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1. CHANNELOPATHIES AND RELATED DISORDERS

Author: S. Vicart, J. Franques, F. Bouhour, A. Magot, Y. Péréon, S. Sacconi, A. Nadaj-Pakleza, A. Behin, N. Zahr, M. Hezode, E. Fournier, C. Payan, L. Lacomblez, and B. Fontaine
Subjects: Neurology, Pediatrics, Perinatology and Child Health, Neurology (clinical), Genetics (clinical)
Published: 2021
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2. Instruments de mesure et échelles d’évaluation utilisés dans la démence fronto-temporale

Author: L. Lacomblez, P. Renou, and Martine Vercelletto
Subjects: Neurology, Behavioral assessment, Neurology (clinical), Psychology, Humanities
Abstract: Resume Les instruments de mesure et les echelles d’evaluation de la demence fronto-temporale (DFT) sont moins bien codifies que ceux de la maladie d’Alzheimer. Differentes echelles sont disponibles, mais peu sont specifiques de la DFT. Deux echelles validees sont tres utiles au diagnostic dans les formes debutantes : l’echelle de dysfonctionnement frontal (EDF) de Lebert et Pasquier, indispensable pour evaluer les troubles du comportement qui sont toujours au premier plan, et la batterie rapide d’efficience frontale (BREF) de Dubois pour les troubles cognitifs. Cependant, ces echelles ne comportent pas assez d’items pour le suivi de la maladie. La seule echelle utilisable pour le suivi comportemental est l’inventaire neuropsychiatrique ou neuropsychiatric inventory (NPI). D’autres inventaires sont proposes tels que l’inventaire comportemental frontal (Frontal Behavioral Inventory) de Kertesz, non valide en France. L’echelle de demence de Mattis, non specifique, permet de mesurer le declin cognitif. Le retentissement des activites de la vie quotidienne dans la DFT est mal connu de meme que la charge de l’aidant.
Published: 2006
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3. Pentoxifylline in ALS: A double-blind, randomized, multicenter, placebo-controlled trial

Author: V, Meininger, B, Asselain, P, Guillet, P N, Leigh, A, Ludolph, L, Lacomblez, and W, Robberecht
Subjects: Adult, Male, Adolescent, Phosphodiesterase Inhibitors, Nausea, Placebo-controlled study, Placebo, law.invention, Pentoxifylline, Placebos, Double-Blind Method, Randomized controlled trial, law, Multicenter trial, medicine, Humans, Drug Interactions, Treatment Failure, Aged, Aged, 80 and over, Muscle Weakness, Riluzole, Proportional hazards model, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, Neuroprotective Agents, Anesthesia, Drug Therapy, Combination, Female, Neurology (clinical), medicine.symptom, business, medicine.drug
Abstract: Objective: To assess the efficacy and safety of pentoxifylline, a US Food and Drug Administration–approved drug, in patients with ALS treated with riluzole. Methods: The authors conducted a double-blind, randomized, placebo-controlled, multicenter trial. Four hundred patients with probable or definite ALS and vital capacity less than 100% were randomly assigned to treatment with placebo or 1.2 g pentoxifylline daily. The primary outcome was death. Secondary outcomes were rates of deterioration of ALS Functional Rating Scale–Respiratory and muscle strength. The primary intention-to-treat analysis was the survival comparison of drug vs placebo, assessed before (log-rank test) and after adjustment (Cox model) for predefined prognostic factors. Results: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In contrast, analysis of secondary outcome functional variables did not show the same negative effect of the drug. The most common adverse reactions were nausea, dysphagia, and flushing, all reversible after stopping the drug. Conclusions: Pentoxifylline is not beneficial in ALS and should be avoided in patients treated with riluzole. The discrepancy between survival and measures of functional changes urges caution in equating these end points in phase III trials, and suggests that both survival and function should be used in phase III trials.
Published: 2006
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4. Emotional Regulation in Amyotrophic Lateral Sclerosis

Author: L, Lacomblez, primary, Bungener, Catherine, additional, and J, Unglik, additional
Published: 2017
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5. A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis

Author: T, Lenglet, L, Lacomblez, J L, Abitbol, A, Ludolph, J S, Mora, W, Robberecht, P J, Shaw, R M, Pruss, V, Cuvier, V, Meininger, and Frank, Hanisch
Subjects: PHASE II/III TRIAL, Adult, Male, medicine.medical_specialty, International Cooperation, Kaplan-Meier Estimate, Placebo, Placebo group, chemistry.chemical_compound, Double-Blind Method, Internal medicine, Multicenter trial, Medicine, Humans, Amyotrophic lateral sclerosis, Cholestenones, Aged, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Surgery, Riluzole, Europe, Neuroprotective Agents, Treatment Outcome, Neurology, Tolerability, chemistry, Case-Control Studies, Olesoxime, Female, Neurology (clinical), business, medicine.drug
Abstract: Background and purpose To assess the efficacy and safety of olesoxime, a molecule with neuroprotective properties, in patients with amyotrophic lateral sclerosis (ALS) treated with riluzole. Methods A double-blind, randomized, placebo-controlled, multicenter trial of 18 months’ duration was conducted in 512 subjects, with probable or definite ALS and a slow vital capacity (SVC) ≥70%, receiving 330 mg olesoxime daily or matching placebo and 50 mg riluzole twice a day in all. The primary intention-to-treat (ITT) outcome analysis was 18 months’ survival. Secondary outcomes were rates of deterioration of the revised ALS functional rating scale (ALSFRS-R), focusing on the 9-month assessment, SVC and manual muscle testing. Blood levels, safety and tolerability of olesoxime were also assessed. Results At 18 months, 154 of the 512 ITT patients had died (79 of 253 placebo, 75 of 259 olesoxime). Estimated overall survival according to Kaplan–Meier analysis was 67.5% (95% CI 61.0%–73.1%) in the placebo group and 69.4% (95% CI 63.0%–74.9%) in the olesoxime group; hence survival was not significantly different between treatment arms (P = 0.71, stratified bulbar/spinal log-rank). The other efficacy end-points evaluated were also negative, with the exception of a small difference in ALSFRS-R global score at 9 months in favor of olesoxime but not sustained after 18 months’ treatment nor evident in either the stratified bulbar or spinal subpopulations. Treatment did not raise any safety concerns. Conclusions Olesoxime, although well tolerated, did not show a significant beneficial effect in ALS patients treated with riluzole.
Published: 2013

6. 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. 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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. 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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. 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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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7. A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis

Author: Vincent Meininger, L Lacomblez, and G Bensimon
Subjects: Randomization, business.industry, General Medicine, medicine.disease, Riluzole, law.invention, Central nervous system disease, Clinical trial, Degenerative disease, Randomized controlled trial, law, Anesthesia, medicine, Amyotrophic lateral sclerosis, business, Prospective cohort study, medicine.drug
Abstract: Background Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis. Methods To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days). Results After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group...
Published: 1994
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8. Methodological aspects of clinical trials in diseases of the nervous system: conventional drug treatment versus gene therapy

