Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Primary care electronic medical records can be used to predict risk and identify potentially modifiable factors for early and late death in adult onset epilepsy.

OBJECTIVE: To use clinically informed machine learning to derive prediction models for early and late premature death in epilepsy. METHODS: This was a population-based primary care observational cohort study. All patients meeting a case definition for incident epilepsy in the Health Improvement Network database for inclusive years 2000-2012 were included. A modified Delphi process identified 30 potential risk factors. Outcome was early (within 4 years of epilepsy diagnosis) and late (4 years or more from diagnosis) mortality. We used regularized logistic regression, support vector machines, Gaussian naive Bayes, and random forest classifiers to predict outcomes. We assessed model calibration, discrimination, and generalizability using the Brier score, mean area under the receiver operating characteristic curve (AUC) derived from stratified fivefold cross-validation, plotted calibration curves, and extracted measures of association where possible. RESULTS: We identified 10 499 presumed incident cases from 11 194 182 patients. All models performed comparably well following stratified fivefold cross-validation, with AUCs ranging from 0.73 to 0.81 and from 0.71 to 0.79 for early and late death, respectively. In addition to comorbid disease, social habits (alcoholism odds ratio [OR] for early death = 1.54, 95% confidence interval [CI] = 1.12-2.11 and OR for late death = 2.62, 95% CI = 1.66-4.16) and treatment patterns (OR for early death when no antiseizure medication [ASM] was prescribed at baseline = 1.33, 95% CI = 1.07-1.64 and OR for late death after receipt of enzyme-inducing ASM at baseline = 1.32, 95% CI = 1.04-1.66) were significantly associated with increased risk of premature death. Baseline ASM polytherapy (OR = 0.55, 95% CI = 0.36-0.85) was associated with reduced risk of early death. SIGNIFICANCE: Clinically informed models using routine electronic medical records can be used to predict early and late mortality in epilepsy, with moderate to high accuracy and evidence of generalizability. Medical, social, and treatment-related risk factors, such as delayed ASM prescription and baseline prescription of enzyme-inducing ASMs, were important predictors.

Risk factors for dementia development, frailty, and mortality in older adults with epilepsy - A population-based analysis.

OBJECTIVE: Although the prevalence of comorbid epilepsy and dementia is expected to increase, the impact is not well understood. Our objectives were to examine risk factors associated with incident dementia and the impact of frailty and dementia on mortality in older adults with epilepsy. METHODS: The CALIBER scientific platform was used. People with incident epilepsy at or after age 65 were identified using Read codes and matched by age, sex, and general practitioner to a cohort without epilepsy (10:1). Baseline cohort characteristics were compared using conditional logistic regression models. Multivariate Cox proportional hazard regression models were used to examine the impact of frailty and dementia on mortality, and to assess risk factors for dementia development. RESULTS: One thousand forty eight older adults with incident epilepsy were identified. The odds of having dementia at baseline were 7.39 [95% CI 5.21-10.50] times higher in older adults with epilepsy (n = 62, 5.92%) compared to older adults without epilepsy (n = 88, 0.86%). In the final multivariate Cox model (n = 326), age [HR: 1.20, 95% CI 1.09-1.32], Charlson comorbidity index score [HR: 1.26, 95% CI 1.10-1.44], and sleep disturbances [HR: 2.41, 95% CI 1.07-5.43] at baseline epilepsy diagnosis were significantly associated with an increased hazard of dementia development over the follow-up period. In a multivariate Cox model (n = 1047), age [HR: 1.07, 95% CI 1.03-1.11], baseline dementia [HR: 2.66, 95% CI 1.65-4.27] and baseline e-frailty index score [HR: 11.55, 95% CI 2.09-63.84] were significantly associated with a higher hazard of death among those with epilepsy. Female sex [HR: 0.77, 95% CI 0.59-0.99] was associated with a lower hazard of death. SIGNIFICANCE: The odds of having dementia were higher in older adults with incident epilepsy. A higher comorbidity burden acts as a risk factor for dementia, while prevalent dementia and increasing frailty were associated with mortality.

Signs and symptoms of the postictal period in epilepsy: A systematic review and meta-analysis.

