Myasthenia gravis

Background

Autoantibody degradation, dysfunction, and blockade of acetylcholine receptor at the NMJ^[1]
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
- Respiratory failure is feared complication
- Much more common
- D/t med non-compliance, infection, surgery, tapering of immunosuppressants, meds
Cholinergic Crisis
- Excessive anticholinesterase medication may cause weakness and cholinergic symptoms
- Rarely if ever seen w/ dose limitation of pyridostigmine to less than 120mg q3hr
- If on usual dose of meds assume exacerbation due to MG even w/ cholinergic side effects
Edrophonium (Tensilon) test to distinguish the two is controversial
- 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.
- Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm
- Treatment: Atropine

Symptoms worsen with repetitive use / as the day progresses^[2]
- 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
Muscle weakness
- Proximal extremities
- Neck extensors
- Facial/bulbar muscles (dysphagia, dysarthria, dysphonia)
Ocular weakness
- Ptosis
- Diplopia
- CN III, IV, or VI weakness

Antibiotics (aminoglycosides, fluroquinolones, clindamycin, metronidazole, macrolides)^[3]
Steroids
Anticonvulsants (phenytoin, barbiturates, lithium)
Psychotropics (haloperidol)
Beta-blockers / calcium-channel blockers
Local anesthetics
Narcotics
Anticholinergics (diphenhydramine)
NMJ blocking agents (roc, sux)

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:
- 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)

Always evaluate tidal volume, FEV, negative inspiratory force, ability to handle secretions
Meds
- Pyridostigmine
  - If pt'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
- Neostigmine
  - 0.5mg IV
Intubation
- If possible avoid depolarizing AND non-depolarizing agents
  - If pt requires paralysis use non-depolarizing agent at smaller dose
  - If must use depolarizing agents, will need higher doses
Plasmapherisis
IVIG

↑ Medications and Myasthenia Gravis (A Reference for Health Care Professionals) PDF
↑ Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders
↑ Sanders DB, Guptill JT. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome. Continuum. 2014 Oct;20(5)

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