Fracture risk with use of liver enzyme inducing antiepileptic drugs in people with active epilepsy: Cohort study using the General Practice Research Database

PurposeLiver enzyme inducing antiepileptic drugs (LEI AEDs) have adverse effects on bone metabolism but it is unclear whether this translates into increased fracture risk. This population based cohort study aimed to evaluate whether treatment with LEI AEDs is associated with increased risk of fracture in people with active epilepsy.MethodsThe cohort included patients diagnosed with epilepsy and prescribed AEDs while registered at a GPRD general practice during 1993–2008. The hazard ratio with current use of LEI AEDs for fracture at any site and hip fracture was estimated using Cox proportional hazards models.ResultsThere were 7356 fractures (788 hip fractures) in 63 259 participants. In women, the adjusted hazard ratio with use of LEI AEDs was 1.22 for fracture (95% CI 1.12–1.34; p < 0.001) and 1.49 for hip fracture (1.15–1.94; p = 0.002). In men, the hazard ratio for fracture was 1.09 (0.98–1.20; p = 0.123) and for hip fracture 1.53 (1.10–2.12; p = 0.011). For every 10 000 women treated with LEI AEDs for one year, there could be 48 additional fractures, including 10 additional hip fractures. For every 10 000 men treated with LEI AEDs for one year, there could be 4 additional hip fractures.ConclusionsLEI AEDs may increase the risk of fracture in people with epilepsy. In patients at high risk of osteoporotic fracture alternative AED therapy may be appropriate. Further information is urgently needed on the safety of valproate and newer AEDs and on strategies to maintain bone health in people who need to be treated with LEI.     

Healthcare utilization and costs in children with stable and uncontrolled epilepsy

ObjectiveEpilepsy adversely affects childhood development, possibly leading to increased economic burden in pediatric populations. We compared annual healthcare utilization and costs between children (< 12 years old) with stable and uncontrolled epilepsy treated with antiepileptic drugs (AEDs).MethodsChildren (< 12 years old) with epilepsy (ICD-9-CM 345.xx or 780.39) in 2008 were identified in the MarketScan claims database from 2007 to 2009. Patients with “stable” epilepsy used the same AED for ≥ 12 months, and patients with “uncontrolled” epilepsy were prescribed additional AED(s) during that period. For patients with uncontrolled epilepsy, the study index date was the start of additional AED(s); for patients with stable epilepsy, the study index date was a random AED fill date. Epilepsy-related utilization included medical services with 345.xx or 780.39 in any diagnosis field and AED fills. Epilepsy-related costs included AEDs, medical claims with epilepsy in any diagnosis field, and certain tests. We adjusted for baseline cohort differences (demographics, region, usual-care physician specialty, and comorbidities) using logistic regression and analysis of covariance.ResultsTwo thousand one hundred seventy patients were identified (mean: 7.5 years; 45.3% were female; Charlson comorbidity index: 0.3; 422 (19.4%) patients with uncontrolled epilepsy). Patients with uncontrolled epilepsy faced more hospitalizations (30.1% vs. 12.0%) and greater overall ($30,343 vs. $18,206) and epilepsy-related costs ($16,894 vs. $7979) (all p < .001). Adjusting for baseline measures, patients with uncontrolled epilepsy had greater odds of hospitalization (OR: 2.5; 95% CI: 1.9–3.3) and costs (overall: $3908, p = .087; epilepsy-related: $5744, p < .001).ConclusionsChildren with uncontrolled epilepsy use significantly more healthcare resources and have a greater economic burden than children with stable epilepsy. However, epilepsy accounted for only half of overall costs, indicating that comorbid conditions may add substantially to the disease burden.     

