Myasthenia Gravis

Contact Hours: 3

Author(s):

Joanna Grayson, BSN, RN

Course Highlights

  • In this Myasthenia Gravis course, we will learn about the pathophysiology, risk factors, and assessment for myasthenia gravis.
  • You’ll also learn the signs and symptoms, diagnostics, and treatment for myasthenia gravis.
  • You’ll leave this course with a broader understanding of the patient education and research findings for myasthenia gravis.

Introduction

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the skeletal muscle’s neuromuscular junction; however, it is considered a rare condition (8, 20, 26, 27, 28). The voluntary muscles affected are those that connect to the bones, including muscles in the face, diaphragm, and throat. The individual’s movement, breathing, swallowing, and facial movements are impacted. Infections, immunizations, medications, and surgeries are the catalysts for myasthenia gravis (16).

Myasthenia gravis has Latin and Greek origins, meaning “grave, or serious, muscle weakness” (18, 26, 27). It affects more than 70,000 individuals in the United States and is difficult to diagnose, with many patients going years without a correct diagnosis (22).

Before the 1930s, when acetylcholinesterase inhibitors were introduced, the prognosis for patients with myasthenia gravis was very grave since many became ill with pneumonia and ensuing respiratory failure within two years of diagnosis. Today, the mortality rate is low due to improved medications, thymectomy, and plasma exchange (PLEX) (1).

Although the mortality rate is very low today, the impact of myasthenia gravis is significant for patients and their families, and the nature of the disease’s fluctuating pattern of exacerbation and remission can prove overwhelming (8, 15). Additionally, comorbidities exist in 74% to 95% of patients that result in hospitalizations, and the emergent complication of myasthenia crisis also increases hospital stays (8).

Ask yourself...
  1. What area of the skeletal muscle does myasthenia gravis affect?
  2. What are the main causes of myasthenia gravis?
  3. What does the phrase “myasthenia gravis” mean and from which languages did it originate?
  4. What makes myasthenia gravis challenging for patients and their families?

Pathophysiology

Myasthenia gravis is an autoimmune disease that affects the neuromuscular junction, the chemical synapse between muscle fiber and motor neurons (7, 10, 18, 28).  Autoantibodies form against the postsynaptic membrane proteins that reduce the electrical impulses across the neuromuscular junction. The neurotransmitter acetylcholine is blocked or disrupted by these antibodies. Antibodies can also form against muscle-specific kinase (MuSK) proteins, nicotinic acetylcholine receptors (n-AChR), and lipoprotein-related protein 4 (LPR4), which can impair neuromuscular junction transmissions (8, 19, 20, 25, 26, 27, 28).

In n-AChR myasthenia gravis, the IgG1 and IgG3 antibodies are present; in MuSK and LPR4 myasthenia gravis subgroups, the IgG4 antibody is present (12, 28). In the n-AChR myasthenia gravis, the muscles experience extreme atrophy, and in the MuSK myasthenia gravis, the mitochondrial abnormalities supersede the muscular atrophic changes (28). The resulting muscle weakness affects the eye, throat, and extremity muscles, and it is most prevalent in the afternoons.

The thymus gland is associated with myasthenia gravis because it controls immune function by producing T-lymphocytes. The thymus gland grows during childhood but starts to shrink during puberty, when it is finally replaced by fat in adulthood. Adults with myasthenia gravis have an enlarged thymus gland post-puberty and often develop thymomas (thymus gland tumors) (25). The disrupted thymus gland negatively impacts the development of immune cells, causing the production of acetylcholine antibodies. Thymomas are generally benign, but they can become cancerous (25).

The most concerning complication of myasthenia gravis is myasthenia crisis. Myasthenia crisis can be caused by infection, stress, surgery, or adverse reaction to medication that impairs the individual’s breathing, resulting in the emergent need for assisted ventilation (25). Myasthenia crisis occurs in 15% to 20% of individuals with myasthenia gravis (19, 20, 25, 26, 27).

Ask yourself...
  1. What is the neuromuscular junction, and where is it located?
  2. Which antibodies are most involved in myasthenia gravis?
  3. How do the n-AChR and MuSK subtypes of myasthenia gravis differ?
  4. What are thymomas, and why are they of concern to patients with myasthenia gravis?

