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.

Drug-resistant epilepsy and ketogenic diet therapy - a qualitative study of families' experiences.

BACKGROUND: A diagnosis of drug-resistant epilepsy is life changing for a family. Ketogenic diet therapy (KDT) can offer hope when other treatments have failed. However, it often requires a significant change in daily routine and dietary habits. This qualitative descriptive study aimed to explore families' experiences of epilepsy and KDT. METHODS: Parents of a child aged ≤18 years with epilepsy, currently or recently treated with KDT, were recruited from the UK and internationally via UK Ketogenic Diet (KD) centres, charities, and social media. Semi-structured interviews were audio recorded, transcribed verbatim, anonymised, coded using Nvivo (V12), and inductive thematic analysis undertaken. RESULTS: Twenty-one parents participated. Four themes and 12 subthemes emerged: 1. 'Epilepsy is all consuming' explored the impact of epilepsy on the family. 2. 'KD provides a window to new opportunities' explores the motivators for KDT and positive outcomes. 3. 'The reality of KD' explores day to day life and how families adapt to KD. 4. 'Looking to the future' explores the factors that may make KD easier for families. All were glad their child trialled KD, even when less successful. The importance of a support network including family, friends, charity organisations and the KD team was evident across all themes. CONCLUSIONS: We conclude with five recommendations to help support families in their management of KDT; Improved access to KDT and transition to adult services, access to quality education and support, enhanced variety of KD foods, regular social education and finally consideration of peer mentoring.

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.

"One size does not fit all" - Barriers to and facilitators of physical activity in adolescents with epilepsy.

OBJECTIVE: To explore the barriers to physical activity and to identify the support needed to facilitate physical activity in adolescents with epilepsy (AWE). METHODS: AWE (aged 11-16 years) and their caregivers completed survey-based open questions regarding perceived barriers to, and facilitators of physical activity in young people with epilepsy. The responses were analysed using Thematic Analysis. RESULTS: Themes concerning barriers to physical activity included concerns about seizure safety, general anxiety and anxiety related to seizures, stigma/negative attitudes associated with having epilepsy, tiredness, and perceived lack of physical competence. Themes regarding the support needed to facilitate physical activity included better education amongst staff/coaches about epilepsy (e.g., seizure management/prevention, associated fatigue/tiredness), improvements in societal attitudes towards epilepsy, flexibility/tailoring of activities to the child's needs (e.g., need for breaks), and peer support for young people with epilepsy to encourage engagement in physical activity. CONCLUSIONS: There is a perception among AWE and caregivers, that significant barriers exist with regard to engaging in physical activity for young people with epilepsy. Barriers are related to concerns about seizure management but also wider safety and social issues. A number of facilitators were identified to promote physical activity engagement in AWE, including education for staff and caregivers, peer support, and tailoring activities to the adolescent's needs. There is a need to develop interventions to reduce barriers to physical activity in young people with epilepsy.

Characterizing Frontal Lobe Seizure Semiology in Children.

OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

BACKGROUND AND PURPOSE: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy. METHODS: A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement. RESULTS: A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted. CONCLUSIONS: These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.

Human milk and breastfeeding during ketogenic diet therapy in infants with epilepsy: Clinical practice guideline.

Ketogenic diet therapy (KDT) is a safe and effective treatment for epilepsy and glucose transporter type 1 (GLUT1) deficiency syndrome in infancy. Complete weaning from breastfeeding is not required to implement KDT; however, breastfeeding remains uncommon. Barriers include feasibility concerns and lack of referrals to expert centres. Therefore, practical strategies are needed to help mothers and professionals overcome these barriers and facilitate the inclusion of breastfeeding and human milk during KDT. A multidisciplinary expert panel met online to address clinical concerns, systematically reviewed the literature, and conducted two international surveys to develop an expert consensus of practical recommendations for including human milk and breastfeeding in KDT. The need to educate about the nutritional benefits of human milk and to increase breastfeeding rates is emphasized. Prospective real-world registries could help to collect data on the implementation of breastfeeding and the use of human milk in KDT, while systematically including non-seizure-related outcomes, such as quality of life, and social and emotional well-being, which could improve outcomes for infants and mothers.

Ketogenic dietary therapy utilization in Kenya: A qualitative exploration of dietitian's perceptions.

