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

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

Cognitive change after DBS in refractory epilepsy: A randomized-controlled trial

Objectives Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) reduces seizure frequency in patients with refractory epilepsy. There are, however, few studies on treatment-related changes in cognitive functions. The main objective of this study was to investigate cognitive changes in patients receiving ANT-DBS. We also explored whether possible effects were related to stimulation duration and whether change in seizure frequency was associated with cognitive changes. Materials and methods Bilateral ANT electrodes were implanted in 18 patients with refractory epilepsy, aged 18–52 years. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the following 6-month open phase, both groups received stimulation. Neuropsychological assessments were conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). Results Groupwise comparisons across the three time points revealed changes in performance in two of 22 cognitive test scores: motor speed and sustained attention. We found no significant group differences in cognitive change from T1 to T2. Patients reported fewer symptoms of executive dysfunction after 12 months of stimulation. Patients showing significant improvement in seizure frequency had better performance in a measure of verbal learning. Conclusion Our results indicate that ANT-DBS has very limited effects on cognitive functioning, as measured by formal tests after 6- or 12-month stimulation. ANT-DBS may have a positive influence on executive function. Our findings provide limited support for an association between change in seizure frequency and cognitive functioning

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

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 ( ± 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

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

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