Risk Factors

Myasthenia gravis affects women and men of all ethnocultural backgrounds, but it has a higher incidence in women under age 40 and men over age 60 (18, 19, 20, 21, 25). In the United States, it has a prevalence of 10 to 20 per 100,000 (14, 16, 19, 20, 28). Myasthenia gravis has an annual incidence of eight to 10 cases per one million persons; the prevalence is 150 to 250 cases per one million persons (6,9).

Precipitating factors of myasthenia gravis include infection, surgery, immunization, heat, pregnancy, emotional stress, medications, and declining health associated with chronic illness (28). Aminoglycosides, fluoroquinolones, beta-blockers, and neuromuscular blocking agents are medications that can be catalysts for myasthenia gravis (28).

First-degree family members of patients with myasthenia gravis have a higher risk for the disease as well as other autoimmune diseases (17, 18). Family members of individuals with myasthenia gravis are 1,000 times more likely to have the disease than the general population (17). Males are more prone to ocular myasthenia gravis than females (18). The MuSK subtype of myasthenia gravis is more prevalent in females, with the onset age being 36 to 38 (18). African Americans and Asians are at higher risk for the disease, particularly the MuSK subtype (9, 18).

Neonatal myasthenia can occur in infants who acquire antibodies from the mother, but the infant’s symptoms typically resolve within two to three months after birth (25). Congenital myasthenia is sometimes seen in children of healthy parents when mutations in the genes of the neuromuscular junction appear and cause myasthenia gravis symptoms (25). Childhood myasthenia gravis is prevalent in Asian countries, with an occurrence rate of 50% in patients aged 15 years and younger, and only occurs in 10% to 15% of the diagnosed cases in North America (20, 28). Extraocular muscle weakness is the primary symptom in this population (28).

Myasthenia gravis is classified into subgroups with different prognostic values based on how each group responds to treatment (28).

The classifications of myasthenia gravis are (6, 9, 17, 28): 
  • Early-onset: Onset age is less than 50 years with thymic hyperplasia
  • Late-onset: Onset age is greater than 50 years with thymic atrophy
  • Thymoma-associated
  • Anti-MuSK antibodies
  • Ocular: The Periocular muscles are the only muscles affected
  • No detectable AChR and MuSK antibodies
The Myasthenia Gravis Foundation of America classifies the disease in this manner (28): 
  • Class I: Any ocular muscle weakness, including weakness of eye closure. All other muscle groups are normal.
  • Class II: Mild weakness of muscles other than ocular muscles. Ocular muscle weakness of any severity may be present.
  • Class IIa: Predominant weakness of the limb, axial muscles, or both. It may also involve the oropharyngeal muscles to a lesser extent.
  • Class IIb: Mostly oropharyngeal, respiratory muscles, or both. It can involve limb, axial muscles, or both to a lesser extent.
  • Class III: Muscles other than ocular muscles moderately. Ocular muscle weakness of any severity can be present.
  • Class IIIa: Limb, axial muscles, or both predominantly. Oropharyngeal muscles can be involved to a lesser degree.
  • Class IIIb: Oropharyngeal, respiratory muscles, or both predominantly. The limb, axial muscles, or both can have lesser or equal involvement.
  • Class IV: Severe weakness of affected muscles. Ocular muscle weakness of any severity can be present.
  • Class IVa: Limb, axial muscles, or both predominantly. Oropharyngeal muscles can be involved to a lesser degree.
  • Class IVb: Oropharyngeal, respiratory muscles, or both predominantly. The limb, axial muscles, or both can have lesser or equal involvement. It also includes patients requiring feeding tubes without intubation.
  • Class V: Intubation with or without mechanical ventilation, except when employed during routine postoperative management.
Ask yourself...
  1. Myasthenia gravis affects which populations the most?
  2. Which medications can precipitate myasthenia gravis?
  3. How does neonatal myasthenia gravis occur?
  4. What are the classifications of myasthenia gravis as outlined by the Myasthenia Gravis Foundation of America?

Assessment

A thorough patient history is paramount to classifying myasthenia gravis and guiding treatment. Most patients (85%) present with ocular symptoms, followed by weakness and fatigue (6, 18).

