ABSTRACT
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.
Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Ependymoma , Glioma, Subependymal , Supratentorial Neoplasms , Child , Humans , Brain Neoplasms/genetics , Cell Cycle Proteins , Central Nervous System Neoplasms/genetics , Ependymoma/pathology , In Situ Hybridization, Fluorescence , Supratentorial Neoplasms/pathology , Transcription Factors/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
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.
Subject(s)
Optic Chiasm , Pituitary Neoplasms , Humans , Optic Chiasm/diagnostic imaging , Prospective Studies , Longitudinal Studies , Visual Fields , Vision Disorders/etiology , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/diagnostic imagingABSTRACT
BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.
Subject(s)
COVID-19 , Male , Humans , Middle Aged , Spin Labels , COVID-19/complications , Magnetic Resonance Imaging , Perfusion , Cerebrovascular CirculationABSTRACT
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.
Subject(s)
COVID-19 , Vasculitis, Central Nervous System , COVID-19/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Neuroimaging , Positron Emission Tomography Computed TomographyABSTRACT
OBJECTIVES: To evaluate the performance of on-call radiology residents in interpreting alone brain and spine MRI studies performed after hours, to describe their mistakes, and to identify influencing factors that increased the occurrence of errors. METHODS: A total of 328 MRI examinations performed during a 13-month period (from December 1, 2019, to January 1, 2021) were prospectively included. Discrepancies between the preliminary interpretation of on-call radiology residents and the final reports of attending neuroradiologists were noted and classified according to a three-level score: level 1 (perfect interpretation or minor correction), level 2 (important correction without immediate change in patient management), or level 3 (major correction with immediate change in patient management). Categorical data were compared using Fisher's exact test. RESULTS: The overall discrepancy rate (level-2 and level-3 errors) was 16%; the rate of major discrepancies (only level-3 errors) was 5.5%. The major-discrepancy rate of second-year residents, when compared with that of senior residents, was significantly higher (p = 0.02). Almost all of the level-3 errors concerned cerebrovascular pathology. The most common level-2 errors involved undescribed aneurysms. We found no significant difference in the major-discrepancy rate regarding time since the beginning of the shift. CONCLUSIONS: The great majority of examinations were correctly interpreted. The rate of major discrepancies in our study was comparable to the data in the literature, and there was no adverse clinical outcome. The level of residency has an effect on the rate of serious errors in residents' reports. KEY POINTS: ⢠The rate of major discrepancies between preliminary MRI interpretations by on-call radiology residents and final reports by attending neuroradiologists is low, and comparable to discrepancy rates reported for head CT interpretations. ⢠The youngest residents made significantly more serious errors when compared to senior residents. ⢠There was no adverse clinical outcome in patient morbidity as a result of an initial misdiagnosis.
Subject(s)
Internship and Residency , Radiology , Clinical Competence , Diagnostic Errors , Humans , Magnetic Resonance Imaging , Radiology/education , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Brain Neoplasms/diagnostic imaging , Contrast Media/administration & dosage , Gadolinium/administration & dosage , Magnetic Resonance Imaging/methods , Meglumine/administration & dosage , Neuroimaging/methods , Organometallic Compounds/administration & dosage , Aged , Cross-Over Studies , Equivalence Trials as Topic , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
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.
Subject(s)
Internship and Residency , Medicine , Students, Medical , Career Choice , Cross-Sectional Studies , France , Humans , Specialization , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations. METHODS: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI. RESULTS: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009). CONCLUSIONS: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF. CLINICALTRIALSGOV IDENTIFIER: NCT04368390.
Subject(s)
Brain Ischemia/diagnostic imaging , Brain/diagnostic imaging , Coronavirus Infections/diagnostic imaging , Meningoencephalitis/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Stroke/diagnostic imaging , Adult , Aged , Aged, 80 and over , Betacoronavirus , Brain Ischemia/physiopathology , COVID-19 , Confusion/physiopathology , Consciousness Disorders/physiopathology , Coronavirus Infections/physiopathology , Encephalitis/diagnostic imaging , Encephalitis/physiopathology , Female , France , Headache/physiopathology , Humans , Magnetic Resonance Imaging , Male , Meningitis/diagnostic imaging , Meningitis/physiopathology , Meningoencephalitis/physiopathology , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Psychomotor Agitation/physiopathology , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/physiopathology , Respiratory Distress Syndrome/physiopathology , Retrospective Studies , SARS-CoV-2 , Stroke/physiopathology , Young AdultABSTRACT
OBJECTIVES: This study analysed CT patterns of the acute dissected aortic arch using original biometric features along with comparison with normal aortas. METHODS: The diagnostic CT scans of 57 patients (42 males, age (mean ± SD: 64.5 ± 13.8 years) admitted with acute Stanford type A dissection involving the aortic arch were analysed by semi-automatic detection protocol of the true lumen of the dissection. We measured the distances from the apex to the ascending and descending aorta, the curvilinear length of the entire arch and of its segments (especially between the brachiocephalic artery trunk and the left subclavian artery), as well as the surface area, angle, height and shift of the arch. These measurements were compared with results previously obtained in a healthy cohort in an analysis adjusted for age, sex and weight. The surface area and rotation of the false lumen were also analysed. RESULTS: Compared to normal aortic arches (N), dissected aortic arches (D) were longer (D: 155 ± 26 mm, N: 135 ± 25 mm, p = 0.002), higher (D: 51 ± 10 mm, N: 45 ± 9 mm, p = 0.04), and with a more anterior apex (shift: D: 1.19 ± 0.56, N: 1.40 ± 0.62, p = 0.007). False lumen occupied between 47-65% of the aorta, turned preferentially clockwise and its rotation decreased progressively along the arch. CONCLUSIONS: The morphology of the dissected aortic arch differs from that of the normal arch. Thus, our compilation of aortic arch measurements may help improve existing endovascular devices and/or design of new endoprostheses. Advances in knowledge: In this article, we provide a comprehensive set of measurements of the dissected aortic arch, and show that dissected aortic arches are longer, higher, and with a more anterior apex than normal arches.