3 Things You Should Know About Identifying SCLC-LEMS

LEARNING OBJECTIVES

Upon successful completion of this activity, you should be better prepared to:

• Identify key clinical features and red flags of paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS)

• Apply guideline-recommended processes for diagnosing LEMS and evaluating patients for underlying malignancy

RELEASE DATE: February 1, 2026

EXPIRATION DATE: February 1, 2027

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Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune neuromuscular disorder that results in muscle weakness, is of importance to oncology because this syndrome can be diagnosed prior to or after a diagnosis of small cell lung cancer (SCLC).¹ Importantly, national guidelines have been updated regarding symptoms, diagnosis, and treatment of SCLC-LEMS. Here are 3 things you should know about identifying SCLC-LEMS.

1) LEMS Is Often Associated With SCLC and Results in Lower Quality of Life Decreased Quality of Life in Patients With LEMS

As many as 60% of cases of LEMS occur in association with SCLC.² There is some evidence that survival is longer in patients with SCLC-LEMS, as a retrospective analysis in 81 patients showed an overall survival of 17 months, compared with 7.0 months in patients with non-LEMS SCLC (P < .0001).³ In general, patients with LEMS experience a decreased quality of life (QOL), with a lower composite score for physical QOL parameters in patients with LEMS compared with the general population (55.9 vs 76.3 points, respectively; P < .0001) (Figure 1).³

In addition to SCLC-LEMS, nonparaneoplastic (autoimmune) LEMS can occur.⁴ In the case of nonparaneoplastic LEMS, the first peak of onset occurs at aged 35 years, with a second peak at aged 60 years; for paraneoplastic LEMS, the typical age of onset is 60 years.

Autoantibodies in LEMS and Diagnostic Testing

Autoantibodies at the neuromuscular junction (NMJ) contribute to the muscle weakness observed in LEMS.¹ Under normal conditions, depolarization of the nerve results in the ingress of calcium ions through voltage-gated calcium channels (VGCCs). As a result, vesicles that contain acetylcholine (ACh) will release the ACh into the NMJ, which ultimately leads to muscle contraction. In patients with LEMS, autoantibodies to the VGCCs block the influx of calcium ions, preventing ACh release and leading to muscle weakness. The presence of the anti-VGCC antibodies provides the basis for a key diagnostic test for LEMS.

2) LEMS Is Likely Underdiagnosed, and Symptomatic Patients Should Be Referred for Testing

Point Prevalence of LEMS

The proportion of a population with LEMS at a specific point in time, known as the point prevalence, was estimated to be 2.6 per 1 million for confirmed cases and 3.3 per 1 million for confirmed and probable cases.⁵ These figures are based on an analysis of 12.5 million records from the US Department of Veterans Affairs population for the period of October 1, 1999, through September 30, 2013, with the latter date used to calculate the point prevalence.⁵ Due to the low prevalence of LEMS, physicians should be aware of the symptoms of LEMS and the appropriate diagnostic procedures.

Key Symptoms of LEMS

The National Comprehensive Cancer Network (NCCN) guidelines for SCLC have been updated to include specific symptoms related to LEMS, particularly proximal muscle weakness and autonomic dysfunction.⁶ Patients with LEMS also exhibit weak or no reflexes.⁴ Symptoms appear to be similar between patients with paraneoplastic and nonparaneoplastic LEMS.⁴

Misdiagnosis and Underdiagnosis of LEMS

The neurologic symptoms of LEMS can overlap or be confused with those of other neurologic disorders. An analysis was carried out in a combined Dutch and British cohort of 241 patients with LEMS.¹ Only 42% of these patients received a correct diagnosis of LEMS (Figure 2).¹ The most common single misdiagnosis was myasthenia gravis (MG); other misdiagnoses included Guillain-Barré syndrome and amyotrophic lateral sclerosis.¹ A key symptomatic difference is that patients with LEMS have reduced or absent reflexes, but patients with MG have normal reflexes.⁷

The high rate of incorrect diagnoses may result in an underestimation of the actual incidence and prevalence of LEMS, with 90% or more cases of LEMS being undiagnosed in patients with SCLC.⁸ Therefore, patients with symptoms suspicious for LEMS should be referred for testing, which is discussed in the next section.

3) Anti-VGCC Antibody Testing and Electrodiagnostic Testing Are Key for Patients With LEMS Symptoms

Antibody Testing for LEMS

If a paraneoplastic neurologic syndrome is suspected, the updated NCCN guidelines for SCLC recommend neurologic workup in consultation with a neurologist, which may include testing for anti-VGCC antibodies (Table).⁶ To facilitate testing, no-cost anti-VGCC antibody testing is available based on a collaboration between a national diagnostic test provider and Catalyst Pharmaceuticals.⁹ A negative antibody testing result should be followed up with electrodiagnostic testing.¹

Electrodiagnostic Testing for LEMS

Repetitive nerve stimulation and analysis of the compound muscle action potential (CMAP) are used to reveal characteristic defects of LEMS.³ A low CMAP is observed in LEMS at rest, in contrast to a normal CMAP observed in patients with MG. With high-frequency stimulation (50 Hz) or postexercise stimulation, an increase in the CMAP of 100% or higher is typical of LEMS, but not in MG.⁴

Cancer Screening for Patients With LEMS-Related Symptoms and/or Anti-VGCC Antibodies

As mentioned at the start of this article, LEMS can occur both before and after a cancer diagnosis.¹ While patients with SCLC and neurologic symptoms should undergo a neurologic workup, similarly, patients with a LEMS profile and no known cancer should be considered for cancer screening. A scoring system known as DELTA-P incorporates factors such as age at onset, smoking history, and bulbar involvement to identify which patients with LEMS are at risk for also having SCLC.¹⁰

Key References

1.Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098-1107. doi:10.1016/S1474-4422(11)70245-9

6. NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 2.2026. Accessed November 5, 2025. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf

9. Diagnostic criteria and testing. Lemsawarehcp.com. Accessed January 8, 2026. https://www.lemsawarehcp.com/lems-testing-and-diagnosis/

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CME Posttest Questions

1. How do reflexes in patients with Lambert-Eaton myasthenic syndrome typically compare with those in patients with myasthenia gravis?

A. Stronger

B. Similar

C. Weaker

2. Your patient with small cell lung cancer (SCLC) is exhibiting proximal muscle weakness and autonomic dysfunction. Based on updated NCCN guidelines, which is the best option?

A. Start treatment with combination checkpoint blockade.

B. Coordinate a focused neurologic workup, including antibody testing for P/Q- and N-type voltage-gated calcium channel.

C. Obtain repeat tumor biopsy to reconfirm SCLC.

D. Initiate empiric intravenous immunoglobulin treatment.

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