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The modification of polymethylmethacrylate will confer antimicrobial resistance to the material and the method of modification, incorporation or coating, can influence the antimicrobial action. The objective of this study is to answer the question "Antimicrobial incorporated or coating polymethylmethacrylate (PMMA), which promotes better antimicrobial action?"

To evaluate the pharmacokinetics, safety, and tolerability of brivaracetam (BRV) as 15-min intravenous (IV) infusion and bolus (≤2-min injection).EP0065 (ClinicalTrials.gov: NCT03405714) was a Phase 2, multicenter, open-label trial in patients ≥1 month to16 years of age with epilepsy. Patients received up to 5 mg/kg/day BRV (not exceeding 200 mg/day). Enrollment was sequential by descending age, depending on safety review. Outcomes included BRV plasma concentrations before and after IV administration, treatment-emergent adverse events (TEAEs), and discontinuations due to TEAEs.Fifty patients were enrolled, received BRV, and completed the trial. Twenty-six patients (52.0%) received 15-min infusions and 24 (48.0%) received bolus injections. Most patients (80.0%) received one IV dose. In the 15-min infusion group, geometric mean (GeoMean) BRV concentrations 15 (±2) min (n = 21) and 3 h (±15 min) (n = 21) post dose were 1903.0 ng/mL (geometric coefficient of variation [GeoCV]: 60.7%) and 1130.3 ng/mL (58.8%), respectively. In the bolus group, GeoMean BRV concentrations 15 (±2) min (n = 19) and 3 h (±15 min) (n = 21) post dose were 1704.8 ng/mL (GeoCV: 74.5%) and 1383.9 ng/mL (85.0%), respectively. Overall, 14 patients (28.0%) had TEAEs (15-min infusion: 8 [30.8%]; bolus: 6 [25.0%]), most commonly (≥5% of patients) somnolence (3 [6.0%]). Ten patients (20.0%) had drug-related TEAEs (15-min infusion: 6 [23.1%]; bolus: 4 [16.7%]). No patients discontinued due to TEAEs, and no deaths occurred.IV BRV (up to 200 mg/day) was well tolerated in patients ≥1 month to16 years of age, regardless of whether BRV was administered as 15-min infusion or bolus. No unexpected safety or pharmacokinetic differences were observed between patients receiving 15-min infusions or bolus, and plasma concentrations were in the expected range. Safety results were consistent with the known safety profile of oral BRV, with no new safety concerns identified.

Children with Benign Epilepsy with Centrotemporal Spikes (BECTS), despite high likelihood for seizure remission, are reported to have subtle difficulties in language and other cognitive skills. We used functional MRI and a story listening task to examine the effect of BECTS on patterns of activation and connectivity. Language and cognitive skills were assessed using standardized measures. Twenty-four children with recently diagnosed BECTS and 40 typically-developing children participated. In a functionally-defined region of interest in right inferior frontal gyrus, BECTS patients showed a lower level of activation. Across both groups combined, increased activation in superior/middle temporal regions of interest was associated with better language scores. Connectivity in the story processing network was similar between groups, but connectivity within left inferior frontal gyrus was decreased in children with BECTS. These results suggest that language networks are largely maintained in new-onset BECTS, but some subtle changes in activation and connectivity can be observed.

Despite a positive prognosis for seizure remission, children with benign epilepsy with centrotemporal spikes (BECTS) have been reported to exhibit subtle neuropsychological difficulties. We examined the relationship between patterns of centrotemporal spikes (the typical electroencephalography [EEG] finding in BECTS) and neuropsychological and motor outcomes in children with new-onset BECTS. Thirty-four patients with new-onset BECTS (not taking antiepileptic medication) and 48 typically developing children participated in the study. In BECTS patients, centrotemporal spikes (CTS) were evaluated in the first hour awake and first 2 h of sleep in a 24-h EEG recording and left or right-sided origin was noted. General intellectual function, language, visuospatial skill, processing speed, and fine motor skill were assessed in all participants. We found no significant difference between BECTS patients and controls on measures of general intellectual function, or visuospatial or language testing. There were significant differences in processing speed index and nondominant hand fine motor scores between groups. Significant negative relationships were observed between rates of left-sided CTS and right hand fine motor scores. This suggests that psychomotor and fine motor speed are affected in BECTS, but the extent of affected domains may be more limited than previously suggested, especially in untreated patients early in the course of their epilepsy.

