Prognostic implications of distinctive imaging characteristics in primary intracranial germ cell tumors: A retrospective analysis.

PURPOSE: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare brain tumors that encompass two subtypes: germinomas and non-germinomatous germ cell tumors (NGGCTs), NGGCTs have less favorable outcome and require multi-modality treatment. Biopsy is recommended for disease diagnosis, the specimen may not adequately reflect the entire tumor. This study aimed to assess distinct imaging characteristics to differentiate between GCT subgroups and to identify possible initial image and subgroup features that influence survival. METHOD: This retrospective study, conducted from January 2006 to March 2023, analyzed patient data and MRI findings of primary CNS GCTs. It evaluated tumor characteristics including cysts, seeding, multifocality, and hemorrhage. Tumor volumes and apparent diffusion coefficient (ADC) values of both tumoral and normal-appearing contralateral white matter were measured. These factors were correlated with overall and 5-year survival rates. RESULTS: This study included 51 participants with CGTs, comprising 19 germinoma and 32 NGGCTs cases. GCTs with hemorrhage had worse overall (P = 0.03) and 5-year (P = 0.01) survival rates. No survival difference between germinoma and non-hemorrhagic NGGCT. NGGCTs were more likely to bleed (P < 0.001) than germ cell tumor, especially those with choriocarcinoma or yolk sac tumor components (P = 0.001). The ADC ratios of germinomas were significantly lower than those of NGGCTs (P = 0.03 for whole tumor; P < 0.01 or solid part), The ADC ratios of choriocarcinoma were also lower than mixed tumor (P = 0.01; P = 0.02). CONCLUSION: Hemorrhage indicates worse prognosis. Intratumoral hemorrhage and ADC ratios differentiate germinoma from NGGCTs. Larger cohorts and advanced MR techniques are needed for future study.

High incidence of cerebrovascular lesions on magnetic resonance imaging in pediatric COVID-19 during omicron outbreak - A retrospective case series.

BACKGROUND: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures. METHODS: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated. RESULTS: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients. CONCLUSION: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection.

Integration of immunohistochemistry, RNA sequencing, and multiplex ligation-dependent probe amplification for molecular classification of pediatric medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is commonly classified into four molecular groups, that is, WNT, SHH, group 3, and group 4, for prognostic and therapeutic purposes. METHODS: Here we applied immunohistochemistry (IHC) and RNA sequencing (RNA-seq) for the molecular classification of MB, and utilized multiplex ligation-dependent probe amplification (MLPA) to determine chromosomal alterations and specific gene amplifications. RESULTS: We retrospectively enrolled 37 pediatric MB patients. Twenty-three had genomic material available for gene/RNA analysis. For IHC, ß-catenin, GAB1, and YAP were the biomarkers to segregate MB into three subgroups, WNT (1/23), SHH (5/23), and non-WNT/non-SHH (17/23). However, four cases (17.3%) were found to be misclassified after analysis by RNA-seq. The result of MLPA revealed two group 3 tumors carrying MYC amplification, and three SHH tumors harboring MYCN amplification. While IHC provided rapid subgroup stratification, it might result in incorrect subgrouping. Thus, validation of the IHC result with genomic data analysis by RNA-seq or other tools would be preferred. In addition, MLPA can detect important genetic alterations and is helpful for the identifications of high-risk patients. CONCLUSIONS: Our study revealed that integration of these diagnostic tools can provide a precise and timely classification of MB, optimizing an individualized, risk-directed postoperative adjuvant therapy for these patients. This workflow can be applied in a countrywide fashion to guide future clinical trials for patients with MB.

Episodic weakness and axonal sensorimotor neuropathy caused by a mitochondrial MT-ATP6 mutation.

Episodic weakness is typically associated with a group of disorders so called periodic paralyses. Their major causes are mutation of ion channels, and have rarely been linked to mitochondrial disorders. We report a 20-year-old man with episodic weakness and axonal sensorimotor neuropathy since the age of 10 years. Analysis of the next generation sequencing data of the entire mitochondrial genome extracted from the blood revealed a homoplasmic m.9185T > C variant in MT-ATP6. Acetazolamide may be responsive for episodic weakness, and supplements with l-carnitine with coenzyme-Q10 seem to be beneficial as well. To the best of our knowledge, this is the first report in Taiwan which reveals episodic weakness and sensorimotor polyneuropathy as a unique phenotype of MT-ATP6 mutations.

