Clinical trials for Lennox-Gastaut syndrome: Challenges and priorities.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes. METHODS: The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review. RESULTS: We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on expert consensus and empirical data. Whereas LGS natural history is incompletely understood, prospective studies and use of large retrospective datasets to understand LGS across the lifespan would enable clinical trials that address these dynamics. Recent discoveries related to LGS pathophysiology should enable development of disease-modifying therapies, which are currently lacking. Finally, clinical trials have focused chiefly on seizures involving "drops," but should incorporate additional patient-centered outcomes, using emerging measures adapted to people with LGS. INTERPRETATION: Clinicians and researchers should enact these priorities, with the goal of patient-centered clinical trials that are tailored to LGS pathophysiology and natural history.

Pediatric Palliative Epilepsy Surgery: A Report From the Pediatric Epilepsy Research Consortium (PERC) Surgery Database.

BACKGROUND: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a "last resort" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired. RESULTS: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group. CONCLUSIONS: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications.

Implications of Large Language Models for Quality and Efficiency of Neurologic Care: Emerging Issues in Neurology.

Large language models (LLMs) are advanced artificial intelligence (AI) systems that excel in recognizing and generating human-like language, possibly serving as valuable tools for neurology-related information tasks. Although LLMs have shown remarkable potential in various areas, their performance in the dynamic environment of daily clinical practice remains uncertain. This article outlines multiple limitations and challenges of using LLMs in clinical settings that need to be addressed, including limited clinical reasoning, variable reliability and accuracy, reproducibility bias, self-serving bias, sponsorship bias, and potential for exacerbating health care disparities. These challenges are further compounded by practical business considerations and infrastructure requirements, including associated costs. To overcome these hurdles and harness the potential of LLMs effectively, this article includes considerations for health care organizations, researchers, and neurologists contemplating the use of LLMs in clinical practice. It is essential for health care organizations to cultivate a culture that welcomes AI solutions and aligns them seamlessly with health care operations. Clear objectives and business plans should guide the selection of AI solutions, ensuring they meet organizational needs and budget considerations. Engaging both clinical and nonclinical stakeholders can help secure necessary resources, foster trust, and ensure the long-term sustainability of AI implementations. Testing, validation, training, and ongoing monitoring are pivotal for successful integration. For neurologists, safeguarding patient data privacy is paramount. Seeking guidance from institutional information technology resources for informed, compliant decisions, and remaining vigilant against biases in LLM outputs are essential practices in responsible and unbiased utilization of AI tools. In research, obtaining institutional review board approval is crucial when dealing with patient data, even if deidentified, to ensure ethical use. Compliance with established guidelines like SPIRIT-AI, MI-CLAIM, and CONSORT-AI is necessary to maintain consistency and mitigate biases in AI research. In summary, the integration of LLMs into clinical neurology offers immense promise while presenting formidable challenges. Awareness of these considerations is vital for harnessing the potential of AI in neurologic care effectively and enhancing patient care quality and safety. The article serves as a guide for health care organizations, researchers, and neurologists navigating this transformative landscape.

Population-based study of rare epilepsy incidence in a US urban population.

OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

Pediatric Mental Health Emergencies During 5 COVID-19 Waves in New York City.

OBJECTIVES: To describe the proportion of pediatric mental health emergency department (MH-ED) visits across 5 COVID-19 waves in New York City (NYC) and to examine the relationship between MH-ED visits, COVID-19 prevalence, and societal restrictions. METHODS: We conducted a time-series analysis of MH-ED visits among patients ages 5 to 17 years using the INSIGHT Clinical Research Network, a database from 5 medical centers in NYC from January 1, 2016, to June 12, 2022. We estimated seasonally adjusted changes in MH-ED visit rates during the COVID-19 pandemic, compared with predicted prepandemic levels, specific to each COVID-19 wave and stratified by mental health diagnoses and sociodemographic characteristics. We estimated associations between MH-ED visit rates, COVID-19 prevalence, and societal restrictions measured by the Stringency Index. RESULTS: Of 686 500 ED visits in the cohort, 27 168 (4.0%) were MH-ED visits. The proportion of MH-ED visits was higher during each COVID-19 wave compared with predicted prepandemic trends. Increased MH-ED visits were seen for eating disorders across all waves; anxiety disorders in all except wave 3; depressive disorders and suicidality/self-harm in wave 2; and substance use disorders in waves 2, 4, and 5. MH-ED visits were increased from expected among female, adolescent, Asian race, high Child Opportunity Index patients. There was no association between MH-ED visits and NYC COVID-19 prevalence or NY State Stringency Index. CONCLUSIONS: The proportion of pediatric MH-ED visits during the COVID-19 pandemic was higher during each wave compared with the predicted prepandemic period, with varied increases among diagnostic and sociodemographic subgroups. Enhanced pediatric mental health resources are essential to address these findings.

