Nonconvulsive Status Epilepticus In Coma Research Articles

Retrospective External Validation of the Status Epilepticus Severity Score (STESS) to Predict In-hospital Mortality in Adults with Nonhypoxic Status Epilepticus: A Machine Learning Analysis.

The objective of this study was to validate the value of the Status Epilepticus Severity Score (STESS) in the prediction of the risk of in-hospital mortality in patients with nonhypoxic status epilepticus (SE) using a machine learning analysis. We included consecutive patients with nonhypoxic SE (aged ≥ 16years) admitted from 2013 to 2021 at the Modena Academic Hospital. A decision tree analysis was performed using in-hospital mortality as a dependent variable and the STESS predictors as input variables. We evaluated the accuracy of STESS in predicting in-hospital mortality using the area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI). Among 629 patients with SE, the in-hospital mortality rate was 23.4% (147 of 629). The median STESS in the entire cohort was 2.9 (SD 1.6); it was lower in surviving compared with deceased patients (2.7, SD 1.5 versus 3.9, SD 1.6; p < 0.001). Of deceased patients, 82.3% (121 of 147) had scores of 3-6, whereas 17.7% (26 of 147) had scores of 0-2 (p < 0.001). STESS was accurate in predicting mortality, with an AUROC of 0.688 (95% CI 0.641-0.734) only slightly reduced after bootstrap resampling. The most significant predictor was the seizure type, followed by age and level of consciousness at SE onset. Nonconvulsive SE in coma and age ≥ 65years predicted a higher risk of mortality, whereas generalized convulsive SE and age < 65years were associated with a lower risk of death. The decision tree analysis using STESS variables correctly classified 90% of survivors and 34% of nonsurvivors after the SE, with an overall risk of error of 23.1%. This validation study using a machine learning system showed that STESS is a valuable prognostic tool. The score appears particularly accurate and effective in identifying patients who are alive at discharge (high negative predictive value), whereas it has a lower predictive value for in-hospital mortality.

Prediction of Long-term Survival After Status Epilepticus Using the ACD Score

Early prediction of long-term mortality in status epilepticus is important given the high fatality rate in the years after diagnosis. To improve prognostication of long-term mortality after status epilepticus diagnosis. This retrospective, multicenter, multinational cohort study analyzed adult patients who were diagnosed with and treated for status epilepticus at university hospitals in Odense, Denmark, between January 1, 2008, and December 31, 2017, as well as in Oslo, Norway; Marburg, Germany; and Frankfurt, Germany. They were aged 18 years or older and had first-time, nonanoxic status epilepticus. A new scoring system, called the ACD score, for predicting 2-year (long-term) mortality after hospital discharge for status epilepticus was developed in the Danish cohort and validated in the German and Norwegian cohorts. The ACD score represents age at onset, level of consciousness at admission, and duration of status epilepticus. Data analysis was performed between September 1, 2019, and March 31, 2020. Long-term follow-up using data from national and local civil registries in Denmark, Norway, and Germany. The predefined end point was 2-year survival for all patients and for a subgroup of patients with status epilepticus causes that were not damaging or were less damaging to the brain. Neurological deficits before and after onset, demographic characteristics, etiological categories of status epilepticus, comorbidities, survival, time points, treatments, and prognostic scores for different measures were assessed. A total of 261 patients (mean [SD] age, 67.2 [14.8] years; 132 women [50.6%]) were included, of whom 145 patients (mean [SD] age, 66.3 [15.0] years; 78 women [53.8%]) had status epilepticus causes that were not damaging or were less damaging to the brain. The validation cohort comprised patients from Norway (n = 139) and Germany (n = 906). At hospital discharge, 29.8% of patients (n = 64 of 215) had new moderate to severe neurological deficits compared with baseline. New neurological deficits were a major predictor of 2-year survival after hospital discharge (odds ratio, 5.1; 95% CI, 2.2-11.8); this association was independent of etiological category. Nonconvulsive status epilepticus in coma and duration of status epilepticus were associated with development of new neurological deficits, and a simple 3-factor score (ACD score) combining these 2 risk factors with age at onset was developed to estimate survival after status epilepticus diagnosis. The ACD score had a linear correlation with 2-year survival (Pearson r2 = 0.848), especially in the subset of patients with a low likelihood of brain damage. This study found that age, long duration, and nonconvulsive type of status epilepticus in coma were associated with the development of new neurological deficits, which were predictors of long-term mortality. Accounting for risk factors for new neurological deficits using the ACD score is a reliable method of prediction of long-term outcome in patients with status epilepticus causes that were not damaging or were less damaging to the brain.

