Regional determinants for outcome and cost of status epilepticus.

OBJECTIVE: Status epilepticus (SE) requires informed management. Since regional differences exist in practice and outcome, we aimed to characterize the epidemiology of SE and identify the factors associated with cost-effective management at the sole level IV epilepsy center of Central New York (CNY). METHODS: We searched for patients aged 18 years or older admitted at our center's hospitals from February 2018 to November 2019 with the discharge diagnosis of SE. Seventy-seven individuals with definite SE were included. We constructed models to determine the main factors that impact the refractoriness of SE, the clinical outcome, and the estimated cost of hospitalization. RESULTS: The rate of SE-related disability was 20.8% and the all-cause mortality 36.4%. Our analysis showed that initial anti-seizure medication (ASM) choice did not have a significant influence on the clinical outcome; nor did it affect the refractoriness of SE. Likewise, our anesthetic regimen did not alter the disease course or outcome. In line with prior studies, we demonstrated that age carried a negative predictive value to the SE-related disability and mortality (CI95% [-0.02, 0], p < 0.001). Interestingly, we found that use of midazolam (CI95% [-20.8, -0.08], p = 0.05) and anoxic brain injury as the underlying etiology (CI95% [-33.5, -1.59], p = 0.03) were marginally associated with shorter hospitalizations and reduced cost. The latter might reflect the rapidly-deteriorating course of anoxic brain injury, complicated by its higher likelihood of refractoriness (CI95% [0.14, 0.79], p = 0.006), and consequently, the decision to withdraw care. CONCLUSION: Taken together, we described the demographics, management, and prognosis of SE locally and further defined the potential determinants for the cost-effective care. We found that similar to other studies, age was the main determinant factor in prognosis. We also noticed that midazolam usage was associated with shorter hospital stay, suggesting that strategic use of midazolam may reduce the direct cost of management of SE. These findings can be adopted to optimize SE management in CNY.

A Simulation-Based Assessment of Levetiracetam Concentrations Following Fixed and Weight-Based Loading Doses: A Meta-Regression and Pharmacokinetic Modeling Analysis.

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight-based loading doses of LEV with respect to established therapeutic target concentrations. Meta-regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight-based dosing) to achieve maximum (Cpeak) and 12-h (C12h) plasma concentrations that exceed 12 mg/L. The meta-regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight-based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight-based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication.

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

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.

Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium-pilocarpine rat model.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma ß-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late-i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

Economic review of point-of-care EEG.

Aims: Point-of-care electroencephalogram (POC-EEG) is an acute care bedside screening tool for the identification of nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE). The objective of this narrative review is to describe the economic themes related to POC-EEG in the United States (US).Materials and methods: We examined peer-reviewed, published manuscripts on the economic findings of POC-EEG for bedside use in US hospitals, which included those found through targeted searches on PubMed and Google Scholar. Conference abstracts, gray literature offerings, frank advertisements, white papers, and studies conducted outside the US were excluded.Results: Twelve manuscripts were identified and reviewed; results were then grouped into four categories of economic evidence. First, POC-EEG usage was associated with clinical management amendments and antiseizure medication reductions. Second, POC-EEG was correlated with fewer unnecessary transfers to other facilities for monitoring and reduced hospital length of stay (LOS). Third, when identifying NCS or NCSE onsite, POC-EEG was associated with greater reimbursement in Medical Severity-Diagnosis Related Group coding. Fourth, POC-EEG may lower labor costs via decreasing after-hours requests to EEG technologists for conventional EEG (convEEG).Limitations: We conducted a narrative review, not a systematic review. The studies were observational and utilized one rapid circumferential headband system, which limited generalizability of the findings and indicated publication bias. Some sample sizes were small and hospital characteristics may not represent all US hospitals. POC-EEG studies in pediatric populations were also lacking. Ultimately, further research is justified.Conclusions: POC-EEG is a rapid screening tool for NCS and NCSE in critical care and emergency medicine with potential financial benefits through refining clinical management, reducing unnecessary patient transfers and hospital LOS, improving reimbursement, and mitigating burdens on healthcare staff and hospitals. Since POC-EEG has limitations (i.e. no video component and reduced montage), the studies asserted that it did not replace convEEG.

