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.     

Fractures in epilepsy children

PurposeTo describe a greater risk of fractures (about 2–6 times more often) in epilepsy children than in children without epilepsy.MethodsThis article describe 126 epilepsy children in age 7–16 who were treated with Antiepileptic Drugs (AEDs) in mono and add-on therapy during 5 years. In the control group were 132 children in age 7–16 without epilepsy and not treated with AEDs, observed in Outpatient Clinic due to headache for 5 years. In both groups we measured bone mineral density (BMD), the calcium and phosphate levels in blood and urine and frequency of fractures. We analyzed both groups statistically (Mann–Whitney test).ResultThe frequency of fractures is 2–3 times greater in children with epilepsy then in the control group. Osteoporosis and osteopenia is more often present in children who have taken AEDs.Differences in calcium and phosphate levels in blood and urine between study and control group are statistically significant (p < 0.001).ConclusionFractures are an important adverse effect in children who are 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.     

Neighborhood,family, and childhood and adolescent epilepsy: A nationwide epidemiological study from Sweden

PurposeTo examine whether neighborhood deprivation increases the odds of hospital registration for childhood and adolescent epilepsy, after accounting for family- and individual-level sociodemographic characteristics.MethodsAn open cohort of all children aged 2–17 years was followed between January 1, 2000 and December 31, 2010. Children's residential addresses were geocoded and classified according to neighborhood deprivation. Data were analyzed by multilevel logistic regression, with family- and individual-level characteristics at the first level and level of neighborhood deprivation at the second level.ResultsDuring the study period, among a total of 1,020,766 children, 9309 (0.9%) were registered with childhood and adolescent epilepsy. Age-adjusted cumulative hospital rates of childhood and adolescent epilepsy increased with increasing neighborhood-level deprivation across all family- and individual-level sociodemographic categories. The odds ratio (OR) for hospital registration for childhood and adolescent epilepsy for those living in high-deprivation neighborhoods versus those living in low-deprivation neighborhoods was 1.15. High level deprivation remained significantly associated with higher odds of childhood and adolescent epilepsy after adjustment for family- and individual-level sociodemographic characteristics (OR = 1.12, 95% CI = 1.04–1.21, p = 0.003).ConclusionsOur results suggest that neighborhood characteristics modestly affect the odds of hospital registration for childhood and adolescent epilepsy independently of family- and individual-level sociodemographic characteristics.     

What do epileptologists recommend about discontinuing antiepileptic drugs for a second time in children?

ObjectiveThere is a broad consensus that antiepileptic drugs (AEDs) may be withdrawn after two years of seizure freedom for most children with epilepsy. If seizures recur and are, again, completely controlled with AEDs, little is known about discontinuing a second time. We surveyed American and Canadian pediatric epileptologists to understand their current practice.MethodsIn 2014, a survey was sent via e-mail to 193 pediatric epileptologists to learn about AED discontinuation practices in children. The survey asked direct questions about practice and posed five “real-life” cases where the decision to discontinue might be difficult. Participants were identified through membership lists of several US and Canadian epilepsy organizations.ResultsThere were 94 (49%) completed surveys. Sixty-three participants had ≥ 10 years in practice (“more experienced”: mean 23 ± 9 years), and 31 had < 10 years (“less experienced”: mean 6 ± 2). Overall, 62% recommended AED discontinuation for the first time after 2–3 years of seizure freedom, and 61% recommended discontinuation for the second time after 2–3 years. Fifty-six percent of “more experienced” clinicians required a longer seizure-free period prior to a second discontinuation (p < 0.001) compared with 26% of “less experienced” clinicians (p = ns). Overall, most participants suggested an AED taper duration of 2–6 months for the first and second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly during the second attempt (p < 0.001). There was only 40–60% agreement among participants to discontinue AEDs in four of the cases.ConclusionNearly half (46%) of pediatric epileptologists require a longer seizure-free period the second time they attempt to discontinue AEDs compared with the first attempt and wean down AEDs somewhat more slowly. Although a variety of factors influence decision-making, there was a high level of disagreement to discontinue AEDs a second time in “real-life” cases.     

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.     

Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A

BackgroundFrom October 2009 to January 2010, approximately 470,000 children and adolescents in Norway ages 4–19 years were vaccinated with Pandemrix® against influenza A (H1N1 subtype). The vaccination coverage in this age cohort was approximately 50%.ObjectivesOur study was performed to evaluate the possible association between Pandemrix® vaccination and narcolepsy in Norway.MethodsChildren and adolescents with sudden onset of excessive daytime sleepiness (EDS) and cataplexy occurring after the 2009–2010 vaccination period were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy.ResultsFifty-eight vaccinated children and adolescents (35 girls, 23 boys) ages 4–19 years (mean age, 10.5 years) were diagnosed as new cases of confirmed narcolepsy and were included in our study during 2010 and 2011. Forty-two children had onset of symptoms within 6 months after vaccination, with 12 of them having symptoms within the first 6 weeks. All had EDS, 46 had documented cataplexy, 47 had mean sleep latency less than 8 min, and 43 had two or more sleep-onset rapid eye movement sleep (SOREM) periods in multiple sleep latency tests (MSLT). Cerebrospinal fluid (CSF) hypocretin levels were measured in 41 patients, with low levels in all. Thirty seven patients that were analyzed had tissue type HLADQB1*0602. During the same period, 10 unvaccinated cases were reported (mean age, 12.5 years).ConclusionThe data collected during 3 years following vaccination showed a significantly increased risk for narcolepsy with cataplexy (P < .0001) and reduced CSF hypocretin levels in vaccinated children ages 4–19 years the first year after Pandemrix® vaccination, with a minimum incidence of 10 of 100,000 individuals per year. The second year after vaccination, the incidence was 1.1 of 100,000 individuals per year, which was not significantly different from the incidence of 0.5–1 of 100,000 per year in unvaccinated children during the same period.     

An association between benzodiazepine use and occurrence of benign brain tumors

ObjectiveThis study was designed to evaluate the impact of long-term benzodiazepine use on the subsequent risk of benign brain tumor (BBT) or malignant brain tumor (MBT) development.MethodWe used data from the National Health Insurance System of Taiwan. For the study cohort, we identified 62,186 patients who had been prescribed benzodiazepine for at least 2 months between January 1, 2000 and December, 31, 2009. For each of the benzodiazepine cases, we randomly selected one insured person from the non-benzodiazepine cohort with frequency matching sex, age, and year of index date. The non-benzodiazepine cohort comprised 62,050 patients. The related hazard ratios (HRs) and 95% confidence intervals (CIs) of developing brain tumors were investigated.ResultsThe overall BBT incidence rate was 3.33-fold higher in the benzodiazepine cohort than the non-benzodiazepine cohort (46.3 vs 13.9 per 100,000 person-years) with an adjusted HR of 3.15 (95% CI = 2.37–4.20). Similarly, the MBT incidence rate was 84% higher in the benzodiazepine cohort (3.71 vs 2.02 per 1000 person-years), and the adjusted HR of 1.21 (95% CI = 0.52–2.81) was not statistically significant. When compared with the non-benzodiazepine cohort, the adjusted HRs of BBTs increased with benzodiazepine dosage (adjusted HR = 2.12, 95% CI = 1.45–3.10, for 36–150 mg/year; adjusted HR = 7.03, 95% CI = 5.19–9.51, for ≥ 151 mg/year).ConclusionIn this population-based study, we found a significant increase in the risk of benign brain tumor development in a cohort of long-term BZD users.     

Febrile convulsions increase risk of Tourette syndrome

PurposeFebrile convulsion (FC) and Tourette syndrome (TS) are both common neurological disorders in infants and children. Both disorders share clinical similarities, such as paroxysmal symptoms with normal neurodevelopment and expected remission over time. This population-based study investigated the association between FC with TS during childhood neurodevelopment.MethodWe used the Taiwan National Health Insurance Research Database to conduct a retrospective cohort analysis on 1586 FC patients. A reference cohort of 6344 non-FC patients, matched for age, sex, urbanization level, parental occupation, and index year, was used for comparison. The risk of the occurrence of TS in FC patients was assessed using a Cox proportional hazard regression model.ResultsThe overall incidence of TS was higher in the FC cohort than in the non-FC cohort (28.5 vs 13.9 per 10,000 person-years; adjusted hazard ratio = 1.91, 95% confidence interval = 1.32–2.75). The associated risk factors for FC patients to develop TS were boys, children living in rural areas, and children whose parents held blue-collar positions. Moreover, the risk of TS in FC patients rose from 0.89 to 16.0 (trend test P < 0.0001) when the frequency of FC-related medical visits increased from 1 to 2 times to more than 4 times. The adjusted hazard ratio for TS in related to FC-related medical visits was 1.02 (95% CI = 1.02–1.03) per one frequency increment.ConclusionFC may increase the risk of subsequent TS occurrence in children. Children who had frequent medical visits for FC were particularly vulnerable.     

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.     

