Myasthenia gravis

Background

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

Drugs that may unmask or worsen myasthenia gravis

• Antibiotics (Aminoglycosides, Clinda, Fluoroquinolones, Vancomyacin)
• Cardiovasular drugs (Beta blockers, procainamide)
• Other (Botox, quinines, Magnesium)

Drugs Usually well-tolerated in myasthenia gravis but occasionally associated with an exacerbation

• Local anesthetics
• Antibiotics (Tetracycline/doxy, Macrolides, Flagyl, nitrofurantoin)
• Anticonvulsants (carbamazepine, ethosuximide, gabapentin, phenobarbital, phenytoin)
• Butyrophenones (haldol)
• Phenothiazines (chlorpromazine/prochlorpromazine)
• Calcium Channel Blockers
• Steroids
• Opthalmic drugs (betaxolol/timolol/proparacaine)
• Other (Iodinated contrast agent)

Clinical Features

• Muscle weakness
  • Proximal extremities
  • Neck extensors
  • Facial/bulbar muscles (dysphagia, dysarthria, dysphonia)
• Ocular weakness
  • Ptosis
  • Diplopia
  • 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
• Opioids
• Anticholinergics (diphenhydramine)
• NMJ blocking agents (rocuronium, succinylcholine)

Weakness

• Neuromuscular weakness
  • UMN:
    • CVA
    • Hemorrhagic stroke
    • Multiple sclerosis
    • Amyotrophic Lateral Sclerosis (ALS) (UMN & LMN)
  • Spinal cord disease:
    • Infection (Epidural abscess)
    • Infarction/ischemia
    • Trauma (Spinal Cord Syndromes)
    • Inflammation (Transverse Myelitis)
    • Degenerative (Spinal muscular atrophy)
    • Tumor
  • Peripheral nerve disease:
    • Guillain-Barre syndrome
    • Toxins (Ciguatera)
    • Tick paralysis
    • DM neuropathy (non-emergent)
  • NMJ 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
  • Other causes of weakness and paralysis
    • Acute intermittent porphyria (ascending weakness)

Evaluation

• Symptoms worsen with repetitive use / as the day progresses
  • Ice Pack Test- should improve symptoms temporarily (usually ptosis; high specificity)
    • Place ice-pack on eyes for 2 mins, if ptosis decreases by ≥2mm the test is positive
• Acetylcholine receptor antibodies (AcHR-Ab). Positive in 80-90% of generalized MG and 40-55% in Ocular MG.

Myasthenic Crisis versus Cholinergic Crisis

• Myasthenic Crisis
  • Respiratory failure is feared complication
  • Much more common
  • Due to medication non-adherence, infection, surgery, tapering of immunosuppressants, meds
• Cholinergic Crisis
  • Excessive anticholinesterase medication may cause weakness and cholinergic symptoms
  • Rarely if ever seen with dose limitation of pyridostigmine to less than 120mg q3hr
  • If on usual dose of meds assume exacerbation due to MG even with cholinergic side effects
• Edrophonium (Tensilon) test to distinguish the two is controversial
  • Give 1-2mg IV slow push. If any fasciculations, respiratory 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 10mg and observe improvement in case of myasthenic crisis.
  • Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm
  • Thus, need to be on a monitor, with atropine on hand
  • Treatment: Atropine

Management

Always evaluate:

• Tidal volume
• Forced Vital capacity (normal is 10-12cc/kg)
• FEV
• Negative inspiratory force (NIF) (normal is -80 to -100 and greater than +20 respiratory support indicated)
• Ability to handle secretions

Medications

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

See Also

• Weakness

References

Authors

Ross Donaldson