, we found a responder rate of 48% in adult patients with difficult-to-treat epilepsy. The drug was largely well tolerated, but one third experienced psychiatric adverse effects. The combination of clinical and pharmacokinetic data provides insight into factors contributing to efficacy and tolerability of new ASMs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit., Methods: Long-term outcomes are reported in 436 epilepsy patients from a VNS quality registry (52.8% adults, 47.2% children), with a median follow-up of 75 months. Patients were stratified according to evolution of response into constant responders, fluctuating responders, and nonresponders. The effect was evaluated at 6, 12, 24, 36, and 60 months. Multivariate regression analysis was used to identify predictors of response., Results: The cumulative probability of ≥50% seizure reduction was 60%; however, 15% of patients showed a fluctuating course. Of those becoming responders, 89.5% (230/257) did so within 2 years. A steady increase in effect was observed among constant responders, with 48.7% (19/39) of those becoming seizure-free and 29.3% (39/133) with ≥75% seizure reduction achieving these effects within 2-5 years. Some effect (25%-<50%) at 6 months was a positive predictor of becoming a responder (odds ratio [OR] = 10.18, p < .0001) and having ≥75% reduction at 2 years (OR = 3.34, p = .03). Patients without intellectual disability had ORs of 3.34 and 3.11 of having ≥75% reduction at 2 and 5 years, respectively, and an OR of 6.22 of being seizure-free at last observation. Patients with unchanged antiseizure medication over the observation period showed better responder rates at 2 (63.0% vs. 43.1%, p = .002) and 5 years (63.4% vs. 46.3%, p = .031) than patients whose antiseizure medication was modified. Responder rates were higher for posttraumatic (70.6%, p = .048) and poststroke epilepsies (75.0%, p = .05) than other etiologies (46.5%)., Significance: Our data indicate that the effect of VNS increases over time and that there are important clinical decision points at 6 and 24 months for evaluating and adjusting the treatment. There should be better selection of candidates, as certain patient groups and epilepsy etiologies respond more favorably., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Those affected with epilepsy have long been subject to stigmatization. This may have manifold negative effects, for example social isolation, low self-esteem, reduced quality of life and worsening of seizures. In Norway educational programs have been arranged at the National Centre for Epilepsy, aiming at reducing stigma and shame associated with epilepsy, and thereby increase the quality of life for those affected and their families. Thus, we wanted to explore the extent of self-reported perceived stigma and experienced discrimination in a Norwegian cohort with epilepsy., Materials and Methods: We conducted a web-based questionnaire survey in Norway. Participants were asked to provide background and epilepsy-related information. In addition, they were encouraged to answer questions regarding felt stigmatization in different situations and to rate stigma according to the Jacoby stigma scale., Results: Of 1182 respondents, 56% reported to have felt being stigmatized, and 35% reported to have experienced discrimination solely on the ground of the disease. 70% of respondents reported at least one type of perceived or experienced stigma. After controlling for gender, age, perceived depression and seizure freedom, reports of experienced stigmatization was a statistically significant independent predictor for reduced quality of life., Conclusions: A considerable proportion of people with epilepsy in Norway feel stigmatized and/or subject to discrimination, which negatively affects their quality of life., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Objective: Perampanel is one of the most recently approved antiseizure medications. The aim of the present study was to assess clinical efficacy and tolerability, in combination with pharmacokinetic variability, of perampanel treatment in patients at a tertiary referral center for epilepsy., Methods: We performed a retrospective observational study of patients given perampanel as adjunctive treatment in the period January 2013 - February 2019 at the National Center for Epilepsy at Oslo University Hospital, Norway., Results: Clinical data were available for 175 mainly adult patients with drug-resistant epilepsy with mean treatment duration of 16.1 months. We found that 23% (40 patients) were responders (i.e., achieving more than 50% reduction in seizure frequency), four of whom became seizure free, 29% (51 patients) experienced a modest effect, whereas for 29% (50 patients) perampanel had no seizure-reducing effect. A paradoxical effect, with seizure aggravation, was reported in 9% (15 patients). The responder rate was significantly higher in those with slow vs. fast dosage titration. Logistic regression analysis showed better efficacy among those with generalized vs. those with focal epilepsy. Adverse effects were reported by 135 patients (77%), ranging from mild (34%), to moderate (41%) and severe (2%). In 55 patients (41%), these adverse effects resulted in discontinuation of treatment with perampanel. The most frequent adverse effects were psychiatric symptoms (34%), dizziness (31%), and sleepiness (26%). Of the 31 patients for whom serum concentration measurements were available, the mean daily perampanel dose was 6.3 mg (SD 3.0), with a