Generalised convulsive status epilepticus in Singapore: Clinical outcomes and potential prognostic markers

PurposeTo study the characteristics, outcomes and prognostic markers of convulsive status epilepticus (SE) in Singapore.Methods62 adult admissions to the National University Hospital Singapore from 2002 to 2005 were studied. Ethnicity, history of epilepsy, educational subnormality, neuroimaging, seizure duration, length of stay, Modified Rankin Scale (MRS) pre and post discharge, blood glucose, creatine kinase, potassium, white cell and platelet count were recorded. An MRS ≥ 3 at discharge was defined as a poor outcome. ROCs of significant variables were plotted to identify the best test cut-offs.ResultsMean age was 59.2 years (range 20–94). 75.9% patients had epilepsy. Mean length of stay was 14 days (range 1–75). Univariate analyses revealed age (p = 0.01, OR 1.075, 95% CI 1.030–1.122), length of stay in ICU (p = 0.03, OR 1.299, 95% CI 1.014–1.665) and hospital (p = 0.014, OR 1.203, 95% CI 1.038–1.393) and hyperglycemia (p = 0.045, OR 1.327, 95% CI 1.007–1.750) associated with poor outcome. Test cut-off values for prognostic markers were established: age ≥ 55 years (ROC 0.790, sensitivity 72.3, specificity 85.7, PPV9 4.4%, NPV 48.8%) and serum glucose ≥ 7 mmol/L (ROC 0.737, sensitivity 72.3, specificity 80.0, PPV 93.5%, NPV 36.4%). A discriminant model using these variables was then constructed with probability scores for poor outcome.DiscussionAge, hyperglycemia and length of stay in hospital influenced outcome from convulsive SE in the local population with hyperglycemia being a novel prognostic marker. Some prognostic markers cited in the literature differed, highlighting the possibility that these indicators may vary across population groups.     

GABRG2 rs211037 polymorphism and epilepsy: A systematic review and meta-analysis

PurposeThe gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.MethodsEight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.ResultsMeta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30–0.73, p = 0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42–0.83, p = 0.003) and dominant (OR 0.54, 95% CI 0.39–0.75, p = 0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.ConclusionThis study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.     

Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data

ObjectiveDrug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood.MethodUsing the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥ 12 months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement.ResultsAfter VNS therapy, physicians reported patient improvement in alertness (58–63%, range over follow-up period), post-ictal state (55–62%), cluster seizures (48–56%), mood change (43–49%), verbal communication (38–45%), school/professional achievements (29–39%), and memory (29–38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1–1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0–1.4), female gender (OR, 1.2; 95% CI, 1.0–1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0–1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ²] = 148.1, p < 0.001) and more likely to undergo VNS generator replacement (χ² = 68.9, p < 0.001) than those with worsened/unchanged QOL.SignificanceVNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL metrics in neuromodulation for epilepsy, given the deleterious effects of seizures on patient QOL.     

Self-esteem in adolescents with epilepsy: Psychosocial and seizure-related correlates

PurposeThis study evaluated self-esteem in adolescents with epilepsy and its association with psychosocial and disease-related variables.MethodsThis was a cross-sectional study with patients enrolled between January and June 2010. Culture-Free Self-Esteem Inventory for Children (CFSEI-2) was administered to 140 children with epilepsy and 50 children with asthma, aged 10–18 years attending mainstream schools.ResultsAdolescents with epilepsy had a significantly lower overall self-esteem score when compared with those with asthma, 17 ± 5.21 versus 19.4 ± 3.83, respectively (P = 0.005). Thirty-one (22.1%) children with epilepsy compared with 4 (8.3%) with asthma had overall self-esteem score below the cutoff (P = 0.034). There was a significant correlation between overall self-esteem score and duration of epilepsy, Hospital Anxiety and Depression Scale (HADS) anxiety score, HADS depression score, and Strengths and Weaknesses of ADHD symptoms and Normal-Behaviors (SWAN) rating combined score. The impact of various correlates on individual domains was not identical. Independent factors associated with low overall self-esteem were HADS depression score (OR: 1.62; 95% CI: 1.2, 2.2; P = 0.002), duration of epilepsy (OR: 1.4; 95% CI: 1.04, 1.88; P = 0.024), and father employment status economically inactive (OR: 11.9; 95% CI: 1.07, 125; P = 0.044). Seizure-free ≥ 12 months was a favorable factor that was less likely to be associated with low self-esteem (OR: 0.14; 95% CI: 0.02, 0.81; P = 0.028).ConclusionSelf-esteem was compromised in adolescents with epilepsy. A significant correlation between self-esteem and psychological comorbidities was demonstrated. Enhancing social support and education programs may improve the self-esteem and, ultimately, the lives of adolescents living with epilepsy.     

