Neonatal Central Nervous System Research Articles

Fosfomycin-Containing Regimens for the Treatment of Central Nervous System Infections in a Neonatal Intensive Care Unit: A Case Series Study.

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.

Central nervous system tumours in neonates: what should the neonatologist know?

Central nervous system (CNS) tumours in neonates are relatively rare and present differently when compared with those occurring later in childhood in terms of aetiology, clinical features, location, histology and prognosis. The clinical presentation is extremely variable. Even if the most frequent clinical sign is a macrocephaly, there are many other non-specific symptoms associated. The prognosis is usually poor with overall survival of less than 30%. Surgery continues to be the primary treatment for neonatal CNS tumours, aiming for a gross total resection, directly correlated with prognosis and the overall outcome. The chemotherapy is the only adjuvant therapy whereas the radiotherapy is avoided under three years of age because of the severe sequelae. Hence the importance of molecular characterization of these neoplasms in order to improve the accuracy of the diagnosis and identify new therapeutic targets. The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to recognize these pathologies in the prenatal period and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications. Neonatologists play a key role in the early detection, diagnostic evaluation, management and supportive care of these neonates. Conclusion: The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to ensure the essential knowledge that will help the neonatologist identify them and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications. What is Known: • Neonatal CNS tumours are relatively rare and their early identification is important to identify the best diagnostic-therapeutic management. • Surgery is the main treatment of neonatal CNS tumours. The extent of surgical resection directly correlates with prognosis and outcome. What is New: • Predisposing conditions such as Cancer Predisposition Syndromes must be considered. • Targeted drugs and other therapeutic strategies can be identified through molecular characterization.

Characteristics of neonatal herpes simplex central nervous system disease in Australia (1997-2020).

Neonatal herpes simplex virus (HSV) central nervous system (CNS) disease can occur in isolation or as part of disseminated infection. We sought to describe neonatal HSV CNS disease in Australia over 24 years. Neonates (≤28 days) with confirmed HSV infection, reported prospectively to the Australian Paediatric Surveillance Unit (1997-2020), were evaluated for HSV CNS disease (laboratory confirmation with clinical evidence of encephalitis, e.g., lethargy, seizures, focal signs; and/or abnormalities on neuroimaging or electroencephalogram), and compared with neonates without CNS disease. CNS-restricted disease was compared with CNS-disseminated disease. Of 195 neonates with HSV disease; 87 (45%) had CNS disease (1.29 cases/100,000 live births per year, 95% CI: 1·04-1·59). Neonates with CNS disease were significantly more likely to be male than neonates without CNS disease (60% versus 39%, OR=2·32, 95% CI 1·29-4·18). Of the neonates with CNS disease, those with CNS-restricted disease (52/87, 60%) presented later than neonates with CNS-disseminated disease (35/87, 40%), (mean 12 versus 6 days). Twenty (23%) neonates with CNS disease died, the majority with CNS-disseminated disease (n=19). Most neonates received aciclovir therapy (94·3%), however five neonates with unrecognised CNS disseminated disease (diagnosed at autopsy) had not been treated. Survivors of CNS disease were significantly more likely to have adverse neurological sequelae, compared with those without CNS disease (30% versus 4%, OR: 9·60, 95% CI: 2·6-35·0). Male neonates have a higher burden of HSV CNS disease. Despite the use of antiviral agents, morbidity following neonatal HSV CNS disease remains high. Evaluation of adjunctive therapies to improve outcomes is needed.

Management of neonatal central nervous system viral infections: Knowledge gaps and research priorities.

Congenital CMV, enteroviruses, human parechovirus and herpes simplex virus are all common causes of severe central nervous system (CNS) infection in neonates. The introduction of screening (i.e. newborn hearing screening programme), integration of molecular syndromic testing (i.e. multiplex polymerase chain reaction assays) and increase in sexually transmitted infections (i.e. anogenital herpes) have contributed to increases in each of these infections over the last decade. However, therapeutic options are highly limited in part due to the lack of epidemiological data informing trials. This review will describe our current understanding of the clinical burden and epidemiology of these severe neonatal CNS infections, outline the novel antiviral and vaccines in the pipeline and suggest future research studies which could help develop new therapeutics.

