Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis
Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis
Background: Studies on the capability of cerebrospinal fluid neurofilament light chain (cNfL) to predict multiple sclerosis (MS) conversion in clinically isolated syndromes have yielded varying results. Objectives: To expand our understanding of cNfL in optic neuritis (ON) and investigate whether incorporating cNfL into the 2017 McDonald criteria could accelerate the diagnosis of MS in patients with ON. Methods: cNfL was measured in diagnostic samples from 74 patients with verified ON. MS was diagnosed using the 2017 McDonald criteria with a minimum observation time of two years from ON onset. Results: 20.5% of 44 MS-converters did not fulfil the 2017 McDonald criteria at ON onset. A doubling of cNfL was associated with 207% (74%–514%) higher odds of MS (p = 0.00042, adjusted for age). Fulfilment of ≥ 1 MRI criterion for dissemination in space (DIS) and presence of brain contrast-enhancing lesions were associated with higher cNfL. Furthermore, cNfL correlated with inter-eye differences in retinal nerve fiber layer (RNFL) thickness (Spearman’s ρ = 0.46, p = 8 × 10
–5). Incorporating cNfL ≥ 906 pg/mL as a substitute for either dissemination in time or one MRI criterion for DIS increased the sensitivity (90.9% vs. 79.6%) and accuracy (91.9% vs. 87.8%), but also reduced the specificity (93.3% vs. 100%) of the 2017 McDonald criteria. Conclusion: cNfL was related to MS diagnostic parameters and the degree of RNFL swelling. Clinical use of cNfL may aid in identification of ON patients with increased risk of MS until larger studies have elaborated on the potential loss of specificity if used diagnostically.
Biomarkers, Clinically isolated syndrome, Early diagnosis, Multiple sclerosis, Neurofilament light chain, Optic neuritis
6127-6135
Passali, Moschoula
28de59d8-0870-4f75-adad-70173ea8c568
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Knudsen, Maria Højberg
d103f1f2-62f9-499e-a091-c7ddac0328d0
Lau, Laurie Chi
2af8045d-6162-4939-aba7-28dd2f60f6a8
Cramer, Stig Præstekjær
ed3fe479-8e5e-4e38-bc02-bac30263db63
Frederiksen, Jette Lautrup
59c78865-41b1-4641-85a0-ab25f67841ad
25 July 2024
Passali, Moschoula
28de59d8-0870-4f75-adad-70173ea8c568
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Knudsen, Maria Højberg
d103f1f2-62f9-499e-a091-c7ddac0328d0
Lau, Laurie Chi
2af8045d-6162-4939-aba7-28dd2f60f6a8
Cramer, Stig Præstekjær
ed3fe479-8e5e-4e38-bc02-bac30263db63
Frederiksen, Jette Lautrup
59c78865-41b1-4641-85a0-ab25f67841ad
Passali, Moschoula, Galea, Ian, Knudsen, Maria Højberg, Lau, Laurie Chi, Cramer, Stig Præstekjær and Frederiksen, Jette Lautrup
(2024)
Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis.
Journal of Neurology, 271 (9), .
(doi:10.1007/s00415-024-12587-8).
Abstract
Background: Studies on the capability of cerebrospinal fluid neurofilament light chain (cNfL) to predict multiple sclerosis (MS) conversion in clinically isolated syndromes have yielded varying results. Objectives: To expand our understanding of cNfL in optic neuritis (ON) and investigate whether incorporating cNfL into the 2017 McDonald criteria could accelerate the diagnosis of MS in patients with ON. Methods: cNfL was measured in diagnostic samples from 74 patients with verified ON. MS was diagnosed using the 2017 McDonald criteria with a minimum observation time of two years from ON onset. Results: 20.5% of 44 MS-converters did not fulfil the 2017 McDonald criteria at ON onset. A doubling of cNfL was associated with 207% (74%–514%) higher odds of MS (p = 0.00042, adjusted for age). Fulfilment of ≥ 1 MRI criterion for dissemination in space (DIS) and presence of brain contrast-enhancing lesions were associated with higher cNfL. Furthermore, cNfL correlated with inter-eye differences in retinal nerve fiber layer (RNFL) thickness (Spearman’s ρ = 0.46, p = 8 × 10
–5). Incorporating cNfL ≥ 906 pg/mL as a substitute for either dissemination in time or one MRI criterion for DIS increased the sensitivity (90.9% vs. 79.6%) and accuracy (91.9% vs. 87.8%), but also reduced the specificity (93.3% vs. 100%) of the 2017 McDonald criteria. Conclusion: cNfL was related to MS diagnostic parameters and the degree of RNFL swelling. Clinical use of cNfL may aid in identification of ON patients with increased risk of MS until larger studies have elaborated on the potential loss of specificity if used diagnostically.
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s00415-024-12587-8
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More information
Accepted/In Press date: 16 July 2024
e-pub ahead of print date: 25 July 2024
Published date: 25 July 2024
Keywords:
Biomarkers, Clinically isolated syndrome, Early diagnosis, Multiple sclerosis, Neurofilament light chain, Optic neuritis
Identifiers
Local EPrints ID: 492765
URI: http://eprints.soton.ac.uk/id/eprint/492765
ISSN: 0340-5354
PURE UUID: 451c42d5-df10-4163-b624-ce9143b88ab7
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Date deposited: 13 Aug 2024 16:56
Last modified: 19 Dec 2024 02:38
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Contributors
Author:
Moschoula Passali
Author:
Maria Højberg Knudsen
Author:
Laurie Chi Lau
Author:
Stig Præstekjær Cramer
Author:
Jette Lautrup Frederiksen
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