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Myasthenia gravis in a collegiate football player

LEDDY, JOHN J.; CHUTKOW, JERRY G.

Medicine and Science in Sports and Exercise : December 2000 - Volume 32 - Issue 12 - p 1975-1979
CLINICAL SCIENCES: Case Study

LEDDY, J. J., and J. G. CHUTKOW. Myasthenia gravis in a collegiate football player. Med. Sci. Sports Exerc., Vol. 32, No. 12, 2000, pp. 1975–1979. A 17-yr-old Division I-AA collegiate offensive lineman developed unilateral ptosis shortly after minor head trauma during a scrimmage. The subsequent temporal profile of the ptosis, a history of a similar event lasting a short period of time 2 yr earlier, and the results of his clinical and electrophysiologic examinations established a diagnosis of very mild, generalized, antibody-negative myasthenia gravis (MG). His desire to continue playing football posed several additional management problems for which there was no published guidance. We started him on alternate-day, high-dose prednisone therapy with potassium and calcium supplementation, and allowed him to partake in conditioning but no contact. Except for residual decreased exercise tolerance, he improved symptomatically and experienced no serious adverse effects from the illness or the treatment during his first season, despite imperfect drug compliance. His MG eventually came under excellent symptomatic control, allowing initiation of a slow taper of the prednisone before his second season. Shortly thereafter, he abruptly stopped the prednisone without seeking medical advice. He continued to experience mild left ptosis and a mild decrease in intense exercise tolerance. He decided to forego his senior season of collegiate football after a bout of severe mechanical low-back pain incurred during spring football practice and limited his athletic activity thereafter to recreational sports.

Department of Orthopaedics and Neurology and the Sports Medicine Institute, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY

March 2000

March 2000

Myasthenia gravis (MG) is an autoimmune disease in which both antibody and cellular immunologic attacks are directed against postsynaptic components of the myoneural junction (6). It is an uncommon but not rare illness (prevalence of 50–125 cases per million population) (4) with two incidence peaks, one in the second to third decades (women > men) and the other in the sixth to seventh decades (men > women) (4). Onset begins below the age of 20 yr in 20% of patients. About 57% of female and 33% of male patients are under the age of 30 yr (4,17,20,26) and, therefore, fall into the age groups participating in many of the major organized sports. Its cardinal manifestation is weakness that usually fluctuates over short time intervals, is precipitated or exacerbated by repetitive contraction of the clinically symptomatic muscles, and improves with rest. The prognosis depends on the muscle groups involved and the severity of the weakness. In the past, morbidity and mortality were considerable (4). Approximately 25–30% of patients died from respiratory failure and/or infection (4,5,16,26). Presumably for these reasons, few if any physicians practicing sports medicine or neurology have more than anecdotal experience managing myasthenic athletes—an assumption supported by the paucity of reports found from a review of the literature and by personal communication. The introduction of several types of immunosuppressive treatments and improved respiratory intensive care management of myasthenic patients in bulbo-respiratory crisis have significantly improved the outcomes in MG (4,5,16,26) and increased the probability that more myasthenic athletes will be able to participate in organized sports. We present an instructive case of a young football player that shows how a somewhat misleading symptom led to the diagnosis of MG, the effect that the patient’s desire to continue playing football had on his medical management, and how the illness and its treatment affected his athletic career. The subject gave his written consent for personal data to be used in this case study.

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CASE REPORT

In August of 1996, a 17-yr-old Division I-AA collegiate offensive lineman received a minor blow to the left side of his orbital area. An experienced trainer noted no local orbital or obvious ocular motor problems shortly after the injury. Several hours later, the athlete developed a painless, partial left ptosis without diplopia. The symptom remitted overnight, only to recur to the point of complete eye closure the next morning during a scrimmage that did not involve head trauma. Thereafter, the ptosis continued to fluctuate, clearly worsening during workouts and weight lifting (a thermogenic or “Walker” effect (18,27)) and improving several hours after the activity was over—an observation confirmed by team trainers. He denied any other current ocular motor, ophthalmologic, neurologic, or general medical symptoms. On close questioning, he recalled an episode of transient, poorly defined diplopia for 2 d after a left temporo-parietal head injury during high school football practice at age 15 yr. Two weeks later, he developed a painless, partial left ptosis that lasted for several weeks. A head CT was reportedly negative, the symptom remitted completely, and he was allowed to return to football. He used a beta2-agonist inhaler infrequently as needed for mild asthma, without any adverse muscular effects. His developmental, past medical, and family histories were otherwise unremarkable.

The initial detailed general and neurologic examinations in this very powerful, muscular, moderately obese (height 6';3″, weight 335 lbs, BMI 42 kg·m−2) male were normal except for the following: a left ptosis (palpebral fissures = 14 mm OD, 9 mm OS) without any further increase during 2 min of sustained upgaze, and a momentary decrease in the severity of the ptosis (eyelid “overshoot”) when the patient abruptly looked up after approximately 10-s down-gaze (Cogan’s lid twitch sign) (1). An intravenous Tensilon® test (10 mg) and an intramuscular neostigmine test (1.5 mg) had no clear effect on the ptosis. A subsequent neurologic examination, performed about 2 h after the patient had completed a weight-lifting session, showed the following reproducible findings: a 3-mm ptosis that exacerbated to almost complete eye closure on sustained upgaze (levator “fatigability” or “decremental response”) and improved after resting the levator for 10 s; and mild weakness of the neck flexors, deltoids, and triceps brachii, each of which worsened significantly with rapidly repeated (approximately every 2 s) isometric, manual muscle testing and recovered after 5–10 s of rest. The patient stated that he had recently noticed a progressive decrease in his exercise tolerance during weight lifting and other vigorous, repetitive exercises. This symptom took several hours to subside.

