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1. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial

Author

Walgaard, Christa, Jacobs, Bart C., Lingsma, Hester F., Steyerberg, Ewout W., Van den Berg, Bianca, Doets, Alexandra Y., Leonhard, Sonja E., Verboon, Christine, Huizinga, Ruth, Drenthen, Judith, Arends, Samuel, Kleine Budde, Ilona, Kleyweg, Ruud P., Kuitwaard, Krista, Van der Meulen, Marjon F.G., Samijn, Johnny P.A., Vermeij, Frederique H., Kuks, Jan B.M., Van Dijk, Gert W., Wirtz, Paul W., Eftimov, Filip, Van der Kooi, Anneke J., Garssen, Marcel P.J., Gijsbers, Cees J., De Rijk, Maarten C., Visser, Leo H., Blom, Roderik J., Linssen, Wim H.J.P., Van der Kooi, Elly L., Verschuuren, Jan J.G.M., Van Koningsveld, Rinske, Dieks, Rita J.G., Gilhuis, H. Job, Jellema, Korné, Van der Ree, Taco C., Bienfait, Henriette M.E., Faber, Karin G., Lovenich, Harry, Van Engelen, Baziel G.M., Groen, Rutger J., Merkies, Ingemar S.J., Van Oosten, Bob W., Van der Pol, W. Ludo, Van der Meulen, Willem D.M., Badrising, Umesh A., Stevens, Martijn, Breukelman, Albert-Jan J., Zwetsloot, Casper P., Van der Graaff, Maaike M., Wohlgemuth, Marielle, Hughes, Richard A.C., Cornblath, David R., Van Doorn, Pieter A., Althingh van Geusau, R.B., Van Boheemen, C.J.M., Bronner, I.M., Feenstra, B., Fokke, C., Hoogendoorn, T.A., Van Houten, R., Hovestad, A., Jansen, P.J.H.W., Keuter, E., Krudde, J., Linn, F.H.H., Lion, J., Manschot, S.M., Mellema, S.J., Molenaar, D.S.M., Nieuwkamp, D.J., Oenema, D.G., Van Oostrom, J.C.H., Van Orshoven, N.P., Van der Ploeg, R.J.O., Polman, S., Ruitenberg, A., Ruts, L., Schyns-Soeterboek, A.J.G.M., Trip, R., Jacobs, Bart C, Lingsma, Hester F, Steyerberg, Ewout W, van den Berg, Bianca, Doets, Alexandra Y, Leonhard, Sonja E, Budde, Ilona Kleine, Kleyweg, Ruud P, van der Meulen, Marjon F G, Samijn, Johnny P A, Vermeij, Frederique H, Kuks, Jan B M, van Dijk, Gert W, Wirtz, Paul W, van der Kooi, Anneke J, Garssen, Marcel P J, Gijsbers, Cees J, de Rijk, Maarten C, Visser, Leo H, Blom, Roderik J, Linssen, Wim H J P, van der Kooi, Elly L, Verschuuren, Jan J G M, van Koningsveld, Rinske, Dieks, Rita J G, Gilhuis, H Job, van der Ree, Taco C, Bienfait, Henriette M E, Faber, Catharina G, van Engelen, Baziel G M, Groen, Rutger J, Merkies, Ingemar S J, van Oosten, Bob W, van der Pol, W Ludo, van der Meulen, Willem D M, Badrising, Umesh A, Breukelman, Albert-Jan J, Zwetsloot, Casper P, van der Graaff, Maaike M, Hughes, Richard A C, Cornblath, David R, and van Doorn, Pieter A

Published
2021
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2. CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome

Author

Al-Hakem, Helle, Doets, Alex Y, Stino, Amro Maher, Zivkovic, Sasha A, Andersen, Henning, Willison, Hugh J, Cornblath, David R, Gorson, Kenneth C, Islam, Zhahirul, Mohammad, Quazi Deen, Sindrup, Søren Hein, Kusunoki, Susumu, Davidson, Amy, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Arends, Samuel, Luijten, Linda W G, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Martín-Aguilar, Lorena, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Waheed, Waqar, Lehmann, Helmar C, Granit, Volkan, Stein, Beth, Samijn, Johnny P A, van Dijk, Gert W, Jacobs, Bart C, Neurology, Medical Microbiology & Infectious Diseases, Public Health, and Immunology