Disturbance of utero-placental-fetus blood flow in pregnant women with community-acquired pneumonia of bacterial and viral (COVID-19) etiology

Introduction. Placental insufficiency is one of the most frequently developing complications in pregnant women with acute respiratory failure, which is a consequence of community-acquired pneumonia (CAP), including viral etiology. The impact of COVID-19 infection on the course of pregnancy, the condition of the fetus and newborns has not been studied enough. Aim. To study the state of uteroplacental-fetal circulation, placenta and fetus in women with bacterial and COVID-19-associated CAP in the second and third trimesters of pregnancy. Materials and methods. The history of childbirth and the results of examinations of 120 women in the second and third trimesters of pregnancy were analyzed, including 37 women with moderate CAP of bacterial etiology, 48 women with COVID-19 infection. The comparison group consisted of 35 women with uncomplicated pregnancy. The state of the placenta and fetus was assessed according to the data of ultrasound and utero-placental-fetal blood flow – Doppler study. Pulsation indices (PI) and cerebro-placental ratio (CPR) were analyzed. Results. According to our data, the risk of developing chronic placental insufficiency in pregnant women with COVID-19-associated CAP of moderate severity was higher than in groups of women with CAP of bacterial etiology and in the comparison group. In groups with CAP, significant differences were found in the indices of CPR, PI of the uterine arteries, umbilical cord arteries and middle cerebral artery, corresponding to I (A, B) or II degree of disturbance of the uteroplacental and/or placental-fetal blood flow. Chronic intrauterine fetal hypoxia and fetal growth retardation were more frequently detected in the group with COVID-19-associated CAP. Newborns born to mothers with COVID-19 infection have an increased risk of neonatal damage to the central nervous system (CNS). Conclusion. COVID-19-associated CAP, compared with CAP of bacterial etiology, increases the risk of chronic placental insufficiency, intrauterine fetal hypoxia and fetal growth retardation, and the development of neonatal CNS damage.

Echoencephalography of encephalopathy due to congenital lymphocytic choriomeningitis virus.

AbstractCongenital lymphocytic choriomeningitis virus (LCMV) infection is a transient intrauterine viral infection with selective teratogenicity depending on the timing of the primary maternal infection. LCMV is cleared from the body of the fetus after the acute phase of illness and, in most cases, has lost its virulence at the time of birth. LCMV competes with extracellular matrix proteins for its tropism toward heavily glycosylated alpha‐dystroglycan. In the first trimester, while tropism toward heart myoblasts is high, intrauterine infection (IUI) can lead to miscarriage or fetal demise. Later in pregnancy, LCMV becomes neurotropic with tropism toward retina and brain. Most often systemic symptoms are subtle or absent at the time of birth. The timing of the IUI determines the neuroteratogenic phenotypes of congenital LCMV infection. IUI that occurs early during gestation can lead to isolated cerebellar dysgenesis and hypoplasia. When IUI occurs during neural radial migration, echoencephalography shows defective cerebral opercularization, intracranial calcifications at the gray‐white matter junction, enlarged extra‐axial subarachnoid space, and cortical dysplasia. When IUI occurs after the completion of insular opercularization (late second trimester), echoencephalography shows extensive cystic periventricular leukomalacia with bi‐occipital porencephaly and mild defects in gyrogenesis. A late gestation IUI induces aseptic LCMV meningitis with occlusion of the aqueduct of Sylvius, leading to congenital obstructive hydrocephalus. Congenital LCMV remains underdiagnosed as clinical manifestations are predominantly neurologic. As echoencephalography remains the preferred screening strategy for detecting neonatal central nervous system pathology, prior knowledge of echoencephalography of congenital LCMV may facilitate its recognition, prompting a serological evaluation.

Variation in ampicillin dosing for lower respiratory tract infections and neonatal bacterial infections in US children's hospitals.

