Burden of illness in patients with possible Lennox-Gastaut syndrome: A retrospective claims-based study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe and treatment-resistant epilepsy syndrome characterized by multiple subtypes of intractable seizures, moderate to severe cognitive impairment, and slow spike-wave complexes on electroencephalographic (EEG) recordings. Lennox-Gastaut syndrome is also associated with increased risk for injury, reduced quality of life, long-term disability, and early mortality. By evaluating private and public US medical insurance claims, we quantified healthcare utilization and direct costs in patients with possible LGS. METHODS: Commercial and Medicaid insurance claims (Truven Health Analytics) from October 2010 to September 2015 were queried to identify patients with intractable epilepsy, intellectual disability, ≥1 prescription for selected antiepileptic drugs (AEDs), and ≥2 years of continuous enrollment. To identify patients with LGS in the absence of a specific International Classification of Diseases ICD-9 diagnosis code, current or prior rufinamide use was selected as a disease indicator of LGS per previously published methodology. Characteristics significantly predictive of rufinamide use were identified with multivariate regression by comparing groups with and without LGS, then assessed in non-rufinamide users fulfilling all other inclusion criteria. Controls without epilepsy, seizures, or prescriptions for selected AEDs were matched to patients with possible LGS by age, gender, US region, and dates of insurance coverage. Average healthcare utilization and costs per patient per year (PPPY) were evaluated for a 2-year postindex period and compared between the cohort with LGS and controls by insurance type. Costs were normalized to 2017 dollars at 3% per annum. RESULTS: In the study, 6019 patients with possible LGS (53% male, mean age of 13 years, in both insurance groups) were identified: 2270 with commercial insurance and 3749 with Medicaid. The cohort with LGS used >8 times more services and >7 times more drugs than controls (all p < 0.001) in both insurance groups. The biggest contributors to service use PPPY were outpatient physician visits and home health services in the commercial-insured cohort with LGS and other outpatient visits and home health services in the Medicaid-insured cohort with LGS. Average total costs PPPY (services + drugs) were significantly higher for the cohort with LGS vs. controls: $65,026 (SD $34,324) vs. $2442 (SD $10,670) for commercial-insured and $63,930 (SD $45,761) vs. $3849 (SD $13849) for Medicaid-insured patients. The biggest cost contributors PPPY were inpatient care in the commercial-insured cohort with LGS and home health services in the Medicaid-insured cohort with LGS. CONCLUSIONS: Patients with possible LGS have significantly higher healthcare utilization and costs than patients without epilepsy or seizures. Our results suggest that direct costs associated with LGS are substantial and highlight the need for new and effective treatments.

Assessment of treatment patterns and healthcare costs associated with probable Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a chronic and severe form of epilepsy characterized by intractable seizures, cognitive impairment, and abnormal electroencephalogram findings with slow spike-wave complexes. It typically presents before age 8, but symptoms continue into adulthood and require lifelong treatment associated with significant clinical burden. Data on LGS-associated healthcare utilization and costs are limited. In this study we use a claims-based LGS classifier based on random forest methodology to identify patients with probable LGS from the a Medicaid multi-state database and assess its prevalence across the age spectrum, healthcare utilization, treatment patterns, costs, and comorbid conditions. The classifier identified patients with probable LGS across all ages, with up to 8% of 10-year-old patients with epilepsy identified as having probable LGS. The prevalence of probable LGS was lower in older age cohorts, indicating that it may be under-recognized in older patients. Our analysis showed that probable LGS is associated with considerably higher total healthcare and medical costs than non-LGS patients. The costs were generally consistent between age cohorts, suggesting that the cost burden extends beyond childhood and has a lifelong impact. Analysis of treatment patterns suggest that while the majority of probable LGS patients in this study received widest-spectrum AEDs, a considerable proportion did not and therefore may have been inadequately treated. Further, usage of clobazam and rufinamide was decreased in older compared to younger patient cohorts, indicating that older patient cohorts are less likely to be receiving optimum treatment for LGS. These findings indicate the need for increased clinical attention to LGS beyond pediatric years, with a focus on optimization of treatment for LGS patients of all ages with widest-spectrum AEDs. Timely recognition and adequate treatment of LGS are likely to result in improved outcomes and less costly management of this condition.

