Refractory Status Epilepticus Patients Research Articles

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.

NORSE seasonality may vary geographically in adults.

The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital. Clinical characteristics and seasonality of patients fulfilling the diagnostic criteria for NORSE were compared with patients with refractory SE (RSE) due to other reasons and with the seasonal variation of autoantibodies associated with autoimmune encephalitis in the Danish autoimmune encephalitis register. In this cohort, 26 patients met NORSE criteria. As compared to RSE patients not fulfilling NORSE criteria (n = 152), NORSE patients were more likely to have symptoms of systemic inflammation (C-reactive protein concentrations ≥10 mg/L or fever ≥38°C) at admission; nine fulfilled the criteria for febrile infection related epilepsy syndrome (FIRES). In contrast to the even seasonal distribution of patients with RSE not fulfilling the NORSE criteria, admissions due to NORSE peaked during the winter (46.1%, p = 0.04 as compared to non-NORSE RSE); six out of nine FIRES episodes occurred in the winter season. The seasonal variation was not explained by a seasonal variation of the detection rates of autoantibodies associated with autoimmune encephalitis (incl. NMDAR, LGI1, CASPR2, GABAR, GFAP) in a Danish nationwide register (n = 259). In conclusion, we confirm the seasonality of NORSE in a Danish cohort, however, with a peak during winter suggesting a geographical variation not solely explained by autoimmune encephalitis associated with known autoantibodies. PLAIN LANGUAGE SUMMARY: The study investigated the seasonal patterns of new-onset refractory status epilepticus (NORSE), i.e. severe seizures that occur without an obvious cause and require very intensive treatment. In contrast to the previously observed peak frequency in summer, this Danish study found that NORSE cases peak in winter. Furthermore, the seasonal variation in NORSE cases was not found to be associated with autoimmune encephalitis caused by known autoantibodies. Together with the high rate of patients showing symptoms of systemic inflammation compared to other status epilepticus patients, the data suggest a link between misdirected immune system responses and NORSE. The study can therefore help in the further search for the currently unknown causes of NORSE.

High-definition transcranial direct current stimulation desynchronizes refractory status epilepticus

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz (“gamma”) and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, −5.25%, −1.88%, −1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +4.13%, −5.44%, −1.81%, −3.23%, and +5.41% in the referential Laplacian montage (p ​= ​0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: −2.74%, +4.20%, +1.74%, +1.75%, and −4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and −5.12% in the referential Laplacian montage (p ​= ​0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE.

Cardiac Abnormalities in Refractory Status Epilepticus-an Exploratory Study.

Cardiac abnormalities have been reported during ongoing seizures and refractory status epilepticus (RSE). Reduced heart rate variability (HRV) and cardiac arrhythmias may contribute to sudden unexpected death in epilepsy. We sought to explore the utility of electrocardiographic and echocardiographic changes in patients with RSE prognosis and functional outcome. Patients of RSE underwent electrocardiogram (ECG), holter, troponin-I (Trop I), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and 2-dimensional echocardiogram (2D Echo) along with continuous electroencephalogram in first 24 hours and admission. Heart rate changes/arrhythmias, corrected QT interval (QTc) and HRV, ventricular dysfunction or regional motion wall abnormality were studied on 2D Echo. These parameters were also at baseline, at discharge or death and 30 days post discharge. This prospective observational study conducted over 18 months enrolled 20 patients with RSE, fulfilling the inclusion criteria. Mean age was 47.75±17.2 years with male: female ratio of 1:1. Mean time to presentation from seizure onset was 8.80±7.024 hours. Central nervous system infection (35.0%), autoimmune encephalitis (20.0%) and cerebrovascular disease (20.0%) were the common etiologies. Amongst cardiac injury markers, cardiac enzymes and QTc prolongation were the commonest abnormalities in RSE. Both reduced HRV and presence of cardiac injury markers had significant correlation with poor outcome along with poor Glasgow coma scale (GCS) and modified Rankin scale (mRS) at presentation, and presence of non convulsive status epilepticus (NCSE). Presence of poor GCS, poor mRS, markers of cardiac injury, reduced HRV and occurrence of NCSE have a consistent correlation with mortality and poor clinical outcome. Therefore, routine assessment of cardiac abnormalities using affordable, easily accessible and non-invasive tools such as ECG, 2D Echo, holter NT-proBNP and Trop I is recommended in RSE patients.

