Prognostic value of intrathecal IgM synthesis determined by various laboratory methods in patients with early multiple sclerosis - a prospective observational study

Revendová, Kamila; Zeman, David; Kušnierová, Pavlína; Bunganic, R.; Hanzlíková, Pavla; Karasova, Katerina; Volný, Ondřej; Bar, Michal

doi:10.1016/j.msard.2022.103847

Cited by 2 publications

(5 citation statements)

References 37 publications

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Section: Discussionmentioning

confidence: 97%

“…Recently, another approach to analyse the intrathecal fraction of Ig synthesis has been proposed by Auer et al (46). The Auer formula has been shown to have less false positives compared to the Reiber formula, but in a recent study that compared all quantitative formulas to analyse IgM, results did not significantly differ in terms of prognostic value (47). The reason why ITMS in comparison to ITGS shows both in our analysis as well as in previously published data (12,20) a more convincing prognostic value is not completely known.…”

Section: Discussionmentioning

confidence: 99%

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Increased intrathecal neurofilament light and immunoglobulin M predict severe disability in relapsing-remitting multiple sclerosis

et al. 2022

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BackgroundEmerging evidence supports that determination of intrathecal immunoglobulin M (IgM) synthesis (ITMS) and neurofilament light (NfL) concentration in cerebrospinal fluid (CSF) may be clinically useful as disease severity biomarkers in relapsing-remitting multiple sclerosis (RRMS).MethodsMonocentric observational longitudinal cohort study in which prospectively collected data were retrospectively retrieved. Included were patients with RRMS (n=457) who had a diagnostic investigation including analysis of ITMS and CSF neurofilament light (cNfL). ITMS was calculated with the linear index formula, the intrathecal fraction of IgM according to Reiber (IgMIF), and by qualitative determination of oligoclonal IgM bands (OCMB). Univariable and multivariable models were performed to predict Evidence of Disease Activity-3 (EDA-3) status within 24 months from onset, and the risk of Expanded Disability Status Score (EDSS) ≥3 and ≥6.ResultsAll investigated methods to calculate ITMS significantly predicted evidence of disease activity (EDA-3) within 24 months. IgMIF>0% showed the strongest association with EDA-3 status (adjusted hazard ratio [aHR] 3.7, 95%CI 2.7-5, p<0.001). Combining IgM-index>0.1 or OCMB with increased cNfL were strong predictors of EDSS≥3 (for cNfL+/IgM-index+: aHR 4.6, 95%CI 2.6-8.2, p<0.001) and EDSS≥6 (aHR 8.2, 95%CI 2.3-30, p<0.001).ConclusionsIn a real-world setting, ITMS was a useful biomarker in early RRMS to predict disabling MS and its prognostic value was even stronger in combination with cNfL. Our data suggest that determination of ITMS and cNfL should be included in the diagnostic work-up of RRMS for prognostic purposes and in decisions of disease-modifying therapy.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Increased intrathecal neurofilament light and immunoglobulin M predict severe disability in relapsing-remitting multiple sclerosis

et al. 2022

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“…The standard MS protocol for the brain is comprised of the T2W TSE axial, axial fluid-attenuated inverse recovery (T2 TSE FLAIR), axial diffusionweighted imaging (DWI) sequences with b value 0, 500, 1000, and with the automatically computed map of apparent diffusion coefficient (ADC). All sequences were performed in 5 mm layers, gap 20%, T1 GRE MPRAGE 3D and T2 TSE SPACE FLAIR 3D with the acquisition in isometric voxel 1 mm, primarily in the sagittal plane 23,24 . T2 TSE sagittal, T2 GRE medic axial, and T2 TSE Stir sagittal sequences with a layer thickness of 3 mm were acquired on the C spine as a gold standard 24,25 .…”

Section: Mri Scansmentioning

confidence: 99%

“…All sequences were performed in 5 mm layers, gap 20%, T1 GRE MPRAGE 3D and T2 TSE SPACE FLAIR 3D with the acquisition in isometric voxel 1 mm, primarily in the sagittal plane 23,24 . T2 TSE sagittal, T2 GRE medic axial, and T2 TSE Stir sagittal sequences with a layer thickness of 3 mm were acquired on the C spine as a gold standard 24,25 . MRI activity was defined as an evident diffusion-restricted lesion at b 1000 with a correlation on the ADC map -hypersignal margin at b 1000 with a correlation in the hyposignal margin at the ADC, a lesion without explicit restriction or a facilitated diffusion lesion was not evaluated as an active lesion 24,26 .…”

Section: Mri Scansmentioning

confidence: 99%

“…T2 TSE sagittal, T2 GRE medic axial, and T2 TSE Stir sagittal sequences with a layer thickness of 3 mm were acquired on the C spine as a gold standard 24,25 . MRI activity was defined as an evident diffusion-restricted lesion at b 1000 with a correlation on the ADC map -hypersignal margin at b 1000 with a correlation in the hyposignal margin at the ADC, a lesion without explicit restriction or a facilitated diffusion lesion was not evaluated as an active lesion 24,26 . Another marker of MRI activity was defined as progression in time or space according to McDonald and MAGNIMS criteria of a new lesion or enlargement of any existing lesion 19,27 .…”

Section: Mri Scansmentioning

confidence: 99%

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Cerebrospinal fluid neurofilament light chains and CXCL13 as predictive factors for clinical course of multiple sclerosis

Hradílek¹,

Revendová²,

Hořáková³

et al. 2023

BIOMED PAP

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The aim of this study was to identify whether NfL and CXCL13 cerebrospinal fluid (CSF) concentrations at diagnostic lumbar puncture can predict the course of multiple sclerosis (MS) in terms of relapses, higher expanded disability status scale (EDSS) and magnetic resonance imaging (MRI) activity. Methods. We conducted a single-centre prospective observational cohort study at the MS center, University Hospital Ostrava, Czech Republic. CSF NfL (cNfL) and CXCL13 concentrations were examined (ELISA method) in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) at the time of diagnostic lumbar puncture. Results. A total of 44 patients with CIS or early RRMS were enrolled, 31 (70.5%) of whom were women. The median age at the time of CSF sampling was 31.21 years , and the follow-up period was 54.6 months ). In the simple and multiple logistic regression models, CXCL13 levels did not predict relapses, MRI activity or EDSS > 2.5. Similarly, cNfL concentrations did not predict relapses or MRI activity in either model. In the multiple regression, higher cNfL levels were associated with reaching EDSS > 2.5 (odds ratio [OR] 1.002, 95% confidence interval [CI] 1.000 to 1.003). Conclusions. Our data did not confirm cNfL and/or CXCL13 CSF levels were predictive factors for disease activity such as relapses and MRI activity at the time of diagnostic lumbar puncture in patients with RRMS. While cNfL CSF levels predicted higher disability only after adjustment for other known risk factors, elevated CSF CXCL13 did not predict higher disability at all.

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Prognostic value of intrathecal IgM synthesis determined by various laboratory methods in patients with early multiple sclerosis - a prospective observational study

Cited by 2 publications

References 37 publications

Increased intrathecal neurofilament light and immunoglobulin M predict severe disability in relapsing-remitting multiple sclerosis

Increased intrathecal neurofilament light and immunoglobulin M predict severe disability in relapsing-remitting multiple sclerosis

Cerebrospinal fluid neurofilament light chains and CXCL13 as predictive factors for clinical course of multiple sclerosis

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