3 Things You Should Know About Recognizing LEMS in Patients With SCLC
In patients with small cell lung cancer, Lambert-Eaton myasthenic syndrome leads to muscle weakness and can be discovered with no-cost testing such as anti-VGCC antibody testing.
The panel
RELEASE DATE: March 1, 2025
EXPIRATION DATE: March 1, 2026
LEARNING OBJECTIVES
Upon successful completion of this activity, you should be better prepared to:
• Identify clinical presentations of Lambert-Eaton myasthenic syndrome (LEMS) in SCLC patients.
• Apply diagnostic protocols for accurate and timely detection of LEMS in SCLC.
Accreditation/Credit Designation
Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Acknowledgment of commercial support
This activity is supported by an educational grant from Catalyst Pharmaceuticals, Inc.
Off-label disclosure/disclaimer
This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members, and do not reflect those of PER or any company that provided commercial support for this activity.
Instructions for participation/how to receive credit
1. Read this activity in its entirety.
2. Go to https://www.gotoper.com/hil25lems-postref to access and complete the posttest.
3. Answer the evaluation questions.
4. Request credit using the drop-down menu.
YOU MAY IMMEDIATELY DOWNLOAD YOUR CERTIFICATE.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disorder that results in muscle weakness.1 In this first of 2 articles on LEMS, the biology, key symptoms, and antibody testing related to LEMS will be discussed. The second article will further address diagnostic tests and treatment. Here are 3 things you should know about recognizing LEMS in patients with small cell lung cancer (SCLC).
1. Although LEMS is a rare disorder, it is often associated with SCLC.
LEMS Pathophysiology
In the normal neuromuscular junction, depolarization of the nerve results in the ingress of calcium ions through voltage-gated calcium channels (VGCCs).1 This results in vesicles containing the neurotransmitter acetylcholine (ACh) to migrate to the presynaptic membrane of the nerve and release ACh, which leads to muscle contraction (Figure 1A).1 In LEMS, autoantibodies to VGCCs inhibit the influx of calcium ions, ultimately leading to reduced release of ACh and symptoms such as muscle weakness (Figure 1B).1
Figure 1. Pathophysiology of LEMS
Prevalence of LEMS
The point prevalence of LEMS (ie, the proportion of a population with LEMS at a specific point in time) was estimated to be 2.6 per 1 million for confirmed cases and 3.3 per 1 million for confirmed and probable cases.2 This was based on an analysis of 12.5 million records from the US Veterans Affairs population from October 1, 1999, through September 30, 2013, with the latter date used to calculate the point prevalence.2
LEMS and SCLC
LEMS can be classified into 2 main subtypes: paraneoplastic LEMS that is associated with cancer and nonparaneoplastic (autoimmune) LEMS.3 The typical age of onset for paraneo-plastic LEMS is 60 years; for nonparaneoplastic LEMS, the first peak occurs at 35 years of age, and a second peak is noted at 60 years of age.
Approximately half of LEMS cases occur in association with SCLC.4 Patients with SCLC-LEMS may have improved survival. In a retrospective analysis involving 81 patients, those with SCLC-LEMS had an overall survival of 17 months, which was significantly longer than the 7.0 months seen in patients with non-LEMS SCLC (P < .0001).5 However, the quality of life score related to physical health was significantly worse in patients with LEMS than in the general population (55.9 vs 76.3 points, respectively; P < .0001).5
2. LEMS may be confused with other diseases, and it is likely underdiagnosed.
Key Symptoms of LEMS
The key symptoms in patients with LEMS are (1) weakness in the proximal muscles, particularly in the legs; (2) weak or no reflexes; and (3) autonomic dysfunction.3 There does not appear to be a major difference in symptoms between paraneoplastic and nonparaneoplastic LEMS.3
Confusion With Other Neurologic Disorders and Underreporting of LEMS
The symptoms present in patients with LEMS may be mistaken for those of other disorders. Indeed, in a combined Dutch and British cohort of 241 patients, 58% of patients with LEMS received a different diagnosis first; these incorrect diagnoses included myasthenia gravis (MG), Guillain-Barré syndrome, and amyotrophic lateral sclerosis.1
The second article in this series will go more into detail regarding differential symptoms, but 1 key difference is that patients with LEMS have reduced or absent reflexes, but patients with MG have normal reflexes.6 Because of incorrect diagnoses, the actual incidence and prevalence of LEMS may be underestimated, with 90% or more cases of LEMS being undiagnosed in patients with SCLC (Figure 2).7
Figure 2. Potential Underdiagnosis of SCLC-LEMS in Real-World Data
3. No-cost testing is available for patients with symptoms related to LEMS.
Testing of Patients With LEMS Symptoms
To ensure timely detection and diagnosis of LEMS, the NCCN guidelines for SCLC recommend a neurologic consult and/or a comprehensive paraneoplastic antibody panel if a paraneoplastic neurologic syndrome is suspected.8 No-cost anti-VGCC antibody testing is available for patients who have symptoms suggestive of LEMS as a result of a collaboration between a national diagnostic test provider and Catalyst Pharmaceuticals.9 It should be noted that 10% to 15% of patients with LEMS may not demonstrate the presence of anti-VGCC antibodies, so a negative antibody test should be followed up with electrodiagnostic testing.1
Cancer Screening for Patients With LEMS
LEMS can precede cancer and can be discovered after cancer diagnosis.7 Therefore, cancer screening should be considered for patients with LEMS-related symptoms and/or positive results on an anti-VGCC antibody test. The Dutch-English LEMS Tumor Association Prediction (DELTA-P) scoring system was developed to predict which patients with LEMS are at risk for also having SCLC (Figure 3).10 Various factors such as age at onset, smoking history, and bulbar involvement contribute to the score; patients with a score of 0 or 1 have an extremely low risk (0% or 3%, respectively) of having SCLC, whereas those with a score of 3 or higher have a high risk (≥ 84%).
Figure 3. DELTA-P Scoring System to Evaluate Patients with LEMS for SCLC10
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
8. NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 4.2025. Accessed January 18, 2025. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
9. Free LEMS antibody test from Catalyst. Firdapse. Accessed February 9, 2025. https://f9rdapsehcp.com/access-and-support/diagnostic-test/
For full reference list visit https://www.gotoper.com/hil25lems-postref
CME Posttest Questions
Claim Your CME Credit at https://www.gotoper.com/hil25lems-postref
1. How do reflexes in patients with LEMS typically compare with those in patients with MG?
A. Stronger
B. Similar
C. Weaker
2. Which of the following is TRUE regarding diagnostic
testing for LEMS?
A. A negative anti-VGCC antibody test is sufficient to rule out LEMS.
B. Cancer screening is not necessary for patients with a positive
anti-VGCC antibody test.
C. No-cost anti-VGCC antibody testing is available for patients with LEMS-related symptoms.
D. All of the above
To learn more about this topic, including information on comprehensive diagnostic testing and treatment of LEMS, go to https://www.gotoper.com/hil25lems-activity.
CME Provider Contact information
Physicians’ Education Resource®, LLC
2 Commerce Drive, Suite 110, Cranbury, NJ 08512
Toll-Free: 888-949-0045
Local: 609-378-3701
Fax: 609-257-0705
info@gotoper.com
Expanding Horizons in T-Cell Lymphoma Therapy: Focus on Personalized Treatment Strategies
Several lymphoma experts discuss the current T-cell lymphoma landscape, the need for new therapies, and ongoing research in the space.
