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Neurofilament light chain and C reactive protein explored as predictors of survival in amyotrophic lateral sclerosis
  1. Maxim De Schaepdryver1,
  2. Christian Lunetta2,
  3. Claudia Tarlarini2,
  4. Lorena Mosca3,
  5. Adriano Chio4,
  6. Philip Van Damme5,6,
  7. Koen Poesen1,7
  1. 1 Department of Neurosciences, Leuven Brain Institute, Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
  2. 2 NEuroMuscular Omnicenter (NEMO), Fondazione Serena Onlus, Milan, Italy
  3. 3 Department of Laboratory Medicine, Medical Genetics Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
  4. 4 Department of Neuroscience, ALS Center ‘Rita Levi Montalcini’, University of Turin, Torino, Italy
  5. 5 Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  6. 6 Department of Neurosciences, Leuven Brain Institute, Experimental Neurology, Laboratory of Neurobiology, VIB KU Leuven Center for Brain and Disease Research, Leuven, Belgium
  7. 7 Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
  1. Correspondence to Professor Koen Poesen, Department of Neurosciences,Leuven Brain Institute Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven 3000, Belgium; koen.poesen{at}

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Amyotrophic lateral sclerosis (ALS) is a fatal disease defined by the progressive degeneration of both upper and lower motor neurons. The median survival after symptom onset is 3 to 5 years. Prognostic parameters have been identified and are associated with survival in ALS.1 2

Levels of neurofilament light chain (NfL) and C reactive protein (CRP) are both altered in serum of patients with ALS.3 4 Interestingly, these markers are linked to functional disability and survival in ALS.3 4

Prognostic protein biomarkers in blood are not taken into account yet when counselling patients with ALS. It is not clear to what extent these biomarkers contribute to predict survival in ALS. Here, we assessed the ability of serum NfL and CRP to predict survival in a multivariate survival model including eight other established prognostic parameters in ALS.2


In total, 383 patients with ALS, diagnosed between 2009 and 2018 according to the revised El Escorial criteria (10.4% suspected ALS, 21.9% possible ALS, 48.6% probable ALS and 19.1% definite ALS), were included in this retrospective study. Patients were recruited at the NeuroMuscular Reference Center of the University Hospital in Leuven, Belgium and at the NEuroMuscular Omnicenter of the Niguarda Ca’ Granda Hospital in Milan, Italy. Blood samples were consecutively collected during the first visit, providing a wide variety of patient inclusions going from early symptomatic to second opinions. Serum was aliquoted, transported on dry ice and stored at −80°C until analysis. Assay specifications can be retrieved in the supplemental data. The FVC and the revised ALS Functional Rating Score (ALSFRS-r) were obtained at the latest within 3 months from sampling. For each survival analysis, the patients were classified into …

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  • Contributors Concept and design: MDS, CL, PvD, KP. Drafting of the manuscript and figures: MDS, PvD, KP. Acquisition, analysis or interpretation of data: all authors. Critical revision of the manuscript for important intellectual content: all authors.

  • Funding This work was supported by a TBM grant from the Flemish Fund for Scientific Research (FWO-Vlaanderen, no. T003519N). MDS has a PhD Fellowship of FWO-Vlaanderen (11E6319N) and is supported by the Rotary’s ‘Espoir en Tête—Hoofdzaak er is Hoop’. KP received a start-up grant of the Group of Biomedical Sciences KU Leuven and holds a Clinical Research fund of the University Hospitals Leuven. PvD is a senior clinical investigator of the FWO-Vlaanderen and is supported by the ALS Liga België and the KU Leuven funds ‘een Hart voor ALS’, ‘Laeversfonds voor ALS Onderzoek’ and ‘the Valéry Perrier Race against ALS fund’.

  • Disclaimer No funder or sponsor had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

  • Competing interests CL participated in a scientific advisory board for Neuraltus, Cytokinetics, Mitsubishi Tanabe (Europe) and Italfarmaco; received research support from Agenzia Italiana per la Ricerca sulla SLA (ARISLA) and Ministry of Health (CCM2011). AC reported serving on the editorial advisory board of Amyotrophic Lateral Sclerosis; received research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Turin, Fondazione Vialli e Mauro onlus and the European Commission (Health Seventh Framework Programme); participated in scientific advisory boards for Biogen, Cytokinetics, Italfarmaco, Neuraltus and Mitsubishi. PvD participated in advisory board meetings for Genzyme, Pfizer, Biogen, Cytokinetics, Mitsubishi Tanabe (Japan), CSL Behring (USA), Alexion Pharmaceuticals (USA). MDS, KP, CT and LM declare no competing interests.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by both ethical committees: S50354 (Leuven) and 74-022019 (Milan).

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