Evaluating the utility of Rapid Response EEG in emergency care.

BACKGROUND: Timely management of non-convulsive status epilepticus (NCSE) is critical to improving patient outcomes. However, NCSE can only be confirmed using electroencephalography (EEG), which is either significantly delayed or entirely unavailable in emergency departments (EDs). We piloted the use of a new bedside EEG device, Rapid Response EEG (Rapid-EEG, Ceribell), in the ED and evaluated its impact on seizure management when used by emergency physicians. METHODS: Patients who underwent Rapid-EEG to rule out NCSE were prospectively enrolled in a pilot project conducted at two ED sites (an academic hospital and a community hospital). Physicians were surveyed on the perceived impact of the device on seizure treatment and patient disposition, and we calculated physicians' sensitivity and specificity (with 95% CI) for diagnosing NCSE using Rapid-EEG's Brain Stethoscope function. RESULTS: Of the 38 patients enrolled, the one patient with NCSE was successfully diagnosed and treated within minutes of evaluation. Physicians reported that Rapid-EEG changed clinical management for 20 patients (53%, 95% CI 37% to 68%), primarily by ruling out seizures and avoiding antiseizure treatment escalation, and expedited disposition for 8 patients (21%, 95% CI 11% to 36%). At the community site, physicians diagnosed seizures by their sound using Brain Stethoscope with 100% sensitivity (95% CI 5% to 100%) and 92% specificity (95% CI 62% to 100%). CONCLUSION: Rapid-EEG was successfully deployed by emergency physicians at academic and community hospitals, and the device changed management in a majority of cases. Widespread adoption of Rapid-EEG may lead to earlier diagnosis of NCSE, reduced unnecessary treatment and expedited disposition of seizure mimics.

Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies.

OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). RESULTS: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%-26.8%); ESL 1,200 mg = 30.8% (23.0%-40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. CONCLUSIONS: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. CLASSIFICATION OF EVIDENCE: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective.

Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study.

BACKGROUND: Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. The possible role of ESL as monotherapy to treat POS has not yet been established. METHODS: This study was an 18-week, multicenter, randomized double-blind trial of gradual conversion to ESL monotherapy in adults with POS not well controlled by 1-2 antiepileptic drugs (AEDs), using historical data as the control. The study comprised an 8-week baseline period, a 2-week titration period, a 6-week AED conversion period, a 10-week monotherapy period, and either a 1-week taper period or optional entry to an open-label extension study. The primary endpoint compared the Kaplan-Meier (KM)-estimated 112-day exit rate with a threshold value calculated from the historical controls. RESULTS: There were 172 randomized patients; 154 (90%) entered the AED conversion period and 121 (70%) completed the study. The KM-estimated exit rates [confidence interval (CI)] were 15.6% [8.1-28.7%] for ESL 1200 mg, and 12.8% [7.5-21.5%] for ESL 1600 mg. The upper limits of the 95% CI KM-estimates were below the pre-specified threshold for historical control of 65.3%, indicating that ESL was efficacious in reducing seizure-related exits, compared with historical control. During the 18-week double-blind treatment period, median reductions in standardized seizure frequency occurred with ESL 1200 mg (36.1%) and ESL 1600 mg (47.5%). The responder rates (a 50% or greater reduction in seizure frequency from baseline) during the 18-week double-blind period and the monotherapy period, respectively, were 35.2% and 38.9% for ESL 1200 mg, and 46.0% and 46.0% for ESL 1600 mg. The overall adverse event profile was consistent with the known safety profile of ESL. CONCLUSIONS: These findings indicate that ESL monotherapy (1200 and 1600 mg QD) was efficacious and well tolerated in this study. TRIAL REGISTRATION: NCT01091662 ; EudraCT No. 2010-018684-42.

Characteristics and acute outcomes of ICU patients with initial presentation of seizure.

