Myasthenia gravis (MG) is an autoimmune disease that directly attacks acetylcholine receptors at the neuromuscular junctions. The attacks are both antibody directed and related to cellular immunological phenomena (3). The hallmark of this disease is muscular weakness and fatigability that usually increases with repeated activity and improves with rest. MG presents with a prevalence of 50 to 125 cases per million (14). It also occurs in two peaks, one being in women in the second and third decade of life and the other in men during their sixth and seventh decades (3). The estimated cost of treating one MG patient per year is roughly over $20,000 (9). This disease had considerable mortality in the past with more than one quarter of patients dying from respiratory failure and an expected mortality of 50% within 10 years of diagnosis. Due to new treatment strategies and immunotherapy, many MG patients can expect a life expectancy similar to non-MG patients. However, they may have decreased quality of life due to symptoms of fatigue and weakness. As a result of the activity component of MG and the age of first peak incidence being in active sporting populations, sports medicine providers likely are to find themselves treating or consulting on this disease.
Exam findings should be limited to the motor system, as the destruction of the postsynaptic receptors should cause no sensory deficits, loss of reflexes, or alteration of coordination or proprioception. Muscle strength testing should be evaluated prior to exercise as a baseline and can be retested after a vigorous workout. Usually, weakness will accompany selected muscle groups and should improve with a reexamination following a rest period. Muscles affected are often proximal and also usually include the diaphragm and neck extensors. Ptosis or diplopia may be early presenting signs and often remain localized to the extraocular and eyelid muscles but may progress to facial and bulbar muscles (8).
After ruling out severe intracranial pathology, suspected cases of MG are handled best by neurology consultation. Typical studies that are done are anticholinesterase testing with edrophonium (Tensilon), repetitive nerve stimulation testing, and assay for antiacetylcholine receptor antibody. Edrophonium inhibits acetylcholinesterase thereby increasing circulating acetylcholine levels and improving muscle weakness. During repetitive nerve stimulation, electric impulses are delivered to a motor nerve at 3 to 5 Hz, while surface electrodes record the compound muscle action potentials. The action potentials rapidly decrease in myasthenic muscles, whereby normal muscle action potential amplitudes remain stable over repetitive stimulation. Acetylcholine receptor antibodies are found in up to 90% of patients with MG and generalized weakness (21).
Pharmacotherapy and immunotherapy have been studied extensively in the field of MG. There are several randomized controlled trials (RCTs), systematic reviews, and Cochrane reviews. Table 1 summarizes Cochrane reviews on the currently available treatment strategies (Table 1). All new patients diagnosed with MG should get a computed tomography scan of their mediastinum to evaluate for a thymoma. Surgical thymectomy is used for its therapeutic effect or to prevent spread of a thymoma. Some recommend thymectomy for all patients between puberty to 60 years old. Some can expect remission after thymectomy, and others may expect improvement enough to eliminate or reduce medications.
Exercise and MG
Due to the uncommon occurrence of MG, there is a paucity of research on the subject of exercise-related therapy and guidelines on activity. Most research on MG is related to pharmaceutical treatment. There are few RCTs in the literature. There does exist a handful of case studies and crossover studies. When randomized controlled studies are limited, these studies can be useful and potentially relevant (11). Exercise therapy has been shown to be beneficial in motoneuron diseases, motor nerve root and peripheral nerve disorders, neuromuscular transmission disorders, and muscle disorders (2). Interventions that have been reviewed include muscle strengthening, aerobic exercises, breathing exercises, and other interventions such as balance training and flexibility (2,13).
Exercise for symptom control and improving quality of life have been neglected fairly in MG research, but a fatigue survey given to MG patients by Becker et al. (1) shows that activity is essential in improving their symptoms and quality of life. In this sample of patients, nearly 60% participated in activity as often as possible to improve quality of life and decrease symptoms. Activity also helped to reduce their fatigue, which is crucial in MG.
In reviewing the literature on MG, there existed studies on aerobic, strength, and breathing exercises, and these will be reviewed in the following sections.
Becker et al. (1) found in their sample a surprising amount of MG patients who used aerobic activity to combat fatigue. Twenty percent of the respondents in their survey used low impact aerobic exercises in their activity regiments. This included swimming, walking, or running. Of note, this group of patients demonstrated the highest levels of functioning in the survey.
There is one case report by Scheer et al. (24) of an ultra endurance athlete with MG who completed a 220-km, 5-d ultramarathon. This athlete experienced fatigue, leg weakness, dysphagia, and breathing problems throughout the race. Usually, these symptoms resolved rapidly when resting in the shade. He would also self-medicate with pyridostigmine at the onset of symptoms. He increased medication according to symptoms at a dose of 60 mg every 90 min. The maximum daily dose of pyridostigmine is 720 mg, and the authors felt he experienced some adverse effects of the high dosing (mouth fasciculations, involuntary eye movements, and cramps).
Finally, a case report of a patient with McCardle’s disease and MG showed improvement in sense of overall well-being and ability to perform activities of daily living with a progressively increasing mild-intensity walking program (16).
