Mortality in patients with psychogenic nonepileptic seizures.

OBJECTIVE: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population. METHODS: This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports. RESULTS: A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0-3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4-19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and "epilepsy" was recorded as the cause of death in 24%. CONCLUSIONS: Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.

Global, regional, and national burden of epilepsy, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Seizures and their consequences contribute to the burden of epilepsy because they can cause health loss (premature mortality and residual disability). Data on the burden of epilepsy are needed for health-care planning and resource allocation. The aim of this study was to quantify health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study. METHODS: We assessed the burden of epilepsy in 195 countries and territories from 1990 to 2016. Burden was measured as deaths, prevalence, and disability-adjusted life-years (DALYs; a summary measure of health loss defined by the sum of years of life lost [YLLs] for premature mortality and years lived with disability), by age, sex, year, location, and Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility). Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). FINDINGS: In 2016, there were 45·9 million (95% UI 39·9-54·6) patients with all-active epilepsy (both idiopathic and secondary epilepsy globally; age-standardised prevalence 621·5 per 100 000 population; 540·1-737·0). Of these patients, 24·0 million (20·4-27·7) had active idiopathic epilepsy (prevalence 326·7 per 100 000 population; 278·4-378·1). Prevalence of active epilepsy increased with age, with peaks at 5-9 years (374·8 [280·1-490·0]) and at older than 80 years of age (545·1 [444·2-652·0]). Age-standardised prevalence of active idiopathic epilepsy was 329·3 per 100 000 population (280·3-381·2) in men and 318·9 per 100 000 population (271·1-369·4) in women, and was similar among SDI quintiles. Global age-standardised mortality rates of idiopathic epilepsy were 1·74 per 100 000 population (1·64-1·87; 1·40 per 100 000 population [1·23-1·54] for women and 2·09 per 100 000 population [1·96-2·25] for men). Age-standardised DALYs were 182·6 per 100 000 population (149·0-223·5; 163·6 per 100 000 population [130·6-204·3] for women and 201·2 per 100 000 population [166·9-241·4] for men). The higher DALY rates in men were due to higher YLL rates compared with women. Between 1990 and 2016, there was a non-significant 6·0% (-4·0 to 16·7) change in the age-standardised prevalence of idiopathic epilepsy, but a significant decrease in age-standardised mortality rates (24·5% [10·8 to 31·8]) and age-standardised DALY rates (19·4% [9·0 to 27·6]). A third of the difference in age-standardised DALY rates between low and high SDI quintile countries was due to the greater severity of epilepsy in low-income settings, and two-thirds were due to a higher YLL rate in low SDI countries. INTERPRETATION: Despite the decrease in the disease burden from 1990 to 2016, epilepsy is still an important cause of disability and mortality. Standardised collection of data on epilepsy in population representative surveys will strengthen the estimates, particularly in countries for which we currently have no or sparse data and if additional data is collected on severity, causes, and treatment. Sizeable gains in reducing the burden of epilepsy might be expected from improved access to existing treatments in low-income countries and from the development of new effective drugs worldwide. FUNDING: Bill & Melinda Gates Foundation.

Pre-hospital ambulance care of patients following a suspected seizure: A cross sectional study.

PURPOSE: We aimed to investigate the characteristics of patients presenting to the ambulance service with suspected seizures, the costs of managing these patients and the factors which predicted transport to hospital. METHODS: We employed a cross-sectional design using routine clinical data from a UK regional ambulance service. Logistic regression was used to identify predictors of transport to hospital from ambulance response times, demographics, clinical (physiological) findings and treatments. RESULTS: There were 177,715 emergency incidents recorded in 2011/12 of which 2.9% (5139/177,715) were classified as seizures by ambulance call handlers and 2.7% (4884/177,715) by paramedics on the scene. Suspected seizures were the seventh most common call type. The annual cost of managing these incidents was £890,148. Clinical and physiological variables were normal for most patients. 59.3% (2894/4884) of patients were transported to hospital. 1/4884 (0.02%) patient died. Administration of diazepam, insertion of an airway and pyrexia perfectly predicted transport to hospital, tachycardia had a modest association, but other variables were only weak predictors of transport to hospital. CONCLUSIONS: This study shows that most patients after a suspected seizure are not acutely unwell but nevertheless most patients are transported to hospital. Further research is required to determine which factors are important in decisions to transport to hospital and to create evidence-based tools to help paramedics identify patients who could be safely managed without transport to hospital.

Stroke Burden in Rwanda: A Multicenter Study of Stroke Management and Outcome.

