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Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis

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Abstract

Background

Cognitive impairment (CI) is a disabling symptom of multiple sclerosis (MS). Axonal damage disrupts neural circuits and may play a role in determining CI, but its detection and monitoring are not routinely performed. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a promising marker of axonal damage in MS.

Objective

To retrospectively examine the relationship between CSF NfL and CI in MS patients.

Methods

CSF NfL concentration was measured in 28 consecutive newly diagnosed MS patients who underwent a neuropsychological evaluation with the Brief Repeatable Battery of Neuropsychological tests (BRBN).

Results

CSF NfL was higher in patients with overall CI (947.8 ± 400.7 vs 518.4 ± 424.7 pg/mL, p < 0.01), and with impairment in information processing speed (IPS) (820.8 ± 413.6 vs 513.6 ± 461.4 pg/mL, p < 0.05) and verbal fluency (1292 ± 511 vs 582.8 ± 395.4 pg/mL, p < 0.05), and it positively correlated with the number of impaired BRBN tests (r = 0.48, p = 0.01) and cognitive domains (r = 0.47, p = 0.01). Multivariate analyses taking into account potential confounders confirmed these findings.

Conclusion

CSF NfL is higher in MS patients with CI and impaired IPS and verbal fluency. Large myelinated axons injury, causing neural disconnection, may be an important determinant of CI in MS and can be reliably measured through CSF NfL.

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Authors and Affiliations

  1. Section of Neurology, Department of Medicine, Santa Maria Della Misericordia Hospital, University of Perugia, 06132, Perugia, Italy

    Lorenzo Gaetani, Nicola Salvadori, Viviana Lisetti, Paolo Eusebi, Andrea Mancini, Lucia Gentili, Angela Borrelli, Paola Sarchielli, Lucilla Parnetti, Paolo Calabresi & Massimiliano Di Filippo

  2. SOC Neurologia, San Giovanni Di Dio Hospital, AUSL Toscana Centro, Florence, Italy

    Emilio Portaccio

  3. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy At the University of Gothenburg, Mölndal, Sweden

    Kaj Blennow & Henrik Zetterberg

  4. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

    Kaj Blennow & Henrik Zetterberg

  5. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK

    Henrik Zetterberg

  6. UK Dementia Research Institute at UCL, London, UK

    Henrik Zetterberg

  7. IRCCS Fondazione Santa Lucia, Rome, Italy

    Paolo Calabresi

Authors
  1. Lorenzo Gaetani
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  2. Nicola Salvadori
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  3. Viviana Lisetti
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  4. Paolo Eusebi
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  5. Andrea Mancini
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  6. Lucia Gentili
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  7. Angela Borrelli
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  8. Emilio Portaccio
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  11. Henrik Zetterberg
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  12. Lucilla Parnetti
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  13. Paolo Calabresi
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  14. Massimiliano Di Filippo
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Corresponding author

Correspondence to Lorenzo Gaetani.

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Conflicts of interest

LGa participated on advisory boards for and received speaker or writing honoraria and funding for travelling from Almirall, Biogen, Biogen-Idec, Genzyme, Mylan, Novartis, Roche, Teva. AM received travel grants from Teva and Sanofi Genzyme to attend national conferences. PC received/receive research support from Bayer Schering, Biogen-Dompé, Boehringer Ingelheim, Eisai, Lundbeck, Merck-Serono, Novartis, Sanofi-Aventis, Sigma-Tau, and UCB Pharma. KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. HZ has served at advisory boards for Eli Lilly, Roche Diagnostics and Pharmasum Therapeutics and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. MDF participated on advisory boards for and received speaker or writing honoraria and funding for travelling from Bayer, Biogen Idec, Genzyme, Merck, Novartis, Roche and Teva. NS, VL, PE, LGe AB, EP, PS and LP report no conflict of interest.

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The study was approved by the local ethics committee.

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Gaetani, L., Salvadori, N., Lisetti, V. et al. Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. J Neurol 266, 2157–2163 (2019). https://doi.org/10.1007/s00415-019-09398-7

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  • DOI: https://doi.org/10.1007/s00415-019-09398-7

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