Efficacy and tolerability of the first antiepileptic drug in children with newly diagnosed idiopathic epilepsy

PurposeLimited data are available for the effectiveness of the antiepileptic drugs in children in daily clinical practice. The aim of this study was to investigate the efficacy and tolerability of the first prescribed old and new antiepileptic drugs in children with newly diagnosed idiopathic epilepsy during a 12-month period.MethodA total of 289 children (141 females and 148 males) who received phenobarbital (n = 33), valproate (n = 142), carbamazepine (n = 42), oxcarbazepine (n = 38), or levetiracetam (n = 34) as the first-line treatment, were enrolled in the study. Seizure control and the occurrence of adverse events were assessed during a treatment period of 12 months.ResultsOverall, 245 (84.8%) patients remained seizure-free during the study period. The rate of seizure control did not differ significantly between the drug groups (p = 0.099). Forty-four (15.2%) patients including 1 (3.0%) treated with phenobarbital, 22 (15.5%) with valproate, 7 (16.7%) with carbamazepine, 10 (26.3%) with oxcarbazepine, and 4 (11.8%) with levetiracetam had treatment failure. There was no significant difference between seizure-free and failure groups in terms of age, gender, seizure type, and drugs used. Overall, 80 (27.7%) patients had adverse events, of those the most common ones were behavioral problems, nausea and/or vomiting, weight gain, and learning difficulties. The reasons for treatment failures were lack of seizure control in 29 (10.0%) patients and intolerable adverse events in 15 (5.2%) patients.ConclusionIt appears that old (phenobarbital, valproate and carbamazepine) and new antiepileptic drugs (oxcarbazepine and levetiracetam) have similar efficacy and tolerability profiles.Institutional ethic number is 28.3.2013/14.     

Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy

PurposeA study was conducted to investigate the frequency of potential pharmacokinetic drug-to-drug interactions in elderly patients with newly diagnosed epilepsy. We also investigated co-morbid conditions associated with epilepsy.MethodFrom the register of Kuopio University Hospital (KUH) we identified community-dwelling patients aged 65 or above with newly diagnosed epilepsy and in whom use of the first individual antiepileptic drug (AED) began in 2000–2013 (n = 529). Furthermore, register data of the Social Insurance Institution of Finland were used for assessing potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. We extracted all patients aged 65 or above who had received special reimbursement for the cost of AEDs prescribed on account of epilepsy in 2012 where their first AED was recorded in 2011–2012 as monotherapy (n = 1081). Clinically relevant drug interactions (of class C or D) at the time of starting of the first AED, as assessed via the SFINX–PHARAO database, were analysed.ResultsHypertension (67%), dyslipidemia (45%), and ischaemic stroke (32%) were the most common co-morbid conditions in the hospital cohort of patients. In these patients, excessive polypharmacy (more than 10 concomitant drugs) was identified in 27% of cases. Of the patients started on carbamazepine, 52 subjects (32%) had one class-C or class-D drug interaction and 51 (31%) had two or more C- or D-class interactions. Only 2% of the subjects started on valproate exhibited a class-C interaction. None of the subjects using oxcarbazepine displayed class-C or class-D interactions. Patients with 3–5 (OR 4.22; p = 0.05) or over six (OR 8.86; p = 0.003) other drugs were more likely to have C- or D-class interaction. The most common drugs with potential interactions with carbamazepine were dihydropyridine calcium-blockers, statins, warfarin, and psychotropic drugs.ConclusionsElderly patients with newly diagnosed epilepsy are at high risk of clinically relevant pharmacokinetic interactions with other drugs, especially if exposed to carbamazepine, but these interactions can be controlled via rational drug choices and with prediction of the possible drug-to-drug interactions. Patients on dihydropyridine calcium-channel blockers, statins, warfarin, and risperidone face the highest risk of interactions.     

Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy

This study aimed to identify factors predicting the response to antiepileptic drugs in patients with newly diagnosed epilepsy. We prospectively studied 176 patients with newly diagnosed epilepsy. Patients were included if they had a history of two or more clinically definite unprovoked seizures, or had a definite epileptic focus on MRI or epileptiform discharges on electroencephalography if they had suffered only one seizure. The primary endpoint was seizure freedom during the initial 6 months of antiepileptic drug treatment. The secondary endpoint was the time to the first seizure during the maintenance period of antiepileptic drug treatment. A total of 100 patients were included, and seizure freedom for 6 months was achieved in 73 patients. The response to antiepileptic drugs was significantly lower in patients with early age at seizure onset (⩽16 versus >16 years old, odds ratio = 4; 95% confidence interval [CI] 1.5–12.9; relative risk = 1.4; 95% CI 1.1–1.8). In addition, the time to the first seizure during the maintenance period was significantly earlier in patients with age at seizure onset ⩽16 years compared with those with age at seizure onset >16 years on the Kaplan–Meier survival analysis (p = 0.011). Early age at seizure onset is an important factor influencing the response to antiepileptic drugs in patients with newly diagnosed epilepsy.     

Presence of epileptiform discharges on initial EEGs are associated with failure of retention on first antiepileptic drug in newly diagnosed cryptogenic partial epilepsy: A 2-year observational study

ObjectivesApproximately two-thirds of the patients with newly diagnosed partial epilepsy remained on their first antiepileptic drug (AED) for 2 years in clinical practice. We aimed to analyze retention on the first AED for 2 years in newly diagnosed cryptogenic partial epilepsy patients in clinical practice and whether the presence of epileptiform discharges on the initial EEG was a predictor of the failure of retention on the first AED.MethodsFor the purpose of this study, we retrospectively reviewed epilepsy database. On the Epilepsy Database, we found 495 newly diagnosed epilepsy patients who had been followed up for at least 2 years. Of these 495 newly diagnosed epilepsy patients, 172 patients had cryptogenic partial epilepsy. The outcome of this study was the retention rate for the first AED for 2 years. In addition, we analyzed the retention on first AED according to the presence or absence of epileptiform discharges on the initial EEG using Kaplan–Meier survival analysis.ResultsOverall, retention rate on the first AED for 2 years was 51%. The main lesion of retention failure was a lack of tolerance. The presence of epileptiform discharges on the initial EEGs was significantly related to the failure of retention on the first AED (p = 0.003).ConclusionsIn newly diagnosed cryptogenic partial epilepsy, overall retention on the first AED was not significantly different from that in newly diagnosed partial epilepsy. In clinical practice, epileptiform discharges on the initial EEG could predict the failure of retention on the first AED for 2 years.     

The effect of antiepileptic drugs on thyroid function in children

BackgroundLimited and conflicting data exist for the influence of antiepileptic drugs on thyroid function in children.ObjectiveThe aim of this study was to investigate the effects of phenobarbital, valproate, carbamazepine, oxcarbazepine, and levetiracetam monotherapy on thyroid function in daily clinical practice during a 12-month treatment period.MethodA total of 223 children (103 females and 120 males) with new onset and controlled epilepsy treated with valproate (n = 129), phenobarbital (n = 33), carbamazepine (n = 36), oxcarbazepine (n = 14), levetiracetam (n = 11) were enrolled in the study. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels were measured before and at first, sixth and twelfth months of therapy.ResultsAt baseline, average fT4 and TSH concentrations were not different between the drug groups. Valproate-treated patients had decreased fT4 and increased TSH levels at months 1, 6, and 12. Carbamazepine-treated patients had decreased fT4 levels at months 1, 6, and 12 and increased TSH levels at months 1, and 6. Phenobarbital-treated patients had decreased fT4 levels at months 1, and 6, and increased TSH levels at months 6 and 12. Oxcarbazepine-treated patients had decreased fT4 levels at month 1. Levetiracetam-treated patients showed no significant change of fT4 and TSH at any times. The frequency of subclinical hypothyroidism at month 12 was 28% in valproate, 21.4% in oxcarbazepine, 18.2% in phenobarbital, 13.9% in carbamazepine, and 0% in levetiracetam groups.ConclusionOur data suggest that all antiepileptic drugs studied except levetiracetam had varying degrees of deleterious effects on thyroid function.     

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly

PurposeEpidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan.MethodsWe searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3 T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded.ResultsWe identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n = 33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n = 50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n = 51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year.ConclusionThe most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.     