Author: V. Meininger, D. Klatzman, G. Bensimon, L Lacomblez, and C. A. Valery
Subjects: Nervous system, Chemotherapy, medicine.medical_specialty, Versus gene, business.industry, medicine.medical_treatment, Genetic enhancement, Genetic transfer, Bioinformatics, Surgery, Clinical trial, Drug treatment, Text mining, medicine.anatomical_structure, Developmental Neuroscience, Neurology, Medicine, Neurology (clinical), business
Published: 2011

9. Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses

Author: D. Warot, P Bouhours, T. Hergueta, Ph. Danjou, Alain J. Puech, and L. Lacomblez
Subjects: medicine.drug_class, business.industry, Ritanserin, Flicker fusion threshold, Anxiolytic, Arousal, Psychiatry and Mental health, Alprazolam, Anesthesia, medicine, Anxiety, Pharmacology (medical), medicine.symptom, Psychomotor disorder, business, Diazepam, medicine.drug
Abstract: The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.
Published: 1992
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10. Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease

Author: I, Le Ber, A, Camuzat, E, Berger, D, Hannequin, A, Laquerrière, V, Golfier, D, Seilhean, G, Viennet, P, Couratier, P, Verpillat, S, Heath, W, Camu, O, Martinaud, L, Lacomblez, M, Vercelletto, F, Salachas, F, Sellal, M, Didic, C, Thomas-Anterion, M, Puel, B-F, Michel, C, Besse, C, Duyckaerts, V, Meininger, D, Campion, B, Dubois, A, Brice, Patrice, Verpillat, Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Service de Neurologie [CHU Limoges], and CHU Limoges
Subjects: Male, Candidate gene, Pathology, Genetic Linkage, DNA Mutational Analysis, Penetrance, MESH: Genetic Markers, MESH: Genotype, 0302 clinical medicine, MESH: Genetic Screening, MESH: Aged, 80 and over, MESH: Penetrance, MESH: Motor Neuron Disease, Copy-number variation, MESH: DNA Mutational Analysis, Age of Onset, Genetics, MESH: Aged, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, Autosomal dominant trait, Chromosome Mapping, Middle Aged, MESH: Dementia, Pedigree, MESH: Young Adult, Female, Psychology, Chromosomes, Human, Pair 9, Frontotemporal dementia, Adult, Genetic Markers, medicine.medical_specialty, MESH: Mutation, Genotype, MESH: Pedigree, MESH: Age of Onset, Locus (genetics), 03 medical and health sciences, Young Adult, medicine, Dementia, Humans, Genetic Predisposition to Disease, Genetic Testing, Motor Neuron Disease, 030304 developmental biology, Aged, MESH: Humans, MESH: Adult, medicine.disease, MESH: Male, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Age of onset, MESH: Chromosome Mapping, MESH: Chromosomes, Human, Pair 9, MESH: Linkage (Genetics), MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). METHODS: Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. RESULTS: We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. CONCLUSIONS: This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.
Published: 2009
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11. Antagonism by modafinil of the psychomotor and cognitive impairment induced by sleep-deprivation in 12 healthy volunteers

Author: D. Warot, JS Weil, E Weiller, L Lacomblez, Alain J. Puech, D Benoit, and G. Bensimon
Subjects: Psychomotor learning, medicine.medical_specialty, business.industry, Modafinil, Flicker fusion threshold, Audiology, Frequency determination, 030226 pharmacology & pharmacy, 03 medical and health sciences, Psychiatry and Mental health, Sleep deprivation, 0302 clinical medicine, 030220 oncology & carcinogenesis, Healthy volunteers, medicine, medicine.symptom, business, Cognitive impairment, Antagonism, medicine.drug
Abstract: SummaryModafinil is a new psychotropic compound with central α1, adrenergic-stimulant activity in animals. In the present study, its pharmacological activity in man was evaluated in the sleep-deprivation induced psychomotor and cognitive impairment paradigm. This was a double-blind placebo-controlled study involving 12 healthy volunteers. Standard psychomotor and memory tasks were used, including critical flicker fusion frequency determination (CFF), choice reaction time and short- and long-term memory evaluation. Results revealed a clear antagonism by modafinil of the psychomotor and cognitive impairment induced by sleep-deprivation in most tasks 6 h after drug administration, and marginal effects 18 h after. These results therefore support a psychostimulant activity of modafinil in man.
Published: 1991
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12. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis

Author: L. Dupuis, P. Corcia, A. Fergani, J. -L. Gonzalez De Aguilar, D. Bonnefont-Rousselot, R. Bittar, D. Seilhean, J. -J. Hauw, L. Lacomblez, J. -P. Loeffler, and V. Meininger
Subjects: Adult, Male, medicine.medical_specialty, Statin, Endosome, medicine.drug_class, Comorbidity, Central nervous system disease, chemistry.chemical_compound, Degenerative disease, Internal medicine, medicine, Prevalence, Humans, Amyotrophic lateral sclerosis, Muscle, Skeletal, Aged, Dyslipidemias, Cholesterol, business.industry, Nutritional Support, Amyotrophic Lateral Sclerosis, Lipid metabolism, Middle Aged, medicine.disease, Lipid Metabolism, Surgery, Up-Regulation, Fatty Liver, Lipoproteins, LDL, Survival Rate, Endocrinology, chemistry, Cytoprotection, Female, Neurology (clinical), business, Dyslipidemia
Abstract: Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. High prevalence of malnutrition and weight loss adversely affect quality of life. Moreover, two thirds of patients develop a hypermetabolism of unknown cause, leading to increased resting energy expenditure. Inasmuch as lipids are the major source of energy for muscles, we determined the status of lipids in a population of patients with ALS and investigated whether lipid contents may have an impact on disease progression and survival.Blood concentrations of triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured in a cohort of 369 patients with ALS and compared to a control group of 286 healthy subjects. Postmortem histologic examination was performed on liver specimens from 59 other patients with ALS and 16 patients with Parkinson disease (PD).The frequency of hyperlipidemia, as revealed by increased plasma levels of total cholesterol or LDL, was twofold higher in patients with ALS than in control subjects. As a result, steatosis of the liver was more pronounced in patients with ALS than in patients with PD. Correlation studies demonstrated that bearing an abnormally elevated LDL/HDL ratio significantly increased survival by more than 12 months.Hyperlipidemia is a significant prognostic factor for survival of patients with amyotrophic lateral sclerosis. This finding highlights the importance of nutritional intervention strategies on disease progression and claims our attention when treating these patients with lipid-lowering drugs.
Published: 2008

