Diagnosis & Management of a Patient with Myasthenia Gravis

Question:

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

1. What is the 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?

Answers:

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 also given to decrease muscarinic effects of these drugs.

Other drugs for Myasthenia Gravis if these Reversible anticholinestrases do not work include corticosteroids, penicillamine and other immunosuppressants like Methotrexate, Azathioprine, Cyclophosphamide, cyclosporine etc
Plasmapheresis (plasma exchange) or thymectomy are the last resort

5. How to differentiate toxicity (cholinergic crisis) from drug failure (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
• If improvement occurs—Myasthenic crisis
• If condition worsens–Cholinergic Crisis

(From my book Nauman’s Textbook of Pharmacology)

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