mean serum concentration at steady state of 1.03 μmol/L (range: 0.15-3.59 μmol/L). There were pronounced differences between patients, as demonstrated by a 12-fold variability in the range of concentration/dose (C/D)-ratios (0.06 to 0.69 μmol/L/mg), where enzyme inducers contributed., Conclusion: Our results demonstrate that perampanel had a modest seizure-reducing effect in this very treatment-resistant patient group. Predictors of treatment success were generalized epilepsy and slow dosage titration. In patients without a history of psychiatric problems, clinicians could consider increasing dose of perampanel beyond 6 mg daily, taking co-medication and serum concentrations into account., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES., Methods: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project., Results: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ± 19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ± 7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project., Conclusion: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Among patients with epilepsy, almost 70% become seizure-free with the current antiseizure drugs (ASDs) within 20 years following seizure onset. Of those who have been seizure-free for many years, around 70% remain seizure-free after withdrawal of ASDs. The purpose of this study was to determine the extent to which seizure-free patients with epilepsy in Norway discuss drug discontinuation with their physician. An online questionnaire was used; among the respondents were 186 adult patients who had been seizure-free for at least five years and were still using ASDs. Of these, 60 patients (32%) reported that they had discussed the question of drug withdrawal with their treating physician. Those patients who reported being involved in treatment decisions were more likely to have discussed ASD withdrawal. In conclusion, it is our opinion that discontinuation of drug treatment in patients with long-term seizure freedom is discussed far too seldom and that many patients may be living with an unnecessary drug burden., Competing Interests: Declaration of competing interest Oliver Henning has received speaker's honoraria from Eisai, UCB, and Livanova. Morten I Lossius has been giving talks and participated in expert panels for Eisai and UCB. Tone E.M. Medalen and Karl Otto Nakken have no conflict of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Lacosamide (LCM) is an antiepileptic drug (AED) with insufficient clinical experience in patients with intellectual disability (ID). They often have more severe epilepsy with comorbidities. The objective was to evaluate the efficacy and tolerability of lacosamide (LCM) in patients with refractory epilepsy with and without ID in a real-life setting, taking drug monitoring (TDM) data into account therapeutic., Methods: Retrospectively, we identified 344 patients using LCM from the TDM service covering the majority of the country, at the National Center for Epilepsy in Norway (2013-2018). Clinical and TDM data were available for 132 patients., Results: Forty-four of the 132 patients (33%) had ID. The retention rate was significantly higher in the ID vs the non-ID group after 1 year (84% vs 68%, P < .05). By combining clinical and TDM data, we demonstrated that 37/38 responding patients had serum concentrations above the lower limit of the reference range (>10 µmol/L), and 16/17 with lower concentrations were non-responders. Mean serum concentration/dose ratios were similar in both groups, 0.06 and 0.07 µmol/L/mg. There were no significant differences regarding efficacy and tolerability. The risk of LCM withdrawal was significantly higher when LCM was added to sodium channel blockers, even if the latter was discontinued., Significance: Lacosamide was generally well tolerated in patients with drug-resistant epilepsy, where one third had ID, and in these patients the retention rate was higher. The combination of clinical and TDM data could possibly facilitate LCM therapy in these vulnerable patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Women with epilepsy give birth to fewer children than women without epilepsy. We wished to compare the use of assisted reproductive technology in Norwegian women who have epilepsy with Norwegian women in general., Material and Method: In an international prospective registry study, the purpose of which was to identify the teratogenic effects of antiepileptic drugs, we included a total of 1510 births among Norwegian women who have epilepsy in the period 2000-2017. The women were recruited from 18 hospital neurological departments, and a protocol was completed for each pregnancy with demographic and clinical data. The use of assisted fertility among Norwegian women in general in the same period was retrieved from the medical birth registry., Results: In women with epilepsy, altogether 96 of 1510 births (6.4 %) were a result of assisted reproductive technology, whereas the corresponding figure in the general population in the same period was 285 474 of 1 052 901 (2.7 %) (p<0.001). Among women with epilepsy, the proportion who used carbamazepine in pregnancy was significantly higher among those who conceived using assisted reproductive technology than among those who had become pregnant in the regular manner (p=0.02)., Interpretation: Compared to healthy Norwegian women, the use of assisted reproductive technology was more than twice as high among women with epilepsy. This may be an intimation of reduced fertility among these women.