We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications. Retrospective cohort study. The study included data from 32 children's hospitals in the United States. We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, and presence of antimicrobial stewardship program (ASP) review. LRTI prescriptions were compared to IDSA recommendations for community-acquired pneumonia. Neonatal prescriptions were compared to recommendations from the American Academy of Pediatrics (AAP). Prescriptions were categorized as "optimal" (80%-120% of recommended dosing), "suboptimal" (<80% of recommended dosing), or "excessive" (>120% of recommended dosing). Among 1,038 ampicillin prescriptions, we analyzed 88 prescriptions for LRTI, 499 prescriptions for neonatal sepsis, and 27 prescriptions for neonatal CNS infection. Of the LRTI prescriptions, 77.3%were optimal. Of prescriptions for neonatal sepsis, 81.6% were excessive compared to AAP bacteremia recommendations but 78.8% were suboptimal compared to AAP meningitis guidelines. Also, 48.1% of prescriptions for neonatal CNS infection were suboptimal, and 50.6% of prescriptions were not reviewed by the ASP. LRTI dosing is generally within the IDSA-recommended range. However, dosing for neonatal sepsis often exceeds the recommendation for bacteremia but is below the recommendation for meningitis. This variability points to an important opportunity for future antimicrobial stewardship efforts.

Role of MRI in the prognosis of hypoxic–ischemic encephalopathy

BackgroundNeonatal encephalopathy is a heterogeneous syndrome characterized by signs of central nervous system dysfunction in newborn infants. The main cause of neonatal encephalopathy can be broadly divided into perinatal asphyxia [hypoxic–ischemic encephalopathy (HIE)], perinatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital neonatal central nervous system infections, and severe birth trauma.ObjectivesTo highlight the predictive value of MRI as a safe and superior neuroimaging technique in cases of HIE.Patients and methodsThis progressive study was conducted on 30 neonates with HIE referred to the Radiology Department at Menoufia University Hospitals for advanced magnetic resonance techniques assessment during the period from July 2019 to December 2020. The study received the approval of Ethics Committee of Faculty of Medicine, Menoufia University. A written informed consent was taken from the parents or caregivers and written informed consent was obtained from them.ResultsApparent diffusion coefficient (ADC) value was significantly increased with hypertonia (1.75 ± 1.21), hypotonia (1.52 ± 1.51), and MRI than flaccid (0.86 ± 0.67). There was no statistically significant relation between ADC value with time of birth, causes of admission, Apgar score, time of birth at 5 min, Tendon reflex, seizures, periventricular leukomalacia, and intraventricular hemorrhage.ConclusionMRI findings were significantly related with diffusion-weighted (DW) and ADC value. MRI findings indicated that periventricular leukomalacia and basal ganglia ischemia were significantly related with DW. Moreover, it was noted that MRI is a very efficient tool in evaluating morphometric HIE. It's noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for accurate diagnosis. Also, DW and ADC values may add value to routine MRI examination. However, there is limitation in our study as regards the small number of cases, lack of clinical data, and long-term follow-up of cases.

Neural Injury and Repair in a Novel Neonatal Mouse Model of Listeria Monocytogenes Meningoencephalitis.

To improve the therapy of neonatal central nervous system infections, well-characterized animal models are urgently needed. The present study analyzes neuropathological alterations with particular focus on neural injury and repair in brains of neonatal mice with Listeria monocytogenes (LM) meningitis/meningoencephalitis using a novel nasal infection model. The hippocampal formation and frontal cortex of 14 neonatal mice with LM meningitis/meningoencephalitis and 14 uninfected controls were analyzed by histology, immunohistochemistry, and in situ tailing for morphological alterations. In the dentate gyrus of the hippocampal formation of mice with LM meningitis/meningoencephalitis, an increased density of apoptotic neurons visualized by in situ tailing (p = 0.04) and in situ tailing plus immunohistochemistry for activated Caspase-3 (p < 0.0001) was found. A decreased density of dividing cells stained with an anti-PCNA-antibody (p < 0.0001) and less neurogenesis visualized by anti-calretinin (p < 0.0001) and anti-calbindin (p = 0.01) antibodies were detected compared to uninfected controls. The density of microglia was higher in LM meningitis (p < 0.0001), while the density of astrocytes remained unchanged. Infiltrating monocytes and neutrophilic granulocytes likely contributed to tissue damage. In conclusion, in the brains of LM-infected mice a strong immune response was observed which led to neuronal apoptosis and an impaired neural regeneration. This model appears very suitable to study therapies against long-term sequelae of neonatal LM meningitis.

