Myasthenia Gravis: An Autoimmune Disease Affecting Neuromuscular Transmission

Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular transmission, causing localized or generalized muscle weakness. It occurs when the immune system attacks acetylcholine receptors at the post-synaptic membrane of the neuromuscular junction, resulting in impaired neuromuscular transmission.

Causes:

• Autoimmune disease: The body produces antibodies against acetylcholine receptors (AchR) or antibodies against muscle-specific tyrosine kinase (MuSK).

• Role of the thymus: The thymus can produce epithelial cells that present acetylcholine receptors and acetylcholine receptor-specific B lymphocytes, leading to the production of anti-acetylcholine receptor antibodies.

• Mechanism of impaired neuromuscular transmission:

• Anti-AchR antibodies block acetylcholine molecules from binding to receptors, while also accelerating the rate of receptor degradation by 2-3 times.

• Anti-AchR antibodies also mediate complement-mediated destruction of the post-synaptic membrane folds, leading to a decrease in the number of acetylcholine receptors.

• About 10-20% of patients do not have anti-AchR antibodies, but may have other types of antibodies that bind to the synapse terminal.

Age and Gender:

• Myasthenia gravis often occurs between the ages of 20-40 or over 60.

• Women are more likely to develop the disease than men under the age of 40, while the opposite is true for men over the age of 50.

Factors that can worsen the disease:

• Stress

• Infections

• Post-surgery

• Pregnancy

• Neuromuscular blocking drugs (such as antibiotics, muscle relaxants, sedatives, beta-blockers)

Symptoms:

• Fluctuating muscle weakness throughout the day, increasing with exertion and decreasing with rest.

• Not consistent with any specific nerve injury.

• Common symptoms:

• Eye muscle weakness: Drooping eyelids, eye movement paralysis (double vision, difficulty moving eyes).

• Weakness of chewing muscles, throat muscles: Difficulty swallowing, jaw fatigue when chewing, nasal voice, difficulty speaking.

• Neck muscle weakness: Difficulty holding the head straight, head drooping.

• Respiratory muscle weakness: Respiratory failure due to weakness of the diaphragm and accessory respiratory muscles.

Disease Progression:

• The disease often recurs, with varying degrees of severity among patients.

• Myasthenic crisis: A rapid progression of myasthenia gravis, causing quadriplegia accompanied by respiratory failure.

• Warning signs of a myasthenic crisis: Restlessness, fear, sweating, slurred speech, difficulty speaking, neck muscle weakness, respiratory failure, shortness of breath, shallow breathing, paradoxical abdominal-thoracic breathing, decreased vital capacity.

Classification:

• Based on Osserman criteria:

• Group I: Pure ocular myasthenia gravis (accounts for 15-20% of all patients).

• Group IIA: Mild generalized myasthenia gravis, slow progression, no myasthenic crisis, responsive to medication (accounts for 30%).

• Group IIB: Moderate generalized myasthenia gravis, severe impact on skeletal muscles and cranial nerve-related muscles, no myasthenic crisis, responsive to medication but not completely (accounts for 25%).

• Group III: Acutely explosive, severe myasthenia gravis, rapid development with respiratory failure, poor response to medication, high thymus tumor rate (accounts for 15%).

• Group IV: Symptoms similar to Group III, but the transition from I to IV usually takes more than 2 years (accounts for 10%).

• Modified Osserman Classification:

• Grade I: Only affects eye muscles.

• Grade II: Mild generalized weakness.

• Grade III: Moderate generalized weakness.

• Grade IV: Severe generalized weakness.

• Grade V: Intubated, with or without mechanical ventilation.

Diagnosis:

• Edrophonium test (Tensilon test): Administration of anticholinesterase medication (Edrophonium) into the body, if the myasthenia gravis symptoms regress after injection and last for 4-5 minutes, the result is positive.

• Neostrigmin test (Prostrigmine test): Administration of anticholinesterase medication (Neostrigmin), if myasthenia gravis symptoms decrease after 10-15 minutes and last for 2-3 hours, the result is positive.

• Chest and mediastinal CT or MRI: Thymus hypertrophy or tumor, lymphoid follicular hyperplasia in the thymus.

• Repetitive nerve stimulation electromyography: >10% decline is seen in at least 2 muscle groups (sternocleidomastoid, trapezius or deltoid, orbicularis oculi).

• Single fiber electromyography: Increased jitter of muscle fibers.

• Respiratory function monitoring: When severe generalized myasthenia gravis is suspected, monitor for respiratory failure.

Treatment:

• Acetylcholinesterase inhibitors:

• Increase the amount of Acetylcholine in the synaptic cleft, compensating for the deficiency caused by antibody blockade.

• Indications: Mild myasthenia gravis without thymoma, ocular myasthenia gravis.

• Acetylcholinesterase inhibitor medications: Pyridostigmine bromide (Mestinon), Neostigmine (Prostigmine), Sustained-release pyridostigmine (Mestinon Timespan).

• Cholinergic side effects: Nausea, vomiting, abdominal cramps, diarrhea, sweating, increased salivation, increased bronchial secretions, miosis, bradycardia.

• Cholinergic crisis due to overdose of acetylcholinesterase inhibitors: Rapid progression of muscle weakness accompanied by cholinergic side effects.

• Distinguish between cholinergic crisis due to medication and myasthenic crisis: Use Tensilon test.

• Management of cholinergic crisis: Stop acetylcholinesterase inhibitors, use anticholinergics (Atropine).

• Corticosteroids: Suppress the immune system, reducing antibody production.

• Immunosuppressants: Azathioprine, Mycophenolate mofetil, Methotrexate.

• Plasma exchange: Remove disease-causing antibodies.

• Intravenous immunoglobulin: Provide healthy antibodies to suppress disease-causing antibodies.

• Thymectomy: Indicated for patients with thymoma, may help improve disease symptoms.

Note:

• This article is for informational purposes only and does not substitute for medical advice.

• If you suspect you may have myasthenia gravis, please consult a doctor for appropriate diagnosis and treatment.