De Novo KAT5 Variants Cause a Syndrome with Recognizable Facial Dysmorphisms, Cerebellar Atrophy, Sleep Disturbance, and Epilepsy.

KAT5 encodes an essential lysine acetyltransferase, previously called TIP60, which is involved in regulating gene expression, DNA repair, chromatin remodeling, apoptosis, and cell proliferation; but it remains unclear whether variants in this gene cause a genetic disease. Here, we study three individuals with heterozygous de novo missense variants in KAT5 that affect normally invariant residues, with one at the chromodomain (p.Arg53His) and two at or near the acetyl-CoA binding site (p.Cys369Ser and p.Ser413Ala). All three individuals have cerebral malformations, seizures, global developmental delay or intellectual disability, and severe sleep disturbance. Progressive cerebellar atrophy was also noted. Histone acetylation assays with purified variant KAT5 demonstrated that the variants decrease or abolish the ability of the resulting NuA4/TIP60 multi-subunit complexes to acetylate the histone H4 tail in chromatin. Transcriptomic analysis in affected individual fibroblasts showed deregulation of multiple genes that control development. Moreover, there was also upregulated expression of PER1 (a key gene involved in circadian control) in agreement with sleep anomalies in all of the individuals. In conclusion, dominant missense KAT5 variants cause histone acetylation deficiency with transcriptional dysregulation of multiples genes, thereby leading to a neurodevelopmental syndrome with sleep disturbance, cerebellar atrophy, and facial dysmorphisms, and suggesting a recognizable syndrome.

High field brain proton magnetic resonance spectroscopy and volumetry in children with chronic, compensated liver disease - A pilot study.

BACKGROUND: There is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood. AIM: Therefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease. METHODS: Patients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS. RESULTS: Five children aged 8-16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range. CONCLUSION: Children with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects.

Prenatal magnetic resonance imaging of complex female genitourinary system abnormalities, what the fetal medicine specialist needs to know.

Complex female genitourinary system anomalies include a wide spectrum of uncommon pathologies, caused from the abnormal separation of the urorectal septum and the urogenital sinus in early embryonic life. The resulting fusion of the distal urinary, genital and intestinal tracts increases the risk of death in utero and alters the normal organ functionality and the quality of life in survivors. An accurate prenatal identification of these pathologies depends mainly on prior suspicion at ultrasound screening, but also requires a solid knowledge of embryology and familiarity with the different patterns of malformation. Prenatal MRI provides an excellent anatomic evaluation of the fetal anatomy that may improve the diagnosis in complex cases with inconclusive echographic findings. The additional information can help both families and medical teams to better evaluate the severity of the pathology and the postnatal prognosis and therefore to better orientate the management during pregnancy, at delivery and after birth. This review article describes the embryological basis and the clinical findings of the most relevant pathologies included in the spectrum. It also describes the imaging signs on prenatal MRI studies in a series of confirmed cases and proposes a diagnostic algorithm based on imaging findings for guiding prenatal diagnosis.

Early arterial pressure monitoring and term-equivalent age MRI findings in very preterm infants.

INTRODUCTION: Variability of arterial blood pressure (ABP) has been associated with intraventricular hemorrhage in very preterm neonates (VPT) and may predict other brain lesions assessed at term-equivalent of age (TEA). METHODS: This was a prospective single-center study including VPT with early invasive continuous ABP monitoring and assessed at TEA using brain magnetic resonance imaging (TEA-MRI). The association between early mean ABP (MABP) and TEA-MRI findings was modeled by multivariate logistic regression analysis using covariates selected by the LASSO method. RESULTS: Among 99 VPT, the LASSO procedure selected consecutive periods of lowest MABP of 30 min on day 1 (d1) and 10 min on day 2 (d2) as the most relevant durations to predict TEA-MRI findings (OR [95% CI], 1.11 [1.02-1.23], p = 0.03 and 1.13 [1.01-1.27], p = 0.03, respectively). ROC curve analysis showed optimal thresholds at 30.25 mmHg on d1 and 33.25 mmHg on d2. This significant association persisted after adjustment with covariates including birthweight, gestational age, sex, and inotrope exposure. Final models selected by LASSO included the decile of the birthweight and lowest MABP for 30 min on d1 and 10 min on d2, for which the areas under the ROC curve were 74% and 75%, respectively. CONCLUSION: Early continuous ABP monitoring may predict brain TEA-MRI findings in VPT. IMPACT: Early arterial blood pressure monitoring may contribute to predicting brain damage upon MRI at term-equivalent of age for infants born very preterm. Careful blood pressure continuous monitoring in very preterm infants may identify infants at risk of long-term brain damage. Umbilical artery catheterization provides the best option for continuously monitoring arterial blood pressure in very preterm infants.