A noninvasive index to predict liver cirrhosis in biliary atresia.

BACKGROUND: Biliary atresia is a progressive obliterative cholangiopathy affecting both extrahepatic and intrahepatic biliary trees, resulting in fibrous obliteration of the biliary tract and subsequent development of cirrhosis. OBJECTIVE: The aim of this study was to find noninvasive indices to predict the status of hepatic fibrosis in children with biliary atresia. MATERIALS AND METHODS: We retrospectively measured the volume of the hepatic lobes and spleen from MR images, obtained biochemical data and analyzed the relationship between the imaging and biochemical indices, and the pathological status of hepatic fibrosis in 35 children with biliary atresia. RESULTS: A combined index was obtained by logistic regression: logit (likelihood of cirrhosis) = 0.00043 x age at MR examination + 1.67 x aspartate aminotransferase and platelet ratio index (APRI) + 0.0029 x body-surface-area-adjusted left liver lobe volume (BSA adLLV) - 6.57 (log-likelihood chi-square P<0.05, pseudo-R2=0.59). The area under the receiver operator characteristic curve of age at MR examination, APRI, BSA adLLV and the combined index for prediction of cirrhosis were 0.91, 0.86, 0.83 and 0.94, respectively. The optimal cut-off value (sensitivity and specificity) of age at MR examination, APRI, BSA adLLV and combined index were 132 (86% and 92%), 1.3 (91% and 85%), 855.5 (96% and 62%) and 0.689 (91% and 92%). The accuracy of age at MR examination, APRI, BSA adLLV and combined index were 89%, 89%, 83% and 91%, respectively. CONCLUSION: A combined noninvasive index of age, aspartate aminotransferase and platelet ratio index, and the body-surface-area-adjusted left liver lobe volume measured from MR images is a potential marker of liver cirrhosis in children with biliary atresia.

Intracerebral large artery disease in Aicardi-Goutières syndrome with TREX1 mutation: a case report.

We report a patient diagnosed with Aicardi-Goutières syndrome (AGS) with homozygous TREX1 gene mutation. Her magnetic resonance angiography (MRA) showed intracerebral large artery disease, which was rarely reported in the past in TREX1 AGS patients. Her younger sister also had homozygous TREX1 gene mutation and died of necrotizing enterocolitis. Intracerebral large artery involvement has been seen as a particular feature of SAMHD1-related disease. Our patient also had arthropathy, which is a finding more commonly mentioned in SAMHD1-related diseases. The observations in our case may contribute to our understanding of the pathogenetic mechanism of TREX1 AGS, involving the intracerebral large arteries, arthropathy, and possibly the gastrointestinal tract.

Transient elastography correlated with diffusion-weighted magnetic resonance imaging and cholestatic complications.

BACKGROUND/PURPOSE: The study aim to investigate the correlation between diffusion-weighted magnetic resonance imaging (DW-MRI) and transient elastography (TE) liver fibrosis findings in children with cholestatic liver diseases, and the utility of TE findings to predict cholestatic complications in children. METHODS: This cross-sectional study enrolled 36 cholestatic children (21 boys and 15 girls). All study subjects underwent TE and DW-MRI studies to assess liver stiffness. All study subjects were followed prospectively, and their cholestatic complications were analyzed. The optimum cut-off TE value for the prediction of cholestatic complications was determined by receiver operating characteristic (ROC) analysis. RESULTS: A significant negative correlation between liver stiffness measurements (LSMs) and right-liver-to-psoas apparent diffusion coefficient ratios (LTPARs) was found in the study cohort (correlation coefficient = -0.52, p = 0.001). An LSM cut-off > 8.6 kPa was optimal for predicting complications of cholestasis in 6 months of this cohort (p < 0.001). Survival analysis revealed that an LSM of >8.6 kPa was significantly predictive of cholestatic complications in 6 months (hazard ratio = 4.89; 95% CI = 1.41-16.97; p = 0.01). CONCLUSION: TE and DW-MRI findings showed a similar ability to predict liver fibrosis in cholestatic children. The LSMs measured by TE are predictive of the occurrence of cholestatic complications in 6 months in children with cholestatic liver diseases.

