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Myasthenia Gravis

Myasthenia gravis (MG) is a long-term neuromuscular junction disease characterised by varying degrees of skeletal muscle weakness. This autoimmune condition predominantly affects muscles of the eyes, face, and those involved in swallowing, leading to symptoms such as double vision, drooping eyelids, and difficulties in speaking and walking. Onset can be sudden, often affecting women under 40 and men over 60.

Pathophysiology

MG is an autoimmune synaptopathy where antibodies attack nicotinic acetylcholine receptors (AChR) at the neuromuscular junction, preventing nerve impulses from triggering muscle contractions. This results in muscle weakness. Most cases are due to IgG1 and IgG3 antibodies. Additionally, the thymus gland is often abnormal in MG patients, sometimes containing clusters indicative of lymphoid hyperplasia.

Neuromuscular junction
Neuromuscular junction: 1. Axon 2. Muscle cell membrane 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion
A juvenile thymus shrinks with age
A juvenile thymus shrinks with age.
The nicotinic acetylcholine receptor
The nicotinic acetylcholine receptor

Signs and Symptoms

The primary symptom of MG is painless muscle weakness that worsens with activity and improves with rest. Symptoms are typically worse towards the end of the day. MG often begins with ocular weakness but can progress to generalised muscle weakness affecting extremities and essential life functions.

Eyes

In about two-thirds of cases, MG starts with ocular symptoms like ptosis (drooping eyelids) and diplopia (double vision). Watching TV, reading, or driving can exacerbate these symptoms, and some individuals wear sunglasses to mitigate discomfort.

Eating

Weakness in swallowing muscles can lead to dysphagia, where food may remain in the mouth or regurgitate into the nose. Chewing tough foods becomes tiring due to muscle fatigue.

Speaking

Weakness in speaking muscles may result in dysarthria and hypophonia, causing slow, slurred, or nasal speech. Some may need to abandon singing hobbies or professions.

Head and Neck

Facial muscles' weakness may manifest as a hanging jaw or a snarling expression. Drooping eyelids and facial weakness can make individuals appear sleepy or sad. Holding the head upright may also become difficult.

Other

Respiratory muscles can be affected, leading to severe complications like myasthenic crises, necessitating mechanical ventilation.

Eye deviation and a drooping eyelid in a person with myasthenia gravis trying to open her eyes
Eye deviation and a drooping eyelid in a person with myasthenia gravis trying to open her eyes

Diagnosis

Diagnosis can be challenging due to subtle symptoms. Blood tests for specific antibodies, the edrophonium test, electromyography (EMG), and nerve conduction studies support the diagnosis.

Blood Tests

Serology can identify antibodies against AChR or MuSK proteins.

Electrodiagnostics

Tests such as repetitive nerve stimulation and single-fibre electromyography can diagnose MG by measuring muscle fatigue and action potentials.

A chest CT-scan showing a thymoma
A chest CT-scan showing a thymoma (red circle)
Photograph showing ptosis improvement after an edrophonium test
Photograph showing ptosis improvement after an edrophonium test

Treatment

Treatment involves medications, surgery, and physical measures.

Medications

Main treatments include acetylcholinesterase inhibitors like neostigmine and pyridostigmine to improve muscle function. Immunosuppressants such as prednisone or azathioprine may also be used. Newer treatments like efgartigimod alfa (Vyvgart) and rozanolixizumab (Rystiggo) have been approved for use.

Neostigmine, chemical structure
Neostigmine, chemical structure
Azathioprine, chemical structure
Azathioprine, chemical structure

Plasmapheresis and IVIG

In severe cases, plasmapheresis and intravenous immunoglobulins (IVIG) are used to remove or bind circulating antibodies. These treatments are generally reserved for hospital settings due to their high cost and short-lived benefits.

Surgery

Thymectomy, the surgical removal of the thymus, is often performed, especially in the presence of thymoma. Recent studies suggest it may benefit MG patients even without thymoma.

Physical Measures

Patients should be educated on symptom fluctuation and encouraged to exercise with frequent rest. Programmes including diaphragmatic breathing and muscle therapy may improve respiratory and overall muscle strength.

Prognosis and Epidemiology

With treatment, the prognosis for MG patients is generally good, with a near-normal life expectancy. However, continuous monitoring is essential as myasthenic crises can occur. MG affects all ethnic groups and sexes, with a higher prevalence in women under 40 and men over 60. The condition is rare in children.


Self-assessment MCQs (single best answer)

What is the primary characteristic of Myasthenia Gravis (MG)?



Which of the following antibodies is most commonly involved in MG?



What is a common initial symptom of MG?



Which diagnostic test involves measuring muscle fatigue and action potentials?



What is the function of acetylcholinesterase inhibitors in MG treatment?



Which treatment option involves removing circulating antibodies from the blood?



Which age groups are predominantly affected by MG?



What is the role of the thymus gland in MG?



What type of speech difficulty is associated with MG?



Which of the following is NOT a typical symptom of MG?



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