Biobehavioural correlates of physical and mental health-related quality of life in relapsing- remitting multiple sclerosis

Background

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, and relapsing-remitting MS (RRMS) is its most common clinical course [1]. Beyond neurological disability [2], health-related quality of life may depend on psychological, behavioural and immunological factors, but their joint contribution in RRMS remains insufficiently defined [3]. We examined clinical, psycho-behavioural, and immunological correlates of self-perceived physical and mental health in RRMS, testing whether biological markers add explanatory information beyond disability, fatigue, sleep, and affective symptoms. Methods: In this single-centre cross-sectional observational study, 86 clinically stable patients with RRMS were recruited at Udine University Hospital between February 2021 and August 2023. Self-reported fatigue, sleep quality, daytime sleepiness, anxiety, depression, and perceived neuropsychological dysfunction were measured using validated questionnaires. Peripheral blood samples were analysed for complete blood counts, lymphocyte subpopulations, and systemic inflammatory indices. Health Related Quality of Life was assessed using the 36-item Short Form Health Survey, yielding Physical Component Summary (PCS) and Mental Component Summary(MCS) scores. Multiple linear regression models tested correlates of PCS and MCS, adjusting for sociodemographic and MS-related covariates.

Results

Participants were predominantly female (77.9%), with mean age 40.5 ± 10.3 years, mean disease duration of 8.3 ± 6.5 years, and mild neurological disability (Expanded Disability Status Scale [EDSS], 2.1 ± 1.3). Mean PCS and MCS were 61.4 ± 22.6 and 61.0 ± 22.9, respectively, indicating broad interindividual variation in perceived physical and mental health. In multivariable models, lower PCS was associated with higher disability (B = -9.241, β = -0.342, p < 0.001), older age at MS diagnosis (B = -15.443, β = -0.2954, p = 0.021), greater fatigue (B = -14.161, β = -0.282, p= 0.005), poorer sleep quality (B = -8.507, β = -0.199, p = 0.041), and more depressive symptoms (B= -13.409, β = -0.261, p = 0.031). Biological variables provided only modest, statistically non-significant explanatory information for PCS beyond clinical and psycho-behavioural variables (ΔR^2 =0.028, p = 0.424). In contrast, lower MCS was associated with poorer sleep quality (B = -15.989, β =-0.372, p < 0.001) and more depressive symptoms (B = -16.850, β = -0.324, p = 0.002), while higher lymphocyte count was associated with higher MCS after adjustment for behavioural and clinical variables (B = +10.958, β = +0.184, p = 0.035, with overall ΔR^2 = 0.046, p = 0.037). Higher systemic immune-inflammation index (SII) was associated with lower MCS (B = -2.702, β = -0.142, p = 0.034; with ΔR^2 = 0.018), consistent with a link between low-grade systemic inflammation and reduced perceived mental well-being.

Conclusions

Self-perceived physical and mental health in RRMS showed distinct but partly overlapping clinical, behavioural, and immunological correlates. These findings support a biobehavioural model of MS in which immune-inflammatory variation may contribute to subjective well-being beyond neurological disability and psychological symptoms. Clinical care and future trials may benefit from jointly assessing psychological symptoms, sleep, fatigue, neurological disability, and immune-inflammatory markers when evaluating health-related qualityof life in RRMS.

References

1. Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018;4(1):43.
2. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622-36.
3. Pilotto S, Floris M, Solla P, Pugliatti M, Zarbo IR. Determinants of self-perceived quality of life in mildly disabled multiple sclerosis patients: a cross-sectional study. J Neurol. 2024;271(6):3455-61.