Current Evidence: Seizures in Extremely Low Gestational Age Newborns (ELGANs).

Extremely low gestational age newborns (ELGANs) are born at or below 28 weeks of gestational age. Despite improved obstetric care, the incidence of preterm birth continues to rise in advanced countries. Preterm birth remains a major cause of infant mortality, and for infants who survive, neonatal seizures are a significant predictor of later neurologic morbidity. However, little is known about risk factors for neonatal seizures in ELGANs. Understanding the association between neonatal seizures and the development of other neurologic disorders is important given the increasing prevalence of ELGANs. Identifying risk factors that contribute to the development of neonatal seizures in ELGANs may offer insights into novel mechanisms of epileptogenesis in the developing brain and improvements in the prevention or treatment of seizures in preterm infants, including ELGANs. In this literature review, we outline the limitations of epidemiologic studies of neonatal seizures in ELGANs and discuss risk factors for neonatal seizures.

Evolution of antiseizure medication use and cost in the United States of America 2006-2021.

OBJECTIVE: To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA). METHODS: Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator. RESULTS: We evaluated 347,158 patients (46.9 % males; median (p25-p75) age: 33 (17-49) years; 28 % with pediatric-onset epilepsy and 72 % with adult-onset epilepsy) with a total of 1,385,382 person-years and 588,285,065 ASM prescription days. The most commonly prescribed (as percentage of prescription days) ASMs in 2006 were valproate (18 %) and lamotrigine (17 %) in pediatric-onset epilepsy and phenytoin (21 %) and carbamazepine (17 %) in adult-onset epilepsy, but starting in the 2010s, levetiracetam and lamotrigine became the most commonly prescribed ASMs in both pediatric-onset (in 2021, levetiracetam 25 %, lamotrigine 16 %) and adult-onset (in 2021, levetiracetam 27 %, lamotrigine 20 %) epilepsy. The proportion of generic ASM use increased 3.6-fold: from 23 % of prescription days in 2006 to 83 % of prescription days in 2021. The median (p25-p75) average wholesale price (AWP) per person-year increased by 102 % from $2,684 ($990-$5,509) in 2006 to $5,417 ($2,858-$12,310) in 2021. The increases were greater in absolute terms for brand-name ASMs by 419 %: $3,109 ($1,564-$5,068 in 2006 and $16,149 ($12,950-$23,377) in 2021 than for generic ASMs by 462 %: $699 ($457-$1,678) in 2006 and $3,931 ($2,618-$6,081) in 2021. The costs directly borne by the patient (copay, coinsurance, deductibles, and pharmacy processing fees) increased by 69 % for brand-name ASMs from $393 ($246-$570) in 2006 to $665 ($335-$1,308) in 2021, but decreased by 37 % for generic ASMs from $147 ($98-$213) in 2006 to $92 ($51-$141) in 2021. CONCLUSIONS: The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83 % of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

Health care resource utilization and costs before and after epilepsy surgery.

OBJECTIVE: To describe the demographics of epilepsy surgery utilization and its impact on health care resource use. METHODS: Retrospective descriptive study using the MarketScan commercial claims database. We studied children and adults who underwent epilepsy surgery in the USA in the period 2006-2019. Our main outcome was health care resource utilization. RESULTS: Among the 87,368 patients with refractory epilepsy, 2,011 (2.3%) patients underwent resective epilepsy surgery, 188 (0.2%) patients underwent partial or total hemispherectomy, and 183 (0.2%) patients underwent corpus callosotomy. The proportion of patients undergoing epilepsy surgery has barely increased in the period 2006 to 2019. The year of resective epilepsy surgery was associated with high healthcare costs per person-year [median (p25-p75): $140,322 ($88,749-$225,862)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of resective epilepsy surgery [$7,691 ($2,738-$22,092) versus $18,750 ($7,361-$47,082), p-value < 0.0001]. This result held in all resective epilepsy surgery subgroups: children, adults, temporal, extratemporal, subdural EEG monitoring, stereoEEG monitoring, and no intracranial monitoring. Similarly, the year of hemispherectomy was associated with high healthcare costs per person-year [$260,983 ($154,791-$453,986)], but healthcare costs per person-year substantially decreased in the 5 years after compared to the 5 years before the year of hemispherectomy [$26,834 ($12,842-$52,627) versus $54,596 ($19,547-$136,412), p-value < 0.0001]. In contrast, the year of corpus callosotomy was associated with high healthcare costs per person-year [$162,399 ($108,150-$253,156)], but healthcare costs per person-year did not substantially decrease in the 5 years after than in the 5 years before the year of corpus callosotomy [$25,464 ($10,764-$69,338) versus $36,221 ($12,841-$85,747), p-value = 0.2142]. CONCLUSION: In privately insured patients in the USA, resective epilepsy surgery and hemispherectomy substantially decrease healthcare utilization in subsequent years. Epilepsy surgery may help contain costs in the field of epilepsy.

