History

Fact Explanation
Drooping of eyelids It may be unilateral or bilateral but is usually asymmetrical initially. More pronounced in the evening or after exertion. Anti-Acetylcholine receptor antibodies cause destruction of nicotinic receptors at neuromuscular junction, this interferes with post synaptic transmission. [1] When the above process occurs in levator palpebrae superioris, it result in ptosis.
Double vision Fatigue of extra-ocular muscles results in diplopia.
Difficulty in chewing Involvement of muscles of mastication.
Difficulty in swallowing This may occur due to fatigue of the bulbar muscles due to anti-Acetylcholine receptor antibodies but even if they are absent there can be anti- MuSK (Muscle Specific Kinase) antibodies which also results in bulbar muscle involvement. [2]
Difficulty in lifting objects and standing from seated position. Shoulder and pelvic girdle involvement.
Difficulty in breathing Occurs due to a myasthenic crisis that is due to severe weakness of oropharyngeal muscles, diaphragm and accessory muscles of breathing.[3]
References
  1. LISAK R P,HANDBOOK of myasthenia gravis and myasthenic syndromes, New York: Marcel Dekker, inc. 1994
  2. AMELIA Evoli, TONALI P A, PADUA Luca, MONACO M L, SCUDERI Favia , BATOCCHI A P, MARINO Mariapaola and BARTOCCIONI Emanuela, Clinical correlates with anti‐MuSK antibodies in generalized seronegative myasthenia gravis,Oxford journals, Brain-A journal of neurology, Volume 126, Issue 10, Pp. 2304-2311, June 23rd 2003
  3. AGNES Jani-Acsadi, LISAK R P. Myasthenic crisis: Guidelines for prevention and treatment. Journal of the Neurological Sciences, Elsevier 261 (2007) 127-133,

Examination

Fact Explanation
Positive peek sign Patient "peeks" after sustained closure of eyes. Orbicularis occuli fatigue [1]
Positive Cogan lid twitch sign After sustained downward gaze, which relaxes the levator palpebrae superioris(LPS), if the patient looks straight ahead, there would be an excessive contraction of LPS thus an upward twitch [2]
Paradoxical reversal of ptosis caused by edrophonium Edrophonium administration alleviates ptosis, relaxing compensatory contraction (according to Hering's law of equal innervation) of LPS in the unaffected eye causing it to droop. [3]
Enhanced ptosis Elevation of the ptotic eyelid manually results in drooping of the contralateral eye [4] Due to same reason as above. (Removal of compensatory elevation of "normal" eyelid)
Deteriorating voice on counting Due to weakness of the bulbar muscles involved in phonation.
Wasting of muscles In long standing disease due to chronic acetylcholine depletion. [5]
Normal reflexes But on repetitive elicitation may fatigue
References
  1. OSHER RH, GRIGGS RC. Orbicularis fatigue: the 'peek' sign of myasthenia gravis. PubMed.gov, Arch Ophthalmol. 1979 Apr;97(4):677-9
  2. SINGMAN EL, MATTA NS, SILBER DI. Use of the Cogan lid twitch to identify myasthenia gravis. Pubmed.gov, J neuroophthalmol. 2011 Sep;31(3):239-40.
  3. A KOMIYAMA., HIRAYAMA K. Paradoxical reversal of ptosis in myasthenia gravis by edrophonium administration, J neuro neurosurg psychiatry. Volume 51(2); Feb 1988
  4. LEONID Skorin Jr, OD, DO. Testing for myathenia gravis, Optometry today, april 9-1999
  5. HANS OOSTERHUIS., BETHLEM Jaap. Neurogenic muscle involvement in myathenia gravis, Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 244-254

Differential Diagnoses

Fact Explanation
Lambert-Eaton myasthenic syndrome Unlike myasthenic weakness, improves with repetitive movement[1]. There is autonomic involvement (dry mouth, constipation, postural hypotension) [2] and gait difficulty occurring early in disease. Associated with small cell carcinoma of lung. Antibody against voltage gated calcium channels prevents release of acetylcholine in neuromuscular junction[3]
Botulism Foodborne botulism is associated with gastrointestinal symptoms. Wound botulism is associated with intravenous drug abuse. [4] Descending type of paralysis occurs unlike in myasthenia gravis. [4] Botulinum toxin binds to presynaptic nerve ending resulting in block of acetylcholine release resulting in muscle weakness. [5]
References
  1. MICHAEL MARESKA, GUTMANN Laurie. Lambert-Eaton Myasthenic Syndrome, seminars in neurology, vol 24, number 2, 2004
  2. ANDREW G.ENGEL. Myasthenia and myasthenic disorders, Oxford university press Inc., 1999
  3. TAKAMORI M, MARUTA T, KOMAI K. Lambert-Eaton myasthenic syndrome as an autoimmune calcium-channelopathy. PubMed.gov. Neurosci Res. 2000 Mar;36(3):183-91
  4. CHERINGTON Michael, Clinical spectrum of botulism, Muscle & Nerve Volume 21, Issue 6, pages 701–710, June 1998
  5. AOKI K R, Review of a Proposed Mechanism for the Antinociceptive Action of Botulinum Toxin Type A,Neuro Toxicology, Volume 26, Issue 5, October 2005, Pages 785-793

Investigations - for Diagnosis

Fact Explanation
Serum anti-Acetylcholine receptor and anti-MuSK antibodies 90% of patients with generalized myasthenia gravis and 75% with ocular myasthenia have anti-Acetylcholine receptor antibody [1]; 39-49% of patients with generalized myasthenia yet without Acetylcholine receptor antibodies have anti-MuSK antibodies. [2]
Repetitive nerve stimulation (RNS) Positive RNS features are; decrement in compound muscle action potential amplitude, post-tetanic potentiation and post-exercise exhaustion. Decrement pattern is only positive in 50% of ocular myasthenia and 75% of generalized myasthenia.
Single fibre electromyography (SFEMG) The most sensitive test for myasthenia. More than 95% positive in both generalized & ocular myasthenia. It simultaneously records potentials of two muscle fibers innervated by an individual axon and measures this variability called "Jitter".
Positive Tensilon test Admission of edrophonium results in transient improvement in symptoms. Edrophonium is a short acting acetylcholinesterase inhibitor leading to accumulation of acetylcholine thus transient improvement in symptoms.
Positive ice test Placing ice on the ptotic eyelid, relieves ptosis [3] Thought to be due to reduced temperature reducing the efficacy of anticholinesterase, resulting in reduced breakdown of acetylcholine, thus accumulation of it, improving the weakness. [4]
Mediastinal CT Sixty five percent of patients with myasthenia have thymic hyperplasia, 10-28% have thymoma and rest have normal or involuted thymus. [5]
CPK/ESR - normal Needed in the evaluation of a patient with muscle weakness. CPK and ESR would be raised in myopathies that can cause symptoms similar to myasthenia. [6]
References
  1. VINCENT A and DAVIS J N, Anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiatry. Jul 1980; 43(7): 590–600.
  2. GUPTILL J T, SANDERS D B, EVOLI A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. PubMed. Muscle Nerve. 2011 Jul;44(1):36-40. doi: 10.1002/mus.22006.
  3. GOLNIK K C, PENA Raul, LEE A G, EGGENBERGER E R. An ice test for the diagnosis of myasthenia gravis, Ophthalmology, Volume 106, Issue 7, 1 July 1999, Pages 1282-1286
  4. TABASSI A,DEHGHANI A and SABERI B. The ice test for diagnosing myasthenia gravis, Acta Medica Iranica 2005;43:60-62
  5. NAIDICH D P, WEBB W R, MULLER N L, VLAHOS L, KRINSKY G A. Computed tomography and magnetic resonance of the thorax. 4th edition. 2007. Philadelphia.
  6. SAGUIL Aaron. Evaluation of the Patient with Muscle Weakness. Am Fam Physician. [Online[ 2005 Apr 1;71(7):1327-1336. [viewed 25 April] Available from: http://www.aafp.org/afp/2005/0401/p1327.html

