A Framework for Evaluation of the Higher-Risk Infant After a Brief Resolved Unexplained Event.

In 2016, the American Academy of Pediatrics published a clinical practice guideline that more specifically defined apparent life-threatening events as brief resolved unexplained events (BRUEs) and provided evidence-based recommendations for the evaluation of infants who meet lower-risk criteria for a subsequent event or serious underlying disorder. The clinical practice guideline did not provide recommendations for infants meeting higher-risk criteria, an important and common population of patients. Therefore, we propose a tiered approach for clinical evaluation and management of higher-risk infants who have experienced a BRUE. Because of a vast array of potential causes, the initial evaluation prioritizes the diagnosis of time-sensitive conditions for which delayed diagnosis or treatment could impact outcomes, such as child maltreatment, feeding problems, cardiac arrhythmias, infections, and congenital abnormalities. The secondary evaluation addresses problems that are less sensitive to delayed diagnosis or treatment, such as dysphagia, intermittent partial airway obstruction, and epilepsy. The authors recommend a tailored, family-centered, multidisciplinary approach to evaluation and management of all higher-risk infants with a BRUE, whether accomplished during hospital admission or through coordinated outpatient care. The proposed framework was developed by using available evidence and expert consensus.

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Epilepsy in Papua New Guinea: a longitudinal cohort study.

Epilepsy affects up to 1-4% of children living in low income and middle countries, however there are few studies of the problems faced by children with epilepsy in such settings. We aimed to document the situation for children with epilepsy in Port Moresby, an urban area in Papua New Guinea, a low-middle income country in the Western Pacific region. We conducted longitudinal cohort study using mixed methods, with serial data collected over 2 years which assessed seizure control, neurodevelopment, and structured interviews with children and parents. For quantitative data descriptive statistics are reported; for qualitative data common responses, themes, experiences and perceptions were grouped and reported in narrative. Forty-seven children with epilepsy were followed for a median of 18 months. Twenty six (55%) children had some associated neurodevelopmental disability. Children gave detailed and vivid descriptions of their experience of seizures. Most children and parents had a positive view of the future but faced many challenges including financial difficulties, fear of having seizures especially at school, restriction of activity that isolated them from peers, and significant stigma and discrimination. Seizure control improved over time for some children, but inconsistent supply of phenobarbitone hindered better control. Comprehensive care for children with epilepsy requires a good knowledge of the individual patient -including their seizure type and comorbidities, their family, and their strengths and vulnerabilities. Children with epilepsy face many problems that can lead to isolation, discrimination and restricted opportunities.

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Age, sex and ethnic differentials in the prevalence and control of epilepsy among Sri Lankan children: a population-based study.

To estimate the prevalence of childhood epilepsy in Sri Lanka by different age groups (0-5, 6-10 and 11-16 years), sex and ethnicity, and to describe the types and outcomes of epilepsy.A population-based, cross-sectional study was conducted in the district considered to be ethnically most balanced in Sri Lanka. A door-to-door survey was performed in the 0-5?year age group (60 geographically defined areas as clusters; 19 children per cluster), and a school-based survey in the 6-16?year age group (150 classes as clusters; 25 children per cluster). The screened children with epilepsy were reviewed individually for confirmation of the diagnosis of epilepsy, typing of the underlying epilepsy syndrome and assessment of control. The same group of children were re-evaluated 1?year later to reconfirm the syndromic diagnosis and to assess the stability of control of epilepsy.The overall prevalence of childhood epilepsy was 5.7 per 10?000 children aged 0-16 years (95%?CI: 38 to 87). It was higher with younger ages (73.4 per 10?000 children aged 0-5 years; 55.1 per 10?000 children aged 6-10 years and 50.4 per 10?000 children aged 11-16 years). A male dominance was noted in both age groups. In each age group, the prevalence was highest in children of Sinhalese ethnicity. Symptomatic focal epilepsy was the single most common group of epilepsy in both age groups. Majority of children remained well controlled on medications.The findings indicate a relatively high burden of epilepsy among children in Sri Lanka, however, these were comparable to the burden of disease reported from other countries in the region.

