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52. Reproducibility of fMRI in the clinical setting: Implications for trial designs

Author

Bosnell, R., Wegner, C., Kincses, Z.T., Korteweg, T., Agosta, F., Ciccarelli, O., De Stefano, N., Gass, A., Hirsch, J., Johansen-Berg, H., Kappos, L., Barkhof, F., Mancini, L., Manfredonia, F., Marino, S., Miller, D.H., Montalban, X., Palace, J., Rocca, M., Enzinger, C., Ropele, S., Rovira, A., Smith, S., Thompson, A., Thornton, J., Yousry, T., Whitcher, B., Filippi, M., and Matthews, P.M.

Published
2008
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55. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage

Author

Filippi, Massimo, Rocca, Maria A, Pagani, Elisabetta, De Stefano, Nicola, Jeffery, Douglas, Kappos, Ludwig, Montalban, Xavier, Boyko, Alexei N, Comi, Giancarlo, Filippi, M, Rocca, MA, Absinta, M, Longoni, G, Galantucci, S., Pagani, E, DallʼOcchio, L., Misci, P., Petrolini, M., Sala, S., Vuotto, R., Comi, G, Boyko, A, Filippi, M, Jeffery, D, Kappos, L, Montalban, x, McFarland, H, Bauer, K, Galay, N, Weber, J, Franta, C, Lampi, C, Shotekov, P, Bozhinov, S, Deleva, N, Haralanov, L, Ivanova Hristova, S, Petrov, I, Milanov, I, Kremenchutzky, M, Rabinovitch, H, Ayotte, C, GrandMaison, F, Lamontagne, A, Leckey, R, Lee, L, Hradilek, P, Kanovsky, P, Gross-Paju, K, Taba, P, Vermersch, P, Rumbach, L, Clavelou, P, Confavreux, C, Pelletier, J, Edan, G, Shakarishvili, R, Tsiskaridze, A, Becker, E, Chan, A, Eggers, J, Haas, J, Heesen, C, Heidenreich, F, Koehler, J., Koelmel, H W, Linker, R, Oschmann, P, Rauer, S, Maschke, M, Mueller, M, Reifschneider, G, Wildemann, B, Steinbrecher, A, Tumani, H, Ziebold, U, Ziemssen, T, Kanya, J, Jakab, G, Valikovics, A, Bartos, L, Karussis, D, Rawashdeh, H, Karni, A, Chapman, J, Comi, G, Caputo, D, Centonze, D, Cottone, S, Ghezzi, A, Maimone, D, Montanari, E, Plewnia, K, Scarpini, E, Metra, M, Rastenyte, D, Sceponaviciute, S, De Jong, B, Frequin, S, Visser, L, Zwanikken, C., Selmaj, K, Blaszczyk, B., Wajgt, A, Nowak, R, Jasinska, E, Brola, W, Sobkowiak-Osinska, M, Kapustecki, J, Zaborski, J, Panea, CA, Simu, M, Bulboaca, AC, Balasa, RI, Carciumaru, N, Boyko, A, Skoromets, A, Stolyarov, I, Perfilyev, S, Odinak, M, Amelina, O, Malkova, N, Gustov, A, Volkova, L, Shutov, A, Drulovic, J, Vojinovic, S, Montalban, Arroyo, R, Saiz Hinarejos, A, Brieva, L, Ramio, L, Meca Lallana, J, Amigo Jorrin, MdC, Prieto, JM, Munoz Gracia, D, Aladro, Y, Coret, F, Escartin, A, Diez Tejedor, E, Hillert, J, Olddon, T, Martin, C, Idiman, E, Sharrack, B, Giovannoni, G, Young, C, Nehrych, T, Moskovko, S, Kobys, T, AIpatov, Loganovskyi, K, AbouZeid, N, Jeffery, D, Dihenia, B, Carpenter, A, Flitman, S, Gazda, S, Goodman, A, Green, B, Gupta, A, Herbert, J, Hughes, B, Jacobs, A, Khatri, B, Lynch, S, Miller, T, Markowitz, C, Murray, R, Pardo, G, Parry, G, Gottschalk, G, Rossman, H, Scaberry, S, Thomas, F, Turel, A, Anderson, G, CTwyman, and Wyn, D

Published
2014
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65. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author

