Outcomes following a multi-disciplinary pediatric-to-adult transition and transfer clinic at a level four epilepsy center.

OBJECTIVE: Transition and transfer from the pediatric to adult care model is crucial to the continued long-term health and well-being of patients impacted by life-long diseases. This project explores the impact of a novel epilepsy transition collaboration between Nationwide Children's Hospital (NCH) and Ohio State University (OSU) Wexner Medical Center. METHODS: We retrospectively analyzed the characteristics and outcomes of 56 consecutive patients transferred to an adult health care system. These patients were divided into two groups. A cohort of 23 patients transferred in 2019 prior to clinic implementation were compared to a cohort of 33 consecutive patients transferred in 2019 and early 2020 using the epilepsy transition and transfer clinic model. Data points of interest included demographic information, age at transfer, epilepsy diagnosis, pharmacoresistance of epilepsy, surgical history and compliance with follow-up. RESULTS: Patients transferred to OSU through the transition clinic were statistically more likely to be followed at OSU (p = .037) within 6 months (p = .013). Additionally, there was improved patient retention at OSU following transition clinic implementation (p = .037). SIGNIFICANCE: Data demonstrating statistically significant improvement in care has not been reported for an epilepsy transition clinic. This study establishes that our novel approach improves continuity of care in this at-risk population. Our clinic model also successfully transitioned and transferred medically complex patients, including those with pharmacoresistant and/or genetically mediated epilepsy. Additionally, this work suggests that this clinic structure has potential to foster the growth of associated adult epilepsy subspecialty practices. These findings are encouraging as they offer potential for improved health care in the youth and young adult epilepsy population.

The Spike-Wave Index of the First 100 Seconds of Sleep Can Be a Reliable Scoring Method for Electrographic Status Epilepticus in Sleep.

INTRODUCTION: Electrical status epilepticus in sleep (ESES) is an electrographic pattern in which interictal epileptiform activity is augmented by the transition to sleep, with non-rapid eye movement sleep state characterized by near-continuous lateralized or bilateral epileptiform discharges. The aim of this study was to measure the reliability of the spike-wave index (SWI) of the first 100 seconds of sleep as a tool for the diagnosis of ESES. METHODS: One hundred forty studies from 60 unique patients met the inclusion. Two neurophysiologists calculated the SWI of the first 100 seconds of spontaneous stage II non-rapid eye movement sleep. This was compared with the SWI of the first 5 minutes of non-rapid eye movement sleep and the cumulative SWI of three 5-minute bins of sleep. Agreement between the three SWI methods were analyzed using several statistical tools and methods. RESULTS: Using an SWI of 50% as a diagnostic cutoff, 57% of records had a diagnosis of ESES based on the first 100 seconds of sleep. Fifty-four percent of records had a diagnosis of ESES based on the method of using the SWI of three bins. This resulted in a diagnostic accuracy of 92%, sensitivity of 96%, and specificity of 88%. Positive predictive values of children diagnosed with ESES using the first 100 seconds of sleep, compared with 3 combined bins, was determined to be 90% and a negative predictive value was determined to be 95%. CONCLUSIONS: This analysis confirmed the diagnostic accuracy of using the SWI of the first 100 seconds of sleep and the cumulative total of three 5-minute bins.

La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity.

BACKGROUND: La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse. METHODS: This was a single-center, retrospective cohort study, followed by recruitment for a cross-sectional analysis of long-term neurobehavioral outcomes, among children aged 0-18 years with proven or probable LACV neuroinvasive disease (LACV-ND) between January 2009 and December 2018. Case ascertainment was assured by International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes cross-referenced with laboratory results detecting LACV. Demographics, diagnostics, radiographs, and outcomes were evaluated. Recruitment of patients with prior diagnosis of LACV-ND occurred from January 2020 to March 2020, with assessment performed by validated pediatric questionnaires. RESULTS: One-hundred fifty-two children (83 males; median age, 8 years [interquartile range, 5-11.5 years]) were diagnosed with proven (n = 61 [47%]) and probable (n = 91 [60%]) LACV-ND. Sixty-five patients (43%) had severe disease. Altered mental status (AMS) (odds ratio [OR], 6.36 [95% confidence interval {CI}, 2.03-19.95]; P = .0002) and seizures at presentation (OR, 10.31 [95% CI, 3.45-30.86]; P = .0001) were independent predictors of severe disease. Epileptiform discharges on electroencephalogram (EEG) were independently associated with epilepsy diagnosis at follow-up (OR, 13.45 [95% CI, 1.4-128.77]; P = .024). Fifty-four patients were recruited for long-term neurobehavioral follow-up, with frequent abnormal assessments identified (19%-54%) irrespective of disease severity. CONCLUSIONS: Severe disease was observed frequently among children with LACV-ND. Seizures and AMS at presentation were independent predictors of severe disease. EEG may help determine long-term epilepsy risk. Long-term neurobehavioral issues are frequent and likely underrecognized among children with LACV-ND.