Predictors of outcome in super refractory status epilepticus

PurposeWe conducted this study to determine the clinical, electrophysiological and radiological predictors of outcome in Super Refractory Status Epilepticus (SRSE). MethodsData of patients treated for SRSE between January 2000 and November 2019, archived prospectively in our SE registry were analyzed. Functional outcome was measured by Glasgow outcome score (GOS) at the time of hospital discharge and was divided into: good i.e. GOS ≥ 3 and bad outcome i.e. GOS < 3. The predictors of outcome were determined using appropriate statistical tests by univariate and multivariate analysis, p < 0.05 was considered as statistically significant. ResultsOf the 384 patients with status epilepticus (SE) identified during the study, 28 (8%) were diagnosed as SRSE and were included in the final analysis. Acute symptomatic SE comprising 15 (53.6%) patients was the most common etiology of SRSE. Thirteen patients (three patients with viral encephalitis and 10 patients with clinically possible autoimmune encephalitis) had New Onset Refractory Status Epilepticus (NORSE) like clinical presentation.12 patients (42.9%) had good outcome and 16 patients (57.1%) had bad outcome. Multivariate logistic regression analysis showed that independent predictors of poor outcome were: duration of ICU stay (p < 0.001); EEG findings such as non-convulsive SE in coma (0.032), spontaneous burst suppression (0.001) and postictal diffuse attenuation (<0.001); delay in starting anesthesia (0.002); and delay in starting immunotherapy in NORSE due to autoimmune encephalitis (0.002). ConclusionWe could determine independent therapeutic and electrophysiological prognostic factors for SRSE. Early initiation of treatment and stringent management of these factors especially in an younger age-group, aided by continuous EEG monitoring and a thorough etiological work-up can result in good outcomes in more than one-third of cases.

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

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. 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 <18years 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. The incidence of first-time, nonanoxic SE in 2014 was 10.7/100000 persons at risk (n=41). Median Status Epilepticus Severity Score was 3; in-hospital mortality was 24.4%. After median follow-up of 39.2months, 53.7% of the patients had died (age- and gender-adjusted mortality rate of 5.2/100000). Mortality stabilized 2years after diagnosis. Analysis of the cohort from 2008-2013 confirmed stabilization of survival after 2-3years and the high mortality 2years 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 = 3.5/100000). 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. 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 2years. The degree of disability as indicated by mRS at discharge was associated with long-term mortality after discharge.

Factors associated with refractoriness and outcome in an adult status epilepticus cohort

PurposeSeveral multinational prospective registers have shown that a significant proportion of status epilepticus (SE) patients are not treated in line with international guidelines. The aim of this study was to assess quality of treatment and to identify factors associated with refractoriness and outcome in a cohort of adult SE patients in Norway. Methods151 patients treated in Oslo University Hospital from 2001 to 2017 were included. One SE-episode was selected per patient and variables related to the patient, SE-episode, treatment and outcome entered into a database. Status Epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in SE (EMSE) were calculated for each episode. Results68% (n = 102) of SE-episodes were responsive, 20% (n = 30) refractory and 12% (n = 19) superrefractory. Mortality was 9%, with a significant difference between responsive episodes (1%) and refractory (superrefractory included) episodes (24%), p < 0.001. 86% of patients received a benzodiazepine as 1st antiepileptic drug. Multivariate analysis showed that non-convulsive SE in coma was significantly associated with refractoriness (p = 0.04), while focal non-convulsive SE without coma was associated with responsiveness (p = 0.03). Younger age was associated with superrefractoriness (p = 0.02). Regarding outcome, EMSE-EtiologyAgeComorbiditiesEEG (EACE)≥64 (p = 0.02) and use of vasopressors (p = 0.03) were associated with a worsening of the modified Rankin scale at discharge. STESS was only associated with outcome in univariate analysis. ConclusionIn this cohort in which international guidelines for treatment of SE were well followed, semiology of the SE was found to be the most important determinant of refractoriness, and the new clinical scoring system EMSE-EACE was robustly associated with outcome.

Does semiology of status epilepticus have an impact on treatment response and outcome?

ObjectiveThis study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. MethodTwo hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18–97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). ResultsThe most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). ConclusionStatus epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE.

