Quantitative Fatigue and Muscle Performance in Multiple Sclerosis

Study Overview
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Brief Summary
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Fatigue is consistently rated as the top symptomatic complaint for individuals with multiple sclerosis (MS). Currently, the MS Fatigue Impact Scale (MFIS), a subsection of the Multiple Sclerosis Quality of Life (MSQoL), is the clinical standard used by neurologists for monitoring and tracking fatigue in individuals with MS. However, fatigue is multidimensional phenomenon and subjective measures have had poor or limited relationships with functional status. While previous study has focused on contributing factors to fatigue such as sleep disorders and diminished cortical excitability, this line of inquiry has neglected the role of muscle structure and function on fatigue in every day functional tasks. An alternative approach is to assess quantitative fatigue using anaerobic testing methods. However, more knowledge is needed to understand the role that quantitative fatigue plays in self-reported fatigue measures and function of daily activities. Our purpose is to determine the association between quantitative fatigue tests with performance-based measures of mobility and self-reported health-related quality of life. Our secondary goal is to understand how the intrinsic properties of muscle tissue influence muscle performance in Veterans with MS.

Detailed Description
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Participants will complete study assessments at the DC VAMC. Disease severity will be assessed by medical staff completing the EDSS. Peak torque assessment for the knee flexors and extensors will be performed on an isokinetic dynamometer (Biodex System 4). Muscle morphology measures of the rectus femoris will be obtained using diagnostic musculoskeletal B-mode ultrasound (Phillips EPIQ 7 180 Plus) with a 10 Mhz linear transducer. The sonographic measures will include muscle thickness and echogenicity. The mode of exercise testing and the type of muscle action will influence the assessment of fatigue. Therefore, isokinetic fatigue measures for the knee extensors will be assessed on separate visits (at least 48 hours apart). Performance-based measures of function will include an assessment of patient mobility and the 25-foot walk test. Muscle power will be estimated by the timed sit to stand test. Subjective measures of fatigue and quality of life include the MSQoL, MFIS, and Neurology Quality of Life Adult Fatigue Bank (AFB).

Official Title
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Quantitative Fatigue and Muscle Performance in Multiple Sclerosis

Conditions
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Fatigue, Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female Veteran participant must have a medical diagnosis of multiple sclerosis Veteran will be between the ages of 20 and 85 years old Exclusion Criteria: Veterans with an EDSS score > 7.0 Veterans with any cardiac condition that may cause sudden decompensation during exertional fatigue testing (e.g., severe congestive heart failure and uncontrolled hypertension) Veterans found to have severe depression (BDI score >28) Veterans with lower extremity amputation Steroid Infusion less than 2 weeks prior to enrollment Veterans with a lower extremity joint replacement Veterans that exhibit severe cognitive impairment Defined as loss of orientation to person, place and/or time and an inability to follow three step commands. Veterans that are unable to perform a stand pivot transfer with minimal assist

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Multiple Sclerosis Fatigue (MSF) Cohort<br>Participants will complete study assessments over 4 visits to the DC VAMC. Disease severity will be assessed by the EDSS, and a cognitive battery will be completed. Peak torque assessment for the knee flexors and extensors will be performed on an isokinetic dynamometer (Biodex System 4). Muscle morphology measures of the rectus femoris will be obtained using diagnostic musculoskeletal ultrasound. The sonographic measures will include muscle thickness and echogenicity. Isokinetic and isoinertial mode fatigue measures for the knee extensors will be assessed on separate visits (at least 48 hours apart). Performance-based measures of function will include an assessment of patient mobility and the 25-foot walk test. Muscle power will be estimated by the timed sit to stand test. Subjective measures of fatigue and quality of life include the MSQoL, MFIS, and Neurology Quality of Life Adult Fatigue Bank (AFB). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Index | Initial visit | Day 1 | 
| Maximal Volitional Contraction | Initial visit | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Adult Myopathy Assessment Tool | Initial visit | Day 1 | 
| 25 foot walk Test | Initial visit | Day 1 | 
| Chair Stand Test | Initial visit | Day 1 | 
| Modified Fatigue Impact Scale | Initial visit | Day 1 | 
| Multiple Sclerosis Quality of Life | Initial visit | Day 1 | 
| Adult Fatigue Bank | Initial visit | Day 1 | 
| Ultrasound caliper measure of rectus femoris thickness | Initial visit | Day 1 | 
| Ultrasound image post-processing of rectus femoris grayscale | Initial visit | Day 1 |