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1. Deleterious functional consequences of perfluoroalkyl substances accumulation into the myelin sheath

Author

L. Butruille, P. Jubin, E. Martin, M.S. Aigrot, M. Lhomme, J.B. Fini, B. Demeneix, B. Stankoff, C. Lubetzki, B. Zalc, and S. Remaud

Subjects
Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Myelin, Remyelination, Oligodendrocyte, Xenopus, Environmental sciences, GE1-350
Abstract

Exposure to persistent organic pollutants during the perinatal period is of particular concern because of the potential increased risk of neurological disorders in adulthood. Here we questioned whether exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) could alter myelin formation and regeneration. First, we show that PFOS, and to a lesser extent PFOA, accumulated into the myelin sheath of postnatal day 21 (p21) mice, whose mothers were exposed to either PFOA or PFOS (20 mg/L) via drinking water during late gestation and lactation, suggesting that accumulation of PFOS into the myelin could interfere with myelin formation and function. In fact, PFOS, but not PFOA, disrupted the generation of oligodendrocytes, the myelin-forming cells of the central nervous system, derived from neural stem cells localised in the subventricular zone of p21 exposed animals. Then, cerebellar slices were transiently demyelinated using lysophosphatidylcholine and remyelination was quantified in the presence of either PFOA or PFOS. Only PFOS impaired remyelination, a deleterious effect rescued by adding thyroid hormone (TH). Similarly to our observation in the mouse, we also showed that PFOS altered remyelination in Xenopus laevis using the Tg(Mbp:GFP-ntr) model of conditional demyelination and measuring, then, the number of oligodendrocytes. The functional consequences of PFOS-impaired remyelination were shown by its effects using a battery of behavioural tests. In sum, our data demonstrate that perinatal PFOS exposure disrupts oligodendrogenesis and myelin function through modulation of TH action. PFOS exposure may exacerbate genetic and environmental susceptibilities underlying myelin disorders, the most frequent being multiple sclerosis.

Published
2023
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2. Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination

Author

R. Ronzano, T. Roux, M. Thetiot, M. S. Aigrot, L. Richard, F. X. Lejeune, E. Mazuir, J. M. Vallat, C. Lubetzki, and A. Desmazières

Subjects
Science
Abstract

Microglia are important for brain homeostasis and plasticity. The mechanisms underlying microglia-neuron interactions are still unclear. Here, the authors show that microglia preferentially interact with the nodes of Ranvier along axons. This interaction is modulated by neuronal activity and contributes to remyelination in mice.

Published
2021
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3. Patterns of Objective and Subjective Burden of Informal Caregivers in Multiple Sclerosis

Author

E. Bayen, C. Papeix, P. Pradat-Diehl, C. Lubetzki, and M. E. Joël

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background. Home care for patients with Multiple Sclerosis (MS) relies largely on informal caregivers (ICs). Methods. We assessed ICs objective burden (Resource Utilization in Dementia measuring informal care time (ICT)) and ICs subjective burden (Zarit Burden Inventory (ZBI)). Results. ICs (N=99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean EDSS (Expanded Disability Status Scale) of 5.5, with executive dysfunction (mean DEX (Dysexecutive questionnaire) of 25) and a duration of MS ranging from 1 to 44 years. Objective burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas coresidency and IC’s female gender correlated with objective burden only and IC’s poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early dysexecutive function and for patients classified as fast progressors according to the Multiple Sclerosis Severity Score. Conclusion. Evaluation of MS disability course and IC’s personal situation is crucial to understand the burden process and to implement adequate interventions in MS.

Published
2015
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6. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author

