Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey.

OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

Epilepsy center characteristics and geographic region influence presurgical testing in the United States.

OBJECTIVE: Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy. METHODS: We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank-sum, Kruskal-Wallis, and chi-squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables. RESULTS: The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2-6.86; p = .018) and fluorodeoxyglucose-positron emission tomography (OR = 2.74, 95% CI = = 1.14-6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23-.93; p = .031) and West (OR = .41, 95% CI = .19-.87; p = .022), odds of performing single-photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates. SIGNIFICANCE: Presurgical testing for drug-resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.

Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors.

OBJECTIVE: The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)-positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice. METHODS: We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables. RESULTS: The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose-positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06-3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60-5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27-6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19-4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28-3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24-7.89; p = .016). SIGNIFICANCE: In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.

Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration.

OBJECTIVES: To determine how continuous spike and wave during slow wave sleep (CSWS) is currently managed and to compare the effectiveness of current treatment strategies using a database from 11 pediatric epilepsy centers in the US. STUDY DESIGN: This retrospective study gathered information on baseline clinical characteristics, CSWS etiology, and treatment(s) in consecutive patients seen between 2014 and 2016 at 11 epilepsy referral centers. Treatments were categorized as benzodiazepines, steroids, other antiseizure medications (ASMs), or other therapies. Two measures of treatment response (clinical improvement as noted by the treating physician; and electroencephalography improvement) were compared across therapies, controlling for baseline variables. RESULTS: Eighty-one children underwent 153 treatment trials during the study period (68 trials of benzodiazepines, 25 of steroids, 45 of ASMs, 14 of other therapies). Children most frequently received benzodiazepines (62%) or ASMs (27%) as first line therapy. Treatment choice did not differ based on baseline clinical variables, nor did these variables correlate with outcome. After adjusting for baseline variables, children had a greater odds of clinical improvement with benzodiazepines (OR 3.32, 95%CI 1.57-7.04, P = .002) or steroids (OR 4.04, 95%CI 1.41-11.59, P = .01) than with ASMs and a greater odds of electroencephalography improvement after steroids (OR 3.36, 95% CI 1.09-10.33, P = .03) than after ASMs. CONCLUSIONS: Benzodiazepines and ASMs are the most frequent initial therapy prescribed for CSWS in the US. Our data suggests that ASMs are inferior to benzodiazepines and steroids and support earlier use of these therapies. Multicenter prospective studies that rigorously assess treatment protocols and outcomes are needed.

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort).

OBJECTIVE: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). METHODS: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks-24 h), and without fever. RESULTS: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. SIGNIFICANCE: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

The epileptic network and cognition: What functional connectivity is teaching us about the childhood epilepsies.

Our objective was to summarize and evaluate the rapidly expanding body of literature studying functional connectivity in childhood epilepsy. In the self-limited childhood epilepsies, awareness of cognitive comorbidities has been steadily increasing, and recent advances in our understanding of the network effects of these disorders promise insights into the underlying neurobiology. We reviewed publications addressing functional connectivity in children with epilepsy with an emphasis on studies of children with self-limited childhood epilepsies. The majority of studies have been published in the past 10 years and predominantly examine childhood epilepsy with centrotemporal spikes and childhood absence epilepsy. Cognitive network alterations are commonly observed across the childhood epilepsies. Some of these effects appear to be nonspecific to epilepsy syndrome or even to category of neurological disorder. Other patterns, such as changes in the connectivity of cortical language areas in childhood epilepsy with centrotemporal spikes, provide clues to the underlying cognitive deficits seen in affected children. The literature to date is dominated by general observations of connectivity patterns without a priori hypotheses. These data-driven studies build an important foundation for hypothesis generation and are already providing useful insights into the neuropathology of the childhood epilepsies. Future work should emphasize hypothesis-driven approaches and rigorous clinical correlations to better understand how the knowledge of network alterations can be applied to guidance and treatment for the children in our clinics.

Duration of use of oral cannabis extract in a cohort of pediatric epilepsy patients.

