Abstract
Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC). Biomarkers were related to Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) over a long period of follow-up [median (interquartile range) 9 (5.5–12.5) years] in 19 PPMS and 4 SPMS patients, and to T2 lesion load, T1 lesion load, and brain parenchymal fraction at the time of lumbar puncture. Nf light was higher in PPMS (p < 0.005) and Nf heavy was increased in both SPMS and PPMS (p < 0.05 and p < 0.01) compared to NINDC, but were comparable between the two MS subtypes. Nf heavy was a predictor of the ongoing disability measured by MSSS (R 2 = 0.17, β = 0.413; p < 0.05). Conversely, Nf light was the only predictor of the EDSS annual increase (R 2 = 0.195, β = 0.441; p < 0.05). The frequency of abnormal biomarkers did not differ between the two MS progressive subtypes. Our data suggest that PP and SPMS likely share similar mechanisms of axonal damage. Moreover, Nf heavy can be a biomarker of ongoing axonal damage. Conversely, Nf light can be used as a prognostic marker for accumulating disability suggesting it as a good tool for possible treatment monitoring in the progressive MS forms.
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Acknowledgments
This study was performed in the context of the BioMS-eu network (http://www.bioms.eu).
Conflicts of interest
The authors declare no financial or other conflicts of interest. In addition, Dr. Korth has a patent EPA 05715297.7-2403 issued. Dr. Teunissen provided consultation for Fujirebio/Innogenetics, and for Roche International Advisory Board; received a grant from Grant of National Science Foundation for joint Programming project BIOMARKAPD, outside the submitted work. In addition, Dr. Teunissen has a patent Novel CSF biomarkers for Alzheimer’s disease pending, and a patent Bri2 as a biomarker for Alzheimer’s disease pending. Dr Killestein received grants from Biogen Idec, Bayer Schering, Teva, Merck-Serono, Genzyme, Novartis, Glaxo SK, UCB. Dr. Tintore reports personal fees and non-financial support for scientific meetings from Biogen-Idec, Bayer, Merck-Serono, Genzyme, Novartis, Teva and Sanofi-Aventis outside the submitted work.
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This study have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.
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Trentini, A., Comabella, M., Tintoré, M. et al. N-Acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis. J Neurol 261, 2338–2343 (2014). https://doi.org/10.1007/s00415-014-7507-4
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DOI: https://doi.org/10.1007/s00415-014-7507-4