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9. Reduced-dose craniospinal irradiation is feasible for standard-risk adult medulloblastoma patients

Author

Massimino, M, Sunyach, M, Barretta, F, Gandola, L, Garegnani, A, Pecori, E, Spreafico, F, Bonneville-Levard, A, Meyronet, D, Mottolese, C, Boschetti, L, Biassoni, V, Schiavello, E, Giussani, C, Carrabba, G, Diletto, B, Pallotti, F, Stefini, R, Ferrari, A, Terenziani, M, Casanova, M, Luksch, R, Meazza, C, Podda, M, Chiaravalli, S, Puma, N, Bergamaschi, L, Morosi, C, Calareso, G, Giangaspero, F, Antonelli, M, Buttarelli, F, Frappaz, D, Massimino M., Sunyach M. P., Barretta F., Gandola L., Garegnani A., Pecori E., Spreafico F., Bonneville-Levard A., Meyronet D., Mottolese C., Boschetti L., Biassoni V., Schiavello E., Giussani C., Carrabba G., Diletto B., Pallotti F., Stefini R., Ferrari A., Terenziani M., Casanova M., Luksch R., Meazza C., Podda M., Chiaravalli S., Puma N., Bergamaschi L., Morosi C., Calareso G., Giangaspero F., Antonelli M., Buttarelli F. R., Frappaz D., Massimino, M, Sunyach, M, Barretta, F, Gandola, L, Garegnani, A, Pecori, E, Spreafico, F, Bonneville-Levard, A, Meyronet, D, Mottolese, C, Boschetti, L, Biassoni, V, Schiavello, E, Giussani, C, Carrabba, G, Diletto, B, Pallotti, F, Stefini, R, Ferrari, A, Terenziani, M, Casanova, M, Luksch, R, Meazza, C, Podda, M, Chiaravalli, S, Puma, N, Bergamaschi, L, Morosi, C, Calareso, G, Giangaspero, F, Antonelli, M, Buttarelli, F, Frappaz, D, Massimino M., Sunyach M. P., Barretta F., Gandola L., Garegnani A., Pecori E., Spreafico F., Bonneville-Levard A., Meyronet D., Mottolese C., Boschetti L., Biassoni V., Schiavello E., Giussani C., Carrabba G., Diletto B., Pallotti F., Stefini R., Ferrari A., Terenziani M., Casanova M., Luksch R., Meazza C., Podda M., Chiaravalli S., Puma N., Bergamaschi L., Morosi C., Calareso G., Giangaspero F., Antonelli M., Buttarelli F. R., and Frappaz D.

Abstract

Introduction: Medulloblastoma is the most common malignant brain tumor in children, but accounts for only 1% of brain cancers in adults. For standard-risk pediatric medulloblastoma, current therapy includes craniospinal irradiation (CSI) at reduced doses (23.4 Gy) associated with chemotherapy. Whereas most same-stage adult patients are still given CSI at 36 Gy, with or without chemotherapy, we report here on our use of reduced-dose CSI associated with chemotherapy for older patients. Methods: We gathered non-metastatic patients over 18 years old (median age 28 years, range 18–48) with minimal or no residual disease after surgery, no negative histological subtypes, treated between 1996–2018 at the Centre Léon Bérard (Lyon) and the INT (Milano). A series of 54 children with similar tumors treated in Milano was used for comparison. Results: Forty-four adults were considered (median follow-up 101 months): 36 had 23.4 Gy of CSI, and 8 had 30.6 Gy, plus a boost to the posterior fossa/tumor bed; 43 had chemotherapy as all 54 children, who had a median 83-month follow-up. The PFS and OS were 82.2 ± 6.1% and 89 ± 5.2% at 5 years, and 78.5 ± 6.9% and 75.2 ± 7.8% at ten, not significantly different from those of the children. CSI doses higher than 23.4 Gy did not influence PFS. Female adult patients tended to have a better outcome than males. Conclusion: The results obtained in our combined series are comparable with, or even better than those obtained after high CSI doses, underscoring the need to reconsider this treatment in adults.