Subjects
Neurology (clinical)
Abstract

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was

Published
2023

4. Predicting Outcome in Guillain-Barre Syndrome International Validation of the Modified Erasmus GBS Outcome Score

Author

Doets, Alex Y., Lingsma, Hester F., Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Kusunoki, Susumu, Dimachkie, Mazen M., Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H., Chavada, Govindsinh, Willison, Hugh J., Casasnovas, Carlos, Bateman, Kathleen, Miller, James A. L., van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E., Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A., Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Burmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P., Marchesoni, Cintia, Tous, Maria J. Sedano, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H., Lehmann, Helmar C., Granit, Volkan, Cavaletti, Guido, Gutierrez-Gutierrez, Gerardo, Barroso, Fabio A., Visser, Leo H., Katzberg, Hans D., Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J., Eftimov, Filip, Wirtz, Paul W., Samijn, Johnny P. A., Gilhuis, H. Jacobus, Hadden, Robert D. M., Holt, James K. L., Sheikh, Kazim A., Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E., Faber, Catharina G., Gijsbers, Cees J., Busby, Mark, Roberts, Rhys C., Silvestri, Nicholas J., Fazio, Raffaella, van Dijk, Gert W., Garssen, Marcel P. J., Straathof, Chiara S. M., Gorson, Kenneth C., Jacobs, Bart C., Doets, Alex Y., Lingsma, Hester F., Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Kusunoki, Susumu, Dimachkie, Mazen M., Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H., Chavada, Govindsinh, Willison, Hugh J., Casasnovas, Carlos, Bateman, Kathleen, Miller, James A. L., van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E., Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A., Shahrizaila, Nortina, Galassi, Giuliana, Pereon, Yann, Burmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P., Marchesoni, Cintia, Tous, Maria J. Sedano, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H., Lehmann, Helmar C., Granit, Volkan, Cavaletti, Guido, Gutierrez-Gutierrez, Gerardo, Barroso, Fabio A., Visser, Leo H., Katzberg, Hans D., Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J., Eftimov, Filip, Wirtz, Paul W., Samijn, Johnny P. A., Gilhuis, H. Jacobus, Hadden, Robert D. M., Holt, James K. L., Sheikh, Kazim A., Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E., Faber, Catharina G., Gijsbers, Cees J., Busby, Mark, Roberts, Rhys C., Silvestri, Nicholas J., Fazio, Raffaella, van Dijk, Gert W., Garssen, Marcel P. J., Straathof, Chiara S. M., Gorson, Kenneth C., and Jacobs, Bart C.

Abstract

Background and Objectives The clinical course and outcome of the Guillain-Barre syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods We used prospective data from the first 1,500 patients included in IGOS, aged >= 6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, a