Amplitude Integrated Electroencephalography: Simulated Assessment of Neonatal Seizure Detection in PICU Patients.

OBJECTIVES: Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital. DESIGN: Retrospective study. SETTING: PICU/Neurophysiology Department in Dublin. PATIENTS: One hundred twenty patients (2 mo to 16 yr old) were chosen from a database of formal 10-20 system, 21-lead electroencephalography recordings (2012-2020), comprising 30 studies with seizures, 90 without. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalography studies containing electrographic seizures (ESzs) were annotated to describe number, duration, distribution, and spread. Two-channel aEEG (using leads C3-P3, C4-P4) recordings were generated and independently reviewed by a professional specialist in clinical neurophysiology blinded to outcome and without reference to the raw electroencephalography trace. Logistic regression was used to identify factors associated with correct seizure identification on aEEG. Median patient age was 6.1 years. Abnormal recordings featured 123 seizures. Status epilepticus (SE) was evident by electroencephalography in 10 cases. Using neonatal criteria, aEEG had a sensitivity of 70% and negative predictive value of 90% for identifying any ESz. Accurate detection of individual seizures was diminished when seizures were very short or occurred during waking. Sensitivity for individual seizures was 81% when seizures less than 1 minute were excluded. aEEG correctly identified SE in 70% of the 10 cases, although ESz were confirmed to be present in 80% of this subpopulation. CONCLUSIONS: aEEG criteria for neonatal seizure identification can be applied with caution to older children and should be supplemented by formal electroencephalography. Seizure identification is better for longer seizures and those arising from sleep. SE is not always recognized by aEEG among older children.

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score.

BACKGROUND: The risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. METHODS: The study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. RESULTS: We included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE. A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13-4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03-4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07-3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40-5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3-84.3 %, p < 0.001). CONCLUSIONS: The AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment.

BACKGROUND: Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown. OBJECTIVE: The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients. METHODS: We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment. RESULTS: Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone). CONCLUSION: Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.

Short- vs long-term assessment of heart rate variability: Clinical significance in Dravet Syndrome.

PURPOSE: Heart rate variability (HRV) is a promising prognostic biomarker in Dravet Syndrome (DS), but different studies are not always comparable, limiting its clinical application. In fact, multiple HRV parameters, analyzed over different timescales and in different states are reported. The aim of this study was to assess which HRV parameter is more reproducible and clinically significant, analyzing differences between wake and sleep. METHOD: Patients with DS, with available 24 h-ECG Holter-derived HRV, were screened to evaluate if they had EEG-derived ECG traces available within one month before/after the Holter. A 5-minute period in the awake and sleep state were analyzed and correlated with the 24 h-HRV. Several relevant clinical features such as age, a recent history of status epilepticus (SE), and frequent generalized tonic-clonic seizures (GTCS) were correlated to HRV parameters with multiple linear regression models. RESULTS: Thirty-oneawake recordings and 22 sleep recordings were included. HF was the parameter with the highest correlation in awake (Rho 0.745, p < 0.001) and in sleep (Rho 0.727, p < 0.001). Age was a significant factor in simple models for most of the parameters except RMSSD. A recent history of SE was associated with a significant reduction of HRV, both in simple and multiple regressions for all parameters except for awake LF and for sleep RMSSD and PNN50. Frequent GTCS were associated with a significant decrease in sleep RMSSD, HF, and LF, also when correcting for the effect of age and history of SE. When compared pairwise, a significant increase in sleep was seen for HF (median + 24.45 ms2, IQR -7.51/+172.18 ms2, p = 0.036; increase in 15/22 patients). CONCLUSION: A moderate degree of correlation between long- and short-term HRV was seen both in sleep and in awake, and a strong correlation for awake HF. HF, both in awake and sleep, was significantly associated with high seizure burden, including SE and frequent GTCS.