Bastard, P. Gervais, A. Voyer, T.L. Rosain, J. Philippot, Q. Manry, J. Michailidis, E. Hoffmann, H.-H. Eto, S. Garcia-Prat, M. Bizien, L. Parra-Martínez, A. Yang, R. Haljasmägi, L. Migaud, M. Särekannu, K. Maslovskaja, J. De Prost, N. Tandjaoui-Lambiotte, Y. Luyt, C.-E. Amador-Borrero, B. Gaudet, A. Poissy, J. Morel, P. Richard, P. Cognasse, F. Troya, J. Trouillet-Assant, S. Belot, A. Saker, K. Garçon, P. Rivière, J.G. Lagier, J.-C. Gentile, S. Rosen, L.B. Shaw, E. Morio, T. Tanaka, J. Dalmau, D. Tharaux, P.-L. Sene, D. Stepanian, A. Megarbane, B. Triantafyllia, V. Fekkar, A. Heath, J.R. Franco, J.L. Anaya, J.-M. Solé-Violán, J. Imberti, L. Biondi, A. Bonfanti, P. Castagnoli, R. Delmonte, O.M. Zhang, Y. Snow, A.L. Holland, S.M. Biggs, C.M. Moncada-Vélez, M. Arias, A.A. Lorenzo, L. Boucherit, S. Coulibaly, B. Anglicheau, D. Planas, A.M. Haerynck, F. Duvlis, S. Nussbaum, R.L. Ozcelik, T. Keles, S. Bousfiha, A.A. El Bakkouri, J. Ramirez-Santana, C. Paul, S. Pan-Hammarström, Q. Hammarström, L. Dupont, A. Kurolap, A. Metz, C.N. Aiuti, A. Casari, G. Lampasona, V. Ciceri, F. Barreiros, L.A. Dominguez-Garrido, E. Vidigal, M. Zatz, M. Van De Beek, D. Sahanic, S. Tancevski, I. Stepanovskyy, Y. Boyarchuk, O. Nukui, Y. Tsumura, M. Vidaur, L. Tangye, S.G. Burrel, S. Duffy, D. Quintana-Murci, L. Klocperk, A. Kann, N.Y. Shcherbina, A. Lau, Y.-L. Leung, D. Coulongeat, M. Marlet, J. Koning, R. Reyes, L.F. Chauvineau-Grenier, A. Venet, F. Monneret, G. Nussenzweig, M.C. Arrestier, R. Boudhabhay, I. Baris-Feldman, H. Hagin, D. Wauters, J. Meyts, I. Dyer, A.H. Kennelly, S.P. Bourke, N.M. Halwani, R. Sharif-Askari, N.S. Dorgham, K. Sallette, J. Sedkaoui, S.M. AlKhater, S. Rigo-Bonnin, R. Morandeira, F. Roussel, L. Vinh, D.C. Ostrowski, S.R. Condino-Neto, A. Prando, C. Bondarenko, A. Spaan, A.N. Gilardin, L. Fellay, J. Lyonnet, S. Bilguvar, K. Lifton, R.P. Mane, S. Anderson, M.S. Boisson, B. Béziat, V. Zhang, S.-Y. Andreakos, E. Hermine, O. Pujol, A. Peterson, P. Mogensen, T.H. Rowen, L. Mond, J. Debette, S. De Lamballerie, X. Duval, X. Mentré, F. Zins, M. Soler-Palacin, P. Colobran, R. Gorochov, G. Solanich, X. Susen, S. Martinez-Picado, J. Raoult, D. Vasse, M. Gregersen, P.K. Piemonti, L. Rodríguez-Gallego, C. Notarangelo, L.D. Su, H.C. Kisand, K. Okada, S. Puel, A. Jouanguy, E. Rice, C.M. Tiberghien, P. Zhang, Q. Cobat, A. Abel, L. Casanova, J.-L. Alavoine, L. Behillil, S. Burdet, C. Charpentier, C. Dechanet, A. Descamps, D. Ecobichon, J.-L. Enouf, V. Frezouls, W. Houhou, N. Kafif, O. Lehacaut, J. Letrou, S. Lina, B. Lucet, J.-C. Manchon, P. Nouroudine, M. Piquard, V. Quintin, C. Thy, M. Tubiana, S. Van Der Werf, S. Vignali, V. Visseaux, B. Yazdanpanah, Y. Chahine, A. Waucquier, N. Migaud, M.-C. Deplanque, D. Djossou, F. Mergeay-Fabre, M. Lucarelli, A. Demar, M. Bruneau, L. Gerardin, P. Maillot, A. Payet, C. Laviolle, B. Laine, F. Paris, C. Desille-Dugast, M. Fouchard, J. Malvy, D. Nguyen, D. Pistone, T. Perreau, P. Gissot, V. Le Goas, C. Montagne, S. Richard, L. Chirouze, C. Bouiller, K. Desmarets, M. Meunier, A. Lefevre, B. Jeulin, H. Legrand, K. Lomazzi, S. Tardy, B. Gagneux-Brunon, A. Bertholon, F. Botelho-Nevers, E. Christelle, K. Nicolas, L. Roufai, L. Amat, K. Couffin-Cadiergues, S. Esperou, H. Hendou, S. Townsend, L. Cheallaigh, C.N. Bergin, C. Martin-Loeches, I. Dunne, J. Conlon, N. O'Farrelly, C. Abad, J. Accordino, G. Achille, C. Aguilera-Albesa, S. Aguilo-Cucurull, A. Ozkan, E.A. Darazam, I.A. Albisures, J.A.R. Aldave, J.C. Ramos, M.A. Khan, T.A. Aliberti, A. Nadji, S.A. Alkan, G. AlKhater, S.A. Allardet-Servent, J. Allende, L.M. Alonso-Arias, R. Alshahrani, M.S. Alsina, L. Alyanakian, M.-A. Borrero, B.A. Amoura, Z. Antoli, A. Aubart, M. Auguet, T. Avramenko, I. Aytekin, G. Azot, A. Bahram, S. Bajolle, F. Baldanti, F. Baldolli, A. Ballester, M. Feldman, H.B. Barrou, B. Barzaghi, F. Basso, S. Bayhan, G.I. Bezrodnik, L. Bilbao, A. Blanchard-Rohner, G. Blanco, I. Blandinieres, A. Blazquez-Gamero, D. Bleibtreu, A. Bloomfield, M. Bolivar-Prados, M. Borghesi, A. Borie, R. Botdhlo-Nevers, E. Bousquet, A. Boutolleau, D. Bouvattier, C. Bravais, J. Briones, M.L. Brunner, M.-E. Bruno, R. Bueno, M.R.P. Bukhari, H. Bustamante, J. Agra, J.J.C. Capra, R. Carapito, R. Carrabba, M. Casasnovas, C. Caseris, M. Cassaniti, I. Castelle, M. Castelli, F. De Vera, M.C. Castro, M.V. Catherinot, E. Celik, J.B. Ceschi, A. Chalumeau, M. Charbit, B. Cheng, M.P. Clave, P. Clotet, B. Codina, A. Cohen, Y. Comarmond, C. Combes, A. Comoli, P. Corsico, A.G. Coşkuner, T. Cvetkovski, A. Cyrus, C. Danion, F. Darley, D.R. Das, V. Dauby, N. Dauger, S. De Munter, P. De Pontual, L. Dehban, A. Delplancq, G. Demoule, A. Desguerre, I. Di Sabatino, A. Diehl, J.-L. Dobbelaere, S. Dubost, C. Ekwall, O. Bozdemir, Ş.E. Elnagdy, M.H. Emiroglu, M. Endo, A. Erdeniz, E.H. Aytekin, S.E. Lasa, M.P.E. Euvrard, R. Fabio, G. Faivre, L. Falck, A. Fartoukh, M. Faure, M. Arquero, M.F. Ferrer, R. Ferreres, J. Flores, C. Francois, B. Fumado, V. Fung, K.S.C. Fusco, F. Gagro, A. Solis, B.G. Gaussem, P. Gayretli, Z. Gil-Herrera, J. Gatineau, A.G. Girona-Alarcon, M. Godinez, K.A.C. Goffard, J.-C. Gonzales, N. Gonzalez-Granado, L.I. Gonzalez-Montelongo, R. Guerder, A. Gulhan, B. Gumucio, V.D. Hanitsch, L.G. Gunst, J. Gut, M. Hadjadj, J. Hancerli, S. Hariyan, T. Hatipoglu, N. Heppekcan, D. Hernandez-Brito, E. Ho, P.-K. Holanda-Pena, M.S. Horcajada, J.P. Hraiech, S. Humbert, L. Hung, I.F.N. Iglesias, A.D. Inigo-Campos, A. Jamme, M. Arranz, M.J. Jimeno, M.-T. Jordan, I. Kanik-Yuksek, S. Kara, Y.B. Karahan, A. Karbuz, A. Yasar, K.K. Kasapcopur, O. Kashimada, K. Demirkol, Y.K. Kido, Y. Kizil, C. Kilic, A.O. Koutsoukou, A. Krol, Z.J. Ksouri, H. Kuentz, P. Kwan, A.M.C. Kwan, Y.W.M. Kwok, J.S.Y. Lam, D.S.Y. Lampropoulou, V. Lanternier, F. Le Bourgeois, F. Leo, Y.-S. Lopez, R.L. Levin, M. Levy, M. Levy, R. Li, Z. Lilleri, D. Lima, E.J.A.B. Linglart, A. Lopez-Collazo, E. Lorenzo-Salazar, J.M. Louapre, C. Lubetzki, C. Lung, K.-C. Lye, D.C. Magnone, C. Mansouri, D. Marchioni, E. Marioli, C. Marjani, M. Marques, L. Pereira, J.M. Martin-Nalda, A. Pueyo, D.M. Marzana, I. Mata-Martinez, C. Mathian, A. Matos, L.R.B. Matthews, G.V. Mayaux, J. McLaughlin-Garcia, R. Meersseman, P. Mege, J.-L. Mekontso-Dessap, A. Melki, I. Meloni, F. Meritet, J.-F. Merlani, P. Akcan, O.M. Mezidi, M. Migeotte, I. Millereux, M. Million, M. Mirault, T. Mircher, C. Mirsaeidi, M. Mizoguchi, Y. Modi, B.P. Mojoli, F. Moncomble, E. Melian, A.M. Martinez, A.M. Morange, P.-E. Mordacq, C. Morelle, G. Mouly, S.J. Munoz-Barrera, A. Nafati, C. Nagashima, S. Nakagama, Y. Neven, B. Neves, J.F. Ng, L.F.P. Ng, Y.-Y. Nielly, H. Medina, Y.N. Cuadros, E.N. Ocejo-Vinyals, J.G. Okamoto, K. Oualha, M. Ouedrani, A. Ozkaya-Parlakay, A. Pagani, M. Papadaki, M. Parizot, C. Parola, P. Pascreau, T. Paz-Artal, E. Pedraza, S. Pellecer, N.C.G. Pellegrini, S. De Diego, R.P. Perez-Fernandez, X.L. Philippe, A. Picod, A. De Chambrun, M.P. Piralla, A. Planas-Serra, L. Ploin, D. Poncelet, G. Poulakou, G. Pouletty, M.S. Pourshahnazari, P. Qiu-Chen, J.L. Quentric, P. Rambaud, T. Raoult, V. Rebillat, A.-S. Redin, C. Resmini, L. Ricart, P. Richard, J.-C. Rivet, N. Rocamora-Blanch, G. Rodero, M.P. Rodrigo, C. Rodriguez, L.A. Rodriguez-Palmero, A. Romero, C.S. Rothenbuhler, A. Roux, D. Rovina, N. Rozenberg, F. Ruch, Y. Ruiz, M. Del Prado, M.Y.R. Ruiz-Rodriguez, J.C. Sabater-Riera, J. Saks, K. Salagianni, M. Sanchez, O. Sanchez-Montalva, A. Sanchez-Ramon, S. Schidlowski, L. Schluter, A. Schmidt, J. Schmidt, M. Schuetz, C. Schweitzer, C.E. Scolari, F. Sediva, A. Seijo, L. Seminario, A.G. Seng, P. Senoglu, S. Seppanen, M. Llovich, A.S. Shahrooei, M. Siguret, V. Siouti, E. Smadja, D.M. Smith, N. Sobh, A. Soler, C. Sozeri, B. Stella, G.M. Stepanovskiy, Y. Stoclin, A. Taccone, F. Taupin, J.-L. Tavernier, S.J. Terrier, B. Thiery, G. Thorball, C. Thorn, K. Thumerelle, C. Tipu, I. Tolstrup, M. Tomasoni, G. Toubiana, J. Alvarez, J.T. Tsang, O.T.Y. Tserel, L. Tso, E.Y.K. Tucci, A. Oz, Ş.K.T. Ursini, M.V. Utsumi, T. Uzunhan, Y. Vabres, P. Valencia-Ramos, J. Van Den Rym, A.M. Vandernoot, I. Velez-Santamaria, V. Veliz, S.P.Z. Vidigal, M.C. Viel, S. Vilain, C. Vilaire-Meunier, M.E. Villar-Garcia, J. Vincent, A. Vogt, G. Voiriot, G. Volokha, A. Vuotto, F. Wauters, E. Wu, A.K.L. Wu, T.-C. Yahşi, A. Yesilbas, O. Yildiz, M. Young, B.E. Yukselmiş, U. Zecca, M. Zuccaro, V. Van Praet, J. Lambrecht, B.N. Van Braeckel, E. Bosteels, C. Hoste, L. Hoste, E. Bauters, F. De Clercq, J. Heijmans, C. Slabbynck, H. Naesens, L. Florkin, B. Boulanger, C. Vanderlinden, D. Allavena, C. Andrejak, C. Angoulvant, F. Azoulay, C. Bachelet, D. Bartoli, M. Basmaci, R. Behillill, S. Beluze, M. Benech, N. Benkerrou, D. Bhavsar, K. Bitker, L. Bouadma, L. Bouscambert-Duchamp, M. Paz, P.C. Cervantes-Gonzalez, M. Chair, A. Coelho, A. Cordel, H. Couffignal, C. D'Ortenzio, E. De Montmollin, E. Debard, A. Debray, M.-P. Desvallee, M. Diallo, A. Diouf, A. Dorival, C. Dubos, F. Eloy, P. Epaulard, O. Esposito-Farase, M. Etienne, M. Garot, D. Gault, N. Gaymard, A. Ghosn, J. Gigante, T. Gilg, M. Goehringer, F. Guedj, J. Hoctin, A. Hoffmann, I. Houas, I. Hulot, J.-S. Jaafoura, S. Kaguelidou, F. Kali, S. Kerroumi, Y. Khalil, A. Khan, C. Kimmoun, A. Laouenan, C. Laribi, S. Le, M. Le Bris, C. Le Gac, S. Le Hingrat, Q. Le Mestre, S. Le Nagard, H. Lemaignen, A. Lemee, V. Lescure, F.-X. Levy, Y. Lingas, G. Lucet, J.C. MacHado, M. Mambert, M. Manuel, A. Meziane, A. Mouquet, H. Mullaert, J. Neant, N. Noret, M. Papadopoulos, A. Paul, C. Peiffer-Smadja, N. Peigne, V. Petrov-Sanchez, V. Peytavin, G. Pham, H. Picone, O. Puechal, O. Rosa-Calatrava, M. Rossignol, B. Rossignol, P. Roy, C. Schneider, M. Su, R. Tardivon, C. Tellier, M.-C. Teoule, F. Terrier, O. Timsit, J.F. Tual, C. Vanel, N. Veislinger, A. Wiedemann, A. Danielson, J.J. Dobbs, K. Kashyap, A. Ding, L. Dalgard, C.L. Sottini, A. Quaresima, V. Quiros-Roldan, E. Rossi, C. Bettini, L.R. D'Angio, M. Beretta, I. Montagna, D. Licari, A. Marseglia, G.L. Storgaard, M. Jorgensen, S. Al-Muhsen, S. Al-Mulla, F. Arias, A.A. Bogunovic, D. Bolze, A. Brodin, P. Bryceson, Y. Bustamante, C.D. Butte, M.J. Chakravorty, S. Christodoulou, J. Constantinescu, S.N. Cooper, M.A. Desai, M. Drolet, B.A. El Baghdadi, J. Espinosa-Padilla, S. Froidure, A. Henrickson, S.E. Hsieh, E.W.Y. Husebye, E.S. Imai, K. Itan, Y. Jarvis, E.D. Karamitros, T. Ku, C.-L. Ling, Y. Lucas, C.L. Maniatis, T. Marodi, L. Milner, J.D. Mironska, K. Novelli, A. Novelli, G. Renia, L. Resnick, I. Sancho-Shimizu, V. Seppanen, M.R.J. Shahrooei, M. Slaby, O. Tayoun, A.A. Ramaswamy, S. Turvey, S.E. Furkan Uddin, K.M. Uddin, M.J. Von Bernuth, H. Zawadzki, P. Bigio, B. De La Chapelle, A. Chen, J. Chrabieh, M. Liu, D. Nemirowskaya, Y. Cruz, I.M. Materna, M. Pelet, S. Seeleuthner, Y. Thibault, C. Liu, Z. Foti, G. Bellani, G. Citerio, G. Contro, E. Pesci, A. Valsecchi, M.G. Cazzaniga, M. Batten, I. Reddy, C. McElheron, M. Noonan, C. Connolly, E. Fallon, A. Erikstrup, C. Pedersen, O.B. Sorensen, E. Mikkelsen, S. Dinh, K.M. Larsen, M.A.H. Paulsen, I.W. Von Stemann, J.H. Hansen, M.B. Annereau, J.-P. Briseno-Roa, L. Gribouval, O. Pelet, A. Alcover, A. Aschard, H. Bousso, P. Bruhns, P. Cerf-Bensussan, N. Cumano, A. D'Enfert, C. Deriano, L. Dillies, M.-A. Di Santo, J. Dromer, F. Eberl, G. Enninga, J. Gomperts-Boneca, I. Hasan, M. Hedestam, G.K. Hercberg, S. Ingersoll, M.A. Lantz, O. Kenny, R.A. Menager, M. Michel, F. Patin, E. Pellegrini, S. Rausell, A. Rieux-Laucat, F. Rogge, L. Fontes, M. Sakuntabhai, A. Schwartz, O. Schwikowski, B. Shorte, S. Tangy, F. Toubert, A. Touvier, M. Ungeheuer, M.-N. Zimmer, C. Albert, M.L. Van Agtmael, M. Algera, A.G. Appelman, B. Van Baarle, F. Bax, D. Beudel, M. Bogaard, H.J. Bomers, M. Bonta, P. Bos, L. Botta, M. De Brabander, J. De Bree, G. De Bruin, S. Buis, D.T.P. Bugiani, M. Bulle, E. Chouchane, O. Cloherty, A. Dijkstra, M. Dongelmans, D.A. Dujardin, R.W.G. Elbers, P. Fleuren, L. Geerlings, S. Geijtenbeek, T. Girbes, A. Goorhuis, B. Grobusch, M.P. Hafkamp, F. Hagens, L. Hamann, J. Harris, V. Hemke, R. Hermans, S.M. Heunks, L. Hollmann, M. Horn, J. Hovius, J.W. De Jong, M.D. Lim, E.H.T. Van Mourik, N. Nellen, J. Nossent, E.J. Paulus, F. Peters, E. Pina-Fuentes, D.A.I. Van Der Poll, T. Preckel, B. Prins, J.M. Raasveld, J. Reijnders, T. De Rotte, M.C.F.J. Schinkel, M. Schultz, M.J. Schrauwen, F.A.P. Schuurman, A. Schuurmans, J. Sigaloff, K. Slim, M.A. Smeele, P. Smit, M. Stijnis, C.S. Stilma, W. Teunissen, C. Thoral, P. Tsonas, A.M. Tuinman, P.R. Van Der Valk, M. Veelo, D. Volleman, C. De Vries, H. Vught, L.A. Van Vugt, M. Wouters, D. Zwinderman, A.H. Brouwer, M.C. Joost Wiersinga, W. Vlaar, A.P.J. Nadif, R. Goldberg, M. Ozguler, A. Henny, J. Lemonnier, S. Coeuret-Pellicer, M. Le Got, S. Tzourio, C. Dufouil, C. Soumare, A. Lachaize, M. Fievet, N. Flaig, A. Martin, F. Bonneaudeau, B. Cannet, D. Gallian, P. Jeanne, M. Perroquin, M. Hamzeh-Cognasse, H. CoV-Contact Cohort St James's Hospital, SARS CoV2 Interest group COVID Clinicians French COVID Cohort Study Group NIAID Immune Response to COVID Group Danish CHGE COVID Human Genetic Effort HGID Lab COVID-STORM Clinicians NH-COVAIR Study Group The Danish Blood Donor Study (DBDS) Imagine COVID-Group The Milieu Interieur Consortium Amsterdam UMC Covid-19 Biobank CONSTANCES cohort 3C-Dijon Study Cerba HealthCare Etablissement du Sang study group

Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases. © 2021 The Authors, some rights reserved.

Published
2021

7. New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

Author

Jean-Christophe Brisset, Stephane Kremer, Salem Hannoun, Fabrice Bonneville, Francoise Durand-Dubief, Thomas Tourdias, Christian Barillot, Charles Guttmann, Sandra Vukusic, Vincent Dousset, Francois Cotton, R. Ameli, R. Anxionnat, B. Audoin, A. Attye, E. Bannier, C. Barillot, D. Ben Salem, M.-P. Boncoeur-Martel, G. Bonhomme, F. Bonneville, C. Boutet, J.C. Brisset, F. Cervenanski, B. Claise, O. Commowick, J.-M. Constans, F. Cotton, P. Dardel, H. Desal, V. Dousset, F. Durand-Dubief, J.-C. Ferre, A. Gaultier, E. Gerardin, T. Glattard, S. Grand, T. Grenier, R. Guillevin, C. Guttmann, A. Krainik, S. Kremer, S. Lion, N. Menjot De Champfleur, L. Mondot, O. Outteryck, N. Pyatigorskaya, J.-P. Pruvo, S. Rabaste, J.-P. Ranjeva, J.-A. Roch, J.-C. Sadik, D. Sappey-Marinier, J. Savatovsky, B. Stankoff, J.-Y. Tanguy, A. Tourbah, T. Tourdias, B. Brochet, R. Casey, J. De Sèze, P. Douek, F. Guillemin, D. Laplaud, C. Lebrun-Frenay, L. Mansuy, T. Moreau, J. Olaiz, J. Pelletier, C. Rigaud-Bully, S. Vukusic, M. Debouverie, G. Edan, J. Ciron, C. Lubetzki, P. Vermersch, P. Labauge, G. Defer, E. Berger, P. Clavelou, O. Gout, E. Thouvenot, O. Heinzlef, A. Al-Khedr, B. Bourre, O. Casez, P. Cabre, A. Montcuquet, A. Créange, J.-P. Camdessanché, S. Bakchine, A. Maurousset, I. Patry, T. De Broucker, C. Pottier, J.-P. Neau, C. Labeyrie, C. Nifle, Hôpital de Hautepierre [Strasbourg], Nehme and Therese Tohme Multiple Sclerosis Center [Beyrouth, Liban] (AUBMC), American University of Beirut Medical Center [Beyrouth, Liban] (AUBMC), American University of Beirut [Beyrouth] (AUB)-American University of Beirut [Beyrouth] (AUB), Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Empenn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Center for Neurological Imaging, Departments of Radiology and Neurology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-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), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Service de neuroradiologie [Lyon], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neuroradiologie [Grenoble], CHU Grenoble, Laboratoire de Traitement de l'Information Medicale (LaTIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de Radiologie et Imagerie Médicale [CHU Limoges], CHU Limoges, Auteur indépendant, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Clermont-Ferrand, CHU Amiens-Picardie, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital des Charpennes [CHU - HCL], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pasteur [Nice] (CHU), Hôpital Roger Salengro [Lille], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aix Marseille Université (AMU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Raymond Poincaré [AP-HP], CHU de Bordeaux Pellegrin [Bordeaux], Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Union pour la lutte contre la sclérose en plaques (UNISEP), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), Fondation Eugène Devic EDMUS, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Gabriel Montpied [Clermont-Ferrand], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Hôpital Charles Nicolle [Rouen], Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Hôpital Dupuytren [CHU Limoges], Hôpital Henri Mondor, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), French State, 'Investments for the Future', Eugène Devic EDMUS Foundation, ARSEP Foundation, Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroimagerie: méthodes et applications (Empenn), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), 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)-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 Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Gui de Chauliac [CHU Montpellier], Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), 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 Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, and 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)

Subjects
medicine.medical_specialty, Consensus, Multiple Sclerosis, Gadolinium, chemistry.chemical_element, Contrast Media, Fluid-attenuated inversion recovery, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Quality of life, Medicine, Humans, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, Brain, Magnetic resonance imaging, medicine.disease, Image Enhancement, Magnetic Resonance Imaging, 3. Good health, chemistry, OFSEP, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Abstract

Purpose New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain. Methods A consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up. Recommendations The French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences.

Published
2020
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8. Melanoma during fingolimod treatment for multiple sclerosis

Author

C. Lubetzki, M. Thomas, Andrea Cavalcanti, C. Velter, F. Chochon, Emilie Routier, Caroline Robert, and M. Bastien

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Side effect, business.industry, Multiple sclerosis, Melanoma, medicine.disease, Fingolimod, Internal medicine, medicine, Adverse effect, business, medicine.drug
Published
2019
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10. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author

C. Lebrun, S. Vukusic, V. Abadie, C. Achour, F. Ader, H. Alchaar, A. Alkhedr, F. Andreux, G. Androdias, R. Arjmand, B. Audoin, D. Audry, D. Aufauvre, C. Autreaux, X. Ayrignac, M. Bailbe, M. Benazet, C. Bensa, D. Bensmail, E. Berger, P. Bernady, Y. Bertagna, D. Biotti, A. Blanchard-Dauphin, J. Bonenfant, M. Bonnan, B. Bonnemain, F. Borgel, E. Botelho-Nevers, S. Boucly, B. Bourre, C. Boutière, P. Branger, D. Brassat, S. Bresch, V. Breuil, B. Brochet, H. Brugeilles, P. Bugnon, P. Cabre, J.-P. Camdessanché, C. Carra-Dalière, O. Casez, J.-M. Chamouard, B. Chassande, P. Chataignier, M. Chbicheb, A. Chenet, J. Ciron, P. Clavelou, M. Cohen, R. Colamarino, N. Collongues, I. Coman, P.-R. Corail, S. Courtois, M. Coustans, A. Creange, E. Creisson, N. Daluzeau, C. Davenas, J. De Seze, M. Debouverie, R. Depaz, N. Derache, L. Divio, X. Douay, C. Dulau, F. Durand-Dubief, G. Edan, Z. Elias, O. Fagniez, M. Faucher, J.-M. Faucheux, M. Fournier, A. Gagneux-Brunon, P. Gaida, P. Galli, P. Gallien, J. Gaudelus, D. Gault, A. Gayou, M. Genevray, A. Gentil, J. Gere, L. Gignoux, M. Giroux, P. Givron, O. Gout, J. Grimaud, A.-M. Guennoc, N. Hadhoum, P. Hautecoeur, O. Heinzlef, M. Jaeger, S. Jeannin, L. Kremer, A. Kwiatkowski, P. Labauge, C. Labeyrie, S. Lachaud, I. Laffont, C. Lanctin-Garcia, J. Lannoy, L. Lanotte, D. Laplaud, D. Latombe, M. Lauxerois, E. Le Page, C. Lebrun-Frenay, P. Lejeune, P. Lejoyeux, B. Lemonnier, E. Leray, C.-M. Loche, C. Louapre, C. Lubetzki, A. Maarouf, B. Mada, L. Magy, E. Maillart, E. Manchon, R. Marignier, P. Marque, G. Mathey, A. Maurousset, C. Mekies, M. Merienne, L. Michel, A.-M. Milor, X. Moisset, A. Montcuquet, T. Moreau, N. Morel, M. Moussa, J.-P. Naudillon, M. Normand, P. Olive, J.-C. Ouallet, O. Outteryck, C. Pacault, C. Papeix, I. Patry, D. Peaureaux, J. Pelletier, B. Pichon, S. Pittion, E. Planque, M.-C. Pouget, V. Pourcher, C. Radot, I. Robert, F. Rocher, A. Ruet, C. Saint-Val, J.-Y. Salle, A. Salmon, E. Sartori, S. Schaeffer, B. Stankhof, F. Taithe, E. Thouvenot, C. Tizon, A. Tourbah, P. Tourniaire, M. Vaillant, P. Vermersch, S. Vidil, A. Wahab, M.-H. Warter, S. Wiertlewski, B. Wiplosz, B. Wittwer, C. Zaenker, H. Zephir, Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], CHU Saint-Etienne, Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Comité de Développement Horticole du Centre Val de Loire (CDHRC), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service d'Etudes du Comportement des Matériaux de Conditionnement (SECM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Rennes] = Neurology [Rennes], Excitabilité nerveuse et thérapeutique (ENT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), RMN et optique : De la mesure au biomarqueur, 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Combustion Research Facility, Sandia National Laboratories - Corporation, Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kuriwa Observatory, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Euromov (EuroMov), Université de Montpellier (UM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'automatique et de génie des procédés (LAGEP), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Haras National Suisse, Centre Hospitalier Universitaire de Reims (CHU Reims), Center for health studies, Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hospices Civils de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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)-Université Claude Bernard Lyon 1 (UCBL), 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 de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Comité de développement horticole de la région Centre-Val-de-Loire (CDHR CENTRE-VAL-DE-LOIRE), 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), 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 Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Ecole Centrale de Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie, CHU Clermont-Ferrand, Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
medicine.medical_specialty, Vaccination schedule, MEDLINE, Scientific literature, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Health care, Medicine, Humans, 030212 general & internal medicine, Immunization Schedule, Societies, Medical, Vaccines, business.industry, Risk of infection, Prevention, Vaccination, medicine.disease, 3. Good health, Neurology, Immunization, Family medicine, Evidence-Based Practice, Practice Guidelines as Topic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, business, Infection, Vaccine, 030217 neurology & neurosurgery
Abstract

Objectives To establish recommendations on immunization for patients with multiple sclerosis (MS). Background Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. Methods The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. Results Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. Conclusion Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.

Published
2019
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11. Impact du vaccin contre la fièvre jaune sur l’évolution clinique de la sclérose en plaques

Author

J. Vidal, C. Papeix, J. Mazoyer, Valérie Pourcher, C. Lebrun, E. Maillart, and C. Lubetzki

Subjects
Infectious Diseases
Abstract

Introduction Le vaccin contre la fievre jaune est requis pour voyager en zone d’endemie de fievre jaune mais il est deconseille chez les patients atteints de sclerose en plaques (SEP) en raison du risque potentiel de poussees post-vaccinales mis en evidence dans une seule publication incluant 7 patients. Materiels et methodes Evaluer chez les patients SEP recurrentes-remittentes, ayant beneficie d’une vaccination fievre jaune, le risque de survenue d’une activite de la maladie dans les 12 mois suivant la vaccination. Dans cette etude retro-prospective et observationnelle exposes/non-exposes, chaque patient vaccine contre la fievre jaune apres le debut de la maladie SEP a ete apparie a 3 patients SEP sans historique de vaccination contre la fievre jaune et identifies par la base de donnees locale European Database for Multiple Sclerosis (EDMUS). Les criteres d’appariement etaient : l’âge et l’activite de la maladie avant vaccination. Le delai de survenue d’une poussee des exposes et non-exposes a ete analyse par un test log-rank. Un modele de Cox a estime les hazard ratio bruts et ajustes. Resultats Trente et un (20 F/11 H) patients vaccines ont ete inclus. L’âge moyen de debut de la maladie etait de 38 ans et la duree moyenne de la maladie avant la vaccination etait de 10,8 ans. Parmi les patients, 19,35 % avaient une activite clinique l’annee precedant la vaccination, l’Expanded Disability Status Scale (EDSS) moyen etait a 0,78 lors de la vaccination. La moitie des patients n’etaient pas traites pour le SEP au moment de la vaccination (51,6 %), 41,9 % d’entre eux avaient un traitement de 1re ligne et 6,4 % etaient traites par natalizumab. Les resultats complets de cette etude exposes/non-exposes seront disponibles fin fevrier. Conclusion La fievre jaune est une maladie grave potentiellement mortelle, pouvant etre contractee en zones d’endemie (Afrique subsaharienne et Amerique du Sud) et ne disposant pas de traitement. Le vaccin anti-amaril, tres efficace, est exige pour entrer sur le territoire de certains pays en zone d’endemie. Ce vaccin vivant attenue est contre-indique chez les patients traites par immunosuppresseurs. Les resultats de cette etude epidemiologique cas/temoin permettront de faire evoluer les pratiques et les recommandations vaccinales contre la fievre jaune et de conseiller au mieux les patients atteints de SEP se rendant en zone d’endemie.

Published
2020
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12. Informal care in multiple sclerosis

Author

Marie-Eve Joël, Eleonore Bayen, Pascale Pradat-Diehl, C Lubetzki, C Papeix, UPMC - Faculté de médecine Pitié Salpétrière, Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Sorbonne Université (SU), Physiologie et physiopathologie de la motricité chez l'homme, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (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), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)

Subjects
Gerontology, medicine.medical_specialty, Multivariate analysis, Psychological intervention, Burden, Multiple sclerosis, medicine, Orthopedics and Sports Medicine, 10. No inequality, Expanded Disability Status Scale, [QFIN]Quantitative Finance [q-fin], business.industry, Rehabilitation, Mean age, Cognition, medicine.disease, Mental health, 3. Good health, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I12 - Health Behavior, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I11 - Analysis of Health Care Markets, Informal caregiver, Multiple Sclerosis Severity Scale, Physical therapy, business, Executive dysfunction
Abstract

International audience; BackgroundHome care for patients with multiple sclerosis relies largely on informal caregivers (ICs).MethodsWe assessed ICs objective burden (Informal Care Time, ICT) and ICs subjective burden (Zarit Burden Inventory, ZBI) and their explanatory factors.ResultsICs (n = 99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean Expanded Disability Status Scale (EDSS) of 5.5, with executive dysfunction (mean DysExecutive Questionnaire [DEX] of 25) and a duration of MS ranging from 1 to 44 years. Objective burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas co-residency and IC's female gender correlated with objective burden only and IC's poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early cognitive dysfunction and for patients classified as fast progressors according to the Multiple Sclerosis Severity Scale.ConclusionMS disability course and IC's personal situation must be evaluated to understand the burden process and to implement adequate interventions in MS.

