Neurodevelopmental Outcomes and Brain Volumetric Analysis of Low-Grade Intraventricular Hemorrhage

Purpose@#Extremely preterm infants are prone to brain injury and underdevelopment. Intraventricular hemorrhage (IVH) is the most common cause of brain injury and a significant risk factor for neurodevelopmental delay in preterm infants. Severe IVH is known to have a poor outcome; however, the outcomes of low-grade IVH remain controversial. This study aimed to evaluate neurodevelopmental outcomes and brain segmental volumes of preterm infants with low-grade IVH. @*Methods@#This retrospective cohort study included 109 extremely preterm infants who underwent term equivalent age-magnetic resonance imaging and neurodevelopmental evaluation at a corrected age of 18 to 24 months. We compared infants with and without low-grade IVH. @*Results@#Among the 109 extremely preterm infants, 25 had low-grade IVH and 84 had no IVH. There were no significant differences in the neurodevelopmental outcomes between the low-grade and no IVH groups. In multivariate analysis, low-grade IVH was associated with a smaller medullary volume (adjusted odds ratio, 0.575; 95% confidence interval, 0.346 to 0.957; P=0.034). @*Conclusion@#We found no significant differences in the neurodevelopmental outcomes of extremely preterm infants at a corrected age of 18 to 24 months between those with low-grade IVH and those without IVH. Low-grade IVH was associated with a smaller medullary volume.

Factors Associated with Clinical Response to Low-Dose Dexamethasone Therapy for Bronchopulmonary Dysplasia in Very Low Birth Weight Infants

Purpose@#To identify factors associated with the clinical response to low-dose dexamethasone therapy (LDDT) in preterm infants for bronchopulmonary dysplasia (BPD). @*Methods@#We used a retrospective medical record review to evaluate preterm infants who were born before 32 weeks of gestation or with a birth weight less than 1,500 g. All infants were admitted to the neonatal intensive care unit at a tertiary academic hospital between January 2010 and June 2019, and received LDDT for BPD. The preterm infants’ respiratory severity scores (RSS) were calculated from the first day of LDDT to the day of extubation, or the last day of LDDT. A good response was defined as a decreasing RSS with a slope greater than 0.181. A poor response was defined as a non-decreasing RSS, or a decreasing RSS with a slope less than 0.181 during LDDT. A total dose of 1.1 mg/kg was administered for 10 days for each single course of LDDT. @*Results@#A total of 51 preterm infants were included in the final analysis. Thirty preterm infants (58.8 %) were in the good response group, and 21 preterm infants (41.2%) were in the poor response group. There were no significant differences in gestational age, birth weight, and sex between the good response group and poor response group. Preterm premature rupture of membrane and histologic chorioamnionitis were significantly associated with a poor response to LDDT. Higher RSS on the first day of the LDDT was associated with a good response to LDDT. @*Conclusion@#Antenatal infection and/or inflammation may be associated with an unfavorable response to postnatal LDDT for BPD. Preterm infants with more severe respiratory failure seem to benefit more from LDDT for BPD.

A Rare Case of Cerebral Sinovenous Thrombosis Associated with MTHFR A1298C and C677T Mutations

Neonatal cerebral sinovenous thrombosis (CSVT) is a rare disease with severe neurological sequelae. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate cycle, and mutations in MTHFR are associated with vascular diseases. Here, we report the case of a newborn with MTHFR mutation-associated CSVT. Analysis of MTHFR in the patient detected heterozygous C677T (677CT) and A1298C (1298AC) mutations. Analysis of MTHFR in the patient's mother did not detect a C677T (677CC) mutation but detected a homozygous A1298C (1298CC) mutation. Our results suggest that the presence of heterozygous MTHFR C677T and A1298C mutations affect thrombophilic activity in the neonate, resulting in the development of refractory seizure and CSVT. Moreover, presence of the homozygous MTHFR A1298C mutation in the patient's mother, who did not show any symptoms associated with thrombophilic activity, and conditions during gestation may have affected the patient's condition.

Neuroprotective effects of mild hypoxia in organotypic hippocampal slice cultures / 소아과

PURPOSE: The aim of this study was to investigate the potential effects of mild hypoxia in the mature and immature brain. METHODS: We prepared organotypic slice cultures of the hippocampus and used hippocampal tissue cultures at 7 and 14 days in vitro (DIV) to represent the immature and mature brain, respectively. Tissue cultures were exposed to 10% oxygen for 60 minutes. Twenty-four hours after this hypoxic insult, propidium iodide fluorescence images were obtained, and the damaged areas in the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis. RESULTS: In the 7-DIV group compared to control tissue, hypoxia-exposed tissue showed decreased damage in two regions (CA1: 5.59%+/-2.99% vs. 4.80%+/-1.37%, P=0.900; DG: 33.88%+/-12.53% vs. 15.98%+/-2.37%, P=0.166), but this decrease was not statistically significant. In the 14-DIV group, hypoxia-exposed tissue showed decreased damage compared to control tissues; this decrease was not significant in the CA3 (24.51%+/-6.05% vs. 18.31%+/-3.28%, P=0.373) or DG (15.72%+/-3.47% vs. 9.91%+/-2.11%, P=0.134), but was significant in the CA1 (50.91%+/-5.90% vs. 32.30%+/-3.34%, P=0.004). CONCLUSION: Although only CA1 tissues cultured for 14 DIV showed significantly less damage after exposure to hypoxia, the other tissues examined in this study showed a tendency towards less damage after hypoxic exposure. Therefore, mild hypoxia might play a protective role in the brain.

A Rare Case of Rapidly Progressive Severe Encephalitis Associated with Epstein-Barr Virus Infection

Epstein-Barr virus rarely causes encephalitis which has a benign outcome. About 90% of children have a benign clinical course without neurologic sequelae. However, 10% have residual persistent deficits and a mortality rate of up to 10% has also been reported. An 11-month-old boy was admitted after general weakness and poor oral intake. On day 7 of hospitalization, three vomiting episodes occurred and followed by a seizure. Brain T1-weighted magnetic resonance imaging (MRI) showed a hyperintensity with mild diffusion restriction in the cortex and subcortical white matter of the bilateral frontal, parietal, and occipital lobes. Analysis of a cerebrospinal fluid (CSF) sample revealed WBC count of 10 /microL (neutrophils 21%, lymphocytes 78%), red blood cell count of 19,000 /uL. CSF EBV polymerase chain reaction (PCR) was positive. Positive results were also obtained for serum EBV viral capsid antigen (VCA) IgM (>4 U/mL), IgG (>8 U/mL), EBV Ebstein Barr nuclear antigen (EBNA) IgG (>8 U/mL). Despite therapy with acyclovir, phenobarbital and steroids, a brain MRI conducted on day 34 showed extensive parenchymal volume atrophy and secondary ventricular dilatation, diffuse progressive signal change in the entire cerebrum and diffuse gyral enhancement in the entire cerebrum. The patient was discharged on day 129 and was transferred to other hospital. After 3month of discharge, the patient's mental status was still drowsy, both arms and legs showed rigidity, and deep tendon reflex were hyperactive. We report an 11-month-old child with rapidly progressive severe encephalitis associated with Epstein-Barr virus.