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Differential Diagnosis of Myasthenia Gravis

Fatigue (Ptosis): Familial MG

• Prominent ocular signs
  • Mitochondrial Myopathy: PEO
  • Oculopharyngeal muscular dystrophy
  • Intracranial mass lesion
  • Senile ptosis
• Bulbar dysfunction
  • Motor neuron syndromes
  • Polymyositis
  • Thyroid disorders
  • Oculopharyngeal dystrophy
• Generalized MG
  • Lambert-Eaton syndrome (LES)
  • Botulism
  • Congenital myasthenic syndromes
  • Myopathies or muscular dystrophies
• Serum creatine kinase (CK)
  • Usually normal in MG
  • Elevated in ~10% of MG
• Inherited MG
  • Consider when
    • Persistent weakness begins in infancy or early childhood
    • Muscle biopsy changes do not explain degree of weakness
  • Frequency: Uncommon
  • Usually an autosomal recessive disorder: Positive family histories in minority
  • Muscle biopsy: Type 2 muscle fiber atrophy; Small NMJs
  • Treatment
    • Some forms of hereditary MG improve with anti-cholinesterases or quinidine
    • None respond to immunosuppression

AUTOIMMUNE MG: Neonatal & Juvenile Forms

• Epidemiology
  • Frequency
    • 10% to 30% of infants born to mothers with autoimmune MG
    • Less common when MG in mother treated with immunosuppression
    • ? more common when infant inherits maternal HLA type (A1, B8, DR3)
  • Antibody associations
    • High anti-fetal/anti-adult muscle anti-AChR antibody ratio in mother
    • No correlation with maternal antibody titer or disease severity
• Clinical
  • Local or generalized weakness
  • Respiratory depression
  • Symptoms subside over 1 to 4 weeks
• Associated disorders: Arthrogryposis
• Diagnosis
  • Confirm MG in mother
  • Anti-AChR antibodies: Usually positive; May occur in children of mothers with Antibody - MG
  • Anticholinesterase inhibitors
    • Edrophonium: 0.1 mg/kg; IV over 1 minute
      
    • Neostigmine: 0.04 mg/kg IM
• Treatment
  • Pyridostigmine
    • p.o.: 1 mg q3h; 20 min before feeding
      
    • IM: 0.2 to 0.4 mg / dose
  • Neostigmine
    • p.o.: 0.2 mg, 20 min before feeding
      
    • IM: 0.01 to 0.04 mg/kg/dose
      
    • iv: 2% to 3% of total daily oral Pyridostigmine dose/24 hours
          as constant infusion

• Occurs with Maternal MG
  • Usually in untreated MG patients
  • Some patients with antibodies are asymptomatic
• Clinical
  • Recurrent congenital arthrogryposis
  • Pena-Shokeir phenotype
    • Fetal akinesia
    • Arthrogryposis
    • Facial anomalies
    • Lung hypoplasia: May be fatal
    • Survivor: Dysarthria; Myopathic faces; high arched palate
• AChR antibody: Maternal
  • Antibodies more common in patients with previous childbirths
  • Antigenic target: Fetal AChR
    • Binds to γ subunit of AChR
    • Overlaps ACh binding site
  • Antibody effect: Abolishes AChR function
• Treat MG in mother: Reduces risk of arthrogryposis in subsequent pregnancies
• Analogus hereditary disorder
  • Multiple pterygium syndrome: AChR, γ-subunit mutations

• Clinical
  • Onset
    • Age: 1 year to Teens
    • Often generalized MG
  • Weakness: See Myasthenia gravis, acquired
  • Associated disorders: Thyroid
  • Course
    • Remission: 25% to 50%
    • Improved on treatment: > 90%
    • Ocular MG: Often remains localized
• AChR antibodies
  • Pre-pubertal: 50% to 64% positive
  • Post-pubertal: 90% positive
• Treatment
  • Anti-AChE medications
  • Immunomodulating agents: Prednisone
  • Thymectomy: Thymus normal or hyperplastic

Myasthenia Gravis: History Original description: Thomas Willis

Thomas Willis 1621-1675