Effect of iron overload on impaired fertility in male patients with transfusion-dependent beta-thalassemia.

BackgroundTo investigate the fertility of male patients with transfusion-dependent beta-thalassemia, and to use magnetic resonance imaging (MRI) as a novel method to assess the iron overload status of testis in such patients.MethodsTwenty-one male patients with transfusion-dependent beta-thalassemia and five normal male controls enrolled in this study. Hormonal profiles, iron levels, MRI testicular dimension, MRI T2 values, parameters for sperm quality, and sperm DNA fragmentation (SDF) of participants were measured.ResultsThe MRI T2 values of the testis were significantly lower in transfusion-dependent beta-thalassemia patients than in normal controls (P=0.027), and they correlated to serum ferritin levels in all enrolled subjects (R2=0.258, P=0.008). There were significantly lower sperm concentrations (P=0.037), a lower percentage of sperm with normal morphology (P=0.001), and a higher percentage of SDF (P=0.009) in transfusion-dependent beta-thalassemia patients without hypogonadotropic hypogonadism and with spontaneous spermatogenesis compared with normal controls. The percentage of SDF was significantly correlated with serum ferritin levels in transfusion-dependent beta-thalassemia male patients with spontaneous spermatogenesis (R2=0.48, P=0.009).ConclusionOur study is the first demonstration of iron deposition in the testis of patients with transfusion-dependent beta-thalassemia based on imaging, and such findings might explain the high prevalence of impaired fertility in above patients with normal pituitary function.

Microstructural changes of brain in patients with aromatic L-amino acid decarboxylase deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is an uncommon inherited neurometabolic disease. The clinical presentations and MR findings in children with AADC deficiency were investigated. Total 12 children (6 boys, 6 girls), aged from 9 to 50 months (mean, 23 ±13 months), with AADC deficiency, were enrolled for analysis. Of 12 patients enrolled, clinical presentations included global developmental delay with generalized hypotonia in 12 (100%), dystonia in 12 (100%), oculogyric crisis in 12 (100%), and excessive sweating in 8 (67%). Sleep problem was also found in 4 (33%). Of 15 MR examinations, the major changes included 6 (40%) with diffusely prominent bilateral frontal sulci, 10 (67%) with prominent frontal horns, and 12 (80%) with hypomyelination. In AADC patients, the frontal horn was significantly widened (P < 0.01), and the volume of caudate nucleus was also significantly smaller than that of controls (P = 0.02). The ratios of thickness of the splenium to that of the genu of corpus callosum were also significantly increased (P < 0.01). There was also significant decrease of fiber density indices in major white matter fiber tracts. Using Tract-Based Spatial Statistics approach, we also revealed significant change in major fiber tracts related to language function and motor function. In conclusion, the present study indicated that AADC deficiency may have significant impact on brain development, especially the frontal lobe and fiber tracts related to language function and motor function. Long-term follow-up of brain MRI in patients with AADC deficiency may clarify the possible effect of AADC deficiency on brain development. Hum Brain Mapp 38:1532-1540, 2017. © 2016 Wiley Periodicals, Inc.

The long-term efficacy and tolerability of oral deferasirox for patients with transfusion-dependent ß-thalassemia in Taiwan.