Should we treat patients with impaired consciousness and periodic patterns on EEG?

PurposeThe significance of periodic EEG patterns in patients with impaired consciousness is controversial. We aimed to determine if treating these patterns influences clinical outcome.MethodWe studied all patients who had periodic discharges on their EEG recordings from January 2007 to December 2009. Patients with clinical seizures within the preceding 24 h, or with unequivocal electrographical seizure activity were excluded. Logistic regression was performed to analyze for factors associated with (a) mortality (b) functional status (c) resolution of EEG pattern.ResultsOf the 4246 patients who had EEG, 111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted analysis, higher mortality was associated with acute symptomatic etiology (OR 17.74, 95% CI 1.61–196.07, p = 0.019), and presence of clinical seizures (OR 4.73, 95% CI 1.10–20.34, p = 0.037). For each unit decrement of GCS, the odds of inpatient mortality and a poorer functional state on discharge increased by 23% (95% CI 7–37%, p = 0.009) and 33% (95% CI 9–51%, p = 0.011) respectively. Administration of abortive therapy was an independent risk factor for poorer functional status on discharge (adjusted OR 41.39, 95% CI 2.88–594.42, p = 0.006), while patients with history of pre-existing cerebral disease appeared more likely to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI 1.40–17.86, p = 0.013).ConclusionTreatment of periodic EEG patterns does not independently improve clinical outcome of patients with impaired conscious levels. Occurrence of seizures remote to the time of EEG and lower GCS scores independently predict poor prognoses.     

Prognostic value of periodic electroencephalographic discharges for neurological patients with profound disturbances of consciousness

ObjectiveTo examine if periodic EEG discharges (PDs) predict poor outcome and development of epilepsy in patients with acute brain illnesses irrespective of underlying cerebral pathology.MethodsIn case-control study we retrospectively analyzed outcome of 102 patients with PDs and 102 age-, gender- and etiology matched controls without PDs.ResultsOf cases, 46.1% had lateralized PDs (LPDs), 3.9% bilateral PDs (BIPDs), 15.7% generalized PDs (GPDs) and 34.3% had combinations thereof. Etiology: Stroke was most common cause of LPDs (53%), cardiac arrest of GPDs (10.5%), previous stroke, CNS infection, anoxia and metabolic encephalopathy all caused 1 case of BIPDs. Outcome: Mortality rate and acquired disability was significantly higher in patients with PDs than in controls, odds ratio (OR) 2.5, 95% CI 1.43–4.40 (p = 0.001). Patients with PDs without superimposed EEG activity had worse outcome than patients with superimposed EEG activity. Tardive epilepsy: Patients with LPDs associated with fast superimposed EEG activity (LPDs-plus) had higher risk for tardive epilepsy than patients with LPDs alone (p = 0.034).ConclusionPDs predicted poor functional outcome and patients with LPDs-plus had higher risk for later development of epilepsy.SignificanceDetailed evaluation of PDs provided valuable prognostic information in neurological patients with disturbed consciousness.     

Disobedience and driving in patients with epilepsy in Greece

ObjectiveRegulations and guidelines regarding driving privileges of patients with epilepsy vary greatly worldwide. The aim of our study was twofold: firstly, to evaluate disobedient drivers in Greece and to elucidate their awareness of the law, emotional responses, and seizure profile and, secondly, to identify determinants of disobedience regarding driving among patients with epilepsy.MethodsAll consecutive patients with epilepsy who visited the epilepsy outpatient clinic of two tertiary epilepsy centers were invited to participate in the study. One hundred ninety patients met our inclusion criteria.ResultsFifty-two percent of our study population was aware of the driving restrictions. More than one out of three patients were disobedient (35.8%). Being a male was associated with a 6.07-fold increase in the odds of being disobedient (95% CI: 2.73–13.47, p < 0.001); being employed was associated with a 4.62-fold increase in the odds of being disobedient (95% CI: 2.20–9.68, p < 0.001); and each extra antiepileptic drug (AED) was associated with a decrease in the odds of disobedience by a factor of 0.41 (95% CI: 0.26–0.63, p < 0.001).ConclusionMale gender, employment, and number of AEDs are important determinants of disobedience regarding driving among patients with epilepsy.     

Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein

BackgroundPrior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated.MethodsWe recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, > 6 weeks after, and > 6 months after. An untreated control group (n = 14) underwent similar measurement. We combined these data with those of our previous investigation (n = 34 patients and 16 controls) of a very similar design.ResultsThere were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24 mg/dL higher, 95% CI: 17.5–29.9, p < 0.001) and CRP (72% higher, 95% CI: 41%–111%, p < 0.001). The difference between drug treatments was clinically meaningful for atherogenic lipids (16%, 95% CI: 11%–20%, p < 0.001) but small for high-density lipoprotein cholesterol (5%, 95% CI: 1%–9%, p < 0.05). All measures were stable between 6 weeks and 6 months after drug switch.ConclusionsWe demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs.     

Association between MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population: A systematic review and meta-analysis

The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and region. We have performed a systematic review and meta-analysis to assess the link between the MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population. We searched the Cochrane Library, MIDLINE, EMBASE, CBM disc, CNKI, VIP, and WANFANG databases for literature published through August 2013 for case–control studies that evaluated the association between the MDR1 C3435T polymorphism and refractory epilepsy. Twenty-one case–control studies involving 4269 patients (1863 cases in the group with drug-resistant epilepsy and 2406 in the group with drug-responsive epilepsy) were included in the systematic review and meta-analysis. The analysis showed that there were significantly more cases with the MDR1 3435 CC genotype in the group with drug-resistant epilepsy than in the group with drug-responsive epilepsy [odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.09–2.06, P = 0.01]. In a subanalysis of patients from the southern regions of China, the correlation was not significant [odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.89–1.64, P = 0.24]. The relationship established in a subset of the Chinese population between the MDR1 C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.     

Predicting drug resistance in adult patients with generalized epilepsy: A case–control study

ObjectivesUsing an adult cohort of patients with generalized epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy (DRE), which if identifiable would allow patients to receive earlier treatment and more specifically individualized treatment plans.MethodsFor the case–control study, 118 patients with generalized epilepsy (GE) between the ages of 18 and 75 were included after selection from a database of 800 patients referred from throughout the Saskatchewan Epilepsy Program. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis.ResultsForty-four (37%) patients fulfilled the definition of DRE (cases), and seizures in 74 (63%) patients were not intractable (controls). Patients with DRE were significantly younger than the controls at the onset of epilepsy (6.6 vs. 18.8 years, p = < 0.001). Significant variables on univariate analysis were the following: epilepsy diagnosed prior to 12 years (OR: 12.1, CI: 4.8–29.9, p < 0.001), previous history of status epilepticus (OR: 15.1, CI: 3.2–70.9, p < 0.001), developmental delay (OR: 12.6, CI: 4.9–32, p < 0.001), and cryptogenic epilepsy (OR: 10.5, CI: 3.9–27.8, p < 0.001). Our study showed some protective factors for DRE such as a good response to first AED, idiopathic etiology, and history of febrile seizures. In the logistic regression analysis, two variables remained statistically significant: developmental delay and more than one seizure type.ConclusionOur study has identified a set of variables that predict DRE in patients with generalized epilepsy. Risk factors identified in our study are similar to those previously identified in pediatric studies, however, our study is specifically tailored to adult patients with generalized epilepsy.     

ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: A systematic review and meta-analysis

ObjectiveThe C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case–control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.MethodsDatabases were obtained from the Cochrane Library, MEDLINE, EMBASE, major American and European conference abstracts, and www.google.my for genetic association studies up to February 2010. All the case–control association studies evaluating the role of ABCB1 C3435T in pharmacoresistance to AEDs were identified. The new definition of treatment outcome from International League Against Epilepsy (ILAE) was used for including studies for sub-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using models of both fixed- and random-effects for comparisons of the alleles and genotypes with co-dominant (C/C vs. T/T, C/T vs. T/T), dominant (C/C + C/T vs. T/T), and recessive (C/C vs. C/T + T/T) models in overall and in ethnicity subgroups. The 19 studies were selected for the next sub-analysis based on the new definition of drug-responsiveness and drug-resistance from ILAE. The same analysis was also performed for treatment outcome and ethnicity subgroups.ResultsA total of 22 association studies including 3231 (47.8%) drug-resistant patients and 3524 (52.2%) drug-responsive patients or healthy controls (genotyped for C3435T) were pooled in this meta-analysis. The allelic association of ABCB1 C3435T with risk of drug-resistance was not significant under fixed-effects model, 1.06 (95% CI 0.98–1.14, p = 0.12) and random-effects model, 1.10 (0.93–1.30, p = 0.28) in overall and in the subgroup analysis by ethnicity. Similar results were also obtained for all genetic models in the stratified analyses by new definition of drug-resistance by ILAE and ethnicity subgroups. There was no publication bias.ConclusionWe failed to show an association between the ABCB1 C3435T polymorphism and the risk of drug-resistance suggesting a revision in contribution of this polymorphism in the multi-drug transporters hypothesis of pharmacoresistance to AEDs in epilepsy.     

El insomnio y la pobre calidad de sueño se asocian a un mal control de crisis en pacientes con epilepsia

ObjectivesThis study aimed to assess the presence of sleep disorders in patients with epilepsy and to analyse their association with seizure control.MethodsWe performed a cross-sectional study of patients with epilepsy, recruited consecutively between September 2017 and December 2018. Patients were classified as having good seizure control (no seizures in the last 4 weeks) or poor seizure control (at least one seizure in the last 4 weeks). We performed intergroup comparisons for demographic and clinical data, insomnia (Insomnia Severity Index [ISI]), excessive daytime sleepiness (Epworth Sleepiness Scale [ESS]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), depression (Beck Depression Inventory-II [BDI-II]), and quality of life (Quality of Life in Epilepsy Inventory-10 [QOLIE-10]).ResultsThe sample included a total of 123 patients, of whom 31.7% had excessive daytime sleepiness (ESS ≥ 10), 50.4% had insomnia (ISI ≥ 10), and 53.6% had poor sleep quality (PSQI ≥ 5). According to our multivariate analysis, presence of seizures was associated with unemployment (odds ratio [OR] = 4.7; 95% confidence interval [CI], 1.36-19.2; P = .02), a higher number of antiepileptic drugs (OR = 5.87; 95% CI, 1.81-27.1; P < .001), insomnia (OR = 1.9; 95% CI, 1.1-9.3; P = .04), and poor sleep quality (OR = 2.8; 95% CI, 1.9-10.32; P = .01).ConclusionsSleep disorders are common in patients with epilepsy. Insomnia and poor sleep quality were associated with poor seizure control. These findings support the hypothesis that sleep disorders constitute a significant comorbidity of epilepsy, especially in patients with poor seizure control.     

Medication prescribing and patient-reported outcome measures in people with epilepsy in Bhutan