Perceived need for restrictions on activity for children with epilepsy

BackgroundChildren and youth with epilepsy have long been subjected to excessive restrictions on extracurricular activities due to concerns over risk of injury. Over time physicians and medical regulatory associations have liberalized the advice given for people with epilepsy to promote independence, self-esteem and general health benefits of physical activity. Current evidence suggests that few restrictions are needed for children with epilepsy beyond water-related precautions and avoidance of very high-risk activities. However, more stringent restrictions on daily activities may be imposed by caregivers. This study was aimed at exploring current perceptions of parents regarding restrictions on activity for children with epilepsy and the child’s perspective on restrictions related to the diagnosis.MethodsA self-administered questionnaire was offered to a sample of parent-child dyads of children/youth with epilepsy attending summer camp for children with epilepsy age 8–18 years. A 10-item validated HARCES Parent Scale of Childhood Epilepsy was completed by the parent/guardian and a modified-HARCES completed by the child. The primary objective was to assess the degree of restrictions placed on children with epilepsy from the perspective of child and parent assessed independently. Agreement of perceived restrictions between parent-child dyads was also determined.Results21 parent/guardian-child pairs were recruited with mean age of children/youth 12.7 years (range 9–16 years). Total HARCES scores for parents and guardians ranged from 11–26 (x = 16.5; SD 4.9) while total scores for children with epilepsy similarly ranged from 10–25 (x = 15.2; SD 4.9). There were no differences in total parent scores when analyzed by child's age (< 13 or > 13 years), gender, age of seizure onset, seizure frequency or seizure type. Total HARCES scores showed no agreement between parent and child pairs with correlation of 0.2798 (95% CI − 0.173–0.635).ConclusionsChildren and youth with epilepsy often face activity restrictions based on fear of perceived risk of injury. This small sample shows evidence that even more permissive parents and his/her children still feel limited by such restrictions. Parents and children do not perceive these restrictions in the same way despite similar education by physicians highlighting an important secondary role of epilepsy camps in targeting misperceptions and educating families on appropriate precautions.     

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.     

Specific adverse effects of antiepileptic drugs — A true-to-life monotherapy study

BackgroundIn patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.MethodsAll patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.ResultsOut of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.ConclusionIndividual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.     

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-related injuries in children and adolescents with epilepsy

BackgroundChildren with epilepsy are reported to be at a greater risk of injuries compared with their peers who do not have epilepsy.ObjectivesWe set out to determine the frequency and pattern of seizure-related injuries in children with epilepsy seen at the University College Hospital (UCH), Ibadan, Nigeria.MethodsConsecutive cases of epilepsy seen at the pediatric neurology clinic of the UCH, Ibadan over a period of 6 months were evaluated for injuries in the preceding 12 months using a structured questionnaire. These were compared with age- and sex-matched controls.ResultsA total of 125 children with epilepsy and 125 age- and sex-matched controls were studied. Injuries occurred more frequently in children with epilepsy than in their peers (p = 0.01, OR 1.935, 95% CI 1.142–3.280). Epilepsy was generalized in 80 (64.0%), and localization-related in 45 (36.0%). Idiopathic epilepsy accounted for 74 (59.2%), and the remaining 51 (40.8%) had remote symptomatic epilepsy. Fifty-seven (45.6%) children had suffered seizure-related injuries with multiple injuries in 31 (24.8%). The most frequent were skin/soft tissue lacerations (26.4%), injuries to the tongue and soft tissues of the mouth (19.2%), minor head injuries (15.2%), and dental injuries with tooth loss (8.0%). There was a statistically significant association between seizure frequency and seizure-related injuries (p = 0.002). Children on polytherapy had a significantly higher frequency of seizure-related injuries (p < 0.001).ConclusionEpilepsy is a major risk factor for injuries in childhood. High seizure frequency increases the risk of multiple injuries in children with epilepsy.     