Published
2022

5. Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score

Author

Doets, A, Lingsma, H, Walgaard, C, Islam, B, Papri, N, Davidson, A, Yamagishi, Y, Kusunoki, S, Dimachkie, M, Waheed, W, Kolb, N, Islam, Z, Mohammad, Q, Harbo, T, Sindrup, S, Chavada, G, Willison, H, Casasnovas, C, Bateman, K, Miller, J, van den Berg, B, Verboon, C, Roodbol, J, Leonhard, S, Benedetti, L, Kuwabara, S, Van den Bergh, P, Monges, S, Marfia, G, Shahrizaila, N, Galassi, G, Péréon, Y, Bürmann, J, Kuitwaard, K, Kleyweg, R, Marchesoni, C, Sedano Tous, M, Querol, L, Illa, I, Wang, Y, Nobile-Orazio, E, Rinaldi, S, Schenone, A, Pardo, J, Vermeij, F, Lehmann, H, Granit, V, Cavaletti, G, Gutiérrez-Gutiérrez, G, Barroso, F, Visser, L, Katzberg, H, Dardiotis, E, Attarian, S, van der Kooi, A, Eftimov, F, Wirtz, P, Samijn, J, Gilhuis, H, Hadden, R, Holt, J, Sheikh, K, Karafiath, S, Vytopil, M, Antonini, G, Feasby, T, Faber, C, Gijsbers, C, Busby, M, Roberts, R, Silvestri, N, Fazio, R, van Dijk, G, Garssen, M, Straathof, C, Gorson, K, Jacobs, B, Doets, Alex Y, Lingsma, Hester F, Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M, Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H, Chavada, Govindsinh, Willison, Hugh J, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Lehmann, Helmar C, Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A, Visser, Leo H, Katzberg, Hans D, Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J, Eftimov, Filip, Wirtz, Paul W, Samijn, Johnny P A, Gilhuis, H Jacobus, Hadden, Robert D M, Holt, James K L, Sheikh, Kazim A, Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E, Faber, Catharina G, Gijsbers, Cees J, Busby, Mark, Roberts, Rhys C, Silvestri, Nicholas J, Fazio, Raffaella, van Dijk, Gert W, Garssen, Marcel P J, Straathof, Chiara S M, Gorson, Kenneth C, Jacobs, Bart C, Doets, A, Lingsma, H, Walgaard, C, Islam, B, Papri, N, Davidson, A, Yamagishi, Y, Kusunoki, S, Dimachkie, M, Waheed, W, Kolb, N, Islam, Z, Mohammad, Q, Harbo, T, Sindrup, S, Chavada, G, Willison, H, Casasnovas, C, Bateman, K, Miller, J, van den Berg, B, Verboon, C, Roodbol, J, Leonhard, S, Benedetti, L, Kuwabara, S, Van den Bergh, P, Monges, S, Marfia, G, Shahrizaila, N, Galassi, G, Péréon, Y, Bürmann, J, Kuitwaard, K, Kleyweg, R, Marchesoni, C, Sedano Tous, M, Querol, L, Illa, I, Wang, Y, Nobile-Orazio, E, Rinaldi, S, Schenone, A, Pardo, J, Vermeij, F, Lehmann, H, Granit, V, Cavaletti, G, Gutiérrez-Gutiérrez, G, Barroso, F, Visser, L, Katzberg, H, Dardiotis, E, Attarian, S, van der Kooi, A, Eftimov, F, Wirtz, P, Samijn, J, Gilhuis, H, Hadden, R, Holt, J, Sheikh, K, Karafiath, S, Vytopil, M, Antonini, G, Feasby, T, Faber, C, Gijsbers, C, Busby, M, Roberts, R, Silvestri, N, Fazio, R, van Dijk, G, Garssen, M, Straathof, C, Gorson, K, Jacobs, B, Doets, Alex Y, Lingsma, Hester F, Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M, Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H, Chavada, Govindsinh, Willison, Hugh J, Casasnovas, Carlos, Bateman, Kathleen, Miller, James A L, van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E, Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A, Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P, Marchesoni, Cintia, Sedano Tous, María J, Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H, Lehmann, Helmar C, Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A, Visser, Leo H, Katzberg, Hans D, Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J, Eftimov, Filip, Wirtz, Paul W, Samijn, Johnny P A, Gilhuis, H Jacobus, Hadden, Robert D M, Holt, James K L, Sheikh, Kazim A, Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E, Faber, Catharina G, Gijsbers, Cees J, Busby, Mark, Roberts, Rhys C, Silvestri, Nicholas J, Fazio, Raffaella, van Dijk, Gert W, Garssen, Marcel P J, Straathof, Chiara S M, Gorson, Kenneth C, and Jacobs, Bart C

Abstract

Background and objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with

Published
2022

6. Guillain-Barr�� syndrome after SARS-CoV-2 infection in an international prospective cohort study

Author

Luijten, Linda W G, Leonhard, Sonja E, van der Eijk, Annemiek A, Doets, Alex Y, Appeltshauser, Luise, Arends, Samuel, Attarian, Shahram, Benedetti, Luana, Briani, Chiara, Casasnovas, Carlos, Castellani, Francesca, Dardiotis, Efthimios, Echaniz-Laguna, Andoni, Garssen, Marcel P J, Harbo, Thomas, Huizinga, Ruth, Humm, Andrea M, Jellema, Korn��, van der Kooi, Anneke J, Kuitwaard, Krista, Kuntzer, Thierry, Kusunoki, Susumu, Lascano, Agustina M, Martinez-Hernandez, Eugenia, Rinaldi, Simon, Samijn, Johnny P A, Scheidegger, Olivier, Tsouni, Pinelopi, Vicino, Alex, Visser, Leo H, Walgaard, Christa, Wang, Yuzhong, Wirtz, Paul W, Ripellino, Paolo, and Jacobs, Bart C

Subjects
610 Medicine & health
Abstract

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barr�� syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.

