Is Your MG Actually LEMS?

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by BNS Staff |

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Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG) are two types of autoimmune disorders that disrupt the communication between nerves and muscles. Since MG and LEMS can have similar symptoms, they may be misdiagnosed for one or the other. If you were diagnosed with MG and your symptoms are not getting better with treatment, it’s important not to dismiss the possibility of your condition being LEMS. Learn the difference between the two disorders below to help ensure you’re on the right treatment path.

What Is LEMS?

LEMS occurs when the immune system attacks the place where a muscle and nerve connect, known as the neuromuscular junction.1 At the neuromuscular junction, one of your nerve cells communicates with your muscle by releasing acetylcholine—a chemical messenger that enables your muscle to contract.

If you have LEMS, however, antibodies attack the calcium channels located at the end of the nerve cell that allows acetylcholine to be released.1 This leads to less acetylcholine release, which results in a reduction of muscle contraction, and ultimately a weakening of the muscle.

About 50% to 60% of LEMS cases are caused by cancer, commonly by a type known as small cell lung cancer.2 In small cell lung cancer, the cancer cells also use calcium channels for communication.3 When the body creates antibodies to fight these cancer cells, it mistakenly recognizes the calcium channels at the end of nerve cells as cancer cells also and attacks them.

LEMS can occur in the absence of cancer, but the reason for this is still unknown. Studies have associated that having a family history of LEMS can be a possible factor in addition to having other autoimmune disorders such as diabetes and rheumatoid arthritis.2, 4

Symptoms

Muscle weakness, especially in the legs, is the most common symptom associated with LEMS, but other symptoms can include:5, 6

  • Weight loss
  • Muscle pain
  • Slurred speech
  • Difficulty swallowing
  • Drooping eyelids
  • Dry mouth
  • Constipation
  • Dizziness
  • Erectile dysfunction

What Is MG?

Similar to LEMS, MG is a result of the immune system’s attack on the neuromuscular junction. But unlike LEMS, antibodies attack acetylcholine receptors on your muscles instead of the calcium channels at the end of your nerve cells.7 This prevents acetylcholine from enabling the muscles to contract.

The reason why MG occurs is unclear. Experts suggest that an abnormal thymus gland may be a factor. From infancy to puberty, the thymus gland helps control the immune system and creates infection-fighting white blood cells known as T-lymphocytes or T cells.

After puberty, the thymus gland usually becomes smaller and is replaced by fat. For many adults with MG, however, the thymus gland remains large.7 Scientists believe that the abnormal thymus gland may be giving incorrect instructions to the immune system, leading to MG.7 Research suggests that a family history of MG and other autoimmune disorders may be risk factors of MG as well.8

Symptoms

Weakness of the eye muscles is the most common symptom of MG, but others can include:7

  • Drooping of one or both eyelids
  • Blurred or double vision
  • Slurred speech
  • Difficulty swallowing
  • Difficulty showing facial expressions
  • Shortness of breath
  • Weakness in the neck, arms, fingers, and legs

Telling the Difference

One study revealed that more than one-third of misdiagnosed LEMS patients were diagnosed with MG.2 Since MG and LEMS can have similar symptoms, it may be difficult to distinguish them from each other. However, differences in symptom patterns and antibodies can help tell them apart, which can help ensure an accurate diagnosis.

Symptom Patterns

LEMS and MG are known to have distinct symptom patterns. LEMS commonly affects your lower body first, causing leg weakness. Weakness may then spread up your body and affect the upper limbs, such as your arms.5 Contrarily, MG often affects your upper body first, most notably your eye, and then spreads to your lower body.2

In addition, signs of autonomic dysfunction and how your body feels after exercise can also be distinguishing factors.5 Autonomic dysfunction refers to an improper function of the autonomic nervous system—the system responsible for involuntary body functions like heart rate and blood pressure.

Symptoms of autonomic dysfunction can include decreased sweating, constipation, and erectile dysfunction. Those with LEMS usually have such kind symptoms, but it is uncommon for those with MG.2

If you have LEMS, you may see a slight improvement of symptoms temporarily during exercise. But with MG, exercise usually makes your symptoms worse.5

LEMS and Myasthenia Gravis Comparison Chart

Antibody Differences

People with LEMS and MG typically produce certain types of antibodies that attack the neurotransmitter junction. A majority of those with LEMS have specific antibodies known as P/Q-type voltage-gated calcium channel (VGCC) antibodies.10 These antibodies are the ones that attack calcium channels.