Benefits of diffusion-weighted imaging in pediatric acute osteoarticular infections.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (MRI) is recommended for the diagnosis of acute osteoarticular infections in children. Diffusion-weighted imaging (DWI) may be an alternative to the injection of gadolinium. OBJECTIVE: To evaluate unenhanced MRI with DWI in comparison to contrast-enhanced MRI for the diagnostic work-up of acute osteoarticular infections in children. MATERIALS AND METHODS: This retrospective study included 36 children (age range: 7 months-12 years) with extra-spinal osteoarticular infections and MRI performed within 24 h of admission. MRI protocol included short tau inversion recovery (STIR), water-only T2 Dixon, T1, DWI, and gadolinium-enhanced T1 sequences. Two readers reviewed three sets of images: 1) unenhanced sequences, 2) unenhanced sequences with DWI and 3) unenhanced followed by contrast-enhanced sequences (reference standard). Sensitivity and specificity of sets 1 and 2 were compared to set 3 and assessed to identify osteoarticular infections: osteomyelitis (long bones, metaphyseal equivalents), septic arthritis and abscess (soft tissues, bone). RESULTS: All 14 cases of osteomyelitis in the metaphyses and diaphyses of long bones and all 27 cases of septic arthritis were identified by unenhanced sequences, but 4/16 abscesses were missed. For the diagnosis of abscess, DWI increased sensitivity to 100%. Among the 18 osteomyelitis in metaphyseal equivalents, 4 femoral head chondroepiphyses were identified by contrast-enhanced sequences only. CONCLUSION: MRI for suspected pediatric acute osteoarticular infections is the best diagnostic modality to guide patient management. An unenhanced protocol with DWI may be an alternative to a contrast-based protocol, even in the presence of an abscess. However, gadolinium remains necessary to assess for chondroepiphyseal involvement of the femoral head.

Acoustic radiation force impulse imaging: normal values of spleen stiffness in healthy children.

BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a noninvasive ultrasound elastography technique for evaluating tissue stiffness. The association of liver and spleen stiffness provides additional information in the assessment of portal hypertension. The technique and normal values of spleen stiffness by point shear wave elastography (p-SWE) in pediatrics have not been well documented. OBJECTIVE: Our aim is to describe the feasibility and normal ARFI elastography values in the spleen for healthy children and to compare measurements in two different probe positions (the axial and sagittal planes). MATERIALS AND METHODS: Spleen p-SWE using ARFI values were measured with a 6C1 probe in 102 healthy children (age range: 8 weeks to 17 years) divided into four age groups. An average of nine (standard deviation: two) spleen stiffness measurements were taken during free breathing in each plane (axial and sagittal). The impact of age and measurement plane in the spleen was analyzed using multivariate models. RESULTS: There was no significant difference in spleen stiffness values taken at different ages, with an average of the medians of 2.43±0.31 m/s. There was no significant difference based on probe orientation: sagittal plane (median: 2.46±0.29 m/s) and axial plane (median: 2.43±0.32 m/s) with Student's t-test P=0.18. The mean depth of measurement varied between 2.3 cm and 3.7 cm, according to age. CONCLUSION: Normal spleen stiffness values using ARFI imaging in children do not vary with age and correspond to a median of 2.43 m/s. No significant difference was found when using different probe positions.

Contribution of magnetic resonance imaging to the prenatal diagnosis of common congenital vascular anomalies.