13. Antidepressant Profile of Bupropion and three Metabolites in Mice

Author: Jacques Massol, Alain J. Puech, L Lacomblez, Patrick Martin, and J N Colin
Subjects: Male, medicine.medical_specialty, Reserpine, Apomorphine, medicine.medical_treatment, Motor Activity, Pharmacology, Body Temperature, Mice, Pimozide, health services administration, Internal medicine, mental disorders, medicine, Prazosin, Animals, Pharmacology (medical), Bupropion, chemistry.chemical_classification, Propiophenones, Depression, Yohimbine, Hydroxybupropion, General Medicine, Drug interaction, Propranolol, Antidepressive Agents, Stimulant, Psychiatry and Mental health, Endocrinology, chemistry, behavior and behavior mechanisms, Antidepressant, Psychology, psychological phenomena and processes, medicine.drug, Tricyclic
Abstract: Bupropion is a novel antidepressant, distinct from tricyclic antidepressants both neurochemically and behaviorally. Bupropion forms several metabolites in both rodents and humans. Three chemically different molecules - BW 306, BW 494, and BW 287 - were selected. Comparative assessment of antidepressant activity of bupropion and its metabolites in mice, and pharmacological analysis of possible mechanisms of action of the parent drug and its metabolites (using interaction studies with pimozide, D,L-propranolol, and prazosin) were carried out. The results obtained show that: bupropion has a pharmacological spectrum in various animal models which predicts both antidepressant and stimulatory activity in man. BW 306 is the most active of the metabolites studied and, compared to bupropion, seems more "antidepressant" and less stimulant. BW 494, compared to bupropion or BW 306, has a lower degree of activity in various tests used to evaluate antidepressants. BW 287 has no effect in any of the tests used in this study. The interaction studies with pimozide, D,L-propranolol, and prazosin in the various tests have shown that: the stimulatory effect of bupropion, BW 306, and BW 494 is antagonized by both pimozide and prazosin. in the behavioral despair test, the reduction in the duration of immobility by bupropion and BW 494 is antagonized by pimozide, but not by prazosin or D,L-propranolol. the antagonism of reserpine-induced hypothermia by bupropion and BW 306 is significantly decreased by prazosin and D,L-propranolol, but not by pimozide. These data suggest that the clinical antidepressant profile (without a major stimulatory effect) observed in man after administration of bupropion is related to metabolite BW 306 and possibly to BW 494, rather than to bupropion itself.
Published: 1990
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14. Psychomotor, subjective and neuroendocrine effects of acute tryptophan depletion in the healthy volunteer

Author: A.J. Puech, P. Danjou, S Kecskemeti, L. Lacomblez, D. Warot, and M Hamon
Subjects: Psychomotor learning, medicine.medical_specialty, Tryptophan, Plasma levels, Prolactin, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Endocrinology, Oral administration, Internal medicine, Healthy volunteers, medicine, 030212 general & internal medicine, Serotonin, Psychology, After treatment
Abstract: SummaryThe effects of acute tryptophan depletion were investigated in 20 healthy volunteers. Ten of them received a balanced amino acid solution and 10 a tryptophan-free solution. The fall in tryptophan levels induced by the oral administration of a mixture tryptophan-free of L-amino acids was - 77% for free tryptophan and - 81% for total tryptophan. Before treatment, there were intergroup differences affecting alertness parameters (critical flicker threshold, recognition reaction time), plasma levels of prolactin and baseline performance in the proofreading correction test. In the tryptophan-depleted group, the number of errors reported during the unpleasant sound signal was increased (+ 48%) after treatment, whereas the number of errors fell (— 15%) in the group receiving the tryptophan supplement. Conversely the levels of prolactin were correlated with those of serum tryptophan. Few subjective effects were reported.
Published: 1990
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15. [Parkinson disease and amyotrophic lateral sclerosis. Tauopathies, TDP-43 and SOD mutations]

Author: N, Le Forestier, L, Lacomblez, and V, Meininger
Subjects: DNA-Binding Proteins, Basal Ganglia Diseases, Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Mutation, Animals, Humans, Parkinson Disease, tau Proteins
Abstract: In addition to a large number of clinical descriptions of atypical cases, recent pathological, biochemical and genetic studies challenge the view that amyotrophic lateral sclerosis (ALS) is a disorder restricted to the pyramidal motor system. Relations between ALS, Parkinson disease, fronto-temporal dementia, progressive supranuclear paralysis, and cortico-basal degeneration have now been identified. We propose a review of the topic and discuss the contribution of various clinical and pathological features leading to consider motoneuron diseases as neurodegenerative processes included in a broad spectrum of tauopathies.
Published: 2007

16. [Amyotrophic lateral sclerosis: cognitive and behavioral evaluation]

Author: L, Lacomblez, A, Piquard, and M, Vercelletto
Subjects: Behavior, Cognition, Amyotrophic Lateral Sclerosis, Humans
Abstract: Cognitive impairment in nondemented ALS patients has been demonstrated, although its incidence remains to be determined. FTD is the most frequently form of dementia in ALS. The clinical profile of patients with dementia or mild cognitive deficit evokes neuropsychological deficits and behavioural changes resulting from executive dysfunction. The psychometric evaluation, centred on executive disturbances, goes with behavioural scales in order to accurately appreciate the repercussion of cognitive and behavioural changes on daily life.
Published: 2006

17. [Measurement instruments and assessment scales for frontotemporal dementia]

Author: M, Vercelletto, L, Lacomblez, and P, Renou
Subjects: Diagnosis, Differential, Behavior, Psychological Tests, Cognition, Alzheimer Disease, Humans, Dementia, Temporal Lobe, Frontal Lobe
Abstract: In frontotemporal dementia (FTD), evaluation scales and measurement instruments are less codified than in Alzheimer's disease. Some nonspecific scales are available, two of which are very useful for early diagnose of the disease: Lebert and Pasquier's Frontotemporal Behavioral Scale (FBS) to assess behavioral disturbances and Dubois's Frontal Assessment Battery (FAB) to assess executive ability. However, these scales do not contain enough items to follow up FTD. The main scale used to follow up the disease is the Neuropsychiatric Inventory (NPI). The Frontal Behavioural Inventory (Kertesz) seems to be interesting, but has not yet been validated in France. The Mattis Dementia Rating Scale, not specific for FTD, is used to assess the cognitive rate. The activities of daily living scales and caregiver burden are not well known in FTD.
Published: 2006

18. [Tolerance of riluzole in a phase IIIb clinical trial]