Prioritizing Hormone Therapy Over Vigabatrin as the First Treatment for Infantile Spasms: A Quality Improvement Initiative.

BACKGROUND AND OBJECTIVES: Infantile spasms (IS) are early childhood seizures with potentially devastating consequences. Standard therapies (adrenocorticotropic hormone [ACTH], high-dose prednisolone, and vigabatrin) are strongly recommended as the first treatment for IS. Although this recommendation comes without preference for one standard therapy over another, early remission rates are higher with hormone therapy (ACTH and high-dose prednisolone) when compared with vigabatrin. Using quality improvement (QI) methodology that included hormone therapy as the first treatment, we sought to increase the percentage of children with new-onset nontuberous sclerosis complex (TSC)-associated IS achieving 3-month electroclinical remission from a mean of 53.8% to ≥70%. METHODS: This was an observational consecutive sample cohort study at a single academic tertiary care hospital that compared a prospective intervention cohort (May 2019-January 2022, N = 57) with a retrospective baseline cohort (November 2015-April 2019, N = 67). Our initiative addressed key drivers such as the routine use of vigabatrin over hormone therapy as first treatment and the common initiation of a second treatment after 14 days for initial nonresponders. We included consecutive children without TSC presenting with new-onset IS diagnosed and treated between ages 2 and 24 months. We displayed our primary outcome and process measures as control charts in which the centerline is the quarterly (previous 3 months) mean based on statistical process control methodology. RESULTS: QI interventions that included the standardization of hormone therapy as the first treatment resulted in higher rates of 3-month remission, rising from 53.8% (baseline cohort) to 75.9% (intervention cohort). Process measure results included an increased rate of children receiving hormone therapy as first treatment (mean, 44.6%-100%) and a decreased number of days to both clinical follow-up after first treatment (mean, of 16.3-12.6 days) and starting a second treatment within 14 days for initial nonresponders (mean, 36.3-17.2 days). DISCUSSION: For children with IS, improved rates of 3-month electroclinical remission can be achieved with QI methodology. Implementation of similar QI initiatives at other centers may likewise improve local remission rates.

The COVID-19 Pandemic and Pregnancy: Impact on Mothers and Newborns.

The severe acute respiratory syndrome coronavirus 2 pandemic has markedly, and likely permanently, changed health care. This includes changing the obstetric and perinatal care of mothers and infants, and by extension, the care of their families. Infection during pregnancy is associated with an increased risk for severe coronavirus disease 2019 illness and related complications that can significantly impact maternal health and the health of the neonate. Viral transmission from mother to fetus is possible, but rare during pregnancy, and current health care policies focusing on maternal masking, and hand washing allows infected mothers to safely care for neonates (including nursing or feeding with expressed breast milk). The newly developed vaccines have been shown to be safe and effective for pregnant and breast-feeding mothers, with measurable antibody levels in cord blood and breast milk potentially providing a level of passive immunity to neonates. While studies looking at short-term outcomes for neonates have been reassuring, it is critical that we continue to work to understand and improve the care of pregnant woman and newborns with coronavirus disease 2019 to optimize long term outcomes. Although the knowledge base continues to evolve, the available evidence influencing the care of pregnant women and their infants is summarized in this focused review.

Diagnosis and Management of Seizures in the Preterm Infant.

The risk of seizure is increased in premature neonates compared to full term infants, with a distinct profile of etiologies, timing and character. Despite improvements in neonatal care, preterm infants with seizure continue to have higher risk of abnormal neurodevelopmental outcomes when compared to preterm infants without seizures, or to full term infants with seizures. Very limited evidence guides the care of this challenging population, therefore, management of the preterm neonate with seizure is largely extrapolated from the care of full-term neonates. A critical need exists for well-designed clinical trials investigating and validating the safety, efficacy, and outcomes of seizure management in this vulnerable population.

Electroencephalography Technologist Inter-rater Agreement and Interpretation of Pediatric Critical Care Electroencephalography.

OBJECTIVES: Electroencephalography (EEG) technologists commonly screen continuous EEG. Until now, the inter-rater agreement or sensitivity for important EEG findings has been unknown in this group. METHODS: Twenty-nine EEG technologists and three clinical neurophysiologists interpreted 90 five-minute samples of pediatric critical care EEG. Inter-rater agreement was examined with Cohen's kappa and Fleiss' kappa for EEG findings. A gold-standard consensus agreement was developed for examining sensitivity and specificity for seizures or discontinuity. Kruskal-Wallis tests with Benjamani-Hochberg corrections for multiple comparisons were utilized to examine associations between correct scoring and certification status and years of experience. RESULTS: Aggregate agreement was moderate for seizures and fair for EEG background continuity among EEG technologists. Individual agreement for seizures and continuity varied from slight to substantial. For individual EEG technologists, sensitivity for seizures ranged from 44 to 93% and sensitivity for continuity ranged from 81 to 100%. Raters with Certified Long Term Monitoring credentials were more likely to identify seizures correctly. SIGNIFICANCE: This is the first study to evaluate inter-rater agreement and interpretation correctness among EEG technologists interpreting pediatric critical care EEG. EEG technologists demonstrated better aggregate agreement for seizure detection than other EEG findings, yet individual results and internal consistency varied widely. These data provide important insight into the common practice of utilizing EEG technologists for screening critical care EEG.