The effects of lacosamide on cognition,quality-of-life measures,and quality of life in patients with refractory partial epilepsy

ObjectiveThe objective of this study was to examine cognitive and quality-of-life measures/quality of life outcomes with adjunctive lacosamide therapy in patients with treatment-resistant partial epilepsy.MethodsThis was a prospective, open-label, nonblinded, adjunctive therapy test–retest (within subjects) study of patients with treatment-resistant partial epilepsy in which outcome (cognitive functioning and mood/quality of life) was measured in the same subject before and after adjunctive lacosamide administration for 24 weeks. The cognitive assessment included the following: Controlled Oral Word Association Test, Buschke Selective Reminding Test, Brief Visuospatial Memory Test—Revised, Stroop Color Word Test, Symbol Digit Modalities Test, Digit Span, Digit Cancellation, and Trails A and B. The quality-of-life measures/quality-of-life assessment included the following: Beck Depression Inventory—II, Profile of Mood States, and Quality of Life Inventory—89. Lacosamide was started at 100 mg (50 mg twice daily) and could be titrated as needed up to 400 mg/day (200 mg twice daily). Baseline concomitant AEDs were kept constant. Composite scores were calculated for a pre–post difference score for the cognitive and mood/quality-of-life measures separately and used in regression analyses to correct for the effects of age, education, seizure frequency, seizure severity, dose of lacosamide, and number of AEDs at baseline.ResultsThirty-four patients were enrolled (13 males, 21 females). Mean age was 38.8 ± 2.43 years. Mean seizure frequency decreased significantly from 2.0 ± 2.55 seizures per week at baseline to 1.02 ± 1.72 seizures per week at posttreatment (t = 4.59, p < .0001) with a 50% responder rate seen in 18 patients (52.9%). No significant differences were found on the composite scores of the cognitive or the mood/quality-of-life measures after 6 months of lacosamide.SignificanceLacosamide appeared to have low risks of significant changes in cognition or mood/quality of life. In addition, the present study supports prior studies that have proven lacosamide as an effective adjunctive therapy for the treatment of resistant partial epilepsy.     

Management of focal epilepsy in adults treated with polytherapy in France: The direct cost of drug resistance (ESPERA study)

PurposeTo estimate the direct costs associated with the current management of focal epilepsy in adults treated with a combination of antiepileptic drugs (AEDs) in France and the supplementary costs of drug resistant epilepsy as defined by the International League Against Epilepsy (ILAE) in 2009.MethodsESPERA was a multicentre, observational, cross-sectional study conducted in France in 2010. A random sample of neurologists, including specialists in epilepsy, prospectively enrolled adults with focal epilepsy treated with a combination of AEDs. Investigators classified their patients according to the 2009 ILAE criteria for drug resistance and this classification was then reviewed by two experts. All items of healthcare resource use associated with epilepsy over the previous year were documented retrospectively and valued from a societal perspective.ResultsSeventy-one neurologists enrolled 405 patients. After experts’ review, 70.6% of patients were classified with drug-resistant epilepsy, 22.4% with drug-responsive epilepsy and 7% with undefined epilepsy. The mean annual epilepsy-related direct costs per patient were €4485 ± €4313 in patients with drug-resistant epilepsy compared to €1926 ± €1795 in patients with drug-responsive epilepsy. In these two groups, costs of AEDs were estimated at €2603 and €1544, respectively. Patients with drug-resistant epilepsy were more often hospitalised (mean annual cost: €1270 vs. €97) and underwent more additional tests (mean annual cost: €194 vs. €53).ConclusionThe direct cost of focal epilepsy in adults on AED combinations was estimated at €3850/patient/year. Drug resistance, as defined by the 2009 ILAE criteria, resulted in significant extra costs which varied with seizure frequency.     

Seizure precipitants in Dravet syndrome: What events and activities are specifically provocative compared with other epilepsies?

ObjectivesThis study aimed to describe seizure precipitants in Dravet syndrome (DS) compared with other epilepsies.MethodsSeizure precipitants as reported in a Dutch cohort of patients with DS with pathogenic SCN1A mutations (n = 71) were compared with those of a cohort with childhood epilepsy (n = 149) and of a community-based cohort with epilepsy (n = 248); for all three Dutch cohorts, the same type of questionnaire was used. Seizure precipitants were categorized as ‘fever’, ‘visual stimuli’, ‘sleep deprivation’, ‘stress, including physical exercise’, ‘auditory stimuli’, and ‘other’.ResultsFor 70 (99%) of 71 patients with DS, at least one seizure precipitant was recalled by parents. Seizure precipitants that were reported in more than half of the cohort with DS were as follows: having a fever (97%), having a cold (68%), taking a bath (61%), having acute moments of stress (58%), and engaging in physical exercise (56%). Seizure precipitants freely recalled by parents were often related to ambient warmth or cold–warmth shifts (41%) and to various visual stimuli (18%).Patients with DS had more positive seizure precipitant categories (median 4) compared with the cohort with childhood epilepsy (median 2) and the community-based cohort with epilepsy (median 0) (p < 0.001) and showed the highest percentage in each category (all p < 0.001). Within the category ‘stress, including physical exercise’, physical exercise was more often reported to provoke seizures in stress-sensitive patients in the cohort with DS than in the cohort with childhood epilepsy (78% vs. 35%, p < 0.001). In the cohort with childhood epilepsy, physical exercise was more often reported in fever-sensitive children than in other children (25% vs. 12%, p = 0.042).ConclusionsOur study shows a high prevalence of a range of seizure precipitants in DS. Our results underscore elevated body temperature as an important seizure precipitant, whether caused by fever, warm bath, ambient warmth, or physical exercise. Knowledge of these seizure precipitants may improve preventive strategies in the otherwise difficult treatment of DS.     

