OBJECTIVE: Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. METHODS: We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. RESULTS: Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10-4 ; p < 0.001), TNF (β = 3.1*10-3 ; p = 0.004), LIGHT (β = 2.6*10-4 ; p = 0.003), sCD163 (β = 4.3*10-3 ; p = 0.009), and TWEAK (β = 3.4*10-3 ; p = 0.024) were associated with more severe cortical thinning. INTERPRETATION: A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.
OBJECTIVE: Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. METHODS: We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. RESULTS: Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10-4 ; p < 0.001), TNF (β = 3.1*10-3 ; p = 0.004), LIGHT (β = 2.6*10-4 ; p = 0.003), sCD163 (β = 4.3*10-3 ; p = 0.009), and TWEAK (β = 3.4*10-3 ; p = 0.024) were associated with more severe cortical thinning. INTERPRETATION: A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.
Authors: Lynn van Olst; Carla Rodriguez-Mogeda; Carmen Picon; Svenja Kiljan; Rachel E James; Alwin Kamermans; Susanne M A van der Pol; Lydian Knoop; Iliana Michailidou; Evelien Drost; Marc Franssen; Geert J Schenk; Jeroen J G Geurts; Sandra Amor; Nicholas D Mazarakis; Jack van Horssen; Helga E de Vries; Richard Reynolds; Maarten E Witte Journal: Acta Neuropathol Date: 2021-03-29 Impact factor: 17.088
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Authors: Lida Zoupi; Sam A Booker; Dimitri Eigel; Carsten Werner; Peter C Kind; Tara L Spires-Jones; Ben Newland; Anna C Williams Journal: Acta Neuropathol Date: 2021-01-15 Impact factor: 17.088
Authors: Carmen Picon; Anusha Jayaraman; Rachel James; Catriona Beck; Patricia Gallego; Maarten E Witte; Jack van Horssen; Nicholas D Mazarakis; Richard Reynolds Journal: Acta Neuropathol Date: 2021-02-10 Impact factor: 17.088
Authors: Roberta Magliozzi; Valentina Mazziotti; Luigi Montibeller; Anna I Pisani; Damiano Marastoni; Agnese Tamanti; Stefania Rossi; Francesco Crescenzo; Massimiliano Calabrese Journal: Front Cell Neurosci Date: 2020-10-16 Impact factor: 5.505