PURPOSE: Seizures are a common cause of presentation to the emergency department (ED) but vary widely in severity and prognostic significance, with some cases requiring ICU management. Most evidence regarding seizure outcomes in the ICU comes from patients exclusively with status epilepticus (SE) or with new seizures detected after ICU admission. To aid in determining early prognosis of ICU patients with and without SE, we performed an analysis of patients initially presenting with any type of seizure and requiring ICU management. METHOD: Analysis of hospital records of 247 consecutive patients presenting to the ED initially with seizure and directly admitted to the ICU between January 2010 and June 2013. The primary outcome was composite in-hospital death or discharge to hospice, and the secondary outcome was recurrent ICU seizures. RESULTS: The primary outcome occurred in 7.7% of patients. Both early mechanical ventilation and an acute intracranial process on neuroimaging were associated with a poor outcome. About half of this cohort presented with SE. Although SE was associated with recurrent seizures in the ICU, the primary outcome was similar between patients presenting with and without SE. Patients with SE had greater rates of early intubation in the ED and were treated more aggressively with medication, whereas patients without SE had greater rates of first ever seizure, acute intracranial disease including intracranial hemorrhage, and neurosurgical intervention. CONCLUSION: Patients presenting to the ED with and without SE requiring ICU admission may have similar acute outcomes, yet differ in risk factors and seizure etiologies.

EEG asymmetry during aortic arch surgeries associated with selective preferential cerebral hypothermia.

Intraoperative EEG monitoring is increasingly used during aortic arch procedures for early detection of acute neurologic dysfunction. In those procedures involving cardiopulmonary bypass, increased neuroprotection may be gained by using hypothermic circulatory arrest and selective cerebral perfusion. Several techniques for cerebral perfusion exist; yet no studies have noted distinct EEG patterns associated with different techniques. In this study, we reviewed EEG records of six aortic arch procedures that used cannulation of the innominate artery to provide selective antegrade cerebral perfusion. In each case, a transient hemispheric asymmetry was noted within 2 minutes of the start of head cooling, consisting of enhanced suppression over the right compared with the left hemisphere, which was confirmed by power analysis. The EEG returned to baseline during passive-head rewarming in five cases, whereas a brief left-sided partial seizure occurred during rewarming in one case. These findings suggest that antegrade cerebral perfusion using cannulation of the innominate artery results in enhanced cooling of the right hemisphere as detected by intraoperative EEG monitoring. Characterization of this finding is necessary to prevent misinterpretation of ischemia by EEG.

Generic substitution of levetiracetam resulting in increased incidence of breakthrough seizures.

OBJECTIVE: We report on 4 patients having an increased incidence of seizures when treatment was switched from brand name levetiracetam (Keppra) to generic levetiracetam formulations. CASE SUMMARY: Patients reported an increase in seizure activity to their neurologists after treatment was switched from Keppra to generic levetiracetam formulations. To confirm the timeline of increased seizure activity with use of the generic drug and report these adverse events to MedWatch, we made a telephone call to each patient's pharmacy to collect information on dispensing dates and the generic formulations' manufacturers. Subsequent to the increase in seizure frequency with generic levetiracetam, treatment in all 4 patients was switched back to Keppra. Seizure frequency in all patients returned to baseline when Keppra was reinstituted. DISCUSSION: The Food and Drug Administration (FDA) considers generic medications to be therapeutically equivalent to their corresponding brand name formulation when the generic meets bioequivalence criteria. Considering the linear pharmacokinetic profile of levetiracetam, loss of seizure control or fluctuations of serum concentrations are unexpected if the patient remains on a consistent dose. However, there is growing evidence to support the concept that brand name antiepileptic drugs (AEDs) are not clinically equivalent to their generic counterparts. Because the FDA relies on voluntary reporting of adverse events from health-care professionals and consumers to their MedWatch program, underreporting makes it difficult to quantify the significance of brand to generic switches, and, equally important, generic to generic switches. CONCLUSIONS: Until the use of generic AEDs can be evaluated in a large randomized blinded controlled study, clinicians must be vigilant in their efforts to report to MedWatch adverse events resulting from the switch from an AED brand to generic formulation of an AED.

Osteoprotective knowledge in a multiethnic epilepsy population.

