Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis

Lorenzo Gaetani, Nicola Salvadori, Viviana Lisetti, Paolo Eusebi, Andrea Mancini, Lucia Gentili, Angela Borrelli, Emilio Portaccio, Paola Sarchielli, Kaj Blennow, Henrik Zetterberg, Lucilla Parnetti, Paolo Calabresi, Massimiliano Di Filippo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2157-2163
Number of pages7
JournalJournal of Neurology
Volume266
Issue number9
DOIs
Publication statusPublished - Sep 1 2019

Fingerprint

Intermediate Filaments
Multiple Sclerosis
Cerebrospinal Fluid
Light
Neuropsychological Tests
Automatic Data Processing
Axons
Cognitive Dysfunction
Multivariate Analysis
Wounds and Injuries

Keywords

  • Cerebrospinal fluid
  • Cognitive impairment
  • Information processing speed
  • Multiple sclerosis
  • Neurofilament light chain
  • Verbal fluency

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Gaetani, L., Salvadori, N., Lisetti, V., Eusebi, P., Mancini, A., Gentili, L., ... Di Filippo, M. (2019). Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. Journal of Neurology, 266(9), 2157-2163. https://doi.org/10.1007/s00415-019-09398-7

Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. / Gaetani, Lorenzo; Salvadori, Nicola; Lisetti, Viviana; Eusebi, Paolo; Mancini, Andrea; Gentili, Lucia; Borrelli, Angela; Portaccio, Emilio; Sarchielli, Paola; Blennow, Kaj; Zetterberg, Henrik; Parnetti, Lucilla; Calabresi, Paolo; Di Filippo, Massimiliano.

In: Journal of Neurology, Vol. 266, No. 9, 01.09.2019, p. 2157-2163.

Research output: Contribution to journalArticle

Gaetani, L, Salvadori, N, Lisetti, V, Eusebi, P, Mancini, A, Gentili, L, Borrelli, A, Portaccio, E, Sarchielli, P, Blennow, K, Zetterberg, H, Parnetti, L, Calabresi, P & Di Filippo, M 2019, 'Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis', Journal of Neurology, vol. 266, no. 9, pp. 2157-2163. https://doi.org/10.1007/s00415-019-09398-7
Gaetani L, Salvadori N, Lisetti V, Eusebi P, Mancini A, Gentili L et al. Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. Journal of Neurology. 2019 Sep 1;266(9):2157-2163. https://doi.org/10.1007/s00415-019-09398-7
Gaetani, Lorenzo ; Salvadori, Nicola ; Lisetti, Viviana ; Eusebi, Paolo ; Mancini, Andrea ; Gentili, Lucia ; Borrelli, Angela ; Portaccio, Emilio ; Sarchielli, Paola ; Blennow, Kaj ; Zetterberg, Henrik ; Parnetti, Lucilla ; Calabresi, Paolo ; Di Filippo, Massimiliano. / Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis. In: Journal of Neurology. 2019 ; Vol. 266, No. 9. pp. 2157-2163.
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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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AU - Salvadori, Nicola

AU - Lisetti, Viviana

AU - Eusebi, Paolo

AU - Mancini, Andrea

AU - Gentili, Lucia

AU - Borrelli, Angela

AU - Portaccio, Emilio

AU - Sarchielli, Paola

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Parnetti, Lucilla

AU - Calabresi, Paolo

AU - Di Filippo, Massimiliano

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N2 - 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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