Biventricular function in preterm infants with patent ductus arteriosus ligation: A three-dimensional echocardiographic study.

BACKGROUND: The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function. METHODS: Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA). RESULTS: Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased. CONCLUSIONS: PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles. IMPACT: Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery.

Right to left ventricular volume ratio is associated with mortality in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.

Predictive value of the Thompson score for short-term adverse outcomes in neonatal encephalopathy.

BACKGROUND: To explore the predictive value of the Thompson score during the first 4 days of life for estimating short-term adverse outcomes in neonatal encephalopathy. METHODS: This observational study evaluated infants with neonatal encephalopathy (≥36 weeks of gestation) registered in a multicenter cohort of cooled infants in Japan. The Thompson score was evaluated at 0-24, 24-48, 48-72, and 72-90 h of age. Adverse outcomes included death, survival with respiratory impairment (requiring tracheostomy), or survival with feeding impairment (requiring gavage feeding) at discharge. RESULTS: Of the 632 infants, 21 (3.3%) died, 59 (9.3%) survived with respiratory impairment, and 113 (17.9%) survived with feeding impairment. The Thompson score throughout the first 4 days accurately predicted death, respiratory impairment, or feeding impairment. The 72-90 h score showed the highest accuracy. A cutoff of ≥15 had a sensitivity of 0.85 and specificity of 0.92 for death or respiratory impairment, while a cutoff of ≥14 had a sensitivity of 0.71 and a specificity of 0.92 for death, respiratory or feeding impairment. CONCLUSION: A high Thompson score during the first 4 days of life, especially at 72-90 h could thus be useful for estimating the need for prolonged life support. IMPACT: The Thompson score on days 1-4 of age was useful in predicting death and respiratory or feeding impairments. The 72-90 h Thompson score showed the highest predictive capability. Owing to the rarity of withdrawal of life-sustaining treatment in Japan, 43% of infants with persistent severe encephalopathy with a Thompson score of ≥15 at 72-90 h of age could regain spontaneous breathing, be extubated, and survive without tracheostomy. Meanwhile, approximately 50% of infants who survived without tracheostomy required gavage feeding. Our results could provide useful information for clinical decision making regarding infants with persistent severe encephalopathy.

Prolonged requirements for mechanical ventilation and tube feeding support predicted 18-month outcomes for neonatal encephalopathy.

AIM: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia. METHODS: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. RESULTS: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85). CONCLUSION: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia.

Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates.

BACKGROUND: A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3-4 years. METHODS: We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34-42 weeks' postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70-84, 85-100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes. RESULTS: We observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85-100 groups (post hoc, p = 0.024). CONCLUSIONS: In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3-4 years. IMPACT: In very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3-4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1-2 years, we used brain metabolite concentrations.

Body temperature, heart rate and long-term outcome of cooled infants: an observational study.

BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.

A new phenotype of amniotic band syndrome with occipital encephalocele-like morphology: a case report.

Amniotic band syndrome (ABS) is a congenital abnormality that can cause a variety of deformities. Here, we report a case of ABS in which the amniotic band adhered to the skull, causing a partial cranial defect that was difficult to differentiate from an occipital encephalocele. The mother was a 24-year-old with an unremarkable medical and family history. Ultrasonography performed at 16 weeks showed that the fetus had a membranous structure in the occipital region. Occipital encephalocele was suspected, and she underwent cesarean section at 38 weeks. A male newborn was delivered, and his left occipital skin had a defect measuring 2 cm, from which a cystic structure had prolapsed. Cranial magnetic resonance imaging showed that the cystic structure had homogeneous high signal intensity on T2-weighted images. The neonate then underwent repair of the occipital encephalocele. During the operation, the membranous structures and dura were not continuous. Histological examination revealed that the membranous structures were composed of amnion, suggesting that this was a case of ABS. ABS may present with an encephalocele-like morphology without affecting the brain tissue and meninges. If an atypical encephalocele is found after birth, examination of the placenta may be helpful for a definitive diagnosis.

