Multiple Sclerosis (MS) is a chronic immune-mediated and neurodegenerative disease of the central nervous system that often affects young adults and is more common in women. In addition to neurological disability, individuals with MS frequently experience frailty, a condition characterized by reduced physiological reserve, weakness, fatigue, decreased physical activity, and increased vulnerability to stressors. Frailty in MS is associated with poorer mobility, higher fall risk, reduced quality of life, and increased healthcare utilization. Irisin, a hormone released from skeletal muscles during exercise, is linked to energy metabolism and muscle function, and lower levels have been associated with reduced physical performance and sarcopenia. However, the relationship between frailty, physical fitness, and irisin levels in individuals with MS has not been sufficiently explored.

This study aims to compare frailty status, physical fitness parameters, and circulating irisin levels between patients with MS and healthy volunteers aged 18-65 years. Participants will undergo assessments including the Functional Independence Measure, Frailty Index, Berg Balance Scale, 6-Minute Walk Test, and handgrip strength measurement. Blood samples will also be collected to determine irisin levels using the ELISA method. Statistical analyses will evaluate differences between groups and correlations among frailty, functional performance, and irisin levels. The findings are expected to improve understanding of frailty mechanisms in MS and contribute to developing targeted rehabilitation and management strategies.

Multiple Sclerosis (MS) is a chronic, immune-mediated, and neurodegenerative disorder of the central nervous system, characterized by inflammation, demyelination, and progressive axonal damage. It predominantly affects young adults and has a higher prevalence among women. The disease course is highly variable, often leading to a wide range of physical, cognitive, and psychosocial impairments that can significantly impact daily functioning and long-term quality of life.

In addition to neurological disability, individuals with MS frequently experience frailty, a multidimensional clinical syndrome marked by diminished physiological reserve and reduced resilience to internal and external stressors. Frailty is typically characterized by symptoms such as generalized weakness, persistent fatigue, decreased physical activity, slowed motor performance, and increased vulnerability to adverse health outcomes. In the context of MS, frailty represents an important but underrecognized condition that may exacerbate disease burden and accelerate functional decline.

The presence of frailty in individuals with MS has been associated with poorer mobility, impaired balance, increased risk of falls, reduced independence in activities of daily living, and a decline in overall quality of life. Furthermore, frailty contributes to higher rates of hospitalization, increased healthcare utilization, and greater economic burden. Despite its clinical significance, the underlying biological and functional mechanisms contributing to frailty in MS remain insufficiently understood.

Recent attention has been directed toward irisin, a myokine released from skeletal muscle in response to physical activity and exercise. Irisin is known to play a role in energy homeostasis, glucose metabolism, and the browning of white adipose tissue, thereby contributing to improved metabolic efficiency. Additionally, irisin has been linked to muscle strength, physical performance, and the prevention of sarcopenia. Lower circulating levels of irisin have been associated with decreased muscle function, reduced exercise capacity, and increased frailty in various populations. However, the relationship between irisin levels, frailty status, and physical fitness in individuals with MS has not yet been adequately investigated.

Therefore, the primary aim of this study is to compare frailty status, physical fitness parameters, and circulating irisin levels between patients diagnosed with MS and age- and sex-matched healthy individuals between the ages of 18 and 65 years. A secondary objective is to explore the potential associations between these variables within the MS population.

Participants will undergo a comprehensive evaluation protocol before rehabilitation protocol starts and without any intervention to the patients., including validated clinical and functional assessments. Functional independence will be measured using the Functional Independence Measure (FIM), while frailty status will be assessed through the Frailty Index. Balance performance will be evaluated using the Berg Balance Scale, and aerobic capacity and endurance will be measured with the 6-Minute Walk Test. In addition, upper extremity muscle strength will be assessed via handgrip dynamometry. To complement these functional assessments, venous blood samples will be collected from all participants, and circulating irisin levels will be quantified using the enzyme-linked immunosorbent assay (ELISA) method.

Statistical analyses will be conducted to determine differences between the MS and healthy control groups in terms of frailty, physical fitness parameters, and irisin levels. Furthermore, correlation analyses will be performed to investigate potential relationships among frailty status, functional performance measures, and circulating irisin concentrations.

It is anticipated that the findings of this study will provide valuable insights into the interplay between frailty, physical fitness, and biochemical markers in individuals with MS. A better understanding of these relationships may help clarify the mechanisms underlying frailty in this population and support the development of more targeted, multidisciplinary rehabilitation and disease management strategies aimed at improving functional outcomes and overall quality of life.

Inclusion Criteria:

• Patients aged 18-65 evaluated by neurology and diagnosed with definitive MS via objective methods (MRI, lumbar puncture, etc.).
• Healthy volunteers aged 18-65.
• Being literate in Turkish.
• Participants who provide a consent form to participate in the study.

Exclusion Criteria:

• Being younger than 18 or older than 65.
• Presence of any concomitant neurological disease other than MS.
• Presence of an uncontrolled systemic disease at a level that would affect the evaluation.
• Presence of cognitive impairment or psychiatric illness at a level that would affect the evaluation.
• Having had an MS attack or received steroid treatment in the last month.
• Presence of an orthopedic disability that prevents evaluations.

Patients aged 18-65 diagnosed with MS who applied to the Başkent University Alanya Hospital Center Physical Medicine and Rehabilitation outpatient clinic between April 1, 2026, and May 30 2026, and healthy volunteers aged 18-65 years with similar demographic characteristics (age, gender, etc.) will be included.