OBJECTIVE:To assess the prognostic value of interictal epileptiform discharges (iEDs) on postoperative video-EEG in children and adolescents undergoing epilepsy surgery for low-grade developmental and epilepsy-associated tumors (LEATs). METHODS:This retrospective single-center study analyzed prospectively collected pre- and postoperative EEG data from pediatric LEAT patients. Associations between iED characteristics and seizure outcomes ≥ 24 months after surgery were examined. RESULTS:Fifty-nine patients with a median postoperative follow-up of 59.0 months (IQR: 36.0-118.0) were included. Univariate analysis identified the presence of a secondary iED focus at 3 months (p = 0.04), persistent iEDs at 12 months (p = 0.007), and a ≥ 50 % increase in iED frequency over time (p = 0.009) as predictors of unfavorable seizure outcomes. Multivariate analysis confirmed that a ≥ 50 % increase in iED frequency within the first 12 months post-surgery was independently associated with unfavorable outcomes (OR: 16.2, 95 % CI: 1.2-555.0, p = 0.037). CONCLUSIONS:Postoperative iEDs, particularly their evolution over time, are valuable predictors of long-term seizure outcomes following LEAT surgery. SIGNIFICANCE:Prognostic models for seizure outcomes in LEAT patients should not only include clinical, radiological and surgical characteristics, but also presence and progression of iEDs in postoperative EEGs.

Epilepsy is one of the most common chronic neurological diseases in adolescents. The hormonal changes often lead to alterations in clinical presentation (including associated comorbidities) in childhood-onset epilepsies, and also the manifestation of a variety of new syndromes over time, while age-dependent syndromes may spontaneously go into permanent remission. Gender-specific hormonal changes influence the pharmacodynamic and pharmacokinetic profiles of antiseizure medications (ASM) and thus their range of effects and side effects. Finally, the specific psychosocial aspects of this age group have to be considered, and special programs to support coping strategies, personal responsibility and adherence to treatment have to be offered. This review highlights particularities of ASM treatment for adolescents with epilepsy. Differences to the recently published guidelines for adults are discussed.

Although not a type of epilepsy, febrile seizures (FS) are the most common pediatric seizure disorder, affecting 2-5% of all infants and children. According to the International League against Epilepsy (ILAE) definition proposal, FS occur in neurologically healthy children between 6 and 60 months of age, associated with fever (> 38 degrees C body temperature) but without evidence of central nervous system infection, a defined cause or a history of prior afebrile seizures. Subcategories include simple FS (70-90% of all FS), complex FS (10-35% of all FS) and febrile status epilepticus (FSE). The pathophysiology of FS is unclear, a multifactorial (poly)genetic and environmental etiology seems most probable. The long-term prognosis of FS is generally favorable (spontaneous remission rate 95%), although an increased risk for comorbid neuropsychiatric disorders has recently been reported. The risk for subsequent epilepsy depends on FS subcategory but does not substantially differ from that observed in the general population. However, there are conditions similar to FS at the onset but associated with an increased risk of subsequent epilepsy and neurological long-term sequelae: febrile infection related epilepsy syndrome (FIRES), hemiconvulsion-hemiplegia epilepsy (HHE) syndrome and genetic/generalized epilepsy with febrile seizures plus (GEFS+). Preclinical as well as clinical data no longer support the hypothesis of a causal role of complex FS or FSE for subsequent hippocampal sclerosis (HS) and pharmacoresistant mesial temporal epilepsy (mTLE) but suggest a pre-existing hippocampal pathology. Based on previously published evidence this update addresses recommendations for the (differential) diagnostic work-up and management of FS.

Vaginal colonization with Ureaplasma (U.) spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with U. spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal U. spp. colonization and spontaneous preterm birth. U. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal U. spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, p = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, p = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, p = 0.005). The data suggest an association between vaginal U. spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.

