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1. Management of adverse renal events related to alemtuzumab treatment in multiple sclerosis: a Belgian consensus

Author

D Decoo, Ben Sprangers, Dominique Dive, Ludo Vanopdenbosch, Andreas Lysandropoulos, and Christophe Bovy

Subjects
Male, Nephrology, medicine.medical_specialty, Pediatrics, Consensus, Multiple Sclerosis, 030232 urology & nephrology, Autoimmunity, Consensus paper and Guideline, Disease, Multiple sclerosis, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Belgium, Membranous nephropathy, Internal medicine, Neurologie, medicine, Humans, Renal adverse event, Adverse effect, Alemtuzumab, business.industry, Consensus guideline, Disease Management, General Medicine, medicine.disease, Clinical trial, Early Diagnosis, Female, Kidney Diseases, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Patient education
Abstract

Alemtuzumab is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing–remitting multiple sclerosis with active disease. Multiple sclerosis (MS) patients treated with alemtuzumab are at increased risk for autoimmune adverse events (thyroid disorders, immune thrombocytopenia, and renal disease). The use of alemtuzumab has been associated with the development of renal immune-mediated adverse events in 0.3% of patients in clinical trials in MS, which generally occurred within 39 months of the last administration. Both anti-GBM disease and membranous nephropathy have been associated with the use of alemtuzumab. Early detection is necessary to allow for early diagnosis and prevent adverse renal and patient outcomes. Through the implementation of the risk minimization measures, patients can be diagnosed, and treated if needed, early allowing for generally favorable outcomes. This important goal can be reached through health care professional and patient education, careful analysis of the monthly lab tests, and close collaboration between the patient, neurologist, and the nephrologist. This article presents the consensus of Belgian MS specialists and nephrologists on the practicalities of diagnosis, management, and treatment of alemtuzumab-associated renal adverse events based on good clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

2. Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program

Author

Marie-Claire D'Hooghe, Véronique Bissay, Eric De Smet, Erwin Van Ingelghem, Olivier Bouquiaux, Etienne Urbain, Katelijne Peeters, Daniel Guillaume, Andreas Lysandropoulos, Johan Caekebeke, Jana Debruyne, Pierrette Seeldrayers, Annick Melin, Pierre Denayer, Vincent Van Pesch, Ludo Vanopdenbosch, D Decoo, Inge Declercq, Patrick Vanderdonckt, Robert Medaer, Rémy Phan Ba, Bart Van Wijmeersch, Christian Sindic, Christiana Willems, Souraya El Sankari, Michel Dupuis, Anoek Symons, Barbara Willekens, Alain Maertens De Noordhout, Cécile Retif, Bénédicte Dubois, William van Landegem, Michel Bureau, Karine Geens, Emmanuel Bartholomé, Erwin Vanroose, Physics, Elementary Particle Physics, Clinical sciences, and Neuroprotection & Neuromodulation

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, International Cooperation, Subgroup analysis, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Cohort Studies, Disability Evaluation, Young Adult, Age Distribution, Natalizumab, Belgium, Internal medicine, Severity of illness, Product Surveillance, Postmarketing, medicine, Humans, Immunologic Factors, Aged, business.industry, Multiple sclerosis, Progressive multifocal leukoencephalopathy, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Treatment Outcome, Cohort, Physical therapy, Female, Observational study, Neurology (clinical), Human medicine, business, Cohort study, medicine.drug
Abstract

Natalizumab (Tysabri(A (R))) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Published
2014

3. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author

H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. Murray, M. Parent, M. Koepp, V. Dimova, D. De Leo, K. Jellinger, G. Salemi, S. Mientus, M. L. Hansen, F. Mazzucchelli, J. Vieth, M. Mauri, E. Bartels, L. Johannsen, C. Humphreys, J. Emile, D. N. Landon, E. Kansu, R. Sanchez-Pernaute, Rsj Frackowiak, M. Gonzalez Torres, L. Oller, C. Machedo, J. Kother, M. Billiard, H. Durak, T. Schindler, A. Frank, A. Uncini, A. Sbriccoli, C. Farinas, D. W. Paty, N. Fast, A. T. Zangaladze, A. Kerkhofs, J. M. Pino Garcia, I. De la Fuente, B. Marini, L. Gomez, I. Rubio, Alessandra Bardoni, C. Brodie, P. Acin, U. Sliwka, S. A. Hawkins, S. Tardieu, F. Vitullo, J. M. Pereira Monteino, R. Gagliardi, T. Jezewski, A. Cano, T. Lempert, F. Abad Alegria, G. Rotondo, D. Ince, C. Martinez Parra, Y. Huang, H. Luders, Y. Steinvil, F. G. A. Van Der Meche, R. Bianchi, A. Sanchez, T. Sevilla, J. M. Ketelslegers, A. Domzal-Stryga, M. Pandolfo, M. O. Josse, K. W. Neff, I. Blanco, G. W. Bruyn, O. W. Witte, J. L. Thibault, G. Andersen, J. Pariset, A. Marcone, R. J. M. Lane, A. Hofman, M. Verin, T. Matilla, P. Bedoucha, J. Roche, M. Lai, M. Collard, A. Ugarte, F. Gallecho, D. Silbersweig, C. Kennard, J. P. Azulay, T. W. Ho, P. L. I. Dellemijn, R. Girardello, F. Baas, B. Voss, F. Rozenberg, E. M. Brocker, V. Stanev, A. A. J. Soeterboek, A. Marra, A. Rey, E. Ertem, M. Sawradewicz-Rybak, J. De Keyser, P. Cavallari, F. Proust, Y. Chevalier, H. C. Hansen, D. Leys, C. A. Davie, K. Hoang-Xuan, C. Bairati, H. van Crevel, Thomas T. Warner, B. Bompais, A. Dobbeleir, T Campbell, C. Macko, C. J. M. Klijn, M. Dussallant, T. P. Berlit, W. Rozenbaum, M. J. van den Bent, W. A. Rocca, M. Muller, H. Hundemer, U. Zifko, M. Campera, F. Drislane, D. Ranoux, T. M. Kloss, Anil Kumar, I. Ruolt, C. Bargnani, B. Marescau, N. A. Losseff, S. Notermans, B. Kint, E. T. Burke, C. Aykut, J. Matias Guiu, P. Maquet, T. Drogendijk, M. Leone, K. von Ammon, M. Pepeliarska, C. Prados, L. DiGiamberardino, T. Logtenberg, G. Lenoir, I. Castaldo, Damhaut, M. Radionova, G. Sirabian, R. Navon, Giovanni Antonini, K. Al Moutaery, E. Chamas, R. Schönhuber, M. Giannini, B. Debilly, I. Labatut, H. Henon, J. A. Egido, M. Baudrimont, J. N. Lorenzo, J. E. C. Bromberg, R. Antonacci, J. J. Vilchez, T. Moulin, B. Rautenstrauss, Giovanni Meola, J. Noth, S Mammi, P. Laforet, F. Lopez, C. Gehring, S. Bort, G. Rancurel, D. Decamps, S. Kostadinova, Y. Shapira, B. Neundoerfer, D. Chavrot, M. Solimena, J. P. Salier, W. Deberdt, R. Hoff-Jörgensen, A. Messina, S. Meairs, G. Rosoklija, E. Nelis, I. Bertran, C. Ertekin, J. Lohmeyer, Mitermayer Galvao dos Reis, L. Calo, E. Maccagnano, A. P. Hays, J. Verlooy, M. G. Forno, T. Blanco, L. Bail, Gabriella Silvestri, J. Montero, F. Bertrand, R. T. Ghnassia, C. Besses, T. Sereghy, F. Shalit, G. Bogliun, S. Braghi, St. Baykouchev, C. Franke, A. Lasa, L. C. Archard, J. Kriebel, S. Shaunak, M. Nocito, Alexander Tsiskaridze, E. Manfredini, T. Seigal, David G. Gadian, M. Barlas, J. D. Degos, C. Seeber, J. Caemert, J. L. Mas, R. B. Pepinsky, M. G. D'Angelo, N. Baumann, S. Yorifuji, H. P. Endtz, M. A. Cassatella, R. A. C. Hughes, V. Golzi, A. Bittencourt, A. Ferreira, M. Sanson, C. Alper, M. Vermeulen, M. A. A. van Walderveen, E. Alexiou, C. H. Lucas, M. Fiorelli, Y. N. Debbink, R. Gil, S. Congia, T. Banerjee, J. M. Bouchard, A. N. Pinto, A. Ceballos-Baumann, G. Grollier, P. I. M. Schmitz, M. D. Catata, N. Lahat, N. S. Rao, P. Papathanasopoulos, J. Valls-Solé, D. Claus, G. Schroter, A. Castro, C. Videbaek, R. Martinez Dreke, A. D. Platts, M. Hermesl, A. C. PeÇanha-Martins, M. Cardoso Silva, P. Masnou, M. J. A. Tanner, Ch. Confavreux, B. Mishu, H. Rasmussen, L. Valenciano, Carlo Pozzilli, S. W. Li, V. Salzman, Y. Vashtang, Massimo Franceschi, M. Severo, G. Deuschl, S. Setien, G. Mariani, A. Protti, J. Castillo, M. J. B. Taphoorn, M. Frontali, I. Milonas, D. Decoq, J. A. Navarro, S. Castellvi-Pel, C. Ertikin, M. Urtasun, Y. Lajat, B. E. Kendall, E. Verdu, B. Gueguen, E. Boisen, R. Couderc, A Danek, JM Stevens, F. Nicoli, L. Feltri, M. L. Vazquez-Andre, J. A. Morgan-Hughes, L. D'Angelo, F. Y. Liew, L. F. Pascual, J. Patrignani Ochoa, Vittorio Martinelli, J. Cophignon, L. Zhang, S. Martin, J. F. Meder, H. C. Buschmann, L. Bertin, J. van Gijn, A. Barreiro, A. Cools, C. Leon, A. Berod, E. A. Anllo, E. Zanette, L. Petrov, R. Barona, B. Gallicchio, P. J. Cozzone, N. Diederich, G. Cancel, L. Schelosky, P. Orizaola, K. Yulug, S. Ozer, Valeria A. Sansone, B. Guiraud-Chaumeil, K. Voigt, P. Labauge, M. Eoli, J. Zhu, J. Aguirre, M. Ferrarini, B. Zyluk, E. Planas, A. Cadilha, C. Tortorella, H. Bismuth, C. E. Counsell, A. Laun, A. Ferlini, Rio J. Montalban, N. Biary, L. Becker, M. Fardeau, M. Poloni, V. M. S. de Bruin, C. Fornada, J. Barros, E. Ganzmann, E. Touze, D. Wallach, J. Peila, H. Fujimura, M. T. Iba-Zizen, G. Macchi, C. Villoslada, R. Gouider, Ph. Rondepierre, P. Grummich, P. Chiodi, C. Conte, M. Michels, P. Annunziata, G. Semana, C. Sommer, J. Vajsar, D. Zekin, J. Kulisevsky, David G. Munoz, B. Jacotot, M. Magoni, A. Luxen, T. Garcia-Silva, S. Di Cesare, Christophe Tzourio, M. Gomori, I. Picomell, L. Santoro, F. Villa, Giovanni Pennisi, T. Ribalta, J. M. Molto, L. Marzorati, P. Loiseau, F. Gemignani, A. Gironell, J. Wissel, A. Prusinski, F. Cailloux, P. Villanueva-Hemandez, P. Cozzone, T. Del Ser, J. Sans-Sabrafen, M. Zappia, P. W. A. Willems, G. Tchernia, D. Gardeur, R. Bauer, F. Palomo, H. Metz, S. Lamoureux, C. Chastang, I. Reinhard, A. Goldfarb, S. Harder, Jordi Río, C. Ozkara, E. Tekinsoy, P. Vontobell, J. De Recondo, M. Rabasa, L. Lacomblez, F. Boon, Dgt Thomas, V. Palma, Renato Mantegazza, A. Dervis, M. Nueckel, B. YalÇinerner, I. Duran, G. Dalla Volta, A. Zubimendi, J. Pinheiro, A. Marbini, Xavier Montalban, H. Wekerle, X. Pereira Monteino, F. Crespo, F. Koskas, N. Battistini, C. Ruiz, H. Offner, J. de Pommery, P. Kanovsky, J. Y. Barnett, J. Pardo, G. Tomei, R. Rene, H. M. Lokhorst, P. Thajeb, H. Bilgin, D. McGehee, R. Fahsold, L. Morgante, Katie Sidle, C. Delwaide, M. N. Diaye, P. H. Rice, A. Creange, C. Sabev, K. Stephan, K. WeilBenborn, G. Magnani, L. Grymonprez, F. Cardellach, M. Kaps, N. G. Meco, F. Vega, V. Bonifati, A. Desomer, M. Baldy-Moulinier, G. Kvale, F. J. Authier, B. Yegen, T. Ho, J. M. Rozet, E. A. Cabanis, L. Bruce, L. Ambrosoli, M. A. Petrella, M. Hernandez, P. Timmings, H. B. van der Worp, F. Mahieux, A. Urbano-Marquez, D. A. Krendel, A. A. Garcia, R. Divari, R. Michalowicz, M. R. Piedmonte, M. Bondavalli, M. Zanca, P. F. Ippel, Onofre Combarros, B. Tavitian, E. Hirsch, I. Anastasopoulos, A. Roses, A. Köhler, P. Vienna, V. Timmerman, P. Sergi, F. Cornelio, A. Di Pasquale, R. Verleger, S. Castellvirel, J. Proano, B. van Moll, F. Rubio, W. Hacke, I. Lavenu, L. Zetta, M. W. Tas, N. Bittmann, M. Bonamini, O. R. Hommes, V. Dousset, N. Afsar, S. Belal, R. R. Myers, J. Goes, Giuseppe Vita, E. Clementi, V. G. Karepov, M. Jueptner, A Vincent, P. Emmrich, Th. Heb, A. Caballo, J. Gallego, T. Mokrusch, C. Perla, L. Gebuhrer, O. Titlbach, Alessandro Prelle, A. Czlonkowska, M. Russo, D. Hadjiev, T. S. Chkhikvishvili, M. Oehlschlager, G. Becker, I. Günther, E. N. Stenager, J. Garcia Agundez, J. Casademont, J. Batlle, S. Podobnik-Sarkanji, C. Alonso-Villaverde, B. Delaguillaume, B. Genc, B. Mazoyer, A. Rodriguez-Al-barino, Ch. Hilger, B. Ferrero, R. Price, W. Grisold, L. Fuhry, D. Oulbani, D. Ewing, A. Petkov, W. Walther, A. Gokyigit, John Newsom-Davis, J. Tayot, D. Seliak, G. Pelliccioni, D. Campagne, K. Kessler, F. Boureau, D. Perani, J. P. N'Guyen, N. Tchalucova, B. A. Antin-Ozerkis, C. Lacroix, B. D. Aronovich, I. H. Jenkins, E. A. dos Reis, M. Hortells, H. M. Meinck, H. Ch. Buschmann, S. C. J. M. Jacobs, T. Wetter, P. Creissard, N. Martinez, J. Weidenfeldl, H. J. Sturenburg, G. Damlacik, V. Gracia, J. C. Turpin, A. Pou-Serradell, J. P. Vincent, T. Gagoshidze, U. Ozkutlu, M. McLeod, K. Siegfried, I. Tchaoussoglou, J. Hildebrand, S. Kowalska, M. C. Picot, G. Galardin, L. Crevits, F. Andreetta, S. Larumbe-Lobalde, G. de la Sierra, J. C. Alvarez-Cermeno, R. J. Seitz, P. L. Oey, L. Ptacek, A. M. J. Paans, A. Wirrwar, A. Schmied, J. Uilchez, H. Tounsi, D. Hipola, V. Avoledo, Y. Hirata, P. Vermersch, T. M. Aisonobe, J. Valls-SoIè, H. Staunton, J. Dichgans, R. Karabudak, I. Dones, G. Porta, E. Janssens, Maria Martinez, J. M. Fernandez-Real, R. Villagra, Y. Yoshino, C. Kabus, K. Schimrigk, I. Girard-Buttaz, F. Piccoli, F. Aichner, P. Zuchegna, S. M. Al Deeb, F. Bono, N. Busquets, A. Jobert, Patrizia Ciscato, M. Martin, L. Polman, S. Darbra, V. Le Cam-Duchez, F. Baldissera, B. Baykan-Kurt, D. Guez, M. Bratoeva, H. Matsui, M. Mila, H. Perron, L. Bjorge, G. Husby, Steven T. DeKosky, D. R. Cornblath, J. M. Gabriel, J. J. Poza, Y. Wu, A. Toscano, R. P. Kleyweg, J. Kuhnen, S. O. Confort-Gouny, A. Barcelo, A. M. Conti, C. Fiol, C. Steichen-Wiehn, J. Rodes, M. Cavenaile, C. Vedeler, M. Drlicek, C. Argentino, M. L. Peris, A. Cervello, A. Z. GinaÏ, S. Yancheva, D. Passingham, S. Aoba, D. L. 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Frigo, Leif Østergaard, J. L. Munoz Blanco, A. Cruz-Matinez, J. De Reuck, C. Theillet, T. Barroso, V. Oikonen, Florence Lebert, M. Kilinc, C. Cordon-Cardon, G. Stoll, E. Thiery, F. Pulcinelli, J. Solski, M. Schmiegelow, L. J. Polman, P. Fernandez-Calle, C. Wikkelso, M. Ben Hamida, M. Laska, E. Kott, W. Sulkowski, C. Lucas, N. M. Bornstein, D. Schmitz, M. W. Lammers, A. de Louw, R. J. S. Wise, P. A. van Darn, C. Antozzi, P. Villanueva, P. H. E. Hilkens, C. Constantin, W. Ricart, A. Wolf, M. Gamba, P. Maguire, Alessandro Padovani, B. M. Patten, Marie Sarazin, H. Ackermann, L. Durelli, S. Timsit, Sebastian Jander, B. W. Scheithauer, G. Demir, J. P. Neau, P. Barbanti, A. Brand, N. AraÇ, V. Fischer-Gagnepain, R. Marchioli, G. Serratrice, C. Maugard-Louboutin, G. T. Spencer, D. Lücke, G. Mainardi, K. Harmant Van Rijckevorsel, G. B. Creel, R. Manzanares, Francesco Fortunato, A. May, J. Workman, K. Johkura, E. Fernandez, Carlo Colosimo, L. Calliauw, L. Bet, Félix F. Cruz-Sánchez, M. Dhib, H. Meinardi, F. Carrara, J. Kuehnen, C. Peiro, H. Lassmann, K. Skovgaard Olsen, A. McDonald, L. Sciulli, A. Cobo, A. Monticelli, B. Conrad, J. Bagunya, J. Benitez, V. Desnizza, B. Dupont, O. Delrieu, D. Moraes, J. J. Heimans, F. Garcia Rio, M. Matsumto, A. Fernandez, R. Nermni, R. Chalmers, M. J. Marchau, F. Aguado, P. Velupillai, P. J. Martin, P. Tassan, V. Demarin, A. Engelien, T. Gerriets, Comar, J. L. Carrasco, J. P. Pruvo, A. Lopez de Munain, D. Pavitt, J. Alarcon, Chris H. Polman, B. Guldin, N. Yeni, Hartmut Brückmann, N. Wilczak, H. Szwed, R. Causaran, G. Kyriazis, M. E. Westarp, M. Gasparini, N. Pecora, J. M. Roda, E. Lang, V. Scaioli, David R. Fish, D. Caputo, O. Gratzl, R. Mercelis, A. Perretti, G. Steimetz, I. Link, C. Rigoletto, A. Catafau, G. Lucotte, M. Buti, G. Fagiolari, A. Piqueras, C. Godinot, J. C. Meurice, Erodriguez J. Dominigo, F. Lionnet, H. Grzelec, David J. Brooks, P. M. G. Munro, F. X. Weilbach, M. Maiwald, W. Split, B. Widjaja-Cramer, V. Ozturk, J. Colas, E. Brizioli, J. Calleja, L. Publio, M. Desi, R. Soffietti, P. Cortinovis-Tourniaire, E. F. Gonano, G. Cavaletti, S. Uselli, K. Westerlind, H. Betuel, C. O. Dhiver, H. Guggenheim, M. Hamon, R. Fazio, P. Lehikoinen, A. Esser, B. Sadzot, G. Fink, Angelo Antonini, D. Bendahan, V. Di Carlo, G. Galardi, A. F. Boller, M. Aksenova, Del Fiore, V. de la Sayette, H. Chabriat, A. Nicoletti, A. Dilouya, M. L. Harpin, E. Rouillet, J. Stam, A. Wolters, M. R. Delgado, Eduardo Tolosa, G. Said, A. J. Lees, L. Rinaldi, A. Schulze-Bonhage, MA Ron, C. Lefebvre, E. W. Radü, R. Alvarez, M. L. Bots, P. Reganati, S. Palazzi, A. Poggi, N. J. Scolding, V. Sazdovitch, T. Moreau, E. Maes, M. A. Estelies, P. Petkova, Jose-Felix Marti-Masso, G De La Meilleure, N. Mullatti, M. Rodegher, N. C. Notermans, T. A. T. Warner, S. Aktan, J. P. Louboutin, L. Volpe, C. Scheidt, W. Aust, C. M. Wiles, U. Schneider, S. K. Braekken, W. R. Willems, K. Usuku, Peter M. Rothwell, C. Talamon, M. L. Sacchetti, A. Codina, M. H. Marion, A. Santoro, J. Roda, A. Bordoni, D. J. Taylor, S. Ertas, H. H. Emmen, J. Vichez, V. BesanÇon, R. E. Passingham, M. L. Malosio, A. Vérier, M. Bamberg, A. W. Hansen, E. Mostacero, G. Gaudriault, Marie Vidailhet, B. Birebent, K. Strijckmans, F. Giannini, T. Kammer, I. Araujo, J. Nowicki, E. Nikolov, A. Hutzelmann, R. Gherardi, J. Verroust, L. Austoni, A. Scheller, A. Vazquez, S. Matheron, H. Holthausen, J. M. Gerard, M. Bataillard, S. Dethy, V. H. Patterson, V. Ivanez, N. P. Hirsch, F. Ozer, M. Sutter, C. Jacomet, M. Mora, Bruno Colombo, A. Sarropoulos, T. H. Papapetropoulos, M. Schwarz, D. S. Dinner, N. Acarin, B. Iandolo, J. O. Riis, P. R. J. Barnes, F. Taroni, J. Kazenwadel, L. Torre, A. Lugaresi, I. L. Henriques, S. Pauli, S. Alfonso, Pedro Quesada, A. S. T. Planting, J. M. Castilla, Thomas Gasser, M. Van der Linden, A. Alfaro, E. Nobile-Orazio, G. Popova, W. Vaalburg, F. G. A. van der Mech, L. Williams, F. Medina, J. P. Vernant, J. Yaouanq, B. Storch-Hagenlocher, A. Potemkowski, R. Riva, M. H. Mahagne, M. Ozturk, Ve. Drory, N. Konic, C. Jungreis, A. Pou Serradell, J. L. Gauvrit, G. J. Chelune, S. Hermandez, T. Dingus, L. Hewer, Ch. Koch, M. N. Metz-Lutz, G. Parlato, M. Sinaki, Charles Pierrot-Deseilligny, H. C. Diener, J. Broeckx, J. Weill-Fulazza, M. L. Villar, M. Rizzo, O. Ganslandt, C. Duran, N. A. Fletcher, G. Di Giovacchino, Susan T. Iannaccone, C. Kolig, N. Fabre, H. A. Crockard, Rita Bella, M. Tazir, E. Papagiannuli, K. Overgaard, Emma Ciafaloni, I. Lorenzetti, F. Viader, P. A. H. Millac, I. Montiel, L. H. Visser, M. Palomar, P. L. Murgia, H. Pedersen, Rafael Blesa, S. Seddigh, W. O. Renier, I. Lemahieu, H. M. L. Jansen, L. Rosin, J. Galofre, K. Mattos, M. Pondal, G. M. Hadjigeorgiou, D. Francis, L. Cantin, D. Stegeman, M. Rango, A. B. M. F. Karim, S. Schraff, B. Castellotti, I. Iriarte, E. Laborde, T. J. Tjan, R. Mutani, D. Toni, B. Bergaasco, J. G. Young, C. Klotzsch, A. Zincone, X. Ducrocq, M. Uchuya, O. J. Kolar, A. Quattrone, T. Bauermann, Nereo Bresolin, J. Vallée, B. C. Jacobs, A. Campos, Werner Poewe, J. A. Villanueva, A. W. Kornhuber, A. Malafosse, E. Diez-Tejedor, G. Jungreia, M. J. A. Puchner, A. Komiyama, O. Saribas, V. Volpini, L. Geremia, S. Bressi, A. Nibbio, Timothy E. Bates, T. z. Tzonev, E. Ideman, G. A. Damlacik, G. Martino, G. Crepaldi, T. Martino, Kjell Någren, E. Idiman, D. Samuel, J. M. Perez Trullen, Y. van der Graaf, J. O. Thorell, M. J. M. Dupuis, E. Sieber, R. D'Alessandro, C. Cazzaniga, J. Faiss, A. Tanguy, A. Schick, I. Hoksergen, A. Cardozo, R. Shakarishvili, G. K. Wennlng, J. L. Marti-Vilalta, J. Weissenbach, I. L. Simone, Amalia C. Bruni, Darius J. Adams, C. Weiller, A. Pietrangeli, F. Croria, C. Vigo-Pelfrey, Patricia Limousin, A. Ducros, G. Conti, O. Lindvall, E. Richter, M. Zuffi, A. Nappo, T. Riise, J. Wijdenes, M. J. Fernandez, J. Rosell, P. Vermersh, S. Servidei, M. S. C. Verdugo, F. Gouttiere, W. Solbach, M. Malbezin, I. S. Watanabe, A. Tumac, W. I. McDonald, D. A. Butterfield, P. P. Costa, F. deRino, F. Bamonti, J. M. Cesar, C. H. Lahoz, I. Mosely, M. Starck, M. H. Lemaitre, K. M. Stephan, S. Tex, R. Bokonjic, I. Mollee, L. Pastena, M. Gutierrez, F. Boiler, M. C. Martinez-Para, M. Velicogna, O. Obuz, A. Grinspan, M. Guarino, L. M. Cartier, E. Ruiz, D. Gambi, S. Messina, M. Villa, Michael G. Hanna, J. Valk, Leone Pascual, M. Clanet, Z. Argov, B. Ryniewicz, E. Magni, B. Berlanga, K. S. Wong, C. Gellera, C. Prevost, F. Gonzalez-Huix, R. Petraroli, J. E. G. Benedikz, I. Kojder, C. Bommelaer, L. Perusse, M. R. Bangioanni, Guy M. McKhann, A. Molina, C. Fresquet, E. Sindern, Florence Pasquier, M. J. Rosas, M. Altieri, O. Simoncini, M. Koutroumanidis, C. A. F. Tulleken, M. Dary-Auriol, S. Oueslati, H. Kruyer, I. Nishisho, C. R. Horning, A. Vital, G. V. Czettritz, J. Ph. Neau, B. Mihout, A. Ameri, M. Francis, S. Quasthoff, D. Taussig, S. Blunt, P. Valentin, C. Y. Gao, O. Heinzlef, H. d'Allens, C. Coudero, M. Erfas, G. Borghero, P. J. Modrego Pardo, M. C. Patrosso, N. L. Gershfeld, P. A. J. M. Boon, O. Sabouraud, M. Lara, J. Svennevig, G. L. Lenzi, A. Barrio, H. Villaroya, JosÇ M. Manubens, O. Boespflug-Tanguy, M. Carreras, D. A. Costiga, J. P. Breux, S. Lynn, C. Oliveras Ley, A. G. Herbaut, J. Nos, C. Tornali, Y. A. Hekster, J. L. Chopard, J. M. Manubens, P. Chemouilli, A. Jovicic, F. Dworzak, S. Smirne, S. E. Soudain, B. Gallano, D. Lubach, G. Masullo, G. Izquierdo, A. Pascual Leone Pascual, A. Sessa, V. Freitas, O. Crambes, L. Ouss, G. W. Van Dijk, P. Marchettini, P. Confalonieri, M. Donaghy, A. Munnich, M. Corbo, and M. E. L. van der Burg

