Proposed Pathway for the Utilization of Pediatric Ambulatory EEG.

PURPOSE: The clinical utility of pediatric ambulatory-EEG (A-EEG) has been studied for decades, but limited information exists regarding which variables influence its utility. The authors aimed to evaluate clinical/EEG variables that may influence A-EEG yields and to develop a pathway for A-EEG utilization in children. METHODS: Single-center retrospective review of A-EEGs performed from July 2019 to January 2021 in a tertiary referral center. The primary outcome was whether the A-EEG test successfully answered the referring physician's clinical question or influenced therapy. When it did, the A-EEG test was deemed useful. Clinical and EEG variables were assessed for their ability to predict utility. Further, the literature review generated 10 relevant prior studies whose details were used to generate a pathway for A-EEG utilization in children. RESULTS: One hundred forty-two A-EEG studies were included (mean age 8.8 years, 48% male patients, mean A-EEG duration 33.5 hours). Overall, A-EEG was considered useful in 106 children (75%) but heavily influenced by A-EEG indication. Specifically, it was deemed useful for 94% of patients evaluated for electrical status epilepticus in slow-wave sleep, 92% of those evaluated for interictal/ictal burden, and 63% of those undergoing spell classification. The test indication (P < 0.001), a diagnosis of epilepsy (P = 0.02), and an abnormal routine EEG (P = 0.04) were associated with A-EEG test utility, although the multivariate analysis confirmed the test indication as the only independent outcome predictor of A-EEG. CONCLUSIONS: Pediatric A-EEG is extremely useful for evaluating electrical status epilepticus in slow-wave sleep and interictal/ictal burden and is often helpful for spell classification. Among all clinical and EEG variables analyzed, the test indication was the only independent outcome predictor of obtaining a helpful A-EEG.

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.

Creation and implementation of an electronic health record note for quality improvement in pediatric epilepsy: Practical considerations and lessons learned.

OBJECTIVE: To describe the development of the Pediatric Epilepsy Outcome-Informatics Project (PEOIP) at Alberta Children's Hospital (ACH), which was created to provide standardized, point-of-care data entry; near-time data analysis; and availability of outcome dashboards as a baseline on which to pursue quality improvement. METHODS: Stakeholders involved in the PEOIP met weekly to determine the most important outcomes for patients diagnosed with epilepsy, create a standardized electronic note with defined fields (patient demographics, seizure and syndrome type and frequency and specific outcomes- seizure type and frequency, adverse effects, emergency department visits, hospitalization, and care pathways for clinical decision support. These were embedded in the electronic health record from which the fields were extracted into a data display platform that provided patient- and population-level dashboards updated every 36 hours. Provider satisfaction and family experience surveys were performed to assess the impact of the standardized electronic note. RESULTS: In the last 5 years, 3,245 unique patients involving 13, 831 encounters had prospective, longitudinal, standardized epilepsy data accrued via point-of-care data entry into an electronic note as part of routine clinical care. A provider satisfaction survey of the small number of users involved indicated that the vast majority believed that the note makes documentation more efficient. A family experience survey indicated that being provided with the note was considered "valuable" or "really valuable" by 86% of respondents and facilitated communication with family members, school, and advocacy organizations. SIGNIFICANCE: The PEOIP serves as a proof of principle that information obtained as part of routine clinical care can be collected in a prospective, standardized, efficient manner and be used to construct filterable process/outcome dashboards, updated in near time (36 hours). This information will provide the necessary baseline data on which multiple of QI projects to improve meaningful outcomes for children with epilepsy will be based.

Neck Circumference-Height Ratio as a Predictor of Sleep Related Breathing Disorder in Children and Adults.

STUDY OBJECTIVES: While neck circumference (NC) is a useful predictor of obstructive sleep apnea (OSA) in adults, childhood OSA is difficult to predict clinically. We utilized the neck circumference-height ratio (NHR) to normalize NC in growing children. Our study aimed to determine if (1) NC is a reproducible clinical measurement; (2) NHR predicts OSA in children; (3) this metric translates to adults. METHODS: For this retrospective study, paired NC measurements (from clinic and sleep laboratory) in 100 consecutive adult subjects were used to confirm inter-observer reproducibility. Polysomnographic (PSG) and anthropometric data from children aged 5-18 years presenting consecutively between July 2007 and February 2012 was obtained. Children with genetic syndromes, severe neurological disorders, craniofacial abnormalities, tracheostomy, past adenotonsillectomy, in-hospital PSG or sleep efficiency < 80% were excluded. Data were analyzed using χ(2) test and logistic and linear regression models. These analyses were also applied to 99 adult patients with similar exclusion criteria. RESULTS: Adult NC measurement had inter-observer correlation of 0.85 (N = 100). Among children, after correcting for BMI-Z scores, NHR conferred additional predictive value, in both logistic regression and linear models, for both apnea-hypopnea index (AHI) > 2 and > 5 (N = 507). In children, for NHR > 0.25, the odds ratio of AHI > 2 was 3.47. In adults, for NHR > 0.25, the odds ratio of AHI > 5 was 18. CONCLUSIONS: NHR can be included as a simple screening tool for OSA in children and adults, which along with other predictors, may improve the ability of clinicians to triage children and adults at risk for OSA for further evaluation with PSG.

Prevalence of Interictal Epileptiform Discharges in Children Less Than One Year of Age Referred for Polysomnography.

This study aimed to identify the prevalence of interictal epileptiform discharges (IEDs) in patients less than one year of age referred for polysomnogram (PSG), to quantify the number of IEDs and characterize sleep stage(s) during which IEDs occur, and to relate the reason for PSG referral and IED frequency. This was a retrospective cohort study of children less than 12 months of age referred for PSG studies. Fifty study participants had sufficient EEG data, and 49 were included in the study analysis. We identified an IED prevalence rate of 28% over the 2-year study period. The mean number (Standard Deviation; SD) of IEDs per hour of total sleep time was 0.4 (1.2). IEDs occurred most frequently in non-rapid eye movement (NREM) stages 2 and 3 of sleep. The most common reason for PSG referral in this patient cohort was for obstructive sleep apnea (OSA) (42/50). We concluded that patients less than 12 months of age referred for PSG may have abnormal brain activity. The relationship of that activity to PSG findings is unclear. This study offers a systematic process of identifying IEDs that should prompt referral to a neurologist for further evaluation.