Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Myasthenia Gravis

During this pilot study, the investigators will examine the effects of whole-body electrical muscle stimulation exercise (WB-EMS Exercise) on neuromuscular junction (NMJ) transmission and fatigability in adults with Generalized Myasthenia Gravis (gMG). The investigators will also test whether a relationship exists between NMJ transmission dysfunction and fatigability in gMG, which has long been presumed but never directly assessed. Participants will undergo clinical and electrophysiologic testing before and after the WB-EMS Exercise intervention. The WB-EMS Exercise intervention will be delivered 2 times per week for 4 weeks. Long-term follow up is optional. The hypotheses are (a) that the WB-EMS exercise will improve fatigability and NMJ transmission, and (b) that NMJ transmission dysfunction is related to fatigability.

During this pilot study, the investigators will examine the effects of a novel paradigm, whole-body electrical muscle stimulation exercise (WB-EMS Exercise), on neuromuscular junction (NMJ) transmission and fatigability in adults with Generalized Myasthenia Gravis (gMG). The investigators will also test whether a relationship exists between NMJ transmission dysfunction and fatigability in gMG, which has long been presumed but never directly assessed. The investigators will use single fiber electromyography (SFEMG) to capture pre- and post-treatment jitter, which measures NMJ transmission variability. The investigators will use decomposition electromyography and clinical measures to assess pre- and posttreatment fatigability of motor units and muscles. and associate these with baseline values for NMJ transmission to determine the relationship between these variables. At the conclusion of the study, expected outcomes include: (1) preliminary data regarding the efficacy of WB-EMS Exercise to address fatigability, (2) an indication of whether this type of exercise may promote NMJ remodeling, and (3) clarification of mechanistic connections between NMJ transmission and fatigability. These findings will provide new insights into mechanisms of fatigability and responses to exercise in gMG. The long-term goal is to define the effects of exercise on gMG pathophysiology and identify effective and tolerable modes of exercise that can be recommended to manage and prevent gMG-related fatigue.

Eligibility Criteria:
Inclusion Criteria for Participants with MG:

* Age 18 or older
* Diagnosed with Generalized Myasthenia Gravis (gMG) via seropositive test for acetylcholine receptor (AChR) antibodies or seronegative test with clinical symptoms consistent with gMG
* On stable MG therapy for at least 1 month
* Ability to stand for approximately 15 minutes continuously with or without an assistive device (i.e. the length of time to stand to take a shower, complete meal preparation, wait in line at the bank, etc.)
* Score of 1 (Mild) or 2 (Moderate) on at least one side of the "arm outstretched" and "leg outstretched" items of the QMG, demonstrating fatigability
* At least some anti-gravity strength in major muscle groups as assessed by manual muscle testing (i.e. 2+/5 strength or better)
* Medical clearance to participate in an exercise program
* Ability to provide informed consent
* Ability to conform to the requirements of the study (i.e. attendance at assessment and intervention visits, maintain current level of non-study physical activity for the duration of the study, no intention to relocate mid-study)

Exclusion Criteria for Participants with MG:

* Concurrent participation in another interventional research study
* Unable to tolerate 15 minutes of continuous standing with or without an assistive device
* Regular participation in strength training (2x per week or more over the past 6 months)
* Score of 0 (None) on all "arm outstretched" and "leg outstretched" items of the QMG
* Presence of a pacemaker, metal implants, or other implanted medical devices that could impact participant safety during WB-EMS intervention
* Presence of unstable acute or chronic disease (i.e. renal failure, rheumatologic disease, cardia arrhythmia, neoplasm, uncontrolled hypertension)
* Known pregnancy at time of screening
* Presence of a terminal disease (i.e. receiving hospice services)
* Current or previous use of any drugs known to influence muscle mass or performance within 6 months; these may include but are not limited to anabolic steroids, IGF01, growth hormone, replacement androgen therapy, anti-androgen therapy
* Presence of an additional neuromuscular or neurologic condition affecting somatosensory or motor function/control (i.e. motor neuron disease, muscle disease, peripheral neuropathy, other NMJ condition, Parkinson's disease, Multiple Sclerosis, h/o stroke, traumatic brain injury, spinal cord injury, ataxia, apraxia, hemiplegia, etc.)
* Musculoskeletal condition or surgery in the past year that would confound results of exercise interventions (i.e. knee replacement, hip replacement, rotator cuff repair, spinal fusion)
* Other medical conditions, signs, or symptoms that would interfere with study conduct or interpretation of results as determined by an investigator

Inclusion Criteria for Healthy Controls:

* Age 18-39 years
* Ability to provide informed consent

Exclusion Criteria for Healthy Controls:

* Concurrent participation in an interventional research study
* Presence of unstable acute or chronic disease (i.e. renal failure, rheumatologic disease, cardia arrhythmia, neoplasm, uncontrolled hypertension)
* Presence of a terminal disease (i.e. receiving hospice services)
* Current or previous use of any drugs known to influence muscle mass or performance within 6 months; these may include but are not limited to anabolic steroids, IGF01, growth hormone, replacement androgen therapy, anti-androgen therapy
* Presence of an additional neuromuscular or neurologic condition affecting somatosensory or motor function/control (i.e. motor neuron disease, muscle disease, peripheral neuropathy, other NMJ condition, Parkinson's disease, Multiple Sclerosis, h/o stroke, TBI, SCI, ataxia, apraxia, hemiplegia, etc.)
* Musculoskeletal condition or surgery in the past year that would confound results of exercise interventions (i.e. TKA, THA, RTC repair, spinal fusion)
* Other medical conditions, signs, or symptoms that would interfere with study conduct or interpretation of results as determined by an investigator

Healthy controls will complete dEMG testing only during a one-time session.