Subjects
Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published
1994
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4. Contents, Vol 32, 1992

Author

J.J. Van der Sande, D. Decoo, Hikari Yamashita, Takeshi Nakano, J. De Reuck, C. Álvarez, Shu-ichi Ikeda, P.L. Timmings, José C. Garrido, A. Ling-Andersson, C. Collin, Shinji Ohara, Shinya Yamaguchi, Jun-Ichi Yokota, E. Varela de Seijas, Yoshiharu Yonekura, Julio Pascual, Hidenao Fukuyama, J M Polo, Nobuyuki Kawate, Junji Konishi, A. Richens, Taneyoshi Nozawa, Jun Kimura, Atsushi Yamadori, José Berciano, J.P.W.F. Lakke, K. Strijckmans, J.A. Cabranes, Francisco Aguayo, Hisamasa Imai, Etsuro Mori, Masamitsu Nakazato, Hiroo Ichikawa, Koujiro Sugita, I. Lemahieu, Julio Miró, Hiroshi Tsukagoshi, J.A. Haas, Nobuo Yanagisawa, A. Staal-Schreinemachers, Chiho Ninomiya, J.A. Arias, H. Rico, G. Tiger, Kohichi Seki, Yukihiro Yoneda, S.-Å. Eckernäs, Yoshikuni Mizuno, E.N.H. Jansen, A. Grahnén, Chang-Sung Koh, Toshiya Fukui, M. Nilsson, and J. Vienne

Subjects
Neurology, Neurology (clinical)
Published
1992
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5. Assistive smartphone for people with special needs : The Personal Social Assistant

Author

F. De Pauw, D. Decoo, D. Van Nieuwenhuyse, Steven Verstockt, and R. Van de Walle

Subjects
Multimedia, business.industry, Computer science, Interface (computing), Mobile computing, computer.software_genre, Mobile phone, Human–computer interaction, Assisted GPS, User interface, business, computer, Design for All, User-centered design, Content management
Abstract

The goal of the Personal Social Assistant (PSA) is to help those people who just cannot handle a mobile phone, a GPS, etc. The PSA is a novel multimodal assistive interface for smartphones, i.e., a customizable, scalable layer above the standard software that is already available on these devices. Hence, not only the interface is made more usable, but also new accessible technologies are included in the PSA to simplify certain daily living tasks. Some examples of our helpful technological innovations are photo-based GPS, scalable interfaces and an externally accessible content management system that uses SMS push technology. By using the PSA, everyone can get access to ICT. For elderly and people with cognitive, visual and/or motor disabilities the PSA can be the key to integration into society.

Published
2009
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6. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Affirm, Investigators, Fazekas, SENTINEL Investigators including: F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher, A., Rothenfusser Körber, E., Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky D. Karusiss, O. Abramsky D. Karusiss, Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fern ez Fern ez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, L., Achtnichts, L., Wilmes, S., Karabudak, R., Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni ET Lim, G. Giovannoni E. T. Lim, Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss V. Gupta, M. Reiss V. Gupta, Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel A. Babu, A. Perel A. Babu, Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor S. Humphries, P. Fodor S. Humphries, Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., S. M, El, Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Kaiser, J. Javerbaum, Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo R. Kishner, B. Steingo R. Kishner, Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan M. Yerby, S. Cohan M. Yerby, Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., KoD Gelber C. Fortin, M. K. o. D. Gelber C. Fortin, Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, J., Nicholas, A., Slaughter, R., Archer, R., Harik, S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Ch ler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., R. T, On, Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Ari, D. B, Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair EW Radue, M. S. i. n. c. l. a. i. r. E. W. Radue, de Vera, A., Bacelar, O., Kuster, P., and Kappos, L. .

Subjects
medicine.medical_specialty, Multiple Sclerosis, Enzyme-Linked Immunosorbent Assay, Relapsing-Remitting, Antibodies, Monoclonal, Humanized, Gastroenterology, Antibodies, law.invention, Disability Evaluation, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, Double-Blind Method, law, Antibody Specificity, Internal medicine, Monoclonal, medicine, Secondary Prevention, Humans, Adverse effect, Antibodies, Blocking, Humanized, Antibodies, Monoclonal, Brain, Flow Cytometry, Interferon-beta, Magnetic Resonance Imaging, Placebo Effect, Treatment Outcome, Neuroscience (all), Expanded Disability Status Scale, business.industry, Multiple sclerosis, Incidence (epidemiology), Interferon beta-1a, medicine.disease, Blocking, Multiple sclerosis functional composite, Immunology, Neurology (clinical), business, medicine.drug
Abstract

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.

Published
2007

7. The incidence and significance of anti-natalizumab antibodies. Results from the AFFIRM and SENTINEL

Author

Calabresi, Pa, Giovannoni, G, Confavreux, C, Galetta, Sl, Havrdova, E, Hutchinson, M, Kappos, L, Miller, Dh, O'Connor, Pw, Phillips, Jt, Polman, Ch, Radue, Ew, Rudick, Ra, Stuart, Wh, Lublin, Fd, Wajgt, A, Weinstock Guttman, B, Wynn, Dr, Lynn, F, Panzara, Ma, Fazekas, The following investigators participated in the SENTINEL study: F., Enzinger, * C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, * E., Egg, R., Deisenhammer, F., Lampaert, D. Decoo* J., Bier, E. Bartholome* J., Stenager, Denmark: E., Rasmussen, * M., Binzer, M., Ravnborg, M., Soelberg Sørensen, * P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, * E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, * J., Soilu Hänninen, M., Reunanen, M., Remes, * A., Keskinarkaus, I., Moreau, T., Noblet, * M., Rouaud, O., Couvreur, G., Edan, G., Lepage, * E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Gout, O., Deschamps, * R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, * J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittion Vouyouvitch, * S., Lacour, J. C., Pelletier, J., Feuillet, * L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, * K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, * D., Renouil Guy, N., Cesaro, P., Degos, * F., Benisty, S., Decavel, L. Rumbach* P., Confavreux, C., Blanc, * S., Aubertin, P., Riche, G., Brochet, B., Ouallet, * J. C., Anne, O., Menck, S., Grupe, * A., Guttman, E., Lensch, E., Fucik, * E., Heitmann, S., Hartung, H. P., Schröter, * M., Kurz, F. M. W., Heidenreich, F., Trebst, * C., Pul, R., Hohlfeld, R., Krumbholz, * M., Pellkofer, H., Haas, J., Segert, * A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, * K., Hoffmann, V., Zettl, U., Steinhagen, * V., Adler, S., Steinbrecher, A., Rothenfusser Körber, * E., Zellner, R., Baum, K., Günther, * A., Bläsing, H., Stoll, G., Gold, * R., Bayas, * A., Kleinschnitz, C., Limmroth, V., Katsarava, * Z., Kastrup, O., Haller, P., Stoeve, * S., Höbel, D., Oschmann, P., Voigt, * K., Burger, C. V., Karusiss, O. Abramsky* D., Achiron, A., Kishner, * I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, * D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, Paolo, Ranzato, * F., Tiberio, M., Perini, P., Laroni, A., Marrosu, M., Marchi, * E. Cocco P., Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, * A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, G., Pizzorno, * M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, * V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, * M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, * E., Tacken, H., Frequin, S. T. F. M., Siegers, * H. P., Mauser, H. W., Fernandez Fernandez, O., León, * A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, * C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, * L., Moral, E., Martinez, S., Kappos, L., Achtnichts, * L., Wilmes, S., Karabudak, R., Kurne, * A., Erdem, S., Siva, A., Saip, * S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, * F., Topcular, B., Lim, G. Giovannoni* E. T., Lava, N., Murnane, * M., Dentinger, M., Zimmerman, E., Gupta, M. Reiss* V., Scott, T., Brillman, * J., Kunschner, L., Wright, D., Babu, A. Perel* A., Rivera, V., Killian, * J., Hutton, G., Lai, E., Picone, Bernard W. M., Cadivid, * D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, * A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, * P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, * M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, * C., Tyler, R., Horvit, A., Humphries, P. Fodor* S., Wynn, D., Nagar, * C., O’Brien, D., Allen, N., Turel, A., Friedenberg, * S., Carlson, J., Hosey, J., Crayton, H., Richert, * J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, * Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, * C., Rorick, M., Reed, R., Elias, S., Feit, * H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, * K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, * C., Fleck, J., Horak, H., Javerbaum, J., Elmore, * R., Garcia, E., Tasch, E., Gruener, G., Celesia, * G., Chawla, J., Miller, A., Drexler, * E., Keilson, M., Wolintz, R., Drasby, E., Muscat, * P., Belden, J., Sullivan, R., Cohen, J., Stone, * L., Marrie, R. A., Fox, R., Hughes, B., Babikian, * P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, * W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, * G., Martin, J., Kaufman, D., Stuart, W., English, * J. B., Stuart, D. S., Gilbert, R. W., Kaufman, MS M., Putman, . *. S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, * E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, * H., Rizo, M., Kitaj, M., Blevins, Neurolo J., Smith, * T., Mcgee, F., Honeycutt, W., Brown, * M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, * J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, * S., Dorn, D., Groeschel, A., Kishner, B. Steingo* R., Cohen, B., Melen, * O., Simuni, T., Zee, P., Yerby, S. Cohan* M., Hendin, B., Levine, * T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, * R., Ferrell, W., Stefoski, D., Stevens, * S., Katsamakis, G., Topel, J., Ko, M., Fortin, D. Gelber* C., Green, B., Logan, * W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, * A., Sim, G., Mihai, C., Vertino, * M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, * A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, * A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, * J., Nicholas, A., Slaughter, R., Archer, R., Harik, * S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, * G., Olek, M., Demetriou, M., Shin, R., Cala bresi, * P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, * S., Sherbert, R., Herndon, R., Uschmann, * H., Chandler, A., Markowitz, C., Jacobs, * D., Balcer, L., Mitchell, G., Chakra vorty, * S., Heyman, R., Stauber, Z., Goodman, A., Segal, * B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, * M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, * M., Hawker, K., Ulrich, R., Panitch, H., Hamill, * R., Tandon, R., Dulaney, E., Simnad, V., Miller, * J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, * M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, * R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, * B., Hart, D., Moses, H., Sriram, * S., Fang, J., O’Duffy, A., Kita, M., Taylor, * L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, * S., Lefkowitz, D., Kumar, S., and Sinclair, M.