Published
2021
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7. The association of Epstein-Barr virus infection with CXCR3+ B-cell development in multiple sclerosis impact of immunotherapies

Author

van Langelaar, Jamie, Wierenga-Wolf, Annet F, Samijn, Johnny P A, Luijks, Caroline J M, Siepman, Theodora A, van Doorn, Pieter A, Bell, Andrew, van Zelm, Menno C, Smolders, Joost, van Luijn, Marvin M, van Langelaar, Jamie, Wierenga-Wolf, Annet F, Samijn, Johnny P A, Luijks, Caroline J M, Siepman, Theodora A, van Doorn, Pieter A, Bell, Andrew, van Zelm, Menno C, Smolders, Joost, and van Luijn, Marvin M

Abstract

Epstein-Barr virus (EBV) infection of B cells is associated with increased multiple sclerosis (MS) susceptibility. Recently, we found that CXCR3-expressing B cells preferentially infiltrate the central nervous system of MS patients. In chronic virus-infected mice, these types of B cells are sustained and show increased antiviral responsiveness. How EBV persistence in B cells influences their development remains unclear. First, we analyzed ex vivo B-cell subsets from MS patients who received autologous bone marrow transplantation (n=9), which is often accompanied by EBV reactivation. The frequencies of non-class-switched and class-switched memory B cells were reduced at 3-7 months, while only class-switched B cells returned back to baseline at 24-36 months post-transplantation. At these time points, EBV DNA load positively correlated to the frequency of CXCR3+ , and not CXCR4+ or CXCR5+ , class-switched B cells. Second, for CXCR3+ memory B cells trapped within the blood of MS patients treated with natalizumab (anti-VLA-4 antibody n=15), latent EBV infection corresponded to enhanced in vitro formation of anti-EBNA1 IgG-secreting plasma cells under germinal center-like conditions. These findings imply that EBV persistence in B cells potentiates brain-homing and antibody-producing CXCR3+ subsets in MS. This article is protected by copyright. All rights reserved.

Published
2021

8. Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study

Author

Luijten, L, Leonhard, S, van der Eijk, A, Doets, A, Appeltshauser, L, Arends, S, Attarian, S, Benedetti, L, Briani, C, Casasnovas, C, Castellani, F, Dardiotis, E, Echaniz-Laguna, A, Garssen, M, Harbo, T, Huizinga, R, Humm, A, Jellema, K, van der Kooi, A, Kuitwaard, K, Kuntzer, T, Kusunoki, S, Lascano, A, Martinez-Hernandez, E, Rinaldi, S, Samijn, J, Scheidegger, O, Tsouni, P, Vicino, A, Visser, L, Walgaard, C, Wang, Y, Wirtz, P, Ripellino, P, Jacobs, B, Cavaletti, G, Luijten, Linda W G, Leonhard, Sonja E, van der Eijk, Annemiek A, Doets, Alex Y, Appeltshauser, Luise, Arends, Samuel, Attarian, Shahram, Benedetti, Luana, Briani, Chiara, Casasnovas, Carlos, Castellani, Francesca, Dardiotis, Efthimios, Echaniz-Laguna, Andoni, Garssen, Marcel P J, Harbo, Thomas, Huizinga, Ruth, Humm, Andrea M, Jellema, Korné, van der Kooi, Anneke J, Kuitwaard, Krista, Kuntzer, Thierry, Kusunoki, Susumu, Lascano, Agustina M, Martinez-Hernandez, Eugenia, Rinaldi, Simon, Samijn, Johnny P A, Scheidegger, Olivier, Tsouni, Pinelopi, Vicino, Alex, Visser, Leo H, Walgaard, Christa, Wang, Yuzhong, Wirtz, Paul W, Ripellino, Paolo, Jacobs, Bart C, Cavaletti, Guido, Luijten, L, Leonhard, S, van der Eijk, A, Doets, A, Appeltshauser, L, Arends, S, Attarian, S, Benedetti, L, Briani, C, Casasnovas, C, Castellani, F, Dardiotis, E, Echaniz-Laguna, A, Garssen, M, Harbo, T, Huizinga, R, Humm, A, Jellema, K, van der Kooi, A, Kuitwaard, K, Kuntzer, T, Kusunoki, S, Lascano, A, Martinez-Hernandez, E, Rinaldi, S, Samijn, J, Scheidegger, O, Tsouni, P, Vicino, A, Visser, L, Walgaard, C, Wang, Y, Wirtz, P, Ripellino, P, Jacobs, B, Cavaletti, G, Luijten, Linda W G, Leonhard, Sonja E, van der Eijk, Annemiek A, Doets, Alex Y, Appeltshauser, Luise, Arends, Samuel, Attarian, Shahram, Benedetti, Luana, Briani, Chiara, Casasnovas, Carlos, Castellani, Francesca, Dardiotis, Efthimios, Echaniz-Laguna, Andoni, Garssen, Marcel P J, Harbo, Thomas, Huizinga, Ruth, Humm, Andrea M, Jellema, Korné, van der Kooi, Anneke J, Kuitwaard, Krista, Kuntzer, Thierry, Kusunoki, Susumu, Lascano, Agustina M, Martinez-Hernandez, Eugenia, Rinaldi, Simon, Samijn, Johnny P A, Scheidegger, Olivier, Tsouni, Pinelopi, Vicino, Alex, Visser, Leo H, Walgaard, Christa, Wang, Yuzhong, Wirtz, Paul W, Ripellino, Paolo, Jacobs, Bart C, and Cavaletti, Guido