Comparison of Predictive Values of Magnetic Resonance Biomarkers Based on Scan Timing in Neonatal Encephalopathy Following Therapeutic Hypothermia.

OBJECTIVE: To determine the optimal quantitative magnetic resonance (MR) biomarker in neonatal encephalopathy following therapeutic hypothermia based on scan timing. STUDY DESIGN: This retrospective study included 98 neonates (35-41 weeks of gestation) with neonatal encephalopathy, who underwent therapeutic hypothermia; diffusion-weighted imaging and proton MR spectroscopy were performed at 24-96 hours (n = 56) and 7-14 days (n = 92) after birth, respectively, to estimate apparent diffusion coefficient (ADC) values, N-acetylaspartate and N-acetylaspartylglutamate (tNAA), lactate, and choline concentrations, and lactate/tNAA, tNAA/choline ratios in the deep gray matter. Adverse outcomes included death or neurodevelopmental impairment at 18-22 months of age. We used receiver operating characteristic curves to examine the prognostic accuracy of each MR biomarker. RESULTS: Deep gray matter tNAA concentrations showed the best prognostic value, with an area under the curve (AUC) of 0.97 and 1.00 at 24-96 hours and 7-14 days after birth, respectively. At 24-96 hours of age, ADC values, lactate concentrations, and lactate/tNAA ratios showed prognostic value with AUCs of 0.90, 0.95, and 0.97, respectively. At 7-14 days of age, the AUCs of ADC values, lactate, and lactate/tNAA ratios were 0.61, 0.67, and 0.80, respectively; these were lower than those at 24-96 hours of age. CONCLUSIONS: During the first 2 weeks of life, the deep gray matter tNAA concentration was the most accurate quantitative MR biomarker. Although ADC values, lactate levels, and lactate/tNAA ratios also showed high prognostic value during 24-96 hours of life, only tNAA retained high prognostic value in the second week of life.

Identification of new biomarkers of pyridoxine-dependent epilepsy by GC/MS-based urine metabolomics.

α-Aminoadipic semialdehyde and its cyclic form (Δ1-piperideine-6-carboxylate) accumulate in patients with α-aminoadipic semialdehyde dehydrogenase (AASADH; antiquitin; ALDH7A1) deficiency. Δ1-Piperideine-6-carboxylate is known to react with pyridoxal 5'-phosphate (PLP) to form a Knoevenagel condensation product, resulting in pyridoxine-dependent epilepsy. Despite dramatic clinical improvement following pyridoxine supplementation, many patients still suffer some degree of intellectual disability due to delayed diagnosis. In order to expedite the diagnosis of patients with suspected AASADH deficiency and minimize the delay in treatment, we used gas chromatography-mass spectrometry-based metabolomics to search for potentially diagnostic biomarkers in urine from four patients with ALDH7A1 mutations, and identified Δ2-piperideine-6-carboxylate, 6-oxopipecolate, and pipecolate as candidate biomarkers. In a patient at postnatal day six, but before pyridoxine treatment, Δ2-piperideine-6-carboxylate and pipecolate were present at very high concentrations, indicating that these compounds may be good biomarkers for untreated AASADH deficiency patients. On the other hand, following pyridoxine/PLP treatment, 6-oxopipecolate was shown to be greatly elevated. We suggest that noninvasive urine metabolomics screening for Δ2-piperideine-6-carboxylate, 6-oxopipecolate, and pipecolate will be useful for prompt and reliable diagnosis of AASADH deficiency in patients within any age group. The most appropriate combination among Δ2-piperideine-6-carboxylate, 6-oxopipecolate, and pipecolate as biomarkers for AASADH deficiency patients appears to depend on the age of the patient and whether pyridoxine/PLP supplementation has been implemented. We anticipate that the present bioanalytical information will also be useful to researchers studying glutamate, proline, lysine and ornithine metabolism in mammals and other organisms.