本回顾性横断面研究评估了将深度学习的难治性癫痫患儿的结构性磁共振成像(MRI)纳入到规划立体定向脑电图(SEEG)植入的可行性和潜在益处.本研究旨在评估自动病变检测与SEEG检测出癫痫发作起始区(SOZ)之间的共定位程度.将神经网络分类器应用于基于皮层MRI数据的三个队列:①对34例局灶性皮质发育不良(FCD)患者的神经网络进行学习、训练和交叉验证;②对20名健康儿童对照者进行特异性评估;③ 对34例患儿纳入SEEG植入计划的可行性进行了评价.SEEG电极触点的坐标与分类器预测的病变进行核验.临床神经生理学家鉴定癫痫发作起源和易激惹区的SEEG电极触点位置.若SOZ坐标点和分类器预测的病变之间的距离＜10 mm则被认为是共定位的.影像学诊断病灶的分类敏感度为74％(25/34).对照组中未检测到异常(特异性=100％).在34例SEEG植入患者中,21例有局灶性皮层SOZ,其中8例经病理证实为FCD.分类器正确地检测了这8例FCD患者中的7例(86％).组织病理学存在异质性的局灶性皮层病变患者中,62％的患者分类器输出结果与SOZ之间存在共定位.3例患者中,电临床提示为局灶性癫痫,SEEG上无SOZ定位点,但在这些患者中,分类器识别了尚未植入的额外异常点.自动病变检测与SEEG之间的共定位存在高度的一致性.我们已经建立了一个框架,将基于深度学习的MRI自动病变检测纳入到SEEG植入计划.我们的发现支持了对自动MRI分析的前瞻性评估,以规划最佳电极植入轨迹方案.

Zusammenfassung Obwohl nicht unmittelbar den Epilepsien zuzuordnen, gehören Fieberkrämpfe (FK) zu den häufigsten Anfallserkrankungen des Kindesalters (Lebenszeitprävalenz: 2–5 %). Entsprechend Definitionsvorschlag der Internationalen Liga gegen Epilepsie (ILAE) sind FK epileptische Anfälle, die im Rahmen fieberhafter Infekte (Temperatur > 38 °C) bei neurologisch gesunden Kindern zwischen 6 und 60 Monaten auftreten. Drei Subkategorien sind beschrieben: einfacher FK (70–90 % aller FK), komplizierter FK (10–35 % aller FK) und febriler Status epilepticus (FSE). Die Pathophysiologie von FK ist unklar, aktuell wird eine multifaktorielle – (poly)genetische und durch Umweltfaktoren bedingte – Genese favorisiert. Die Langzeitprognose ist günstig (Spontanremission in 95 %). Rezente Studien berichten jedoch über gehäuft auftretende neuropsychiatrische Störungen. Das Risiko, nach FK eine Epilepsie zu entwickeln, variiert je nach FK-Typ, ist aber generell nicht wesentlich höher als jenes in der Allgemeinbevölkerung. Folgende, mit FK assoziierte Syndrome weisen ein erhöhtes Risiko für eine nachfolgende Epilepsie bzw. irreversible neurologische Folgeschäden auf: die fieberinduzierte refraktäre epileptische Enzephalopathie von Schulkindern (FIRES), das Hemikonvulsions-Hemiplegie-Epilepsie(HHE)-Syndrom und die genetische/generalisierte Epilepsie mit Fieberkrämpfen plus (GEFS+). Die kausale Rolle komplizierter FK oder FSE für nachfolgende Ammonshornsklerose (AHS) und pharmakoresistente mesiale Temporallappenepilepsie (mTLE) ist aktuellen experimentellen und klinischen Daten zufolge nicht bewiesen, eine primäre Vorschädigung des Hippocampus als wahrscheinlicher anzunehmen. Das folgende Update beinhaltet – basierend auf aktueller Evidenz – Empfehlungen für (Differenzial‑)Diagnostik und Management von FK.

AIMS:We aim to evaluate if the myelin pathology observed in epilepsy-associated focal cortical dysplasia type 2B (FCD2B) and-histologically indistinguishable-cortical tubers of tuberous sclerosis complex (TSC) is primarily related to the underlying malformation or constitutes a secondary phenomenon due to the toxic microenvironment created by epileptic seizures. We also aim to investigate the possible beneficial effect of the mTOR pathway regulator everolimus on white matter pathology.METHODS:Primary mixed glial cell cultures derived from epilepsy surgery specimens of one TSC and seven FCD2B patients were grown on polycaprolactone fibre matrices and analysed using immunofluorescence and electron microscopy. Unaffected white matter from three age-matched epilepsy patients with mild malformations of cortical development (mMCD) and one with FCD3D served as controls. Additionally, TSC2 knock-out was performed using an oligodendroglial cell line. Myelination capacities of nanofibre grown cells in an inflammatory environment after mTOR-inhibitor treatment with everolimus were further investigated.RESULTS:Reduced oligodendroglial turnover, directly related to a lower myelin content was found in the patients' primary cells. In our culture model of myelination dynamics, primary cells grown under 'inflammatory condition' showed decreased myelination, that was repaired by treatment with everolimus.CONCLUSIONS:Results obtained in patient-derived primary oligodendroglial and TSC2 knock-out cells suggest that maturation of oligodendroglia and production of a proper myelin sheath seem to be impaired as a result of mTOR pathway disturbance. Hence, oligodendroglial pathology may reflect a more direct effect of the abnormal genetic programme rather than to be an inactive bystander of chronic epilepsy.

