Differences Between Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) differ primarily in their pathophysiology, with MG affecting postsynaptic acetylcholine receptors and LEMS affecting presynaptic voltage-gated calcium channels, resulting in distinct clinical presentations and treatment approaches.
Pathophysiology
Myasthenia Gravis
- Autoimmune disorder affecting the postsynaptic membrane at the neuromuscular junction
- B-cell mediated autoimmune disorder with antibodies against acetylcholine receptors (AChR) in 80-85% of cases 1
- Some patients have antibodies against muscle-specific kinase (MuSK) instead 2
- Associated with thymus abnormalities (hyperplasia or thymoma) 2
Lambert-Eaton Myasthenic Syndrome
- Autoimmune disorder affecting the presynaptic membrane
- Antibodies directed against P/Q-type voltage-gated calcium channels (VGCC) 1, 3
- Often paraneoplastic (associated with small-cell lung cancer in 50-60% of cases) 1
- Prevents release of acetylcholine vesicles, decreasing synaptic transmission 1
Clinical Presentation
Myasthenia Gravis
- Initial symptoms involve extraocular muscles in 59% of patients 4
- Ocular symptoms (ptosis, diplopia) are the first presentation in 50% of patients 2
- Bulbar symptoms (dysarthria, dysphagia) in 29% as initial presentation 4
- Weakness follows a craniocaudal pattern (head to toe) 4
- Fatigable weakness that worsens throughout the day 2
- Symptoms improve with rest 2
Lambert-Eaton Myasthenic Syndrome
- Initial symptoms involve limb muscles in 95% of patients 4
- Weakness follows a caudocranial pattern (legs to head) 4
- Proximal leg weakness is present in all patients 4
- Ocular symptoms are rarely the presenting feature (0%) 4
- Autonomic symptoms (dry mouth, constipation) are common 1
- Strength may temporarily improve with brief exercise (post-tetanic potentiation) 3
Diagnostic Features
Myasthenia Gravis
- Anti-acetylcholine receptor antibodies positive in 80-85% of patients 2
- Anti-MuSK antibodies in some seronegative cases 2
- EMG shows decremental response to repetitive nerve stimulation 2
- Ice pack test and Tensilon (edrophonium) test are highly specific 2
- Single-fiber EMG has >90% sensitivity 2
Lambert-Eaton Myasthenic Syndrome
- Anti-VGCC antibodies (type P/Q) positive in >90% of cases 1
- EMG shows incremental response to high-frequency stimulation 1
- Requires screening for underlying malignancy, especially small-cell lung cancer 1
- Diagnosis generally made by clinical characteristics, EMG, and anti-VGCC antibodies 1
Treatment Approaches
Myasthenia Gravis
- Acetylcholinesterase inhibitors (pyridostigmine) 2
- Immunosuppressive therapy (corticosteroids, azathioprine, mycophenolate) 2
- Thymectomy indicated for all cases of thymoma 2
- Plasma exchange and IVIG for crisis or severe symptoms 2
Lambert-Eaton Myasthenic Syndrome
- Treatment of underlying malignancy if present 3
- Acetylcholinesterase inhibitors (less effective than in MG) 3
- Agents that augment quantal release of acetylcholine (3,4-diaminopyridine) 3
- Immunosuppressive therapy 3
- IVIG may be beneficial 1
Clinical Pearls and Pitfalls
- In a patient with suspected neuromuscular junction disorder, ocular weakness as the first symptom virtually excludes LEMS 4
- Limb weakness confined to the arms is found only in MG, not in LEMS 4
- Both conditions can cause respiratory compromise requiring close monitoring 2
- Certain medications can worsen both conditions (β-blockers, fluoroquinolones, aminoglycosides) 2
- LEMS should prompt thorough cancer screening, especially for small-cell lung carcinoma 1
Rare Presentations
- Concomitant MG and LEMS can occur in rare cases, presenting a significant treatment challenge 5
- Emerging therapies like anti-CD19 CAR T cells show promise for refractory cases of combined MG/LEMS 5
Understanding these key differences is essential for accurate diagnosis and appropriate management of these neuromuscular junction disorders, ultimately improving patient outcomes and quality of life.