BACKGROUND: Screening ultrasound (US) has increased the detection of congenital vascular anomalies in utero. Complementary magnetic resonance imaging (MRI) may improve the diagnosis, but its real utility is still not well established. OBJECTIVES: We aimed to describe the imaging findings on prenatal US and MRI of the most frequent congenital vascular anomalies (lymphatic malformations and congenital hemangiomas) to assess the accuracy of prenatal US and MRI exams for diagnosis and to evaluate the relevance of the additional information obtained by complementary fetal MRI. MATERIALS AND METHODS: All confirmed postnatal congenital vascular anomalies detected in the last 10 years at 3 university hospitals were retrospectively identified. The prenatal diagnosis was compared with the final diagnosis for both methods and the clinical relevance of additional MRI information was evaluated. A second MRI in advanced pregnancy was performed in fetuses with lesions in a sensitive anatomical location and the clinical relevance of the additional information was evaluated. RESULTS: Twenty-four cases were included in the study, 20 lymphatic malformations and 4 hemangiomas. MRI slightly improved the diagnosis of lymphatic malformation, 85% vs. 80% at US, especially for abdominal lesions. Both methods had a low identification rate (25%) for tumors. MRI performed late in five fetuses with lymphatic malformation allowed optimized management at birth. CONCLUSION: MRI improves the diagnosis of congenital lymphatic malformations whereas hemangiomas remain difficult to identify in utero. The main role of MRI is to provide high-defined anatomical data to guide management at birth.

Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay.

PURPOSE: To elucidate the novel molecular cause in two unrelated consanguineous families with autosomal recessive intellectual disability. METHODS: A combination of homozygosity mapping and exome sequencing was used to locate the plausible genetic defect in family F162, while only exome sequencing was followed in the family PKMR65. The protein 3D structure was visualized with the University of California-San Francisco Chimera software. RESULTS: All five patients from both families presented with severe intellectual disability, aggressive behavior, and speech and motor delay. Four of the five patients had microcephaly. We identified homozygous missense variants in LINGO1, p.(Arg290His) in family F162 and p.(Tyr288Cys) in family PKMR65. Both variants were predicted to be pathogenic, and segregated with the phenotype in the respective families. Molecular modeling of LINGO1 suggests that both variants interfere with the glycosylation of the protein. CONCLUSION: LINGO1 is a transmembrane receptor, predominantly found in the central nervous system. Published loss-of-function studies in mouse and zebrafish have established a crucial role of LINGO1 in normal neuronal development and central nervous system myelination by negatively regulating oligodendrocyte differentiation and neuronal survival. Taken together, our results indicate that biallelic LINGO1 missense variants cause autosomal recessive intellectual disability in humans.

Diagnostic accuracy of MR imaging for direct visualization of lumbar pars defect in children and young adults: a systematic review and meta-analysis.

PURPOSE: The accurate diagnosis of spondylolysis is widely made with CT scan considered as the gold standard. However, CT represents significant radiation exposure particularly substantial in a young and sometimes still growing population. Although the role of MRI in identifying edema/inflammation within the pars as an active lesion is proved, its ability to demonstrate and classify pars fracture line as same as CT is still controversial. This meta-analysis aimed to determine sensitivity and specificity of MRI in the direct visualisation of the pars defect. METHODS: The PubMed and Embase databases were systematically searched for relevant studies from the earliest researchable time to December 2016 for cases in which the accuracy of MRI was reported for the diagnosis of spondylolysis in young patients. Two reviewers independently assessed the methodological quality for each selected study using the quality assessment of diagnostic accuracy studies 2 tool. A meta-analysis of the reported sensitivity and specificity of pooled data of selected studies was performed by a systematic review. For each selected study, sensitivity and specificity was recalculated, by considering only direct visualisation of a fracture line of the pars. The hierarchic summary receiver operating characteristic curve was generated to estimate the diagnostic performance of MR imaging. Heterogeneity was also tested. RESULTS: The systematic review identified 4 out of a total of 1300 studies to be included in the meta-analysis. On a per-pars basis (a total of 1122 pars), the pooled sensitivity and specificity of the MRI for the direct diagnosis of a pars defect were 81% (95% CI 54-94%) and 99% (95% CI 98-100%), respectively. A high overall heterogeneity (I2 = 79.5%) was computed with respective high and low heterogeneity on sensitivity (I2 = 87.9%) and specificity (I2 = 38.4%). CONCLUSIONS: This meta-analysis demonstrated a high diagnostic performance of MR imaging for the diagnosis of a pars defect in young adults. This technique may be considered as a first-line imaging technique as it helps to avoid exposure to ionising radiation.

Benefit of Temporomandibular Joint Lavage With Intra-Articular Steroids Versus Lavage Alone in the Management of Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis.

