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Original research
Serum neurofilament light chain predicts long-term prognosis in Guillain-Barré syndrome patients
  1. Lorena Martín-Aguilar1,
  2. Pol Camps-Renom2,
  3. Cinta Lleixà1,
  4. Elba Pascual-Goñi1,
  5. Jordi Díaz-Manera1,3,
  6. Ricardo Rojas-García1,3,
  7. Noemi De Luna1,3,
  8. Eduard Gallardo1,3,
  9. Elena Cortés-Vicente1,3,
  10. Laia Muñoz4,5,
  11. Daniel Alcolea4,5,
  12. Alberto Lleó4,5,
  13. Carlos Casasnovas6,7,
  14. Christian Homedes6,
  15. Gerardo Gutiérrez-Gutiérrez8,
  16. María Concepción Jimeno-Montero8,
  17. José Berciano5,9,
  18. María José Sedano-Tous9,
  19. Tania García-Sobrino10,
  20. Julio Pardo-Fernández10,
  21. Celedonio Márquez-Infante11,
  22. Iñigo Rojas-Marcos12,
  23. Ivonne Jericó-Pascual13,
  24. Eugenia Martínez-Hernández14,
  25. Germán Morís de la Tassa15,
  26. Cristina Domínguez-González16,
  27. Isabel Illa1,3,
  28. Luis Querol1,3
  1. 1Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  2. 2Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
  4. 4Department of Neurology, Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  5. 5Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
  6. 6Neuromuscular Diseases Unit, Department of Neurology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain
  7. 7Neurometabolic Diseases Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
  8. 8Department of Neurology, Hospital Universitario Infanta Sofia, Madrid, Spain
  9. 9Department of Neurology, Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander, Spain
  10. 10Department of Neurology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
  11. 11Department of Neurology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
  12. 12Department of Neurology, Hospital Universitario Reina Sofia, Cordoba, Spain
  13. 13Department of Neurology, Complejo Hospitalario de Navarra, Pamplona, Spain
  14. 14Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain
  15. 15Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain
  16. 16Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain
  1. Correspondence to Dr Luis Querol, Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain; lquerol{at}santpau.cat

Abstract

Objective To study baseline serum neurofilament light chain (sNfL) levels as a prognostic biomarker in Guillain-Barré syndrome (GBS).

Methods We measured NfL in serum (98 samples) and cerebrospinal fluid (CSF) (24 samples) of patients with GBS prospectively included in the International GBS Outcome Study (IGOS) in Spain using single-molecule array (SiMoA) and compared them with 53 healthy controls (HCs). We performed multivariable regression to analyse the association between sNfL levels and functional outcome at 1 year.

Results Patients with GBS had higher NfL levels than HC in serum (55.49 pg/mL vs 9.83 pg/mL, p<0.0001) and CSF (1308.5 pg/mL vs 440.24 pg/mL, p=0.034). Patients with preceding diarrhoea had higher sNfL than patients with respiratory symptoms or no preceding infection (134.90 pg/mL vs 47.86 pg/mL vs 38.02 pg/mL, p=0.016). sNfL levels correlated with Guillain-Barré Syndrome Disability Score and Inflammatory Rasch-built Overall Disability Scale (I-RODS) at every timepoint. Patients with pure motor variant and Miller Fisher syndrome showed higher sNfL levels than patients with sensorimotor GBS (162.18 pg/mL vs 95.50 pg/mL vs 38.02 pg/mL, p=0.025). Patients with acute motor axonal neuropathy cute motor axonal neuropathy had higher sNfL levels than other variants (190.55 pg/mL vs 46.79 pg/mL, p=0.013). sNfL returned to normal levels at 1 year. High baseline sNfL levels were associated with inability to run (OR=1.65, 95% CI 1.14 to 2.40, p=0.009) and lower I-RODS (β −2.60, 95% CI −4.66 to −0.54, p=0.014) at 1 year. Cut-off points predicting clinically relevant outcomes at 1 year with high specificity were calculated: inability to walk independently (>319 pg/mL), inability to run (>248 pg/mL) and ability to run (<34 pg/mL).

Conclusion Baseline sNfL levels are increased in patients with GBS, are associated with disease severity and axonal variants and have an independent prognostic value in patients with GBS.

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Footnotes

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  • Contributors LM-A contributed to acquisition of data, performed the experiments, analysed the data and drafted the manuscript for intellectual content. PC-R had a major role in analysing the data and performing all statistical analyses. MCL, EPG, JD-M, RR-G, EC-V, CC, CH, GG-G, MCJ-M, JB, MJS, TG-S, JP, CM, IR-M, IJ-P, EM-H, GM and CDG collected the samples and data and revised the manuscript for intellectual content. LM and DA helped to perform the experiments and revised the manuscript for intellectual content. NDL, EG, AL and II revised the manuscript for intellectual content. LAQ designed and conceptualised the study, interpreted the data and revised the manuscript for intellectual content.

  • Funding This work was supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain and FEDER under grant FIS19/01407, personal grant Rio Hortega CM19/00042, personal grant SLT006/17/00131 of the Pla estratègic de recerca i innovació en salut (PERIS), Departament de Salut, Generalitat de Catalunya, and the ER20P3AC7624 project of the ACCI call of the CIBERER network, Madrid, Spain. AL is supported by Fundació Bancaria La Caixa. DA is supported by Instituto Carlos III under grants PI18/00435 and INT19/00016 and personal grant SLT006/17/125 of the Pla estratègic de recerca i innovació en salut (PERIS).

  • Competing interests LAQ has provided expert testimony for Grifols, Sanofi-Genzyme, Novartis, UCB, Roche and CSL Behring and received research funds from Novartis Spain, Sanofi-Genzyme and Grifols. LM-A has received speaking honoraria from Roche. EP-G has received speaking honoraria from Roche and Biogen. JD-M has provided expert testimony for PTC and Sanofi-Genzyme, has been external advisor for Sanofi, Sarepta and Audentes and received research funds from Sanofi-Genzyme and Boehringer. DA participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Nutricia and from Krka Farmacéutica S.L. GG-G has received speaking honoraria from Sanofi-Genzyme, Takeda and has provided expert testimony for Biogen and CSL Behring. The other authors report no disclosures.

  • Patient consent for publication Not required.

  • Ethics approval The study general IGOS protocol and the study of biomarkers (including NfL) were approved by the Ethics Committee of the Hospital de la Santa Creu i Sant Pau (IGOS protocol, code 12/142; biomarker/NfL research in GBS, codes 17/033 and 20/034) and the local Institutional Review Boards of participating hospitals or universities.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Anonymised data not published within this article will be made available by request from any qualified investigator.

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