What are the different grades of myasthenia gravis based on symptom severity and muscle weakness?

Myasthenia Gravis Grading Systems

MGFA Clinical Classification System

Myasthenia gravis severity is graded using the Myasthenia Gravis Foundation of America (MGFA) classification system, which stratifies patients from Grade 1 (ocular symptoms only) through Grade 4 (severe generalized weakness requiring respiratory support). 1, 2

Grade 1: Ocular Myasthenia Gravis

• Symptoms limited exclusively to extraocular muscles causing ptosis, diplopia (double vision), and ophthalmoparesis 1, 2
• Affects approximately 15% of all myasthenia gravis patients 3
• No bulbar, limb, or respiratory muscle involvement 1
• Management: Hold immune checkpoint inhibitors temporarily; may resume only if symptoms completely resolve 1
• Treatment: Pyridostigmine starting at 30 mg orally three times daily, gradually increasing to maximum 120 mg four times daily based on response 1, 2

Grade 2: Mild Generalized Weakness

• Mild weakness affecting muscles beyond the ocular muscles, with some interference in activities of daily living (ADL) 1
• Typically involves facial, oropharyngeal, axial, and limb muscles in varying combinations 4
• Bulbar symptoms may include mild dysphagia, dysarthria, and facial muscle weakness 1, 2
• Proximal muscle weakness more prominent than distal weakness 1
• Management: Hold immune checkpoint inhibitors temporarily; may resume only if symptoms resolve to Grade 1 or less 1
• Treatment approach:
  • Start pyridostigmine 30 mg orally three times daily, titrating to maximum 120 mg four times daily 2, 5
  • Add corticosteroids (prednisone 1-1.5 mg/kg daily) if pyridostigmine provides insufficient control 2
  • Neurology consultation required 1

Grade 3: Moderate to Severe Generalized Weakness

• Severe weakness limiting self-care activities of daily living 1
• Significant bulbar dysfunction with dysphagia, dysarthria, and difficulty protecting airway 2, 5
• Respiratory muscle weakness requiring frequent pulmonary function monitoring 1, 2
• Neck and proximal limb weakness severely limiting mobility 1
• Management: Permanently discontinue immune checkpoint inhibitors 1
• Treatment protocol:
  • Immediate hospitalization with ICU-level monitoring 6, 5
  • High-dose corticosteroids: methylprednisolone 1-2 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 2, 6
  • IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day) OR plasmapheresis (5 sessions over 5 days) 2, 6, 5
  • Frequent pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) 1, 6
  • Daily neurologic evaluation 2, 6

Grade 4: Myasthenic Crisis

• Life-threatening respiratory failure requiring intubation and mechanical ventilation 1, 6
• Severe bulbar weakness compromising airway protection and ability to clear secretions 5
• Rapid respiratory decompensation with diaphragm weakness 5
• The "20/30/40 rule" identifies patients at risk: vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 6
• Management: Permanently discontinue immune checkpoint inhibitors 1
• Critical treatment algorithm:
  • ICU admission with continuous respiratory monitoring 6, 5
  • Immediate intubation if respiratory arrest, peri-arrest, or inability to protect airway 5
  • High-dose IV corticosteroids: methylprednisolone 1-2 mg/kg/day 6, 5
  • IVIG 2 g/kg over 5 days (0.4 g/kg/day) OR plasmapheresis 5 sessions over 5 days 6, 5
  • Pyridostigmine should be discontinued or withheld in intubated patients 6, 5
  • If IV pyridostigmine needed: 1 mg IV = 30 mg oral pyridostigmine 6, 5

Critical Medication Precautions Across All Grades

Immediately discontinue medications that worsen myasthenia gravis: 2, 6, 5

• β-blockers 2, 6
• IV magnesium (absolutely contraindicated) 6, 5
• Fluoroquinolone antibiotics 2, 6, 5
• Aminoglycoside antibiotics 2, 6, 5
• Macrolide antibiotics 2, 6, 5
• Metoclopramide 2

Diagnostic Workup Requirements

All grades warrant complete diagnostic evaluation given potential for progression to respiratory compromise: 1

• Acetylcholine receptor (AChR) antibodies and anti-striated muscle antibodies 1, 6
• If AChR negative: muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1, 6
• Pulmonary function testing with NIF and VC 1, 6
• CPK, aldolase, ESR, CRP to evaluate concurrent myositis 1, 6
• If respiratory insufficiency or elevated CPK/troponin: ECG and transthoracic echocardiogram to rule out myocarditis 1, 6
• Electrodiagnostic studies including repetitive nerve stimulation and single-fiber EMG 1

Common Pitfalls

Non-invasive ventilation frequently fails in Grade 3-4 patients with bulbar dysfunction due to inability to protect airway and clear secretions—do not delay intubation 5

Pulse oximetry and arterial blood gases are unreliable early indicators of respiratory failure in myasthenia gravis—rely on NIF, VC, and clinical assessment 6

Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided 2