Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Estimating the active and lifetime prevalence and incidence of epilepsy in Asian Countries: A systematic review and meta-analysis.

OBJECTIVE: In the current era of the World Health Organization's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP), precise and updated estimates of epilepsy burden are vital in formulating policies to improve the care of persons with epilepsy, especially in Asian countries with significant treatment gap. Hence, we aimed to consolidate the available data and quantify epilepsy prevalence and incidence estimates in Asian countries. METHODS: We systematically searched PubMed, Embase, Ovid, and Scopus databases from inception until March 2023 for studies reporting epilepsy prevalence and incidence in Asian countries. We applied random effects meta-analysis to generate the pooled prevalence and incidence using the Meta package in R. Additionally, we performed a subgroup meta-analysis to explore the potential sources of heterogeneity. A meta-regression analysis was conducted to examine the trend of epilepsy over time. RESULTS: A total of 99 studies with 100,654,124 participants were included in the meta-analysis. The pooled prevalence was 5.6 per 1000 (95 % confidence interval (CI) 4.4-6.8) for active epilepsy and 6.7 per 1000 (95 % CI 5.7-7.9) for lifetime epilepsy. The pooled incidence rate of epilepsy was 52.5 per 100,000 person-years (95 % CI 42.7-79.4). The subgroup analysis revealed a higher prevalence of active epilepsy (6.7/1000) and lifetime epilepsy (8.6/1000) in West Asia than in other regions. The funnel plot and Egger's test (p-value =<0.0001) revealed publication bias for active epilepsy. CONCLUSION: Our findings highlight a high prevalence of active and lifetime epilepsy in West Asia and emphasize the necessity of implementing and formulating specific strategies to tackle the epilepsy burden in this region. Furthermore, high-quality epidemiological studies incorporating economic burdens and comorbidities associated with epilepsy in Asia are still needed.

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING: National Institute for Health Research Health Technology Assessment programme.

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. METHODS: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. INTERPRETATION: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

What really matters? A mixed methods study of treatment preferences and priorities among people with epilepsy in the UK.

The widening range of treatment options for epilepsy, and their potential outcomes, mean decisions about treatment for people with epilepsy (PWE) are often complex. While antiepileptic drugs (AEDs) represent the mainstay of treatment, other potential nondrug interventions are gaining in importance. These treatments all have the potential for harming those using them, as well as bringing benefits. This study examined the views and experiences of PWE about a range of treatment options. We used both qualitative and quantitative approaches - a series of depth-narrative interviews, followed by a large-scale survey. Treatment options and healthcare priorities deemed important by at least 10% of interview participants were then addressed as a series of statements in the follow-on survey questionnaire. Quantitative responses supported healthcare priorities identified through the qualitative interviews. The key goal of treatment among study participants was to be able to live 'a normal life'. Important physical, psychological, and life benefits of treatment were identified - most being the direct consequence of improved seizure control. One psychological benefit, reduced worry, was also identified as an important treatment goal. All participants viewed AEDs as appropriate first-line treatment; and since adverse effects of AEDs had implications for individual levels of daily function and wellbeing, their appropriate management was considered important. In contrast, surgery was almost always regarded as the treatment of last resort. Despite lack of research evidence supporting their use, participants were interested in complementary therapies as adjunctive treatment and a means of coping with having epilepsy, with yoga and meditation of particular interest. An important finding was the desire for targeted services to help with memory problems, as was the call to increase availability of psychological/counseling services. Our findings emphasize the importance of providing treatment responsive to the life context of individual patients. They highlight not only the level of demand for specific treatment options, but also the need for high-quality evidence to support future investment in their provision.

Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study.

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.

A voxel-based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients.

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole-brain voxel-based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty-four controls were also studied. Right-handed controls and right-handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo-occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right-handed. These results suggest that structural asymmetries of an insular-fronto-temporal network may be related to HLD.