Objectives: For most people with epilepsy (PWE), problems that are not directly related to seizures may constitute major challenges in everyday life. The purpose of this study was to determine the extent of these challenges and any risk factors for their occurrence among PWE in Norway, based on the patients' own perspective., Materials and Methods: We used a web-based survey to ask PWE visiting the homepage of the Norwegian Epilepsy Association about different everyday challenges. A link to the survey was accessible via the members' homepage for a 4-month period during 2017., Results: One thousand one hundred eighty-two PWE responded to the questionnaire. Although more than 40% of the cohort reported that they had been seizure free for at least 1 year, the majority reported that tiredness (71%), memory problems (70%), concentration problems (68%), headache or vertigo (51%), and feeling depressed (59%) continued to represent challenges. In addition, fear of being alone, sexual problems or difficulties in social settings were reported by about one-third of the patients. Reporting having these challenges was significantly associated with female gender, polytherapy, experiencing seizures during the previous 12 months and feeling blue or depressed., Conclusions: The results of this study, reflecting a self-selected Norwegian population, provide insights into the challenges not directly associated with seizures that impact on the quality of life of PWE. The impacts of such challenges may be underestimated as components of the entire burden of epilepsy., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: For people with epilepsy (PWE), insufficient information and knowledge about the disease might have a negative influence on outcome and lead to poorer quality of life. In contrast, good information may increase empowerment and reduce stigma. This study investigated whether Norwegian PWE want information about different epilepsy-related issues, whether they actually obtain the information that they seek, and the extent to which they are satisfied with the information they receive. Furthermore, we examined which factors that might have influenced the degree of specific information given to PWE., Methods: We invited PWE visiting the homepage of the Norwegian Epilepsy Association to complete a web-based questionnaire about their perspective on obtaining information about epilepsy-related issues. The survey was accessible for a four-month period during 2017., Results: More than 90% of respondents (n = 1182) wished general information about epilepsy, and over 75% wanted information on more specific issues, like epilepsy surgery. Depending on the subject, the proportion of respondents that reported receiving the information they wished varied from 6.6% to 91.9%. Obtaining information about epilepsy surgery and neurostimulation was significantly associated with male gender. Having tonic-clonic seizures was associated with obtaining information about the diagnosis, an organized lifestyle, regular sleep, and consumption of alcohol., Conclusions: This study provides insights on how PWE experience provision of relevant information about epilepsy. Although most PWE considered that they obtained information on general epilepsy issues, most PWE interested in information on non-medical treatments and psychosocial issues reported that they did not obtain the information they wanted., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Nonadherence to recommended antiepileptic drug (AED) treatment regimens can result in seizure relapse with increased health risks. Nonadherence can be unintentional (eg, patients forget to take a dose), or intentional, when patients consciously decide not to follow the agreed AED treatment regimen. We aimed to determine the extent to which Norwegian patients with epilepsy (PWEs) report taking their AED differently from prescribed, either intentionally or unintentionally, and to identify risk factors for either form of nonadherence. Of 1182 PWEs who completed an online survey presented on the website of the Norwegian Epilepsy Association, 40% reported that they sometimes or often forget to take their AED as scheduled, and about 30% reported that they consciously chose not to follow the AED treatment plan agreed upon with their physician. Independent variables significantly associated with unintentional nonadherence include the following: feeling depressed, being younger than the mean age, and having memory problems. Independent factors significantly associated with intentional nonadherence include the following: feeling depressed, male gender, and perceptions of stigmatization. To improve the treatment of PWEs, it is important to distinguish between intentional and unintentional nonadherence to AED treatment regimens, as different risk factors and reasons associated with nonadherence to AED treatment regimens might require different interventions., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Background and Purpose: Studies in women with epilepsy (WWE) regarding pregnancy and labour complications have disclosed contradictory results. Our purpose was to investigate whether WWE have a higher risk of acute caesarean section (CS) or pregnancy complications than women without epilepsy or women with other chronic diseases and, if we found a higher risk, to explore potential explanations., Methods: The study used prospectively registered obstetric data from the Oppland Perinatal Database in the period 2001-2011, containing information on 18 244 births, including 110 singleton pregnancies in mothers with validated epilepsy. Data regarding epilepsy were collected retrospectively from medical records., Results: Epilepsy was a significant risk factor for acute CS, breech presentation and low birth weight in offspring [odds ratio (OR), 1.93, 95% confidence interval (CI), 1.2-3.1; OR, 2.29, 95% CI, 1.2-4.6 and OR, 2.10, 95% CI, 1.0-4.2, respectively]. In multivariate logistic regression analysis, antiepileptic drug exposure was an independent risk factor for acute CS (OR, 2.00; 95% CI, 1.06-3.77) and polytherapy was a significant risk factor for breech presentation (OR, 5.37; 95% CI, 1.13-25.57). Seizure frequency during pregnancy had no influence on the complication rate., Conclusions: We found that WWE using antiepileptic drugs during pregnancy had increased rates of acute CS, breech presentation and low birth weight, and that seizure frequency during pregnancy did not influence the complication rate., (© 2018 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: Seizure freedom is the optimal response to antiepileptic treatment. In previous studies, it has been shown that between 61% and 71% of children with epilepsy achieve seizure freedom, whereas 7% to 20% have drug-resistant epilepsy. The definition of drug resistance has not been consistent across studies, and there is a lack of contemporary