Health-related quality of life in adults with drug-resistant focal epilepsy treated with modified Atkins diet in a randomized clinical trial.

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.

Norwegian population-based study of long-term effects, safety, and predictors of response of vagus nerve stimulation treatment in drug-resistant epilepsy: The NORPulse study.

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.

The effect of attachment style on long-term outcomes in psychogenic nonepileptic seizures: Results from a prospective study.

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.

Incidence and prevalence of psychogenic nonepileptic seizures in a Norwegian county: A 10-year population-based study.

OBJECTIVE: This study was undertaken to measure the incidence and prevalence of active psychogenic nonepileptic seizures (PNES) in a Norwegian county. METHODS: Using the Norwegian patient registry, we identified patients in Møre and Romsdal County in Norway diagnosed with F44.5 (conversion disorder with seizures or convulsions) or R56.8 (convulsions, not elsewhere classified) in the period January 2010 to January 2020. A review of the patients' medical records and an assessment of diagnostic validity were performed. PNES were diagnosed according to the recommendations by the International League Against Epilepsy Nonepileptic Seizures Task Force. Point prevalence of PNES on January 1, 2020 and incidence rates for the period 2010-2019 were determined. RESULTS: Based on PNES within the past 5 years, we found a PNES prevalence of 23.8/100 000 (95% confidence interval [CI] = 17.9-29.6), including all levels of diagnostic certainty. For the highest level of diagnostic certainty (video-electroencephalographically confirmed), the prevalence was 10.6/100 000 (95% CI = 6.7-14.5). The highest prevalence was found in the age group 15-19 years, at 59.5/100 000 (95% CI = 22.6-96.3). The mean annual incidence rate between 2010 and 2019 was 3.1/100 000/year (95% CI = 2.4-3.7). SIGNIFICANCE: We report for the first time a population-based estimate of the prevalence of PNES. Our findings suggest that the prevalence of PNES is within the range of estimates from non-population-based data. We found a strikingly high prevalence of PNES in the 15-19-year age group.

Effect and tolerability of perampanel in patients with drug-resistant epilepsy.

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.

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

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 ( ±â€¯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 ±â€¯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.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

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.

Role of the glymphatic system and perivascular spaces as a potential biomarker for post-stroke 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.

Norwegian population-based study of effectiveness of vagus nerve stimulation in patients with developmental and epileptic encephalopathies.

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.

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

PURPOSE: The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. METHOD: A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. RESULTS: Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. CONCLUSION: This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe.

Epilepsy and eating disorders during pregnancy: Prevalence, complications and birth outcome.

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.

[Restless legs]. / Rastløse bein.

BACKGROUND: Restless legs syndrome is a common and not fully appreciated disorder. Improved treatment options require knowledge about the condition. MATERIAL AND METHODS: The article is based on a literature search on Medline, PubMed and Scirus for the years 1988-2003 with the keyword "restless legs". RESULTS AND INTERPRETATION: Restless legs syndrome is a chronic condition defined as an irresistible desire to move one's limbs, usually associated with paraesthesia/dysaesthesia and motor restlessness. The symptoms start or worsen at rest and improve with activity. The prevalence is between 5% and 15%. 80% of patients suffer from periodic limb movements in sleep. A current hypothesis is that the condition results from a deficiency of iron that lead to the underlying dopaminergic abnormalities. Therapeutically, studies have confirmed the effect of levodopa and dopamine agonists; dopamine agonists seem to imply less risk of side effects.

[Post-stroke epilepsy]. / Epilepsi etter hjerneslag.

BACKGROUND: Stroke (infarction or haemorrhage) is an important cause of epilepsy in adulthood, especially in the elderly. Because of a high incidence and improved survival, post-stroke epilepsy (PSE) is a great contemporary challenge for physicians. In our studies we have defined PSE as two or more seizures occurring more than four weeks after the stroke. MATERIAL AND METHODS: Based on our studies and a review of the literature, we give an account of the incidence, predictors, pathophysiology, and prognosis of PSE. RESULTS: The incidence in the literature varies greatly, from 2.3% to 43%. Our data shows an incidence of 2.5% after one year, increasing to 4.4% after five years. Severe strokes have higher incidence of PSE than minor strokes. INTERPRETATION: The variation in incidence reflects differences in the patient populations studied, definition of PSE, and study design. Our studies were prospective and in a well-defined area with high focus on admitting patients with any sign of stroke to hospital. This results in a "population" of stroke patients with severe strokes with high mortality rate, and patients with minor strokes not likely to develop PSE. In our material, severe strokes increased the incidence of PSE five-fold compared to minor strokes. We saw almost a doubling of the incidence one year to five years after the stroke. This might be explained by a long epileptogenesis, but it could also be due to high morbidity in this age group.

Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study).

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.