Published
2020

10. Characteristics of IDH-mutant gliomas with non-canonical IDH mutation

Author

Poetsch, L., Bronnimann, C., Loiseau, H., Frénel, J., Siegfried, A., Seizeur, R., Gauchotte, G., Cappellen, D., Carpentier, C., Figarella‑Branger, Dominique, Eimer, S., Meyronet, D., Ducray, F., Network, POLA, Rigaud, V., CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), CRLCC René Gauducheau, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, IDH1, [SDV]Life Sciences [q-bio], Mutant, IDH2, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Glioma, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Family history, neoplasms, ComputingMilieux_MISCELLANEOUS, Brain Neoplasms, business.industry, Cancer, Prognosis, medicine.disease, Combined Modality Therapy, Isocitrate Dehydrogenase, nervous system diseases, 3. Good health, Idh mutation, Survival Rate, Neurology, Oncology, 030220 oncology & carcinogenesis, Mutation, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Approximately 10% of IDH-mutant gliomas harbour non-canonical IDH mutations (non-p.R132H IDH1 and IDH2 mutations). The aim of this study was to analyse the characteristics of non-canonical IDH-mutant gliomas. We retrospectively analysed the characteristics of 166 patients with non-canonical IDH mutant gliomas and compared them to those of 155 consecutive patients with IDH1 p.R132H mutant gliomas. The median age at diagnosis was 38 years in patients with non-canonical IDH mutant gliomas and 43 years in glioma patients with IDH1 p.R132H-mutant tumours. Family history of cancer was more frequent among glioma patients harbouring non-canonical IDH mutations than in patients with IDH1 p.R132H mutations (22.2% vs 5.1%; P

Published
2020

13. The TeloDIAG: how telomeric parameters can help in glioma rapid diagnosis and liquid biopsy approaches

Author

Billard, P., primary, Guerriau, C., additional, Carpentier, C., additional, Juillard, F., additional, Grandin, N., additional, Lomonte, P., additional, Kantapareddy, P., additional, Dufay, N., additional, Barritault, M., additional, Rimokh, R., additional, Verrelle, P., additional, Maucort-Boulch, D., additional, Figarella-Branger, D., additional, Ducray, F., additional, Dehais, C., additional, Charbonneau, M., additional, Meyronet, D., additional, and Poncet, D.A., additional

Published
2021
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14. RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells

Author

Diaz J, Sébastien Durand, Isaac C, Meyronet D, Huyghe A, Gabut M, Bennychen B, Bruelle M, A Seyve, Catez F, Vanbelle C, Bourdelais F, Lavial F, Blin-Gonthier J, Emiliano P. Ricci, and Ducray F

Subjects
Homeobox protein NANOG, biology, embryonic structures, biology.protein, Ribosome biogenesis, Translation (biology), Stem cell, PRC2, Induced pluripotent stem cell, Embryonic stem cell, Chromatin, Cell biology
Abstract

Embryonic stem cell (ESC) fate decisions are regulated by a complex molecular circuitry that requires tight and coordinated gene expression regulations at multiple levels from chromatin organization to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key regulatory pathways that efficiently control stem cell homeostasis. However, the molecular mechanisms underlying the regulation of these pathways remain largely unknown to date. Here, we analyzed the expression, in mouse ESCs, of over 300 genes involved in ribosome biogenesis and we identified RSL24D1 as the most differentially expressed between self-renewing and differentiated ESCs. RSL24D1 is highly expressed in multiple mouse pluripotent stem cell models and its expression profile is conserved in human ESCs. RSL24D1 is associated with nuclear pre-ribosomes and is required for the maturation and the synthesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors, including POU5F1 and NANOG, as well as components of the polycomb repressive complex 2 (PRC2). Consistently, RSL24D1 is required for mouse ESC self-renewal and proliferation. Taken together, we show that RSL24D1-dependant ribosome biogenesis is required to both sustain the expression of pluripotent transcriptional programs and silence developmental programs, which concertedly dictate ESC homeostasis.

