What are the symptoms and treatment of myasthenia gravis?

Symptoms and Treatment of Myasthenia Gravis

Myasthenia gravis is characterized by fatigable or fluctuating muscle weakness that typically affects proximal more than distal muscles, with ocular and bulbar involvement being common presenting features that can progress to potentially life-threatening respiratory compromise. 1

Clinical Presentation

Characteristic Symptoms

• Muscle weakness that worsens with activity and improves with rest - the hallmark of myasthenia gravis 2
• Proximal muscle weakness more pronounced than distal weakness 1
• Bilateral presentation is common, although weakness can be asymmetrical 1

Ocular Manifestations (Often Initial Symptoms)

• Ptosis (drooping eyelids) - may be unilateral or bilateral 1
• Diplopia (double vision) from extraocular muscle weakness 1
• Variable strabismus and slow ocular saccades 1

Bulbar Manifestations

• Dysarthria (slurred speech) 1
• Dysphagia (difficulty swallowing) 1
• Facial weakness 1
• Neck weakness 1

Respiratory Involvement

• Respiratory muscle weakness - can lead to respiratory insufficiency or failure, representing the most serious manifestation 1
• May progress to myasthenic crisis requiring ventilatory support 1

Disease Classification (MGFA)

• Class I: Ocular MG only (ptosis, diplopia) 1
• Class II: Mild generalized weakness 1
• Class III: Moderate generalized weakness 1
• Class IV: Severe generalized weakness 1
• Class V: Myasthenic crisis requiring intubation 1

Diagnostic Approach

Laboratory Testing

• Acetylcholine receptor (AChR) and antistriated muscle antibodies in blood 3
• If AChR antibodies are negative, consider muscle-specific kinase and lipoprotein-related 4 antibodies 3
• CPK, aldolase, ESR, CRP to evaluate for possible concurrent myositis 3

Functional Testing

• Pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) 3
• Electrodiagnostic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies 3
• Ice pack test for ocular symptoms (highly specific) 4

Imaging

• MRI of brain and/or spine to rule out CNS involvement or alternative diagnoses 3
• If respiratory insufficiency or elevated CPK/troponin T, perform cardiac examination with ECG and TTE for possible concomitant myocarditis 3

Treatment Options

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor) 5
  • Starting at 30 mg orally three times daily
  • Gradually increase to maximum of 120 mg orally four times daily as tolerated 3

Second-Line Treatment

• Corticosteroids for moderate to severe symptoms 3
  • Prednisone 1-1.5 mg/kg orally daily for Grade 2 symptoms
  • Methylprednisolone 1-2 mg/kg daily for more severe cases 3

For Severe Disease (Grade 3-4)

• Intravenous immunoglobulin (IVIG) 2 g/kg IV over 5 days (0.4 g/kg/day) 3
• OR plasmapheresis for 5 days 3
• Hospitalization with possible ICU-level monitoring 3

Additional Treatment Options

• Thymectomy (especially if thymoma is present) 6, 7
• Immunosuppressive agents (azathioprine, mycophenolate mofetil) 7, 8
• For refractory cases: rituximab, cyclophosphamide, or eculizumab 8

Important Considerations and Pitfalls

Medications to Avoid

• β-blockers 3
• IV magnesium 3
• Fluoroquinolones 3
• Aminoglycosides 3
• Macrolides 3

Monitoring

• Frequent pulmonary function assessment for patients with generalized MG 3
• Daily neurologic review for hospitalized patients 3
• Regular monitoring of symptoms and medication side effects 6

Disease Progression

• 50-80% of patients who initially present with ocular symptoms may progress to generalized MG 1
• ICPi-associated myasthenia gravis may be monophasic and may not require additional corticosteroid-sparing agents 3