Serum antibody against neuromuscular junction Ach- receptors is found in 85–90% of patients with generalized MG (14). Some patients (10–20%) with acquired MG, however, are Ach-receptor antibody negative. In seronegative MG, a circulating immunoglobulin somehow interferes with neuromuscular transmission by binding to non-Ach-receptor determinants at the neuromuscular junction (4,14). Seronegative MG predominantly involves the ocular muscles and has a milder disease course than seropositive MG (14,25). This appears to be especially true in male subjects, which may be related to the immunomodulatory effects of testosterone (25).
Myasthenia gravis may be congenital or drug-induced (penicillamine can induce a myasthenic syndrome (4)). Intracranial lesions can masquerade as MG or occur in conjunction with it (13,21,28). Usually parasellar tumors or aneurysms, these lesions may produce fluctuating ptosis and a positive response to Tensilon®. Thus, patients with signs and symptoms limited to the ocular muscles may need a neuroimaging study. Other conditions, such as hyperthyroidism, Grave’s disease, multiple sclerosis, Lambert-Eaton myasthenic syndrome, botulism, Guillain-Barre syndrome, amyotrophic lateral sclerosis, and progressive external ophthalmoplegia are usually readily distinguished by the temporal course of the illness, associated sensory or autonomic symptoms, and/or by systemic symptoms not seen with isolated MG (4,17).
To our knowledge, there are no published reports on the participation of myasthenic male or female subjects in organized athletics. In part this reflects the fact that MG was often disabling or fatal in the past, even with the use of anticholinesterases. This is no longer true. Most patients with MG now lead active, productive lives due largely to newer immunosuppressive approaches to treatment. This athlete’s desire to play collegiate football, therefore, raised some unique clinical management issues about limitations to his participation in a contact/collision sport for which the available data on exercise in MG (7,9,19) provided little help. These limitations fall into three general categories: those imposed by the illness itself, those resulting from complications seen with MG, and those due to current therapy for MG.
Complications and certain associated conditions of MG may limit sports participation. Not only will athletes with decremental strength be unable to maintain required activities at an optimal level throughout the game, but also weakened muscles may predispose them to soft tissue and orthopedic injuries. A thermogenic or “Walker” effect, described by Dr. Mary Walker in 1938, is the delayed appearance of weakness in a muscle distant from those being exercised (27) —a problem, which when present, further complicates training and sustained competition. Dr. Walker theorized that myasthenics release a circulating “curare-like” substance during anaerobic exercise causing weakness in remote muscles. This “curarizing” substance may be antibodies released into the circulation from exercising muscle or, more likely, lactic acid released during anaerobic exercise binds and lowers serum calcium (18), which weakens muscles in myasthenics, who already have precarious neuromuscular function. Our patient’s pronounced postexercise ptosis and proximal muscle weakness are classic examples of the Walker phenomenon. Proximal upper and lower extremity muscle atrophy (16) and weak respiratory muscles (16) could limit exercise tolerance. Myasthenics have a greater incidence of several neoplastic and immune disorders. Thymic tumors (thymomas) occur in 12%(4) and are generally associated with more severe symptoms. Hypothyroidism occurs in 3–8% of patients and may aggravate myasthenic weakness (4). Myasthenics also have a greater incidence of rheumatoid arthritis and lupus, both of which would limit physical activity.
Current therapy for MG could significantly impact on sports participation. Anticholinesterases are the first line of treatment, but the initial improvement, as in our athlete, often wanes after weeks or months (4). Side effects include gastrointestinal hyperactivity, excessive oral and upper airway secretions, and bradycardia (12). Surgical thymectomy is used for its therapeutic effect or to prevent the spread of a thymoma. It is recommended that patients with generalized MG between puberty and age 60 undergo thymectomy (20,22). The benefits of thymectomy, however, are usually delayed for months to years after surgery, yet about a third of patients enter remission and approximately 50% will improve so that immunosuppressives can be reduced or eliminated (3–5,20). Why thymectomy is effective is unclear. Altered thymic myoid cells may be the source of autoimmunity in myasthenia (4,20). Removal of the thymus may thus eliminate a source of continued antigenic stimulation, or it may remove a reservoir of acetylcholine receptor antibody secreting B-lymphocytes (4). Clinical improvement after thymectomy is directly related to the extent of resection of the thymus (4,12). Cervical mediastinoscopy produces less operative morbidity, but median sternotomy with cervical exploration is the procedure of choice because it removes the most thymic tissue (4,12). Healing of the sternotomy would limit participation in contact/collision sports for 6–12 wk after surgery. Our athlete wanted to avoid thoracic surgery for as long as possible since he was doing well on a medical regimen.
