Amyloid angiopathy represents 20% of causes of intraparenchymal hematoma. The histopathological examination must carefully look for characteristic vascular abnormalities and the immunohistochemistry for the beta A4 peptide must be carried out systematically. In practice, the evacuation products of an intracerebral hematoma must be fully included, because the lesions may be focal. The existence of a neurosurgical history may suggest an iatrogenic etiology when patients are less than 55 years-old. (c) 2024 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background: Contrast-enhanced magnetic resonance imaging (MRI) is the imaging modality routinely used to follow up patients who have undergone surgical resection of brain meningiomas. There are growing concerns about the massive use of gadolinium-based contrast agents (GBCA). Our aim was to evaluate the performance of a new imaging protocol, performed without GBCA injection, in the detection of tumoral residue or local recurrence after surgery of parafalcine and convexity meningiomas. Materials and methods: Only adult patients with a documented resected parafalcine or convexity meningioma were included. We performed a dedicated MRI protocol that included non-contrast and post-contrast sequences. The presence or absence of residue on the unenhanced sequences was independently recorded by three observers: first blindly, then in comparison with a baseline enhanced MRI examination. Results: A total of 51 patients were included. 37 of them featured a tumor residue on the reference enhanced sequence. Overall, an average of 32 of 37 (87%) residues were identified on the unenhanced sequences that were blindly reviewed; and more than 34 of 37 (93%) were identified with the help of the comparative baseline enhanced examination, with a high sensitivity. The missed cases were related to small residues. Conclusion: Unenhanced MRI sequences are highly sensitive and specific in identifying a tumor residue or a local recurrence in the post operative follow up of brain meningiomas. Sensitivity is even higher with the help of a comparative baseline enhanced MRI examination, whatever the strength of magnetic field. (c) 2023 Elsevier Masson SAS. All rights reserved.

Le lymphome cérébral possède un certain nombre de caractéristiques typiques en imagerie tant en TDM qu’en IRM, sur les séquences conventionnelles comme avancées. Au scanner, il se présente classiquement sous la forme d’une lésion spontanément hyperdense, avec un rehaussement homogène après injection de produit de contraste ; en IRM, il montre une restriction forte de la diffusion, un hyposignal T2, une prise de contraste homogène sans néoangiogenèse et avec rupture de barrière hémato-encéphalique en séquence de perfusion. Ces caractéristiques, lorsqu’elles sont réunies comme dans cet exemple, permettent d’évoquer précocement le diagnostic, aidant à optimiser la prise en charge du patient.

Abstract BACKGROUND The current WHO classification of Central Nervous System tumors recognizes several glioma types driven by the BRAFV600E mutation. These tumors mostly encompass pediatric low-grade gliomas. Nevertheless, a subset of them behaves as anaplastic gliomas and, currently, the unique predictive criterion linked to anaplasia is an elevated mitotic index (more than 2.5 mitoses/mm2). Histologically, the high-grade gliomas harboring BRAFV600E alteration mostly correspond to WHO grade 3 pleomorphic xanthoastrocytoma, IDH wild-type glioblastoma, entering the WHO grade 4 subset like the epithelioid subtype, and the rarer high-grade gliomas with piloïd features. These tumor types share their histomolecular features making differential diagnoses difficult. In this setting, DNA methylation profiling may be very useful to precise the integrative diagnosis. However, some of those high-grade forms failed in our experience to be classified in any methylation class with v11b4 version of the Heidelberg classifier. METHODS To understand the reasons explaining this standard classification failure, we investigated with multi-omics approaches (epigenetics, next-generation sequencing, RNAseq, proteomics and metabolomics) a well clinical characterized cohort of 17 high-grade pediatric intracranial tumors harboring this mutation. RESULTS Interestingly, almost all tumors show similar morphological features and associated passenger molecular alterations mostly CDKN2A homozygous deletion. When using the new v12.5 brain tumor classifier, the methylation profiling of the 2/17 unclassified tumors was clustering with a new MPNST (Malignant Peripheral Nerve Sheath Tumor) methylation entity. The RNAseq and proteomics analyses were showing a different molecular pattern from standard BRAF-mutated high-grade gliomas, even the clinical, radiological and histomolecular characteristics were comparable. CONCLUSION So, methylation profiling should be part of the mandatory molecular assessments to perform when a BRAF-mutated tumor is seen by neuropathologists. Furthermore, the multiomics analyses helped us to define a specific molecular pattern of this new BRAF-driven entity, where frequency and prognosis need to be determined on another larger series.

