Hospital variation of outcomes in status epilepticus.

OBJECTIVE: Understanding factors driving variation in status epilepticus outcomes would be critical to improve care. We evaluated the degree to which patient and hospital characteristics explained hospital-to-hospital variability in intubation and postacute outcomes. METHODS: This was a retrospective cohort study of Medicare beneficiaries admitted with status epilepticus between 2009 and 2019. Outcomes included intubation, discharge to a facility, and 30- and 90-day readmissions and mortality. Multilevel models calculated percent variation in each outcome due to hospital-to-hospital differences. RESULTS: We included 29 150 beneficiaries. The median age was 68 years (interquartile range [IQR] = 57-78), and 18 084 (62%) were eligible for Medicare due to disability. The median (IQR) percentages of each outcome across hospitals were: 30-day mortality 25% (0%-38%), any 30-day readmission 14% (0%-25%), 30-day status epilepticus readmission 0% (0%-3%), 30-day facility stay 40% (25%-53%), and intubation 46% (20%-61%). However, after accounting for many hospitals with small sample size, hospital-to-hospital differences accounted for 2%-6% of variation in all unadjusted outcomes, and approximately 1%-5% (maximally 8% for 30-day readmission for status epilepticus) after adjusting for patient, hospitalization, and/or hospital characteristics. Although many characteristics significantly predicted outcomes, the largest effect size was cardiac arrest predicting death (odds ratio = 10.1, 95% confidence interval = 8.8-11.7), whereas hospital characteristics (e.g., staffing, accreditation, volume, setting, services) all had lesser effects. SIGNIFICANCE: Hospital-to-hospital variation explained little variation in studied outcomes. Rather, certain patient characteristics (e.g., cardiac arrest) had greater effects. Interventions to improve outcomes after status epilepticus may be better focused on individual or prehospital factors, rather than at the inpatient systems level.

Health care disparities in morbidity and mortality in adults with acute and remote status epilepticus: A national study.

OBJECTIVE: Although disparities have been described in epilepsy care, their contribution to status epilepticus (SE) and associated outcomes remains understudied. METHODS: We used the 2010-2019 National Inpatient Sample to identify SE hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM codes. SE prevalence was stratified by demographics. Logistic regression was used to assess factors associated with electroencephalographic (EEG) monitoring, intubation, tracheostomy, gastrostomy, and mortality. RESULTS: There were 486 861 SE hospitalizations (2010-2019), primarily at urban teaching hospitals (71.3%). SE prevalence per 10 000 admissions was 27.3 for non-Hispanic (NH)-Blacks, 16.1 for NH-Others, 15.8 for Hispanics, and 13.7 for NH-Whites (p < .01). SE prevalence was higher in the lowest (18.7) compared to highest income quartile (18.7 vs. 14, p < .01). Older age was associated with intubation, tracheostomy, gastrostomy, and in-hospital mortality. Those ≥80 years old had the highest odds of intubation (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.43-1.58), tracheostomy (OR = 2, 95% CI = 1.75-2.27), gastrostomy (OR = 3.37, 95% CI = 2.97-3.83), and in-hospital mortality (OR = 6.51, 95% CI = 5.95-7.13). Minority populations (NH-Black, NH-Other, and Hispanic) had higher odds of tracheostomy and gastrostomy compared to NH-White populations. NH-Black people had the highest odds of tracheostomy (OR = 1.7, 95% CI = 1.57-1.86) and gastrostomy (OR = 1.78, 95% CI = 1.65-1.92). The odds of receiving EEG monitoring rose progressively with higher income quartile (OR = 1.47, 95% CI = 1.34-1.62 for the highest income quartile) and was higher for those in urban teaching compared to rural hospitals (OR = 12.72, 95% CI = 8.92-18.14). Odds of mortality were lower (compared to NH-Whites) in NH-Blacks (OR = .71, 95% CI = .67-.75), Hispanics (OR = .82, 95% CI = .76-.89), and those in the highest income quartiles (OR = .9, 95% CI = .84-.97). SIGNIFICANCE: Disparities exist in SE prevalence, tracheostomy, and gastrostomy utilization across age, race/ethnicity, and income. Older age and lower income are also associated with mortality. Access to EEG monitoring is modulated by income and urban teaching hospital status. Older adults, racial/ethnic minorities, and populations of lower income or rural location may represent vulnerable populations meriting increased attention to improve health outcomes and reduce disparities.