Objective: We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient's status. The following hypotheses are then tested: 1) machine learning methods can identify epilepsy surgery candidates as well as physicians do and 2) machine learning methods can identify candidates earlier than physicians do. These hypotheses are tested by systematically evaluating the effects of the data source, amount of training data, class balance, classification algorithm, and feature set on classifier performance. The results support both hypotheses, with F-measures ranging from 0.71 to 0.82. The feature set, classification algorithm, amount of training data, class balance, and gold standard all significantly affected classification performance. It was further observed that classification performance was better than the highest agreement between two annotators, even at one year before documented surgery referral. The results demonstrate that such machine learning methods can contribute to predicting pediatric epilepsy surgery candidates and reducing lag time to surgery referral.

Summary Objective To describe the natural history of electroencephalography (EEG) changes in patients with benign epilepsy with centrotemporal spikes (BECTS) over 1 year. Methods Centrotemporal spikes were visually evaluated based on 24-h ambulatory EEG studies to determine the total, left, right, and bilateral centrotemporal spikes patients were awake and asleep. These spike rates were then used to compare the entire night of sleep to the first 2 h of sleep, the repeatability of spike frequency over two recordings (done within days to weeks), and longitudinal changes in spike rate over 6 and 12 months. Results Nineteen children with newly diagnosed and untreated BECTS were included in this analysis. An excellent correlation was found between the centrotemporal spike rate during the entire duration of sleep and the first 2 h of sleep (intraclass correlation [ICC] 0.87, 95% confidence interval [CI] 0.67–0.95). In addition, an excellent correlation was found between two recordings completed an average of 23 days apart while patients were asleep (ICC 0.92, 95% CI 0.80–0.97) and good correlation while patients were awake (ICC 0.70, 95% CI 0.39–0.87). The average change in spike rate between recordings at baseline and at 6 months was a decrease of 64.7% (range −100% to +51.5%, p = 0.01) and the average change in rate between recordings at baseline and at 12 months was a decrease of 57.7% (range −100% to +29.1%, p = 0.01). In addition, within 6 months, most children had decreased centrotemporal rates, with 30% of children being spike-free. This absence of spikes did not continue in all children, since the majority (60%) had some spikes at 1 year following diagnosis. Significance Centrotemporal spike rates during sleep are stable when compared over days to weeks; however, when comparing spike rates over months there is a larger degree of variability.

Childhood neurologic disorders, as a group, include relatively common conditions such as migraine (prevalence between 3% and 10.6% in children 3–15 years of age1,2), transient tic disorders (TDs) (3%),3 and specifically Tourette syndrome (TS) (0.8%),3 and rarer disorders such as infantile spasms that may occur in only about 1,200 infants each year in the United States. These disorders account for a disproportionately higher number of emergency department visits, intensive care admissions, deaths, and higher costs when compared to other childhood illness.4 Generally, delivery of quality care should improve outcomes and result in decreased unnecessary utilization of health services.4

Youth with epilepsy have impaired health-related quality of life (HRQOL). Existing epilepsy-specific HRQOL measures are limited by not having parallel self- and parent-proxy versions, having a restricted age range, not being inclusive of children with developmental disabilities, or being too lengthy for use in a clinical setting. Generic HRQOL measures do not adequately capture the idiosyncrasies of epilepsy. The purpose of the present study was to develop items and content validity for the PedsQL™ Epilepsy Module. Methods An iterative qualitative process of conducting focus group interviews with families of children with epilepsy, obtaining expert input, and conducting cognitive interviews and debriefing was utilized to develop empirically derived content for the instrument. Eleven health providers with expertise in pediatric epilepsy from across the country provided feedback on the conceptual model and content, including epileptologists, nurse practitioners, social workers, and psychologists. Ten pediatric patients (age 4–16 years) with a diagnosis of epilepsy and 11 parents participated in focus groups. Thirteen pediatric patients (age 5–17 years) and 17 parents participated in cognitive interviews. Results Focus groups, expert input, and cognitive debriefing resulted in 6 final domains including restrictions, seizure management, cognitive/executive functioning, social, sleep/fatigue, and mood/behavior. Patient self-report versions ranged from 30 to 33 items and parent proxy-report versions ranged from 26 to 33 items, with the toddler and young child versions having fewer items. Conclusions Standardized qualitative methodology was employed to develop the items and content for the novel PedsQL™ Epilepsy Module. The PedsQL™ Epilepsy Module has the potential to enhance clinical decision-making in pediatric epilepsy by capturing and monitoring important patient-identified contributors to HRQOL.