Congenital malformations in infants exposed to antiepileptic medications in utero at Boston Medical Center from 2003 to 2010.

OBJECTIVE: The aim of this study was to determine the frequency of association of major congenital malformations in pregnancy in women exposed to antiepileptic drugs (AEDs) in an inner city population. BACKGROUND: Approximately 0.3-0.5% of all pregnancies involve women with epilepsy. The risk of congenital malformations associated with AED therapy has been well documented, ranging from 2 to 10% as compared to a rate of 3% in the general population. However, the risk of these occurring in a higher risk population, such as an inner city tertiary care center, with multiple comorbidities is not as well known. DESIGN/METHODS: Using the Boston Medical Center Database between the years 2003 and 2010, a list of all infants born with major congenital malformations (MCMs) to mothers on AEDs was compiled. Major congenital malformations were defined as cleft lip and/or palate, ventricular or atrial septal defect, other cardiac malformations, and urogenital defects. During pregnancy, AED exposure including serum levels, other medication exposures, breakthrough seizure frequency, positive toxicology tests, and other maternal comorbidities were also analyzed. RESULTS: Of 17,246 live births between 2003 and 2010, 330 of those births demonstrated a MCM (malformation rate of 1.91%). Of those births, 64 mothers had epilepsy and were exposed to AED therapy during pregnancy, accounting for 0.37% of all births during this time period. Overall, three pregnancies in women with epilepsy resulted in a baby with a MCM, accounting for a 4.7% malformation rate in this patient population. In mothers on AEDs for other indications, the MCM rate was slightly higher, 5.0%, and in women on benzodiazepine monotherapy during pregnancy, the rate was quite high, 10.6%.

The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that appears in childhood. LGS is characterized by a slow spike-wave pattern on electroencephalogram (EEG), cognitive impairment, and multiple seizure types. This mixture of seizure types, along with the need to use more than one type of medication, makes LGS one of the most complicated epilepsies to treat successfully. Recent developments in approved therapies for the treatment of LGS offer physicians more options, but also make developing a treatment strategy that minimizes adverse events more challenging. There are currently 5 treatment options for LGS: felbamate, lamotrigine, topiramate, rufinamide, and clobazam, and several others that are used off-label, each of which has benefits and limitations. There are several factors that must be considered when determining which medication to use when treating patients with LGS, including efficacy, which is assessed by seizure frequency, tolerability, and the anticipated duration of treatment. In this article, data supporting current treatment options are discussed, and important considerations about the treatment of LGS are reviewed.

Rational approach to treatment options for Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is an intractable childhood-onset epileptic encephalopathy. Seizure freedom is rare in LGS. One of the hallmarks of LGS is medical intractability, with generally poor response to antiepileptic drugs (AEDs). Nevertheless, several treatment options are available that can mitigate the severity of seizures and curtail their frequency. New AEDs have been validated in randomized, controlled trials for the treatment of seizures in LGS. In some cases, nonpharmacologic options may be effective, although more data are needed to confirm efficacy outcomes. Comprehensive patient assessments are critical to achieve an optimal AED treatment regimen and minimize the potential for adverse effects.

Report of the American Epilepsy Society and the Epilepsy Foundation joint task force on sudden unexplained death in epilepsy.

The American Epilepsy Society and the Epilepsy Foundation jointly convened a task force to assess the state of knowledge about sudden unexplained death in epilepsy (SUDEP). The task force had five charges: (1) develop a position statement describing if, when, what, and how SUDEP should be discussed with patients and their families and caregivers; (2) design methods by which the medical and lay communities become aware of the risk of SUDEP; (3) recommend research directions in SUDEP; (4) explore steps that organizations can take to perform large-scale, prospective studies of SUDEP to identify risk factors; and (5) identify possible preventive strategies for SUDEP. Some of the major task force recommendations include convening a multidisciplinary workshop to refine current lines of investigation and to identify additional areas of research for mechanisms underlying SUDEP; performing a survey of patients and their families and caregivers to identify effective means of education that will enhance participation in SUDEP research; conducting a campaign aimed at patients, families, caregivers, coroners, and medical examiners that emphasizes the need for complete autopsy examinations for patients with suspected SUDEP; and securing infrastructure grants to fund a consortium of centers that will conduct prospective clinical and basic research studies to identify preventable risk factors and mechanisms underlying SUDEP. For now, the principal effort in preventing SUDEP should be prompt and optimal control of seizures, especially generalized convulsive seizures.