Uncommon acute neuroimaging findings in severe neonatal herpes simplex virus 2 and consequences of delayed diagnosis

Neonatal herpes simplex virus (HSV) infection of the central nervous system (CNS) is an emergency that can have devastating structural consequences and clinical outcomes. As it presents non-specifically in neonates, it is difficult to rapidly diagnose without neuroimaging. Although once thought to cause widespread parenchymal destruction, neonatal CNS HSV infection may present with more focal parenchymal injury on neuroimaging, not involving the medial temporal lobes as in adults. We report a case of a three-week-old girl with herpes simplex virus type 2 (HSV-2) encephalitis with exclusive bilateral corticospinal and frontal opercular involvement, which remained undiagnosed and untreated until three months of age. Neuroimaging upon presentation to the emergency room demonstrates a highly suggestive pattern of severe neonatal CNS HSV-2 infection which followed the natural history on subsequent imaging, highlighting the importance of emergency neuroimaging as well as having a high index of suspicion for making the diagnosis.

Neonatal Ureaplasma parvum meningitis complicated with subdural hematoma: a case report and literature review

BackgroundNeonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection.Case presentationWe herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks.ConclusionsConsidering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

Etiology and Types of Seizures in Patients Presenting to a Tertiary Care Hospital in Karachi: A Cross-Sectional Study.

IntroductionEpilepsy is a burdensome disorder for affected individuals and community. There is limited data available on the epidemiological aspects of seizures in Pakistan and further research is necessary. We aimed to fill this gap by studying this information in epilepsy patients presenting to our neurology department. The purpose of this study is to evaluate the causes and types of seizures among the target population.MethodThis is a cross-sectional study conducted at the Department of Neurology, Dr. Ruth K.M. Pfau Civil Hospital Karachi. In this study we evaluated the causes and types of seizures among patients presenting to our department during the two-year study duration (January 2018-December 2019). Informed consent was taken. Detailed history was taken including features of seizure episodes, age at first seizure, family history and comorbid conditions. Relevant investigations were carried out. The data was compiled to deduce the relevant information using SPSS v20.0. T-test and Chi-square were used for analyzing the data.ResultsA total of 996 patients presented during the study duration. Primary seizures were found in 58% cases while secondary seizures were found in 42% cases. This distribution was more equal in children with 49.6% primary seizures and 50.4% secondary seizures; the gap widened in adults with 64.3% primary seizures and 35.7% secondary seizures. The most common cause of secondary seizures was neonatal encephalopathy which was present in 18.7% patients, followed by traumatic head injury in 18.2% patients. Central nervous system (CNS) infection was the cause in 17.9% patients, cerebral tumors in 14.1% patients, stroke in 11.5%, metabolic encephalopathy in 7.4%, febrile seizures in 6.5% and CNS malformations in 5.7% patients. The top three causes in children were neonatal encephalopathy (28.3%), CNS infections (19.3%) and febrile seizures (12.7%). Adults with secondary seizures were diagnosed most often with head trauma (25.2%), cerebral tumors (19.9%) and stroke (18.4%) as causative factors. The most common type of seizures was generalized onset tonic-clonic seizures which was found in 73.0% patients followed by focal to bilateral tonic-clonic seizures in 8.9% patients. Other types of seizures included focal aware seizures in 5.0%, mixed seizure types in 4.2%, focal impaired awareness seizures in 3.1%, absence seizures in 2.7%, myoclonic seizures in 2.0% and atonic seizures in 1.0% patients. Seizures in children were mostly generalized onset tonic-clonic seizures (75.4%), mixed seizure types (5.7%) and focal to bilateral tonic-clonic seizures (5.2%). In adults the three most common types corresponded to the overall result: generalized onset tonic-clonic seizures (71.2%), focal to bilateral tonic-clonic seizures (11.6%) and focal aware seizures (6.6%).ConclusionWe found that the most common cause of seizures overall in our study population was primary seizures, though primary and secondary seizures were more evenly present in children. Among secondary causes neonatal encephalopathy stood out as the most common cause in children; head trauma was the predominant cause in adults. Most common type of seizures overall and in adults was generalized onset tonic-clonic seizures, followed by focal to bilateral tonic-clonic and focal aware seizure types. Pediatric patients presented most often with generalized onset tonic-clonic seizures, followed by mixed seizure types and focal to bilateral tonic-clonic seizures.