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How fair is our service? Evaluating access to specialist paediatric care.

To assess equity of access to paediatric outpatient clinics in our hospital.Retrospective analysis of consecutive accepted referrals to allergy, asthma, epilepsy, general paediatrics, rapid access, chronic fatigue syndrome, diabetes and endocrine outpatient clinics.32?369 new patients, April 2007 to June 2018.Among local patients (58.1%) 0.2%-2.5% of patients referred to each clinic lived in the least deprived quintile, and 43.5%-48.4% in the most deprived quintile-similar to inpatient admissions and the local population. Tertiary clinics showed a much higher proportion of patients from the least deprived quintiles (15.9%-26.2%).Local outpatient referrals broadly reflected the socioeconomic distribution, although not necessarily the distribution of need, of our local population. A relatively high proportion of patients in tertiary clinics were from more affluent postcodes, highlighting the need for referral inequalities to be evaluated across networks or regions.

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Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control.

Piperine, an alkaloid from black pepper, has demonstrated beneficial effects in central nervous system, especially in epilepsy control. However, its therapeutic application remains limited due to the low aqueous solubility of piperine. Thus, the present study aimed to formulate piperine into a more solubilized form to enhance its oral bioavailability and facilitate its development as a potential anti-epileptic treatment. The nanoprecipitation method was applied to prepare piperine nanoparticles, which were then examined under transmission electron microscopy. A spherical nanosized particle was obtained with small particle size (average particle size 130.20?±?1.57?nm), narrow size distribution (polydispersity index 0.195?±?0.002) and efficient entrapment (entrapment efficiency 92.2?±?2.5%). Compared with the unformulated piperine, nanosized piperine had a much faster dissolution rate with 3 times higher accumulated drug release after 24?h. After oral administration at 3.5?mg/kg in rats, the nanosized piperine formulations could improve its oral bioavailability by 2.7-fold with 16 times higher concentrations in brain at 10?h postdosing. Moreover, the piperine nanoparticles exhibited effective protection against pentylenetetrazol-induced seizures in both zebrafish and mice. In summary, the present study provided a simple formulation strategy for oral administration of piperine to overcome its limitation in water solubility. The developed formulations could effectively enhance oral bioavailability of piperine with promising anti-epileptic effect, which could be applied as a potential therapy in epilepsy control.

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Late Health Outcomes After Contemporary Lymphome Malin de Burkitt Therapy for Mature B-Cell Non-Hodgkin Lymphoma: A Report From the Childhood Cancer Survivor Study.

The widely used, risk-based Lymphome Malin de Burkitt (LMB) chemotherapy regimen has improved survival rates for children with mature B-cell non-Hodgkin lymphoma (NHL); however, associated late effects remain understudied. We assessed late health outcomes after LMB treatment in the Childhood Cancer Survivor Study.Multivariable regression models compared chronic health conditions, health status, and socioeconomic and neurocognitive outcomes between survivors of NHL treated with the LMB regimen (n = 126), survivors of NHL treated with non-LMB regimens (n = 444), and siblings (n = 1,029).LMB survivors were a median age of 10.2 years (range, 2.5 to 20.5 years) at diagnosis and 24.0 years (range, 10.3 to 35.3 years) at evaluation. Compared with siblings, LMB survivors were at increased risk for adverse health outcomes. However, survivors of NHL treated with LMB and non-LMB regimens did not differ with regard to risk of having any chronic health conditions, impaired health status, neurocognitive deficits, or poorer socioeconomic outcomes. Increased risk for the following specific neurologic conditions was observed in LMB survivors compared with non-LMB survivors: epilepsy (relative risk [RR], 15.2; 95% CI, 3.1 to 73.4); balance problems (RR, 8.9; 95% CI, 2.3 to 34.8); tremors (RR, 7.5; 95% CI, 1.9 to 29.9); weakness in legs (RR, 8.1; 95% CI, 2.5 to 26.4); severe headaches (RR, 3.2; 95% CI, 1.6 to 6.3); and prolonged arm, leg, or back pain (RR, 4.0; 95% CI, 2.2 to 7.1). The survivors from the group C LMB risk group (n = 50) were at the highest risk for these conditions; however, except for worse functional status (odds ratio, 2.7; 95% CI, 1.2 to 5.8), they were not at increased risk for other adverse health status or socioeconomic outcomes compared with non-LMB survivors.Survivors treated with LMB and non-LMB regimens are largely comparable in late health outcomes except for excess neurotoxicity among LMB survivors. These data inform treatment efforts seeking to optimize disease control while minimizing toxicity.

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Seizure frequency, healthcare resource utilisation and mortality in childhood epilepsy: a retrospective cohort study using the THIN database.

To understand the association of seizure frequency with healthcare resource utilisation (HCRU) and mortality in UK children with epilepsy (CWE).Retrospective cohort study.Routinely collected data in primary care from The Health Improvement Network UK database.CWE ?1?and<18 years of age with a record of seizure frequency were included in mortality analyses from 2005 to 2015 and HCRU analyses from 2010 to 2015.Frequency of HCRU contacts during the year following latest seizure frequency and mortality (descriptive and Cox proportional hazards regression) from first record of seizure frequency.Higher seizure frequency was related to increased HCRU utilisation and mortality. In negative binomial regression, each category increase in seizure frequency related to 11% more visits to general practitioners, 35% more inpatient admissions, 15% more outpatient visits and increased direct HCRU costs (24%). 11 patients died during 12?490 patient-years follow-up. The unadjusted HR of mortality per higher category of seizure frequency was 2.56 (95% CI: 1.52 to 4.31). Adjustment for age and number of prescribed anti-epileptic drugs at index attenuated this estimate to 2.11 (95% CI: 1.24 to 3.60).Higher seizure frequency is associated with greater HCRU and mortality in CWE in the UK. Improvement in seizure control may potentially lead to better patient outcomes and reduced healthcare use.

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Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy.

Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic drug treatment. To date, risk of subsequent seizure relapse across the four idiopathic generalised epilepsy syndromes is largely unknown, and so are the clinical variables associated.For this retrospective observational study, 256 adult outpatients with idiopathic generalised epilepsy were evaluated. Data were obtained from outpatient charts and, if possible, from additional telephone or mail interviews.In 84 patients (33%), antiepileptic medication was discontinued at least once. Median patient age at antiepileptic drug withdrawal was 33 years, and median duration of subsequent follow-up was 20 years. Seizures recurred in 46% of patients after a median latency of 11 months. Following multivariable analysis, seizure relapse was independently associated with short duration of seizure remission beforehand. If medication was withdrawn after? » Read more

Prognostic patterns and predictors in epilepsy: a multicentre study (PRO-LONG).

To describe the long-term prognosis of epilepsy and prognostic patterns in a large cohort of newly diagnosed patients and identify prognostic factors.Study participants were 13 Italian epilepsy centres with accessible records dating back to 2005 or earlier, complete data on seizure outcome and treatments, precise epilepsy diagnosis, and follow-up of at least 10 years. Records were examined by trained neurology residents for demographics, seizure characteristics, neurological signs, psychiatric comorbidity, first electroencephalogram (EEG) and MRI/CT, epilepsy type and aetiology, antiepileptic drugs (AEDs), and 1-year, 2-year, 5-year and 10-year seizure remissions. Five predefined prognostic patterns were identified: early remission, late remission, relapsing-remitting course, worsening course and no remission. Prognostic factors were assessed using multinomial logistic regression models.1006 children and adults were followed for 17?892 person-years (median 16 years; range 10-57). During follow-up, 923 patients (91.7%) experienced 1-year remission. 2-year, 5-year and 10-year remissions were present in 89.5%, 77.1% and 44.4% of cases. 5-year remission was associated with one to two seizures at diagnosis, generalised epilepsy, no psychiatric comorbidity, and treatment with one or two AEDs during follow-up. 10-year remission was associated with one or two AEDs. The most common prognostic pattern was relapsing-remitting (52.2%), followed by early remission (24.5%). 8.3% of cases experienced no remission. Predictors of a relapsing-remitting course were <6 seizures at diagnosis, (presumed) genetic aetiology and no psychiatric comorbidity.Few seizures at diagnosis, generalised epilepsy and no psychiatric comorbidity predict early or late seizure freedom in epilepsy. Achieving remission at any time after the diagnosis does not exclude further relapses.

