From the Guidelines
Myasthenia gravis is an autoimmune neuromuscular disorder characterized by antibody-mediated attack on acetylcholine receptors at the neuromuscular junction, leading to fluctuating muscle weakness and fatigability, particularly affecting ocular, bulbar, and proximal limb muscles. The pathophysiology of myasthenia gravis involves the reduction of functional acetylcholine receptors through several mechanisms, including direct blocking of receptor binding sites, increased receptor degradation, and complement-mediated destruction of the postsynaptic membrane 1. This results in a defect in neuromuscular transmission, causing the characteristic symptoms of the disease. The thymus gland plays a crucial role in this pathology, with thymic hyperplasia present in about 65% of patients and thymomas in 10-15% 1.
Key Features of Myasthenia Gravis
- Autoimmune disorder characterized by antibody-mediated attack on acetylcholine receptors
- Fluctuating muscle weakness and fatigability, particularly affecting ocular, bulbar, and proximal limb muscles
- Thymus gland plays a crucial role in the pathology, with thymic hyperplasia and thymomas present in a significant proportion of patients
- Disease severity often fluctuates, with exacerbations triggered by infections, stress, certain medications, and surgery
Treatment Approaches
- Enhancing neuromuscular transmission with acetylcholinesterase inhibitors, such as pyridostigmine bromide 1
- Suppressing the immune response with immunosuppressants, such as corticosteroids and azathioprine
- Surgical removal of the thymus gland in some cases, particularly in the presence of thymoma or in certain subpopulations with myasthenia gravis 1
Important Considerations
- Patients with myasthenia gravis are at risk for experiencing prolonged neuromuscular blockade due to a prolonged inactivation of succinylcholine, and may require careful management of anesthesia and neuromuscular blocking agents 1
- Discontinuing cholinesterase inhibitors on the day of surgery increases the risk of respiratory distress, highlighting the need for careful perioperative management 1
From the Research
Pathophysiology of Myasthenia Gravis
The pathophysiology of Myasthenia Gravis (MG) is characterized by:
- An autoimmune response against components of the neuromuscular junction (NMJ) 2
- Production of antibodies that attack the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) receptors, leading to impaired neuromuscular transmission 2, 3
- Loss of AChR from the postsynaptic membrane, resulting in weakness and fatigue of skeletal muscle 2
Mechanisms of Autoantibody-Mediated Damage
The mechanisms of autoantibody-mediated damage in MG include:
- Complement-mediated damage to the postsynaptic membrane 2
- Increased rate of AChR turnover, leading to loss of AChR from the postsynaptic membrane 2
- Disassembly of the neuromuscular junction by MuSK antibodies, disrupting synapse maintenance and adaptation 2
Clinical Presentation
The clinical presentation of MG can vary, but common symptoms include:
- Fluctuating muscle weakness, particularly in ocular, respiratory, bulbar, and skeletal muscles 3
- Fatigable ptosis, blurry vision, diplopia, change in facial expression, dysphagia, dysarthria, dyspnea, and limb weakness 3
Treatment and Management
Treatment and management of MG may involve:
- Acetylcholinesterase inhibitors to enhance neuromuscular transmission 4
- Immunotherapy, such as corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin 5
- Rituximab for severe seronegative juvenile MG 5
- Supportive general and ventilatory therapy for myasthenia gravis crisis (MGC) 6