Comparison of three types of Epilepsy Surgery for the treatment of Refractory Status Epilepticus: A Single Center Experience (P9-1.005)

<h3>Objective:</h3> Comparing outcomes for three categories of epilepsy surgery in Refractory Status Epilepticus Patients (RSE). <h3>Background:</h3> Literature comparing morbidity and mortality outcomes between three types of epilepsy surgery for RSE patients is scarce. Previous case series have focused on one type of surgery or does not directly compare outcomes between the modalities. <h3>Design/Methods:</h3> A retrospective analysis for RSE between 2010 and 2021 was done. Sociodemographic data, semiology and etiology were collected. The patients were deidentified using our institute’s software, and comparison data was extracted from the secure system. Data collected included lag time between diagnosis and surgery, number of anti-seizure medications (ASMs) tried, EEG and imaging data, type of surgery performed, level of post-operative care, number of post-operative days admitted, complications and seizure freedom outcomes. <h3>Results:</h3> The mean age was 35.6 ± 23.5 years, with 4/12 patients being female. Seizure types were primarily generalized tonic-clonic or focal seizures with impaired awareness. A plethora of etiologies were included. The mean number of ASMs tried was 2.3 ± 1.4. Every patient had EEG and MRI Brain with ancillary testing such as grid placement. Out of 12, 6 had resection, 5 disconnections and 2 neuromodulations. 11/12 patients required an ICU admission and mean post-operative days admitted was 12 ± 11.2. Minor to no complications occurred in 33 % of all resection patients, and minor complications occurred in 40 % and 50 % patients of the disconnection and modulation patients. 3/4 and 3/5 of patients that had undergone resections and disconnections respectively had Class 1 outcomes in. Patients that received modulation had a Class 4 outcome and 1 patient death. <h3>Conclusions:</h3> Our study reveals that while there is no substantial difference between resection and disconnection, resections have slightly better outcomes and fewer complications. Modulation had poorer seizure freedom and may only be considered as a temporizing measure. <b>Disclosure:</b> Dr. Khan has received personal compensation for serving as an employee of University of Kentucky. Dr. Mirza has nothing to disclose. Dr. Mathias has received research support from My Epilepsy Society Non Profit Organization.

Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed. The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Specific characteristics and current diagnostic and treatment modalities performance of super refractory status epilepticus in children: A comparative study

Super-refractory status epilepticus (SRSE) is associated with significant morbidity and mortality in children. We explored the clinical spectrum, specific characteristics, and outcome in SRSE patients admitted in a pediatric intensive care unit (PICU) and investigated how well current diagnostic or treatment modalities perform compared to Status Epilepticus (SE) and Refractory SE (RSE) patients. Retrospective analysis of PICU patients admitted with convulsive SE during 2009-2019. Eighty-six patients were classified as SE, RSE, and SRSE. New-onset RSE (NORSE) and febrile infection-related epilepsy syndrome (FIRES) were also identified. Functional outcome was evaluated by the modified Rankin scale. Patients with SRSE (n=20) had longer weaning off anesthetics (p=0.014), length of stay, mechanical ventilation duration, higher illness severity scores, and poorer outcome compared to SE (n=13) or RSE (n=53) patients (all p<0.001). Diagnosis, mainly expressed by high prevalence of NORSE (n=13) and FIRES (n=9), was independently associated with SRSE (p=0.024). Abnormal MRI findings (p=0.005), and epilepsy-related pathogenic variants identified by whole-exome sequencing (WES) were mostly found in SRSE patients. Compared to intravenous immunoglobulins and steroid pulses, plasmapheresis and ketogenic diet, more often used in SRSE (p<0.01), contributed better to seizure control. Only SRSE (AUROC > 0.80, 95% CI=0.68-0.94, p<0.001) and diagnosis (AUROC > 0.70, 95% CI=0.55-0.83, p=0.02) could predict a poor outcome. The majority of SRSE patients are characterized by considerable functional decline and morbidity. WES analysis may reveal epilepsy-related pathogenic variants while early aggressive immunotherapy and/or ketogenic diet might prove beneficial. Multicenter studies for prediction models of outcome are needed.