Ultrasound-Guided Umbilical Venous Catheter Insertion With Alignment of the Umbilical Vein and Ductus Venosus.

Previous studies have highlighted the importance of confirming the position of an umbilical venous catheter (UVC) tip by an ultrasound (US) examination. However, methods for preventing insertion into the portal circulation under US guidance have not yet been established. We report 15 cases in which a UVC was successfully passed through the ductus venosus by compressing the upper abdomen near the portal sinus of the liver to align the umbilical vein and ductus venosus under US guidance. The UVC was inserted into the correct position in 14 of the 15 neonates (93%) without complications.

Changes in Brain Metabolite Concentrations after Neonatal Hypoxic-ischemic Encephalopathy.

Purpose To investigate the time-course changes and predictive utility of brain metabolite concentrations in neonatal hypoxic-ischemic encephalopathy (HIE). Materials and Methods Sixty-eight neonates (age, 35-41 gestational weeks) with HIE were admitted to a neonatal intensive care unit between September 2009 and March 2016 and examined by using proton MR spectroscopy at 18-96 hours (n = 25) and 7-14 days (n = 64) after birth (35-43 postmenstrual weeks) to estimate metabolite concentrations in the deep gray matter. Adverse outcome was defined as death or neurodevelopmental impairment at 18-22 months of age. Areas under the receiver operating characteristic curves were calculated to evaluate the prognostic values of metabolites. Results At 18-96 hours, N-acetylaspartate and creatine concentrations were lower, whereas lactate, and glutamate and glutamine (Glx) concentrations were higher in neonates with adverse outcomes than in those with favorable outcomes. Metabolite concentrations at 18-96 hours decreased during days 7-14 in neonates with adverse outcomes but did not change in those with favorable outcomes. For N-acetylaspartate, creatine, lactate, and Glx concentrations measured at 18-96 hours to predict adverse outcomes, areas under the receiver operating characteristic curve were 0.98, 0.89, 0.96, and 0.88, respectively, whereas at 7-14 days, the areas under the receiver operating characteristic curve were 0.97, 0.97, 0.59, and 0.36, respectively. Conclusion Time-dependent reductions in N-acetylaspartate and creatine concentrations at both 18-96 hours and 7-14 days accurately predicted adverse outcomes. However, higher lactate and glutamate and glutamine concentrations were often transient.

In vivo estimation of gamma-aminobutyric acid levels in the neonatal brain.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, and plays a key role in brain development. However, the in vivo levels of brain GABA in early life are unknown. Using edited MRS, in vivo GABA can be detected as GABA+ signal with contamination of macromolecule signals. GABA+ is evaluated as the peak ratio of GABA+/reference compound, for which creatine (Cr) or water is typically used. However, the concentrations and T1 and T2 relaxation times of these references change during development. Thus, the peak ratio comparison between neonates and children may be inaccurate. The aim of this study was to measure in vivo neonatal brain GABA+ levels, and to investigate the dependency of GABA levels on brain region and age. The basal ganglia and cerebellum of 38 neonates and 12 children were measured using GABA-edited MRS. Two different approaches were used to obtain GABA+ levels: (i) multiplying the GABA/water ratio by the water concentration; and (ii) multiplying the GABA+/Cr by the Cr concentration. Neonates exhibited significantly lower GABA+ levels compared with children in both regions, regardless of the approach employed, consistent with previous ex vivo data. A similar finding of lower GABA+/water and GABA+/Cr in neonates compared with children was observed, except for GABA+/Cr in the cerebellum. This contrasting finding resulted from significantly lower Cr concentrations in the neonate cerebellum, which were approximately 52% of those of children. In conclusion, care should be taken to consider Cr concentrations when comparing GABA+/Cr levels between different-aged subjects.

Association between cord blood cystatin C levels and early mortality of neonates with congenital abnormalities of the kidney and urinary tract: a single-center, retrospective cohort study.

