Lambert-Eaton Myasthenic Syndrome
Clinical Features
Proximal lower extremity weakness
LEMS begins proximally, symmetrically in the lower extremities: patients present with trouble standing or climbing stairs. Oculobulbar in involvement in LEMS is milder than in MG.
Reflex Facilitation
There are typically reduced reflexes, which increase with muscle facilitation. This is unlike in MG where the reflexes are typically normal.
Autonomic Dysfunction
LEMS is associated with autonomic dysfunction, often dry mouth, constipation, or erectile dysfunction.
Pathophysiology & Treatment
Pathology
LEMS is autoimmune in ~ 50% of cases and paraneoplastic due to small cell lung cancer (SCLC) in the other ~ 50%.
P/Q type voltage-gated calcium channel antibodies
Antibodies to the P/Q type voltage-gated calcium channel are ~ 95% sensitive in LEMS (90% in autoimmune, 100% in paraneoplastic).
- VGCC antibodies help differentiate LEMS from MG, in which they are only rarely positive.
SOX1 antibody
SOX1 antibody carries a high specificity (but low sensitivity) for SCLC; thus LEMS patients with positive SOX1 antibody have a high risk of an associated SCLC (note that these antibodies are present in non-LEMS patients with SCLC, as well).
SOX1 is an intracellular protein (specifically a transcription factor); it's alternate name: anti-glial nuclear-antibody (AGNA) helps us remember this.
Treatment: 3,4-diaminopyridine (3,4-DAP)
3,4-diaminopyridine (3,4-DAP) is the most effective management in LEMS. It blocks voltage-gated potassium channels, which lengthens depolarization and, thus, augments acetylcholine release.