Author: L, Lacomblez, M, Dib, V, Doppler, A, Faudet, V, Robin, F, Salachas, G, Bensimon, and V, Meininger
Subjects: Male, Neuroprotective Agents, Riluzole, Amyotrophic Lateral Sclerosis, Product Surveillance, Postmarketing, Humans, Female, France, Middle Aged, Aged
Abstract: Within the framework of an early drug access programme launched in 1995, a multicentre open study was initiated in France in order to assess, inter alia, the safety of riluzole (50 mg twice a day) in a total of 2069 patients from 28 centres. This programme, a phase IIIb study with direct individual benefit, had two main objectives: to enable patients to receive riluzole therapy pending regulatory approval and commercial availability and to provide further data on the safety of riluzole in a broader ALS population. The most frequent adverse events related to riluzole treatment were: asthenia, nausea and elevation of serum transaminase levels. These observations, similar to data derived from previous pivotal clinical trials, confirm that riluzole has a satisfactory tolerability profile.
Published: 2002

19. [Nocturnal oxymetry in patients with amyotrophic lateral sclerosis: role in predicting survival]

Author: R, Velasco, F, Salachas, E, Munerati, N, Le Forestier, P F, Pradat, L, Lacomblez, E, Orvoen Frija, and V, Meininger
Subjects: Male, Risk, Vital Capacity, Middle Aged, Prognosis, Survival Analysis, Oxygen, Death, Sudden, Predictive Value of Tests, Humans, Female, Life Tables, Oximetry, Prospective Studies, Motor Neuron Disease, Hypoxia, Respiratory Insufficiency, Sleep, Aged, Monitoring, Physiologic, Proportional Hazards Models
Abstract: Death is the most important end point along the course of amyotrophic lateral sclerosis (ALS). It is commonly attributed to a respiratory failure in relation with a restrictive respiratory disorder. However, in clinical practice, it is frequent to observe that death has not direct relation with the values of the respiratory function, at least measured with vital capacity. It is also frequent that relatives report sudden death during nocturnal sleep. All these features raised the question of the possible relation between death and nocturnal oxymetry in ALS patients. In a prospective study, we studied 69 ALS patients. We recorded demographic data, clinical parameters as manual muscle testing and functional scales, various parameters of oxymetry measured by pulse oxymetry recorded during night, slow vital capacity and survival time. There is a strong correlation between survival time measured by Kaplan Meier curves and log rank and the mean nocturnal saturation. We determined 93 mmHg as a threshold value. Below this threshold, mean survival time was 7.5+/-1.6 months and above it was equal to 18.5+/-1.5; relative risk was 3.31. These data confirm the importance of nocturnal oxymetry on survival in ALS patients both in clinical practice and in view of therapeutic trials.
Published: 2002

20. Blood Markers of Oxidative Stress in Patients with Amyotrophic Lateral Sclerosis

Author: L. Lacomblez, C. Bizard, G. Bensimon, F. Salachas, J. Delattre, V. Doppler, V. Meininger, B. Bourely, D. Bonnefont-Rousselot, and M C Jaudon
Subjects: Pathology, medicine.medical_specialty, business.industry, medicine, In patient, Blood markers, Amyotrophic lateral sclerosis, medicine.disease_cause, business, medicine.disease, Oxidative stress
Published: 2002
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21. Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS)

Author: P, Lechat, H, Lardoux, A, Mallet, P, Sanchez, G, Derumeaux, T, Lecompte, L, Maillard, J L, Mas, F, Mentre, F, Pousset, L, Lacomblez, G, Pisica, S, Solbes-Latourette, P, Raynaud, and P, Chaumet-Riffaud
Subjects: Male, Aspirin, Dose-Response Relationship, Drug, Administration, Oral, Anticoagulants, Hemorrhage, Phenindione, Drug Combinations, Treatment Outcome, Double-Blind Method, Risk Factors, Thromboembolism, Atrial Fibrillation, Humans, Female, Vascular Diseases, Aged
Abstract: A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation.Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin (100 mg) in patients with high-risk atrial fibrillation.A multicenter, placebo-controlled, double-blind, randomized trial was conducted at 49 investigating centers in France. Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension, a recent episode of heart failure or decreased left ventricular function were included in the study. Patients were treated with fluindione plus placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination therapy), with an international normalized ratio target of between 2 and 2.6. The combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. The secondary endpoint was the incidence of hemorrhagic complications.The 157 participants (average age 74 years; 52% women; 42% with paroxysmal atrial fibrillation) were followed for an average of 0.84 years. Three nonfatal thromboembolic events were observed (1 in the anticoagulation group, 2 in the combination group) and 6 patients died (3 in the anticoagulation group, 3 in the combination group), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2 in the combination group). Nonfatal hemorrhagic complications occurred more often in the combination group (n = 10, 13.1%) compared to the anticoagulation group (n = 1, 1.2%) (p = 0.003).The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients. The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events.
Published: 2001

22. [Noncognitive symptoms in Alzheimer's disease. A study of 150 community-dwelling patients using a questionnaire completed by the caregiver]

Author: C, Derouesné, A, Piquard, S, Thibault, V, Baudouin-Madec, and L, Lacomblez
Subjects: Male, Psychiatric Status Rating Scales, Paris, Time Factors, Affect, Cognition, Caregivers, Alzheimer Disease, Surveys and Questionnaires, Humans, Female, Age of Onset, Aged, Follow-Up Studies
Abstract: We studied the noncognitive symptoms in 150 community-dwelling Alzheimer's patients using a questionnaire completed by the caregiver, the Echelle Psychopathologique de la Démence de Type Alzheimer, EPDTA (Psychopathologic Scale of Dementia of Alzheimer Type). EPDTA is a 44-item questionnaire derived from the BEHAVE-AD and the Depressive Mood Scale, covering many aspects of the behavior, affective and psychiatric disturbances. Each item is rated from 0 (never observed) to 6 (most of the time). Frequency (percentage of symptom present) and severity (mean score when the symptom was present) were assessed for each item. The cognitive status and severity of the disease were assessed by the MMSE and two scales completed by the caregiver assessing the Activities of Daily Living scale (ADL) and the Cognitive Difficulties Scale (CDS). Noncognitive symptoms were present in all patients but remained moderate in severity. A principal component analysis of the 33 items exploring the affective disturbances showed seven clinically relevant factors: apathy, anxiety, anosognosia-irritability, euphoria, dysphoria, emotional incontinence and agitation. The most frequent noncognitive symptoms were the affective disturbances, especially apathy, and the sexual behavioural disturbances. No correlation were found between the overall severity of behavioural disturbances and cognitive status, duration of the disease nor demographic variables. However, a slight negative correlation was found between scores on apathy and on the MMSE. A second evaluation was performed in 59 patients after a mean follow-up of 18,2 months. The patients showed a progression of the disease evidenced by the scores on the MMSE, ADL and CDS scales. However, the frequency and severity of the noncognitive symptoms remained identical except for eating disorders, psychotic symptoms and agitation which were more frequent at the second examination and negatively correlated with the MMSE score. Most patients showed affective disturbances and scored high for apathy and anxiety-emotional incontinence dimensions. Like in a previous study, we found a double dissociation between these two dimensions in some patients, suggesting that they depend from different mechanisms. Agressivity, mostly verbal, was found in three quarters of the patients and was correlated to apathy, anosognosia and psychotic symptoms.The relationship between noncognitive manifestations and cognitive deficits in AD is not clear, suggesting that they depend from different biological and psychological mechanisms. Various dimensions may be described in the behavioural disturbances but their relationship with hypothetical biological mechanisms remains difficult. Our study stresses the importance of apathy, which was corelated with various noncognitive psychobehavioral manifestations in AD patients.
Published: 2001