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Retrospective Analysis of Oxcarbazepine in Pregnant Women With Substance Use Disorders: Focus on Safety.

Published safety data in pregnant epileptic women suggests that oxcarbazepine (OXC) may be a treatment option in nonepileptic pregnant women with substance use disorders (SUDs) and psychiatric symptomatology.To compare safety outcomes associated with OXC exposure versus non-exposure in nonepileptic pregnant women with SUD and comorbid psychiatric symptomatology.A retrospective chart review was conducted to identify pregnant women 18 years or older with a SUD who delivered at the study site. Exclusion criteria included a current diagnosis of epilepsy/seizure disorder; concurrent use of lithium, anticonvulsants, medications with a Risk Evaluation and Mitigation Strategy program or a black box warning for potential fetal toxicity; and multi-parity. Eligible patients were divided into two groups based on OXC exposure.The OXC group included 94 mother-neonate pairs versus 194 mother-neonate pairs in the non-OXC group. Baseline characteristics differed in mean number of prior pregnancies (2.8 vs 2.2 in the OXC and non-OXC group, respectively, P = .03). No significant differences were found regarding emergent cesarean or maternal hyponatremia. Average gestational age at OXC initiation was 19.8 weeks. No significant differences were found in the rates of prematurity, physical characteristics, malformation, and neonatal abstinence syndrome.OXC may be considered for management of SUD with comorbid psychiatric symptomatology in nonepileptic pregnant women. Further studies should be conducted to determine statistical significance in larger sample sizes.

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The inhibitory role of curcumin derivatives on AMPA receptor subunits and their effect on the gating biophysical properties.

Curcumin is a natural polyphenol that has a broad spectrum of therapeutic characters, including neuroprotective actions against various neurological diseases. However, the molecular mechanism behind its neuroprotective properties remains obscure. The current study investigated the neuroprotective properties of 7 different curcumin derivatives on the gating biophysical properties of AMPA receptors, specifically on the calcium-permeable homomeric GluA1 and calcium impermeable heteromeric GluA1/A2 subunits. Due to the association between excessive activation of AMPARs and neurotoxicity linked to numerous pathologies, we aim to target and manipulate the kinetics of AMPARs through these derivatives. The current study used patch-clamp electrophysiology to measure the whole-cell currents in the presence and absence of the curcumin derivatives onto HEK293 cells expressing AMPA subunits. Our results showed that some of the curcumin derivatives showed an inhibitory effect and altered the gating biophysical properties, namely, deactivation and desensitization. In the presence of those derivatives, the peak current measured was significantly reduced, and the desensitization and deactivation rates decreased as well, achieving slower kinetics of the receptor and depressing its activity. These results suggest that the two most promising derivatives have inhibitory actions and act as allosteric modulators. Many neurological diseases like epilepsy, ALS, and strokes are associated with overactivation of AMPA receptors. We can potentially synthesize a more potent neuroprotective drug to treat those neurological diseases, by understanding the most stable chemical interaction between the derivative and the receptor underlying the reported neuronal depressive properties.

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Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events.

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma.Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score =?0) to strong (score =?3). Low immunoreactivity (IR) corresponded to scores ?0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12).Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p?=?0.025). Low staining ratio (??0.5) associated with higher NPAE occurrence compared to SR?>?0.5 (85.7% vs 0%, p? » Read more