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To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS).Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator.1,131 patients received at least one first-line treatment [median (pThe gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has markedly widened from 2006 to 2020, while the relative proportion of ACTH use has decreased.

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.

OBJECTIVE: Describe hospital readmission for status epilepticus (SE) in the United States, and study potential risk factors for readmission. METHODS: This is a retrospective observational study using the Healthcare Cost and Utilization Project's 2016 Nationwide Readmissions Database. We studied patients of all ages admitted to the hospital due to SE. RESULTS: We included 32 327 patients admitted for SE in 2016. 8.4% of these patients were readmitted for SE at least one more time within 2016 (cross-sectional analysis). The incidence rate was 18 readmissions for SE per 1000 patient-months. Among the survivors of the index admission for SE who had at least 6 months of follow-up within this database (16 043 patients), the cumulative probability of having a readmission for SE at 1, 3, and 6 months from the index admission was approximately 3.5%, 7.5%, and 11%, respectively (time-to-event analysis). Patients with refractory epilepsy were more likely to have a readmission for SE compared to patients without refractory epilepsy (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.23-1.82, adjusted P =.0006), and pediatric patients were more likely to have a readmission for SE compared to adult patients (HR 1.53, 95% CI 1.26-1.87, adjusted P = .0003) during 6-month follow-up. SIGNIFICANCE: Hospital readmissions for SE in the United States are frequent. Independent factors associated with readmission in this database were refractory epilepsy and pediatric age.

We reviewed 37 studies reporting long-term outcomes after a status epilepticus (SE) episode in pediatric and adult populations. Study design, length of follow-up, outcome measures, domains investigated (mortality, SE recurrence, subsequent epilepsy, cognitive outcome, functional outcome, or quality of life), and predictors of long-term outcomes are summarized. Despite heterogeneity in the design of prior studies, overall risk of poor long-term outcome after SE is high in both children and adults. Etiology is the main determinant of outcome, and the effect of age or SE duration is often difficult to distinguish from the underlying cause. The effect of the treatment on long-term outcome after SE is still unknown., SCOPUS: ar.j, info:eu-repo/semantics/published

SummaryObjective To identify factors associated with in-hospital mortality in neonates and children undergoing continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU). Methods We performed a retrospective observational study in patients from birth to 21 years of age who underwent clinically indicated cEEG in the ICU from 2011 to 2013. The main outcome measure was in-hospital mortality. Results Six-hundred and twenty-five patients (54.2% male) met eligibility criteria, of whom 211 were neonates (55% male, 24.8% premature) and 414 were pediatric patients (53.9% male). Electrographic seizures occurred in 176 patients (28.2%) and status epilepticus (SE) occurred in 20 (11.4%). The time from ICU admission to cEEG initiation was 16.7 (5.1–94.4) h. Eighty-nine patients (14.2%) (30 [14.2%] neonates, and 59 [14.3%] pediatric patients) died in the hospital. In neonates—after controlling for gender and prematurity—independent factors associated with mortality were prematurity (odds ratio [OR] 2.63. 95% confidence interval [CI] 1.06–6.5, p = 0.037), presence of status epilepticus (SE); OR 8.82, 95% CI 1.74–44.57, p = 0.008), and time from ICU admission to initiation of cEEG (OR 1.002, 95% CI 1.001–1.004 per hour, p = 0.008]. In pediatric patients—after controlling for gender and age—independent factors associated with mortality were the absence of seizures factors associated with mortality were absence of seizures (OR = 4.3, (95% CI: 1.5–12.4), p = 0.007), the presence of SE (OR 7.76, 95% CI 1.47–40.91, p = 0.016), and the time from ICU admission to initiation of cEEG (OR 1.001, 95% CI 1.0002–1.001, per hour, p = 0.005]. Significance Both presence of electrographic SE and time from ICU admission to cEEG initiation were independent factors associated with mortality in neonates and pediatric patients with cEEG in the ICU.