BACKGROUND: Some fetuses with congenital abnormalities of the kidney and urinary tract (CAKUT) have severe renal dysfunction during the prenatal period that can result in oligohydramnios, pulmonary hypoplasia, and death following birth. We hypothesized that cord blood cystatin C (CysC) levels are elevated in neonates who have life-threatening pulmonary hypoplasia and oligohydramnios due to severe renal dysfunction. In this study we compared cord blood CysC levels between a non-survivor group with CAKUT and a survivor group. METHODS: This was a single-center, retrospective cohort study conducted between January 2007 and December 2015. Eighty-seven neonates who were prenatally diagnosed with CAKUT were included in the study. Cord blood CysC and creatinine levels were compared between the survivor and non-survivor groups at discharge from hospital. RESULTS: Of the 87 neonates enrolled in the study, 67 survived and 21 died before discharge. Median cord blood CysC levels were higher in the non-survivor group than in the survivor group (4.28 vs. 1.96 mg/L, respectively; p < 0.001). Cord blood creatinine levels were not significantly different between the two groups. In patients with oligohydramnios (n = 28), cord blood CysC levels were significantly higher in the non-survivor group than in the survivor group (4.28 vs. 2.23 mg/L, respectively; p = 0.002). CONCLUSIONS: In this study population, cord blood CysC levels were significantly higher in the non-survivor group with CAKUT than in the survivor group. These results suggest that cord blood CysC levels may be a good marker of the severity of renal dysfunction at birth.

Interhemispheric Lipoma, Callosal Anomaly, and Malformations of Cortical Development: A Case Series.

Intracranial lipomas are rare congenital malformations. The most common type of intracranial lipoma is the interhemispheric lipoma, which is frequently associated with callosal anomalies such as hypogenesis or agenesis of the corpus callosum. In contrast, interhemispheric lipomas are less often accompanied with malformations of cortical development (MCD). We report magnetic resonance imaging findings of three infants with an interhemispheric lipoma, associated with a callosal anomaly, and MCD: two infants with nodular interhemispheric lipoma, agenesis of the corpus callosum, and polymicrogyria, and one infant with interhemispheric curvilinear lipoma, hypoplasia of the corpus callosum, and heterotopias. An association was suggested regarding the occurrence of these malformations.

Temporal Relationship between Serum Levels of Interleukin-6 and C-Reactive Protein in Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy.

Objective C-reactive protein (CRP) is a useful marker of neonatal infection. Recent studies have shown that neonatal therapeutic hypothermia delays an elevation of CRP in infants with hypoxic-ischemic encephalopathy (HIE). This study investigated the time difference of peak levels of serum CRP and other inflammatory responses during therapeutic hypothermia. Study design We prospectively studied the serial serum data of CRP, interleukin-6 (IL-6), procalcitonin (PCT), and complete blood counts during the first week of life in HIE infants receiving therapeutic hypothermia. Results We identified 22 infants who received therapeutic hypothermia between August 2013 and July 2015. No infants developed clinically overt infections. The peak of serum levels of IL-6, PCT, and CRP were postnatal days 1, 2, and 4, respectively. White blood cells, neutrophils, and platelet counts gradually decreased from days 1 to 7. Early postnatal serum levels of IL-6 correlated with CRP on day 4 (IL-6 on day 2; r = 0.78, p < 0.001). Conclusion The peak value of CRP on day 4 might reflect the early production and secretion of IL-6 rather than an actual infection. Serial measurement of IL-6 might help avoid invasive sepsis workup and unnecessary change of antibiotics in infants.

Indocyanine green lymphography and lymphaticovenous anastomosis for generalized lymphatic dysplasia with pleural effusion and ascites in neonates.