Psychiatric comorbidity in children and youth with epilepsy: An association with executive dysfunction?

ObjectivesPsychopathology in children and youth with epilepsy has previously been related to executive dysfunction, but the nature of the association is uncertain. We sought to explore risk factors for psychiatric disorders in children and youth with epilepsy, with emphasis on executive dysfunction, along with seizure-related and psychosocial factors.MethodsThe cohort consisted of one hundred and one consecutive patients aged 10–19 years with focal (n = 52) or genetic generalized (n = 49) epilepsy. All were screened for psychiatric symptoms, using part of an extensive questionnaire, the Strengths and Difficulties Questionnaire (SDQ) for both patients and their parents. Participants scoring in the borderline or abnormal range on the SDQ received a psychiatric interview (Kiddie-SADS-PL). All participants underwent a neuropsychological examination, and those with general cognitive abilities (IQ) < 70 were excluded.ResultsForty-seven of 101 participants (46.5%) had a SDQ score in the borderline or abnormal range and underwent a psychiatric evaluation. Of these, 44 (93.6%) met the criteria for a psychiatric diagnosis, the most common being ADHD and anxiety. An executive deficit was identified in 26.8% of the participants with a psychiatric diagnosis, but in only 5.4% of those without such a diagnosis (p = 0.003). Multivariate logistic regression analysis showed that executive dysfunction was an independent risk factor for having a psychiatric disorder (OR 8.2, CI 1.8–37.2, p = 0.006), along with male gender (OR 2.9, CI 1.2–7.3, p = 0.02), and early seizure onset (0.86—that is one year older equals risk of psychiatric disorder reduced by 14%—CI 0.77–0.96, p = 0.01). Other epilepsy-related or psychosocial factors were not significantly associated with psychiatric disorders.ConclusionsMultiple factors are associated with psychiatric problems in children and youth with epilepsy. In this study, executive dysfunction, male gender, and early epilepsy onset were independent risk factors for having a psychiatric disorder. An evaluation of psychiatric and cognitive problems is important to enable a positive long-term outcome in childhood epilepsy.     

Seizure severity in children with epilepsy is associated with their parents' perception of stigma

AimsTo develop and implement interventions to improve the quality of life (QOL) in children with epilepsy, it is important for clinicians and researchers to understand the effects of the children's parents' perception of stigma. The purpose of this study was to identify a relationship between patient clinical characteristics and perception of stigma in the parents of children with epilepsy.MethodsParents of children with epilepsy were recruited from our university hospital between April 1, 2005 and March 31, 2012. Items for the Parent Stigma Scale were developed from the literature and open-ended interviews with parents of children with epilepsy about their concerns and fears, including those related to stigma. Parents were asked to respond to five items, each on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). Assessments were performed for each clinical characteristic, such as child's sex, age at seizure onset, family history of epilepsy, seizure frequency, presence of status epilepticus (SE), presence of treatment-related adverse events, and the scores of each scale.ResultsA total of 52 parents of children with epilepsy and 10 parents of healthy children were enrolled in the study. Parents of children with epilepsy showed significantly higher scores on the questionnaire than parents of healthy children. In multiple regression analysis, greater perceptions of stigma were associated with a seizure frequency of more than one per month (p = 0.0036, B = 1.104, β = 0.402). In contrast, the presence of prior febrile seizures (p = 0.0034, B = − 1.297, β = − 0.308) and family history of epilepsy (p = 0.0066, B = − 1.613, β = − 0.277) were associated with lower perceptions of stigma. Greater parental perceptions of stigma were seen with the presence of monthly seizures.ConclusionsParents of children with epilepsy are at risk of significant perceptions of stigma. Seizure severity, indicated by the presence of monthly seizures, was associated with greater perceptions of stigma in parents. In addition, the presence of prior febrile seizures and family history of epilepsy were associated with fewer perceptions of stigma. The findings of this study emphasize the importance of acknowledging and addressing parental perceptions of stigma.