Myaesthenia Gravis

Question 1

Definition

Answer 1

Chronic autoimmune disorder of the post synaptic membrane at the neuromuscular junction of the skeletal muscle. Autoantibodies attack nicotinic acetylcholine receptor (AChR) or muscle-specific kinase (MuSK), which is a postsynaptic protein

Question 2

Epidemiology

Answer 2

Age =
- 20-30’s for women (related to autoimmune disease)
- 50-60’s for men (related to THYMOMA)

Question 3

Risk factors

Answer 3

Autoimmunity: (rheumatoid arthritis and systemic lupus erythematosus)
Thymoma or thymic hyperplasia: 10-15% of patients have a thymoma, whilst up to 70% have thymic hyperplasia

Question 4

Pathophysiology

Answer 4

AChR autoantibodies produced by immune system, this blocks the receptor + prevents the ACh from being able to stimulate the receptor + trigger muscle contraction. This leads to less than effective stimulation of the muscle with increased activity. There is more muscle weakness the more muscles are used. This improves with rest as more receptors are freed up for use again.
These antibodies also activate the complement system within the neuromuscular junction, leading to damage cells at the post synaptic membrane. This further worsens the symptoms

Question 5

Signs

Answer 5

Proximal muscle weakness with fatiguability: often affecting the face and neck
Ptosis exacerbated on upward gaze: bilateral or unilateral
Complex ophthalmoplegia: can’t be isolated to one cranial nerve
Head drop: rare sign due to weakness of cervical extensor muscles
Myaesthenic snarl: a ‘snarling’ expression when attempting to smile

Question 6

Symptoms

Answer 6

LETHARGY
Extra ocular muscles = first effected presenting as diplopia
Muscle weakness work at the end of the day
Double vision
Slurred speech
Dysphagia
Shortness of breath: may suggest a myasthenic crisis

Question 7

Investigations

Answer 7

FIRST LINE = AChR antibodies
- anti-MuSK can also be tested in patients who are AchR antibody negative
Electrophysiological studies: repetitive nerve stimulation shows a decremental muscle response
CT thorax: all patients should have a CT chest to exclude a thymoma; MRI is an alternative 1
Thyroid function: all patients require thyroid function tests, as there is a higher prevalence of autoimmune thyroiditis

Question 8

Treatment

Answer 8

FIRST LINE = AChase INHIBITORS
- NEOSTIGMINE/ PYRODSTIGMINE
SECOND LINE = Immunosuppression
- steroids

Question 9

Differential diagnosis

Answer 9

Autoimmune disease where the voltage-gated calcium channel on the nerve is affected, characterised by muscle weakness of the limb
- commonly associated with small cell lung cancer
Symptoms start at extremities, then move to HEAD + NECK. There is autonomic involvement (e.g. dry eyes + mouth)
TREATMENT = STEROIDS (prednisolone) + immunosuppression (IVIg)