OVERVIEW

What is generalized myasthenia gravis?

Myasthenia gravis is the most common autoimmune disorder of the neuromuscular junction, primarily characterized by fluctuating muscle weakness and fatigue. When limb muscle groups are affected, it is referred to as generalized myasthenia gravis.

The disease may develop acutely or chronically, with symptoms progressing slowly or rapidly. Prognosis varies significantly among individuals. Involvement of respiratory muscles can lead to myasthenic crisis, causing respiratory failure and life-threatening conditions.

Is generalized myasthenia gravis common?

Relatively common.

The incidence of myasthenia gravis is approximately 1–2 cases per 10,000 people, with a prevalence of about 5 cases per 10,000. Generalized myasthenia gravis accounts for the majority of cases. The disease can occur at any age, with higher rates in women aged 20–40 and men aged 50–70. A minority of cases may have a family history.

SYMPTOMS

What are the manifestations of generalized myasthenia gravis?

Generalized myasthenia gravis usually has an insidious onset, with varying manifestations depending on the affected muscle groups. Its hallmark features are pathological fatigability and fluctuating muscle weakness, meaning muscle weakness worsens significantly with repeated or sustained activity of a muscle group and improves to varying degrees after rest. This fatigue differs markedly from normal fatigue, as even minimal activity can noticeably exacerbate weakness.

Additionally, muscle weakness often fluctuates, with symptoms typically milder in the morning, worsening by evening, aggravated by activity, and relieved by rest.

Which areas are commonly affected by generalized myasthenia gravis? How does it progress?

The progression of generalized myasthenia gravis is as follows:

• Initially, extraocular muscles are most frequently involved, leading to ptosis (drooping eyelids) and diplopia (double vision);
• It then progresses to limb or pharyngeal muscle involvement, causing difficulty raising or holding up arms, trouble lifting heavy objects, unstable grip, difficulty squatting or standing up, climbing stairs, or walking due to fatigue, hoarseness, dysphagia, and choking while drinking. In severe cases, patients may lose the ability to dress, comb hair, eat, use the toilet, or walk independently;
• It may also first present with limb or pharyngeal muscle weakness, with or without extraocular muscle involvement. At any stage, respiratory muscle involvement may occur, leading to labored breathing, suffocation, or even respiratory failure (myasthenic crisis).

What severe complications can generalized myasthenia gravis cause?

The most serious complication of generalized myasthenia gravis is a crisis, where muscle weakness rapidly worsens, severely affecting respiratory and bulbar muscles, leading to respiratory paralysis, quadriplegia, and potentially life-threatening conditions. This is a common cause of death in myasthenia gravis.

Crises can be classified as myasthenic crisis, cholinergic crisis, or refractory crisis, with myasthenic crisis being the most common.

What conditions should generalized myasthenia gravis be differentiated from?

Generalized myasthenia gravis must be distinguished from other conditions causing limb weakness, including Lambert-Eaton syndrome, Guillain-Barré syndrome, periodic paralysis, polymyositis, and other muscular disorders.

CAUSES

What is the cause of generalized myasthenia gravis?

The etiology and pathogenesis of generalized myasthenia gravis remain incompletely understood. The currently identified possible mechanisms involve a reduction in the number of acetylcholine receptors at the neuromuscular junction and impaired signal transmission, leading to muscle weakness and pathological fatigue.

The neuromuscular junction synapse is a signal transduction device. Electrical impulses from the central nervous system travel along the nervous system to the motor nerve endings, where the electrical signal is converted into acetylcholine (which can be understood as a "signal") and released into the synaptic cleft. Under normal circumstances, this signal can be "captured" by acetylcholine receptors (which can be understood as "receivers") located on the postsynaptic membrane (on the muscle). This signaling factor then enters the muscle cell, ultimately triggering muscle contraction and completing signal transmission.

In some patients with generalized myasthenia gravis, the body produces antibodies that "block" acetylcholine receptors on the postsynaptic membrane for unknown reasons, causing some "receivers" to fail to "function." This often results in insufficient muscle fiber contraction, leading to muscle weakness and fatigue. However, some patients do not have acetylcholine receptor antibodies but instead have other antibodies that affect neuromuscular junction signal transmission. Additionally, the specific causes and mechanisms of antibody production are not entirely clear.

DIAGNOSIS

How is generalized myasthenia gravis diagnosed?

The diagnosis of generalized myasthenia gravis is primarily based on the patient's medical history, such as systemic or partial skeletal muscle fatigue, fluctuating muscle weakness symptoms that worsen with activity, improve with rest, and exhibit morning improvement with evening worsening. It is combined with auxiliary diagnostic methods like neuroelectrophysiological tests, fatigue tests, edrophonium or neostigmine tests, effective response to cholinesterase inhibitor treatment, and elevated serum AChR-Ab antibodies. Other similar diseases must also be ruled out.

What tests do patients with generalized myasthenia gravis need to undergo? Why are these tests necessary?

