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Eur J Neurol. 2020 Feb;27(2):251-257. doi: 10.1111/ene.14063. Epub 2019 Sep 18.

Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis.

Author information

1
Service de Neurologie, CHU Nîmes, CNRS, INSERM, Univ Montpellier, Nîmes, France.
2
Département d'Information Médicale, CHU Nîmes, Univ Montpellier, Nîmes, France.
3
Laboratoire de Biochimie et Plateforme de Protéomique Clinique, CHU Montpellier, INSERM, Univ Montpellier, Montpellier, France.
4
Centre de référence SLA, CHU Montpellier, INSERM, Univ Montpellier, Montpellier, France.
5
Laboratoire d'Immunologie, CHU Montpellier, INSERM, Univ Montpellier, Montpellier, France.

Abstract

BACKGROUND AND PURPOSE:

The prognostic value of serum neurofilament light chain (sNfL), a biomarker of neurodegeneration, compared to other prognostic factors of amyotrophic lateral sclerosis (ALS) at the time of diagnosis, remains unclear.

METHODS:

Sera from ALS patients were prospectively collected at the first diagnostic visit in our centre. sNfL levels were determined by single molecule array in 207 ALS patients and in 21 healthy controls. The prognostic value of sNfL was compared with that of other known clinical prognostic factors using a Cox regression model and multivariate analysis.

RESULTS:

Serum neurofilament light chain levels were higher in ALS patients than in controls (P < 0.0001). Seven parameters were predictive of death in ALS: older age, bulbar onset, higher ALS Functional Rating Scale revised (ALSFRS-R) score, greater weight loss, lower maximal inspiratory pressure, forced vital capacity and higher sNfL levels. A Cox regression model showed that sNfL (P < 0.0001), weight loss (P = 0.040) and site at onset (P = 0.048) were independent predictive factors of death. In a sub-cohort restricted to 139 patients with complete spirometry data, sNfL level (P < 0.005) and forced vital capacity (P = 0.022) were independent factors predictive of death. In a subgroup of 142 patients in whom ALSFRS-R score was available at several time points, sNfL levels positively correlated with ALSFRS-R rate of decline (r = 0.571, P < 10-12 ).

CONCLUSIONS:

Higher sNfL concentration is a strong and independent prognostic factor of death in ALS as early as the time of diagnosis.

KEYWORDS:

amyotrophic lateral sclerosis; biomarker; multivariate analysis; neurofilament light chain; prognosis

PMID:
31437330
DOI:
10.1111/ene.14063

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