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, or cerebellar deficits
• Respiratory failure is feared complication
  • Often precipitated by infection, surgery, or rapid tapering of immunosuppressive drugs

Clinical Features

1. Symptoms worsen with repetitive use / as the day progresses
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

DDX

1. Lambert-Eaton Syndrome
2. Drug-induced myasthenia (penicillamine, procainamide, quines, aminoglycosides)
3. Botulism
4. Thyroid disorders

Management

• Always evaluate tidal volume, FEV, 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

Testing

1. Always test FEV, consider ABG, Look for infections (resp) or meds, electrolyte problems that may have induced problem.
2. Edrophonium - use caution in trying to test for crisis vs. cholinergic crisis
3. Ach receptor antibodies - found 90%
4. CT of thymus, TFTs, search for other immun dz

Treatment

1. Plasmapherisis or plasma exchenge in acute setting
2. Anticholinesterase agent such as Pyridostigmine 60 mg tid
3. Corticosteroids produce good results in >80% but are reserved for those who don't respond to anti-cholinesterases and thymectomy due to adverse effects. Decreases levels of antiAch receptor Ab. Also may initially aggravate muscle weakness so usually begun in hosp & at low doses

1. don't treat Myasthenic with meds that may exacerbate weakness
2. search for source of infection or electrolyte problem w/ weakness

Myasthenic Crisis vs. Cholinergic

1. Cholinergic - usually present w/ signs of cholinergic overactivity (miosis, sweats, salivation, GI distress-musc) & cramps, fasciculations (nicotinic)
2. Myasthenic - more common, caused by noncompliance, drug interaction, infection, stress
   1. aminoglycosides, flouroquinolones, clinda, sulfas, erythro, ampicillin, Dilantin, phenobarb, B blockers, Ca channel Blk, procainamide, steroids, lithium, phenothiazines, MSO4, benzos, antihistamines

VERY DANGEROUS & UNRELIABLE to use Tensilon Test to distinguish between the two.

Source

Harwood Nuss p.1002