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

Initial Treatment for Myasthenia Gravis

The initial treatment for myasthenia gravis should be pyridostigmine, starting at 30 mg orally three times a day and gradually increasing to a maximum of 120 mg orally four times a day as tolerated and based on symptoms. 1

Diagnostic Workup Before Treatment

Before initiating treatment, a thorough diagnostic workup should be performed:

• Test for acetylcholine receptor (AChR) antibodies in blood; if negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1
• Perform pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) 1
• Check CPK, aldolase, ESR, and CRP to evaluate for possible concurrent myositis 1
• Consider MRI of brain and/or spine depending on symptoms to rule out CNS involvement 1
• If respiratory insufficiency or elevated CPK/troponin is present, perform cardiac examination with ECG and transthoracic echocardiogram to evaluate for possible myocarditis 1
• Obtain neurological consultation 1
• Conduct electrodiagnostic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies 1

Treatment Algorithm Based on Disease Severity

Mild Disease (MGFA Class I-II: Ocular or Mild Generalized Weakness)

• Start pyridostigmine at 30 mg PO three times daily 1, 2
• Gradually increase to maximum of 120 mg PO four times daily as tolerated 1
• If symptoms persist despite optimal pyridostigmine dosing, add prednisone 0.5-1.5 mg/kg orally daily 1
• Wean medications based on symptom improvement 1

Moderate to Severe Disease (MGFA Class III-V)

• Initiate pyridostigmine as above 1
• Add corticosteroids (prednisone 1-1.5 mg/kg orally daily) 1, 3
• Consider hospital admission, possibly ICU-level monitoring for respiratory concerns 1
• If rapid improvement needed, initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/d) or plasmapheresis for 5 days 1
• Perform frequent pulmonary function assessment and daily neurologic review 1

Important Considerations and Precautions

• Avoid medications that can worsen myasthenia: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 1
• Monitor for side effects of pyridostigmine, which occur in up to 91% of patients, including flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 4
• Be aware that diarrhea, abdominal cramps, and muscle twitching are common reasons for discontinuation of pyridostigmine 4
• For patients with thymoma, thymectomy should be considered as part of the treatment plan 3, 5
• Immunosuppressive therapies such as azathioprine may be considered for patients who cannot tolerate or do not respond adequately to corticosteroids 3, 6

Long-term Management Considerations

• Pyridostigmine provides only partial benefit in many cases, and most patients eventually require long-term immunosuppressive therapies 7
• Different MG subtypes (early-onset, late-onset, thymoma-associated, MuSK-positive, LRP4-positive, seronegative, ocular) may respond differently to various treatments 5
• Patients with ocular MG who fail to respond to symptomatic treatment may benefit from early treatment with corticosteroids 3
• For refractory cases, consider rituximab, especially in MuSK-positive patients 3, 6

Remember that myasthenia gravis can rapidly progress to respiratory compromise, so close monitoring is essential, particularly when initiating treatment 1.