Nurses should ask patients the following questions (28): 
  1. When did your symptoms begin?
  2. What time of day do the symptoms occur?
  3. What time of day do you feel most comfortable/physically active?
  4. Which activities make the symptoms worse? Better?
  5. Do you become fatigued by climbing stairs, walking across parking lots, etc.?
  6. Do you experience slowness in writing or typing? Do you experience frequent errors in these actions?
  7. Do you experience swallowing or chewing difficulties? When do these occur? What makes swallowing or chewing easier/more difficult?
  8. Do you have pain when swallowing or chewing?
  9. Do you cough frequently? Do you cough after swallowing or when chewing food?
  10. Do you choke when eating?
  11. Does it take you a while to finish eating?
  12. Do you experience hoarseness or pain when speaking?
  13. Does your neck tend to droop? Is it difficult to hold up your head?
  14. Do you see double or have blurry vision? Do your eyes droop?
  15. Have you ever experienced difficulty breathing or had a breathing emergency?
  16. Which modalities most effectively improve symptoms (rest, medication, ice, gentle movement, etc.)?

Pupils, sensory reactions, and deep tendon reflexes should yield normal findings in patients with myasthenia gravis (18, 28). These patients typically do not have pain or changes in mental status or cognition (18).

Several assessment tools can aid the nurse in developing the patient’s care plan, including (2, 11):

  • EQ-5D-5L measures patients’ general health-related quality of life. It uses a visual analog scale and descriptive system with five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
  • EQ-5D-5L Bolt-On Items. This utilizes the EQ-5D-5L tool but adds single-question questions about myasthenia gravis-related symptoms involving vision, respiratory function, fatigue, sleep/rest, social relationships, and self-confidence.
  • Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale. This scale uses myasthenia gravis-specific questions to assess speech, chewing, swallowing, respiratory function, ptosis, diplopia, and physical activities like brushing teeth, combing hair, and rising from a chair.
  • Myasthenia Gravis Quality of Life 15-Item Revised (MG-QOL15r) Scale. Self-care, social life, role, physical health, and emotions are evaluated utilizing this scale.
  • Hospital Anxiety and Depression Scale (HADS). This measures psychological distress in non-psychiatric patients with an emphasis on anxiety and depression.
  • Health Utilities Index III (HUI3). This tool assesses vision, hearing, speech, ambulation, mobility, pain, dexterity, emotion, and cognition.

Additional instruments include the Patient-Reported Outcomes Measurement Information System (PROMIS) Dyspnoea Characteristics, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and COVID-19 Survey (2).

Patients with myasthenia gravis experience anxiety, depression, and post-traumatic stress disorder (PTSD) at rates of 14% to almost 60% (15). These conditions impact the patient’s health-related quality of life and contribute to caregiver role strain, necessitating the nurse to assess patients for mental health challenges (15) thoroughly.

Ask yourself...
  1. With which type of symptoms do most patients with myasthenia gravis present?
  2. Which assessment questions should nurses ask patients about their myasthenia gravis symptoms?
  3. Which normal findings should the nurse expect in patients with myasthenia gravis?
  4. Which pain and cognitive symptoms should the nurse expect in patients with myasthenia gravis?

Signs and Symptoms

The onset of myasthenia gravis can be sudden, and the symptoms are not easily recognizable (25, 26, 27). The degree of muscle weakness varies among patients but worsens with physical activity and improves with rest (28). Symptoms can fluctuate daily, weekly, or monthly, thus leading to frustration for patients and their families (21). MuSK myasthenia gravis is more common in females and typically involves the bulbar, facial, and neck muscles while sparing the extraocular muscles (28).

Common signs and symptoms include (17, 21, 25, 26, 27, 28): 
  • Ptosis
  • Diplopia
  • Dyspnea
  • Dysphagia
  • Dysarthria
  • Ocular myasthenia
  • Facial expression changes
  • Muscle weakness (extremities, neck)

Myasthenia gravis doesn’t create autonomic symptoms like cardiac palpitations or bladder and bowel disturbances since it only affects the nicotinic cholinergic receptors (28). However, roughly 85% of patients initially present with extraocular muscle weakness that manifests as diplopia or ptosis, or both. Within two years, these symptoms can progress in 50% of patients, causing myasthenia gravis of the bulbar, axial, and limb muscles (14). In 15% of patients, the initial presentation includes difficulty swallowing and chewing, frequent choking, dysphagia, dysarthria, and hoarseness. A flat, expressionless affect and dropped-head syndrome can result (28).

Extremity muscle weakness tends to occur mainly in the upper limbs and proximal muscles versus the lower limbs and distal muscles. Myasthenic crisis involves the intercostal muscles and diaphragm, making it a medical emergency (28).

