What are the management options for a patient with Myasthenia Gravis (MG), considering factors such as age, medical history, and disease severity?

Management 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 immediately escalate to corticosteroids (prednisone 1-1.5 mg/kg daily) for any patient with Grade 2 or higher symptoms (weakness interfering with activities of daily living), as approximately 50% of patients show minimal response to pyridostigmine alone while 66-85% respond positively to corticosteroids. 1, 2

Initial Diagnostic Workup

Before initiating treatment, confirm the diagnosis and assess disease severity:

• Test anti-acetylcholine receptor (AChR) antibodies first—present in 80% of generalized MG and 50% of purely ocular MG 1
• If AChR antibodies are negative, immediately test anti-muscle-specific kinase (MuSK) antibodies—positive in approximately one-third of seronegative patients 1
• Perform single-fiber electromyography (SFEMG)—the gold standard with >90% sensitivity for ocular myasthenia 1
• Order CT chest with contrast to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 1
• Obtain baseline pulmonary function tests with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 3, 1
• Check CPK, aldolase, ESR, CRP to evaluate for concurrent myositis 3, 1
• Obtain troponin and ECG (consider echocardiogram) to rule out concomitant myocarditis 3, 1

Treatment Algorithm by Disease Severity

Grade 2 Disease (Mild Generalized Weakness, MGFA Class I-II)

Symptoms interfering with activities of daily living, ocular symptoms only, or mild generalized weakness:

• Start pyridostigmine 30 mg orally three times daily, gradually increase to maximum 120 mg four times daily as tolerated 3, 1
• Add prednisone 0.5-1.5 mg/kg orally daily if symptoms persist despite pyridostigmine 3, 1
• May hold checkpoint inhibitors (if applicable) and resume only if symptoms resolve 3
• Consult neurology for all patients 3

Grade 3-4 Disease (Moderate to Severe Weakness, MGFA Class III-V)

Limiting self-care, weakness limiting walking, ANY dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms:

• Permanently discontinue checkpoint inhibitors (if applicable) 3
• Admit patient immediately—ICU-level monitoring may be necessary 3, 1
• Continue corticosteroids (prednisone 1-2 mg/kg daily or methylprednisolone) and initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 3-5 days 3, 1
• Perform frequent pulmonary function assessment with daily neurologic evaluation 3, 1
• Consult neurology urgently 3

Third-Line Immunosuppressive Therapy

If inadequate response to corticosteroids or need for steroid-sparing agents:

• Azathioprine is the preferred third-line agent for moderate to severe disease 1, 4, 5, 6
• Mycophenolate mofetil can be considered as adjunctive therapy in refractory or steroid-dependent MG 5
• Cyclosporine is effective but limited by renal toxicity and hypertension 5, 6
• Rituximab should be reserved for refractory MG 7, 6
• Efgartigimod alfa-fcab is FDA-approved specifically for AChR-positive patients refractory to conventional therapy 1

Thymectomy Indications

Thymectomy should be performed in the following patients:

• All patients with thymoma—thymomectomy is mandatory 1, 4, 5, 6
• AChR-positive generalized MG patients aged 18-65 years within the first 6-12 months of disease duration 1, 5, 6
• Early thymectomy substantially reduces symptoms and may induce remission 1, 4

Critical Medication Avoidance

Immediately review and discontinue the following medications that worsen myasthenia:

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

Critical drug interaction: Concomitant use of anticholinesterase agents (pyridostigmine) and corticosteroids may produce severe weakness—if possible, withdraw anticholinesterase agents at least 24 hours before initiating corticosteroid therapy, though if concomitant therapy must occur, provide close supervision with respiratory support available 8

Management of Ocular Myasthenia Gravis

Approximately 50% of patients present with ocular symptoms only (ptosis, variable strabismus, diplopia), and 50-80% will develop generalized systemic myasthenia within a few years:

• Start pyridostigmine, but recognize that approximately 50% of ocular MG patients show minimal response 3, 1, 9
• Escalate early to corticosteroids when ocular motility abnormalities persist despite pyridostigmine 1, 9
• Ice pack test (apply over closed eyes for 2 minutes) may temporarily reduce symptoms and aid diagnosis 1, 2, 9
• Ocular symptoms are highly variable and not readily remedied with prisms 1, 9
• Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 3, 1, 9
• Monitor vigilantly for generalization to systemic disease with regular respiratory assessments 1, 9

Monitoring and Follow-Up

Regular assessment is crucial given the risk of disease progression:

• Daily neurologic evaluation for Grade 3-4 patients 3, 1
• Frequent pulmonary function testing (NIF and vital capacity) for all patients with generalized MG 3, 1
• 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years—maintain high vigilance 3, 1, 9
• Regular assessment for respiratory compromise is essential as progressive myasthenia can lead to respiratory failure 3, 1

Common Pitfalls to Avoid

Cholinergic crisis versus myasthenic crisis: Overdosage of pyridostigmine may result in cholinergic crisis characterized by increasing muscle weakness that can lead to death through respiratory muscle involvement—this is difficult to distinguish from myasthenic crisis on symptomatic basis alone and may require edrophonium chloride testing and clinical judgment 10

Masking overdosage signs: Atropine may abolish gastrointestinal side effects but can mask signs of overdosage, leading to inadvertent induction of cholinergic crisis 10

Acute myopathy with high-dose corticosteroids: An acute myopathy has been observed with high doses of corticosteroids in patients with neuromuscular transmission disorders like myasthenia gravis—this is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis 8

Pupillary involvement excludes myasthenia: Pupils are characteristically not affected in myasthenia gravis—if pupils are abnormal, immediately prioritize evaluation for third nerve palsy, Horner syndrome, or other neurologic causes over myasthenia 2

Preoperative antibody testing: Any patient with suspected myasthenia requiring surgery must have serum anti-AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia 2