Cerebrospinal Fluid Of Infants Research Articles

Quantitative proteomics on the cerebrospinal fluid of hydrocephalus in neonatal bacterial meningitis.

ObjectiveHydrocephalus in bacterial meningitis (BM) is a devastating infectious neurological disease and the proteins and pathways involved in its pathophysiology are not fully understood.Materials and methodsLabel-free quantitative (LFQ) proteomics analyses was used to identify differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples from infants with hydrocephalus and bacterial meningitis (HBM group, N = 8), infants with bacterial meningitis (BM group, N = 9); and healthy infants (N group, N = 11). Bioinformatics analysis was subsequently performed to investigate Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched signaling pathways of these DEPs. Six proteins (AZU1, COX4I1, EDF1, KRT31, MMP12, and PRG2) were selected for further validation via enzyme-linked immunosorbent assay (ELISA).ResultsCompared with BM group and N group, HBM group had a higher whole CSF protein level (5.6 ± 2.7 vs. 1.7 ± 1.0 vs. 1.2 ± 0.5 g/l) and lower whole CSF glucose level (0.8 ± 0.6 vs. 1.8 ± 0.7 vs. 3.3 ± 0.8 mmol/l) (both P < 0.05). Over 300 DEPs were differentially expressed in HBM group compared with BM group and BM compared with N group, of which 78% were common to both. Cluster analysis indicated that the levels of 226 proteins were increased in BM group compared with N group and were decreased in HBM group compared with BM group. Bioinformatics analysis indicated the involvement of the cell adhesion, immune response and extracellular exosome signaling were significantly enriched in HBM compared with BM group and BM compared with N group. 267 DEPs were identified between HBM group with N group, KEGG analysis indicated that DEPs mainly involved in filament cytoskeleton and immune response. The ELISA results further verified that the expression levels of AZU1 were significantly different from among three groups (both P < 0.05).ConclusionThis is the first reported characterization of quantitative proteomics from the CSF of infants with HBM. Our study also demonstrated that AZU1 could be a potential biomarker for the diagnosis of hydrocephalus in bacterial meningitis.

A Case of Meningitis in an Infant Due to Hypervirulent Klebsiella pneumoniae Transmission Within a Family

Hypervirulent Klebsiella pneumoniae (hvKP), an emerging pathotype derived from K. pneumoniae, frequently causes invasive infections of multiple organs and is associated with both high disability and fatality rates. In this study, a case of meningitis in a young infant caused by hvKP is presented. Cytological and biochemical examinations of the cerebrospinal fluid (CSF) revealed purulent meningitis, a diagnosis that was confirmed by a positive CSF culture result. The pathogen was identified as hvKP through analysis of positive virulence-associated genes. Meanwhile, hvKP was also isolated from stool samples of both the infant and her father. Antimicrobial susceptibility, capsular typing, and multilocus sequence typing (MLST) of three isolates from the infant’s CSF and stool and her father’s stool samples were analyzed. The three K. pneumoniae isolates were susceptible to all antibiotics except ampicillin and were identified as capsular serotype K2 and sequence type 86. These genetic relatedness analyses indicated that the strain isolated from the infant’s CSF might have originated from her father’s stool via familial transmission. This case is the first report of meningitis in an infant due to hvKP transmitted within a family.

Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation.

Newborn infants are prone to sepsis and related inflammation of different organs. Neuroinflammation has been associated with long-term adverse neuronal (neuropsychiatric/neurodegenerative) outcomes, including attention deficit hyperactivity disorder (ADHD) or even Alzheimer's disease. Despite a vast number of findings on sepsis-induced inflammatory responses in the central nervous system (CNS), how neuroinflammation affects brain development remains largely elusive. In this study, neonates with clinical sepsis and screened for meningitis were included and classified by the neuroinflammation status based on cerebrospinal fluid (CSF) parameters (INF vs. NOINF). CSF samples collected from clinical screening were subjected to proteomics analysis. Proteins with differential abundance were subjected to enrichment analysis to reveal affected biological pathways. INF and NOINF infants had similar demographic data and hematological and biochemical parameters in blood and CSF. The CSF proteomes were essentially different between the two groups. All 65 proteins with differential abundance showed lower abundance in the INF group and functionally covered pivotal developmental processes, including axonal and synaptic function and extracellular homeostasis. CSF proteins, PTPRZ1 and IGFBP4, were correlated with C-reactive protein (CRP) and ratios of immature/total neutrophils in blood. In general, a substantial change in the CSF protein profile was found under neuroinflammation, and these changes are related to systemic conditions. The results suggest that changes in CSF proteins may be involved in sepsis-affected neurodevelopment, such as disturbances in circuit formation, which has the potential to predispose neonates to long-term adverse outcomes.

