Clinical Validation of Selected NIH Cognitive Toolbox Tasks in Pediatric Epilepsy.

The NIH Toolbox Cognition Battery (NIHTB-CB) is designed to assess cognitive functioning across the lifespan. We aimed to evaluate the clinical validity of two NIHTB-CB tasks as cognitive screening tools in pediatric epilepsy by comparing them to standard neuropsychological measures and their association with epilepsy characteristics. Forty-seven patients with epilepsy ages 5-18, including ten repeat evaluations, were assessed. Correlational analyses and agreement statistics were conducted to validate NIHTB-CB tasks (Flanker Inhibitory Control and Attention test (Flanker) and Pattern Comparison Processing Speed test (Pattern Comparison)) with standard clinical measures. We also examined if performance was related to epilepsy characteristics, including polytherapy, age of seizure onset, seizure type, and history of Electrical Status Epilepticus in Sleep (ESES). The NIHTB-CB tests had moderate to strong correlations with neuropsychological measures of executive functioning, processing speed, and intelligence. Agreement statistics indicated better sensitivity than specificity. Polytherapy and later age of seizure onset were associated with lower performance on Pattern Comparison. ESES patients did not significantly differ in performance on the tests compared to non-ESES patients. Pilot data from a subset of repeated measures indicated a good range of change scores. These two NIHTB tasks are feasible as a screening tool in a clinic given their correlation with clinical measures that assess executive function, processing speed, and IQ. This study supports the use of these tasks as brief, easily accessible screener tools to identify cognitive dysfunction in domains commonly impacted in patients with epilepsy and potential use for monitoring over time.

Comparison of psychosocial screeners in an epilepsy clinic.

Screenings are recommended for co-occurring conditions in pediatric epilepsy. However, there is limited research regarding which screener to implement in the clinic. This study aimed to compare different screening measures for attention-deficit/hyperactivity disorder (ADHD) and emotional concerns in a pediatric epilepsy population during a routine neurology clinic visit. Fifty (22%) of 226 contacted parents of children with epilepsy ages 5-17 years old agreed to participate. Screening measures included the Strengths and Difficulties Questionnaire (SDQ; Hyperactivity/Inattention (ADHD), Emotional Problems (E) subscales), the Pediatric Quality of Life Inventory Epilepsy Module (PedsQL-EM; Executive Functioning (EF), Mood/Behavior (M/B) subscales), and the ADHD Rating Scale (ADHD-RS). Analyses comparing measures included Chi Square, Pearson's correlation, and agreement statistics (Cohen's kappa, overall agreement). Consistent with prior literature, positive screening rates ranged from 40% to 72% for ADHD concerns and 38% to 46% for emotional concerns. Agreement between measures ranged from fair to substantial, with the highest agreement (85%; κ = 0.70) between the SDQ-E and PedsQL-EM-M/B. Although all measures rendered positive screens within expected rates, there are differences among the measures that inform screening measure selection.

Focal to bilateral tonic-clonic seizures predict pharmacoresistance in focal cortical dysplasia-related epilepsy.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy (75% is pharmacoresistant epilepsy [PRE]). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks. METHODS: Patients were selected retrospectively from radiology and surgical databases from Children's National Hospital. INCLUSION CRITERIA: 3T magnetic resonance imaging (MRI)-confirmed FCD from January 2011 to January 2020; ages 0 days to 22 years at MRI; and 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age at seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age at seizure onset, pathology, lobe, percentage default mode network [DMN] overlap) of FTBTC seizures. RESULTS: One hundred seventeen patients had a median age at seizure onset of 3.00 years (interquartile range [IQR] .42-5.59 years). Eighty-three patients had PRE (71%); 34 had pharmacosensitive epilepsy (PSE) (29%). Twenty patients (17%) had FTBTC seizures. Seventy-three patients underwent epilepsy surgery. Multivariate regression showed that FTBTC seizures are associated with an increased risk of PRE (odds ratio [OR] 6.41, 95% confidence interval [CI] 1.21-33.98, p = .02). FCD hemisphere/lobe was not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. Seventy-two percent (n = 52) overall and 53% (n = 9) of patients with FTBTC seizures achieved Engel class I outcome. SIGNIFICANCE: In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE and can flag patients for earlier consideration of potentially curative surgery. The FCD-dominant network also contributes to FTBTC seizure clinical expression.

The Impact of Magnetoencephalography-Directed Stereo-Electroencephalography Depth Electrode Implantation on Seizure Control Outcome in Children.

