Recognizing and Managing Cancer-Associated Lambert-Eaton Myasthenic Syndrome - Episode 2
Understanding CA-LEMS Pathophysiology
Panelists discuss how CA-LEMS biology reflects an off-target antitumor immune response (often with SCLC) that generates antibodies against presynaptic VGCCs, reducing acetylcholine release and causing proximal weakness with brief strength improvement after repeated activation.
In this segment, the expert faculty shift from clinical presentation to the underlying biology of cancer-associated Lambert-Eaton myasthenic syndrome (LEMS). They explain that approximately 60% of LEMS cases occur alongside cancer—most commonly small cell lung cancer—driven by an off-target immune response initially directed at the tumor. The panel notes that emerging data suggest patients with concurrent LEMS may experience longer survival, likely reflecting a heightened antitumor immune activity that inadvertently targets presynaptic voltage-gated calcium channels. These antibodies impair calcium influx at the neuromuscular junction, reducing acetylcholine release and preventing proper depolarization of muscle fibers. This mechanistic failure produces the hallmark proximal weakness of LEMS. The faculty also highlight a unique clinical clue: temporary improvement in strength with repeated muscle activation, as repeated depolarization can briefly increase acetylcholine availability. Together, these insights help clinicians better understand the physiologic basis of symptoms in cancer-associated LEMS.
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