Quantitative assessment of burst suppression as a predictor of seizure recurrence in refractory status epilepticus.

OBJECTIVE: To determine whether quantitative EEG analysis of burst suppression can predict seizure recurrence in patients with refractory status epilepticus (RSE) being treated with anesthetic doses of continuous IV antiseizure medications (cIVASM). METHODS: Quantitative assessment of burst suppression (including epileptiform discharges [EDs] and evolution) in 31 occasions (from 27 patients), and correlation with seizure recurrence up to 48 hours post sedative wean. RESULTS: Occasions resulting in seizure recurrence (vs. no seizure recurrence) had lower burst (8.4 vs. 10.6 µV) and interburst interval (IBI) (4.2 vs. 4.8 µV) average amplitude, duration (bursts 2.8 vs. 3.6 s: IBIs 3.6 vs. 4.4 s); and burst total power (0.4 vs. 0.7 µV2). Bursts (0.86 vs. 0.60) and IBIs (0.28 vs. 0.07) with EDs, higher number of EDs within bursts (mean 2.1 vs. 1.4) and IBIs (0.6 vs. 0.2), and positive evolution measures all predicted seizure recurrence, although EDs had the greatest adjusted odds ratio on multivariate analysis. CONCLUSIONS: For patients in burst suppression, successful wean of cIVASM was not determined by classical burst suppression measures, but instead how "epileptiform" bursts and IBIs were, as determined by EDs in both bursts and IBIs and surrogates for evolution within bursts. SIGNIFICANCE: If confirmed, these objective measures could be used during clinical care to help determine when to wean cIVASM in patients with RSE.

Toward Evidence-Based Severity Assessment in Mouse Models with Repeated Seizures: (II.) Impact of Surgery and Intrahippocampal Kainate.

INTRODUCTION: Chronic epilepsy models require neurosurgical procedures including depth electrode implants. The intrahippocampal kainate model is a frequently used chronic paradigm, which is based on chemoconvulsant administration and status epilepticus induction during the surgical procedure. This experimental approach raises the question of the extent to which this approach affects postsurgical recovery. In addition to the short- and long-term impact of the surgical intervention, a potential impact of highly frequent electrographic seizure events needs to be considered in the context of severity assessment. METHODS: Various behavioral, biochemical, and telemetric parameters were analyzed in four experimental groups of mice: 1st naive, 2nd with transmitter implants, 3rd with transmitter and electrode implants, and 4th with transmitter implants, electrode implants, and kainate-induced status epilepticus. RESULTS: During the early postsurgical phase, transmitter implants caused a transient impact on Mouse Grimace scores and intragroup increase of fecal corticosterone metabolites. Additional craniotomy was associated with an influence on total heart rate variability and fecal corticosterone metabolites. Heart rate and Irwin score increases as well as a prolonged increase in Mouse Grimace scores pointed to an added burden related to the induction of a nonconvulsive status epilepticus. Data from the chronic phase argued against a relevant influence of frequent electrographic seizures on behavioral patterns, fecal corticosterone metabolites, heart rate, and its variability. However, Irwin scores indicated long-term changes in some animals with increased reactivity, body tone, and Straub tail. Interestingly, selected behavioral and telemetric data from the early post-status epilepticus phase correlated with the frequency of electrographic seizure events in the chronic phase. CONCLUSION: In conclusion, our findings argue against the pronounced impact of highly frequent electrographic seizures on the well-being of mice. However, an increased level of nervousness in a subgroup of animals should be considered for handling procedures and refinement measures. In the early postsurgical phase, several parameters indicate an influence of the interventions with evidence that the nonconvulsive status epilepticus can negatively affect the recovery. Thus, the development and validation of refinement efforts should focus on this experimental phase. Finally, the datasets suggest that simple readout parameters may predict the long-term consequences of the epileptogenic insult. Respective biomarker candidates require further validation in the follow-up studies in models with subgroups of animals with or without epilepsy development.