Published
2007

8. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

Author

Richard, A. Rudick, William, H. Stuart, Peter, A. Calabresi, Christian, Confavreux, Steven, L. Galetta, Ernst Wilhelm, Radue, Fred, D. Lublin, Bianca, Weinstock Guttman, Daniel, R. Wynn, Frances, Lynn, Msc, M. S. c., Michael, A. Panzara, Alfred, W. Sandrock, For, the SENTINEL Investigators including: F. Fazekas, Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Eisenhammer, F., Decoo J. Lampaert, D. Decoo J. Lampaert, Bartholome J. Bier, E. Bartholome J. Bier, Stenager, E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Ravnborg, M., Soelberg Sørensen, P., Blinkenberg, M., Petersen, B., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, T., Noblet, M., Rouaud, O., Couvreur, G., Edan, G., Lepage, E., Drapier, S., De Burghgraeve, V., Yaouanq, J., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, A., Ferriby, D., Debouverie, M., Pittionvouyouvitch, S., Lacour, J. C., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach P. Decavel, L. Rumbach P. Decavel, Confavreux, C., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, S., Grupe, A., Guttman, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher, A., Rothenfusser Körber, E., Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky D. Karusiss, O. Abramsky D. Karusiss, Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Nielsen, J., Kragt, J. J., Jongen, P. J. H., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fern ez Fern ez, O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, L., Achtnichts, L., Wilmes, S., Karabudak, R., Kurne, A., Erdem, S., Siva, A., Saip, S., Altintas, A., Atamer, A., Eraksoy, M., Bilgili, F., Topcular, B., Giovannoni ET Lim, G. Giovannoni E. T. Lim, Lava, N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss V. Gupta, M. Reiss V. Gupta, Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel A. Babu, A. Perel A. Babu, Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Weinstock Guttman, B., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor S. Humphries, P. Fodor S. Humphries, Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., S. M, El, Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Kaiser, J. Javerbaum, Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Rossman, H., Boudoris, W., Belkin, M., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Guarnaccia, J., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo R. Kishner, B. Steingo R. Kishner, Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan M. Yerby, S. Cohan M. Yerby, Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., KoD Gelber C. Fortin, M. K. o. D. Gelber C. Fortin, Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Phillips, J. T., Martin, A., Heitzman, D., Greenfield, C. F., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir, K., Brockington, J., Nicholas, A., Slaughter, R., Archer, R., Harik, S., Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sheremata, W., Delgado, S., Sherbert, R., Herndon, R., Uschmann, H., Ch ler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., R. T, On, Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Bowen, J., Doherty, M., Wundes, A., Garden, G. A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Ari, D. B, Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair EW Radue, M. S. i. n. c. l. a. i. r. E. W. Radue, de Vera, A., Bacelar, O., Kuster, P., and Kappos, L. .

Subjects
Adult, Male, Infusions, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Combination therapy, Integrin alpha4, Peripheral edema, Progressive Multifocal, Relapsing-Remitting, Gastroenterology, Antibodies, Natalizumab, Drug Therapy, Leukoencephalopathy, Internal medicine, Monoclonal, Secondary Prevention, medicine, Humans, Humanized, Proportional Hazards Models, Expanded Disability Status Scale, business.industry, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Brain, Cell Adhesion Molecules, Disease Progression, Drug Therapy, Combination, Female, Infusions, Intravenous, Interferon-beta, JC Virus, Leukoencephalopathy, Progressive Multifocal, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Medicine (all), Progressive multifocal leukoencephalopathy, Multiple sclerosis, Hazard ratio, Interferon beta-1a, General Medicine, medicine.disease, Surgery, Combination, medicine.symptom, Intravenous, business, medicine.drug
Abstract

Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P

Published
2006

9. Long-term follow up of glatiramer acetate compassionate use in Belgium

Author

C J M, Sindic, P, Seeldrayers, L, Vande Gaer, E, De Smet, G, Nagels, P P, De Deyn, R, Medaer, D, Guillaume, M B, D'Hooghe, M C, Deville, D, Decoo, B, Sadzot, W, Van Landegem, T, Strauven, J, Pepin, H, Merckx, J, Caekebeke, and M A, van der Tool

Subjects
Adult, Male, Time Factors, Adolescent, Luxembourg, Glatiramer Acetate, Middle Aged, Health Surveys, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Belgium, Disease Progression, Secondary Prevention, Humans, Patient Compliance, Female, Peptides, Immunosuppressive Agents, Follow-Up Studies, Netherlands
Abstract

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

Published
2005

10. 57Co SPECT, 99mTc-ECD SPECT, MRI and neuropsychological testing in senile dementia of the Alzheimer type

Author

Eric Achten, Yves D'Asseler, Rudi Dierckx, J Korf, D Decoo, Guido Slegers, Koenraad Van Laere, Jan Versijpt, Kurt Audenaert, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Vrije Universiteit Brussel, and Cellular and Molecular Immunology

Subjects
Male, Single-photon emission computed tomography, Neuropsychological Tests, Neuroimaging, Alzheimer Disease, medicine, Dementia, Humans, ECD, Radiology, Nuclear Medicine and imaging, Cobalt Radioisotopes, Vascular dementia, Aged, Aged, 80 and over, Tomography, Emission-Computed, Single-Photon, medicine.diagnostic_test, business.industry, Dementia, Vascular, Magnetic resonance imaging, General Medicine, Neuropsychological test, medicine.disease, Magnetic Resonance Imaging, Co-senile dementia of the Alzheimer type, Frontal Lobe, Perfusion, inflammation, Radiology Nuclear Medicine and imaging, Positron emission tomography, Female, Alzheimer's disease, Radiopharmaceuticals, Nuclear medicine, business, MRI
Abstract

Inflammatory mechanisms contribute to the pathophysiology of senile dementia of the Alzheimer type (sDAT). Previous studies have shown that 57Co single photon emission computed tomography (SPECT) is able to visualize inflammatory lesions, probably by means of the final common pathway of Ca2+ homeostasis disturbance in both neuronal degeneration and inflammation. The aims of this study were: (1) to detect 57Co SPECT changes in sDAT patients; (2) to correlate these findings with those of conventional neuroimaging techniques and neuropsychological testing (NPT); and (3) to compare 57Co SPECT findings in sDAT patients with those in other types of dementia. Six patients suffering from probable sDAT were included and compared with four patients suffering from other types of dementia. All patients had a magnetic resonance imaging (MRI) scan, NPT, 57Co and 99mTc-ethyl cysteinate dimer (ECD) SPECT scan. Perfusion SPECT images were semiquantitatively evaluated by comparison with an age-matched normal database, while 57Co SPECT scans were assessed qualitatively. MRI and 99mTc-ECD SPECT scans yielded conclusive results with regard to the exclusion of other pathologies and the confirmation of the diagnosis. Using visual analysis, 57Co SPECT scans were unable to show any regional raised uptake, irrespective of the disorder, depth or extent of the perfusion defects, presence of atrophy on MRI or the results of NPT.

Published
2001

11. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [

Author

Hani T S, Benamer, Jim, Patterson, Donald G, Grosset, J, Booij, K, de Bruin, E, van Royen, J D, Speelman, M H I M, Horstink, H J W A, Sips, R A, Dierckx, J, Versijpt, D, Decoo, C, Van Der Linden, D M, Hadley, M, Doder, A J, Lees, D C, Costa, S, Gacinovic, W H, Oertel, O, Pogarell, H, Hoeffken, K, Joseph, K, Tatsch, J, Schwarz, and V, Ries

Published
1999

12. Biodistribution and dosimetry of carbon-11-methoxyprogabidic acid, a possible ligand for GABA-receptors in the brain

Author

P, Santens, F, De Vos, H, Thierens, D, Decoo, G, Slegers, R A, Dierckx, and J, De Reuck

Subjects
Adult, Male, Mice, Receptors, GABA, Animals, Brain, Humans, Tissue Distribution, Carbon Radioisotopes, gamma-Aminobutyric Acid, Tomography, Emission-Computed
Abstract

Carbon-11-methoxyprogabidic acid (11C-MPGA) was recently synthetized as a possible ligand for PET studies of gamma-amino-butyric acid (GABA) receptors in the brain. The data for human absorbed dose estimates are calculated based on the biodistribution of 11C-MPGA in mice and humans.Eighteen mice were killed at preset time intervals after an intravenous bolus injection of 3.7 MBq (100 microCi) 11C-MPGA. Time-activity curves were reconstructed for several organs. Three healthy men each had whole-body PET scans after an intravenous bolus injection of 37 MBq (1 mCi) to determine activity in the critical organs. Animal data were fitted into these human findings to calculate residence times, and the MIRDOSE 3 protocol was used to calculate the radiation absorbed dose.Animal studies demonstrated a rapid distribution of 11C-MPGA in several organs. The highest activity was detected in the intestines, liver and kidneys. Brain activity was low throughout compared to these organs. The human whole-body study yielded similar results, with the intestines, liver and kidneys showing the highest activity. The estimated dose to the urinary bladder compartment turned out to be significant. The mean effective dose was 4.8 microSv/MBq (s.d.= 0.5 microSv/MBq).PET studies using 185 MBq (5 mCi) 11C-MPGA are within the International Commission on Radiological Protection risk Category II for healthy volunteers.

Published
1998

13. Co-registration of PET and MRI in different courses of MS using Cobalt-55 as a Calcium-tracer

Author

H M, Jansen, D, Decoo, and J M, Minderhoud

Subjects
Inflammation, Multiple Sclerosis, Treatment Outcome, T-Lymphocytes, Brain, Humans, Calcium, Tissue Distribution, Cobalt Radioisotopes, Magnetic Resonance Imaging, Tomography, Emission-Computed
Abstract

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (SPM-96)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and eight healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS.

Published
1997

14. PET studies in epilepsy

Author

D, Decoo and A, Destée

Subjects
Flumazenil, Tomography, Emission-Computed, Single-Photon, Fluorine Radioisotopes, Epilepsy, Brain, Receptors, GABA-A, Magnetic Resonance Imaging, Fentanyl, Fluorodeoxyglucose F18, Humans, Epilepsy, Generalized, Carbon Radioisotopes, Epilepsies, Partial, Tomography, Emission-Computed
Abstract

Positron emission tomography (PET) plays a major role in the pre-surgical evaluation of patients with refractory partial epilepsy. In this review we discuss the limitations of PET data, the possibilities of fluorodeoxyglucose PET studies, neuroreceptor PET studies and alternatives, such as SPECT and MRI.

Published
1997

15. Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related (Neurobiol aging. — 2003 Jul.—Aug. — 24(4). — P. 553—561: англ.)

Author

J. Versijpt, K Van Laere, F. Dumont, D. Decoo, M. Vandecapelle, P. Santens, and S. Goethal

Abstract

The activity of the serotonin 5-HT2A subtype receptors is differently expressed in patients with the development of Alzheimer's disease. The 5-HT2A subtype serotonin receptors play an important role in the regulation of mind-related and non-conscious behavior, as well as in the pathogenesis of Alzheimer's disease.

Published
2003
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16. Neurotropin treatment of brain edema accompanying acute middle cerebral artery infarction

Author

J, De Reuck, D, Decoo, P, Boon, and C, Van der Linden

Subjects
Male, Neurologic Examination, Survival Rate, Double-Blind Method, Polysaccharides, Brain, Humans, Brain Edema, Female, Cerebral Infarction, Tomography, X-Ray Computed, Aged
Abstract

The present study is a second analysis of a randomized double-blind controlled trial on the efficacy of neurotropin on brain edema in a subgroup of patients with acute middle cerebral artery infarct treated within 24 hours. Neurotropin is a biological extract that specifically inhibits the release of bradykinin. The mortality rate was significantly lower in the neurotropin than in the placebo group. In the surviving patients the neurological deficit decreased to a significantly greater extent by neurotropin therapy after 15 days. The CT scan findings in the brain of the neurotropin-treated patients demonstrated a significant reduction in the size of the infarct and of the edematous area. Patients with middle cerebral artery infarct, which is prone to give rise to fatal intracranial hypertension, may derive great benefit from treatment of brain edema with neurotropin.

Published
1994

17. Does the severity of leukoaraiosis contribute to senile dementia? A comparative computerized and positron emission tomographic study

Author

J, De Reuck, D, Decoo, K, Strijckmans, and I, Lemahieu

Subjects
Cerebral Cortex, Male, Brain, Middle Aged, Brain Ischemia, Dementia, Multi-Infarct, Oxygen Consumption, Regional Blood Flow, Hypertension, Humans, Dementia, Female, Tomography, X-Ray Computed, Aged, Demyelinating Diseases, Tomography, Emission-Computed
Abstract

The present study evaluates the origin, severity and location of leukoaraiosis in senile dementia and in normal ageing. The regional white-matter lucency scores, determined on computed-tomographic scan of the brain, are compared to the regional blood flow, oxygen extraction rate and oxygen consumption, determined by the [15O] steady-state technique with positron emission tomography. Thirty patients, classified according to the presence or absence of leukoaraiosis and their mental status, are examined. The occurrence and severity of dementia appear to be mainly correlated to decreased blood flow and oxygen metabolism in the frontal, temporal and parietal cerebral cortex. Leukoaraiosis in demented and nondemented patients is associated with lowered blood flow in the frontal and parietal white matter. The regional lucency score is increased, and blood flow and oxygen consumption decreased in the frontal white matter of severely demented patients. Frontal leukoaraiosis contributes to dementia and is probably of ischemic origin, while parietal and occipital leukoaraiosis is due to wallerian degeneration.

