What are the clinical features of myasthenia gravis and how are they classified?

Clinical Features and Classification 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, 2

Core Clinical Features

• Fluctuating weakness: The hallmark of myasthenia gravis is muscle weakness that worsens with continued activity and improves with rest 2
• Fatigability: Symptoms typically worsen as the day progresses or with repetitive use of affected muscles 2
• Variable presentation: The pattern of weakness can change during examination, making myasthenia gravis a "great masquerader" 2
• Proximal muscle involvement: Weakness generally affects proximal muscles more than distal ones 1
• Bilateral presentation: While weakness can be asymmetrical, it is always bilateral 1

Ocular Manifestations

• Ptosis (drooping eyelids): Often the first symptom to appear and may be unilateral or bilateral 1, 2
• Diplopia (double vision): Results from extraocular muscle weakness 2
• Variable strabismus: Misalignment of eyes that can change during examination 2
• Slow ocular saccades: Characteristic finding in myasthenia gravis 2
• Ice pack test: Temporary improvement of ocular symptoms with application of ice is characteristic 2

Bulbar Manifestations

• Dysarthria: Slurred speech due to weakness of speech muscles 1, 2
• Dysphagia: Difficulty swallowing that can lead to choking or aspiration 1, 2
• Facial weakness: Reduced facial expressions and difficulty closing eyes 1, 2
• Neck weakness: Difficulty holding up the head (head drop) 2

Limb and Respiratory Manifestations

• Limb weakness: Typically more proximal than distal, affecting shoulders and hips more than hands and feet 1
• Respiratory muscle weakness: Can lead to respiratory insufficiency or failure, representing the most serious manifestation 1, 2
• Neck and trunk weakness: Can affect posture and mobility 1

Disease Classification

By Antibody Profile

• AChR antibody-positive MG: Found in 80-85% of patients with generalized MG 3
• MuSK antibody-positive MG: Found in 5-8% of patients 3
• LRP4 antibody-positive MG: Found in <1% of patients 3
• Seronegative MG: Approximately 10% of patients have no detectable antibodies to known antigens 3

By Distribution of Weakness

• Ocular MG: Affects only eye muscles (15% of cases), causing ptosis and diplopia 4, 2
• Generalized MG: Affects multiple muscle groups beyond the eyes (85% of cases) 4

By MGFA Clinical Classification

• Class I: Ocular MG only (ptosis, diplopia) 1
• Class II: Mild generalized weakness 1
  • IIa: Predominantly affecting limbs, axial muscles, or both
  • IIb: Predominantly affecting oropharyngeal, respiratory muscles, or both
• Class III: Moderate generalized weakness 1
  • IIIa: Predominantly affecting limbs, axial muscles, or both
  • IIIb: Predominantly affecting oropharyngeal, respiratory muscles, or both
• Class IV: Severe generalized weakness 1
  • IVa: Predominantly affecting limbs, axial muscles, or both
  • IVb: Predominantly affecting oropharyngeal, respiratory muscles, or both
• Class V: Myasthenic crisis requiring intubation 1

By Age of Onset

• Neonatal MG: Transient form passed from mother to infant 2
• Congenital MG: Non-immune mediated form present at birth 2
• Juvenile MG: Autoimmune form in children 2
• Adult-onset MG: Most common form, typically affects women in their 30s-40s and men later in life 2

Natural History and Complications

• Disease progression: 50% of patients initially present with ocular symptoms only, with 50-80% of these developing generalized MG within a few years 2
• Exacerbations: Most patients experience at least one exacerbation during the course of their illness 5
• Myasthenic crisis: Life-threatening respiratory failure requiring ventilatory support 1, 2
• Thymoma association: About 10-20% of patients with AChR MG have thymoma 2, 3
• Comorbid autoimmune diseases: Increased risk of other autoimmune conditions such as thyroid disorders 6

Diagnostic Approach

• Clinical examination: Demonstration of fatigable weakness with improvement after rest 7
• Antibody testing: AChR, MuSK, and LRP4 antibodies 1, 3
• Electrodiagnostic studies: Repetitive nerve stimulation and single-fiber EMG 1, 3
• Pulmonary function assessment: Vital capacity and negative inspiratory force measurements 1
• Imaging: Consider MRI of brain/spine to rule out other causes 1
• Cardiac evaluation: If respiratory insufficiency or elevated CPK/troponin present 1

Treatment Considerations Based on Classification

• All grades of myasthenia gravis warrant thorough evaluation due to potential for respiratory compromise 1
• Grade 2 (MGFA class 1-2): Consider pyridostigmine and corticosteroids if symptoms interfere with daily activities 1
• Grade 3-4 (MGFA class 3-4): May require hospitalization, IVIG or plasmapheresis, and higher doses of corticosteroids 1
• Thymectomy: Consider especially if thymoma is present 2

Important Clinical Pitfalls

• Medications to avoid: Beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides can worsen myasthenia 1
• Atypical presentations: Young children may present with nonspecific symptoms like pain, refusal to bear weight, or unsteady gait 1
• Differential diagnosis: Consider Miller Fisher variant of Guillain-Barré syndrome and oculobulbar myositis which can have overlapping symptoms 1
• Monitoring: Regular assessment of respiratory function is critical to prevent life-threatening complications 2