Reproductive and Sexual Health Concerns in Transition-Age Adolescents and Young Adults With Epilepsy.

A plethora of hormonal and physical changes occur as adolescents grow into adulthood. These changes pose additional challenges for youth with epilepsy. Providers, parents, and patients must be well educated about the hormonal influences, both intrinsic and pharmaceutical, on seizures and antiepileptics (AEDs). In addition, they must be made aware of safe/effective contraception, the importance of pregnancy planning, and potential menstrual and sexual health disturbances related to epilepsy and AEDS. Reproductive and sexual health should be an integral component of transition education and planning for all youth, but is especially important for the youth with epilepsy. While many clinicians will collaborate with adolescent gynecologists or pediatricians, it is important for all child neurologists to be aware of these issues.

Expert opinion: Proposed diagnostic and treatment algorithms for Lennox-Gastaut syndrome in adult patients.

Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy diagnosed in childhood that persists through adolescence and into adulthood. While the characteristics of LGS in pediatric patients are well defined, including "drop attacks", interictal slow spike and wave electroencephalogram (EEG) activity, and intellectual disability, these features can evolve over time, and different EEG activities may be present in adult patients with LGS. This may result in missed diagnoses in these patients and subsequent challenges for the adequate treatment of their seizures. Based on discussions held during the LGS Transition of Care advisory board meeting and thereafter, we developed proposed diagnostic and treatment algorithms for LGS in adult patients. We highlight readily available assessments to facilitate diagnosis of LGS, based on past medical history and physical examination. The LGS diagnostic algorithm recommends that clinicians consider the occurrence of wider seizure types and abnormal EEG activities to be potentially indicative of LGS. Seizure types may include atypical absence seizures, myoclonic seizures, focal seizures, and tonic-clonic seizures, and EEG may demonstrate background slowing, focal or multifocal epileptiform discharges, and diffuse fast rhythms during sleep, among other activities. Extended EEG during sleep and video-EEG should be used in equivocal cases. Treatment of LGS in adult patients should incorporate both antiseizure drug (ASD) therapy and nonpharmacologic approaches. Frequent reassessment of patients is considered a central aspect. ASDs were categorized based on order of preference for use in the treatment of LGS; Tier 1 comprises recommended first-line ASDs, and includes valproate, clobazam, lamotrigine, rufinamide, topiramate, and cannabidiol. Other treatment options include diet, neurostimulation, and surgical approaches. Developments with the potential to improve diagnosis in the future include genetic screening, while novel ASDs and advances in neurostimulation techniques may provide valuable treatment options. These algorithms should be frequently revisited to incorporate improved techniques and therapies.

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.

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.

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.

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.

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.

Cultural Barriers to Medication Adherence in Epilepsy.

Antiepileptic drugs can prevent seizures in most patients; however, nonadherence is frequently reported. Nonadherence is associated with a higher incidence of emergency department visits, increased hospital admissions, and an increased risk of mortality. Misconceptions about epilepsy, level of education, and language barriers are contributors to nonadherence. Misconceptions about epilepsy and antiepileptic drugs are prevalent among economically disadvantaged predominantly minority persons with epilepsy. Educational interventions may improve adherence.

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%.

Efficacy and safety of perampanel in patients with drug-resistant partial seizures after conversion from double-blind placebo to open-label perampanel.

OBJECTIVE: To evaluate the efficacy and safety of perampanel in patients with drug-resistant partial seizures after the conversion from double-blind placebo in three phase III studies to open-label perampanel, and to assess the impact of perampanel titration rates through a comparison of weekly vs biweekly dose increases. METHODS: Patients who completed the three multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) were eligible to enroll in the extension study (study 307). Patients completing the double-blind treatment (6-week titration, 13-week maintenance) with placebo (DB-PBO) or perampanel (DB-PER) began the extension study with a 16-week blinded conversion period, during which DB-PBO patients were switched to perampanel. Doses were titrated in 2-mg increments (biweekly) to an individualized maximum tolerated dose of perampanel (up to 12 mg/day). Patients then entered a planned, open-label treatment period. RESULTS: Perampanel treatment during the extension study reduced total seizure frequency/28 days relative to the double-blind prerandomization baseline regardless of prior perampanel or placebo treatment in the core studies. In the DB-PBO patients, median percent reductions in seizure frequency at the end of the double-blind period, at the end of the conversion period, and at Weeks 40-52 in the open-label maintenance period were 18.6%, 44.3%, and 55.0%, respectively. Seizure control was also improved in the DB-PER patients during the extension period compared to the end of the double-blind period. Responder rates were similar between the 2 patient groups at the end of the conversion period. Perampanel was well tolerated, with the most common treatment-emergent adverse events being dizziness, somnolence, weight increase, irritability, fatigue, and headache. For those patients randomized to the 12 mg group (DB-PER 12 mg), 78.4% reached the daily dose of 10 or 12 mg by the end of the 6-week titration period of the double-blind phase. By the end of the 16-week conversion period of the extension study, 64.0% of DB-PBO patients reached the daily dose of 10 or 12 mg. Seizure frequency reduction was greater after the first 13-week maintenance period of the extension study in the DB-PBO group compared to patients assigned to DB-PER 12mg during the 13-week maintenance period of the double-blind study. CONCLUSION: Patients who received placebo in the phase III core DB studies and transitioned to perampanel in the open-label extension study (DB-PBO) achieved seizure control at the end of the conversion period similar to that of patients who had been previously exposed to perampanel (DB-PER) as well as comparable safety outcomes. Patients who received perampanel during the core studies and continued with treatment during the extension study (DB-PER) also showed sustained improvements in seizure control with long-term exposure to perampanel.

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.

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.

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.

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.

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.

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.

Tiagabine in clinical practice: effects on seizure control and behavior.

OBJECTIVE: Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. METHODS: Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. RESULTS: Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). CONCLUSIONS: Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug.

Evaluating racial/ethnic variations in outpatient epilepsy care.

This study evaluated the quality of epilepsy care in an ambulatory population of a major medical center and determined if there were any racial/ethnic variations. The well-established 'Quality Indicators in Epilepsy Treatment (QUIET)' study dataset was used. Medical record, phone interview, and mail-out survey data of 311 patients with epilepsy were linked and analyzed. Evaluation of care from provider and patient perspectives was performed. Overall, the patients with epilepsy received 40.9% of QI recommended care. The black patients were more likely to receive 50% or more QI recommended care compared with non-Hispanic whites (odds ratio [OR]=2.16, 95% confidence interval [CI] 1.09-4.27). Black patients scored significantly worse than non-Hispanic whites for two patient-reported measures--perceived racial/ethnic disparities (OR=3.14, 95% CI 1.15-8.53) and difficulties getting follow-up appointments (OR=3.37, 95% CI 1.55-7.32). The results indicate the need to evaluate both provider- and patient-centered measures in quality-of-care studies in disparities research.