OBJECTIVE: Oral cannabis extracts (OCEs) are being used in the treatment of epilepsy with increasing rates in the United States following product legalization; however, no studies demonstrate clear efficacy. We evaluated the duration of use of OCEs as a measure of perceived benefit in a cohort of patients with pediatric epilepsy. METHODS: Retrospective chart review was performed of children and adolescents who were given OCEs for treatment of epilepsy. RESULTS: Of the 119 patients included in the analysis, 71% terminated use of their OCE product during the study period. The average length of use of OCE was 11.7 months (range 0.3-57 months). Perceived seizure benefit was the only factor associated with longer duration of treatment with OCE (p < 0.01). Relocation to Colorado was associated with perceived benefit of OCEs for seizures (65% vs. 38%, p = 0.01), but was not independently associated with longer OCE use. Factors associated with shorter use included adverse effects (p = 0.03) and a diagnosis of Dravet syndrome (p = 0.02). Twenty-four percent of patients were considered OCE responders, which was defined by a parent's report of a > 50% reduction in seizures while on this therapy. Adverse events (AEs) were reported in 19% of patients, with the most common side effects being somnolence and worsening of seizures. SIGNIFICANCE: Parental report of OCE use in refractory pediatric epilepsy suggests that some families perceive benefit from this therapy; however, discontinuation of these products is common. Duration appears to be affected by logical factors, such as perceived benefit and side effect profile. Surprisingly, families of patients with Dravet syndrome terminated use of OCEs more quickly than patients with other epilepsy syndromes. Results from this study highlight the need for rigorous clinical studies to characterize the efficacy and safety of OCEs, which can inform discussions with patients and families.

EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI.

BACKGROUND: Traumatic brain injury (TBI) causes substantial morbidity and mortality in US children. Post-traumatic seizures (PTS) occur in 11-42% of children with severe TBI and are associated with unfavorable outcome. Electroencephalographic (EEG) monitoring may be used to detect PTS and antiepileptic drugs (AEDs) may be used to treat PTS, but national rates of EEG and AED use are not known. The purpose of this study was to describe the frequency and timing of EEG and AED use in children hospitalized after severe TBI. METHODS: Retrospective cohort study of 2165 children at 30 hospitals in a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007-2010. We included children (age <18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] <8) TBI, hospital length of stay >24 h, and non-missing disposition. The primary outcomes were EEG and AED use. RESULTS: Overall, 31.8% of the cohort had EEG monitoring. Of those, 21.8% were monitored on the first hospital day. The median duration of EEG monitoring was 2.0 (IQR 1.0, 4.0) days. AEDs were prescribed to 52.0% of the cohort, of whom 61.8% received an AED on the first hospital day. The median duration of AED use was 8.0 (IQR 4.0, 17.0) days. EEG monitoring and AED use were more frequent in children with known risk factors for PTS. EEG monitoring and AED use were not related to hospital TBI volume. CONCLUSION: EEG use is relatively uncommon in children with severe TBI, but AEDs are frequently prescribed. EEG monitoring and AED use are more common in children with known risk factors for PTS.

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

OBJECTIVE: To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. DESIGN: Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. SETTING: Nine pediatric hospitals in the United States. PATIENTS: In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. MAIN RESULTS: The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. CONCLUSIONS: Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

Seizing control of epileptic activity can improve outcome.

In epileptic encephalopathy, the seizures and interictal epileptiform activity create additional neurocognitive dysfunction beyond that due to the underlying etiology. Treatment leading to a reduction in seizures or interictal abnormalities may help improve neurocognitive function in these situations. The focus of our discussion is reviewing data that support the concept that treatment can impact outcome independent of the etiology in some cases.

Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

OBJECTIVE: Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center. METHODS: A retrospective chart review of children and adolescents who were given OCE for treatment of their epilepsy was performed. RESULTS: Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a >50% reduction in seizures (responders). If the family had moved to CO for OCE treatment, the responder rate was 47% vs. 22% for children who already were in CO. The responder rate varied based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available was not improved. Additional benefits reported included: improved behavior/alertness (33%), improved language (10%), and improved motor skills (10%). Adverse events (AEs) occurred in 44% of patients including increased seizures (13%) and somnolence/fatigue (12%). Rare adverse events included developmental regression, abnormal movements, status epilepticus requiring intubation, and death. SIGNIFICANCE: Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment; however, we also found a variety of challenges and possible confounding factors in studying OCE retrospectively in an open-labeled fashion. We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker. This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE: To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN: This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS: Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS: After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Unmet needs in epileptic encephalopathy with spike-and-wave activation in sleep: A systematic review.