Ask yourself...
  1. What improves myasthenia gravis symptoms in patients?
  2. What are the common signs and symptoms of myasthenia gravis?
  3. Which symptoms should the nurse anticipate in patients with extraocular muscle weakness?
  4. Which muscles are involved in myasthenia crisis?

Diagnostics and Treatment

Myasthenia gravis requires a therapeutic approach focused on symptom management and minimizing adverse effects (29). The condition is diagnosed via physical and neurological examination, during which the individual’s coordination, sense of touch, eye movements, muscle strength, and tone are tested (25). Blood tests may reveal elevated levels of acetylcholine receptor antibodies and anti-MuSK antibodies. Incidents occur when acetylcholine receptors and MuSK antibodies are absent, resulting in seronegative myasthenia (25).

The first-line antibody diagnostics include anti-AChR, anti-MuSK, and anti-LRP4. More than 90% of patients have anti-AChR antibodies (18). In patients who are seronegative for anti-AChR antibodies, up to 37% possess anti-MuSK antibodies. However, the sensitivity of anti-AChR antibodies is about 50% in those with purely ocular myasthenia gravis. In patients with purely ocular myasthenia gravis, anti-MuSK antibodies rarely occur. Three percent to 50% of the remaining patients with generalized myasthenia gravis who are seronegative to anti-AChR and anti-MuSK antibodies have anti-LRP4 antibodies (7).

Anti-striated muscle antibodies are a functional determinant in thymoma in non-elderly patients, but this test should not be used alone to diagnose myasthenia gravis (18).

Repetitive nerve stimulation (RNS) uses small pulses of electricity to test muscle responses, and single fiber electromyography (SFEMG) is used to detect impaired nerve-muscle transmission. RNS has a sensitivity range of 30% to 80% for generalized myasthenia gravis; its sensitivity is 10% to 30% in ocular myasthenia gravis (18). Single-fiber electromyography is the most sensitive test for myasthenia gravis, especially in patients with mild muscle weakness or whose weakness is confined to just a few muscles, making diagnosis difficult (18, 25). SFEMG’s sensitivity is 75% to 98% in generalized myasthenia gravis and 62% to 99% in ocular myasthenia gravis (18). Additionally, electrophysiologic tests help diagnose seronegative patients (28).

The edrophonium tensilon test detects ocular myasthenia gravis since electrophysiologic testing cannot be performed in these patients. When edrophonium testing is contraindicated, an ice-pack test to the eyes for two to five minutes can help assess ptosis improvement. Still, it is ineffective in determining extraocular muscle involvement (28). Chest magnetic resonance imaging (MRI) and computed tomography (CT) help diagnose thymoma. Pulmonary function testing can predict respiratory resiliency in myasthenic crises (26, 27).

Although no cure for myasthenia gravis exists, most individuals live to average life expectancy due to effective medication treatment (1, 25, 28). Anticholinesterase medications, such as mestinon and pyridostigmine bromide, decrease the breakdown of acetylcholine to improve neuromuscular transmission and thus increase muscle strength (1, 25, 28). Pyridostigmine bromide is preferred over neostigmine due to its longer duration of action (28). Ambenonium chloride is prescribed for patients who experience gastrointestinal intolerance of bromides (28).

Eculizumab is U.S. Food and Drug Administration (FDA) approved in adults who have the anti-acetylcholine receptor (AchR) antibody since it inhibits a complement protein that causes neuromuscular junction damage (25, 28). However, the Centers for Disease Control (CDC) warns that complement inhibitors like eculizumab can cause an increased risk of meningococcal disease two thousand times in immunocompromised patients who receive the medication (3, 4). The CDC recommends that patients taking complement inhibitors receive regular meningococcal vaccinations, including booster shots. It also states that patients receiving a complement inhibitor can still get meningococcal disease even if they are taking antibiotics and have been vaccinated (3, 4).

Immunosuppressants like prednisone, prednisolone, methylprednisolone, azathioprine, cyclosporine, methotrexate, mycophenolate, cyclophosphamide, and tacrolimus suppress abnormal antibodies and improve muscle strength (1, 25, 28, 29). These are used in individuals who continue to experience symptoms after pyridostigmine treatment (28). However, some physicians treat with immunosuppressants aggressively at the outset of myasthenia gravis diagnosis and then ease back (18). Patients taking immunosuppressants should be closely monitored for signs of infection.

Beta-adrenergic agonists, like terbutaline and salbutamol, help relieve fatigue and are used in patients who cannot tolerate cholinesterase inhibitors or experience decreased effectiveness over time (1).