23. [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]

Author: P, Lechat, H, Lardoux, A, Mallet, P, Sanchez, G, Derumeaux, T, Lecompte, L, Maillard, J L, Mas, F, Mentré, F, Pousset, L, Lacomblez, G, Pisica, S, Solbes-Latourette, P, Raynaud, and P, Chaumet-Riffaud
Subjects: Male, Aspirin, Patient Selection, Anticoagulants, Phenindione, Double-Blind Method, Recurrence, Risk Factors, Thromboembolism, Atrial Fibrillation, Humans, Drug Therapy, Combination, Female, Aged, Follow-Up Studies
Abstract: A combination of low-dose aspirin (A) and anticoagulation (AC) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation (AF).We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin (A) (100 mg) or placebo (P) to anticoagulant treatment in patients with high-risk atrial fibrillation. A total of 157 patients were included, with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension, a recent episode of heart failure or a left ventricular dysfunction. All patients received fluindione (F) and P or F and A, with an INR target between 2 and 2.6. The primary endpoint was a combined endpoint of stroke (ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or vascular death.The study had to be stopped prematurely owing to a too low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications occurred more often in group A (n = 10, 13.1 pour cent) compared with group P (n = 1, 1.2 pour cent), p = 0.003.The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF. Such a combination increased the incidence rate of bleeding complications, which therefore greatly reduces its potential overall benefit.
Published: 2001

24. [Memory complaints: epidemiology and diagnostic approach]

Author: C, Derouesné and L, Lacomblez
Subjects: Adult, Aged, 80 and over, Aging, Memory Disorders, Motivation, Adolescent, Mental Disorders, Age Factors, Middle Aged, Diagnosis, Differential, Alzheimer Disease, Memory, Activities of Daily Living, Mental Recall, Humans, Cues, Aged
Abstract: IN THE ELDERLY: Complaints of poor memory for everyday activities are common in the young as well as in the elderly. However, in the elderly, memory complaints are especially of interest on account of their frequency and the fear of being related to early Alzheimer's disease. Two types of memory complaints should distinguished. ENCODING/STORAGE DEFECTS: Memory difficulties related to early Alzheimer's disease are mainly related to a deficit in encoding and/or storage. They are restricted to the recent past and rapidly associated with temporal disorientation, limitation in everyday activities and behavioral modifications alerting the family responsible for seeking medical advice in most cases. Short examination of memory performance shows a free recall deficit which is not improved by cued recall. BENIGN DIFFICULTIES: Memory difficulties of benign type are due to a pure recall deficit: they are experienced as well for ancient as for recent past and the difficulty in recall is transient. There are no behavioral modifications or limitation in everyday activities: the disorder is purely subjective. At examination, the deficit in free recall is corrected by cueing. Benign type of memory complaints is mostly related to psychoaffective disturbances and subjects experiencing this type of memory difficulties are not at high risk for developing dementia.
Published: 2000

25. Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations?

Author: J, Tassin, A, Dürr, A M, Bonnet, R, Gil, M, Vidailhet, C B, Lücking, J Y, Goas, F, Durif, M, Abada, B, Echenne, J, Motte, A, Lagueny, L, Lacomblez, P, Jedynak, B, Bartholomé, Y, Agid, and A, Brice
Subjects: Adult, Family Health, Male, Adolescent, Genotype, Reverse Transcriptase Polymerase Chain Reaction, RNA Splicing, Ubiquitin-Protein Ligases, DNA Mutational Analysis, Mutation, Missense, Proteins, Middle Aged, Pedigree, Antiparkinson Agents, Levodopa, Ligases, Dystonia, Phenotype, Humans, Female, Child, GTP Cyclohydrolase, Gene Deletion
Abstract: Autosomal dominant DOPA-responsive dystonia (DRD) is usually caused by mutation in the gene encoding guanosine triphosphate-cyclohydrolase I (GTPCH I). We studied 22 families with a phenotype of levodopa-responsive dystonia by sequencing the six coding exons, the 5'-untranslated region and the exon-intron boundaries of the GTPCH I gene. Eleven heterozygous mutations were identified, including five missense mutations, one splice site mutation, two small deletions and two nonsense mutations, in 12 families that included 27 patients and 13 asymptomatic carriers. Six mutations were new and five had already been reported. Four of the mutations caused truncation of the GTPCH I protein. One family carried a base-pair change in the 5'-untranslated region, not detected in controls, that could be responsible for the phenotype. Three of the remaining 10 families had deletions in the parkin gene on chromosome 6, underlining how difficult it is to distinguish, in some cases, between DRD and parkin mutations. No mutations were identified in seven families. The clinical spectrum extended from the classical DRD phenotype to parkinsonism with levodopa-induced dyskinesias, and included spastic paraplegia as well as the absence of dystonia.
Published: 2000

26. Diaphragmatic dysfunction and dyspnoea in amyotrophic lateral sclerosis

Author: G Bensimon, Valérie Attali, Vincent Meininger, Thomas Similowski, Isabelle Arnulf, Selma Mehiri, Jean-Philippe Derenne, M. Zelter, L Lacomblez, and François Salachas
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Diaphragm, Diaphragmatic breathing, Electromyography, Pulmonary function testing, Magnetics, Predictive Value of Tests, Internal medicine, Medicine, Humans, Respiratory system, Amyotrophic lateral sclerosis, Phrenic nerve, medicine.diagnostic_test, business.industry, Respiratory disease, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Surgery, Diaphragm (structural system), Phrenic Nerve, Dyspnea, Case-Control Studies, Multivariate Analysis, Cardiology, Female, business
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive disorder of unknown origin. Respiratory involvement is the principal cause of death, and dyspnoea is a major source of discomfort. In this study, diaphragm function is described and its relationship with dyspnoea examined in 48 ALS patients (32 male, age 26-80 yrs). The detailed neurological and respiratory evaluation (clinical examination, pulmonary function tests, static pressures, mouth twitch pressures (Pm,t), electromyographic responses to phrenic nerve stimulation and cortical magnetic stimulation were analysed after stratification according to dyspnoea. Dyspnoeic (group I) and nondyspnoeic (group II) patients were similar, bulbar signs being more frequent in group I. Vital capacity was lower in group I (mean+/-SD 67.9+/-22.7 versus 87.9+/-15.6% of the predicted value, p=0.0028), as were maximal static inspiratory pressure (41+/-24 versus 60+/-27% pred, p=0.0242) maximal static inspiratory pressure (18+/-11 versus 32+/-14% pred, p=0.0042), and Pm,t (3.71+/-2.5 versus 7.26+/-3.45 cmH2O, p=0.0011). Abdominal (Abd) paradox and respiratory pulse were frequent in group I (15 of 25 and 14 of 25) but absent or rare in group II (0 of 23 and four of 23) (p
Published: 2000