population-based data. We used data from a large nationwide child cohort to provide such information, implementing the current standard definition of drug resistance., Methods: The study was based on the Norwegian Mother and Child Cohort Study. Potential epilepsy cases were identified through registry linkages and parental questionnaires. Medical record reviews and parental interviews were used to collect clinical information and to classify seizures, epilepsies, and etiologies., Results: The cohort included 112 745 eligible children aged 3 to 13 years (median age 7 years) at end of follow-up. Of these, 600 were epilepsy cases with at least 1 year of follow-up since epilepsy onset (median follow-up time: 5.8 years). There were 178 (30%) who had developed drug-resistant epilepsy, 353 (59%) who had been seizure free for ≥1 year, and 69 (12%) with intermediate seizure outcomes. Having an identified cause of epilepsy (genetic, structural, metabolic, or infectious) was associated with unsatisfactory seizure outcome (48% drug resistance) and influenced the relative risk associated with other prognostic factors. Sociodemographic characteristics were not associated with short-term seizure outcomes., Conclusions: Drug resistance occurs in 3 out of 10 children with epilepsy, whereas 6 out of 10 become seizure free. Having an identified cause of epilepsy is associated with poor response to treatment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

For most people with chronic diseases such as epilepsy, thorough knowledge of the disease is important in order to reduce feelings of insecurity and to enable better management of everyday life. Whether and when to inform patients and their families about all the risks associated with epilepsy is a matter of controversy. Using a web-based survey, patients with epilepsy (PWE) (n=1183) and carers, family members, or guardians of PWE, who could either answer on behalf of the patients (CBP) (n=676) or on their own behalf (CAR) (n=231) were asked whether they wanted information about the risk of epilepsy-related injuries and premature death and also whether they had received such information. Ninety percent or more of PWE, CBP, and CAR reported that they wanted such information, and 50% of CAR, 81% of CBP, and 70% of PWE had received some information about seizure-related injuries. Regarding risk of unexpected death, 31% of PWE, 35% of CBP, and 28% of CAR had received information on this issue. Those with tonic-clonic seizures were most eager to obtain information on these matters, and those best informed about epilepsy-related risks were males and the youngest part of the cohort. The wish for more information or the likelihood of having already received information was independent of the individual's seizure situation. This study demonstrates that there is a considerable gap between what the patients want regarding information and what they are actually given by healthcare providers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Executive problems in children and youth with epilepsy influence their ability to handle important aspects of daily life activities. The present study sought to explore factors associated with executive problems for patients with epilepsy in this age group., Methods: The cohort consisted of 97 consecutive patients at the National Centre for Epilepsy in Norway, aged 10-19 years, with focal or genetic generalized epilepsy. All underwent tests of executive functions (D-KEFS), the Behavior Rating Inventory for Executive Function (BRIEF), and screening for psychiatric symptoms, using the Strengths and Difficulties Questionnaire (SDQ)., Results: Parent-reported cognitive executive dysfunction (BRIEF, Metacognitive Index) was the strongest independent predictor for tested executive dysfunction and vice versa. Furthermore, male gender correlated strongest with parent-reported behavioral regulation problems (BRIEF, Behavioral Regulation Index) along with borderline/pathological score on the SDQ and parent-reported cognitive executive dysfunction., Conclusions: A strong association between parent-reported cognitive executive dysfunction and tested executive dysfunction was found. Male gender correlated strongest with parent-reported behavioral regulation problems. The latter was probably related to a higher frequency of symptoms associated with psychopathology among the boys than the girls. The frequency of executive deficits according to the different modes of measurement varied from 16% to 43%, suggesting that they capture different aspects of behavior under the executive umbrella.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Background and Objectives: Epilepsy affects 0.5% to 1% of children and is the most frequent chronic neurologic condition in childhood. Incidence rates appear to be declining in high-income countries. The validity of epilepsy diagnoses from different data sources varies, and contemporary population-based incidence studies are needed., Methods: The study was based on the Norwegian Mother and Child Cohort Study. Potential epilepsy cases were identified through registry linkages and parental questionnaires. Cases were validated through medical record reviews and telephone interviews of parents., Results: The study population included 112 744 children aged 3 to 13 years (mean 7.4 years) at end of registry follow-up (December 31, 2012). Of these, 896 had registry recordings and/or questionnaire reports of epilepsy. After validation, 587 (66%) met the criteria for an epilepsy diagnosis. The incidence rate of epilepsy was 144 per 100 000 person-years in the first year of life and 58 per 100 000 for ages 1 to 10 years. The cumulative incidence of epilepsy was 0.66% at age 10 years, with 0.62% having active epilepsy. The 309 children (34%) with erroneous reports of epilepsy from the registry and/or the questionnaires had mostly been evaluated for nonepileptic paroxysmal events, or they had undergone electroencephalography examinations because of other developmental or neurocognitive difficulties., Conclusions: Approximately 1 out of 150 children is diagnosed with epilepsy during the first 10 years of life, with the highest incidence rate observed during infancy. Validation of epilepsy diagnoses in administrative data and cohort studies is crucial because reported diagnoses may not meet diagnostic criteria for epilepsy., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: Patients treated with carbamazepine (CBZ) have increased serum levels of total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL). We aimed to investigate whether these changes of serum lipids are reversible after CBZ withdrawal., Material and Methods: We used a prospective, randomized double-blinded design. A total of 160 patients who had been seizure free on anti-epileptic drug monotherapy for more than 2 years were included and randomized to