Brain tumors are the most common solid tumors in childhood. There is the need for biomarkers of residual disease, therapy response and recurrence. Cerebrospinal fluid (CSF) is a source of brain tumor ...biomarkers. We analyzed the proteome of waste CSF from extraventricular drainage (EVD) from 29 children bearing different brain tumors and 17 controls needing EVD insertion for unrelated causes. 1598 and 1526 proteins were identified by liquid chromatography-coupled tandem mass spectrometry proteomics in CSF control and brain tumor patients, respectively, 263 and 191 proteins being exclusive of either condition. Bioinformatic analysis revealed promising protein biomarkers for the discrimination between control and tumor (TATA-binding protein-associated factor 15 and S100 protein B). Moreover, Thymosin beta-4 (TMSB4X) and CD109, and 14.3.3 and HSP90 alpha could discriminate among other brain tumors and low-grade gliomas plus glyoneuronal tumors/pilocytic astrocytoma, or embryonal tumors/medulloblastoma. Biomarkers were validated by ELISA assay. Our method was able to distinguish among brain tumor vs non-tumor/hemorrhagic conditions (controls) and to differentiate two large classes of brain tumors. Further prospective studies may assess whether the biomarkers proposed by our discovery approach can be identified in other bodily fluids, therefore less invasively, and are useful to guide therapy and predict recurrences.
Cystic pancreatic lesions (CPLs) are frequently casual findings in radiological examinations performed for other reasons in patients with unrelated symptoms. As they require different management ...according to their histological nature, differential diagnosis is essential. Radiologist plays a key role in the diagnosis and management of these lesions as imaging is able to correctly characterize most of them and thus address to a correct management. The first step for a correct characterization is to look for a communication between the CPLs and the main pancreatic duct, and then, it is essential to evaluate the morphology of the lesions. Age, sex and a history of previous pancreatic pathologies are important information to be used in the differential diagnosis. As some CPLs with different pathologic backgrounds can show the same morphological findings, differential diagnosis can be difficult, and thus, the final diagnosis can require other techniques, such as endoscopic ultrasound, endoscopic ultrasound-fine needle aspiration and endoscopic ultrasound-through the needle biopsy, and multidisciplinary management is important for a correct management.
Summary
Magnetic resonance imaging (MRI) has proved to be an essential tool in the assessment of pituitary stalk lesions including lymphocytic infundibulo‐hypophysitis, Langerhans cell histiocytosis ...(LCH), germ cell tumours, nongerminomatous germ cell tumours, pituicytomas and other tumours, metastases from lymphoma or breast cancer, Wegener's hypophysitis, neurosarcoidosis and inflammatory infiltrations by infectious diseases. The diagnosis of lesions determining pituitary stalk thickness is challenging, and the identification of the underlying condition may require a long‐term follow‐up. Thus, clinicians should readily recognize that, when the diagnosis of central diabetes insipidus has been established, specific MRI sequences should be used in the assessment of the hypothalamic–pituitary region, and whole‐brain evaluation is recommended. For clinical practice, a timely diagnosis is advisable to avoid central nervous system damage, pituitary defects and the risk of dissemination of germ cell tumours or organ involvement by LCH. Proper aetiological diagnosis can be achieved via a series of steps that start with careful observation of several neuroimaging predictors and endocrine dysfunction and then progress to more sophisticated and advanced imaging techniques.
Purpose
In moyamoya vasculopathy, prolonged arterial transit time may increase the arterial spin labeling (ASL) signal heterogeneity, which can be quantitatively expressed by the spatial coefficient ...of variation of ASL-CBF (ASL-sCoV). The aim was to compare the accuracy of ASL-sCoV and ASL-CBF with dynamic susceptibility contrast (DSC)-CBF and time-to-peak (DSC-TTP) in the evaluation of perfusion changes and clinical outcome after encephalo-duro-arterio-myo-synangiosis (EDAMS) in pediatric moyamoya patients.
Methods
A total of 37 children with moyamoya vasculopathy (mean age 6.31 years (1.12–15.42)) underwent ASL and DSC perfusion imaging at 3T before and up to 24 months after EDAMS. Mean DSC-CBF, mean DSC-TTP, mean ASL-CBF, and ASL-sCoV were calculated in middle cerebral artery territories. Generalized linear model analyses were used to evaluate temporal variations of postoperative perfusion changes and to compare these variations between patients developing valid pial collateralization and those without angiographic improvement. Relationship between perfusion parameters and clinical outcome after surgery was tested using multivariate regression analysis.
Results
Significant reduction was observed after EDAMS for ASL-sCoV (
P
= .002; eta-squared (η
2
) = 0.247) and DSC-TTP (
P
< .001; η
2
= 0.415), whereas only a trend of increase was observed for DSC-CBF and ASL-CBF, with larger discrepancy before and 6 months after surgery. At last follow-up, children developing pial collateralization showed lower absolute ASL-sCoV (
P
= .002 Cohen’s d = 0.84) and DSC-TTP (
P
= .027; Cohen’s d = 0.64) and higher DSC-CBF (
P
= .002; Cohen’s d = − 0.55) compared with those without vascular improvement. Low preoperative and early post-surgical ASL-sCoV predicted better long-term neurological outcome (
P
< .001; ß = − 0.631).
Conclusions
ASL-sCoV may contribute to predict surgical outcomes in pediatric moyamoya patients undergoing EDAMS.
Abstract
The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously ...developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.
Background
Germinal matrix‐intraventricular hemorrhage (GMH‐IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the ...primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products.
Purpose/Hypothesis
To evaluate magnetic susceptibility of normal‐appearing white (WM) and gray matter regions in preterm neonates with and without GMH‐IVH.
Study Type
Retrospective case‐control.
Population
A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH‐IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH‐IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks).
Field Strength/Sequence
QSM at 1.5 Tesla.
Assessment
QSM analysis was performed for each brain hemisphere with a region of interest‐based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami).
Statistical Tests
Changes in magnetic susceptibility were explored using a one‐way analysis of covariance, according to GMH‐IVH severity (P < 0.05).
Results
In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH‐IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus ‐0.0014 ppm; P < 0.001), temporal WM (0.0011 versus ‐0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus ‐0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH‐IVH and controls (P = 0.236).
Data Conclusion
Paramagnetic susceptibility changes occur in several normal‐appearing WM regions of neonates with severe GMH‐IVH, likely related to the accumulation of hemosiderin/ferritin iron secondary to diffusion of extracellular hemoglobin from the ventricle into the periventricular WM.
Level of Evidence: 4
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2018;47:1199–1207.
Conventional T1- and T2-weighted magnetic resonance imaging (MRI) of the pancreas can vary significantly due to factors such as scanner differences and pulse sequence variations. This review explores ...T1 and T2 mapping techniques, modern MRI methods providing quantitative information about tissue relaxation times. Various T1 and T2 mapping pulse sequences are currently under investigation. Clinical and research applications of T1 and T2 mapping in the pancreas include their correlation with fibrosis, inflammation, and neoplasms. In chronic pancreatitis, T1 mapping and extracellular volume (ECV) quantification demonstrate potential as biomarkers, aiding in early diagnosis and classification. T1 mapping also shows promise in evaluating pancreatic exocrine function and detecting glucose metabolism disorders. T2* mapping is valuable in quantifying pancreatic iron, offering insights into conditions like thalassemia major. However, challenges persist, such as the lack of consensus on optimal sequences and normal values for healthy pancreas relaxometry. Large-scale studies are needed for validation, and improvements in mapping sequences are essential for widespread clinical integration. The future holds potential for mixed qualitative and quantitative models, extending the applications of relaxometry techniques to various pancreatic lesions and enhancing routine MRI protocols for pancreatic pathology diagnosis and prognosis.
The 2021 World Health Organization Classification of Tumors of the Central Nervous System, Fifth Edition (WHO-CNS5), has strengthened the concept of tumor grade as a combination of histologic ...features and molecular alterations. The WHO-CNS5 tumor type "Diffuse midline glioma, H3K27-altered," classified within the family of "Pediatric-type diffuse high-grade gliomas," incarnates an ideally perfect integrated diagnosis in which location, histology, and genetics clearly define a specific tumor entity. It tries to evenly characterize a group of neoplasms that occur primarily in children and midline structures and that have a dismal prognosis. Such a well-defined pathological categorization has strongly influenced the pediatric oncology community, leading to the uniform treatment of most cases of H3K27-altered diffuse midline gliomas (DMG), based on the simplification that the mutation overrides the histological, radiological, and clinical characteristics of such tumors. Indeed, multiple studies have described pediatric H3K27-altered DMG as incurable tumors. However, in biology and clinical practice, exceptions are frequent and complexity is the rule. First of all, H3K27 mutations have also been found in non-diffuse gliomas. On the other hand, a minority of DMGs are H3K27 wild-type but have a similarly poor prognosis. Furthermore, adult-type tumors may rarely occur in children, and differences in prognosis have emerged between adult and pediatric H3K27-altered DMGs. As well, tumor location can determine differences in the outcome: patients with thalamic and spinal DMG have significantly better survival. Finally, other concomitant molecular alterations in H3K27 gliomas have been shown to influence prognosis. So, when such additional mutations are found, which one should we focus on in order to make the correct clinical decision? Our review of the current literature on pediatric diffuse midline H3K27-altered DMG tries to address such questions. Indeed, H3K27 status has become a fundamental supplement to the histological grading of pediatric gliomas; however, it might not be sufficient alone to exhaustively define the complex biological behavior of DMG in children and might not represent an indication for a unique treatment strategy across all patients, irrespective of age, additional molecular alterations, and tumor location.
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal ...disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD.
We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 -0.63 to 1.75 ml/min/1.73 m2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio HR 95% CI adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 0.127 to 0.742, p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR 95% CI: 0.121 0.017 to 0.866, p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size.
In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4.
ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12.
De novo DDX3X variants account for 1-3% of syndromic intellectual disability (ID) in females and have been occasionally reported in males. Furthermore, somatic DDX3X variants occur in several ...aggressive cancers, including medulloblastoma. We report three unrelated females with severe ID, dysmorphic features, and a common brain malformative pattern characterized by malformations of cortical development, callosal dysgenesis, basal ganglia anomalies, and midbrain-hindbrain malformations. A pilocytic astrocytoma was incidentally diagnosed in Patient 1 and trigonocephaly was found in Patient 2. With the use of family based whole exome sequencing (WES), we identified three distinct de novo variants in DDX3X. These findings expand the phenotypic spectrum of DDX3X-related disorders, demonstrating unique neuroradiological features resembling those of the tubulinopathies, and support a role for DDX3X in neuronal development. Our observations further suggest a possible link between germline DDX3X variants and cancer development.
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