L’angiopathie amyloïde représente 20 % des causes d’hématome intra-parenchymateux. L’examen histopathologique doit rechercher attentivement les anomalies vasculaires caractéristiques et l’examen immunohistochimique avec un anticorps anti-peptide βA4 doit être réalisé de façon systématique. En pratique, les produits d’évacuation d’un hématome intracérébral doivent être inclus en totalité, car les lésions peuvent être focales. L’existence d’antécédents neurochirurgicaux peut faire suggérer une étiologie iatrogène chez les patients de moins de 55 ans.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare mesenchymal neoplasm defined in the WHO classification of soft tissue tumor as a "rare malignant fibroblastic neoplasm characterized by epithelioid fibroblasts arranged in cords and nests and embedded in a dense sclerotic hyalinized stroma." These morphological features are associated with a unique immunohistochemical pattern (particularly MUC4 hyperexpression) and with characteristic gene rearrangements, mostly involving EWSR1 and CREB3L1 or CREB3L2. If it usually arises in deep soft tissues of various locations, SEF has also been reported in bones or viscera. Nevertheless, to our knowledge, no primary brain location has been described. Here, we report a left occipital SEF arising in a middle-aged woman with no evidence of systemic location after a comprehensive clinic-radiological assessment. We discuss the main differential neuropathological diagnoses and provide a comprehensive genetic and epigenetic description of this tumor comparatively to the more frequent systemic locations.

Over the last few decades, deciphering the alteration of molecular pathways in brain tumors has led to impressive changes in diagnostic refinement. Among the molecular abnormalities triggering and/or driving gliomas, alterations in the MAPK pathway reign supreme in the pediatric population, as it is encountered in almost all low-grade pediatric gliomas. Activating abnormalities in the MAPK pathway are also present in both pediatric and adult high-grade gliomas. Across those alterations, BRAF p.V600E mutations seem to define homogeneous groups of tumors in terms of prognosis. The recent development of small molecules inhibiting this pathway retains the attention of neurooncologists on BRAF-altered tumors, as conventional therapies showed no significant effect, nor prolonged efficiency on the high-grade or low-grade unresectable forms. Nevertheless, tumoral heterogeneity and especially molecular alteration(s) associated with MAPK-pathway abnormalities are not fully understood with respect to how they might lead to the specific dismal prognosis of those gliomas and/or affect their response to targeted therapies. This review is an attempt to provide comprehensive information regarding molecular alterations related to the aggressiveness modulation in BRAF-mutated gliomas and the current knowledge on how to use those targeted therapies in such situations.

Diffuse midline (DMG) and brainstem (DIPG) high-grade gliomas (HGG) bearing H3.3K27M driver mutation are aggressive and uncurable brain tumors. We evidenced by the past HIF-2a and its transcriptional gene, EPAS1, as a marker of resistance when targeting mTor/HIF-1a pathway. To understand HIF-2α potential role in chronically active hypoxic environment in DIPG/DMG, we investigate its status in a cohort of pediatric HGGs comprising notably H3.3K27M mutant tumors and in their paired in vitro derived models. Using concomitantly the low-input chromatin immunoprecipitation sequencing method CUT&RUN, RNAsequencing and metabolomics, we profiled the landscape of promoters and pathways regulated by HIF-2a in HGGs, where H3.3K27M and TP53 mutations are associated. Elucidation of HIF-2a downstream genes reveal statistically significant pathways linked to DIPGs (e.g., mTor and canonical Wnt pathways) and to DMGs (glutamatergic synapse and non-canoncial Wnt signaling). Finally, HIF-2a was evidenced as a new therapeutic target opening the path for its use concomitantly to irradiation.

