Frailty Exacerbates Disability in Progressive Multiple Sclerosis

To evaluate frailty in severe progressive multiple sclerosis (PMS) and to investigate the underlying mechanisms.

This prospective, cross-sectional, multicenter study enrolled a late severe PMS group requiring skilled nursing (n = 53) and an age, sex, and disease duration-matched control PMS group (n = 53). Participants received neurological and MRI assessments and provided blood samples. Frailty was measured on the Edmonton Frail Scale. Disability was measured on the Expanded Disability Status Scale (EDSS), and fatigue was assessed on the Fatigue Severity Scale. The inflammatory vulnerability index (IVX) and metabolic vulnerability index (MVX) were computed from nuclear magnetic resonance spectroscopy-derived metabolomic profiling. Serum neurofilament (sNfL), glial fibrillary acidic protein (GFAP), and growth differentiation factor 15 (GDF15) levels were obtained.

The late severe PMS group had a higher median EDSS (8.0 vs. 6.0, p < 0.001) than the matched control PMS group. The late severe PMS group had a higher prevalence of frailty (73.1% vs. 23.1%, p < 0.001) and higher frailty scores (8.87 vs. 5.52, p < 0.001) than the control PMS group. EFS was associated with EDSS in both PMS groups. Positive frailty status was associated with a 1.19-point greater EDSS (p = 0.012) in the control PMS group and a 0.436-point greater EDSS in the late severe PMS group (p = 0.002). In PMS controls, the EFS and frailty status were associated with IVX (p = 0.044 for EFS) and MVX (p = 0.036 for EFS).

Frailty is positively associated with MS disability. Inflammatory and metabolic vulnerability are associated with frailty in PMS.