Status epilepticus in Auckland, New Zealand: Treatment patterns and determinants of outcome in a prospective population-based cohort.

OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE). METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously. RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups. SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

Health care utilization and mortality for people with epilepsy during COVID-19: A population study.

OBJECTIVE: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic. METHODS: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs). RESULTS: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15). SIGNIFICANCE: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research.

α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Plasticity Sustains Severe, Fatal Status Epilepticus.

OBJECTIVE: Generalized convulsive status epilepticus is associated with high mortality. We tested whether α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor plasticity plays a role in sustaining seizures, seizure generalization, and mortality observed during focal onset status epilepticus. We also determined whether modified AMPA receptors generated during status epilepticus could be targeted with a drug. METHODS: Electrically induced status epilepticus was characterized by electroencephalogram and behavior in GluA1 knockout mice and in transgenic mice with selective knockdown of the GluA1 subunit in hippocampal principal neurons. Excitatory and inhibitory synaptic transmission in CA1 neurons was studied using patch clamp electrophysiology. The dose response of N,N,H,-trimethyl-5-([tricyclo(3.3.1.13,7)dec-1-ylmethyl]amino)-1-pentanaminiumbromide hydrobromide (IEM-1460), a calcium-permeable AMPA receptor antagonist, was determined. RESULTS: Global removal of the GluA1 subunit did not affect seizure susceptibility; however, it reduced susceptibility to status epilepticus. GluA1 subunit knockout also reduced mortality, severity, and duration of status epilepticus. Absence of the GluA1 subunit prevented enhancement of glutamatergic synaptic transmission associated with status epilepticus; however, γ-aminobutyric acidergic synaptic inhibition was compromised. Selective removal of the GluA1 subunit from hippocampal principal neurons also reduced mortality, severity, and duration of status epilepticus. IEM-1460 rapidly terminated status epilepticus in a dose-dependent manner. INTERPRETATION: AMPA receptor plasticity mediated by the GluA1 subunit plays a critical role in sustaining and amplifying seizure activity and contributes to mortality. Calcium-permeable AMPA receptors modified during status epilepticus can be inhibited to terminate status epilepticus. ANN NEUROL 2020;87:84-96.

Diazepam Monotherapy or Diazepam-Ketamine Dual Therapy at Different Time Points Terminates Seizures and Reduces Mortality in a Status Epilepticus Animal Model.

BACKGROUND Being refractory to drugs remains an urgent treatment problem in status epilepticus (SE). The fact that γ-aminobutyric acid A receptors (GABAARs) become internalized and inactive, N-methyl-D-aspartate receptors (NMDARs) become externalized and active during SE may explain the refractoriness to benzodiazepine. However, the real-time dynamic efficacy of antiepileptic drugs remains unclear. Therefore, we propose a hypothesis that diazepam monotherapy or diazepam-ketamine dual therapy could terminate seizures and reduce mortality in the SE model at different time points during ongoing SE. MATERIAL AND METHODS An SE model was established in adult Sprague-Dawley rats with lithium and pilocarpine. The GABAAR agonist diazepam was injected at 5, 10, 20, or 30 min when SE continued. In addition, diazepam and the NMDAR antagonist ketamine were injected at 10 to 60 min at 6 different time points. We measured seizure-free rates, seizure duration, degree of behavioral seizure, and mortality. RESULTS Diazepam monotherapy at 5 min and 10 min from the beginning of SE was able to terminate seizures and improved survival rates. Diazepam-ketamine dual therapy at 10 min, 20 min, and 30 min from the beginning of SE terminated seizures and achieved high survival rates. CONCLUSIONS In this parallel randomized controlled trial with a rat model, we found that diazepam monotherapy was an effective antiepileptic strategy at the early stage of SE less than 10 min after SE onset. If SE lasts more than 10 min but less than 30 min, the diazepam-ketamine dual therapy strategy may be an appropriate choice.