Deferasirox is a novel once-daily, oral iron chelator. The aim of this study was to evaluate the long-term efficacy and tolerability of deferasirox in Taiwanese patients with transfusion-dependent ß-thalassemia who have been treated with deferasirox for 7 years. Taiwanese patients aged ≥2 years with transfusion-dependent ß-thalassemia whose serum ferritin levels were ≥1000 ng/mL and had started deferasirox treatment since December 2005 at the National Taiwan University Hospital were enrolled. Sixty patients were recruited for analysis, and 11 (18.3 %) patients discontinued deferasirox during the study. In the 42 patients included in the efficacy analysis, the mean serum ferritin levels decreased significantly by 2566 ng/mL after 7 years of treatment (P < 0.001). Forty-one of these patients received a cardiac T2* evaluation after 3 years of deferasirox treatment, and the mean cardiac T2* value increased significantly from 30.6 ± 16.6 to 45.9 ± 22.6 ms after 7 years of deferasirox treatment (P < 0.001). Deferasirox-related adverse events assessed by investigators were reported in 46 (76.7 %) patients. The most common adverse events related to deferasirox were skin rashes (n = 29, 48.3 %), followed by abdominal pain (n = 23, 38.3 %) and diarrhea (n = 16, 26.7 %). Most adverse events were manageable. This study demonstrated that long-term treatment with deferasirox was effective in improving iron overload, including cardiac iron overload, in patients with transfusion-dependent ß-thalassemia. Deferasirox was well tolerated; however, the incidences of common adverse events related to deferasirox appeared higher in our Taiwanese patients than other studies.

Hepatic ADC map as an adjunct to conventional abdominal MRI to evaluate hepatic fibrotic and clinical cirrhotic severity in biliary atresia patients.

OBJECTIVES: Hepatic apparent diffusion coefficient (ADC) values and ADC-related indices were correlated with the Mayo risk score for primary biliary cirrhosis (MRSPBC) and METAVIR scores of liver specimens to determine the clinical and pathological significance of diffusion-weighted magnetic resonance imaging (DWMRI). METHODS: Thirty-two patients with biliary atresia (BA; mean age 461 days, range 11-4616 days) received magnetic resonance examinations from March 2009 to August 2013. A free-breathing DWMRI sequence was performed with the single-shot echo-planar imaging technique with b = 0 and 500 s/mm(2) in all 32 BA patients and 24 controls. We used the ordinal logistic regression test and Spearman rank correlation test to analyse the relationships between the MRSPBC and METAVIR fibrosis scores and right liver-to-psoas ADC ratios (LTPARs). RESULTS: BA patients had significantly lower LTPARs in both hepatic lobes than controls (p < 0.01). Right LTPARs, showing moderate intraobserver agreement (intraclass correlation coefficient = 0.736) and interobserver reliability (intraclass correlation coefficient = 0.659), were negatively correlated with MRSPBC and METAVIR fibrosis scores (R(2) = 0.398, p = 0.024 and R(2) = 0.628, p < 0.001, respectively). CONCLUSION: Right LTPARs may be used for long-term follow-up of cirrhosis severity in BA patients. KEY POINTS: • Hepatic ADC values by DWI correlates well with clinical/pathologic fibrosis scores • Periodic, non-invasive, quantitative imaging follow-up of patients with biliary cirrhosis is feasible • Information on cirrhosis severity could help decide on management options in children with BA • ADC values may be useful in this regard.

The relationship of neuroimaging findings and neuropsychiatric comorbidities in children with tuberous sclerosis complex.

BACKGROUND/PURPOSE: To clarify the relationship between neuroimaging findings, neuropsychiatric comorbidities, and epilepsy in patients with tuberous sclerosis complex (TSC) in Taiwan. METHODS: Medical records from 32 patients with TSC were retrospectively reviewed, including mutational analysis, neuroimaging findings, electroencephalogram findings, and neuropsychiatric comorbidities. RESULTS: Of these patients, six (18.75%) were diagnosed to have autism spectrum disorders (ASD), and 10 (31.25%) were diagnosed to have attention-deficit-hyperactivity disorder. In the latter patients, there were no differences in the regional distribution of tuber burden. In addition to a high prevalence of cystic-like tubers, tubers in insular and temporal areas were associated with ASD. Nonsense mutations in the TSC2 gene group had a correlation with autistic behavior. In 26 (81.25%) patients with a history of epilepsy, infantile spasms and partial seizures were the predominant type of epilepsy. Most of them developed seizures prior to age 1 year. CONCLUSION: ASD is a common comorbidity in TSC. Cortical tubers in the temporal lobe and insular area were associated with ASD. The presence of cystic-like tubers on magnetic resonance imaging may also offer a structural marker for ASD in TSC.