Objective: To develop and validate a measure of antiepileptic drug (AED) side effects in children with a variety of seizure types, treatments, and therapy durations. Methods: Content for an initial 44-item measure was developed using the previously published Hague Scale and expert opinion from recognized pediatric epileptologists (n = 12) and caregivers of children with epilepsy (n = 21). The measure was completed by caregivers during routine clinic visits. Demographic and medical data were collected through chart reviews. Factor analysis was conducted and internal consistency, test-retest reliability, and construct validity were assessed. Results: Questionnaires were analyzed from 495 children with epilepsy (M age = 10.1 years; range 2–21 years; 42% female; 14% African American; 32% new onset vs 68% chronic epilepsy). The final questionnaire, the Pediatric Epilepsy Side Effects Questionnaire (PESQ), is a 19-item measure with 5 subscales (i.e., cognitive, motor, behavioral, general neurological, and weight) that accounts for 99% of the variance. Internal consistency coefficients and test-retest reliabilities ranged from 0.72 to 0.93 and 0.74 to 0.97, respectively. Construct validity was demonstrated by increasing side effects as the number of drugs increased. Participants on valproic acid had significantly higher scores on the Weight Scale compared to those on carbamazepine. Conclusions: The PESQ is a reliable and valid measure of AED side effects in children across the epilepsy spectrum that can be used in both clinical and research settings.

In children with benign childhood epilepsy with centrotemporal spikes, centrotemporal spikes may cause language dysfunction via disruption of underlying functional neuroanatomy. Fifteen patients with benign childhood epilepsy with centrotemporal spikes and 15 healthy controls completed 3 functional magnetic resonance imaging (MRI) language paradigms; standardized cognitive and language assessments were also performed. For all paradigms, children with benign childhood epilepsy with centrotemporal spikes showed specific regional differences in activation compared to controls. Children with benign childhood epilepsy with centrotemporal spikes also differed from controls on neuropsychological testing. They did not differ in general intelligence, but children with benign childhood epilepsy with centrotemporal spikes scored significantly lower than controls on tests of language, visuomotor integration, and processing speed. These results extend previous findings of lower language and cognitive skills in patients with benign childhood epilepsy with centrotemporal spikes, and suggest epilepsy-related remodeling of language networks that may underlie these observed differences.

Summary Purpose: Both a single seizure and chronic recurrent seizures (epilepsy) occur commonly in childhood. Although several studies have documented the impact of pediatric epilepsy on psychosocial functioning, such as health-related quality of life (HRQOL), no studies have examined the impact of a single seizure on HRQOL. The primary objectives of this study were: (1) to compare parent–proxy HRQOL in children with a single seizure and newly diagnosed untreated epilepsy to normative data and (2) to examine differences in parent–proxy HRQOL between children with single seizure and newly diagnosed untreated epilepsy. Methods: A retrospective medical chart review was conducted on a consecutive cohort of children being evaluated for seizures at a New-Onset Seizure Disorder Clinic. Information from the medical chart review included demographic data, seizure information, and the parent–proxy Pediatric Quality of Life Inventory (PedsQL), a well-validated measure of HRQOL in pediatric chronic illnesses. Results: Participants included 109 children (n = 53 single seizure; n = 56 newly diagnosed untreated epilepsy). Results indicated that both children with a single seizure and children with newly diagnosed untreated epilepsy had significant impairments in HRQOL compared to normative data. However, no significant HRQOL differences were found between the single seizure and the untreated epilepsy groups. Discussion: Children diagnosed with a single seizure or epilepsy have similar clinically significant impairments in HRQOL. Evaluation of HRQOL, even after a first seizure, is important and will identify children at risk at the earliest opportunity, allowing for timely psychosocial intervention.

