What is the difference between myasthenic crisis and the use of acetylcholinesterase (AChE) inhibitors, such as pyridostigmine, in the management of myasthenia gravis?

Difference Between Myasthenic Crisis and Acetylcholinesterase Inhibitors

Myasthenic crisis and cholinergic crisis (caused by acetylcholinesterase inhibitors) are two distinct conditions that can occur in myasthenia gravis patients, with opposite treatment approaches - myasthenic crisis requires increasing acetylcholinesterase inhibitors while cholinergic crisis requires immediate withdrawal of these medications. 1

Myasthenic Crisis

• Myasthenic crisis is characterized by worsening muscle weakness due to an increase in the severity of the underlying myasthenia gravis disease, often requiring respiratory support 2
• It represents an exacerbation of the autoimmune process that targets nicotinic acetylcholine receptors, reducing the number of functional receptors at the neuromuscular junction 2
• Clinical features include increasing muscle weakness, particularly of respiratory and bulbar muscles, which may lead to respiratory failure 2
• Treatment approach includes:
  • Intensification of acetylcholinesterase inhibitor therapy (such as pyridostigmine) 1
  • Intravenous immunoglobulin (IVIG) or plasma exchange for severe cases 3
  • Corticosteroids (methylprednisolone 2-4 mg/kg/day or pulse dosing of 1g/day for 5 days) 2
  • Consultation with a neurologist is mandatory 2

Cholinergic Crisis (Acetylcholinesterase Inhibitor Overdose)

• Cholinergic crisis occurs due to excessive acetylcholinesterase inhibitor medication, leading to an accumulation of acetylcholine at neuromuscular junctions and muscarinic receptors 1
• It is characterized by increasing muscle weakness that can mimic myasthenic crisis, making differential diagnosis challenging but critically important 1
• Additional symptoms include muscarinic effects: increased secretions, lacrimation, salivation, bronchospasm, abdominal cramping, diarrhea, and bradycardia 1
• Treatment approach is opposite to myasthenic crisis:
  • Prompt withdrawal of all acetylcholinesterase inhibitor medications 1
  • Administration of atropine to counteract muscarinic effects 1
  • Supportive care including possible ventilatory support 1

Acetylcholinesterase Inhibitors in Management

• Pyridostigmine is the most commonly used acetylcholinesterase inhibitor for myasthenia gravis, typically started at 30mg orally three times daily and increased as needed up to 600mg daily 4, 5
• These medications work by inhibiting the enzyme acetylcholinesterase, thereby increasing acetylcholine availability at the neuromuscular junction 5
• In myasthenic crisis, pyridostigmine may be continued or increased, whereas in cholinergic crisis it must be discontinued 1
• For patients unable to take oral medications, pyridostigmine can be administered intravenously (30mg oral equivalent to 1mg IV) or neostigmine can be given intramuscularly (0.75mg) 2, 6
• During intubation for severe crisis, pyridostigmine may be temporarily discontinued or withheld 2

Differential Diagnosis Between the Two Crises

• Differential diagnosis is critical as treatment approaches are radically different 1
• The edrophonium (Tensilon) test may be used to distinguish between the two conditions:
  • Improvement after edrophonium suggests myasthenic crisis
  • Worsening after edrophonium suggests cholinergic crisis 1, 7
• Clinical features that may help differentiate:
  • Prominent muscarinic symptoms (increased secretions, abdominal cramping) suggest cholinergic crisis 1
  • Recent reduction or missed doses of acetylcholinesterase inhibitors suggests myasthenic crisis 6

Special Considerations

• Patients with myasthenia gravis have higher sensitivity to non-depolarizing neuromuscular blocking agents and require reduced dosing 2
• Certain medications should be avoided in myasthenia gravis patients as they may exacerbate symptoms: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 4
• Regular monitoring of pulmonary function is crucial in patients with generalized myasthenia gravis to detect early signs of respiratory compromise 4
• Patients with myasthenia gravis who are treated with cholinesterase inhibitors express reduced plasma cholinesterase activity and are at risk for prolonged neuromuscular blockade with certain anesthetic agents 2