P.019 A machine learning approach to asymmetric burst suppression and refractory status epilepticus outcome

Background: Treatment of refractory status epilepticus (RSE) is often titrated to achieve EEG burst suppression. However, optimal burst suppression characteristics are largely unknown. We used an unsupervised machine learning algorithm to predict RSE outcome based on the quantitative burst suppression ratio (QBSR). Methods: We conducted principal component analysis (PCA) as a linear combination of 22 QBSR features from non-anoxic adult RSE patients at the Winnipeg Health Sciences Centre. We also determined the most predictive components that significantly differed between survivors and non-survivors. Results: Using 135,765 QBSRs from 7 survivors and 10 non-survivors, PCA identified a predominantly non-survivor cluster of 8 patients (75% non-survivors). The first 2 PCA components comprised 75% data variance. The most important first component feature was skewness of QBSR distribution in the right or left hemisphere (0.52 each). The most important second component feature was third QBSR quantile of the left hemisphere (0.49). Only right hemispheric QBSR features significantly differed between groups: QBSR skewness for the first component (Benjamini-Hochberg adjusted p=0.038) and average QBSR for the second component (0.32, Benjamini-Hochberg adjusted p=0.046). Conclusions: Our pilot study shows that RSE patient survival may be impacted by QBSR, with differential hemispheric EEG burst suppression characteristics predicting poor RSE outcome.

Quantitative burst suppression on serial intermittent EEG in refractory status epilepticus

ObjectivesIn refractory status epilepticus (RSE), the optimal degree of suppression (EEG burst suppression or merely suppressing seizures) remains unknown. Many centers lacking continuous EEG must default to serial intermittent recordings where uncertainty from lack of data may prompt more aggressive suppression. In this study, we sought to determine whether the quantitative burst suppression ratio (QBSR) from serial intermittent EEG recording is associated with RSE patient outcome. MethodsWe screened the EEG database to identify non-anoxic adult RSE patients for EEG and chart review. QBSR was calculated per 10-second EEG epoch as the percentage of time during which EEG amplitude was <3 µV. Patients who survived 1–3 months after discharge from ICU and hospital comprised the favorable group. Further to initial unadjusted univariate analysis of all pooled QBSR, we conducted multivariate analyses to account for individual patient confounders (“per-capita analysis”), uneven number of EEG recordings (“per-session analysis”), and uneven number of epochs (“per-epoch analysis”). We analyzed gender, anesthetic number, and adjusted status epilepticus severity score (aSTESS) as confounders. ResultsIn 135,765 QBSR values over 160 EEG recordings (median 2.17 h every ≥24 h) from 17 patients on Propofol, Midazolam, and/or Ketamine, QBSR was deeper in the favorable group (p < 0.001) on initial unadjusted analysis. However, on adjusted multivariate analysis, there was consistently no association between QBSR and outcome. Higher aSTESS consistently associated with unfavorable outcome on per-capita (p = 0.033), per-session (p = 0.048) and per-epoch (p < 0.001) analyses. Greater maximal number of non-barbiturate anesthetic associated with favorable outcome on per-epoch analysis (p < 0.001). ConclusionsThere was no association between depth of EEG suppression using non-barbiturate anesthetic and RSE patient outcome based on QBSR from serial intermittent EEG. A per-epoch association between non-barbiturate anesthetic and favorable outcome suggests an effect from non-suppressive time-varying EEG content. SignificanceTargeting and following deeper burst suppression through non-barbiturate anesthetics on serial intermittent EEG monitoring of RSE is of limited utility.