The effectiveness of a group self-management education course for adults with poorly controlled epilepsy, SMILE (UK): A randomized controlled trial.

OBJECTIVE: Epilepsy is one of the most common neurological conditions affecting about 1% of adults. Up to 40% of people with epilepsy (PWE) report recurring seizures while on medication. And optimal functioning requires good self-management. Our objective was to evaluate a group self-management education courses for people with epilepsy and drug-resistant seizures by means of a multicenter, pragmatic, parallel group, randomized controlled trial. METHODS: We recruited adults with epilepsy, having ≥2 seizures in the prior 12 months, from specialist clinics. Consenting participants were randomized 1:1 to a group course or treatment as usual. The primary outcome measure was quality of life 12 months after randomization using Quality of Life 31-P (QOLIE-31-P). Secondary outcome measures were seizure frequency and recency, psychological distress, impact and stigma of epilepsy, self-mastery, medication adherence, and adverse effects. Analysis of outcomes followed the intention-to-treat principle using mixed-effects regression models. RESULTS: We enrolled 404 participants (intervention: n = 205, control: n = 199) with 331 (82%) completing 12-month follow-up (intervention: n = 163, control: n = 168). Mean age was 41.7 years, ranging from 16 to 85, 54% were female and 75% were white. From the intervention arm, 73.7% attended all or some of the course. At 12-month follow-up, there were no statistically significant differences between trial arms in QOLIE-31-P (intervention mean: 67.4, standard deviation [SD]: 13.5; control mean: 69.5, SD 14.8) or in secondary outcome measures. SIGNIFICANCE: This is the first pragmatic trial of group education for people with poorly controlled epilepsy. Recruitment, course attendance, and follow-up rates were higher than expected. The results show that the primary outcome and quality of life did not differ between the trial arms after 12 months. We found a high prevalence of felt-stigma and psychological distress in this group of people with drug-resistant seizures. To address this, social and psychological interventions require evaluation, and may be necessary before or alongside self-management-education courses.

Concordance between the Wada test and neuroimaging lateralization: Influence of imaging modality (fMRI and MEG) and patient experience.

The Wada test remains the traditional test for lateralizing language and memory function prior to epilepsy surgery. Functional imaging, particularly functional MRI (fMRI), has made progress in the language domain, but less so in the memory domain. Magnetoencephalography (MEG) has received less research attention, but shows promise, particularly for language lateralization. We recruited a consecutive sample of 19 patients with epilepsy who had completed presurgical work-up, including the Wada test, and compared fMRI (memory) and MEG (language and memory) with Wada test results. The main research question was the concordance between Wada and these two imaging techniques as preepilepsy surgery investigations. We were also interested in the acceptability of the three techniques to patients. Concordance rates (N=16) were nonsignificant (Cohen's Kappa) between fMRI and Wada test (memory) and between MEG and Wada test (memory and language). The Wada test was a well-established protocol used at several epilepsy surgery centers in the UK. Patients generally found the Wada test an odd, but not aversive procedure. Sixteen (84%) patients who were scanned reported some level of obtundation in MEG. We present these discordant findings in support of the position that functional imaging and the Wada test are distinctive procedures, with little in the way of overlapping mechanisms, and that patient's experience should be taken into account when procedures are selected and offered to them.

A randomized controlled trial of a manual-based psychosocial group intervention for young people with epilepsy [PIE].