Immunosuppressive therapy is indicated when anticholinesterase drugs do not adequately control weakness. Prednisone is the most widely used and most effective but also has the most side effects (4,10). Generally, the dose starts at 15–20 mg per day, gradually increasing to 60 mg per day and gradually changing to alternate-day therapy (4). Glucocorticoids can produce a myopathy involving predominantly the proximal limb muscles (10) but, on an alternate-day regimen and through regular exercise, our athlete maintained excellent muscle strength and endurance and had no orthopedic problems until he developed mechanical low-back pain during a sprint. Though alternate-day glucocorticoids have been shown to reduce bone mass in adolescents (23) and can increase the risk for fracture (especially of the trabecular bone-rich vertebral spine (10)), our athlete did not have a vertebral compression fracture. Testosterone deficiency is a cause of osteoporosis, and serum testosterone is reduced in men taking glucocorticoids chronically (10). It is therefore reasonable to replace testosterone in men on chronic glucocorticoids who have low serum levels, provided blood lipids are monitored closely (10). NCAA prohibitions on the use of anabolic agents might, however, pose problems for athletes requiring testosterone therapy (15). As opposed to anabolic steroids, the NCAA has no restrictions on the use of oral glucocorticoid (15). Our athlete’s serum testosterone level was normal while on glucocorticoid therapy. He was able to maintain an intense regimen of weight-bearing exercise (StairMaster), which is a primary preventive measure for steroid-induced myopathy and osteoporosis (10,11). Nevertheless, there are no data on the effectiveness of these measures in preventing fractures in the setting of chronic glucocorticoid excess, and no studies of glucocorticoid-dependent athletes in contact/collision sports.
Sports physicians must make several decisions when faced with a myasthenic athlete. Should the athlete be allowed to participate at all? If so, what modifications in training and competition will be required? Depending on the medical regimen, what observations will be necessary to be sure that he/she is in optimal competitive condition and not suffering from the side effects outlined above? What is the role of each member of the sports medicine team (primary and/or team physician, specialist physician, athletic trainer, and coach) in the management of the myasthenic athlete? There are, unfortunately, no research data to answer these questions, thus each case must be addressed individually.
Whether a myasthenic athlete can participate in an organized sport will necessarily depend on the severity of the disease and the physical demands of the sport. A myasthenic athlete with more than mild generalized symptoms probably cannot participate in a high-intensity or contact/collision sport but may be able to engage in a low-intensity noncontact sport such as golf or bowling (2). Issues to consider include any debilitating Walker effect, the particular muscle groups involved, the potential for injury (to the athlete and to other participants) if certain muscle groups slowly weaken during repetitive use, assessment of vital functions (e.g., pulmonary function, swallowing) that may worsen with exercise, and environmental conditions (MG may be exacerbated by the heat (12)). For example, diplopia treated with an eye patch might not bother a swimmer, but it could be a real problem for a tennis player or a wide receiver. Exercise during the summer might need to be scheduled during the early morning or evening to avoid the extremes of heat and humidity. Respiratory insufficiency, difficulty swallowing, or decremental weakness of the cervical muscles would eliminate training for and participation in most sports except, perhaps, those of very low aerobic and anaerobic intensity (golf, bowling, cricket, curling, etc.).
This case was presented to educate health professionals about myasthenia gravis, its effect on the athletic career of a collegiate athlete, and to discuss some of the general implications of myasthenia in athletes. Formerly fatal or disabling, myasthenia gravis can now be treated effectively, allowing patients to lead more normal lives. Certain patients with myasthenia may be able to participate in organized sports. Physical activity and participation in organized sports should be encouraged for those myasthenics who want to participate and who have the physical capacity to do so. More specific recommendations concerning the benefits and risks of physical activity and sports participation in myasthenia gravis await the systematic observation of a population of active myasthenics over time.
We gratefully acknowledge Howard Lippes, M.D., Mike Rielly, A.T.C., Mike Lahood, M.D., and Donald Tingley, M.D., for their assistance with technical details and manuscript review.
This paper was presented in part at the 1997 Annual Meeting of the American College of Sports Medicine, Denver, CO.
Address for correspondence: John Leddy, M.D., FACSM, University Sports Medicine, 160 Farber Hall, 3435 Main St., Buffalo, NY, 14214; E-mail: firstname.lastname@example.org.
1. Adams, R. D., and M. Victor. Disorders of ocular movement and pupillary function. In:Principles of Neurology
. New York, NY: McGraw-Hill, p. 188, 1981.
2. American Academy of Pediatrics. Committee on Sports Medicine and Fitness: medical conditions affecting sports participation. Pediatrics
3. Buckingham, J. M., F. M. Howard, Jr., P. E. Bernatz,et al. The value of thymectomy in myasthenia gravis: a computer-assisted matched study. Ann. Surg. 184: 453–458, 1976.
