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.

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.

Correlation of dystonia severity and iron accumulation in Rett syndrome.

Individuals with Rett syndrome (RTT) commonly demonstrate Parkinsonian features and dystonia at teen age; however, the pathological reason remains unclear. Abnormal iron accumulation in deep gray matter were reported in some Parkinsonian-related disorders. In this study, we investigated the iron accumulation in deep gray matter of RTT and its correlation with dystonia severity. We recruited 18 RTT-diagnosed participants with MECP2 mutations, from age 4 to 28, and 28 age-gender matched controls and investigated the iron accumulation by susceptibility weighted image (SWI) in substantia nigra (SN), globus pallidus (GP), putamen, caudate nucleus, and thalamus. Pearson's correlation was applied for the relation between iron accumulation and dystonia severity. In RTT, the severity of dystonia scales showed significant increase in subjects older than 10 years, and the contrast ratios of SWI also showed significant differences in putamen, caudate nucleus and the average values of SN, putamen, and GP between RTT and controls. The age demonstrated moderate to high negative correlations with contrast ratios. The dystonia scales were correlated with the average contrast ratio of SN, putamen and GP, indicating iron accumulation in dopaminergic system and related grey matter. As the first SWI study for RTT individuals, we found increased iron deposition in dopaminergic system and related grey matter, which may partly explain the gradually increased dystonia.

Long-term Outcome of Schilder Disease Treated With Interferon-ß.

Schilder disease, also termed diffuse myelinoclastic sclerosis, is characterized by a large demyelinating lesion involving 1 or both sides of the centrum semiovale of the cerebral hemispheres. It often presents with tumorlike features and poses a diagnostic challenge. Schilder disease can be monophasic or relapsing, and disease-modifying therapy for the latter scenario is largely empirical. Here, we report a 14-year-old girl with relapsing Schilder disease within 1 year after disease onset. She has been followed-up for nearly 10 years and remains in sustained remission ever since interferon-ß therapy was prescribed after the second attack. In this case study, it is suggested that interferon-ß may induce long-term remission in relapsing Schilder disease and is therefore worth considering in this regard.

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.

A multidisciplinary team care approach improves outcomes in high-risk pediatric neuroblastoma patients.

We assessed the impact of a multidisciplinary team care program on treatment outcomes in neuroblastoma patients. Newly diagnosed neuroblastoma patients received treatment under the Taiwan Pediatric Oncology Group (TPOG) N2002 protocol at the National Taiwan University Hospital beginning in 2002. A multidisciplinary team care approach that included nurse-led case management for patients treated under this protocol began in January 2010. Fifty-eight neuroblastoma patients, including 29 treated between 2002 and 2009 (Group 1) and 29 treated between 2010 and 2014 (Group 2), were enrolled in the study. The 5-year overall survival (OS) and event-free survival (EFS) rates for all 58 patients were 59% and 54.7%, respectively. Group 2 patients, who were treated after implementation of the multidisciplinary team care program, had better 3-year EFS (P = 0.046), but not OS (P = 0.16), rates than Group 1 patients. In a multivariate analysis, implementation of the multidisciplinary team approach was the only significant independent prognostic factor for neuroblastoma patients. In further subgroup analyses, the multidisciplinary team approach improved EFS, but not OS, in patients with stage 4 disease, those in the high-risk group, and those with non-MYCN amplified tumors. These data indicate a multidisciplinary team care approach improved survival outcomes in high-risk neuroblastoma patients. However, further investigation will be required to evaluate the long-term effects of this approach over longer follow-up periods.

Breath-hold spin echosequence for assessing liver iron content.

