A quality improvement initiative to improve folic acid supplementation counseling for adolescent females with epilepsy.

OBJECTIVE: We designed a quality improvement (QI) project to improve rates of documented folic acid supplementation counseling for adolescent females with epilepsy, consistent with a quality measure from the American Academy of Neurology and American Epilepsy Society. Our SMART aim was to increase the percentage of visits at which folic acid counseling was addressed from our baseline rate of 23% to 50% by July 1, 2020. METHODS: This initiative was conducted in female patients ≥12 years old with epilepsy who were prescribed daily antiseizure medication and were seen by the 13 providers in our Neurology QI Program. Using provider interviews, we undertook a root cause analysis of low counseling rates and identified the following main factors: insufficient time during clinic visit to counsel, lack of provider knowledge, and forgetting to counsel. Countermeasures were designed to address these main root causes and were implemented through iterative plan-do-study-act (PDSA) cycles. Interventions included provider education and features within the electronic health record, which were introduced sequentially, culminating in the creation of a best practice advisory (BPA). We performed biweekly chart reviews of visits for applicable patients to establish baseline performance rate and track progress over time. We used a statistical process control p-chart to analyze the outcome measure of documented counseling. As a balancing measure, clinicians were surveyed using the Technology Adoption Model survey to assess acceptance of the BPA. RESULTS: From September 2019 to August 2022, the QI team improved rates of documented folic acid counseling from 23% to 73% through several PDSA cycles. This level of performance has been sustained over time. The most successful and sustainable intervention was the BPA. Provider acceptance of the BPA was overall positive. SIGNIFICANCE: We successfully used QI methodology to improve and sustain our rates of documented folic acid supplementation counseling for adolescent females with epilepsy.

Assessing seizure burden in pediatric epilepsy using an electronic medical record-based tool through a common data element approach.

OBJECTIVE: Improvement in epilepsy care requires standardized methods to assess disease severity. We report the results of implementing common data elements (CDEs) to document epilepsy history data in the electronic medical record (EMR) after 12 months of clinical use in outpatient encounters. METHODS: Data regarding seizure frequency were collected during routine clinical encounters using a CDE-based form within our EMR. We extracted CDE data from the EMR and developed measurements for seizure severity and seizure improvement scores. Seizure burden and improvement was evaluated by patient demographic and encounter variables for in-person and telemedicine encounters. RESULTS: We assessed a total of 1696 encounters in 1038 individuals with childhood epilepsies between September 6, 2019 and September 11, 2020 contributed by 32 distinct providers. Childhood absence epilepsy (n = 121), Lennox-Gastaut syndrome (n = 86), and Dravet syndrome (n = 42) were the most common epilepsy syndromes. Overall, 43% (737/1696) of individuals had at least monthly seizures, 17% (296/1696) had a least daily seizures, and 18% (311/1696) were seizure-free for >12 months. Quantification of absolute seizure burden and changes in seizure burden over time differed between epilepsy syndromes, including high and persistent seizure burden in patients with Lennox-Gastaut syndrome. Individuals seen via telemedicine or in-person encounters had comparable seizure frequencies. Individuals identifying as Hispanic/Latino, particularly from postal codes with lower median household incomes, were more likely to have ongoing seizures that worsened over time. SIGNIFICANCE: Standardized documentation of clinical data in childhood epilepsies through CDE can be implemented in routine clinical care at scale and enables assessment of disease burden, including characterization of seizure burden over time. Our data provide insights into heterogeneous patterns of seizure control in common pediatric epilepsy syndromes and will inform future initiatives focusing on patient-centered outcomes in childhood epilepsies, including the impact of telemedicine and health care disparities.

Targeted treatment of migrating partial seizures of infancy with quinidine.

Migrating partial seizures of infancy is an early onset epileptic encephalopathy syndrome that is typically resistant to treatment. The most common cause is a gain of function mutation in the potassium channel KCNT1. The antiarrhythmic drug quinidine is a partial antagonist of KCNT1 and hence may be a candidate drug for treatment of this condition. We report the case of a child with migrating partial seizures of infancy secondary to an activating mutation in KCNT1 treated with quinidine. Treatment with quinidine was correlated with a marked reduction in seizure frequency and improved psychomotor development.

Video Ambulatory EEG in Children: A Quality Improvement Study.