BACKGROUND: The fatality rate of generalized lymphatic dysplasia (GLD) with chylous pleural effusion and ascites is particularly high when it persists over a prolonged period. The purpose of this report was to determine the utility of indocyanine green (ICG) lymphography and lymphaticovenous anastomosis (LVA) in GLD with chylous pleural effusion and ascites in neonates. METHODS: We tested the lymphatic function in the 4 extremities for 8 GLD neonate patients using ICG lymphography, and on the basis of the results, we performed LVA for 5 of them. LVA was performed at the extremities under general anesthesia using incisions <1 cm in length. The outcome of LVA was evaluated with the amount of ascites discharged from thoracostomy tube or abdominal tube, except for 1 patient who had no drainage tube. RESULTS: In all cases, ICG lymphography showed varying degrees of dermal backflow in the limbs with lymphostasis. After LVA surgery, effusion stopped in 2 cases and decreased in 1 case. In the cases where effusion stopped, backflow as observed with ICG lymphography was minimal, and in the case where effusion decreased but did not stop, backflow was moderate. CONCLUSIONS: The application of ICG and LVA could possibly be used to diagnose and treat lymphatic pleural effusion or ascites.

Evaluation of lymphatic dysplasia in patients with congenital pleural effusion and ascites using indocyanine green lymphography.

OBJECTIVES: To investigate the use of indocyanine green (ICG) lymphography in the diagnosis and assessment of the severity of lymphatic dysfunction in infants and neonates with congenital lymphatic pleural effusion and ascites. STUDY DESIGN: We performed ICG lymphography on 10 neonates and infants with congenital lymphatic pleural effusion and ascites. After the subcutaneous injection of ICG, circumferential fluorescent images of lymphatic drainage channels in the extremities and trunk were identified using an infrared camera system. The lymphographic findings were classifiable into 2 patterns-those showing a linear lymphatic pattern, suggesting normal lymphatic flow, and those showing lymphatic channels with retrograde lymphatic flow (dermal backflow pattern), suggesting an abnormal lymphatic flow. We analyzed the severity of the ICG lymphography findings and the clinical outcomes. RESULTS: Based on the ICG lymphography, the severity of lymphatic dysplasia were classified into 4 categories: mild dysplasia, moderate dysplasia, severe dysplasia, and lymphatic hypoplasia. All cases diagnosed with mild (n = 3) or moderate dysplasia (n = 2) survived, and 2 of the 4 cases diagnosed with severe dysplasia died. The duration of endotracheal intubation ranged from 1 to 17 days (median, 7) in the patients with mild or moderate dysplasia and from 25 to 110 days (median, 77) in those with severe dysplasia. CONCLUSIONS: The ICG lymphographic findings were consistent with the clinical conditions. This imaging technique may be important to the future clinical management of lymphatic dysplasia in neonates and infants.

Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction.

BACKGROUND: Knowledge of MRI findings in pediatric cerebral infarction is limited. OBJECTIVE: To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. MATERIALS AND METHODS: Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. RESULTS: Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. CONCLUSION: In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one.

Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome.

BACKGROUND: Neurooculocardiogenitourinary syndrome (NOCGUS), a multisystemic syndrome characterized by motor disorder, intellectual disability, seizures, abnormal brain structure, ocular diseases, and cardiac diseases, has been reported with missense variant of WD repeat-containing protein 37 (WDR37) in humans. This report aimed to identify the cause of NOCGUS in an affected patient. CASE PRESENTATION: We identified a de novo intronic 4-bp deletion of WDR37, c.727-27_727-24del, which were predicted to cause abnormal splicing by SpliceAI, in the patient with NOCGUS. Reverse transcription polymerase chain reaction (RT-PCR) revealed intron retention of 63 base pairs before exon 10 in messenger RNA, which was predicted to insert 21 additional aberrant amino acids (p.S242_I243insLCQKKLKISRKCLFWPSLWQQ). The patient had novel phenotypes, anal atresia, and polycystic kidney, in addition to intellectual disability, seizures, cerebellar vermian anomaly, and coloboma, which are typical in NOCGUS. We did not observe motor impairments or cardiovascular anomalies. CONCLUSION: This is the first reported case of NOCGUS with the splicing variant of WDR37, which manifests with distinctive but variable features. Our findings may expand a possible phenotypic expression of NOCGUS.