Myasthenia Gravis

Condition: Myasthenia Gravis

Brief Overview: Myasthenia gravis is a chronic autoimmune neuromuscular disorder that causes fluctuating weakness and easy fatigability of voluntary muscles. In MG, abnormal antibodies interfere with communication between nerves and muscles at the neuromuscular junction. The most commonly affected muscles are those controlling the eyes and eyelids, facial expression, chewing, swallowing, speech, neck movement, breathing, and movement of the arms and legs.

A key characteristic of MG is that weakness often worsens with repeated activity and improves with rest, although the pattern and severity vary considerably between patients. Some people have symptoms limited primarily to the eyes (ocular MG), while others develop generalized myasthenia gravis (gMG), affecting additional muscle groups.

Prevalence: According to UpToDate, “MG is a relatively uncommon disorder with an annual incidence of approximately 7 to 23 new cases per million. The prevalence is approximately 70 to 320 per million.”

Etiology: MG is most often an autoimmune disorder. The immune system produces antibodies that interfere with proteins involved in nerve-to-muscle signaling.

Risk Factors: There are no well-established lifestyle risk factors that patients can modify to prevent autoimmune MG.

Factors associated with MG include:

Increasing age.
Female sex in younger-onset MG.
Male sex becomes more prominent in later-onset MG.
Presence of other autoimmune disease.
Thymic abnormalities, including thymoma.
Certain cancer immunotherapies known as immune checkpoint inhibitors can rarely cause new MG or worsen pre-existing MG.

Commonly Associated Conditions:

Conditions that may coexist with MG include:

Thymoma.
Autoimmune thyroid disease.
Other autoimmune disorders.
Diabetes mellitus.
Hypertension.
Osteoporosis, particularly in patients receiving long-term corticosteroid therapy.
Chronic respiratory disease, which may complicate assessment of respiratory symptoms.
Dysphagia and aspiration risk.
Fall risk related to lower-extremity or axial weakness.

Common Medications:

Acetylcholinesterase inhibition – pyridostigmine
Chronic immunotherapies (glucocorticoids and nonsteroidal immunosuppressive and immunomodulatory agents)
- Prednisone, azathioprine, cyclosporine, tacrolimus
Antibody-based biologic therapy – efgartigimod alfa, rozanolixizumab, nipocalimab, eculizumab, ravulizumab, zilucoplan, rituximab, inebilizumab
Plasma exchange, IVIG

Common Labs, Imaging, and Tests:

Ice pack test
Pharmacologic testing – edrophonium test, failure of neuromuscular blockade reversal
Antibody testing: AChR antibody, MuSK antibody, LRP4 antibody
Electrodiagnostic studies: nerve conduction testing with repetitive nerve stimulation, electromyography (EMG), single-fiber EMG
MRI of the brain
CT or ultrasound of the orbits
Lumbar puncture for CSF analysis
Chest CT or MRI, CT/MRI of the mediastinum to evaluate for thymoma
Thyroid function studies

Common Treatments:

Medication (see above)
Plasma exchange
Thymectomy

Common Symptoms:

MG symptoms can vary during the day and from day to day.

Eye Symptoms

Drooping eyelid(s), or ptosis.
Double vision.
Difficulty keeping eyes open.

Facial, Speech, and Swallowing Symptoms

Facial weakness.
Reduced facial expression.
Difficulty smiling.
Slurred or nasal speech.
Voice becoming softer or weaker with prolonged talking.
Difficulty chewing, especially later during a meal.
Difficulty swallowing.
Choking or coughing while eating or drinking.
Difficulty managing saliva.

Neck and Limb Symptoms

Difficulty holding the head upright.
Arm weakness.
Difficulty raising arms overhead.
Difficulty washing or styling hair.
Difficulty carrying objects.
Leg weakness.
Difficulty rising from a chair.
Difficulty climbing stairs.
Difficulty walking longer distances.
Falls or near-falls.

Respiratory Symptoms

Shortness of breath.
Difficulty taking a deep breath.
Weak cough.
Increasing difficulty clearing secretions.
Breathing difficulty when lying down.

The combination of symptoms varies considerably between patients.

An Important Feature: Fatigable Weakness

One of the most characteristic patterns in MG is fatigability.

For example, a patient may initially:

Speak normally but develop slurred or weak speech during a long conversation.
Chew normally at the beginning of a meal but struggle toward the end.
Walk normally for a short distance but develop weakness with continued activity.
Hold their eyes open initially but develop increasing eyelid drooping later.

Rest may improve the weakness.

Neurology Symptom-Change Guidance

For any new neurologic symptom or change/worsening of an existing neurologic symptom, advise the patient or caregiver to contact the patient's neurologist to report the change.

Examples may include new or worsening:

Weakness.
Numbness or tingling.
Balance or walking difficulty.
Falls.
Tremor or other movement changes.
Vision changes.
Speech or swallowing difficulty.
Cognitive or behavioral changes.
Hallucinations.
Changes in level of alertness.
Pain or other symptoms related to the patient's neurologic condition.

If the reported symptoms meet criteria for urgent or emergency evaluation, do not delay care while waiting for the neurologist to respond. Follow organizational escalation protocols and direct the patient to the appropriate level of urgent or emergency care.

Care coordinators should not independently determine that a new or worsening neurologic symptom is an expected part of the patient's chronic condition.

If Patient Reports a New Symptom:

New or changed neurologic symptoms should be reported to the patient's neurologist. If symptoms warrant urgent or emergency evaluation, follow organizational escalation protocol rather than waiting for routine neurology follow-up.

Physical Findings:

Ptosis.
Diplopia with sustained gaze.
Facial weakness.
Weak eye closure.
Dysarthria.
Nasal speech.
Neck flexion or extension weakness.
Proximal arm or leg weakness.
Weakness that worsens with repeated muscle use.
Improvement following rest.
Reduced respiratory muscle strength during severe disease.
Sensation is generally normal in MG, which helps distinguish MG from many peripheral neuropathies.

Potential Complications and Contraindications:

Myasthenic Exacerbation

An exacerbation or flare means MG weakness has worsened but the patient does not yet require respiratory assistance.

Possible symptoms include:

Increasing limb weakness.
Worsening double vision or ptosis.
Increasing difficulty walking.
Falls.
Worsening speech.
Increasing chewing or swallowing difficulty.

Myasthenic Crisis

A myasthenic crisis is a life-threatening emergency in which respiratory muscles become too weak to maintain adequate breathing, potentially requiring noninvasive or invasive ventilatory support.

Respiratory weakness can occur with or without dramatic limb weakness. Pulse oximetry alone may not adequately reflect early neuromuscular respiratory failure.

Patients with new or worsening shortness of breath in the setting of MG require urgent assessment.

Other Potential Complications

Aspiration.
Aspiration pneumonia.
Falls and injuries.
Malnutrition or dehydration from significant chewing/swallowing impairment.
Medication adverse effects.
Infections related to immunosuppressive treatment.
Complications related to thymoma.
Functional decline or loss of independence.

⚠️ Medications That May Worsen MG

Certain medications have been associated with worsening MG. This does not mean every medication on this list is absolutely contraindicated. In some cases the medication is appropriate or necessary, and the decision must be made by the patient's healthcare provider.

Examples:

Antibiotics

Fluoroquinolones such as ciprofloxacin, levofloxacin, and moxifloxacin.
Macrolides such as azithromycin, clarithromycin, and erythromycin.
Aminoglycosides such as gentamicin, neomycin, and tobramycin.
Telithromycin should generally not be used in patients with MG and carries an FDA boxed warning related to MG.

Cardiovascular medications

Beta-blockers may worsen MG in some patients.
Procainamide may worsen MG.

Other medications/substances

IV magnesium can significantly worsen neuromuscular transmission.
Botulinum toxin should generally be avoided.
Quinine may worsen MG.
Hydroxychloroquine and chloroquine may worsen or precipitate MG.
Statins have occasionally been associated with worsening or precipitating MG.
Certain anesthetic/neuromuscular blocking medications require special consideration.
Immune checkpoint inhibitor cancer treatments can cause or worsen MG.

Care Coordinator Action: If a patient reports new or worsening MG symptoms after starting any new prescription, OTC medication, supplement, antibiotic, or infusion, document the timing and notify the appropriate clinical team. Do not instruct the patient to discontinue a prescribed medication independently.

General Health and Lifestyle Guidance:

Take medications exactly as prescribed.
Avoid skipping or delaying pyridostigmine or other scheduled MG treatment unless instructed by the treating clinician.
Keep regular neurology appointments.
Maintain an updated medication list.
Tell every healthcare professional, dentist, pharmacist, urgent-care provider, and hospital clinician about the MG diagnosis before medications or procedures are given.
Consider carrying an MG emergency information card.
Track changes in symptoms and function.
Balance activity with adequate rest.
Schedule more physically demanding tasks during times when strength is typically best.
Avoid becoming excessively fatigued.
Use prescribed mobility or assistive devices consistently.
Reduce fall hazards in the home.
Follow swallowing recommendations if dysphagia is present.
Notify the healthcare provider promptly of infections, fever, or worsening MG symptoms.
Maintain appropriate vaccinations according to the treating clinician's recommendations, especially when receiving immunomodulatory treatment.
Discuss planned surgery or anesthesia with the neurologist and surgical/anesthesia team in advance.
Avoid overheating when heat clearly worsens symptoms.
Maintain adequate hydration and nutrition.

Suggested Questions to Ask Patients:

MG Symptoms

Have you noticed any change in your muscle strength since our last call?
Are your symptoms improving, worsening, or staying about the same?
Do your symptoms become worse later in the day or after activity?
Do they improve after you rest?
Have you noticed increased drooping of your eyelids or double vision?
Has your speech become more slurred, nasal, or difficult to understand?
Have you noticed difficulty holding your head up?