Published
1992

18. Subject Index Vol. 32, 1992

Author

J M Polo, K. Strijckmans, D. Decoo, I. Lemahieu, G. Tiger, J.J. Van der Sande, Hidenao Fukuyama, Julio Miró, A. Grahnén, Hiroshi Tsukagoshi, A. Ling-Andersson, C. Álvarez, Hikari Yamashita, A. Richens, José C. Garrido, Junji Konishi, A. Staal-Schreinemachers, Chiho Ninomiya, Hisamasa Imai, Yukihiro Yoneda, Shinji Ohara, Etsuro Mori, Nobuyuki Kawate, Shu-ichi Ikeda, Jun Kimura, Jun-Ichi Yokota, J.P.W.F. Lakke, Masamitsu Nakazato, H. Rico, José Berciano, Yoshiharu Yonekura, Francisco Aguayo, Taneyoshi Nozawa, Nobuo Yanagisawa, J.A. Arias, Takeshi Nakano, J. De Reuck, Julio Pascual, Shinya Yamaguchi, C. Collin, J.A. Cabranes, Hiroo Ichikawa, Koujiro Sugita, Atsushi Yamadori, M. Nilsson, J. Vienne, P.L. Timmings, E. Varela de Seijas, E.N.H. Jansen, Yoshikuni Mizuno, Chang-Sung Koh, Toshiya Fukui, J.A. Haas, Kohichi Seki, and S.-Å. Eckernäs

Subjects
Cognitive science, Index (economics), Neurology, Subject (documents), Neurology (clinical), Psychology, Cognitive psychology
Published
1992
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19. A double-blind study of neurotropin in patients with acute ischemic stroke

Author

J. Reuck, D. Decoo, P. Vanderdonckt, A. Dallenga, W. Ceusters, J. P. Kalala, K. Meulemeester, J. Abdullah, P. Santens, J. Huybrechts, R. Spiers, J. Bleecker, I. Tack, E. Tack, C. Vogels, and P. Boon

Subjects
Male, medicine.medical_treatment, Ischemia, Brain Edema, Pilot Projects, Placebo, Brain Ischemia, Cerebral edema, law.invention, Placebos, Central nervous system disease, Double-Blind Method, Randomized controlled trial, Polysaccharides, law, medicine, Humans, Stroke, Aged, Chemotherapy, business.industry, Vascular disease, Brain, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Neurology, Anesthesia, Female, Neurology (clinical), Tomography, X-Ray Computed, business
Abstract

Neurotropin was found to reduce brain oedema in an experimental model of brain infarction in the guinea-pig. A randomized double-blind controlled trial with Neurotropin was performed in 220 patients admitted within 24 h after an acute ischemic stroke. 35 of the neurotropin and 41 of the placebo-randomized patients had to be excluded. 10 included patients in the neurotropin and 13 in the placebo-treated group died within the study period of 15 days. A better clinical outcome was observed in the 65 included surviving neurotropin compared with the 56 placebo-treated patients. The size of the infarct and of the oedema zones was significantly more decreased on CT scans from Day 11 compared with Day 3 after stroke in the neurotropin than in the placebo treated group. Neurotropin is helpful in treating brain oedema, related to acute ischemic stroke.

20. The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.

Author

Levitz D, Chao Foong Y, Sanfilippo P, Spelman T, Rath L, Roldan A, Lal A, Monif M, Jokubaitis V, Ozakbas S, Alroughani R, Boz C, Terzi M, Kalincik T, Blanco Y, Foschi M, Surcinelli A, Buzzard K, Skibina O, Laureys G, Van Hijfte L, Ramo-Tello C, Soysal A, Sanchez-Menoyo JL, Habek M, Cartechini E, Rojas JI, Karabudak R, Willekens B, Al-Harbi T, Fragoso Y, Castillo-Triviño T, Decoo D, Aragon de Vecino MC, Skromne E, Sirbu CA, Zhu C, Merlo D, Gresle M, Butzkueven H, and Van Der Walt A

Abstract

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort., Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort., Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years., Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed., Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection., Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS., (© The Author(s), 2024.)

Published
2024
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21. Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study.

Author

De Brouwer E, Becker T, Werthen-Brabants L, Dewulf P, Iliadis D, Dekeyser C, Laureys G, Van Wijmeersch B, Popescu V, Dhaene T, Deschrijver D, Waegeman W, De Baets B, Stock M, Horakova D, Patti F, Izquierdo G, Eichau S, Girard M, Prat A, Lugaresi A, Grammond P, Kalincik T, Alroughani R, Grand'Maison F, Skibina O, Terzi M, Lechner-Scott J, Gerlach O, Khoury SJ, Cartechini E, Van Pesch V, Sà MJ, Weinstock-Guttman B, Blanco Y, Ampapa R, Spitaleri D, Solaro C, Maimone D, Soysal A, Iuliano G, Gouider R, Castillo-Triviño T, Sánchez-Menoyo JL, Laureys G, van der Walt A, Oh J, Aguera-Morales E, Altintas A, Al-Asmi A, de Gans K, Fragoso Y, Csepany T, Hodgkinson S, Deri N, Al-Harbi T, Taylor B, Gray O, Lalive P, Rozsa C, McGuigan C, Kermode A, Sempere AP, Mihaela S, Simo M, Hardy T, Decoo D, Hughes S, Grigoriadis N, Sas A, Vella N, Moreau Y, and Peeters L

Abstract

Background: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking., Methods: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms&#95;benchmark, making this task an ideal benchmark for predicting disability progression in MS., Findings: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history., Conclusions: Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study., Competing Interests: The authors declare no competing non-financial interests but the following competing financial interests: - Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, as well as support for research activities from Biogen and Czech Minsitry of Education [project Progres Q27/LF1]. - Francesco Patti received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. He received research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association and University of Catania. - Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva. - Sara Eichau received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. - Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. - Alessandra Lugaresi has served as a Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche, Sanofi/ Genzyme and Teva Advisory Board Member. She received congress and travel/accommodation expense compensations or speaker honoraria from Biogen, Merck, Mylan, Novartis, Roche, Sanofi/Genzyme, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institutions received research grants from Novartis and Sanofi Genzyme. - Pierre Grammond has served in advisory boards for Novartis, EMD Serono, Roche, Biogen idec, Sanofi Genzyme, Pendopharm and has received grant support from Genzyme and Roche, has received research grants for his institution from Biogen idec, Sanofi Genzyme, EMD Serono. - Tomas Kalincik served on scientific advisory boards for BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. - Raed Alroughani received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. - Francois Grand’Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals. - Murat Terzi received travel grants from Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. - Jeannette Lechner-Scott travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis. - Samia J. Khoury received compensation for participation in the Novartis Maestro program. - Vincent van Pesch has received travel grants from Merck, Biogen, Sanofi, Bristol Myers Squibb, Almirall and Roche; his institution receives honoraria for consultancy and lectures and research grants from Roche, Biogen, Sanofi, Merck, Bristol Myers Squibb, Janssen, Almirall and Novartis Pharma. - Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion. - Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. - Claudio Solaro served on scientific advisory boards for Merck, Genzyme, Almirall, and Biogen; received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen, Merck, Genzyme and Teva. - Davide Maimone served on scientific advisory boards for Bayer, Biogen, Merck, Sanofi-Genzyme, Novartis, Roche, and Almirall; received honoraria and travel grants from Sanofi Genzyme, Novartis, Biogen, Merck, and Roche. - Gerardo Iuliano (retired - no PI successor but has approved ongoing use of data) had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva. - Bart Van Wijmeersch received research and travel grants, honoraria for MS-Expert advisor and Speaker fees from Bayer-Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche and Teva. - Tamara Castillo Triviño received speaking/consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. - Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Merck and Roche - Guy Laureys received travel and/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen. - Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche She has received speaker’s honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. - Jiwon Oh has received research funding from the MS Society of Canada, National MS Society, Brain Canada, Biogen, Roche, EMD Serono (an affiliate of Merck KGaA); and personal compensation for consulting or speaking from Alexion, Biogen, Celgene (BMS), EMD Serono (an affiliate of Merck KGaA), Novartis, Roche, and Sanofi-Genzyme. - Ayse Altintas received speaker honoraria from Merck, Alexion,; received travel and registration grants from Merck, Biogen - Gen Pharma, Roche, Sanofi-Genzyme. - Yara Fragoso received honoraria as a consultant on scientific advisory boards by Novartis, Teva, Roche and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva, Roche and Merck. - Tunde Csepany received speaker honoraria/ conference travel support from Bayer Schering, Biogen, Merck, Novartis, Roche, Sanofi-Aventis and Teva. - Suzanne Hodgkinson received honoraria and consulting fees from Novartis, Bayer Schering and Sanofi, and travel grants from Novartis, Biogen Idec and Bayer Schering. - Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis. - Bruce Taylor received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. - Fraser Moore participated in clinical trials sponsored by EMD Serono and Novartis. - Orla Gray received honoraria as consultant on scientific advisory boards for Genzyme, Biogen, Merck, Roche and Novartis; has received travel grants from Biogen, Merck, Roche and Novartis; has participated in clinical trials by Biogen and Merck. - Csilla Rozsa received speaker honoraria from Bayer Schering, Novartis and Biogen, congress and travel expense compensations from Biogen, Teva, Merck and Bayer Schering. - Allan Kermode received speaker honoraria and scientific advisory board fees from Bayer, BioCSL, Biogen, Genzyme, Innate Immunotherapeutics, Merck, Novartis, Sanofi, Sanofi-Aventis, and Teva. - Magdolna Simo received speaker honoraria from Novartis, Biogen, Bayer Schering; congress/travel compensation from Teva, Biogen, Merck, Bayer Schering. - Todd Hardy has received speaking fees or received honoraria for serving on advisory boards for Biogen, Merck, Teva, Novartis, Roche, Bristol-Myers Squibb and Sanofi-Genzyme, is Co-Editor of Advances in Clinical Neurosciences and Rehabilitation, and serves on the editorial board of Journal of Neuroimmunology and Frontiers in Neurology. - Nikolaos Grigoriadis received honoraria, consultancy/lecture fees, travel support and research grants from Biogen Idec, Biologix, Novartis, TEVA, Bayer, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE, Cellgene, ELPEN and research grants from Hellenic Ministry of Development., (Copyright: © 2024 De Brouwer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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22. Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

Author

Van Hijfte L, Cambron M, Capron B, Dachy B, Decoo D, Dive D, Dubois B, Sankari SE, London F, Perrotta G, Popescu V, Van Pesch V, Van Wijmeersch B, Willekens B, and Laureys G

Subjects
Humans, Female, Male, Middle Aged, Adult, Belgium, Surveys and Questionnaires, Health Services Accessibility statistics & numerical data, Patient Care Team, Multiple Sclerosis therapy, Multiple Sclerosis economics, Neurologists statistics & numerical data
Abstract

Background: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed RESULTS: The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level CONCLUSION: MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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23. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable.

