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.

Estimating the economic burden of status epilepticus to the health care system.

PURPOSE: Status epilepticus (SE) is a major neurological condition associated with significant morbidity and mortality. No studies to evaluate the cost burden of SE have been performed to date. This study estimates the direct cost related to an inpatient admission for SE in an urban academic medical center. METHODS: Cases of SE were defined based on a standard 30 min or greater seizure duration. The inpatient claims data were analyzed for 192 patients admitted with SE from 1 July 1993 through 30 June 1994. Patient demographic and clinical characteristics associated with increased cost were identified using multiple regression. The direct costs for SE were compared with other common DRGs. RESULTS: The median reimbursement for a patient with SE was dollar 8417. The average length of stay for all SE patients was 12.9 days. Age groups (17-45 and 46-64) and etiology (acute CNS) were the only patient factors significantly associated with increased cost. SE patients had 30-60% higher reimbursements than patients admitted for other acute health problems including acute myocardial infarction or congestive heart failure. CONCLUSIONS: The direct inpatient costs for SE are high compared with the direct costs of admissions for other major conditions such as acute myocardial infarction or congestive heart failure. Data from this study were used to estimate a dollar 4 billion annual direct cost for inpatient admissions for SE. Given the incidence and the high costs, further more detailed evaluation of these costs may be useful in assessing the adequacy of reimbursement for this subset of patients with epilepsy.

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. CONCLUSION: This large-scale EEG evaluation of comatose patients without clinical signs of seizure activity found that NCSE is an underrecognized 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.

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.

Epidemiology of status epilepticus.

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.

Prognostic value of EEG monitoring after status epilepticus: a prospective adult study.

Despite the significant morbidity and mortality associated with status epilepticus (SE), little is known about changes in cortical function that occur after SE. We evaluated cortical function after clinical SE using continuous EEG monitoring lasting at least 24 h in 180 patients admitted to the Medical College of Virginia Hospitals (MCVH). The major EEG patterns observed after SE were a normal record, burst suppression, after SE ictal discharge (ASIDs), periodic lateralizing epileptiform discharges (PLEDs), attenuation, focal and generalized slowing, and epileptiform discharges. Normalization of the EEG after SE was highly correlated with good outcome. The presence of burst suppression and ASIDs was highly statistically significantly associated with mortality. PLEDs were also highly correlated with mortality, but not to the same degree as burst suppression and ASIDs. In addition, these EEG patterns were still significantly correlated with morbidity and mortality when we controlled for etiology using multivariate logistic statistical analysis. Persistent ictal activity was observed in many patients despite control of clinical seizure activity, indicating the importance of EEG monitoring to determine treatment patterns after clinical seizure activity in SE is controlled. The results indicate that certain EEG patterns (normalization of the EEG, ASIDs, burst suppression and PLEDs) are useful predictors of outcome in SE in addition to etiology. EEG monitoring after control of clinical SE is important to guide treatment of SE and is a useful technique for evaluating prognosis.

Hemodynamic monitoring prior to and at the time of death in status epilepticus.

Status epilepticus (SE) is a common neurological and medical emergency. Despite the significant mortality associated with SE, no human data have been available regarding cardiovascular changes prior to death in patients with this condition. This study was conducted to measure hemodynamic trends in the 24 h prior to death in a series of 24 prospectively evaluated SE patients. Two distinct cardiovascular patterns of mean arterial pressure (MAP) and heart rate (HR) were observed. Ten patients had a gradual decline in MAP and/or HR, and this group was designated as having gradual cardiac decompensation (GCD). The remaining 14 patients showed no significant changes in either MAP or HR up to the time of death. This group of patients was designated as having acute cardiac decompensation (ACD). The changes in MAP and HR over the last 24 h prior to death between the GCD and ACD groups were statistically significant. Ninety percent of the GCD patients had a history of multiple risk factors for arteriosclerotic cardiovascular disease (ASCVD), while only 30% of the ACD group had a history of multiple risk factors for ASCVD. The results provide the first human data of cardiovascular events immediately preceding death in SE patients. We propose that further investigation of the cardiovascular pathophysiology of SE may provide new therapeutic interventions which could decrease the significant mortality associated with SE.

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.

Use of intramuscular midazolam for status epilepticus.

Although intravenous (i.v.) administration of antiepileptic drugs is the preferred route of therapy in status epilepticus, intramuscular (i.m.) delivery may provide a valuable alternative when there are obstacles to venous access. Compared to other treatment options such as rectal drug administration, which is as challenging as the i.v. route in a convulsing patient, the i.m. route is easier and less invasive. The two most commonly used first-line anticonvulsants, diazepam and lorazepam, may be administered i.m., but are absorbed from the i.m. site more slowly than midazolam. Midazolam, a fairly new benzodiazepine, is a potent anticonvulsant with a fast onset of effect. Because of its water solubility, midazolam is rapidly absorbed from the injection site and has excellent local tolerability. The pharmacodynamic effects of midazolam can be seen within seconds of its administration, and seizure arrest is usually attained within 5 to 10 min. Case reports and a recent randomized trial that demonstrate the successful use of i.m. midazolam in the termination of epileptic seizures are reviewed.

New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine.

OBJECTIVE: To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy. METHODS: This was an 18-center, randomized, double-blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed seizures. Patients were randomly assigned to one of three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/day. The primary outcome measure was retention in trial for 12 months. RESULTS: Mean age was 72 years. The most common etiology was cerebral infarction. Patients had multiple medical conditions and took an average of seven comedications. Mean plasma levels at 6 weeks were as follows: GBP 8.67 +/- 4.83 microg/mL, LTG 2.87 +/- 1.60 microg/mL, CBZ 6.79 +/- 2.92 microg/mL. They remained stable throughout the trial. Early terminations: LTG 44.2%, GBP 51%, CBZ 64.5% (p = 0.0002). Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008. Terminations for adverse events: LTG 12.1%, GBP 21.6%, CBZ 31% (p = 0.001). Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p = 0.015. There were no significant differences in seizure free rate at 12 months. CONCLUSIONS: The main limiting factor in patient retention was adverse drug reactions. Patients taking lamotrigine (LTG) or gabapentin (GBP) did better than those taking carbamazepine. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures.

Evaluation of the efficacy of reincubation and subsequent subculture of initially positive blood cultures in the detection of additional clinically significant isolates.

Polymicrobial bacteremias are associated with higher mortality than are unimicrobial bacteremias, and their incidence appears to be increasing. Other researchers have recently shown that the prevalence of polymicrobial bacteremias may be underestimated when blood cultures are not evaluated further after identification of an initial isolate. We investigated this possibility by reincubating and further subculturing blood cultures initially positive for a single organism. We failed to show a clinically important increase in recovery of multiple isolates.

Status epilepticus in children, adults, and the elderly.

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.

Determinants of mortality in status epilepticus.

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 approximately 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 > or = 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.

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.

Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus.

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. METHODS: One hundred sixty-four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected. RESULTS: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after-SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported. CONCLUSIONS: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.

Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes.

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 > or =30 min. Epilepsy monitoring unit data indicate that many seizures self-terminate within minutes. Thus consideration was recently given to include seizure episodes lasting > or =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.

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.