Myasthenia Gravis

Myasthenia gravis (MG) is a condition where the body produces antibodies against the nicotinic acetylcholine receptors on the post-synaptic membrane of the neuromuscular junction.
 

Pathophysiology

The underlying pathology of myasthenia gravis involves auto-antibodies. In normal cells, an action potential reaches the end of a pre-synaptic neuron and triggers the release of acetylcholine, a neurotransmitter. Acetylcholine binds to nicotinic acetylcholine receptors (nAChR) on the muscle fibre to trigger an action potential and subsequent muscle contraction.

In myasthenia gravis, most patients (roughly 85%), produce antibodies against the nAChRs which causes several problems with nerve transmission.

1. These antibodies block the receptors, meaning acetylcholine cannot bind to the receptor and trigger an action potential in the post-synaptic neuron
    
2. The antibodies will activate the complement pathway, leading to localised damage to the post-synaptic membrane
    
3. Anti-nAChR antibodies can also lead to internalisation and subsequent degredation of the receptors, thus reducing the number of nAChRs on the membrane

Ultimately, the antibodies will prevent an action potential forming post-synaptically, effectively removing the trigger that causes muscle contraction.

Anti-Muscle-Specific Kinase (Anti-MuSK)

A smaller proportion of patients with MG will have Anti-MuSK antibodies. MuSK is a receptor tyrosine kinase which is found on the neuromuscular junction with AChRs. Activation of MuSK is important in the functioning of AChRs.

Antibodies to MuSK stops the proper formation of AChRs and will lead to a reduction in the amount of AChRs on the endplate of the neuromuscular junction

Associations

Myasthenia gravis is associated with diseases of the thymus gland, particularly thymomas or thymic hyperplasia, suggesting the thymus may also play a role in this condition. Additionally, patients who develop myasthenia gravis may also have pre-existing autoimmune conditions such as rheumatoid arthritis.

Clinical Features

• Weakness which usually affects the bulbar and extra-ocular muscles though the limbs and face can also be involved.
• Ptosis
• Weak smile, also known as a myasthenic snarl.
• Diplopa as a result of the weak extra-ocular muscles.
• Fatigability: Symptoms will become worse the more patients use their muscle. For example, you may notice a patient speaking and their voice becoming weaker after some time due to weakness in the bulbar muscles. Similarly, patients may also complain that their symptoms are worse at the end of the day.

Posey & Spiller, Public domain, via Wikimedia Commons

Patient with Myasthenia Gravis Exhibiting Ptosis