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

Leonhard SE 1 , van der Eijk AA 1 , Andersen H 1 , Antonini G 1 , Arends S 1 , Attarian S 1 Show all authors , Barroso FA 1 , Bateman KJ 1 , Batstra MR 1 , Benedetti L 1 , van den Berg B 1 , Van den Bergh P 1 , Bürmann J 1 , Busby M 1 , Casasnovas C 1 , Cornblath DR 1 , Davidson A 1 , Doets AY 1 , van Doorn PA 1 , Dornonville de la Cour C 1 , Feasby TE 1 , Fehmi J 1 , Garcia-Sobrino T 1 , Goldstein JM 1 , Gorson KC 1 , Granit V 1 , Hadden RDM 1 , Harbo T 1 , Hartung HP 1 , Hasan I 1 , Holbech JV 1 , Holt JKL 1 , Jahan I 1 , Islam Z 1 , Karafiath S 1 , Katzberg HD 1 , Kleyweg RP 1 , Kolb N 1 , Kuitwaard K 1 , Kuwahara M 1 , Kusunoki S 1 , Luijten LWG 1 , Kuwabara S 1 , Lee Pan E 1 , Lehmann HC 1 , Maas M 1 , Martín-Aguilar L 1 , Miller JAL 1 , Mohammad QD 1 , Monges S 1 , Nedkova-Hristova V 1 , Nobile-Orazio E 1 , Pardo J 1 , Pereon Y 1 , Querol L 1 , Reisin R 1 , Van Rijs W 1 , Rinaldi S 1 , Roberts RC 1 , Roodbol J 1 , Shahrizaila N 1 , Sindrup SH 1 , Stein B 1 , Cheng-Yin T 1 , Tankisi H 1 , Tio-Gillen AP 1 , Sedano Tous MJ 1 , Verboon C 1 , Vermeij FH 1 , Visser LH 1 , Huizinga R 1 , Willison HJ 1 , Jacobs BC 2 , IGOS Consortium