PURPOSE: The aim of the present investigation was to evaluate, in patients with juvenile idiopathic arthritis, the effect of lavage with or without intra-articular corticosteroid (IACS) injection on clinical temporomandibular joint (TMJ) signs and symptoms of inflammation and changes in acute inflammation as assessed using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty-one patients (mean age, 13.6 ± 4.0 yr) with juvenile idiopathic arthritis participating in a large prospective juvenile inflammatory rheumatism cohort study (JIRcohorte) were included in this study. Clinical history, examination, and MRI were carried out at baseline and 6 months after intervention, if any. Twenty-one patients underwent lavage and IACS injection in at least 1 TMJ, 8 patients underwent lavage of at least 1 TMJ, and 12 patients were followed with no intervention. Outcomes measured were maximal mouth opening, Helkimo dysfunction index scores, pain intensity, and acute inflammation as assessed using MRI. RESULTS: All groups showed a mean increase in mouth opening and mean decrease in pain intensity. The mean Helkimo clinical dysfunction score decreased for the 2 intervention groups but not for the control group. The mean Helkimo anamnestic dysfunction score decreased for the lavage with IACS group but not for the lavage-only group. The only statistically relevant difference was found for the Helkimo anamnestic dysfunction score comparing the lavage-only with the lavage with IACS group, with a more positive effect found in the lavage with IACS group. More than 50% of joints in each group showed no change at MRI examination. Joints with lavage and ICAS injection showed better improvement than joints that had lavage only or no intervention. CONCLUSION: TMJ lavage with or without IACS injection cannot be claimed to systematically decrease pain, increase mouth opening, or resolve acute inflammation. Despite a tendency for improvement, response to this treatment is very patient dependent and can be determined by an array of other variables.

Iterative algorithms for metal artifact reduction in children with orthopedic prostheses: preliminary results.

BACKGROUND: Increased computational power allows computed tomography (CT) software to process very advanced mathematical algorithms to generate better quality images at lower doses. One such algorithm, iterative metal artifact reduction (iMAR) has proven to decrease metal artifacts seen in CT images of adults with orthopedic implants. OBJECTIVES: To evaluate artifact reduction capability of the algorithm in lower-dose pediatric CT compared to our routine third-generation advanced modeled iterative reconstruction (ADMIRE) algorithm. MATERIALS AND METHODS: Thirteen children (11-17 years old) with metal implants underwent routine clinically indicated CT. Data sets were reconstructed with an iMAR algorithm. Hounsfield units and image noise were measured in bone, muscle and fat in the streak artifact (near the implant) and at the greatest distance from the artifact (far from the implant). A regression model compared the effects of the algorithm (standard ADMIRE vs. iMAR) near and far from the implant. RESULTS: Near the implant, Hounsfield units with iMAR were significantly different in our standard ADMIRE vs. iMAR for bone, muscle and fat (P<0.001). Noise was significantly different in standard ADMIRE vs. iMAR in bone (P<0.003). Far from the implant, Hounsfield units and noise were not significantly different for ADMIRE vs. iMAR, for the three tissue types. CONCLUSION: These preliminary results demonstrate that iMAR algorithms improves Hounsfield units near the implant and decreases image noise in bone in low-dose pediatric CT. It does this without changing baseline tissue density or noise far from the implant.

Tracheal agenesis: optimization of computed tomography diagnosis by airway ventilation.

Tracheal agenesis is a rare and often lethal congenital defect that leads to airway emergency at birth. Computed tomography (CT) is the modality of choice to evaluate anomalous tracheal anatomy. The absence of spontaneous aeration of the tracheobronchial tree in children with tracheal agenesis makes CT interpretation difficult. We describe a procedure of airway management applied in two newborns with suspected tracheal agenesis. Correct airway management was performed immediately prior to CT examination by airway ventilation, with bag-valve mask alone in one case, and attached to an endotracheal tube placed into the esophagus in the other case. The images allowed for classification of tracheal agenesis. Computed tomography with appropriate airway ventilation is fundamental for the diagnosis of tracheal agenesis.

Globus pallidus MR signal abnormalities in children with chronic liver disease and/or porto-systemic shunting.