PURPOSE: We implemented a video ambulatory EEG (VA-EEG) Program as an alternative to inpatient video EEG monitoring for some patients given potential benefits related to quicker access, greater convenience, and lower cost. To evaluate the newly initiated program, we performed a quality improvement study to assess whether VA-EEG yielded studies with interpretable EEG and video quality that generated clinically beneficial data. METHODS: This was a single-center prospective quality improvement study. We surveyed ordering clinicians, electroencephalographers, and caregivers regarding consecutive children who underwent clinically indicated VA-EEG. The primary outcome was the percentage of VA-EEG studies in which the ordering clinician reported that the study had answered the question of interest. RESULTS: We evaluated 74 consecutive children selected to undergo clinically indicated VA-EEG by their clinicians and caregivers. Ordering clinicians reported that 77% of studies answered the question of interest. Electroencephalographers reported that the quality of the EEG and video was excellent or adequate in 100% and 92% of patients, respectively. Additionally, 84% of caregivers reported preferring VA-EEG if EEG data were needed in the future. CONCLUSIONS: Video ambulatory EEG may be an effective diagnostic modality among children selected by clinicians and caregivers to undergo long-term EEG monitoring. Given it is effective as well as convenient, accessible, and lower cost than inpatient EEG monitoring, all of which align with our institution's quality goals, we intend to expand our VA-EEG Program.

Interrater and Intrarater Agreement in Neonatal Electroencephalogram Background Scoring.

PURPOSE: Many neonates undergo electroencephalogram (EEG) monitoring to identify and manage acute symptomatic seizures. Information about brain function contained in the EEG background data may also help predict neurobehavioral outcomes. For EEG background features to be useful as prognostic indicators, the interpretation of these features must be standardized across electroencephalographers. We aimed at determining the interrater and intrarater agreement among electroencephalographers interpreting neonatal EEG background patterns. METHODS: Five neonatal electroencephalographers reviewed 5-to-7.5-minute epochs of EEG from full-term neonates who underwent continuous conventional EEG monitoring. The EEG assessment tool used to classify background patterns was based on the American Clinical Neurophysiology Society's guideline for neonatal EEG terminology. Interrater and intrarater agreement were measured using Kappa coefficients. RESULTS: Interrater agreement was consistently highest for voltage (binary: substantial, kappa = 0.783; categorical: moderate, kappa = 0.562), seizure presence (fair-substantial; kappa = 0.375-0.697), continuity (moderate; kappa = 0.481), burst voltage (moderate; kappa = 0.574), suppressed background presence (moderate-substantial; kappa = 0.493-0.643), delta activity presence (fair-moderate; kappa = 0.369-0.432), theta activity presence (fair-moderate; kappa = 0.347-0.600), presence of graphoelements (fair; kappa = 0.381), and overall impression (binary: moderate, kappa = 0.495; categorical: fair-moderate, kappa = 0.347, 0.465). Agreement was poor or inconsistent for all other patterns. Intrarater agreement was variable, with highest average agreement for voltage (binary: substantial, kappa = 0.75; categorical: substantial, kappa = 0.714) and highest consistent agreement for continuity (moderate-substantial; kappa = 0.43-0.67) and overall impression (moderate-substantial; kappa = 0.42-0.68). CONCLUSIONS: This study demonstrates substantial variability in neonatal EEG background interpretation across electroencephalographers, indicating a need for educational and technological strategies aimed at improving performance.

Engrailed2 modulates cerebellar granule neuron precursor proliferation, differentiation and insulin-like growth factor 1 signaling during postnatal development.

BACKGROUND: The homeobox transcription factor Engrailed2 (En2) has been studied extensively in neurodevelopment, particularly in the midbrain/hindbrain region and cerebellum, where it exhibits dynamic patterns of expression and regulates cell patterning and morphogenesis. Because of its roles in regulating cerebellar development and evidence of cerebellar pathology in autism spectrum disorder (ASD), we previously examined an ENGRAILED2 association and found evidence to support EN2 as a susceptibility gene, a finding replicated by several other investigators. However, its functions at the cell biological level remain undefined. In the mouse, En2 gene is expressed in granule neuron precursors (GNPs) just as they exit the cell cycle and begin to differentiate, raising the possibility that En2 may modulate these developmental processes. METHODS: To define En2 functions, we examined proliferation, differentiation and signaling pathway activation in En2 knockout (KO) and wild-type (WT) GNPs in response to a variety of extracellular growth factors and following En2 cDNA overexpression in cell culture. In vivo analyses of cerebellar GNP proliferation as well as responses to insulin-like growth factor-1 (IGF1) treatment were also conducted. RESULTS: Proliferation markers were increased in KO GNPs in vivo and in 24-h cultures, suggesting En2 normally serves to promote cell cycle exit. Significantly, IGF1 stimulated greater DNA synthesis in KO than WT cells in culture, a finding associated with markedly increased phospho-S6 kinase activation. Similarly, there was three-fold greater DNA synthesis in the KO cerebellum in response to IGF1 in vivo. On the other hand, KO GNPs exhibited reduced neurite outgrowth and differentiation. Conversely, En2 overexpression increased cell cycle exit and promoted neuronal differentiation. CONCLUSIONS: In aggregate, our observations suggest that the ASD-associated gene En2 promotes GNP cell cycle exit and differentiation, and modulates IGF1 activity during postnatal cerebellar development. Thus, genetic/epigenetic alterations of EN2 expression may impact proliferation, differentiation and IGF1 signaling as possible mechanisms that may contribute to ASD pathogenesis.