Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study.

BACKGROUND: The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear. OBJECTIVE: Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years. METHODS: 85 patients, originally enrolled in a multicentre, randomised trial of ω-3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer. RESULTS: Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (ß=-0.399, p=0.040) and deep (ß=-0.556, p=0.010) GM volume, lower mean cortical thickness (ß=-0.581, p=0.010) and higher T2 lesion count (ß=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (ß=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression. CONCLUSION: Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS). METHODS: We included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months. Smoking status was decided for each patient by 2 separate definitions: by serum cotinine levels measured regularly for the first 2 years of the follow-up (during the clinical trial) and by retrospective patient self-reporting. At the 10-year follow-up visit, clinical tests were repeated, and brain atrophy measures were obtained from MRI using FreeSurfer. Differences in clinical and MRI measurements at the 10-year follow-up between smokers and nonsmokers were investigated by 2-sample t tests or Mann-Whitney tests and linear mixed-effect regression models. All analyses were conducted separately for each definition of smoking status. RESULTS: After 10 years, smoking (defined by serum cotinine levels) was associated with lower total white matter volume (ß = -21.74, p = 0.039) and higher logT2 lesion volume (ß = 0.22, p = 0.011). When defining smoking status by patient self-reporting, the repeated analyses found an additional association with lower deep gray matter volume (ß = -2.35, p = 0.049), and smoking was also associated with a higher score (higher walking impairment) on the log timed 25-foot walk test (ß = 0.050, p = 0.039) after 10 years and a larger decrease in paced auditory serial addition test (attention) scores (ß = -3.58, p = 0.029). DISCUSSION: Smoking was associated with brain atrophy and disability progression 10 years later in patients with RRMS. The findings imply that patients should be advised and offered aid in smoking cessation shortly after diagnosis, to prevent long-term disability progression.

Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis.

BACKGROUND: Low vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. METHODS: In this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During 24 months, serum 25-hydroxyvitamin D (25(OH)D), serum cotinine (nicotine metabolite), and BMI were repeatedly measured. In 2017, a follow-up study was conducted among 80 of the participants, including disability assessment by the Expanded Disability Status Scale (EDSS). Linear regression was used to explore associations between the lifestyle factors and the EDSS change over 10 years. RESULTS: Higher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Further adjustments for potential confounders related to lifestyle and disease status gave similar results. The association was mainly driven by low 25(OH)D levels during spring, as well as seasonally adjusted levels below 80 nmol/L. No clear association was found for BMI and cotinine. CONCLUSION: Lower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS.