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Abstract
Objective: To investigate whether brain total sodium accumulation assessed by 23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS).
Methods: Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction).
Results: The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0–4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively.
Conclusions: This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.
GLOSSARY
- ANOVA=
- analysis of variance;
- AUC=
- area under the receiver operating characteristic curve;
- BA=
- Brodmann area;
- CI=
- cognitively impaired;
- CII=
- Cognitive Impairment Index;
- CP=
- cognitively preserved;
- EDSS=
- Expanded Disability Status Scale;
- FDR=
- false discovery rate;
- FOV=
- field of view;
- GM=
- gray matter;
- GMF=
- gray matter fraction;
- HC=
- healthy controls;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- MR=
- magnetic resonance;
- MS=
- multiple sclerosis;
- NAWM=
- normal-appearing white matter;
- RRMS=
- relapsing-remitting multiple sclerosis;
- TE=
- echo time;
- TR=
- repetition time;
- TSC=
- total sodium concentration;
- WM=
- white matter;
- WMF=
- white matter fraction
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received April 4, 2016.
- Accepted in final form October 6, 2016.
- © 2016 American Academy of Neurology
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