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The much-loved fictional character of Jonas Fjeld is a heroic surgeon. But who was he modelled on? It may have been Dr. Tandberg at Lillehammer.

In patients with epilepsy, nonadherence to agreed antiepileptic drug (AED) treatment may result in seizure relapse, and at worst sudden unexpected death. The aim of this study was to examine the extent of both unintentional and intentional nonadherence among Norwegian patients with refractory epilepsy and try to identify possible risk factors. At the National Centre for Epilepsy in Norway, 333 consecutive adult in‐ and outpatients with refractory epilepsy participated in an anonymous survey about adherence to drug treatment. Twenty‐two percentages admitted that they sometimes or often forgot to take their drugs as scheduled, and 19% reported that they, rarely, sometimes or often intentionally did not follow the AED treatment plan agreed upon with their physician. Young age and depression were significantly correlated with unintentional nonadherence. Intentional nonadherence was associated with young age (36 years or younger). We found nonadherence not to be associated with any specific AED. In conclusion, about one‐fifth of patients with refractory epilepsy admitted that they did not adhere to the agreed drug treatment plan, either intentionally or unintentionally. Measures to reduce nonadherence in this patient group may improve seizure control and should be tailored to address both unintentional and intentional lack of adherence.

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.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.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.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.

Purpose To report the clinical outcome of nicotine exposure in patients with autosomal dominant sleep-related hypermotor epilepsy (ADSHE), along with serum concentrations of the major nicotine metabolite cotinine. Methods We recruited 17 ADSHE patients with CHRNA4 mutations (12 with p.S280F and 5 with p.L291 dup). Clinical characteristics were collected from hospital records. A telephone interview was performed on the use and seizure-reducing effect of nicotine applying a six-point rating scale from “none” to very good“. Serum concentrations of cotinine were measured in 14 nicotine users. Results All patients but one had ever used nicotine. Nine had used snuff; seven were current users. Eleven had used transdermal nicotine; nine were current users. Seven reported long-lasting seizure control, all used nicotine, four transdermal nicotine and three snuff. In 78% of patients using continuous transdermal nicotine, the effect was rated as good or very good. Cotinine concentrations were 453 ± 196 (mean ± SD) nmol/l in seven patients using transdermal nicotine only vs. 1241 ± 494 nmol/l in seven using other forms of nicotine. No correlation with seizure control was found. Three patients experienced improvement with transdermal delivery compared to snuff. Conclusion This is the hitherto largest observational study supporting a favorable effect of nicotine in this specific seizure disorder. Better seizure control from transdermal nicotine compared to only day-time consumption suggests benefit from exposure throughout the night. According to current clinical experience, patients with uncontrolled ADSHE harboring relevant mutations should be offered precision treatment with transdermal nicotine.

Can COVID-19 cause epilepsy, or increase the tendency to seizures in those with epilepsy? Is it safe for persons with epilepsy to be vaccinated against COVID-19?

Objective The aim was to examine the influence of modified Atkins diet on serum concentration of antiepileptic drugs (AEDs). Methods Prospective data from 63 adult patients with either focal or generalized drug‐resistant epilepsy recruited to 12‐week dietary treatment as add‐on to AEDs are analyzed. AED serum concentrations, ketones, glucose, and hemoglobin A1c were measured before and after the dietary intervention. Paired t test was used and Spearman correlation coefficient, r, was estimated. Results Mean age was 37 years (range 16‐65 years). Mean serum concentrations of carbamazepine, clobazam, and valproate were significantly reduced after 4 and 12 weeks of the diet period (

Juvenile myoclonic epilepsy (JME) constitutes about 10% of all epilepsies. Because of executive dysfunction, people with JME may be prone to impulsivity and risk-taking behavior. Our aim was to investigate whether psychosocial issues associated with impulsivity are more prominent in people with JME than in those with other types of genetic generalized epilepsy (GGE). Patients with GGE were recruited retrospectively through the Drammen Hospital records in Buskerud County, Norway, 1999–2013. They were invited to a semi-structured interview, either at the hospital or at home. Ninety-two patients with JME and 45 with other types of GGE were interviewed. Variables were evaluated in terms of their association with JME versus other GGE diagnosis using a logistic regression model. Juvenile myoclonic epilepsy was associated with use of illicit recreational drugs and police charges, although with borderline significance (odds ratio [OR] 3.4, p = 0.087 and OR 4.2, p = 0.095); JME was also associated with being examined for attention-deficit hyperactivity disorder (ADHD) in females (OR 15.5, p = 0.015), a biological parent with challenges like addiction or violent behavior (OR 3.5, p = 0.032), and use of levetiracetam (OR 5.1, p = 0.014). After controlling for group differences, we found psychosocial complications to be associated with JME, potentially influencing the lives of the individuals and their families to a greater extent than the seizures per se. Thus, JME should be considered a disorder of the brain in a broader sense than a condition with seizures only.

In 1912, an epilepsy colony was established in Bærum, inspired by similar colonies in other countries. Its first years were marked by financial constraints and limited treatment options. In the basement of the National Centre for Epilepsy in Bærum we recently came across a number of historical documents. These give an insight into the first years of what can be referred to as organised epilepsy care in Norway, and include patient protocols for the period 1913–20, five copybooks for the period 1905–23 and a ledger for the period 1905–20.

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. Keywords: Antiseizure medications drugs; Serum concentrations; Therapeutic drug monitoring. Copyright © 2021 Elsevier Inc. All rights reserved.

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

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.

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. This article will not be available due to copyright restrictions. (c) 2019 by Wiley.

Purpose To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. Methods Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected. Results 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24–81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges. Conclusions ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful.

Objective Ketogenic diets reduce seizures in children with drug-resistant epilepsy. Whether adults benefit from similar treatment has not been clarified. We therefore examined the efficacy of the modified Atkins diet in adults with drug-resistant focal epilepsy. Methods We performed a randomized clinical trial (RCT) with patients >16 years who had at least 3 seizures per month despite having tried at least 3 antiepileptic drugs. They were randomized to either 12 weeks on the modified Atkins diet (diet group) or habitual diet (control group). Primary endpoint was a change in seizure frequency from baseline to the intervention period, comparing those on diet with controls. Results We assigned 37 patients to the diet group and 38 to the control group. Nine of the patients in the diet group and 4 controls were excluded. Of those who completed the dietary intervention (n = 24), median seizure change was -1.0 (interquartile range [IQR] -13.7-8.8), while in the control group (n = 32) the median change was 4.5 (IQR -4.8-33.5). The median difference between the groups was -7.0 (95% confidence interval [CI] -37.0-3.0; P = .21). In the intention-to-treat analysis, the relative risk (RR) for achieving >50% seizure reduction was 1.8 (95% CI 0.3-10.2; P = .65), while for achieving >25% seizure reduction RR was 2.43 (95% CI 0.94-6.28; P = .06). We observed no serious adverse events. Significance In this RCT investigating the effect of an adjunctive modified Atkins diet on seizure frequency in adults with difficult-to-treat focal epilepsy, we found a significant reduction in seizure frequency in the diet group compared to the controls, but only for moderate benefit (>25% seizure reduction) among those who completed the intervention. However, seizure response varied considerably between individuals, perhaps negatively influenced by a drop in serum concentrations of antiepileptic drugs.

Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p

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.

Aicardi syndrome is a rare neurodevelopmental disorder with agenesis of corpus callosum, chorioretinal lacunae, and infantile spasms as the main features. The outcome is in general severe, with poor cognitive development and difficult-to-treat epilepsy. In this study, we assessed the level of cognitive function of five girls with Aicardi syndrome, using normed population based tests and questionnaires. Their cognitive abilities varied from mild to profound intellectual disabilities. The more severe the epilepsy, the poorer were the cognitive skills. To the best of our knowledge, this is the first study that systematically applies validated cognitive assessment tools to study patients with this syndrome. Knowledge about cognitive functioning is crucial for providing optimal special education and finding appropriate alternative communication with parents and caregivers.

In Norway and Sweden, epilepsy has for many centuries been considered a strange and mysterious disease. The explanations of its causes have been many and imaginative. One being that epilepsy was caused by the hidden people inhabiting the woods and the mountains. To avoid the disease, these hidden people should not be annoyed. One commonly used treatment principle was to try to place the disease back to the ground, or passing the diseased through a hole or an opening in the nature. Fresh blood from criminals was also considered to have strong antiepileptic properties. In the Scandinavian countries, some of these folk beliefs have been very tenacious.

Introduction Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variation of clinical phenotypes. Familial variants are often milder than de novo cases, and may therefore remain undiagnosed. The aim of this study was to characterize the clinical course of GLUT1-DS in a four-generation Norwegian family where the oldest generations had never received any treatment. Method Through interviews and clinical investigations, we characterized a family of 26 members, where 11 members had symptoms strongly suggesting GLUT1-DS. All members were offered genetic testing of the SLC2A1 gene. Affected members were offered treatment with ketogenic diet, and the effect of the treatment was registered. Results We sequenced the SLC2A1 gene in 13 members, and found that 10, all with symptoms, had the c.823G > A (p.Ala275Thr) variant. All affected members had experienced early-onset epilepsy, paroxysmal exercise-induced dyskinesias, and most had mild learning disability. Moreover, some had symptoms and signs of a distal neuropathy in addition to reduced sense of orientation and excessive daytime sleep. Their load of symptoms had decreased over the years, although that they never had received any treatment. Nevertheless, those who started dietary treatment all experienced an improved quality of life. Conclusion We report a four-generation family with GLUT1-DS where the disease has a mild course, even when untreated. In addition to classical GLUT1-DS features, we also describe symptoms which have never been reported in GLUT1-DS previously. As such, this family extends the phenotypic spectrum of GLUT1-DS and underlines the importance of diagnosing also relatively mildly affected patients, even in adult life, as they also seem to benefit from dietary treatment.

In seizure-free patients with epilepsy, the question of whether, and if so when, it is acceptable to withdraw treatment may be difficult to answer. A thorough risk-benefit assessment should be undertaken with the patient and next of kin, during which the consequences of a relapse must be weighed against the disadvantages of continued administration of the drug. As a main rule, adult patients should have been seizure-free for at least two years before discontinuation is considered. In children with epilepsy with a known good prognosis, discontinuation may be considered even earlier.

SummaryObjective Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria. Methods This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999–2013. The study population consisted of 98,152 people

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. This research was supported by a research grant from the Norwegian Epilepsy Association.