OBJECTIVE: The postictal period has many physical, behavioral, and cognitive manifestations associated with it. These signs and symptoms are common, can be quite debilitating, and can have a continued impact long after the seizure has ended. The purpose of this systematic review was to quantify the occurrence of postictal signs and symptoms, along with their frequency and duration in persons with epilepsy. METHODS: Cochrane Database of Systematic Reviews, CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, and Scopus were searched from inception to November 29, 2017. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards were followed. Search terms included subject headings and text words such as convulsion, epilepsy, seizure, postictal, post seizure, seizure recovery, seizure end, Todd's paresis, and Todd's paralysis. Standardized forms were used to collect various study variables. Abstract and full-text review, data abstraction, and quality assessment were all done in duplicate. Study heterogeneity was assessed using the I-squared test, and a random effects model was used to determine estimates. Publication bias was evaluated using funnel plots. RESULTS: From 7811 abstracts reviewed, 78 articles met eligibility criteria, with 31 postictal manifestations (signs and/or symptoms) described and 45 studies included in the meta-analysis. The majority of studies described postictal headaches, migraines, and psychoses, with mean weighted frequency of 33.0% [95% confidence interval (CI) 26.0-40.0], 16.0% [95% CI 10.0-22.0], and 4.0% [95% CI 2.0-5.0], respectively. The mean weighted proportions of manifestations ranged from 0.5% (subacute postictal aggression) to 96.2% (postictal unresponsiveness) with symptom duration usually lasting <24 h but up to 2 months for physical and cognitive/behavioral symptoms respectively. SIGNIFICANCE: Examining data on the various signs and symptoms of the postictal period will have practical applications for physicians by raising their awareness about these manifestations and informing them about the importance of optimizing their prevention and treatment in epilepsy.

The association between dementia and epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Dementia is among the top 15 conditions with the most substantial increase in burden of disease in the past decade, and along with epilepsy, among the top 25 causes of years lived with disability worldwide. The epidemiology of dementia in persons with epilepsy, and vice versa, is not well characterized. The purpose of this systematic review was to examine the prevalence, incidence, and reported risk factors for dementia in epilepsy and epilepsy in dementia. METHODS: Embase, PsycINFO, MEDLINE, and the Cochrane databases were searched from inception. Papers were included if they reported the incidence and/or prevalence of dementia and epilepsy. Two individuals independently performed duplicate abstract and full-text review, data extraction, and quality assessment. Random-effects models were used to generate pooled estimates when feasible. RESULTS: Of the 3,043 citations identified, 64 were reviewed in full text and 19 articles were included. The period prevalence of dementia ranged from 8.1 to 17.5 per 100 persons among persons with epilepsy (insufficient data to pool). The pooled period prevalence of epilepsy among persons with dementia was 5 per 100 persons (95% confidence interval [CI] 1-9) in population-based settings and 4 per 100 persons (95% CI 1-6) in clinic settings. There were insufficient data to report a pooled overall incidence rate and only limited data on risk factors. SIGNIFICANCE: There are significant gaps in knowledge regarding the epidemiology of epilepsy in dementia and vice versa. Accurate estimates are needed to inform public health policy and prevention, and to understand health resource needs for these populations.

Sensitivity and specificity of alternative screening methods for systematic reviews using text mining tools.

OBJECTIVES: To evaluate the impact of text mining (TM) on the sensitivity and specificity of title and abstract screening strategies for systematic reviews (SRs). STUDY DESIGN AND SETTING: Twenty reviewers each evaluated a 500-citation set. We compared five screening methods: conventional double screen (CDS), single screen, double screen with TM, combined double screen and single screen with TM, and single screen with TM. Rayyan, Abstrackr, and SWIFT-Review were used for each TM method. The results of a published SR were used as the reference standard. RESULTS: The mean sensitivity and specificity achieved by CDS were 97.0% (95% confidence interval [CI]: 94.7, 99.3) and 95.0% (95% CI: 93.0, 97.1). When compared with single screen, CDS provided a greater sensitivity without a decrease in specificity. Rayyan, Abstrackr, and SWIFT-Review identified all relevant studies. Specificity was often higher for TM-assisted methods than that for CDS, although with mean differences of only one-to-two percentage points. For every 500 citations not requiring manual screening, 216 minutes (95% CI: 169, 264) could be saved. CONCLUSION: TM-assisted screening methods resulted in similar sensitivity and modestly improved specificity as compared to CDS. The time saved with TM makes this a promising new tool for SR.

Is Living with Persons with Dementia and Depression Correlated to Impacts on Caregivers? A Scoping Review.

Caregivers of persons with dementia and depression experience adverse effects associated with their role. The aim of this scoping review was to identify the challenges faced by caregivers of people with dementia and depression, along with interventions to support them. The MEDLINE®, Embase and PsycINFO databases were searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Grey literature was assessed using the Canadian Agency for Drugs and Technologies in Health's Gray Matter tool.The population consisted of caregivers of people with dementia and depression; the concept was to identify the negative impacts that caregivers experience and whether there are interventions to reduce them; the context was any study design targeting family or friends who were caregivers. A total of 12,835 citations were identified; 139 studies were included. Dementia and depression have variable impacts on outcomes experienced by caregivers, including burden/strain (n = 52), depression (n = 27), distress (n = 53), quality of life (n = 5) and health/well-being (n = 9). Pharmacological and non-pharmacological interventions have mixed effects. This study is important considering that depression in people with dementia is associated with caregiver distress. The use of a variety of non-pharmacological interventions could be beneficial to the latter.