Affiliations 

  • 1 From the Departments of Neurology (S.E.L., S. Arends, B.v.d.B., A.Y.D., P.A.v.D., K.K., L.W.G.L., W.V.R., J.R., C.V., B.C.J.), and Viroscience (A.A.v.d.E.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology (H.A., T.H.), Aarhus University Hospital, Denmark; Department of Neurology (G.A.), Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome "Sapienza," Sant' Andrea Hospital, Italy; Department of Neurology (S. Arends), Haga Teaching Hospital, The Hague, the Netherlands; Department of Neurology (S. Attarian), Reference Centre for NMD, CHU Timone, Marseille, France; Department of Neurology (F.A.B.), Instituto de Investigaciones Neurológicas Raúl Carrea, FLENI, Buenos Aires, Argentina; Division of Neurology (K.J.B., E.L.P.), Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa; Department RH-MDC-Immunology (M.R.B., M.M.), Reinier de Graaf Gasthuis, Delft, the Netherlands; Department of Neurology (L.B.), IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Neurology (B.v.d.B., F.H.V.), Franciscus Gasthuis & Vlietland, Schiedam, the Netherlands; Department of Neurology (P.V.d.B.), University Hospital St. Luc, University of Louvain, Brussels, Belgium; Department of Neurology (J.B.), Saarland University Medical School, Homburg (previous hospital), and MVZ Pfalzklinikum (J.B.), Kusel, Germany (current hospital); Department of Neurology (M.B.), Leeds Teaching Hospitals, United Kingdom; Department of Neurology (C.C., V.N.-H.), Neuromuscular Unit, Bellvitge University Hospital-IDIBELL, CIBERER, Barcelona, Spain; Department of Neurology (D.R.C.), Johns Hopkins University, Baltimore, MD; Institute of Infection, Immunity and Inflammation (A.D., H.J.W.), University of Glasgow, United Kingdom; National Hospital Copenhagen (C.D.d.l.C.), Copenhagen, Denmark; Department of Clinical Neurosciences (T.E.F.), University of Calgary, Alberta, Canada; Nuffield Department of Clinical Neurosciences (J.F., S.R.), University of Oxford, John Radcliffe Hospital, United Kingdom; Department of Neurology (T.G.-S., J.P.), Hospital Clínico de Santiago, Spain; Neurology, Neuromuscular Diseases, Electromyography (J.M.G.), Hospital for Special Surgery; Weill Medical College of Cornell University (J.M.G.), New York; Department of Neurology (K.C.G., B.S.), Tufts University School of Medicine, Boston, MA; Department of Neurology (V.G.), Montefiore Medical Center, New York; Department of Neurology (R.D.M.H.), King's College Hospital, London, United Kingdom; Department of Neurology (H.-P.H.), University of Düsseldorf, Germany; Brain and Mind Centre (H.-P.H.), University of Sydney, Australia; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Laboratory of Gut-Brain Signaling (I.H., I.J., Z.I., Q.D.M.), Laboratory Sciences and Services Division, icddr,b, Dhaka, Bangladesh; Department of Neurology (J.V.H., S.H.S.), Odense University Hospital, Denmark; Department of Neurology (J.K.L.H.), The Walton Centre, Liverpool, United Kingdom; Department of Neurology (S. Karafiath), Utah Valley University, Orem; Department of Neurology (H.D.K.), University Health Network, University of Toronto, ON, Canada; Department of Neurology (R.P.K., K.K.), Albert Schweitzer Hospital, Dordrecht, the Netherlands; Department of Neurology (N.K.), University of Vermont Medical Centre, Burlington; Department of Neurology (M.K., S. Kusunoki), Kindai University, Faculty of Medicine, Osaka, Japan; Department of Neurology (L.W.G.L., L.H.V.), St. Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (S. Kuwabara), Chiba University, Japan; Department of Neurology (H.C.L.), University Hospital of Cologne, Germany; Department of Neurology (L.M.-A., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Department of Neurology (J.A.L.M.), Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom; Department of Neurology (S.M.), Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina; Neuromuscular and Neuroimmunology Service (E.N.-O.), IRCCS Humanitas Research Hospital, Milan University, Italy; Department of Clinical Neurophysiology (Y.P.), Reference Centre for NMD, CHU Nantes, France; Department of Neurology (R.R.), Hospital Británico, Buenos Aires, Argentina; Department of Immunology (W.V.R., A.P.T.-G., R.H., B.C.J.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology (S.R.), Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital; Department of Neurology (R.C.R.), Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge Biomedical Campus, United Kingdom; Department of Medicine (N.S., T.C.-Y.), University of Malaya, Kuala Lumpur; Department of Neurology (S.H.S.), University of Southern Denmark, Odense; Department of Clinical Neurophysiology (H.T.), Aarhus University Hospital, Denmark; and Hospital Universitario Marques de Valdecilla (M.J.S.T.), Santander, Cantabria, Spain