Using an animated video to promote an informed discussion on SUDEP with adolescents.

PURPOSE: The purpose of this study was to create and test an animated video to teach adolescent patients about Sudden Unexpected Death in Epilepsy (SUDEP). METHOD: Thirty-nine patients and thirteen parents watched the SUDEP video and completed at least one survey. Patients with epilepsy aged 14+ and their parents were recruited to watch the video during neurology clinic visits. Parents of minors provided verbal permission for their child to view the video. Participants were asked to complete pre- and post-video surveys. Data analysis included Fischer's exact tests for comparative data and percentages for categorical variables. RESULTS: After watching the SUDEP video, 100% of parents and patients agreed that the video provided helpful knowledge, and 100% of parents and 96% of patients agreed that patients with epilepsy should know about SUDEP. Half of the parents surveyed, and 20% of patients, felt increased concerns after watching the video. Patients rated their understanding of SUDEP significantly higher after watching the video (p < 0.001). CONCLUSION: Participants in this study thought that it was important for patients with epilepsy to know about SUDEP, and all agreed that the animated SUDEP video provided helpful knowledge. While some parents endorsed increased concerns after watching the video, the majority of parents still agreed to allow their child to watch the video. Adolescent education on SUDEP using a family-centered approach may be an important method of encouraging harm-reducing behaviors that can be lifesaving for patients with epilepsy. The standard of practice for SUDEP disclosure should continue to be face-to-face discussion with providers, and we propose this video as a tool to elevate and inform those discussions.

Assessment and Treatment of Concussion in the Pediatric Population.

Traumatic brain injury (TBI) is common in children. The evaluation and management of children with TBI is based on the research performed in adults. There is a relative paucity of research in the literature involving children and many of the practice recommendations for this age are based on expert opinion in the absence of good research studies in both sports and non-sports-related injuries. The pediatric population is heterogeneous and the approach might be specific for infants, preschoolers, school age children, and adolescents. Children may also suffer from neurodevelopmental disabilities, making their evaluation even more challenging. Adult neurologists are often asked to see children due to increasing demands. This review will focus on specific issues related to TBI in children that might be useful to adult neurologists. Science, however, is evolving rapidly and physicians should make sure to remain up to date to offer evidence-based services to their patients.

A Novel Parent Questionnaire for the Detection of Seizures in Children of Spanish-Speaking Families.

BACKGROUND: We developed and validated a Spanish seizure screen for children based on a previously validated English seizure screen that could be administered by a trained research assistant in a 2-step process, approximating the clinical diagnostic process of a pediatric epilepsy specialist. This questionnaire was designed to study seizure prevalence in a research population of children at risk for epilepsy. METHODS: Spanish-speaking parents of children 6 months to 17 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. A computerized algorithm of parent responses rendered a seizure classification of positive or negative. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using a 4-level scale based on clinical history and examination: (1) not likely, (2) indeterminate, (3) probable, and (4) almost certain where rankings of 3 or 4 lead to a diagnosis of seizure. RESULTS: The questionnaire was completed by 163 enrolled parents. The seizure screen demonstrated a 94.2% sensitivity and 93.7% specificity for identifying seizures. The positive predictive value was 87.5%, and the negative predictive value was 97.2%. CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to clinicians and researchers in screening large populations of children, decreasing the time and cost of added neurologic assessments.

Mentorship for Youth With Chronic Neurological Conditions in the Digital Era: An Innovative Approach to Supporting Transition.

This article aims to highlight the impact of mentorship on the lives of youth with chronic conditions (YCC). Here, we focus on the concepts of mentoring and technology as a means to support transitioning YCC. This is in response to the urgent need for effective healthcare transition strategies and the increasing importance and prevalence of technology in healthcare and health systems. This article also highlights an e-mentoring program for youth with epilepsy, an intervention that bridges the fields of mentoring, transition, and technology. While there is need for further research in these areas, consideration of these factors are highly relevant to the effort to improve health for this generation of YCC.

