AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Myasthenia gravis (MG) is a disorder of neuromuscular transmission characterized by weakness and fatigability of skeletal muscles. The basic pathology is a reduced number of acetylcholine receptors (AChR) at the postsynaptic muscle membrane brought about by an acquired autoimmune reaction producing anti-AChR antibodies. Two major clinical forms of MG are distinguished, ocular MG and generalized MG.

Pathophysiology

When an action potential travels down a motor nerve and reaches the nerve terminal, acetylcholine (ACh) molecules are released from the presynaptic vesicles and adhere to AChR at the peaks of postsynaptic folds. Channels in the AChR open, allowing Na⁺ and other cations to enter into the muscle fiber endplate and depolarize it. The multiple depolarizations will sum up and, if large enough, trigger an action potential, which travels along the muscle fiber to produce contraction.

With every nerve impulse, the amount of ACh released by the presynaptic motor neuron normally decreases due to a temporal depletion of the presynaptic ACh stores (presynaptic rundown).

In MG, there is a reduction in the number of AChR available at the muscle endplate and flattening of the postsynaptic folds. The fewer endplate potentials produced by the yet normal amount of ACh released might fail to be translated into an action potential. The end result is an inefficient neuromuscular transmission.

This inefficient neuromuscular transmission together with the normally present presynaptic rundown phenomenon results in a decremental amount of nerve fibers being activated by successive nerve fiber impulses. This explains the fatigability in the involved patients.

The decrease in number of the postsynaptic AChR is believed to be due to an autoimmune process whereby anti-AChR antibodies are produced and act to block the target receptors, increase their turnover, and damage the postsynaptic membrane in a complement-mediated manner.

Although the primary etiology remains speculative, there is increasing evidence that the thymus might play an important role. Histopathologic studies showed prominent germinal centers. Epithelial myoid cells normally present in the thymus do resemble skeletal muscle cells and possess AChR on their surface membrane. These cells may become antigenic and unleash an autoimmune attack on the muscular endplate AChR by molecular mimicry.

Why the disease afflicts first and predominantly the extraocular muscles remains unanswered. It probably has to do with the physiology and antigenicity of the muscles in question.

Frequency

United States

The annual incidence is 2 cases per 1,000,000. The prevalence of MG in the United States is approximately 14 cases in 100,000.

International

Prevalence of MG in the United Kingdom is 15 cases per 100,000 population and 10 cases per 100,000 in Croatia. In Sardinia, Italy, prevalence increased from 0.75 to 4.5 cases per 100,000, respectively, for the years 1958 and 1986.

Mortality/Morbidity

In the era before corticosteroids were used for treatment, one third of patients died of the disease. With modern treatment options, MG is no more as serious at it was before, rendering the word gravis a misnomer in most cases.

Today, the only feared condition is when the weakness involves the respiratory muscles. Weakness might become so severe as to require ventilatory assistance. Those patients are said to be in myasthenic crisis.

Sex

Overall, women are affected more than men with a female-to-male ratio of 3:2. Yet, recent studies show that with increased life expectancy, males are becoming as equally affected as females. Ocular MG shows a male preponderance.

Age

MG can occur at any age but peaks in females in the fourth to fifth decade of life and in males in the sixth to seventh decade. Neonatal forms do occur but are rare. Infantile and juvenile forms have different courses than in adults.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The usual initial complaint is a specific muscle weakness rather than generalized muscle weakness. The severity of the weakness typically fluctuates over hours being least severe in the morning and worse as the day progresses. It also varies over the course of weeks or months, with exacerbations and remissions.

Exposure to bright sunlight, viral illness, surgery, immunization, emotional stress, menstruation, and physical factors might trigger or worsen the exacerbations.

• Ophthalmic symptoms
  
  
  • Of the patients, 75% initially complain of ocular disturbance, mainly ptosis and diplopia. Eventually, 90% of patients with MG develop ocular symptoms. About 50% of patients will present solely with ocular symptoms, and about 50-60% of these patients will progress to develop generalized disease.
  • Ptosis may be unilateral or bilateral, and it may shift from eye to eye.
• Nonophthalmic symptoms
  
  
  • Oropharyngeal muscle disturbances come second in presentation, with 15% of patients first experiencing difficulty in swallowing, talking, and chewing.
  • Limb and trunk weakness is the initial complaint of 10% of patients. Yet, 85% of patients with MG develop a generalized weakness also affecting the limb muscles.
  • MG can involve the respiratory muscles and can lead to respiratory failure. This can sometimes be the first presentation of the disease. Qureshi et al showed that out of 51 patients with MG and respiratory failure, 7 (14%) had no previous diagnosis of MG.¹

