Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative

The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively

Methylprednisolone-induced toxic hepatitis after intravenous pulsed therapy for multiple sclerosis relapses

High-dose, intravenous methylprednisolone (MP) is the only recommended first-line treatment for multiple sclerosis relapses. However, there are increasing reports on liver toxicity induced by this treatment regimen. We report of 4 multiple sclerosis patients with no history of viral/metabolic liver disorders or alcohol/hepatotoxic drug intake, who developed hypertransaminasaemia following intravenous MP. In 2 of the patients, liver biopsy showed periportal fibrosis, piecemeal necrosis, and inflammatory cell infiltrates. A rechallenge test confirmed a causal association in 1 case. MP-induced liver toxicity may be more frequent than commonly thought and it is important to report this adverse reaction, which is potentially lethal, and to raise awareness on the potential hepatotoxicity of corticosteroid pulses

Pronounced structural and functional damage in early adult pediatric-onset multiple sclerosis with no or minimal clinical disability

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15) in comparison with age- and disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p â\u89¤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term

EGFR gene amplification in monocentric and multicentric glioblastoma.

International audienc

Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative

The 2021 WHO classification of the CNS Tumors identifies as “Peripheral nerve sheath tumors” (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively

The influence of cystathionine on neurochemical quantification in brain tumor in vivo magnetic resonance spectroscopy

International audiencePurpose: To evaluate the ability of the PRESS sequence (TE = 97 ms, optimized for 2-hydroxyglutarate detection) to detect cystathionine in gliomas and the effect of the omission of cystathionine on the quantification of the full neurochemical profile.Methods: Twenty-three subjects with a glioma were retrospectively included based on the availability of both MEGA-PRESS and PRESS acquisitions at 3T, and the presence of the cystathionine signal in the edited MR spectrum. In eight subjects, the PRESS acquisition was performed also in normal tissue. Metabolite quantification was performed using LCModel and simulated basis sets. The LCModel analysis for the PRESS data was performed with and without cystathionine.Results: All subjects with glioma had detectable cystathionine levels >1 mM with Cramér-Rao lower bounds (CRLB) <15%. The mean cystathionine concentrations were 3.49 ± 1.17 mM for MEGA-PRESS and 2.20 ± 0.80 mM for PRESS data. Cystathionine concentrations showed a significant correlation between the two MRS methods (r = 0.58, p = .004), and it was not detectable in normal tissue. Using PRESS, 19 metabolites were quantified with CRLB <50% for more than half of the subjects. The metabolites that were significantly (p < .0028) and mostly affected by the omission of cystathionine were aspartate, betaine, citrate, γ-aminobutyric acid (GABA), and serine.Conclusions: Cystathionine was detectable by PRESS in all the selected gliomas, while it was not detectable in normal tissue. The omission from the spectral analysis of cystathionine led to severe biases in the quantification of other neurochemicals that may play key roles in cancer metabolism

Frequent early multiple sclerosis relapses during treatment with fingolimod: a paradoxical effect?

This is the case report of a multiple sclerosi patient who presented frequent relapses early after beginning a treatment with fingolimo

Progressive multifocal leukoencephalopathy after first-line radiotherapy and temozolomide for glioblastoma

International audienc

Apport du Transfer Learning pour la segmentation automatique de lésions cérébrales radio-induites chez des patients atteints de glioblastome à partir d’un nombre restreint d’IRMs annotées

International audienceCes travaux sont issus du projet de recherche RAAI (Radiotherapy Assisted by AI, MIAI@Grenoble Alpes) dont l’objectif était de proposer un algorithme d’apprentissage automatique pour la segmentation d’hyper-intensités de la substance blanche à partir d’imageries par résonnance magnétique (IRMs) cérébrales obtenues lors du suivi clinique de patients de la cohorte EPIBRAINRAD, traités par radio-chimiothérapie pour une tumeur cérébrale de haut grade. En effet, ces hyper-intensités constituent des biomarqueurs d’imagerie potentiellement associés à l’occurrence de leuco-encéphalopathies et de troubles neurocognitifs radio-induits. Aujourd’hui, les méthodes d’apprentissage profond constituent les meilleures techniques utilisées pour la segmentation d’images dans le domaine médical. Elles nécessitent néanmoins une importante quantité de données pour apprendre à réaliser cette tâche avec une certaine robustesse. Or, les données d’imagerie médicale publiques préalablement segmentées sont très peu nombreuses étant donné la difficulté et le temps requis pour un spécialiste pour annoter manuellement de telles images. Les méthodes d’apprentissage profond actuelles doivent donc apprendre à fonctionner avec cette faible quantité de données. Dans un premier temps, les algorithmes de segmentation 3D les plus performants actuellement - le réseau 3D Attention V-Net1 - ont été appliqués de manière « classique », en collaboration avec la société Pixyl, en utilisant en entrée différents dataset de données publiques préalablement segmentées issues du challenge BraTS2 et/ou des données de patients atteints de sclérose en plaques couplées à des acquisitions IRM 3D FLAIR issues de la cohorte EPIBRAINRAD. Dans un second temps, une méthode d’apprentissage par transfert (Transfer Learning) a été mise en oeuvre : un premier modèle a été entraîné à partir de données pré-segmentées du challenge BraTS2 puis les connaissances tirées de ce premier apprentissage ont été transférées lors de l’apprentissage de nouveaux modèles à partir de quelques IRMs cérébrales 3D de la cohorte EPIBRAINRAD. Plusieurs métriques ont été calculées afin de comparer la qualité des segmentations obtenues : le dice score, la sensibilité, la précision et la distance de Hausdorff. Les méthodes d’apprentissage classiques utilisées dans un premier temps n’ont pas permis d’obtenir des résultats de segmentation satisfaisants (Figure 1). En revanche, notre technique d’apprentissage par Transfer Learning a montré des résultats remarquables (Figure 2) en utilisant seulement 9 acquisitions IRM 3D FLAIR issues de la cohorte EPIBRAINRAD, lors de la phase d’entrainement et 11 acquisitions IRM 3D FLAIR lors de la phase de test. Ces travaux ont permis de mettre en évidence la supériorité et l’apport des méthodes de Transfer Learning par rapport aux méthodes d’apprentissage classiques dans un contexte où la quantité de données cliniques annotées à disposition est faible. Ils seront poursuivis dans le cadre du projet de recherche ANR RADIO-AIDE (RADIation-induced neurOtoxicity assessed by spatio-temporal modelling combined with Artificial Intelligence after brain raDiothErapy) (2022-2026)