Patsopoulos, NA, Baranzini, SE, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, AH, James, T, Replogle, J, Vlachos, IS, McCabe, C, Pers, TH, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, IP, Robbins, A, Andlauer, TFM, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, HB, Sellebjerg, F, Sorensen, PS, Ullum, H, Thorner, LW, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, CM, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, MD, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, MA, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, SD, Celius, EG, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, IL, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, SJ, Calabresi, P, Cree, BAC, Cross, A, Davis, M, de Bakker, PWI, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, IY, Gourraud, PA, Haines, JL, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, MH, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, CP, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, MA, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, RJ, Lechner-Scott, J, Leal, R, Moscato, P, Booth, DR, Stewart, GJ, Vucic, S, Pame, G, BamettO, M, Mason, D, GriffithS, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, BV, Charlesworth, J, Kilpatrick, TJ, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, WM, Kermode, AG, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, JF, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, JP, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, GW, Ng, SME, Oikonomnou, J, Peeters, H, Proctor, DD, Rahier, JF, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, DA, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, HF, Hauser, SL, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, LF, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, McCauley, JL, Oksenberg, JR, Oturai, A, Sawcer, S, Ivinson, AJ, Olsson, T, De Jager, PL, Patsopoulos, Na, Baranzini, Se, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, Ah, James, T, Replogle, J, Vlachos, I, Mccabe, C, Pers, Th, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, Ip, Robbins, A, Andlauer, Tfm, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, Hb, Sellebjerg, F, Sorensen, P, Ullum, H, Thorner, Lw, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, Cm, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, Md, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, Ma, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, Sd, Celius, Eg, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, Il, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, Sj, Calabresi, P, Cree, Bac, Cross, A, Davis, M, de Bakker, Pwi, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, Iy, Gourraud, Pa, Haines, Jl, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, Mh, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, Cp, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, Ma, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, Rj, Lechner-Scott, J, Leal, R, Moscato, P, Booth, Dr, Stewart, Gj, Vucic, S, Pame, G, Bametto, M, Mason, D, Griffiths, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, Bv, Charlesworth, J, Kilpatrick, Tj, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, Wm, Kermode, Ag, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, Jf, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, Gw, Ng, Sme, Oikonomnou, J, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, Km, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H, Mathew, Cg, Palmer, Cna, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cca, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, Da, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, Hf, Hauser, Sl, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, Lf, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, Mccauley, Jl, Oksenberg, Jr, Oturai, A, Sawcer, S, Ivinson, Aj, Olsson, T, De Jager, Pl, Neurology, and Immunology

Subjects
0301 basic medicine, Multiple Sclerosis, Quantitative Trait Loci, Inheritance Patterns, Cell Cycle Proteins, Genome-wide association study, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Major Histocompatibility Complex, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Gene Frequency, Autoimmune Process, medicine, Humans, RNA-Seq, X chromosome, Genetics, Chromosomes, Human, X, Multidisciplinary, Microglia, Multiple sclerosis, GTPase-Activating Proteins, Chromosome Mapping, Genomics, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Genetic Loci, Case-Control Studies, biology.protein, Genome-Wide Association Study, 030217 neurology & neurosurgery
Abstract

Genetic roots of multiple sclerosis The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis. Science , this issue p. eaav7188 ; see also p. 1383

Published
2019

67. Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition

Author

Manson, S. C., Wegner, C., Filippi, M., Barkhof, F., Beckmann, C., Ciccarelli, O., De Stefano, N., Enzinger, Christian, Fazekas, F., Agosta, F., Gass, A., Hirsch, J., Johansen-Berg, H., Kappos, L., Korteweg, T., Polman, C., Mancini, L., Manfredonia, F., Marino, S., Miller, D. H., Montalban, X., Palace, J., Rocca, M., Ropele, S., Rovira, A., Smith, S., Thompson, A., Thornton, J., Yousry, T., Frank, J. A., and Matthews, P. M.

Published
2008
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72. Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event

Author

Lebrun-Frenay, C., Kantarci, O., Siva, A., Sormani, M. P., Pelletier, D., Okuda, D. T., Azevedo, C., Amato, M. P., Bensa, C., Berger, E., Brochet, B., Ciron, J., Cohen, M., Inglese, M., Keegan, B. M., Labauge, P., Laplaud, D. -A., Le Page, E., Louapre, C., Makhani, N., Mathey, G., Mondot, L., Montalban, X., Pelletier, J., de Seze, J., Destefano, N., Thouvenot, E., Tintore, M., Tutuncuoglu, M., Uygunoglu, U., Vermersch, P., Weinshenker, B., and Zeydan, B.

Subjects
0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, Journal Club, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, medicine, Humans, Young adult, Child, Event (probability theory), Aged, medicine.diagnostic_test, Clinical events, business.industry, Proportional hazards model, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Demyelinating Diseases, Female, Magnetic Resonance Imaging, Disease Progression, 030104 developmental biology, Risk Estimate, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10-year, multinational, retrospectively identified RIS dataset. Methods RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models. Results Additional follow-up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11-74 years), with a median clinical follow-up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium-enhanced lesions during follow-up was also associated with the risk of a seminal event. The reason for MRI and gadolinium-enhancing lesions at baseline did not influence the risk of a subsequent clinical event. Interpretation Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407-417.

