Non-refractory Status Epilepticus Research Articles

Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review

ObjectiveBrain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population.MethodsThis retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017.ResultsThe 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001).ConclusionsSE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors.

Clinical Outcomes and Systemic Complications Related to the Severity and Etiology of Status Epilepticus Using a Common Data Model.

Status epilepticus (SE) is a critical neurological emergency in patients with neurological and nonneurological diseases. Mortality rises with SE severity. However, whether brain injury or systemic organ dysfunction causes death after SE remains unclear. We studied clinical outcomes and systemic dysfunctions associated with SE using standardized data from the common data model. This model includes clinical evaluations and treatments that provide real-world evidence for standard practice. This retrospective cohort study used the common data model database of a single tertiary academic medical center. Patients diagnosed with SE (corresponding to G41 of the International Classification of Diseases 10 and administration of antiseizure medication) between January 1, 2001, and January 1, 2018, were enrolled. Demographics, classifications of SE severity, and outcomes were collected as operational definitions by using a common data model format. Systemic complications were defined based on the Sequential Organ Failure Assessment criteria. The electronic medical records of 1,825,196 patients were transformed into a common data model, and 410 patients were enrolled. The proportion of patients classified as having nonrefractory SE was 65.4% (268/410), followed by refractory (28.5%, 117/410) and super-refractory SE (6.1%, 25/410). Patients with more severe SE had longer intensive care unit and hospital stays. Renal dysfunction and thrombocytopenia were higher in the in-hospital death group (P = 0.002 and 0.003, respectively). In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II score and platelet count were significantly different in the in-hospital death group (odds ratio, 1.169, P = 0.004; and 0.989, P = 0.043). Systemic complications after SE, especially low platelet counts, were linked to worse outcomes and increased mortality in a common data model. The common data model offers expandability and comprehensive analysis, making it a potentially valuable tool for SE research.

Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes

BackgroundMultiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses.MethodsIn this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection.ResultsWe identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21–91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic–clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients.ConclusionsThis retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.

Clinical, etiological profile and outcomes of convulsive refractory and non-refractory status epilepticus at a tertiary care centre: A prospective observational study

Introduction: Epidemiological data on childhood status epilepticus (SE) limited in India. This study depicts clinical profiles, etiology, and outcomes of convulsive refractory SE (RSE) and compares the results with cases of nonrefractory SE (NRSE).Subjects and Methods: This observational, cross-sectional study enrolled 300 children aged 1 month to 18 years, presenting with convulsive SE at a tertiary care hospital. Details of children who progressed to RSE were compared to those without RSE.Results: In the acute symptomatic etiology group, common causes for RSE were central nervous system infections (33.8%), cryptogenic etiology (13.8%), and remote symptomatic etiology (7%). RSE iwas associated with a higher rate of complications (58% Vs 24%) as compared to NRSE. Thirty percent of cases that progressed to RSE needed ventilator support as compared to only 8% of cases in the NRSE group. RSE was also associated with higher rates of shock (25%), AKI (16%), transaminitis (25%), acute liver failure (5.69%), multiple organ dysfunction score (12.6%), and acidosis (53%) as compared to NRSE. RSE was associated with higher mortality (28%) and morbidity (32%) as compared to NRSE cases. Cryptogenic etiology led to the highest mortality (33.3%) in cases of RSE while acute symptomology was associated with the highest morbidity (62%). Conclusions: RSE is a serious pediatric emergency that requires prompt recognition and management. Clinical knowledge and early administration of appropriate antiepileptic drugs at health-care facilities is the key to reduce morbidity and mortality.

HMGB1 Is a Therapeutic Target and Biomarker in Diazepam-Refractory Status Epilepticus with Wide Time Window.