Creating rare epilepsy cohorts using keyword search in electronic health records.

OBJECTIVE: Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an alternative method for rare epilepsy cohort creation using electronic health records data. METHODS: Data included clinical notes from encounters with International Classification of Diseases, Ninth Revision (ICD-9) codes for seizures, epilepsy, and/or convulsions during 2010-2014, across six health care systems in New York City. We identified cases with rare epilepsies by searching clinical notes for keywords associated with 33 rare epilepsies. We validated cases via manual chart review. We compared the performance of keyword search to manual chart review using positive predictive value (PPV), sensitivity, and F-score. We selected an initial combination of keywords using the highest F-scores. RESULTS: Data included clinical notes from 77 924 cases with ICD-9 codes for seizures, epilepsy, and/or convulsions. The all-keyword search method identified 6095 candidates, and manual chart review confirmed that 2068 (34%) had a rare epilepsy. The initial combination method identified 1862 cases with a rare epilepsy, and this method performed as follows: PPV median = .64 (interquartile range [IQR] = .50-.81, range = .20-1.00), sensitivity median = .93 (IQR = .76-1.00, range = .10-1.00), and F-score median = .71 (IQR = .63-.85, range = .18-1.00). Using this method, we identified four cohorts of rare epilepsies with over 100 individuals, including infantile spasms, Lennox-Gastaut syndrome, Rett syndrome, and tuberous sclerosis complex. We identified over 50 individuals with two rare epilepsies that do not have specific ICD-10 codes for cohort creation (epilepsy with myoclonic atonic seizures, Sturge-Weber syndrome). SIGNIFICANCE: Keyword search is an effective method for cohort creation. These findings can improve identification and surveillance of individuals with rare epilepsies and promote their referral to specialty clinics, clinical research, and support groups.

COVID-19 is Observed in Older Children During the Omicron Wave in New York City.

BACKGROUND: The Omicron variant of SARS-CoV-2 has a predilection for the upper airways, causing symptoms such as sore throat, hoarse voice, and stridor. OBJECTIVE: We describe a series of children with COVID-19-associated croup in an urban multicenter hospital system. METHODS: We conducted a cross-sectional study of children ≤18 years of age presenting to the emergency department during the COVID-19 pandemic. Data were extracted from an institutional data repository comprised of all patients who were tested for SARS-CoV-2. We included patients with a croup diagnosis by International Classification of Diseases, 10th revision code and a positive SARS-CoV-2 test within 3 days of presentation. We compared demographics, clinical characteristics, and outcomes for patients presenting during a pre-Omicron period (March 1, 2020-December 1, 2021) to the Omicron wave (December 2, 2021-February 15, 2022). RESULTS: We identified 67 children with croup, 10 (15%) pre-Omicron and 57 (85%) during the Omicron wave. The prevalence of croup among SARS-CoV-2-positive children increased by a factor of 5.8 (95% confidence interval 3.0-11.4) during the Omicron wave compared to prior. More patients were ≥6 years of age in the Omicron wave than prior (19% vs. 0%). The majority were not hospitalized (77%). More patients ≥6 years of age received epinephrine therapy for croup during the Omicron wave (73% vs. 35%). Most patients ≥6 years of age had no croup history (64%) and only 45% were vaccinated against SARS-CoV-2. CONCLUSION: Croup was prevalent during the Omicron wave, atypically affecting patients ≥6 years of age. COVID-19-associated croup should be added to the differential diagnosis of children with stridor, regardless of age. © 2022 Elsevier Inc.

Multicenter Assessment of Sturge-Weber Syndrome: A Retrospective Study of Variations in Care and Use of Natural History Data.