OBJECTIVES: Detection of subclinical hepatic encephalopathy in children is difficult. We aimed to assess the changes in imaging of the central nervous system in children with chronic liver disease using MR imaging, diffusion, and 1H -spectroscopy. METHODS: Forty three children with chronic liver disease and/or porto-systemic shunting (111.4±56.9 months) and 24 controls (72.0±51.8 months) underwent brain MRI/spectroscopy on a 1.5T to examine T1, T2, ADC, Cho/Cr, ml/Cr, Glx/Cr ratio spectroscopy in the globus pallidus. Patients were divided into 3 groups according to the ratios of globus pallidus/putamen T1 signal : isointense (i), hyperintense (h), much more hyperintense (h+). The relationship with clinical and biological data was analyzed. RESULTS: T1 signal intensity and ml/Cr were significantly different between controls and group h+ (p=0.001). ADC did not differ significantly between groups. Age correlated strongly with the presence of a T1 signal ratio (p > 0.001). There was no correlation between imaging findings and biological parameters. CONCLUSIONS: In children with chronic liver disease and/or porto-systemic shunting, the presence of a hyperintense T1 signal in the globus pallidus correlated strongly with age. Biological and clinical parameters were not predictive of these changes. MRI may become a useful screening tool for hepatic encephalopathy in children. KEY POINTS: • Children with chronic liver disease should undergo brain MRI during their follow-up • T1 hyperintensity of globus pallidus is suggestive of liver-related CNS involvement • MRS mI/Cr is decreased in children with chronic liver disease • Biological parameters (ammonium) were not predictive of hepatic encephalopathy • Duration of chronic liver disease may be causative the hepatic encephalopathy.

Severe and Progressive Fetal Ventriculomegaly Leading to the Diagnosis of Periventricular Nodular Heterotopias with Good Outcome.

Severe fetal ventriculomegaly is generally associated with poor prognosis in terms of survival and neurodevelopment outcome. As such, many parents opt to terminate the pregnancy independently of a known etiology. We report here the case of a female fetus with severe progressive ventriculomegaly due to the unexpected presence of bilateral nodular periventricular heterotopias visualized on MRI of a fetal brain. Reaching a structural diagnosis was perceived as a relief for the parents and the pregnancy was continued. Neurodevelopment assessment at 3 years of age is normal with no epilepsy.

Acoustic radiation force impulse sonography in assessing children with biliary atresia for liver transplantation.

BACKGROUND: Children with biliary atresia are prone to developing progressive hepatic fibrosis and biliary cirrhosis following the Kasai operation. The only treatment is liver transplantation. OBJECTIVE: To assess liver fibrosis by acoustic radiation force impulse elastography (ARFI) in children who had Kasai operation, with the goal of identifying an ARFI value cut-off for children requiring liver transplantation. MATERIALS AND METHODS: Of the 32 post-Kasai children included, 19 were transplanted or listed for transplantation (group A), while 13 were not on the list during their follow-up (group B). We recorded biopsies, blood samples and ARFI values over time, including at Kasai operation and at transplantation. We estimated an association between groups and continuous variables using generalized estimating equations, and we compared categorical variables using the Fisher exact test. RESULTS: Portal hypertension signs were similar in both groups, whereas ARFI values were higher in group A (mean±standard deviation=3.3±1.2 m/s) than in group B (2.0±0.7 m/s; P=.0003). Eighteen of 19 (94.7%) children in group A and 6/13 (46.2%) children in group B presented with two consecutive ARFI values ≥2 m/s (sensitivity=7%, specificity=53.8%; P=0.003). CONCLUSION: We found that children who were transplanted had two consecutive ARFI values ≥2 m/s during follow-up. ARFI for evaluation of post-Kasai liver fibrosis may assist the long-term assessment of biliary atresia and may even guide treatment decisions.

Microstructural changes in thickened corpus callosum in children: contribution of magnetic resonance diffusion tensor imaging.

