Myasthenia Gravis: Causes, Symptoms and Treatment

Myasthenia gravis affects about 20 out of every 100,000 people in the United States. It is a chronic illness that causes muscle weakness, making simple tasks like holding a cup or walking up stairs difficult.

Myasthenia gravis is an autoimmune disorder that disrupts communication between nerves and muscles. Awareness of its symptoms and treatments is key for early diagnosis and management. This article explains its causes, symptoms, diagnosis, and treatments.

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What is Myasthenia Gravis? 

Let's start with a basic overview and explore how the condition was discovered and understood over time.

Definition and Overview

Myasthenia gravis (MG) is a chronic autoimmune disorder that weakens voluntary muscles, such as those used for breathing, swallowing, and eye movement. The hallmark symptom of MG is muscle weakness that worsens with activity and improves with rest.

Understanding Autoimmune Disorders

Autoimmune disorders occur when the body’s immune system, which normally fights infections, mistakenly attacks healthy tissues. In MG, the immune system produces autoantibodies that block the communication between nerves and muscles. This prevents muscles from contracting properly, causing weakness.

How Myasthenia Gravis Affects the Nervous System

In a healthy nervous system, nerves send signals to muscles through a chemical messenger called acetylcholine. This chemical binds to receptors on the muscles, signaling them to contract. In people with MG, autoantibodies destroy or block these receptors, preventing the muscles from receiving signals. This disruption leads to muscle fatigue and weakness.

History and Discovery

The first descriptions of MG appeared in the 1600s, but the condition wasn’t formally named until the late 19th century. Early cases documented symptoms like drooping eyelids and muscle fatigue.

In the mid-20th century, scientists discovered that MG was an autoimmune disease. This breakthrough led to the development of treatments such as anticholinesterase medications and immunosuppressants, which are still used today to manage MG.

Symptoms of Myasthenia Gravis

Early recognition of symptoms is key to managing MG effectively and preventing complications. MG symptoms can vary from person to person, ranging from mild to life-threatening.

Common Symptoms

Most people with MG experience fluctuating muscle weakness, which often worsens with activity and later in the day and improves with rest.  

Muscle Weakness and Fatigue

The most common symptom is muscle weakness that worsens with activity and improves with rest. Different muscles may be affected, for example:

• Eye muscles (ocular MG): Drooping eyelids (ptosis) and double vision (diplopia) are common early signs.
• Face and throat muscles (bulbar symptoms): Difficulty speaking (dysarthria), chewing, and swallowing (dysphagia) may occur.
• Limb muscles: Weakness in the arms and legs can make walking, lifting objects, or climbing stairs difficult.

Rare Symptoms

Although less common, people with MG may experience unusual or severe symptoms. Identifying these signs is important for timely diagnosis and treatment.

• Respiratory issues: Weakness in chest muscles can lead to shortness of breath or respiratory failure (myasthenic crisis).
  
  • Myasthenic crisis is a life-threatening complication of MG where the muscles used for breathing become very weak. This can cause severe breathing problems, and patients may need a machine called a ventilator to help them breathe.
• Neck and trunk muscle weakness: Difficulty holding up ones head or maintaining posture.
• Speech difficulties: Slurred or nasal speech, especially after talking for extended periods.

Not all individuals with MG experience every symptom listed. Symptom severity varies from person to person.

Impact on Daily Activities

The muscle weakness caused by MG can interfere with daily tasks such as brushing teeth, eating, or driving. As symptoms worsen throughout the day, even simple activities may become exhausting. 

Causes and Risk Factors

Understanding the causes of myasthenia gravis (MG) can help identify those at risk and explain how the condition develops.

Primary Cause

The primary cause of MG is an autoimmune reaction. Let’s explore how this reaction leads to muscle weakness.

Autoantibodies and Their Role

• Acetylcholine receptors (AChR) - Most people with MG produce antibodies that block or destroy AChR in muscle cells. Without enough working receptors, nerve signals cannot reach the muscles, resulting in weakness. 
• Muscle-specific kinase (MuSK) - Less commonly, some people produce antibodies against a protein called muscle-specific kinase (MuSK), essential for forming nerve-muscle connections. This also results in muscle weakness.