27. C19 Démences : perspectives thérapeutiques

Author: L. Lacomblez
Subjects: Neurology, Neurology (clinical)
Abstract: Pendant longtemps la maladie d’Alzheimer a ete consideree comme l’etiologie quasi exclusive des demences d’origine degenerative du sujet âge. Les recherches menees durant ces dernieres annees ont permis d’identifier et de caracteriser d’autres pathologies degeneratives responsables de demence dont la plus frequente est sans doute la demence avec corps de Lewy (DCL). Le trait commun a ces pathologies neurodegenerative par ailleurs fort differentes est la surproduction d’une proteine (s-amyloide, tau, synucleine, prion…….) et son agregation conduisant a une reaction tissulaire et a une neurotoxicite agressive ainsi que la mise en evidence dans bon nombre d’entre elles d’un lien avec une mutation genetique. D’autres facteurs interviennent en se surajoutant ou en precedant tels que les facteurs apoptotiques et d’inflammation, les reactions astrocytaires, microgliales, le stress oxydatif, l’intervention de facteurs trophiques, de neuromediateurs, de neurosteroides etc… La connaissance tant des causes que des mecanismes sous-jacents a cette agression neuronale pourrait conduire a la mise au point de veritables traitements etiopathogeniques des differentes affections considerees. Si l’application a la therapeutique de toutes ces donnees moleculaires et genetique semble imminente dans le cadre de la maladie d’Alzheimer (immunisation, inhibiteur de secretases…), cette procedure serait, en theorie, applicable a toutes les autres pathologies dans la mesure ou elles reposent sur un processus identique de formation et d’agregation d’une proteine particuliere. Mais d’autres facteurs en modulant tres possiblement leur seuil d’expression (facteurs vasculaires, reserve neuronale, phenomenes de reparation, facteurs environnementaux…) doivent egalement etre pris en compte. La comprehension des mecanismes moleculaires, biologiques, genetiques de la neurodegenerescence reste la cle majeure dans l’identification des voies de recherche therapeutique.
Published: 2009
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28. Plasma and cerebrospinal fluid human immunodeficiency virus type-1 (HIV-1) RNA levels in HIV-related cognitive impairment

Author: B, Stankoff, V, Calvez, S, Suarez, P, Bossi, O, Rosenblum, L, Conquy, E, Turell, T, Dubard, A, Coutellier, L, Baril, F, Bricaire, L, Lacomblez, and C, Lubetzki
Subjects: Adult, AIDS Dementia Complex, Reverse Transcriptase Polymerase Chain Reaction, HIV-1, Brain, Humans, RNA, Messenger, Middle Aged, Neuropsychological Tests, Viral Load, Cognition Disorders, CD4 Lymphocyte Count
Abstract: Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.
Published: 1999

29. Brain SPECT perfusion of frontotemporal dementia associated with motor neuron disease

Author: K. Abe, E . Guedj, I. L. Ber, L . Lacomblez, B . Dubois, P . Verpillat, M . Didic, F . Salachas, P . Vera, D . Hannequin, J .-A. Lotterie, M . Puel, M . Decousus, C . Thomas-Anterion, C . Magne, M . Vercelletto, A .-M. Bernard, V . Golfier, J . Pasquier, B .-F. Michel, I . Namer, F . Sellal, J . Bochet, M . Volteau, A . Brice, V . Meininger, and M .-O. Habert
Subjects: Neurology (clinical)
Published: 2008
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30. [Cognitive disorders in AIDS: clinical, virological and neuroradiological features]

Author: B, Stankoff, S, Suarez, O, Rosemblum, L, Conquy, E, Turell, F, Bricaire, A, Coutellier, V, Calvez, L, Lacomblez, A, Tourbah, and C, Lubetzki
Subjects: Acquired Immunodeficiency Syndrome, Retroviridae, DNA, Viral, Brain, Humans, Cognition Disorders, Magnetic Resonance Imaging, Cerebrospinal Fluid
Abstract: HIV-associated neurocognitive disorders are mainly reported during the late stages of the disease, in deeply immunosuppressed patients Clinically, they present as a subcortical cognitive impairment, dominated by reduced psychomotor speed and memory deficit. Encephalic magnetic resonance imaging shows in most cases a diffuse leucoencephalopathy, and there is often a poor correlation between clinical status and neuroradiological findings. The diagnostic and prognostic value of HIV load in blood and cerebrospinal fluid is currently under investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia remains uncertain.
Published: 1999

31. Mutations du gène de la progranuline dans les démences frontotemporales : fréquence, spectre mutationnel et phénotypes associés

Author: I. Le Ber, A. Camuzat, D. Hannequin, F. Pasquier, J. van der Zee, D. Campion, M. Puel, A. Laquerrière, F. Sellal, L. Lacomblez, M. Vercelletto, C. Thomas-Antérion, B.-F. Michel, V. Golfier, M. Didic, F. Salachas, Ch. Duyckaerts, M. Cruts, P. Verpillat, Ch. Van Broeckhoven, B. Dubois, and A. Brice
Subjects: Neurology, Neurology (clinical)
Published: 2007
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32. [Drug therapy strategies in Alzheimer's disease]

Author: L, Lacomblez
Subjects: Sleep Wake Disorders, Clinical Trials as Topic, Depression, Mental Disorders, Phenylcarbamates, Rivastigmine, Antidepressive Agents, Aggression, Neuroprotective Agents, Anti-Anxiety Agents, Piperidines, Alzheimer Disease, Indans, Tacrine, Humans, Donepezil, Carbamates, Cholinesterase Inhibitors, Cognition Disorders, Nootropic Agents, Antipsychotic Agents
Abstract: Treatments in Alzheimer's disease include treatment of cognitive impairment and behavioral manifestations (agitation, depression, anxiety, delusions). It should be noted that many non cognitive behaviors may have some relations to underlying cognitive impairment. In the not too distant future, physicians can expect to see a variety of medications and controversies over the benefits of slowing symptoms with cholinergic therapeutics approved for clinical use and (or) preventing progression of Alzheimer's disease assessed in clinical trials will emerge.
Published: 1998

33. [Clinical significance of treatment with riluzole]

Author: V, Meininger, L, Lacomblez, and G, Bensimon
Subjects: Riluzole, Amyotrophic Lateral Sclerosis, Humans, Excitatory Amino Acid Antagonists
Published: 1998