Inpatient treatment costs of status epilepticus in adults in Germany

PurposeStatus epilepticus (SE) is an important neurological emergency and a significant source of direct costs related to hospitalization; however, no cost-of-illness (COI) studies have been performed in Europe. The objective of this study was to determine and characterize hospital costs related to the acute inpatient treatment of SE and to provide national estimates of SE hospitalization costs.MethodsAdult inpatient treatment costs related to SE and costs attributable to epilepsy-related hospital admissions were derived from billing data of participating hospitals.ResultsDuring the 4-month study period a total of 96 patients (59.5 ± 21.6 years; 52 male) received inpatient treatment for epilepsy-related reasons, 10 of these (10.4%) were treated for SE. Epilepsy was newly diagnosed in 30/96 patients (31.3%), of whom five presented with SE. The admission costs related to SE (€8347 ± 10,773 per patient per admission) were significantly higher than those related to admissions of patients with newly diagnosed (€1998 ± 1089; p = 0.014) or established epilepsy (€3475 ± 4413; p = 0.026). Of the total inpatient costs (€346,319) 24.4% were attributable to SE, 14.4% to newly diagnosed epilepsy without SE (n = 25) and 61.2% to complications of established epilepsy (n = 61). Extrapolation to the whole of Germany (population 82 million) indicates that SE causes hospital costs of more than €83 million per year while the total of epilepsy-related inpatient treatment costs amounts to €342 million.ConclusionAcute treatment of SE is responsible for a high proportion of hospital costs associated with epilepsy. With a high incidence of SE in the elderly population, the health care systems will face an increasing number of presentations with SE and its associated costs, underlining the necessity to further evaluate the burden and optimize the treatment of SE.     

Long-term changes in the incidence of childhood epilepsy. A population study from Finland

BackgroundThe incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased.MethodsChanges in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤ 15 years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000 person-years in each calendar year during 1968 to 2012.ResultsThe annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000 person-years in the 1990s and decreased thereafter to 61 per 100,000 person-years. Since 1996, the incidence density decreased 1–2% per year in children aged < 1, 1–5, or 6–10 years (all 95% confidence intervals within 0.3%–3%), while no substantial change was seen in older children.ConclusionThe incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.     

Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes

PurposeTo investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies.MethodsThis was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n = 51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n = 81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test.ResultsCompared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P = 0.049) and those not requiring valproic acid (77% vs. 56%, P = 0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P = 0.018) and changes in antiepileptic drugs (24% vs. 41%, P = 0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations.ConclusionFor women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs.     

Seizure outcome after AED failure in pediatric focal epilepsy: Impact of underlying etiology

ObjectiveThis study aimed to identify long-term seizure outcome in pediatric nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs) due to lack of efficacy.MethodsChildren (1 month–17 years) with new-onset focal epilepsy not meeting the criteria for a defined electroclinical syndrome diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were retrospectively identified. Medical records of those followed for ≥ 2 years were reviewed to assess etiology, the number of AEDs that failed due to lack of efficacy, and seizure outcome at final follow-up. Etiology was classified into structural/metabolic, genetic, or unknown. Favorable outcome was defined as seizure freedom ≥ 1 year, on or off AEDs, without prior epilepsy surgery. Poor outcome was defined as ongoing seizures in the preceding year or having undergone prior epilepsy surgery.ResultsNonsyndromic focal epilepsy accounted for 275/468 (59%) of all patients with newly diagnosed epilepsy — of these, 256 (93%) were followed for a minimum of two years and were included in the study. Median duration of follow-up was 10.0 years. At least one AED had failed due to lack of efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%) children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED failures, the seizures of nearly one-quarter of children who had epilepsy with an unknown cause responded favorably to the third AED compared with only 7.8% of the cohort that had epilepsy with a structural/metabolic cause. Children with a remote brain insult had a significantly higher likelihood of favorable outcome with serial AEDs than those with other structural abnormalities.SignificanceEtiology is an important determinant of pharmacoresistance in nonsyndromic focal epilepsy. Surgical evaluation should be considered after failure of 1–2 AEDs in those who have epilepsy with structural causes, excluding remote brain insults. Conversely, as surgical success is lower with normal MRI or more diffuse brain insults, it appears reasonable to hold off surgical evaluation until 2–3 AEDs have failed in such children.     

Epilepsia en el anciano: ¿la edad de inicio marca la diferencia?