withdrawal or not. The intervention was completed by 150 (80 females, 53%) patients. Serum samples from before and 4 months after completed withdrawal or no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with CBZ, 28 with valproate, nine with phenytoin, four with phenobarbital, and five with lamotrigine. Of the patients who had been treated with CBZ, 47 were randomized to the withdrawal group, and 37 were randomized to the non-withdrawal group., Results: Among the CBZ-treated patients, a significant decrease in serum levels of TC, LDL, and apolipoprotein B (ApoB) were found in the withdrawal group compared with the non-withdrawal group. Mean differences in change were as follows: TC 0.68 mmol/l (P = 0.005, CL - 1.15 to -0.21); LDL - 0.67 mmol/l (P = 0.001, CL - 1.03 to -0.29); ApoB - 0.13 g/l (P = 0.02, CL - 0.23 to -0.03). No significant changes in HDL, apolipoprotein A, and C-reactive protein were detected., Conclusion: Our results indicate that CBZ may have unfavorable effects on serum levels of TC, LDL, and ApoB. However, these changes seem to be reversible even after years of treatment., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Children with epilepsy are at increased risk of other disorders and difficulties, preceding, cooccurring with, or after the diagnosis of epilepsy. Risk estimates vary, few studies are population-based, and few provide comprehensive assessments of comorbidities. We used nationwide registry data to describe frequencies of medical, neurologic, developmental, and psychiatric conditions occurring before and after children are diagnosed with childhood epilepsy., Methods: Data were obtained from the Norwegian Patient Registry, which is an administrative database recording International Classification of Diseases, 10th Revision diagnoses from all government-funded specialist health services in Norway (outpatient consultations and hospitalizations). We included data from the years 2008 through 2013 for all children born in Norway between 1996 and 2013 (0-17 years of age at the end of follow-up). Children with epilepsy were compared with the general child population, adjusting for sex and age. We also compared children with complicated epilepsies (ie, epilepsies with additional neurologic and/or developmental disorders) to children with uncomplicated epilepsies., Results: The study population included 1 125 161 children. There were 6635 (0.6%) children with epilepsy. Nearly 80% of children with epilepsy had ≥1 comorbid disorder. All types of disorders were more frequent in children with epilepsy, with additional medical disorders recorded in 55%, neurologic disorders in 41%, and developmental/psychiatric disorders in 43%. Children with complicated epilepsies had the highest overall levels of comorbidity, but the risk of medical and psychiatric comorbidities was also substantial among children with uncomplicated epilepsies., Conclusions: The overall frequency of comorbid disease is high in children with epilepsy, including children with presumably uncomplicated epilepsies., (Copyright © 2016 by the American Academy of Pediatrics.)

Sleep problems are common in pediatric epilepsy and may influence seizure control, daytime functioning, and overall quality of life. Knowledge of factors contributing to sleep problems is likely to improve treatment. The aim of this study was to investigate associations between psychiatric comorbidity and parent-reported and self-reported sleep problems in a sample of children and adolescents with epilepsy. Participants were children and adolescents (N=94), aged 10-19years, with generalized or focal epilepsy who had been referred to a tertiary epilepsy treatment center in Norway. Participants underwent a thorough clinical assessment and 24h of EEG registration. Information on sleep problems was obtained from parents using the Children's Sleep Habit Questionnaire (CSHQ) and from self-reporting using the Sleep Self-Report (SSR) questionnaire. Psychiatric diagnoses were established using the semistructured psychiatric interview Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (Kiddie-SADS-PL). Both the total and subdomain CSHQ and SSR scores were high in comparison with scores from population-based samples. Having one or more psychiatric disorder(s) was significantly associated with elevated scores on both the CSHQ and the SSR. With the exception of parent-reported parasomnias, associations between sleep problems and psychiatric disorders remained significant after adjusting for relevant epilepsy variables. Psychiatric comorbidity explained about one-third of the variance of the reported sleep problems in children and adolescents with epilepsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Objective: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers., Methods: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations., Results: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used., Significance: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objectives: Psychopathology in children and youth with epilepsy has previously been related to executive dysfunction, but the nature of the association is uncertain. We sought to explore risk factors for psychiatric disorders in children and youth with epilepsy, with emphasis on executive dysfunction, along with seizure-related and psychosocial factors., Methods: The cohort consisted of one hundred and one consecutive patients aged 10-19 years with focal (n=52) or genetic generalized (n=49) epilepsy. All were screened for psychiatric symptoms, using part of an extensive questionnaire, the Strengths and Difficulties Questionnaire (SDQ) for both patients and their parents. Participants scoring in the borderline or abnormal range on the SDQ received a psychiatric interview (Kiddie-SADS-PL). All participants underwent a neuropsychological examination, and those with general cognitive abilities (IQ)<70 were excluded., Results: Forty-seven of 101 participants (46.5%) had a SDQ score in the borderline or abnormal range and underwent a psychiatric evaluation. Of these, 44 (93.6%) met the criteria for a psychiatric diagnosis, the most common being ADHD and anxiety. An executive deficit was identified in 26.8% of the participants with a psychiatric diagnosis, but in only 5.4% of those without such a diagnosis (p=0.003). Multivariate logistic regression analysis showed that executive dysfunction was an independent risk factor for having a psychiatric disorder (OR 8.2, CI 1.8-37.2, p=0.006), along with male gender (OR 2.9, CI 1.2-7.3, p=0.02), and early seizure onset (0.86-that is one year older equals risk of psychiatric disorder reduced by 14%-CI 0.77-0.96, p=0.01). Other epilepsy-related or psychosocial factors were not significantly associated with psychiatric disorders., Conclusions: Multiple factors are associated with psychiatric problems in children and youth with epilepsy. In this