Myasthenia Gravis

• Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction.
• Myasthenia gravis causes muscle weakness that progressively worsens with activity and improves with rest.
• Myasthenia gravis affects men and women at different ages, typically affecting women under 40 and men over 60.
• There is a strong link with thymomas (thymus gland tumours) in myasthenia gravis.
• 10-20% of patients with myasthenia gravis have a thymoma.
• 30% of patients with a thymoma develop myasthenia gravis.
• Motor neurones communicate with muscles via the neuromuscular junction.
• On one side of the synapse is the presynaptic membrane of the axon terminal of the motor neurone.
• On the other side is the postsynaptic membrane of the motor end plate of the muscle cell.
• The axons release a neurotransmitter called acetylcholine from the presynaptic membrane.
• Acetylcholine travels across the synapse and attaches to receptors on the postsynaptic membrane, simulating muscle contraction.
• Acetylcholine receptor ( AChR ) antibodies are found in most patients with myasthenia gravis.
• These antibodies bind to the postsynaptic acetylcholine receptors, blocking them and preventing stimulation by acetylcholine.
• The more the receptors are used during muscle activity, the more they become blocked.
• There is less effective stimulation of the muscle with increased activity.
• With rest, the receptors are cleared, and the symptoms improve.
• These antibodies also activate the complement system within the neuromuscular junction, leading to cell damage at the postsynaptic membrane, further worsening symptoms.
• Myasthenic crisis is a potentially life-threatening complication of myasthenia gravis that causes an acute worsening of symptoms, often triggered by another illness, such as a respiratory tract infection.
• Treatment options for myasthenia gravis include pyridostigmine, immunosuppression, thymectomy, and rituximab.
• Treatment for myasthenic crisis includes IV immunoglobulins and plasmapheresis.
• A CT or MRI of the thymus gland is used to look for a thymoma.
• Edrophonium blocks the cholinesterase enzymes in the neuromuscular junction, temporarily relieving the weakness.
• Symptoms of myasthenia gravis are typically best in the morning and worst at the end of the day.
• Investigations for myasthenia gravis include checking for a thymectomy scar, testing the forced vital capacity (FVC), and antibody tests for AChR antibodies, MuSK antibodies, and LRP4 antibodies.
• The symptoms of myasthenia gravis affect the proximal muscles of the limbs and small muscles of the head and neck, causing difficulty with climbing stairs, standing from a seat, raising their hands above their head, extraocular muscle weakness, eyelid weakness, weakness in facial movements, difficulty with swallowing, and fatigue in the jaw when chewing.
• Fatiguability in the muscles can be elicited by repeated blinking, prolonged upward gazing, and repeated abduction of one arm.
• The edrophonium test can be helpful in diagnosing myasthenia gravis where there is doubt about the diagnosis.
• Two other antibodies can cause myasthenia gravis: Muscle-specific kinase ( MuSK ) antibodies and Low-density lipoprotein receptor-related protein 4 ( LRP4 ) antibodies.
• MuSK and LRP4 are important proteins for the creation and organisation of the acetylcholine receptor.
• Destruction of these proteins leads to inadequate acetylcholine receptors.
• Symptoms vary dramatically between patients, ranging from mild to life-threateningly severe.
• The critical feature is weakness that worsens with muscle use and improves with rest.