On the other hand, most MG patients have specific antibodies known as acetylcholine receptor (AChR) antibodies.10 These antibodies attack the acetylcholine receptors on muscles.

Although rare, MG patients who do not have AChR antibodies may instead have antibodies known as muscle-specific kinase (MuSK) antibodies.11 These antibodies target proteins in the neuromuscular junction that help with the transmission of acetylcholine.

An antibody (serological) test looks to see which antibodies your immune system is making, telling which condition you may have. It is important to know that your body may not always produce enough antibodies that a test can detect, and other testing methods will be needed to help form a correct diagnosis. Typically, nerve conduction studies and an imaging test such as a computed tomography (CT) scan is used for further testing.

A nerve conduction study measures how fast and how well your muscles respond to electrical stimulation. With MG, it is common for your muscles to fatigue in the initial stages of the study from the application of low-frequency electrical stimulation.12 If you have LEMS, muscle fatigue from low-frequency stimulation is more common in the later stages of the study.12

A CT scan is generally used to see if you have an enlarged thymus gland or small cell lung cancer, which can help clarify if you have MG or LEMS.12

Stay Informed with LEMS Aware

If you or someone you know is affected by LEMS, it can be helpful to have a resource to look to for information and updates about this condition. The number of those with LEMS is small, which is why LEMS Aware allows patients to be a part of a LEMS community where the sharing of information, lifestyle tips, and stories take place.

To learn more about LEMS and how LEMS Aware helps you stay informed, visit www.lemsaware.com, and be sure to sign-up to receive updates on emerging LEMS news and information.

And if you suspect your MG may be LEMS, talk with your doctor to ensure you received a correct diagnosis, and check out the “Could it be LEMS?” page on lemsaware.com, where you can download the symptom tracker and further your understanding of LEMS symptoms.

References:

  1. Jayarangaiah A, Theetha Kariyanna P. Lambert-Eaton myasthenic syndrome. Updated July 12, 2020. https://www.ncbi.nlm.nih.gov/books/NBK507891/
  2. Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011 Dec;10(12):1098-107. doi: 10.1016/S1474-4422(11)70245-9
  3. Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ. Lambert-Eaton myasthenic syndrome. Neurol Clin. 2018;36(2):379-394. doi:10.1016/j.ncl.2018.01.008
  4. Schoser B, Eymard B, Datt J, Mantegazza R. Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer. J Neurol. 2017 Sep;264(9):1854-1863. doi: 10.1007/s00415-017-8541-9
  5. 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. doi: 1017/cjn.2016.268
  6. John Hopkins Medicine. Lambert-Eaton syndrome. https://www.hopkinsmedicine.org/health/conditions-and-diseases/lamberteaton-syndrome
  7. National Institute of Neurological Disorders and Stroke (NINDS). Myasthenia gravis fact sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet. Modified April 27, 2020.
  8. Green JD, Barohn RJ, Bartoccion E, et al. Epidemiological evidence for a hereditary contribution to myasthenia gravis: a retrospective cohort study of patients from North America. BMJ Open. 2020;10:e037909. doi: 10.1136/bmjopen-2020-037909
  9. Cleveland Clinic. Myasthenia gravis (MG). Reviewed April 7, 2021.
  10. Ivanovski T, Miralles F. Lambert-Eaton myasthenic syndrome: early diagnosis is key. Degener Neurol Neuromuscul Dis. 2019;9:27-37. doi:10.2147/DNND.S1
  11. Koneczny I, Cossins J, Vincent A. The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J Anat. 2014;224(1):29-35. doi:10.1111/joa.12034
  12. Nicolle MW. Myasthenia gravis and Lambert-Eaton myasthenic Syndrome. Continuum. 2016;22(6):1978-2005. doi: 10.1212/CON.0000000000000415

2021 Myasthenia Gravis Survey Results

BioNews Survey Infographic

Myasthenia Gravis News conducted a survey from Feb. 11-March 28 to gain greater insight into the characteristics of the MG community and disease management. Results of the survey have now been published. Click on the image to view the infographic, and click here to read the story.