INTRODUCTION: Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS), also referred to as electrical status epilepticus during sleep (ESES) or epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS or EE-CSWS), is a spectrum of rare childhood epileptic encephalopathies that can lead to long-term cognitive impairment. Despite the importance of early diagnosis and intervention for D/EE-SWAS, there is a paucity of well-controlled clinical trial data to inform treatment, and no approved treatments are available. To assess correlations between diagnosis, treatment, and outcomes in D/EE-SWAS, we carried out a systematic review of the literature. METHODS: In August 2020, we conducted comprehensive database searches using search terms including "electrical status epilepticus," "ESES," "CSWS," and "Landau-Kleffner syndrome." Two or more independent reviewers screened titles, abstracts, and full-text articles for those that met the following criteria: prospective studies (randomized controlled trials [RCTs] or open-label trials), retrospective studies (drug evaluations or observational studies/chart reviews), and case series with ≥ 10 participants. Both interventional and non-interventional studies were included (i.e., drug intervention was not an inclusion criterion). Articles published before 2012, review articles, animal studies, and studies of surgical or dietary interventions were excluded. Standardized data extraction templates were used to capture data on study design, patient characteristics, interventions, and outcomes from each of the selected publications. Study quality was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for retrospective, observational studies. RESULTS: A total of 34 studies were included for full data extraction, most of which were uncontrolled and observational. Interpretation of study outcomes was limited by small study populations, variability in inclusion criteria, and inconsistency in methods of assessment and reporting of outcomes, which resulted in large heterogeneity in patients and their presenting symptoms. Despite these limitations, some patterns could be discerned. Several studies found that longer duration of ESES and younger age at onset were correlated with more severe language and cognitive deficits. In addition, several studies reported an association between improvement in cognitive outcomes and reduction in electroencephalogram (EEG) abnormalities and/or seizure frequency. In the 16 prospective or retrospective studies that evaluated drug treatments (e.g., antiseizure medications, corticosteroids, and high-dose diazepam), there was some improvement in EEG, seizure, and/or cognitive outcomes, although the specific outcomes and rates of improvement reported varied from study to study. CONCLUSION: Long-term cognitive deficits remain common in D/EE-SWAS, and data gaps exist in the literature that preclude an evidence-based approach to managing this complex epilepsy indication. Early intervention with more effective medications is needed to optimize long-term outcomes. Sufficiently powered, randomized, double-blind, controlled trials with standardized methods and predefined primary and secondary outcomes are needed.

The tower of Babel: survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America.

PURPOSE: The terms "electrical status epilepticus during sleep (ESES)" and "continuous spikes and waves during sleep (CSWS)" have been used interchangeably when referring to related but different concepts. In addition, the quantification of epileptiform activity has not been standardized, and different approaches to quantification have been used. The aim of this study was to evaluate the extent to which pediatric neurologists and epileptologists use a homogeneous terminology and conceptualization in CSWS and ESES and to characterize the current understanding of these conditions. METHODS: A survey addressing the use of terminology in "ESES" and "CSWS" and the understanding of related concepts was distributed online to all members of the Child Neurology Society and the American Epilepsy Society mailing lists. Surveys were self-administered and collected using an online survey website (http://www.surveymonkey.com). KEY FINDINGS: Two hundred nineteen surveys were completed, 137 from the Child Neurology Society mailing list and 82 from the American Epilepsy Society mailing list. ESES and CSWS were considered synonymous by 117 respondents, not synonymous by 61, 21 respondents did not know, and 20 did not respond. Most respondents (63.1%) considered CSWS as a devastating epileptic encephalopathy with severe sequelae even if treated correctly, but 25.1% of respondents indicated that it does not leave sequelae if epilepsy was treated early and another 11.8% noted that cognitive difficulties resolved with age. Cognitive and/or language regression were considered mandatory for the diagnosis of CSWS by only 27% of the respondents. The diagnosis of CSWS was based on electroencephalography (EEG) assessment alone by 31% of respondents. Respondents used different methods for calculation of the epileptiform activity, different EEG samples for calculation, and considered differently the lateralized epileptiform activity. The cut-off values for percentage of the sleep record occupied by spike-waves were variable depending on the respondent. There was no agreement on whether these cutoff values were mandatory for the diagnosis of ESES and CSWS. SIGNIFICANCE: Our data show that the professionals caring for children with ESES and CSWS in North America use the terms, concepts, and defining features heterogeneously. The lack of a common language may complicate communication among clinicians and jeopardize research in this field. We anticipate that our data will fuel the development of much needed common terminology and conceptualization of ESES and CSWS.