Published
2015
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13. Patterns of Objective and Subjective Burden of Informal Caregivers in Multiple Sclerosis

Author

Marie-Eve Joël, E. Bayen, C Papeix, C Lubetzki, Pascale Pradat-Diehl, Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Economie et de Gestion des Organisations de Santé (Legos), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Health Economics Department, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Gerontology, medicine.medical_specialty, Multiple Sclerosis, Multivariate analysis, Activities of daily living, Adolescent, Article Subject, Psychological intervention, Neurosciences. Biological psychiatry. Neuropsychiatry, Severity of Illness Index, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Activities of Daily Living, Severity of illness, medicine, Humans, Dementia, Disabled Persons, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, Young adult, 10. No inequality, Aged, Expanded Disability Status Scale, business.industry, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, General Medicine, Middle Aged, medicine.disease, 3. Good health, Neuropsychology and Physiological Psychology, Caregivers, Neurology, Physical therapy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery, Research Article, RC321-571, Executive dysfunction
Abstract

Background. Home care for patients with Multiple Sclerosis (MS) relies largely on informal caregivers (ICs). Methods. We assessed ICs objective burden (Resource Utilization in Dementia measuring informal care time (ICT)) and ICs subjective burden (Zarit Burden Inventory (ZBI)). Results. ICs (N=99) were spouses (70%), mean age 52 years, assisting disabled patients with a mean EDSS (Expanded Disability Status Scale) of 5.5, with executive dysfunction (mean DEX (Dysexecutive questionnaire) of 25) and a duration of MS ranging from 1 to 44 years. Objective burden was high (mean ICT = 6.5 hours/day), mostly consisting of supervision time. Subjective burden was moderate (mean ZBI = 27.3). Multivariate analyses showed that both burdens were positively correlated with higher levels of EDSS and DEX, whereas coresidency and IC’s female gender correlated with objective burden only and IC’s poor mental health status with subjective burden only. When considering MS aggressiveness, it appeared that both burdens were not correlated with a higher duration of MS but rather increased for patients with severe and early dysexecutive function and for patients classified as fast progressors according to the Multiple Sclerosis Severity Score. Conclusion. Evaluation of MS disability course and IC’s personal situation is crucial to understand the burden process and to implement adequate interventions in MS.

Published
2015
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14. [Editorial]

Author

J.-C. Antoine, R. Liblau, and C. Lubetzki

Subjects
Neurology, Allergy and Immunology, Neurology (clinical)
Published
2014

15. A rat G protein-coupled receptor selectively expressed in myelin-forming cells

Author

Bernard Zalc, S. Barrón, J. ‐C. Schwartz, C. Lubetzki, P. Sokoloff, Julien Allard, and J. Diaz

Subjects
Orphan receptor, Nervous system, Glial fibrillary acidic protein, General Neuroscience, Schwann cell, Biology, Oligodendrocyte, Cell biology, Neuroepithelial cell, Myelin, medicine.anatomical_structure, nervous system, Myelin maintenance, medicine, biology.protein, Neuroscience
Abstract

By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.

Published
1998
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16. Intravascular lymphoma mimicking a Vogt-Koyanagi-Harada disease

Author

P Kaminsky, C Lubetzki, Karine Angioi, K Mokhtari, Phuc LeHoang, and Bahram Bodaghi

Subjects
Vogt–Koyanagi–Harada disease, Adult, Male, Pathology, medicine.medical_specialty, Lymphoma, Biopsy, Vision Disorders, Diagnosis, Differential, Stereotaxic Techniques, Fatal Outcome, Blurred vision, medicine, Immunology and Allergy, Humans, Fluorescein Angiography, Confusion, Paraplegia, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, eye diseases, Vascular Neoplasms, Ophthalmology, Stereotaxic technique, Steroids, medicine.symptom, business, Uveomeningoencephalitic Syndrome, Meningitis, Uveitis
Abstract

Purpose: To report a case of intravascular lymphoma (IVL) mimicking a Vogt-Koyanagi-Harada disease (VKH).Design: Case report.Methods: A 38-year-old man was referred for blurred vision, headache, and hearing loss. Examination demonstrated vitritis and subretinal detachments in each eye. Cerebral fluid analysis showed lymphocytic meningitis. Cerebral MRI was normal. A diagnosis of VKH disease was made.Results: Steroid treatment was introduced, after which all symptoms disappeared. Six months later, the patient returned with paraplegia and confusion. Cerebral MRI revealed hypodense periventricular lesions. A stereotaxic biopsy confirmed the diagnosis of IVL. The patient died a few months later.Conclusion: IVL may have many revealing aspects, including ophthalmologic symptoms.

Published
2011

18. Fecundity in women with multiple sclerosis: An observational monocentric study

Author

C. Papeix, T. Roux, Carine Courtillot, Philippe Touraine, C. Lubetzki, and Rabab Debs

Subjects
education.field_of_study, medicine.medical_specialty, Pregnancy, business.industry, Obstetrics, Endocrinology, Diabetes and Metabolism, Multiple sclerosis, Population, Retrospective cohort study, General Medicine, Disease, Fecundity, medicine.disease, Endocrinology, Cohort, Medicine, Observational study, business, education
Abstract

Multiple sclerosis (MS) is a neurological disease mostly affecting women of childbearing age. When counseling MS patients, many questions arise on the reciprocal influence of MS and pregnancy. However, little is known on the impact of MS and its treatments on the time to pregnancy. The objective was to evaluate fecundity (pregnancy and time to pregnancy) in a French cohort of MS women. One hundred and fifteen women with MS were included consecutively in this observational retrospective study. Pregnancy and time to pregnancy were collected using self-questionnaires. Among the 115 patients, 216 pregnancies (from 84 women) were reported. Mean time to pregnancy, which was available for 124 of these pregnancies, was 8.57 months when pregnancy occurred before MS onset, and 7.53 months after MS onset. Among the 95 patients who had a parental project, 2.27 spontaneous pregnancies per woman were recorded. The mean number of children per woman with MS was 1.37. Spontaneous pregnancies per woman and time to pregnancy were not different from the general French population. However, despite a normal fecundity, the mean number of children per woman with MS (1.37) was lower than in the general French population (1.99).

Published
2015
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19. [Adult onset hereditary leukoencephalopathies]

Author

F, Sedel, A, Tourbah, N, Baumann, B, Fontaine, P, Aubourg, C, Lubetzki, and O, Lyon-Caen

Subjects
Brain Diseases, Mutation, Humans, Age of Onset, Demyelinating Diseases
Abstract

In clinical practice, the term "genetic leukoencephalopathy" refers to a group of genetic diseases whose common point is to give an aspect of diffuse leukoencephalopathy on MRI. With progress in diagnostic techniques including radiology, biochemistry or genetics, a large number of hereditary diseases causing leukoencephalopathy have been identified. Although generally beginning in childhood, these diseases often have more insidious clinical forms which can begin in adulthood. These forms remain poorly known. Some are accessible to treatment so their diagnosis appears essential. The diagnostic steps must be guided by clinical examination (neurological, ophthalmological and systemic), electromyography and MRI. The purpose of this review is to propose a classification of the genetic leukoencephalopathies and to give a progress report applicable in neurological practice.

Published
2005

21. MR spectroscopic pulvinar sign in a case of variant Creutzfeldt-Jakob disease

Author

D, Galanaud, D, Dormont, D, Grabli, P, Charles, J J, Hauw, C, Lubetzki, J P, Brandel, C, Marsault, and P J, Cozzone

Subjects
Adult, Aspartic Acid, Magnetic Resonance Spectroscopy, Phosphocreatine, Biopsy, Creatine, Prognosis, Pulvinar, Sensitivity and Specificity, Creutzfeldt-Jakob Syndrome, Choline, Case-Control Studies, Humans, Female, Inositol
Abstract

We report MR spectroscopic findings in a patient hospitalized with biopsy-proven variant Creutzfeldt-Jakob (vCJD) disease. N-acetyl aspartate was markedly decreased in the postero-medial part of the thalami (pulvinar) but was not diminished in the parieto-occipital white matter and cortical grey matter. These observations, which are in accordance with the pathological findings in this disease, suggest that MR spectroscopy, a highly sensitive method for the detection of subtle brain metabolic dysfunction, could be of interest for the diagnosis, prognosis and therapeutic follow-up of vCJD.

Published
2003

22. Klinische Diagnose und Verlauf der multiplen Sklerose

Author

C. Lubetzki, B. Fontaine, and O. Lyon-Caen

Abstract

Die Definition der multiplen Sklerose (MS) ist eine anatomische [1]. MS ist eine Erkrankung, die zur Bildung multipler, deutlich umschriebener Lasionen innerhalb der weisen Substanz des zentralen Nervensystems fuhrt. Diese Lasionen, die so genannten „Plaques“, bilden sich aus einem entzundlichen Infiltrat, das sich um die Venolen entwickelt. Die Zerstorung des Myelins ist elektiv, zumindest am Beginn der Erkrankung verschont sie die Axone. Fur die klinische Praxis ist das Kriterium der anatomischen Definition der MS untauglich: Die Autopsie und die Gehirnbiopsie sind zwar mogliche, aber ganz ausergewohnliche Umstande fur die Diagnose einer MS. Die anatomischen Untersuchungen haben gezeigt, dass bei ein und demselben Patienten Plaques unterschiedlichen Alters vorhanden sind. Mittels MRT lasst sich der naturliche Verlauf einer MS in vivo prazisieren. Die MRT bildet Lasionen in der weisen Substanz des zentralen Nervensystems ab, deren Aussehen sich mit der Zeit andert und die bei sukzessiven Untersuchungen sichtbar werden und wieder verschwinden konnen. Bei den remittierenden Formen der MS gibt es mindestens zwanzigfach mehr radiologische als klinische Ereignisse. Die Plaques sind fur klinische Symptome verantwortlich, sofern sie „klinisch sprechende“ Areale im zentralen Nervensystem befallen. Im Verlauf der MS mit Schuben und Remissionen spiegelt sich die Geschichte der Plaque, die fur die objektiven und subjektiven Zeichen beim Patienten verantwortlich ist.