This study utilized a qualitative design to explore dietitians' perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were conducted, followed by thematic analysis of verbatim transcripts to identify recurring patterns. The study enrolled 18 dietitians, fourteen of whom correctly described their understanding of KDT for managing drug-resistant epilepsy. There was a lack of confidence in their capacity to initiate the KDT with all expressing the need for further training and facilitation. Only one dietitian reported having initiated and maintained KDT. There was an overall positive view regarding KDT and willingness to implement KDT for patients with drug-resistant epilepsy. Dietitians expressed concerns regarding the availability of national policies, inadequate staffing to support families who require KDT, and the cost of implementing this intervention. Dietitians expressed interest in virtual training to enhance their understanding of KDT. Dietitians in Kenya are mostly aware of KDT utilization for the management of drug-resistant epilepsy. However, they cited poor capability and various barriers to implementation. There is a need for policies to facilitate KDT as a treatment option for the benefit of patients with drug-resistant epilepsy.

Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = [7.8,15.0]) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., ßFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., ßFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

Accelerometer and Survey Assessed Physical Activity in Children With Epilepsy: A Case-Controlled Study.

PURPOSE: Anecdotal evidence suggests that children with epilepsy (CWE) are limited in the frequency of their daily physical activity (PA). However, there is limited research utilizing device-based measures of PA. We compared levels of PA and sedentary behavior in CWE (11-15 y) and age- and gender-matched healthy controls. METHOD: Participants (n = 60 CWE [25 males, 35 females] and n = 49 controls [25 males, 24 females]) wore a Actigraph accelerometer (GT3X or GT3X+) for 7 consecutive days during waking hours and self-reported their PA and sedentary behaviors. CWE were compared with control children on time spent in different intensities of PA and on self-reported PA and sedentary behavior. Factors associated with PA were analyzed using linear regression. RESULTS: CWE spent less time in accelerometer assessed light (189.15 vs 215.01 min/d, P < .05) and vigorous PA (35.14 vs 44.28 min/d, P < .05) on weekdays compared with controls. There were no significant differences between CWE and control participants in accelerometer assessed time spent sedentary or time spent in PA on weekends. Among CWE, older children engaged in more reported sedentary behavior and younger children spent more time in most domains of PA (P < .05). Furthermore, CWE reported less PA than controls (P = .006). Sixteen percent of controls met World Health Organization PA guidelines compared with 10% of CWE. There was a positive relationship between accelerometer assessed PA and quality of life for CWE. CONCLUSION: CWE spent less time in light and moderate to vigorous PA on weekdays. Further research is needed to understand reasons for these differences.

Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK.

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

A comprehensive systematic literature review of the burden of illness of Lennox-Gastaut syndrome on patients, caregivers, and society.

Fully elucidating the burden that Lennox-Gastaut syndrome (LGS) places on individuals with the disease and their caregivers is critical to improving outcomes and quality of life (QoL). This systematic literature review evaluated the global burden of illness of LGS, including clinical symptom burden, care requirements, QoL, comorbidities, caregiver burden, economic burden, and treatment burden (PROSPERO ID: CRD42022317413). MEDLINE, Embase, and the Cochrane Library were searched for articles that met predetermined criteria. After screening 1442 deduplicated articles and supplementary manual searches, 113 articles were included for review. A high clinical symptom burden of LGS was identified, with high seizure frequency and nonseizure symptoms (including developmental delay and intellectual disability) leading to low QoL and substantial care requirements for individuals with LGS, with the latter including daily function assistance for mobility, eating, and toileting. Multiple comorbidities were identified, with intellectual disorders having the highest prevalence. Although based on few studies, a high caregiver burden was also identified, which was associated with physical problems (including fatigue and sleep disturbances), social isolation, poor mental health, and financial difficulties. Most economic analyses focused on the high direct costs of LGS, which arose predominantly from medically treated seizure events, inpatient costs, and medication requirements. Pharmacoresistance was common, and many individuals required polytherapy and treatment changes over time. Few studies focused on the humanistic burden. Quality concerns were noted for sample representativeness, disease and outcome measures, and reporting clarity. In summary, a high burden of LGS on individuals, caregivers, and health care systems was identified, which may be alleviated by reducing the clinical symptom burden. These findings highlight the need for a greater understanding of and better definitions for the broad spectrum of LGS symptoms and development of treatments to alleviate nonseizure symptoms.

Diagnosis of Lennox-Gastaut syndrome and strategies for early recognition.

