Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis.

Disanto, Giulio; Barro, Christian; Benkert, Pascal; Naegelin, Yvonne; Schädelin, Sabine; Giardiello, Antonella; Zecca, Chiara; Blennow, Kaj; Zetterberg, Henrik; Leppert, David; Kappos, Ludwig; Gobbi, Claudio; Kuhle, Jens (2017). Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Annals of neurology, 81(6), pp. 857-870. Wiley-Blackwell 10.1002/ana.24954

[img]
Preview
Text
Disanto_et_al-2017-Annals_of_Neurology.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (2MB) | Preview

OBJECTIVE Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS). METHODS sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes. RESULTS sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease-modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034). INTERPRETATION These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857-870.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0364-5134

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Stefanie Hetzenecker

Date Deposited:

15 Feb 2018 10:54

Last Modified:

26 Oct 2019 08:18

Publisher DOI:

10.1002/ana.24954

PubMed ID:

28512753

Additional Information:

Anke Salmen (Universitätsklinik für Neurologie) ist Teil der Swiss Multiple Sclerosis Cohort Study Group.

BORIS DOI:

10.7892/boris.110596

URI:

https://boris.unibe.ch/id/eprint/110596

Actions (login required)

Edit item Edit item
Provide Feedback