What is the recommended approach to diagnose and treat myasthenia gravis in a child or adolescent?

Myasthenia Gravis in Pediatric Patients: Diagnosis and Management

Pediatric myasthenia gravis should be diagnosed using anti-acetylcholine receptor (AChR) antibody testing combined with repetitive nerve stimulation or single-fiber EMG, and treated first-line with pyridostigmine (starting at 30 mg orally three times daily), escalating to corticosteroids (prednisone 0.5 mg/kg daily) when pyridostigmine alone provides inadequate control, which occurs in approximately 50% of pediatric patients. 1, 2, 3

Diagnostic Approach

Clinical Presentation

Pediatric myasthenia gravis typically presents with:

• Fatigable weakness that worsens with exertion and improves with rest 2, 4
• Ocular symptoms (ptosis, diplopia, extraocular movement abnormalities) are the most common initial presentation 2, 4
• Bulbar involvement (dysphagia, dysarthria, facial weakness) may occur 2
• Generalized weakness affecting proximal more than distal muscles 2
• Pupils are characteristically NOT affected—this is a critical distinguishing feature from third nerve palsy 2

The mean age at onset in pediatric patients is approximately 12.8-12.9 years, with generalized myasthenia being the most common form in hospitalized children 5, 6

Bedside Diagnostic Tests

Ice pack test is highly specific and should be performed early:

• Apply ice pack over closed eyes for 2 minutes (for ptosis) or 5 minutes (for strabismus) 7, 2
• Positive test shows reduction of ptosis by approximately 2 mm or improvement in ocular alignment 7, 2
• This test is highly specific for myasthenia gravis 7, 2

Rest test (without ice) can also provide supportive diagnostic information 7

Serologic Testing (Perform in This Order)

1. Anti-AChR antibodies (first-line test):

   • Present in approximately 80% of generalized myasthenia gravis 3, 8
   • Sensitivity drops to only 50% in purely ocular myasthenia 2, 3
   • In pediatric studies, 62.5% of tested patients were AChR-positive 5, 6

2. Anti-MuSK antibodies (if AChR-negative):

   • Approximately one-third of seronegative patients will be MuSK-positive 7, 2, 3
   • Found in 5-8% of all myasthenia gravis patients 8

3. Anti-LRP4 antibodies (if both AChR and MuSK negative):

   • Associated with both generalized and ocular myasthenia gravis 7, 2
   • Found in <1% of patients 8

4. Anti-striated muscle antibodies should be included in initial workup 3

Electrophysiologic Testing

Single-fiber electromyography (SFEMG) is the gold standard:

• Sensitivity >90% for ocular myasthenia 7, 2, 3
• A negative SFEMG is atypical and warrants reconsideration of the differential diagnosis 2

Repetitive nerve stimulation (RNS):

• More widely available but less sensitive 3
• Positive in only one-third of ocular myasthenia cases 7, 3
• In pediatric studies, decremental response of 4:1 ranged from 26% to 88% 5, 6
• Amplitude during first response is typically normal 5, 6

Critical caveat: Electrophysiological findings do not always correlate with clinical state—clinical remission can occur despite persistent electrophysiological abnormalities 5, 6

Pharmacologic Testing

Edrophonium (Tensilon) test:

• Sensitivity: 95% for generalized MG, 86% for ocular MG 7, 2
• Must be performed by experienced practitioners in monitored setting 7, 2
• Atropine (0.4-0.5 mg IV) must be immediately available for muscarinic side effects (tearing, salivation, sweating, bradycardia, bronchospasm, hypotension, syncope) 7, 2

Essential Supplementary Workup

After diagnosis confirmation:

• CT chest with contrast to evaluate for thymoma (occurs in 10-20% of AChR-positive patients) 3
  • In pediatric studies: persistent thymus in 3 patients, thymic hypertrophy in 6-7 patients, thymoma in 2 patients 5, 6
• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) 3
• CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 3
• Troponin and ECG (consider echocardiogram or cardiac MRI) to rule out myocarditis 3

Treatment Algorithm

First-Line: Pyridostigmine

Start pyridostigmine at 30 mg orally three times daily, gradually increasing to maximum 120 mg four times daily based on symptoms 1, 2, 3

Critical limitation: Approximately 50% of pediatric patients, particularly those with ocular/strabismus manifestations, show minimal response to pyridostigmine alone and require escalation to immunosuppressive therapy 7, 1, 2, 3

Second-Line: Corticosteroids

Add prednisone when pyridostigmine provides inadequate symptom control:

• For mild generalized weakness: Start prednisone at 0.5 mg/kg orally daily 1
• For moderate to severe disease: Prednisone 1-1.5 mg/kg orally daily 3
• Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 7, 1, 2, 3
• Tapering should begin 3-4 weeks after initiation based on symptom improvement 1

Oral administration is preferred over intramuscular formulations in pediatric myasthenia gravis 1

Third-Line: Steroid-Sparing Immunosuppressants

Azathioprine is the first-choice steroid-sparing agent:

• Used in pediatric patients with moderate to severe disease 1, 2
• Requires several months to achieve therapeutic effect 1
• In pediatric studies, used in combination with pyridostigmine in 3-4 patients 5, 6

Acute/Rescue Therapy for Moderate to Severe Disease

For MGFA Class III-V or myasthenic crisis:

• IVIG: 2 g/kg IV over 5 days (0.4 g/kg/day) 1, 3
• Plasmapheresis: 3-5 days 1, 3
• Used in 3-5 pediatric patients during myasthenic crisis in published series 5, 6

Surgical Intervention: Thymectomy

Thymectomy should always be performed when thymoma is present 1, 3

Thymectomy should be evaluated in appropriate AChR-positive pediatric patients without thymoma, as it may substantially reduce symptoms 1, 3

In pediatric studies, thymectomy was performed in 40-42% of patients during the first year after diagnosis, contributing to clinical remission rates of 88.9-90.9% 5, 6

Critical Medication Avoidance

Immediately discontinue or avoid these medications that worsen myasthenic symptoms:

• β-blockers 1, 2, 3
• IV magnesium 1, 2, 3
• Fluoroquinolones 1, 2, 3
• Aminoglycosides 1, 2, 3
• Macrolide antibiotics 1, 2, 3

Monitoring and Prognosis

Regular Assessment

• Daily neurologic review for patients with moderate to severe disease 3
• Frequent pulmonary function assessment given risk of respiratory compromise 2, 3
• Pediatric ophthalmology monitoring for development of amblyopia from ptosis or strabismus 4

Prognosis

• 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years, most commonly within the first two years 2, 3
• Clinical remission achieved in 88.9-90.9% of pediatric patients with appropriate treatment 5, 6
• Remission or stabilization often possible after 2-3 years of treatment 7

Important Caveat for Ocular Symptoms

Ocular symptoms and strabismus are highly variable and not readily remedied with prisms 7, 3. Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 7, 3. Particular care is indicated with anesthetic agents given potential respiratory muscle weakness 7, 3.

Multidisciplinary Management

Diagnosis and management requires collaboration between experienced pediatric neurologist and ophthalmologist, with potential involvement of cardiothoracic surgery for thymectomy 7, 3. For severe disease, ICU-level monitoring capability may be necessary 3.