eprintid: 10056837 rev_number: 22 eprint_status: archive userid: 608 dir: disk0/10/05/68/37 datestamp: 2018-09-26 15:40:42 lastmod: 2021-09-19 22:21:17 status_changed: 2018-09-26 15:40:42 type: article metadata_visibility: show creators_name: Håkansson, I creators_name: Tisell, A creators_name: Cassel, P creators_name: Blennow, K creators_name: Zetterberg, H creators_name: Lundberg, P creators_name: Dahle, C creators_name: Vrethem, M creators_name: Ernerudh, J title: Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Multiple sclerosis, Clinically isolated syndrome, Disease activity, Neurofilament light chain, CHI3L1, CXCL10, Brain volume note: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). abstract: BACKGROUND: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. METHODS: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. “No evidence of disease activity-3” (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI®) were recorded during 4 years of follow-up. RESULTS: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p < 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. CONCLUSIONS: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively. date: 2018-12 date_type: published publisher: BMC official_url: https://doi.org/10.1186/s12974-018-1249-7 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1571568 doi: 10.1186/s12974-018-1249-7 language_elements: English lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Journal of Neuroinflammation volume: 15 number: 1 article_number: 209 pages: 10 issn: 1742-2094 citation: Håkansson, I; Tisell, A; Cassel, P; Blennow, K; Zetterberg, H; Lundberg, P; Dahle, C; ... Ernerudh, J; + view all <#> Håkansson, I; Tisell, A; Cassel, P; Blennow, K; Zetterberg, H; Lundberg, P; Dahle, C; Vrethem, M; Ernerudh, J; - view fewer <#> (2018) Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis. Journal of Neuroinflammation , 15 (1) , Article 209. 10.1186/s12974-018-1249-7 <https://doi.org/10.1186/s12974-018-1249-7>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10056837/1/Zetterberg_Neurofilament%20levels%2C%20disease%20activity%20and%20brain%20volume%20during%20follow-up%20in%20multiple%20sclerosis_VoR.pdf