Abstract
Background and Objectives To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS).
Methods Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment.
Results Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT.
Discussion Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.
Glossary
- BDI=
- Beck Depression Inventory;
- BPF=
- brain parenchymal fraction;
- BRB-N=
- Brief Repeatable Battery of Neuropsychological Tests;
- CAT=
- Computation Anatomy Toolbox;
- CI=
- cognitively impaired;
- CP=
- cognitively preserved;
- CT=
- cortical thickness;
- EDSS=
- Expanded Disability Status Scale;
- FDR=
- false discovery rate;
- FIRST=
- FMRIB's Integrated Registration and Segmentation Tool;
- FLAIR=
- fluid-attenuated inversion recovery;
- FSS=
- fatigue severity scale;
- GM=
- gray matter;
- GMF=
- gray matter fraction;
- HC=
- healthy control;
- IFOG=
- inferior frontal orbital frontal gyrus;
- MS=
- multiple sclerosis;
- NI=
- neuropsychological impairment;
- ROI=
- regions of interest;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SDMT=
- Symbol Digit Modalities Test; secondary progressive MS;
- sNfL=
- serum neurofilament light chain;
- SP=
- secondary progressive;
- SRT=
- Selective Reminding Test;
- STAI=
- State-Trait Anxiety Inventory;
- TTG=
- transverse temporal gyrus;
- WM=
- white matter;
- ZG=
- global cognitive Z score
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by Spanish Ministry of Science, Innovation and Universities and the Institute of Biomedical Research and Innovation of Cadiz (INiBICA).
- Received February 18, 2021.
- Accepted in final form July 13, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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