IntroductionEpilepsy is most frequent in children and elderly people. Today's population is ageing and epilepsy prevalence is increasing. The type of epilepsy and its management change with age.MethodsWe performed a retrospective, observational study comparing patients aged ≥ 65 years with epilepsy diagnosed before and after the age of 65, and describing epilepsy characteristics and comorbidities in each group.ResultsThe sample included 123 patients, of whom 61 were diagnosed at < 65 years of age (group A), 62 at ≥ 65 of age (group B). Sex distribution was similar in both groups, with 39 men (62.9%) in group A and 37 (60.7%) in group B. Mean age was 69.97 ± 5.6 years in group A and 77.29 ± 6.73 in group B. The most common aetiology was unknown in group A (44.3%, n = 27) and vascular in group B (74.2%, n = 46). History of stroke was present in 12 patients from group A (19.7%) and 32 (51.6%) in group B. Antiepileptic drugs were prescribed at lower doses in group A. Statistically significant differences were found between groups for history of ischaemic stroke, cognitive impairment, psychiatric disorders, and diabetes mellitus; degree of dependence; and number of antiepileptic drugs.ConclusionAge of onset ≥ 65 years is closely related to cardiovascular risk factors; these patients require fewer antiepileptic drugs and respond to lower doses. Some cases initially present as status epilepticus.     

Computerized Cognitive Testing in Epilepsy (CCTE): A new method for cognitive screening

PurposeOptimized therapy in epilepsy should include individual care for cognitive functions. Here we introduce a computerized screening instrument, called “Computerized Cognitive Testing in Epilepsy” (CCTE), which allows for time-efficient repetitive assessment of the patient's cognitive profile regarding the domains of memory and attention, which are frequently impaired due to side effects of antiepileptic medication.MethodsThe CCTE battery takes 30 min and covers tasks of verbal and figural memory, cognitive speed, attention and working memory. The patient's results are displayed immediately in comparison to age-related normative data. For evaluation of psychometrics and clinical correlations, data from patients of a tertiary referral epilepsy center (n = 240) and healthy subjects (n = 83) were explored.ResultsCCTE subtests show good reliability and concurrent validity compared to standard neuropsychological tests (p < 0.01). Adverse cognitive effects of antiepileptic medication can be detected (p < 0.05), e.g. significant negative effects of increasing drug load. Specific epilepsy subgroups, e.g. focal versus primary generalized epilepsy or right versus left mesial temporal lobe epilepsy, showed different CCTE profiles.ConclusionCCTE appears valuable for early detection of individual cognitive alterations related to medication. In addition, it displays interesting differences between epilepsy syndromes. The CCTE battery provides a standardized, time- and personnel-efficient assessment of cognitive functions open to a large number of patients and applicable for clinical and scientific use in epilepsy.     

An evaluation of the impact of memory and mood on antiepileptic drug adherence

RationaleAntiepileptic drugs are the mainstay of treatment for patients with epilepsy. Adherence to the prescribed regimen is a major factor in achieving a reduced seizure burden, which can decrease morbidity and mortality. Patients with epilepsy oftentimes complain about difficulty with memory. Because little is known about the relationship between memory and mood and adherence, the purpose of this project was to determine the impact of the confounding factors of memory and mood on antiepileptic drug adherence in patients with epilepsy.MethodsOne hundred adult patients with epilepsy were recruited from the outpatient neurology clinic for this cross-sectional study. Patients who met the inclusion criteria completed measures of subjective memory (subset of 6 memory questions from the QOLIE-89) and objective memory (Hopkins Verbal Learning Test — Revised), subjective adherence (Morisky scale) and objective adherence (medication possession ratio), and mood (Neurological Disorders Depression Inventory for Epilepsy). Refill records from each patient's community pharmacy were used to objectively assess adherence. Medication possession ratios were calculated based on the antiepileptic drug refill records over the previous 6 months. Patients were considered adherent if their MPR was > 80%.ResultsWomen made up the majority of the sample (n = 59), and, on average, patients had been living with epilepsy for nearly 20 years. Approximately 40% of the sample were on antiepileptic drug monotherapy; most patients (> 70%) took their antiepileptic drugs twice daily, and the mean number of total medications was 4.25 ± 2.98. Based on the objective measure of adherence, 35% of the patients were nonadherent. Patients self-reported better adherence than what was objectively measured. Only the retention metric of the objective memory measure differentiated adherent patients from nonadherent patients. Patients in the adherent group had significantly lower depression scores (indicating better mood) compared with those in the nonadherent group (p = 0.04).ConclusionsObjective memory measures were not robustly correlated with adherence. However, we observed that patients with higher depressed mood scores were more likely to be nonadherent. By targeting patients with epilepsy and comorbid depression, practitioners may identify patients at greatest risk of nonadherence and subsequent harm.     