Author

Sharmin S, Roos I, Simpson-Yap S, Malpas C, Sánchez MM, Ozakbas S, Horakova D, Havrdova EK, Patti F, Alroughani R, Izquierdo G, Eichau S, Boz C, Zakaria M, Onofrj M, Lugaresi A, Weinstock-Guttman B, Prat A, Girard M, Duquette P, Terzi M, Amato MP, Karabudak R, Grand'Maison F, Khoury SJ, Grammond P, Lechner-Scott J, Buzzard K, Skibina O, van der Walt A, Butzkueven H, Turkoglu R, Altintas A, Maimone D, Kermode A, Shalaby N, Pesch VV, Butler E, Sidhom Y, Gouider R, Mrabet S, Gerlach O, Soysal A, Barnett M, Kuhle J, Hughes S, Sa MJ, Hodgkinson S, Oreja-Guevara C, Ampapa R, Petersen T, Ramo-Tello C, Spitaleri D, McCombe P, Taylor B, Prevost J, Foschi M, Slee M, McGuigan C, Laureys G, Hijfte LV, de Gans K, Solaro C, Oh J, Macdonell R, Aguera-Morales E, Singhal B, Gray O, Garber J, Wijmeersch BV, Simu M, Castillo-Triviño T, Sanchez-Menoyo JL, Khurana D, Al-Asmi A, Al-Harbi T, Deri N, Fragoso Y, Lalive PH, Sinnige LGF, Shaw C, Shuey N, Csepany T, Sempere AP, Moore F, Decoo D, Willekens B, Gobbi C, Massey J, Hardy T, Parratt J, and Kalincik T

Subjects
Humans, Ultraviolet Rays, Disease Progression, Neoplasm Recurrence, Local, Multiple Sclerosis, Chronic Progressive epidemiology, Multiple Sclerosis epidemiology, Multiple Sclerosis diagnosis, Multiple Sclerosis, Relapsing-Remitting epidemiology
Abstract

Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2023
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24. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

Author

Daruwalla C, Shaygannejad V, Ozakbas S, Havrdova EK, Horakova D, Alroughani R, Boz C, Patti F, Onofrj M, Lugaresi A, Eichau S, Girard M, Prat A, Duquette P, Yamout B, Khoury SJ, Sajedi SA, Turkoglu R, Altintas A, Skibina O, Buzzard K, Grammond P, Karabudak R, van der Walt A, Butzkueven H, Maimone D, Lechner-Scott J, Soysal A, John N, Prevost J, Spitaleri D, Ramo-Tello C, Gerlach O, Iuliano G, Foschi M, Ampapa R, van Pesch V, Barnett M, Shalaby N, D'hooghe M, Kuhle J, Sa MJ, Fabis-Pedrini M, Kermode A, Mrabet S, Gouider R, Hodgkinson S, Laureys G, Van Hijfte L, Macdonell R, Oreja-Guevara C, Cristiano E, McCombe P, Sanchez-Menoyo JL, Singhal B, Blanco Y, Hughes S, Garber J, Solaro C, McGuigan C, Taylor B, de Gans K, Habek M, Al-Asmi A, Mihaela S, Castillo Triviño T, Al-Harbi T, Rojas JI, Gray O, Khurana D, Van Wijmeersch B, Grigoriadis N, Inshasi J, Oh J, Aguera-Morales E, Fragoso Y, Moore F, Shaw C, Baghbanian SM, Shuey N, Willekens B, Hardy TA, Decoo D, Sempere AP, Field D, Wynford-Thomas R, Cunniffe NG, Roos I, Malpas CB, Coles AJ, Kalincik T, and Brown JWL

Subjects
Humans, Prognosis, Recurrence, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis
Abstract

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear., Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS., Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up., Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n  = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n  = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n  = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically., Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Published
2023
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25. Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

Author

Zhou Y, Claflin SB, Stankovich J, van der Mei I, Simpson S Jr, Roxburgh RH, Kalincik T, Blizzard L, Lugaresi A, Alroughani R, Sajedi SA, Butzkueven H, Pucci E, Spitaleri D, Granella F, Cristiano E, Yamout B, Hughes S, Gouider R, Sánchez Menoyo JL, Olascoaga J, McGuigan C, Shaw C, Kermode AG, Kasa K, Al-Harbi T, Altintas A, Laureys G, Fragoso Y, Hardy TA, Csepany T, Sirbu CA, Decoo D, Sas A, Alvarez-Cermeño JC, Kotkata K, Millán-Pascual J, and Taylor BV

Subjects
Disability Evaluation, Disease Progression, Female, Humans, Male, Phenotype, Recurrence, Severity of Illness Index, Multiple Sclerosis diagnosis, Multiple Sclerosis epidemiology
Abstract

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups., Objective: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets., Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis., Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( p  > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( p  < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex., Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Published
2020
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26. Management of adverse renal events related to alemtuzumab treatment in multiple sclerosis: a Belgian consensus.

Author

Sprangers B, Decoo D, Dive D, Lysandropoulos A, Vanopdenbosch L, and Bovy C

Subjects
Belgium epidemiology, Early Diagnosis, Female, Humans, Male, Multiple Sclerosis epidemiology, Alemtuzumab adverse effects, Antineoplastic Agents, Immunological adverse effects, Consensus, Disease Management, Kidney Diseases chemically induced, Kidney Diseases diagnosis, Kidney Diseases therapy, Multiple Sclerosis drug therapy
Abstract

Alemtuzumab is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease. Multiple sclerosis (MS) patients treated with alemtuzumab are at increased risk for autoimmune adverse events (thyroid disorders, immune thrombocytopenia, and renal disease). The use of alemtuzumab has been associated with the development of renal immune-mediated adverse events in 0.3% of patients in clinical trials in MS, which generally occurred within 39 months of the last administration. Both anti-GBM disease and membranous nephropathy have been associated with the use of alemtuzumab. Early detection is necessary to allow for early diagnosis and prevent adverse renal and patient outcomes. Through the implementation of the risk minimization measures, patients can be diagnosed, and treated if needed, early allowing for generally favorable outcomes. This important goal can be reached through health care professional and patient education, careful analysis of the monthly lab tests, and close collaboration between the patient, neurologist, and the nephrologist. This article presents the consensus of Belgian MS specialists and nephrologists on the practicalities of diagnosis, management, and treatment of alemtuzumab-associated renal adverse events based on good clinical practice.

Published
2018
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27. Improving fatigue in multiple sclerosis by smartphone-supported energy management: The MS TeleCoach feasibility study.

Author

D'hooghe M, Van Gassen G, Kos D, Bouquiaux O, Cambron M, Decoo D, Lysandropoulos A, Van Wijmeersch B, Willekens B, Penner IK, and Nagels G

Subjects
Adult, Disability Evaluation, Fatigue etiology, Feasibility Studies, Female, Humans, Male, Middle Aged, Motivation, Multiple Sclerosis, Relapsing-Remitting complications, Multiple Sclerosis, Relapsing-Remitting psychology, Patient Satisfaction, Prospective Studies, Severity of Illness Index, Surveys and Questionnaires, Therapy, Computer-Assisted instrumentation, Treatment Outcome, Young Adult, Exercise psychology, Fatigue therapy, Multiple Sclerosis, Relapsing-Remitting therapy, Self-Management methods, Smartphone, Telemedicine instrumentation
Abstract

Background: Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period. The goal of the MS TeleCoach, conceived as a combination of monitoring, self-management and motivational messages, is to enhance levels of physical activity thereby improving fatigue in pwMS in an accessible and interactive way, reinforcing self-management of patients., Methods: We conducted a prospective, open-label feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status Scale ≤ 4 and moderate to severe fatigue as measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess the baseline activity level per patient, the target number of activity counts was gradually increased over the 12-week period through telecoaching. The primary efficacy outcome was change in FSMC total score from baseline to study end. A subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire, to evaluate the satisfaction with the MS TeleCoach device and the experienced service., Results: Seventy-five patients were recruited from 16 centres in Belgium, of which 57 patients (76%) completed the study. FSMC total score (p = 0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively) decreased from baseline to week 12, indicating an improvement in fatigue. One third of participants with severe fatigue changed to a lower FSMC category for both FSMC total score and subscores. The post-study evaluation of patient satisfaction showed that the intervention was well accepted and that patients were very satisfied with the quality of the professional services., Conclusion: Using MS TeleCoach as a self-management tool in pwMS suffering from mild disability and moderate to severe fatigue appeared to be feasible, both technically and from a content perspective. Its use was associated with improved fatigue levels in the participants who completed the study. The MS Telecoach seems to meet the need for a low-cost, accessible and interactive self-management tool in MS., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2018
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28. Treatment adherence in multiple sclerosis: a survey of Belgian neurologists.

Author

Decoo D and Vokaer M

Abstract

Background: Poor treatment adherence is common among patients with multiple sclerosis (MS). This survey evaluated neurologists' perception of treatment adherence among MS patients., Materials and Methods: This questionnaire-based survey of Belgian neurologists treating MS patients was conducted between June and July 2014. Face-to-face interviews with the neurologists were based on a semistructured questionnaire containing questions regarding the perception of the treatment-adherence level., Results: A total of 41 neurologists participated in the survey. Of these, 88% indicated frequent discussions about treatment adherence as beneficial for treatment efficacy. The mean time spent on the treatment-adherence discussion during the initial consultation was 11 minutes, with 24% of doctors spending 5 minutes and 24% of doctors spending 10 minutes discussing this issue. The majority of neurologists (56%) perceived the adherence level in MS as good, and 12% perceived it as excellent. The majority of neurologists (64%) indicated intolerance as a main cause of poor adherence, and all neurologists reported insufficient efficacy as a consequence of nonadherence. The importance of adherence in the neurologists' practice was evaluated on a scale of 1-10, with 1= "not very important" and 10= "very important": 44% of doctors indicated a score of 10, and the mean score was 9.0., Conclusion: Belgian neurologists consider treatment adherence in MS as essential for the benefits of therapies. However, although neurologists are aware of the consequences of nonadherence, they generally spend limited time discussing the importance of treatment adherence with their patients.

Published
2015
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29. Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program.

Author

van Pesch V, Bartholomé E, Bissay V, Bouquiaux O, Bureau M, Caekebeke J, Debruyne J, Declercq I, Decoo D, Denayer P, De Smet E, D'hooghe M, Dubois B, Dupuis M, Sankari SE, Geens K, Guillaume D, van Landegem W, Lysandropoulos A, de Noordhout AM, Medaer R, Melin A, Peeters K, Ba RP, Retif C, Seeldrayers P, Symons A, Urbain E, Vanderdonckt P, Van Ingelghem E, Vanopdenbosch L, Vanroose E, Van Wijmeersch B, Willekens B, Willems C, and Sindic C

Subjects
Adolescent, Adult, Age Distribution, Aged, Belgium epidemiology, Cohort Studies, Disability Evaluation, Female, Humans, International Cooperation, Magnetic Resonance Imaging, Male, Middle Aged, Natalizumab, Product Surveillance, Postmarketing, Severity of Illness Index, Time Factors, Treatment Outcome, Young Adult, Antibodies, Monoclonal, Humanized therapeutic use, Immunologic Factors therapeutic use, Multiple Sclerosis drug therapy
Abstract

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Published
2014
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30. Cerebral blood flow and oxygen metabolism in symptomatic internal carotid artery occlusion by (traumatic) cervical artery dissection.

Author

De Reuck J, Paemeleire K, Decoo D, Van Maele G, Strijckmans K, and Lemahieu I

Subjects
Adult, Aortic Dissection complications, Carotid Artery Injuries complications, Carotid Artery Injuries physiopathology, Carotid Artery Thrombosis physiopathology, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Stroke etiology, Aortic Dissection physiopathology, Brain physiopathology, Carotid Artery Thrombosis etiology, Cerebrovascular Circulation physiology, Oxygen metabolism
Abstract

The present study investigates whether cerebral infarction resulting from internal carotid artery occlusion by cervical dissection is due to emboli, released from a superimposed luminal thrombus, or is due to haemodynamic failure and hypoperfusion. Ten patients with a history of stroke and with a visible cerebral infarct on computed tomographic scan, due to cervical dissection and thrombosis of the internal carotid artery, were studied with positron emission tomography in order to assess the regional cerebral blood flow (rCBF), the regional cerebral metabolic rate of oxygen (rCMRO2) and the regional oxygen extraction fraction (rOEF) in different regions of the brain. rCBF and rCMRO2 were only decreased in the infarct area but not in the peri-infarct zone or elsewhere in the brain. As rOEF was not increased in the affected cerebral hemisphere, the present study suggests artery-to-artery embolism rather than a haemodynamic event as the cause of the stroke. Use of anticoagulants thus appears to be the appropriate treatment in the acute stage.

Published
2005

31. Long-term follow up of glatiramer acetate compassionate use in Belgium.

Author

Sindic CJ, Seeldrayers P, Vande Gaer L, De Smet E, Nagels G, De Deyn PP, Medaer R, Guillaume D, D'Hooghe MB, Deville MC, Decoo D, Sadzot B, Van Landegem W, Strauven T, Pepin J, Merckx H, Caekebeke J, and van der Tool MA

Subjects
Adolescent, Adult, Belgium, Disease Progression, Female, Follow-Up Studies, Glatiramer Acetate, Health Surveys, Humans, Immunosuppressive Agents adverse effects, Luxembourg, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting physiopathology, Netherlands, Patient Compliance, Peptides adverse effects, Secondary Prevention, Time Factors, Treatment Outcome, Immunosuppressive Agents administration & dosage, Multiple Sclerosis, Relapsing-Remitting drug therapy, Peptides administration & dosage
Abstract

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

Published
2005

32. Cerebral bloodflow and oxygen metabolism in borderzone and territorial infarcts due to symptomatic carotid artery occlusion.