To determine whether neurofilament light chain (NfL), a promising serum and cerebrospinal fluid (CSF) biomarker of neuroaxonal damage, predicts functional outcome in preterm infants with neonatal brain injury. Our prospective observational study used a sensitive single-molecule array assay to measure serum and CSF NfL concentrations in preterm infants with moderate to severe peri/intraventricular hemorrhage (PIVH). We determined temporal serum and CSF NfL profiles from the initial diagnosis of PIVH until term-equivalent age and their association with clinical and neurodevelopmental outcome until 2 years of age assessed by Bayley Scales of Infant Development (3rd edition). We fitted univariate and multivariate logistic regression models to determine risk factors for poor motor and cognitive development. The study included 48 infants born at < 32 weeks of gestation. Median serum NfL (sNfL) at PIVH diagnosis was 251 pg/mL [interquartile range (IQR) 139–379], decreasing markedly until term-equivalent age to 15.7 pg/mL (IQR 11.1–33.5). CSF NfL was on average 113-fold higher (IQR 40–211) than corresponding sNfL values. Additional cerebral infarction (n = 25)-but not post-hemorrhagic hydrocephalus requiring external ventricular drainage (n = 29) nor any other impairment-was independently associated with sNfL. Multivariate logistic regression models identified sNfL as an independent predictor of poor motor outcome or death at 1 and 2 years. Serum neurofilament light chain dynamics in the first weeks of life predict motor outcome in preterm infants with PIVH.

This retrospective, cross‐sectional study evaluated the feasibility and potential benefits of incorporating deep‐learning on structural magnetic resonance imaging (MRI) into planning stereoelectroencephalography (sEEG) implantation in pediatric patients with diagnostically complex drug‐resistant epilepsy. This study aimed to assess the degree of colocalization between automated lesion detection and the seizure onset zone (SOZ) as assessed by sEEG.

Organising Institutions: Supported by: Powered by: ID: 9 TITLE: CEREBRAL OXYGENATION OVER THE FIRST 72H OF LIFE IN VERY LOW BIRTHWEIGHT INFANTS WITH AND WITHOUT INTRAVENTRICULAR HEMORRHAGE OR PERIVENTRICULAR LEUKOMALACIA AUTHORS: Angelika L. Schwab 1, Hans W. Fuchs 1,2, Reinhard J. Hopfner 1, Benjamin Mayer 3, Helmut D. Hummler 1,4, Manuel B. Schmid 1,5,6 AFFILIATIONS: 1 Ulm University Medical Center, Department of Pediatrics and Adolescent Medicine, Division of Neonatology and Pediatric Intensive Care, Ulm, Germany 2 Medical Center University of Freiburg, Center for Pediatrics, General Pediatrics, Adolescent Medicine and Neonatology, Freiburg, Germany 3 Ulm University, Institue of Epidemiology and Medical Biometry, Ulm, Germany 4 Sidra Medicine, Doha, Qatar 5 University Hospital Zurich, Department of Neonatology, Zurich, Switzerland 6 University of Zurich, Zurich, Switzerland

