Myasthenia Gravis

Question 1

Define

Answer 1

An auto-immune disease affecting the neuromuscular junction producing weakness of the skeletal muscles

→ Fluctuating muscle weakness and fatigue
Most commonly due to antibodies blocking ACh receptors I.e. antibodies to POST-synaptic ACh receptors

Most commonly due to autoantibodies against the nicotinic AChR

Associated with: other AI conditions (e.g. pernicious anaemia) and thymoma development (→breakdown in immune tolerance)

Question 2

Causes

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

Twice as common in women in younger ages Equal gender distribution in middle age

Often 30-60 years Prevalence 8/100 000

Question 4

Symptoms

Answer 4

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

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

Ocular symptoms

• Drooping eyelids
• Diplopia

Bulbar symptoms

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

Question 5

SIgns

Answer 5

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)

• NOTE: bulbar = relating to the medulla oblongata (cranial nerves 9, 10, 11 and 12 have their nuclei in the medulla)

May be ocular

Eye Signs

• Ptosis
• Complex ophthalmoplegia
• 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

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

Bulbar Signs

• Reading aloud may cause dysarthria or nasal speech

Limbs

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

Question 6

Investigations

Answer 6

Bloods

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

Tensilon Test

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

Nerve Conduction Study

• Repetitive stimulation shows decrements of muscle action potential

EMG

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