Antiepileptic drugs (AEDs) are known to cause bone loss. People with epilepsy have twice the fracture rate of nonepilepsy populations. Osteoprotective knowledge related to calcium and exercise has not been assessed in people with epilepsy. The Osteoporosis Knowledge Test (OKT), a validated, 24-item test, was administered to 94 epilepsy patients (28 males and 66 females) to measure knowledge of risk factors for osteoporosis and strategies for prevention related to calcium and exercise. The mean age of participants was 45 years with an average AED exposure of 20 years. Fifty participants were Caucasian and 44 were non-Caucasian. No significant differences related to age or gender for the OKT were found. One-way analysis of variance (ANOVA) of ethnicity showed that non-Caucasians had much lower calcium (F = 8.15, p = .005) and exercise (F = 7.71, p = .007) knowledge. The total mean OKT score was 11.71 (4.92), reflecting a correct response rate of 49%. In previous studies of nonepilepsy populations, the mean OKT score ranged from 7.83 to 21.8, with a correct response ranging from 32.9% to 90.8%. Independent t tests of the individual OKT questions revealed specific knowledge deficiencies in the areas of risk factors, exercise, and reasons for calcium supplementation for non-Caucasians. Results of this study reveal that people with epilepsy, who are at greater risk for metabolic bone loss, have lower knowledge scores for calcium and exercise than nonepilepsy populations of various ages and genders. Culturally relevantepilepsy materials and programs may improve knowledge and adoption of preventative behavior.

Cardiovascular risk factors and homocysteine in epilepsy.

Epidemiological studies have found the risk for heart disease and stroke are increased in persons with epilepsy. Anti-epileptic drugs (AEDs) have varying effects on serum lipids and homocysteine-an independent risk factor for coronary disease. The prevalence of cardiovascular risk factors (high cholesterol, hypertension, diabetes, obesity and smoking) and homocysteine were investigated in a multiethnic epilepsy population. Data included demographics, clinical factors, lab assessments and supplementation patterns. Mean age was 45 years (71 males and 94 females)-75 were African American, 27 Latino and 60 Caucasian. Fifty-two percent of participants had two or more cardiovascular risk factors when compared with rates for the general population of 28%. The Framingham risk score (FRS) assessment was also used to compare risk levels. Twenty-nine percent of men and 1% of women had a FRS indicating >5% level of risk, only 7% had a FRS>10%. Cardiovascular screening and primary preventative recommendations based on the American Heart Association and supplementation should be suggested for the adult epilepsy population when appropriate.

Use of the Precaution Adoption Process Model to examine predictors of osteoprotective behavior in epilepsy.

In the neurology literature it is well established that anti-epileptic drugs (AEDs) lead to bone loss (osteopenia and osteoporosis). Several large epidemiologic studies have found twice the fracture rate in persons with epilepsy compared to the non-epilepsy population. While an increasing level of awareness for preventative measures and screening by neurologists and primary care physicians are recommended, so far no one has attempted to address how knowledge related to calcium and exercise, health beliefs (based on the Health Belief Model) and self-efficacy (confidence in abilities) impact osteoprotective behaviors in epilepsy, based on the Precaution Adoption Process Model (PAPM). The seven-stage PAPM, unlike other health behavior theories where a person is either practicing or not practicing the behavior, conceptualizes behavior change as dynamic and occurring over time. Validated instruments were used to assess knowledge, health beliefs, self-efficacy and stages of the precaution adoption process for four osteoprotective behaviors. For dietary calcium; exercise knowledge and calcium self-efficacy predicted higher stages of precaution adoption. For calcium supplements; age perceived susceptibility for osteoporosis and perceived benefits of calcium predicted higher stages. Exercise adoption stage was most predicted by exercise knowledge and health motivation. For DEXA screening adoption; age and perceived susceptibility predicted higher stages. This study provides hints how persons with epilepsy could be influenced to move from the unaware/unengaged positions into to the stages of adoption and maintenance for osteoprotective behaviors.

Homocysteine and bone loss in epilepsy.