• Neuroelectrophysiological tests: Including repetitive nerve stimulation, which helps assess muscle fatigue, localize the neuromuscular junction, and differentiate from other neuromuscular disorders like Lambert-Eaton syndrome.
• Serum autoimmune antibodies: Including AChR-Ab, which aids in detecting myasthenia gravis-specific antibodies, confirming the diagnosis, and assessing disease prognosis. However, some myasthenia gravis cases may test negative for antibodies.
• Pulmonary function tests: Help evaluate whether respiratory muscles are affected.
• Thymus CT: Many myasthenia gravis patients have thymic hyperplasia or thymoma, which requires screening.

What precautions should be taken for neuroelectrophysiological tests?

Neuroelectrophysiological tests are an important method for diagnosing neuromuscular junction disorders, muscle diseases, and peripheral nerve disorders.

Before the test, patients must confirm they have no history of cardiac pacemakers or similar conditions. During the examination, they should follow the doctor's instructions and avoid unnecessary movement. Some tests may involve a slight sensation of electric current, and minor needle-like discomfort may occur afterward, which usually resolves with rest.

TREATMENT

Which department should I visit for generalized myasthenia gravis?

Neurology.

Can generalized myasthenia gravis resolve on its own?

No.

Does generalized myasthenia gravis require hospitalization?

Not necessarily.

Hospitalization is needed if the condition progresses rapidly or there is a risk of crisis.

How is generalized myasthenia gravis treated?

Treatment for generalized myasthenia gravis mainly includes symptomatic therapy, immunotherapy, crisis management, and thymus surgery.

• Symptomatic therapy: Primarily involves anticholinesterase drugs, which reversibly inhibit cholinesterase, increasing acetylcholine levels at neuromuscular junctions to improve muscle weakness symptoms. However, this does not address the underlying cause.
  The commonly used drug is pyridostigmine bromide, typically started at a low dose. Common side effects include abdominal cramps, nausea, vomiting, diarrhea, excessive salivation, increased bronchial secretions, tearing, sweating, muscle cramps, spontaneous contractions, and weakness. Atropine can be used for symptomatic relief if side effects are severe.
• Immunotherapy:
  • Corticosteroids: Their mechanism involves suppressing the production of autoimmune antibodies, reducing "attacks" on postsynaptic membrane receptors. High-dose prednisone is commonly used, but caution is needed as muscle weakness may worsen initially.
  • Immunosuppressants: These drugs work through antiproliferative and antimetabolic effects. Common options include azathioprine, cyclophosphamide, methotrexate, cyclosporine, and mycophenolate mofetil. Long-term use requires monitoring for adverse effects such as bone marrow suppression and infections.
• Crisis management: In cases of myasthenic crisis, ensuring oxygen supply and stabilizing vital signs are priorities. Intubation or mechanical ventilation may be necessary. Immunotherapy such as plasma exchange, high-dose immunoglobulins, or corticosteroids can help alleviate symptoms.
• Thymus surgery: Patients with thymic hyperplasia or thymoma may require surgery based on their condition. Pre- and post-operative monitoring is crucial due to the risk of myasthenic crisis.

DIET & LIFESTYLE

What should patients with generalized myasthenia gravis pay attention to in their diet?

There are no special dietary restrictions for patients with generalized myasthenia gravis. Maintaining healthy eating habits and a balanced diet is sufficient.

What should patients with generalized myasthenia gravis pay attention to in daily life?

• Patients should avoid overexertion, cold infections, diarrhea, and other conditions that may trigger myasthenic crisis.
• Medication use requires caution, as many drugs may worsen myasthenia gravis, including certain antibiotics (especially aminoglycosides; known safe antibiotics include penicillins, cephalosporins, erythromycin, and chloramphenicol), some immunosuppressants (such as adrenocorticotropic hormone), sedatives, and hypnotics. Exposure to certain toxins or pesticides should also be avoided.
• Additionally, any factors that weaken immunity or activate immune responses (e.g., unauthorized vaccination, surgery, trauma) may cause symptom fluctuations. Close monitoring is necessary before and after essential surgeries.

What are the postoperative precautions and care measures for generalized myasthenia gravis?

Recovery varies depending on the condition and surgical approach. Vital signs and disease progression must be closely monitored. Patients should rest in a quiet environment with minimal visits. A balanced diet is recommended to prevent constipation.

Do patients with generalized myasthenia gravis need follow-up examinations?

Yes.

Regular outpatient follow-ups are required, with the schedule determined by the attending physician.

Can patients with generalized myasthenia gravis fly, engage in strenuous exercise, or travel to high-altitude areas?

Not recommended before the disease is effectively treated.

PREVENTION

Can generalized myasthenia gravis be prevented?

Currently, the cause and pathogenesis of this disease remain unclear, and there is no effective prevention method.

What is the prognosis for patients with generalized myasthenia gravis?

Most patients with generalized myasthenia gravis experience a prolonged disease course lasting over a decade or even decades, requiring medication for symptom management. Symptoms often fluctuate during the course, with risks of myasthenic crisis. A small number of cases may achieve spontaneous remission within 2–3 years.