A Multimodal Telehealth Strategy to Improve Pediatric Epilepsy Care.

A team of providers, researchers, patients, and families created a novel telehealth tool to improve communication across a variety of systems involved in pediatric epilepsy care. This tool facilitates in-home telemedicine appointments and saves costs for patients and hospital systems alike within the context of a population highly affected by health care disparities.

Clinical Implementation of a Parent Questionnaire to Identify Seizures in High-Risk Children.

BACKGROUND: This study evaluated the effectiveness of a parent-completed questionnaire for detecting seizures in high-risk children. METHODS: A 2-part seizure screen for children up to 12 years of age with suspected autism spectrum disorder, developmental delay, or seizure, was implemented in 12 Massachusetts clinics serving populations with high health disparities. Primary care providers and developmental behavioral pediatricians administered part 1, a brief highly sensitive screen. If the result was positive, a research assistant administered part 2, a more detailed screen with higher specificity. Positive part 2 results prompted a specialized assessment by a pediatric neurologist. Screening data were evaluated for detection of seizures or other diagnoses, reason for conducting the screen, and appointment outcomes. Data analysis included chi-squared tests, percentages for categorical variables, and means for numerical data. RESULTS: Of 207 administered seizure questionnaires, 78% of children screened positive on part 1. Of those, 94% of families completed part 2 by telephone, and 64 individuals screened positive. The screen helped to detect 15 new seizure diagnoses and 35 other neurologic diagnoses. Average time to first scheduled appointment was 23.8 days. The no-show rate was 7%. CONCLUSIONS: The seizure questionnaire effectively identified seizures and other disorders in a diverse population of high-risk children. Broader use of this low-cost screening tool could improve access to care for children with suspected seizures, increase seizure recognition, and help allocate resources more effectively.

A Novel Parent Questionnaire for the Detection of Seizures in Children.

BACKGROUND: We developed a seizure questionnaire that could be administered by a trained research assistant in a two-step process, approximating the clinical diagnostic process of a pediatric epileptologist. This questionnaire was designed to study seizure prevalence in a research population of 10-year-old children at risk for epilepsy. METHODS: English-speaking parents of children 6 months to 12 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. An algorithm of parent responses rendered a 4-level ranking scale of seizure probability for events: (1) not likely, (2) indeterminate, (3) probable, (4) almost certain. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using the same four-level scale based on clinical history and examination. RESULTS: The questionnaire was completed by 150 of 177 (84.7%) enrolled parents. Seizure prevalence among participants was 38.6%. The seizure questionnaire yielded a fitted receiver operating characteristic area of 0.93 (95% confidence interval [CI], 0.89-0.97). Based on optimal sensitivity and false-positive fraction, we dichotomized the questionnaire results as consistent with seizure (levels 3 and 4) or without seizure (levels 1 and 2). Overall, findings included a 91.4% sensitivity (95% CI, 84.2%-98.6%) and an 82.6% specificity (95% CI, 74.9%-90.4%). The positive predictive value was 76.8% (95% CI, 66.9%-86.8%) and the negative predictive value was 93.8% (95% CI, 88.6%-99.1%). CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to researchers and clinicians in screening large populations of children, decreasing the time and cost of added neurological assessments.

Quality-of-care indicators for infantile spasms.

We developed a comprehensive set of quality-of-care indicators for the management of children with infantile spasms in the United States, encompassing evaluation, diagnosis, treatment, and prevention and management of side effects and comorbidities. The indicators were developed using the RAND/UCLA Modified Delphi Method. After a focused review of the literature and guidelines by the study team, an expert panel (nominated by leaders of Child Neurology Society, American Epilepsy Society, and National Institute for Neurologic Disorders) rated the draft indicators anonymously, met face-to-face to discuss each indicator, and rerated the revised indicators on validity, feasibility, and importance. The panel recommended 21 indicators, of which 8 were identified as most likely to have a large positive impact on improving quality of life and/or health outcomes for children with infantile spasms. The proposed indicators can be used to assess and document variations and gaps in quality-of-care and inform future research and quality improvement interventions.

A quick and reliable EEG montage for the detection of seizures in the critical care setting.

