Diagnosis & Management of a Patient with Myasthenia Gravis


Patient presents with signs & symptoms of progressive ptosis, dysphagia, weakness and slurred speech over last few weeks.

1. What is the most probable Diagnosis?
2. Which test is used to diagnose it?
3. How to conduct this test?
4. What is the management of this patient?
5. How will you differentiate the toxicity of drug treatment from drug failure?

6. Classify drugs used to treat this condition


1.Diagnosis: Myasthenia Gravis
This is an autoimmune disease in which antibodies are produced against the nicotinic receptors at the neuromuscular junction. Therefore synaptic transmission at the neuromuscular junction is severely impaired.
The patient complains of severe muscular weakness worsened by even slight physical exertion. Ptosis reflects the muscle weakness. Respiratory muscles may even be affected causing respiratory embarrassment.

2.Test to Diagnose: Tensilon Test (Edrophonium Test)

3. How to conduct: Give Edrophonium IV- an effective acetylcholinesterase inhibitor – will reduce the muscle weakness by blocking the enzymatic effect ofacetylcholinesterase enzymes, prolonging the presence of acetylcholine in the synaptic cleft. If improvement occurs on administration the diagnosis of myasthenia gravis is confirmed.
Edrophonium is preferred over other reversible acetylcholinesterase inhibitors because of its ultra-short duration of action, so that even if does not improve the condition, its adverse effects will only be for a short duration (about 10 minutes).

4. Management:
Reversible anticholinestrases are used to treat this condition because they increase the duration and intensity of action of acetylcholine at the synaptic cleft.
Neostigmine is preferred over physostigmine because:

  1. Neostigmine has both direct as well as in direct action at the neuromuscular junction & thus more effective
  2. Neostigmine has less/minimal CNS adverse effects as it doesnt cross BBB that readily, due to its polar nature

Other quaternary amines like Pyridostigmine or Ambenonium may be given; these have longer duration of action

Atropine may also given to decrease disturbing muscarinic actions of these drugs like increased frequency of urination, diarrhea etc

Other Drugs: See classification below

5. How to differentiate cholinergic crisis from Myasthenic crisis:
a) During the treatment of myasthenia gravis with neostigmine, muscle weakness may suddenly occur
b) In case of MYASTHENIC CRISIS, the dose of neostigmine is insufficient —-muscle weakness occurs
c) In case of CHOLINERGIC CRISIS, the dose of neostigmine is excess—-muscle weakness occurs (Due to persistent depolarization, there is depolarization block causing skeletal muscle weakness)
d) Edrophonium is given to differentiate and plan further action/treatment:
• If improvement occurs—Myasthenic crisis, so increase dose of neostigmine
• If condition worsens–Cholinergic Crisis, so decrease dose of neostigmine

Treatment of Myasthenia Gravis

A. Pharmacological Treatment

  1. Anticholinestrases

               Neostigmine                                                   Pyridostigmine

Ambenonium                                                  Physostigmine

  1. Immunosuppressants

              a) Corticosteroids

Prednisone                                          Methylprednisolone

b) Other Immunosuppressants

                       Azathioprine                                      Cyclosporine

Mycophenolate Mofetil                      Methotrexate

Cyclophosphamide                             Rituximab

                c) Immunoglobulin

Immune Intravenous Globulin G (IVIG)

B. Plasma Exchange (Plasmapheresis)

C. Thymectomy

(From my book Nauman’s Textbook of Pharmacology)

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