What is the management, diagnostic approach, goal of management, prognosis, and complications of Myasthenia Gravis (MG)?

Management of Myasthenia Gravis: Diagnostic Approach, Treatment, Prognosis, and Complications

Myasthenia gravis (MG) requires a systematic diagnostic approach followed by targeted therapy, with the primary goal of reducing morbidity and mortality through symptom control and prevention of respiratory compromise.

Diagnostic Approach

Clinical Presentation

• MG 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 1
• Bilateral presentation is common, although weakness can be asymmetrical 1
• Ocular symptoms include ptosis (drooping eyelids) and diplopia (double vision) from extraocular muscle weakness 1
• Bulbar symptoms include dysarthria (slurred speech), dysphagia (difficulty swallowing), facial weakness, and neck weakness 1

Diagnostic Testing

• Acetylcholine receptor (AChR) antibody testing is the first-line serological test 2, 1
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 2, 3
• Electrodiagnostic studies are essential, with single-fiber electromyography being the gold standard (positive in >90% of patients with ocular MG) 3
• Repetitive nerve stimulation testing is less sensitive (positive in only one-third of patients with ocular MG) 3
• The ice pack test (applying ice over closed eyes for 2 minutes) is highly specific for MG, particularly for ocular symptoms 2, 3

Disease Classification

• The Myasthenia Gravis Foundation of America classifies MG into five classes: Class I (ocular MG only), Class II (mild generalized weakness), Class III (moderate generalized weakness), Class IV (severe generalized weakness), and Class V (myasthenic crisis requiring intubation) 1

Management

First-Line Treatment

• Pyridostigmine (acetylcholinesterase inhibitor) is the first-line treatment, starting at 30 mg orally three times daily and gradually increasing to a maximum of 120 mg orally four times daily as tolerated 2, 1
• About half of patients with strabismus-associated myasthenia show minimal response to pyridostigmine 3

Second-Line Treatment

• Corticosteroids are used as second-line treatment for moderate to severe symptoms, with 66-85% of patients showing a positive response 3, 2
• Careful monitoring is required due to potential initial worsening of symptoms and long-term side effects 1

Third-Line and Advanced Treatments

• Immunosuppressive therapy with azathioprine is effective as a steroid-sparing agent 3, 2
• Newer biological therapies include complement inhibitors (eculizumab, ravulizumab) and FcRn inhibitors (efgartigimod alfa-fcab) for refractory cases 4, 3
• Efgartigimod alfa-fcab has recently been FDA approved for patients who test positive for anti-acetylcholine receptor antibodies 3
• Thymectomy is indicated in all cases with thymoma and may substantially reduce symptoms in certain subpopulations 3

Crisis Management

• Differentiation between myasthenic crisis (disease exacerbation) and cholinergic crisis (medication overdose) is critical 5
• Myasthenic crisis requires more intensive anticholinesterase therapy 5
• Cholinergic crisis necessitates prompt withdrawal of all anticholinesterase drugs and possible use of atropine 5
• Intravenous immunoglobulin (IVIG) or plasmapheresis for 5 days are used to treat severe MG exacerbations 1

Goals of Management

• Reduction of diplopia and strabismus 3
• Restoration of normal ocular alignment, appearance, and improved self-image 3
• Restoration of binocular function 3
• Reduction of compensatory head position (if present) 3
• Prevention of morbidity and mortality from generalized MG 3

Prognosis

• 50-80% of patients who initially present with ocular symptoms may progress to generalized MG within a few years 1, 3
• Remission or stabilization of the disease is often possible after 2-3 years of treatment 3
• Surgical intervention for strabismus may be considered after disease stabilization if prism use is insufficient 3
• Modern targeted therapies provide new optimism for substantially more patients reaching minimal manifestation status 6
• Recurrence risk is relatively low (2-5%) 3

Complications

Respiratory Compromise

• Respiratory muscle weakness can lead to respiratory insufficiency or failure, which is potentially life-threatening 1
• Regular pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) is essential 2, 1

Medication-Related Complications

• Cholinergic crisis can occur with overdosage of pyridostigmine, characterized by increasing muscle weakness that may affect respiratory muscles 5
• Long-term steroid use can cause significant side effects 6

Surgical Considerations

• Particular care is needed with anesthetic agents due to potential respiratory muscle weakness 3
• More than one strabismus surgery may be necessary for patients with stabilized primary deviation 3

Medication Precautions

• Avoid β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides due to potential exacerbation of symptoms 2, 1

Multidisciplinary Management

• Diagnosis and management require collaboration between an experienced ophthalmologist and neurologist, particularly for patients with ocular involvement 3, 2
• Rehabilitation programs with physical and occupational therapy are crucial for recovery 3
• Psychological support may be beneficial as rapid loss of physical function can cause anxiety and/or depression 3