Genetic Predispositions

A family history of autoimmune disorders (e.g.,  lupus or rheumatoid arthritis) increases the likelihood of developing MG. Scientists believe specific genes, particularly those related to immune system function, may make people more susceptible to MG.

Less Common Causes

In some cases, myasthenia gravis (MG) is triggered by unusual factors or associated with other medical conditions.

Triggers

• Infections: Viral infections sometimes trigger autoimmune responses. Examples include Epstein-Barr Virus, coxsackievirus B3, herpes simplex virus, cytomegalovirus, and influenza. 
• Medications: Certain antibiotics, beta-blockers, and anesthesia drugs can worsen MG symptoms.

Associated Conditions and Syndromes

• Thymoma: Up to 15% of people with MG have a tumor in their thymus gland (thymoma), which plays a role in immune system function.
• Autoimmune Disorders: MG is more common in people with other autoimmune diseases, such as thyroiditis or lupus.

Diagnosis of Myasthenia Gravis

A neurologist or neuromuscular specialist should evaluate persistent symptoms for an accurate diagnosis.

Medical Evaluation

The first step in diagnosing MG is obtaining a thorough medical history and physical exam. Healthcare providers may ask about:

• Time of day that symptoms (fatigue) onset
• Factors that worsen or relieve fatigue
• Recent changes in voice or speech 
• Difficulty or coughing while swallowing 
• Increased fatigue with daily activities like climbing stairs
• Recent changes in writing or typing ability (slowness or frequent errors)

Clinical Assessments and Physical Exams

• Doctors will check for signs such as drooping eyelids or muscle weakness that worsens with repeated activity. 
• A simple test, such as holding the arms up for a few minutes, may show muscle fatigue, a common sign of MG.

Laboratory Tests 

• Blood tests: A blood test can confirm the presence of autoantibodies commonly seen in MG, such as:
  
  • Acetylcholine receptor (AChR) antibody test - Detects antibodies that block or destroy acetylcholine receptors.
  • Muscle-specific kinase (MuSK) antibody test - Identifies antibodies against MuSK, a protein necessary for forming and maintaining nerve-muscle connections.
  • Lipoprotein-Related Protein 4 (LRP4) antibody test - Used to diagnose patients who are AChR and MuSK antibody negative.
  • Striational antibody test - Detects antibodies that target muscle fibers. Helps identify MG associated with thymoma.
  • Anti-Titin and Anti-Ryanodine receptor antibody test - Detects antibodies against these muscle proteins. Best for diagnosing MG in older adults and patients with thymoma.
• Ice pack test: Placing an ice pack on the drooping eyelid can temporarily improve the symptom, indicating MG.

Advanced Diagnostic Techniques

Advanced techniques can help confirm a diagnosis of MG when further testing is needed.

Electromyography 

Electromyography (EMG) measures the electrical activity of muscles. A repetitive nerve stimulation test, a type of EMG, can detect the communication problems between nerves and muscles typical of MG.

Imaging Studies

A computed tomography (CT) scan or magnetic resonance imaging (MRI) can be used to check for thymomas, tumors in the thymus gland that can cause or worsen MG.

Treatment Options

Although there is no cure for myasthenia gravis, various treatments can effectively manage symptoms and improve quality of life.

Conventional Medical Treatments

Medications and/or surgery are used to manage MG symptoms.

Medications 

• Anticholinesterase inhibitors: Medications like pyridostigmine (Mestinon) improve nerve signal transmission, reducing muscle weakness.
• Immunosuppressants: Drugs such as prednisone, azathioprine, and mycophenolate suppress the immune system, helping to reduce antibody production.
• Monoclonal Antibodies: Newer treatments, such as eculizumab (Soliris) and rituximab (Rituxan), target specific parts of the immune system and are FDA-approved for certain types of MG.  

Thymectomy and Its Role in Myasthenia Gravis

Thymectomy is FDA-recognized for patients with thymomas and may also benefit some patients with generalized MG.

• A thymectomy is a surgical procedure to remove the thymus gland, an organ located behind the breastbone that plays a key role in the immune system. In people with MG, the thymus may contribute to the abnormal immune response that causes the disease.