OBJECTIVES. Adherence to antiepileptic drug therapy plays an important role in the effectiveness of pharmacologic treatment of epilepsy. The purpose of this study was to use an objective measure of adherence to (1) document patterns of adherence for the first month of therapy for children with new-onset epilepsy, (2) examine differences in adherence by demographic and epilepsy variables, and (3) determine whether treatment adherence improves for a short time before a clinic visit (eg, “white-coat compliance”). METHODS. Participants included 35 children with new-onset epilepsy (mean age: 7.2 years; 34% female; 66% white) and their caregivers. Children had a diagnosis of partial (60%), generalized (29%), or unclassified (11%) epilepsy. Adherence to treatment was electronically monitored with Medication Event Monitoring System TrackCap, starting with the first antiepileptic drug dose. Adherence was calculated across a 1-month period and for the 1, 3, and 5 days before and 3 days after the clinic appointment. RESULTS. Adherence for the first month of treatment in children with new-onset epilepsy was 79.4%. One-month adherence was higher in children of married parents and those with higher socioeconomic status but did not correlate with child's gender, age, epilepsy type, prescribed medication, seizure frequency, or length of time since seizure onset. Adherence across the entire 1-month period was not different from adherence for the 1, 3, or 5 days before or 3 days after the clinic visit. CONCLUSIONS. Poor adherence seen for children with new-onset epilepsy during the first month of antiepileptic drug therapy is a cause for concern. Several demographic variables influence adherence to treatment, whereas the proximity to a clinic visit does not. Additional studies are needed to document whether this trend continues longitudinally and determine the clinical impact of poor adherence.

Epilepsy is a common, debilitating, and costly disease. It is estimated that 2.2 million people in the United States are diagnosed with epilepsy, and 150,000 new cases of epilepsy are diagnosed in the United States annually.1 However, epilepsy prevalence might be underestimated due to numerous social issues that accompany a diagnosis of epilepsy.2 People with epilepsy have poorer overall health status, impaired intellectual and physical functioning, and a greater risk for accidents and injuries.1–3 It is estimated that the annual direct medical cost of epilepsy in the United States is $9.6 billion, and this estimate does not include indirect costs from losses in quality of life or productivity.1 The authors thank all the Epilepsy Update Quality Measurement Set Workgroup members for their dedication, time, energy, contributions, and work that supported the development of this manuscript: Nathan Fountain, MD (American Academy of Neurology); Paul C. Van Ness, MD (American Academy of Neurology); Jerome Engel, Jr., MD, PhD, FAAN (American Academy of Neurology); David S. Gloss, MD (American Academy of Neurology); Christiane Heck, MD, MMM (American Academy of Neurology); Diego A. Morita, MD (American Academy of Neurology); Marianna Spanaki, MD, PhD, MBA (American Academy of Neurology); Thaddeus Walczak, MD (American Academy of Neurology); Mark Potter, MD (American Academy of Family Physicians); Edwin Trevathan, MD, MPH (American Academy of Pediatrics); Joseph Neimat, MD (American Association of Neurological Surgeons/Congress of Neurosurgeons); Mona Stecker, DNP, NP-BS, CNRN, SCRN (American Association of Neuroscience Nurses); Sharon Hibay, RN, DNP (American Board of Internal Medicine); Susan Herman, MD (American Clinical Neurophysiology Society); J. Stephen Huff, MD (American College of Emergency Physicians); Gabriel U. Martz, MD (American Epilepsy Society); Marvin Nelson, MD (American Society of Neuroradiology/American College of Radiology); Inna Hughes, MD, PhD (Child Neurology Society); Tracy Dixon-Salazar, PhD (Citizens United for Research in Epilepsy); Janice Buelow, RN, PhD (Epilepsy Foundation); Daniel Drane, PhD, ABPP(CN) (National Academy of Neuropsychology); Ramon Bautista, MD, MBA (National Associations of Epilepsy Centers); Kay Schwebke, MD, MPH, MA (OptumInsight); Karen Parko, MD, FAAN (Veterans Affairs Epilepsy Centers of Excellence); Laurie Olmon; Mary Jo Pugh, PhD, RN; John Absher, MD, FAAN (American Academy of Neurology Facilitator); Anup D. Patel, MD (American Academy of Neurology Facilitator); Kevin N. Sheth, MD, FAHA, FCCM, FNCS (American Academy of Neurology Facilitator); Amy Bennett, JD (American Academy of Neurology staff); Gina Gjorvad (American Academy of Neurology staff); Rebecca J. Swain-Eng, MS, CAE (Former American Academy of Neurology staff); Becky Schierman, MPH (American Academy of Neurology staff).

