Congenital interdural arachnoid cyst of the tentorium cerebelli.

BACKGROUND: Intracranial interdural cyst is a rare lesion. The exact pathophysiology of these cysts remains unknown. CLINICAL PRESENTATION: We report an infant with interdural cyst of the tentorium cerebelli. Although the cyst mimicked an arachnoid cyst on pre- and postnatal magnetic resonance images, lateral suboccipital craniotomy revealed the cyst within the tentorium. Fenestration on the infratentorial side was performed with successful results. Histologically, the inner surface of the cyst was lined with arachnoid cells. CONCLUSION: We report detailed neuroradiological, intraoperative, and histological findings, and discuss the pathophysiology of the cyst in this case.

Terminal syringomyelia associated with lumbar limited dorsal myeloschisis.

PURPOSE: Limited dorsal myeloschisis (LDM) is characterized by a fibroneural tethering stalk linking the skin lesion to the underlying spinal cord. Terminal syringomyelia, which is located at the lower third of the cord, is often associated with a tethered cord caused by various spinal dysraphisms; however, terminal syringomyelia has not been documented in LDM. The purpose of this study was to clarify the pathophysiological mechanisms of syringomyelia in LDM. METHODS: In our 16 patients with lumbar LDM, three patients had terminal syringomyelia. We retrospectively analyzed the clinical, neuroradiological, intraoperative, and histopathological findings for these patients, with particular attention to the clinical course of the syrinx. RESULTS: Patient 1 had a saccular skin lesion and patients 2 and 3 had flat lesions. In all patients, the syringomyelic cavity was located in the lower thoracolumbar cord, immediately rostral to the stalk-cord attachment at the lumbar level. The caudal pole of the syrinx extended to the thickened stalk at the attachment instead of at the caudal cord. Patient 3 had another syrinx in the stalk itself. The longitudinal axis of the syrinx and central canal coincided with the traveling angle of the LDM stalk at the stalk-cord attachment. In patient 1, histology revealed an ependyma-lined central canal in both the LDM stalk and meningocele sac. Patients 1 and 2 underwent syringostomy, but long-term effects were not obtained. Preoperative spontaneous resolution occurred in patient 3. CONCLUSIONS: The histological findings in patient 1 supported the idea that segmental myelocystocele is involved in the development of saccular LDM. The hydromyelic central canal herniates and distends the stalk, resulting in the formation of the myelocystocele. It is possible that the hydromyelic central canal also distends the stalk of flat LDM lesions. The syrinx in patient 3 differed from that in patients 1 and 2, in that the syrinx resolved spontaneously. Further studies are needed to clarify the outcomes of syrinxes associated with LDM stalks.

Prolonged PR Interval at Birth Predicting the High Occurrence of Fatal Atrioventricular Block in Hypoplastic Left Heart Syndrome.

Infants with hypoplastic left heart syndrome (HLHS) are at high mortality especially when they are associated with bradyarrhythmias. However, the risk factor of developing high-grade atrioventricular block (HAVB) is still unclear. Seventy-three patients with HLHS in our institutions from 2002 to 2011 were enrolled. The survival rate was assessed by the anatomical types, treatments, occurrence of HAVB, severe tricuspid regurgitation (TR), and restrictive atrial septal defect (ASD) along with electrocardiogram findings at birth. There were 23 (32%) cardiogenic and 7 (10%) non-cardiogenic deaths. The occurrence rate of HAVB but not severe TR or restrictive ASD was higher in 30 deceased patients than in 43 survived patients [7 (23%) vs. 1 (2.3%), p = 0.0038]. The overall mortality rate was higher in patients with HAVB than in those without it (p = 0.0002). Of 7 deceased patients with HAVB, 6 HAVB occurred within 10 days post-surgery, and 3 HAVB led to the early death. The mortality rate of patients with prolonged PR (≥ 0.15 s) but not wide QRS (> 0.08 s) or prolonged QTc (> 0.43 s) at birth was higher than each without it (p = 0.0106). Multivariate analysis indicated that prolonged PR but no other variables was independently associated with the mortality (hazard ratio: 2.948, p = 0.0104). Prolonged PR at birth in HLHS infants predicts the development of fatal HAVB.

Aortic regurgitation associated with critical aortic stenosis in a fetus.