Intravenous immunoglobulin reduces antibodies that inhibit neuromuscular activity. Plasmapheresis, or plasma exchange, can remove harmful antibodies from plasma. Both modalities are implemented in severe cases of myasthenia gravis and the perioperative period to stabilize surgical patients, but they are only effective for a few weeks or months (1, 24, 25, 28).

Despite the varied medication treatments for myasthenia gravis, some physicians feel that standard therapies are ineffective in up to 15% of patients (13). These physicians feel that the emergence of molecular therapies, including monoclonal antibodies, B-cell-depleting agents, and chimeric antigen receptor T cell-based therapies, will lead to the next generation of medication therapies for patients with myasthenia gravis (13).

A thymectomy may be performed to remove the thymus gland, which can rebalance the immune system and decrease symptoms—roughly 50% of patients who undergo a thymectomy experience long-term remission (25).

Conditions that are often associated with myasthenia gravis include Lambert-Eaton syndrome, cavernous sinus thrombosis, brainstem glioma, multiple sclerosis, botulism, tick-borne disease, polymyositis/dermatomyositis, and Graves ophthalmopathy (28). Recent research indicates that myasthenia gravis is also linked to Epstein-Barr syndrome (EBS), parvovirus, and herpes simplex virus (HSV) infections (12). Since myasthenia gravis often coexists with other autoimmune disorders, anti-nuclear antibody (ANA), rheumatoid factor, and thyroid function tests are encouraged (28).

Ask yourself...
  1. What is seronegative myasthenia gravis?
  2. Which diagnostic test is most accurate for patients who have mild muscle weakness?
  3. Which medication is prescribed to patients who experience gastro-intolerance of bromides?
  4. What are the benefits of thymectomy?

Complications and Long-Term Effects

Myasthenia gravis is best managed by a healthcare team that includes primary care physicians, neurologists, nurses, pharmacists, physical and occupational therapists, and mental health providers. Due to current treatment modalities, most patients with myasthenia gravis live a normal life span (28).

Myasthenia crisis is an acute respiratory paralysis that requires ventilated breathing assistance in an intensive care environment (28). It is typically precipitated by infection, stress, or acute illness. Long-term medication use can lead to opportunistic infections, such as tuberculosis, pneumonia, and fungal infections, as well as lymphoproliferative malignancies. Steroids can cause osteoporosis, hyperglycemia, cataracts, weight gain, hypertension, and avascular necrosis of the hip (28). It is important to note that the mortality rate for myasthenia gravis in myasthenia crisis has dropped significantly in the past fifty years from 50% to 80% to only 4.5% (28). Death occurs from the adverse effects of medications and aspiration pneumonia resulting from muscle weakness.

Cholinergic crisis due to excessive acetylcholine found at the nicotinic and muscarinic receptors occurs from cholinesterase inhibitor therapy. Symptoms of cholinergic crisis include muscular weakness, cramps, fasciculation, paralysis, lacrimation, increased salivation, diarrhea, and blurry vision (28). Ten percent of patients with myasthenia gravis develop thymoma (28).

Several medications have been linked with causing complications in patients with myasthenia gravis. These include (21, 24): 
  • Telithromycin: The FDA has issued a black box warning for this drug in myasthenia gravis and advises against its use.
  • Fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin): The FDA has issued a black box warning for this drug in myasthenia gravis and advises using cautiously, if at all.
  • Botulinum toxin: Should be avoided.
  • D-penicillamine: Should be avoided.
  • Chloroquine: Should be used with caution.
  • Hydroxychloroquine: Should be used with caution.
  • Quinine: Should only be used in malaria in the United States.
  • Magnesium: Should only be used if necessary.
  • Macrolide antibiotics: Should be used with caution, if at all.
  • Aminoglycoside antibiotics: Should be used with caution if no other option is available.
  • Procainamide: Should be used with caution.
  • Desferrioxamine: Should be used with caution.
  • Beta-blockers: Should be used with caution.
  • Statins: Should be used with caution and at the lowest dose needed.
  • Iodinated radiologic contrast agents: Should be used cautiously.
  • Checkpoint inhibitors: Should be used with caution.

The risk of myasthenia gravis relapse is decreased in patients younger than 40 and in those who are prescribed prednisolone and undergo early thymectomy. Relapse is higher in patients with concomitant autoimmune disease (28). Remission occurs in roughly 20% of patients, with the average remission duration lasting five years (19, 20). Some patients have experienced remission for twenty years or longer (19, 20).