Prognosis of status epilepticus in patients requiring intravenous anesthetic drugs (a single center experience)

PurposeThere is concern about the safety of anesthetic drugs (IVADs) in the management of status epilepticus (SE). To clarify this aspect, we aimed to assess the factors associated with a poor prognosis in SE requiring anesthetics. MethodWe analyzed all SE requiring IVADs between October 2011 and December 2015. Demographics, clinical data, etiology, SE duration, indications for sedation, electroencephalography features, complications and the prognosis at discharge were collected. Hypoxic etiology was ruled out. Results73 patients needed IVADs. These were indicated as third-line treatment for SE in 58.9%, for decreased level of consciousness resulting from previous treatments in 27.4%, and for the underlying etiology in 13.7%.At discharge 41(56.2%) patients showed a bad outcome and 32 a good outcome. Outcome was poorer in patients with higher STESS (p=0.003), lower level of consciousness (p=0.025), non-convulsive SE in coma (p=0.040), potentially fatal etiology-PFE (p=0.006), longer duration (p=0.026), presence of complications (p=0.022), use of IVADs due to the underlying etiology (p=0.020), and periodic epileptiform discharges on electroencephalography (p=0.032).Following multivariate analysis, SE duration >12h (OR=3.266; 95%CI=1.077–9.908; p=0.037), STESS ≥3 (OR=4.816; 95%CI=1.435–16.165; p=0.011), and PFE (OR=3.526; 95%CI=1.184–10.506; p=0.024) were independently associated with a poor functional prognosis. Regarding mortality, duration >12h (OR=7.07; 95%CI=1.836–27.220; p=0.004), low level of consciousness (OR=6.97; 95%CI=1.194–40.718; p=0.031), and presence of complications (OR=21.32; 95%CI=2.440–186.295; p=0.006) were independent predictors of death. ConclusionsLengthy duration of SE in patients requiring IVADs is associated with a poorer prognosis and death. A STESS ≥3 and the etiology seem mainly related to the functional status at discharge, whereas more severely impaired consciousness and complications during sedation are related to mortality.

New ILAE versus previous clinical status epilepticus semiologic classification: Analysis of a hospital-based cohort.

In 2015, the International League Against Epilepsy (ILAE) issued a new status epilepticus (SE) classification, including a detailed semiologic axis. This study assesses frequencies of SE forms in a cohort of adult patients, and explores differences and practical implications as compared to a seizure-type-bound classification. The prospective adult SE registry of the Lausanne University Hospital (CHUV) was considered over 5 years (2011-2015); each SE episode was retrospectively reclassified for its semiology according to the new ILAE scheme. Mortality rates were retrieved for each subgroup of SE. Among 488 SE episodes, according to the seizure-type-bound classification, 230 (47%) had a generalized convulsive, and 29 (6%) had a nonconvulsive SE in coma; both categories overlapped almost perfectly between the two classifications. However, the 84 episodes with focal SE without consciousness impairment and the 141 episodes with consciousness impairment were each translated into two major (and five sub-) categories of the new ILAE classification, having markedly different mortality rates. In addition, of 140 episodes labeled as focal motor SE according to the new classification, 54% had concomitant consciousness impairment, whereas 46% did not; again, mortality rates were heterogeneous. Although generalized convulsive and nonconvulsive SE in coma show an almost perfect correspondence across SE semiologic classifications, focal SE is markedly heterogeneous and appears to be better reflected in the new classification, offering more clinically relevant subdivisions, also differing in mortality rates. This refined knowledge may allow the development of clinical prognostic scores that are more precise than existing tools, and should be taken into account for epidemiologic studies.

Which EEG patterns in coma are nonconvulsive status epilepticus?

Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma. Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary. The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future. This article is part of a Special Issue entitled "Status Epilepticus".

Status epilepticus: impact of therapeutic coma on outcome.

Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. Retrospective assessment of a prospectively collected cohort. Academic hospital. Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.

P38. Effect of anaesthetic agents on the prognosis of refractory status epilepticus

Anaesthetic agents (AAs) are advocated in guidelines for management of refractory status epilepticus (SE), although their effect on prognosis has not been established. The aim of this study was to determine their impact on clinical outcome, after adjustment for all relevant prognostic factors. We included consecutive adults with incident SE lasting ⩾30 min, admitted between 2006 and 2013. Demographics, clinical SE features, treatment type and functional outcome at discharge were prospectively recorded, while medical comorbidities were retrospectively retrieved. The association between potential predictors and clinical outcome was analyzed using multinomial logistic regressions. We identified 467 episodes of SE; 238 (51.1%) patients returned to baseline, 162 (34.6%) had new disability, and 67 (14.3%) died. Of 50 subjects managed with AAs, 14 presented with non-convulsive SE (NCSE) without coma (mostly complex partial SE) (28%), and 36 with generalized convulsive SE (GCSE) or NCSE in coma (72%). Multinomial logistic regression showed that AAs were independently associated with poorer outcome at discharge [risk ratio (RR) for new disability: 6.9, 95% CI 2.8–16.6; RR for mortality: 9.1, 95% CI 3.2–26.2]. The effect was higher in the group of patients with NCSE without coma, especially for mortality [RR for new disability: 8.6, 95% CI 1.4–52.0; RR for mortality: 26.6, 95% CI 3.4–205.4]. Management with AAs is independently associated with poorer outcome in SE. This study suggests caution in the indiscriminate use of this approach, especially in patients with complex partial SE.

