Myasthenia gravis

Background

• Autoantibody degradation, dysfunction, and blockade of acetylcholine receptor at the NMJ
• Thymus is abnormal in 75% of pts
  • Thymectomy resolves or improves symptoms in most pts, especially those with a thymoma
• No sensory, reflex, pupillary, or cerebellar deficits

Myasthenic Crisis versus Cholinergic Crisis

1. Myasthenic Crisis
   1. Respiratory failure is feared complication
   2. Much more common
   3. D/t med non-compliance, infection, surgery, tapering of immunosuppressants, meds
2. Cholinergic Crisis
   1. Excessive anticholinesterase medication may cause weakness and cholinergic symptoms
   2. Rarely if ever seen w/ dose limitation of pyridostigmine to less than 120mg q3hr
   3. If on usual dose of meds assume exacerbation due to MG even w/ cholinergic side effects
3. Edrophonium (Tensilon) test to distinguish the two is controversial
   1. Give 1-2 mg IV slow push. If any fasciculations, resp depression, or cholinergic symptoms within a few minutes, problem is likely cholinergic crisis (no more edrophonium). If no evidence of cholinergic excess, give total of 10 mg and observe improvement in case of myasthenic crisis.
   2. Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm
   3. Treatment: Atropine

Clinical Features

1. Symptoms worsen with repetitive use / as the day progresses
   1. Ice Pack Test- should improve symptoms temporarily (usually ptosis; high specificity)
2. Muscle weakness
   1. Proximal extremities
   2. Neck extensors
   3. Facial/bulbar muscles (dysphagia, dysarthria, dysphonia)
3. Ocular weakness
   1. Ptosis
   2. Diplopia
   3. CN III, IV, or VI weakness

Differential Diagnosis

Drug-induced myasthenia

• Antibiotics (aminoglycosides, fluroquinolones, clindamycin, metronidazole, macrolides)
• Steroids
• Anticonvulsants (phenytoin, barbiturates, lithium)
• Psychotropics (haloperidol)
• Beta-blockers / calcium-channel blockers
• Local anesthetics
• Narcotics
• Anticholinergics (diphenhydramine)
• NMJ blocking agents (roc, sux)

Weakness

• Neuromuscular weakness
  • Upper motor neuron:
    • CVA
    • Hemorrhagic stroke
    • Multiple sclerosis
    • Amyotrophic Lateral Sclerosis (ALS) (upper and lower motor neuron)
  • Lower motor neuron:
    • Spinal and bulbar muscular atrophy (Kennedy's syndrome)
  • Spinal cord disease:
    • Infection (Epidural abscess)
    • Infarction/ischemia
    • Trauma (Spinal Cord Syndromes)
    • Inflammation (Transverse Myelitis)
      • Acute flaccid myelitis
    • Degenerative (Spinal muscular atrophy)
    • Tumor
  • Peripheral nerve disease:
    • Guillain-Barre syndrome
    • Toxins (Ciguatera)
    • Tick paralysis
    • Diabetic peripheral neuropathy
  • Neuromuscular junction disease:
    • Myasthenia gravis crisis
    • Botulism
    • Organophosphate toxicity
    • Lambert-Eaton myasthenic syndrome
  • Muscle disease:
    • Rhabdomyolysis
    • Dermatomyositis
    • Polymyositis
    • Alcoholic myopathy
• Non-neuromuscular weakness
  • Can't miss diagnoses:
    • ACS
    • Arrhythmia/Syncope
    • Severe infection/Sepsis
    • Hypoglycemia
    • Periodic paralysis (electrolyte disturbance, K, Mg, Ca)
      • Hypokalemic periodic paralysis
      • Thyrotoxic periodic paralysis
    • Respiratory failure
  • Emergent Diagnoses:
    • Symptomatic Anemia
    • Severe dehydration
    • Hypothyroidism
    • Polypharmacy
    • Malignancy
    • Aortic disease - occlusion, stenosis, dissection
  • Other causes of weakness and paralysis
    • Acute intermittent porphyria (ascending weakness)

Treatment

• Always evaluate tidal volume, FEV, negative inspiratory force, ability to handle secretions

1. Meds
   1. Pyridostigmine
      1. If pt's usual dose has been missed the next dose is usually doubled
      2. PO route: 60-90mg q4hr
      3. IV route: 1/30th of the PO dose (2-3mg) by slow IV infusion
   2. Neostigmine
      1. 0.5mg IV
2. Intubation
   1. If possible avoid depolarizing AND non-depolarizing agents
      1. If pt requires paralysis use non-depolarizing agent at smaller dose
      2. If must use depolarizing agents, will need higher doses
3. Plasmapherisis
4. IVIG

See Also

• Lambert-Eaton Myasthenic Syndrome

Source

• Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders