What is the treatment for Myasthenia Gravis (MG)?

Treatment of Myasthenia Gravis

Start all patients with pyridostigmine 30 mg orally three times daily, gradually increasing to a maximum of 120 mg four times daily based on symptom response, and escalate to corticosteroids (prednisone 1-1.5 mg/kg daily) for Grade 2 or higher disease when symptoms interfere with daily activities or fail to respond adequately to pyridostigmine alone. 1, 2, 3

Initial Symptomatic Treatment

• Pyridostigmine is FDA-approved and serves as first-line symptomatic therapy for all forms of myasthenia gravis, providing temporary enhancement of neuromuscular transmission through acetylcholinesterase inhibition 3, 1
• Begin at 30 mg orally three times daily and titrate upward based on clinical response, with maximum dosing of 120 mg four times daily 4, 1, 2
• Approximately 50% of patients, particularly those with ocular manifestations, show minimal response to pyridostigmine monotherapy and require immunosuppressive escalation 1, 2

Immunosuppressive Therapy Algorithm

Grade 2 Disease (Mild Generalized Weakness)

• Add prednisone 1-1.5 mg/kg orally daily when symptoms interfere with activities of daily living despite pyridostigmine optimization 4, 1
• Corticosteroids demonstrate 66-85% positive response rates compared to pyridostigmine's 50% response rate 1, 2
• Wean corticosteroids gradually based on symptom improvement 4
• Consider holding checkpoint inhibitors in immune-related MG and resume only if symptoms resolve to Grade 2 or better 4

Grade 3-4 Disease (Moderate to Severe Weakness, Respiratory Compromise)

• Permanently discontinue checkpoint inhibitors if immune-related MG 4
• Admit to hospital with ICU-level monitoring capability 4, 2
• Continue corticosteroids and immediately initiate either IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days 4, 1, 2
• Perform frequent pulmonary function assessment with negative inspiratory force and vital capacity monitoring 4, 1, 2
• Daily neurologic evaluation is mandatory 4, 2

Third-Line Steroid-Sparing Agents

• Azathioprine serves as the preferred third-line immunosuppressive option for moderate to severe disease or as adjunctive therapy with corticosteroids 1, 2
• Alternative agents include cyclosporine (limited by renal toxicity and hypertension) and mycophenolate mofetil for refractory or steroid-dependent disease 5, 6
• Rituximab or cyclophosphamide reserved only for severely drug-resistant patients 7

Surgical Intervention: Thymectomy

• Perform thymectomy in all patients with thymoma-associated MG 2, 7
• Evaluate thymectomy for all AChR-positive patients with generalized MG aged 18-65 years, ideally within the first 6-12 months of disease duration 2, 6, 8
• Thymectomy increases probability of remission or improvement, though evidence from controlled trials remains limited 5, 7
• Obtain CT chest with contrast after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 2

Essential Diagnostic Workup

Antibody Testing

• Test anti-acetylcholine receptor (AChR) antibodies first—present in approximately 80% of generalized MG and 50% of purely ocular MG 1, 2
• If AChR antibodies negative, test anti-muscle-specific kinase (MuSK) antibodies, as approximately one-third of seronegative patients are MuSK-positive 4, 2
• Include anti-striated muscle antibodies in initial workup 4, 2

Electrodiagnostic Studies

• Single-fiber EMG is the gold standard with >90% sensitivity for ocular myasthenia 1, 2
• Repetitive nerve stimulation has lower sensitivity (positive in only one-third of ocular cases) but is more widely available 2

Concurrent Disease Evaluation

• Measure CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 4, 2
• If respiratory insufficiency or elevated CPK present, obtain troponin T, ECG, and transthoracic echocardiogram to rule out concomitant myocarditis 4, 2
• Consider MRI of brain and/or spine depending on symptoms to exclude CNS involvement or alternative diagnoses 4

Critical Medication Avoidance

Immediately discontinue medications that worsen myasthenia, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 4, 1, 2

Novel Therapies for Refractory Disease

• Efgartigimod alfa-fcab is FDA-approved specifically for AChR-positive patients refractory to conventional therapy 2
• Complement inhibitors and FcRn inhibitors represent new add-on treatment options with improved evidence from phase 3 trials 9

Monitoring and Prognosis

• Regular pulmonary function assessment is crucial, as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 1, 2
• Neurology consultation is mandatory for all grades of disease 4, 1
• Collaboration between experienced ophthalmologist and neurologist is necessary for diagnosis and management, particularly with ocular involvement 1

Special Considerations for Ocular Myasthenia

• Ice pack test is highly specific—apply ice pack over closed eyes for 2 minutes and observe for symptom reduction 1, 2
• Pupils are characteristically not affected in myasthenia gravis, serving as an important distinguishing feature from third nerve palsy 1
• Ocular symptoms are highly variable and not readily remedied with prisms 2
• Early corticosteroid treatment is warranted when ocular motility abnormalities persist despite pyridostigmine, as approximately 50% show minimal response to pyridostigmine alone 1, 2
• Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 1, 2