Uric acid is a useful marker to differentiate between responsive and refractory status epilepticus

ObjectivesEarly recognition of refractory status epilepticus (RSE) is essential to select an appropriate treatment strategy and is closely associated with the outcome. Only few studies of RSE biomarkers exist; hence, we investigated the serum levels of uric acid (UA), albumin, and C-reactive protein (CRP) as potential serologic biomarkers for RSE. Patients and MethodsConsecutive status epilepticus (SE) patients who had serial conventional blood tests in a referral hospital over a period of 10 years were retrospectively analyzed. Patients with anoxic encephalopathy, renal failure, acute stroke, and myocardial infarction were excluded. RSE was defined as seizure continuing after the first- and second-line treatments. We also assessed SE severity in all included patients using the Status Epilepticus Severity Score (STESS). General demographics and blood test findings were compared between responsive SE and RSE patients. ResultsA total of 141 patients (99 responsive and 42 refractory) were recruited from our SE registry. Compared to responsive patients, patients with RSE showed a higher STESS, lower initial albumin levels, lower initial UA levels, lower follow-up UA levels, and greater reduction of UA levels. The RSE group more frequently had acute symptomatic etiology, showed longer hospitalization, and had poorer functional outcomes compared to the responsive-SE group. All evaluated UA level parameters exhibited significant areas under the curve in receiver operating characteristic analyses, predictive of RSE. Initial UA levels, as well as changes therein, were significantly associated with RSE in multivariate logistic regression analysis. ConclusionUA levels at initial and follow-up evaluations, and changes therein differentiated responsive SE and RSE, demonstrating the feasibility of UA serum levels as a biomarker for RSE.

Schizophrenia following new-onset refractory status epilepticus secondary to antiphospholipid syndrome

New-onset refractory status epilepticus (NORSE) is a drug-resistant status epilepticus that often has a catastrophic outcome. Our patient was diagnosed with NORSE and had an EEG reading that showed status epilepticus persisting for 8 months in general anesthesia. After autoimmune workup showed positive antiphospholipid antibodies, his seizure was controlled, and he was discharged with good condition apart from moderate cognitive impairment. However, he later developed schizophrenia. Although psychiatric disorders have been associated with antiphospholipid syndrome, to the best of our knowledge, it has not been reported to be associated with status epilepticus. We recommend vigilance of psychological complications of refractory status epilepticus’ patients for early psychiatric referral, diagnosis, and treatment.

Perampanel Treatment for Refractory Status Epilepticus in a Neurological Intensive Care Unit.

Perampanel is a novel anti-epileptic drug (AED) which acts as a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist to reduce glutamate-mediated postsynaptic excitation. Previous animal studies and a few case reports/series have suggested that it may be effective to treat refractory status epilepticus (RSE). We retrospectively reviewed 67 consecutive patients with RSE, of whom 22 received perampanel. The clinical features, epidemiology-based mortality score in status epilepticus, status epilepticus severity score, seizure control, functional outcome, RSE etiology, and electroencephalogram findings were collected. Responder to perampanel was defined as seizure resolution within 4days of therapy with perampanel being the last AED used plus no recurrence during hospitalization. Eight of the 22 (36.4%) RSE patients fulfilled the definition of responder to perampanel. An additional 1 patient responded to perampanel after 4days of treatment. In total, perampanel was the last AED in 9 (40.1%) patients. Among the 8 responders to perampanel, 5 had convulsive SE, 1 had non-convulsive SE, and 2 had focal motor SE. The responders accounted for both of the patients with focal motor SE (100%), 5 (33.3%) of the 15 patients with convulsive SE, and 1 (20%) of the 5 patients with non-convulsive SE. The ictal and inter-ictal activities also decreased after perampanel therapy, and three patients (13.6%) had preferable outcomes at last follow-up. Perampanel may be an effective add-on treatment for RSE even in patients who failed multiple AEDs. Our study suggests that perampanel may be more effective for focal motor SE and convulsive SE than non-convulsive SE. As most previous studies have focused on non-convulsive SE, further studies are warranted to clarify the effectiveness of perampanel for different subtypes of SE.

