LEMS Linked to Lung Cancer Highlights Importance of Antibody Testing, Case Report Says

A case of Lambert-Eaton myasthenic syndrome (LEMS) that occurred secondary to lung cancer highlights the need for comprehensive antibody testing when doctors suspect that the immune system might be attacking the nervous system.

The case was described in Thoracic Cancer, in the paper, “Anti-SOX1 antibody-positive paraneoplastic neurological syndrome presenting with Lambert-Eaton myasthenic syndrome and small cell lung cancer: A case report.”

When cells in the body become cancerous, the immune system is responsible for killing them. To do this, immune cells ‘look’ for the proteins that cells are expressing and, if those proteins seem suspicious, they become activated and work to kill the cancer cells.

However, cancer cells also express many proteins that are expressed by healthy cells, like those in the nervous system.

Sometimes this results in a ‘cross-wiring’ that leads the immune system to make antibodies that attack the body’s own nervous system. Such conditions are called paraneoplastic neurological syndromes (PNSs).

These syndromes are estimated to affect about 1% of people with cancer, most commonly people with small-cell lung cancer (SCLC).

“PNS of the peripheral nervous system can present as neuropathy [nerve diseases], disorders of the neuromuscular transmission such as Lambert‐Eaton myasthenic syndrome (LEMS) or myasthenia gravis (MG),” the study from China states.

A 61-year-old man who came to the researchers’ hospital in Hohhot, in Inner Mongolia, with complaints of a bitter taste, which caused discomfort during meals, for three months. During this time, the patient also experienced some weakness in the lower limbs and difficulty walking.

Over the next few days, irregular eye movements were observed, and the man reported feelings of vertigo, dizziness, and difficulty moving. These were later followed by evidence of confusion that is characteristic of brain inflammation.

A number of diagnostic laboratory tests were performed; these included screening to detect common nervous system-targeting antibodies associated with inflammatory processes, which are called onconeural antibodies.

“Well characterized onconeural antibodies including Hu‐Ab, Ri‐Ab, Tr‐Ab, GAD‐Ab, Yo‐Ab, CV2‐Ab, ANNA‐3‐Ab, PCA2‐Ab, Ma2‐Ab, and anti Amphiphysin‐Ab all tested negative,” the scientists wrote.

Researchers found that the anti‐SOX1 antibody was positive. Electrodiagnostic studies also pointed to LEMS. This, along with the positive anti-SOX1 antibodies, led researchers to diagnose the patient with LEMS.

Proteins in the SOX family — which play important roles in development — are often the target of antibodies that cause LEMS in people with tumors, but it’s rare to find these antibodies in people without tumors. Therefore, SCLC was suspected.

This lung cancer was diagnosed through a subsequent biopsy, and the patient was started on chemotherapy.

“[T]his finding encourages the testing of comprehensive onconeural antibodies,” the report’s authors concluded, adding, “when neurologists evaluate a patient with LEMS, routine screening for an underlying tumor should be carried out.”