BACKGROUND: Thickened corpus callosum is a rare finding and its pathophysiology is not well known. An anomalous supracallosal bundle has been depicted by fiber tracking in some cases but no diffusion tensor imaging metrics of thickened corpus callosum have been reported. OBJECTIVE: To use diffusion tensor imaging (DTI) in cases of thickened corpus callosum to help in understanding its clinical significance. MATERIALS AND METHODS: During a 7-year period five children (ages 6 months to 15 years) with thickened corpus callosum were studied. We determined DTI metrics of fractional anisotropy (FA), mean diffusivity, and axial (λ1) and radial (λ2, λ3) diffusivity and performed 3-D fiber tracking reconstruction of the thickened corpus callosum. We compared our results with data from the literature and 24 age-matched controls. RESULTS: Brain abnormalities were seen in all cases. All children had at least three measurements of corpus callosum thickness above the 97th percentile according to age. In all children 3-D fiber tracking showed an anomalous supracallosal bundle and statistically significant decrease in FA (P = 0.003) and λ1 (P = 0.001) of the corpus callosum compared with controls, but no significant difference in mean diffusivity and radial diffusivity. CONCLUSION: Thickened corpus callosum was associated with abnormal bundles, suggesting underlying axonal guidance abnormality. DTI metrics suggested abnormal fiber compactness and density, which may be associated with alterations in cognition.

Contribution of acoustic radiation force impulse (ARFI) elastography to the ultrasound diagnosis of biliary atresia.

BACKGROUND: Children with biliary atresia rapidly develop liver fibrosis secondary to inflammatory destruction of the biliary tract. Noninvasive detection of liver fibrosis in neonatal/infantile cholestasis is an additional criterion for the diagnosis of biliary atresia, leading to prompt surgical exploration. OBJECTIVE: To assess the value of US with acoustic radiation force impulse (ARFI) elastography to detect biliary atresia in the workup of neonatal/infantile cholestasis. MATERIALS AND METHODS: In this retrospective study, 20 children with cholestasis suspected of having biliary atresia were investigated by US and ARFI. We evaluated the association between US findings and the diagnosis of biliary atresia and with two scores of liver fibrosis obtained from liver biopsy. RESULTS: In univariate analyses, gallbladder size, triangular cord sign, spleen size and ARFI values were found to be associated with biliary atresia, though only the triangular cord sign remained significant when elevated gamma glutamyltransferase (GGT) was included as a predictor. In contrast, spleen size and ARFI correlated with the degree of liver fibrosis on biopsy (r > 0.70, P < 0.001), which remained significant when gamma glutamyltransferase elevation was included as a predictor. CONCLUSION: The addition of ARFI to a standard abdominal US in the initial workup of the neonate with possible infantile cholestasis can provide reliable information on liver fibrosis and help in the diagnosis of biliary atresia.

Neurometabolism and brain morphometry in an adolescent female with an extra-hepatic congenital portosystemic shunt.

Background: Chronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto-systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5-3T MRI systems. However, the in-depth study of brain metabolism requires the high spectral resolution of high magnetic fields. Objectives and Methods: We analyzed the neurometabolic profile, brain volumes and T1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy (1H MRS, 7T) combined with MRI and compared it to an age-matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests. Results: 7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure. Conclusions: In this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients.

Inflammatory myofibroblastic tumor of the lung: a rare cause of atelectasis in children.

Although rare, inflammatory myofibroblastic tumor is the most common primary lung mass in children. We report the case of an 11-year-old boy investigated for persistent cough and dyspnea with complete left lung atelectasis mimicking pneumonia. CT and MRI showed an endobronchial mass of the left main bronchus. The boy underwent endoscopic resection of the tumor and histology was in favor of an inflammatory myofibroblastic tumor of the lung. This diagnosis should be suspected in children with recurrent pneumonia. The prognosis is good after complete resection.

Acoustic radiation force impulse imaging-normal values of liver stiffness in healthy children.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a recent ultrasound technique to assess tissue stiffness. OBJECTIVE: Our aim was to describe the feasibility and to define normal ARFI values in liver in children. MATERIALS AND METHODS: ARFI values were measured in 103 children (ages 2 weeks to 17 years) divided into four age groups, at a minimum depth of 3 cm. In 20 children, measurements were done at 3-, 4- and 5-cm depth in the liver to assess the suitability of measurement location. The impact of age groups and of depth groups was examined using multilevel models. The precision of the measurements was determined using intraclass correlation coefficient (ICC). RESULTS: There was no statistical difference between measurements taken at different ages, with a mean propagation velocity of 1.12 m/s (range: 0.73 to 1.45 m/s). There was no significant difference according to the depth of the regions of interest (up to 5 cm). The ICC was 0.77 (95% CI 0.69-0.83). CONCLUSION: ARFI is feasible in children at any age with an acceptable reliability. The depth of measurements in the liver seems to have no influence on test results. We set the standard ARFI elastography values for healthy liver in children.