BACKGROUND:Ureaplasma species (spp) are the bacteria most often isolated from the amniotic cavity of women with preterm labor or preterm premature rupture of membranes; thus, the link between intrauterine Ureaplasma spp infection and adverse pregnancy outcome clearly is established. However, because vaginal Ureaplasma spp colonization is very common in pregnant women, the reason that these microorganisms cause ascending infections in some cases but remain asymptomatic in most pregnancies is not clear. Previous studies suggested an association between vaginal colonization with Ureaplasma parvum as opposed to U urealyticum and preterm delivery. However, because of the high frequency of vaginal Ureaplasma spp colonization during pregnancy, additional risk factors are needed to select a group of women who might benefit from treatment.OBJECTIVE:To further identify pregnant women who are at increased risk for preterm delivery, the aim of the present study was to investigate U parvum serovar-specific pathogenicity in a large clinical cohort.STUDY DESIGN:We serotyped 1316 samples that were positive for U parvum using a high-resolution melt polymerase chain reaction assay, and results were correlated with pregnancy outcome.RESULTS:Within U parvum positive samples, serovar 3 was the most common isolate (43.3%), followed by serovar 6 (31.4%) and serovar 1 (25.2%). There was a significantly increased risk for spontaneous preterm birth at very low (<32 weeks gestation; P<.005) and extremely low (<28 weeks gestation; P<.005) gestational age in the group with vaginal U parvum serovar 3 colonization compared with the control group of pregnant women who tested negative for vaginal Ureaplasma spp colonization. This association was found for neither serovar 1 nor serovar 6. The combination of vaginal U parvum serovar 3 colonization and diagnosis of bacterial vaginosis in early pregnancy or a history of preterm birth further increased the risk for adverse pregnancy outcome.CONCLUSION:Colonization with U parvum serovar 3, but not serovar 1 or serovar 6, in early pregnancy is associated with preterm delivery at very and extremely low gestational age. The combination of U parvum serovar 3 colonization and a history of preterm birth or bacterial vaginosis further increases the risk for spontaneous preterm birth at low gestational age and may define a target group for therapeutic intervention studies.

Background: While there is a proven association of upper genital tract Ureaplasma infection during pregnancy with adverse pregnancy outcome, the effect of vaginal Ureaplasma colonization on preterm delivery has been controversially debated. Objectives: We hypothesized that women with isolation of vaginal U. parvum but not U. urealyticum are at increased risk for spontaneous preterm birth (SPB) compared to women with negative results. Methods: A vaginal swab taken between 12 and 14 weeks of gestation was analyzed for the presence of Ureaplasma biovars by PCR in 4,330 pregnant women. Results: Of the study cohort, 37% were positive for U. parvum, 5.9% for U. urealyticum, and 3.1% for both. The rates of SPB were 10.4% (OR 1.7, 95% CI 1.3, 2.2, p < 0.001) and 8.9% (OR 1.4, 95% CI 0.9, 2.3, p = 0.193) in the groups with isolation of U. parvum and U. urealyticum, respectively, compared to 6.4% in the group with negative PCR results. Multiple logistic regression and interaction analyses showed that vaginal colonization with U. parvum but not U. urealyticum was a statistically significant risk factor for SPB (adjusted OR 1.6, 95% CI 1.2, 2.1, p < 0.001), independent of other risk factors such as bacterial vaginosis and history of SPB. Conclusion: Our study demonstrates a statistically significant and independent association between first-trimester vaginal colonization with U. parvum and subsequent SPB.

[This corrects the article DOI: 10.1371/journal.pone.0123530.].

Objective To determine whether the complementary approach of manipulative osteopathic treatment accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants. Methods This study was a prospective, randomised, controlled trial in premature infants with a birth weight 1500 g and a gestational age 32 weeks who received a visceral osteopathic treatment algorithm 3 times during their first week of life or no treatment. Results Passage of last meconium occurred after a median of 7.5 days (95% confidence interval: 6–9 days, n = 20) in the intervention group and after 6 days (95% confidence interval: 5–9 days, n = 21) in the control group (p = 0.11). However, osteopathic treatment was associated with a 12 day longer time to full enteral feedings (p = 0.02), and a longer hospital stay (44 days longer in the intervention group; n.s). Osteopathic treatment was tolerated well and no adverse events were observed. Conclusions Visceral osteopathic treatment oft the abdomen did not accelerate meconium excretion in VLBW-infants. However infants in the osteopathic group had a longer time to full enteral feedings and a longer hospital stay what must be interpreted as negative side effect. Further investigations are needed with modified protocols focussed on cranial osteopathy in this vulnerable group of patients. Currently the application of visceral osteopathic techniques cannot be recommended in VLBW-infants without further clinical trials.