Ask yourself...
  1. Which factors precipitate myasthenia crisis?
  2. What causes cholinergic crisis?
  3. Myasthenia gravis relapse is decreased in which patients?
  4. What is the average patient remission duration in myasthenia gravis?

Patient Education

The nurse should teach the patient the pathophysiology of myasthenia gravis, precipitating factors, treatment modalities, medication interactions, and long-term complications, including the risk of relapse. Medication compliance is a major factor in the patient maintaining optimal health (28).

Regular gentle exercise is helpful in improving physical function and emotional mood in patients with myasthenia gravis (25). Activities such as yoga, tai chi, and balance training are effective (18).

When the individual’s physical mobility and activities of daily living are affected, assistive devices can help increase independence (21, 25). Encouraging a nutritious soft diet and breathing exercises during flare-ups can prevent serious complications. Removing fall hazards from the home and wearing a medical bracelet are recommended (21, 28).

Patients should also be taught that pregnancy, emotional stress, and surgery can worsen myasthenia gravis symptoms (18).

Nurses should teach patients the following safety measures (21):

  • Avoid overheating the home since this can exacerbate symptoms.
  • Always wear comfortable and supportive footwear.
  • Have vision checked annually.
  • Install handrails in the bathroom and other rooms as necessary.
  • Ensure the interior and exterior of the home are properly lit.
  • Program emergency phone numbers into telephones.

Regular handwashing, smoking cessation, and vaccinations can prevent infections that can trigger a myasthenic attack (28). Excessive exertion and fatigue, emotional stress, and worsening the symptoms of other chronic medical conditions should also be avoided.

If the patient is prescribed pyridostigmine, the nurse should teach the patient that the onset is 30 to 60 minutes and lasts three to six hours. The drug should be taken 30 minutes before meals if the patient is experiencing dysphagia. The typical starting dose is 60 milligrams every six hours during the daytime. The medication can be titrated up to 240 to 360 milligrams daily, but side effects increase at higher doses, and increased weakness can be a side effect. The sustained-release formula of pyridostigmine, Mestinon Timespan 180 milligrams, can be administered at bedtime in those patients who experience weakness upon awakening (1).

The most common side effects of pyridostigmine are abdominal cramping, loose stool, flatulence, bradycardia, bronchospasm, hidrosis, excessive lacrimation, and muscle twitching. Glycopyrrolate or hyoscyamine can be taken with pyridostigmine to manage the side effects (1, 18).

Ask yourself...
  1. Which physical activities are beneficial for patients with myasthenia gravis?
  2. Which patient conditions can worsen myasthenia gravis symptoms?
  3. Which safety measures should nurses teach patients with myasthenia gravis?
  4. Which steps should patients with myasthenia gravis take to decrease the risk of infection?

Research Findings

The National Institutes of Health (NIH) Myasthenia Gravis Rare Disease Clinical Research Network (MGNet) and Exploring Outcomes and Characteristics of Myasthenia Gravis 2 (EXPLORE MG-2) collect biospecimens and clinical data from people with myasthenia gravis to enhance clinical trials and find a cure for the disease (25). The NIH is currently encouraging patients with myasthenia gravis to participate in their research efforts via the NIH Clinical Research Trials and You program (25).

Conquer MG is an organization that supports small academic pilot studies, and it lists ongoing clinical trials on its website (5). Many of these trials involve new medications and are sponsored by pharmaceutical companies. It also supports research of Decartes-08 CAR-T Cells, a magnetic levator prosthesis that helps improve ocular symptoms (5).

A study by the National Institute of Neurological Disorders and Stroke (NINDS) found that in 126 patients with myasthenia gravis and no visible thymoma, thymectomy reduced muscle weakness and the need for immunosuppressive drugs (26, 27).

Immune checkpoint inhibitors (ICI) are used in cancer treatment, but they have been found to cause myasthenia gravis in patients (21). Patients who had myasthenia gravis before starting ICIs have reported a worsening of symptoms, and patients who did not have a diagnosis of myasthenia gravis before taking ICI therapy have developed the disease. Patients have reported the onset of myasthenia gravis symptoms within six weeks of starting ICIs. ICIs include pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentriq), avelumab (Bavencio), durvalumab (Imfinzi), and ipilimumab (Yervoy) (21).