Development of a novel outcome prediction score (PEDSS) for pediatric convulsive status epilepticus: A longitudinal observational study.

OBJECTIVE: The objectives of this study were to evaluate ENDIT score and develop a novel outcome prediction score for outcome of pediatric convulsive status epilepticus (CSE) at the hospital and 3 months postdischarge. METHODS: Children and adolescents aged 1 month to 14 years, presenting with CSE to a tertiary care teaching center in North India from January 2017 to March 2019, were screened for enrollment. In-hospital and 3-month postdischarge outcome were defined as poor if Pediatric Cerebral Performance Category Scale (PCPCS) score dropped by ≥2 levels. RESULTS: Overall, 61 patients were enrolled for final analysis after applying exclusion and inclusion criteria. The area under the receiver operating characteristic (ROC) curve for ENDIT score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge was 0.74 (95% confidence interval [CI] = 0.58-0.89), 0.7 (95% CI = 0.57-0.83), and 0.72 (95% CI = 0.6-0.82), respectively. Based on predictors in the present cohort that were significantly different between good and poor outcome cases at the hospital and 3 months postdischarge, a new six-point score named PEDSS (pre-status epilepticus PCPCS, background electroencephalographic abnormalities, drug refractoriness, semiology, and critical sickness) was developed. The area under ROC curves for PEDSS score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge were 0.93 (95% CI = 0.87-0.99), 0.8 (95% CI = 0.7-0.9), and 0.89 (95% CI = 0.8-0.96), respectively. The best cutoff PEDSS scores for predicting mortality and poor outcome at the hospital and at 3 months postdischarge were ≥4, ≥3, and ≥3, respectively. SIGNIFICANCE: The PEDSS score has high predictive accuracy for mortality and differentiating good from poor outcome at the hospital and 3 months postdischarge in pediatric CSE. Future studies should be planned to validate it in various geographical and health care settings and in adults.

Admission patterns and survival from status epilepticus in critical care in the UK: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

BACKGROUND AND PURPOSE: Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. METHODS: The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro-CCU (NCCU), general CCU with 24-h neurological support (GCCU-N) or general CCU with limited neurological support (GCCU-L). RESULTS: There were 35 595 CCU cases of SE with a 3-fold increase over time (4739 in 2001-2004 to 14 166 in 2013-2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001-2004 to 4.4% in 2013-2016 compared to 5.1% and 4.1% for GCCU-L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU-L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. CONCLUSIONS: The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease.

Fatality From Status Epilepticus After Myelography.

OBJECTIVE. Myelography is a commonly used procedure to evaluate the spinal canal. However, the procedure is not without risk, chiefly risk of seizure after intrathecal administration of iodinated contrast material. CONCLUSION. The risk of seizure remains an important concern for radiologists, who should strongly consider practice parameter guidelines that address this risk.

Factors affecting mortality of refractory status epilepticus.

OBJECTIVE: The aim of this study was to determine the factors affecting the mortality of refractory status epilepticus (RSE) in comparison with non-refractory status epilepticus (non-RSE). MATERIAL-METHOD: Included in this retrospective study were 109 status epilepticus cases who were hospitalized in the neurological intensive care unit Katip Celebi University. Fifty-two were RSE and 57 were non-RSE. All clinical data were gathered from the hospital archives. Factors which may cause mortality were categorized for statistical analysis. RESULTS: While elderly age, continuous clinical seizure activity, absence of former seizure, infection, prolonged stay of ICU, anesthesia, and cardiac comorbidity were significantly related to mortality in the RSE subgroup, potentially fatal accompanying diseases were significantly related to mortality in the non-RSE subgroup. No significant relationship was found between mortality and refractoriness. Multivariate analysis revealed that a Glasgow Coma Score (GCS) at presentation of 8 or lower was the independent predictor of mortality both in the general SE population (P = .017) and in the RSE subgroup (P = .007). Intubation (P = .011) and hypotension (P = .011) were the other independent predictors of mortality in the general SE population. No independent predictor of mortality was detected in the non-RSE subgroup. DISCUSSION/CONCLUSION: Intubation, hypotension, and a low GCS at presentation could be the main factors which could alert clinicians of an increased risk of mortality in SE patients. Although non-RSE and RSE had similar rates of mortality in the ICU, the mortality-related factors of SE vary in the RSE and the non-RSE subgroups.

