CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Is the OCT a predictive tool to assess visual impairment in optic chiasm compressing syndrome in pituitary macroadenoma? A prospective longitudinal study.

Visual dysfunction is a prevalent symptom in patients with non-functioning pituitary macroadenoma (NFPM); the role of OCT in such patients has not been yet determined. This is a prospective longitudinal observational study over a period of 6 years, on 20 patients presenting a radiological compression of the optic chiasma without visual acuity (VA) and visual field (VF) disturbances. The primary endpoint was to evaluate the impact of NFPA on neuro-axonal loss by measuring RNFL thickness using OCT at inclusion (T0), 12 months (T1), 24 months (T2), and 36 months (T3), respectively. The secondary endpoint was to monitor the evolution of OCT over time and assess any relationship between the degree of OCT alteration and the degree of radiological and clinical optic chiasm compression syndrome. Among the 20 patients included, eight (40%) showed an altered RNFL-OCT at diagnosis, while the remaining 12 (60%) showed a normal pattern. During a mean ophthalmologic follow-up of 60 months, 4 patients (20%) presented an asymptomatic reduction of RNFL-OCT thickness although all 20 had a VA/VF stable. To our knowledge, this study represents the first attempt to longitudinally evaluate the natural history and evolution of RNFL-OCT in patients with radiologically asymptomatic chiasmatic compression syndrome. The results do not clearly demonstrate the role of the OCT as an early prognostic factor for visual dysfunction.

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study.

BACKGROUND AND OBJECTIVES: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. METHODS: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). RESULTS: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. CONCLUSION: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

Clinical Efficacy of Reduced-Dose Gadobutrol Versus Standard-Dose Gadoterate for Contrast-Enhanced MRI of the CNS: An International Multicenter Prospective Crossover Trial (LEADER-75).

BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol's higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers' mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, -0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI. CLINICAL IMPACT. Use of reduced-dose gadobutrol should be considered for brain MRI, particularly in patients undergoing multiple contrast-enhanced examinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT03602339; EU Clinical Trials Register EudraCT 2018-00690-78.

How and why do French medical students choose the specialty of infectious and tropical diseases? A national cross-sectional study.

BACKGROUND: Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students. METHODS: We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n = 100) to assess the factors influencing their choice of specialty and their career plan. RESULTS: We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n = 100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary. CONCLUSIONS: The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.