What is the treatment approach for a patient with suspected Myasthenia Gravis?

Treatment Approach for Suspected Myasthenia Gravis

Begin immediate diagnostic workup and initiate pyridostigmine 30 mg orally three times daily while awaiting confirmatory testing, escalating to corticosteroids if symptoms are moderate-to-severe or if pyridostigmine provides inadequate control. 1, 2

Immediate Diagnostic Workup

When myasthenia gravis (MG) is suspected, proceed with the following tests without delay:

Serologic Testing

• Acetylcholine receptor (AChR) antibodies - positive in 80-85% of generalized MG and 40-77% of ocular MG 2, 3
• Antistriated muscle antibodies - particularly important if thymoma is suspected 1
• Muscle-specific kinase (MuSK) antibodies if AChR is negative - found in 5-8% of patients 3
• Lipoprotein-related protein 4 (LRP4) antibodies if both AChR and MuSK are negative - present in <1% 1, 3

Electrodiagnostic Studies

• Repetitive nerve stimulation - shows decremental response in affected muscles 1, 2
• Single-fiber EMG - has >90% sensitivity for ocular MG, most sensitive test available 2
• Nerve conduction studies to exclude peripheral neuropathy 1

Bedside Clinical Tests

• Ice pack test - apply ice over closed eyes for 2 minutes for ptosis or 5 minutes for strabismus; improvement of ≥2 mm in ptosis is highly specific for MG 1, 2
• Rest test - symptoms improve after period of rest 1
• Fatigability testing - prolonged upgaze worsens ptosis, repetitive movements worsen weakness 1

Additional Essential Testing

• Pulmonary function tests with negative inspiratory force and vital capacity - critical for assessing respiratory compromise risk 1, 2
• Creatine phosphokinase (CPK), aldolase, ESR, CRP - to evaluate for concurrent myositis 1
• Chest CT or MRI - to evaluate for thymoma (present in 10-20% of AChR-positive patients) 1, 3
• ECG and transthoracic echocardiogram if elevated CPK or respiratory symptoms - to exclude myocarditis 1

Neurology Consultation

• Obtain urgent neurology consultation for all suspected cases 1, 2

Initial Treatment Algorithm

Grade 2 (Mild-to-Moderate Symptoms)

Mild generalized weakness or ocular symptoms limiting instrumental activities of daily living:

• Start pyridostigmine 30 mg orally three times daily, gradually increase every 2-3 days to maximum 120 mg orally four times daily based on symptom response 1, 2, 4
• May continue immune checkpoint inhibitors if this is the suspected trigger 1
• Escalate to corticosteroids (prednisone 1-1.5 mg/kg orally daily) if inadequate response to pyridostigmine within 2-4 weeks 1, 2
• Resume immune checkpoint inhibitors only if symptoms completely resolve 1

Grade 3-4 (Severe Symptoms or Myasthenic Crisis)

Severe generalized weakness, respiratory compromise, or dysphagia:

• Permanently discontinue immune checkpoint inhibitors if applicable 1
• Admit to hospital with ICU-level monitoring capability 1, 2
• Initiate high-dose corticosteroids (prednisone 1-1.5 mg/kg orally daily or IV methylprednisolone) 1, 2
• Add IVIG 2 g/kg over 5 days OR plasmapheresis for 5 days - both are equally effective for acute exacerbations 1, 2
• Continue pyridostigmine unless contraindicated 1
• Perform frequent pulmonary function assessments (every 4-6 hours initially) 1, 2
• Daily neurologic evaluation to monitor progression 1

Long-Term Management Considerations

Thymectomy Evaluation

• Indicated for all patients with thymoma regardless of age 1
• Consider for non-thymomatous AChR-positive patients age 18-65 years with generalized disease 1, 2
• May substantially reduce clinical symptoms in appropriately selected patients 1

Steroid-Sparing Immunosuppressants

• Azathioprine - consider as third-line for moderate-to-severe disease requiring chronic corticosteroids 2, 3
• Mycophenolate mofetil - alternative steroid-sparing agent 5, 3
• Latency to effect is months to years - do not expect immediate improvement 6

Treatment-Refractory Disease

For patients failing standard therapy:

• Rituximab - particularly effective in MuSK-positive MG 5, 6
• Complement inhibitors (eculizumab, ravulizumab) - approved for refractory generalized MG 6
• FcRn inhibitors (efgartigimod, rozanolixizumab) - newer targeted therapies showing efficacy 2, 6
• High-dose cyclophosphamide - reserved for severe refractory cases 5

Critical Medications to Avoid

The following medications can precipitate or worsen myasthenic crisis and must be strictly avoided: 1, 2, 7

• β-blockers (propranolol, metoprolol, atenolol) 1, 7
• Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin) 1, 7
• Aminoglycoside antibiotics (gentamicin, tobramycin) 1, 7
• Macrolide antibiotics (azithromycin, erythromycin) 1, 7
• Intravenous magnesium 1, 7
• Cholinesterase inhibitors for Alzheimer's disease (donepezil, rivastigmine, galantamine) - absolutely contraindicated 7
• Metoclopramide - can worsen neuromuscular transmission 8

Common Pitfalls and How to Avoid Them

Pitfall 1: Delaying Treatment While Awaiting Antibody Results

• Start empirical treatment immediately if clinical suspicion is high - antibody results can take days to weeks 1, 2
• Negative antibodies do not exclude MG - approximately 10% are seronegative 3, 9

Pitfall 2: Missing Ocular-to-Generalized Progression

• 50-80% of patients with isolated ocular symptoms develop generalized MG within 2-3 years 1, 2
• Counsel all patients about warning signs of generalized disease (dysphagia, dysarthria, limb weakness, dyspnea) 2
• Regular pulmonary function monitoring even in purely ocular cases 2

Pitfall 3: Inadequate Respiratory Monitoring

• Respiratory failure can develop rapidly and is the leading cause of MG-related mortality 1
• Monitor negative inspiratory force and vital capacity - not just oxygen saturation 1, 2
• Threshold for intubation should be low in myasthenic crisis 1

Pitfall 4: Confusing MG with Other Conditions

Key distinguishing features:

• Pupils are characteristically spared in MG - pupillary involvement suggests third nerve palsy or other etiology 1, 2
• Thyroid eye disease shows tendon-sparing muscle enlargement on imaging versus normal muscles in MG 2
• Lambert-Eaton syndrome shows incremental response on repetitive stimulation (opposite of MG) 2
• Botulism presents with symmetric cranial nerve palsies and gastrointestinal symptoms 2

Pitfall 5: Prescribing Contraindicated Medications

• Always screen medication lists before prescribing new drugs to MG patients 1, 7, 8
• Educate patients to inform all providers about their MG diagnosis 7
• Use ondansetron or promethazine instead of metoclopramide for nausea 8

Prognosis and Quality of Life Outcomes

• Treatment should aim for clinical remission or minimal manifestation status - not just symptom reduction 6, 9
• Most patients achieve good-to-excellent results with appropriate treatment and acceptable quality of life 10, 9
• Mortality is not increased in well-managed MG without thymoma 10
• Active physical training should be encouraged once disease is controlled 9
• Comorbidity management is essential, particularly in elderly patients 9