Risk factors for valproic acid resistance in childhood absence epilepsy

AimsValproic acid (VPA) is reported to be effective for the control of absence seizures in 75% of children. The aim of this study was to determine the clinical and socio-demographic factors associated with VPA response in newly diagnosed childhood absence epilepsy (CAE) and to determine if these factors also influence the chances of achieving long-term seizure freedom.MethodsMedical charts of 180 children with CAE were retrospectively reviewed. Clinical, electroencephalographic and imaging findings were recorded to correlate with complete VPA response and long-term epilepsy outcome. Factors associated with non-responsiveness were identified individually and in a multivariable logistic regression analysis.ResultsTreatment was successful in 112 (58.3%) children. More children that were non-responsive to VPA experienced generalized tonic clonic seizures (GTCS) (33.8% vs. 13.4% for responders; p = 0.001) and 52.9% had a pre-treatment seizure frequency greater than 10/day (vs. 27.0% for responders; p < 0.001). Finally, responders were older at time of diagnosis versus non-responders (p = 0.001). Absence of long-term seizure freedom was linked to the presence of GTCS, the absence of initial response and the need for multiple AEDs to control seizures.InterpretationOur results suggest that clinical phenotypes are associated with reduced response rates to VPA. This should be taken into account when counselling families of children with newly diagnosed absence epilepsy.     

Medical care costs of newly diagnosed children with structural-metabolic epilepsy: A one year prevalence-based approached

PurposeAims of this study were to estimate the first-year medical care costs of newly diagnosed children with structural-metabolic epilepsy and to determine the cost-driving factors in the selected population.MethodThis was a prevalence-based retrospective chart review that included patients who attended a pediatric neurology clinic in a tertiary referral center in Malaysia. The total first-year medical care costs were estimated from the provider (i.e., hospital) perspective, using a bottom-up, microcosting analysis. Medical chart/billing data (i.e., case reports) obtained from the hospital (i.e., provider) were collected to determine the resources used. Prices or cost data were standardized for the year 2010 (One Malaysian Ringgit MYR is equivalent to 0.26 Euro or 0.32 USD).ResultsThe most expensive item in the costs list was antiepileptic drugs, whereas ultrasound examination represented the cheapest item. Hospitalization and the use of non-antiepileptic drugs were the second and third most costly items, respectively. The cost of therapeutic drug monitoring comprised only a small proportion of the total annual expenditure. None of the demographic variables (i.e., gender, race, and age) significantly impacted the first-year medical care costs. Similarly, child development, seizure type, therapy type (i.e., polytherapy versus monotherapy), and therapeutic drug monitoring utilization were also not associated with the cost of management. The first-year medical care costs positively correlated with seizure frequency (r_s = 0.294, p = 0.001). However, the only variable that significantly predict the first-year medical care costs was the type of antiepileptic drugs (R² = 0.292, F = 7.772, p < 0.001).ConclusionThis investigation was the first cost analysis study of epilepsy in Malaysia. The total first-year medical care costs for 120 patients with structural-metabolic epilepsy were MYR 202,816 (i.e., MYR 1690.13 per patient per year). The study findings highlight the importance of optimizing seizure control in reducing the cost of management.     

Comorbidities and risk factors associated with newly diagnosed epilepsy in the U.S. pediatric population

Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤ 18 years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2 years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8 years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI = 122–129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI = 58.1–61.0 vs. 23%, CI = 23.1–23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI = 34.3–37.1) than those without epilepsy (8%, 99% CI = 7.45–7.51, P < 0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI = 26.9–29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR = 29.8, 99% CI = 23.7–37.3, P < 0.001). Compared with children with risk factors but no epilepsy, those with both epilepsy and risk factors were more likely to have intellectual disabilities (OR = 13.4, 99% CI = 11.9–15.0, P < 0.001). The epilepsy and intellectual disabilities could share the common pathophysiology in the neuronal network.     