Aortic regurgitation in association with aortic stenosis is rare in the fetus. Findings have shown that severe aortic regurgitation is worsened by the increase in systemic vascular resistance after birth, resulting in low cardiac output, hypoxemia, and neonatal death. This report describes a unique case of aortic regurgitation with aortic stenosis, severe mitral regurgitation, retrograde flow in the aortic arch, and an enormous left atrium with a restrictive foramen ovale in a fetus. In this case, aortic regurgitation was diminished immediately after birth, indicating that spontaneous improvement in aortic regurgitation after birth should be taken into account when the final prognosis is predicted.

Critical Ebstein anomaly in a fetus successfully managed by elective preterm delivery and surgical intervention without delay after birth.

This report describes a case of Ebstein anomaly in a fetus with cardiomegaly, severe tricuspid regurgitation, pulmonary regurgitation, and retrograde ductal flow that showed a marked increase in the size of the right atrium with advancing gestational age. Elective preterm delivery was performed at 35 weeks gestation. The prostaglandin E1 infusion resulted in more pronounced systemic hypotension and acidosis secondary to circular shunt across the patent ductus arteriosus as well as pulmonary regurgitation and tricuspid regurgitation. Emergency surgical intervention consisting of main pulmonary artery ligation, ductus arteriosus ligation, central shunt creation, and plication of the right atrium without cardiopulmonary bypass was performed 4 h after birth. At the age of 16 days, the Starnes procedure was performed. The infant's postoperative course was uneventful. A fetus that has Ebstein anomaly associated with pulmonary regurgitation is at risk for circular shunt across the patent ductus arteriosus after delivery. Planned delivery and surgical intervention without delay after birth are useful for the treatment of such cases.

Serum prohepcidin concentrations at birth and 1 month after birth in premature infants.

BACKGROUND: Premature newborns are vulnerable to iron imbalance, although the iron homeostasis during the perinatal period remains unclear. To clarify the iron metabolism of premature infants, we measured serum prohepcidin concentrations of preterm infants, and analyzed the association with iron parameters. METHODS: Seventy-one (61 preterm and 10 term) infants were enrolled for the study, that had no underlying diseases including asphyxia, bleedings, infection, and anomalies. Serum concentrations of prohepcidin at birth and 1 month after birth were determined by enzyme-linked immunosorbent assay. RESULTS: Prohepcidin levels at birth but not 1 month postnatal age positively correlated with gestational age (correlation coefficient [CC]:0.334, P = 0.005) and birth weight (CC: 0.367, P = 0.002). The levels at birth of preterm infants (median: 29.93 ng/ml, range: 4.0-110.6) were lower than those of full-term infants, and increased thereafter. On the other hand, the levels in small-for-gestational age infants were not associated with gestational age or birth weight. Prohepcidin levels at birth correlated positively with red cell counts (CC = 0.487, P = 0.025), unsaturated iron binding capacity (CC = 0.755, P = 0.001), total protein (CC = 0.624, P = 0.005), and serum albumin levels (CC = 0.500, P = 0.025), and negatively with serum iron levels (CC = -0.688, P = 0.003), but not ferritin levels. Multivariate analyses indicated that prohepcidin levels at birth were lower in infants with pregnancy-induced hypertension (P = 0.03) or premature rupture of membrane (P = 0.01). CONCLUSIONS: Prohepcidin production was physiologically low at birth of preterm infants according to the gestational age, and the levels might be susceptible to the in utero stress. The postnatal increase might reflect the maturation and/or adaptation of iron homeostasis.

Effect of delayed palivizumab administration on respiratory syncytial virus infection-related hospitalisation: A retrospective, observational study.

ABSTRACT: Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in infants and young children. Monthly administration of palivizumab during the RSV season is effective in preventing severe infections in children with comorbidities. However, determining the onset of the RSV season for starting palivizumab is often challenging. The present study aimed to evaluate the ideal timing to start palivizumab and its effect on hospitalization in the real world.We performed a retrospective, observational study to identify the relationship between the timing of the first dose of palivizumab administration and RSV-related hospitalization. Medical records from 2015 to 2019 were reviewed. We included patients who had indications for palivizumab as of July 1 in each year. We counted the proportion of children receiving palivizumab and the number of RSV infection-related hospitalizations each month. We also evaluated the differences in background and underlying disease between children with and without hospitalization.A total of 498 patients were included, and 105 (21.0%) completed the first dose in July when the RSV season usually begins in Japan. Twenty-three (4.6%) patients were hospitalized for RSV infection during the observation period, with 13 (56.5%) hospitalizations before their first dose of palivizumab. The remaining 10 patients were hospitalized after receiving 1 or more doses of palivizumab. Children living with siblings and children with cyanosis originating from congenital heart disease had a higher risk of RSV with odds ratios of 5.1 (95% confidence interval 1.48-17.6, P < .01) and 3.3 (95% confidence interval 1.33-7.94, P < .01), respectively.Delays in administering palivizumab at the beginning of the season increases the rate of RSV infection-related hospitalization. To maximize prophylactic effectiveness, administering the first dose as early as possible in the RSV season is crucial, with priority for cyanotic children or those with siblings.