Statins are associated with decreased mortality risk after status epilepticus

Statins display anti-inflammatory and anti-epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed. This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into 'return to baseline', 'new disability' and 'mortality'. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model. Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046). This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti-epileptogenic role. Other studies are needed to confirm this intriguing finding.

Mortality and recovery from refractory status epilepticus in the intensive care unit: A 7‐year observational study

Refractory status epilepticus (RSE) is a life-threatening neurologic emergency with high mortality and morbidity. The aim of this study was to identify and quantify associations between clinical characteristics of adult RSE patients and outcome. Comprehensive medical chart review was performed of all consecutive adult RSE patients treated on the intensive care units of an academic tertiary care center between 2005 and 2011. Demographics, RSE etiologies and duration, comorbidities, as well as outcomes were assessed. Associations between clinical characteristics and death were quantified. Of 260 patients with status epilepticus, 111 developed RSE. Hypoxic encephalopathy (23%), brain tumors (14%), known and uncontrolled epilepsy (10%), and ischemic stroke (8%) were the main etiologies. During hospitalization 38% of patients died. Hypoxic encephalopathy (HE) and brain tumors were independently associated with death (relative risk [RR] 2.41, 95% confidence interval [CI] 1.40-4.12; p = 0.001 and RR 2.81, 95%CI 1.59-4.96; p < 0.0001). The estimated hazard ratio of death was 3.1 (95% CI1.6-6.0; p = 0.001) for patients with HE and 1.1 (95% CI 0.5-2.3; p = 0.745) for patients with brain tumors. RSE duration and nonconvulsive status epilepticus in coma were independently associated with death (for every hour RR 1.001; 95%CI 1.00-1.002; p = 0.011 and RR 3.62; 95%CI 1.34-9.77; p = 0.005). Brain tumors and HE had high relative risks for death and were independently associated with mortality in our cohort of critically ill RSE patients. Other clinical characteristics, as well as the use of intravenous anesthetic drugs and mechanical ventilation, may not be strongly related to outcome and should therefore be used cautiously for informed decision making regarding treatment.

Diagnosis and treatment of nonconvulsive status epilepticus.

Nonconvulsive status epilepticus (SE) is not uncommon and comprises at least one-third of all cases of SE. However, nonconvulsive SE consists of very different syndromes, a common feature being the difficulty in making the diagnosis. In this review, nonconvulsive SE is divided into typical absence SE, complex partial SE, nonconvulsive SE in patients with learning difficulties (including electrical SE during sleep, atypical absence SE and tonic SE), and nonconvulsive SE in coma. These conditions have different prognoses and treatments. The diagnosis of these conditions is critically dependent on EEG. When the EEG demonstrates typical ictal patterns, the diagnosis is usually straightforward. However, in many circumstances the EEG has to be differentiated from encephalopathic patterns, and this differentiation can prove troublesome, although the clinical and electrographic response to treatment can prove helpful. Nonconvulsive SE in patients with learning difficulties possibly provides the greatest diagnostic difficulty; the clinical presentation can be subtle resulting in the diagnosis being frequently missed. Whether the neuronal damage that occurs in convulsive SE and in animal models of limbic SE also occurs in nonconvulsive SE in humans is still a matter of debate. There are critical differences between the animal models and the human condition. Indeed, the prognosis of nonconvulsive SE is usually dependent on the underlying aetiology rather than the persistence of electrographic discharges. Because of these doubts, a more conservative approach to the treatment of particular types of nonconvulsive SE (those with a better prognosis) has been taken in this article. Thus, in most instances, oral benzodiazepines for the treatment of typical absence SE and complex partial SE are recommended. In some circumstances intravenous medication is necessary, but in neither condition is anaesthetic coma recommended. This contrasts with nonconvulsive SE in coma in which a more aggressive approach is suggested. Until there are more relevant animal models, and controlled trials of conservative versus more aggressive treatment, treatment regimens for nonconvulsive SE will remain largely speculative.