Dr Masserelli on the Clinical Presentation and Management of LEMS in SCLC

“It's very important to recognize that patients with [SCLC experiencing with LEMS] live long, therefore you know the need to recognize LEMS [earlier], and [giving] them appropriate treatment is important.”

Erminia Massarelli, MD, PhD, MS, chief of Oncology and Hematology at the UT Health East Texas HOPE Cancer Center, discussed the clinical presentation and management of Lambert–Eaton myasthenic syndrome (LEMS) in the context of small cell lung cancer (SCLC), emphasizing the importance of early recognition by oncologists.

LEMS is a paraneoplastic neuromuscular disorder caused by impaired acetylcholine release at the neuromuscular junction, leading to characteristic deficits in presynaptic transmission. Because its symptoms can overlap with other neuromuscular conditions—most notably myasthenia gravis—accurate differentiation is essential for timely diagnosis and appropriate treatment.

Massarelli highlighted several key distinctions between LEMS and myasthenia gravis, beginning with the pattern of muscle weakness. Myasthenia gravis typically presents with ocular and bulbar involvement, including ptosis, diplopia, and dysphagia. In contrast, LEMS is characterized predominantly by proximal muscle weakness, especially affecting the lower extremities, although the upper extremities may also be involved. This distribution of weakness should raise suspicion for LEMS in patients with suspected paraneoplastic syndromes.

Deep tendon reflexes offer an additional diagnostic clue, Massarelli noted. Reflexes are often decreased or absent in LEMS, whereas they tend to remain normal in myasthenia gravis. This distinction is clinically meaningful and may guide neurologic evaluation. Furthermore, the therapeutic approaches differ substantially. Myasthenia gravis is typically managed with acetylcholinesterase inhibitors, whereas LEMS responds to amifampridine, a potassium channel blocker that enhances presynaptic acetylcholine release. Amifampridine can improve symptoms rapidly and is considered the cornerstone of symptomatic management.

Importantly, Massarelli noted that although LEMS occurs in a minority of patients with SCLC, its presence may have prognostic implications. Data from a small cohort of patients suggested that those with LEMS had improved survival compared with patients with SCLC who did not present with the syndrome. Although the mechanism underlying this observation is not fully understood, it reinforces the value of recognizing LEMS promptly and initiating appropriate treatment.

Massarelli concluded that awareness of LEMS is critical for oncologists who manage patients with SCLC. Early identification, accurate differentiation from other neuromuscular disorders, and initiation of targeted therapy such as amifampridine may improve patient function and quality of life. Given the possible correlation between LEMS and improved survival, appropriate diagnosis and management may also have prognostic relevance in SCLC, she said.