study, executive dysfunction, male gender, and early epilepsy onset were independent risk factors for having a psychiatric disorder. An evaluation of psychiatric and cognitive problems is important to enable a positive long-term outcome in childhood epilepsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: In comparison with controls, youth with epilepsy (YWE) have greater psychosocial problems. However, information about their sexual behavior is sparse. We have performed a large, population-based questionnaire study to examine differences in sexual behavior between YWE and controls., Methods: A randomly chosen cohort of youth (13-19 years) from Akershus county, Norway (n=19,995) was asked to complete a questionnaire anonymously with questions on epilepsy and sexual activity., Results: The response rate was 85%. Two hundred forty-seven participants reported having or having had epilepsy, i.e., a lifetime epilepsy prevalence of 1.2%. Compared with controls, a higher proportion of YWE reported having had sexual intercourse (43.6% vs. 35.3%, p=0.009). The mean age at sexual debut was significantly lower in YWE than in controls (14.0 years vs. 15.0 years, p<0.001), and this was particularly marked among boys. A higher proportion of YWE reported not having used contraceptives at their last sexual intercourse compared with controls (31.6% vs. 22.3%, p=0.03). Ten percent of YWE, compared with 2% of the controls, reported that they had been forced into their first sexual intercourse., Conclusion: In YWE, some aspects of sexual behavior differ from those of their peers, with earlier sexual debut and less frequent use of contraceptives. More attention should be directed toward this subject, aiming at avoiding unwanted pregnancies and potential emotional traumas in this already vulnerable patient group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Sudden unexpected death is the most frequent cause of seizure-related death in cases of epilepsy. Those primarily affected are young adults with a long disease duration and regular seizures. The deaths are often related to a nocturnal generalised tonic-clonic seizure attack. In Norway around 30 persons are thought to be affected each year. Optimisation of epilepsy treatment will probably prevent some of these deaths.

Purpose: The aim was to investigate the prevalence of eating disorders and its relation to pregnancy and delivery complications in childbearing women with epilepsy (WWE)., Method: This study is based on The Norwegian Mother and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway. Epilepsy was reported in 706 pregnancies. The remaining cohort (n=106,511) served as the reference group. Eating disorders were diagnosed using DSM-IV criteria adjusted for pregnancy. The risk of preeclampsia, gestational hypertension, diabetes and weight gain during pregnancy as well as delivery outcome (small for gestational age, large for gestational age, ponderal index, low APGAR score, small head circumference) were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for maternal age, smoking, parity and socioeconomic factors., Results: Pregnant WWE were significantly more likely to have binge eating disorder (6.5% vs. 4.7%, p<0.05). WWE and comorbid eating disorders had significantly more preeclampsia (7.9% vs. 3.7%, p<0.05), peripartum depression and/or anxiety (40.4% vs. 17.8%, p<0.001) and operative delivery (38.2% vs. 23.5%, p<0.001) than the reference group without epilepsy or eating disorders. After adjustment for confounders, a significantly increased risk of operative delivery (OR 1.96, CI 1.26-3.05) and peripartum depression and/or anxiety (OR 2.17, CI 1.40-3.36) was demonstrated., Conclusion: Eating disorders in WWE contribute to the increased risk of pregnancy and delivery complications. Health personnel should be aware of eating disorders in WWE and refer them for treatment before pregnancy., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Diagnostic work-up and treatment of patients who have developed epilepsy after the age of 65 can both be difficult. Epilepsy is one of the most common neurological conditions in the elderly, and the incidence of de novo geriatric epilepsy is rising. The aim of this review is to provide guidance on the management of epilepsy in this patient group., Method: The review is based on a discretionary selection of original articles and reviews found in PubMed using the search term combination 'epilepsy' and 'elderly', and the authors' personal experience., Results: The seizures, which are most commonly of the focal type, are not infrequently overlooked or misdiagnosed. Cerebrovascular disease is the underlying cause of about half of the cases. When selecting an anticonvulsant, it is important to take age-related physiological changes and comorbidities into consideration. Because elderly patients have a narrower therapeutic window than younger persons and greater susceptibility to cognitive and other side effects, a low starting dose and slower dose titration are particularly important., Interpretation: The results of studies of young epilepsy patients cannot be extrapolated to apply to elderly patients. More studies directly targeting this patient population are therefore needed. As a general rule, we do not recommend starting on enzyme-inducing drugs such as phenytoin, phenobarbital and carbamazepine, partly because of their high interaction potential.

Background: The majority of patients with epilepsy are seizure-free, and repeated neuropsychological assessment may be highly relevant in this group. However, previous studies have not addressed the possible influence of important clinical variables on repeated neuropsychological assessment in this population., Methods: Using data from a large antiepileptic drug (AED) withdrawal study, we calculated the neuropsychological practice effects for 139 seizure-free patients with epilepsy and analysed the influence of different epilepsy-related factors on improvement that were observable 7 months after the initial neuropsychological assessment., Results: A clear and significant improvement in neuropsychological test performance was found for all the tests employed, regardless of AED withdrawal. Furthermore, patients characterized by evidence of brain pathology, such as known cerebral aetiology, pathological MRI and pathological EEG, showed less practice effects than patients not characterized by these variables. The differences were primarily evident for measures of verbal learning and memory., Conclusion: The data obtained from this study suggest that the development of general norms for change in the particular patient population, as well as specific norms for change related to important clinical variables, might be necessary to be able to determine whether genuine neuropsychological changes have occurred in individual patients in this group., (© 2012 John Wiley & Sons A/S.)