Diabetes mellitus in patients with thalassemia major.

BACKGROUND: Diabetes mellitus is a major endocrinopathy for patients with thalassemia major. Although diabetes mellitus is multifactorial, iron loading is its primary cause and its management poses a clinical challenge. Detecting the pre-diabetes stage is critical because clinical diabetes can potentially be reversed or prevented. PROCEDURE: Patients with thalassemia major who received regular blood transfusion therapy from 1994 to 2010 were evaluated for the incidence of diabetes mellitus and glucose dysregulation. The association between patients' clinical, biochemical, and image parameters was also evaluated. RESULTS: The patients with diabetes were significantly older, had higher ferritin levels, a smaller pancreas volume, and lower cardiac T2* magnetic resonance imaging (MRI) values than the patients without diabetes. The pancreas T2* MRI values were higher in the patients without diabetes, but the difference was not statistically significant. The liver iron concentration did not differ between the patients with and without diabetes. The prevalence of hepatitis C infection and hypogonadism was also higher in the patients with diabetes. In the patients without diabetes, the cardiac T2* MRI values were higher in patients with normal fasting glucose levels (P = 0.03), and the homeostasis model assessment of insulin resistance level was associated with hepatitis C infection (P = 0.024, r = 0.32) and hypogonadism (P = 0.034, r = 0.301). CONCLUSIONS: Fasting glucose and insulin levels were appropriate screening tools for evaluating glucose dysregulation and complemented the MRI findings. The cardiac T2* and pancreas volumes were significant predictors of diabetes.

Using volume index and lateral hepatic angle to differentiate biliary atresia from TPN-associated cholestasis.

OBJECTIVES: Differential diagnosis between biliary atresia (BA) and total parenteral nutrition-associated cholestasis (TPN-AC) and early treatment for cholestatic infants are challenges for evaluating neonatal or infantile cholestasis. The aim of our retrospective study was to apply noninvasive indices of magnetic resonance images to differentiate BA from TPN-AC. METHODS: A total of 44 patients diagnosed as having BA (n = 30) or TPN-AC (n = 14) were included in the present retrospective study and underwent abdominal magnetic resonance imaging to evaluate the possibility of BA. The left lateral hepatic angle was determined from the coronal image of the left portal vein and portal vein of segment II. Adjusted volume indices of the right hepatic lobe (AVIR) and left lateral segment (AVILL) were calculated as the product of 3 diameters (centimeters) divided by each patient's body weight. RESULTS: The left lateral hepatic angles of patients with BA (74°â€Š±â€Š21°) were significantly larger than for patients with TPN-AC (33°â€Š±â€Š9°) and controls (36°â€Š±â€Š5°, P < 0.05). AVILL of the BA (0.037 ±â€Š0.012 cm/g) and TPN-AC groups (0.042 ±â€Š0.030 cm/g) were not significantly different (P = 0.61) but were significantly larger than for controls (0.020 ±â€Š0.011 cm/g) (P < 0.05). The right hepatic lobe to left lateral hepatic segment ratio (RLR) of patients with BA was significantly (P < 0.05) smaller (1.61 ±â€Š0.58) than for patients with TPN-AC (3.08 ±â€Š2.43) and controls (2.98 ±â€Š0.92). Patients with BA could have relative sparing and selective enlargement of the left lateral liver with a resultant lobar difference and blunt left lateral hepatic angle. CONCLUSIONS: Noninvasive indices of lobar difference and left lateral hepatic angle help differentiate patients with BA from those with TPN-AC.

Neuroimaging and electroencephalographic changes after vagus nerve stimulation in a boy with medically intractable myoclonic astatic epilepsy.

Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta-gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria-fornix, indicating improved diffusion of the white matter tract, and (18)F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social-emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria-fornix and glucose metabolism in MAE.

Developmental change of brain volume in Rett syndrome in Taiwan.

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.

The magnetic resonance imaging and age-adjusted matrix metalloproteinase-7 assist the diagnosis of biliary atresia.

