Resource manipulation reveals interactive phenotype-dependent foraging in free-ranging lizards.

Recent evidence suggests that individuals differ in foraging tactics and this variation is often linked to an individual's behavioural type (BT). Yet, while foraging typically comprises a series of search and handling steps, empirical investigations have rarely considered BT-dependent effects across multiple stages of the foraging process, particularly in natural settings. In our long-term sleepy lizard (Tiliqua rugosa) study system, individuals exhibit behavioural consistency in boldness (measured as an individual's willingness to approach a novel food item in the presence of a threat) and aggressiveness (measured as an individual's response to an 'attack' by a conspecific dummy). These BTs are only weakly correlated and have previously been shown to have interactive effects on lizard space use and movement, suggesting that they could also affect lizard foraging performance, particularly in their search behaviour for food. To investigate how lizards' BTs affect their foraging process in the wild, we supplemented food in 123 patches across a 120-ha study site with three food abundance treatments (high, low and no-food controls). Patches were replenished twice a week over the species' entire spring activity season and feeding behaviours were quantified with camera traps at these patches. We tracked lizards using GPS to determine their home range (HR) size and repeatedly assayed their aggressiveness and boldness in designated assays. We hypothesised that bolder lizards would be more efficient foragers while aggressive ones would be less attentive to the quality of foraging patches. We found an interactive BT effect on overall foraging performance. Individuals that were both bold and aggressive ate the highest number of food items from the foraging array. Further dissection of the foraging process showed that aggressive lizards in general ate the fewest food items in part because they visited foraging patches less regularly, and because they discriminated less between high and low-quality patches when revisiting them. Bolder lizards, in contrast, ate more tomatoes because they visited foraging patches more regularly, and ate a higher proportion of the available tomatoes at patches during visits. Our study demonstrates that BTs can interact to affect different search and handling components of the foraging process, leading to within-population variation in foraging success. Given that individual differences in foraging and movement will influence social and ecological interactions, our results highlight the potential role of BT's in shaping individual fitness strategies and population dynamics.

Proposed Pathway for the Utilization of Pediatric Ambulatory EEG.

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

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort).

PURPOSE: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). METHODS: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. RESULTS: We included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001). CONCLUSION: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Brain network properties of clinical versus subclinical seizures among critically ill children.

OBJECTIVE: Electrographic seizures are common among critically ill children, and have been associated with worse outcomes. Despite their often-widespread cortical representation, most of these seizures remain subclinical, a phenomenon which remains poorly understood. We compared the brain network properties of clinical versus subclinical seizures to gain insight into their relative potential deleterious effects. METHODS: Functional connectivity (phase lag index) and graph measures (global efficiency and clustering coefficients) were computed for 2178 electrographic seizures recorded during 48-hours of 19-channel continuous EEG monitoring obtained in 20 comatose children. Frequency-specific group differences in clinical versus subclinical seizures were analyzed using a non-parametric ANCOVA, adjusting for age, sex, medication exposure, treatment intensity and seizures per subject. RESULTS: Clinical seizures demonstrated greater functional connectivity than subclinical seizures at alpha frequencies, but less connectivity than subclinical seizures at delta frequencies. Clinical seizures also demonstrated significantly higher median global efficiency than subclinical seizures (p < 0.01), and significantly higher median clustering coefficients across all electrodes at alpha frequencies. CONCLUSIONS: Clinical expression of seizures correlates with greater alpha synchronization of distributed brain networks. SIGNIFICANCE: The stronger global and local alpha-mediated functional connectivity observed during clinical seizures may indicate greater pathological network recruitment. These observations motivate further studies to investigate whether the clinical expression of seizures may influence their potential to cause secondary brain injury.

Temporal Encephalocele: A Treatable Etiology of Drug-Resistant Pediatric Temporal Lobe Epilepsy.