Compliance With Standard Therapies and Remission Rates After Implementation of an Infantile Spasms Management Guideline.

BACKGROUND: We implemented an infantile spasms management guideline recommending standard therapies and, early start of next treatment. After six years, we determined (1) our compliance with standard therapies, (2) time to next treatment, and (3) rate of initial and three-month electroclinical remission with first, second, and third treatments. METHODS: This is a retrospective record review of newly diagnosed spasms from September 2012 to September 2018, with the onset age of two months to two years. RESULTS: Standard therapies (hormone or vigabatrin) were the first treatments in 114 of 115 consecutive patients. The second and third treatments were started within 14 days of failed treatment in only 21% and 24%, respectively. Remission with the first and second treatments was similar (41% and 40%). Remission was lower for the third treatment (15%), although higher if standard therapy was used (36%). Initial and three-month remission by the first treatment was significantly higher for adrenocorticotropic hormone (ACTH, 66% and 79%, respectively) and prednisolone (53% and 83%, respectively) than for vigabatrin (19% and 40%, respectively). There were no significant differences in patient characteristics or rates of remission between ACTH and prednisolone. CONCLUSIONS: Although we achieved excellent compliance with standard therapies as initial treatment, a next treatment often started after two weeks. Given the superiority of hormone therapies over vigabatrin and standard therapies over nonstandard therapies, as well as the potentially negative impact of delays in effective treatment, future interventions need to focus on increasing the use of hormone over vigabatrin (for patients without tuberous sclerosis complex), use of standard therapies as second and third treatments, and reducing delays to next treatment.

Attention Deficit Hyperactivity Disorder and Associated Cognitive Dysfunction in Pediatric Epilepsy.

Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric comorbidity associated with childhood epilepsy, affecting about a third of children with epilepsy. In contrast, ADHD in the general population occurs in 4%-12% of school-aged children. The cause of this association remains unclear. It is likely that common mechanisms underlie the vulnerability for both executive deficits and epileptogenesis. There are characteristics unique to children with ADHD and epilepsy. The inattentive type of ADHD is more prevalent than the combined presentation in children with epilepsy, while the combined type is more common in the general population. Interestingly, there is an equal sex distribution of ADHD in patients with epilepsy, while in the general population, ADHD is 3-7 times more prevalent in boys. Specific features of ADHD seen in different epilepsy syndromes are frequently associated with executive deficits. Early screening of ADHD symptoms in children with epilepsy is essential, as timely interventions can improve academic and social function and outcomes. The mainstays of therapy include behavioral interventions and pharmacotherapy, with evidence demonstrating that stimulants are both safe and effective in children with ADHD and epilepsy.

Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms.

BACKGROUND: There is poor inter-rater agreement in determining the presence or absence of hypsarrhythmia among patients with infantile spasms. Yet, remission of hypsarrhythmia has been used as a clinical and research outcome measure. Two important features of hypsarrhythmia are the burden of epileptiform discharges and the amplitudes of background slow waves. We hypothesized that an electroencephalogram (EEG) grading scale emphasizing epileptiform discharge burden and the amplitudes of background slow waves would improve inter-rater agreement in interpreting hypsarrhythmia. Our aim was to assess inter-rater agreement of hypsarrhythmia using a novel and simplified EEG grading scale called the 'BASED' (Burden of Amplitudes and Epileptiform Discharges) score and compare this to the traditional method of EEG analysis. METHODS: Twenty patients with infantile spasms were prospectively evaluated and electroclinical outcomes were determined. Forty EEG clips (20 pre-treatment and 20 post-treatment), representing the most severely abnormal five minute sleep epoch of each study, were assessed by three reviewers blinded to treatment and clinical outcome. Fleiss' kappa (К) was used to assess the inter-rater agreement in the interpretation of hypsarrhythmia when using the BASED score compared to the traditional method of EEG analysis. RESULTS: Reviewers had favorable inter-rater agreement using the BASED score in interpreting hypsarrhythmia (К: 0.87) compared to when using the traditional method of EEG analysis to interpret hypsarrhythmia (К: 0.09). The three reviewers all agreed on the presence or absence of hypsarrhythmia in 37/40 (93%) epochs using the BASED score but in only 15/40 (38%) epochs using the traditional method of EEG analysis, p=<0.001. CONCLUSION: When compared to the traditional method of EEG analysis, the BASED score allowed for better inter-rater agreement in the interpretation of hypsarrhythmia. Future infantile spasms clinical trials must better define criteria for hypsarrhythmia.