Crosswalk sign that reads don't stop at seronegative MG

Recognize the Differences Between LEMS and MG

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On This Page LEMS VS MG TESTING

Acetylcholine receptor (AChR) antibody-negative results are a critical call for a second look1,2

When your patients test negative for myasthenia gravis (MG) antibodies, such as AChR, don’t stop at seronegative. Look out for Lambert-Eaton myasthenic syndrome (LEMS).1,2

The symptoms of LEMS can overlap with those of MG, increasing the risk of misdiagnosis or delayed diagnosis.1,2
This makes it critical to:

  • Maintain a high index of clinical suspicion throughout the evaluation1
  • Incorporate anti-voltage-gated calcium channel (VGCC) antibody testing and/or early electrodiagnostic testing in the initial workup1
  • Reassess patients with unresolved, atypical, or treatment-refractory symptoms promptly3

of people with LEMS receive 
at least 1 misdiagnosis,

most commonly MG2

A targeted diagnostic approach can influence your patient’s clinical course by enabling timely, appropriate management of their condition.1

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Symptoms and disease course help distinguish LEMS

Although LEMS can present with symptoms similar to MG, early identification of subtle clinical differences provides guidance for diagnosis.1



Detecting these nuances quickly can help you make informed decisions and implement the most appropriate treatment strategy.1

MG
LEMS

Craniocaudal pattern of spread, initial asymmetrical weakness

Caudal-to-cranial pattern of spread, symmetrical weakness

Early and prominent
oculobulbar involvement

Late-onset and mild
oculobulbar involvement

Preserved tendon reflexes

Hyporeflexia or areflexia

No autonomic dysfunction

Autonomic dysfunction

Muscle weakness worsens with exercise

Transient improvement of muscle strength with exercise, with fatigue that follows

Antibodies to AChR or MuSK
are usually found

Antibodies to VGCCs are usually found

Differentiating between LEMS and MG is critical, as a missed LEMS diagnosis could close the window for early cancer detection.4,5

Green walk sign

If you suspect LEMS, add a VGCC antibody test to your panels or treatment algorithm.1,3,5

Anti-VGCC antibody testing is critical to establishing a definitive diagnosis

Patients with seronegative MG may not have been screened for anti-VGCC antibodies. If your patient displays neurologic and/or autonomic symptoms or is refractory to treatment, follow up on your suspicions with a comprehensive autonomic neuromuscular/paraneoplastic panel.6,7

Ensure that VGCC antibodies are part of the panel of neurological/paraneoplastic tests that you request. Remember, if you are requesting an MG panel, VGCC antibody is not automatically included and may need to be requested separately.8,9

MuSK, muscle-specific kinase.

References: 1. Merino-Ramírez MÁ, Bolton CF. Review of the diagnostic challenges of Lambert-Eaton syndrome revealed through three case reports. Can J Neurol Sci. 2016;43(5):635-647. 2. Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098-1107. (appendix 1) 3. Nguyen A, Chukwuemeka A, Umeh JP. Lambert-Eaton myasthenic syndrome unmasked by administration of aggravating medications. Am J Med Case Rep. 2022;10(8):194-196. 4. Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ. Lambert-Eaton myasthenic syndrome. Neurol Clin. 2018;36(2):379-394. 5. Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098-1107. 6. Evoli A, Palace J, Spagni G, et al. 275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management. February 9-11, 2024; Hoofddorp, the Netherlands. Neuromuscul Dis. 2024;44:104468. doi:10.1016/j.nmd.2024.104468. 7. Evoli A, Palace J, Spagni G, et al. 275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management. February 9-11, 2024; Hoofddorp, the Netherlands. Neuromuscul Dis. 2024;44:104468(appendix 1). 8. Mayo Clinic Laboratories. MGMR. Accessed March 30, 2026. https://www.mayocliniclabs.com/test-catalog/overview/608980. 9. Mayo Clinic Laboratories. PAVAL. Accessed March 30, 2026. https://www.mayocliniclabs.com/test-catalog/overview/83380. 10. Harms L, Sieb J-P, Williams AE, et al. Long-term disease history, clinical symptoms, health status, and healthcare utilization in patients suffering from Lambert Eaton myasthenic syndrome: results of a patient interview survey in Germany. J Med Econ. 2012;15(3):521-530.