BACKGROUND: Temporal lobe encephaloceles (TEs) are a rare cause of drug-resistant temporal lobe epilepsy (DR-TLE), with head trauma and obesity identified as risk factors in adults. This study evaluated the clinical characteristics of childhood-onset DR-TLE due to TE. METHODS: This is a single-institution retrospective review of childhood-onset DR-TLE with radiographic TE identified between 2008 and 2020. The epilepsy history, brain imaging features, and surgical outcomes were collected. RESULTS: Eleven children with DR-TLE due to TE were included (median age at epilepsy onset was 11 years, interquartile range 8.5 to 13.5 years). Median latency between epilepsy diagnosis and TE detection was 3 years (range of 0 to 13 years). None had history of head trauma. Body mass index greater than 85 percentile for age and sex was seen in 36% of the children. No patient had bilateral TE identified. TEs were diagnosed based on epilepsy surgery conference re-review of imaging in 36% of cases. All herniations were contained defects without osseous dehiscence. Regional fluorodeoxyglucose (FDG) hypometabolism ipsilateral to the encephalocele was seen in all children who had FDG-positron emission tomography (PET) of the brain. Of the children who had surgery, 70% were seizure free or had nondisabling seizures at last follow-up (mean follow-up 52 months). CONCLUSIONS: TE is a surgically remediable etiology of DR-TLE in childhood. TEs are often overlooked at pediatric epilepsy diagnosis, calling for the need to increase awareness of this entity. FDG-PET temporal hypometabolism in children with presumed nonlesional DR-TLE should be carefully examined for occult TEs.

Machine learning to support triage of children at risk for epileptic seizures in the pediatric intensive care unit.

Objective.Epileptic seizures are relatively common in critically-ill children admitted to the pediatric intensive care unit (PICU) and thus serve as an important target for identification and treatment. Most of these seizures have no discernible clinical manifestation but still have a significant impact on morbidity and mortality. Children that are deemed at risk for seizures within the PICU are monitored using continuous-electroencephalogram (cEEG). cEEG monitoring cost is considerable and as the number of available machines is always limited, clinicians need to resort to triaging patients according to perceived risk in order to allocate resources. This research aims to develop a computer aided tool to improve seizures risk assessment in critically-ill children, using an ubiquitously recorded signal in the PICU, namely the electrocardiogram (ECG).Approach.A novel data-driven model was developed at a patient-level approach, based on features extracted from the first hour of ECG recording and the clinical data of the patient.Main results.The most predictive features were the age of the patient, the brain injury as coma etiology and the QRS area. For patients without any prior clinical data, using one hour of ECG recording, the classification performance of the random forest classifier reached an area under the receiver operating characteristic curve (AUROC) score of 0.84. When combining ECG features with the patients clinical history, the AUROC reached 0.87.Significance.Taking a real clinical scenario, we estimated that our clinical decision support triage tool can improve the positive predictive value by more than 59% over the clinical standard.

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) incl. Febrile Infection-Related Epilepsy Syndrome (FIRES): Statements and Supporting Evidence.

OBJECTIVE: To develop consensus-based recommendations for the management of adult and paediatric patients with NORSE/FIRES based on best evidence and experience. METHODS: The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater or equal to 7, and inappropriate if the median score was less than or equal to 3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey. RESULTS: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article. SIGNIFICANCE: This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) including Febrile Infection-Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools.

OBJECTIVE: To develop consensus-based recommendations for the management of adult and pediatric patients with NORSE/FIRES based on best available evidence and expert opinion. METHODS: The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater than or equal to 7, and inappropriate if the median score was less than or equal to 3. RESULTS: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. These are summarized in this article along with two practical clinical flowsheets: one for diagnosis and evaluation and one for acute treatment. A corresponding evidence-based analysis of all 85 recommendations alongside responses by the Delphi panel is presented in a companion article. SIGNIFICANCE: The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

Sentinel Epileptiform Discharges Activating Two Seizure Networks on Intracranial EEG.

SUMMARY: Sentinel epileptiform discharges (SEDs) are epileptiform transients preceding the onset of a focal seizure seen on scalp EEG. Despite their potential localizing value, formal study of SED has been limited. The authors report a patient with MRI-negative focal-onset epilepsy whose seizures on scalp and intracranial EEG were always preceded by SED. Although the location and morphology of the SED was invariable, the seizures after the discharge were of two clearly distinct types, each with different semiology and region of spread on intracranial EEG. This suggests that the SED played a role in activating two distinct seizure networks. A right temporal lobectomy with amygdalohippocampectomy was performed. The resection included both the region of the SED as well as the seizure-onset zone of the more common seizure type, achieving seizure freedom at 3 years after surgery. Further research exploring whether the localization of SED is a reliable indicator of the seizure-onset zone could aid surgical planning in patients whose seizures are preceded by SED.

Personality, spatiotemporal ecological variation and resident/explorer movement syndromes in the sleepy lizard.

