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3. Prospective multicenter validation of CSF protein biomarkers in patients with CIS and early MS

Author

Huss, A., Otto, M., Tackenberg, B., Stangel, M., Aktas, O., Meuth, S., Gross, C. C., Bayas, A., Wildemann, B., Luessi, F., Seipelt, M., Puetz, M., Antony, G., Weber, F., Uhr, M., Bischof', F., Ruprecht, K., Buck, D., Retzlaff, N., Zettl, U. K., Haghikia, A., Lukas, C., Hartung, H. -P., Bergh, F. Then, Warnke, C., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Tumani, H., Huss, A., Otto, M., Tackenberg, B., Stangel, M., Aktas, O., Meuth, S., Gross, C. C., Bayas, A., Wildemann, B., Luessi, F., Seipelt, M., Puetz, M., Antony, G., Weber, F., Uhr, M., Bischof', F., Ruprecht, K., Buck, D., Retzlaff, N., Zettl, U. K., Haghikia, A., Lukas, C., Hartung, H. -P., Bergh, F. Then, Warnke, C., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., and Tumani, H.

Published
2018

4. Absence of Epstein-Barr virus seronegativity in a large cohort of patients with early multiple sclerosis

Author

Abrahamyan, S., Eberspaecher, B., Ambrosius, B., Hessler, N., Antony, G., Koenig, I. R., Hoshi, M. -M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., Ruprecht, K., Abrahamyan, S., Eberspaecher, B., Ambrosius, B., Hessler, N., Antony, G., Koenig, I. R., Hoshi, M. -M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., and Ruprecht, K.

Published
2018

5. Changes of disease characteristics and disease-modifying treatment within one year in the National German MS cohort

Author

Ambrosius, B., Hessler, N., Antony, G., Konig, I. R., Hoshi, M-M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., Ambrosius, B., Hessler, N., Antony, G., Konig, I. R., Hoshi, M-M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., and Salmen, A.

Published
2018

6. Absence of Epstein-Barr virus seronegativity in a large cohort of patients with early multiple sclerosis

Author

Abrahamyan, S., Eberspaecher, B., Ambrosius, B., Hessler, N., Antony, G., Koenig, I. R., Hoshi, M. -M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., Ruprecht, K., Abrahamyan, S., Eberspaecher, B., Ambrosius, B., Hessler, N., Antony, G., Koenig, I. R., Hoshi, M. -M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., and Ruprecht, K.

Published
2018

7. Changes of disease characteristics and disease-modifying treatment within one year in the National German MS cohort

Author

Ambrosius, B., Hessler, N., Antony, G., Konig, I. R., Hoshi, M-M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Salmen, A., Ambrosius, B., Hessler, N., Antony, G., Konig, I. R., Hoshi, M-M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Tackenberg, B., Stoppe, M., Bergh, F. Then, Tumani, H., Kuempfel, T., Stangel, M., Heesen, C., Wildemann, B., Paul, F., Bayas, A., Warnke, C., Weber, F., Linker, R. A., Ziemann, U., Zettl, U. K., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., and Salmen, A.

Published
2018

8. Prospective multicenter validation of CSF protein biomarkers in patients with CIS and early MS

Author

Huss, A., Otto, M., Tackenberg, B., Stangel, M., Aktas, O., Meuth, S., Gross, C. C., Bayas, A., Wildemann, B., Luessi, F., Seipelt, M., Puetz, M., Antony, G., Weber, F., Uhr, M., Bischof', F., Ruprecht, K., Buck, D., Retzlaff, N., Zettl, U. K., Haghikia, A., Lukas, C., Hartung, H. -P., Bergh, F. Then, Warnke, C., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., Tumani, H., Huss, A., Otto, M., Tackenberg, B., Stangel, M., Aktas, O., Meuth, S., Gross, C. C., Bayas, A., Wildemann, B., Luessi, F., Seipelt, M., Puetz, M., Antony, G., Weber, F., Uhr, M., Bischof', F., Ruprecht, K., Buck, D., Retzlaff, N., Zettl, U. K., Haghikia, A., Lukas, C., Hartung, H. -P., Bergh, F. Then, Warnke, C., Zipp, F., Wiendl, H., Hemmer, B., Gold, R., and Tumani, H.

Published
2018

9. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), Terzi M., Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), and Terzi M.

Abstract

Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative

Published
2018

10. Mutations in the gene tripeptidyl peptidase II (TPP2) and multiple sclerosis

Author

Reinthaler, E. M., Graf, E., Zrzavy, T., Wieland, T., Hotzy, C., Kopecky, C., Schmied, C., Leutmezer, F., Keilani, M., Lill, C. M., Hoffjan, S., Epplen, J. T., Zettl, U. K., Hecker, M., Deutschlaender, A., Ahram, M., Mustafa, B., El-Khateeb, M., Vilarino-Guell, C., Sadovnick, D. A., Zimprich, F., Tomkinson, B, Strom, T. M., Kristoferitsch, W., Lassmann, H., Zimprich, A., Reinthaler, E. M., Graf, E., Zrzavy, T., Wieland, T., Hotzy, C., Kopecky, C., Schmied, C., Leutmezer, F., Keilani, M., Lill, C. M., Hoffjan, S., Epplen, J. T., Zettl, U. K., Hecker, M., Deutschlaender, A., Ahram, M., Mustafa, B., El-Khateeb, M., Vilarino-Guell, C., Sadovnick, D. A., Zimprich, F., Tomkinson, B, Strom, T. M., Kristoferitsch, W., Lassmann, H., and Zimprich, A.

Published
2016

11. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

Author

Jarius, S, Ruprecht, K, Wildemann, B, Kuempfel, T, Ringelstein, M, Geiser, C, Kleiter, I, Kleinschnitz, C, Berthele, A, Brettschneider, J, Hellwig, K, Hemmer, B, Linker, R A, Lauda, F, Mayer, C A, Tumani, H, Melms, A, Trebst, C, Stangel, M, Marziniak, M, Hoffmann, F, Schippling, S, Faiss, J H, Neuhaus, O, Ettrich, B, Zentner, C, Guthke, K, Hofstadt-van Oy, U, Reuss, R, Pellkofer, H, Ziemann, U, Kern, P, Wandinger, K P, Bergh, F, Boettcher, T, Langel, S, Liebetrau, M, Rommer, P S, Niehaus, S, Münch, C, Winkelmann, A, Zettl U, U K, Metz, I, Veauthier, C, Sieb, J P, Wilke, C, Hartung, H P, Aktas, O, Paul, F, Jarius, S, Ruprecht, K, Wildemann, B, Kuempfel, T, Ringelstein, M, Geiser, C, Kleiter, I, Kleinschnitz, C, Berthele, A, Brettschneider, J, Hellwig, K, Hemmer, B, Linker, R A, Lauda, F, Mayer, C A, Tumani, H, Melms, A, Trebst, C, Stangel, M, Marziniak, M, Hoffmann, F, Schippling, S, Faiss, J H, Neuhaus, O, Ettrich, B, Zentner, C, Guthke, K, Hofstadt-van Oy, U, Reuss, R, Pellkofer, H, Ziemann, U, Kern, P, Wandinger, K P, Bergh, F, Boettcher, T, Langel, S, Liebetrau, M, Rommer, P S, Niehaus, S, Münch, C, Winkelmann, A, Zettl U, U K, Metz, I, Veauthier, C, Sieb, J P, Wilke, C, Hartung, H P, Aktas, O, and Paul, F

Abstract

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis

Published
2012

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