ObjectiveThe aim of this study was to assess medication prescribing and patient-reported outcomes among people with epilepsy (PWE) in Bhutan and introduce criteria for evaluating unmet epilepsy care needs, particularly in resource-limited settings.MethodsPeople with epilepsy in Bhutan (National Referral Hospital, 2014–2015) completed a questionnaire, the Quality of Life in Epilepsy Inventory (QOLIE-31), and an electroencephalogram (EEG). Management gap was the proportion of participants meeting any of six prespecified criteria based on best practices and the National Institute for Health and Care Excellence (NICE) guidelines.ResultsAmong 253 participants (53% female, median: 24 years), 93% (n = 235) were treated with antiepileptic drugs (AEDs). Seventy-two percent (n = 183) had active epilepsy (≥ 1 seizure in the prior year). At least one criterion was met by 55% (n = 138) of participants, whereas the treatment gap encompassed only 5% (n = 13). The criteria were the following: 1. Among 18 participants taking no AED, 72% (n = 13) had active epilepsy. 2. Among 26 adults on subtherapeutic monotherapy, 46% (n = 12) had active epilepsy. 3. Among 48 participants reporting staring spells, 56% (n = 27) were treated with carbamazepine or phenytoin. 4. Among 101 female participants aged 14–40 years, 23% (n = 23) were treated with sodium valproate. 5. Among 67 participants reporting seizure-related injuries, 87% (n = 58) had active epilepsy. 6. Among 111 participants with a QOLIE-31 score below 50/100, 77% (n = 86) had active epilepsy. Years since first AED treatment (odds ratio: 1.07, 95% CI: 1.03, 1.12) and epileptiform discharges on EEG (odds ratio: 1.95, 95% CI: 1.15, 3.29) were significantly associated with more criteria met.ConclusionsBy defining the management gap, subpopulations at greatest need for targeted interventions may be prioritized, including those already taking AEDs.     

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.     

Infections in status epilepticus: A retrospective 5-year cohort study

PurposeStatus epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort.MethodWe performed a retrospective observational study and included all patients with a diagnosis of SE during 2008–2012 at a Swedish tertiary referral centre.ResultsThe cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19–87 years). In house mortality was less than 2 and 70% of the patients’ were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% CI 1.44–7.79) as well as not being discharged home (OR2.705, 95% CI 1.14–6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p < 0.001).ConclusionWe conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology.     

Habitual sleep duration associated with self-reported and objectively determined cardiometabolic risk factors

BackgroundSelf-reported short or long sleep duration has been associated with adverse cardiometabolic health outcomes in laboratory and epidemiologic studies, but interpretation of such data has been limited by methodologic issues.MethodsAdult respondents of the 2007–2008 US National Health and Nutrition Examination Survey (NHANES) were examined in a cross-sectional analysis (N = 5649). Self-reported sleep duration was categorized as very short (<5 h), short (5–6 h), normal (7–8 h), or long (⩾9 h). Obesity, diabetes mellitus (DM), hypertension, and hyperlipidemia were objectively assessed by self-reported history. Statistical analyses included univariate comparisons across sleep duration categories for all variables. Binary logistic regression analyses and cardiometabolic factor as outcome, with sleep duration category as predictor, were assessed with and without covariates. Observed relationships were further assessed for dependence on race/ethnicity.ResultsIn adjusted analyses, very short sleep was associated with self-reported hypertension (odds ratio [OR], 2.02, [95% confidence interval {CI},1.45–2.81]; P < 0.0001), self-reported hyperlipidemia (OR, 1.96 [95% CI, 1.43–2.69]; P < 0.0001), objective hyperlipidemia (OR, 1.41 [95% CI, 1.04–1.91]; P = 0.03), self-reported DM (OR, 1.76 [95% CI, 1.13–2.74]; P = 0.01), and objective obesity (OR, 1.53 [95% CI, 1.03–1.43]; P = 0.005). Regarding short sleep (5–6 h), in adjusted analyses, elevated risk was seen for self-reported hypertension (OR, 1.22 [95% CI, 1.02–1.45]; P = 0.03) self-reported obesity (OR, 1.21 [95% CI, 1.03–1.43]; P = 0.02), and objective obesity (OR, 1.17 [95% CI, 1.00–1.38]; P < 0.05). Regarding long sleep (⩾9 h), no elevated risk was found for any outcomes. Interactions with race/ethnicity were significant for all outcomes; race/ethnicity differences in patterns of risk varied by outcome studied. In particular, the relationship between very short sleep and obesity was strongest among blacks and the relationship between short sleep and hypertension is strongest among non-Hispanic whites, blacks, and non-Mexican Hispanics/Latinos.ConclusionsShort sleep duration is associated with self-reported and objectively determined adverse cardiometabolic outcomes, even after adjustment for many covariates. Also, these patterns of risk depend on race/ethnicity.