Development of a classifier to identify patients with probable Lennox-Gastaut syndrome in health insurance claims databases via random forest methodology.

Objective: Describe the development of a claims-based classifier utilizing machine learning to identify patients with probable Lennox-Gastaut syndrome (LGS) from six state Medicaid programs. Methods: Patients were included if they had ≥2 medical claims ≥30 days apart for specified or unspecified epilepsy, excluding those with ≥1 claim for petit mal status. The LGS classifier utilized a random forest algorithm, a compilation of thousands of binary decision trees in which machine-generated predictor variables split the data set into branches that predict the presence or absence of LGS. To construct the splitting rules, the importance of each candidate variable was determined by calculating the mean decrease in Gini impurity. Training and testing were performed on two data sets (30% and 70%) using a "true" LGS and non-LGS patient population. Performance was compared with logistic regression and single tree methodology. Results: Using a 60% probability threshold, which yielded the highest sensitivity (97.3%) and specificity (95.6%), the classifier identified approximately 4% of patients with epilepsy as probable LGS. The most important input variables included number of distinct antiepileptic drugs received, epilepsy-related outpatient/inpatient visits, electroencephalogram procedures and claims for delayed development. The random forest methodology outperformed logistic regression and single tree methodology. Most of the important LGS predictor characteristics identified by the classifier were statistically significantly associated with LGS status (p < .05). Conclusions: The claims-based LGS classifier showed high sensitivity and specificity, outperformed single tree and logistic regression methodologies and identified a prevalence of probable LGS that was similar to previously published estimates.

Levetiracetam Pregnancy Registry: Final results and a review of the impact of registry methodology and definitions on the prevalence of major congenital malformations.

BACKGROUND: To evaluate pregnancy outcomes among women participating in the antiepileptic drug (AED) Levetiracetam Registry (LEV-Registry), and to review the impact of using two other registries' outcome definitions on the number of major congenital malformations (MCMs). METHODS: This US-based prospective study (ClinicalTrials.gov NCT00345475) was overseen by an independent Expert Panel. Women exposed to levetiracetam at any time during pregnancy enrolled, directly, or via their healthcare provider. The primary outcome was prevalence of MCMs, defined according to a modified version of the Metropolitan Atlanta Congenital Defects Program criteria. RESULTS: Of 491 women enrolled, 465 (94.7%) had a documented outcome. Most (92.3%) received levetiracetam for epilepsy; 323 (69.4%) as monotherapy and 142 (30.5%) as polytherapy. With three twin pregnancies, there were 468 outcomes-444 livebirths, 3 stillbirths, 19 miscarriages, and 2 terminations. Based on the MCM definition used by LEV-Registry, 46 infants among 444 livebirths had MCMs resulting in 10.4% (95% CI 7.7, 13.6) for overall prevalence, 9.4% (95% CI 6.4, 13.2) with monotherapy, and 12.6% (95% CI 7.5, 19.4) with polytherapy. When MCM reports were reviewed independently by staff at EURAP (International Registry of AEDs) and North American AED Pregnancy Registry according to their respective criteria, only 22 and 7 infants of the 46, respectively, were classified as having MCMs. CONCLUSION: The LEV-Registry Expert Panel did not find evidence suggestive of teratogenic association with prenatal exposure to levetiracetam. The substantial differences in which physical findings were considered MCMs highlight the major impact of pregnancy registry methodology on MCM prevalence estimates.

Challenges in identifying Lennox-Gastaut syndrome in adults: A case series illustrating its changing nature.

The variable presentation and progression of Lennox-Gastaut syndrome (LGS) can make it difficult to recognize, particularly in adults. To improve diagnosis, a retrospective chart review was conducted on patients who were diagnosed as adults and/or were followed for several years after diagnosis. We present 5 cases that illustrate changes in LGS features over time. Cases 1 and 2 were diagnosed by age 8 with intractable seizures, developmental delay, and abnormal EEGs with 1.5-2 Hz SSW discharges. However, seizure type and frequency changed over time for both patients, and the incidence of SSW discharges decreased. Cases 3, 4, and 5 were diagnosed with LGS as adults based on current and past features and symptoms, including treatment-resistant seizures, cognitive and motor impairment, and abnormal EEG findings. While incomplete, their records indicate that an earlier LGS diagnosis may have been missed or lost to history. These cases demonstrate the need to thoroughly and continuously evaluate all aspects of a patient's encephalopathy, bearing in mind the potential for LGS features to change over time.