34. [Meeting of consultations of memory. 1 February 1997 Paris]

Author: F, Mahieux and L, Lacomblez
Subjects: Memory Disorders, Paris, Memory, Humans, Referral and Consultation
Published: 1998

35. Pentoxifylline in ALS: A double-blind, randomized, multicenter, placebo-controlled trial

Author: B. Levin, T. G, L. H. Mitsumoto, P. Kaufmann, V . Meininger, B . Asselain, P .N. Leigh, A . Ludolph, L . Lacomblez, and P . Guillet
Subjects: Amyotrophic Lateral Sclerosis, Placebo Effect, Prognosis, Risk Assessment, Survival Analysis, Placebos, Survival Rate, Neuroprotective Agents, Double-Blind Method, Risk Factors, Data Interpretation, Statistical, Outcome Assessment, Health Care, Humans, Multicenter Studies as Topic, Treatment Failure, Neurology (clinical), Pentoxifylline, Randomized Controlled Trials as Topic
Published: 2006
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36. A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II

Author: L, Lacomblez, G, Bensimon, P N, Leigh, P, Guillet, L, Powe, S, Durrleman, J C, Delumeau, and V, Meininger
Subjects: Male, Thiazoles, Riluzole, Dose-Response Relationship, Drug, Amyotrophic Lateral Sclerosis, Humans, Female, Middle Aged, Excitatory Amino Acid Antagonists, Survival Analysis
Abstract: ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.
Published: 1996

37. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II

Author: L, Lacomblez, G, Bensimon, P N, Leigh, P, Guillet, and V, Meininger
Subjects: Male, Riluzole, Time Factors, Dose-Response Relationship, Drug, Amyotrophic Lateral Sclerosis, Middle Aged, Prognosis, Survival Analysis, Thiazoles, Neuroprotective Agents, Tracheostomy, Treatment Outcome, Double-Blind Method, Humans, Female, Follow-Up Studies, Proportional Hazards Models
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive disease with no effective treatment. In an initial study, riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients. We have carried out a double-blind, placebo-controlled, multicentre study to confirm those findings and to assess drug efficacy at different doses.959 patients with clinically probable or definite ALS of less than 5 years' duration were randomly assigned treatment with placebo or 50 mg, 100 mg, or 200 mg riluzole daily; randomisation was stratified by centre and site of disease onset (bulbar or limb). The primary outcome was survival without a tracheostomy. Secondary outcomes were rates of change in functional measures (muscle strength, functional status, respiratory function, patient's assessments of fasciculation, cramps, stiffness, and tiredness). The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat. Drug-effect on survival was assessed before (log-rank test) and after adjustment for known prognostic factors (Cox's model).At the end of the study, after median follow-up of 18 months, 122 (50.4%) placebo-treated patients and 134 (56.8%) of those who received 100 mg/day riluzole were alive without tracheostomy (unadjusted risk 0.79, p = 0.076; adjusted risk 0.65, p = 0.002). In the groups receiving 50 mg and 200 mg riluzole daily, 131 (55.3%) and 141 (57.8%) patients were alive without tracheostomy (relative to placebo 50 mg adjusted risk 0.76, p = 0.04; 200 mg 0.61, p = 0.0004). There was a significant inverse dose response in risk of death. No functional scale discriminated between the treatment groups. The most common adverse reactions were asthenia, dizziness, gastrointestinal disorders, and rises in liver enzyme activities; they were commonest with the 200 mg dose.Overall, efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio. This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS.
Published: 1996

38. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group

Author: G, Bensimon, L, Lacomblez, and V, Meininger
Subjects: Adult, Male, Riluzole, Amyotrophic Lateral Sclerosis, Middle Aged, Prognosis, Survival Analysis, Thiazoles, Treatment Outcome, Double-Blind Method, Humans, Female, Prospective Studies, Excitatory Amino Acid Antagonists, Aged, Follow-Up Studies, Proportional Hazards Models
Abstract: Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis.To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days).After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantage with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlled period, but it remained significant in the overall population (P = 0.046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group.The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.
Published: 1994

39. Economic Analysis of Alzheimer’s Disease in Outpatients: Impact of Symptom Severity

Author: E. J. Souêtre, W. Qing, I. Vigoureux, H. Lozet, J. F. Dartigues, L. Lacomblez, and C. Derousené
Published: 1994
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40. Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses

Author: P, Danjou, D, Warot, T, Hergueta, L, Lacomblez, P, Bouhours, and A J, Puech
Subjects: Adult, Male, Diazepam, Alprazolam, Anxiety, Feedback, Flicker Fusion, Acoustic Stimulation, Double-Blind Method, Memory, Ritanserin, Reaction Time, Humans, Psychomotor Performance, Stress, Psychological
Abstract: The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.
Published: 1992

41. [Pharmacology of the memory. Review of cognition activator pharmacology]

Author: L, Lacomblez, G, Bensimon, and D, Warot
Subjects: Pharmacology, Memory Disorders, Cognition, Memory, Animals, Humans, In Vitro Techniques, Stimulation, Chemical
Abstract: The pharmacology of memory is fraught with problems. For one thing, the lack of consensus on the definition of memory and the absence of reference compound create clinical validation problems for new drugs. Then, it is difficult to predict clinical effectiveness on the basis of animal experiments and data obtained from healthy subjects, and this is due to the lack of analogy between animal models and clinical situations. Finally, to this must be added the complexity and variety of the possible modes of action of the agents under study. Thus, the pharmacology of cognition activators is closely dependent upon both fundamental research and clinical research.
Published: 1991

42. [Personality of healthy volunteers. Normality and paradox]

Author: P, Danjou, D, Warot, E, Weiller, L, Lacomblez, and A J, Puech
Subjects: Adult, Male, Personality Inventory, MMPI, Psychopharmacology, Humans, Cattell Personality Factor Questionnaire, Female, France, Healthy Worker Effect, Personality
Abstract: The personality characteristics of 62 subjects to be screened for eligibility in psychopharmacology studies have been assessed. The psychological screening comprised the Cattell anxiety scale (CAS), the Eysenck Personality inventory (EPI) and the Minnesota Multiphasic Personality Inventory (MMPI) in its complete version (550 items). The comparison of the results to a population matched for age and status showed that the anxiety level was not different, extraversion factor was higher (p less than 0.001) and various personality traits were different. The most striking differences were observed on the factors: Psychopathic deviation, Mania, Schizophrenia greater than controls and social introversion lower than controls. These differences may evoke several biases, such as a recruitment bias or a specific personality pattern of young healthy subjects. In order to discuss these hypothesis, further comparisons with other centers are required to conclude.
Published: 1991

43. [Comparative effects of ginkgo biloba extracts on psychomotor performances and memory in healthy subjects]