Clinical pharmacology of teicoplanin in infants and children

Teicoplanin is a glycopeptide and is a mixture of related glycopeptides. Teicoplanin inhibits the synthesis of the cell wall in sensitive bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units. Because of its large molecular size, teicoplanin is unable to penetrate the outer membrane of gram-negative bacteria. The intravenous dosage of teicoplanin consists in a loading dose of 16 mg/kg followed by a maintenance dose of 8 mg/kg once-daily to infants aged &lt; one month and in older infants the dosage of teicoplanin consists in a loading dose of 12 mg/kg twice-daily followed by a maintenance dose of 10 mg/kg once daily. In children, the oral dose is 100 to 200 mg twice-daily and the intravenous dosage consists in 12 mg/kg twice-daily followed by 12 mg/kg once-daily. Teicoplanin has been found efficacy and safe in infants and children. The elimination half-life of teicoplanin is 73.9 hours in infants and children and teicoplanin is cleared from the body by renal and extra-renal routes. The total body clearance of teicoplanin is 0.09 L/h in children aged &lt; 12 months and 0.29 L/h in older children. The treatment and the prophylaxis with teicoplanin have been described in infants and children. Teicoplanin administered intravenously and/or intraventricularly treats the cerebral infections caused by staphylococci and enterococci. The aim of this study is to review the published data on teicoplanin dosing, efficacy and safety, pharmacokinetics, drug-interactions, treatment, prophylaxis, and penetrates into the cerebrospinal fluid in infants and children.

Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy.

Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy.

Derivation of a metabolic signature associated with bacterial meningitis in infants

Background:Diagnosis of bacterial meningitis (BM) is challenging in newborn infants. Presently, biomarkers of BM have limited diagnostic accuracy. Analysis of cerebrospinal fluid (CSF) metabolites may be a useful diagnostic tool in BM.Methods:In a nested case-control study, we examined over 400 metabolites in CSF of uninfected infants and infants with culture-confirmed BM using gas- and liquid-chromatography mass spectrometry. Preterm and full-term infants in a Level III or IV Neonatal Intensive Care Unit were prospectively enrolled when evaluated for serious bacterial infection.Results:Over 200 CSF metabolites significantly differed in uninfected infants and infants with BM. Using machine-learning, we found as few as 6 metabolites distinguished infants with BM from uninfected infants in this pilot cohort. Further analysis demonstrated 3 metabolites associated with Group B Streptococcal meningitis.Conclusions:We report the first comprehensive metabolic analysis of CSF in infants with BM. In our pilot cohort, we derived a metabolic signature that predicted the presence or absence of BM, irrespective of gestational age, postnatal age, sex, race and ethnicity, presence of neurosurgical hardware, white blood cell count in CSF, and red blood cell contamination in CSF. Metabolic analysis may aid diagnosis of BM and facilitate clinical decision-making in infants.

Neuron-Specific Enolase in Cerebrospinal Fluid Predicts Brain Injury After Sudden Unexpected Postnatal Collapse

BackgroundBiomarkers of brain injury with high predictive value in newborns in critical neurological status are increasingly required. Neuron-specific enolase in cerebrospinal fluid has been shown to be highly predictive in newborns with perinatal hypoxic-ischemic encephalopathy, but its utility has not been examined in sudden unexpected postnatal collapse. PurposeWe analyzed whether the levels of neuron-specific enolase in cerebrospinal fluid can be a useful biomarker to estimate the severity of brain injury in neonates after a sudden unexpected postnatal collapse. MethodsThis is a prospective observational study of near-term infants who were consecutively admitted with sudden unexpected postnatal collapse in two neonatal intensive care units during a nine-year period. Variables were collected and analyzed regarding the perinatal period, clinical course, severity of encephalopathy, amplitude-integrated encephalography, magnetic resonance imaging findings, and outcome. Neuron-specific enolase in cerebrospinal fluid samples were obtained in 18 infants with sudden unexpected postnatal collapse between 12 and 72 hours after the collapse and compared with those of 29 controls. ResultsThe levels of neuron-specific enolase in cerebrospinal fluid were higher in patients than in controls (P < 0.001). Levels of neuron-specific enolase in cerebrospinal fluid in infants with sudden unexpected postnatal collapse were significantly higher in patients who presented severe encephalopathy, seizures, abnormal amplitude-integrated encephalography background, or brain injury on magnetic resonance imaging. Receiver operator characteristic curve analysis revealed a neuron-specific enolase in cerebrospinal fluid cutoff value of maximum predictive accuracy of 61 ng/mL (area under the curve, 1.0; sensitivity, specificity, positive predictive value, and negative predictive value, 100%) for identifying infants who died or had adverse outcomes. ConclusionsLevels of neuron-specific enolase in cerebrospinal fluid obtained between 12 and 72 hours after a sudden unexpected postnatal collapse event seem to be a useful biomarker for identifying newborns with severe brain injury and for predicting outcome.