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

OBJECTIVE: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. METHODS: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg-1·d-1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg-1·d-1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. RESULTS: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. CONCLUSIONS: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. CLINICALTRIALSGOV IDENTIFIER: NCT00518713 and NCT01160770. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment.

Two patients with Hashimoto's encephalopathy and uncontrolled diabetes successfully treated with levetiracetam.

Hashimoto's encephalopathy (HE) is a rare syndrome of progressive or relapsing-remitting encephalopathy associated with elevated serum anti-thyroid antibody concentrations. It is thought to be an autoimmune process that generally responds well to high-dose corticosteroids and other immunomodulatory therapies. However, some patients are unresponsive to steroids or are unable to receive immune therapy. A viable alternative is needed for this group. Given that seizure and EEG abnormalities are commonly associated with this syndrome, we postulate that treatment with levetiracetam, which has duel anti-inflammatory and anti-seizure mechanisms, might show clinical benefit. We present the cases of two patients who met the criteria for HE but were unable to receive steroids due to labile diabetes. They were both successfully treated with levetiracetam.

De Novo Nonepileptic Seizures after Cranial Surgery for Epilepsy: Incidence and Risk Factors.

We evaluated the incidence of de novo nonepileptic seizures (NES), confirmed by EEG monitoring, after cranial surgery for intractable epilepsy in 228 surgery patients. Eight patients (3.5%) developed de novo NES at 6 weeks to 6 years (mean, 23 months) after surgery. Six had undergone a resection and two complete callosotomy. They did not differ from a larger surgical group with respect to sex, side of surgery, age at onset, or duration of epilepsy, Full Scale Intelligence Quotient, seizure outcome, or preoperative interictal dysphoric disorder (IDD), but there was a significant excess of postoperative IDD and operative complications (bone flap infections); the callosotomy patients had marked hemisphere disconnection syndromes. Repeat EEG videotelemetry monitoring is important to detect postoperative NES so that inappropriate therapeutic measures may be avoided. Risk factors may be exacerbation or persistence of IDD and surgical complications. The etiology of NES is discussed.

Reproductive disturbances in patients with epilepsy.

In persons with epilepsy, both seizures and antiepileptic drugs can disturb reproductive health. For example, seizures can alter the release of hypothalamic and pituitary hormones, while some antiepileptic drugs alter concentrations of sex steroid hormones. Women with epilepsy are at increased risk for polycystic ovary syndrome and disorders of the menstrual cycle. Studies have found reduced fertility rates among men and women with epilepsy. The reasons for this reduction in fertility are likely to be both psychosocial and physiologic, and again, both epilepsy itself and antiepileptic drugs are implicated. Sexual dysfunction is common among patients with epilepsy and can have a somatic, psychological, or social basis. To provide the best care for patients with epilepsy, particularly women of reproductive age, clinicians must consider both the gender-based biology of epilepsy and the effects of antiepileptic drugs on reproductive health.

Levetiracetam as a possible contributor to acute kidney injury.

PURPOSE: Levetiracetam is an antiepileptic medication that has been reported to be both well-tolerated and effective in treating generalized tonic-clonic, myoclonic, and partial-onset seizures. The adverse effects most commonly reported in tolerability trials include somnolence, fatigue/asthenia, headaches, dizziness, and nausea. However, there have been a few reports suggesting possible detrimental effects of levetiracetam on renal function. METHODS: Here we describe the case of a previously healthy 23-year-old female patient who developed acute kidney injury 1 day after the initiation of levetiracetam therapy for new-onset seizures. FINDINGS: Based on the time course of the patient's rise in serum creatinine and the exclusion of other causes, this case suggests that levetiracetam use contributed to the acute kidney injury. IMPLICATIONS: Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function. This potential consequence of therapy should be considered when deciding whether or not to prescribe this medication, and renal function should be monitored during treatment.

Patient and caregiver quality of life in psychogenic non-epileptic seizures compared to epileptic seizures.

