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

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

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

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

Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice.

Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the in vitro evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the in vivo assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The in vitro results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the in vivo studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The in vitro confirmed protective effect of C11 on astrocytes, as well as the in vivo demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.

Clinical predictors of adverse events during continuous video-EEG monitoring in an epilepsy unit.

Patients admitted to epilepsy monitoring units (EMUs) for diagnostic and presurgical evaluation have an increased risk of seizure-related injury, particularly in the many cases in which medication is withdrawn. The purpose of this study was to assess the prevalence of adverse events (AEs) in this setting and to analyse associated clinical factors and costs. We evaluated consecutive patients admitted to an EMU at a tertiary care hospital over a 10-year period based on a descriptive, longitudinal study. We analysed the occurrence of AEs (traumatic injury, psychiatric complications, status epilepticus, cardiorespiratory disturbances, and death), investigated potential risk factors using univariate and multivariate logistic regression analysis, and compared admission costs between patients with and without AEs. In total, 411 EMU admissions were studied corresponding to 352 patients (55% women; mean [SD] age: 41.7 [12.1] years). Twenty-five patients (6%) experienced an AE. The most common event was traumatic injury (n=9), followed by status epilepticus (n=8), psychiatric complications (n=7), and cardiorespiratory disturbances (n=1). On comparing patients with and without AEs, we observed that the former were more likely to experience generalized seizures (OR: 7.81; 95% CI: 3.51-12.23; p<0.001) or have more seizures overall during admission (OR: 3.2; 95% CI: 1.42-6.8; p=0.002). Patients with AEs also had longer EMU stays (6.91 [2.64] vs 5.08 [1.1]; p=0.004), longer hospital stays (8.45 [3.6] vs 5.18 [1.2]; p<0.001), and higher costs (€7277.71 [€2743.9] vs €5175.7 [€1182.5]; p<0.001). Patients with generalized seizures and more seizures during admission were at greater risk of AEs, which were associated with higher admission costs.

Etiological assessment of status epilepticus.

Status epilepticus (SE) is a potentially serious condition that can affect vital and functional prognosis and requires urgent treatment. Etiology is a determining factor in the patient's functional outcome and in almost half of all cases justifies specific treatment to stop progression. Therefore, identifying and addressing the cause of SE is a key priority in SE management. However, the etiology can be difficult to identify among acute and remote causes, which can also be multiple and interrelated. The most common etiologies are the discontinuation of antiepileptic medication in patients with a prior history of epilepsy, and acute brain aggression in cases of new onset SE (cerebrovascular pathologies are the most common). The list of remaining possible etiologies includes heterogeneous pathological contexts. Refractory SE and especially New-Onset Refractory Status Epilepticus (NORSE) lead to an extension of the etiological assessment in the search for encephalitis of autoimmune or infectious origin in adults and in children, as well as a genetic pathology in children in particular. This is an overview of current knowledge of SE etiologies and a pragmatic approach for carrying out an etiological assessment based on the following steps: - Which etiological orientation is identified according to the field and clinical presentation?; - Which etiologies to look for in an inaugural SE?; - Which first-line assessment should be carried out? The place of the biological, EEG and imaging assessment is discussed; - Which etiologies to look for in case of refractory SE?

Arterial Spin Labeling Magnetic Resonance Imaging in the Assessment of Non-Convulsive Status Epilepticus in Alzheimer's Disease: A Report of Two Cases.

BACKGROUND The diagnosis of early non-convulsant status epilepticus (NCSE) can be challenging and can overlap with other critical conditions. Two patients with Alzheimer's disease are reported with clinically suspected NCSE presenting in the emergency setting who were diagnosed using arterial spin-labeling magnetic resonance imaging (ASL-MRI) sequences. CASE REPORT In Case 1, a 69-year-old woman with mild Alzheimer's disease and diabetes presented with acute worsening of cognitive status and fluctuating level of consciousness. In Case 2, a 70-year-old man with mild cognitive impairment due to Alzheimer's disease and hypertension presented with acute loss of consciousness and left hemiparesis, without evidence of hypoglycemia or a hypertensive crisis. In both cases, ASL-MRI perfusion images showed focal cerebral hyperperfusion in the posterior cingulate and parietal associative cortex, which involved neurodegenerative areas associated with epilepsy in early Alzheimer's disease. In both cases, the patients developed generalized tonic-clonic epileptic seizures that lasted for 5 minutes or more, which indicated the emergence of status epilepticus that developed from the initial presentation of NCSE. In both cases, electroencephalogram (EEG) findings confirmed that the seizures were controlled by intravenous administration of antiepileptic drugs. Both patients discharged home from the hospital without recurrence of seizures, between 10-12 days after the onset of symptoms. CONCLUSIONS These two cases have demonstrated that ASL-MRI is feasible as an emergency diagnostic tool in clinically suspected NCSE in patients with Alzheimer's disease.