Status epilepticus (SE), a life-threatening neurologic emergency, is often poorly controlled by the current pharmacological therapeutics, which are limited to a narrow time window. Here, we investigated the proinflammatory cytokine high mobility group box-1 (HMGB1) as a candidate therapeutic target for diazepam (DZP)-refractory SE. We found that HMGB1 was upregulated and translocated rapidly during refractory SE period. Exogenous HMGB1 was sufficient to directly induce DZP-refractory SE in nonrefractory SE. Neutralization of HMGB1 with an anti-HMGB1 monoclonal antibody decreased the incidence of SE and alleviated the severity of seizure activity in DZP-refractory SE, which was mediated by a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, anti-HMGB1 mAb reversed DZP-refractory SE with a wide time window, extending the therapeutic window from 30 to 180 min. Furthermore, we found the upregulation of plasma HMGB1 level is closely correlated with the therapeutic response of anti-HMGB1 mAb in DZP-refractory SE. All these results indicated that HMGB1 is a potential therapeutic target and a useful predictive biomarker in DZP-refractory SE.

Factors affecting mortality of refractory status epilepticus.

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

First Attack of Status Epilepticus in Adults: Etiology and Risk Factors

AbstractBackground: Status Epilepticus (SE) is a common life-threatening neurological emergency the etiology of SE varies according to age and prior history of seizures. In people known to be epileptic poor compliance and drug withdrawal are the commonest causes of SE. On the other hand in patients with no prior seizure history strokes, head traumas, CNS infections, cardiac arrests and metabolic disturbances are the most com-mon causes.Aim of Study: Is to study the possible etiologies and outcome of first attack of SE in adults.Patients and Methods: This was a 6-month duration cross sectional study done at Neuropsychiatry Department, Tanta University Hospital, started from July 2016. All patients presented by first attack of SE over the age of 18 years and didn't have previous history of SE, were considered.Results: Of 42 patients included in the study 35 (83.3%) had non refractory SE while 7 (16.7%) had RSE. 37 patients survived (88.1%) and 5 patients died (11.9%). Analysis of statistically significant and most clinically important variables showed that these factors were significantly higher in RSE, cryptogenic etiology (p=0.024), EEG changes (p=0.015). number of AEDs (p=0.001), duration of hospitalization (p= 0.037), complications due to hospitalization (p=0.015), EMSE scores (p=0.001).Conclusion: Most patients presented by SE over the age of 18 has no prior history of epilepsy. CVAs are the leading cause of de novo SE in adults followed by metabolic derange-ments. Refractory Status Epilepticus (RSE) is associated with prolonged duration of hospitalization and higher rates of complications compared to non-refractory SE. Complications due to seizures were the most common followed by side effects of AEDs while complications of prolonged hospitali-zation were the least common. EEG monitoring is an important tool both in managing and predicting the outcome of status epilepticus. STESS and EMSE scoring systems are easy to use bed side tools to help in predicting the outcome of SE.

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data.

Status epilepticus (SE) is an important medical emergency condition with particularly unfavorable outcome in refractory and superrefractory SE (SRSE). The economic impact of SE and especially of SRSE in the pediatric population remains unclear. We aimed to determine the burden of illness of SE in a pediatric patient population. Insurance records for patients aged 0-18years admitted between 2008 and 2015 were selected from a nationwide insurance research database utilizing International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for SE (G41), epilepsy (G40), or febrile convulsions (R56). Patients were further classified based on admission to the intensive care unit and use of mechanical ventilation. The algorithm identified 11693 seizure-related admissions and classified 4% as SE. Of these cases, 282 (60.4%) were classified by the algorithm as nonrefractory SE (NRSE), 125 (26.8%) as refractory SE (RSE), and 60 (12.8%) as SRSE. The crude SE incidence was 17.6/100000, with NRSE being 11.4/100000, RSE 3.9/100000, and SRSE 2.3/100000. SRSE incidence peaked in the 0- to 1-year-old age subgroup accounting for 48.3% of all pediatric SRSE admissions. The median length of stay (LOS) for all SE cases was 7days, with median 44.5days in SRSE, 5days in NRSE, and 12days in RSE. Mean admission costs for total SE were €15880, with a mean expense for SRSE of €75358, for NRSE of €4119, and for RSE of €13864. The mean LOS for non-SE epilepsy admissions was 3days, with mean costs of €2697 for epilepsy and €1614 for febrile convulsion admissions. There were no deaths in non-SE and NRSE admissions, whereas the overall mortality for SE was 3%, with 5.6% in RSE and 11.7% in SRSE. Although cases classified as SE represented 4% of the seizure-associated admissions, they accounted for 22% of the overall costs. These costs were disproportionately represented by SRSE cases, which accounted for 62% of all SE-associated costs.

