Post-exercise facilitation may help in LEMS diagnosis: Case report

Case shows need to monitor for LEMS with gallbladder carcinoma

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The lack of a reflex response that was relieved temporarily after exercise, a phenomenon known as post-exercise facilitation, is an early sign of Lambert-Eaton myasthenic syndrome (LEMS), a case report suggests.

The report described the case of a woman, 62, who had a neuroendocrine tumor in the gallbladder that had spread by the time she was diagnosed with LEMS. The case shows how “patients with small cell neuroendocrine carcinoma of the gallbladder probably need close monitoring for the development of LEMS,” the researchers wrote in  “Postexercise reflex facilitation in Lambert-Eaton myasthenic syndrome,” which was published in Practical Neurology.

In LEMS, the immune system attacks protein receptors on nerve cells called voltage-gated calcium channels (VGCCs), impairing nerve-muscle communication. The classical and typical signs of LEMS are leg muscle weakness, absence of deep tendon reflexes, and dysautonomia, or malfunction of the autonomic nervous system, which governs involuntary functions like heartbeat and breathing.

Diagnosing people without these signs is challenging as symptoms may overlap with other diseases that affect nerve-muscle communication, such as myasthenia gravis. Here, researchers in Singapore described the case of a 62-year-old woman whose LEMS was identified by post-exercise facilitation.

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Diagnosing LEMS

The patient had muscle weakness in the legs and occasional double vision for six months. She also had excessive facial sweating. An examination showed muscle leg weakness and mild droopiness on the left eyelid. Deep tendon reflexes were absent at first, but improved after brief exercise.

Dysautonomia was suspected, so the patient took a nerve-muscle conduction test, which measures a muscle’s electrical activity in response to nerve stimulation.

The results confirmed reduced muscle activity in response to stimulation of the left median nerve, which runs down the upper arm and continues into the forearm and hand, as well as the ulnar and tibial nerves. The ulnar nerve transmits electrical signals to muscles in the forearm and hand, and the tibial nerve transmits electrical signals to leg and foot muscles. The woman’s muscle response increased by more than 100% after 10 seconds of exercise, consistent with LEMS.

Blood work revealed antibodies against P/Q-type VGCCs, leading doctors to diagnose LEMS. The woman was started on 3,4-diaminopyridine, also known as amifampridine, Firdapse’s active ingredient.

Since many LEMS cases are linked to an aggressive form of lung cancer called small cell lung cancer (SCLC), a CT lung scan was ordered but before the woman could have it, she developed fever, jaundice (yellowing of the skin and eyes), low blood pressure, and began vomiting. Liver function tests indicated a problem with bile release and flow.

Tests confirmed small cell neuroendocrine carcinoma of the gallbladder, which had spread into the thorax, abdomen, and pelvis. The woman also had Klebsiella pneumoniae bacteria in her bloodstream.

She received antibiotics into the vein and had a procedure to drain bile from her body. Treatment with 3,4-diaminopyridine was halted due to liver dysfunction and she was given antibodies into the vein (intravenous immunoglobulin).

Since her cancer had spread, she received a palliative combination of chemo and immunotherapy. After four cycles, a partial response was detected with a reduction in the size of the primary tumor, as well in the lymph nodes in the liver and around the gallbladder. The therapy eased her fatigue, double vision, and facial sweating. At the time of publication, she was independent and scheduled to continue her anti-cancer therapy.

Physicians should “consider screening for extrapulmonary malignancy in people with LEMS who are nonsmokers and who do not appear to have a pulmonary malignancy,” the researchers said, adding “post-exercise testing of tendon reflex is an important bedside clinical test that may help provide early diagnostic clues for LEMS.”