Abstract

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological feat

Published
2021

9. Drug adherence and multidisciplinary care in patients with multiple sclerosis: Protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study)

Author

Siepman Theodora, de Schryver Els, Samijn Johnny, van Munster Eric, van Huizen Marc, Hoogervorst Erwin, Vliegen Joseph H, Gilhuis Job, Schrijver Hans, Hupperts Raymond, Hengstman Gerald, Jongen Peter J, Tonk Martijn, Zandbergen Eveline, ten Holter Jacques, van der Kruijk Ruud, and Borm George

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months. Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care. In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA. Methods/design The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiated, prospective, web-based, patient-centred, nation-wide cohort study in the Netherlands. The primary objective is to investigate whether GA adherence is associated with specific disciplines of care or quantities of specific care. The secondary objective is to investigate whether GA adherence is associated with specific aspects of the socio-economic situation, health care and caregivers, disease, treatment or patient characteristics. All data are acquired on-line via a study website. All RRMS patients in the Netherlands starting GA treatment are eligible. Patients are informed by neurologists, nurses, and websites from national MS patient organisations. All data, except on disability, are obtained by patient self-reports on pre-defined and random time points. The number of missed doses and the number of patients having discontinued GA treatment at 6 and 12 months are measures of adherence. Per care discipline the number of sessions and the total duration of care are measures of received care. The full spectrum of non-experimental care that is available in the Netherlands is assessed. Care includes 'physical' contacts, contacts by telephone or internet, health-promoting activities and community care activities. Care received over the preceding 14 days is assessed by patients at baseline and every other week thereafter up to month 12. Every 3 months neurologists and nurses record care disciplines to which patients have been referred. The Dutch Adherence Questionnaire-90 (DAQ-90) is a 90-item questionnaire based on the World Health Organisation (WHO) 2003 report on adherence and comprehensively assesses five domains of evidence-based determinants of adherence: socio-economic, health care and caregivers, disease, treatment, and patient-related factors. In addition, self-efficacy is assessed by the MS Self-Efficacy Scale (MSSES), and mood and health-related quality of life (HRQoL) by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Relapses and adverse events probably or definitively related to GA are also reported. Discussion In this study data is mainly acquired by patients' self-reporting via the internet. On-line data acquisition by patients does not require study visits to the hospital and can easily be integrated into daily life. The web-based nature of the study is believed to prevent missing data and study drop-outs. Moreover, the automated process of filling in questionnaires ensures completeness and consistency, thus improving data quality. The combination of patient-reported outcomes, fully web-based data capture and nation-wide information to all eligible patients are distinguishing features of the study and contribute to its scientific potential. Trial registration Netherlands Trial Register (NTR): NTR2432

Published
2011
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10. Predicting Outcome in Guillain-Barré Syndrome