  • 2 From the Departments of Neurology (S.E.L., S. Arends, B.v.d.B., A.Y.D., P.A.v.D., K.K., L.W.G.L., W.V.R., J.R., C.V., B.C.J.), and Viroscience (A.A.v.d.E.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology (H.A., T.H.), Aarhus University Hospital, Denmark; Department of Neurology (G.A.), Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome "Sapienza," Sant' Andrea Hospital, Italy; Department of Neurology (S. Arends), Haga Teaching Hospital, The Hague, the Netherlands; Department of Neurology (S. Attarian), Reference Centre for NMD, CHU Timone, Marseille, France; Department of Neurology (F.A.B.), Instituto de Investigaciones Neurológicas Raúl Carrea, FLENI, Buenos Aires, Argentina; Division of Neurology (K.J.B., E.L.P.), Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa; Department RH-MDC-Immunology (M.R.B., M.M.), Reinier de Graaf Gasthuis, Delft, the Netherlands; Department of Neurology (L.B.), IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Neurology (B.v.d.B., F.H.V.), Franciscus Gasthuis & Vlietland, Schiedam, the Netherlands; Department of Neurology (P.V.d.B.), University Hospital St. Luc, University of Louvain, Brussels, Belgium; Department of Neurology (J.B.), Saarland University Medical School, Homburg (previous hospital), and MVZ Pfalzklinikum (J.B.), Kusel, Germany (current hospital); Department of Neurology (M.B.), Leeds Teaching Hospitals, United Kingdom; Department of Neurology (C.C., V.N.-H.), Neuromuscular Unit, Bellvitge University Hospital-IDIBELL, CIBERER, Barcelona, Spain; Department of Neurology (D.R.C.), Johns Hopkins University, Baltimore, MD; Institute of Infection, Immunity and Inflammation (A.D., H.J.W.), University of Glasgow, United Kingdom; National Hospital Copenhagen (C.D.d.l.C.), Copenhagen, Denmark; Department of Clinical Neurosciences (T.E.F.), University of Calgary, Alberta, Canada; Nuffield Department of Clinical Neurosciences (J.F., S.R.), University of Oxford, John Radcliffe Hospital, United Kingdom; Department of Neurology (T.G.-S., J.P.), Hospital Clínico de Santiago, Spain; Neurology, Neuromuscular Diseases, Electromyography (J.M.G.), Hospital for Special Surgery; Weill Medical College of Cornell University (J.M.G.), New York; Department of Neurology (K.C.G., B.S.), Tufts University School of Medicine, Boston, MA; Department of Neurology (V.G.), Montefiore Medical Center, New York; Department of Neurology (R.D.M.H.), King's College Hospital, London, United Kingdom; Department of Neurology (H.-P.H.), University of Düsseldorf, Germany; Brain and Mind Centre (H.-P.H.), University of Sydney, Australia; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Laboratory of Gut-Brain Signaling (I.H., I.J., Z.I., Q.D.M.), Laboratory Sciences and Services Division, icddr,b, Dhaka, Bangladesh; Department of Neurology (J.V.H., S.H.S.), Odense University Hospital, Denmark; Department of Neurology (J.K.L.H.), The Walton Centre, Liverpool, United Kingdom; Department of Neurology (S. Karafiath), Utah Valley University, Orem; Department of Neurology (H.D.K.), University Health Network, University of Toronto, ON, Canada; Department of Neurology (R.P.K., K.K.), Albert Schweitzer Hospital, Dordrecht, the Netherlands; Department of Neurology (N.K.), University of Vermont Medical Centre, Burlington; Department of Neurology (M.K., S. Kusunoki), Kindai University, Faculty of Medicine, Osaka, Japan; Department of Neurology (L.W.G.L., L.H.V.), St. Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (S. Kuwabara), Chiba University, Japan; Department of Neurology (H.C.L.), University Hospital of Cologne, Germany; Department of Neurology (L.M.-A., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Department of Neurology (J.A.L.M.), Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom; Department of Neurology (S.M.), Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina; Neuromuscular and Neuroimmunology Service (E.N.-O.), IRCCS Humanitas Research Hospital, Milan University, Italy; Department of Clinical Neurophysiology (Y.P.), Reference Centre for NMD, CHU Nantes, France; Department of Neurology (R.R.), Hospital Británico, Buenos Aires, Argentina; Department of Immunology (W.V.R., A.P.T.-G., R.H., B.C.J.), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology (S.R.), Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital; Department of Neurology (R.C.R.), Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge Biomedical Campus, United Kingdom; Department of Medicine (N.S., T.C.-Y.), University of Malaya, Kuala Lumpur; Department of Neurology (S.H.S.), University of Southern Denmark, Odense; Department of Clinical Neurophysiology (H.T.), Aarhus University Hospital, Denmark; and Hospital Universitario Marques de Valdecilla (M.J.S.T.), Santander, Cantabria, Spain. b.jacobs@erasmusmc.nl
Neurology, 2022 Sep 20;99(12):e1299-e1313.
PMID: 35981895 DOI: 10.1212/WNL.0000000000200885

Abstract

BACKGROUND AND OBJECTIVES: Infections play a key role in the development of Guillain-Barré 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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