The following laboratory studies were either negative or within normal limits: WBC, differential, platelets, and ESR; sickle cell screen; serum electrolytes, calcium, glucose, and BUN; serum protein electrophoresis, TSH, total T4, T3 uptake, and nicotinic acetylcholine receptor binding antibodies; and a chest x-ray. He had a very mild normochromic, normocytic anemia (RBC = 4.7 m·mm−3, HCT = 38.8%, Hb =133 g·L−1). There was no evidence for occult blood loss or hemolysis, and iron studies and a hemoglobin electrophoresis were normal. Repetitive nerve stimulation studies at 2–4 Hz showed decremental responses in the amplitude of the compound motor unit action potentials in the left trapezius muscle of up to 15% in two independent tests, consistent with the diagnosis of myasthenia gravis. A second study 1–2 h after the patient finished vigorous weight lifting showed no further increase in the size of the decrement.

We made a diagnosis of very mild, generalized, antibody-negative MG. The patient wanted to continue in the football program. Pyridostigmine, 60 mg four times daily, was of little or no benefit, despite the fact that he experienced mild gastrointestinal side effects. We then started him on prednisone, 60 mg every other day (qod), and 40 mEq potassium, 1500 mg of calcium and 400 U of vitamin D supplements a day. We allowed him to work out with the team but not to partake in contact or games. His strength returned to normal (minimal, unchanging ptosis and normal exercise capacity) within 6 wk. Failure to keep clinical appointments and self-adjustment of medications complicated his subsequent medical management. These led to a reversible relapse after he abruptly decreased the prednisone dose to 40 mg qod and to a delay in initiating slow tapering of prednisone, which had been increased to 80 mg after the relapse. At the beginning of the second season, he was clinically asymptomatic on 70 mg of prednisone qod with marginal compliance. Bone densitometry by DEXA, after almost a year on high dose corticosteroid, indicated normal bone density of the radius (unable to measure the lumbar spine due to the patient’s weight). He continued to train with the team during his second year while his medications were adjusted, but he did not participate in contact practices or games. In the spring of his junior year, he again discontinued prednisone abruptly without seeking medical advice. He remained asymptomatic off all therapy with good exercise tolerance. He participated in full spring football practice his senior year but decided to leave the team after suffering a severe episode of mechanical low-back pain during a sprint drill. Computed tomography of the thoraco-lumbar spine was normal. He remained well off prednisone and played recreational sports. After personal reflection and on the advice of his physicians, he did not try to return to intercollegiate competition.

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DISCUSSION

Injury to the third cranial nerve after blunt head trauma has been reported to cause unilateral ptosis, but the ptosis in this setting is fixed and is usually associated with severe head injury (28). Our athlete developed fluctuating unilateral ptosis and excessive fatigability to strenuous exercise after mild head trauma. The ptosis clearly worsened after intense physical activity. This pattern coupled with a history of remitting ptosis 2 yr earlier suggested that his symptoms were the result of a widespread rather than a local process.

A clinical suspicion of MG must be confirmed by laboratory testing (Table 1). Tensilon® (edrophonium) and pyridostigmine inhibit the enzyme acetylcholinesterase and improve muscle weakness in MG by allowing acetylcholine (Ach) to interact repeatedly with a decreased number of functional Ach receptors. Our athlete did not have a diagnostic response because the dosages we used did not take into account his large size. During repetitive nerve stimulation, electric shocks are delivered to a motor nerve at 3–5 Hz, while surface electrodes record the resulting compound muscle action potentials (CMAPs) from the innervated muscle (8,24). An experienced electromyographer should perform and interpret the test results because of the different techniques that may have to be employed to demonstrate a myasthenic response; because the point at which a decremental response becomes pathologic varies from one muscle to another and because of the potential for technical errors. In normal muscle, the CMAPs show little change in amplitude over many repetitions (Fig. 1), whereas the CMAPs in a myasthenic muscle rapidly decrease (“decremental response”) (Fig. 1). A “decremental response” in a repetitive nerve stimulation test is highly specific for the diagnosis of MG. In the context of his clinical findings, the 15% decrement in our patient’s left trapezius muscle CMAPs established the diagnosis of MG. Another procedure, single-fiber electromyography, detects delayed or failed neuromuscular transmission in pairs of muscle fibers supplied by branches of a single nerve fiber (4). It is helpful if repetitive nerve stimulation is equivocal but its specificity is limited (4).

Table 1

Table 1

FIGURE 1

FIGURE 1

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: leddy@buffalo.edu.

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REFERENCES

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 94:757–760, 1994.
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:

MYASTHENIA GRAVIS,; SPORTS,; EXERCISE,; MUSCLE WEAKNESS

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