Physical

• Ptosis
  
  
  • Ptosis can be unilateral or bilateral.
  • The ptosis is usually most prominent upon sustained upward gaze (see Media file 1) or repeated eyelid closure.
  • In cases of unilateral ptosis, the contralateral lid may assume a ptotic position upon occluding the eye with the ptosis or lifting the ptotic lid with a finger (Herring phenomenon).
  • The lid twitch sign described by Cogan can be elicited by having the patient change gaze from the downward position to the primary position.² The lid will be seen to overshoot in a twitch before gaining its initial ptotic position (see Media file 2). A recent study, however, has questioned the validity of such a sign, as its sensitivity and specificity were shown to be relatively low.³
  • A subtle lid flutter is occasionally encountered.
• Extraocular muscle involvement
  
  
  • Extraocular muscle involvement does not follow a certain pattern. However, the superior rectus and/or the medial rectus are commonly involved (see Media file 1).
  • Isolated inferior rectus palsy is rare, but, when present, it raises the suspicion of MG since it is extremely rare to be encountered otherwise.
  • The spectrum of affection stretches from isolated muscle palsies to total external ophthalmoplegia.
  • Any acquired ocular motility disturbance with or without ptosis, but normally reacting pupils, should raise the clinical suspicion of MG.
• Orbicularis involvement
  
  
  • Orbicularis involvement consistently is present when ocular symptoms are reported.
  • Weakness in forceful closure of the eyes against resistance is present.
• Pupils and ciliary muscles: Traditionally, pupils and ciliary muscles were believed not to be involved, although recent studies suggest the contrary, notably in a case analysis by Cooper and coworkers.⁴
• Weakness in facial, oropharyngeal, limbal, and trunk muscles, without any other sign of neurologic deficit, such as sensory loss, change in deep tendon reflexes, or muscle atrophy
  
  
  • Facial weakness frequently imparts a snarling expression upon attempted smiling. Speech may have a nasal quality.
  • Upper extremities fatigue is demonstrated best by having patients sit with arms stretched in front of them. Lower extremities fatigue is tested by stepping up and down over a footstool. Grip strength is measured best by a dynamometer.
• Fatigability: Patients show incremental weakness upon repeating the motor power test over and over.

Causes

The main cause behind the development of MG remains speculative. The end result is a derangement in the immune system regulation. Associated findings with MG are many.

• Anti-AChR antibodies are present in most but not all patients with MG.
• Thymic enlargement: Of patients with MG, 75% have thymic disease, 85% have thymic hyperplasia, and 10-15% have thymoma.
• Histocompatibility complex profile
  
  
  • Human leukocyte antigens B8, DRw3, and DQw2
  • These were not shown to be associated with the strictly ocular form of the disease.
• Autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), may be associated with MG.
• Extrathymic tumors may include small cell lung cancer and Hodgkin disease.
• Hyperthyroidism is present in 3-8% of patients with MG and especially is associated with ocular MG.
• Drugs
  
  
  • D-penicillamine can induce true myasthenia with elevated anti-AChR antibody titers. However, the weakness is mild, and full recovery is achieved weeks to months after discontinuation of the drug.
  • Nitrofurantoin has been linked to the development of ocular MG in one case report. Discontinuation of the drug also resulted in complete recovery.
  • Aminoglycosides, polymyxins, and many other drugs are associated with MG.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Kearns-Sayre syndrome
Brainstem etiology
Drug-induced myasthenialike syndrome
Lambert-Eaton myasthenic syndrome
Amyotrophic lateral sclerosis
Depression
Congenital myasthenic syndromes

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Anti-AChR antibodies assay
• • Anti-AChR antibodies assays are positive in as many as 90% of patients with generalized MG. The test is only positive in 50-70% of patients afflicted with strictly ocular MG.
  • This test is highly specific (as many as 100% specific as shown by Padua and coworkers).⁵
• Thyroid function tests are indicated to rule out associated Graves disease or hyperthyroidism. This is essential, especially in patients with ocular MG where the concomitant hyperthyroidism is most frequent.
• Rheumatoid factor and antinuclear antibodies are indicated to rule out SLE and RA.

Imaging Studies

• MRI or CT scan of the brain and orbit is essential in ocular MG to rule out mass lesions compressing cranial nerves.
• MRI or CT of the mediastinum (thin sections) is indicated to rule out a thymoma or thymic enlargement (see Media file 3).

Other Tests

• Anticholinesterase test
  
  • The strength of an involved group of muscles is assessed before and after administration of intravenous edrophonium chloride (Tensilon) 10 mg/mL.
    