Author: D, Warot, L, Lacomblez, P, Danjou, E, Weiller, C, Payan, and A J, Puech
Subjects: Adult, Male, Analysis of Variance, Psychotropic Drugs, Double-Blind Method, Memory, Humans, Psychomotor Performance, Drugs, Chinese Herbal
Abstract: The effect on psychomotor and mnesic performances of acute oral dose (600 mg) of 2 Ginkgo biloba extracts were evaluated in twelve healthy female in a dummy placebo-controlled double blind study. Tests were performed comprising: objective measures of vigilance [critical flicker frequency (CFF), choice reaction time (CRT)], memory tasks (pictures and Sternberg scanning tests) and self-rating evaluation (visual analogue scales). Tests session took place before and 1 hour post-dosing. No statistically significant changes from placebo were observed on CFF, CRT or subjective rating of drug effects. No differences between treatment were evidenced on Sternberg scanning test and pictures recognition. Comparing to baseline, free recall score, while decreasing under placebo and Ginkgo, remained the same under Tanakan. As the differences between treatment are localized on one test, it appears important to examine the reproductility in healthy subjects. In order to verify the clinical relevance of these results, they need to be replicated in older healthy volunteers with age-associated memory impairment.
Published: 1991

44. Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo

Author: G Bensimon, L. Lacomblez, D. Warot, P. Simon, J Foret, and JF Thiercelin
Subjects: Multiple Sleep Latency Test, Adult, Male, Zolpidem, Pyridines, Administration, Oral, Flicker fusion threshold, Flunitrazepam, Placebo, Bedtime, Surveys and Questionnaires, medicine, Humans, Hypnotics and Sedatives, Pharmacology (medical), Wakefulness, Pharmacology, medicine.diagnostic_test, business.industry, musculoskeletal, neural, and ocular physiology, Alertness, Anesthesia, Drug Evaluation, business, Sleep, psychological phenomena and processes, Psychomotor Performance, medicine.drug, Research Article
Abstract: 1. The effects of zolpidem 20 mg, flunitrazepam 2 mg and placebo, administered at bed time, were studied in 12 healthy young male volunteers. 2. The assessments included, at awakening, subjective ratings of overnight sleep, cognitive function, psychomotor performance (digit symbol substitution, choice reaction time, flicker fusion threshold), subjective ratings of alertness, and plasma assay of residual drug concentration. Daytime sleep propensity during the day after dosing was evaluated with the multiple sleep latency test. 3. Compared with placebo, both active drugs improved subjective assessment of the ease of getting to sleep. At awakening, under flunitrazepam treatment, the reduction of performance, on memory and psychomotor tests, paralleled an increased subjective rating of sleepiness, but zolpidem treatment left subjects unimpaired compared with placebo. Similarly, daytime sleep propensity was enhanced throughout the following day under flunitrazepam treatment, but not under zolpidem treatment. Plasma assay for residual drug concentration at awakening found significant amounts of flunitrazepam and marginal amounts of zolpidem. 4. Results indicate that zolpidem 20 mg is devoid of residual effects in a range of tasks that were sensitive enough to demonstrate a prolonged wakefulness impairment following flunitrzepam 2 mg in healthy volunteers.
Published: 1990

45. [Myasthenia gravis and drugs]

Author: L, Lacomblez and D, Warot
Subjects: Myasthenia Gravis, Humans, Neuromuscular Nondepolarizing Agents
Abstract: Several drugs are known to aggravate myasthenia gravis or to induce myasthenia like syndromes. Drugs which interfere with neuro-muscular transmission act either through a direct effect at the neuro-muscular junction or as with D. Penicillamine through an immunological action. For some drugs, the information available indicate their harmfulness in myasthenia gravis, so they are contraindicated. For others, the clinical effect is not so well established, nevertheless if necessary they can be used with caution.
Published: 1990

46. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Français d'Etude de la Tetrahydroaminoacridine

Author: G Chatellier and L Lacomblez
Subjects: Male, medicine.medical_specialty, Letter, Visual analogue scale, Placebo, law.invention, Cognition, Randomized controlled trial, Double-Blind Method, law, Alzheimer Disease, Internal medicine, medicine, Humans, Multicenter Studies as Topic, Stroke, General Environmental Science, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, Behavior, Psychological Tests, business.industry, Aminoacridines, General Engineering, General Medicine, Middle Aged, medicine.disease, Crossover study, Surgery, Clinical trial, Tacrine, Phosphatidylcholines, General Earth and Planetary Sciences, Drug Therapy, Combination, Female, Alzheimer's disease, Chemical and Drug Induced Liver Injury, business, Research Article, medicine.drug, Follow-Up Studies
Abstract: OBJECTIVE--To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer's disease. DESIGN--Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING--Outpatient departments at six university neurological centres. PATIENTS--67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer's disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS--Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES--Cognitive state as assessed by Folstein's mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS--Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician's score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS--Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer's disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series).
Published: 1990

47. Glutamate levels in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. A reappraisal using a new HPLC method with coulometric detection in a large cohort of patients

Author: Pierre-François Pradat, A. Marouan, F. Salachas, L. Lacomblez, O. Spreux-Varoquaux, P. Julien, G. Bensimon, M. Dib, N. LeForestier, and V. Meininger
Subjects: Pharmacology, Pathology, medicine.medical_specialty, business.industry, Glutamate receptor, medicine.disease, Large cohort, Psychiatry and Mental health, Cerebrospinal fluid, Neurology, Medicine, Pharmacology (medical), Neurology (clinical), Amyotrophic lateral sclerosis, business, Hplc method, Biological Psychiatry
Published: 2001
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48. Riluzole and amyotrophic lateral sclerosis

Author: Vincent Meininger, Peter Leigh, P. Guillet, L Lacomblez, and G Bensimon
Subjects: business.industry, Medicine, General Medicine, Amyotrophic lateral sclerosis, business, medicine.disease, Neuroscience, Riluzole, medicine.drug
Published: 1996
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49. Psychopharmacological effects of low doses of fluoxetine in healthy volunteers: a comparative amphetamine controlled study

Author: Alain J. Puech, B. Diquet, D. Warot, Ph. Danjou, L. Lacomblez, and Emmanuelle Corruble
Subjects: Pharmacology, Fluoxetine, Subjective effects, business.industry, Low dose, Psychiatry and Mental health, Neurology, Anesthesia, Healthy volunteers, medicine, Antidepressant, Pharmacology (medical), Neurology (clinical), Amphetamine, business, Biological Psychiatry, medicine.drug
Published: 1994
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50. Psychopharmacological effects of Ginkgo Biloba extract (EGb 761) In healthy volunteers

Author: T. Tarrade, D. Warot, L. Lacomblez, and Alain J. Puech
Subjects: Pharmacology, Traditional medicine, biology, business.industry, Ginkgo biloba, Healthy volunteers, Medicine, business, biology.organism_classification
Published: 1990
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