Introduction The use of magnetoencephalography (MEG) in localizing epileptic foci and directing surgical treatment of medically refractory epilepsy is well established in clinical practice; however, it has not yet been incorporated into the routine planning of stereo-electroencephalography (EEG) (SEEG) depth electrode trajectories during invasive intracranial evaluation for epileptic foci localization. In this study, we assess the impact of MEG-directed SEEG on seizure outcomes in a pediatric cohort. Methods A retrospective analysis was performed on a single-institution cohort of pediatric patients with medically refractory epilepsy who underwent epilepsy surgery. The primary endpoint was the reduction in seizure burden as determined by dichotomized Engel scores (favorable outcome: Engel scores I and II; poor outcome: Engel scores III and IV). Results Thirty-seven patients met the inclusion criteria (24 males and 13 females). The median age at seizure onset was three years, the median age at surgery was 14.1 years, and the median follow-up length was 30.8 months. Concordance was noted in 7/10 (70%) patients who received MEG-directed SEEG. Good clinical outcomes were achieved in 70% of MEG-directed SEEG patients, compared to 59.4% in their counterparts; however, this difference was not statistically significant (p=0.72). We noted no statistically significant association between sex, disease laterality, or age at surgery and good clinical outcomes. Conclusions Patients who underwent MEG-directed SEEG had favorable clinical outcomes, which demonstrated the practicability of this technique for determining SEEG electrode placement. Although no significant difference in clinical outcomes was obtained between the two groups, this may have been due to low statistical power. Future prospective, multi-institutional investigations to assess the benefit of MEG-directed SEEG are warranted.

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.

Virtual reality-based 3-dimensional localization of stereotactic EEG (SEEG) depth electrodes and related brain anatomy in pediatric epilepsy surgery.

INTRODUCTION: The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. METHODS: An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. RESULTS: Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. DISCUSSION: Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.

Telehealth for patients with rare epilepsies.

Recent developments in technology and exigencies of the COVID-19 pandemic have spurred innovations for telehealth in patients with rare epilepsies. This review details the many ways telehealth may be used in the diagnosis and management of rare, pharmacoresistant epilepsy and documents our experience as measured by surveying caregivers of pediatric patients with epilepsy. Most components of the epilepsy evaluation, including history and examination, neuroimaging, and electroencephalogram (EEG) can be performed or reviewed remotely, assuming similar technique and quality of diagnostic studies. Seizure and epilepsy diagnosis is enhanced through the assistance of caregiver smart phone video recordings and 'ambulatory' EEG. Monitoring patient seizure frequency through paper seizure diaries is now increasingly being replaced by electronic diaries in both clinical and research settings. Electronic seizure diaries have numerous advantages such as data durability, increased accessibility, real-time availability, and easier analysis. Telehealth enhances access to specialized epilepsy care, which has been shown to reduce mortality and improve patient compliance and outcomes. Telehealth can also enable evaluation of patients with rare epilepsy in centers of excellence and enhance enrollment in clinical trials. Reducing mortality risk in patients with epilepsy can be accomplished through remote counseling and addressing psychiatric co-morbidities. Findings from surveying caregivers of children with epilepsy treated at Children's National Hospital showed that 54/56 (96.4%) found that not having to commute to the appointment positively contributed to their telemedicine experience. Overall, most respondents had a positive experience with their telemedicine visit. Almost all respondents (98%) were either 'very happy' or 'happy' with their telemedicine visit and their ability to communicate over telemedicine with the provider and either 'very likely' or 'likely' to want to use telemedicine for some future clinic visits. Telehealth in rare epilepsies is feasible and, in many ways, comparable with traditional evaluation and management.

Telehealth for patients with rare epilepsies Recent technological advancements and constraints caused by the COVID-19 pandemic have spurred innovations for telehealth in patients with rare epilepsies. This review details the many ways telehealth may be used in the diagnosis and management of rare, drug-resistant epilepsy and documents our experience as measured by surveying caregivers of pediatric patients with epilepsy. Most components of the epilepsy evaluation can be performed or reviewed remotely, assuming similar technique and quality of diagnostic studies. Seizure and epilepsy diagnosis is enhanced through the assistance of caregiver smart phone video recordings and 'ambulatory' electroencephalogram (EEG). Monitoring patient seizure frequency through paper seizure diaries is now increasingly being replaced by electronic diaries in both clinical and research settings. Electronic seizure diaries have numerous advantages such as data durability, increased accessibility, real-time availability, and easier analysis. Telehealth enhances access to specialized epilepsy care, which has been shown to reduce mortality and improve patient compliance and outcomes. Telehealth can also enable evaluation of patients with rare epilepsy in centers of excellence and enhance enrollment in clinical trials. Reducing mortality risk in patients with epilepsy can be accomplished through remote counseling and addressing related mental health issues. Findings from surveying caregivers of children with epilepsy treated at Children's National Hospital showed that most respondents found not having to commute to the appointment positively contributed to their telemedicine experience. Almost all respondents were either 'very happy' or 'happy' with their telemedicine visit and their ability to communicate over telemedicine with the provider and either 'very likely' or 'likely' to want to use telemedicine for some future clinic visits. Telehealth in rare epilepsies is feasible and, in many ways, comparable with traditional evaluation and management.