The usefulness of the head-up tilt test in patients with suspected epilepsy

PurposeIt is estimated that approximately 20–30% of patients diagnosed with epilepsy have been misdiagnosed, and neurocardiogenic syncope (NCS) might frequently be the real cause of transient loss of consciousness (TLOC) episodes.We assessed the role of the head-up tilt test (HUTT) in patients previously diagnosed with refractory epilepsy to evaluate the ability of this test to correctly diagnose patients with NCS.MethodWe retrospectively analysed the clinical records of 107 consecutive patients with a previous diagnosis of refractory epilepsy that were taking antiepileptic drugs and who were referred for HUTT between January 2000 and December 2010. During the subsequent follow-up, we recorded the treatments performed and the recurrence of symptoms.ResultsComplete follow-up data were available for 94 (88%) patients, and the mean follow-up period was 80 ± 36 months. The HUTT was positive in 54% of patients. Thirty-one (33%) patients were misdiagnosed with epilepsy, and 20 (21%) patients had a dual diagnosis of NCS and epilepsy. The recurrence of TLOC was reported in 55% of the patients, but it was significantly lower in the misdiagnosed group (42% versus 64%; P = 0.039).ConclusionNCS is an important cause of epilepsy misdiagnosis. The HUTT is often critical for making an accurate diagnosis and subsequently selecting the appropriate treatment for patients presenting with TLOC. The diagnostic overlap between epilepsy and NCS is not uncommon, suggesting that electroencephalographic monitoring during a HUTT may play an important role in diagnosing patients with recurrent, undiagnosed TLOC episodes.     

Comparing sleep profiles between patients with juvenile myoclonic epilepsy and symptomatic partial epilepsy: Sleep questionnaire-based study

ObjectivesPatients with epilepsy commonly report excessive daytime sleepiness and daytime fatigue, which may be attributed to the direct effect of seizures, a side effect of antiepileptic drugs or a combination of the two. The aim of the study was to compare sleep profiles in patients with juvenile myoclonic epilepsy (JME) and symptomatic partial epilepsy (PE) in drug naïve and treated patients using standardized sleep questionnaires.MethodsThree study groups: - 1) juvenile myoclonic epilepsy (N = 40) [drug naïve (N = 20); On sodium valproate (SVA) (N = 20)]; 2) symptomatic partial epilepsy (N = 40) [drug naïve (N = 20); On carbamazepine (CBZ) (N = 20)]; 3) healthy controls (N = 40) completed 3 standardized sleep questionnaires – Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and NIMHANS Comprehensive Sleep Disorders Questionnaire. Scores were compared using t-test and Chi-squared tests (P ≤ 0.005).ResultsThe mean PSQI scores as well as the proportion of subjects with abnormal PSQI scores were higher in patients with JME and PE compared to controls. Although the mean ESS scores were comparable between patients with epilepsy and controls, the percentage of patients with partial epilepsy having abnormal ESS scores was higher. No significant differences were present between drug naïve and treatment monotherapy groups. Excessive daytime somnolence was reported more often by patients with JME compared to patients with partial epilepsy and controls.ConclusionThis study found that patients with epilepsy have a higher prevalence of poor sleep quality compared to controls. Moreover, a significantly higher percentage of patients with partial epilepsy had higher ESS scores compared to healthy controls. However, there was no difference between ESS and PSQI scores between drug naïve and treated patients with JME or PE.SignificancePoor sleep quality is more prevalent in patients with epilepsy irrespective of the use of antiepileptic medications. Excessive daytime somnolence is more commonly seen in patients with partial epilepsy when compared to the general population.     

Behavioral predictors of medication adherence trajectories among youth with newly diagnosed epilepsy

ObjectiveThis study aimed to identify psychosocial predictors of two-year antiepileptic drug (AED) adherence trajectories among youth with newly diagnosed epilepsy, controlling for known demographic and medical factors.MethodThis study is part of a large, prospective, longitudinal observational study of AED adherence and medical outcomes in youth with newly diagnosed epilepsy. Parents completed questionnaires of psychosocial and family functioning at one month and one year following diagnosis. Chart review and questionnaires were used to collect medical variables and seizure outcomes. Previously established two-year AED adherence trajectories (Severe Early Nonadherence, Variable Nonadherence, Moderate Nonadherence, High Adherence) were used as the outcome variable.ResultsParticipants were 91 parents of youth with epilepsy (7.3 ± 2.8 years of age; 60% male) and their families. Early (one month following diagnosis) predictors of two-year adherence trajectories included socioeconomic status, epilepsy knowledge, family problem-solving, and family communication. Significant predictors one year following diagnosis included socioeconomic status, parent fears and concerns, and parent life stress.ConclusionThere are modifiable parent and family variables that predict two-year adherence trajectories above and beyond known medical (e.g., seizures, side effects) factors. Psychosocial interventions delivered at key points during the course of epilepsy treatment could have a positive impact on adherence outcomes.