Limb amputation of an infant with transposition of great arteries using spinal anesthesia

Introduction: Spinal and caudal anesthesia are useful anesthetic techniques for infants compared to general anesthesia. In case of infants lumbar puncture can be safely performed at or just below the intercristal line. Due to the presence of loose fatty tissues in the caudal extradural space, it becomes safe and easy to insert a cannula enabling easy cranial spread of local anesthetic drugs. Increased production and absorption of cerebrospinal fluid in infants lead to administration of higher doses of local anesthetics. However, this spinal and caudal anesthesia has lesser risk of post-operative apnea in infants compared to general anesthesia. Case Report: A three-month-old male infant, whose body weight was seven and half kilograms, was afflicted with ischemia which extended to half of his right leg. There was gangrene on his right big toe as well. These developments occurred after cardiac catheterization was implemented through right femoral vein cannulation. Due to high-risk of transposition of great arteries in general anesthesia, the surgeons finalized under spinal anesthesia in order to bypass the infected respiratory system, prevent aspiration because of full stomach, and to get better postoperative analgesia. Conclusion: Spinal anesthesia is an alternative option to general anesthesia in high risk patients owing to its safety. However, in case of spinal complications or failure of spinal anesthesia, the anesthetist should always get ready with the high risk general anesthesia.

CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural Tube Defects.

The protein composition of cerebrospinal fluid (CSF) in neural tube defects (NTDs) remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation (iTRAQ). We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs. We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, and apolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.

Lessons Learned at the Epicenter of Brazil's Congenital Zika Epidemic: Evidence From 87 Confirmed Cases.

Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS.

Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up.

DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.

Late-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study

This study aimed to investigate the incidence of late-onset sepsis (LOS) in neonatal intensive care units (NICUs) in Arab states in the Gulf region and to describe the main causative organisms and their antibiotic resistance. This observational prospective cohort study was conducted over a 2-year period in five NICUs in Kuwait, Saudi Arabia, and the United Arab Emirates. LOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants >3days of age with clinical and laboratory findings consistent with infection. Seven hundred and eighty-five cases of LOS occurred among 67 474 live births. The overall incidence of LOS was 11.63 (95% confidence interval (CI) 10.84-12.47) per 1000 live births, or 56.14 (95% CI 52.38-60.08) per 1000 admissions. Coagulase-negative staphylococci and Klebsiella spp were the most common organisms, causing 272 (34.65%) and 179 (22.80%) of LOS cases, respectively. No evidence of a seasonal variation in the incidence of Klebsiella spp or in the incidence of all Gram-negative organisms was found. More than half of the Klebsiella spp were resistant to third-generation cephalosporins. LOS poses a major burden in this area, which could be due to the increasing care of premature babies. Gram-negative organisms, particularly Klebsiella spp, are having an increasing role in LOS in this region, with high levels of resistance to third-generation cephalosporins. NICUs in the area should create a platform through which to share experience in reducing neonatal sepsis and contribute to a common antibiotic stewardship program.

Culture-proven early-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study

To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72h of birth, with clinical and laboratory findings consistent with infection. Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2-1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections.

Differential fatty acid analysis of cerebrospinal fluid in infants and young children with suspected meningitis

Meningitis is relatively common in infants and young children and can cause permanent brain damage. The aim of this study was to determine whether meningitis is associated with fatty acids in cerebrospinal fluid (CSF). CSF samples from children between 3months and 6years of age admitted to the Tabriz public hospitals who met clinical criteria of meningitis were collected at enrollment. A total of 81 samples were analyzed for fatty acid profile by gas-liquid chromatography. Children with a purulent meningitis demonstrated a higher percentage of oleic acid (p<0.05, >10%) and lower percentages of omega-3 polyunsaturated fatty acids (p<0.001, <-40%) than aseptic meningitis and nonmeningitis groups did. There was an inverse relationship between CSF long-chain omega-3 fatty acids and the total number of leukocytes and differential counts of neutrophils and lymphocytes in the purulent meningitis group. Moreover, significantly lower omega-3 fatty acids (p=0.001, -37%) and higher ratio of n-6/n-3 (p=0.02, -29%) were found in patients with purulent meningitis with sepsis than in those with meningitis and no sepsis. This study provides evidence that purulent meningitis and its complication with sepsis are associated with important disturbances in CSF fatty acids, mainly deficiency in long-chain omega-3 polyunsaturated fatty acids.

998Detection of Cytomegalovirus (CMV) in Cerebrospinal Fluid of Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture?

Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture? Christopher Ouellette, MD; Andrea Ronchi, MD; Asuncion Mejias, MD, PhD; Susana Chavez-Bueno, MD; Douglas Salamon, MB(ASCP)SV; Lorenza Pugni; Fabio Mosca; Pablo J. Sanchez MD, FIDSA; Pediatrics, Division of Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH; Pediatrics, University of Texas Southwestern, Dallas, TX; Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Department of Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH; Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Alterations in Protein Regulators of Neurodevelopment in the Cerebrospinal Fluid of Infants with Posthemorrhagic Hydrocephalus of Prematurity

Neurological outcomes of preterm infants with posthemorrhagic hydrocephalus are among the worst in newborn medicine. There remains no consensus regarding the diagnosis or treatment of posthemorrhagic hydrocephalus, and the pathological pathways leading to the adverse neurological sequelae are poorly understood. In the current study, we developed an innovative approach to simultaneously identify potential diagnostic markers of posthemorrhagic hydrocephalus and investigate novel pathways of posthemorrhagic hydrocephalus-related neurological disability. Tandem multi-affinity fractionation for specific removal of plasma proteins from the hemorrhagic cerebrospinal fluid samples was combined with high resolution label-free quantitative proteomics. Analysis of cerebrospinal fluid obtained from infants with posthemorrhagic hydrocephalus demonstrated marked differences in the levels of 438 proteins when compared with cerebrospinal fluid from age-matched control infants. Amyloid precursor protein, neural cell adhesion molecule-L1, neural cell adhesion molecule-1, brevican and other proteins with important roles in neurodevelopment showed profound elevations in posthemorrhagic hydrocephalus cerebrospinal fluid compared with control. Initiation of neurosurgical treatment of posthemorrhagic hydrocephalus resulted in resolution of these elevations. The results from this foundational study demonstrate the significant promise of tandem multi-affinity fractionation-proteomics in the identification and quantitation of protein mediators of neurodevelopment and neurological injury. More specifically, our results suggest that cerebrospinal fluid levels of proteins such as amyloid precursor protein or neural cell adhesion molecule-L1 should be investigated as potential diagnostic markers of posthemorrhagic hydrocephalus. Notably, dysregulation of the levels these and other proteins may directly affect ongoing neurodevelopmental processes in these preterm infants, providing an entirely new hypothesis for the developmental disability associated with posthemorrhagic hydrocephalus.

Population Pharmacokinetics of Meropenem in Plasma and Cerebrospinal Fluid of Infants With Suspected or Complicated Intra-abdominal Infections

Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM. In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1.46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

髄液中の酵素 (GOT, LDH), CRPによる細菌性髄膜炎の診断

髄液中の酵素 (GOT, LDH), CRPによる細菌性髄膜炎の診断

Increased expression of matrix metalloproteinase-9 and hepatocyte growth factor in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus

Background In approximately 60% of infants with posthemorrhagic hydrocephalus (PHH), ventricular dilation resolves by unknown intrinsic mechanisms, without the need for a shunt operation. A pathological hallmark of PHH is extensive deposition of extracellular matrix (ECM) proteins in the subarachnoid space. Our previous study revealed that matrix metalloproteinase (MMP)-9, which degrades ECM proteins, may play an important role in the resolution of ventricular dilation. MMP-9 is known to be induced by hepatocyte growth factor (HGF) in various cell lines. Aims The aim of this study is to confirm our earlier finding that MMP-9 contributes to the resolution of PHH, and to investigate whether HGF also contributes to this process. Study design Cerebrospinal fluid (CSF) samples were collected from 13 infants who developed ventricular dilation after intraventricular hemorrhage (IVH). Of these infants, 9 exhibited resolution of ventricular dilation without shunt operation; however, 4 infants had to be treated with shunt operation. The CSF levels of MMP-9 and HGF were measured using an enzyme immunoassay. Results Significantly higher CSF levels of MMP-9 and HGF were detected in patients in whom the ventricular dilation resolved without shunt operation than in those with progressive ventricular dilation (MMP-9: median, 128 ng/ml; range, 47–900 ng/ml vs median, 50 ng/ml; range, 12–110 ng/ml; p < 0.05; HGF: median, 2.42 ng/ml; range, 0.81–7.04 ng/ml vs median, 1.42 ng/ml; range, 0.67–3.87 ng/ml; p < 0.05). Conclusions Our results indicate that MMP-9 and HGF may participate in the resolution of ventricular dilation following IVH.

Report of Neonatal Meningitis Due to Salmonella enterica Serotype Agona and Review of Breast Milk-Associated Neonatal Salmonella Infections

We present the first documented case of Salmonella enterica serotype Agona meningitis in a 6-day-old baby. S. enterica serotype Agona was isolated concurrently from infant cerebrospinal fluid and parental fecal samples, and Salmonella was isolated from breast milk. The role of breast milk in transmission of Salmonella enterica is discussed.