BACKGROUND: We summarize the history of individuals with Sturge-Weber syndrome (SWS) to inform clinical trial design and identify variations in care. METHODS: We performed retrospective chart review of individuals with SWS from centers in New York City. We characterized data quality using a novel scoring system. For 13 clinical concepts, we evaluated if data were present and if they were of high quality. RESULTS: We included 26 individuals with SWS (58% female; median age at initial visit 7 years; absolute range 1 month to 56 years]). Twenty-two had nevus flammeus, 13 glaucoma, four homonymous hemianopia, and 15 hemiparesis. Nineteen of 21 had at least one confirmed seizure with a known first seizure date, all before 24 months. Most (18 of 26, 69%) epilepsy was controlled. A plurality (10 of 23, 43%) had either normal cognitive function or mild cognitive delays. Aspirin use varied by site (P = 0.02)-at four sites, use was 0% (zero of three), 0% (zero of four), 80% (four of five), and 64% (nine of 14). Data were present for more than 75% of cases for 11 of 13 clinical concepts (missing: age of diagnosis, age of glaucoma onset). There were gaps in level of detail for motor impairments, glaucoma severity, seizure history, cognition, and medication history. CONCLUSIONS: Clinical charts have important gaps in the level of detail around core SWS clinical features, limiting value for some natural history studies. Any clinical trial in SWS designed to prevent epilepsy should begin in the first year of life. Variations in use of aspirin suggest de facto clinical equipoise and warrant a comparative effectiveness study.

Indications for Hospitalization in Children with SARS-CoV-2 Infection during the Omicron Wave in New York City.

The emergence of the Omicron variant was accompanied by an acute increase in COVID-19 cases and hospitalizations in New York City. An increased incidence of COVID-19-associated croup in children during the Omicron wave has been recognized, suggesting that there may be other changes in clinical symptoms and severity. To better understand clinical outcomes and health care utilization in children infected with SARS-CoV-2 during the Omicron wave, we performed a cross-sectional study in pediatric patients aged ≤18 years who were tested for SARS-CoV-2 in pediatric emergency departments within a large medical system in New York City from 2 December 2021 to 23 January 2022. We described the clinical characteristics and outcomes of pediatric patients who presented to the pediatric emergency department and were hospitalized with SARS-CoV-2 infection during the Omicron wave in New York City. There were 2515 children tested in the ED for SARS-CoV-2 of whom 794 (31.6%) tested positive. Fifty-eight children were hospitalized for a COVID-19-related indication, representing 7.3% of all COVID-19-positive children and 72% of hospitalized COVID-19-positive children. Most (64%) children hospitalized for a COVID-19-related indication were less than 5 years old. Indications for hospitalization included respiratory symptoms, clinical monitoring of patients with comorbid conditions, and exacerbations of underlying disease. Eleven (19%) hospitalized children were admitted to the ICU and six (10%) required mechanical ventilation. Children infected with COVID-19 during the Omicron wave, particularly those less than 5 years old, were at risk for hospitalization. A majority of hospitalizations were directly related to COVID-19 infection although clinical indications varied with less than a half being admitted for respiratory diseases including croup. Our findings underscore the need for an effective COVID-19 vaccine in those less than 5 years old, continued monitoring for changes in clinical outcomes and health care utilization in children as more SARS-CoV-2 variants emerge, and understanding that children are often admitted for non-respiratory diseases with COVID-19.

Leveraging electronic patient diaries in SUDEP risk evaluation.

OBJECTIVE: Our aim was to describe the risk factors known to be related to sudden unexpected death in epilepsy (SUDEP) that can be extracted from patients that utilizes an online seizure diary tool (SeizureTracker™). METHOD: We conducted a descriptive analysis of SeizureTracker™ users across factors relevant to SUDEP risk. We also compared our app-using cohort to published SUDEP case-control studies. RESULTS: We report across seven risk factors from 30,813 users of SeizureTracker™ who had a median length of time using the app of 5.69 years (range from 1 month to 15 years). We found that they are at greater risk for SUDEP than groups from published studies (p < .00001) based on the risk factor of generalized tonic-clonic seizures. SIGNIFICANCE: We demonstrated that the population using the SeizureTracker™ tool can be a valuable population for expanding investigation of SUDEP risk factors and is a first step towards establishing a large sample with a method to ascertain data prospectively that might be critical to developing a SUDEP risk algorithm.

Reproductive Health Counseling in Adolescent Women With Epilepsy: A Single-Center Study.

