Myasthenia gravis

Background

• Due to autoantibody destruction of the nicotinic acetylcholine receptor at the NMJ
  • Autoantiboides compete w/ acetycholine for these receptors

DDX

1. Toxin Induced
   1. Botulism
   2. Tick Paralysis
   3. Envenomation (coral snake, black widow spider), paralytic shellfish
2. Autoimmune - Lambert-Eaton Myasthenic syndrome
3. Drug-Induced - aminoglycosides, dilantin, procainamide, chloroquine
4. Poisoning - Organophosphates, Carbamates
5. Miller Fisher Variant Guillen Barre
6. Causes of oculomotor palsy - DM, MS, aneurysm

Lambert-Eaton

1. rare, defect in release of AcH from presynapse
2. Usually paraneoplastic (part. small cell Ca of lung)
3. Clinically proximal weakness of limb muscles, hyporeflexia, dry mouth, impotence.
4. Extraocular & facial muscles usually spared.

Diagnosis

History

1. pts report worse sxs as day progresses.
2. insidious onset, can develop over wks to months.
3. precipitated by stress, preg, infec

Symptoms

1. diplopia, ptosis (later in day)
2. weakness in eye closure, swallowing muscles of facial expression, difficulty chewing, dysarthria, dysphagia.

Physical Exam

1. Provocative tests - ptosis with prolonged upward gaze, hold arms up, clench tongue blade, dysarthria w/ loud counting
2. sensation, reflexes usually normal
3. always eval tidal volume, FEV & ability to handle secretions

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