For some people with MG, a thymectomy can significantly reduce symptoms. The surgery removes or reduces a potential source of the antibodies that impede communication between nerves and muscles. By lowering antibody production, a thymectomy may improve muscle strength and reduce the need for medications.

Note:  Thymectomy is not appropriate for every patient with MG. Results from thymectomy can vary, and improvements may take months or years to become noticeable. Consult a neurologist and surgeon to determine if this procedure is right for you.

Integrative and Functional Approaches

Complementary therapies such as lifestyle modifications and physical therapy are supportive and should be used alongside conventional medical care.

Lifestyle Modifications

• Rest and pacing: Taking frequent breaks and avoiding overexertion helps manage fatigue.
• Heat management: Staying cool is important, as heat can worsen MG symptoms.

Complementary Therapies

• Nutritional support: A healthy diet rich in anti-inflammatory foods may help reduce flare-ups.
• Physical therapy: Gentle exercises improve mobility and prevent muscle atrophy without overexertion.

Always consult your healthcare provider before starting new therapies to ensure they are safe and appropriate for your condition.

Living with Myasthenia Gravis

Physical adjustments and emotional support can help manage some of the challenges of living with MG.

Daily Management Strategies

By adopting effective strategies, people with MG can maintain independence and reduce symptom impact.

• Plan activities: Schedule demanding tasks for times when energy is highest.
• Use assistive devices: Tools like shower chairs and lightweight utensils reduce muscle strain.
• Mobility aids: Devices like walkers or canes help balance and reduce fatigue.
• Smart home technology: Voice-activated assistants can make daily tasks easier.

Emotional and Psychological Support

Living with a chronic illness can be emotionally challenging, so psychological support is essential.

• Mindfulness and relaxation: Techniques like deep breathing and meditation help reduce stress.
• Journaling: Tracking symptoms can help identify triggers and measure progress.‍
• Support groups: Connecting with others with MG offers shared experiences, tips, and emotional support.
• Professional counseling: Therapists can help MG patients and their caregivers manage anxiety and depression.

Every individual with MG has a unique experience. Management strategies should be tailored to personal needs.

Recent Research and Future Directions

Research into MG continues to advance, bringing new hope to patients through better treatments and potential cures. For example:

• Recent studies have highlighted the role of complement inhibitors in reducing inflammation at the neuromuscular junction.
• New FDA-approved drugs: Rozanolixizumab-noli (Rystiggo) and Zilucoplan (Zilbrysq), approved in 2023, offer new options for patients with refractory MG. 
• Gene therapy research: Ongoing trials are exploring ways to modify immune responses, potentially offering long-term remission for some patients.

Gene therapies and other emerging treatments are investigational and have not yet received FDA approval for routine use in MG.

This article is for informational purposes only and is not a substitute for professional medical advice. Myasthenia gravis treatments should be discussed with a licensed healthcare provider. FDA-approved therapies such as anticholinesterase inhibitors and thymectomy are recognized treatments, but individual results may vary. Investigational therapies mentioned are not FDA-approved for routine care.

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Key Takeaways

• Myasthenia gravis (MG) is a chronic autoimmune disease that causes muscle weakness by disrupting communication between nerves and muscles.
• Common symptoms include muscle weakness, drooping eyelids, double vision, and difficulty swallowing, which often worsen with activity and improve with rest.
• The primary cause of MG is autoantibodies that attack acetylcholine receptors, blocking signals from nerves to muscles.
• Diagnosis involves a combination of tests, including blood tests for autoantibodies, electromyography (EMG), and imaging to check for thymomas.
• Treatment options include medications such as anticholinesterase inhibitors, immunosuppressants, and, in some cases, thymectomy (surgical removal of the thymus gland).
• Lifestyle modifications and supportive care such as physical therapy, energy conservation techniques, and participation in support groups can help patients manage symptoms.
• Recent research is advancing new therapies, including targeted immunotherapies and promising clinical trials for emerging treatments.

If you or someone you know is experiencing symptoms of myasthenia gravis, consult a healthcare provider for an accurate diagnosis and personalized treatment plan. Stay informed about new treatment options and research developments.