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January 2021; 8 (1) ArticleOpen Access

High serum neurofilament associates with diffuse white matter damage in MS

View ORCID ProfileMaija Saraste, View ORCID ProfileSvetlana Bezukladova, View ORCID ProfileMarkus Matilainen, View ORCID ProfileJouni Tuisku, Eero Rissanen, Marcus Sucksdorff, Sini Laaksonen, Anna Vuorimaa, Jens Kuhle, David Leppert, Laura Airas
First published December 8, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000926
Maija Saraste
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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  • ORCID record for Maija Saraste
Svetlana Bezukladova
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Markus Matilainen
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Jouni Tuisku
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Eero Rissanen
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Marcus Sucksdorff
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Sini Laaksonen
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Anna Vuorimaa
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Jens Kuhle
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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David Leppert
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Laura Airas
From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.
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Citation
High serum neurofilament associates with diffuse white matter damage in MS
Maija Saraste, Svetlana Bezukladova, Markus Matilainen, Jouni Tuisku, Eero Rissanen, Marcus Sucksdorff, Sini Laaksonen, Anna Vuorimaa, Jens Kuhle, David Leppert, Laura Airas
Neurol Neuroimmunol Neuroinflamm Jan 2021, 8 (1) e926; DOI: 10.1212/NXI.0000000000000926

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    Figure 1 Correlation of serum NfL and DTI indices of the whole NAWM in the NfL(high) subgroup

    The serum level of NfL is moderately associated with fractional anisotropy (A), mean diffusivity (B), axial diffusivity (C), and radial diffusivity (D). The NfL(high) subgroup is comprised of patients with serum NfL above the median value of healthy controls (23.1 pg/mL). Shown are Spearman correlation coefficients (ρ) and p values. The black lines indicate the level and direction of the relationship. AD = axial diffusivity; DTI = diffusion tensor imaging; FA = fractional anisotropy; MD = mean diffusivity; NAWM = normal-appearing white matter; NfL = neurofilament light chain; RD = radial diffusivity.

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    Figure 2 The effect of DTI-MRI indices or volumetric MRI data on NfL in the NfL(high) subgroup

    The NfL(high) subgroup is comprised of patients with serum NfL above the median value of healthy controls (23.1 pg/mL). Logarithmic serum NfL was modeled separately by DTI indices of the entire and parcellated NAWM and volumetric brain MRI data using multiple regression analyses. Models were adjusted by sex, age, disease type (RRMS/SPMS), the EDSS score, treatment (no, first, and second line), and presence of relapses within 1 year before sampling (yes/no). The results are illustrated using dot and whisker plots in which red dots represent standardized regression coefficients and red lines represent the CIs of the estimates. Significant p values of the DTI parameters and the percentage of variance in the response that can be explained by the independent variables (R2) are also shown. The results were ordered according to the R2 value. All except 2 of the p values (fractional anisotropy of the frontal and deep NAWM) shown in the figure remained significant after adjustment using the false discovery rate method for the number of investigated variables (n = 32). AD = axial diffusivity; DTI = diffusion tensor imaging; EDSS = Expanded Disability Status Scale; FA = fractional anisotropy; GMctx = cortical gray matter; MD = mean diffusivity; NAWM = normal-appearing white matter; NfL = neurofilament light chain; PF = parenchymal fraction; RD = radial diffusivity; RRMS = relapsing-remitting MS; SPMS = secondary progressive MS; WM = white matter.

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