Influence of fetal sex on perinatal outcomes in women with gestational diabetes mellitus.

Fetal sex has recently been considered to be related to maternal glucose homeostasis and perinatal outcomes during pregnancy. Here, we investigated the effects of fetal sex on the perinatal outcomes of pregnancies with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). This was a retrospective cohort study of 1292 women with NGT and 1155 women with GDM. Pregnant women were divided into four groups according to the maternal glucose level and fetal sex. Logistic regression was used to evaluate the risks for adverse perinatal outcomes among NGT-males, NGT-females, GDM-males and GDM-females. NGT-males had higher risks for macrosomia and large for gestational age (LGA) than NGT-females with an odds ratio (OR) of 1.9 (95% CI 1.2-2.9). Additionally, GDM-males had higher risks for neonatal infection (OR, 3.0; 95% CI, 1.3-6.9), acute respiratory disorders (OR, 3.9; 95% CI, 1.1-13.7) and abnormal neonatal central nervous system development (OR, 3.1; 95% CI, 1.1-8.4) than GDM-females. Furthermore, there was a significantly higher risk for newborn infection (OR, 8.5; 95% CI, 1.1-66.8) in the GDM-male group than in the GDM-female group with a glycosylated hemoglobin A1c (HbA1c) level ≥5.5% in the late trimester of pregnancy, which was not observed with an HbA1c level of <5.5%. Male fetuses have worse perinatal outcomes than female fetuses, and the difference is more pronounced in GDM pregnancies. More postpartum care is needed for male fetuses, especially in GDM pregnancies with substandard glycemic control.

Differential effects of glucose deprivation on the survival of fetal versus adult neural stem cells-derived oligodendrocyte precursor cells.

Impaired myelination is a key feature in neonatal hypoxia/ischemia (HI), the most common perinatal/neonatal cause of death and permanent disabilities, which is triggered by the establishment of an inflammatory and hypoxic environment during the most critical period of myelin development. This process is dependent on oligodendrocyte precursor cells (OPCs) and their capability to differentiate into mature oligodendrocytes. In this study, we investigated the vulnerability of fetal and adult OPCs derived from neural stem cells (NSCs) to inflammatory and HI insults. The resulting OPCs/astrocytes cultures were exposed to cytokines to mimic inflammation, or to oxygen-glucose deprivation (OGD) to mimic an HI condition. The differentiation of both fetal and adult OPCs is completely abolished following exposure to inflammatory cytokines, while only fetal-derived OPCs degenerate when exposed to OGD. We then investigated possible mechanisms involved in OGD-mediated toxicity: (a) T3-mediated maturation induction; (b) glutamate excitotoxicity; (c) glucose metabolism. We found that while no substantial differences were observed in T3 intracellular content regulation and glutamate-mediated toxicity, glucose deprivation lead to selective OPC cell death and impaired differentiation in fetal cultures only. These results indicate that the biological response of OPCs to inflammation and demyelination is different in fetal and adult cells, and that the glucose metabolism perturbation in fetal central nervous system (CNS) may significantly contribute to neonatal pathologies. An understanding of the underlying molecular mechanism will contribute greatly to differentiating myelination enhancing and neuroprotective therapies for neonatal and adult CNS white matter lesions.