Clinical Features and Outcome of Refractory Status Epilepticus Patients in an Eastern Indian Tertiary Care Hospital

Clinical Features and Outcome of Refractory Status Epilepticus Patients in an Eastern Indian Tertiary Care Hospital

Does burst-suppression achieve seizure control in refractory status epilepticus?

BackgroundThe general principles in the administration of anesthetic drugs entail not only the suppression of seizure activity but also the achievement of electroencephalography burst suppression (BS). However, previous studies have reported conflicting results, possibly owing to the inclusion of various anesthetic agents, not all patients undergoing continuous electroencephalography (cEEG), and the inclusion of anoxic encephalopathy. This study aimed to analyze the effects of midazolam-induced BS on the occurrence outcomes in refractory status epilepticus patients.MethodsBased on a prospective database of patients who had been diagnosed with status epilepticus via cEEG, multivariate Poisson regression modules were used to estimate the effect of midazolam-induced BS on breakthrough seizure, withdrawal seizure, intra-hospital complications, functional outcome at 3 months, and mortality. Modules were based on a pre-compiled directed acyclic graph (DAG).ResultsWe included 51 non-anoxic encephalopathy, refractory status epilepticus patients. Burst suppression was achieved in 26 patients (51%); 25 patients (49%) had non-burst suppression on their cEEG. Breakthrough seizure was less often seen in the burst suppression group than in the non-burst suppression group. The incidence risk ratio [IRR] was 0.30 (95% confidence interval = 0.13–0.74). There was weak evidence of an association between BS and increased withdrawal seizure, but no association between BS and intra-hospital complications, mortality or functional outcomes was observed.ConclusionThis study provides evidence that BS is safe and associated with less breakthrough seizures. Additionally, it was not associated with an increased rate of intra-hospital complications or long-term outcomes.

Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus: a population-based study

BackgroundThe aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study.MethodsThis was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010–2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded.ResultsWe identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04–3.71). Hospital mortality was 7.4% (95% CI 0–16.9%), and 1-year mortality was 25.4% (95% CI 21.2–29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104–1.051, p = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051–1.271, p = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20–3.84, p = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537–4.243, p < 0.0001).ConclusionsDespite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality.Trial registrationRetrospective registry study; no interventions on human participants.

Status epilepticus: Refractory and super-refractory.

Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

Early-onset status epilepticus in patients with acute encephalitis.

Status epilepticus (SE) is a common complication of acute encephalitis, but its determinants and prognostic value in this setting are not known.Risk factors for early-onset SE (within 48 hours of intensive care unit [ICU] admission) in consecutive adult patients with all-cause encephalitis admitted to the medical ICU of a university hospital (1991-2013) were evaluated by multivariate logistic regression analysis. To examine the prognostic value of SE, patients were classified into 3 groups: no SE, nonrefractory SE (NRSE), and refractory SE (RSE). Poor neurologic outcome was defined by a modified Rankin score of 4 to 6.Among the 290 patients, 58 (20%, 95% CI: 15%-25%) developed early-onset SE, comprising 44 patients with NRSE and 14 patients with RSE. Coma (adjusted odds ratio [OR]: 3.1, 95% CI: 1.5-6.3), cortical lesions on neuroimaging (adjusted OR: 3.7, 95% CI: 1.8-7.8), and nonneurologic organ failure(s) (adjusted OR: 13.6, 95% CI: 4.9-37.7) were found to be independent risk factors for SE. By contrast, a bacterial etiology had a protective effect (adjusted OR: 0.3, 95% CI: 0.1-0.7). Age, body temperature, and blood sodium levels were not independently associated with SE. Poor neurologic outcomes were observed at day 90 in respectively 23% (95% CI: 17%-28%), 23% (95% CI: 10%-35%), and 71% (95% CI: 48%-95%) of no SE, NRSE, and RSE patients (P < 0.01). After adjusting for confounders, RSE, but not NRSE, remained independently associated with 90-day mortality (adjusted OR: 6.0, 95% CI: 1.5-23.3).Coma, cortical involvement on neuroimaging, and nonneurologic organ failure(s) are independent risk factors for SE in patients with acute encephalitis. Conversely, a bacterial etiology is associated with a lower risk of SE.These findings may help identify patients who may benefit from prophylactic antiepileptic drugs.