Improving the ability to predict hospital mortality among adults by combining two status epilepticus outcome scoring tools.

OBJECTIVE: The goal of this study was to compare the predictive ability of the Status Epilepticus Severity Score (STESS), the Encephalitis-nonconvulsive status epilepticus (NCSE)-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT), and the combination of these two scoring tools to predict mortality among inhospital patients with status epilepticus (SE). METHODS: A retrospective analysis was conducted of adult patients with SE who were admitted to the neurology department, the emergency department, and the intensive care unit from January 2013 to December 2017. The patients were divided into two groups: survivors and nonsurvivors. The STESS data were obtained when the patient arrived at the hospital, and the END-IT data were collected 24 h after patients were initially treated in the hospital. The ability of the scoring tools to predict death in patients with SE, alone or in combination, was evaluated. RESULTS: A total of 123 patients with SE were included in the study, of which 22 died, for a mortality rate of 17.9%. The STESS and END-IT scores of nonsurvivors were both significantly higher than those of survivors (median STESS 4 vs. 2, p = 0.003; median END-IT 3 vs. 1, p < 0.001). The area under the receiver operating characteristic curve (AUC) was 0.698 for the STESS and 0.852 for the END-IT, and the cutoff values were 4 and 3, respectively. The AUC of the END-IT with the optimal cutoff value was larger than that of the STESS (p = 0.024). The sensitivity and specificity of combining the STESS and END-IT by the serial method (STESS ≥ 4∩END-IT ≥ 3) were 0.50 and 0.95, respectively, and the specificity was significantly higher than the STESS or END-IT (both p's < 0.001). The sensitivity and specificity of combining the STESS and END-IT by the parallel method (STESS ≥ 4⋃END-IT ≥ 3) were 0.91 and 0.53, respectively, and the sensitivity was higher than the STESS was (p = 0.016). CONCLUSION: Our results indicated that the combined score of the STESS and END-IT systems was a better predictor of survival of patients with SE than the scores of either the STESS system or the END-IT system alone and that combining the scores may be considered to be a new method for early identification of patients for both good and bad outcomes.

External validation of STESS and EMSE as outcome prediction scores in an Egyptian cohort with status epilepticus.

PURPOSE: There is a lack of data concerning the performance of the outcome prediction scores in patients with status epilepticus (SE) in developing countries. The aim of this study was to compare the predictive performances of the status epilepticus severity score (STESS) and the epidemiology-based mortality score in status epilepticus (EMSE) and adaptation of such scoring system to be compatible with the nature of society. METHOD: This is a prospective study, conducted in Egypt from the period of January 2017 to June 2018. The main outcome measure was survival versus death, on hospital discharge. The cutoff point with the best sensitivity and specificity to predict mortality was determined through a receiver operating characteristic (ROC) curve. RESULTS: Among the 144 patients with SE with a mean age of 39.3 ±â€¯19.5 years recruited into the study, 38 patients (26.3%) died in the hospital with the survival of 99 patients while 7 patients (4.9%) were referred to other centers with an unknown outcome. Although EMSE had a bit larger area under the curve (AUC) (0.846) than STESS-3 (AUC 0.824), STESS-3 had the best performance as in-hospital death prediction score as it has a higher negative predictive value (94.6%) than that of EMSE (90.9%) in order not to miss high-risk patients. CONCLUSION: In the Egyptian population, STESS and EMSE are useful tools in predicting mortality outcome of SE. The STESS performed significantly better than EMSEE combinations as a mortality prediction score.