BACKGROUND: Counseling adolescent women with epilepsy (WWE) about reproductive health (contraception, sexual activity, and menstruation) is important given the teratogenicity of many antiseizure medications and high rates of contraception failure. Only a third of adolescent WWE report discussing contraception with their epileptologists, demonstrating a significant gap in counseling. METHODS: We assessed factors associated with reproductive health counseling by pediatric neurologists via a retrospective chart review of adolescent (aged 12-18 years) WWE seen at a pediatric neurology clinic from 2018 to 2020. RESULTS: We analyzed 219 visits among 89 unique WWE. There were 23 documented discussions on contraception (11% of visits), 8 on sexual activity (4%), and 127 on menstruation (58%). When contraception was discussed, sexual activity and menstruation were more frequently discussed. Female providers were more likely to document a discussion of menstruation (OR = 3.2, 95% CI = [1.6, 6.4]). WWE who were older at the time of visit or who had their first seizure at an older age were more likely to have documented discussions of contraception and sexual activity. Neither details of treatment regimen nor epilepsy type was associated with documentation of counseling. CONCLUSIONS: A minority of adolescent WWE have documented reproductive health discussions, demonstrating a need for quality improvement projects to address this gap in care.

Inequities in Therapy for Infantile Spasms: A Call to Action.

OBJECTIVE: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity. METHODS: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together. RESULTS: Of 555 children, 324 (58%) were non-Hispanic white, 55 (10%) non-Hispanic Black, 24 (4%) non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non-Hispanic Black children had lower odds of receiving a standard treatment course compared with non-Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20-0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21-0.84; p = 0.01). INTERPRETATION: Non-Hispanic Black children were more often treated with non-standard IS therapies than non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32-44.

Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2): A novel health-related quality of life prompt for children with epilepsy.

OBJECTIVE: Pediatric epilepsy is often associated with diminished health-related quality of life (HRQOL). Our aim was to establish the validity of the Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2) questions, a novel two-item HRQOL prompt for children with epilepsy, primarily for use in clinical care. METHODS: We performed a multicenter cross-sectional study to validate the PELHS-QOL-2. Construct validity was established through bivariate comparisons with four comparator measures and known drivers of quality of life in children with epilepsy, as well as by creating an a priori multivariable model to predict the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Validity generalization was established through bivariate comparisons with demographic and clinical information. Content validity and clinical utility were established by assessing how well the PELHS-QOL-2 met eight design criteria for an HRQOL prompt established by a multistakeholder group of experts. RESULTS: The final participant sample included 154 English-speaking caregivers of children with epilepsy (mean age = 9.7 years, range = .5-18, 49% female, 70% White). The PELHS-QOL-2 correlated with the four comparator instruments (ρ = .44-.56), was significantly associated with several known drivers of quality of life in children with epilepsy (p < .05), and predicted QOLCE-55 scores in the multivariate model (adjusted R2 = .54). The PELHS-QOL-2 item was not associated with the age, sex, and ethnicity of the children nor with the setting and location of data collection, although PELHS-QOL-Medications was significantly associated with race (worse for White race). Following both quantitative and qualitative analysis, the PELHS-QOL-2 met seven of eight design criteria. SIGNIFICANCE: The PELHS-QOL-2 is a valid HRQOL prompt and is well suited for use in clinical care as a mechanism to routinely initiate conversations with caregivers about quality of life in children with epilepsy. The association of PELHS-QOL-Medications with race merits further study.

Automated Identification of Surgical Candidates and Estimation of Postoperative Seizure Freedom in Children - A Focused Review.

Surgery is an effective but underused treatment for drug-resistant epilepsy in children. Algorithms to identify surgical candidates and estimate the likelihood of postoperative clinical improvement may be valuable to improve access to epilepsy surgery. We provide a focused review of these approaches. For adults with epilepsy, tools to identify surgical candidates and predict seizure and cognitive outcomes (Ie, Cases for Epilepsy (toolsforepilepsy.com) and Epilepsy Surgery Grading Scale) have been validated and are in use. Analogous tools for children need development. A promising approach is to apply statistical learning tools to clinical datasets, such as electroencephalogram tracings, imaging studies, and the text of clinician notes. Demonstration projects suggest these techniques have the potential to be highly accurate, and await further validation and clinical application.

Medication selection, health services outcomes, and cost trajectories for Medicaid beneficiaries with infantile spasms.