We conducted an exploratory RCT to examine feasibility and preliminary efficacy for a manual-based psychosocial group intervention aimed at improving epilepsy knowledge, self-management skills, and quality of life in young people with epilepsy. METHOD: Eighty-three participants (33:50m/f; age range 12-17years) were randomized to either the treatment or control group in seven tertiary paediatric neuroscience centres in the UK, using a wait-list control design. Participants were excluded if they reported suicidal ideation and/or scored above the cut off on mental health screening measures, or if they had a learning disability or other neurological disorder. The intervention consisted of six weekly 2-hour sessions using guided discussion, group exercises and role-plays facilitated by an epilepsy nurse and a clinical psychologist. RESULTS: At three month follow up the treatment group (n=40) was compared with a wait-list control group (n=43) on a range of standardized measures. There was a significant increase in epilepsy knowledge in the treatment group (p=0.02). Participants receiving the intervention were also significantly more confident in speaking to others about their epilepsy (p=0.04). Quality of life measures did not show significant change. Participants reported the greatest value of attending the group was: Learning about their epilepsy (46%); Learning to cope with difficult feelings (29%); and Meeting others with epilepsy (22%). Caregiver and facilitator feedback was positive, and 92% of participants would recommend the group to others. CONCLUSION: This brief psychosocial group intervention was effective in increasing participants' knowledge of epilepsy and improved confidence in discussing their epilepsy with others. We discuss the qualitative feedback, feasibility, strengths and limitations of the PIE trial.

Predicting the psychosocial outcome of epilepsy surgery: A longitudinal perspective on the 'burden of normality'.

Good seizure outcomes and good psychosocial outcomes following epilepsy surgery do not necessarily follow one from the other. This study explored the relationship between several presurgical psychosocial characteristics and postsurgical quality-of-life outcomes. The study aimed to develop the concept of 'the burden of normality' and identify risk factors for a poor psychosocial outcome that could be targeted with ameliorative presurgery cognitive behavioral techniques. Data were collected from 77 epilepsy surgery patients from three UK epilepsy centers and presurgery and postsurgery follow-up data were obtained from 30-34 patients, depending on the measure. Measures were self-report. Postsurgery intervals were determined by the epilepsy surgery care pathway at individual centers. Presurgery poor levels of mental health, poor social functioning, increased belief in illness chronicity, and associating epilepsy with social role limitations were all associated with poor postsurgical quality of life. Adopting an accepting coping strategy presurgery was associated with good postoperative quality of life. Regression analysis showed that a good postsurgical quality of life was positively predicted by a presurgical coping style of being able to make the best of a situation and see challenges in a positive light (i.e., positive reinterpretation and growth from the COPE scale) and negatively predicted by presurgical levels of anxiety. These data are presented as an important step in identifying psychological red flags for an adverse psychosocial outcome to epilepsy surgery, as exemplified by the concept of the 'burden of normality' and specifying targets for preoperative ameliorative psychological advice.

Does the concept of resilience contribute to understanding good quality of life in the context of epilepsy?

A significant body of research highlights negative impacts of epilepsy for individual quality of life (QOL). Poor seizure control is frequently associated with reporting of poor QOL and good seizure control with good QOL; however, this is not a universal finding. Evidence suggests that some people enjoy good QOL despite ongoing seizures while others report poor QOL despite good seizure control. Understanding the factors that influence QOL for people with epilepsy and the processes via which such factors exert their influence is central to the development of interventions to support people with epilepsy to experience the best possible QOL. We present findings of a qualitative investigation exploring influences and processes on QOL for people with epilepsy. We describe the clinical, psychological, and social factors contributing to QOL. In particular, we focus on the value of the concept of resilience for understanding quality of life in epilepsy. Based on our analysis, we propose a model of resilience wherein four key component sets of factors interact to determine QOL. This model reflects the fluid nature of resilience that, we suggest, is subject to change based on shifts within the individual components and the interactions between them. The model offers a representation of the complex influences that act and interact to either mitigate or further compound the negative impacts of epilepsy on individual QOL.

NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy.

Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy. A total of 82 patients who had previously undergone detailed neuropsychological assessment were genotyped for single nucleotide polymorphisms (SNPs) across the NRSF and BDNF genes. Putatively functional SNPs were included in a genetic association analysis with specific cognitive domains, including memory, psychomotor speed, and information processing. Cross-sectional and longitudinal designs were used to explore genetic influences on baseline cognition at diagnosis and change from baseline over the first year since diagnosis, respectively. We found a statistically significant association between genotypic variation and memory function at both baseline (NRSF: rs1105434, rs2227902 and BDNF: rs1491850, rs2030324, rs11030094) and in our longitudinal analysis (NRSF: rs2227902 and BDNF: rs12273363). Psychomotor speed was also associated with genotype (NRSF rs3796529) in the longitudinal assessment. In line with our previous work on general cognitive function in the healthy aging population, we observed an additive interaction between risk alleles for the NRSF rs2227902 (G) and BDNF rs6265 (A) polymorphisms which was again consistent with a significantly greater decline in delayed recall over the first year since diagnosis. These findings support a role for the NRSF-BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy.

Quality-of-life outcomes of initiating treatment with standard and newer antiepileptic drugs in adults with new-onset epilepsy: findings from the SANAD trial.

OBJECTIVE: To compare quality-of-life (QoL) outcomes over 2 years following initiation of treatment with a standard or newer antiepileptic drug (AED) in adults with new-onset epilepsy. To examine the impact of seizure remission and failure of initial treatment on QoL outcomes measured over 2 years. METHODS: We conducted a pragmatic, randomized, unblinded, multicenter, parallel-group clinical trial (the Standard and New Antiepileptic Drugs [SANAD] trial) comparing clinical and cost effectiveness of initiating treatment with carbamazepine versus lamotrigine, gabapentin, oxcarbazepine and topiramate, and valproate versus lamotrigine and topiramate. QoL data were collected by mail at baseline, 3 months, and at 1 and 2 years using validated measures. These data were analyzed using longitudinal data models. Continuous QoL measures, time to 12-month remission and time to treatment withdrawal were explored using joint models. RESULTS: Baseline questionnaires were returned by 1,575 adults; 1,439 returned the 3-month questionnaire, 1,274 returned the 1-year questionnaire, and 1,121 returned the 2-year questionnaire. There were few statistically significant differences between drugs over 2 years in QoL outcomes. Significant association was identified between QoL scores over the 2-year time frame and the risk of experiencing a 12-month remission or treatment withdrawal over that period. SIGNIFICANCE: The choice of initial treatment had no significant effect on QoL by 2-year follow-up. However, overall QoL was reduced with continued seizures, adverse events, and failure of the initial treatment.

Indications and expectations for neuropsychological assessment in routine epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013-2017.

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy.

Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

AIM: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. METHODS: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. RESULTS: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. CONCLUSION: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.

Self-reported anxiety and sleep problems in people with epilepsy and their association with quality of life.

Comorbidities are common in epilepsy, and their role in quality of life (QOL) is receiving increasing scrutiny. Considerable attention has been focused on the role of depression, the most common comorbidity, with rather less attention paid to its frequent concomitant, anxiety, and other conditions known to be at increased prevalence among people with epilepsy (PWE) when compared to the general population. In this paper, we report findings from a UK-based survey in which we examined self-reporting of two common comorbidities, anxiety and sleep problems, factors associated with them, and their role in QOL in people with and without epilepsy. Data were obtained via mailed questionnaires, supplemented by an internet survey, from PWE and age- and gender-matched controls. Based on self-reported symptoms, PWE were at higher risk of anxiety and sleep problems. Contributory factors for anxiety included poorer general health, worry about seizures, and self-reported antiepileptic drug (AED) side effects. Good social support emerged as protective for anxiety in PWE. Nighttime sleep problems were very common even in controls but were further elevated in PWE. Antiepileptic drug adverse events emerged as an important contributory factor for sleep problems. Trait anxiety emerged as significant for defining overall QOL, and its importance over state anxiety supports the notion of anxiety in PWE as a primarily premorbid condition. In contrast, sleep quality was not consistently predictive of QOL. Our study has important implications for clinical management, emphasizing the need for a holistic approach to address wider patient-reported problems as well as any epilepsy-specific ones.