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Myasthenia Gravis: Differential Diagnoses & Workup

Author: Shady Awwad, MD, Staff Physician, Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas
Coauthor(s): Riad Ma'luf, MD, Head, Division of Oculoplastics, Department of Ophthalmology, Clinical Assistant Professor, American University of Beirut Medical Center; Nicolas Hamush, MD, Consulting Staff, Department of Ophthalmology, Eye & Ear Hospital International, Naccache, Lebanon
Contributor Information and Disclosures

Updated: Jul 13, 2007

Differential Diagnoses

Botulism
Chronic Progressive External Ophthalmoplegia

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

Laboratory 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.

More on Myasthenia Gravis

Overview: Myasthenia Gravis
Differential Diagnoses & Workup: Myasthenia Gravis
Treatment & Medication: Myasthenia Gravis
Follow-up: Myasthenia Gravis
Multimedia: Myasthenia Gravis
References
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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].

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  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].

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Further Reading

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Keywords

MG, ocular myasthenia gravis, generalized myasthenia gravis, ocular MG, generalized MG, neuromuscular disorder

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Contributor Information and Disclosures

Author

Shady Awwad, MD, Staff Physician, Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas
Shady Awwad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, and American Society of Cataract and Refractive Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Riad Ma'luf, MD, Head, Division of Oculoplastics, Department of Ophthalmology, Clinical Assistant Professor, American University of Beirut Medical Center
Disclosure: Nothing to disclose.

Nicolas Hamush, MD, Consulting Staff, Department of Ophthalmology, Eye & Ear Hospital International, Naccache, Lebanon
Nicolas Hamush, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

Kilbourn Gordon III, MD, FACEP, Urgent Care Physician, Primary Medical, Huntington Walk-In and Greenwich Convenient Medical Center
Kilbourn Gordon III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Pan-American Association of Ophthalmology, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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