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NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.

ABSTRACT: Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35-40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. ¹H-NMR serum spectra were acquired on 400?MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.

SUBMITTER: Boguszewicz L

PROVIDER: S-EPMC6803684 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.

Boguszewicz Łukasz Ł Jamroz Ewa E Ciszek Mateusz M Emich-Widera Ewa E Kijonka Marek M Banasik Tomasz T Skorupa Agnieszka A Sokół Maria M

Scientific reports 20191021 1

Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35-40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG ...[more]

PMID: 31636291

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Project description:IntroductionEpilepsy affects millions of children worldwide, with 20-40% experiencing drug-resistant epilepsy (DRE) who are recommended for epilepsy surgery evaluation and may benefit from surgical management. However, many patients live with DRE for multiple years prior to surgical epilepsy referral or treatment or are never referred at all.ObjectiveWe aimed to describe factors associated with referral for epilepsy surgery in the USA, in order to identify disparities in DRE, characterize why they may exist, and recognize areas for improvement.MethodsPediatric patients diagnosed with DRE between January 1, 2004 and December 31, 2020 were identified from the Pediatric Health Information System (PHIS) Database. Patients treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery were studied regarding access to epilepsy surgery and disparities in care. This study used chi-square tests to determine associations between treatment time and preoperative factors. Preoperative factors studied included epilepsy treatment type, age, sex, race/ethnicity, insurance type, geographic region, patient type, epilepsy type, and presence of pediatric complex chronic conditions (PCCCs).ResultsA total of 18,292 patients were identified; 10,240 treated with ASMs, 5019 treated with ASMs + VNS, and 3033 treated with ASMs + cranial epilepsy surgery. Sex was not found to significantly vary among groups. There was significant variation in age, census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and insurance (p < 0.001). Those treated surgically, either with VNS or cranial epilepsy surgery, were 2 years older than those medically treated. Additionally, those medically treated were less likely to be living in the Midwest (25.46%), identified as non-Hispanic white (51.78%), have a focal/partial epilepsy diagnosis (8.74%), and be privately insured (35.82%).ConclusionsWe studied a large administrative US database examining variables associated with surgical epilepsy evaluation and management. We found significant variation in treatment associated with age, US census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and health insurance type. We believe that these disparities in care are related to access and social determinants of health, and we encourage focused outreach strategies to mitigate these disparities to broaden access and improve outcomes in children in the USA with DRE.

Project description:ImportanceStructural integrity of cortex following cortical resection for epilepsy management has been previously characterized, but only in adult patients.ObjectiveThis study sought to determine whether morphometrics of the preserved hemisphere in pediatric cortical resection patients differ from non-neurological controls.DesignThis was a case-control study, from 2013-2022.SettingThis was a single-site study.Participants32 patients with childhood epilepsy surgery and 51 age- and gender-matched controls participated.Main measuresWe quantified morphometrics of the preserved hemisphere at the level of gross anatomy (lateral ventricle size, volume of gray and white matter). Additionally, cortical thickness, volume, and surface area were measured for 34 cortical regions segmented with the Desikan-Killiany atlas, and, last, volumes of nine subcortical regions were also quantified.Results13 patients with left hemisphere (LH) surgery and a preserved right hemisphere (RH) (median age/median absolute deviation of age: 15.7/1.7 yr; 6 females, 7 males) and 19 patients with RH surgery and a preserved LH (15.4/3.7 yr; 11 females, 8 males) were compared to 51 controls (14.8/4.9 yr; 24 females, 27 males). Patient groups had larger ventricles and reduced total white matter volume relative to controls, and only patients with a preserved RH, but not patients with a preserved LH, had reduced total gray matter volume relative to controls. Furthermore, patients with a preserved RH had lower cortical thickness and volume and greater surface area of several cortical regions, relative to controls. Patients with a preserved LH had no differences in thickness, volume, or area, of any of the 34 cortical regions, relative to controls. Moreover, both LH and RH patients showed reduced volumes in select subcortical structures, relative to controls.Conclusions and relevanceThat left-sided, but not right-sided, resection is associated with more pronounced reduction in cortical thickness and volume and increased cortical surface area relative to typically developing, age-matched controls suggests that the preserved RH undergoes structural plasticity to an extent not observed in cases of right-sided pediatric resection. Future work probing the association of the current findings with neuropsychological outcomes will be necessary to understand the implications of these structural findings for clinical practice.

Project description:Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1-5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children's plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.

Project description:ObjectiveThe objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children.Data sourcesA literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012.Review methodsSystematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed.ResultsThe search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children.LimitationsWe found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance.ConclusionsBased on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as effective at reducing seizure frequency, but children had significantly fewer hospitalizations and ED visits after VNS implantation. Despite the considerable risks associated with these invasive procedures, long-term adverse events appear to be limited.Plain language summaryElectrical stimulation of specific areas of the brain is a procedure used to control epileptic seizures when more conventional treatments are not working. Most adults and children with epilepsy are able to control their seizures with medication, but for some patients, drugs are not effective and surgery to remove the part of the brain where the seizures start is not an appropriate option. This study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; we found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures.

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NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.

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NMR-based metabolomics in pediatric drug resistant epilepsy - preliminary results.

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