LEMS-associated Respiratory Problems May Lead to Heart Dysfunction, Case Report Shows

Lambert‐Eaton myasthenic syndrome-associated diaphragm weakness and subsequent respiratory problems may impair heart function, a case study shows.

The report, “Lambert Eaton Myasthenic Syndrome Presenting as Hypoventilation-Induced Right Heart Dysfunction,” was accepted for presentation at the American Thoracic Society (ATS) 2020 International Conference, which was planned for May 15–20 in Philadelphia but was canceled due to the COVID-19 pandemic. ATS is planning to hold a virtual conference in August.

The study’s abstract was published in the American Journal of Respiratory and Critical Care Medicine.

Lambert‐Eaton myasthenic syndrome (LEMS) is characterized by the production of autoantibodies — antibodies that wrongly attack the body’s own tissues — against voltage-gated calcium channels (VGCC). These proteins are found at the neuromuscular junction — the site where motor nerve cells meet with muscle cells — and are key for nerve-muscle communication.

In up to 60% of cases, LEMS is caused by an underlying cancer, most commonly small cell lung cancer (SCLC). Cancer cells may be targeted by antibodies produced by the immune system, which may cross-react with VGCC and result in LEMS symptoms.

Regardless of the cause, immune responses against VGCC impair the communication between nerve and muscle cells, leading to muscle weakness mainly affecting the lower limbs, but also the muscles involved in swallowing and breathing, such as the diaphragm.

“Respiratory failure can occur late in the disease course and thus LEMS should be considered as part of the differential diagnosis in patients with chronic hypoventilation,” the researchers wrote. Hypoventilation is breathing that is too shallow or too slow to meet the body’s oxygen needs.

These researchers in the U.S. reported the case of a 57-year-old man with hypoventilation-associated heart dysfunction in the setting of underlying LEMS.

The man, who was a former smoker and was underweight, with a body mass index of 17, was admitted to the hospital with weakness, shortness of breath, and swelling in his lower extremities. An echocardiogram showed right-sided heart dysfunction, meaning the right side of his heart was not efficiently pumping blood.

Chest imaging did not detect lung tissue abnormalities or blockage in any lung arteries. But additional tests revealed impaired lung function, suggesting that the cause of his hypoventilation could be diaphragm weakness.

He underwent an electromyography — a muscle test that measures electrical impulses sent by the brain to the muscles via nerve cells — which confirmed the presence of weak nerve cell signals and alterations after exercise, consistent with LEMS.

A LEMS diagnosis was confirmed through a blood test that detected the presence of antibodies against VGCC.

“In this unique case the patient also developed right heart dysfunction as a result of pulmonary vasoconstriction in the setting of chronic [low oxygen in the blood],” the researchers wrote.

Prior to discharge, the man was given intravenous immunoglobulin therapy. As of the study’s completion, he was being treated with prednisone and azathioprine (two immunosuppressants), which considerably eased his symptoms.

While further tests did not detect the presence of any underlying cancer, but he continues to be monitored closely for any signs of cancer.

“The diagnosis of LEMS can aid in early diagnosis and treatment of SCLC,” the researchers wrote, adding that “aggressive [cancer] screening and treatment is critical to the management of these patients.”