Author

Doets, Alex Y., Lingsma, Hester F., Walgaard, Christa, Islam, Badrul, Papri, Nowshin, Davidson, Amy, Yamagishi, Yuko, Kusunoki, Susumu, Dimachkie, Mazen M., Waheed, Waqar, Kolb, Noah, Islam, Zhahirul, Mohammad, Quazi Deen, Harbo, Thomas, Sindrup, Soren H., Chavada, Govindsinh, Willison, Hugh J., Casasnovas, Carlos, Bateman, Kathleen, Miller, James A.L., van den Berg, Bianca, Verboon, Christine, Roodbol, Joyce, Leonhard, Sonja E., Benedetti, Luana, Kuwabara, Satoshi, Van den Bergh, Peter, Monges, Soledad, Marfia, Girolama A., Shahrizaila, Nortina, Galassi, Giuliana, Péréon, Yann, Bürmann, Jan, Kuitwaard, Krista, Kleyweg, Ruud P., Marchesoni, Cintia, Sedano Tous, María J., Querol, Luis, Illa, Isabel, Wang, Yuzhong, Nobile-Orazio, Eduardo, Rinaldi, Simon, Schenone, Angelo, Pardo, Julio, Vermeij, Frederique H., Lehmann, Helmar C., Granit, Volkan, Cavaletti, Guido, Gutiérrez-Gutiérrez, Gerardo, Barroso, Fabio A., Visser, Leo H., Katzberg, Hans D., Dardiotis, Efthimios, Attarian, Shahram, van der Kooi, Anneke J., Eftimov, Filip, Wirtz, Paul W., Samijn, Johnny P.A., Gilhuis, H. Jacobus, Hadden, Robert D.M., Holt, James K.L., Sheikh, Kazim A., Karafiath, Summer, Vytopil, Michal, Antonini, Giovanni, Feasby, Thomas E., Faber, Catharina G., Gijsbers, Cees J., Busby, Mark, Roberts, Rhys C., Silvestri, Nicholas J., Fazio, Raffaella, van Dijk, Gert W., Garssen, Marcel P.J., Straathof, Chiara S.M., Gorson, Kenneth C., Jacobs, Bart C., Hughes, R.A.C., Cornblath, D.R., Hartung, H.P., van Doorn, P.A., de Koning, L.C., van Woerkom, M., Mandarakas, M., MPhty, BHIthSci(Hons), Reisin, R.C., Reddel, S.W., Ripellino, P., Hsieh, S.T., Addington, J.M., Ajroud-Driss, S., Andersen, H., Badrising, U.A., Bella, I.R., Bertorini, T.E., Bhavaraju-Sanka, R., Bianco, M., Brannagan, T.H., Briani, Chiara, Butterworth, S., Chao, C.C., Chen, S., Claeys, K.G., Conti, M.E., Cosgrove, J.S., Dalakas, M.C., Dornonville de la Cour, C., Echaniz-Laguna, A., Fehmi, J., Fokke, C., Fujioka, T., Fulgenzi, E.A., García-Sobrino, T., Gilchrist, J.M., Goldstein, J.M., Goyal, N.A., Grisanti, S.G., Gutman, L., Holbech, J.V., Homedes, C., Htut, M., Jellema, K., Pascual, I. Jericó, JimenoMontero, M.C., Kaida, K., Khoshnoodi, M., Kiers, L., Kimpinski, K., Köhler, A.A., Kokubun, N., Kuwahara, M., Kwan, J.Y., Ladha, S.S., Lassen, L. Landschoff, Lawson, V., Pan, E.B. Lee, Cejas, L. Léon, Lunn, M.P.T., Magot, A., Manji, H., Infante, C. Márquez, Martín-Aguilar, L., Hernandez, E. Martinez, Mataluni, G., Mattiazzi, M.G., McDermott, C.J., Meekins, G.D., Morís de la Tassa, G., Nascimbene, C., Nowak, R.J., Osei-Bonsu, M., Pascuzzi, R.M., Prada, V., Rojas-Marcos, I., Rudnicki, S.A., Sachs, G.M., Samukawa, M., Santoro, L., Savransky, A.G., Schwindling, L., Sekiguchi, Y., Sommer, C.L., Spyropoulos, A., Stein, B., Stino, A.M., Tan, C.Y., Tankisi, H., Twydell, P.T., van Damme, P., van der Ree, T., van Koningsveld, R., Varrato, J.D., Xing, C., Zhou, L., and Zivkovic, S.

Published
2022
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11. Application of the 2017 Revised McDonald Criteria for Multiple Sclerosis to Patients With a Typical Clinically Isolated Syndrome

Author

van der Vuurst de Vries, Roos M., primary, Mescheriakova, Julia Y., additional, Wong, Yu Yi M., additional, Runia, Tessel F., additional, Jafari, Naghmeh, additional, Samijn, Johnny P., additional, de Beukelaar, Janet W. K., additional, Wokke, Beatrijs H. A., additional, Siepman, Theodora A. M., additional, and Hintzen, Rogier Q., additional

Published
2018
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12. High neurofilament levels are associated with clinically definite multiple sclerosis in children and adults with clinically isolated syndrome

Author

van der Vuurst de Vries, Roos M, primary, Wong, Yu Yi M, additional, Mescheriakova, Julia Y, additional, van Pelt, E Daniëlle, additional, Runia, Tessel F, additional, Jafari, Naghmeh, additional, Siepman, Theodora AM, additional, Melief, Marie-José, additional, Wierenga-Wolf, Annet F, additional, van Luijn, Marvin M, additional, Samijn, Johnny P, additional, Neuteboom, Rinze F, additional, and Hintzen, Rogier Q, additional

Published
2018
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13. High neurofilament levels are associated with clinically definite multiple sclerosis in children and adults with clinically isolated syndrome.