Neonatal Growth, Neurotrophine, Zinc, and Ferritin Concentration in Normal and Iron Deficience Pregnancy: An Observational Analitic Study.

BACKGROUND:Anemia in pregnancy was one of the national problems. Insufficient iron deposits before pregnancy and inadequate iron intake during pregnancy could lead to iron deficiency anaemia in pregnancy, followed by iron deficiency in neonates.AIM:This study aimed to assess the molecular relationship of maternal iron deficiency with the function of the neonatal central nervous system to know the cognitive aspects of learning ability of children.METHODS:This study was an observational analytic study with cross-sectional design underwent in RSUP Dr M. Djamil Padang, RSI Ibnu Sina Padang, and RSU BMC Padang. The sample size was 80 pregnant women at term. After a maternal and neonatal physical examination, maternal and umbilical blood samples were obtained to assess maternal ferritin levels and neonates ferritin, neurotrophin and zinc levels using the Enzyme-Linked Immunosorbent Assay (ELISA). Data were analysed using the IBM SPSS Statistics for Windows. The independent sample t-test was performed to assess the relationship for normally distributed data and Mann-Whitney test for abnormal data distribution with significance level p < 0.05.RESULTS:There were differences in mean neonatal ferritin (p < 0.001), neonatal neurotrophin (p < 0.001), and neonatal zinc (p < 0.001) to normal maternal ferritin levels (≥ 15 μg/ml) and low maternal ferritin levels (< 15 μg/ml). The difference in mean neonatal head circumference (0.92; CI95% -0.79-0.98) was associated with neonatal ferritin levels.CONCLUSIONS:The mean neonatal ferritin, neurotrophin, and zinc levels were found lower in iron deficiency maternal. Maternal iron deficiency correlates with neonate growth, iron deficiency, and neurotrophin expression that affected neonate cognition.

Etiology and Short Term Outcome of Neonatal Convulsion in NICU at Benghazi Children Hospital

Background: Neonatal seizures are the most prominent feature of neurological dysfunction during neonatal period, which are abnormal electrical discharges in the central nervous system of neonates, usually manifest as stereotyped muscular activity or autonomic changes, occurring in approximately 1.8 - 3.5/1000 live birth. Objective: The aims of study are to determine prevalence rate, natural history, time of onset, etiological factors, clinical types and the short term outcome of neonatal convulsion. Settings: This study conducted in Neonatal Department at Benghazi Children Hospital—Libya. Patients and Methods: Descriptive cross sectional study, included all neonates who developing clinically identifiable seizures, admitted from 1st of March 2013 to 1st of March 2014. The data collected by using a designed perform including; gender, nationality, residence, place of transfer, gestational age, time of onset, mode of delivery, and history of maternal diseases, family history of neonatal seizures in previous siblings or death, jaundice and exchange transfusion were taken. Details examination include dysmorphic features, weight, head circumference were recorded. Types of seizures were diagnosed by clinical observations, and the etiology of neonatal seizures had been identified from imaging study and from initial relevant investigations which include blood glucose levels, arterial blood gases, serum calcium, electrolytes, phosphate and cerebrospinal fluid examination for evidence of infection. In addition to treatments received, as well as causes of deaths. Results: A total of 2842 neonates were admitted to NNW, out of which 150 had seizures. 86 (57%) were male with M:F ratio of 1.3:1. (97%) were Libyan and (76%) from Benghazi, (42%) admitted directly from home. 131 (87%) were term and 15 (10%) preterm. Most of neonatal seizures (76%) were seen in the 1st week of life, and during initial 72 hours of life (63%), with 24% presented in 1st 24 hours of life. Vaginal delivery conducted in 101 (67%), C/S 49 (33%). Among babies with birth asphyxia, 76% delivered vaginally. 43/150 mothers presented with different medical problems, 32% of them had preeclampsia followed by diabetes in 28%. 127 (85%) babies had normal birth weight and 128 (86%) lie within normal range of head circumference. The most common type of seizure was subtle (48%) followed by clonic (36%). Cranial ultrasound performed to 110 (73%), among them, 16 babies MRI or CT scan were done. The most common cause of seizure was birth asphyxia (30%) followed by infection (16%), hypocalcemia (14%). Phenobarbitone was the most common drug used in treatment (60%), followed by phenytoin (40%) and resistant cases for treatment received pyridoxine (2%). 77 (52%) improved and discharged home without treatment. Mortality rate was 15%; among them 44% from IEM, followed by birth asphyxia 22%. There is strong association between main causes and the outcome with p = 0.005. Conclusion: The majority of neonates in our study were full term and male. The most common etiology of seizures is birth asphyxia. Hypocalcemia is the most common biochemical abnormality. Subtle represents the commonest type of seizure. Phenobarbitone is still the most commonly prescribed anticonvulsant. Inborn error of metabolism carries a higher mortality rate. Statically analysis showed there is significant association between main causes of neonatal convulsions and the outcome with p = 0.005.

