Contributions
Abstract: 140
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
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.
Disclosure:
Dr Brownlee has nothing to disclose.
Miss Alves Da Mota has nothing to disclose.
Dr Prados has nothing to disclose.
Dr Solanky has nothing to disclose.
Dr Riemer has nothing to disclose.
Dr Cardoso has nothing to disclose.
Prof Ourselin has nothing to disclose.
Prof Golay has nothing to disclose.
Prof Gandini Wheeler-Kingshott is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis.
Prof Miller has received honoraria through payments to UCL Institute of Neurology from Biogen-Idec, Novaritis, Bayer-Schering and Mitsubishi Pharma Europe.
Prof Ciccarelli is an Associate Editor of Neurology and serves as a consultant for GE Healthcare, Novartis, Roche, Biogen, Genzyme and Teva.
Abstract: 140
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Imaging
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.
Disclosure:
Dr Brownlee has nothing to disclose.
Miss Alves Da Mota has nothing to disclose.
Dr Prados has nothing to disclose.
Dr Solanky has nothing to disclose.
Dr Riemer has nothing to disclose.
Dr Cardoso has nothing to disclose.
Prof Ourselin has nothing to disclose.
Prof Golay has nothing to disclose.
Prof Gandini Wheeler-Kingshott is on the editorial board of Functional Neurology and receives research grants (PI and co-applicant) from ISRT, EPSRC, Wings for Life, UK MS Society, Horizon2020, Biogen and Novartis.
Prof Miller has received honoraria through payments to UCL Institute of Neurology from Biogen-Idec, Novaritis, Bayer-Schering and Mitsubishi Pharma Europe.
Prof Ciccarelli is an Associate Editor of Neurology and serves as a consultant for GE Healthcare, Novartis, Roche, Biogen, Genzyme and Teva.