Perinatal Adversities and Risk of Epilepsy After Traumatic Brain Injury: A Danish Nationwide Cohort Study

Abstract found in DocWire News

OBJECTIVES: Traumatic brain injury (TBI) and perinatal adversities such as low gestational age at birth, low birth weight, low Apgar, and being born small for gestational age are well-established risk factors for epilepsy. We examined whether perinatal adversities modified the risk of epilepsy after TBI in a nationwide cohort study of Danish singletons born from 1982 to 2011.

MATERIALS AND METHODS: We categorized perinatal adversities as a composite measure of preterm delivery, low birth weight, low Apgar score, or being born small for gestational age. Cox regression and competing risk regression were used to estimate the risk of epilepsy after TBI according to such perinatal adversities. The study included 1,715,095 singletons (51.1% males). The mean age at end of follow-up was 19.3 years (Interquartile range [IQR] = 12.1-26.3). During follow-up, 85,636 persons (58.2% males) sustained a TBI and 18,064 developed epilepsy (50.7% males), of whom 1329 persons had a preceding TBI.

RESULTS: The hazard ratio (HR) of epilepsy in persons with perinatal adversities was 1.19 (95% confidence interval [CI] 1.15-1.24), compared to persons without. The HR of epilepsy in persons with TBI was 2.31 (95% CI 2.18-2.45) compared to persons without TBI, but this risk was not modified by perinatal adversities (p = 0.2460).

CONCLUSIONS: Perinatal adversities and TBI both increased the risk of epilepsy, but the risk of epilepsy after TBI was not modified by these perinatal adversities.

An Evaluation of the Knowledge, Attitudes, and Behaviors of Parents Regarding Epilepsy

Abstract found in PubMed originally published in Epilepsy & Behavior

Background and aims: Knowledge about epilepsy and attitudes toward people with epilepsy can influence measures taken to manage epilepsy and seizures. The support and understanding of parents of children with epilepsy are invaluable in helping develop ordinary living skills. To determine the educational needs of parents of children with epilepsy, their knowledge, attitudes, and behaviors should be evaluated. Therefore, we interviewed parents who had a child with epilepsy who was treated at the pediatric neurology clinic of a university hospital. We aimed to evaluate parents’ knowledge, attitudes, and behaviors toward children with epilepsy to determine their educational needs.

Methods: This descriptive study included 221 parents of children with epilepsy who applied to Hatay Mustafa Kemal University Medical Faculty Hospital. A questionnaire was used to collect data. Pearson and exact chi-square tests were used for analysis.

Results: In the present study, 221 parents were interviewed. A total of 66.5% of the participants were at the primary education level. The rate of participants who preferred healthcare professionals as a source of information about epilepsy was 78.9%. Forty-eight percent of the parents did not see consanguineous marriage as a reason. While some parents stated that epilepsy was supernatural, others had no idea whether it was contagious or not, and 46.2% of the participants stated that epilepsy is not a hereditary disease. The rate of those who tried nonphysician treatment was 16.3%. The rate of participants who thought that drinking alcohol would not trigger seizures was 86.9%. It was determined that 30.8% of the participants pulled the patient’s tongue out during seizures. 16.7% of participants thought that patients with epilepsy were disabled. 50.7% of the participants stated that their children with epilepsy could do any profession.

Conclusions: Our study documented parents’ lack of knowledge about epilepsy. Many parents have significant misunderstandings, negative attitudes, and parenting practices, and their knowledge and understanding of epilepsy needs to be improved.

Predictors of Outcome Among 31 Children with Infantile Spasms Syndrome

Abstract found in John Libbey Eurotext

Objective: Infantile spasms syndrome is a severe epileptic encephalopathy. Management of infantile spasms remains challenging because of pharmacoresistant forms and relapsing seizures. A high number of patients with this syndrome have neurodevelopmental delay. The main objective of our study was to determine predictors to measure the neurodevelopmental outcome of patients with infantile spasms.