Weaning from antiseizure drugs after new onset status epilepticus.

In patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE). Retrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected. One hundred seventy-seven patients with mean age 63±18years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow-up was 3.8±3.2years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow-up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P=0.009) and those with RSE (P=0.048, odds ratio = 2.12, 95% confidence interval = 1.00-4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence. We found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

Oxidative stress in status epilepticus: A clinical-radiological correlation

PurposeTo report oxidative stress in the patients with status epilepticus (SE), and correlate these with severity, MRI and outcome. MethodsThirty-five patients with SE and 34 controls were included. Blood sample was collected at admission for measuring superoxide dismutase (SOD), catalase, protein carbonyl, glutathione, total antioxidant capacity (TAC), malondialdehyde (MDA) and nitric oxide (NO). The type of SE, duration and Status Epilepticus Severity Score (STESS) at admission and refractoriness to treatment were noted. Cranial magnetic resonance imaging (MRI) findings, in-hospital deaths and disability at discharge were noted. ResultsThe median age of the patients was 35 and 14 were females. The median STESS was 3 (0–5), and the score was unfavorable in 21(60%) patients. MRI was abnormal in 27(77%) patients. The patients with SE had significantly lower concentrations of SOD, catalase, protein carbonyl, GSH and TAC and higher concentrations of MDA and NO compared to the controls. These levels did not differ between refractory and non-refractory SE. Glutathione level inversely correlated with age. Malondialdehyde and NO levels positively correlated with age and inversely with GSH level. Five (14.3%) patients died in hospital. At discharge, 14 patients had good and 16 had poor outcome. The oxidative stress markers did not correlate with death or disability. ConclusionOxidative stress is increased in the patients with SE. Further study is needed in larger sample size to explore probable adjunctive treatment option.

Status epilepticus associated with acute encephalitis: long-term follow-up of functional and cognitive outcomes in 72 patients.

Continued care in patients with encephalitis and prolonged status epilepticus (SE) is controversial. Limited data are available on the functional and cognitive outcomes. In a prospective cohort study from 2007 to 2016, patients with acute encephalitis and SE were reviewed. Long-term outcomes including motor disability (modified Rankin Scale, mRS), daily living skills (activities of daily living, ADL), cognitive ability (modified Telephone Interview for Cognitive Status, TICS-M) and epilepsy sequelae were evaluated in survivors at the 12-month follow-up. At the 12-month follow-up, 72 patients were recruited who got a median score of 14 on the total ADL. 68% patients remained independent in their daily activities (mRS ≤ 2). Post-SE symptomatic epilepsy was observed in 49% of patients. Sixty-two patients achieved a median score of 40 on the TICS-M and 14 on the TICS-M Memory. Patients with autoimmune encephalitis were less prone to post-SE symptomatic epilepsy (18% vs. 58%, P = 0.005) but had lower TICS-M Memory score than those with viral encephalitis (8.5 vs. 15, P = 0.017). Compared to non-refractory status epilepticus (non-RSE), patients with RSE had a longer stay in the neurocritical care unit (39 vs. 26, P = 0.002), more in-hospital complications and post-SE symptomatic epilepsy (67% vs. 33%, P = 0.005). Long-term outcomes including ADL, mRS and TICS-M were not significantly different between patients with RSE and non-RSE or between patients with long (≥4 h) and short (<4 h) duration of SE. Survival with favorable functional recovery was promising after prolonged RSE in patients with acute encephalitis.