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism.

It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4 months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10 months.

Improvement in the outcome of patients with antenatally diagnosed congenital diaphragmatic hernia using gentle ventilation and circulatory stabilization.

BACKGROUND/OBJECTIVES: No definitive treatment strategy has been established for patients with an antenatal diagnosed congenital diaphragmatic hernia (AD-CDH). From 1997 to 2003 in this department fetal stabilization (FS) was administered using both morphine and diazepam via the placenta just before delivery of the fetus by cesarean section. In contrast, from 2004 to the present, a combination of gentle ventilation (GV) and a delayed operation was selected, which was performed when the patient's circulatory stabilization (CS) was achieved. PATIENTS AND METHODS: This study included 22 patients in the FS group and 16 patients in the GV + CS group, respectively. The outcomes in both groups were compared and the outcome in AD-CDH patients with a patch repaired operation, liver-up or lower lung-to-thorax transverse area ratio (L/T, <0.10) was further investigated in both groups. RESULTS: The overall survival rate (SR) was 93.8% in the GV + CS group and 59.1% in the FS group, respectively (P = 0.04). For the patients with the lower L/T, the SR was 85.7% in GV + CS group and 53.8% in the FS group (P = 0.33). Regarding the patients using a patch and liver-up, the SR in GV + CS group was better than that in the FS group (patch: FS 44.4%, GV +/- CS 87.5%, P = 0.18; liver-up: FS 57.8 and 87.5%, P = 0.30). CONCLUSION: Our strategy of using GV +/- CS might thus be considered to be more effective than that using FS in the treatment of AD-CDH patients.

Prenatal findings in a case of massive fetomaternal hemorrhage associated with intraplacental choriocarcinoma.

We describe biochemical assessment of maternal circulation in a case of massive fetomaternal hemorrhage at term associated with intraplacental choriocarcinoma. Markedly elevated maternal serum hCG level at 37 weeks of gestation suggested choriocarcinoma as a cause of fetomaternal hemorrhage in this case. Measurement of maternal hCG may be a useful parameter when intraplacental choriocarcinoma is in the differential diagnosis. In addition, the placenta should be examined in all cases of fetomaternal hemorrhage.

Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.

BACKGROUND: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. METHODS: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into "progression group" (n = 7) that required any therapy and "spontaneous resolution group" (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-ß1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. RESULTS: Three patients developed leukemia during the study period (median, 1147 days; range, 33-3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = -0.46, p = 0.02). CONCLUSION: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.

Spontaneous resolution of cystic hygroma and hydrops in a fetus with Noonan's syndrome.

Many studies have shown that the prognosis of cystic hygroma associated with hydrops fetalis is poor. We report a rare case of fetal cystic hygroma and hydrops fetalis that spontaneously resolved with subsequent delivery at 37 weeks of a living female infant with Noonan's syndrome. The prognostic significance of prenatal resolution of cystic hygroma and hydrops is uncertain. Serial evaluation of affected fetuses with ultrasound imaging may help clarify pathogenesis of cystic hygroma with associated hydrops, as well as mechanisms underlying spontaneous resolution.

Intraventricular hemorrhage possibly extending from an infratentorial subdural hematoma via a perforated suprapineal recessus in a full-term neonate.

BACKGROUND: Although intraventricular hemorrhage (IVH) is very rarely reported in full-term neonates, it may occur in children with perinatal trauma, asphyxia, and coagulation disorders, and may originate in the choroid plexus and residual subependymal germinal matrix layer. CASE DESCRIPTION: We present the case of a full-term baby with IVH. She had no perinatal problems or coagulation disorders. Sagittal views of neuroimages demonstrated that the IVH possibly extended from a subdural hemorrhage (SDH) in the infratentorial area via a perforated suprapineal recessus. This was barely visible on a conventional axial view of a computed tomographic scan. CONCLUSION: When the etiopathogenesis of IVH in a full-term baby with an uncomplicated delivery cannot be clearly defined, multi-directional and multi-modal neuroimaging may be useful.

CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene.

OBJECTIVE: To address the role of cord blood (CB) CD25+CD4+ T cells, the gene expressions and function of this subset were analyzed. MATERIALS AND METHODS: CD25+CD4+ T cells fractionated from CB of term and preterm infants were subjected to flow cytometry, quantitative polymerase chain reaction analysis for cytokines, costimulatory molecules, and transcription factors, and functional assays. RESULTS: Human preterm CB contained a high proportion of CD25+CD4+ T cells that declined with gestational age to the level of adult peripheral blood (PB). CD25+ or CD25-CD4+ T cells in CB had a higher frequency of CD45RA+ and CD38+ cells than in PB. CB CD25+CD4+ T cells less frequently expressed CD45RO, CD71, and HLA-DR than PB CD25+CD4+ T cells, despite similar expressions on CB and PB CD25-CD4+ T cells. No expression of IL-10, transforming growth factor-beta, interleukin-4, and interferon-gamma mRNA differed between CB CD25+CD4+ and CD25-CD4+ T cells, in contrast to the high interleukin-10 expression in PB CD25+CD4+ T cells. CTLA-4 was more transcribed in CB and PB CD25+CD4+ T cells than in the counterpart CD25-CD4+ T cells. CD28 or ICOS was similarly expressed in CB and PB T cells. CB CD25+CD4+ T cells effectively suppressed the proliferation of CB CD25-CD4+ T cells in a dose-dependent manner. Human CB and PB CD25+CD4+ T cells preferentially transcribed Foxp3, which governs the regulatory function of this subset in mice. CONCLUSIONS: These results suggest that CB contains CD25+CD4+ regulatory T cells as a functionally mature population with naive phenotype. This subset may naturally arise and decline in fetus to play a potential immunoregulatory role in intrauterine life.

Interferon-gamma, interleukin-18, monokine induced by interferon-gamma and interferon-gamma-inducible protein-10 in histiocytic necrotizing lymphadenitis.

Apoptosis of histiocytes is a characteristic feature of necrotizing lymphadenitis (HNL). Recent studies have indicated that Fas and perforin-based pathways are involved in the apoptotic process of HNL. Elevated levels of serum interferon (IFN)-gamma are reported in HNL. The CXC chemokine interferon-gamma-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) cause tissue necrosis, and interleukin (IL)-18 induces the expression of IFN-gamma and Fas ligand (FasL) by T and natural killer (NK) cells. This study was designed to determine the expression of IFN-gamma, IL-18, MIG and IP-10 in HNL. Ten cases of HNL were analyzed by using immunohistochemical staining and/or reverse transcriptase-polymerase chain reaction (RT-PCR). As a control, we included four cases of non-specific lymphadenitis. MIG and IP-10 proteins, which enhance the release of granzyme, showed a similar distribution pattern in viable tissues surrounding dead tissue, mostly within histiocytes, and lymphocytes in HNL. IL-18 was located within histiocytes, especially phagocytic histiocytes, but not within lymphocytes. In addition, IFN-gamma-positive lymphocytes were frequently detected in the surrounding dead tissue, and the lymphocytes in the same area were frequently positive for CXCR3, a specific receptor of MIG and IP-10. In non-specific lymphadenitis, MIG, IP-10 and IL-18 positive cells were detected, but their numbers were relatively small compared with HNL, while IFN-gamma positive cells were rarely encountered. Our findings suggest that the cytokine and chemokine pathways of IFN-gamma, IL-18, MIG and IP-10 play an important role in the pathogenesis of apoptosis associated with HNL.

Neurotrophin-4 and glial cell line-derived neurotrophic factor in cerebrospinal fluid from meningitis/encephalitis patients.