Published
2003
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23. Axonal Signals and Central Nervous System Myelination

Author

C. Lubetzki and B. Zalc

Subjects
Multiple sclerosis, Saltatory conduction, Central nervous system, Schwann cell, Biology, medicine.disease, Oligodendrocyte, medicine.anatomical_structure, nervous system, Peripheral nervous system, medicine, Optic nerve, Axon, Neuroscience
Abstract

Myelination is a fascinating model of cell-cell interactions, in which the process of a myelinating cell wraps around an axon to form the insulating myelin sheath, allowing the establishment of saltatory conduction of action potentials along the axon. Myelination is achieved by Schwann cells in the peripheral nervous system, whereas in the central nervous system the myelinating cells are oligodendrocytes. While a myelinating Schwann cell forms a myelin sheath around a single axonal segment, an oligodendrocyte is able, in the optic nerve for instance, to myelinate up to 50 axons. On each axon, a myelin-forming cell myelinates only a segment of axon (internode) between two nodes of Ranvier. This close interaction between the axons and the myelin-forming cells suggests the existence of reciprocal signaling between the oligodendrocytes (or the Schwann cells) and the axons to be myelinated.

Published
2001
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24. [Pivotal role of axonal adhesion molecules in central nervous system myelination]

Author

C, Lubetzki, P, Charles, B, Stankoff, P, Hernandez, and B, Zalc

Subjects
Neurons, Multiple Sclerosis, Cell Adhesion Molecules, Neuronal, Humans, Axonal Transport, Neuroglia, Axons, Myelin Sheath
Abstract

Close relationship between neurons and oligodendrocytes seems to be of the greatest importance during oligodendrocyte maturation and myelin formation within central nervous system. Two major factors are likely to play the decisive role in CNS myelination--adhesion molecules and electrical activity. It has been shown, both in vitro and in vivo, that blocking or stimulating electrical activity may inhibit or induce myelination respectively. The fact that even in culture oligodendrocytes myelinate solely axons and not other cellular processes present within CNS as well as the finding that normal myelin sheath compaction is encountered only around axons suggest that close interaction between oligodendrocytes and neurons is required for normal myelin formation. Adhesion molecules are most likely involved in this interaction by not only bringing the axon and the glial cell close to each other but also by transducing signals to initiate myelination. The neural cell adhesion molecule (NCAM) is a candidate molecule that could regulate axon/glial cell interaction. It is abundantly present in all growing fiber tracts of the developing CNS. Since its polysialylated from (PSA-NCAM) has been shown to disappear from axonal surface as myelination progresses and that its removal increases 4 to 5 fold myelination, it is thought to be a negative factor for myelin formation. These observations may have important implications in therapeutic strategies in demyelinating disorders like multiple sclerosis.

Published
2000

25. Cognitive Function in Adult Adrenoleukodystrophy: Comparison with Leukoaraiosis and Multiple Sclerosis

Author

N. Benoit, Nicole Baumann, O Lyon-Caen, Ayman Tourbah, M. Montreuil, M.T. Iba-Zizen, E A Cabanis, C. Lubetzki, P. Menage, and V. Carreau

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Multiple Sclerosis, Corpus callosum, Nerve Fibers, Myelinated, White matter, Cognition, Developmental Neuroscience, Internal medicine, medicine, Humans, Cognitive decline, Adrenoleukodystrophy, Multiple sclerosis, Leukodystrophy, Cognitive disorder, Leukoaraiosis, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Endocrinology, medicine.anatomical_structure, Neurology, Female, Cognition Disorders, Psychology
Abstract

Cognitive evaluation of 6 cases of adult adrenoleukodystrophy (ALD) included in a brain magnetic resonance (MR) study are reported: 2 males with adrenomyeloneuropathy and 4 women heterozygous for ALD. Cognition was normal in 4 and MR scan in 2 of them. In the 2 others, there were mild modifications of the white matter. One patient suffered of visual retention disturbances with abnormalities of the white matter in MR scan. In the last, cognitive decline was observed; MR scan showed atrophy of cortex and corpus callosum and periventricular high signal areas. Comparison with leukoaraiosis in healthy adults and with multiple sclerosis suggests that there is probably a relationship between cognition and extension of brain MR abnormalities. Time of appearance and frequency of cognitive dysfunction might be explained by the natural history of each of these diseases.

Published
1991
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26. [Multiple sclerosis: one or several diseases?]

Author

J J, Hauw, C, Lubetzki, and A, Tourbah

Subjects
Diagnosis, Differential, Inflammation, Multiple Sclerosis, Neuromyelitis Optica, Disease Progression, Humans, Peripheral Nervous System Diseases, Prognosis
Abstract

The various clinical courses of multiple sclerosis (relapsing-remitting, primary progressive, secondary progressive, progressive-relapsing) are likely related to different severity or distribution of the main lesions that constitute the plaques (inflammation, demyelination, axonal injury and loss, necrosis). They might lead to different therapeutic approaches. Some cases of the other clinico-radiological or clinico-pathological variants (pseudo-tumoral, concentric sclerosis of Baló, acute disseminate encephalomyelitis, Devic's neuromyelitis optica) obviously share similar mechanisms with multiple sclerosis. Other cases are, on the contrary, linked to different diseases. Do the variants of multiple sclerosis could be the consequence of different diseases? This is, today, a highly speculative conjecture. The prevalent hypothesis suggests that the clinico-pathological heterogeneity of multiple sclerosis is linked to the variability of the reaction of the nervous tissue to an initial injury. This different vulnerability, that depends on unknown factors, would explain the variants of the disease.

Published
1999

27. Plasma and cerebrospinal fluid human immunodeficiency virus type-1 (HIV-1) RNA levels in HIV-related cognitive impairment

Author

B, Stankoff, V, Calvez, S, Suarez, P, Bossi, O, Rosenblum, L, Conquy, E, Turell, T, Dubard, A, Coutellier, L, Baril, F, Bricaire, L, Lacomblez, and C, Lubetzki

Subjects
Adult, AIDS Dementia Complex, Reverse Transcriptase Polymerase Chain Reaction, HIV-1, Brain, Humans, RNA, Messenger, Middle Aged, Neuropsychological Tests, Viral Load, Cognition Disorders, CD4 Lymphocyte Count
Abstract

Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.

Published
1999

28. [Unique medullary neurosarcoidosis]

Author

M, Obadia, S, Crozier, A, Azoulay, D, Dormont, S, Clémenceau, K, Mokhtari, and C, Lubetzki

Subjects
Male, Sarcoidosis, Biopsy, Anti-Inflammatory Agents, Humans, Prednisone, Gadolinium, Middle Aged, Radiopharmaceuticals, Magnetic Resonance Imaging, Spinal Cord Diseases
Published
1999

29. [Cognitive disorders in AIDS: clinical, virological and neuroradiological features]

Author

B, Stankoff, S, Suarez, O, Rosemblum, L, Conquy, E, Turell, F, Bricaire, A, Coutellier, V, Calvez, L, Lacomblez, A, Tourbah, and C, Lubetzki

Subjects
Acquired Immunodeficiency Syndrome, Retroviridae, DNA, Viral, Brain, Humans, Cognition Disorders, Magnetic Resonance Imaging, Cerebrospinal Fluid
Abstract

HIV-associated neurocognitive disorders are mainly reported during the late stages of the disease, in deeply immunosuppressed patients Clinically, they present as a subcortical cognitive impairment, dominated by reduced psychomotor speed and memory deficit. Encephalic magnetic resonance imaging shows in most cases a diffuse leucoencephalopathy, and there is often a poor correlation between clinical status and neuroradiological findings. The diagnostic and prognostic value of HIV load in blood and cerebrospinal fluid is currently under investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia remains uncertain.

Published
1999

30. A rat G protein-coupled receptor selectively expressed in myelin-forming cells

Author

J, Allard, S, Barrón, J, Diaz, C, Lubetzki, B, Zalc, J C, Schwartz, and P, Sokoloff

Subjects
Brain Chemistry, Male, Neurons, Genomic Library, Brain, Nuclear Proteins, Receptors, Cell Surface, Immunohistochemistry, Corpus Callosum, Rats, Receptors, G-Protein-Coupled, Oligodendroglia, Glial Fibrillary Acidic Protein, Animals, Peripheral Nerves, RNA, Messenger, Schwann Cells, Rats, Wistar, Receptors, Lysophosphatidic Acid, DNA Probes, In Situ Hybridization, Myelin Sheath, Transcription Factors
Abstract

By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.

Published
1998

32. Myelin/oligodendrocyte glycoprotein (MOG) expression is associated with myelin deposition

Author

S K, Solly, J L, Thomas, M, Monge, C, Demerens, C, Lubetzki, M V, Gardinier, J M, Matthieu, and B, Zalc

Subjects
Brain Chemistry, Brain, Myelin Basic Protein, Immunohistochemistry, Coculture Techniques, Cell Line, Mice, Myelin-Associated Glycoprotein, Animals, Myelin-Oligodendrocyte Glycoprotein, RNA, Messenger, In Situ Hybridization, Myelin Proteins, Myelin Sheath
Abstract

We investigated the onset of expression of the myelin/oligodendrocyte glycoprotein (MOG) mRNA and protein in the developing mouse central nervous system. In situ hybridization on brain sections at different stages of embryonic and postnatal development showed that MOG transcripts were first detected at birth in the medulla oblongata. During the first week after birth, cells expressing MOG mRNA were located in the ventral longitudinal funiculus. During the second postnatal week, the pattern of MOG mRNA expression extended rostrally to the mid-forebrain regions and reached completion by the beginning of the third week. MOG transcription was delayed by several days with respect to myelin basic protein (MBP), and it appeared that while the MBP probe labeled both non-myelinating and myelinating oligodendrocytes, only the latter were MOG-positive. In vitro, immunocytochemical analysis of MOG protein expression, performed on myelinating cultures derived from mouse brain embryos at 15 days of gestation, confirmed the strict restriction of MOG expression to myelinating oligodendrocytes. In particular, oligodendrocytes lining up their processes along axons, but not yet having started to deposit a myelin sheath, were still MOG negative. However, in the same cultures, pseudo-myelinating oligodendrocytes (i.e., cells not associated with neurites, but forming whorls of myelin-like figures) were MOG positive. Similarly, rat CG4 cells, an oligodendrocyte-like cell line, expressed MOG only after they had extended sheet-like processes, which suggested that the activation of MOG transcription depends more on an intrinsic oligodendroglial maturation program of myelination than on a neuronal signal.

