What is the primary treatment approach for a pediatric patient with Myasthenia Gravis (MG)?

Primary Treatment Approach for Pediatric Myasthenia Gravis

Start pyridostigmine at 30 mg orally three times daily as first-line therapy for all children with myasthenia gravis, gradually titrating to a maximum of 120 mg four times daily based on symptom response. 1, 2

Initial Symptomatic Management

• Pyridostigmine is the FDA-approved first-line treatment for myasthenia gravis in all age groups, including children. 2
• Begin at 30 mg orally three times daily and increase gradually to maximum 120 mg four times daily as tolerated. 1, 3
• Most pediatric patients with ocular myasthenia gravis achieve stabilization using pyridostigmine alone or in combination with oral prednisone. 4
• However, approximately 50% of patients—particularly those with ocular/strabismus manifestations—show minimal response to pyridostigmine alone and require escalation to immunosuppressive therapy. 1, 4

When to Escalate to Corticosteroids

Add prednisone 0.5-1.5 mg/kg orally daily if symptoms interfere with activities of daily living despite adequate pyridostigmine dosing. 1, 3

• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate. 1, 5
• For mild generalized weakness (MGFA Class I-II), add prednisone if pyridostigmine is insufficient. 1, 3
• For moderate to severe weakness (MGFA Class III-V), initiate combination therapy with pyridostigmine and prednisone immediately. 3
• Early corticosteroid treatment is warranted when ocular motility abnormalities persist despite pyridostigmine, as ocular symptoms are highly variable and not readily remedied with prisms. 1

Critical Diagnostic Workup Before Treatment

• Test anti-acetylcholine receptor (AChR) antibodies first—present in 80% of generalized myasthenia gravis but only 40-77% of purely ocular cases. 1, 5
• If AChR antibodies are negative, test anti-muscle-specific kinase (MuSK) antibodies, as approximately one-third of seronegative patients will be MuSK-positive. 1
• Perform CT chest with contrast after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients. 1
• Single-fiber electromyography has >90% sensitivity for ocular myasthenia and is the gold standard diagnostic test. 1
• Ice pack test is highly specific—apply ice pack over closed eyes for 2 minutes and observe for symptom reduction. 1, 3

Treatment Algorithm Based on Disease Severity

For Ocular Myasthenia (MGFA Class I)

• Start pyridostigmine 30 mg three times daily, titrate to effect. 1, 4
• Add prednisone if symptoms persist after adequate pyridostigmine trial. 1, 4
• Close ophthalmology involvement is required in young children to prevent amblyopia. 6
• Rates of generalization from ocular to generalized disease range from 15-35%, with higher rates in adolescents. 4

For Mild Generalized Weakness (MGFA Class II)

• Pyridostigmine plus prednisone 0.5 mg/kg orally daily if symptoms interfere with activities of daily living. 1
• Monitor closely as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years. 1, 3

For Moderate to Severe Weakness (MGFA Class III-IV)

• Immediate combination therapy: pyridostigmine plus prednisone 1-1.5 mg/kg orally daily. 3
• Add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days for rapid symptom control. 1
• Admit with ICU-level monitoring capability for rapidly progressive symptoms or respiratory muscle weakness. 1, 3

For Myasthenic Crisis (MGFA Class V)

• Immediate ICU admission with ventilatory support. 3
• Urgent neurology consultation. 3
• Aggressive immunotherapy with corticosteroids, IVIG, or plasmapheresis. 3
• Plasmapheresis is preferred over IVIG in crisis due to rapid onset of action, though feasibility in very young children must be considered. 6

Second-Line Immunosuppressive Therapy

Consider azathioprine or mycophenolate mofetil as steroid-sparing agents when: 1, 4, 6

• No response to steroids after adequate trial

• Inability to wean to a reasonable minimum effective dose

• Intolerable steroid side effects

• Azathioprine can be used as third-line immunosuppressive therapy for moderate to severe disease. 1, 3

• Tacrolimus has shown evidence for improving symptoms of juvenile myasthenia gravis refractory to prednisone in open-label trials. 4

Special Considerations for MuSK-Positive Patients

• MuSK-positive juvenile myasthenia gravis shows poorer response to pyridostigmine. 6
• Anecdotal evidence suggests rituximab should be considered as second-line immunosuppression in MuSK-positive cases. 6
• Thymectomy is not advised in MuSK-positive myasthenia gravis. 6

Role of Thymectomy

Perform thymectomy in all patients with thymoma. 1, 5

• Consider thymectomy in AChR-positive juvenile myasthenia gravis, allowing time for spontaneous remission first. 1, 6
• Evidence suggests thymectomy is effective in controlling pediatric ocular myasthenia gravis and shows a pattern toward preventing generalization, reducing prednisone dosing, and increasing disease resolution. 4
• The benefit is less clear in ocular myasthenia gravis alone. 6
• Thymectomy may substantially reduce symptoms in appropriate AChR-positive patients. 1, 5

Critical Medication Avoidance

Immediately review and discontinue medications that worsen myasthenia: 1, 3, 5

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

Monitoring Requirements

• Daily neurologic review and frequent pulmonary function assessment (negative inspiratory force and vital capacity) for moderate to severe patients. 1
• Regular assessment is crucial as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years. 1, 3
• Approximately 25% of pediatric patients with ocular myasthenia gravis can achieve complete remission. 4
• Remission or stabilization is often possible after 2-3 years of treatment. 5

Common Pitfalls to Avoid

• Do not delay immunosuppression in children with poor pyridostigmine response—early use of immunosuppression where good control is not achieved is important to avoid long-term physical and psychosocial morbidity. 6
• Do not assume pupils will be affected—pupils are characteristically not affected in myasthenia gravis, which distinguishes it from third nerve palsy. 3
• Do not consider strabismus surgery until disease stabilization—typically requires 2-3 years of medical treatment and should be decided in collaboration with experienced ophthalmologist and neurologist. 1, 5
• Do not use the 2-day IVIG regimen in children—one study showed treatment-related fluctuations were more frequent with a 2-day regimen (5 of 23 children) than with the standard 5-day regimen (0 of 23 children). 7

Novel Therapies for Refractory Disease

• Efgartigimod alfa-fcab is FDA-approved specifically for AChR-positive patients who are refractory to conventional therapy. 1
• Recent randomized controlled trials focus on novel therapeutic strategies including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, suggesting a change in myasthenia gravis management over coming years. 8