Seizure outcomes in patients with anti‐NMDARencephalitis: A follow‐up study

To evaluate the long-term seizure outcome and potential factors associated with seizure outcome in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. In the setting of a prospective, single-center, longitudinal cohort study, 109 patients were evaluated with ongoing follow-up. Patients underwent clinical evaluation every 3 months. Seizure outcomes and the potential risk factors were assessed with a median follow-up of 24 months (6-60 months). Of 109 patients (47 men; 62 women) with anti-NMDAR encephalitis, 88 patients (80.7%) had reported seizures at acute phase, including single seizure (17/88, 19.3%), repetitive seizures (27/88, 30.7%), nonrefractory status epilepticus (22/88, 25%), refractory status epilepticus (SE; 13/88, 14.8%), and super refractory status epilepticus (9/88, 10.2%). Seizure was more likely to recur in patients with tumor presence, status epilepticus (SE) development, coma, or intensive care unit (ICU) admission in the acute phase (p < 0.05). Seizure freedom was achieved within 2 years in all patients. More than 80% of the whole cohort with acute seizures had their last seizure within 6 months of disease onset. Seizure is a common feature in the acute stage of anti-NMDAR encephalitis but not thereafter. The presence of tumor, SE, coma, and/or ICU admission in the acute phase predicts early seizure occurrence after the acute phase. Seizure freedom was typically achieved in our follow-up, and long-term use of antiepileptic drugs may not be necessary.

Socioeconomic Outcome and Quality of Life in Adults after Status Epilepticus: A Multicenter, Longitudinal, Matched Case-Control Analysis from Germany.

There is a lack of data concerning socioeconomic outcome and quality of life (QoL) in patients after status epilepticus (SE) in Germany. Adult patients treated between 2011 and 2015 due to SE at the university hospitals in Frankfurt, Greifswald, and Marburg were asked to fill out a questionnaire regarding long-term outcome of at least 3 months after discharge. The SE cohort consisted of 25.9% patients with an acute symptomatic, 42% with a remote symptomatic and previous epilepsy, 22.2% with a new-onset remote symptomatic, and 9.9% with other or unknown etiology. A matched case-control analysis was applied for comparison with patients with drug refractory epilepsy and seizure remission, both not previously affected by SE. A total of 81 patients (mean age: 58.7 ± 18.0 years; 58% female) participated. A non-refractory course was present in 59.3%, while 27.2% had a refractory SE (RSE) and 13.6% had a superrefractory SE (SRSE). Before admission, a favorable modified Rankin Scale (mRS) of 0-3 was found in 82.7% (67/81), deteriorating to 38.3% (31/81) (p = 0.003) at discharge. The majority returned home [51.9% (42/81)], 32.1% entered a rehabilitation facility, while 12.3% were transferred to a nursing home and 3.7% to another hospital. The overall mRS at follow-up did not change; 61.8% (45/74) reached an mRS of 0-3. In RSE and SRSE, the proportion with a favorable mRS increased from 45.5% at discharge to 70% at follow-up, while QoL was comparable to a non-refractory SE course. Matched epilepsy controls in seizure remission were treated with a lower mean number of anticonvulsants (1.3 ± 0.7) compared to controls with drug refractory epilepsy (1.9 ± 0.8; p < 0.001) or SE (1.9 ± 1.1; p < 0.001). A major depression was found in 32.8% of patients with SE and in 36.8% of drug refractory epilepsy, but only in 20.3% of patients in seizure remission. QoL was reduced in all categories (QOLIE-31) in SE patients in comparison with patients in seizure remission, but was comparable to patients with drug refractory epilepsy. Patients after SE show substantial impairments in their QoL and daily life activities. However, in the long term, patients with RSE and SRSE had a relatively favorable outcome comparable to that of patients with a non-refractory SE course. This underlines the need for efficient therapeutic options in SE.

