What is the initial treatment for Myasthenia Gravis (MG)?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine at 30 mg orally three times daily and titrate upward to a maximum of 120 mg four times daily based on symptom response—this is the first-line treatment for all patients with myasthenia gravis. 1, 2

Symptomatic Treatment Algorithm

• Pyridostigmine (Mestinon) is FDA-approved and serves as the foundation of initial therapy, beginning at 30 mg PO three times daily and gradually increasing based on clinical response and tolerability 1, 2
• The maximum dose is 120 mg orally four times daily; titrate slowly to avoid cholinergic side effects 1, 3
• Pyridostigmine works by inhibiting acetylcholinesterase, thereby prolonging acetylcholine availability at the neuromuscular junction 4, 5

Disease Severity-Based Treatment Escalation

Mild Disease (MGFA Class I-II)

• For patients with mild symptoms affecting only ocular muscles or minimal generalized weakness, pyridostigmine monotherapy may be sufficient 1
• Start at 30 mg PO three times daily and increase gradually to optimal dosing 1
• If symptoms persist despite optimal pyridostigmine dosing (up to 120 mg four times daily), add prednisone 0.5-1.5 mg/kg orally daily 1

Moderate to Severe Disease (MGFA Class III-V)

• Immediately add corticosteroids (prednisone 1-1.5 mg/kg orally daily) to pyridostigmine for patients with moderate to severe generalized weakness 1, 3
• Hospital admission is necessary if respiratory concerns are present 1
• For acute crisis with respiratory compromise (Grade 3-4), admit to ICU and initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis 1, 3

Critical Medications to Avoid

Educate all patients to strictly avoid medications that worsen myasthenic symptoms:

• β-blockers 1, 3
• IV magnesium 1, 3
• Fluoroquinolone antibiotics 1, 3
• Aminoglycoside antibiotics 1, 3
• Macrolide antibiotics 6, 1, 3

These agents can precipitate myasthenic crisis and must be avoided in all patients with MG 1, 3.

Essential Pre-Treatment Workup

Before initiating therapy, confirm the diagnosis with:

• Acetylcholine receptor (AChR) antibodies in blood; if negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1
• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) to evaluate respiratory function 1, 3
• Neurological consultation to evaluate disease severity and develop a treatment plan 1

Rapid Improvement Strategies

For patients requiring rapid symptom control (myasthenic crisis or severe exacerbations):

• IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) is the preferred rapid intervention 1, 3
• Plasmapheresis for 5 days is an alternative when IVIG is contraindicated or unavailable 1
• Continue corticosteroids and pyridostigmine concurrently during acute treatment 3
• Perform frequent pulmonary function monitoring with NIF and vital capacity 3

Common Pitfalls and Caveats

• Pyridostigmine can cause bradycardia and AV block through muscarinic effects; monitor cardiac rhythm, especially in older patients 7
• About 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone, while 66-85% respond to corticosteroids 6
• IVIG should never be used for chronic maintenance therapy in myasthenia gravis—it is reserved only for acute exacerbations or crisis situations 3
• Close monitoring is essential when initiating treatment, as the disease can rapidly progress to respiratory compromise requiring ICU-level care 1, 3
• Corticosteroid initiation may transiently worsen symptoms in the first 1-2 weeks; this requires careful monitoring 4