Myasthenia Gravis

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder that causes weakness in the skeletal muscles. The hallmark of the disease is muscle weakness that worsens with activity and improves with rest. Affecting about 20 per 100,000 people, MG occurs when the immune system mistakenly attacks the communication between nerves and muscles. With proper treatment, most people with MG can lead normal or nearly normal lives.

🚨 Myasthenic Crisis Emergency

CALL 911 IMMEDIATELY for: severe breathing difficulty, inability to swallow saliva, rapid worsening of weakness, choking, or respiratory distress. Myasthenic crisis requires immediate intubation and intensive care. Tell responders about MG diagnosis - certain medications can worsen the condition!

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Myasthenia Gravis

MG is caused by a breakdown in communication between nerves and muscles at the neuromuscular junction. The immune system produces antibodies that block or destroy acetylcholine receptors, preventing muscle contraction signals from reaching the muscles effectively.

The Neuromuscular Junction

  • Nerve endings release acetylcholine (ACh)
  • ACh binds to receptors on muscle cells
  • This binding triggers muscle contraction
  • In MG, antibodies interfere with this process
  • Fewer functional receptors = weaker contractions

Types of Myasthenia Gravis

  • Ocular MG (15-20%):
    • Weakness limited to eye muscles
    • Ptosis and diplopia only
    • May progress to generalized MG
  • Generalized MG (80-85%):
    • Affects multiple muscle groups
    • Eye, facial, limb, respiratory muscles
    • Variable severity
  • Antibody subtypes:
    • AChR-positive (85%)
    • MuSK-positive (5-8%)
    • LRP4-positive (1-2%)
    • Seronegative (5-10%)

Demographics

  • Bimodal age distribution:
    • Women: Peak at 20-30 years
    • Men: Peak at 60-70 years
  • Overall female:male ratio 3:2
  • Can occur at any age
  • Rare in children (10-15% of cases)

Signs and Symptoms

Cardinal Feature

Fluctuating weakness: Muscle weakness that worsens with repeated use (fatigability) and improves with rest. Symptoms often worse later in the day.

Ocular Symptoms (90% have at onset)

  • Ptosis (drooping eyelids):
    • Often asymmetric
    • May alternate between eyes
    • Worsens with upward gaze
  • Diplopia (double vision):
    • Horizontal or vertical
    • Variable throughout day
    • Improves with one eye closed

Bulbar Symptoms

  • Dysarthria:
    • Slurred or nasal speech
    • Voice fades with talking
    • Difficulty with certain consonants
  • Dysphagia:
    • Difficulty swallowing
    • Choking on liquids
    • Nasal regurgitation
  • Facial weakness:
    • Difficulty smiling
    • "Myasthenic snarl"
    • Difficulty closing mouth

Limb and Axial Weakness

  • Proximal > distal weakness:
    • Difficulty climbing stairs
    • Problems lifting arms overhead
    • Getting up from chair
  • Neck weakness:
    • Head drop
    • Difficulty holding head up
  • Fine motor problems:
    • Difficulty with buttons
    • Dropping objects
    • Handwriting deterioration

Respiratory Symptoms

  • Shortness of breath
  • Orthopnea (difficulty breathing lying flat)
  • Weak cough
  • Morning headaches (CO2 retention)
  • May be subtle until crisis

Symptom Patterns

  • Fluctuation: Hour to hour, day to day
  • Triggers:
    • Physical exertion
    • Emotional stress
    • Heat exposure
    • Infection
    • Surgery
    • Certain medications
  • Improvement:
    • Rest
    • Cool temperature
    • Sleep

Diagnosis

Clinical Evaluation

  • Detailed history of fluctuating weakness
  • Physical examination
  • Fatigability testing
  • Ice pack test for ptosis
  • Rest test improvement

Antibody Testing

  • AChR antibodies:
    • Binding antibodies (most sensitive)
    • Blocking antibodies
    • Modulating antibodies
    • Positive in 85% generalized MG
    • 50% in ocular MG
  • MuSK antibodies:
    • 5-8% of MG patients
    • More severe bulbar involvement
    • Poor response to AChE inhibitors
  • Other antibodies:
    • LRP4 antibodies
    • Agrin antibodies
    • Striational antibodies (thymoma)

Electrophysiological Tests

  • Repetitive nerve stimulation (RNS):
    • >10% decrement diagnostic
    • 3-5 Hz stimulation
    • Multiple muscles tested
    • Positive in 75% generalized MG
  • Single fiber EMG:
    • Most sensitive test (>95%)
    • Shows increased jitter
    • Blocking in severe cases

Edrophonium (Tensilon) Test

  • Short-acting AChE inhibitor
  • Rapid improvement in symptoms
  • Must have cardiac monitoring
  • Less commonly used now
  • Risk of bradycardia, bronchospasm

Imaging

  • Chest CT or MRI:
    • Look for thymoma (10-15%)
    • Thymic hyperplasia
    • All MG patients need imaging

Additional Tests

  • Thyroid function (30% have thyroid disease)
  • Pulmonary function tests
  • Other autoimmune markers
  • Exclude mimics (Lambert-Eaton, botulism)

