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Frailty Exacerbates Disability in Progressive Multiple Sclerosis
Taylor R Wicks1, Anna Wolska2, Diala Ghazal1
1Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Annals of Clinical and Translational Neurology
|November 14, 2025
Summary
Frailty is common in severe progressive multiple sclerosis (PMS) and linked to increased disability. Inflammatory and metabolic factors contribute to frailty in PMS patients.
Area of Science:
- Neurology
- Immunology
- Metabolomics
Background:
- Progressive multiple sclerosis (PMS) is a debilitating neurological disease.
- Frailty is a significant concern in aging populations and can exacerbate disease severity.
- Understanding frailty mechanisms in PMS is crucial for patient care.
Purpose of the Study:
- To evaluate the prevalence and severity of frailty in patients with severe progressive multiple sclerosis (PMS).
- To investigate the potential underlying mechanisms, including inflammatory and metabolic factors, associated with frailty in PMS.
Main Methods:
- A prospective, cross-sectional, multicenter study comparing a late severe PMS group (n=53) with a matched control PMS group (n=53).
- Assessments included neurological status (EDSS), frailty (Edmonton Frail Scale), fatigue (Fatigue Severity Scale), and MRI.
- Metabolomic profiling (IVX, MVX) and serum biomarkers (sNfL, GFAP, GDF15) were analyzed.
Main Results:
- The late severe PMS group exhibited significantly higher disability (EDSS) and a greater prevalence and severity of frailty compared to controls.
- Frailty was positively associated with disability (EDSS) in both PMS groups.
- In the control PMS group, frailty and EFS correlated with inflammatory vulnerability index (IVX) and metabolic vulnerability index (MVX).
Conclusions:
- Frailty is a significant clinical issue in severe progressive multiple sclerosis, directly correlating with disease disability.
- Inflammatory and metabolic vulnerabilities are key underlying mechanisms contributing to frailty in PMS.
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