Methods: We prospectively evaluated 31 patients with infantile spasms from 2014 to 2017 at three hospitals in Tbilisi, Georgia. Various demographic data were evaluated at the first visit; video-EEG, brain MRI and neurodevelopmental evaluation were performed upon admission. A diary to record spasms was provided and completed by all parents/caregivers. Seizures were recorded on video and the phenomenology of infantile spasms was studied. Children were followed for one and two years after the first assessment.

Results: Neurodevelopmental deterioration was revealed in 61.1% on the second and 53% on the third evaluation in patients with onset of spasms before seven months of age. The mean score on the ASQ communication domain was low among structural cases. Eleven patients with pre-existing delay had developmental regression based on the second evaluation (Fisher’s exact test: 7.2; df 1; p=0.01).

Significance. Our study reveals that age at onset of infantile spasms at less than seven months, pre-existing developmental delay, low ASQ scores and structural abnormalities on MRI are predictors of poor developmental outcome. Our data suggest that clinicians should inform parents at the first clinical evaluation about prognosis, and intervention should be started as early as possible in order to improve development.

Interictal Pattern on Scalp Electroencephalogram Predicts Excellent Surgical Outcome of Epilepsy Caused by Focal Cortical Dysplasia

Abstract found in Wiley Online Library

Objective: Focal cortical dysplasia (FCD) represents an essential cause of drug-resistant epilepsy with surgery as an effective treatment option. This study aimed to identify the important predictors of favorable surgical outcomes and the impact of the interictal scalp electroencephalogram (EEG) patterns in predicting postsurgical seizure outcomes.

Methods: We retrospectively evaluated 210 consecutive patients between 2015 and 2019. They were diagnosed with FCD by pathology, underwent resection, and had at least one year of postsurgical follow-up. Predictors of seizure freedom were analyzed.

Results: Based on the information at the latest follow-up, seizure outcome was classified as Engel Class I (seizure-free) in 81.4% and Engel Class II-IV (non-seizure-free) in 18.6% of patients. There were 43, 105, and 62 cases of FCD type I, type II, and type III, respectively. The interictal EEG showed a repetitive discharge pattern (REDP) in 87 (41.4%) patients, polyspike discharge pattern (PDP) in 41 (19.5%), and the coexistence of REDP and PDP in the same location in 32 (15.2%) patients. The analyzed patterns in order of frequency were repetitive discharges lasting 5 seconds or more (32.4%); polyspikes (16.7%); RED type 1 (11.4%); continuous epileptiform discharges occupying >80% of the recording (11.4%); RED type 2 (6.2%); brushes (3.3%); focal, fast, continuous spikes (2.4%); focal fast rhythmic epileptiform discharges (1.43%); and frequent rhythmic bursting epileptiform activity (1.4%). The coexistence of REDP and PDP in the same location on scalp EEG and complete resection of the assumed epileptogenic zone (EZ) was independently associated with favorable postsurgical prognosis.

Significance: Resective epilepsy surgery for intractable epilepsy caused by FCD has favorable outcomes. Interictal scalp EEG patterns were revealed to be predictive of excellent surgical outcomes and may help clinical decision-making and enable better presurgical evaluation.

COVID-19 Vaccines Safe for People with Epilepsy? A Cross-Sectional Study

Abstract found in DocWire News

Background: COVID-19 disease was first seen in December 2019 and was declared a pandemic soon after. To fight the pandemic, there is an immense need for effective vaccines. The purposes of our study were to investigate the effect of coronavirus vaccines on seizures in people with epilepsy (PWE) and assess the adverse events of COVID-19 vaccine in PWE.

Methods: This was a cross-sectional study. We included epilepsy patients who got vaccinated with two or three doses at least 1 month earlier. We gathered the data using a standardized form. The form contained questions about patients’ demographic features, clinical features, and information about the vaccination and its adverse events. The questionnaire included questions about epilepsy-related adverse events.

Results: We included 178 people with epilepsy in our study. The frequency of adverse events was lower than clinical studies of the vaccines. The mean number of seizures in the month before the vaccination was 1.62, between the doses was 1.61, and after vaccination was 1.64. There was no significant difference in the number of monthly seizures before the vaccination, the month between the doses, or the month after the vaccination (p = 0.46).