Individual variation in movement is profoundly important for fitness and offers key insights into the spatial and temporal dynamics of populations and communities. Nonetheless, individual variation in fine-scale movement behaviours is rarely examined even though animal tracking devices offer the long-term, high-resolution, repeatable data in natural conditions that are ideal for studying this variation. Furthermore, of the few studies that consider individual variation in movement, even fewer also consider the internal traits and environmental factors that drive movement behaviour which are necessary for contextualising individual differences in movement patterns. In this study, we GPS tracked a free-ranging population of sleepy lizards Tiliqua rugosa, each Austral spring over 5 years to examine consistent among-individual variation in movement patterns, as well as how these differences were mediated by key internal and ecological factors. We found that individuals consistently differed in a suite of weekly movement traits, and that these traits strongly covaried among-individuals, forming movement syndromes. Lizards fell on a primary movement continuum, from 'residents' that spent extended periods of time residing within smaller core areas of their home range, to 'explorers' that moved greater distances and explored vaster areas of the environment. Importantly, we also found that these consistent differences in lizard movement were related to two ecologically important animal personality traits (boldness and aggression), their sex, key features of the environment (including food availability, and a key water resource), habitat type and seasonal variation (cool/moist vs. hot/drier) in environmental conditions. Broadly, these movement specialisations likely reflect variation in life-history tactics including foraging and mating tactics that ultimately underlie key differences in space use. Such information can be used to connect phenotypic population structure to key ecological and evolutionary processes, for example social networks and disease-transmission pathways, further highlighting the value of examining individual variation in movement behaviour.

Early life experience influences dispersal in coyotes (Canis latrans).

Natal dispersal plays an important role in connecting individual animal behavior with ecological processes at all levels of biological organization. As urban environments are rapidly increasing in extent and intensity, understanding how urbanization influences these long distance movements is critical for predicting the persistence of species and communities. There is considerable variation in the movement responses of individuals within a species, some of which is attributed to behavioral plasticity which interacts with experience to produce interindividual differences in behavior. For natal dispersers, much of this experience occurs in the natal home range. Using data collected from VHF collared coyotes (Canis latrans) in the Chicago Metropolitan Area we explored the relationship between early life experience with urbanization and departure, transience, and settlement behavior. Additionally, we looked at how early life experience with urbanization influenced survival to adulthood and the likelihood of experiencing a vehicle related mortality. We found that coyotes with more developed habitat in their natal home range were more likely to disperse and tended to disperse farther than individuals with more natural habitat in their natal home range. Interestingly, our analysis produced mixed results for the relationship between natal habitat and habitat selection during settlement. Finally, we found no evidence that early life experience with urbanization influenced survival to adulthood or the likelihood of experiencing vehicular mortality. Our study provides evidence that early life exposure influences dispersal behavior; however, it remains unclear how these differences ultimately affect fitness.

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.

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.

Telehealth for Children With Epilepsy Is Effective and Reduces Anxiety Independent of Healthcare Setting.

Objectives: The use of telemedicine has grown exponentially as an alternative to providing care to patients with epilepsy during the pandemic. We investigated the impact of the current pandemic among children with epilepsy from two distinct pediatric epilepsy centers. We also compared perceptions among those who received telemedicine against those who did not. Methods: We developed a questionnaire and invited families followed in Freiburg, Germany, and Calgary, Alberta, Canada, to participate during the initial 9 months of the pandemic. The survey contained 32 questions, 10 of which were stratified according to telemedicine exposure. Results: One hundred twenty-six families (80 in Freiburg, 46 in Calgary) participated, and 40.3% received telemedicine care. Most children (mean age 10.4 years, SD 5.1) had chronic epilepsy but poorly controlled seizures. Negative impacts were reported by 36 and 65% of families who had to reschedule appointments for visits and diagnostics, respectively. Nearly two-thirds of families reported no change in seizure frequency, while 18.2% reported either worsening or improvement of seizures. Although most families did not note behavioral changes, 28.2% reported behavior worsening. Families who received telemedicine care had a statistically significant reduction of parental self-reported anxiety level after virtual visits compared to those who did not experience telemedicine. Families with telemedicine consultations were more likely to consider future virtual care (84 vs. 65.2% of those without), even after the pandemic. Patient data safety, easy access to specialized services, and consistency with the same healthcare provider were graded as important in both centers, while a shorter waiting time was most relevant in Calgary. Conclusion: In our cohort, some children with epilepsy experienced increased seizures and worsening behavior during the first 9 months of the current pandemic. In addition, our data suggest that telemedicine might reduce parental anxiety symptoms, and families who experienced telehealth were more positive and open to similar appointments in the future.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

OBJECTIVES: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN: Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING: Seventeen academic hospitals in the United States. PATIENTS: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

Time to Treatment in Pediatric Convulsive Refractory Status Epilepticus: The Weekend Effect.

BACKGROUND: Time to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency. METHODS: We performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus. RESULTS: We included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01). CONCLUSIONS: The time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.