Distinguishing CA LEMS from Myasthenia Gravis, ICI Toxicities, and Chemotherapy-Related Weakness in Small Cell Lung Cancer

Dr. Primdahl walks through clinical differentiation of CA LEMS from the most important diagnostic mimics encountered in SCLC. Versus myasthenia gravis: myasthenia gravis is more commonly diagnosed and typically presents with ocular and bulbar symptoms first (ptosis, diplopia, dysphagia), worsens with sustained activity (opposite to CA LEMS post-exercise facilitation), and is characterized by preserved reflexes and absent autonomic dysfunction. On bedside testing, sustained upward gaze in myasthenia gravis produces progressive ptosis, whereas CA LEMS produces paradoxical eyelid elevation. Myasthenia gravis has its own antibody profile (acetylcholine receptor and anti-MuSK antibodies) distinct from VGCC. In patients receiving immune checkpoint inhibitors, ICI-induced myasthenia gravis, myositis, and myocarditis can all produce proximal weakness resembling CA LEMS. Checking creatine kinase, acetylcholine receptor and MuSK antibodies, and troponin alongside VGCC antibodies supports differentiation. The presence of ICI exposure does not exclude CA LEMS; ICIs may theoretically exacerbate pre-existing autoimmune neuromuscular junction dysfunction.

Versus chemotherapy-induced peripheral neuropathy (CIPN): CIPN is predominantly sensory and length-dependent (distal before proximal), the opposite distribution from CA LEMS which is primarily motor and proximal. A predominant sensory complaint makes CA LEMS less likely. A key alarm symptom favoring a neuromuscular junction disorder is bulbar involvement (diplopia or dysphagia), warranting more urgent evaluation. CNS involvement from brain or leptomeningeal metastases should also be considered in the differential.

Dr. Shields shares a personal clinical example of a patient on dual immunotherapy with the ICI-toxicity triad of myasthenia gravis, myositis, and myocarditis with markedly elevated creatine kinase and troponin as an illustration of why precise diagnostic differentiation determines treatment.