INTRODUCTION: Lennox Gastaut syndrome (LGS) as an electroclinical diagnosis has been utilized as a clinical entity for more than 70 years. However, with the recognition of other distinct electroclinical epilepsy syndromes, no consistent single etiology, and the variability of criteria used in clinical trials, the clinical utility of such a diagnosis has been questioned. Recently, the International League Against Epilepsy for the first time defined diagnostic criteria for epilepsy syndromes, thereby allowing consistent language and inclusion criteria to be utilized. AREAS COVERED: Recent diagnostic criteria for syndrome diagnosis are explored as defined by the International League Against Epilepsy, with further literature reviewed to highlight relevant features, and differential diagnosis explored. EXPERT OPINION: Developmental and Epileptic Encephalopathy (DEE) is an overall term that may be descriptive of many different epilepsies, most of early onset, whether electroclinically or etiologically defined, of which LGS is one. Although we have moved forward in defining an increasing number of etiologically specific syndromes, this to date remains a minority of the DEEs. Although there is progress with precision medicine targeted at specific causes, the term LGS still remains useful as a diagnosis in defining treatment options, as well as overall prognosis.

A systematic literature review on the global epidemiology of Dravet syndrome and Lennox-Gastaut syndrome: Prevalence, incidence, diagnosis, and mortality.

Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A comprehensive understanding of how many individuals are affected globally, the diagnostic journey they face, and the extent of mortality associated with these conditions is lacking. Here, we summarize and evaluate published data on the epidemiology of DS and LGS in terms of prevalence, incidence, diagnosis, genetic mutations, and mortality and sudden unexpected death in epilepsy (SUDEP) rates. The full study protocol is registered on PROSPERO (CRD42022316930). After screening 2172 deduplicated records, 91 unique records were included; 67 provided data on DS only, 17 provided data on LGS only, and seven provided data on both. Case definitions varied considerably across studies, particularly for LGS. Incidence and prevalence estimates per 100 000 individuals were generally higher for LGS than for DS (LGS: incidence proportion = 14.5-28, prevalence = 5.8-60.8; DS: incidence proportion = 2.2-6.5, prevalence = 1.2-6.5). Diagnostic delay was frequently reported for LGS, with a wider age range at diagnosis reported than for DS (DS, 1.6-9.2 years; LGS, 2-15 years). Genetic screening data were reported by 63 studies; all screened for SCN1A variants, and only one study specifically focused on individuals with LGS. Individuals with DS had a higher mortality estimate per 1000 person-years than individuals with LGS (DS, 15.84; LGS, 6.12) and a lower median age at death. SUDEP was the most frequently reported cause of death for individuals with DS. Only four studies reported mortality information for LGS, none of which included SUDEP. This systematic review highlights the paucity of epidemiological data available for DS and especially LGS, demonstrating the need for further research and adoption of standardized diagnostic criteria.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Patient, parent and carer perspectives surrounding expedited paediatric epilepsy surgery.

OBJECTIVE: Most paediatric epilepsies with MRI visible lesions do not respond to antiseizure pharmacotherapy. Such medication resistance, which often takes years to become formally defined, is commonly required for surgical candidacy. Expedited surgical referral at lesional epilepsy diagnosis may result in better seizure, cognitive and developmental prognoses. This study explored the views of patients, parents and carers regarding epilepsy surgery, treatment priorities, and participation in a proposed expedited surgery trial. METHODS: 205 patients, parents and carers (61% UK-based, 26% North American) responded to electronic surveys from February to May 2022. Participants were recruited through social media sites, epilepsy charities and societies. Categorical choice and free-text questions were used to investigate participant perspectives, and Pearson's chi-squared test was utilised to detect meaningful differences amongst respondent subgroups. RESULTS: Almost 90% of respondents who had experienced epilepsy surgery (either themselves or their child) reported seizure cessation or reduction. Postoperative outcome measures prioritised most frequently were seizure freedom (66%), quality of life (47%), seizure severity (30%), seizure frequency (28%) and independence (27%). Most participants support expedited surgery in suitable patients (65%), with just over half (51%) willing to participate in the proposed trial. Many participants (37%) were undecided, often due to fears surrounding neurosurgery. Subgroup perspectives were broadly similar, with more parents and caregivers favouring expedited surgery compared to patients (p = .016) and more UK-based participants willing to take part in an expedited surgery trial compared to those from North America (p = .01). CONCLUSIONS: Patients, parents and carers are open to considering expedited surgery for lesional epilepsies and would support a trial exploring this approach. Priorities from treatment were largely similar between participant subgroups, with seizure, quality of life and neuropsychological outcomes ranked highly. Accounting for these preferences will facilitate the delivery of a trial that is patient- and caregiver-focused, enhancing feasibility, satisfaction and benefit for prospective participants.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed.