Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.

Background: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach.

Feasibility and antitumour activity of the FGFR inhibitor erdafitnib in three paediatric CNS tumour patients.

Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively.

Lethal Encephalopathy in an Infant with Hypophosphatasia despite Enzyme Replacement Therapy.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization-associated alkaline phosphatase gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6)-responsive seizures due to impaired cerebral B6 passage. Since the introduction of enzyme replacement therapy (ERT), skeletal manifestations and B6-responsive seizures were reported to improve significantly.

Targeting fibroblast growth factor receptors to combat aggressive ependymoma.

Ependymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN.

Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis.

Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM.

Cerebrospinal Fluid Penetration and Combination Therapy of Entrectinib for Disseminated -Fusion Positive Pediatric High-Grade Glioma.

Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination with other treatment modalities such as intrathecal therapy, radiotherapy and other targeted agents is missing.

Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities.

Diffuse gliomas with K27M histone mutations (H3K27M glioma) are generally characterized by a fatal prognosis, particularly affecting the pediatric population. Based on the molecular heterogeneity observed in this tumor type, personalized treatment is considered to substantially improve therapeutic options. Therefore, clinical evidence for therapy, guided by comprehensive molecular profiling, is urgently required.

Hand MRI and the Greulich-Pyle atlas in skeletal age estimation in adolescents.

Objective: To evaluate the feasibility of hand MRI in age assessment in adolescents using the Greulich-Pyle (GP) atlas criteria.

Materials And Methods: Two radiologists, who were blinded to the study subjects' chronologic ages, semi-objectively evaluated 1.5-T MRIs of the left hands of ten patients (13.

Childhood onset temporal lobe epilepsy: Beyond hippocampal sclerosis.

Objective: Hippocampal Sclerosis (HS) is widely recognized as a significant underlying cause of drug-resistant temporal lobe epilepsy (TLE) in adults. In contrast, HS is a rare finding in pediatric surgical series, and a higher incidence of HS associated with cortical dysplasia (i.e.

MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy.

Unlabelled: Infantile movement disorders are rare and genetically heterogeneous. We set out to identify the disease-causing mutation in siblings with a novel recessive neurodegenerative movement disorder. Genetic linkage analysis and whole-exome sequencing were performed in the original family.

Intracranial hypertension in siblings with infantile hypercalcemia.

Background: Idiopathic intracranial hypertension is a clinical condition with elevated intracranial pressure of uncertain etiology. Although various underlying causes are suspected and familial occurrence has also been reported, however, it still remains an unexplained phenomenon.

Case Report: We report the case of dizygotic siblings with a known CYP24A1 mutation resulting in chronic hypercalcemia and impairment of kidney function.

Trabectedin has promising antineoplastic activity in high-grade meningioma.

Background: Meningiomas are common intracranial tumors arising from the meninges and usually are benign. However, a few meningiomas have aggressive behavior and, for such patients, effective treatment options are needed. Trabectedin is a novel, marine-derived, antineoplastic agent that has been approved and is used routinely as therapy for advanced soft tissue sarcoma and ovarian cancer.

Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27.

Introduction: Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27.

Diagnostic pitfalls in fetal brain MRI.

Recent technological advances in fetal magnetic resonance imaging (MRI) and increased reliability of MRI in depicting abnormalities and lesions, especially in the central nervous system, are increasingly bringing up challenging issues with regard to accurate diagnosis. There are also pitfalls not only attributable to image acquisition but also in clinical interpretation. The misinterpretation of findings because of insufficient knowledge about fetal brain development as visualized by MRI may also be regarded as an important limitation of fetal MRI.

CT-MR image data fusion for computer-assisted navigated surgery of orbital tumors.

Purpose: To demonstrate the value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative assessment of orbital tumors, and to present, particularly, CT and MR image data fusion for surgical planning and performance in computer-assisted navigated surgery of orbital tumors.

Materials And Methods: In this retrospective case series, 10 patients with orbital tumors and associated complaints underwent MDCT and MRI of the orbit. MDCT was performed at high resolution, with a bone window level setting in the axial plane.

Quantification and detectability of in-stent stenosis with CT angiography and MR angiography in arterial stents in vitro.

Objective: The purpose of this study was to compare CT angiography (CTA) and MR angiography (MRA) for the detectability of 75% and 95% stenoses in phantoms using six different stents.

Materials And Methods: Six different stents (Expander, Hemobahn, SelfX, Smart, Symphony, and Wallstent) were inserted into tubes filled with contrast agent (ioversol or gadoteric acid). To mimic stenoses of 75% and 95% of the patent lumen, 8-mm-diameter nylon cylinders were bored in the central axis (2 mm and 4 mm, respectively) and placed into the stent lumen.

Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate.

We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700 micron) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed.

Atypical focal nodular hyperplasia of the liver: imaging features of nonspecific and liver-specific MR contrast agents.

Objective: The objective of our study was to describe the functional and differential uptake features of atypical focal nodular hyperplasia using different MR contrast agents and to evaluate their potential role in the diagnosis and characterization of focal nodular hyperplasia.

Materials And Methods: Contrast-enhanced MR images of 45 patients with 85 focal nodular hyperplasia lesions were retrospectively reviewed. In these patients, sonographic findings were nonspecific (n = 37), or CT features were inconclusive (n = 8).