Author

van der Vuurst de Vries, Roos M, Wong, Yu Yi M, Mescheriakova, Julia Y, van Pelt, E Daniëlle, Runia, Tessel F, Jafari, Naghmeh, Siepman, Theodora AM, Hintzen, Rogier Q, Melief, Marie-José, Wierenga-Wolf, Annet F, van Luijn, Marvin M, Samijn, Johnny P, and Neuteboom, Rinze F

Subjects
MULTIPLE sclerosis, CYTOPLASMIC filaments, ENZYME-linked immunosorbent assay, MAGNETIC resonance imaging
Abstract

Background: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. Objective: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. Methods: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62.8 months (standard deviation (SD) ±38.7 months) and 43.8 months (SD ±27.1 months) in children). Thirty control patients were also included. Lumbar puncture was done within 6 months after onset of symptoms. NfL was determined in CSF using enzyme-linked immunosorbent assay (ELISA). COX regression analyses were used to calculate hazard ratios (HR) for clinically definite multiple sclerosis (CDMS) diagnosis. Results: After adjustments for age, oligoclonal bands (OCB), and asymptomatic T2 lesions on baseline magnetic resonance imaging (MRI), increased NfL levels in both paediatric and adult CIS patients were associated with a shorter time to CDMS diagnosis (children HR = 3.7; p = 0.007, adults HR = 2.1; p = 0.032). For CIS patients with a future CDMS diagnosis, children showed higher NfL levels than adults (geometric mean 4888 vs 2156 pg/mL; p = 0.007). Conclusion: CSF NfL levels are associated with CDMS diagnosis in children and adults with CIS. This makes NfL a promising predictive marker for disease course with potential value in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2019
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16. Copy number variation upstream of PMP22 in Charcot–Marie–Tooth disease.

Author

Weterman, Marian A. J., van Ruissen, Fred, de Wissel, Marit, Bordewijk, Lou, Samijn, Johnny P. A., van der Pol, W. Ludo, Meggouh, Farid, and Baas, Frank

Subjects
CHROMOSOMES, DENTAL caries, GENETIC mutation, GENETICS, NERVE tissue proteins
Abstract

In several individuals with a Charcot–Marie–Tooth (CMT) phenotype, we found a copy number variation (CNV) on chromosome 17p12 in the direct vicinity of the peripheral myelin protein 22 (PMP22) gene. The exact borders and size of this CNV were determined by Southern blot analysis, MLPA, vectorette PCR, and microarray hybridization analyses. All patients from six apparently unrelated families carried an identical 186-kb duplication different from the commonly reported 1.5-Mb duplication associated with CMT1A. This ancestral mutation that was not reported in the human structural variation database was only detected in affected individuals and family members. It was absent in 2124 control chromosomes and 40 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and therefore should be regarded as causative for the disease. This variant escapes most routine diagnostic screens for CMT1A, because copy numbers of PMP22 probes were all normal. No indications were found for the involvement of the genes that are located within this duplication. A possible association of this duplication with a mutation in the PMP22 coding regions was also excluded. We suggest that this CNV proximal of the PMP22 gene leads to CMT through an unknown mechanism affecting PMP22 expression. [ABSTRACT FROM AUTHOR]

Published
2010
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17. PRRT2phenotypes and penetrance of paroxysmal kinesigenic dyskinesia and infantile convulsions

Author

van Vliet, Rianne, Breedveld, Guido, de Rijk-van Andel, Johanneke, Brilstra, Eva, Verbeek, Nienke, Verschuuren-Bemelmans, Corien, Boon, Maartje, Samijn, Johnny, Diderich, Karin, van de Laar, Ingrid, Oostra, Ben, Bonifati, Vincenzo, and Maat-Kievit, Anneke

Abstract

To describe the phenotypes and penetrance of paroxysmal kinesigenic dyskinesia (PKD), a movement disorder characterized by attacks of involuntary movements occurring after sudden movements, infantile convulsion and choreoathetosis (ICCA) syndrome, and benign familial infantile convulsions (BFIC), caused by PRRT2mutations.

