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Cerebrospinal fluid NCAM levels are modulated by disease-modifying therapies

Artikel i vetenskaplig tidskrift
Författare Markus Axelsson
N. Dubuisson
Lenka Novakova
Clas Malmeström
G. Giovannoni
Jan Lycke
S. Gnanapavan
Publicerad i Acta Neurologica Scandinavica
Volym 139
Nummer/häfte 5
Sidor 411-427
ISSN 0001-6314
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Sidor 411-427
Språk en
Länkar dx.doi.org/10.1111/ane.13069
Ämnesord Cerebrospinal fluid (CSF), Disease-modifying therapies (DMTs), EDSS, Multiple sclerosis (MS), Soluble neural cell adhesion molecule (sNCAM)
Ämneskategorier Neurovetenskaper

Sammanfattning

Background: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. Methods: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. Results: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole. Conclusions: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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