BACKGROUND: Cerebrovascular accidents or stroke constitute the second leading cause of mortality worldwide. Low- and middle-income countries bear most of the stroke burden worldwide. The main objective of this study is to determine the burden of stroke in Rwanda. METHODS: This was a prospective observational study in 2 parts: 6 months baseline data collection and outcome assessment sessions at 1 year. RESULTS: A total of 96 patients were enrolled in our series. Stroke constituted 2100 per 100,000 population. Of all patients, 55.2% were male and most (60%) were 55 years and older. Of all patients and/or caretakers, 22% were not aware of their previous health status and 53.5% of hypertensive patients were not on treatment by the time of the event. Median presentation delay was 72 hours for patients with ischemic stroke and 24 hours for patients with hemorrhagic stroke. Most patients had hemorrhagic stroke (65% vs. 35%), and more patients with hemorrhagic stroke presented with loss of consciousness (80% vs. 51%). Many patients (62% ischemic group and 44% hemorrhagic group) presented with severe stroke scores, and this was associated with worst outcome (P = 0.004). At 1 year follow-up, 24.7% had no or mild disability, 14.3% were significantly disabled, and 61% had died. CONCLUSIONS: Our results show that stroke is a significant public health concern in Rwanda. Risk factor awareness and control are still low and case fatality of stroke is significantly high. The significant delay in presentation to care and presentation with severe stroke are major contributors for the high mortality and severe disability rates.

A reappraisal of mortality after epilepsy surgery.

OBJECTIVE: To assess whether epilepsy surgery is associated with a reduction in mortality rate and if postoperative seizure frequency and severity affect mortality. METHODS: A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Deaths were ascertained through database and Social Security Death Index query. Patients were grouped by surgery type and seizure status; standardized mortality ratio and deaths per 1,000 person-years were calculated. Survival analysis and Cox proportional hazard regression were performed. RESULTS: Eighty-nine deaths were observed. Surgically treated patients had a lower mortality rate (8.6 per 1,000 person-years [95% confidence interval (CI) 6.58-11.15]) than nonsurgically treated patients (25.3 per 1,000 person-years [14.50-41.17]; p < 0.001). Seizure-free patients had a lower mortality rate (5.2 per 1,000 person-years [95% CI 2.67-9.02]) than non-seizure-free patients (10.4 per 1,000 person-years [95% CI 7.67-13.89] p = 0.03). More frequent postoperative tonic-clonic seizures (>2 per year) were associated with increased mortality (p = 0.006) whereas complex partial seizure frequency was not related to death rate. Mortality was similar in temporal and extratemporal epilepsy patients (p = 0.7). CONCLUSIONS: Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.

Recent Developments in Health Insurance, Life Insurance, and Disability Insurance Law.

This year's article covers key recent developments in life, health, and disability insurance law, including Supreme Court decisions on the constitutionality of the Affordable Care Act's contraception coverage provisions and on the enforceability of legal actions limitations period provisions in Employee Retirement Income Security Act (ERISA) plan documents; an alarming (but potentially short-lived) expansion of restitution as a form of "equitable relief" under ERISA; the latest battles in the stranger originated life insurance (STOLI) wars; and perennial issues arising out of disability and accident insurance cases.

Assessment of the convulsant liability of antidepressants using zebrafish and mouse seizure models.

In the past, antidepressants have been thought to possess proconvulsant properties. This assumption remains controversial, however, because anticonvulsant effects have been attributed to certain antidepressants. To date, it remains unclear which antidepressants can be used for the treatment of patients with epilepsy with depression. The present study was designed to determine the anticonvulsant and/or proconvulsant effects of three antidepressants (citalopram, reboxetine, bupropion) against pilocarpine- and pentylenetetrazole-induced acute seizures in larval zebrafish and mice. In zebrafish, all antidepressants were anticonvulsant in the pentylenetetrazole model. In addition, citalopram was anticonvulsant in the zebrafish pilocarpine model, whereas reboxetine and bupropion were without significant effect. In mice all three antidepressants increased some thresholds for pentylenetetrazole-induced convulsive-like behaviors at varying doses, whereas thresholds for pilocarpine-induced convulsive-like behaviors were generally lowered, particularly at the highest doses tested. In general we conclude that the convulsant liability of antidepressants is model and concentration dependent.

Risk assessment of severe tricyclic antidepressant overdose.

