Delays and Misdiagnosis Common With Lung Cancer-linked LEMS

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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LEMS lung cancer | Lambert-Eaton News | delay diagnosis | Illustration of lungs

Misdiagnosis and delayed diagnosis are common among people with lung cancer-associated Lambert-Eaton myasthenic syndrome (LEMS), according to a small study in China.

Most patients showed signs of LEMS before their lung cancer diagnosis — such as muscle weakness and problems in the autonomic nervous system, which controls involuntary functions such as blood pressure, heart and respiratory rate, body temperature, and digestion. Slightly more than half of its 14 patients experienced respiratory symptoms.

These findings highlight the need to increase awareness of LEMS and its strong association with lung cancer to help avoid diagnostic delay and misdiagnosis, and ultimately improve the outcomes of both conditions, the researchers noted.

The study, “Developments in High Content Cellular Imaging Systems for Molecular Devices,” was published in the journal Contrast Media & Molecular Imaging.

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LEMS and small cell lung cancer | Lambert-Eaton News | illustration of a case study

Immune-Related Cancer Therapy Triggers LEMS in Elderly Patient

LEMS is caused by the immune system wrongly attacks voltage-gated calcium channels (VGCC) — proteins involved in nerve-muscle communication — leading to muscle weakness.

While this autoimmune disease can occur spontaneously, LEMS is frequently associated with cancer, as this calcium channel is also present at the surface of some cancer cells. In such cases, the antibodies produced by the immune system to fight cancer also end up affecting neuromuscular communication.

Almost yearlong delay in diagnosing lung cancer-associated LEMS

Notably, about 60% of LEMS patients are estimated to have lung cancer, most often small cell lung cancer (SCLC) — an aggressive type of cancer that is commonly seen in smokers.

However, reports on the clinical features of lung cancer-associated LEMS remain limited, especially in China, the researchers wrote.

With this in mind, a research team there retrospectively analyzed the databases of two Chinese hospitals, spanning 2013 to 2020, to identify cases of LEMS co-existing with lung cancer and describe their demographic and clinical data.

A total of 14 adults (nine men and five women) with lung cancer-related LEMS were identified. Their mean age at diagnosis was 67.1 years and most (71.4%) had a smoking history.

SCLC was the most common lung cancer type, being detected in all but one patient (92.9%), and nine patients (64.3%) had advanced stage cancer. Among the 10 tested for antibodies against VGCC, seven had positive results.

A LEMS diagnosis preceded a lung cancer diagnosis in 12 cases (85.7%). In these patients, lung cancer was detected at a median of 5.2 months after a LEMS diagnosis (range, 0.5 to 15 months). In the other two cases (14.3%), LEMS was diagnosed at the same time as cancer.

“The median interval between onset of symptoms and complete diagnosis of lung cancer coexisting with LEMS was 11.9 months,” or nearly one year, with a longest diagnostic delay of three years, the researchers wrote.

Most patients (85.7%) were initially misdiagnosed with other diseases, most often peripheral neuropathy, characterized by damage in the peripheral nervous system, which controls movement and sensation in the limbs.

Symptom onset was gradual in more than three-quarters of all cases (78.6%). The most frequent presenting symptom or sign was muscle weakness in the upper leg (60%), followed by dry mouth (57.1%) and reduced or absent tendon reflexes (50%), such as the reflex that occurs when a person’s knee is tapped.

Patients developed an average of four neurologic symptoms and signs, most commonly muscle weakness and autonomic problems — of which dry mouth and constipation were the most frequent.

Eye problems were reported in 21.4% of cases and bulbar symptoms, or those affecting the muscles responsible for chewing, swallowing, and speaking, were detected in 28.6%.

Respiratory problems were among early symptoms in eight patients (57.1%). All patients showed an abnormal chest CT scan and six had respiratory deficiencies on a lung function test called spirometry.

Cancer treatment eases LEMS symptoms

Three patients developed respiratory muscle weakness requiring noninvasive ventilation after receiving neuromuscular blocking medications typically used for anesthesia in surgery. They were either misdiagnosed or not treated for LEMS at the time of surgery.

Of note, people with LEMS have increased sensitivity to neuromuscular blocking drugs, and are at a higher risk of post-surgical respiratory failure.

Patients were followed for a period ranging from six months to five years. All were treated for lung cancer, most commonly with chemotherapy and radiation therapy to the chest, resulting in the complete or partial resolution of LEMS symptoms in nine patients (64.3%).

Two patients received intravenous immunoglobulin for LEMS, and experienced significant reductions in neurologic symptoms.

Eight patients died, although none of the deaths were due to neurologic symptoms. Median survival time for these patients was 18 months.

These findings highlight the high rate of delayed diagnosis and misdiagnosis in people with lung cancer-related LEMS.

Since “early identification of patients coexisting with LEMS and lung cancer is crucial to improving the prognosis of both conditions,” patients should be screened for cancer, especially in the lungs, as soon as LEMS is diagnosed and every six months for two consecutive years, the researchers wrote.

“Lower extremity weakness accompanying with respiratory symptoms should raise serious suspicion of lung cancer coexisting with [LEMS],” they added.

Large studies following people with lung cancer-related LEMS are needed to further describe this condition and assess treatment effectiveness.