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Autoimmune Myasthenia Gravis: Clinical Manifestations ²

Associated disorders Childhood Differential diagnosis Epidemiology Onset Symptoms & Signs

Autoimmune MG: Epidemiology ⁷

• Incidence, Annual
  • General: 1.7 to 34 per million person-years
  • Mean: 20/1,000,000
  • AChR antibody +: 12.4 per million person-years
  • Peak incidence: 65 to 75 years of age
  • Higher: Western European & Nordic countries
  • Lower: Asia & Africa
• Prevalence
  • Pooled: 77.7 (15 to 350) cases per million
  • Mean: 25/100,000
  • Higher > 40 years
• Lifetime risk: 500 per million
• Sex
  • General: Females 1.6x > Males
  • Young MG onset: Females 3x > Males
  • Older MG onset: Males ≥ Females
  • Mean onset age: Females 50 years; Males 57 years
  • Autoimmune co-morbidity: Females > Males
• Geographic
  • China
    • Ocular MG: Associated with HLA-BW46
    • Juvenile MG more common
  • Mediterranean regions: MuSK MG more common
• Onset Age
  • Childhood (< 18 years), acquied MG
    • Geographic
      • Europe & US: 1.2 to 4 cases per million
      • China & Japan: Up to: 46 cases per million; 30% of MG
  • MG Types
• General adult
  • Patterns of onset age
    • Famales: Bimodal; Peaks at 45 to 55 & 70 to 85 years
    • Males: Unimodal; Peak at 70 to 80 years
  • MG: Early peak
    • Age: 2nd to 5th decade
    • Female predominance
    • Thymus
      • Hyperplasia: Common; 80%
      • Neoplasm: Uncommon < 30 years
    • HLA association
      • Western: B8 & DR3
      • Asia: DR9
  • MG: Intermediate ages (30 to 60 years)
    • Most common ages for associated thymoma
  • MG: Late age peak ⁴
    • Epidemiology
      • Ages
        • Very late ages: ≥ 65 years
        • Peak range: 6th to 9th decade
      • Male ≥ Female: More males with increasing age
      • Genetics
        • HLA association: B7 & DR2
      • Frequency
        • 175.37 per million population > 70 years old
        • May be increasing in Western countries & Japan
      • 20% to 60% of different MG populations
    • Clinical: Onset
      • General: Ocular or Generalized MG; More life-threatening events
      • Japan, Late onset: Ocular increased frequency
      • US: Usually bulbar onset
    • Thymus
      • Thymoma: Infrequent (7%) with onset age ≥ 70 years
      • Hyperplasia: Uncommon
    • Treatments
      • Drugs needed: Fewer
      • Drug refractory: Less common
      • Prognosis
        • General: Good
        • Complete remission: Often
        • MG Exacerbations: Poorer outcomes than younger patients
      • AChE inhibitors: More side effects than younger patients
      • Corticosteroids: Response
        • Common (> 90%)
        • Only low doses (mean 10 mg/day) of daily or intermittent treatment often needed for maintenance
      • Other drugs: Cyclosporin A; Tacrolimus; Azathioprine
      • Thymectomy: Not indicated > 55 years unless thymoma present
    • Antibodies
      • AChR
        • Frequency: 85% to 100%; Greater than younger ages
        • Titer: Lower than in younger patients
        • Sero-negative MG uncommon
      • Striational (50%)
        • Titin
          • Frequency in late onset MG: 30%
          • Early onset MG: Rare except with thymomas
          • Associated with higher frequency of DR 7 antigen & lower frequency of DR 3 antigen
        • Ryanodine receptor
        • Kv1.4: More common in younger patients
• Autoimmune MG may rarely be a familial disorder

Onset

• Age
• Presenting symptoms
  • Ocular (50%): Ptosis; Diplopia
  • Weakness, systemic (35%)
    • Distribution: Variable; Bulbar, Legs, or Arms
    • Painless
  • Fatigue (10%)
  • Respiratory failure: Rare
• Progression: Generally insidious over weeks to months
• Aggravating factors
  • Systemic disease: Infections; Thyroid
  • Emotional stress
  • Pregnancy
  • Medications
• More in: Summer & Higher environmental temperatures ⁶

Symptoms & Signs

• Weakness
  • Variable: May increase through the day, or with prolonged physical activity
  • Onset: Often diplopia or ptosis 2° to extraocular muscle or levator palpebrae weakness
    • Most patients develop weakness in other muscles
    • Ocular myasthenia
      • Weakness remains limited to ocular muscles during entire course of the illness

    From: Baylor

  • Specific muscle groups
    • Ocular
      • Ptosis & Ophthalmoplegia
      • Usually asymmetric & bilateral
      • Pupils: Normal
      • Rule out focal neural lesions
        • III or VI nerve lesion; Internuclear ophthalmoplegia
        • Especially when unilateral signs
    • Bulbar
      • Symptoms: Dysarthria, Dysphagia, Weak mastication
      • Signs: Poor gag reflex & palate elevation; Weak tongue
      • May result in aspiration pneumonia
      • Considered life-threatening
        • Usually an indication for rapidly-acting therapeutic intervention
        • Plasma exchange most commonly used
    • Facial
      • Frequency: > 95% of MG
      • Reduced facial expression, or snarl with attempt to smile
      • Distribution: Orbicularis oculi most common; Also orbicularis oris
    • Respiratory failure
      • Considered life-threatening
      • Usually due to Diaphragmatic and Intercostal muscle weakness
        • Strong indication for rapidly-acting therapeutic intervention
        • Pyridostigmine & Plasma exchange most commonly used
      • May be due to vocal cord paralysis ¹
        • Vocal cords in adductor position: Produces stridor
        • May require intubation
      • Monitor with forced vital capacity
    • Limbs & Trunk
      • Typical
        • Proximal > Distal
        • Arms > Legs
        • Symmetric
      • Weakness in selective areas
        • Posterior neck (head ptosis)
        • Triceps: Especially African-Americans ⁵
        • Quadriceps
        • Occasionally: Distal musculature
    • Differences from LEMS ³
      • LEMS never begins with ocular weakness
      • LEMS usually has weakness in Legs > Arms
• Fatigue
  • Induced by
    • Repetitive muscle strength testing
    • Prolonged tonic contraction
  • Quantitation
    • Timed upward gaze
    • Forward arm abduction
• Muscle wasting: Uncommon, except when MG is chronic & untreated
• Deep tendon reflexes
  • Usually preserved
  • May be brisk in clinically weak muscles
• Sensory
  • Skin sensations: Normal
  • Olfaction: May be reduced ⁸