Published
2020

73. Aggressive multiple sclerosis (2): Treatment

Author

Arrambide, G., Iacobaeus, E., Amato, M. P., Derfuss, T., Vukusic, S., Hemmer, B., Brundin, L., Tintore, M., Berger, J., Boyko, A., Brinar, V., Brownlee, W., Ciccarelli, O., Coles, A., Correale, J., Cutter, G., Edan, G., Evangelou, N., Fernandez, O., Frederiksen, J., Gold, R., Hacohen, Y., Hartung, H. -P., Hellwig, K., Hillert, J., Imitola, J., Kalincik, T., Kappos, L., Khoury, S., Kim, H. J., Havrdova, E. K., Liblau, R., Lycke, J., Montalban, X., Muraro, P., Reingold, S., Schmierer, K., Sellebjerg, F., Sorensen, P. S., Solari, A., Sormani, M. P., Thompson, A., Trapp, B., Tremlett, H., Trojano, M., Tur, C., Uccelli, A., van Pesch, V., and Waubant, E.

Subjects
Aggressive, medicine.medical_specialty, Treatment response, relapsing–remitting, Disease, Permanent disability, multiple sclerosis, disability, highly active, treatment response, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, 2018 ECTRIMS Focused Workshop Group, medicine, Relapsing-remitting, 030212 general & internal medicine, Intensive care medicine, Highly active, Therapeutic window, Neurology & Neurosurgery, Disability, business.industry, 1103 Clinical Sciences, medicine.disease, ddc, Natural history, Neurology, Relapsing remitting, Neurology (clinical), business, 1109 Neurosciences, 030217 neurology & neurosurgery, Meeting Reviews
Abstract

Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The workshop on which the manuscript is based was supported in its entirety by the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS). The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.

Published
2020

74. Aggressive multiple sclerosis (1) : Towards a definition of the phenotype

Author

Iacobaeus, E., Arrambide, G., Amato, M. P., Derfuss, T., Vukusic, S., Hemmer, B., Tintore, M., Brundin, L., Berger, J., Boyko, A., Brinar, V., Brownlee, W., Ciccarelli, O., Coles, A., Correale, J., Cutter, G., Edan, G., Evangelou, N., Fernandez, O., Frederiksen, J., Gold, R., Hacohen, Y., Hartung, H. -P., Hellwig, K., Hillert, J., Imitola, J., Kalincik, T., Kappos, L., Khoury, S., Kim, H. J., Havrdova, E. K., Liblau, R., Lycke, J., Montalban, X., Muraro, P., Reingold, S., Schmierer, K., Sellebjerg, F., Sorensen, P. S., Solari, A., Sormani, M. P., Thompson, A., Trapp, B., Tremlett, H., Trojano, M., Tur, C., Uccelli, A., van Pesch, V., Waubant, E., UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Disease subtype, Aggressive, medicine.medical_specialty, Severe disease, Aggressive disease, multiple sclerosis, Relapsing/remitting, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, disability, highly active, observational studies, relapsing/remitting, 2018 ECTRIMS Focused Workshop Group, medicine, Intensive care medicine, Secondary progressive, Highly active, Observational studies, 030304 developmental biology, 0303 health sciences, Neurology & Neurosurgery, Disability, business.industry, 1103 Clinical Sciences, medicine.disease, Phenotype, Additional research, ddc, Neurology, Observational study, Neurology (clinical), 1109 Neurosciences, business, 030217 neurology & neurosurgery, Meeting Reviews
Abstract

Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The workshop on which the manuscript is based was supported in its entirety by the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS). While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.

Published
2020

77. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author

UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, Van Pesch, Vincent, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, C, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, Van Pesch, Vincent, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, A, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, and Teunissen, C

Abstract

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Published
2020

78. Kappa free light chains is a valid tool in the diagnostics of MS:A large multicenter study

Author

Leurs, C. E., Twaalfhoven, H. A. M., Lissenberg-Witte, B. I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L. M., Alvarez-Cermeño, J. C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L. M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Altintas, A., Rejdak, K., Frederiksen, J. L., Pihl-Jensen, G., Jensen, P. E. H., Khalil, M., Voortman, M. M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B. M. J., Killestein, J., Bridel, C., Teunissen, C., Leurs, C. E., Twaalfhoven, H. A. M., Lissenberg-Witte, B. I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L. M., Alvarez-Cermeño, J. C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L. M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Altintas, A., Rejdak, K., Frederiksen, J. L., Pihl-Jensen, G., Jensen, P. E. H., Khalil, M., Voortman, M. M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B. M. J., Killestein, J., Bridel, C., and Teunissen, C.

Abstract

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Published
2020

87. Diagnosis and Management of Neuromyelitis Optica

Author

Sellner, J., primary, Boggild, M., additional, Clanet, M., additional, Hintzen, R. Q., additional, Illes, Z., additional, Montalban, X., additional, Du Pasquier, R. A., additional, Polman, C. H., additional, Soelberg Sørensen, P., additional, and Hemmer, B., additional

Published
2011
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89. Acute Relapses of Multiple Sclerosis

Author

Sellebjerg, F., primary, Barnes, D., additional, Filippini, G., additional, Midgard, R., additional, Montalban, X., additional, Rieckmann, P., additional, Selmaj, K., additional, Visser, L. H., additional, and Soelberg Sørensen, P., additional

Published
2010
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