  • A test dose (1 mg) should be given first, followed by a 4-mg bolus. If no response is elicited in 1 minute, an additional 5 mg are given.
    
  • This test may give both false-negative results and false-positive results. It has a low sensitivity in ocular MG; 50% of patients presenting with eye symptoms will be missed. On the other hand, diseases such as amyotrophic lateral sclerosis (ALS) and cavernous sinus lesions can score positive on the test, as shown by Phillips and Melnick.⁶
    
  • This test has been combined with electromyography (EMG) and ocular tonography to increase its sensitivity in ocular MG. However, it still produces false-negative and false-positive results.
    
  • Tensilon in combination with the Lancaster red-green screen testing for diplopia is being used. Most patients would show an improvement in some fields of gaze and a worsening in other directions of gaze. Other patients would not appreciate any change.
    
  • Tensilon, combined with electronystagmographic analysis of optokinetic nystagmus, seems promising in diagnosing ocular MG. Toth and coworkers and Yang and coworkers have shown this recently.^{7, 8}
    
• Recently, the ice pack test (ie, placing ice over the lid) has gained interest among ophthalmologists to assess improvement in ptosis and diplopia in ocular MG.
  
  • The rationale behind this test is that cooling might improve neuromuscular transmission.
    
  • Movaghar and Slavin questioned the validity of such a test by demonstrating that patients with ocular MG actually improve on the ice, heat, and modified sleep tests.⁹ Hence, rest might be the cause of the improvement in ocular signs.
    
  • Both the ice test and the rest test are sensitive and specific in ocular MG.¹⁰
    
• Repetitive nerve stimulation
  
  • Repetitive nerve stimulation (RNS) should lead to a decremental response in compound action potentials on EMG.
    
  • A stimulation rate of 1-5 per second should result in a 10% or more decrease in amplitude by the fourth action potential (see Media file 4).
    
  • RNS results are less likely to be positive in patients with ocular MG.
    
• Single fiber electromyography
  
  • Single fiber electromyography (SFEMG) records action potentials from single muscle fibers in a motor unit.
    
  • A "jitter" phenomenon usually is noted (see Media file 5), and it represents variability of the time interval between the action potentials of 2 single muscle fibers in the same motor unit.
    
  • SFEMG is a substitute for the RNS in patients with ocular MG, being much more sensitive. A recent study by Padua and coworkers on 86 patients with ocular MG showed 100% sensitivity.⁵
    
  • This test is technically demanding and operator dependent. It has a lower specificity, and it can give positive results in other neuromuscular disorders.

Procedures

• Muscle biopsy (rarely performed)

Histologic Findings

Studies of muscle biopsy specimens showed that the neuromuscular junctions of patients had only one third of the average AChR found normally. Morphologic changes, such as simplification of the pattern of postsynaptic membrane folding and an increase in the gap between the nerve terminal and the postsynaptic muscle membrane, also are present.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

A wide armamentarium of medical therapy exists for patients with MG. No general consensus exists about which to start first or which to combine. Medical treatment is administered best by a neurologist. The role of the ophthalmologist is to follow up on the ophthalmic symptoms, notably diplopia and ptosis.

• Ptosis, when it becomes bothersome, is treated best by lid crutches, since surgery is contraindicated because of the fluctuation of the disease, producing lagophthalmus with all of its complications. Diplopia is eliminated by Fresnel prisms unless the deviation is large and variable, in which case an opaque lens in front of the involved eye is preferred.
• The neurologist orchestrates the pharmacologic treatment. This includes anticholinesterase medication and immunosuppressive agents, such as corticosteroids, azathioprine, cyclosporine, plasmapheresis, and intravenous immune globulin (IV Ig).
• No evidence-based studies fully prove the usefulness of cholinesterase inhibitors, corticosteroids, and other immunosuppressive agents in improving ocular symptoms. In addition, the effect of corticosteroids and azathioprine on the progression to generalized MG is still uncertain.
• Plasmapheresis (as well as IV Ig) is reserved for myasthenic crisis and refractory cases. It removes anti-AChR antibodies from the circulation. Improvement is noted in a couple of days, but it does not last for more than 2 months.

