Myasthenia Gravis for USMLE Step 1 & COMLEX-USA Level 1
Pathophysiology
Genetics and Immunology
Diagnosis
Pathological Findings
- Autoimmune disorder where antibodies (primarily IgG) target acetylcholine receptors at the neuromuscular junction.
- Results in impaired neuromuscular transmission, leading to muscle weakness.
Genetics and Immunology
- HLA Association: Linked to HLA-DR3.
- Thymus involvement: Thymic hyperplasia or thymoma present in many patients, indicating a role in pathogenesis.
- Ocular Symptoms: Ptosis and diplopia are common initial manifestations.
- Generalized Muscle Weakness: Affects facial, bulbar, and limb muscles; worsens with exertion, improves with rest.
- Respiratory Complications: Risk of myasthenic crisis, a life-threatening exacerbation leading to respiratory failure.
Diagnosis
- Serology: Detection of anti-acetylcholine receptor (AChR) antibodies; anti-MuSK antibodies may be present in AChR-negative cases.
- Electrophysiological Testing: Repetitive nerve stimulation shows decremental response; single-fiber electromyography (EMG) is highly sensitive.
- Pharmacologic Test: Edrophonium (Tensilon) test historically used, though less commonly now.
- Acetylcholinesterase Inhibitors: Pyridostigmine to increase acetylcholine availability at the neuromuscular junction.
- Immunosuppressive Therapy: Corticosteroids, azathioprine, or other agents for long-term control.
- Plasmapheresis/IVIG: Used in acute management or before surgery.
- Thymectomy: Indicated in patients with thymoma and considered in generalized disease.
Pathological Findings
- Muscle Biopsy: Typically normal; however, may show small type II fiber atrophy in chronic cases.
- Thymus Histology: Thymic hyperplasia or thymoma in many cases.
Commonly Tested Items on Step 1
- Autoantibodies: Anti-AChR and anti-MuSK.
- Clinical presentation: Ocular symptoms and generalized weakness that improves with rest.
- Thymus association: Role of thymic abnormalities in pathogenesis.
- Edrophonium test: Historical importance in diagnosis.
- Management principles: Acetylcholinesterase inhibitors and the role of thymectomy.