Epidemiological studies reveal fracture incidence in epilepsy is twice that of the normal population. Much interest has been focused on Vitamin D, however, considering mixed results on non-enzyme inducing anti-epileptic drugs (AEDs) and bone mineral density (BMD) additional metabolic effects may be to blame. AEDs increase serum homocysteine (s-Hcy) by lowering blood folate levels. An association between elevated homocysteine, BMD and increased fracture incidence has been found in non-epilepsy populations. Additionally, folate and Vitamin B12 levels are independently related to bone mineral density in various non-epilepsy populations. This study supports previous research, which found elevated s-Hcy in subjects taking AEDs and that bone loss is related to the use of enzyme-inducing AEDs and changes in alkaline phosphatase. By one-way ANOVA, subjects on phenytoin monotherapy had significantly higher levels of s-Hcy than those on other AEDs (F=5.89, p=.016). Regression analyses revealed homocysteine, fracture history, length of years on AEDs, ethnicity were predictors of spine T scores. Weight and BMI were predictors of both BMD and DEXA T scores. Use of enzyme-inducing AEDs was a negative predictor of spine BMD and T scores, while phenytoin monotherapy was a positive predictor of spine BMD. Lamotrigine was found to be a negative predictor of spine T score. Ambulatory status, menopause and alcohol consumption were predictors of BMD but not T scores. In this study, persons with epilepsy who take nutritional supplementation have 25% lower s-Hcy levels than those who do not. Supplementation continues to be important in preventative epilepsy care.

Self-efficacy, knowledge, health beliefs, quality of life, and stigma in relation to osteoprotective behaviors in epilepsy.

It is well reported in the epilepsy literature that use of antiepileptic drugs (AEDs) leads to bone loss. Validated instruments were administered to assess knowledge, health behavior, quality of life, and stigma, to determine their effects on self-efficacy for osteoprotective and self-management behaviors. This adult epilepsy population had a mean age of 45, with 20 years of AED exposure. Fifty subjects were Caucasian and 44 were non-Caucasian. By one-way ANOVA, there were significant differences in self-efficacy based on ethnicity, medical assistance, status, and seizure frequency. Differences in knowledge based on ethnicity, education, and income were also noted. Regression analysis revealed that the factors that most predict self-efficacy for calcium, exercise, and self-management do not parallel each other. Age and ethnicity were predictive of self-efficacy for epilepsy self-management only. Medical management factors varied among the models. Overall quality of life was a positive predictor for both calcium and exercise self-efficacy.

Bone loss in epilepsy: barriers to prevention, diagnosis, and treatment.

In epilepsy populations there are multiple barriers to the prevention, diagnosis, and treatment of metabolic bone disease. This study explored issues that may be unique to inner-city care. We screened 101 consecutive patient charts from our clinic to identify barriers to optimal care. According to the Health Belief Model, when patients view a condition as not severe and their perceived susceptibility is low, they are unlikely to comply with screening and/or adopt preventative behaviors. Despite routine communications to primary care doctors regarding bone health, its importance is still overlooked. In addition, the managed care referral process makes it difficult for a specialist to prevent, screen, and treat a primary care condition with no symptoms. For optimal patient care and to stimulate prevention and screening compliance, a communication style adapted to the patient's knowledge, beliefs, and attitudes toward antiepileptic drug-induced bone loss is crucial to help reduce barriers against change.

Epilepsy in Aging Populations.

Older adults pose special challenges when seizures or epilepsy occur. Increased risk for seizures is often unrecognized. Older adults may have milder epilepsy, and may not require or tolerate standard doses of anti-epileptic drugs (AEDs). Polypharmacy and drug interactions are potential problems, and altered protein binding, hepatic function, renal clearance, and gastric function can affect AED dosing. Side effects such as ataxia, somnolence, and confusion are of heightened concern in this group. Older adults typically suffer localization or focal onset seizures. Although many AEDs treat these types of seizures, the AED chosen for any given patient is determined by concomitant polypharmacy, side effect profile, as well as underlying medical conditions. Free and total AED levels may be necessary. The goal of seizure management for a hospitalized patient may be rapid seizure control. As the individual moves into the outpatient setting, AED therapy without side effects and with appropriate quality of life must be pursued.