Investigations - Fitness for Management

Fact Explanation
Spirometry If patient is undergoing thymectomy along with other preoperative investigations spirometry should be done, since myasthenic patients may have respiratory depression complicating general anaesthesia.
References

Investigations - Followup

Fact Explanation
Forced vital capacity (FVC) In concordance with other signs and symptoms helps to decide timing of intubation and ventilation. [1]
Bed side single breath count Reducing count indicates deteriorating illness. Ventilatory support may be necessary.
References
  1. KUO P H and FAN Pi-Chuan, Respiratory care for myasthenic crisis, National Taiwan University, Hospital Taiwan, Taiwan

Investigations - Screening/Staging

Fact Explanation
Chest CT To stage thymoma, if present. [1]
References
  1. MAROM E M, MILITO M A, MORAN C A, LIU P, CORREA A M, KIM E S, KOMAKI R, ERAMUS J J, HOFSTETTER W L, RICE D C, SWISHER S G. Computed tomography findings predicting invasiveness of thymoma. PubMed. J Thorac Oncol. 2011 Jul;6(7):1274-81. doi: 10.1097/JTO.0b013e31821c4203.

Management - General Measures

Fact Explanation
Find the cause for relapse and treat the cause or remove triggers. Infections - Pneumonia/upper-respiratory infection. Drugs - Aminoglycosides, Magnesium sulfate enemas, Propranolol, Morphine, Barbiturates, Procainamide, Quinidine. Stress - pain, sleep deprivation, emotional and physical stress, extreme heat/ cold, menstruation, pregnancy, childbirth. [1]
Intubation and ventilation. Patient should be continuously monitored and decision to artificially ventilate should be taken preemptively when adequate. [1]
References
  1. PING-HUNG KUO and Pi-Chuan Fan, Respiratory care for myasthenic crisis, National Taiwan University, Hospital Taiwan, Taiwan

Management - Specific Treatments

Fact Explanation
Oral anti-Cholinesterases Eg: Pyridostigmine 60 mg qds. Provide symptomatic relief by prolonging the availability of Acetylcholine at neuromuscular junction but do not interfere with the immune processes. [1] The dose should be titrated according to treatment outcome and side effects (abdominal cramps, nausea, vomiting, diarrhea,excessive salivation). [1]
Immunosuppressants: Prednisolone, Azathioprine, Mycophenolate. In treatment relapse and if there is no response to oral anti-Cholinesterases.
Thymectomy Improves prognosis, particularly in women less than 50 years of age. Presence of thymoma has worse prognosis. [2]
Plasmapheresis and IV Immunoglobulin Used during exacerbation/Myasthenic crisis to rapidly remove the antibodies. Plasma exchange is more efficient than IV immunoglobulin, but has higher risk. [3] [4] [5]
References
  1. MANTEGAZZA R, BONANNO S, CAMERA G, and ANTOZZI C. Current and emerging therapies for the treatment of myasthenia gravis. Neuropsychiatr Dis Treat. 2011; 7: 151–160.
  2. GILHUS N E, OWE J F, HOFF J M, ROMI F, SKEIE G O and AARLI J A. Myasthenia Gravis: A Review of Available Treatment Approaches, Autoimmune Diseases, Volume 2011 (2011), Article ID 847393, 6 pages, http://dx.doi.org/10.4061/2011/847393
  3. VENUTTA F, RENDINAA E A, GIACOMOA T, ROCCAB G D, ANTONINIC G, CICCONEA A M, RICCIA C and COLONIA G F. Thymectomy for myasthenia gravis: a 27-year experience. European Journal Cardio-Thoracic Surgery Volume 15, Issue 5Pp. 621-625
  4. QURESHI A I, CHOUDHRY M A, AKBAR M S, MOHAMMAD Y, CHUA H C, YAHIA A M, ULATOWSKI J A, KRENDEL D A and LESHNER R T. Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis. Neurology February 1, 1999 vol. 52 no. 3 629 doi: 10.1212/WNL.52.3.629
  5. GAJDOS P, CHEVRET S, CLAIR B, TRANCHANT C, CHASTANG C. Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis, Annals of Neurology, Vol 41 Issue 6, DOI: 10.1002/ana.410410615