Prediction and assessment of acute encephalopathy syndromes immediately after febrile status epilepticus.

OBJECTIVE: This study aimed to predict occurrence of acute encephalopathy syndromes (AES) immediately after febrile status epilepticus in children and to explore the usefulness of electroencephalogram (EEG) in the early diagnosis of AES. METHODS: We reviewed data from 120 children who had febrile status epilepticus lasting >30 min and were admitted to our hospital between 2012 and 2019. AES with reduced diffusion on brain magnetic resonance imaging was diagnosed in 11 of these patients. EEG and serum cytokines were analyzed in AES patients. Clinical symptoms and laboratory data were compared between AES and non-AES patients. Logistic regression analysis was used to identify early predictors of AES. RESULTS: Multivariate logistic regression identified serum creatinine as a risk factor for developing AES. A scoring model to predict AES in the post-ictal phase that included serum creatinine, sodium, aspartate aminotransferase, and glucose was developed, and a score of 2 or more predicted AES with sensitivity of 90.9% and specificity of 71.6%. Post-ictus EEG revealed non-convulsive status epilepticus in four of the seven AES patients. CONCLUSION: Children with febrile status epilepticus may be at risk of developing severe AES with reduced diffusion. Post-ictus EEG and laboratory data can predict the occurrence of severe AES.

Machine learning validation through decision tree analysis of the Epidemiology-Based Mortality Score in Status Epilepticus.

OBJECTIVE: This study was undertaken to validate the accuracy of the Epidemiology-Based Mortality Score in Status Epilepticus (EMSE) in predicting the risk of death at 30 days in a large cohort of patients with status epilepticus (SE) using a machine learning system. METHODS: We included consecutive patients with SE admitted from 2013 to 2021 at Modena Academic Hospital. A decision tree analysis was performed using the 30-day mortality as a dependent variable and the EMSE predictors as input variables. We evaluated the accuracy of EMSE in predicting 30-day mortality using the area under the receiver operating characteristic curve (AUC ROC), with 95% confidence interval (CI). We performed a subgroup analysis on nonhypoxic SE. RESULTS: A total of 698 patients with SE were included, with a 30-day mortality of 28.9% (202/698). The mean EMSE value in the entire population was 57.1 (SD = 36.3); it was lower in surviving compared to deceased patients (47.1, SD = 31.7 vs. 81.9, SD = 34.8; p < .001). The EMSE was accurate in predicting 30-day mortality, with an AUC ROC of .782 (95% CI = .747-.816). Etiology was the most relevant predictor, followed by age, electroencephalogram (EEG), and EMSE comorbidity group B. The decision tree analysis using EMSE variables correctly predicted the risk of mortality in 77.9% of cases; the prediction was accurate in 85.7% of surviving and in 58.9% of deceased patients within 30 days after SE. In nonhypoxic SE, the most relevant predictor was age, followed by EEG, and EMSE comorbidity group B; the prediction was correct in 78.9% of all cases (89.6% in survivors and 46.1% in nonsurvivors). SIGNIFICANCE: This validation study using a machine learning analysis shows that the EMSE is a valuable prognostic tool, and appears particularly accurate and effective in identifying patients with 30-day survival, whereas its performance in predicting 30-day mortality is lower and needs to be further improved.

Prevalence, predictors, and prognosis of mortality among elderly stroke patients with convulsive status epilepticus in the United States.

