• Clinical science

Myasthenia gravis

Summary

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by generalized muscle weakness. The pathophysiology of MG involves autoantibodies directed against postsynaptic acetylcholine receptors (AchR), thereby impairing neuromuscular transmission. Women are more frequently affected and about 10–15% of cases are associated with thymoma. The most common initial symptoms are ptosis and/or diplopia due to ocular muscle weakness, with the disease usually progressing to generalized weakness within two years. At that point, patients have difficulties standing up, climbing stairs, and possibly even swallowing and/or chewing. Muscle weakness worsens throughout the day with increased activity and improves after rest. MG is diagnosed according to patient history, physical examination, antibody testing, and electromyographic evaluation. All patients should be screened for thymomas via CT as they can be surgically removed, allowing for possible curative treatment. The treatment of choice consists of acetylcholinesterase inhibitors, possibly in combination with immunosuppressive drugs if symptoms persist. Acute exacerbations, as seen in myasthenic crisis, should be treated with either IV immunoglobulins or plasma exchange.

Epidemiology

  • Sex: > (3:2)
  • Age of onset
    • Possible at any age
    • Occurs more often in:
      • : 20–40 years
      • : 60–80 years

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[1]

Classification

  • Main clinical forms
    • Ocular myasthenia: only the extraocular and/or eyelid muscles
    • Generalized myasthenia: all skeletal muscles may be involved; especially the ocular, bulbar, limb, and respiratory muscles

Pathophysiology

Clinical features

Clinical course

Clinical manifestations

Smaller muscles responsible for fine movements (i.e., the eye muscles) tend to be affected first, while larger muscles become affected later on.

  • Eye muscle weakness: most common initial symptom
  • Bulbar muscle weakness
    • Slurred speech, difficulty chewing and/or swallowing
  • Proximal limb weakness
    • Rising from a chair
    • Climbing stairs
    • Brushing hair
  • Weakness of respiratory muscles

Muscle fatigue worsens throughout the day and with increased activity!

References:[2]

Diagnostics

Suspected cases of MG are generally confirmed via EMG and AChR antibodies and should receive a chest CT to rule out thymoma.

Patients diagnosed with MG should be tested for other autoimmune disorders, such as thyroiditis, SLE, and/or rheumatoid arthritis!

References:[3]

Differential diagnoses

  • Lambert-Eaton myasthenic syndrome (LEMS)
    • Description: LEMS is a rare autoimmune disease that reduces neuromuscular transmission and leads to muscle weakness.
    • Pathophysiology: Autoantibodies are directed against presynaptic voltage-gated calcium channels → impaired acetylcholine release in the NMJ.
    • Association: small-cell lung carcinoma (in ⅔ of LEMS cases)
    • Clinical features
      • Proximal muscle weakness
      • Reduced or absent reflexes
      • Autonomic symptoms
    • Diagnostics
      • Physical examination
        • Active muscle contraction or repeated muscle tapping increases reflex activity.
        • Lambert's sign: Muscle strength improves after muscle use.
      • EMG: Repetitive nerve stimulation results in incremental responses.
      • Confirmatory test: serologic detection of antibodies directed against voltage-gated calcium channels

Myasthenia gravis vs. Lambert-Eaton myasthenic syndrome
Myasthenia gravis Lambert-Eaton myasthenic syndrome
Associated diseases
Weakness
  • Starts with weakness of the lower legs
  • Improves with exercise and throughout the day
Reflexes
  • Normal
  • Reduced or absent
Repetitive nerve stimulation (RNS)
  • Decremental response
  • Incremental response
Autonomic dysfunction
  • None
  • Common

References:[4]

The differential diagnoses listed here are not exhaustive.

Treatment

Complications

  • Myasthenic crisis
    • Affects 15–20% of patients with MG
    • Generally occurs during the active phase within 5–7 years after onset
    • Acute, life-threatening exacerbation of myasthenic symptoms that leads to respiratory failure; early endotracheal intubation
    • Potential triggers
      • Infection
      • Surgery, anesthesia
      • Pregnancy
      • Medications
    • Not to be confused with cholinergic crisis
Myasthenic crisis Cholinergic crisis
Shared symptoms
  • Muscle weakness, dyspnea, sweating, agitation, disorientation, drowsiness, urinary and fecal urgency
Pupil
  • Normal
Fasciculations
  • None
  • Present
Heart rate
  • Tachycardia
  • Bradycardia
Skin
  • Cold and faint
  • Warm and flushed
Bronchial secretion
  • Normal
  • Increased

References:[3][5]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • The prognosis of ocular MG is good.
  • Mortality
    • Without treatment: up to 30%
    • With treatment: less than 5%