Tumor-associated status epilepticus: A prospective cohort in a tertiary hospital.

INTRODUCTION: Tumor-associated status epilepticus (TASE) follows a relatively benign course compared with SE in the general population. Little, however, is known about associated prognostic factors. METHODS: We conducted a prospective, observational study of all cases of TASE treated at a tertiary hospital in Barcelona, Spain between May 2011 and May 2019. We collected data on tumor and SE characteristics and baseline functional status and analyzed associations with outcomes at discharge and 1-year follow-up. RESULTS: Eighty-two patients were studied; 58.5% (n = 48) had an aggressive tumor (glioblastoma or brain metastasis). Fifty-one patients (62.2%) had a favorable outcome at discharge compared with just 30 patients (25.8%) at 1-year follow-up. Fourteen patients (17.1%) died during hospitalization. Lateralized period discharges (LPDs) on the baseline electroencephalography (EEG), presence of metastasis, and SE severity were significantly associated with a worse outcome at discharge. The independent predictors of poor prognosis at 1-year follow-up were SE duration of at least 21 h, an aggressive brain tumor, and a nonsurgical treatment before SE onset. Lateralized period discharges, super-refractory SE, and an aggressive tumor type were independently associated with increased mortality. CONCLUSIONS: Status epilepticus duration is the main modifiable factor associated with poor prognosis at 1-year follow-up. Accordingly, patients with TASE, like those with SE of any etiology, should receive early, aggressive treatment.

New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes.

OBJECTIVES: To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. DESIGN: A single-center retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients' characteristics, and treatments. CONCLUSIONS: In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

BACKGROUND: Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. METHODS: In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. RESULTS: A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. CONCLUSIONS: In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

The Clinical Spectrum of New-Onset Status Epilepticus.

OBJECTIVES: There is a paucity of data on patients with new-onset status epilepticus in patients without a prior history of epilepsy; we aimed to describe clinical characteristics and assess variables predictive of outcomes. DESIGN: Retrospective cohort. SETTING: Quaternary academic medical center. PATIENTS: Adult patients with new-onset status epilepticus. METHODS: Retrospective review of adults with new-onset status epilepticus admitted to Mayo Clinic, Rochester MN between January 1, 1990, and December 31, 2015, was performed. Patient demographics, status epilepticus etiology, Status Epilepticus Severity Score, and status epilepticus classification per the Status Epilepticus Severity Score were recorded. Six-month mortality and functional outcomes defined as modified Rankin scale (≥3 at last follow-up was considered poor) were primary outcomes. Refractory status epilepticus was a secondary outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred seventy-seven patients were included. Status epilepticus was convulsive in 124 (70.1%) and nonconvulsive in 53 (29.9%); 96 cases (54.2%) were refractory status epilepticus. Mean age at onset was 63 ± 18 years; 52.5% were greater than or equal to 65 years. Etiologies were acute in 50.8%, progressive in 18.1%, remote in 19.2%, and unknown in 11.9% patients. Six-month mortality was 32.2%, and 70.1% had poor modified Rankin scale at mean follow-up 3.1 ± 3.5 years. Age greater than or equal to 65 was a significant predictor of poor functional outcome and 6-month mortality. Loss of consciousness, status epilepticus classification, or age greater than or equal to 65 did not predict progression to refractory status epilepticus. Progression to refractory status epilepticus did not impact functional outcome or mortality at last follow-up. CONCLUSIONS: Poor outcomes in new-onset status epilepticus were associated with older age as well as predominantly progressive or remote symptomatic disease. Further prospective investigations assessing the course and outcomes of these patients would be useful in management and prognostication.

Causes of Death in Status Epilepticus.