OBJECTIVE: To compare a multiple breath-hold, multiecho, multiplanar spin-echo (BHMEMPSE) magnetic resonance (MR) sequence with a TR of 300ms with a traditional multiecho, multiplanar spin-echo (MEMPSE) MR sequence for assessing liver iron content. MATERIALS AND METHODS: This study was approved by the institutional review board; informed consent was waived. Liver R2 measurement was derived from the mono-exponential model by BHMEMPSE and MEMPSE MR sequences of a 1.5T MR machine in 30 thalassemia patients (9men, 21women, aged 27.7±6.8years). Hepatic iron contents were estimated using Ferriscan in all patients. The inter- and intra-observer agreement of the 2 MR sequences was also evaluated. RESULTS: MEMPSE R2 values significantly correlated with Ferriscan iron content values (r=0.895, p<0.001) and serum ferritin concentration (r=0.661, p<0.001). BHMEMPSE R2 values significantly correlated with Ferriscan values (r=0.914, p<0.001) and serum ferritin concentration (r=0.608, p<0.001). The distribution of MEMPSE R2 values against BHMEMPSE R2 values revealed an excellent linear relationship (r=0.978, p<0.001). The inter- and intra-observer agreement of the 2 MR sequences was excellent, with an interclass correlation coefficient exceeding 0.9. The distribution of Ferriscan against BHMEMPSE R2 values revealed a curvilinear relationship (r=0.935, p<0.001). CONCLUSIONS: The BHMEMPSE sequence exhibited comparable estimation for assessing liver iron content, comparable repeatability and a shorter acquisition time compared with the MEMPSE sequence. The BHMEMPSE sequence can serve as an adjunctive sequence to assess liver iron content.

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.

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.

Recurrent bacterial meningitis associated with Mondini dysplasia.

We reported two cases of recurrent meningitis and both of them had Mondini dysplasia, which provides a link between the brain and inner ear and is associated with cerebrospinal fluid, otorrhea/rhinorrhea, hearing impairment, and recurrent meningitis. Patients who have hearing impairment and recurrent meningitis should be evaluated for the possibility of this congenital dysplasia, and early diagnosis and prompt surgical intervention may prevent further episodes.

Management of congenital cystic adenomatoid malformation and bronchopulmonary sequestration in newborns.

BACKGROUND: Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental anomalies. Early surgical excision is becoming an increasingly common option. We investigated the clinical features and management of patients with CCAM and BPS at the National Taiwan University Hospital. METHODS: We conducted a retrospective review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995 to January 2008. Prenatal examination, postnatal presentation, management and patient outcome were analyzed. We also propose a concise algorithm for the practical management of these conditions. RESULTS: Sixteen patients were recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%) with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed antenatally at a median gestational age of 20 weeks. Eleven (69%) patients underwent surgical resection before 6 months of age because of respiratory distress or repeated pulmonary infection. There were no surgery-related complications among the seven patients who underwent early surgery within 1 month of age. Five (31%) patients remained asymptomatic and did not undergo surgery. All patients survived with no limitations to daily activity during follow-up periods of 1-8 years. CONCLUSION: The high proportion of mixed-type lesions suggests that CCAM and BPS may share the same developmental ancestry. Early surgical resection within 1 month of age is safe in symptomatic patients.

Hypocalcemia and tetany caused by vitamin D deficiency in a child with intestinal lymphangiectasia.

Primary intestinal lymphangiectasia is a rare disease of children, which is characterized by chronic diarrhea and complicated with malnutrition, including fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age. She presented initially with chronic diarrhea at 4 months of age. Generalized edema with hypoalbuminemia frequently occurred despite regular albumin supplements. Multiple vitamins initially were not supplied regularly. Episodes of tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low serum 25-hydroxy vitamin D concentration (< 12.48 mmol/L, the detection limit)] and secondary hyperparathyroidism were confirmed via blood testing. Vitamin D supplementation for 3 months improved her bone density, secondary hyperparathyroidism and frequent tetany. Vitamin D status should be monitored in patients with intestinal lymphangiectasia.

Mycoplasma pneumoniae--associated transverse myelitis and rhabdomyolysis.

Mycoplasma pneumoniae is a common cause of respiratory tract infection. Extrapulmonary manifestations of M. pneumoniae infection are also common. The present case is that of a previously healthy 4-year-old boy who displayed a novel simultaneous onset of both acute rhabdomyolysis and transverse myelitis associated with an infection of M. pneumoniae. He had no preceding symptoms or signs of respiratory tract infection. Intravenous immunoglobulin (1 g/kg per day) for 2 days was prescribed initially for the deterioration of neurologic condition. His rhabdomyolysis resolved without complication, but neurologic sequelae remained during 2 years of follow-up. Evaluation for M. pneumoniae infection is recommended in patients with idiopathic rhabdomyolysis and transverse myelitis, even if in the absence of antecedent respiratory symptoms.

Spontaneous multiseptated cystic pneumomediastinum in a term newborn.

