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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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.