OBJECTIVES: To determine the causes of death in patients with status epilepticus. To analyze the relative contributions of seizure etiology, seizure refractoriness, use of mechanical ventilation, anesthetic drugs for seizure control, and medical complications to in-hospital and 90-day mortality, hospital length of stay, and discharge disposition. DESIGN: Retrospective cohort. SETTING: Single-center neuroscience ICU. PARTICIPANTS: Patients with status epilepticus were identified by retrospective search of electronic database from January 1, 2011, to December 31, 2016. INTERVENTIONS: Review of electronic medical records. MEASUREMENTS AND MAIN RESULTS: Demographics, clinical characteristics, treatments, and outcomes were collected. Univariable and multivariable logistic regression analysis were used to determine whether the use of anesthetic drugs, mechanical ventilation, Status Epilepticus Severity Score, refractoriness of seizures, etiology of seizures, or medical complications were associated with in-hospital, 90-day mortality or discharge disposition. Among 244 patients with status epilepticus (mean age was 64 yr [interquartile range, 42-76], 55% male, median Status Epilepticus Severity Score 3 [interquartile range, 2-4]), 24 received anesthetic drug infusions for seizure control. In-hospital and 90-day mortality rates were 9.2% and 19.2%, respectively. Death was preceded by withdrawal of life-sustaining treatment in 19 patients (86.3%) and cardiac arrest in three (13.7%). Only Status Epilepticus Severity Score was associated with in-hospital and 90-day mortality, whereas the use of anesthetic drugs for seizure control, mechanical ventilation, medical complications, etiology, and refractoriness of seizures were not. Hospital length of stay was longer in patients with medical complications (p = 0.0091), refractory seizures (p = 0.0077), and in those who required anesthetic drugs for seizure control (p = 0.0035). Patients who had refractory seizures were less likely to be discharged home (odds ratio, 0.295; CI, 0.143-0.608; p = 0.0009). CONCLUSIONS: In this cohort, death primarily resulted from the underlying neurologic disease and withdrawal of life-sustaining treatment and not from our treatment choices. Use of anesthetic drugs, medical complications, and mechanical ventilation were not associated with in-hospital and 90-day mortality.

High long-term mortality after incident status epilepticus in adults: Results from a population-based study.

OBJECTIVE: To determine annual incidence, etiology, severity, and short- and long-term mortality of first-time, nonanoxic status epilepticus (SE) in adults in a population-based retrospective cohort study. METHODS: We systematically identified all episodes of SE in the year 2014 on the island of Funen. Patients with SE due to anoxia, patients with recurrent SE, and patients <18 years old were excluded. Nonconvulsive SE in coma was diagnosed according to the Salzburg criteria. Etiology, semiology, modified Rankin Scale (mRS) at discharge, survival, and the Status Epilepticus Severity Score were retrospectively determined from patients' records. Patients with first-time nonanoxic SE diagnosed during 2008-2013 from our database (n = 88) were used to confirm the results. RESULTS: The incidence of first-time, nonanoxic SE in 2014 was 10.7/100 000 persons at risk (n = 41). Median Status Epilepticus Severity Score was 3; in-hospital mortality was 24.4%. After median follow-up of 39.2 months, 53.7% of the patients had died (age- and gender-adjusted mortality rate of 5.2/100 000). Mortality stabilized 2 years after diagnosis. Analysis of the cohort from 2008-2013 confirmed stabilization of survival after 2-3 years and the high mortality 2 years after discharge. When correcting for acute symptomatic causes, the in-hospital mortality was 16.7% and 46.7% at follow-up (crude mortality rate of nonhypoxic and nonacute symptomatic SE = 3.5/100 000). An exploratory multivariate analysis of pooled patients with SE from 2008 to 2014 revealed mRS ≥ 2 at discharge as a prognostic factor for long-term mortality. SIGNIFICANCE: In this cohort, the overall mortality of first-time nonhypoxic SE was >50%. Mortality of SE after discharge was substantially higher than in-house mortality and stabilized after 2 years. The degree of disability as indicated by mRS at discharge was associated with long-term mortality after discharge.

Status epilepticus in Auckland, New Zealand: Incidence, etiology, and outcomes.