Treatment

Symptomatic Treatment

Acetylcholinesterase Inhibitors

  • Pyridostigmine (Mestinon):
    • First-line treatment
    • 30-60mg every 4-6 hours
    • Adjust to symptoms
    • Extended-release for nighttime
  • Side effects:
    • GI cramps, diarrhea
    • Increased salivation
    • Muscle cramps
    • Bradycardia
  • Less effective in:
    • MuSK-positive MG
    • Severe generalized MG

Immunosuppressive Therapy

Corticosteroids

  • Prednisone most common
  • Start low, increase gradually
  • Initial worsening possible
  • Effective in 70-80%
  • Taper slowly once stable

Steroid-Sparing Agents

  • Azathioprine:
    • 2-3 mg/kg/day
    • Check TPMT levels first
    • Takes 6-12 months to work
  • Mycophenolate mofetil:
    • 1000-1500mg twice daily
    • Well tolerated
    • Effect in 3-6 months
  • Others:
    • Cyclosporine
    • Tacrolimus
    • Methotrexate

Rapid Immunotherapies

Plasmapheresis

  • Removes circulating antibodies
  • 5-6 exchanges over 10-14 days
  • Rapid improvement (days)
  • Effect temporary (weeks)
  • Used for crisis or pre-surgery

IVIg (Intravenous Immunoglobulin)

  • 2 g/kg over 2-5 days
  • Alternative to plasmapheresis
  • Similar efficacy
  • Easier to administer
  • Risk of thrombosis, renal failure

Targeted Therapies

  • Rituximab:
    • Anti-CD20 monoclonal antibody
    • Especially for MuSK-positive MG
    • Refractory cases
  • Eculizumab:
    • Complement inhibitor
    • For refractory generalized MG
    • Very expensive
    • Requires meningococcal vaccination
  • Efgartigimod:
    • FcRn antagonist
    • Reduces IgG antibodies
    • Cyclic treatment

Thymectomy

  • Indicated for:
    • All patients with thymoma
    • AChR-positive generalized MG
    • Age <65 years
    • Within 5 years of diagnosis
  • Benefits:
    • Improved remission rates
    • Reduced medication needs
    • Better long-term outcomes
  • Approaches:
    • Transsternal
    • Video-assisted (VATS)
    • Robotic

Myasthenic Crisis

Definition

Life-threatening worsening of MG with respiratory failure requiring mechanical ventilation. Occurs in 15-20% of MG patients.

Triggers

  • Infection (most common)
  • Aspiration
  • Surgery/anesthesia
  • Medication changes
  • Pregnancy/delivery
  • Emotional stress
  • Contraindicated drugs

Warning Signs

  • Increasing dyspnea
  • Weak cough
  • Difficulty clearing secretions
  • Use of accessory muscles
  • Paradoxical breathing
  • Unable to count to 20

Management

  • Immediate:
    • ICU admission
    • Monitor vital capacity
    • BiPAP or intubation
    • Hold AChE inhibitors initially
  • Treatment:
    • Plasmapheresis or IVIg
    • High-dose corticosteroids
    • Treat underlying trigger
    • Supportive care

Living with Myasthenia Gravis

Lifestyle Modifications

  • Plan activities for peak strength times
  • Take regular rest periods
  • Avoid extreme temperatures
  • Stress management
  • Maintain healthy weight
  • Regular gentle exercise

Medication Precautions

Drugs that can worsen MG:

  • Certain antibiotics (aminoglycosides, fluoroquinolones)
  • Beta-blockers
  • Calcium channel blockers
  • Magnesium
  • Muscle relaxants
  • Some psychiatric medications
  • Statins (monitor closely)

Monitoring

  • Regular neurologist visits
  • Pulmonary function tests
  • Medication level monitoring
  • Bone density (if on steroids)
  • Eye exams
  • Thyroid function

Special Situations

  • Surgery:
    • Notify anesthesiologist
    • May need pre-op plasmapheresis
    • Avoid certain anesthetics
    • Close post-op monitoring
  • Pregnancy:
    • Can improve, worsen, or stay same
    • Risk of neonatal MG (10-20%)
    • Certain medications contraindicated
    • Plan delivery at specialized center
  • Vaccinations:
    • Live vaccines avoided if immunosuppressed
    • Annual flu vaccine recommended
    • COVID-19 vaccination important

Prognosis

Overall Outlook

  • Most patients have normal life expectancy
  • Quality of life can be excellent with treatment
  • Mortality <5% with modern care
  • Crisis mortality has decreased to 4-8%

Disease Course

  • Maximum severity: Usually within 2-3 years
  • Remission: Possible in 10-20%
  • Stable disease: Most with treatment
  • Ocular MG: 50% progress to generalized

Prognostic Factors

  • Favorable:
    • Younger age at onset
    • Ocular symptoms only
    • Good treatment response
    • Thymectomy in appropriate patients
  • Less favorable:
    • Thymoma
    • MuSK antibodies
    • Respiratory involvement
    • Older age at onset

With advances in treatment, including new targeted therapies, the outlook for people with myasthenia gravis continues to improve. Early diagnosis, appropriate treatment, and careful management allow most patients to achieve good disease control and maintain active, productive lives.