Published
2012
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18. Psychometric evaluation of a new handicap scale in immune‐mediated polyneuropathies

Author

Merkies, Ingemar S.J., Schmitz, Paul I.M., Van Der Meché, Frans G.A., Samijn, Johnny P.A., and Van Doorn, Pieter A.

Abstract

A new handicap measure, the Rotterdam nine‐item handicap scale, was developed and its validity, reliability, and responsiveness evaluated in patients with immune‐mediated polyneuropathies. We evaluated 113 stable patients, of whom 83 had Guillain–Barré syndrome (GBS), 22 had chronic inflammatory demyelinating polyneuropathy (CIDP), and 8 had a gammopathy‐related polyneuropathy. We also studied 20 patients with recently diagnosed GBS (n= 7) or CIDP (n= 13) and changing clinical conditions (longitudinal group). Significant discriminatory validity and correlation with the Rankin scale were demonstrated for the Rotterdam nine‐item handicap scale (stable group: Spearman's test, r= −.76 to −.78; longitudinal group: intraclass correlation coefficient, r= .83; P< .0001). Also, good reliability (r= .89–.98; P< .0001) and high responsiveness values (standardized response mean values > .8) were obtained for the Rotterdam nine‐item handicap scale. In contrast to the Rankin scale, the Rotterdam scale not only provided information regarding mobility but also highlighted physical independence, occupation, and social integration. These results illustrate the clinical usefulness of the Rotterdam nine‐item handicap scale under these conditions. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002

Published
2002
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19. Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study.

Author

Luijten LWG, Leonhard SE, van der Eijk AA, Doets AY, Appeltshauser L, Arends S, Attarian S, Benedetti L, Briani C, Casasnovas C, Castellani F, Dardiotis E, Echaniz-Laguna A, Garssen MPJ, Harbo T, Huizinga R, Humm AM, Jellema K, van der Kooi AJ, Kuitwaard K, Kuntzer T, Kusunoki S, Lascano AM, Martinez-Hernandez E, Rinaldi S, Samijn JPA, Scheidegger O, Tsouni P, Vicino A, Visser LH, Walgaard C, Wang Y, Wirtz PW, Ripellino P, and Jacobs BC

Subjects
Adult, Aged, Cohort Studies, Female, Guillain-Barre Syndrome virology, Humans, Male, Middle Aged, Prospective Studies, SARS-CoV-2, COVID-19 complications, Guillain-Barre Syndrome epidemiology
Abstract

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2021
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20. The association of Epstein-Barr virus infection with CXCR3 + B-cell development in multiple sclerosis: impact of immunotherapies.

Author

van Langelaar J, Wierenga-Wolf AF, Samijn JPA, Luijks CJM, Siepman TA, van Doorn PA, Bell A, van Zelm MC, Smolders J, and van Luijn MM

Subjects
3T3 Cells, Animals, Antibody Formation immunology, Brain immunology, Cells, Cultured, Humans, Immunotherapy methods, Leukocytes, Mononuclear immunology, Lymphocyte Activation immunology, Mice, Receptors, CXCR4 immunology, Receptors, CXCR5 immunology, B-Lymphocytes immunology, Epstein-Barr Virus Infections immunology, Herpesvirus 4, Human immunology, Multiple Sclerosis immunology, Receptors, CXCR3 immunology
Abstract

Epstein-Barr virus (EBV) infection of B cells is associated with increased multiple sclerosis (MS) susceptibility. Recently, we found that CXCR3-expressing B cells preferentially infiltrate the CNS of MS patients. In chronic virus-infected mice, these types of B cells are sustained and show increased antiviral responsiveness. How EBV persistence in B cells influences their development remains unclear. First, we analyzed ex vivo B-cell subsets from MS patients who received autologous bone marrow transplantation (n = 9), which is often accompanied by EBV reactivation. The frequencies of nonclass-switched and class-switched memory B cells were reduced at 3-7 months, while only class-switched B cells returned back to baseline at 24-36 months posttransplantation. At these time points, EBV DNA load positively correlated to the frequency of CXCR3 + , and not CXCR4 + or CXCR5 + , class-switched B cells. Second, for CXCR3 + memory B cells trapped within the blood of MS patients treated with natalizumab (anti-VLA-4 antibody n = 15), latent EBV infection corresponded to enhanced in vitro formation of anti-EBNA1 IgG-secreting plasma cells under GC-like conditions. These findings imply that EBV persistence in B cells potentiates brain-homing and antibody-producing CXCR3 + subsets in MS., (© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Published
2021
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