Myasthenia Gravis

Question 1

Definition

Answer 1

An autoimmune disease affecting the neuromuscular junction producing weakness in skeletal muscles

Question 2

Aetiology

Answer 2

• Impairment of neuromuscular junction transmission
• Most commonly due to autoantibodies against the nicotinic acetylcholine receptor

• Lambert-Eaton Syndrome - paraneoplastic subtype of myasthenia gravis caused by autoantibodies against pre-synaptic calcium channels, leading to impairment of
acetylcholine release

• Myasthenia gravis is associated with other autoimmune conditions (e.g. pernicious anaemia)

Question 3

Epidemiology

Answer 3

• Prevalence: 8-9/100,000
• More common in FEMALES at younger ages
• Equal gender distribution in middle age

Question 4

Presenting symptoms

Answer 4

• Muscle weakness that worsens with repetitive use or towards the end of the day

o NOTE: in Lambert-Eaton syndrome, muscle weakness improves after repeated use

• Ocular symptoms
o Drooping eyelids
o Diplopia

• Bulbar symptoms
o Facial weakness (myasthenic snarl)
o Disturbed hypernasal speech
o Difficulty smiling, chewing or swallowing

Question 5

Signs on physical examination (eyes)

Answer 5

• May be ocular

• Eye Signs
o Ptosis
o Complex ophthalmoplegia
o Check for ocular fatigue by asking the patient to sustain and upward gaze for 1 min and watch the progressive ptosis that develops

• Ice on Eyes Test
o Placing ice packs on closed eyelids for 2 mins can improve neuromuscular
transmission and reduce ptosis

Question 6

Signs on physical examination (other)

Answer 6

• May be generalised (affecting many muscle groups)

• May be bulbar (affecting the bulbar muscles i.e. those associated with cranial nerves 9,
10, 11 and 12)
o NOTE: bulbar = relating to the medulla oblongata (cranial nerves 9, 10, 11 and 12 have their nuclei in the medulla)

• Bulbar Signs
o Reading aloud may cause dysarthria or nasal speech

• Limbs
o Test the power of a muscle before and after repeated use of the muscle

Question 7

Investigations (bloods)

Answer 7

o CK - exclude myopathies
o Serum acetylcholine receptor antibody (positive in 80%)
o TFTs (it is associated with hyperthyroidism)
o Anti-voltage gated calcium channel antibody (in Lambert-Eaton syndrome)

Question 8

Investigations (other)

Answer 8

• Tensilon Test
o Short-acting anti-cholinesterase (edrophonium bromide) increases acetylcholine
levels and causes a rapid and transient improvement in clinical features
o Risk of bradycardia - so is generally avoided

• Nerve Conduction Study
o Repetitive stimulation shows decrements of muscle action potential

• EMG
• CT Thorax/CXR - visualise thymoma in the mediastinum or lung malignancies