Surgical Care

• Thymectomy
  
  
  • In the absence of a thymoma, 85% of patients experience improvement and 35% of these patients achieve drug-free remission.
  • In one study by Nieto and coworkers, the rate of remission in the presence of thymic hyperplasia was 42% compared to 18% in patients with thymoma.¹¹
  • In ocular MG, thymectomy should be delayed at least 2 years to allow for spontaneous remission or for generalized MG to develop.
  • Whether thymectomy is to be performed for prepubescent patients or patients older than 55 years is still controversial. Recent reports encourage surgery for the latter group.
  • Patients often experience some transient worsening of symptoms early in the postoperative period.
  • Improvement usually is delayed for months or years.
  • Complete removal of thymic tissue is of utmost importance because any small remnant might lead to recurrence.
• Strabismus surgery: Muscle surgery for selected patients with a stable course of MG and persistent diplopia has been reported with success.^{12, 13}
• Blepharoptosis surgery: Ptosis surgery for patients with a stable ptosis, which has failed to respond to medical therapy for MG, has recently gained popularity. The surgical technique can include external levator advancement, frontalis suspension sling, or tarsomyectomy.^{14, 15}

Consultations

• Consult neurologists after diagnosing patients with ocular MG. Treatment is initiated best by them rather than the ophthalmologist.
• Consult cardiothoracic surgeons whenever thymectomy is contemplated as part of the treatment.

Diet

• Solid diet might be difficult for some patients to chew in acute oropharyngeal exacerbations.
• Aspiration might occur too, so clear fluids are to be avoided and are supplanted best by full fluids when dysphagia is present.
  

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Anticholinesterase inhibitors

Increase the availability of ACh in the neuromuscular junction. They continue to be used as the first line of treatment of MG. The improvement is usually partial and frequently decreases after many weeks to months of treatment. Besides, they are not as beneficial for ocular MG as for the generalized form of the disease. Hence, they often are complemented (and sometimes substituted) with immunosuppressive therapy.

Drug Category: Immunomodulatory agents

Aim at suppressing the autoimmune process. The armamentarium includes prednisone, azathioprine, cyclosporine, IV Ig, and plasmapheresis.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Intubation and intensive care unit transfer usually are reserved for patients in myasthenic crisis with respiratory failure. Plasmapheresis or IV Ig also will be needed.

Further Outpatient Care

• Follow-up care is conducted mainly by the neurologist, who would orchestrate the treatment. The ophthalmologist is consulted accordingly.

In/Out Patient Meds

• See Medication.

Complications

• Systemically, myasthenic crisis is the most dreadful complication. Aspiration pneumonia also may occur due to the poor oropharyngeal muscle function. Cholinergic crisis may follow excessive treatment with cholinesterase inhibitors.
• Ophthalmologically, a common complication is cataract formation due to chronic steroid intake.

Prognosis

• Approximately 15-17% of patients will remain having strictly ocular symptoms over a mean follow-up period of 17 years, as determined in one study. Those patients are referred to as having ocular MG. The rest develop a generalized weakness and are referred to as having generalized MG.
• Some evidence shows that steroids or azathioprine might prevent the conversion to generalized MG in 75% of patients with ocular MG.
• Bever and coworkers reported that 82% of patients who later developed generalized weakness did so in the first 2 years after diagnosis.¹⁶ Hence, patients who keep having strictly ocular symptoms for 3 or more years are unlikely to revert to the generalized aspect of the disease.
• The juvenile form of the disease usually has a much more favorable prognosis than the adult one, with a better chance of spontaneous remission.

Patient Education

• Patients should be instructed to immediately report any noticeable decrease in their respiratory function.
• It should be made clear to patients that some common medications, such as aminoglycosides, penicillin, and ciprofloxacin, can exacerbate the symptoms. They should always consult their neurologist prior to starting any of the medications listed above.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• It is essential to rule out mass lesions compressing the cranial nerves in strictly ocular MG. A CT scan or MRI of the brain and orbit is indicated.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Increasing left ptosis developing upon sustained upward gaze in a patient with myasthenia gravis (A through F). Note the limited elevation of the left eye denoting superior rectus palsy (A). A initially, C after around 20 seconds, F after 1 minute.
	View Full Size Image
Media type:  Photo

Media file 2:  Cogan sign. The patient changes gaze from the downward position (A) to the primary position (B). Both lids are seen to overshoot in a twitch (B) before gaining their initial ptotic position (D). In this case, the Cogan sign is seen more obviously on the right, whereas the left lid is more ptotic.
	View Full Size Image
Media type:  Photo

Media file 3:  CT scan of chest/mediastinum showing a thymoma in a patient with myasthenia gravis.
	View Full Size Image
Media type:  CT

Media file 4:  Repetitive nerve stimulation at a frequency of 2 Hz showing an increasing decrement in the amplitude of the compound muscle action potential up to the fourth response (42% amplitude loss), after which it stabilizes.
	View Full Size Image
Media type:  Graph

Media file 5:  Single fiber electromyography showing the "jitter" phenomenon (second action potential wave group).
	View Full Size Image
Media type:  Graph

