Status Epilepticus in Children,Adults, and the Elderly

Summary: Status epilepticus (SE) is a major neurological and medical emergency associated with a high morbidity and mortality. Retrospective and prospective studies from the Medical College of Virginia Epilepsy Research Center have been utilized to investigate several clinical and epidemiological factors associated with SE. Univariate and multivariate logistic regression analysis of predictive indicators in patients with SE indicated that seizure duration, certain specific etiologies, and age were predictors of mortality. Sex, race, and certain other etiologies were not found to be factors that significantly affect mortality. These findings demonstrate that specific indicators are important in predicting mortality in SE. Preliminary prospective epidemiological data from Richmond, Virginia suggested that more than 250,000 cases of SE may occur annually in the United States with a mortality greater than 55,000 individuals. Studies comparing community and university hospitals in Richmond indicate that the mortality and clinical variables associated with SE in these two hospital populations are essentially identical. Further investigations employing prospective population-based studies are essential in evaluating the epidemiology and mortality of SE.     

Duration of refractory status epilepticus and outcome: Loss of prognostic utility after several hours

Purpose:   Outcome for patients with status epilepticus (SE) depends strongly on etiology. Duration of SE is also predictive, at least in the first 2 h, but beyond this it is unclear that duration of SE influences outcome significantly. We sought to determine the influence of duration of SE on outcome in patients with prolonged SE, and to compare this influence with that of other factors.
Methods:   We reviewed the clinical course and outcome of 119 patients with SE, diagnosed by both clinical manifestations and electroencephalography (EEG) evidence. Using univariate and multivariate analyses, we sought predictors of outcome (survival vs. death or vegetative state) among age, etiology (epilepsy, anoxia or severe hypoxia, or other), presence of earlier epilepsy, multiple medical problems, presentation in coma, and type of SE (focal or generalized).
Results:   Median duration of SE was 48 h. Survival was greater with a shorter duration, especially when <10 h (69% vs. 31% for longer duration; p < 0.05). Epilepsy as the etiology, and an earlier diagnosis of epilepsy offered a favorable prognosis (p < 0.01), but only the former on multivariate analysis. Coma and SE caused by anoxia/hypoxia were unfavorable factors. Once corrected for etiology, presentation in coma, and type of SE (focal or generalized), duration of SE did not have a significant effect on outcome. Overall mortality was high, 65%, but 10 patients survived SE lasting over 3.5 days.
Conclusions:   A duration of <10 h was associated with better outcome in SE, but this was not significant once etiology, presentation in coma, and type of SE were accounted for. Etiology of SE is still the primary determinant of outcome. Unless it follows anoxia, prolonged SE should not be considered a hopeless condition.     

Pediatric status epilepticus: a perspective from Saudi Arabia

The purpose of this study was to assess risk factors and management of status epilepticus and non–status epilepticus seizures at a community hospital in Saudi Arabia. The research design was a prevalence study of a convenience sample of pediatric seizure episodes admitted to a 350-bed hospital from 1992 to 1997. The mean age at presentation was 2 years, 10 months, 43% of patients had no history of seizures, and 17% were transferred from other hospitals. Fifty-nine (28%) of 212 seizure episodes were status epilepticus (SE). These SE episodes were significantly more likely than non–SE episodes to be associated with a history of seizures, prior antiepileptic drug (AED) therapy, the presence of an acute etiology, and prolonged duration of seizures before hospitalization. SE episodes were also significantly more likely than non–SE episodes to receive an inappropriate AED, to require intensive care unit admission, to suffer morbidity, and to have SE recurrence at follow-up; however, the difference in mortality was not significant. In conclusion, children with SE were more likely than those with non–SE seizures to have a history of seizures and acute brain insults, prolonged seizure duration before hospitalization, and less optimal management and outcomes. Management of SE in this referral population can be improved by more rapid access to appropriate medical care.     

Prospective Population-Based Study of Intermittent and Continuous Convulsive Status Epilepticus in Richmond, Virginia

PURPOSE: Previous work suggested that there is a lower mortality for convulsive status epilepticus (SE) with intermittent seizures (intermittent SE) as opposed to SE with continuous seizure activity (continuous SE). A plausible hypothesis to explain this difference is that the shorter ictal time in intermittent SE is responsible for the lower mortality in this group. This study investigates the relative contributions of total ictal time and SE duration to the differing mortalities of intermittent and continuous SE. METHODS: Six hundred forty-five cases of prospectively identified convulsive SE were examined. Nonparametric statistical methods were used to compare continuous SE and intermittent SE variables. Multivariate logistic regression analyses were used to determine which factors were most highly associated with mortality. Intermittent SE cases were analyzed to evaluate the relative contributions of ictal time versus SE duration to mortality. RESULTS: Intermittent SE had a significantly lower mortality than continuous SE (19.6 vs. 31.4%; p < 0.001) in adults but not in children. Intermittent and continuous SE durations did not significantly differ in adult cases but did differ in pediatric cases. Ictal time was significantly shorter than SE duration for intermittent SE in both adults and children. After adjusting for age, etiology, and SE duration, SE type (continuous SE vs. intermittent SE) was shown to have an independent effect on mortality in adults. The relative risk of mortality for continuous SE was 1.79 times that of intermittent SE (p = 0.04). After controlling for SE duration, ictal time did not significantly affect mortality in adults. CONCLUSIONS: Intermittent and continuous convulsive SE were common in both pediatric and adult populations. Intermittent SE had a significantly lower mortality than did continuous SE. This difference in mortality was not completely explained by differences in SE duration, total ictal time, etiology, or age. Further research is needed to identify the factor(s) contributing to the significant difference in mortality between intermittent SE and continuous SE.     