Published
1996

33. [[Therapeutic perspectives in multiple sclerosis]

Author

C, Lubetzki, T, Dubard, and B, Stankoff

Subjects
Multiple Sclerosis, Pyran Copolymer, Humans, Antineoplastic Agents, Interferons, Glucocorticoids, Immunosuppressive Agents
Abstract

Numerous clinical trials have been performed during the last 5 years in multiple sclerosis patients. Some of the results have been encouraging. However, clinical benefit remains limited. Corticosteroids are indicated during the course of severe relapses but have not proven any long term benefit. Immunosuppressive agents may be of some help during very active stages of the disease. Results of interferon beta-1b trial in relapsing multiple sclerosis have shown a moderate decrease in the frequency of relapses. The same effect has recently been reported with interferon beta-1a. In addition, an effect on disability progression have been suggested with the latter interferon. In France, interferon beta-1b is now authorized in the relapsing forms of the disease. Initial results with copolymer I also suggest an effect on the frequency of relapses. Despite these major therapeutical efforts, further trials, possibly using new therapeutical approaches, are still needed.

Published
1996

34. [AIDS dementia. Prognosis and therapeutic perspectives]

Author

C, Lubetzki

Subjects
Adult, Neurons, AIDS Dementia Complex, Age Factors, Humans, Middle Aged, Prognosis, Receptors, N-Methyl-D-Aspartate
Abstract

AIDS dementia complex is a severe complication related to HIV infection of the central nervous system. It has been estimated to affect about 7% of AIDS patients, with an increased frequency in very young and old patients. In most cases, it appears in severely immuno-deficient patients. Typically, AIDS dementia presents as a subcortical dementia with cognitive, behavioural and motor decline. The mechanism of the dementia remains unclear; the neuronal loss is controversial and a neurotoxicity due to NMDA receptor activation is likely. No treatment proved to be efficient. Beneficial effect of anti-NMDA receptor antagonists are under investigation.

Published
1995

35. [Pure cerebellar syndrome associated with anti-Hu antibodies]

Author

P F, Pradat, M, Uchuya, B, Fontaine, and C, Lubetzki

Subjects
Aged, 80 and over, Male, Neurons, Nucleoproteins, Cerebellar Diseases, Paraneoplastic Syndromes, Humans, Aged, Autoantibodies
Abstract

Anti-Yo is the most frequent antibody associated with pure paraneoplastic cerebellar degeneration. Cerebellar degeneration may be associated with anti-Hu antibody but other signs of nervous system involvement occur during the course of the disease. We report the case of a 69-year old man presenting with a severe acute cerebellar dysfunction of sudden onset. High titers of anti-Hu antibodies were detected in serum and cerebrospinal fluid by immunohistochemistry and western blot. No other neurological symptom was found after a follow-up of 18 months. Biopsy of a mediastinal lymph node revealed a poorly differentiated carcinoma. We suggest that the course of the anti-Hu syndrome may rarely be similar to the anti-Yo syndrome.

Published
1995

36. [Multiple sclerosis: role of growth factors and remyelination]

Author

C, Lubetzki

Subjects
Multiple Sclerosis, Humans, Nerve Growth Factors, Growth Substances, Myelin Sheath, Nerve Regeneration
Abstract

Multiple sclerosis is a frequent and often disabling neurological disease. Its aetiology and treatment remain to be discovered. It has been demonstrated in multiple sclerosis brains that remyelination can occur after the myelin damage. This myelin repair is achieved by oligodendrocytes, which are the myelinating cells of the central nervous system or by oligodendrocytes precursors still present in adult central nervous system. Several recently discovered growth factors can stimulate oligodendrocytes precursors migration and proliferation, or act as survival factors for mature oligodendrocytes. These glial growth factors may represent a new therapeutic approach in multiple sclerosis, aiming at the stimulation of the endogenous capacities of remyelination.

Published
1994

37. [Propriospinal myoclonus in a HIV seropositive patient]

Author

C, Lubetzki, M, Vidailhet, C P, Jedynak, S, Thibault, S, Mrejen, D, Vittecoq, and F, Chain

Subjects
Adult, Male, Myoclonus, Spinal Cord, Electromyography, HIV Seropositivity, Humans
Abstract

We report axial myoclonic jerks causing flexion of the trunk, neck, left shoulder, hips and knees in a 28-years-old HIV positive patient. The clinical and electromyographic features of the jerks were consistent with a spinal origin and corresponded to the new concept of propriospinal myoclonus. No structural lesion was identified in this patient. Neurological examination was otherwise normal. HIV specific antibodies were detected in CSF, suggesting central nervous system infection. Spinal myoclonus should be considered an unusual and early manifestation of central nervous system HIV infection.

Published
1994

38. [Symptomatic heterozygotic adrenoleukodystrophy in adults. 10 cases]

Author

P, Ménage, V, Carreau, A, Tourbah, B, Fontaine, M, Paturneau-Jouas, O, Gout, C, Lubetzki, N, Baumann, and O, Lyon-Caen

Subjects
Adult, Heterozygote, Fatty Acids, Age Factors, Brain, Humans, Female, Neuromuscular Diseases, Middle Aged, Adrenoleukodystrophy, Evoked Potentials, Magnetic Resonance Imaging, Pedigree
Abstract

Adult adrenoleukodystrophy is a X-linked peroxisomal disease associated with the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids. The diagnosis is established on the demonstration of elevated VLCFA in blood and cultured skin fibroblasts. Women are affected in nearly 15% of cases and neurological symptoms and/or signs develop in 53% of them. Identifying these women is important because of genetic counseling and a possible therapeutic approach. Ten cases of symptomatic heterozygous adult adrenoleukodystrophy are reported. Mean age at the time of diagnosis was 44.6 +/- 9.3 years. All patients presented with spastic paraparesis with inconstant and mild sensory or bladder disturbances. Cognitive impairment was present in 1 case. Cerebrospinal fluid was normal. Adrenal function in response to tetracosactide injection was abnormal in 1/7 cases. Electromyography detected a peripheral neuropathy in 1 case. Somatosensory evoked responses were abnormal in all cases, visual and auditory evoked responses in respectively 3/6 cases and 3/4 cases. Brain MRI detected non specific abnormalities in 3/7 cases; spinal cord MRI was normal in 3/3 cases. The familial history was helpful for the diagnosis in 3/10 cases. Examination of pedigrees detected 5 hemizygous and 1 asymptomatic heterozygous cases. All the patients were enrolled in a dietary study which adret with low VLCFA is currently under evaluation.

Published
1993

40. Ganglioside GD1b is the target antigen for a biclonal IgM in a case of sensory-motor axonal polyneuropathy: involvement of N-acetylneuraminic acid in the epitope

Author

A B, Younes-Chennoufi, J M, Léger, J J, Hauw, J L, Preud'homme, P, Bouche, P, Aucouturier, H, Ratinahirana, C, Lubetzki, O, Lyon-Caen, and N, Baumann

Subjects
Male, Staining and Labeling, Blotting, Western, Sensation, Peroneal Nerve, Middle Aged, Motor Activity, N-Acetylneuraminic Acid, Epitopes, Immunoglobulin M, Gangliosides, Sialic Acids, Humans, Antigens, Nervous System Diseases
Abstract

We report on a 54-year-old man with a sensory-motor polyneuropathy associated with a biclonal IgM-kappa gammopathy, which reacted with the ganglioside GD1b. Examination of nerve biopsy specimens showed some reduction in the density of myelinated fibers and axonal degeneration with a loss of large fibers and a relative increase in the density of small fibers. Immunodetection on thin-layer chromatography of the glycolipid antigens showed strong reactivity of the patient's serum IgM-kappa with GD1b ganglioside and weak binding to GD1a. biclonal IgM antibodies did not react with GM1, asialo-GM1, GT1b, GD2, or GD3. Indirect immunofluorescence staining showed binding of IgM-kappa mainly in a crescent-like pattern on the internal side of myelin sheaths, which could correspond either to an enlarged periaxonal (adaxonal) space or to the internal mesaxon or to both. The immunostaining was abolished after absorption of the serum with GD1b.

Published
1992

42. [Glioblastoma after radiotherapy of meningioma]

Author

C, Lubetzki, B, Mercier, C, Duyckaerts, E, Lebiez, and O, Lyon-Caen

Subjects
Adult, Neoplasms, Radiation-Induced, Meningeal Neoplasms, Humans, Female, Glioma, Cerebellar Neoplasms, Meningioma
Abstract

A cerebellar glioblastoma was discovered in a 28 year old woman, 5 years after a focal 50 grays brain irradiation for meningioma of the clivus. This case fulfilled the accepted criteria for radiation-induced neoplasms of the central nervous system, namely a second histologically-proven tumor different from the first lesion, a location within the irradiated area and a long latent period.