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Qureshi AI, Choundry MA, Mohammad Y, Chua HC, Yahia AM, Ulatowski JA, et al. Respiratory failure as a first presentation of myasthenia gravis. Med Sci Monit. Dec 2004;10(12):CR684-689. [Medline].
2. Cogan DG. Myasthenia gravis: A review of the disease and a description of lid twitch as a characteristic sign. Arch Ophthalmol. Aug 1965;74:217-21. [Medline].
3. Van Stavern GP, Bhatt A, Haviland J, Black EH. A prospective study assessing the utility of Cogan's lid twitch sign in patients with isolated unilateral or bilateral ptosis. J Neurol Sci. May 15 2007;256(1-2):84-5. [Medline].
4. Cooper J, Pollak GJ, Ciuffreda KJ, Kruger P, Feldman J. Accommodative and vergence findings in ocular myasthenia: a case analysis. J Neuroophthalmol. Mar 2000;20(1):5-11. [Medline].
5. Padua L, Stalberg E, LoMonaco M, Evoli A, Batocchi A, Tonali P. SFEMG in ocular myasthenia gravis diagnosis. Clin Neurophysiol. Jul 2000;111(7):1203-7. [Medline].
6. Phillips LH 2nd, Melnick PA. Diagnosis of myasthenia gravis in the 1990s. Semin Neurol. Mar 1990;10(1):62-9. [Medline].
7. Toth L, Toth A, Dioszeghy P, Repassy G. Electronystagmographic analysis of optokinetic nystagmus for the evaluation of ocular symptoms in myasthenia gravis. Acta Otolaryngol. 1999;119(6):629-32. [Medline].
8. Yang Q, Wei M, Sun F, Tian J, Chen X, Lu C. Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects. Exp Neurol. Nov 2000;166(1):166-72. [Medline].
9. Movaghar M, Slavin ML. Effect of local heat versus ice on blepharoptosis resulting from ocular myasthenia. Ophthalmology. Dec 2000;107(12):2209-14. [Medline].
10. Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord. Jul 2006;16(7):459-67. [Medline].
11. Nieto IP, Robledo JP, Pajuelo MC, Montes JA, Giron JG, Alonso JG, et al. Prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases. Ann Thorac Surg. Jun 1999;67(6):1568-71. [Medline].
12. Acheson JF, Elston JS, Lee JP, Fells P. Extraocular muscle surgery in myasthenia gravis. Br J Ophthalmol. Apr 1991;75(4):232-5. [Medline].
13. Davidson JL, Rosenbaum AL, McCall LC. Strabismus surgery in patients with myasthenia. J Pediatr Ophthalmol Strabismus. Sep-Oct 1993;30(5):292-5. [Medline].
14. Bradley EA, Bartley GB, Chapman KL, Waller RR. Surgical correction of blepharoptosis in patients with myasthenia gravis. Ophthal Plast Reconstr Surg. Mar 2001;17(2):103-10. [Medline].
15. Bernardini FP, de Conciliis C, Devoto MH. Frontalis suspension sling using a silicone rod in patients affected by myogenic blepharoptosis. Orbit. Sep 2002;21(3):195-8. [Medline].
16. Bever CT Jr, Aquino AV, Penn AS, Lovelace RE, Rowland LP. Prognosis of ocular myasthenia. Ann Neurol. Nov 1983;14(5):516-9. [Medline].
17. Barton JJ, Fouladvand M. Ocular aspects of myasthenia gravis. Semin Neurol. 2000;20(1):7-20. [Medline].
18. Benatar M, Kaminski HJ. Evidence report: The medical treatment of ocular myasthenia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Jun 12 2007;68(24):2144-9. Epub 2007 Apr 25. [Medline].
19. Drachman DB. Myasthenia gravis. N Engl J Med. Jun 23 1994;330(25):1797-810. [Medline].
20. Larner AJ, Thomas DJ. Can myasthenia gravis be diagnosed with the 'ice pack test'? A cautionary note. Postgrad Med J. Mar 2000;76(893):162-3. [Medline].
21. Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med. Nov-Dec 1971;38(6):497-537. [Medline].
22. Wang ZY, Diethelm-Okita B, Okita DK, Kaminski HJ, Howard JF, Conti-Fine BM. T cell recognition of muscle acetylcholine receptor in ocular myasthenia gravis. J Neuroimmunol. Aug 1 2000;108(1-2):29-39. [Medline].
23. Wasserman BN, Chronister TE, Stark BI, Saran BR. Ocular myasthenia and nitrofurantoin. Am J Ophthalmol. Oct 2000;130(4):531-3. [Medline].

Article Last Updated: Jul 13, 2007