Purpose: In this population-based study we wanted to assess the prevalence and impact of psychiatric symptoms in children with epilepsy compared to controls, and investigate possible age and gender differences., Methods: Data were collected using the Strengths and Difficulties Questionnaire-Parent report (SDQ-P) as part of a more extensive questionnaire. A total of 14,699 parents of children aged 8-13 years (response rate 78%) participated. Associations between SDQ scores and epilepsy, other chronic disease, age, gender, and socioeconomic factors were explored using logistic regression analysis., Key Findings: Children with epilepsy (CWE) (n=110) had a significantly higher frequency of psychiatric symptoms (37.8% vs. 17.0% in controls, p<0.001). Gender differences were found in several subscales of the SDQ; girls had more emotional problems, whereas boys had higher scores regarding peer relationship and hyperactivity/inattention problems. Male gender, low socioeconomic status (family income below poverty limit and living in a single parent home), and other chronic disease (asthma/diabetes) were independent risk factors of developing psychiatric symptoms, along with epilepsy. Having or having had epilepsy was, however, a much stronger risk factor for developing psychiatric symptoms in girls than in boys [odds ratio (OR) 4.2 vs. OR 2.3]. A minor effect of age was seen only in girls with epilepsy, with an increased risk of psychiatric symptoms in age group 10-13 years (OR 1.28 for scoring borderline/abnormal on SDQ-total difficulties). Borderline/abnormal impact scores were found in 31.8% of CWE compared with 13.0% of controls (p<0.001)., Significance: Multiple risk factors contribute to the high prevalence of psychiatric symptoms in CWE, perhaps differently in boys and girls. Awareness of this complex interaction may help target intervention toward high risk groups and thus prevent more serious problems from arising., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Objectives: It is well known that behavioural problems and psychiatric disorders occur with greater prevalence in children and adolescents with epilepsy. Youth with epilepsy (YWE) may also be more susceptible to risk-taking behaviour, but this has seldom been studied. The aim of this study was to explore risk-taking behaviour in YWE., Material and Methods: In this study, 19,995 young people (age range: 13-19 years) participated and completed an extensive questionnaire, including The Strengths and Difficulties Questionnaire self-report. A variable, risk-taking behaviour, was identified, including daily consumption of alcohol, substance abuse or having committed a criminal offence such as being in a fight with a weapon, committing a burglary or using threats to obtain money., Results: Two hundred and forty-seven youths reported currently having, or having had, epilepsy (lifetime prevalence: 1.2%). Of these, 8.3% reported daily alcohol consumption (1.0% in controls; P<0.001), 12.4% had tried illegal substances (5.5% of controls; P<0.001), and 19.7% had committed criminal offences (8.5% in controls; P<0.001). A gender difference was found: girls with epilepsy did not exhibit risk-taking behaviour more frequently than controls, but having epilepsy was a risk factor for such behaviour in boys (OR: 3.2)., Conclusion: Boys with epilepsy exhibit risk-taking behaviour more frequently than controls. Other risk factors for this behaviour were living with a single parent, low family income and psychiatric symptoms. This behavioural association should be addressed as it probably contributes to the negative social outcomes that frequently occur in the adult epilepsy population., (© 2011 John Wiley & Sons A/S.)

Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This prospective, randomized study evaluated thyroid function in men and women with epilepsy both before and after double-blinded withdrawal of AED monotherapy, and assessed whether any changes were reversible. One hundred sixty patients were randomized to withdrawal and nonwithdrawal groups; 150 patients completed the intervention and were included in the 12-month study. Serum samples were obtained from 130 patients, from before and 4 months after intervention. Following AED withdrawal, significant increases in free thyroxine (FT(4)) serum concentrations were measured in men and women treated with carbamazepine. In women treated with valproate, serum concentrations of free triiodothyronine (FT(3)) decreased significantly in the withdrawal group. Thus, for both men and women with epilepsy, carbamazepine treatment reduces serum FT(4) concentrations, but valproate treatment of women with epilepsy increases serum FT(3.) Our study demonstrated that these changes can be reversed by treatment withdrawal, even after years of treatment.

Purpose: Most studies of quality of life (QOL) in seizure-free epilepsy patients suggest normal or near-normal function. Previous studies on QOL in well-controlled epilepsy have not investigated determinants for QOL from a database that includes a wide range of health related and epilepsy related variables, as well as demographical data, neuropsychological data, data from a comprehensive personality inventory and results from a QOL-questionnaire. Thus, the aim of this study was to analyze predictors of QOL based on such a range of variables., Methods: Adults with epilepsy on antiepileptic (AED) monotherapy and without epileptic seizures for at least 2 years (n=158) were assessed with the QOLIE-89., Results: The main findings were that QOL in well-controlled epilepsy patients was in the normal range and that presence of substantial health related concerns was a significant predictor of poor QOL., Discussion: The findings that substantial health concerns predict poor QOL may have clinical implications, as seizure-free epilepsy is a relatively benign condition, and careful information and counselling about this may alleviate health concerns and improve quality of life.