Electroencephalography monitoring in critically ill children: current practice and implications for future study design.

PURPOSE: Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome. METHODS: Eleven North American centers retrospectively enrolled 550 consecutive critically ill children who underwent CEEG. We collected data regarding subject characteristics, CEEG indications, and CEEG findings. KEY FINDINGS: CEEG indications were encephalopathy with possible seizures in 67% of subjects, event characterization in 38% of subjects, and management of refractory status epilepticus in 11% of subjects. CEEG was initiated outside routine work hours in 47% of subjects. CEEG duration was <12 h in 16%, 12-24 h in 34%, and >24 h in 48%. Substantial variability existed among sites in CEEG indications and neurologic diagnoses, yet within each acute neurologic diagnosis category a similar proportion of subjects at each site had electrographic seizures. Electrographic seizure characteristics including distribution and duration varied across sites and neurologic diagnoses. SIGNIFICANCE: These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multicenter studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies that address the impact of electrographic seizures on outcome.

Electroencephalographic monitoring in the pediatric intensive care unit.

Continuous electroencephalographic (CEEG) monitoring is used with increasing frequency in critically ill children to provide insight into brain function and to identify electrographic seizures. CEEG monitoring use often impacts clinical management, most often by identifying electrographic seizures and status epilepticus. Most electrographic seizures have no clinical correlate, and thus would not be identified without CEEG monitoring. There are increasing data showing that electrographic seizures and electrographic status epilepticus are associated with worse outcome. Seizure identification efficiency may be improved by further development of quantitative electroencephalography trends. This review describes the clinical impact of CEEG data, the epidemiology of electrographic seizures and status epilepticus, the impact of electrographic seizures on outcome, the utility of quantitative electroencephalographic trends for seizure identification, and practical considerations regarding CEEG monitoring.

Utility and safety of prolonged video-EEG monitoring in a tertiary pediatric epilepsy monitoring unit.

Prolonged video-EEG (vEEG) monitoring helps characterize paroxysmal events and epilepsy. There is limited literature in pediatrics describing the safety and utility of vEEG. We retrospectively reviewed 454 pediatric epilepsy monitoring unit admissions over two years. Final event diagnoses, duration of seizures, and medical complications were analyzed. Two hundred twenty admissions (48.4%) captured epileptic seizures, 150 (33.0%) captured nonepileptic events, and 84 (18.5%) failed to capture any events. Medical complications were seen in 4 patients (1.8%) with no long-term complications. Seventeen episodes of status epilepticus occurred in 13 patients. This constituted 2.9% of all admissions and 5.9% of admissions with epileptic seizures. The median duration of status was 26 min, and three patients required transfer to the pediatric intensive care unit. Video-EEG monitoring had a high yield in capturing events and differentiating epileptic from nonepileptic events. Our pediatric patients experienced greater risk of status epilepticus but lesser risk of injury.

Spike-Associated Networks Predict Postsurgical Outcomes in Children With Refractory Epilepsy.

PURPOSE: Up to half of the children undergoing epilepsy surgery will continue to have seizures (szs) despite a cortical resection or ablation. Functional connectivity has shown promise in better identifying the epileptogenic zone. We hypothesized that cortical areas showing high information outflow during interictal epileptiform discharges are part of the epileptogenic zone. METHODS: We identified 22 children with focal epilepsy who had undergone stereo electroencephalography, surgical resection or ablation, and had ≥1 year of postsurgical follow-up. The mean phase slope index, a directed measure of functional connectivity, was calculated for each electrode contact during interictal epileptiform discharges. The positive predictive value and negative predictive value for a sz-free outcome were calculated based on whether high information outflow brain regions were resected. RESULTS: Resection of high outflow (z-score ≥ 1) and very high outflow (z-score ≥ 2) electrode contacts was associated with higher sz freedom (high outflow: χ 2 statistic = 59.1; P < 0.001; very high outflow: χ 2 statistic = 31.3; P < 0.001). The positive predictive value and negative predictive value for sz freedom based on resection at the electrode level increased at higher z-score thresholds with a peak positive predictive value of 0.86 and a peak negative predictive value of 0.9. CONCLUSIONS: Better identification of the epileptogenic zone has the potential to improve epilepsy surgery outcomes. If the surgical plan can be modified to include these very high outflow areas, more children might achieve sz freedom. Conversely, if deficits from resecting these areas are unacceptable, ineffective surgeries could be avoided and alternative therapies offered.