An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort

Sonja E. Leonhard, Annemiek A. Van Der Eijk, the IGOS Consortium, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A. Barroso, Kathleen J. Bateman, Manou R. Batstra, Luana Benedetti, Bianca Van Den Berg, Peter Van Den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, David R. Cornblath, Amy Davidson, Alex Y. Doets, Pieter A. Van DoornCharlotte Dornonville De La Cour, Thomas E. Feasby, Janev Fehmi, Tania Garcia-Sobrino, Jonathan M. Goldstein, Kenneth C. Gorson, Volkan Granit, Robert D.M. Hadden, Thomas Harbo, Hans Peter Hartung, Imran Hasan, Jakob V. Holbech, James K.L. Holt, Israt Jahan, Zhahirul Islam, Summer Karafiath, Hans D. Katzberg, Ruud P. Kleyweg, Noah Kolb, Krista Kuitwaard, Motoi Kuwahara, Susumu Kusunoki, Linda W.G. Luijten, Satoshi Kuwabara, Wouter Van Rijs, Joyce Roodbol, Anne P. Tio-Gillen, Christine Verboon, Frederique H. Vermeij, Ruth Huizinga, Bart C. Jacobs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Background and Objectives Infections play a key role in the development of Guillain-Barre syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. Methods We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. Results Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). Discussion Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models.

Original languageEnglish
Pages (from-to)E1299-E1313
Number of pages15
JournalNeurology
Volume99
Issue number12
DOIs
Publication statusPublished - 20 Sep 2022

Bibliographical note

Funding Information:
The IGOS was funded by the GBS-CIDP Foundation International, Prinses Beatrix Spierfonds (W.OB18-01), Gain, Erasmus MC University Medical Center Rotterdam, University of Glasgow, CSL Behring, Grifols, Annexon Biosciences, Hansa Biopharma, and the European Union (Horizon 2020, ZikaPLAN Grant Agreement No. 734584).

Funding Information:
S. Attarian received personal fees for advisory or scientific boards from CSL Behring, LFB Biomedicaments and Biotechnologies, Argenx BVBA, Pharnex, InFlectis, Pfizer, and Alnylam-Sanofi, outside the submitted work. P.A. van Doorn received grants from Grifols, Takeda, and Prinses Beatrix Spierfonds and consulting fees from Annexon, Argenx, Hansa Biomedical, Immunics, and Octapharma, outside the submitted work. K.C. Gorson provides consulting services for Annexon, Argenx, Pfizer, and UCB Pharma. R.D.M. Hadden received payments from Argenx, Alnylam, and CSL Behring. H.-P. Hartung received honoraria for serving on steering or data monitoring committees or speaking from Alexion, Bayer HealthCare, Biogen, Celgene BMS, CSL Behring, Merck, MedImmune, Novartis, Octapharma, TG Therapeutics, and VielaBio with permission by the Rector of Heinrich-Heine-University. J.K.L. Holt has received reimbursement for traveling and accommodation for foreign conference attendance and payment for advisory boards from CSL Behring and has received a research grant from Grifols. Z. Islam reports grants from the Fogarty International Center, National Institute of Neurological Disorders and Stroke of the NIH, under Award Number K43 TW011447 and Annexon Biosciences (South San Francisco, CA). N Kolb serves as a consultant for Abalone Bio and is on the Advisory Board for Alexion. S. Kusunoki reports grants from Nihon Pharmaceutical, Teijin, and Japan Blood Product Organization and personal fees from Nihon Pharmaceutical, Teijin, Japan Blood Product Organization, and CSL Behring, outside the submitted work. H.C. Lehman has received personal compensations and/or grant support in the last 3 years from Akcea, Alnylam, Biogen, Celgene, CSL Behring, Grifols, Novartis, and Takeda. E. Nobile-Orazio received personal fees for advisory or scientific boards from Kedrion Biopharma, Italy; Baxter/Baxalta/Shire/Takeda, USA/Japan; CSL Behring, Italy; LFB Biomedicaments and Biotechnologies, France; Astellas, the Netherlands; UCB Biopharma SRL, Belgium; Argenx BVBA, Belgium; and Sanofi US Services, Inc., outside the submitted work, and travel grants to attend scientific meetings from Baxter, Grifols, Kedrion, and Novartis, Italy. L. Querol is funded by the Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain, and FEDER FIS19/1407 and a personal grant SLT006/17/00131 of the Pla estratègic de recerca i innovació en salut (PERIS), Departament de Salut, Generalitat de Catalunya. He received speaker honoraria from Merck, Sanofi-Genzyme, Roche, Biogen, Grifols, and CSL Behring, provided expert testimony for Grifols, Johnson and Johnson, Annexon Pharmaceuticals, Alexion, Sanofi-Genzyme, Novartis, and CSL Behring, and received research funds from Roche and Grifols. R. Reisin has received personal compensations and/or grant support in the last 3 years from PTC, Pfizer, Sanofi, Shire, CSL Behring, Novartis, and Takeda. R.C. Roberts has received reimbursement for traveling and accommodation for foreign conference attendance and payment for advisory boards from CSL Behring. R Huizinga reports grants from the GBS-CIDP Foundation International, Grifols, and Health∼Holland, outside the submitted work. B.C. Jacobs received grants from Grifols, CSL Behring, Annexon, Prinses Beatrix Spierfonds, Hansa Biomedical, and the GBS-CIDP Foundation International and is on the Global Medical Advisory Board of the GBS-CIDP Foundation International. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Publisher Copyright:
© 2022 American Academy of Neurology.

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