What is the classification and treatment of Myasthenia Gravis (MG)?

Classification of Myasthenia Gravis

Myasthenia gravis is classified using the Myasthenia Gravis Foundation of America (MGFA) system into five classes based on severity: Class I (ocular symptoms only), Class II (mild generalized weakness), Class III (moderate generalized weakness), Class IV (severe generalized weakness), and Class V (myasthenic crisis requiring intubation). 1, 2, 3

Primary Classification Systems

MGFA Clinical Classification

The MGFA classification system is the standard framework for categorizing disease severity and guides treatment decisions 1, 2:

• Class I: Ocular myasthenia gravis only—weakness limited to levator palpebrae, orbicularis oculi, and extraocular muscles, presenting with ptosis and/or diplopia 2, 4

• Class II: Mild generalized weakness—some symptoms interfering with activities of daily living, with mild weakness affecting muscles beyond ocular muscles 1, 2

• Class III: Moderate generalized weakness—limiting self-care, with weakness affecting walking, any dysphagia, or facial weakness 1, 2

• Class IV: Severe generalized weakness—aids warranted for self-care, respiratory muscle weakness present 1, 2

• Class V: Myasthenic crisis—requiring intubation and ventilatory support due to respiratory failure 1, 2, 3

Serologic Classification

Myasthenia gravis is further classified based on autoantibody profiles, which have distinct clinical implications and treatment responses 5, 6:

• AChR-antibody positive MG: Found in 80-85% of generalized MG patients and 40-77% of ocular MG patients 2, 4, 5

• MuSK-antibody positive MG: Present in 5-8% of patients, often with prominent bulbar and respiratory involvement 5, 6

• LRP4-antibody positive MG: Found in <1% of patients 5, 6

• Seronegative MG: Approximately 10% of patients test negative for all known antibodies 5, 6

Clinical Subtype Classification

Additional clinically relevant subgroups include 5, 6:

• Early-onset MG: Typically affects women in the third to fourth decade of life 4

• Late-onset MG: More common in men, occurring later in life 4

• Thymoma-associated MG: Present in 10-20% of AChR-positive patients, requiring different management approach 4, 6

• Ocular MG: Remains localized to ocular muscles in 50% of patients, though 50-80% progress to generalized disease within a few years 2, 4, 3

Treatment Algorithm Based on Classification

Grade 2 (MGFA Class I-II)

First-line treatment: Pyridostigmine 30 mg orally three times daily, gradually increasing to maximum 120 mg orally four times daily as tolerated 1, 2, 3, 7

Second-line treatment: Add corticosteroids (prednisone 1-1.5 mg/kg orally daily) if symptoms persist despite pyridostigmine, with 66-85% showing positive response 2, 3

Monitoring: Hold immune checkpoint inhibitors if drug-induced; may resume only if symptoms resolve 1

Grade 3-4 (MGFA Class III-V)

Immediate actions 1, 2:

• Permanently discontinue any causative immune checkpoint inhibitors
• Admit patient with ICU-level monitoring capability
• Obtain urgent neurology consultation

Acute treatment 1, 2, 3:

• Continue or initiate corticosteroids (methylprednisolone 1-2 mg/kg daily)
• Initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days
• Continue pyridostigmine, wean based on improvement
• Frequent pulmonary function assessment with NIF and vital capacity
• Daily neurologic review

Long-term immunosuppression: Azathioprine as steroid-sparing agent for moderate to severe disease 2, 8, 5

Critical Diagnostic Considerations

Mandatory Work-up Components

All grades warrant comprehensive evaluation given potential for rapid progression to respiratory compromise 1, 2:

• Serologic testing: AChR antibodies, antistriated muscle antibodies; if negative, test for MuSK and LRP4 antibodies 2, 3

• Electrodiagnostic studies: Repetitive nerve stimulation and/or single-fiber EMG (>90% sensitivity for ocular MG) 2, 3

• Imaging: Chest CT to screen for thymoma in all patients 4

• Cardiac evaluation: If respiratory insufficiency or elevated CPK/troponin present, perform ECG and echocardiography to rule out concurrent myocarditis 1, 4

• Neuroimaging: MRI brain/spine if atypical features to exclude CNS involvement or alternative diagnosis 1

Medications to Avoid

The following drugs can precipitate or worsen myasthenic crisis and must be avoided 1, 2, 3:

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics

Prognosis by Classification

• Ocular MG (Class I): 50% remain localized; 50-80% progress to generalized disease within 2-3 years 2, 4, 3

• Generalized MG (Class II-IV): Remission or stabilization often achieved after 2-3 years of treatment 3

• Myasthenic crisis (Class V): Life-threatening; requires immediate ventilatory support and aggressive immunotherapy 1, 2