OBJECTIVE: To determine the incidence, etiology, and outcome of status epilepticus (SE) in Auckland, New Zealand, using the latest International League Against Epilepsy (ILAE) SE semiological classification. METHODS: We prospectively identified patients presenting to the public or major private hospitals in Auckland (population = 1.61 million) between April 6, 2015 and April 5, 2016 with a seizure lasting 10 minutes or longer, with retrospective review to confirm completeness of data capture. Information was recorded in the EpiNet database. RESULTS: A total of 477 episodes of SE occurred in 367 patients. Fifty-one percent of patients were aged <15 years. SE with prominent motor symptoms comprised 81% of episodes (387/477). Eighty-four episodes (18%) were nonconvulsive SE. Four hundred fifty episodes occurred in 345 patients who were resident in Auckland. The age-adjusted incidence of 10-minute SE episodes and patients was 29.25 (95% confidence interval [CI] = 27.34-31.27) and 22.22 (95% CI = 20.57-23.99)/100 000/year, respectively. SE lasted 30 minutes or longer in 250 (56%) episodes; age-adjusted incidence was 15.95 (95% CI = 14.56-17.45) SE episodes/100 000/year and 12.92 (95% CI = 11.67-14.27) patients/100 000/year. Age-adjusted incidence (10-minute SE) was 25.54 (95% CI = 23.06-28.24) patients/100 000/year for males and 19.07 (95% CI = 16.91-21.46) patients/100 000/year for females. The age-adjusted incidence of 10-minute SE was higher in Maori (29.31 [95% CI = 23.52-37.14]/100 000/year) and Pacific Islanders (26.55 [95% CI = 22.05-31.99]/100 000/year) than in patients of European (19.13 [95% CI = 17.09-21.37]/100 000/year) or Asian/other descent (17.76 [95% CI = 14.73-21.38]/100 000/year). Seventeen of 367 patients in the study died within 30 days of the episode of SE; 30-day mortality was 4.6%. SIGNIFICANCE: In this population-based study, incidence and mortality of SE in Auckland lie in the lower range when compared to North America and Europe. For pragmatic reasons, we only included convulsive SE if episodes lasted 10 minutes or longer, although the 2015 ILAE SE classification was otherwise practical and easy to use.

One- to 10-year Status Epilepticus Mortality (SEM) score after 30 days of hospital discharge: development and validation using competing risks analysis.

BACKGROUND: Status epilepticus (SE) is an emergency neurological disorder that affects quality of life and is associated with high mortality risk. Three scores have been developed to predict the risk of in-hospital death, but these scores are poor discrimination of mortality after discharge. This study aimed to develop and validate a simple risk score for long-term mortality in SE patients. METHODS: This retrospective cohort study was conducted using SE patient data collected from Thailand's Universal Coverage Scheme database between the fiscal years of 2005 and 2015 and followed-up to 2016. Patients who died in hospital or within 30 days after discharge were excluded. Data were divided at random into either a derivation or validation set. A proportional hazards model for the sub-distribution of competing risks was fitted with backward stepwise method. The coefficients from the model were used to develop a point-based scoring system. The discrimination ability of the model was evaluated using a time-dependent receiver operating characteristic (ROC) curve. RESULTS: A total of 20,792 SE patients (with ages ranging from the first day of life to 99 years at first admission) were randomly separated into two groups: 13,910 in the development group and 6882 in the validation group. A sub-distribution hazard model was used to determine nine predictors to be included in the final model, which was, in turn, used to develop the scoring system: age (0-19 points), male (two points), brain tumor (12 points), stroke (three points), cancer (11 points), diabetes (three points), chronic kidney disease (five points), pneumonia (five points), and urinary tract infection (four points). The possible total score ranged from zero to 64 and the cumulative incidence function was used to determine the probability of mortality associated with each total score within the first 10 years after the first admission. The area under the ROC curve (AUC) of the first to last time point ranged from 0.760 to 0.738. CONCLUSION: A nine-factor risk score for predicting 10-year mortality in SE patients was developed. Further studies should focus on external validity and including a range seizure types and duration of seizure as the predictors.