Alan R. Towne

A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia

This report presents the initial analysis of a prospective, population-based study of status epilepticus (SE) in the city of Richmond, Virginia. The incidence of SE was 41 patients per year per 100,000 population. The frequency of total SE episodes was 50 per year per 100,000 population. The mortality rate for the population was 22%, 3% for children and 26% for adults. Evaluation of the seizure types for adult and pediatric patients demonstrated that both partial and generalized SE occur with a high frequency in these populations. Based on the incidence of SE actually determined in Richmond, Virginia, we project 126,000 to 195,000 SE events with 22,200 to 42,000 deaths per year in the United States. The majority of SE patients had no history of epilepsy. These results indicate that SE is a common neurologic emergency. NEUROLOGY 1996;46: 1029-1035

Prevalence of nonconvulsive status epilepticus in comatose patients

Background: Nonconvulsive status epilepticus (NCSE) is a form of status epilepticus (SE) that is an often unrecognized cause of coma. Objective: To evaluate the presence of NCSE in comatose patients with no clinical signs of seizure activity. Methods: A total of 236 patients with coma and no overt clinical seizure activity were monitored with EEG as part of their coma evaluation. This study was conducted during our prospective evaluation of SE, where it has been validated that we identify over 95% of all SE cases at the Medical College of Virginia Hospitals. Only cases that were found to have no clinical signs of SE were included in this study. Results: EEG demonstrated that 8% of these patients met the criteria for the diagnosis of NCSE. The study included an age range from 1 month to 87 years. Conclusions: This large-scale EEG evaluation of comatose patients without clinical signs of seizure activity found that NCSE is an under-recognized cause of coma, occurring in 8% of all comatose patients without signs of seizure activity. EEG should be included in the routine evaluation of comatose patients even if clinical seizure activity is not apparent.

Determinants of Mortality in Status Epilepticus

Summary: Using univariate and multivariate regression analysis, we studied seizure duration, seizure type, age, etiologies, other clinical features, and mortality among 253 adults with status epilepticus (SE) admitted to the Medical College of Virginia. Cerebral vascular disease and discontinuation of antiepileptic drugs (AEDs) were the most prominent causes of SE, each accounting for ∼22% of all patients in the series. The other principle etiologies were alcohol withdrawal, idiopathic, anoxia, metabolic disorders, hemorrhage, infection, tumor, drug overdose, and trauma. When the patients were divided into two groups, the group with SE lasting < 1 h had a lower mortality as compared with seizure duration ≥ 1 h. Low mortality rates were noted in alcohol and AED discontinuation etiologies. Anoxia and increasing age were significantly correlated with higher mortality. The mortality rates of partial and generalized SE were not significantly different. Race and sex did not affect mortality significantly. Our findings represent the first multivariate analysis of predictive indicators of mortality in SE and demonstrate that specific factors influence mortality rate in SE.

Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus

Summary: Purpose: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures.

Epidemiology of status epilepticus.

Summary: This study presents a review of the epidemiology of status epilepticus (SE) in Richmond, Virginia, U.S.A. The data summarize some of the first population‐based information on the natural presentation of SE in a controlled community setting. SE occurred with an absolute incidence rate of 41 patients per 100,000 residents per year in Richmond. The frequency of total SE occurrences was 50 patients per 100,000 residents per year. Overall mortality in this population was 22%. Absolute incidence and occurrences of SE in this population were shown to be underestimates due to the inability, for multiple reasons, to document all cases of SE. Based on the Richmond data, the number of SE cases, frequencies of occurrence, and deaths per year occurring in the United States were estimated to be 102,000‐152,000, 125,000‐195,000, and 22,000‐42,000, respectively. In Richmond, nonwhites had a much higher incidence of SE than did whites. Partial SE was the most common form of seizure initiating SE. Age and etiology were also found to contribute to mortality. Infants <1 year of age had the highest incidence of SE, but the elderly population represented the largest number of SE cases. This study provides a review of the first prospective, population‐based, epidemiological data on SE and shows that SE is a major medical and neurological emergency in both academic and community hospital settings.

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.

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.

Epidemiological and medical aspects of epilepsy in the elderly

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.

The use of topiramate in refractory status epilepticus

In cases of refractory status epilepticus (RSE) unresponsive to sequential trials of multiple agents, a suspension of topiramate administered via nasogastric tube was effective in aborting RSE, including one patient in a prolonged pentobarbital coma. Effective dosages ranged from 300 to 1,600 mg/d. Except for lethargy, no adverse events were reported.

Synergistic effect of status epilepticus and ischemic brain injury on mortality

Ischemic brain injury (stroke) is a major cause of status epilepticus (SE). In our database of 529 adult SE cases, acute or remote cerebrovascular accidents (CVA) were a primary cause of SE for 41% of the patients overall and for 61% of the elderly patients. SE in the setting of acute CVA has a very high mortality, approaching 35%. The degree to which mortality can be attributed to the severity of the underlying CVA etiology vs. the effect of SE has not been evaluated. To address this issue, we prospectively studied patients with SE and acute CVA and compared them to control populations with acute CVA alone or with SE and remote CVA. The groups did not significantly differ with regard to age, sex, or radiographic lesion size. Mortality was unrelated to lesion size in the CVA and SE group. Overall, acute CVA and SE patients had an almost three-fold increase in mortality compared to the CVA group and an eight-fold increase compared to the SE and the non acute (remote) CVA group. Logistic regression analysis demonstrated a statistically significant synergistic effect of SE and CVA on mortality. This is the first study to document that the high mortality of SE and acute CVA is not solely due to the severity of the underlying CVA etiology, but due to the synergistic effect of combined injuries from SE and cerebral vascular ischemia.