Increased cortical and deep grey matter sodium concentration is associated with physical and cognitive disability in relapse-onset multiple sclerosis.

WJ Brownlee, Patricia Alves Da Mota, Ferran Prados, Bhavana S Solanky, Frank Riemer, Manuel Jorge Cardoso, Sébastien Ourselin, Xavier Golay, CAM Gandini Wheeler-Kingshott, DH Miller, O Ciccarelli

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Abstract

Background: 23Na-MRI is a novel approach to investigating neuroaxonal metabolic dysfunction and neuroaxonal loss in vivo in people with multiple sclerosis (MS). Objective: To investigate the relationship of tissue-specific total sodium concentration (TSC) with disease course and disability in relapse-onset MS. Methods: 70 MS patients (57 relapsing-remitting MS [RRMS] and 13 secondary progressive MS [SPMS], mean disease duration 14.7 years, all followed from disease onset) and 32 healthy controls (HC) had 23Na and 1H-MRI. The TSC in cortical grey matter (CGM), deep grey matter (DGM), normal-appearing white matter (NAWM), T1-isointense and T1-hypointense lesions was calculated. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), timed 25-foot walk test (TWT) and 9-hole peg test (9HPT). Cognition was assessed using the paced auditory serial addition test (PASAT), symbol digit modalities test (SDMT) and tests of verbal and visual memory. Linear regression was used to compare differences in tissue TSC between groups. Multivariable linear regression was used to identify independent associations between TSC and disability with adjustment for age, sex, disease duration, grey/white matter tissue volumes. Results: In MS patients the median EDSS was 2 (range 0-7) and 27 (40%) were cognitively impaired. The brain parenchymal, grey matter and white matter fractions were lower in MS patients compared with HC (p< 0.05). TSC in CGM, DGM and NAWM was higher in MS patients compared with HC (p< 0.01) and higher in T1-hypointense than T1-isointense lesions (p< 0.01). TSC was higher in all tissues and both lesion types in SPMS compared with RRMS patients (p< 0.01). In the multivariable linear regression models, higher CGM sodium concentration was associated with physical disability as measured by the EDSS (β= 0.26, 95%CI 0.16,0.36, R2=0.36) and TWT (β= -0.01, 95%CI -0.013,-0.006, R2=0.42) and higher DGM sodium concentration was associated with cognitive dysfunction as measured by PASAT (β=-0.13, 95%CI -0.19, -0.07, R2=0.35), SDMT (β= -0.18, 95%CI -0.26, -0.11, R2=0.40) and visual memory (β=-0.06, 95%CI -0.11, -.0.02, R2=0.19). Conclusion: Sodium accumulation in cortical and deep grey matter may reflect underlying neurodegeneration that is relevant to the development of long-term disability and cognitive impairment in relapse-onset MS. 23Na-MRI may become a secondary outcome measure in clinical trials of neuroprotective agents.
OriginalsprogEngelsk
Publikationsdato2016
StatusUdgivet - 2016
Begivenhed32nd ECTRIMS Congress - London, Storbritannien
Varighed: 14 sep. 201617 sep. 2016

Konference

Konference32nd ECTRIMS Congress
Land/OmrådeStorbritannien
ByLondon
Periode14/09/201617/09/2016

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