BACKGROUND: Stroke is the most common cause of epilepsy in the elderly. However, despite the high mortality typically associated with convulsive status epilepticus (CSE), there is a dearth of nationwide data on the magnitude and association of CSE with mortality among hospitalized elderly with stroke in the United States. METHODS: We analyzed the 2006-2014 National Inpatient Sample (NIS) to identify elderly patients (65+ years) with a primary discharge diagnosis of stroke using the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) codes 433.X1, 434.X1, 436, 430, 431, 432.0, 432.1, and 432.9. We examined a subgroup with a secondary discharge diagnosis of convulsive status epilepticus (ICD-9-CM: 345.3). We estimated the hospital mortality rate by CSE status and then evaluated the independent association of CSE and other key factors with mortality among hospitalized elderly with stroke. RESULTS: A total of 1220 elderly patients (0.14%) had a secondary discharge diagnosis of CSE. Inpatient mortality rate was 25.8% among those with CSE vs. 7.7% for non-CSE patients. CSE was independently associated with a 4-fold increased odds of in-hospital death. Increased age, medical comorbidities, weekend admissions, being a Medicare beneficiary, and hospitalization in large urban teaching hospitals were also independently associated with a greater likelihood of in-hospital death. The small number of events did not allow analysis by stroke subtypes. CONCLUSION: While CSE occurs in just 14 of 10,000 hospitalized elderly stroke patients in the United States, it is associated with a 4-fold higher odds of in-hospital death.

Costs and cost-driving factors of acute treatment of status epilepticus in children and adolescents: A cohort study from Germany.

OBJECTIVE: To provide data on inpatient costs and cost-driving factors in children and adolescents due to non-refractory (NSE), refractory (RSE), and super-refractory status epilepticus (SRSE). METHODS: All children and adolescents treated for status epilepticus (SE) between 2011 and 2018 at the Frankfurt University Hospital were analyzed for health care utilization. RESULTS: We evaluated 223 admissions in 174 patients (6.8 ± 5.1 years, median 5.5 years, range 0.1-17.5 years, 109 males [62.6%]) treated for SE. Mean costs of hospital treatment were €5,711 (median €2,330, range = €654-€102,414) per patient per admission, with a mean length of stay (LOS) of 9.2 days (median 5.0, range = 1-101), resulting in mean costs of €621 per SE treatment day. Course of SE had a significant impact on the mean costs, which were €3,386 in NSE (median €2,139, range €654-€38,236, €529 per treatment day; 37% of total inpatient costs due to SE), €7,409 in RSE (median €2,772, range €700-€38,236; €612 per treatment day, 38% of total inpatient costs due to SE) and €17,436 in SRSE (median €6,911, range €2,138-102,414; €842 per treatment day, 25% of total inpatient costs due to SE). Independent cost-driving factors were three or more treatment steps, acute-symptomatic etiology, and unfavorable modified Rankin Scale score at admission. Increased LOS was predicted by three or more treatment steps and unfavorable modified Rankin Scale score at admission. Overall mortality at discharge was 1.3% (three patients). CONCLUSIONS: Acute treatment of SE, and particularly RSE and SRSE, is associated with high hospital costs and prolonged LOS. Patients with disabilities are at risk for an unfavorable course of SE, resulting in prolonged LOS. In general, mortality associated with SE is low in children and adolescents, however three or more treatment steps are associated with high treatment costs.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

BACKGROUND: Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. OBJECTIVES: To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. DATA SOURCES: We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. REVIEW METHODS: Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. RESULTS: Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. LIMITATIONS: The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. CONCLUSIONS: Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. STUDY REGISTRATION: This study is registered as PROSPERO CRD42020201953. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Epilepsy is a common condition that results from abnormal electrical activity in the brain and causes seizures (stiffening and uncontrolled jerking ­ known as a 'fit'). The most severe form of epilepsy is called 'convulsive status epilepticus', which involves continuous seizure activity for 5 minutes or more, or repetitive seizures without recovery of consciousness. Convulsive status epilepticus can be very dangerous and requires prompt treatment to avoid hospitalisation and prevent complications. Although several drugs are available for the treatment of convulsive status epilepticus in the community or in the emergency department, it is unclear which one is most effective in stopping seizures. We brought together results from all available clinical studies that looked at the use of drugs to treat adults with convulsive status epilepticus either before arriving at hospital or on arrival at the emergency department. In the literature, we found four studies (1234 adults) assessing drugs delivered by paramedics through an injection into a vein or into muscle. In general, the drugs used by paramedics (benzodiazepines) were effective in stopping seizures, but we were unable to identify any particular drug or way of administering it as being more successful than others. Future research is needed to establish which drugs are most effective and preferable. It is also important to improve adherence to clinical guidelines with regard to the use of these drugs. For the pre-hospital treatment of convulsive status epilepticus, little evidence was available to decide which drug treatment is the best in terms of value for money. Future studies could assess the (1) impact of treatments on costs and outcomes over the whole course of a seizure episode (2) long-term impact of different treatments on patients' quality of life and (3) health and social care needs.

