Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

BACKGROUND: Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). OBJECTIVES: To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. METHODS: In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. RESULTS: Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. CONCLUSIONS: Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy.

Vitamin D metabolites are associated with clinical and MRI outcomes in multiple sclerosis patients.

PURPOSE: The associations between vitamin D and MRI measures of brain tissue injury have not been previously investigated in multiple sclerosis (MS). This research evaluates the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in MS patients. METHODS: The study population consisted of 193 MS patients (152 women and 41 men; mean age 46.1 (SD 8.4) years; disease duration 13.8 (SD 8.4) years). Serum levels of 25-hydroxyvitamin D(3) (25(OH)VD(3)), 25-hydroxyvitamin D(2) (25(OH)VD(2)), 1α, 25-dihydroxyvitamin D(3) (1, 25(OH)(2)VD(3)) and 24(R), 25-dihydroxyvitamin D(3) (24, 25(OH)(2)VD(3)) were measured using a novel capillary liquid-chromatography-mass spectrometry method. Disability was assessed with the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). MRI measures included T2 lesion volume (LV), T1-LV and brain parenchymal fraction. The associations between deseasonalised levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses. RESULTS: Lower deseasonalised levels of total 25(OH)VD (p=0.029), 25(OH)VD(3) (p=0.032) and 24, 25(OH)(2)VD(3) (p=0.005) were associated with higher MSSS. Similarly, lower deseasonalised levels of 24, 25(OH)(2)VD(3) (p=0.012) were associated with higher EDSS. Higher values of the 25(OH)VD(3) to 24, 25(OH)(2)VD(3) ratio were associated with higher MSSS (p=0.041) and lower brain parenchymal fraction (p=0.008). CONCLUSIONS: Vitamin D metabolites have protective associations with disability and brain atrophy in MS. In particular, the results indicate strong associations for the 24, 25(OH)(2)VD(3) metabolite, which has not been extensively investigated in MS patients.

Effect of switching from glatiramer acetate 20 mg/daily to glatiramer acetate 40 mg three times a week on gray and white matter pathology in subjects with relapsing multiple sclerosis: A longitudinal DTI study.

BACKGROUND: Glatiramer acetate (GA) 40 mg × 3/weekly was approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been demonstrated, the effect of GA 40 mg × 3/weekly at the microstructural tissue level has yet to be explored. OBJECTIVE: To investigate the effect of switching from GA 20 mg/daily to GA 40 mg × 3/weekly on the evolution of microstructural changes in the thalamus and normal appearing white matter (NAWM), using diffusion tensor imaging (DTI). METHODS: In this observational, longitudinal, cross-over, 34-month MRI study, we recruited 150 RRMS patients that underwent MRI 12-18 months before switching (pre-index), during the switch (index) and 12-18 months after switching (post-index) from GA 20 mg/daily to GA 40 mg × 3/weekly. Regional DTI metrics and tract-based spatial statistics (TBSS) analyses were performed. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were measured in thalamus and NAWM. RESULTS: Regional DTI measures, measures of whole brain, white and gray matter, and thalamus volumes, as well as lesion volume, showed no significant changes. However, the voxel-wise TBSS analysis showed increased FA both in the NAWM and thalamus, as well as increased MD and AD in NAWM, and decreased RD in NAWM (p < .05). Areas of increased FA and MD as well as decreased RD in the NAWM, and increased AD both in the NAWM and thalamus were detected between index to post-index (p < .05). CONCLUSIONS: This study confirms a comparable effect of GA 40 mg × 3/weekly to GA 20 mg/daily on DTI measures over 34 months.