Pneumomediastinum usually occurs after assisted ventilation. Spontaneous pneumomediastinum without preceding assisted ventilation, and presenting as a huge cystic mass in a term newborn infant has rarely been reported. We report a term baby who developed respiratory distress at 2 days of age. A huge cystic tumor of the thymus or a congenital mediastinal cystic tumor was initially suggested by chest radiography and computed tomography. Follow-up chest film revealed a "spinnaker sail sign" which is a typical radiographic presentation of pneumomediastinum.

Persistent pulmonary hypertension in a neonate with vein of Galen arteriovenous malformation.

Vein of Galen aneurysmal malformation (VGAM) often leads to death in the neonatal period, mainly due to congestive heart failure. Chronic and excessive pulmonary flow in utero and postnatally is attributed to large VGAM and right ventricular overload. We report a male neonate with VGAM complicated by severe heart failure and persistent pulmonary hypertension. Endovascular coil embolization of VGAM was performed, resulting in improvement of congestive heart failure; however, severe persistent pulmonary hypertension led to death 2 days after the embolization. Postmortem examination showed marked right and left ventricular hypertrophy and impressive muscular thickening of intra-alveolar arterioles. Neonatal embolization seems to be beneficial only in babies without suprasystemic pulmonary hypertension. Therefore, early delivery and repair of VGAM should be considered before the onset of persistent pulmonary hypertension.

Diffusion tensor images in children with early-treated, chronic, malignant phenylketonuric: correlation with intelligence assessment.

BACKGROUND AND PURPOSE: Diffusion tensor (DT) images can provide information about the nature of white matter changes, including axonal loss and demyelination. We applied DT imaging to verify white matter changes in patients with malignant phenylketonuria (PKU) and to correlate the findings with clinical intelligence quotients (IQs). METHODS: We compared DT images with T2-weighted images in 12 patients with early-treated, chronic, stable malignant PKU and 12 age-matched control subjects. DT parameters included first, second, and third eigenvalues (EV1-3), apparent diffusion coefficients (ADCs), and fractional anisotropy (FA). Regions of interest were placed the frontoparietal, parieto-occipital, frontal and central white matter and in the anterior and posterior corpus callosum. Eight patients older than 3 years underwent IQ assessment including verbal, performance, and full-scale IQ tests. RESULTS: In the eight patients older than 3 years, no definite abnormal signal intensity changes were found on T2-weighted images. EV2, EV3, and FA of the parieto-occipital white matter were significantly different in patients and control subjects older than 3 years. EV3 and ADC of the parieto-occipital white matter were significantly and negatively correlated with verbal IQ (r = -0.79, P = .04) and performance IQ (r = -0.93, P = .03). FA of the parieto-occipital central white matter was positively correlated with verbal IQ (r = 0.75, P = .05). CONCLUSION: Though treated early, patients with chronic, stable malignant PKU had abnormal DT findings in the parieto-occipital central white matter. EV2, EV3, and FA maps are potential tools for demonstrating brain changes due to malignant PKU.

Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report.

BACKGROUND: In tuberous sclerosis (TS), tubers usually involve the white matter. Diffusion tensor (DT) images are used to demonstrate white-matter tracts. OBJECTIVE: To determine the changes in DT indices in supratentorial tubers and associated changes in the white-matter tracts adjacent to tubers in patients with TS. MATERIALS AND METHODS: The DT imaging indices, including first, second and third eigenvalues (EVs), apparent diffusion coefficients (ADCs), and fractional anisotropy (FA) in the white-matter lesions of tubers, were assessed in seven patients with TS exhibiting developmental delay and compared with controls. RESULTS: EV1, EV2, EV3, ADC and FA of the white-matter lesions of tubers were significantly different from contralateral unremarkable regions of the brain and from controls (P<0.05). The number of frontal and parietal tubers was significantly negatively correlated with EV1 of the superior longitudinal fasciculi of TS patients (r=-0.60, P =0.04). In addition, TS patients had significantly larger ADCs in the corona radiata and sagittal stratum than the control subjects. EV3s of the inferior longitudinal fasciculus and sagittal stratum were significantly more increased in the TS patients than in the control subjects. CONCLUSIONS: EV1, EV2, EV3, ADC and FA maps are potential tools for demonstrating cerebral white-matter changes owing to TS.