OBJECTIVE: There are three recommended first-line treatments for infantile spasms, adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin, though non-standard treatments such as topiramate are sometimes selected. Is it uncertain how treatment selection influences health services outcomes. METHODS: We conducted a retrospective cohort study of Medicaid beneficiaries newly diagnosed with infantile spasms from 2009-2010. We included infants with a new diagnosis of infantile spasms between age 2-9 months who filled ACTH (reference), prednisolone, vigabatrin, or topiramate prescriptions. Multivariable Cox proportional hazards regression compared time to first emergency department (ED) visit or hospitalization across treatment groups during 2 years of follow-up. Monthly costs for each treatment were examined in 6-month intervals and compared in a multivariable generalized linear model. RESULTS: Among 256 children with infantile spasms, 116 received ACTH, 62 prednisolone, 15 vigabatrin, and 63 topiramate. The rate of ED visit or hospitalization per person-year did not differ significantly for prednisolone (0.9 [95 % CI 0.7-1.2]; adjusted hazard ratio [aHR] 0.84, 95 % CI 0.57-1.24), vigabatrin (0.8 [95 % CI 0.4-1.5]; aHR 0.91, 95% CI 0.45-1.84), or topiramate (1.7 [95 % CI 1.3-2.3]; aHR 1.15, 95 % CI 0.80-1.65), when compared to ACTH (1.1 [95 % CI 0.9-1.3]). The median payment for ACTH was $96,406 (interquartile range 70,742-138,476) during the first 6 months. The adjusted mean total payment in the first 6 months was 73% lower for prednisolone (95% CI -82, -61), 69% lower for vigabatrin (95% CI -84, -40), and 73% lower for topiramate (95% CI -82, -59). However, in subsequent 6-month intervals, costs associated with ACTH were not significantly different compared to other treatments. SIGNIFICANCE: Compared to other treatments for infantile spasms, use of ACTH was associated with greater cost in the first 6 months of treatment, but not with reduced ED visits or hospitalizations. The cost effectiveness of ACTH depends on its relative clinical efficacy, and merits additional research.

Patterns of Recording Epileptic Spasms in an Electronic Seizure Diary Compared With Video-EEG and Historical Cohorts.

BACKGROUND: Use of electronic seizure diaries (e-diaries) by caregivers of children with epileptic spasms is not well understood. We describe the demographic and seizure-related information of children with epileptic spasms captured in a widely used e-diary and explore the potential biases in how caregivers report these data. METHODS: We analyzed children with epileptic spasms in an e-diary, Seizure Tracker, from 2007 to 2018. We described variables including sex, time of seizure, percentage of spasms occurring as individual spasms (versus in clusters), cluster duration, and number of spasms per cluster. We compared seizure characteristics in the e-diary cohort with published cohorts to identify biases in caregiver-reported epileptic spasms. We also reviewed seizure patterns in a small cohort of children with epileptic spasms monitored on overnight video-electroencephalography (vEEG). RESULTS: There were 314 children in the e-diary cohort and nine children in the vEEG cohort. The e-diary cohort was more likely than expected to report counts divisible by five. The e-diary cohort had a lower proportion of nighttime spasms than expected based on data from published cohorts. The e-diary cohort had a significantly lower percentage of spasms as individual spasms, a greater number of spasms per cluster, and a greater cluster duration relative to the vEEG cohort. CONCLUSIONS: Caregivers using e-diaries for epileptic spasms may miss individual spams, be more likely to report long clusters, round counts to the nearest five, and underreport nighttime spasms. Clinicians should be aware of these reporting biases when using e-diary data to guide care for children with epileptic spasms.

Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort.

OBJECTIVE: Compare the effectiveness of initial treatment for infantile spasms. METHODS: The National Infantile Spasms Consortium prospectively followed children with new onset infantile spasms that began at age 2-24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations. RESULTS: Freedom from treatment failure rates were: ACTH 88/190 (46%), oral steroids 42/95 (44%), vigabatrin 32/87 (37%), and non-standard therapy 4/51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% CI 34-54]). Changing from non-standard therapy to ACTH would improve response from 8% to 39 [17-67]%, and to oral steroids from 8% to 38 [15-68]%. There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42 [15-75]%), vigabatrin to oral steroids (29% to 42 [28-57]%), and non-standard therapy to vigabatrin (8% to 20 [6-50]%). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p<0.05) CONCLUSION: Compared to non-standard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between ACTH / oral steroids and non-standard therapy, though the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children with new onset infantile spasms, ACTH or oral steroids were superior to non-standard therapies.