Indications for Testing

• Initiate testing based on classic symptoms of fluctuating weakness and muscle fatigability as an adjunct to clinical findings
• Confirm clinical history; testing should not be performed in the absence of appropriate clinical presentation

Laboratory Testing

• Serum antibody testing – positive test is diagnostic of MG
  • Anti-AChR
    • Positive in ~85-90% of patients
      • Specificity approaches 100%
    • Negative AChR does not exclude disease
      • Approximately 50% of ocular MG patients are negative for this antibody
  • Anti-MuSK
    • Detectable in 30-40% of anti-AChR-negative patients
      • Do not order if patient has isolated ocular MG
    • Bulbar symptoms more common if this antibody is present
    • Much more common closer to tropical latitudes
  • Anti-striational protein – titin antibodies
    • Detectable in >80% of thymomatous MG and some cases of nonthymomatous MG patients
    • May occur in the absence of acetylcholine receptor antibody in patients with MG
    • Rare in ocular MG
  • Normal antibodies do not exclude diagnosis – so-called seronegative disease

Other Testing

• Consider anticholinesterase testing (Tensilon test using edrophonium) in AChR-negative patients – improvement in muscle strength is diagnostic of MG
• Repetitive stimulation or single-fiber electromyogram
  • Positive in 90% of MG patients – demonstrates a primary postsynaptic neuromuscular junctional disorder
• Chest x-ray/CT – rule out thymoma

Prognosis

• May predict the presence of thymoma in patients with acetylcholine receptor antibody-positive myasthenia gravis who are <50 years

Differential Diagnosis

• Infectious
  • Enterovirus (poliomyelitis)
  • Clostridium botulinum
• Autoimmune
  • Polymyositis
• Neuropathic 
  • Guillain-Barré syndrome
  • Eaton-Lambert syndrome
  • Miller Fisher syndrome
  • Limbic encephalitis
• CNS disease
  • Amyotrophic lateral sclerosis (Lou Gehrig disease)
  • Brainstem/cavernous sinus lesions
• Acute intermittent porphyria
• Drug-related myopathy
  • Corticosteroids
• Neuromuscular disease
  • Mitochondrial disorders
  • Muscular dystrophy syndromes

Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies that block or destroy receptors for the neurotransmitter acetylcholine, leading to muscle weakness and fatigue.

Epidemiology

• Prevalence – 64-90/1,000,000
• Age – bimodal peaks for onset
  • Women – 20-30 years
  • Men – 55-60 years
• Sex – M<F, 1:2

Pathophysiology

• Autoimmune disorder
  • Immune response creates acetylcholine receptor (AChR) antibodies
    •  AChR antibodies are IgG (predominantly IgG1 or IgG3); MuSK antibodies are predominantly IgG4
    • Binding and activation of complement at the neuromuscular junction can lead to loss of AChR
    • Modulating with accelerated internalization and degradation of AChR molecules crosslinked by antibody result in loss of AChR (correlates most closely with clinical severity of disease)
    • Blocking functional AChR block that impairs binding of acetylcholine to receptor, resulting in poor muscle contraction
  • Postsynaptic membrane is destroyed and decreases available binding sites for acetylcholine, leading to muscle weakness
• Iatrogenic causes of MG – D. penicillamine, alfa-interferon, bone marrow transplantation

Clinical Presentation

• Characteristic sporadic muscle weakness that worsens after affected muscles are used (fatigable weakness)
  • Usually presents first in the extrinsic ocular muscles and progresses to muscles in the extremities
• Bulbar symptoms – dysphagia, dysarthria
• Extraocular muscle (EOM) weakness – diplopia, ptosis
  • Symptoms are present in 2/3 of patients
  • Disease is considered ocular MG if symptoms remain limited to EOM (10% of patients)
• Respiratory failure in small percentage of patients
  • Death in severe cases
  • May be associated with thymoma
• Commonly associated autoimmune disorders (50% of patients)
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Pernicious anemia

Treatment

• Anticholinesterase drugs, thymectomy, immunosuppression and plasmapheresis

Clinical Background

Epidemiology

• Incidence – 1-5/1,000,000  in western countries
• Age
  • Rare in infancy
  • Increases in puberty
• Sex – prepubertal: M:F, equal; postpubertal: F>M
• Ethnicity – much higher in Asian populations

Clinical Presentation

• Severe generalized weakness
• Bulbar symptoms
• Thymoma incidence lower than in adults
• Patients <10 years – aggressive tumor nature

Diagnosis

Indications for Testing

• See Diagnosis tab

Laboratory Testing

• Anti-AChR – lower rate of positivity than in adults
• Anti-MuSK – rare in young children
• Higher rate of seronegative disease

Tests generally appear in the order most useful for common clinical situations

General

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ARUP Institute for Clinical and Experimental Pathology®

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Neuromyelitis Optica
Neuropathic Disease
Paraneoplastic Neurological Syndromes