Prognostic factors for severe complications in tricyclic antidepressant (TCA) overdose remain unclear. We therefore evaluated the value of clinical characteristics and electrocardiograph (ECG) parameters to predict serious events (seizures, arrhythmia, death) in severe TCA overdose of 100 patients using logistic regression models for risk assessment. The overall fatality rate was 6%, arrhythmia occurred in 21% and 31% of the patients developed seizures. Using an univariable logistic regression model, the maximal QRS interval (OR 1.22; 95% CI 1.06-1.41; p = .005), the time lag between ingestion and occurrence of first symptoms of overdose (OR 1.13; 95% CI 0.99-1.29; p = .072) and the age (OR 0.73; 95% CI 0.55-0.98; p = .038) were determined as the solely predictive parameters. In the multivariable logistic regression model, the QRS interval could not be established as independent predictor, however, the terminal 40-ms frontal plane QRS vector (T40) reached statistical significance regarding prediction of serious events (odds ration [OR] 1.70; 95% confidence interval [CI] 1.02-2.84; p = .041), along with age and time lag between ingestion and onset of symptoms of overdose with a sensitivity and specificity of 71% and 70%, respectively. Evaluation of both clinical characteristics and ECG-parameters in the early stage of TCA overdose may help to identify those patients who urgently need further aggressive medical observation and management.

Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV).

OBJECTIVE: To examine the predictors of time-to-seizure occurrence and their impact on damage accrual and mortality in LUMINA, a multiethnic (Hispanic, African American and Caucasian) cohort of patients with systemic lupus erythematosus. METHODS: Seizures were defined as per the American College of Rheumatology (ARC) nomenclature and case definitions for neuropsychiatric lupus syndromes. Factors associated with time-to-seizure occurrence occurring at or after diagnosis (TD) of systemic lupus erythematosus were examined by univariable and multivariable Cox proportional hazard regression analyses. The impact of seizures on damage accrual and mortality was also examined by multivariable analyses after adjusting for variables known to affect these outcomes. RESULTS: A total of 600 patients were included in these analyses. Of them, 40 (6.7%) developed seizures at or after TD; by multivariable analyses, disease activity and younger age were independent predictors of a shorter time-to-seizure occurrence (HR = 1.10 and 1.04; 95% CI 1.04 to 1.15 and 1.00 to 1.08, p = 0.0004 and 0.0304, respectively) whereas mucocutaneous involvement (HR = 0.34, 95% CI 0.16 to 0.41, p = 0.0039) and hydroxychloroquine use (HR = 0.35, 95% CI 0.15 to 0.80, p = 0.0131) were independent predictors of a longer time-to-seizure occurrence. Seizures were an independent contributor to damage accrual but not to mortality. CONCLUSIONS: Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual. Younger age and disease activity are independent predictors of a shorter time-to-seizure occurrence; antimalarials appear to have a protective role in seizure occurrence.

Magnesium for seizure prophylaxis in patients with mild preeclampsia.

OBJECTIVE: To estimate whether magnesium therapy is the optimal management for women with mild preeclampsia. METHODS: A decision analytic model was designed for women with mild preeclampsia to estimate whether empiric magnesium therapy or no magnesium therapy is the optimal management strategy. The model considered relevant clinical events: seizure, placental abruption, and magnesium toxicity. Modeled outcomes were maternal mortality, neonatal mortality, and neurologic neonatal compromise. The two strategies were compared based on the probability of clinical events and outcomes and the utilities or values assigned to the outcomes by prior research. Probabilities and utilities were derived from the literature. RESULTS: The base-case analysis showed that although the no-magnesium strategy results in a 15% reduction in neonatal mortality and avoids most maternal drug toxicity, it produces a twofold increase in maternal death and more neurologically compromised neonates compared with empiric magnesium. The two strategies are essentially equivalent with regard to aggregate maternal and neonatal outcomes (0.9792 compared with 0.9781 utilities). Multivariable sensitivity analysis using Monte Carlo simulation confirmed the decision to be a "toss-up," yielding a similar mean utility for no-magnesium and magnesium strategies (0.9789+/-0.1374 compared with 0.9784+/-0.1390, respectively). CONCLUSION: Our decision model indicates that either strategy, using or not using empiric magnesium sulfate therapy, is acceptable. The clinical decision of whether to use magnesium in patients with mild preeclampsia for seizure prophylaxis should be determined by the physician or institution, considering patient values or preferences and the unique risk-benefit trade-off of each strategy.

An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality.

Of 49 patients with nonconvulsive seizures studied with continuous EEG monitoring, the overall mortality was 33% (16/49). Of the 23 patients with nonconvulsive status epilepticus (NCSE), 13 died (mortality 57%). Individual variables significantly associated with mortality were age, presence of NCSE, seizure duration, hospital and NICU length of stay, and delay to diagnosis and etiology (acute illness versus remote symptomatic). With multivariate logistic regression, only seizure duration (p = 0.0057, OR = 1.131/hour) and delay to diagnosis (p = 0.0351, OR = 1.039/hour) were associated with increased mortality. Acute symptomatic cases could not be adequately classified as either absence, simple, or complex partial status epilepticus when the impairment of consciousness arose form the initial illness. Current classifications of status epilepticus are inadequate for such cases.