Obtaining an emergent EEG for the diagnosis of nonconvulsive status epilepticus and conconvulsive seizures in the intensive care unit raises logistic problems in most hospitals. Previous studies have looked into the hairline EEG for a broader population than the critically ill, with controversial conclusions. The authors created a montage sufficiently simple to be performed and interpreted by residents and rapidly achievable to meet the time constraints of a busy on-call schedule. Seven electrodes (Fp1, Fp2, T3, T4, O1, O2, and Cz), easily applied without the need for tape measure by using only anatomic landmarks (pupils, ears, vertex, and inion), were used to configure three different montages: double diamond, circumferential, and Cz referential. EEG records obtained with the full 10-20 system in critically ill patients were reformatted into these montages and reviewed retrospectively independently by neurology attending physicians with expertise in EEG interpretation and senior neurology residents. A comparison was done with the previously studied hairline EEG. The average sensitivity of the study montage for seizure detection was 92.5%, whereas the average specificity was 93.5%. These results suggest that the seven-electrode montage could potentially be a quick and reliable EEG montage for the detection of seizures in the intensive care unit, when technical support is not available. Further prospective studies are required to validate these promising results in a larger population sample.

Emotional and behavioral outcomes among adolescents with mild developmental deficits in early childhood.

PURPOSES: To evaluate emotional and behavioral outcomes in adolescents who in early childhood were treated for mild developmental deficits; and to identify predictive factors in early childhood, for future emotional and social competence abnormalities. METHODS: The records of children referred to Hanna Khoushi Child Development Center in Haifa for mild developmental delay were reviewed. Parents and adolescents were requested to complete the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR) 12 to 16 years after discharge from the Child Development Center. Analysis of the two questionnaires and identification of predictive variables in early childhood for emotional problems and social competence difficulties during adolescence were performed, using ANOVA Student's T-test, Chi-square, and multiple regression. RESULTS: The most frequent developmental diagnoses on admission to the Child Development Center were mild motor (27.3%) or language (23.2%) deficits. Of the treated children, 53.4% were discharged without any developmental deficit. All CBCL and YSR T-scores were within the nonpsychopathology range. No notable differences were found between the study scores and the scores regarding typical Israeli and American youths. Significant differences were, however, observed in self-perception of internalizing emotional problems between male and female adolescents: T-scores of 51.9 +/- 8.0 vs. 47.4 +/- 10.8, respectively (p < .05). Motor and language deficits were associated with lower general competence than general developmental delay and emotional developmental disturbances (T-scores: 47.9 vs. 49.1 and 50.9, p< .05). Admission to the Center after the age of 18 months was associated with higher T-scores for general as well as externalizing problems when compared with scores associated with admission before the age of 18 months (by 5.75 points for both parameters, p < .001). CONCLUSION: The perception of parents and children with minor developmental deficits observed in early childhood regarding their emotional and social competence during adolescence is similar to typical youths.

Status epilepticus and frequent seizures: incidence and clinical characteristics in pediatric epilepsy surgery patients.

PURPOSE: The literature suggests that pediatric epilepsy surgery cases that present in status epilepticus (SE) are an unusual occurrence. However, this concept is based on case reports, and the incidence and clinical characteristics of these patients have not been systematically assessed. METHODS: The cohort consisted of resective epilepsy surgery cases from 2000 to 2005 (n = 115), and they were classified as presenting with continuous SE requiring medical suppression therapy (n = 6) or intermittent SE (greater than 3 seizures/hour; n = 17). The SE categories were compared with extratemporal surgery patients without SE (non-SE; n = 64) for differences in clinical variables abstracted from the medical record. RESULTS: Continuous SE was noted in 5% and intermittent SE in 15% of resective surgery cases, and all had extratemporal cortical involvement. Compared with continuous SE and non-SE cases, intermittent SE patients were younger at surgery with shorter duration of seizures, and had an increased incidence of active infantile spasms during video scalp EEG monitoring. Compared with non-SE cases, the continuous and intermittent SE groups required a larger number of antiepileptic medications presurgery and 6-months postsurgery, underwent hemispherectomy more frequently, and had an increased incidence of hemimegalencephaly and Rasmussen encephalitis and a lower occurrence of infarct/ischemia and infectious etiologies. Seizure control was over 71% up to 2 years postsurgery, and there were no differences between patient groups. Finally, seizure frequency per hour was greater in continuous SE cases compared with the intermittent SE group. CONCLUSIONS: Children presenting with continuous or intermittent SE are not rare in pediatric epilepsy surgery centers, and such cases are more commonly associated with infantile spasms, Rasmussen's syndrome, and hemimegalencephaly pathologies. Seizure outcome after surgery was not altered in pediatric patients because they had presented with continuous or intermittent SE.