4. Drachman, D. B. Myasthenia gravis. N. Engl. J. Med. 330: 1797–1810, 1994.
5. Grob D., N. G. Brunner, T. Namba. The course of myasthenia gravis and therapies affecting outcome. Ann. N. Y. Acad. Sci. 505: 472–499, 1987.
6. Hopkins, L. C. Clinical features of myasthenia gravis. Neurol. Clin. North Am. 12: 243–261, 1994.
7. Ionasescu, V., and N. Luca. Studies of carbohydrate metabolism in myasthenia gravis in conditions of ischaemic exercise. Acta Neurol. Scand. 42: 244–254, 1966.
8. Keesey, J. C. Electrodiagnostic approach to defects of neuromuscular transmission. Muscle Nerve 12: 613–626, 1989.
9. Kolins, J. , and Gilroy J. Serum enzyme levels in patients with myasthenia gravis after aerobic and ischaemic exercise. J. Neurol. Neurosurg. Psychiatry
35: 34–40, 1972.
10. Lukert, B. P., and L. G. Raisz. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann. Int. Med. 112: 352–364, 1990.
11. Marcus, R. Physical activity and regulation of bone mass. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, M. J. Favus(Ed.). Philadelphia: Lippincott-Raven, 1996, pp. 254–256.
12. Massey, J. M. Treatment of acquired myasthenia gravis. Neurology 48 (Suppl. 5): S46–S51, 1997.
13. Moorthy, G., M. M. Behrens, D. B. Drachman,et al. Ocular pseudomyasthenia or ocular myasthenia “plus.” Neurology 39: 1150–1154, 1989.
14. Mossman, S., A. Vincent, and J. Newsom-Davis. Myasthenia gravis without acetycholine-receptor antibody: a distinct disease entity. Lancet i: 116–118, 1986.
15. NCAA Drug Evaluation and Drug Testing Program. Pamphlet. NCAA, July, 1996.
16. Oosterhius, H. J. G. H. The natural course of myasthenia gravis: a long term follow up study. J. Neurol. Neurosurg. Psychiatry 52: 1121–1127, 1989.
17. Oosterhius, H. J. G. H. Differential diagnosis. In:Myasthenia Gravis
. New York: Churchill Livingstone, 1984, pp. 159–174.
18. Patten, B. M. A hypothesis to account for the Mary Walker phenomenon. Ann. Int. Med. 82: 411–415, 1975.
19. Pease, W. S., and F. P. Lagattuta. Exacerbation of a case of myasthenia gravis during therapeutic electric stimulation. Arch. Phys. Med. Rehabil. 68: 568–570, 1987.
20. Penn, A. S. Thymectomy of myasthenia gravis. In: Handbook of Myasthenia Gravis and Myasthenic Syndromes, R. P. Lisak(Ed.). New York: Marcel Dekker, 1994, pp. 321–339.
21. Ragge, N. K., and W. F. Hoyt. Midbrain myasthenia: fatiguable ptosis, “lid twitch” sign, and ophthalmoparesis from a dorsal midbrain ganglia. Neurology 42: 917–919, 1992.
22. Rowland, L. P. General discussion on therapy in myasthenia gravis. Ann. N. Y. Acad. Sci. 505: 607–609, 1987.
23. Ruegsegger, P., T. C. Medici, and M. Anliker. Corticosteroid-induced bone loss: a longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur. J. Clin. Pharmacol. 25: 615–620, 1983.
24. Sanders, D. B. The electrodiagnosis of myasthenia gravis. Ann. N. Y. Acad. Sci. 505: 539–556, 1987.
25. Sanders, D. B., P. I. Andrews, J. F. Howard, and J. M. Massey. Seronegative myasthenia gravis. Neurology 48 (Suppl. 5): S40–S45, 1997.
26. Simpson, J. F., M. R. Westbery, and K. R. Magee. Myasthenia gravis: an analysis of 295 cases. Acta Neurol. Scand. (Suppl.) 23: 1, 1966.
27. Walker, M. B. Myasthenia gravis: case in which fatigue of forearm muscles could induce paralysis of extraocular muscles. Proc. R. Soc. Med. 31: 722, 1938.
28. Walter, K. A., N. J. Newman, and S. Lessell. Oculomotor palsy from minor head trauma: initial sign of intracranial aneurysm. Neurology 44: 148–150, 1994.
Keywords:© 2000 Lippincott Williams & Wilkins, Inc.
MYASTHENIA GRAVIS,; SPORTS,; EXERCISE,; MUSCLE WEAKNESS