PURPOSE: Little is known about the effect of psychogenic non epileptic seizures (PNES) to caregiver quality of life (QOL), particularly as it compares to epileptic seizures (ES). We sought to characterize this effect and identify its determinants. METHODS: The study population comprised of 126 ES and 33 PNES patients who underwent video EEG monitoring along with 48 and 18 caregivers respectively who accompanied them to their investigations. Patients completed questionnaires providing demographic, disease-related, cognitive, psychiatric, sleep and QOL information on admission, prior to their diagnosis being clarified. Their caregivers completed questionnaires providing demographic, disease burden and generic QOL information. Paraclinical data were also gathered. Regression analysis was used to identify patient and caregiver related determinants of patient and caregiver QOL. RESULTS: QOL scores were significantly worse for PNES than ES patients and were mainly linked to depression levels. PNES and ES caregivers had comparable demographic characteristics and QOL scores. ES caregiver QOL was better in employed caregivers with lower burden scores for the physical component summary (PCS) and worse in female caregivers of depressed patients with higher burden scores for the mental component summary (MCS). Caregiver burden score was the strongest correlate of PNES caregiver MCS QOL score. CONCLUSION: Caregiver QOL in PNES does not differ from caregiver QOL in ES, while patient QOL is worse in PNES. Caregiver burden emerges as a consistent correlate of caregiver QOL both in ES and PNES. These findings advocate for consideration of caregiver burden and QOL in PNES in clinical practice and for future research paradigms.

Caregiver burden in epilepsy: determinants and impact.

Aim. Caregiver burden (CB) in epilepsy constitutes an understudied area. Here we attempt to identify the magnitude of this burden, the factors associated with it, and its impact to caregiver quality of life (QOL). Methods. 48 persons with epilepsy (PWE) underwent video-EEG monitoring and their caregivers completed questionnaires providing demographic, disease-related, psychiatric, cognitive, sleep, QOL, and burden information. Results. On regression analysis, higher number of antiepileptic drugs, poorer patient neuropsychological performance, lower patient QOL score, and lower caregiver education level were associated with higher CB. Time allocated to patient care approximated but did not attain statistical significance. A moderate inverse correlation between CB and caregiver QOL physical component summary score and a stronger inverse correlation between CB and caregiver QOL mental component summary score were seen. Conclusion. In a selected cohort of PWE undergoing video-EEG monitoring, we identified modest degree of CB, comparable to that reported in the literature for other chronic neurological conditions. It is associated with specific patient and caregiver characteristics and has a negative effect on caregiver QOL.

The effect of epilepsy surgery on caregiver quality of life.

PURPOSE: Epilepsy surgery has been shown to improve patient quality of life (QOL). Little is known about its effect on caregiver QOL. METHODS: The study population comprised of 26 persons with epilepsy (PWE) who underwent long term video EEG monitoring at Massachusetts General Hospital for presurgical evaluation along with 16 caregivers. The PWE completed epilepsy directed QOL (QOLIE-31) and psychological (Beck depression-BDI and anxiety inventory-BAI) questionnaires before and after surgery. Their participating caregivers completed generic health related QOL (SF36v2) and disease burden (Zarit caregiver burden inventory-ZCBI) questionnaires before and after surgery. Demographic data for all participants and disease/surgery related data for the PWE were collected. Statistical analysis was performed to compare PWE and caregiver QOL before and after surgery. RESULTS: Mean patient age was 37 years. Most (77%) suffered from symptomatic partial epilepsy for approximately 18 years prior to surgery, averaging 4 seizures per month and 2.2 antiepileptic drugs (AEDs). 78% of them underwent an anterior temporal lobectomy and the rest extra-temporal resections. On follow up at approximately 9 months, 69% had a surgical outcome of Engel class I, 23% of class II and 8% class IV. Postoperatively, the PWE remained on average on 1.9 AEDs. There was a statistically significant improvement for both the aggregate QOLIE-31 score and all its subscales (except for medication effects) as well as the BAI scores. 96% of the PWE felt that the decision to go through surgery was worthwhile. Mean caregivers age was 47 years. Half of them were spouses to the PWE and the majority of the rest their parents. 50% of them stated that their overall time devoted to patient's care decreased after surgery and 50% that it remained unchanged. The mental component scale (SF36v2, MCS) of caregiver QOL showed statistically significant improvement. ZCBI score and the physical component scale of their QOL (SF36v2, PCS) did not significantly vary before and after surgery. 75% of caregivers deemed their QOL better post surgery vs 19% similar. 94% of the caregivers felt that the decision to go through surgery was worthwhile. CONCLUSIONS: Successful epilepsy surgery has a positive impact not only to patient QOL but also to their caregiver. To the best of our knowledge, this is the first pilot study to systematically address the impact of epilepsy surgery on caregivers providing additional support to epilepsy surgery as the optimal treatment modality in carefully selected patients. These findings call for further investigation on the caregiver quality of life in epilepsy and for its inclusion in the treatment plan and quality indicators for epilepsy surgery.