Automated Pupillometry for Assessment of Treatment Success in Nonconvulsive Status Epilepticus.

BACKGROUND: Altered pupillary function may reflect nonconvulsive status epilepticus (NCSE). Neurological pupil index (NPi) assessed by automated pupillometry is a surrogate marker of global pupillary function. We aimed to assess NPi changes in relation to NCSE treatment response. METHODS: In this prospective observational study, serial automated pupillometry was performed in 68 NCSE episodes. In accordance with local standards, patients were treated with clonazepam (1-2 mg), levetiracetam (40 mg/kg), and lacosamide (5 mg/kg) in a stepwise approach under continuous electroencephalography monitoring until NCSE was terminated. Patients with refractory NCSE received individualized regimens. NPi was assessed bilaterally before and after each treatment step. For statistical analysis, the lower NPi of both sides (minNPi) was used. Nonparametric testing for matched samples and Cohen's d to estimate effect size were performed. Principal component analysis was applied to assess the contribution of baseline minNPi, age, sex, and NCSE duration to treatment outcome. RESULTS: In 97.1% of 68 episodes, NCSE could be terminated; in 16.2%, NCSE was refractory. In 85.3% of episodes, an abnormal baseline minNPi ≤ 4.0 was obtained. After NCSE termination, minNPi increased significantly (p < 0.001). Cohen's d showed a strong effect size of 1.24 (95% confidence interval 0.88-1.61). Baseline minNPi was higher in clonazepam nonresponders vs. responders (p = 0.008), minNPi increased in responders (p < 0.001) but not in nonresponders. NCSE refractivity was associated with normal baseline minNPi (principal component analysis, component 1, 32.6% of variance, r = 0.78), male sex, and longer NCSE duration (component 2, 27.1% of variance, r = 0.62 and r = 0.78, respectively). CONCLUSIONS: Automated pupillometry may be a helpful noninvasive neuromonitoring tool for the assessment of patients with NCSE and response to treatment.

Epidemiology, management and outcome of status epilepticus in adults: single-center Italian survey.

The official variations of status epilepticus (SE) International League Against Epilepsy (ILAE, 2015) diagnostic criteria and the non-convulsive SE (NCSE) Salzburg Consensus Criteria (2013), impose the collection of updated population-based epidemiological Italian data. In this study, we aimed at evaluating (a) the frequency of SE in our hospital adopting the new ILAE 2015 SE diagnostic criteria and NCSE Salzburg Consensus Criteria, (b) the frequency of adherence to current treatment guidelines for SE and their relationship with patients' outcome, and (c) reliability of standardized prognostic scales (Status Epilepticus Severity Score-STESS-and modified STESS) for short-term outcome prediction in the setting of the newest diagnostic criteria for SE and NCSE. Detailed clinical and electrophysiological data collected in a 1-year retrospective hospital-based single-center survey on SE at Parma Hospital, Northern Italy are provided. Non-adherence to current treatment guidelines was recorded in around 50% cases, but no relation to outcome was appreciated. Mortality in our cohort increased from 30 to 50% when follow-up was extended to 30 days. STESS score was strongly correlated with short-term mortality risk (OR 18.9, 2.2-163.5, CI), and we confirm its role as easy-to-use tool for outcome evaluation also when the new ILAE diagnostic SE criteria are applied.