Role of Neuromuscular Junction Function in Motor Fatigue in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis; Fatigue
Study type: Observational

Summary: 
      This pilot study will evaluate for the presence of neuromuscular junction (NMJ) defect in
      women with motor fatigue in multiple sclerosis by Single Fiber Electromyography (SFEMG) using
      the concentric needle electrode.
    

Detailed description: 
      The investigators will recruit 20 women with multiple sclerosis (MS) and fatigue and 10
      normal controls with no identified causes of fatigue (no history of thyroid disease, anemia,
      liver disease, kidney disease, myasthenia gravis, and no major fatigue inducing medications).
      We will include MS patients with fatigue severity scale of ≥5. Patients with sleep disorders
      or significant depression will be excluded based on history, Epworth Sleepiness scale, and
      Beck's Inventory of Depression Scale. The study will include two clinic visits and a
      one-study visit. After informed consent is obtained (English and Spanish forms will be
      available), the following will be done during the study visit 1:

        -  Neurological examination: Using handgrip dynamometer of the dominant hand.

             -  Maximum voluntary isometric contraction force (MVIC) of the handgrip; two
                contractions of as long as 5 seconds each.

             -  Single 30 seconds sustained maximal contraction of the handgrip to assess static
                fatigue.

             -  Series of brief maximal contraction over 30 seconds, Contractions will be timed at
                one contraction per second.

        -  Expanded Disability Status Scale (EDSS

        -  Fatigue severity scale (FSS) and modified fatigue impact scale (MFIS)

        -  Epworth Sleepiness scale for screening for sleep disorders.

        -  Beck's Inventory of Depression Scale for screening for depression. Clinic visit 2: The
           clinic visit 2 will be conducted 5-30 days after the clinic visit 1

        -  Neurological examination: Using handgrip dynamometer of the dominant hand.

             -  Maximum voluntary isometric contraction force (MVIC) of the handgrip; two
                contractions of as long as 5 seconds each.

             -  Single 30 seconds sustained maximal contraction of the handgrip to assess static
                fatigue.

             -  Series of brief maximal contraction over 30 seconds, Contractions will be timed at
                one per second.

        -  Fatigue severity scale (FSS) and modified fatigue impact scale (MFIS)

      Study Visit 3:

      Electromyography (EMG) and SFEMG (Single Fiber Electromyography) of the extensor digitorum
      communis muscle (forearm muscle) will be performed on all women with fatigue and healthy
      controls at the TTUHSC electrophysiology lab to evaluate for NMJ abnormalities. The mean
      consecutive difference (MCD) of 20 pairs of single muscle fiber potentials will be collected
      using SFEMG from each of the 20 women with multiple sclerosis and fatigue and will be
      compared to MCD of 200 pair potentials from our recruited 10 normal control subjects and also
      to the previously published normative data.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with relapsing remitting multiple sclerosis (MS) with motor fatigue in MS > 6
        weeks. Motor fatigue equates to muscle fatigue due to physical exertion and is alleviated
        with rest and associated with fatigability.
      
Keywords: Fatigue; multiple sclerosis; neuromuscular junction; SFEMG