A quick and reliable EEG montage for the detection of seizures in the critical care setting.

Obtaining an emergent EEG for the diagnosis of nonconvulsive status epilepticus and conconvulsive seizures in the intensive care unit raises logistic problems in most hospitals. Previous studies have looked into the hairline EEG for a broader population than the critically ill, with controversial conclusions. The authors created a montage sufficiently simple to be performed and interpreted by residents and rapidly achievable to meet the time constraints of a busy on-call schedule. Seven electrodes (Fp1, Fp2, T3, T4, O1, O2, and Cz), easily applied without the need for tape measure by using only anatomic landmarks (pupils, ears, vertex, and inion), were used to configure three different montages: double diamond, circumferential, and Cz referential. EEG records obtained with the full 10-20 system in critically ill patients were reformatted into these montages and reviewed retrospectively independently by neurology attending physicians with expertise in EEG interpretation and senior neurology residents. A comparison was done with the previously studied hairline EEG. The average sensitivity of the study montage for seizure detection was 92.5%, whereas the average specificity was 93.5%. These results suggest that the seven-electrode montage could potentially be a quick and reliable EEG montage for the detection of seizures in the intensive care unit, when technical support is not available. Further prospective studies are required to validate these promising results in a larger population sample.

Management of breakthrough seizures in the emergency department: continuity of patient care.

BACKGROUND: Epilepsy is a chronic disorder requiring long-term management. Communication between emergency physicians, neurologists, and primary care physicians (PCPs) is especially critical for the continuity of care for patients who present in an emergency department (ED) with a breakthrough seizure. Therefore, maximizing communication between the emergency physician and the PCP is of the utmost importance. The emergency physician, who is on the front line, must gather the information necessary to identify the underlying cause of the seizure and decide whether the pharmaceutical management must be changed. SCOPE: This paper provides a clinical commentary on issues to consider when managing breakthrough seizures in the ED, to inform and facilitate communication between emergency physicians, consulting neurologists, and PCPs. CONCLUSIONS: Clinical management decisions, especially when considering adjustment in an antiepileptic drug (AED) regimen, are often best made in coordination with a consulting neurologist. Increasing emergency physicians' comfort level regarding the use of newer-generation AEDs can improve the dialogue between the emergency physician and neurologist and the dialogue with the patient. Understanding the risks and benefits of the newer AEDs will assist the emergency physician in clinical decision making and, it is hoped, improve clinical outcomes. To preserve continuity of patient care, a patient's treating physician should be notified of all the particulars of the ED visit, and an appointment should be scheduled at the time of discharge for follow-up evaluation.

Conversions between monotherapies in epilepsy: expert consensus.

To develop expert consensus for conversion between antiepileptic drug (AED) monotherapies, an 11-member panel used the Delphi Technique over three rounds to: (1) identify relevant issues, (2) vote on the issues, and (3) develop consensus. The panel agreed on the basic principle to taper the existing AED only after a presumably efficacious dose of the planned AED was reached. Application is modified by adverse effects possibly attributable to the existing drug, in which case earlier or more rapid tapering of the existing drug should be considered. Patients with uncontrolled seizures, as well as seizure-free patients for whom driving privileges are a consideration, may benefit from slower tapering by smaller dosage decrements of the existing AED. For 10 of the 12 AEDs considered, the panel made titration recommendations concerning initial and target doses for the planned AED, supplementing limited data in the prescribing information. This expert guidance will aid in the period of transitional polytherapy with AEDs from monotherapy to monotherapy.