Published
2021

16. OS02.6.A The TeloDIAG: How telomeric parameters can help in glioma rapid diagnosis and liquid biopsies approaches

Author

Billard, P, primary, Guerriau, C, additional, Carpentier, C, additional, Juillard, F, additional, Grandin, N, additional, Lomonte, P, additional, Kantapareddy, P, additional, Barritault, M, additional, Rimokh, R, additional, Verrelle, P, additional, Maucort-Boulch, D, additional, Figarella-Branger, D, additional, Ducray, F, additional, Dehais, C, additional, Charbonneau, M, additional, Meyronet, D, additional, and Poncet, D A, additional

Published
2021
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17. KS02.4.A Olaparib in Recurrent IDH-mutant High-Grade Glioma (OLAGLI)

Author

Ducray, F, primary, Sanson, M, additional, Chinot, O, additional, Fontanilles, M, additional, Rivoirard, R, additional, Thomas-Maisonneuve, L, additional, Cartalat, S, additional, Tabouret, E, additional, Bonneville-Levard, A, additional, Darlix, A, additional, Ameli, R, additional, Meyronet, D, additional, Gueyffier, F, additional, Remontet, L, additional, Maucort-Boulch, D, additional, Dehais, C, additional, and Honnorat, J, additional

Published
2021
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22. How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II

Author

Schmitt, A., Bauer, M., Heinsen, H., Feiden, W., Falkai, P., Alafuzoff, I., Arzberger, T., Al-Sarraj, S., Bell, J. E., Bogdanovic, N., Brück, W., Budka, H., Ferrer, I., Giaccone, G., Kovacs, G. G., Meyronet, D., Palkovits, M., Parchi, P., Patsouris, E., Ravid, R., Reynolds, R., Riederer, P., Roggendorf, W., Schwalber, A., Seilhean, D., Kretzschmar, H., and The Consortium of Brainnet Europe II

Published
2007
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24. Comparaison du micro-environnement tumoral de tumeurs bronchiques non à petites cellules et de métastases cérébrales : implications pour l’immunothérapie

Author

Brindel, A., primary, Lopez, J., additional, Desormaux, P., additional, Berhouma, M., additional, Ong, S., additional, Warren, S., additional, Morel, P., additional, Aho, S., additional, Etienne-Mastroianni, B., additional, Ginoux, M., additional, Pérol, M., additional, Swalduz, A., additional, Perrot, E., additional, Gérinière, L., additional, Falchero, L., additional, Odier, L., additional, Kiakouama, L., additional, Kelkel, E., additional, Feillet, N., additional, Beynel, P., additional, Luciani, S., additional, Bombaron, P., additional, Brun, P., additional, Grangeon, V., additional, Petit, L., additional, Bayle, S., additional, Meyronet, D., additional, Brevet, M., additional, and Duruisseaux, M., additional

Published
2020
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32. Virtual histology of animal and human brains with Alzheimer's disease

Author

Fabien Chauveau, Boutin, H., Meyronet, D., Hugo Rositi, Cécile Olivier, Elleaume, H., Emmanuel Brun, Françoise Peyrin, Marlène Wiart, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Wolfson Molecular Imaging Centre (WMIC), University of Manchester [Manchester], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Imagerie Tomographique et Radiothérapie, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Rayonnement Synchrotron et Recherche Medicale (RSRM), Université Joseph Fourier - Grenoble 1 (UJF)-European Synchrotron Radiation Facility (ESRF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), European Synchrotron Radiation Facility (ESRF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and DUGAT, Pascale