The neurotrophin-4 and glial cell line-derived neurotrophic factor levels were measured in cerebrospinal fluid from 61 patients with bacterial meningitis, viral meningitis, or encephalitis, and other diseases by means of two-site enzyme-linked immunoassay. Elevated cerebrospinal fluid levels of neurotrophin-4 were demonstrated in four of the 11 patients with bacterial meningitis, and seven of the 23 patients with viral meningitis or encephalitis. None of the other patients demonstrated elevation of the neurotrophin-4 level in cerebrospinal fluid. The neurotrophin-4 levels in cerebrospinal fluid were correlated with the numbers of total and mononuclear cells in patients with viral meningitis/encephalitis. In patients with bacterial meningitis, three of the four patients with elevated neurotrophin-4 levels exhibited persistent abnormalities on computed tomography, and one revealed transient subdural effusion. On the other hand, none of the seven patients without neurotrophin-4 elevation had persistent computed tomography abnormalities, and five patients demonstrated transient computed tomography abnormalities. The glial cell line-derived neurotrophic factor levels were below the detection limit, or only slightly higher than the detection limit, in the patients with or without central nervous system infections. Although the precise roles of neurotrophin-4 and glial cell line-derived neurotrophic factor in central nervous system infections remain to be determined, neurotrophin-4 might play a neuroprotective or immunomodulatory role in central nervous system infections.

Survival and neurodevelopmental outcome of preterm infants born at 22-24 weeks of gestational age.

BACKGROUND: The limits of viability in extremely premature infants are challenging for any neonatologists in developed countries. The neurological development and growth of extremely preterm infants have come to be the emerging issue following the management in the neonatal intensive care unit. OBJECTIVE: To assess potential associations between changes in practice and survival/neurodevelopmental outcome, and clinical outcomes of extremely preterm infants born at the limit of viability studied in a tertiary center. STUDY DESIGN: A retrospective study enrolled 51 infants who had no congenital disorders, and were born at 22-24 weeks of gestational age (GA) in 2000-2009 in our institution. Clinical variables and interventions were studied with regard to one-year survival and developmental quotient (DQ) at 3 years of age. RESULTS: The one-year survival rate of 24 preterm infants born in 2005-2009 (79%) was higher than that of the 27 infants born in 2000-2004 (52%, p = 0.04). Infants born after 2005 underwent less tocolysis (54 vs. 94%, p < 0.01) and more frequently antenatal steroid therapy (32 vs. 6%, p = 0.01) than those born before 2004. The post-2005 survivors (n = 19) received more frequently indomethacin therapy (89 vs. 50%, p = 0.03) and early parenteral nutrition (95 vs. 36%, p < 0.01) than the pre-2004 survivors (n = 14). There were no differences in the proportion of infants who attained a DQ of >50 at 3 years of age between pre-2004 (9/13, 69%) and post-2005 groups (10/17, 59%). Multivariate analysis indicated that extremely premature birth at GA <24 weeks was the sole critical factor for a DQ of >50 in survivors. CONCLUSIONS: The perinatal care after 2005 improved the overall survival rate, but not the neurological outcome of preterm survivors at the limit of viability. Neurodevelopmental impairments were associated with extremely premature birth at GA <24 weeks.

Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease mostly occurring in preterm infants. The pathogenesis of BPD involves early inflammation and remodeling of the premature lung. AIM: To search for the novel predictive marker of BPD development, we studied serum levels of neutrophil gelatinase-associated lipocalin (NGAL), an innate immune mediator, in preterm infants. METHODS: Serum NGAL concentrations at birth were measured by enzyme-linked immunosorbent assay. The reference levels were determined in 52 infants having no anomalies or inherited diseases. The levels and clinical variables were assessed in association with BPD. RESULTS: Geometric means (95%CI) of serum NGAL levels at birth of infants having no underlying diseases were 32.4 (22.1-47.5), 58.6 (47.9-71.8), and 126.2 (99.0-168.7) ng/mL for <31, 31-36 and >36 gestational weeks (GW), respectively (p<0.001). These levels positively correlated with neutrophil (p<0.0001) or monocyte counts (p<0.0001). The median NGAL levels (307.8 ng/mL) and neutrophil counts (4141/µL) at birth of 16 preterm infants (<31 GW) who developed BPD were higher than those (42.9 ng/mL and 1357/µL) of 20 infants (<31 GW) who did not (p<0.0001 and p=0.012), respectively. In multivariable analysis for 36 infants born less than 31 GW, higher NGAL levels (≥ 82 ng/mL) but not neutrophil counts at birth had a significant association with developing BPD (gestational-age adjusted odds ratio [OR]=37.45 [3.08-455.49], p<0.01). CONCLUSIONS: High serum levels of NGAL at birth could be an early sensitive marker for BPD in preterm infants, because their levels were physiologically low.