A case study by Stout et al.(26) is the sole piece of literature on resistance training in MG. They report a 26-year-old athletic medical student diagnosed with MG. Prior to diagnosis, he played college baseball and was an avid weight lifter. One month after diagnosis, he was not able to accomplish one push up. After completing a 15-wk resistance training program (with creatine supplementation), he increased upper body volume load by 37% and lower body volume load by 15%. Peak strength for leg extension improved 37% and leg flexion strength improved nearly 13%.
Stout does relate that this subject was unable to make gains during bouts of remission. This was attributed to being on regular doses of prednisone. Miller et al. (20) saw this also in a case series of MG patients on regular oral prednisone doses. However, a case report of a division I collegiate football player reports normal strength after a regiment of 60 mg of prednisone daily (15). The football player did, however, suffer a reversible relapse after abrupt discontinuation of steroids.
As a majority of MG patients experience decreasing respiratory volumes during maximal voluntary ventilation or show an obstructive pattern in their spirometry, respiratory muscle endurance training has been investigated (4,12). Rassler et al. (22) performed a small case series on 10 MG patients to determine the effect of home-based respiratory training. They completed five training sessions a week with 30 min of normocapnic hyperpnea training over 4 to 6 wk. The training significantly improved respiratory endurance but also enhanced the perceived physical fitness and alleviated respiratory symptoms. Rassler et al. (23) followed this up with another case study of 10 MG patients and a longer follow-up of 4 months using a maintenance therapy of five sessions over 2 wk. Their results showed continued stable improvement in their functional MG scores, lung scores, and quality of life.
One of the few RCTs in MG research was done by Fregonezi et al. (5) to evaluate the effects of inspiratory muscle training and breathing retraining in an interval-based fashion. The treatment group did breathing retraining, including diaphragmatic breathing and pursed lips breathing, three times a week for 8 wk in an interval fashion. The maximal breathing load was progressively increased followed by rest intervals. The treatment group showed significant improvement in lung function outcomes. This study unfortunately reported no surveys to evaluate the improvement in MG function or quality of life.
Implications for Activity
Available treatment for MG could have negative impact on sports participation. Obviously, undergoing a thymectomy would necessitate a sternotomy, which would limit any athlete as healing occurs for up to 12 wk after surgery.
Adverse effects from medications such as pyridostigmine could cause significant bradycardia, limiting exercise tolerance. They also can cause gastrointestinal upset and hyperactivity as well as excessive oral and upper airway secretions (18). A small case series of 10 MG patients, well controlled on pyridostigmine, also had airway obstruction reflected by a reduced FEV1/FVC on spirometry (4). This likely contributed to their overall fatigue. However, patients not using the acetylcholinesterase inhibitors had lower exercise endurance times (4).
Steroids may limit peak strength as demonstrated by Miller et al. (20). They also can produce a myopathy of the proximal limb muscles, and men taking glucocorticosteroids regularly typically have reduced testosterone levels (17). There is also the concern for the development of osteoporosis in patients taking chronic prednisone. It may be reasonable to treat patients on chronic prednisone who have low testosterone levels, but National Collegiate Athletics Association and other governing body regulations of anabolic steroids need to be considered.
Recommendations for exercise also typically need to be modified (Table 2). Risk factors for exacerbating symptoms include running and exercising in extreme temperatures, prolonged exercise and runs longer than 15 miles, running uphill, activity with stairs, and lack of sleep and stress (24). Exercise may need to be adjusted to cooler times of the day such as morning or evening in summer months. Athletes should also be encouraged to exercise at peak energy times (1). This is a time that is specific to the particular individual and involves a period of their day where they actually feel a relative abundance of energy. For many with MG, these times are early in the morning but should be investigated and adjusted to the individual.
Sports Clearance Issues
There are no guidelines to suggest when a patient with MG can participate in activity. The sports medicine physician must take each situation separately and assess whether the athlete can participate safely for their given sport, noting the potential adverse effects of various treatments and the degree of their symptoms and functional limitations.
MG presents at a peak age distribution that is common for sports participation, and the hallmark of the disease is fatigability and weakness. Due to these factors and the fact that improvement in treatment of MG will lead to longer lifespans of MG patients, sports medicine physicians should be able to recognize, diagnose, and help guide treatment strategies. This is especially important in activity recommendations and guidance. Aerobic activity at mild to moderate exertion on a regular basis seems from the literature to improve MG functional status and quality of life, as well as lead to increased coping ability. The literature is very sparse regarding strength training in MG, noting that medications such as prednisone may limit peak strength. Breathing exercises in MG seem to be very effective for improving quality of life and decreasing fatigability. There are numerous medication regimens available, and specialty consultation with a neurologist is essential for medical management issues. In considering sports and activity clearance, each athlete must be considered individually. First, a comprehensive review of their overall functioning should be evaluated. This should consider the degree of overall strength and weakness of their affected muscle groups and their ability to perform their own activities of daily living and instrumental activities of daily living. Next, a review of their medication and potential adverse effects should be considered to determine safety for competition. Athletes should adjust their activity to avoid risk factors for exacerbating their symptoms. In conclusion, exercise is an important facet to improving the quality of life of athletes and patients with MG while also reducing their overall symptoms.
The authors declare no conflicts of interest and do not have any financial disclosures.
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