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; IntroductionSynchrotron Radiation X-ray Phase Computed Tomography (SR-PCT) of brain tissue can reveal different image contrast depending on sample preparation. Indeed, we have shown that ethanol dehydration of brain samples reveals myelin as a hyper-intense signal while maintaining optimal detection of packed proteinaceous structures such as amyloid plaques [1]. The present work builds on this versatile “virtual histology” tool to characterize amyloid deposits in brain samples from Alzheimer’s disease (AD) animal models and patients.MethodsMono, bi-, and triple transgenic lines of mouse (PDAPP, APP-PS1, 3xTg [2]) were studied, along with one line of transgenic rats [3]. Human samples of frontal cortex were obtained from 6 sporadic AD cases and 1 familial AD case (Cardiobiotec, CRB-HCL, Lyon, France). All samples were scanned after dehydration in ethanol on beamlines ID19 and ID17 at ESRF. In line propagation imaging was performed at 26keV, voxel size of 6.5μm and 3m free space propagation on ID19 (34 keV, 6.5µm and 11m on ID17). Images were reconstructed using Paganin’s method [4].Results/DiscussionAll transgenic animal brains (Fig. 1) and human AD (Fig. 2) cases exhibited amyloid signals in the form of bright spots. Myelin-based hyper-intensities enabled a detailed visualisation of white-matter tracts and subsequent structural connectivity. Additionally, vessels appeared hypo-intense in perfused brains from animals (Fig.1) and hyper-intense in human autopsic brains (Fig. 2), probably because of the presence of blood-related iron in non-perfused tissue. Concurrent immunofluorescence analyses of these observations are in progress.ConclusionsWhole-brain mouse acquisitions were performed faster (3-10 min) than previously described phase contrast approaches [5]. Human amyloid plaques were evidenced for the first time by SR-PCT. Dehydration-added myelin contrast may be used to highlight unexplored associations between amyloid deposition and myelin alterations.References[1] Rositi et al. Abstract #233, presented in European Molecular Imaging Meeting, Mar 18-20, Tübingen, Germany; 2015.[2] Mucke et al. J Neurosci. 2000 ; Blanchard et al. Exp Neurol 2003 ; Oddo et al. Neuron. 2003.[3] Cohen RM, et al. J Neurosci. 2013.[4] Paganin et al. J Microsc. 2002.[5] Noda-Saita et al. Neuroscience 2006 ; Connor et al. NeuroImage 2009 ; Pinzer et al. NeuroImage 2012 ; Astolfo et al. J Synchrotron Radiat. 2016.AcknowledgementWe are grateful to our collaborators (Nicolas Rama, Corinne Perrin, Karen Silva) for their help in gathering animal and human brain samples.

Published
2018

43. OS3.3 Radiological characteristics and natural history of adult IDH wild type astrocytomas with TERT promoter mutations

Author

Izquierdo, C, primary, Barritault, M, additional, Poncet, D, additional, Cartalat, S, additional, Joubert, B, additional, Bruna, J, additional, Jouanneau, E, additional, Guyotat, J, additional, Vasiljevic, A, additional, Fenouil, T, additional, Berthezène, Y, additional, Honnorat, J, additional, Meyronet, D, additional, and Ducray, F, additional

Published
2018
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46. TUMOR GENOMIC COPY NUMBER ABNORMALITIES ANALYZED BY HIGH RESOLUTION SNP ARRAY IMPACT OUTCOME OF PRIMARY CNS LYMPHOMA: A RETROSPECTIVE ANALYSIS ON 68 PATIENTS

Author

Ghesquieres, H., primary, Tesson, B., additional, Courtois-Cox, S., additional, Boyault, S., additional, Nicolas-Virelizier, E., additional, Carrere, M., additional, Traverse-Glehen, A., additional, Perrin, C., additional, Chassagne-Clement, C., additional, Jouanneau, E., additional, Salles, G., additional, Honnorat, J., additional, Blay, J., additional, and Meyronet, D., additional

Published
2017
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47. Erratum to: Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium[Journal of Neural Transmission, (2015), DOI 10.1007/s00702-014-1304-1]