Management of Infantile Spasms During the COVID-19 Pandemic.

Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.

Antiepileptic Drugs in Pediatrics.

Epilepsy affects approximately 1% of the population. First-line treatment for epilepsy is the administration of anti-seizure medication, also referred to as antiepileptic drugs (AEDs), although this nomenclature is erroneous as these medications typically do not impact underlying epileptogenic processes; the goal of these medications is to control symptoms. Over 30% of patients are classified as having "medically refractory" epilepsy, i.e., lack of adequate seizure control despite trials of two or three AEDs (Kwan and Brodie, N Engl J Med 342:314-9, 2000). Epilepsy is associated with worse quality of life in children, adolescents, and their families (Cianchetti et al., Seizure 24:93-101, 2015). Patients with epilepsy have a two to three times greater risk of death than the general population, by various causes including sudden unexplained death in epilepsy patients (SUDEP) (Abdel-Mannan et al., Epilepsy Behav 90:99-106, 2019). It is these factors, among others, that have motivated the continued development of AEDs. This chapter will review the history and evolution of AED development, features of specific AEDs with a focus on the newest generation, and examples of AEDs in development.

Predictive value of early EEG for seizures in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

OBJECTIVES: To assess the prognostic significance of an early normal/mildly abnormal conventional EEG (cEEG) on seizure risk in neonates undergoing therapeutic hypothermia. METHODS: We reviewed the video-EEG recordings from a large cohort of neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy from 2008 to 2017 in a single tertiary center. Continuous video-EEG was started as soon as possible (median 8.2 h) and continued throughout hypothermia and rewarming. We studied those neonates with a normal/mildly abnormal EEG during the first 24 h of monitoring. RESULTS: A total of 331 neonates were treated with hypothermia and 323 had cEEG recordings available for review; 99 were excluded because of a moderately/severely abnormal cEEG background and/or seizure during the first 24 h of recording, and an additional eight because of early rewarming. The remaining 216 had a normal/mildly abnormal cEEG in the first 24 h. None of these patients subsequently developed seizures. CONCLUSION: A normal/mildly abnormal cEEG during the first 24 h indicates a very low risk of subsequent seizures. This suggests that cEEG monitoring can be safely discontinued after 24 h if it has remained normal or excessively discontinuous and no seizures are detected, limiting the need for this resource-intensive and expensive tool.

A Practical Approach to Ketogenic Diet in the Pediatric Intensive Care Unit for Super-Refractory Status Epilepticus.

BACKGROUND: Super-refractory status epilepticus (SRSE) ensues when there is no improvement of seizure control in response to anesthetic therapy or seizure recurrence after reduction of anesthetic agents. There is no consensus on standard of care for SRSE. Ketogenic diet (KD) has reported success, but technical challenges exist including inability to feed patients, concomitant steroid use, acidotic states, and lack of dieticians with experience. The optimal protocol for KD is yet to be determined. We describe our approach to initiation of KD in the pediatric intensive care unit (PICU). METHODS: Patients with SRSE who had KD initiation in the PICU were identified. Data from the hospital course were supplemented by review of the electronic medical record. RESULTS: Nine children with SRSE who had KD initiated in the PICU were identified. Descriptive analysis was performed. Mean age was 5.4 years (SD 2.24). Median number of days to start KD from detection of seizures was 13 [interquartile range (IQR) 10-16]. Mean time to achieve ketosis was 4.2 days (SD 3.4). The median number of antiepileptic drugs (AEDs) trialed before KD was started was 4 [IQR 3-4], and the median number of continuous infusions was 2 [IQR 2-3]. After initiation of KD, most patients were weaned off anesthetic infusions by 1 week. Outcomes were variable. CONCLUSIONS: We demonstrated the feasibility of a practical approach to initiation of KD for children with SRSE. These children were successfully weaned off continuous anesthetic infusions. Larger studies are needed to determine effectiveness, safety, and tolerability of KD in the management of SRSE as well as ease of implementation.