Comparison of Status Epilepticus with Prolonged Seizure Episodes Lasting from 10 to 29 Minutes

Summary: Purpose: Status epilepticus (SE) is a major medical and a neurologic emergency associated with significant morbidity and mortality. The current definition of SE is continuous seizure activity or intermittent seizure activity without regaining consciousness, lasting ≥30 min. Epilepsy monitoring unit data indicate that many seizures self-terminate within minutes. Thus consideration was recently given to include seizure episodes lasting ≥10 min in the definition of SE. Because no large studies have been conducted on seizures lasting 10–29 min, this study was initiated to compare cases of SE and 10 to 29-min seizure episodes seen within the same period. Methods: Patients seen at the Medical College of Virginia Hospitals of Virginia Commonwealth University over the same 2-year period were studied. Two hundred twenty-six prospective SE cases (91 children and 135 adults) and 81 retrospective 10- to 29-min seizure episodes (31 children and 50 adults) were compared. A standardized data-entry-form system was compiled on each patient and was used to evaluate the data collected. Results: The 10- to 29-min seizure patients and the SE cases had similar demographic characteristics, such as sex, race, and age, and also had similar etiologies. The majority (93%) of SE cases required anticonvulsant (AED) treatment to control and stop seizure activity. In the 10- to 29-min group, 43% stopped seizing spontaneously, and the remainder (57%) required AED treatment to stop seizure activity. The mortality for the SE patients was 19% compared with 2.6% for 10- to 29-min group (p <0.001). In the 10- to 29-min group that stopped seizing spontaneously, the mortality was 0. In the 10- to 29-min patients that required AED treatment, the mortality was 4.4%. Conclusions: The results demonstrate that a significant number of patients experience seizure activity lasting from 10- to 29-min. Approximately half of these seizure events stopped spontaneously and did not require AED treatment. The other half of the patients responded quickly to medications and stopped seizing before the 30-min definition for SE. The overall mortality of this group was significantly lower than that of the patients with SE. The results demonstrate that further studies on the 10- to 29-min seizure group are needed to differentiate seizures that will stop spontaneously and those that will only stop with AED treatment. Because almost half of the prolonged seizures stopped spontaneously, further studies are needed before including prolonged seizure activity in the definition of SE.     

Outcome of status epilepticus in children treated in the intensive care unit: a study of 302 cases

Purpose: The aim of the study was to evaluate the outcome of status epilepticus (SE) in children and to define predictors for morbidity, mortality, and SE recurrence. Methods: The study included 302 children (age 2 months to less than 18 years; mean age ± SD 4.7 ± 4.2 years) with 489 episodes of SE. Etiology, treatment, and clinical and electroencephalography (EEG) features of SE and their impact on the outcome were analyzed. The outcome was classified into three categories: unchanged neurologic status, neurologic consequences, and lethal outcome. Univariate and multivariate Cox hazard regression analyses were used to define predictors of mortality, morbidity, and SE recurrence. Key Findings: Neurologic status was unchanged in 235 children (77.8%) and neurologic consequences occurred in 39 patients (12.9%); case‐fatality ratio was 9.3% and recurrence rate was 21%. Mortality was related to progressive encephalopathy, preexisting neurologic abnormalities, specific EEG findings, and generalized convulsive type of SE. Neurologic consequences were associated with younger age, progressive encephalopathy, duration of SE >24 h, prior epilepsy, and specific EEG findings. Multivariate analyses showed that etiology of SE and prior neurologic abnormalities were independent predictors of mortality, whereas younger age, etiology, and very long duration of SE were predictors of morbidity. Significance: Outcome of SE in children is favorable in most of the cases, but mortality and morbidity rates are still high. Etiology and prior neurologic abnormalities were the main predictors of mortality, whereas the main predictor of morbidity was underlying etiology.     

