Neurology - Myasthenia gravis Flashcards
What is MG?
An autoimmune condition that causes muscle weakness that gets progressively worse with activity and improves with rest.
It is a disorder of the NMJ
Typical epidemiology
Women - under the age of 40
Men - over the age of 60
What has a strong association with Myasthenia gravis?
Thymomas
10-20% of patients with myasthenia gravis have a thymoma.
20-40% of patients with a thymoma develop myasthenia gravis.
Normal function of NMJ
Motor nerves communicate with muscles at neuromuscular junctions.
The axons release ACh neurotransmitter from the pre-synaptic membrane.
This acetylcholine travels across the synapse and attached to receptors on the post-synaptic membrane.
They stimulate the receptors, and this signal leads to muscle contraction.
Pathophysiology of Myasthenia gravis
In most MG (85%) patients acetylcholine receptor antibodies are produced by the immune system.
These bind to postsynaptic NMJ receptors and blocks ACh from being able to stimulate the receptor
As the receptors are used more during muscle activity, more of them become blocked up - leads to less effective stimulation of the muscle with increased activity.
= More muscle weakness the more muscles are used
This improves with rest as more receptors are freed up for use again.
The other 15% have either of these antibodies:
- Antibodies against muscle-specific kinase (MuSK)
- Antibodies against low-density lipoprotein receptor-related protein 4 (LRP4)
- These two proteins are important for the creation and organisation of ACh receptors
- So destruction by autoantibodies leads to inadequate ACh receptors
Presentation of MG
Muscle weakness that shows fatiguability
Symptoms are worse at the end of the day
Most affect the proximal muscles and small muscles of the head and neck
Symptoms in MG
Extraocular muscle weakness causing double vision (diplopia)
Eyelid weakness causing drooping of the eyelids (ptosis)
Weakness in facial movements
Difficulty with swallowing
Fatigue in the jaw when chewing
Slurred speech
Progressive weakness with repetitive movements
Good history questions if suspect MG?
When is the muscle weakness worst?
Any difficulty chewing/swallowing?
Any problems with speech
Any double vision or drooping eyelids?
Examination in suspected MG
Full neurological examination
But mostly testing for fatiguability in the muscles
- Repeated blinking - will exacerbate ptosis
- Prolonged upward gazing will exacerbate diplopia on further eye movement testing
- Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides
Check for thymectomy scar (midline sternotomy)
How is diagnosis of MG made?
Testing for the associated antibodies:
- Acetylcholine receptor (ACh-R) antibodies (85% of patients)
- Muscle-specific kinase (MuSK) antibodies (10% of patients)
- LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%)
CT/MRI of thymus to assess for thymoma
The edrophonium test can be helpful where there is doubt about the diagnosis.
What is an edrophonium test?
Patients are given an IV dose of edrophonium chloride (or neostigmine).
Normally, cholinesterase enzymes in the neuromuscular junction break down acetylcholine.
Edrophonium block these enzymes and stop the breakdown of acetylcholine.
- level of acetylcholine at the neuromuscular junction increases.
It briefly and temporarily relieves the weakness.
This establishes a diagnosis of myasthenia gravis.
Treatment options
Reversible acetylcholinesterase inhibitors (usually pyridostigmine or neostigmine) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms
Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
Thymectomy can improve symptoms even in patients without a thymoma
Also can consider monoclonal antibodies if standard treatment is ineffective e.g. rituximab (monoclonal antibody that targets B cells and reduces the production of antibodies)
What is a complication of MG?
The most serious complication is a myasthenic crisis
What is a myasthenic crisis?
An acute worsening of symptoms which can lead to respiratory failure as a result of weakness in the muscle of respiration
Often is triggered by another illness e.g. RTI
What is the treatment for myasthenia crisis?
Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.
Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