Candidiasis of the Central Nervous System in Neonates and Children with Primary Immunodeficiencies.

Candida infections of the central nervous system (CNS) are a life-threatening complication of invasive infections that most often affect vulnerable groups of patients, including neonates and children with primary immunodeficiency disorders (PID). Here, we review the currently known risk factors for CNS candidiasis, focusing predominantly on the PID caused by biallelic mutations in CARD9. How the CNS is protected itself against fungal invasion is poorly understood. CARD9 promotes neutrophil recruitment and function, and is the only molecule shown to be critical for protection against CNS candidiasis in humans thus far. Fundamental insights into the pathogenesis of CNS candidiasis gained from studying rare CARD9-deficient patients has significant implications for other patients at risk for this disease, such as CARD9-sufficient neonates. These findings will be important for the development of adjunctive immune-based therapies, which are urgently needed to tackle the global burden of invasive fungal diseases.

Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial

IntroductionSeveral retrospective or single-centre studies demonstrated the efficacy of transplacental treatment of fetal tachyarrhythmias. Our retrospective nationwide survey showed that the fetal therapy will be successful at an overall rate...

FMRI-based Neuronal Response to New Odorants in the Newborn Brain.

The sense of smell is one of the oldest and the most primitive senses mammals possess, it helps to evaluate the surrounding environment. From birth, smell is an important sensory modality, highly relevant for neonatal behavioral adaptation. Even though human newborns seem to be able to perceive and react to olfactory stimuli, there is still a lack of knowledge about the ontogeny of smell and the underlying central processing involved in odor perception in newborns. Brain networks involved in chemosensory perception of odorants are well described in adults, however in newborns there is no evidence that central olfaction is functional given the largely unmyelinated neonatal central nervous system. To examine this question, we used functional magnetic resonance imaging (fMRI) in the newborn to characterize cortical response to olfactory and trigeminal odorants. Here we show that brain response to odors can be measured and localized using functional MRI in newborns. Furthermore, we found that the developing brain, only few days after birth, processes new artificial odorants in similar cortical areas than adults, including piriform cortex, orbitofrontal cortex and insula. Our work provides evidence that human olfaction at birth relies on brain functions that involve all levels of the cortical olfactory system.

The global threat of Zika virus to pregnancy: epidemiology, clinical perspectives, mechanisms, and impact.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has newly emerged as a significant global threat, especially to pregnancy. Recent major outbreaks in the Pacific and in Central and South America have been associated with an increased incidence of microcephaly and other abnormalities of the central nervous system in neonates. The causal link between ZIKV infection during pregnancy and microcephaly is now strongly supported. Over 2 billion people live in regions conducive to ZIKV transmission, with ~4 million infections in the Americas predicted for 2016. Given the scale of the current pandemic and the serious and long-term consequences of infection during pregnancy, the impact of ZIKV on health services and affected communities could be enormous. This further highlights the need for a rapid global public health and research response to ZIKV to limit and prevent its impact through the development of therapeutics, vaccines, and improved diagnostics. Here we review the epidemiology of ZIKV; the threat to pregnancy; the clinical consequences and broader impact of ZIKV infections; and the virus biology underpinning new interventions, diagnostics, and insights into the mechanisms of disease.