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Myasthenia Gravis

Disorders Of The Neuromuscular Junction

  1. Etiology. Antibodies directed against the acetylcholine receptor on the motor end plate cause an increased rate of receptor destruction and lead to weakness.
  2. Clinical signs. Patients are often young women or older men.
    1. Complaints of fatigue in the evening time, double vision, difficulty swallowing and speaking, and limb weakness are common, snarling face appearance. Deep tendon reflexes are normal.
    2. On examination, ptosis, bilateral eye movement abnormalities, and proximal weakness may be seen. Cranial nerve involved are 3, 4, 6, 9, 10, 12. 
    3. Bulbar palsy is common in MuSK antibody positive MG.
    4. In MG
      1. Pupillary & accommodation reactions are normal          
      2. Proptosis is not feature.
    5. A thymoma is present in 10%-25% of cases.
    6. CPK levels are typically normal.

Extra Edge: Cranial nerve which is not involve is 5th Nerve.

Useful clinical Tests to assess the effect of treatment.

  1. Forward arm abduction                        
  2. FVC
  3. Range of eye movement              
  4. Time of development of ptosis on upward eye movement

Table: Drugs with Interactions in Myasthenia Gravis (MG) (Ref. Hari. 18th ed., Pg- 3486, table 386.4)

1. Drugs That May Exacerbate MG

a. Antibiotics

   i. Aminoglycosides: e.g., streptomycin, tobramycin, kanamycin (AIIMS May 09)

   ii. Quinolones: e.g., ciprofloxacin, levofloxacin, ofloxacin, gatifloxacin

   iii. Macrolides: e.g., erythromycin, azithromycin, telithromycin

b. Nondepolarizing muscle relaxants for surgery, D-Tubocurarine, pancuronium, vecuronium, atracurium

c. Beta-blocking agents,   Propranolol, atenolol, metoprolol

d. Local anesthetics and related agents, Procaine, Xylocaine in large amounts, Procainamide (for arrhythmias) 

e. Botulinum toxin, Botox exacerbates weakness

f. Quinine derivatives, Quinine, quinidine, chloroquine, mefloquine (Lariam) 

g. Magnesium, Decreases ACh release

h. Penicillamine, May cause MG

2. Drugs with Important Interactions in MG

i. Cyclosporine, Broad range of drug interactions, which may raise or lower cyclosporine levels. 

ii. Azathioprine, Avoid allopurinol—combination may result in myelosuppression. 

Diagnostic studies

  1. Administration of intravenous edrophonium (a short-acting cholinesterase inhibitor) usually produces a transient improvement in strength in patients suffering from myas­thenia gravis.

Extra edge: (Ref. Hari. 18th ed., Pg- 3481)


The edrophonium test is now reserved for patients with clinical findings that are suggestive of MG but who have negative antibody and electrodiagnostic test results. False-positive tests occur in occasional patients with other neurologic disorders, such as amyotrophic lateral sclerosis, and in placebo-reactors.

  1. Repetitive nerve stimulation studies can demonstrate a decremental response of the compound muscle action potential.
  2. Acetylcholine receptor antibodies can be detected in the blood of 80%-90% of patients.
  3. A thoracic CT or MRI scan shows a thymoma, if present.
  4. EMG is the most sensitive & most specific test.


  1. The mainstay of therapy is administration of a cholinesterase inhibitor (e.g., pyridostigmine).
  2. Corticosteroids, immunosuppressive agents, intravenous immunoglobulin, or plasma­ pheresis are effective in patients with refractory disease.

Extra edge: (Ref. Hari. 18th ed., Pg- 3484)

  1. Mycophenolate mofetil has become one of the most widely used drugs in the treatment of MG because of its effectiveness and relative lack of side effects.
  2. Azathioprine, the calcineurin inhibitors cyclosporine and tacrolimus (FK506) are also used.
  3. Cyclophosphamide is reserved for occasional patients refractory to the other drugs (see above for discussion of high-dose cyclophosphamide treatment).
  1. Thymectomy
  2. Some time spontaneous remission can occur.

Thymic Abnormalities and myasthenia Gravis (MG) and recommendations for thymectomy


Myasthenia Gravis patients have a high incidence of thymic abnormalities Thymus is abnormal in about 75% of patients

65% of patients have a hyperplastic thymus (LQ 2012)

10% of patient have thymomas

Thymus is believed to play a role in the autoimmune dysfunction in M G and thymectomy leads to significant improvement in upto 85% of patients with MG (35% achieve drug free remission).


Thymectomy is therefore recommended as a form of treatment for MG.

  1. Patients with thymomas
    1. Thymectomy should be carried out in all patients who have thymomas.
    2. Thymectomy in thymomas is necessary because of the possibility of local tumor spread although most thymomas are benign.   
  2. Patients without thymomas
    Thymectomy should be carried out in all patients with generalized MG who are between the ages of puberty and at least 55 years.
  3. Thymectomy not recommended for:
    1. Children (<puberty)
    2. Elderly >55 years
    3. Localized M. G. with weakness limited to extra ocular muscles
    4. Patients with MUSK antibody positive Myasthenia gravis.


  1. Thymoma is a tumor originating from the thymus. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant and probably not neoplastic.
  2. Thymoma usually is benign, and frequently encapsulated; when occasionally malignant, then it is invasive: distant metastasis are rare.
  3. It is not associated with SIADH.


Clinical syndrome associated with Thymomas

Characteristic Syndrome

Rare Syndrome (Other autoimmune Disorders)

1. Myasthenia Gravis (Most common) (LQ 2012)

2. Acquired Hypogammaglobulinemia (10%) (LQ 2012)

3. Pure Red Cell Aplasia (LQ 2012)

1. Connective Tissue Disorders (Rare)

a.  Polymyositis

b.  Dermatomyositis

c.  Granulomatous myocarditis

d.  SLE

e.  Rheumatoid Arthritis

f.  Scleroderma and Sjögren’s syndrome

2. Pemphigus

3. Pernicious Anemia (Rare)

4. Auto immune Thyroiditis and Grave's disease (Rare)


Extra Edge:

  1. Thymoma is associated with Hypogammaglobulinemia and not with hypergammaglobulinemia
  2. Myoid cells are present in thymoma

Immune status with Thymoma:

  1. T-cell number & cell mediated immunity are usually intact
  2. These patients are very deficient in circulating B lymphocytes & pre B cell in the bone marrow
  3. Hypogammaglobulinemia usually occurs relatively late in adult life.
  4. Bacterial infection & severe diarrhea usually reflect this antibody deficiency. 
  5. Frequently have eosinopenia
  6. May develop Red cell (Erythroid) Aplasia.

Extra Edge:

  1. FNAC is not done in case of thymomas (It is inconclusive)
  2. An abscess of the thymus is also known as "Dubois' abscesses" (LQ 2012)

Differential diagnosis

  1. Eaton-Lambert myasthenic syndrome (Ref. Hari. 18th ed., Pg- 3482).
  2. Proximal muscle weakness, specially of legs, ptosis, eye muscle weakness. 
  3. They have antibody against P/Q type of calcium channel.
  4. Diagnostic studies. Repetitive nerve stimulation studies show an incremental response of the compound muscle action potential.
  5. Treatment:
    1. Pyridostigmine
    2. Immuno suppression
    3. Plasmapheresis

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