In one research study that examined myasthenia gravis and comorbidities, hypertension, neurological disease, autoimmune disease, thyroid disorders, heart disease, osteoporosis, gastrointestinal disorders, psychiatric disorders, and diabetes were found to affect 15% to 20% of patients with myasthenia gravis (8). The most prevalent autoimmune diseases linked to myasthenia gravis were thyroid disorders, systemic lupus erythematosus, and rheumatoid arthritis (8). The most prevalent non-autoimmune disorders linked to myasthenia gravis were hypertension, neuropathy, and chronic obstructive pulmonary disease (COPD) (8).

In another study that examined the immunosuppressant medications used to treat myasthenia gravis, azathioprine was found to have more serious side effects than mycophenolate mofetil. It was also deemed effective in the treatment of myasthenia gravis in low doses (24, 29, 30). However, mycophenolate mofetil was found to pose a risk of teratogenicity (24, 30).

New advances in surgical techniques, such as video-assisted thoracoscopic surgery (VATS) thymectomy and robot-assisted thoracoscopic surgery (RATS) thymectomy, provide superior surgical visualization and precise manipulation that improve surgical outcomes in patients with myasthenia gravis (17, 24).

Ask yourself...
  1. What is the purpose of The National Institutes of Health (NIH) Myasthenia Gravis Rare Disease Clinical Research Network (MGNet) and Exploring Outcomes and Characteristics of Myasthenia Gravis 2 (EXPLORE MG-2) program?
  2. Which treatment for myasthenia gravis has the National Institute of Neurological Disorders and Stroke (NINDS) found to be effective?
  3. Which cancer treatment medications have been found to cause symptoms of myasthenia gravis?
  4. Which comorbidities are associated with myasthenia gravis?

Case Study

T.S. is a 35-year-old African American female who presents to the family medicine nurse practitioner with symptoms of fatigue, diplopia, and dysphagia. The patient has a history of post-traumatic stress disorder (PTSD) secondary to being a veteran soldier of the War in Afghanistan and a history of exercise-induced asthma (EIA). T.S. takes sertraline (Zoloft) 50 milligrams a day for the anxiety and depression associated with PTSD and formoterol as needed for exercise-induced asthma. T.S. tells the nurse practitioner that lately, she has been too fatigued to maintain her daily exercise routine and, therefore, has not been using the formoterol.

T.S. works full-time as a self-employed military consultant, which requires her to travel, but she works from home when she is not traveling. The patient tells the nurse that she has difficulty reading and working on the computer due to the diplopia and has choked several times when eating meals, which has resulted in acute coughing fits.

Both patient’s parents are alive, as are her maternal and paternal aunts and uncles. Her paternal uncle was diagnosed with myasthenia gravis at age 62. T.S. is single, lives alone, and does not have children or pets. She does not use tobacco products or recreational drugs, and drinks alcohol one to two times a month when socializing with friends.

Upon assessment, T.S. is alert, oriented, conversational, and portrays a pleasant demeanor. She displays some hoarseness of speech and slight ptosis of the right eye. Vitals are blood pressure 132/68 mmHg, pulse 64 beats per minute, respiratory rate 20 breaths per minute, and temperature 98.7 degrees Fahrenheit.

The patient does not express pain when the lower and upper extremities are put through range of motion (ROM). Further assessment reveals fair bilateral arm and handgrip strength, good bilateral lower extremity strength, and fair neck strength. The Myasthenia Gravis Quality of Life assessment tool reveals a cumulative score of 35/60.

Lab results indicate anti-MuSK antibodies, and single-fiber electromyography (SFEMG) reveals impaired nerve-muscle transmission. T.S. is started on pyridostigmine bromide therapy and is advised of the potential side effects.

The nurse practitioner teaches T.S. not to overheat her home, to ensure her home environment is not conducive to the risk of falls, and to practice meticulous handwashing techniques. The nurse practitioner also advises T.S. of statistics regarding relapse, how to prevent the occurrence, and the signs and symptoms of a myasthenic crisis. T.S. should wear a medical alert bracelet and program emergency phone numbers into her home and cellphone.

