Myasthenia Gravis

Question 1

Define Myasthenia Gravis

Answer 1

Myasthenia gravis (MG) is a chronic autoimmune disorder of the post-synaptic membrane at the neuromuscular junction (NMJ) in skeletal muscle.

Question 2

Explain the aetiology of Myasthenia Gravis

Answer 2

• In myasthenia gravis (MG) with anti-AChRs antibodies, an autoimmune attack against AChRs results in destruction of the post-synaptic membrane.
  
  • The reduced number of available
    binding sites for acetylcholine leads to
    inconsistent generation of muscle fibre action potentials, which manifests as skeletal muscle weakness.
• Muscle-specific tyrosine kinase (MuSK) is a protein on muscle membrane with an essential role in anchoring AChR on postsynaptic membrane so anti-MuSK antibodies also lead to muscle weakness
• Can be paraneoplastic e.g. thymomas produce auto-antibodies against AChR

RISK FACTORS:

• FHx of other autoimmune disorders
• Young woman (20-40)
• Older men

Question 3

Recognise the presenting symptoms of myasthenia gravis (3 categories)

Answer 3

• Muscle fatiguability
  
  • weakness worsens with activity (fatigue) and improves on rest (contrasted to Lambert-Eaton in which muslce gradually becomes stronger the more it is used)
  • fluctuations often, but not always, show diurnal variation (better in morning than in the evening)
• HEAD & NECK manifestations are the most common: Starts with ocular muscle weakness then progresses
  
  • Ptosis (LPS & Superior tarsal) - ocular MG can present with isolated acute ptosis
  • Diplopia (pupil sparing)
  • Dysarthria
  • Dysphagia (difficulty chewing and swallowing)
  • Facial paresis (flattened smile)
• PROXIMAL MUSCLE weakness
  
  • Will complain of difficulty climbing stairs or getting up from a chair
  • This tends to be bilateral & asymmetrical (R>L or L>R)
  • This is much later manifestation
  • Can present with predominantly/exclusively limb weakness (limb-girdle MG)
• MYASTHENIC CRISIS
  
  • Weakness of respiratory muscles leading to shortness of breath
  • Triggered by illness or infection

Question 4

Recognise the signs of myasthenia gravis on physical examination (7)

Answer 4

On neurological examination:

• Ptosis
• WADDLING GAIT
• Positive Simpson test: To cause sustained contraction of LPS muscle, the patient is asked to gaze upward for an extended period of time, without lifting the head. After a few minutes, the patient with myasthenia gravis starts to show drooping of upper eyelids, while normal individuals do not show any drooping
• Diplopia (pupil sparing)
• Fatiguability on repeated motions - initial neurological exam is normal, however after repeated motions you’ll see weakness
• Dysarthia (nasal speech)
• Reduced power in limbs (one side more than other)
• Intact tone, reflexes and sensation
• No muscle wasting

Question 5

Identify appropriate investigations for myasthenia gravis and interpret the results

Answer 5

• Serum anti-AChR levels
• Serm anti-MuSK levels
• EMG this will show how muscle power weakens with use
• Serial pulmonary function test (low FVC)
  
  • Do not wait for ABG as by the time hypoxic & hyoercapnic (T2RF) changes are seen, it will be too late
• CT chest (to show thymic enlargement)

Question 6

Describe Lambert-Eaton Myasthenic Syndrome (LEMS)

Answer 6

• This is also an autoimmune condition
• Auto-antibodies are against pre-synaptic VGCC which stimulate release of ACh
• You regain strength the more you use the muscle
• This is associated with Small Cell Lung Cancer

Question 7

Which drugs can worsen myasthenia gravis

Answer 7

• BETA-BLOCKERS
• Quinolones (levofloxacin)
• Macrolides (erythro, clari, azithro)
• Tetracyclines (doxycycline)