Myasthenia Gravis Flashcards
What is myasthenia gravis?
It is an autoimmune condition, in which there is antibody formation against post-synaptic nicotinic acetylcholine receptors of the neuromuscular junction
What generally occurs at the neuromuscular junction?
There is communication of motor nerves with muscles
Describe the process that occurs at the neuromuscular junction that leads to muscular contraction
The axons of the motor nerves are situated across a synapse from the post-synaptic membrane of the muscle cell
The axons release a neurotransmitter, known as acetylcholine, from the pre-synaptic membrane which then travels across the synapse and attaches to the receptors on the post-synaptic membrane
This causes receptor stimulation, leading to muscle contraction
What is the pathophysiology of myasthenia gravis?
There are acetylcholine receptor antibodies are produced by the immune system
These antibodies bind to the postsynaptic neuromuscular junction receptors, preventing the binding of acetylcholine and therefore muscle contraction
During muscle activity, there is a gradual increase in receptor inhibition, resulting in progressive muscle weakness during periods of activity and gradual improvement during periods of rest
These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane
This causes further worsening of clinical features
What two other antibodies are associated with myasthenia gravis?
Muscle-specific kinase (MuSK) antibodies
Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies
What is the function of MuSK and LRP4?
They are proteins involved in the production and formation of the acetylcholine receptors
How does MuSK and LRP4 antibody formation lead to myasthenia gravis?
The destruction of these proteins results in inadequate acetylcholine receptor formation
What are the six risk factors of myasthenia gravis?
Females < 40 Years Old
Males > 60 Years Old
Thymomas
Thymic Hyperplasia
Autoimmune Disorders
Drug Administration
What are thymomas?
Tumours of the thymus gland
What four autoimmune disorders are associated with myasthenia gravis?
Pernicious anaemia
Autoimmune thyroid disorders
Rheumatoid arthritis
Systemic Lupus Erythematosus
What are ten drugs are associated with myasthenia gravis?
Penicillamine
Quinidine
Procainamide
Beta-Blockers
Lithium
Phenytoin
Gentamicin
Macrolides
Quinolones
Tetracyclines
What is the characteristic clinical feature of myasthenia gravis?
Muscle fatiguability
This is when muscles become progressively weaker during periods of activity and slowly improve after periods of rest
This usually means that clinical features are minimal in the morning and worse at the end of the day
What are the five clinical features of myasthenia gravis?
Diplopia
Ptosis
Facial Muscle Weakness
Dysphagia
Slurred Speech
What muscle weakness causes diplopia?
Extra-ocular muscle weakness
What muscle weakness causes ptosis?
Eyelid muscle weakness
In what three ways can we elicit muscle fatiguability during clinical examination?
We can ask the patients to repeatedly blink, which will exacerbate ptosis
We can ask the patients to prolong upward gazing, which will exacerbate diplopia on further eye movement testing
We can ask the patients to repeat unilateral arm abduction, which will exacerbate unilateral weakness when comparing both sides
What four investigations can be used to diagnose myasthenia gravis?
Blood Tests
Electromyography (EMG)
CT Scans
Edrophonium Test
What is the first line investigation of myasthenia gravis?
Blood tests
What four blood test results indicate myasthenia gravis?
Increased Acetylcholine Receptor (Ach-R) Antibodies
Increased Muscle-Specific Kinase Antibodies (MuSK) Antibodies
Increased Low-Density Lipoprotein Receptor-Related (LPR4) Antibodies
Normal Creatinine Kinase Levels
What is electromyography (EMG)?
It measures muscle response or electrical activity in response to a nerve’s stimulation of the muscle
What are the two features of myasthenia gravis on EMG?
Decremental Response To Repetitive Nerve Stimulation
Single-Fibre Jitter
How are CT scans used to investigate myasthenia gravis?
They can detect underlying causes, such as thymomas
What is a feature of myasthenia gravis on CT scans?
Anterior Mediastinum Mass
What is another term for the edrophonium test?
Tensilon test
What is the edrophonium test?
It involves administrating an IV dose of edrophonium chloride
What is the function of edrophonium?
It is an acetylcholinesterase inhibitor, which means that it inhibits cholinesterase enzymes in the neuromuscular junction – an enzyme involved in the break down acetylcholine
This means that it increases acetylcholine levels at the neuromuscular junction
What edrophonium test result indicates myasthenia gravis?
Once edrophonium has been administered, there should be temporary relief of muscle weaknes
Why is the edrophonium test only reserved for when myasthenia gravis diagnosis is unclear?
This is due to the risk of cardiac arrythmia
What are the three pharmacological management options for myasthenia gravis?
Long Acting Acetylcholinesterase Inhibitors
Immunosuppressants
Monoclonal Antibodies
Name two long acting acetylcholinesterase inhibitors used to treat myasthenia gravis
Pyridostigmine
Neostigmine
What is the first line long acting acetylcholinesterase inhibitor?
Pyridostigmine
What is the function of long acting acetylcholinesterase inhibitors?
They increase the level of acetylcholine in the neuromuscular junction
How are long acting acetylcholinesterase inhibitors used to treat myasthenia gravis?
They provide symptomatic relief
Name four immunosuppressants used to treat myasthenia gravis
Prednisolone
Azathioprine
Cyclosporine
Mycophenolate mofetil
How are immunosuppressants used to treat myasthenia gravis?
They can be added to long acting acetylcholinesterase inhibitors to suppress the production of antibodies
Name two monoclonal antibodies used to treat myasthenia gravis
Rituximab
Eculizumab
What is the function of rituximab? How is it therefore used to treat myasthenia gravis?
They target B cells
They reduce the production of antibodies
What is the function of eculizumab? How is it therefore used to treat myasthenia gravis?
They target complement protein C5
This could potentially prevent the complement activation and destruction of acetylcholine receptors
What surgery can be used to manage myasthenia gravis?
Thymectomy
What is thymectomy?
It involves resection of the thymus gland
How is thymectomy used to treat myasthenia gravis?
It can be used to provide symptomatic relief in individuals with and without a thymoma
What is a complication of myasthenia gravis?
Myasthenic Crisis
What is myasthenic crisis?
It is a life-threatening complication, in which there is an acute worsening of clinical features due to another illness
What illness commonly triggers myasthenic crisis?
Respiratory tract infection
What clinical feature is typical of myasthenic crisis? Why?
Respiratory failure
There is weakness of respiration muscles
How do we manage respiratory failure in myasthenic crisis?
Non-invasive ventilation with BiPAP
OR
Full intubation and ventilation
What two pharmacological management options can be used in myasthenic crisis?
IV immunoglobulins
Plasmapheresis
What is plasmapheresis?
Plasma exchange