Ask yourself...
  1. How does T.S.’s ethnocultural background contribute to her diagnosis of myasthenia gravis?
  2. Which component of T.S.’s family history impacts her myasthenia gravis diagnosis?
  3. How do T.S.’s diagnoses of PTSD and exercise-induced asthma contribute to her diagnosis of myasthenia gravis?
  4. Which of T.S.’s symptoms indicate a potential diagnosis of myasthenia gravis?
  5. Which of T.S.’s assessment findings indicate a potential diagnosis of myasthenia gravis?
  6. Why does the nurse practitioner use SFEMG versus repetitive nerve stimulation (RNS) in diagnosing T.S.?
  7. Which potential side effects of pyridostigmine bromide should the nurse practitioner teach T.S.?
  8. Why does the nurse practitioner teach T.S. not to overheat her home?
  9. Why does the nurse practitioner advise T.S. to practice meticulous handwashing techniques?
  10. Why does the nurse practitioner advise T.S. to wear a medical alert bracelet?

Conclusion

Myasthenia gravis was once thought to have a poor prognosis for patients. Still, today, early diagnosis and effective medication and surgical treatments have reduced the severe impairment previously associated with the disease. Nurses can improve outcomes for these patients by conducting a thorough assessment that includes mental health questions, providing teaching that reinforces patient safety, and monitoring the effectiveness of medication and surgical interventions.

Ask yourself...
  1. In what percentage of patients with myasthenia gravis do comorbidities exist?
  2. How do antibodies cause myasthenia gravis?
  3. Which IgG antibodies are involved in myasthenia gravis?
  4. When is muscle weakness most prevalent in myasthenia gravis patients?
  5. Which gland is associated with myasthenia gravis? What role does it play in the disease?
  6. What is the most concerning complication of myasthenia gravis?
  7. In what percentage of patients with myasthenia gravis does myasthenia crisis occur?
  8. What is the prevalence of myasthenia gravis in the United States?
  9. Which patient conditions are risk factors for myasthenia gravis?
  10. Which gender is more prone to ocular myasthenia gravis?
  11. Which ethnic populations are most affected by MuSK subtype of myasthenia gravis?
  12. How long does it take for neonatal myasthenia gravis to resolve?
  13. Which populations are most affected by childhood myasthenia gravis?
  14. What are the assessment tools that aid nurses in developing care plans for patients with myasthenia gravis?
  15. What percentage of patients with myasthenia gravis experience mental health challenges, such as anxiety and depression?
  16. What is the primary symptom in childhood myasthenia gravis?
  17. How often do myasthenia gravis symptoms fluctuate?
  18. Which subtype of myasthenia gravis is more common in females and which area of the body does it affect?
  19. Which type of symptoms does myasthenia gravis not precipitate?
  20. In what timeframe can the ocular symptoms of myasthenia gravis progress?
  21. Where does extremity muscle weakness occur in patients with myasthenia gravis?
  22. What are the first-line antibody diagnostics in myasthenia gravis?
  23. For what condition is anti-striated muscle antibodies diagnostic?
  24. What is the difference between repetitive nerve stimulation and single fiber electromyography?
  25. When is edrophonium tensilon testing used?
  26. Which diagnostic test detects improvement in ptosis?
  27. Which two diagnostic tests assist in diagnosing thymoma?
  28. What does pulmonary function testing predict in myasthenic crisis?
  29. Which medications decrease the breakdown of acetylcholine to improve neuromuscular transmission and thus increase muscle strength?
  30. Why is pyridostigmine bromide is preferred in lieu of neostigmine?
  31. What is the pharmacological function of eculizumab?
  32. Which complication can complement inhibitors cause in patients with myasthenia gravis?
  33. For which condition should patients taking immunosuppressants be monitored?
  34. Which treatments are given to surgical patients with myasthenia gravis?
  35. Which conditions are often associated with myasthenia gravis?
  36. Which type of diagnostic tests are encouraged in patients with myasthenia gravis and concomitant disorders?
  37. What are the risk factors of long-term medication use in myasthenia crisis?
  38. What health complications can long-term steroid use cause?
  39. What are the symptoms of cholinergic crisis?
  40. Which medications cause complications in patients with myasthenia gravis?
  41. Which patients with myasthenia gravis are more likely to experience relapse?
  42. Which teaching should the nurse provide to the patient who is prescribed pyridostigmine therapy?
  43. To which daily dose can pyridostigmine be titrated?
  44. What are the side effects of pyridostigmine?
  45. Which medications can be used to decrease the side effects of pyridostigmine?
  46. Which non-autoimmune disorders are linked to myasthenia gravis?
  47. What are the research findings surrounding azathioprine and mycophenolate mofetil?
  48. Which new surgical techniques are improving outcomes for patients who undergo thymectomy?
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