Published
1991

43. [Myelin and oligodendrocytes: recent data]

Author

C, Lubetzki and B, Zalc

Subjects
Oligodendroglia, Cell Survival, Stem Cells, Animals, Humans, Cell Differentiation, Optic Nerve, Cell Division, Myelin Sheath
Abstract

Oligodendrocytes are the myelin forming cells of the central nervous system. They are derived from a precursor cell, named O-2A. This precursor cell is bipotential, and can differentiate in vitro into either an oligodendrocyte or a certain type of astrocyte, named type 2 astrocyte, depending on the presence or absence of extracellular factors. The chronology of glial differentiation is now better understood. Some factors influencing the choice of the differentiation pathway have been described. Most of these factors seem to be secreted in vitro by an other type of astrocyte, type 1 astrocyte. The succession of events leading to myelination can now be analyzed at molecular level. These very recent results have mostly been obtained in vitro. Their significance in vivo has now to be ascertained.

Published
1990

44. Clonal analysis of glial cell lineage

Author

C. Goujet Zalc, C. Lubetzki, Olivier Danos, C. Demerens, and B Zalc

Subjects
Cellular and Molecular Neuroscience, Cell Biology, Cell lineage, Biology, Clonal analysis, Cell biology
Published
1992
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45. Effects of various opiates including specific delta and mu agonists on dopamine release from nigrostriatal dopaminergic neurons in the rat and in the cat

Author

T.D. Reisine, C. Lubetzki, Marie-Claude Fournie-Zaluski, M.F. Chesselet, Jacques Glowinski, André Chéramy, and Bernard P. Roques

Subjects
Narcotics, Agonist, medicine.drug_class, Dopamine, Receptors, Opioid, mu, Caudate nucleus, Substantia nigra, (+)-Naloxone, Striatum, In Vitro Techniques, Pharmacology, Tritium, General Biochemistry, Genetics and Molecular Biology, Structure-Activity Relationship, Receptors, Opioid, delta, medicine, Animals, General Pharmacology, Toxicology and Pharmaceutics, Neurons, Chemistry, Dopaminergic, General Medicine, Corpus Striatum, Rats, nervous system, Receptors, Opioid, Cats, Opiate, medicine.drug
Abstract

The effect f various opiates on the release of newly synthesized 3H-dopamine (3H.DA) was studied both in vitro in rat striatal slices and in vivo in caudate nuclei and substantiae nigrae of halothane anaesthetized cats, using a push pull cannula technique. The hexapeptide Tyr-D-Ser -Gly-Phe-Leu-Thre (DSTLE) which acts preferentially on δ receptors stimulates 3H.DA release in vitro and produces a biphasic increase of the local 3H-amine outflow when applied in the cat caudate nucleus in vivo . Similar effects were induced by D Ala2-met-enkephalinamide. By contrast, morphine, fentanyl and the potent μ agonist Tyr-D-Ala-Gly-NH-C6-H13 (Trimu 4) did not affect 3H.DA release in vitro . In vivo their effects differ from those of the δ agonists and from each other: morphine produced a delayed long lasting increase in 3H.DA release while fentanyl and Trimu 4 induced an immediate increase of the 3H-amine outflow followed by a delayed inhibition. The local effects of δ and μ agonists also differed as regard to their sensitivity to naloxone but in addition, when co-applied with the opiate antagonist, D-Ala2-met-enkephalinamide and morphine induced changes in 3H.DA release in the contralateral caudate nucleus and the contralateral or ipsilateral substantia nigra respectively. Therefore, in the striatum, some opiates may, under certain circumstances, act directly or indirectly upon striatal efferences involved in the control of the contralateral nigro-striatal dopaminergic neurons. In conclusion, thanks to the use of recently developed opiate agonists exhibiting a high preference for either δ or μ receptors it has been shown that these receptors are involved in different mechanisms regulating the striatal dopaminergic transmission. In addition, these results suggest that less specific agents, by interacting with several types of receptors, induce a unique combination of events responsible for local and distal control of DA release from nigro-striatal dopaminergic neurons.

Published
1982
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46. Myelination and Remyelination in the Central Nervous System by Transplanted Oligodendrocytes Using the Shiverer Model

Author

Nicole Baumann, A. Gansmuller, O. Gout, M. Gumpel, and C Lubetzki

Subjects
education.field_of_study, Multiple sclerosis, Central nervous system, Population, Biology, medicine.disease, Oligodendrocyte, Transplantation, Lesion, medicine.anatomical_structure, nervous system, Developmental Neuroscience, Neurology, Precursor cell, medicine, Remyelination, medicine.symptom, education, Neuroscience
Abstract

In the early sixties, remyelination was first observed in animal models of demyelination and described a few years later in multiple sclerosis. The spontaneous remyelination process is now well documented. Remyelination by transplantation of myelin-forming cells has been attempted. Transplanted Schwann cells can myelinate a central nervous system lesion but the remyelination is limited to the area of implantation. Oligodendrocytes or precursor cells are much more invasive and have been shown to migrate from the implantation site to the lesion at a distance of several millimeters. Thus, remyelination by transplantation of myelin-forming cells is possible at least in animal models, the oligodendrocytes being more efficient.

Published
1989
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47. A role for striatal beta-adrenergic receptors in the regulation of dopamine release

Author

C. Lubetzki, André Chéramy, Jacques Glowinski, T.D. Reisine, and M.F. Chesselet

Subjects
Male, medicine.medical_specialty, Adrenergic receptor, Dopamine, Caudate nucleus, Substantia nigra, Phentolamine, Internal medicine, Receptors, Adrenergic, beta, medicine, Animals, Adrenergic agonist, Molecular Biology, Chemistry, General Neuroscience, Dopaminergic, Isoproterenol, Rats, Inbred Strains, Propranolol, Corpus Striatum, Rats, Receptors, Adrenergic, Substantia Nigra, Kinetics, Endocrinology, Tyrosine, Neurology (clinical), Caudate Nucleus, Acetylcholine, Developmental Biology, medicine.drug
Abstract

The effect of (−) isoproterenol on the spontaneous release of [3H]dopamine ([3H]DA) continuously formed from [3H]tyrosine has been studied both in vitro using rat striatal slices and in vivo in halothane-anaesthetized cats implanted with push-pull cannulae in each caudate nucleus and each substantia nigra. In vitro, (−) isoproterenol (10−6M) stimulated [3H]DA release. This effect was stereospecific since (+) isoproterenol (10−6M) was without effect. (±) Propranolol (10−6M), which did not block the acetylcholine (10−5M)-induced release of [3H]DA, completely prevented the stimulatory effect of (−) isoproterenol on [3H]DA release. (±) Practolol (10−5M) significantly reduced the (−) isoproterenol-induced release of [3H]DA whereas phentolamine (10−5M) was uneffective. These results suggest that (−) isoproterenol acts on [3H]DA release through β1-receptors. Since the adrenergic agonist still stimulated [3H]DA release in the presence of tetrodotoxin, the β-receptors involved may be located on DA terminals. Confirming in vitro results, (−) isoproterenol (10−6M) enhanced the local release of [3H]DA when applied into one caudate nucleus. This effect was biphasic and prevented by (±) propranolol (10−6M). The β-antagonist by itself slightly reduced [3H]DA spontaneous release suggesting that noradrenergic neurons which may innervate the caudate nucleus could exert a tonic facilitatory influence on DA release. No change in [3H]DA release occured in other structures studied during the application of (−) isoproterenol into one caudate nucleus. These various results indicate that striatal β-adrenergic receptors play a role in the regulation of DA release from DA nerve terminals and suggest an interaction between noradrenergic and dopaminergic neurones in the caudate nucleus.

Published
1982
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48. [Painful legs and unstable toes]

Author

J M, Léger, C, Lubetzki, P, Bouche, Y, Bor, and P, Brunet

Subjects
Adult, Joint Instability, Male, Leg, Pain, Peripheral Nervous System Diseases, Syndrome, Toe Joint, Middle Aged, Electrophysiology, Central Nervous System Diseases, Humans, Female, Aged
Abstract

Five patients presented with the painful legs and moving toes syndrome as defined by Spillane et al. (1971). A peripheral nervous disorder was present in 4 of these cases while the fifth patient showed evidence of a central lesion. Results of clinical and electrophysiologic investigations in the 4 peripheral cases, are compared with data from the literature.

Published
1985

49. [Right hemiasomatognosia and sensation of amputation caused by left subcortical lesion. Role of callosal disconnection]

Author

J, Cambier, D, Elghozi, P, Graveleau, and C, Lubetzki

Subjects
Male, Hematoma, Extremities, Delusions, Self Concept, Corpus Callosum, Parietal Lobe, Agnosia, Body Image, Visual Perception, Humans, Dominance, Cerebral, Tomography, X-Ray Computed, Aged, Cerebral Hemorrhage
Abstract

A 72-year-old right-handed hypertensive man presented with a right brachial monoplegia, and hypesthesia of the right half of the body to touch and pricking, sparing the face. A CT scan 2 weeks later showed a spontaneous hyperdense area corresponding to a left subcortical parietal hematoma. The patient used his spontaneous language to express body image disturbances: intense prolonged feeling of amputation related to the upper limb and foot on the right side, hemiasomatognosia without anosognosia, autotopagnosia. Also associated were a right-sided visual negligence and a more general inability to handle spatial data leading to a temporospatial disorientation. Mild language disorders were suggestive of subcortical aphasia: normal incitation and repetition; with semantic paraphasias, poor verbal fluency. Furthermore comprehension of orders or propositions concerning spatial data were poor. Finally, there were signs suggestive of callosal disconnection: paradoxical extinction of the left ear during dichotic listening, agraphia and anomia of the left hand, ideomotor apraxia of the left upper limb, difficulty in visual transfer. The lesion interrupted thalamic tracts to parietal regions and callosal fibers linking parieto-occipital association areas. This twofold lesion was analyzed for each of the neuropsychological disturbances observed. Certain aspect of cerebral function in this patient were reminiscent of "split-brain" disorders. The left hemisphere which "speaks" fails to understand the feelings of the right hemisphere: unfamiliarity of places, sensations of illness, resulting in an unadapted speech. The pathophysiology of feeling of amputation is discussed.

Published
1984

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