Abstract Diffuse midline (DMG) and brainstem (DIPG) high-grade gliomas (HGG) bearing H3.3K27M driver mutation are aggressive and uncurable brain tumors. We evidenced by the past HIF-2a and its transcriptional gene, EPAS1, as a marker of resistance when targeting mTor/HIF-1a pathway. To understand HIF-2α potential role in chronically active hypoxic environment in DIPG/DMG, we investigate its status in a cohort of pediatric HGGs comprising notably H3.3K27M mutant tumors and in their paired in vitro derived models. Using concomitantly the low-input chromatin immunoprecipitation sequencing method CUT&RUN, RNAsequencing and metabolomics, we profiled the landscape of promoters and pathways regulated by HIF-2a in HGGs, where H3.3K27M and TP53 mutations are associated. Elucidation of HIF-2a downstream genes reveal statistically significant pathways linked to DIPGs (e.g., mTor and canonical Wnt pathways) and to DMGs (glutamatergic synapse and non-canoncial Wnt signaling). Finally, HIF-2a was evidenced as a new therapeutic target opening the path for its use concomitantly to irradiation.

Abstract Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns integrating altogether tumor molecular background, imaging features and patient outcome, a retrospective study was performed in a group of non-NF1 grade 1 PLGGs. So, 78 children, followed from 2004 to 2017, were retrospectively reported. Their therapeutic management comprised surgery or surgery plus chemotherapies (e.g., carboplatin and vincristine). In this population, radiological and molecular patterns were pooled statistically to be able to identify specific prognostic subgroups. Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with post-operative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas 4 deaths occurred only in the highly treated patients. As expected, PLGG with BRAF pV600E and/or CDKN2A loss exhibited poor outcomes. Nevertheless, we were able to evidence statistically significant associations between molecular characteristics and their specific imaging presentation on diagnostic and 24-week MRIs. In the chemo-treated patients, the molecularly good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis (> 50% of the tumor volume (TV)) and the appearance during treatment of a higher cystic proportion that we called “cystic conversion”. So, additionally to the WHO prognostic molecular patterns, precise MRI characteristics (notably cystic part proportions onto TV) were associated to BRAF p.V600E PLGGs, as well as to the more frequent molecular KIAA1549-BRAF fused PLGGs. To summarize, absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy time point were significantly linked to a worst prognosis and response to treatment. In future studies, these imaging features might be considered as innovative prognostic markers to use during treatment.

A significant but reversible inhibition of phenazone elimination was observed in rabbits chronically exposed to CS2. Lack of significant difference of phenazone pharmacokinetics in exposed rabbits 24 h after the last exposure compared with the control group, indicates that alteration of phenazone elimination after chronic exposure to CS2 is reversible. The results obtained with phenazone as a model substance suggest that, during chronic exposure to CS2, elimination of other drugs metabolized by the pathway similar to phenazone may also be altered. This should be taken into account in selecting their dosage.

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.

Background Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non-neurofibromatosis type 1 (non-NF1) grade 1 PLGGs. Patients and methods Seventy-eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies. Results Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo-treated patients, when associating initial and 6-month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion. Conclusion So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.

ABSTRACT We present the case of a 64-year-old man presenting an episode of confusion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection with a positive oropharyngeal swab polymerase chain reaction test. He was hospitalized for dyspnea related to pneumonia demonstrated on chest CT. FDG PET performed after the confusion phase, but still in the COVID-19 (coronavirus disease 2019)-positive phase, showed high glucose metabolism of the inferior colliculi. Morphological MRI was normal. The first-pass perfusion MRI shows hyperperfusion of the inferior colliculi, corresponding to FDG PET hypermetabolism.

Background Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed. Results Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%). Conclusions Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.

