Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Federico Verde, Petra Steinacker, Jochen H Weishaupt, Jan Kassubek, Patrick Oeckl, Steffen Halbgebauer, Hayrettin Tumani, Christine A F von Arnim, Johannes Dorst, Emily Feneberg, Benjamin Mayer, Hans-Peter Müller, Martin Gorges, Angela Rosenbohm, Alexander E Volk, Vincenzo Silani, Albert C Ludolph, Markus Otto

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).

METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.

RESULTS: Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.

CONCLUSIONS: Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalJournal of neurology, neurosurgery, and psychiatry
Volume90
Issue number2
DOIs
Publication statusPublished - Feb 2019

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Intermediate Filaments
Amyotrophic Lateral Sclerosis
Light
Serum
Creutzfeldt-Jakob Syndrome
Neurodegenerative Diseases
Frontotemporal Dementia
Diffusion Tensor Imaging
Parkinson Disease
Longitudinal Studies
Disease Progression
Alzheimer Disease
Differential Diagnosis
Biomarkers
Prospective Studies
Technology
Survival

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Verde, F., Steinacker, P., Weishaupt, J. H., Kassubek, J., Oeckl, P., Halbgebauer, S., ... Otto, M. (2019). Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. Journal of neurology, neurosurgery, and psychiatry, 90(2), 157-164. https://doi.org/10.1136/jnnp-2018-318704

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. / Verde, Federico; Steinacker, Petra; Weishaupt, Jochen H; Kassubek, Jan; Oeckl, Patrick; Halbgebauer, Steffen; Tumani, Hayrettin; von Arnim, Christine A F; Dorst, Johannes; Feneberg, Emily; Mayer, Benjamin; Müller, Hans-Peter; Gorges, Martin; Rosenbohm, Angela; Volk, Alexander E; Silani, Vincenzo; Ludolph, Albert C; Otto, Markus.

In: Journal of neurology, neurosurgery, and psychiatry, Vol. 90, No. 2, 02.2019, p. 157-164.

Research output: Contribution to journalArticle

Verde, F, Steinacker, P, Weishaupt, JH, Kassubek, J, Oeckl, P, Halbgebauer, S, Tumani, H, von Arnim, CAF, Dorst, J, Feneberg, E, Mayer, B, Müller, H-P, Gorges, M, Rosenbohm, A, Volk, AE, Silani, V, Ludolph, AC & Otto, M 2019, 'Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis', Journal of neurology, neurosurgery, and psychiatry, vol. 90, no. 2, pp. 157-164. https://doi.org/10.1136/jnnp-2018-318704
Verde, Federico ; Steinacker, Petra ; Weishaupt, Jochen H ; Kassubek, Jan ; Oeckl, Patrick ; Halbgebauer, Steffen ; Tumani, Hayrettin ; von Arnim, Christine A F ; Dorst, Johannes ; Feneberg, Emily ; Mayer, Benjamin ; Müller, Hans-Peter ; Gorges, Martin ; Rosenbohm, Angela ; Volk, Alexander E ; Silani, Vincenzo ; Ludolph, Albert C ; Otto, Markus. / Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. In: Journal of neurology, neurosurgery, and psychiatry. 2019 ; Vol. 90, No. 2. pp. 157-164.
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abstract = "OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.RESULTS: Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5{\%} sensitivity (95{\%} CI 78{\%} to 91.2{\%}) and 81.8{\%} specificity (95{\%} CI 74.9{\%} to 87.4{\%}). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95{\%} CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.CONCLUSIONS: Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.",
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T1 - Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

AU - Verde, Federico

AU - Steinacker, Petra

AU - Weishaupt, Jochen H

AU - Kassubek, Jan

AU - Oeckl, Patrick

AU - Halbgebauer, Steffen

AU - Tumani, Hayrettin

AU - von Arnim, Christine A F

AU - Dorst, Johannes

AU - Feneberg, Emily

AU - Mayer, Benjamin

AU - Müller, Hans-Peter

AU - Gorges, Martin

AU - Rosenbohm, Angela

AU - Volk, Alexander E

AU - Silani, Vincenzo

AU - Ludolph, Albert C

AU - Otto, Markus

N1 - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2019/2

Y1 - 2019/2

N2 - OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.RESULTS: Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.CONCLUSIONS: Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

AB - OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.RESULTS: Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.CONCLUSIONS: Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

U2 - 10.1136/jnnp-2018-318704

DO - 10.1136/jnnp-2018-318704

M3 - Article

VL - 90

SP - 157

EP - 164

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 2

ER -