Baseline and outcome assessment in pediatric status epilepticus.

PURPOSE: To summarize different aspects of short and long-term outcomes associated with SE, including mortality, recurrence, subsequent epilepsy, neurocognitive dysfunction, imaging abnormalities, and health-related quality of life. METHODS: We searched MEDLINE for studies that assessed the short-term and long-term outcome of status epilepticus in pediatric population, including mortality, recurrence of seizure and status epilepticus, neurological, cognitive, or behavioral impairment, and health-related quality of life. We excluded studies that exclusively assessed the adult population. RESULTS: Mortality in pediatric SE is relatively low, while morbidity poses more challenges. The underlying cause of SE has been shown to be a major determinant in the outcome after SE. However, it is difficult to establish the net effect of SE on outcome due to the heterogeneity of the studies. Notably, this review highlights that health-related quality of life, an important aspect of long-term outcome in pediatric SE, is under-addressed and merits further investigation. CONCLUSION: There is a need to acquire high-quality long-term data evaluating QoL, neuroimaging, use of continuous infusions, and cognitive and behavioral outcome of children who experience SE.

The burden of pediatric status epilepticus: Epidemiology, morbidity, mortality, and costs.

PURPOSE: To summarize the epidemiology, morbidity, mortality, and costs of status epilepticus (SE) in the pediatric population. METHOD: Review of the medical literature. RESULTS: The overall incidence of pediatric SE is roughly 20 per 100,000 children per year, with overall mortality of 3%. Underlying etiology is the biggest risk factor for SE, with symptomatic (acute > remote) etiologies associated with worse outcomes. The most common cause of SE in children is febrile SE, though this entity occurs primarily in early childhood. After a first episode, the risk of recurrence is similar to the risk after a first unprovoked seizure (25-40%). SE is expensive, regularly costing more than $10,000 per episode and often more than $100,000 for refractory cases. CONCLUSION: SE is not an uncommon neurologic emergency and depending on the associated etiology can carry significant morbidity, mortality, and cost especially if treatment is not performed in a timely manner.

Long-term outcomes of status epilepticus: A critical assessment.

We reviewed 37 studies reporting long-term outcomes after a status epilepticus (SE) episode in pediatric and adult populations. Study design, length of follow-up, outcome measures, domains investigated (mortality, SE recurrence, subsequent epilepsy, cognitive outcome, functional outcome, or quality of life), and predictors of long-term outcomes are summarized. Despite heterogeneity in the design of prior studies, overall risk of poor long-term outcome after SE is high in both children and adults. Etiology is the main determinant of outcome, and the effect of age or SE duration is often difficult to distinguish from the underlying cause. The effect of the treatment on long-term outcome after SE is still unknown.

Impact of Prior Authorization of Antiepileptic Drugs in Children With Epilepsy.

OBJECTIVE: We assessed how commonly prior authorization results in treatment delay or missed doses in children with epilepsy. METHODS: Parents of 462 children followed in a pediatric epilepsy clinic were surveyed regarding prior authorization in the preceding year. Epilepsy and insurance details were collected. If prior authorization was required, parents were asked whether it resulted in (1) delayed initiation of a newly-prescribed antiepileptic drug, and/or (2) lapse in coverage of a current medication. Prior authorization was defined as smooth if there was a less than seven day delay in starting a new antiepileptic drug and no lapse in coverage of a current medication. RESULTS: A total of 164 families (35%) returned completed surveys. Mean age of the children was 11.2 (S.D. 5.3) years and 67.4% experienced seizures more than every three months despite trials of two or more antiepileptic drugs. Primary insurance was private in 82.9% and Medicaid in 15.2%. Prior authorization was required in 63 (38.4%) cases, and proceeded smoothly in only 31 (49.2%). Twenty-three children experienced a delay of seven days or more in starting a new drug, and 24 experienced a lapse in coverage of their current medication, 11 of whom missed doses. Of these 11, seven had increased seizures, and one required hospital admission for status epilepticus. CONCLUSIONS: Prior authorization of antiepileptic drugs is common but problematic, often resulting in either a delay of initiation of a new antiepileptic drug or a lapse in coverage of a currently-used antiepileptic drug, with a negative impact on seizure control.

Cost of status epilepticus in a tertiary care hospital in India.

PURPOSE: Status epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. METHODS: SE was defined as continuous seizure for ≥ 5 min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. RESULTS: Fifty-five patients aged 8-90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3-6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1-72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600-574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. CONCLUSION: Acute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation.

Clinical decision making in seizures and status epilepticus.

Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting.

Multimodal MRI assessment of damage and plasticity caused by status epilepticus in the rat brain.

Status epilepticus or other brain-damaging insults launch a cascade of events that may lead to the development of epilepsy. MRI techniques available today, including T(2) - and T(1) -weighted imaging, functional MRI, manganese enhanced MRI (MEMRI), arterial spin labeling (ASL), diffusion tensor imaging (DTI), and phase imaging, can detect not only damage caused by status epilepticus but also plastic changes in the brain that occur in response to damage. Optimal balance between damage and recovery processes is a key for planning possible treatments, and noninvasive imaging has the potential to greatly facilitate this process and to make personalized treatment plans possible.