Author

De Reuck J, Paemeleire K, Decoo D, Van Maele G, Strijckmans K, and Lemahieu I

Subjects
Adult, Aged, Aged, 80 and over, Arteriosclerosis complications, Cerebral Angiography methods, Cerebral Infarction metabolism, Demography, Female, Functional Laterality physiology, Humans, Male, Middle Aged, Perfusion adverse effects, Carotid Artery Diseases complications, Cerebral Infarction etiology, Oxygen metabolism, Regional Blood Flow physiology
Abstract

It remains controversial whether borderzone infarcts are due to compromised cerebral perfusion and whether territorial infarcts are caused by artery-to-artery emboli in case of occlusion of the internal carotid artery. The present positron emission tomography study compares with normal controls, the average regional cerebral bloodflow (rCBF), regional oxygen extraction fraction (rOEF) and regional cerebral metabolic rate for oxygen (rCMRO(2)) in the infarct area, the peri-infarct zone, the remaining homolateral hemisphere and in the contralateral hemisphere of 10 patients with borderzone and 17 patients with territorial infarcts, due to internal carotid artery occlusion by atherosclerosis and by cervical dissection. The steady-state technique with oxygen-15 was used. A nearly significant increase of rOEF with lowered rCBF and rCMRO(2) was observed in the peri-infarct zone of patients with territorial infarcts. In patients with borderzone infarcts rCMRO(2) was decreased in the peri-infarct zone, in the remaining homolateral hemisphere and in the contralateral hemisphere without changes in rCBF and rOEF. The present study finds no arguments that impaired cerebral perfusion is a more frequent cause of borderzone than of territorial infarcts.

Published
2004
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33. Imaging of the 5-HT2A system: age-, gender-, and Alzheimer's disease-related findings.

Author

Versijpt J, Van Laere KJ, Dumont F, Decoo D, Vandecapelle M, Santens P, Goethals I, Audenaert K, Slegers G, Dierckx RA, and Korf J

Subjects
Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Receptor, Serotonin, 5-HT2A, Sex Factors, Statistics, Nonparametric, Tomography, Emission-Computed, Single-Photon methods, Alzheimer Disease diagnostic imaging, Alzheimer Disease metabolism, Brain diagnostic imaging, Brain metabolism, Receptors, Serotonin metabolism
Abstract

Serotonin (5-HT) and more specifically the 5-HT(2A) receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimer's disease (AD). The objective was to assess the 5-HT(2A) binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT(2A) receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT(2A) receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD.

Published
2003
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34. Cerebral blood flow and oxygen metabolism in symptomatic internal carotid artery occlusion by atherosclerosis and by cervical dissection.

Author

De Reuck J, Paemeleire K, Decoo D, Van Maele G, Strijckmans K, and Lemahieu I

Abstract

Symptomatic internal carotid artery occlusion by atherosclerosis and by cervical dissection are distinct conditions with different long-term prognoses. The purpose of the present study is to investigate if regional cerebral blood flow and oxygen metabolism, after onset of stroke, differ between both conditions. Seventeen patients with symptomatic unilateral atherosclerotic internal carotid occlusion and 10 patients with symptomatic internal carotid occlusion due to cervical dissection were submitted to a positron emission tomographic (PET) study between 1 and 2 months after stroke onset. The steady state technique with 15O was used in order to determine regional cerebral blood flow, regional oxygen extraction fraction, and regional cerebral metabolic rate for oxygen in the infarct area, the peri-infarct zone, the remaining homolateral hemisphere, and the contralateral hemisphere. The results were compared between both patient's populations. The patients with cervical dissection were on average much younger than those with atherosclerotic occlusion, but neurological impairment on admission and disability at 3 months were comparable. Between both patient populations, no differences in rCBF, rOEF, and rCMRO2 could be demonstrated in the different regions of interest when the results were age-adjusted. Except for age-related changes, no differences in PET findings could be demonstrated between patients with symptomatic internal carotid occlusion caused by either atherosclerosis or cervical dissection.

Published
2003
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35. Assessment of neuroinflammation and microglial activation in Alzheimer's disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study.

Author

Versijpt JJ, Dumont F, Van Laere KJ, Decoo D, Santens P, Audenaert K, Achten E, Slegers G, Dierckx RA, and Korf J

Subjects
Aged, Aged, 80 and over, Alzheimer Disease immunology, Alzheimer Disease pathology, Brain Mapping, Dominance, Cerebral physiology, Encephalitis immunology, Encephalitis pathology, Female, Humans, Male, Mental Status Schedule, Microglia immunology, Microglia pathology, Middle Aged, Neocortex immunology, Neocortex pathology, Pilot Projects, Radioligand Assay, Reference Values, Up-Regulation physiology, Alzheimer Disease diagnostic imaging, Encephalitis diagnostic imaging, Image Processing, Computer-Assisted, Iodine Radioisotopes, Isoquinolines, Microglia diagnostic imaging, Neocortex diagnostic imaging, Receptors, GABA-A physiology, Tomography, Emission-Computed, Single-Photon methods
Abstract

Objectives: Inflammation contributes to degeneration in Alzheimer's disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [(123)I]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, the latter being expressed on microglia (brain resident macrophages) and upregulated under inflammatory circumstances. The objectives were to assess AD inflammation by detecting [(123)I]iodo-PK11195 uptake changes and investigate how uptake values relate with perfusion SPECT and neuropsychological findings., Methods: Ten AD and 9 control subjects were included. [(123)I]iodo-PK11195 SPECT images were realigned into stereotactic space where binding indices, normalized on cerebellar uptake, were calculated., Results: The mean [(123)I]iodo-PK11195 uptake was increased in AD patients compared with controls in nearly all neocortical regions; however, statistical significance was only reached in the frontal and right mesotemporal regions. Significant correlations were found between regional increased [(123)I]iodo-PK11195 uptake and cognitive deficits., Conclusions: [(123)I]iodo-PK11195 is a cellular disease activity marker and allows in vivo assessment of microglial inflammation in AD., (Copyright 2003 S. Karger AG, Basel)

Published
2003
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36. Longitudinal positron emission tomography study in a patient with presumed extracranial internal carotid dissection.

Author

De Reuck J, Siau B, Decoo D, Strijckmans K, and Lemahieu I

Subjects
Carotid Artery Thrombosis etiology, Carotid Artery, Internal, Dissection complications, Cerebral Infarction diagnostic imaging, Cerebral Infarction etiology, Cerebrovascular Circulation, Collateral Circulation, Follow-Up Studies, Humans, Intracranial Embolism etiology, Male, Middle Aged, Oxygen Radioisotopes, Paresis etiology, Seizures etiology, Carotid Artery, Internal, Dissection diagnostic imaging, Tomography, Emission-Computed methods
Published
2001

37. 57Co SPECT, 99mTc-ECD SPECT, MRI and neuropsychological testing in senile dementia of the Alzheimer type.

Author

Versijpt J, Decoo D, Van Laere KJ, Achten E, Audenaert K, D'Asseler Y, Slegers G, Dierckx RA, and Korf J

Subjects
Aged, Aged, 80 and over, Cobalt Radioisotopes, Dementia, Vascular diagnostic imaging, Dementia, Vascular psychology, Female, Frontal Lobe physiopathology, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Perfusion, Radiopharmaceuticals, Tomography, Emission-Computed, Single-Photon, Alzheimer Disease diagnostic imaging, Alzheimer Disease psychology
Abstract

Inflammatory mechanisms contribute to the pathophysiology of senile dementia of the Alzheimer type (sDAT). Previous studies have shown that 57Co single photon emission computed tomography (SPECT) is able to visualize inflammatory lesions, probably by means of the final common pathway of Ca2+ homeostasis disturbance in both neuronal degeneration and inflammation. The aims of this study were: (1) to detect 57Co SPECT changes in sDAT patients; (2) to correlate these findings with those of conventional neuroimaging techniques and neuropsychological testing (NPT); and (3) to compare 57Co SPECT findings in sDAT patients with those in other types of dementia. Six patients suffering from probable sDAT were included and compared with four patients suffering from other types of dementia. All patients had a magnetic resonance imaging (MRI) scan, NPT, 57Co and 99mTc-ethyl cysteinate dimer (ECD) SPECT scan. Perfusion SPECT images were semiquantitatively evaluated by comparison with an age-matched normal database, while 57Co SPECT scans were assessed qualitatively. MRI and 99mTc-ECD SPECT scans yielded conclusive results with regard to the exclusion of other pathologies and the confirmation of the diagnosis. Using visual analysis, 57Co SPECT scans were unable to show any regional raised uptake, irrespective of the disorder, depth or extent of the perfusion defects, presence of atrophy on MRI or the results of NPT.

Published
2001
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38. Parkinsonism in patients with vascular dementia: clinical, computed- and positron emission-tomographic findings.

Author

De Reuck J, Siau B, Decoo D, Santens P, Crevits L, Strijckmans K, and Lemahieu I

Subjects
Aged, Aged, 80 and over, Brain metabolism, Cerebrovascular Circulation, Dementia, Vascular physiopathology, Female, Humans, Male, Middle Aged, Oxygen Consumption, Tissue Distribution, Dementia, Vascular diagnosis, Dementia, Vascular etiology, Parkinsonian Disorders complications, Tomography, Emission-Computed, Tomography, X-Ray Computed
Abstract

Purpose: The present study investigates the vascular nature of parkinsonian features in patients with 'probable' vascular dementia., Patients and Methods: Forty patients with vascular dementia were studied with positron emission tomography (PET) using the steady state technique with (15)O in order to assess regional cerebral blood flow (rCBF), regional oxygen extraction rate (rOER) and regional metabolic rate for oxygen (rCMRO(2)) in different brain regions. The findings in 10 patients with (VaDP) were compared to 30 without parkinsonism (VaD)., Results: The clinical and computed tomographic findings in the parkinsonian patients were similar to those described in the literature as probable vascular parkinsonism. The PET results showed decreased rCBF and rCMRO(2) in the frontal and parietal cortices and in the striatum of the VaDP compared to the VaD group. The decrease of rCBF and rCMRO(2) in frontal and parietal cortices is due to the more severe mental changes in the VaDP group. In the VaDP patients rCBF and rCMRO(2) were more decreased and rOER increased in the striatum contralateral to the most affected parkinsonian side., Conclusion: Our PET findings show that local ischemic changes in the striatum contribute to parkinsonism in vascular dementia patients., (Copyright 2001 S. Karger AG, Basel.)

Published
2001
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40. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

Author

Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, Speelman JD, Horstink MH, Sips HJ, Dierckx RA, Versijpt J, Decoo D, Van Der Linden C, Hadley DM, Doder M, Lees AJ, Costa DC, Gacinovic S, Oertel WH, Pogarell O, Hoeffken H, Joseph K, Tatsch K, Schwarz J, and Ries V

Subjects
Adult, Aged, Aged, 80 and over, Corpus Striatum diagnostic imaging, Diagnosis, Differential, Dominance, Cerebral physiology, Female, Humans, Male, Middle Aged, Observer Variation, Reference Values, Essential Tremor diagnostic imaging, Iodine Radioisotopes, Parkinson Disease diagnostic imaging, Tomography, Emission-Computed, Single-Photon, Tropanes
Abstract

Objective: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET)., Methods: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken., Results: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection., Conclusion: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Published
2000

41. Acetazolamide vasoreactivity in vascular dementia: a positron emission tomographic study.

Author

De Reuck J, Decoo D, Hasenbroekx MC, Lamont B, Santens P, Goethals P, Strijckmans K, and Lemahieu I

Subjects
Aged, Aged, 80 and over, Ammonia, Brain Ischemia complications, Brain Ischemia diagnostic imaging, Dementia, Multi-Infarct diagnostic imaging, Dementia, Multi-Infarct etiology, Dementia, Multi-Infarct physiopathology, Dementia, Vascular etiology, Dementia, Vascular physiopathology, Female, Humans, Male, Microcirculation drug effects, Middle Aged, Nitrogen Radioisotopes, Risk Factors, Vasodilation drug effects, Vasomotor System physiopathology, Acetazolamide pharmacology, Cerebrovascular Circulation drug effects, Dementia, Vascular diagnostic imaging, Tomography, Emission-Computed, Vasodilator Agents pharmacology, Vasomotor System drug effects
Abstract

The present study investigates the vasoreactivity of the brain in patients with large infarcts and dementia (multi-infarct dementia; MID) and in patients with microangiopathy, lacunes, white matter changes and dementia (lacunar dementia; LD) using positron emission tomography (PET) and 13NH3 as regional cerebral blood flow (rCBF) tracer. In the control group, an increase in rCBF ranging from 32 to 43% was found in all brain regions after intravenous acetazolamide administration. In both the MID group and the group with multiple infarcts without dementia, moderate loss of vasoreactivity was observed in the frontal, temporal and parietal cortex compared to the control values. Vasoreactivity was severely impaired in all cerebral regions of the LD group and restricted to the thalamus in the group with lacunes and white matter changes without dementia (lacunar stroke; LS). This suggests that global loss of vasoreactivity is not a determining factor in the occurrence of MID, but might be important in LD. The present study shows that loss of the vascular reserve leading to exhausted metabolic reserve of the whole brain is one of the possible mechanisms for the occurrence of vascular dementia.

Published
1999
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42. Biodistribution and dosimetry of carbon-11-methoxyprogabidic acid, a possible ligand for GABA-receptors in the brain.