BACKGROUND: We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants. METHODS: In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed. RESULTS: The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1 ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1 ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio. CONCLUSION: The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants.

Large parietal midline defect with unusual ridge-like structure at the rim and persistent falcine sinus.

BACKGROUND: Midline cranial defects can be divided into lesions with intracranial tissue herniation (cranium bifidum cysticum) and lesions mainly with ossification failure (cranium bifidum occultum). Herniated cephaloceles mostly require surgical resection, while persisted parietal foramina might become smaller with age. CLINICAL CASE: Here, we report a neonate with large symmetric midline skull defect at high parietal area. A mild bulging mass was noticed. Interestingly, unlike sac herniation, it was surrounded by bony ridges extended from the rim of the calvarial defect, which suggests aberrant ossification. Persistent falcine sinus was also detected. At the corrected age of 11 months, the size of the skull defect had decreased spontaneously, favoring the diagnosis of parietal bone ossification defect. Potential mechanisms resulting in the special appearance of skull bone were discussed. CONCLUSION: Incomplete closing of the parietal foramina might be expected due to the aberrant ridge formation. We suggest protective measures for the calvarial defect.

Novel heterozygous tissue-nonspecific alkaline phosphatase (TNAP) gene mutations causing lethal perinatal hypophosphatasia.

Hypophosphatasia is a rare inherited disorder characterized by poor bone mineralization and deficiency of alkaline phosphatase activity. It is caused by mutations in the liver/bone/kidney alkaline phosphatase gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNAP), which displays many allelic heterogeneities, leading to different clinical phenotypes. This study reports the case of a patient diagnosed with lethal perinatal hypophosphatasia. His gene analysis showed compound heterozygocity of two novel mutations: c.650delTinsCTAA and c.984_986delCTT, which led to p.217delVinsAK and p.328delF, respectively. The two mutations originated separately from his parents, consistent with autosomal recessive perinatal hypophosphatasia. For these two novel mutations, we analyzed their functions through three-dimensional structural analysis. This revealed that V217 is located in the ß-sheet area, V217 is deleted, and insertion of alanine and lysine alter the secondary structure, causing instability in the hydrophobic region, which may influence the metal-binding vicinity. This mutant structure loses its catalytic activity. Deletion of 328F also results in protein structural alteration and affects TNAP functions. These results may provide an explanation of the two novel mutated alleles correlating with the lethal phenotype of our patient. In conclusion, we demonstrated the case of a patient with lethal perinatal hypophosphatasia caused by two novel heterozygous mutations.

Less-invasive MR indices of clinically evident esophageal variceal bleeding in biliary atresia patients.

BACKGROUND/PURPOSE: Esophageal variceal hemorrhaging is potentially life threatening for long-term survivors of biliary atresia. We evaluated the feasibility of less-invasive parameters for predicting the presence of clinically significant esophageal variceal bleeding in biliary atresia patients. METHODS: A total of 30 patients aged 108-5314 days (median = 285 days) with biliary atresia underwent a magnetic resonance examination with fast spin-echo T2-weighted imaging and spin-echo, T1-weighted images with fat saturation after use of a contrast medium on a 1.5-tesla scanner. The splenic length-platelet ratio was divided by the each patient's body height (m) to produce the corrected splenic length-platelet ratios. In addition, the splenic volume index-to-platelet count ratio was divided by the patient's body weight (kg) to produce a corrected ratio. RESULTS: The corrected splenic length-platelet ratio was more significantly increased in 21 patients with esophageal variceal bleeding (Group A) than in nine patients without variceal bleeding [(Group B) 0.98 ± 0.64 vs. 0.44 ± 0.18, p < 0.01]. The splenic volume index-to-platelet count ratio corrected by body weight was significantly larger in Group A (510.7 ± 536.2) than in Group B (148.1 ± 88.9, p < 0.01). CONCLUSION: Less-invasive indices, including the corrected splenic length platelet ratio and the splenic volume index-to-platelet count ratio, may be valuable predictors of esophageal variceal bleeding in patients with biliary atresia.