From the Guidelines
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are distinct neuromuscular junction disorders with different pathophysiologies, where MG involves antibodies targeting postsynaptic acetylcholine receptors and LEMS involves antibodies targeting presynaptic voltage-gated calcium channels. The pathophysiological differences between MG and LEMS are crucial for diagnosis and treatment. MG is characterized by antibodies targeting nicotinic receptors, reducing the number of functional nicotinic receptors, as noted in a study published in Critical Care Medicine 1. In contrast, LEMS involves antibodies targeting presynaptic voltage-gated calcium channels (VGCCs), which disrupts calcium influx necessary for acetylcholine release from nerve terminals, as discussed in a review published in the Journal of Neurology, Neurosurgery and Psychiatry 1.
Key differences in pathophysiology
- MG: antibodies target postsynaptic acetylcholine receptors (AChRs), reducing the number of functional receptors and impairing muscle contraction
- LEMS: antibodies target presynaptic voltage-gated calcium channels (VGCCs), disrupting calcium influx necessary for acetylcholine release from nerve terminals Some key clinical features of these disorders include:
- MG: initial weakness that worsens with repeated activity (fatigue)
- LEMS: weakness that temporarily improves with repeated muscle use (facilitation) Additionally, LEMS is often paraneoplastic, associated with small cell lung cancer in about 60% of cases, whereas MG is rarely associated with malignancy but often linked to thymic abnormalities, as noted in the study published in the Journal of Neurology, Neurosurgery and Psychiatry 1.
Clinical implications
The differences in pathophysiology between MG and LEMS have significant implications for diagnosis and treatment. For example, patients with MG may require reduced doses of non-depolarizing neuromuscular blocking agents (NMBAs) due to their impaired neuromuscular transmission, as discussed in the study published in Critical Care Medicine 1. In contrast, patients with LEMS may respond to treatments that target the underlying autoimmune disorder, such as immunotherapy, as noted in the review published in the Journal of Neurology, Neurosurgery and Psychiatry 1.
Summary of key points
- MG and LEMS are distinct neuromuscular junction disorders with different pathophysiologies
- MG involves antibodies targeting postsynaptic acetylcholine receptors, while LEMS involves antibodies targeting presynaptic voltage-gated calcium channels
- The differences in pathophysiology have significant implications for diagnosis and treatment
- Patients with MG may require reduced doses of NMBAs, while patients with LEMS may respond to immunotherapy.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Pathophysiological Differences
The pathophysiological differences between Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) are primarily related to the targets of the autoimmune response.
- MG is characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor 2, which is a postsynaptic receptor 3.
- LEMS, on the other hand, is caused by antibodies directed against the PQ-type voltage-gated calcium channels 2, which are presynaptic voltage-operated calcium channels 3.
Clinical Implications
The differences in the targets of the autoimmune response have significant clinical implications.
- MG patients present with variable degrees and distribution of fluctuating weakness, which can be life-threatening 2.
- LEMS patients also experience fluctuating weakness, but the clinical presentation is distinct and often associated with an underlying small cell lung cancer 4.
Diagnostic and Therapeutic Considerations
The diagnosis and treatment of MG and LEMS also differ.