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Myasthenia Gravis

BASICS

Description

  • Autoimmune neuromuscular transmission disorder marked by fluctuating muscle weakness
  • Ocular MG: 15% (eyelids, extraocular muscles)
  • Generalized MG: 85% (ocular, bulbar, limb, respiratory muscles)
  • 50% with ocular symptoms develop generalized MG within 2 years
  • Onset: mild/intermittent, max severity within 3 years (85%)

EPIDEMIOLOGY

  • Bimodal onset: Females 20–40, males 60–80
  • Prevalence: 70–320/1 million (U.S.); increasing
  • Transient neonatal MG: 10–20% infants of affected mothers
  • Juvenile MG: 10–15% (North America)

ETIOLOGY & PATHOPHYSIOLOGY

  • Autoimmune reduction of acetylcholine receptors (AChRs) at muscle end plates β†’ insufficient neuromuscular transmission
  • Anti-AChR antibodies (85% generalized, 50% ocular)
  • MuSK antibodies: 5% (female, severe, bulbar/respiratory, rare thymic abn.)
  • Anti-LRP4: 12–50% of remaining seronegative MG
  • Seronegative MG: 5%
  • Can follow viral infection (measles, EBV, HIV, HTLV)
  • Familial predisposition: 5%

RISK FACTORS

  • Family history
  • D-penicillamine use (drug-induced)
  • Other autoimmune diseases

ASSOCIATED CONDITIONS

  • Thymic hyperplasia (60–70%)
  • Thymoma (10–15%)
  • Autoimmune thyroid disease (3–8%)

DIAGNOSIS

MGFA Clinical Classification

  • Class I: Ocular only
  • Class II–IV: Limb/axial (a), bulbar/respiratory (b); severity: mild (II), moderate (III), severe (IV)
  • Class V: Intubation required

History

  • Fatigability: fluctuating weakness, worse during day/after use, improves with rest
  • Early: transient, asymptomatic periods

  • 50% present with ocular symptoms (ptosis/diplopia)

  • 15%: bulbar symptoms
  • <5%: proximal limb weakness alone

ALERT: Myasthenic crisis = respiratory muscle weakness and impending failure

Physical Exam

  • Ptosis worsens with sustained upward gaze/counter-lid propping ("curtain sign")
  • Myasthenic sneer
  • Proximal, symmetric muscle weakness
  • Test for fatigability (repetition)
  • Monitor respiratory function

Differential Diagnosis

  • Thyroid ophthalmopathy, muscular dystrophies, cranial neuropathies, botulism, ALS, myopathies

Diagnostic Tests

  • Anti-AChR Ab: 74–85% positive
  • Anti-MuSK Ab: for AChR seronegative
  • Anti-LRP4/clustered AChR: if double-negative
  • Anti-striated muscle Ab: thymoma screen
  • Chest X-ray/CT: thymoma
  • Brain/orbit MRI: exclude other lesions
  • Tensilon (edrophonium) test: rarely done (immediate strength improvement)
  • Ice pack test: improves ptosis (80% sensitivity)
  • Electrophysiology:
  • RNS: 76% sensitivity generalized MG
  • SFEMG: 99% sensitivity, technically difficult

Test Interpretation

  • Thymic medullary hyperplasia (65% MG), thymoma (15%)
  • IgG/complement at receptors (seropositive)

TREATMENT

General

  • Symptomatic, immunosuppressive, and supportive approaches
  • Most: symptomatic + immunosuppressive and/or supportive

Medications

First Line

  • Anticholinesterase:
  • Pyridostigmine: start 60 mg PO TID, max 120 mg q3–4h, with food
    • SE: GI, hypotension, syncope, urinary frequency
  • Neostigmine: 0.5 mg SC/IM q3h (if can't take oral)

Second Line

  • Immunosuppressants:
  • Prednisone: inpatient: 60 mg/d, outpatient: start 10–20 mg/d, titrate by 5 mg q3–7d
    • SE: short-term worsening, weight gain, infection, hyperglycemia, osteoporosis
  • Azathioprine: 100–200 mg/d PO, check TPMT before start; effect delayed
  • Mycophenolate, cyclosporine (use with caution)
  • Acute:
  • Plasmapheresis: 2–3 L 3Γ—/week, repeat as needed
  • IVIg: 2 g/kg over 2–5 days
  • Other/refractory: eculizumab, efgartigimod alfa (AChR+), ravulizumab, rituximab, tacrolimus, cyclophosphamide

ALERT: Use caution: aminoglycosides, fluoroquinolones, Ξ²-blockers, CCBs, neuromuscular blockers, statins, diuretics, OCPs, gabapentin, phenytoin, lithium

Surgery

  • Thymectomy: for thymic abnormalities

Pediatric

  • Neonatal MG: oral pyridostigmine, supportive care
  • Steroids: only for severe

Admission

  • Myasthenic/cholinergic crises: monitor, treat respiratory failure
  • Treat infections
  • Acute immunotherapy: plasmapheresis, IVIg

ONGOING CARE

Patient Education

PROGNOSIS

  • Generally good, but variable
  • Myasthenic crisis: morbidity, 4% mortality
  • Seronegative: more likely purely ocular, better outcomes

COMPLICATIONS

  • Acute respiratory arrest, chronic insufficiency

ICD-10

  • G70.01: With (acute) exacerbation
  • G70.00: Without (acute) exacerbation
  • G70.0: Myasthenia gravis

Clinical Pearls

  • Autoimmune; fatigability/weakness relieved by rest

  • 50% present with ocular symptoms

  • Anticholinesterase & thymectomy lessen severity
  • Steroids, plasma exchange, IVIG: for severe/refractory