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.

Purpose: Risk of depression, anxiety, and reduced quality of life is elevated in epilepsy patients, due to a range of factors including aetiology, structural brain lesions, seizure worry, epilepsy surgery, hereditary factors, psychosocial factors, and possible adverse effects of antiepileptic drugs (AEDs). Studies on the relationships between epilepsy-related variables and behavioural adjustment have been mainly conducted on patients with persisting seizures, whereas the present study investigated behavioural function in epilepsy patients seizure-free for more than 2 years on monotherapy., Methods: Adults with epilepsy on AED monotherapy and without epileptic seizures for at least 2 years (n=126) were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), in addition to MRI and EEG., Results: Group analysis found mean MMPI-2 scores on all the clinical and content scales to be within the normal range. Abnormally elevated scores on scales measuring aspects of depression, health-related concerns, low self-esteem, negative treatment indicators, and physical complaints were recorded in a higher proportion of patients than would normally be expected. Multiple regression analysis showed that MRI pathology was a significant predictor for an abnormally poor score on the low self-esteem scale, and that epilepsy onset

Objective: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health-related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied., Methods: Patients, seizure-free for more than 2 years on AED monotherapy, were recruited for a controlled, prospective, randomized, double-blinded withdrawal study lasting for 12 months, or until seizure relapse. Patients were randomized to AED withdrawal (n = 79) and nonwithdrawal (n = 81) groups. The examination program included clinical neurological examinations, neuropsychological testing, EEG-recordings, cerebral MRI, and assessments of HRQOL. Follow-up data on seizure relapse were also collected beyond the 12-month study period (median 47 months)., Results: Seizure relapse at 12 months occurred in 15% of the withdrawal group and 7% of the nonwithdrawal group (RR 2.46; 95% CI: 0.85-7.08; p = 0.095). After withdrawal, seizure relapse rates were 27% after a median of 41 months off medication. A normal result to all 15 neuropsychological tests increased significantly from 11% to 28% postwithdrawal. We found no significant effects of withdrawal on quality of life and EEG. Predictors for remaining seizure-free after AED-withdrawal over 1 year were normal neurological examination and use of carbamazepine prior to withdrawal., Conclusion: Seizure-free epilepsy patients on AED monotherapy who taper their medication may improve neuropsychological performance with a relative risk of seizure relapse of 2.46, compared to those continuing therapy.

Purpose: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine function have complex interactions. In this study, we wanted to investigate the effects of AEDs on reproductive endocrine function after withdrawal of AEDs and look for reversible endocrine effects., Methods: The study was prospective, randomized, and double-blinded. A total of 160 patients were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention and was included in the study for 12 months. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%)., Results: The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the majority of the patients, withdrawal led to significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n = 19) and women (n = 19). Mean differences in change in FAI between the withdrawal group and nonwithdrawal group were in men 17.49 (CI 10.16-24.81, p

The aim of this study was to assess cardiac autonomic control in patients with epilepsy before and after withdrawal of antiepileptic drugs (AEDs). The study was prospective, randomized and double blinded. Spectral analysis of heart rate variability (HRV) in 24 h ECG-registration before and after withdrawal of AEDs was used to assess autonomic cardiac control. The assessment of HRV with spectral analysis was based on sinus rhythm and normal heart beats [normal to normal beat (NN)]. Thirty-nine patients had 24 h rhythms free from any ectopic beats both before and after intervention, and were included in the analysis. Significant differences were found in the withdrawal group: filtered RR intervals for all 5 min segments of the analysis; percentage of differences between adjacent filtered RR intervals that are greater than 50 ms for the whole analysis; very low frequency power; low frequency power and high frequency power. The results demonstrate that slow withdrawal of AEDs in seizure-free patients with epilepsy on drug mono-therapy resulted in an increase in both parasympathetic and sympathetic functions, indicative of increased power amongst patients following cessation of AED treatment. As low HRV has been associated with increased mortality in patients with other diseases, this increased HRV may be beneficial.

The aim of this study was to assess cognitive effects of anticonvulsants in a way that would yield results that are most directly applicable to epilepsy populations. This was done with a placebo-controlled, prospective, randomized, double-blind, parallel group study of anticonvulsant withdrawal in a population of subjects taking a single anticonvulsant with completely controlled seizures. Outcomes of this study on cognitive measures from the California Computerized Assessment Package have recently been reported. To aid comparison with results of prior studies, we report outcomes here on several more standard measures of neuropsychological function. The major findings were that, in subjects with therapeutic drug levels at baseline, drug withdrawal was associated with significant improvement in performance on the Controlled Oral Word Association Test and the Stroop Color-Word Interference Test. Comparable results were achieved in the subgroup taking carbamazepine.