Causes and outcomes of new onset status epilepticus and predictors of refractoriness to therapy

We aimed to evaluate the determinants of outcome in new onset refractory status epilepticus (SE). A retrospective analysis of patients with new onset SE admitted between May 2005 and October 2013 was performed. Regression analysis was used to determine factors that affect progression of new onset SE to refractory status epilepticus (RSE) and mortality. Among 114 patients with new onset SE, 52 patients progressed to RSE. Sixty seven (58.7%) were men. New onset RSE patients were younger than new onset SE patients (mean 35.9±standard deviation18.2 versus 28.7±20.2years; p=0.050). Cryptogenic aetiology was the most significant determinant of progression of new onset SE to RSE (Exp [β]=5.68; p=0.001). The overall mortality in the entire group was 23.7%, significantly higher in new onset RSE group (40.4% versus 9.7%; p<0.0001). New onset RSE patients with symptomatic and cryptogenic etiology did not differ for clinical characteristics and outcome. Acidosis was the strongest predictor of mortality in the entire cohort (Exp [β]=8.72; p=0.005). Nearly half of the patients with new onset SE progressed to RSE. While cryptogenic aetiology determined progression of new onset SE to RSE, acidosis was associated with mortality. The outcome was similar between symptomatic and cryptogenic new onset RSE.

Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus

General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0–2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay.

Prognosis and predictors of outcome of refractory generalized convulsive status epilepticus in adults treated in neurointensive care unit

ObjectiveTo evaluate the etiological profile, clinical characteristics and outcome of patients with refractory generalized convulsive status epilepticus treated in Neurological Intensive Care Unit (NICU). MethodsIn this open cohort study, data of 126 patients, aged 18 years and above, with convulsive status epilepticus (SE) admitted in NICU was collected. Status epilepticus was defined as seizures lasting for more than five minutes without regaining consciousness. Refractory SE (RSE) was defined as SE refractory to 2 antiepileptic drugs and requiring anesthetic agents for seizure control. Survival and regression analysis were done to analyze the outcome and factors predicting outcome respectively in the study population. ResultsOut of 126 patients, 81 patients had non -refractory status epilepticus (NRSE); 45 (35.7%) had RSE. Acute symptomatic etiology was noted in 58.6% of entire cohort. Significantly higher percentage of patients with RSE had an etiology of CNS infections than NRSE group (44.4% vs. 23.5%; P=0.0171). Amongst the CNS infections, viral encephalitis was significantly higher in RSE than NRSE patients (31% vs. 6.2%; P=0.0004). All the patients with RSE required mechanical ventilation. Overall mortality was 19%. The mortality in RSE was 42% (19 out of 45), significantly higher when compared to NRSE where only 6% (5 out of 81) died. On logistic regression, the only predictor of death was fever with an odds ratio of 8.55 (P=0.024). ConclusionCNS infections, especially viral encephalitis and complications of mechanical ventilation were significantly higher in adult RSE patients. Although mortality is higher in adult patients with RSE, etiology does not contribute to mortality; however fever predicts mortality in these patients. Aggressive management of underlying etiology and prevention of systemic complications may improve outcome in adult RSE patients.