To evaluate the impact of epileptiform discharges (EDs) that do not occur within seizure patterns--such as spikes, sharp waves or spike waves--on cognitive function and to discuss the circumstances under which treatment of EDs might be considered. Methods used in this article is "Review of the literature". EDs may disrupt short-term cognition in humans. Frequent EDs for a prolonged period can potentially impair long-term cognitive function in humans. However, there is conflicting evidence on the impact of EDs on long-term cognitive outcome because this relationship may be confounded by multiple factors such as underlying etiology, seizures, and medication effects. Limitations of existing studies include the lack of standardized ED quantification methods and of widely accepted automated spike quantification methods. Although there is no solid evidence for or against treatment of EDs, a non-evidence-based practical approach is suggested. EDs in otherwise asymptomatic individuals should not be treated because the risks of treatment probably outweigh its dubious benefits. A treatment trial for EDs may be considered when there is cognitive dysfunction or regression or neurologic symptoms that are unexplained by the underlying etiology, comorbid conditions, or seizure severity. In patients with cognitive or neurologic dysfunction with epilepsy or EDs, treatment may be warranted to control the underlying epileptic syndrome. EDs may cause cognitive or neurologic dysfunction in humans in the short term. There is conflicting evidence on the impact of EDs on long-term cognitive outcome. There is no evidence for or against treatment of asymptomatic ED.

Summary Objectives To quantify the life expectancy of surgically eligible children with refractory epilepsy comparing two treatment strategies: medical treatment only versus epilepsy surgery. Methods Decision analysis model populated with available parameters from the literature. One- and two-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The time horizon was lifetime and the main outcome was life expectancy. Results Across the range of pediatric ages, epilepsy surgery yielded a higher life expectancy. For a cohort of 10-year-old children with refractory epilepsy, the gain in life expectancy with epilepsy surgery (compared to medical treatment only) was 5.9 years for temporal epilepsy and 5.6 years for extratemporal epilepsy. One- and two-way sensitivity analyses and second-order Monte Carlo simulations demonstrated the robustness of results across a wide variation of input parameters. There was no adjustment for quality of life, but we estimated the percentage of life expectancy spent in seizure freedom. For a cohort of 10-year-old patients with refractory epilepsy: (1) in temporal lobe epilepsy, epilepsy surgery yielded 48.9% of life expectancy years in seizure freedom while medical treatment yielded 14.3%; and (2) in extratemporal epilepsy, epilepsy surgery yielded 43.0% of life expectancy years in seizure freedom while medical treatment yielded 14.3%. Significance Epilepsy surgery yields a substantially higher life expectancy than continued medical treatment for surgically eligible children with refractory epilepsy. This conclusion remains robust across a wide range of parameter variations.

SummaryObjective To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Methods Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. Results The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: −$3.8/SS), intramuscular midazolam (ICER: −$64/SS), and rectal diazepam (ICER: −$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. Significance For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States. Rectal diazepam is not a cost-effective alternative, and this conclusion remains extremely robust to wide variations of the input parameters.

Summary Objective Current literature does not allow an evidence-based approach to the treatment of continuous spikes and waves during sleep (CSWS). The aim of this study was to describe treatment choices made by clinicians caring for patients with CSWS in North America. Methods A 24-question survey on treatment choices for CSWS was distributed to the members of the American Epilepsy Society (AES). The survey presented a clinical vignette of CSWS. The questions addressed treatment choices for that clinical scenario. Surveys were self-administered and collected using an online survey website (www.surveymonkey.com). Results Two-hundred thirty-two surveys were completed. Prominent sleep-potentiated spiking was considered to warrant treatment by 81% of respondents. The proportion of patients in whom cognitive improvement occurs when sleep-potentiated spiking is effectively treated is in >75% of patients (according to 16% of respondents), in 25–75% of patients (according to 52% of respondents), in

Summary 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 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.

Summary 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.

SUMMARY Purpose: To provide an estimate of the frequency of dacrystic seizures in video-electroencephalography (EEG) long-term monitoring units of tertiary referral epilepsy centers and to describe the clinical presentation of dacrystic seizures in relationship to the underlying etiology. Methods: We screened clinical records and video-EEG reports for the diagnosis of dacrystic seizures of all patients admitted for video-EEG long-term monitoring at five epilepsy referral centers in the United States and Germany. Patients with a potential diagnosis of dacrystic seizures were identified, and their clinical charts and video-EEG recordings were reviewed. We included only patients with: (1) stereotyped lacrimation, sobbing, grimacing, yelling, or sad facial expression; (2) long-term video-EEG recordings (at least 12 h); and (3) at least one brain magnetic resonance imaging (MRI) study. Key Findings: Nine patients (four female) with dacrystic seizures were identified. Dacrystic seizures were identified in 0.06–0.53% of the patients admitted for long-term video-EEG monitoring depending on the specific center. Considering our study population as a whole, the frequency was 0.13%. The presence of dacrystic seizures without other accompanying clinical features was found in only one patient. Gelastic seizures accompanied dacrystic seizures in five cases, and a hypothalamic hamartoma was found in all of these five patients. The underlying etiology in the four patients with dacrystic seizures without gelastic seizures was left mesial temporal sclerosis (three