Swallowing and Eating

Have you had any new or worsening difficulty chewing or swallowing?
Do you become tired while chewing toward the end of a meal?
Have you coughed or choked while eating or drinking?
Does food ever feel like it is getting stuck?
Have you had difficulty swallowing your medications?
Have you had any unexplained weight loss or difficulty eating enough?

Breathing

Have you had any new or increased shortness of breath?
Does it feel difficult to take a deep breath?
Are you more short of breath when lying flat?
Has your cough become weaker?
Are you having difficulty clearing mucus or secretions?

Mobility and Function

Are you having more difficulty standing up from a chair?
Are you having more trouble climbing stairs?
Are you having difficulty raising your arms, washing your hair, or reaching above your head?
Are you having difficulty walking your usual distance?
Have you fallen or almost fallen since our last call?
Are you using your prescribed cane, walker, or other assistive device?

Medications

Are you taking your MG medications exactly as prescribed?
Have you missed or delayed any doses?
Do you notice your symptoms getting worse before your next dose?
Have any of your medications recently been started, stopped, or changed?
Have you recently started an antibiotic?
Have you started any new over-the-counter medications, vitamins, minerals, or supplements?
Have you experienced diarrhea, excessive sweating, abdominal cramping, or muscle twitching after taking pyridostigmine?
Are you having difficulty obtaining or affording any of your medications?

Treatment and Follow-Up

When did you last see your neurologist?
When is your next appointment?
Have you had any recent IVIG, plasma exchange, infusion, or injection treatment?
Did your symptoms change after treatment?
Have you had any recent hospital or emergency-room visits related to MG?
Have you had any recent infections, fever, or illnesses?

Suggested Talking Points:

Explaining MG

"Myasthenia gravis affects the communication between your nerves and muscles. That's why your muscles may work normally at first but become weaker with repeated activity."

Discussing fatigue versus weakness

"With MG, we're particularly interested in changes in what your muscles are able to do—for example, whether you're having more trouble getting out of a chair, chewing through a meal, talking for a while, or keeping your eyes open."

Discussing breathing symptoms

"Because MG can sometimes affect the muscles used for breathing, new shortness of breath is something we take seriously. If you are having significant difficulty breathing, you should seek emergency care rather than waiting for your next appointment."

Discussing swallowing

"If you're coughing or choking when you eat or drink, or swallowing is becoming more difficult, your healthcare team needs to know because swallowing muscles can be affected by MG."

Medication safety

"Some medications used for other conditions can occasionally worsen MG, so it's important that every healthcare provider and pharmacist knows you have myasthenia gravis."

Medication adherence

"MG medications may have very specific timing. Take yours exactly as prescribed, and let your healthcare team know if you're noticing that your strength wears off before your next dose."

Symptom tracking

"MG symptoms can fluctuate, so keeping track of when you feel strongest and weakest can give your neurologist useful information about how well your treatment is working."

Suggested SMART Goal Examples

Medication Adherence:
"I will take my MG medications according to my prescribed schedule every day for the next 30 days and contact my healthcare team if I have difficulty following the schedule."
Symptom Tracking:
"I will record my muscle strength and MG symptoms at least 3 days per week for the next 4 weeks and bring my notes to my next neurology appointment."
Activity and Rest:
"I will schedule one rest period before my most physically demanding daily activity at least 5 days per week for the next 4 weeks."
Fall Prevention:
"I will remove loose rugs and clutter from my main walking areas within the next 7 days to reduce my risk of falling."
Assistive Device Use:
"I will use my prescribed walker every time I walk outside my home for the next 30 days."
Medication Safety:
"I will keep an updated medication list with my MG diagnosis and bring it to every healthcare appointment for the next 3 months."
Neurology Follow-Up:
"I will schedule and attend my recommended neurology follow-up appointment within the next ___ days."
Treatment Adherence:
"I will attend all scheduled MG infusions/injections during the next 30 days and notify my healthcare team promptly if I cannot attend."
Nutrition/Swallowing:
For a patient who already has provider-approved swallowing recommendations:
"I will follow the swallowing and meal strategies recommended by my healthcare team during every meal for the next 2 weeks."
Recognizing Worsening Symptoms:
"For the next 30 days, I will notify my healthcare team if I notice worsening difficulty walking, standing, chewing, swallowing, speaking, or holding my head up."
Emergency Preparedness:
"I will place an updated list of my medications, MG diagnosis, neurologist's contact information, and emergency information in an easily accessible location in my home by the end of this week."
Home Safety:
"I will add night-lights between my bedroom and bathroom within the next week to reduce my fall risk."

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⚠️ Medical Disclaimer

This resource is provided for educational and informational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. The information presented is general in nature and may not apply to every individual or health situation.

Individuals should consult their physician or other qualified healthcare professional for personalized medical advice, diagnosis, or treatment recommendations related to their specific health conditions and should not begin any new exercise program or change their diet or medications without consulting their healthcare professional.

Call 911 if you are experiencing a medical emergency.