How is myasthenia gravis graded and treated?

Myasthenia Gravis Grading and Treatment

Disease Severity Classification

Myasthenia gravis is graded using the Myasthenia Gravis Foundation of America (MGFA) classification system, which stratifies patients from Grade 1 (ocular only) through Grade 5 (requiring intubation), with treatment escalating based on severity. 1, 2

MGFA Grading System

• Grade 1: Isolated ocular symptoms (ptosis, diplopia) without generalized weakness 3

• Grade 2: Mild generalized weakness affecting limb, axial, or oropharyngeal muscles, with functional limitations but no respiratory compromise 1

• Grade 3-4: Moderate to severe generalized weakness requiring hospitalization, with Grade 3-4 exacerbations necessitating IVIG or plasmapheresis 1

• Grade 5: Myasthenic crisis requiring intubation and mechanical ventilation due to respiratory failure 1

Treatment Algorithm by Disease Severity

Grade 1 (Ocular Myasthenia)

• Initiate pyridostigmine at 30 mg orally three times daily, titrating upward based on clinical response to a maximum of 120 mg four times daily 1, 3

• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and may require escalation to corticosteroids 3

• Monitor closely as 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years 3

Grade 2 (Mild to Moderate Generalized Weakness)

• Continue or optimize pyridostigmine dosing (30-120 mg four times daily) 1

• Add corticosteroids (prednisone 1-1.5 mg/kg daily) if pyridostigmine provides insufficient control, with 66-85% of patients showing positive response 3

• Taper corticosteroids gradually based on symptom improvement 1

• Consider azathioprine or other steroid-sparing immunosuppressants as third-line therapy for moderate to severe disease 3, 4

Grade 3-4 (Severe Exacerbations/Crisis)

For myasthenic crisis with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate IVIG (2 g/kg total over 5 days, administered as 0.4 g/kg/day for 5 consecutive days) or plasmapheresis 1

Critical management steps include:

• Continue corticosteroids concurrently during IVIG or plasmapheresis 1

• Maintain pyridostigmine throughout crisis management 1

• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 1

• Conduct daily neurologic evaluations 1

• IVIG should be reserved specifically for Grade 3-4 exacerbations and is not recommended for chronic maintenance therapy 1

Diagnostic Confirmation Requirements

Before initiating treatment, confirm diagnosis with:

• Acetylcholine receptor (AChR) antibodies (positive in 80-85% of patients) 1, 5

• Antistriated muscle antibodies 1

• Muscle-specific kinase (MuSK) antibodies if AChR antibodies are negative (positive in 5-8%) 1, 5

• Lipoprotein-related protein 4 (LRP4) antibodies if both AChR and MuSK are negative 1, 5

• Electrodiagnostic studies with repetitive nerve stimulation and/or single-fiber EMG (>90% sensitivity for ocular myasthenia) 3

• Ice pack test for ocular symptoms (highly specific) 3

Critical Medications to Avoid

Strictly educate patients to avoid medications that worsen myasthenic symptoms: 1, 3

• β-blockers 1, 3
• Intravenous magnesium 1, 3
• Fluoroquinolone antibiotics 1, 3
• Aminoglycoside antibiotics 1, 3
• Macrolide antibiotics 1, 3
• Barbiturate-containing medications like Firocet (butalbital and acetaminophen), which can worsen neuromuscular transmission and potentially exacerbate muscle weakness 1, 6

Monitoring and Follow-up

• Plan regular neurology consultation to adjust treatment as needed 1

• Perform regular pulmonary function assessment, especially for patients with generalized disease or respiratory symptoms 1, 3

• Monitor for worsening symptoms including changes in speech or swallowing (bulbar symptoms), respiratory difficulties, and diplopia 1

• Instruct patients to seek immediate medical attention for significant increase in muscle weakness 1

Important Clinical Pitfalls

Cholinergic crisis versus myasthenic crisis differentiation is critical: 7

• Overdosage of pyridostigmine can result in cholinergic crisis, characterized by increasing muscle weakness that may lead to respiratory failure and death 7

• Both cholinergic crisis (from medication overdose) and myasthenic crisis (from disease worsening) present with extreme muscle weakness 7

• Differential diagnosis may require edrophonium chloride testing and clinical judgment 7

• Increasing pyridostigmine doses during cholinergic crisis can have grave consequences; prompt withdrawal of all anticholinesterase drugs is required 7

• Atropine is recommended for cholinergic crisis but can mask signs of overdosage 7

Thymectomy Considerations

• Evaluate for thymectomy in appropriate patients, particularly those with thymoma (present in 10-20% of AChR MG patients) 3, 5

• All patients with suspected thymomas must have serum anti-acetylcholine receptor antibody levels measured preoperatively to avoid respiratory failure during anesthesia 3

• Approximately 30-50% of patients with thymomas have myasthenia gravis 3