Risk factors for fatality and neurological sequelae after status epilepticus in children

Using multivariate regression analysis, we examined risk factors for fatality and neurological sequelae after status epilepticus (SE) in children. Possible risk factors included sex, age at onset, the cause of SE, pyrexia, asthmatic attack during SE, past history of seizure, predisposing neurological abnormality, seizure duration, type of seizure, and medication with theophylline. Consecutive patients with SE, aged 1 month to 18 years, who were referred to Tottori University Hospital from 1984 to 2002 were reviewed. Of the 234 patients enrolled, 45 patients (19.2 %) showed poor outcomes, namely early death in 9 and neurological sequela in 36. Acute neurological insult and progressive neurological disease as the cause of SE were very significantly related to poor outcome (OR = 33.68, p = 0.000). We excluded 21 patients with the etiology of acute neurological insult and progressive neurological disease and then reanalyzed risk factors in the remaining 213 patients. Twenty-nine patients (13.6 %) showed poor outcome, namely early death in 6 and neurological sequela in 23. Seizure duration of more than 2 hours (OR = 12.73, p = 0.000) and moderate to severe asthmatic attack (OR = 31.61, p = 0.010) were associated with poor outcome. These results indicate that long-lasting seizure activity and asthmatic attack can exacerbate SE-associated brain injury.     

Randomized study of intravenous valproate and phenytoin in status epilepticus.

INTRODUCTION: The evidence based data to guide management in patients of benzodiazepine refractory status epilepticus (SE) is still lacking. We conducted a randomized study to evaluate the comparative effect of intravenous (IV) phenytoin and intravenous valproate (IV VA) in patients of benzodiazepine refractory SE. BACKGROUND AND METHODS: Hundred, age and sex matched, patients of benzodiazepine refractory SE were randomly divided into Group A (50 patients), treated with IV VA and Group B (50 patients) treated with IV phenytoin. Twelve patients, in whom SE was not controlled with a single drug, were switched over to the other group. Treatment was considered successful when all motor or EEG seizure activity ceased within 20 min after the beginning of the drug infusion and no return of seizure activity during the next 12h. Secondary study end points were adverse events to treatment, in-hospital complications and the neurological outcome at discharge. RESULTS: In this study, IV VA was successful in 88% and IV phenytoin in 84% (p>0.05) of patients of SE with a significantly better response in patients of SE <2h (p<0.05). The total number of adverse events did not differ significantly between the two groups (p>0.05). There were no differences among the treatments with respect to recurrence after 12-h study period or the outcome at 7 days. CONCLUSION: IV VA is as effective as IV phenytoin. It is easy to use, better tolerated and can be used as an alternative to IV phenytoin in patients of benzodiazepine refractory SE, especially in patients of cardio-respiratory disease. The better outcome in patients having shorter duration of SE (<2h) suggests need of immediate treatment.     

Causes of status epilepticus

Status epilepticus (SE) is the most extreme form of epilepsy. It describes a prolonged seizure that may occur in patients with previous epilepsy or in acute disorders of the central nervous system. It is one of the most common neurologic emergencies, with an incidence of up to 41 per 100,000 per year and an estimated mortality is 20%. The three major determinants of prognosis are the duration of SE, patient age, and the underlying cause. Common and easily recognized causes of SE include cerebrovascular disorders, brain trauma, infections, and low antiepileptic drug levels in patients with epilepsy. Less common causes present a clinical and diagnostic challenge, but are major determinants of prognosis. Among them, inflammatory causes and inborn errors of metabolism have gained wide interest; recent insights into these causes have contributed to a better understanding of the pathophysiology of SE and its appropriate treatment. This review focuses on the different etiologies of SE and emphasizes the importance of prompt recognition and treatment of the underlying causes.     

Comparisons of the mortality and clinical presentations of status epilepticus in private practice community and university hospital settings in Richmond,Virginia

We prospectively compared the clinical course of 119 patients treated for status epilepticus (SE) in private practice community hospitals and 344 SE patients treated in the VCU university hospitals in Richmond, Virginia USA over a 2-year period to test the hypothesis that SE presents with the same mortality and clinical patterns in both clinical settings. Of the patients reviewed, the major etiologies for SE were cerebrovascular disease, decreased anti-epileptic drug levels in epileptic patients, anoxia–hypoxia, and remote symptomatic. The other etiologies included were alcohol related, trauma, central nervous system infections, tumors, systemic infection, metabolic disorders, idiopathic, and hemorrhage. These observations provide the first direct prospective comparison of SE present in university and private practice community hospital settings in the same geographic area. Mortality was the highest in the elderly population while the pediatric population had low mortality in both clinical settings. Etiology risk factors for outcome were similar for both the populations. The data also suggest that the higher degree of illness severity in university hospitals may be associated with a higher incidence of SE, but not with mortality or a different clinical presentation of the condition. The results of this study demonstrate that SE has the same mortality and is present in an essentially identical manner in university and private practice community hospitals and underscores the fact that mortality in SE is not just associated with tertiary care hospitals and the importance of recognizing the severity of SE in the private practice setting.