Conclusions: The vaccines under consideration in our study were tolerated well by the epilepsy patients. The vaccines did not affect the monthly number of seizures of the people with epilepsy. A small number of patients had more seizures than normal after vaccination. We think that benefits of the vaccines outweigh the slightly increased possibility of having a seizure after vaccination.

Impact of Exercise as a Complementary Management Strategy in People with Epilepsy: A Randomized Controlled Trial

Abstract found in DocWire News and originally published in Epilepsy & Behavior

Objective: To measure the impact of 12 weeks of physical exercise as complementary management strategy on quality of life (QOL) in people with epilepsy (PWE).

Methods: In a parallel-group, randomized controlled study with blinded outcome assessment, PWE of 18-65 years old, smartphone users were randomized into two groups. The exercise group was advised minimum 150 min per week of moderate-intense aerobic activity, as per current WHO recommendation [1], in addition to standard medical care; the control group received only standard medical care. QOL was assessed using Quality of Life in Epilepsy (QOLIE-31) inventory [2,3]; physical activity, with Global Physical Activity Questionnaire version 2 (GPAQ), and Pedometer Step Counter (a smartphone-based activity tracker application), at baseline and after 12 weeks. Body weight, body mass index, seizure frequency, and stigma scores (Epilepsy Stigma Scale Austin and colleagues) [4] were also noted.

Results: One hundred and seventeen PWE were recruited (58 exercise, 59 control). Although there was an improvement in the physical activity correlates after 12 weeks compared to mean values at baseline, the differences were not significant between the groups. The total QOL mean scores at baseline in the exercise and control groups were 64.9 and 63.7 (p = 0.597) and after 12 weeks, 68.4 and 66.9 (p = 0.660), respectively. However, intragroup comparison of energy/fatigue score in the exercise group showed significant change with a p value of 0.009 and intragroup comparison of Overall QOL score in the control group showed a significant change with a p value of 0.003. Similar improvement was seen in stigma scores (p = 0.500) and seizure frequency (p = 0.388) at 12 weeks in exercise and control groups. After 12 weeks, mean values of METS ((metabolic equivalents) were 794.81 and 714.27 (p = 0.159), steps per day were 4018.32 and 3730.0 (p = 0.314), calories spent per day were 173.85 and 159.68 (p = 0.320 and distance walked per day in meters were 2576.52 and 2198.42 (p = 0.072), in the exercise and control groups, respectively.

Significance: Regular physical activity for at least 150 min per week, in the form of moderate-intense aerobic exercises resulted in positive yet non-significant improvement of quality of life, seizure frequency, and stigma in people with epilepsy.

Antiseizure Medication Use and Medical Resource Utilization After Resective Epilepsy Surgery in Children in the United States: A Contemporary Nationwide Cross-Sectional Cohort Analysis

Abstract published in Wiley Online Library

Objective: Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization.

Methods: We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared.

Results: One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n = 21, p = .002), and less common in patients with tuberous sclerosis (p = .003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50–2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49–1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery.

Significance: Patterns of antiseizure drug use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

The Global Cost of Epilepsy: A Systematic Review and Extrapolation

Abstract found in Wiley Online Library

Objective: Global action for epilepsy requires information on the cost of epilepsy, which is currently unknown for most countries and regions of the world. To address this knowledge gap, the International League Against Epilepsy Commission on Epidemiology formed the Global Cost of Epilepsy Task Force.

Methods: We completed a systematic search of the epilepsy cost-of-illness literature and identified studies that provided a comprehensive set of direct health care and/or indirect costs, followed standard methods of case identification and cost estimation, and used data on a representative population or subpopulation of people with epilepsy. Country-specific costs per person with epilepsy were extracted and adjusted to generate an average cost per person in 2019 US dollars. For countries with no cost data, estimates were imputed based on average costs per person of similar income countries with data. Per person costs for each country were then applied to data on the prevalence of epilepsy from the Global Burden of Disease collaboration adjusted for the treatment gap.

Results: One hundred one cost-of-illness studies were included in the direct health care cost database, 74 from North America or Western Europe. Thirteen studies were used in the indirect cost database, eight from North America or Western Europe. The average annual cost per person with epilepsy in 2019 ranged from $204 in low-income countries to $11 432 in high-income countries based on this highly skewed database. The total cost of epilepsy, applying per person costs to the estimated 52.51 million people in the world with epilepsy and adjusting for the treatment gap, was $119.27 billion.

Significance: Based on a summary and extrapolations of this limited database, the global cost of epilepsy is substantial and highly concentrated in countries with well-developed health care systems, higher wages and income, limited treatment gaps, and a relatively small percentage of the epilepsy population.

Multicenter, Cross-Sectional Study of the Costs of Illness and Cost-Driving Factors in Adult Patients with Epilepsy in Germany

Abstract published in Wiley Online Library

Objective: This study was undertaken to quantify epilepsy-related costs of illness (COI) in Germany and identify cost-driving factors.

Methods: COI were calculated among adults with epilepsy of different etiologies and severities. Multiple regression analysis was applied to determine any epilepsy-related and sociodemographic factors that serve as cost-driving factors.

Results: In total, 486 patients were included, with a mean age of 40.5 ± 15.5 years (range = 18–83 years, 58.2% women). Mean 3-month COI were estimated at €4911, €2782, and €2598 for focal, genetic generalized, and unclassified epilepsy, respectively. The mean COI for patients with drug-refractory epilepsy (DRE; €7850) were higher than those for patients with non-DRE (€4720), patients with occasional seizures (€3596), or patients with seizures in remission for >1 year (€2409). Identified cost-driving factors for total COI included relevant disability (unstandardized regression coefficient b = €2218), poorer education (b = €2114), living alone (b = €2612), DRE (b = €1831), and frequent seizures (b = €2385). Younger age groups of 18–24 years (b = ?€2945) and 25–34 years (b = ?€1418) were found to have lower overall expenditures. A relevant disability (b = €441), DRE (b = €1253), frequent seizures (b = €735), and the need for specialized daycare (b = €749) were associated with higher direct COI, and poorer education (b = €1969), living alone (b = €2612), the presence of a relevant disability (b = €1809), DRE (b = €1831), and frequent seizures (b = €2385) were associated with higher indirect COI.

Significance: This analysis provides up-to-date cost of illness data for use in further health economics analyses, highlighting the high economic impacts associated with disease severity, disability, and disease-related loss of productivity among adult patients with epilepsy. The identified cost drivers could be used as therapeutic and socioeconomic targets for future cost-containment strategies.

Barriers to Generic Antiseizure Medication Use: Results of a Global Survey by the International League Against Epilepsy Generic Substitution Task Force

Abstract found in Wiley Online Library

The objective of this study was to identify and quantify barriers to generic substitution of antiseizure medications (ASM). A questionnaire on generic ASM substitution was developed by the International League Against Epilepsy (ILAE) Task Force on Generic Substitution. Questions addressed understanding of bioequivalence, standards for generic products, experiences with substitution, and demographic data. The survey was web-based and distributed to ILAE chapters, their membership, and professional colleagues of task force members. Comparisons in responses were between ILAE regions and country income classification. A total of 800 individuals responded, with 44.2% being from the Asia-Oceania ILAE Region and 38.6% from European Region. The majority of respondents had little or no education in generic substitution or bioequivalence. Many respondents indicated lack of understanding aspects of generic substitution. Common barriers to generic substitution included limited access, poor or inconsistent quality, too expensive, or lack of regulatory control. Increase in seizures was the most common reported adverse outcome of substitution. Of medications on the World Health Organization Essential Medication list, problems with generic products were most frequent with carbamazepine, lamotrigine, and valproic acid. Several barriers with generic substitution of ASM revolved around mistrust of regulatory control and quality of generic ASM. Lack of education on generic substitution is also a concern. Generic ASM products may be the only option in some parts of the world and efforts should address these issues. Efforts to address these barriers should improve access to medications in all parts of the world.