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Open Access 27-03-2024 | Multiple Sclerosis | Original Communication

Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury

Authors: Martin A. Schaller-Paule, Michelle Maiworm, Jan Hendrik Schäfer, Lucie Friedauer, Elke Hattingen, Katharina Johanna Wenger, Frank Weber, Jasmin Jakob, Falk Steffen, Stefan Bittner, Yavor Yalachkov, Christian Foerch

Published in: Journal of Neurology

Abstract

Background

Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)).

Methods

We recruited 77 patients with relapsing–remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse.

Results

After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (p_sNfL = 0.00008; p_cNfL = 0.004) as well as the presence of infratentorial lesions on MRI (p_sNfL = 0.0003; p_cNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (p_sNfL = 0.001), presence of more than 20 T2-lesions (p_sNfL = 0.049) as well as the presence of infratentorial lesions on MRI (p_sNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (p_sNfL = 0.011) and presence of more than 20 T2-lesions (p_sNfL = 0.029).

Conclusions

Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.

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Title: Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury
Authors: Martin A. Schaller-Paule
Michelle Maiworm
Jan Hendrik Schäfer
Lucie Friedauer
Elke Hattingen
Katharina Johanna Wenger
Frank Weber
Jasmin Jakob
Falk Steffen
Stefan Bittner
Yavor Yalachkov
Christian Foerch
Publication date: 27-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Sclerosis
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Biomarkers
Published in: Journal of Neurology
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-024-12299-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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