The Clinical Characteristics and Prognostic Analysis of Status Epilepticus in Northeast China

Objective: Status epilepticus (SE) is a neurological emergency that may cause severe neurological deficiency and even death. The aim of this study was to analyze the clinical characteristics and prognosis of SE in northeast China. Additionally, the etiology and classification are discussed. Materials and Methods: We retrospectively collected the clinical profiles of patients diagnosed with SE in the Epilepsy Center of Jilin University between January 2011 and May 2015. The causes and clinical courses were investigated. The individuals were followed up by visit or telephone, and the prognoses were analyzed. Results: A total of 223 patients with SE were enrolled, including 134 cases with non-refractory SE (NRSE) and 89 cases with refractory or super-refractory SE (RSE/SRSE). Fifteen patients died during hospitalization, yielding a mortality of 6.73%; 11 of them succumbed to multiple organ dysfunction syndrome (MODS). Statistical analysis showed significant differences in age, family history of epilepsy, and the incidence of non-convulsive SE (NCSE) between the NRSE group and RSE/SRSE group (p < 0.05). We found no significant differences in the causes of SE (central nervous system infection, autoimmune encephalitis, and epilepsy) between these 2 groups. Conclusion: In northeast China, SE is associated with relatively lower mortality, and MODS is the major cause of death. Older age and NCSE are risk factors predicting potential progression to RSE. Central nervous system infection, autoimmune encephalitis, and epilepsy were common causes of SE, but there was no significant association between any of these causes and the occurrence of RSE.

Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany.

Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was €4,063 for nonrefractory SE, €4,581 (p<0.001) for RSE, and €32,706 (p<0.001) for SRSE. Median length of stay varied significantly between 8days (mean = 13.6) in nonrefractory SE, 14days in RSE, and up to 37days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p<0.001) in RSE and 39.9% (p<0.001) in SRSE. This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE.

The Treatment and Prognosis of Refractory and Super-Refractory Status Epilepticus

AbstractRefractory status epilepticus (RSE) is defined as status epilepticus (SE) persisting over 60 min and resistant to treatment with benzodiazepines and non-sedating antiepileptic drugs. The term super-refractory status epilepticus (SRSE) refers to a refractory episode continuing under general anesthesia for more than 24 h. RSE is treated with a combination of non-sedating AED and i. v. anesthetics; first choice drugs are midazolam, propofol and thiopental. The management of super-refractory status epilepticus (SRSE) is challenging as clear evidence-based guidelines are lacking. Recommendations are mainly based on case reports and small case series. Therapeutic options include ketamine, inhalational anesthetics, steroids and immunoglobulins. Ketogenic diet, electroconvulsive therapy and epilepsy surgery are also considered as potentially effective. A promising new approach is the neurosteroid allopregnanolone. Mortality of RSE and SRSE is largely influenced by the etiology and is markedly higher as compared to non-refractory status epilepticus. It was reported to be about 30% and 50%, respectively.

Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany.

To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise.

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.

Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.

While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled.

Study on etiology and treatment of convulsive status epilepticus in children

The clinical data of 182 children with convulsive status epilepticus (CSE) were analyzed. There were 21 cases with refractory status epilepticus (RSE) and 161 cases with non-refractory status epilepticus (non-RSE). Etiological factors mainly included epilepsy in 54 cases, intracranial infection in 49 cases, and complex febrile seizure in 44 cases. In the ictal stage, 102 cases were treated with clonazepam by intravenous injection, 54 cases with diazepam by intravenous injection, 46 cases with midazolam by intravenous injection, 36 cases with phenobarbital by muscular injection, and 32 cases with 6.5% chloral hydrate by nosal feeding or clyster. The etiology of CSE in children is various. Epilepsy, intracranial infection and complex febrile seizure are the main causes. Poor prognosis and high mortality often occur in RSE caused by severe viral encephalitis. So the fundamental principle of treatment is to control CSE quickly and avoid the damage of brain and other important organs. DOI: 10.3969/j.issn.1672-6731.2015.11.009