Myasthenia Gravis

Question 1

Define myasthenia gravis

Answer 1

An autoimmune disease mediated by antibodies to nicotinic acetylcholine receptors on the post synaptic side of the neuromuscular junction.

Question 2

Is it more common in men or women?

Answer 2

Women

Question 3

While anyone is susceptible, there are 2 main subgroups:

Answer 3

Young women 20-35 and older men 60-75

Question 4

What is the general course of myasthenia gravis?

Answer 4

Periods of remission interrupted by crises

Some can predict when they are due a crisis and others find there is no pattern

Question 5

What is the key feature?

Answer 5

Muscle fatigability - due to destruction of synapses there is decreased conduction at neuromuscular junctions

Question 6

What four sets of muscles are particularly affected?

Answer 6

Ocular - ptosis, diplopia
Bulbar - dysphagia, dysphonia, dysarthria and weak / droopy face
Proximal muscles - shoulder and thigh weakness
Axial - neck and trunk, also muscles involved in respiration

Question 7

Are there sensory abnormalities?

Answer 7

No

Question 8

What are the limb reflexes like?

Answer 8

Normal or brisk

Question 9

Describe the course of muscle weakness

Answer 9

Progressively weaker during periods of activity and slowly improve after periods of rest

Question 10

How can the fatigability of muscles be demonstrated?

Answer 10

Ask patient to do repetitive movement e.g flap arms for 30 -60 seconds

Question 11

Is muscle wasting present?

Answer 11

Usually not unless severe disease

Question 12

Describe the pathophysiology

Answer 12

B and T cell mediated IgG autoantibodies created which attack post synaptic acetylcholine receptors at neuromuscular junction.
Antibodies prevent ACh binding to receptor, so nerve signal not fully transmitted - muscle weakness due to incomplete stimulation rather than inherent muscle disorder

Question 13

Is ACh in synapse for short or long time?

Answer 13

Short - it is quickly broken down by acetylcholinesterase

Question 14

Myasthenia gravis has a strong association with disorders of…

Answer 14

The thymus
In 75% there is hyperplasia of thymus and in 10% this becomes a thymoma
In men - thymic atrophy, thymic tumour

Question 15

Other than an association with the thymus, what else is associated with MG?

Answer 15

Autoimmune disorders- pernicious anaemia, autoimmune thyroid disorders RA, SLE

Question 16

What can exacerbate symptoms?

Answer 16

Pregnancy 
Low K
Infection 
Change in climate
Over treatment 
Emotion
Exercise 
Antibiotics: Gentamicin , macrolides, quinolones, tetracyclines 
Opiates
Lithium 
Phenytoin 
Beta blockers
Quinine

Question 17

What tests are done?

Answer 17

Antibodies: anti AChR in 90% , the remaining positive for muscle specific tyrosine kinase antibodies (MUSK)
Electomyography (EMG) decremental muscle response to repetitive nerve stimulation +/- single fibre jitter
CT thorax to exclude thyoma
CK is normal
Tensilon test (not done anymore due to cardiac arrhythmia risk)

Question 18

How is it managed?

Answer 18

Long acting anti cholinesterase inhibitors e.g pyridostigmine
Immunosuppression- prednisolone for relapses
Azothioprine, ciclosporin, mycophenolate may be used

Thymectomy- has beneficial effects even in those without thymoma

Question 19

What is a myasthenic crisis?

Answer 19

Life threatening weakness of respiratory muscles during relapse
Ventilator support may be needed
Treat with plasmapheresis, IV immunoglobulin
Identify and treat trigger for relapse e.g infection, medications

Question 20

What cholinergic side effects can occur due to treatment?

Answer 20

Increased salivation and lacrimation, sweating, vomiting, miosis

Question 21

What type of hypersensitivity reaction is it?

Answer 21

Type II

Causes cytotoxic injury - results in lysis of cells