The present study extends the utility of the Pediatric Epilepsy Side Effects Questionnaire (PESQ) by determining distribution-based minimally clinically important difference (MCID) scores. Participants (N=682) were youth (ages 2-25) with newly diagnosed and chronic epilepsy pooled from research and clinical data in the Comprehensive Epilepsy Center. Caregivers completed the PESQ. Demographic and medical data were extracted from medical chart reviews or via a questionnaire. The MCIDs, which are the standard errors of measurement for each scale, for the entire sample were as follows: Cognitive=4.66, Motor=4.67, Behavior=8.05, General Neurological=7.41, Weight=9.58, and Total Side Effects=3.25. Additionally, MCIDs for patients with new-onset (12months) epilepsy on monotherapy, new-onset epilepsy on polytherapy, chronic epilepsy on monotherapy (12months), and chronic epilepsy on polytherapy were calculated. Results from the present study extend the utility of the PESQ by providing clinicians and researchers an enhanced understanding about clinically meaningful changes in side effect profiles across the pediatric epilepsy spectrum. These data can inform clinical decision-making for clinicians and researchers.

Magnetoencephalography (MEG) has been shown to be a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy. MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether frequency-dependent ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ.

Summary Purpose Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Methods We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Key findings Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. Significance Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.

Purpose—Study aims were 1) to document and examine associations between parent-report and electronic monitoring of pediatric antiepileptic drug adherence, 2) determine the sensitivity and specificity of parent -reported adherence, and 3) develop a correction factor for parent -reported adherence. Methods—Participants included 111 consecutive children with new-onset epilepsy (Mage = 7.2 ± 2.0; 61.3% males; 75.8% Caucasian) and their primary caregivers. Antiepileptic drug adherence was electronically monitored for three months prior to the 4-month clinic follow-up visit. parentreported adherence captured adherence one-week prior to the clinic visit. For specificity/sensitivity analyses of parent-reported adherence, cut-points of 50%, 80%, and 90% were used with electronically-monitored adherence calculated one-week prior to the clinic visit as the reference criterion. Results—Electronically monitored adherence (80.3%) was significantly lower than parentreported adherence (96.5%; p < 0.0001) one-week prior to the clinic visit, but both were significantly correlated (rho=0.46, p < 0.001). The 90% parent-reported adherence cut-point demonstrated the most sensitivity and specificity to electronically monitored adherence; however, specificity was still only 28%. A correction factor of 0.83 was identified as a reliable adjustment for parent-reported adherence when compared to electronically monitored adherence. Discussion—Although electronic monitoring is the gold standard of adherence measurement for pediatric epilepsy, it is often not clinically feasible to integrate it into routine clinical care. Thus, use of a correction factor for interpreting parent-reported adherence holds promise as a reliable clinical tool. With reliable adherence measurement, clinicians can provide adherence interventions with the hope of optimizing health outcomes for children with pediatric epilepsy.

Sparse information on dose-response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE.Effect of initial valproate monotherapy and doses associated with seizure freedom were examined in consecutive children with IGE identified from a New Onset Seizure Clinic.Of 84 patients identified, 48 (57%) became seizure-free on valproate monotherapy and another 10 patients became seizure-free but discontinued VPA because of adverse effects. The mean dose in seizure-free children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25 mg/kg/day.Half of children became seizure-free on valproate monotherapy and did so at modest doses.

Physicians who treat patients with epilepsy must balance many factors when selecting the appropriate treatment for an individual patient, including seizure type, concomitant antiepileptic drug (AED) therapy, age, comorbid conditions, and even insurance coverage. Optimal management of seizures is further complicated by a continuously increasing pool of AEDs. As seizure type is a main factor in AED selection, this review will provide an evidence-based guide for physicians treating focal epilepsy. This includes a summary of efficacy, safety, and tolerability data from randomized clinical trials as well as findings related to rational polypharmacy, drug–drug interactions, comorbidities, drug administration (titration, dosing, formulation), US Food and Drug Administration (FDA)-approved indications, and cost. Following the review are four case reports that provide real-life examples of clinical challenges physicians face, particularly when dealing with special populations, which highlight the decision-making process entailed when determining the best course of treatment for patients with epilepsy.