Author

Alafuzoff, I. Pikkarainen, M. Neumann, M. Arzberger, T. Al-Sarraj, S. Bodi, I. Bogdanovic, N. Bugiani, O. Ferrer, I. Gelpi, E. Gentleman, S. Giaccone, G. Graeber, M.B. Hortobagyi, T. Ince, P.G. Ironside, J.W. Kavantzas, N. King, A. Korkolopoulou, P. Kovács, G.G. Meyronet, D. Monoranu, C. Nilsson, T. Parchi, P. Patsouris, E. Revesz, T. Roggendorf, W. Rozemuller, A. Seilhean, D. Streichenberger, N. Thal, D.R. Wharton, S.B. Kretzschmar, H.

Published
2015

48. Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

Author

Alafuzoff, I. Pikkarainen, M. Neumann, M. Arzberger, T. Al-Sarraj, S. Bodi, I. Bogdanovic, N. Bugiani, O. Ferrer, I. Gelpi, E. Gentleman, S. Giaccone, G. Graeber, M.B. Hortobagyi, T. Ince, P.G. Ironside, J.W. Kavantzas, N. King, A. Korkolopoulou, P. Kovács, G.G. Meyronet, D. Monoranu, C. Nilsson, T. Parchi, P. Patsouris, E. Revesz, T. Roggendorf, W. Rozemuller, A. Seilhean, D. Streichenberger, N. Thal, D.R. Wharton, S.B. Kretzschmar, H.

Subjects
mental disorders, nutritional and metabolic diseases, nervous system diseases
Abstract

The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome. © 2014, Springer-Verlag Wien.

Published
2015

50. The need to unify neuropathological assessments of vascular alterations in the ageing brain: Multicentre survey by the BrainNet Europe consortium

Author

Alafuzoff, I., Gelpi, E., Al-Sarraj, S., Arzberger, T., Attems, J., Bodi, I., Bogdanovic, N., Budka, H., Bugiani, O., Englund, E., Ferrer, I., Gentleman, S., Giaccone, G., Graeber, M.B., Hortobagyi, T., Hoeftberger, R., Ironside, J.W., Jellinger, K., Kavantzas, N., King, A., Korkolopoulou, P., Kovacs, G.G., Meyronet, D., Monoranu, C., Parchi, P., Patsouris, E., Roggendorf, W., Rozemuller, A.J.M., Seilhean, D., Streichenberger, N., Thal, D.R., Wharton, S.B., Kretzschmar, H., University of Zurich, Alafuzoff, Irina, Pathology, NCA - Neurodegeneration, Alafuzoff I., Gelpi E., Al-Sarraj S., Arzberger T., Attems J., Bodi I., Bogdanovic N., Budka H., Bugiani O., Englund E., Ferrer I., Gentleman S., Giaccone G., Graeber M.B., Hortobagyi T., Höftberger R., Ironside J.W., Jellinger K., Kavantzas N., King A., Korkolopoulou P., Kovács G.G., Meyronet D., Monoranu C., Parchi P., Patsouris E., Roggendorf W., Rozemuller A., Seilhean D., Streichenberger N., Thal D.R., Wharton S.B., and Kretzschmar H.

Subjects
Aging, 1303 Biochemistry, 10208 Institute of Neuropathology, 610 Medicine & health, Klinikai orvostudományok, Severity of Illness Index, Specimen Handling, DIAGNOSTIC CRITERIA, 1307 Cell Biology, 1302 Aging, 1311 Genetics, Surveys and Questionnaires, 1312 Molecular Biology, Humans, VASCULAR DEMENTIA, Staining and Labeling, Brain, Reproducibility of Results, Orvostudományok, 1310 Endocrinology, BRAIN BANKING, Cerebrovascular Disorders, Cerebrovascular Circulation, 570 Life sciences, biology, Dementia, NEUROPATHOLOGY
Abstract

Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres.

Published
2012

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