Myasthenia gravis

Question 1

What is it

Answer 1

Disorder of neuromuscular transmission, resulting from binding of autoantibodies to components of the neuromuscular junction, most commonly the acetylcholine receptor.
This leads to muscular weakness with easy ‘fatiguability’, which is worse on exercise and improves with rest.

Question 2

How is it classified

Answer 2

The antibody specificity: acetylcholine; muscle-specific receptor tyrosine kinase (MuSK); low-density lipoprotein receptor-related protein 4 (LRP4), or seronegative

Thymus histology: thymitis, thymoma, or atrophy

Age at onset: child, or aged less than or more than 50 years

Type of course: ocular or generalised

Question 3

Aetiology

Answer 3

Often associated with Thymic Hyperplasia, and in 10% a thymic tumour can be found (50% of those with thymomas have MG)

Question 4

Pathophysiology

Answer 4

Autoantibodies to nicotinic acetylcholine receptors (anti-AChR antibodies) or MuSK (muscle specific tyrosine kinase) at the post synaptic membrane of the neuromuscular junction.
Immune complex deposition of anti-AChR IgG and complement at the post-synaptic membranes, causing interference with and destruction of receptors.
Blocks the excitatory effect of ACh on nicotinic receptors, causing muscle weakness.

Question 5

Epidemiology

Peak age incidence for men and women

Answer 5

Women > Men
Peak age incidence women = 30 yrs
Peak age incidence men = 60 years

Question 6

Clinical presentation

Answer 6

Weakness, fatiguability of ocular (-> Ptosis), bulbar (dysphasia, dysarthria) and proximal limbs.
Improves after rest.

Question 7

Diagnosis

Answer 7

Anti-AChR (or anti-MuSK) antibodies in serum.
Nerve stimulation tests: characteristic decrement in evoked potential following motor nerve stimulation.
Ice test: improvement of prosis with ice pack

Question 8

Medical Treatment

Answer 8

Anticholinesterases: pyridostigmine 
Immunosuppressant drugs (if anticholinesterases don't work): azathioprine

Question 9

Complications

Answer 9

Myasthenia crisis: weakness of the respiratory muscles

Question 10

Condensed definition

Answer 10

Autoimmune disease against nicotinic acetylcholine receptors (AChR) in the neuromuscular junction

Question 11

Aetiology in women

Answer 11

Other autoimmune disease
e.g. pernicious anaemia
SLE
Rheumatoid arthritis
Thymic Hyperplasia

Question 12

Aetiology in men

Answer 12

Thymic atrophy or Thymic tumour
Rheumatoid arthritis
SLE

Question 13

Order of muscle groups affected

Answer 13

Extra-ocular
Bulbar (swallowing and chewing)
Face
Neck
Trunk

Question 14

How would you monitor and treat myasthenic crisis

Answer 14

Monitor FVC

Treat with Plasmapheresis (antibody removal) and IV immunoglobulin

Question 15

Surgical treatment and when

Answer 15

Thymectomy

Removal of thymus IF onset <50 years and disease poorly controlled with anti-cholinesterases

Question 16

2 types of autoantibodies to the receptors at post synaptic membrane of neuromuscular junction that could be seen in myasthenia gravis

Answer 16

Nicotinic acetylcholine receptors (anti-AChR antibodies)

MuSK (muscle specific tyrosine kinase)