Periodontal Ehlers-Danlos syndrome (pEDS) is a rare condition caused by pathogenic variants in the C1R and C1S genes, encoding subunits C1r and C1s of the first component of the classical complement pathway. It is characterized by early-onset periodontitis with premature tooth loss, pretibial hyperpigmentation and skin fragility. Rare arterial complications have been reported, but venous insufficiency is rarely described. Here we report 13 novel patients carrying heterozygous pathogenic variants in C1R and C1S including three novel C1S variants (c.962G > C, c.961 T > G and c.961 T > A). In addition to the pEDS phenotype, three patients and one relative displayed widespread venous insufficiency leading to persistent varicose leg ulcers. One patient suffered an intracranial aneurysm with familial vascular complications including thoracic and abdominal aortic aneurysm and dissection and intracranial aneurysm rupture. This work confirms that vascular complications can occur, although they are not frequent, which leads us to propose to carry out a first complete non-invasive vascular evaluation at the time of the diagnosis in pEDS patients. However, larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications.

Mucormycosis are infections caused by molds of the order Mucorales. These opportunistic infections are rare, difficult to diagnose, and have a poor prognosis. We aimed to describe common radiographic patterns that may help to diagnose cerebral mucormycosis and search for histopathological correlations with imaging data. We studied the radiological findings (CT and MRI) of 18 patients with cerebral mucormycosis and four patients’ histopathological findings. All patients were immunocompromised and/or diabetic. The type of lesions depended on the infection’s dissemination pathway. Hematogenous dissemination lesions were most frequently abscesses (59 lesions), cortical, cortical–subcortical, or in the basal ganglia, with a halo aspect on DWI for lesions larger than 1.6 cm. Only seven lesions were enhanced after contrast injection, with different presentations depending on patients’ immune status. Ischemia and hemorrhagic areas were also seen. Vascular lesions were represented by stenosis and thrombosis. Direct posterior extension lesions were bi-fronto basal hypodensities on CT and restricted diffusion without enhancement on MRI. A particular extension, perineural spread, was seen along the trigeminal nerve. Histopathological analysis found endovascular lesions with destruction of vessel walls by Mucorales, microbleeds around vessels, as well as acute and chronic inflammation. MRI is the critical exam for cerebral mucormycosis. Weak ring enhancement and reduced halo diffusion suggest the diagnosis of fungal infections. Involvement of the frontal lobes should raise suspicion of mucormycosis (along with aspergillosis). The perineural spread can be considered a more specific extension pathway of mucormycosis.

AbstractWe present the case of a 64-year-old man presenting an episode of confusion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection with a positive oropharyngeal swab polymerase chain reaction test. He was hospitalized for dyspnea related to pneumonia demonstrated on chest CT. FDG PET performed after the confusion phase, but still in the COVID-19 (coronavirus disease 2019)–positive phase, showed high glucose metabolism of the inferior colliculi. Morphological MRI was normal. The first-pass perfusion MRI shows hyperperfusion of the inferior colliculi, corresponding to FDG PET hypermetabolism.

Hyperactivation of the colliculi has been observed in some patients with coronavirus disease 2019.

Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Patients were enrolled according to a 3 + 3 escalation design with ten levels, aiming to determine the MTD (maximum tolerated dose) of rapamycin plus irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m2/day), associating biweekly intravenous irinotecan (125 to 240 mg/m2/dose). Toxicities, pharmacokinetics, efficacy analyses, and pharmacodynamics were evaluated. Forty-two patients, aged from 2 to 18 years, were included. No MTD was reached. Adverse events were mild to moderate. Only rapamycin doses of 1.5 mg/m2/day reached over time clinically active plasma concentrations. Tumor responses and prolonged stable disease were associated with a mean irinotecan area under the curve of more than 400 min.mg/L. Fourteen out of 31 (45.1%) patients had a non-progressive disease at 8 weeks. Most of them were sarcomas and brain tumors. For the phase II trial, we can then propose biweekly 125 mg/m2 irinotecan dose with a pharmacokinetic (PK) follow-up and a rapamycin dose of 1.5 mg/m2/day, reaching a blood concentration above 10 g/L.