Author

Santens P, De Vos F, Thierens H, Decoo D, Slegers G, Dierckx RA, and De Reuck J

Subjects
Adult, Animals, Carbon Radioisotopes, Humans, Male, Mice, Tissue Distribution, gamma-Aminobutyric Acid administration & dosage, gamma-Aminobutyric Acid pharmacokinetics, Brain diagnostic imaging, Brain metabolism, Receptors, GABA analysis, Tomography, Emission-Computed, gamma-Aminobutyric Acid analogs & derivatives
Abstract

Unlabelled: Carbon-11-methoxyprogabidic acid (11C-MPGA) was recently synthetized as a possible ligand for PET studies of gamma-amino-butyric acid (GABA) receptors in the brain. The data for human absorbed dose estimates are calculated based on the biodistribution of 11C-MPGA in mice and humans., Methods: Eighteen mice were killed at preset time intervals after an intravenous bolus injection of 3.7 MBq (100 microCi) 11C-MPGA. Time-activity curves were reconstructed for several organs. Three healthy men each had whole-body PET scans after an intravenous bolus injection of 37 MBq (1 mCi) to determine activity in the critical organs. Animal data were fitted into these human findings to calculate residence times, and the MIRDOSE 3 protocol was used to calculate the radiation absorbed dose., Results: Animal studies demonstrated a rapid distribution of 11C-MPGA in several organs. The highest activity was detected in the intestines, liver and kidneys. Brain activity was low throughout compared to these organs. The human whole-body study yielded similar results, with the intestines, liver and kidneys showing the highest activity. The estimated dose to the urinary bladder compartment turned out to be significant. The mean effective dose was 4.8 microSv/MBq (s.d.= 0.5 microSv/MBq)., Conclusion: PET studies using 185 MBq (5 mCi) 11C-MPGA are within the International Commission on Radiological Protection risk Category II for healthy volunteers.

Published
1998

43. Positron emission tomography in vascular dementia.

Author

De Reuck J, Decoo D, Marchau M, Santens P, Lemahieu I, and Strijckmans K

Subjects
Aged, Brain diagnostic imaging, Brain metabolism, Brain pathology, Cerebral Infarction complications, Cerebral Infarction diagnostic imaging, Cerebral Infarction metabolism, Cerebral Infarction pathology, Cerebrovascular Circulation, Dementia, Vascular complications, Dementia, Vascular metabolism, Dementia, Vascular pathology, Female, Humans, Male, Middle Aged, Oxygen metabolism, Tomography, Emission-Computed, Dementia, Vascular diagnostic imaging
Abstract

Background: Vascular dementia (VaD) is an ill-defined entity. It is not known how acute brain failure related to stroke becomes chronic leading to dementia., Purpose: The present study investigates whether positron emission tomography (PET) can detect different metabolic patterns in VaD., Patients and Methods: Four groups of stroke patients were selected. The PET findings of 14 stroke patients with multiple large infarcts and dementia (MID) and 14 without dementia (MS) were compared. Sixteen stroke patients with lacunes, leukoaraiosis and dementia (LD) were assessed against nine without dementia (LS). The PET examination utilised the 15-O-steady-state technique in order to determine regional cerebral blood flow (rCBF), regional oxygen extraction rate (rOER) and regional cerebral metabolic rate for oxygen (rCMRO2) in different pre-established cortical, subcortical and cerebellar regions., Results: Decreased coupled mean rCBF and rCMRO2 with comparable rOER values were observed in all cerebral regions except in the cerebellum of the MID compared to the MS group. In the LD group mean rCBF and rCMRO2 were decreased with increased rOER in all cerebral regions except in the cerebellum compared to the LS group., Conclusions: The PET findings in demented patients with multiple large infarcts are in agreement with the concept of multi-infarct dementia. In demented patients with lacunes and leukoaraiosis, the PET pattern suggests a state of misery perfusion not only in the deep structures but also in the whole cerebral cortex. The present PET study argues that there are at least two possible mechanisms that can explain the occurrence of VaD in stroke patients.

Published
1998
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44. PET studies in epilepsy.

Author

Decoo D and Destée A

Subjects
Brain diagnostic imaging, Brain metabolism, Carbon Radioisotopes, Epilepsies, Partial diagnostic imaging, Epilepsies, Partial metabolism, Epilepsy metabolism, Epilepsy, Generalized diagnostic imaging, Epilepsy, Generalized metabolism, Fentanyl analogs & derivatives, Flumazenil, Fluorine Radioisotopes, Fluorodeoxyglucose F18 pharmacokinetics, Humans, Magnetic Resonance Imaging, Receptors, GABA-A analysis, Receptors, GABA-A drug effects, Tomography, Emission-Computed, Single-Photon, Epilepsy diagnostic imaging, Tomography, Emission-Computed
Abstract

Positron emission tomography (PET) plays a major role in the pre-surgical evaluation of patients with refractory partial epilepsy. In this review we discuss the limitations of PET data, the possibilities of fluorodeoxyglucose PET studies, neuroreceptor PET studies and alternatives, such as SPECT and MRI.

Published
1997

45. Co-registration of PET and MRI in different courses of MS using Cobalt-55 as a Calcium-tracer.

Author

Jansen HM, Decoo D, and Minderhoud JM

Subjects
Brain diagnostic imaging, Humans, Inflammation, Multiple Sclerosis pathology, T-Lymphocytes pathology, Tissue Distribution, Treatment Outcome, Calcium metabolism, Cobalt Radioisotopes pharmacokinetics, Magnetic Resonance Imaging, Multiple Sclerosis diagnostic imaging, Tomography, Emission-Computed
Abstract

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (SPM-96)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and eight healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS.

Published
1997

46. Crossed cerebellar diaschisis after middle cerebral artery infarction.

Author

De Reuck J, Decoo D, Lemahieu I, Strijckmans K, Goethals P, and Van Maele G

Subjects
Adult, Aged, Brain Mapping, Cerebellar Diseases physiopathology, Cerebellum diagnostic imaging, Cerebellum physiopathology, Cerebral Cortex blood supply, Cerebral Cortex diagnostic imaging, Cerebral Cortex physiopathology, Cerebral Infarction physiopathology, Energy Metabolism physiology, Female, Humans, Male, Middle Aged, Neural Pathways blood supply, Neural Pathways diagnostic imaging, Neural Pathways physiopathology, Neurologic Examination, Oxygen Consumption physiology, Pons blood supply, Pons diagnostic imaging, Pons physiopathology, Regional Blood Flow physiology, Cerebellar Diseases diagnostic imaging, Cerebellum blood supply, Cerebral Infarction diagnostic imaging, Dominance, Cerebral physiology, Tomography, Emission-Computed
Abstract

It is unclear whether crossed cerebellar diaschisis (CCD) is merely an epiphenomenon, as its clinical significance remains uncertain. We retrospectively analysed the positron emission tomographic (PET) findings in 28 patients with a chronic, stable middle cerebral artery (MCA) infarct and in 22 controls, using the steady state technique and 15O. Also, the Orgogozo scores on admission and at the time of the PET examination were compared in the patients with MCA infarction. Based on the asymmetry index and the 95% confidence limits for regional cerebellar blood flow (rCBF) and oxygen consumption (rCMRO2) in the control group, the stroke patients were subdivided in a group with (n = 8) and a group without (n = 20) CCD. The CCD group had lower values of rCMRO2 in the infarct and border areas compared to those of the non-CCD patients. The infarct location within the MCA territory was similar but the size was somewhat larger in the CCC group. The degree of neurological improvement was better in the non-CCD group. Although persistence of CCD has no real clinical significance it appears to be correlated to more severe and widespread ischaemia in the affected MCA territory and to the lack of significant clinical improvement.

Published
1997
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47. Cerebral oxygen metabolism in patients with progressive supranuclear palsy: a positron emission tomography study.

Author

Santens P, De Reuck J, Crevits L, Decoo D, Lemahieu I, Strijckmans K, and Goethals P

Subjects
Aged, Brain diagnostic imaging, Cerebral Cortex blood supply, Cerebral Cortex diagnostic imaging, Diagnosis, Differential, Female, Frontal Lobe blood supply, Frontal Lobe diagnostic imaging, Humans, Male, Middle Aged, Neurologic Examination, Regional Blood Flow physiology, Brain blood supply, Oxygen Consumption physiology, Supranuclear Palsy, Progressive diagnostic imaging, Tomography, Emission-Computed
Abstract

To investigate cerebral oxygen metabolism in progressive supranuclear palsy (PSP), 5 patients with a clinical diagnosis of PSP and a variable degree of cognitive deficit were selected for positron emission tomography (PET) of the brain. In 4 of them, a significant decrease in oxygen metabolism was found in all cortical regions, without frontal accentuation. In the group as a whole, this decrease was even slightly more marked in parietal and temporal regions. These findings are not consistent with earlier PET studies that demonstrated frontal targeting of hypometabolism in PSP patients. Part of this discrepancy can be explained by differences in methodology, although the use of different clinical criteria and overlap of PSP with other neurodegenerative diseases must be taken into account. It is concluded that the absence of frontal hypometabolism on PET examination does not exclude the diagnosis of PSP.

Published
1997
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48. Late-onset epileptic seizures in patients with leukoaraiosis: a positron emission tomographic study.

Author

De Reuck J, Decoo D, Boon P, Strijckmans K, Goethals P, and Lemahieu I

Subjects
Adult, Age of Onset, Aged, Brain Diseases diagnosis, Cognition Disorders diagnosis, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Tomography, X-Ray Computed, Brain Diseases complications, Cognition Disorders etiology, Epilepsy complications, Tomography, Emission-Computed
Abstract

Leukoaraiosis, found on computed tomographic scans of the brain, is suspected to be of ischemic origin and is frequently associated with progressive decline of cognitive functions in elderly persons. Some of them also develop late-onset epilepsy. The present positron emission tomographic study investigates if these seizures in mentally nonaffected patients with leukoaraiosis are related to an underlying ischemic process. Patients with leukoaraiosis and late-onset seizures have a more important decline of regional blood flow and oxygen consumption in the cortical areas, compared to normal age-matched controls, to patients with cryptogenic symptomatic late-onset epilepsy and to patients with a similar degree of leukoaraiosis but without epilepsy. The present study suggests that both the late-onset seizures and the leukoaraiosis in patients with, at that time, no obvious mental deterioration are premonitory signs of an encephalopathy of unknown origin, possibly leading to cognitive decline.

Published
1996
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49. Ipsilateral thalamic diaschisis after middle cerebral artery infarction.

Author

De Reuck J, Decoo D, Lemahieu I, Strijckmans K, Goethals P, and Van Maele G

Subjects
Adult, Aged, Cerebellum blood supply, Cerebrovascular Circulation physiology, Female, Functional Laterality physiology, Humans, Male, Middle Aged, Oxygen blood, Tomography, Emission-Computed, Tomography, X-Ray Computed, Cerebral Infarction complications, Thalamic Diseases etiology
Abstract

The significance of ipsilateral thalamic diaschisis (ITD) among patients with chronic, stable middle cerebral artery (MCA) infarcts was investigated. Twenty eight subjects with chronic MCA infarction and twenty two normal controls were studied with positron emission tomography (PET), using the steady state technique with 15O. Stroke patients were subdivided into a group with ITD (n = 12) and a group without ITD (n = 16). Patients with ITD had greater decreases of regional blood flow (rCBF) and oxygen consumption (rCMRO2) in the infarcted MCA territory, compared to MCA infarction without ITD. The neurological deficits at the time of PET scanning were similar between both groups. Extent of infarction by CT brain scan appeared more predominant in peri-insular regions of patients with ITD, while in non diaschisis patients infarcts were more widely distributed throughout the MCA territories. Occurrence of ITD and of crossed cerebellar diaschisis (CCD) did not correlate. Occurrence of ITD seems to be linked to diffuse reductions of blood flow and oxygen metabolism in cortical territories of the MCA. Mechanisms of ITD were different from those of CCD.

Published
1995
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50. Positron emission tomographic study of late-onset cryptogenic symptomatic seizures.

Author

De Reuck J, Santens P, Decoo D, Crevits L, Van Maele G, Lemahieu I, Strijckmans K, and Goethals P

Subjects
Aged, Aged, 80 and over, Blood Flow Velocity physiology, Brain Damage, Chronic diagnostic imaging, Diagnosis, Differential, Humans, Middle Aged, Oxygen Consumption physiology, Phenytoin therapeutic use, Regional Blood Flow physiology, Risk Factors, Cerebral Cortex blood supply, Energy Metabolism physiology, Epilepsy diagnostic imaging, Tomography, Emission-Computed
Abstract

Ten patients with epilepsy of unknown origin, starting after the age of 50 years, and without clear evidence of cognitive decline were studied with positron emission tomography, using the steady state technique with 15O. Cerebral blood flow and oxygen metabolism were significantly decreased in all cortical areas. No focal areas of hypometabolism were detected. Treatment with phenytoin did not influence the results. It is suggested that late-onset seizures could be the premonitory signs of a progressive encephalopathy of unknown origin.

Published
1995
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