Ethics roundtable: 'Open-ended ICU care: can we afford it?'.

THE CASE: The patient is a 27-year-old previously healthy male with a diagnosis of viral encephalitis with a lymphocytic pleocytosis on cerebrospinal fluid examination. For 3 months, he has been in status epilepticus (SE) on high doses of barbiturates, benzodiazepines, and ketamine and a ketogenic feeding-tube formula. He remains in burst suppression on continuous electroencephalography (EEG). He is trached and has a percutaneous endoscopic gastrostomy (PEG) feeding tube. He has been treated several times for pneumonia, and he is on a warming blanket and is on vasopressors to maintain his blood pressure. His vitals are stable and his lab work is within limits. The sedation is decreased under EEG guidance every 72 hours, after which he goes back into SE and heavy sedation is resumed. The latest magnetic resonance imaging (MRI) shows edema but otherwise no obvious permanent cortical damage. The family wants a realistic assessment of the likely outcome. The neurologist tells them the literature suggests the outlook is poor but not 100% fatal. As long as all of his other organs are functioning on life support, there is always a chance the seizures will stop at some time in the future, and so the neurologist recommends an open-ended intensive care unit (ICU) plan and hopes for that outcome.

A scoring system for early prognostic assessment after neonatal seizures.

OBJECTIVE: The aim of this study was to devise a scoring system that could aid in predicting neurologic outcome at the onset of neonatal seizures. METHODS: A total of 106 newborns who had neonatal seizures and were consecutively admitted to the NICU of the University of Parma from January 1999 through December 2004 were prospectively followed-up, and neurologic outcome was assessed at 24 months' postconceptional age. We conducted a retrospective analysis on this cohort to identify variables that were significantly related to adverse outcome and to develop a scoring system that could provide early prognostic indications. RESULTS: A total of 70 (66%) of 106 infants had an adverse neurologic outcome. Six variables were identified as the most important independent risk factors for adverse outcome and were used to construct a scoring system: birth weight, Apgar score at 1 minute, neurologic examination at seizure onset, cerebral ultrasound, efficacy of anticonvulsant therapy, and presence of neonatal status epilepticus. Each variable was scored from 0 to 3 to represent the range from "normal" to "severely abnormal." A total composite score was computed by addition of the raw scores of the 6 variables. This score ranged from 0 to 12. A cutoff score of > or =4 provided the greatest sensitivity and specificity. CONCLUSIONS: This scoring system may offer an easy, rapid, and reliable prognostic indicator of neurologic outcome after the onset of neonatal seizures. A final assessment of the validity of this score in routine clinical practice will require independent validation in other centers.

Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: To review evidence on the assessment of the child with status epilepticus (SE). METHODS: Relevant literature were reviewed, abstracted, and classified. When data were missing, a minimum diagnostic yield was calculated. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Laboratory studies (Na(++) or other electrolytes, Ca(++), glucose) were abnormal in approximately 6% and are generally ordered as routine practice. When blood or spinal fluid cultures were done on these children, blood cultures were abnormal in at least 2.5% and a CNS infection was found in at least 12.8%. When antiepileptic drug (AED) levels were ordered in known epileptic children already taking AEDs, the levels were low in 32%. A total of 3.6% of children had evidence of ingestion. When studies for inborn errors of metabolism were done, an abnormality was found in 4.2%. Epileptiform abnormalities occurred in 43% of EEGs of children with SE and helped determine the nature and location of precipitating electroconvulsive events (8% generalized, 16% focal, and 19% both). Abnormalities on neuroimaging studies that may explain the etiology of SE were found in at least 8% of children. RECOMMENDATIONS: Although common clinical practice is that blood cultures and lumbar puncture are obtained if there is a clinical suspicion of a systemic or CNS infection, there are insufficient data to support or refute recommendations as to whether blood cultures or lumbar puncture should be done on a routine basis in children in whom there is no clinical suspicion of a systemic or CNS infection (Level U). AED levels should be considered when a child with treated epilepsy develops SE (Level B). Toxicology studies and metabolic studies for inborn errors of metabolism may be considered in children with SE when there are clinical indicators for concern or when the initial evaluation reveals no etiology (Level C). An EEG may be considered in a child with SE as it may be helpful in determining whether there are focal or generalized epileptiform abnormalities that may guide further testing for the etiology of SE, when there is a suspicion of pseudostatus epilepticus (nonepileptic SE), or nonconvulsive SE, and may guide treatment (Level C). Neuroimaging may be considered after the child with SE has been stabilized if there are clinical indications or if the etiology is unknown (Level C). There is insufficient evidence to support or refute routine neuroimaging in a child presenting with SE (Level U).