Summary Purpose: Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS. Methods: We enrolled patients from our video-electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike-wave percentage (SWP) as the percentage of 1-s bins containing at least one spike-wave complex and (2) spike frequency (SF) as the number of spikes per 100 s. Key Findings: Nine children (six boys) met the inclusion criteria during a 15-year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4–7.7 years), and at seizure freedom 8.6 years (6.5–11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth-epilepsy onset median 2 years, range 2 days–4 years), prodromal stage (epilepsy onset-neuropsychological regression 3.9 years, range 0.9–7.7 years), acute stage (neuropsychological regression-seizure freedom 2.9 years, range 2.1–6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow-up (median 11.4 years, range 7.2–20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was 85%. Evolution of electroencephalographic patterns included increasing-decreasing, continuously elevated, and fluctuating patterns (33.3% each). There was good correlation between SWP and SF (Spearman correlation-coefficient = 0.942; p

Summary Objective Reports of studies evaluating rufinamide as an add-on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long-term follow-up period. Methods We retrospectively included patients taking rufinamide from November 2008 to March 2013. Response was defined by a seizure reduction of ≥50% compared to baseline. Results Three hundred patients with a median age of 9.1 years (range 0.4–29.6 years) were reviewed. Median follow-up was 9 months (range 1–37 months). Epilepsy etiology was classified as genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall, rufinamide treatment led to a median seizure frequency reduction of 59.2% from responders to baseline. Seizure reduction was greater in patients with genetic etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p = 0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of those due to both. Most common adverse effects were sleepiness, vomiting, mood changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6 months (range 3–28 months). Significance Rufinamide provides satisfactory seizure reduction as an adjunctive treatment in refractory epilepsy. Results need to be interpreted in the setting of data acquisition, including inherent biases of retrospective studies. Patients with a known genetic etiology may have better responses than patients with structural/metabolic etiology. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE).Multicenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury.Permanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control ("possible" or "likely" responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9 mg/kg/h, when ketamine was introduced at least 8 days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24 h of ketamine initiation (16% vs. 56%, p = 0.0047).Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.

Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS.We enrolled patients from our video-electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike-wave percentage (SWP) as the percentage of 1-s bins containing at least one spike-wave complex and (2) spike frequency (SF) as the number of spikes per 100 s.Nine children (six boys) met the inclusion criteria during a 15-year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4-7.7 years), and at seizure freedom 8.6 years (6.5-11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth-epilepsy onset median 2 years, range 2 days-4 years), prodromal stage (epilepsy onset-neuropsychological regression 3.9 years, range 0.9-7.7 years), acute stage (neuropsychological regression-seizure freedom 2.9 years, range 2.1-6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow-up (median 11.4 years, range 7.2-20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was85% in 13 (42%) of 31 assessments, and after seizure freedom, 3 of 5 patients (60%) had SWP85%. Evolution of electroencephalographic patterns included increasing-decreasing, continuously elevated, and fluctuating patterns (33.3% each). There was good correlation between SWP and SF (Spearman correlation-coefficient = 0.942; p0.0001). SF, which can exceed 100%, reflected changes in electroencephalography pattern in more detail than SWP, which cannot exceed 100% and therefore has a ceiling effect.Our series systematically studied the age of occurrence of the significant clinical events. These may assist in defining clinical stages, which can provide a useful framework for future clinical trials in patients with CSWS. The severity of the epileptiform discharges on EEG did not always correlate with seizure frequency and severity; epileptiform discharges could be prominent after seizure freedom and fluctuated along the course of the disease. The values of SWP and SF correlated well, but SWP based on 1-s bins has the potential disadvantage of a ceiling effect.