Good Long-term Outcomes Seen in Japanese Study, Regardless of Cancer

Japanese patients with Lambert‐Eaton myasthenic syndrome (LEMS) show long-term neurological improvements with treatment regardless of whether they also have small cell lung cancer (SCLC), researchers report.

The study, “Long‐term prognosis of Japanese Lambert–Eaton myasthenic syndrome patients with or without small‐cell lung carcinoma,” was published in the journal Clinical & Experimental Neuroimmunology.

LEMS is characterized by immune system attacks on calcium channels in nerve cell endings, key to control of muscle movement. Patients experience muscle weakness mainly affecting the lower limbs, but can also have problems with speech and swallowing, and drooping eyelids.

Most LEMS cases are linked to an underlying cancer, commonly SCLC. Primary treatment of these patients is directed against the lung tumor, and their prognosis is generally poorer from those without cancer. Patients whose LEMS is not due to cancer typically have a normal life expectancy and in most cases benefit from immunosuppressive therapy.

But little is known about treatment response and long-term outcomes for LEMS patients with or without SCLC in Japan.

Researchers collected data on seven patients with LEMS, three with SCLC (two men and one woman) and four — two men and two women — without. All were seen at Chiba University Hospital between 2003 and 2019.

Their median age at LEMS onset was 63.

One man died within 18 months of his SCLC diagnosis due to cancer progression. His neurological symptoms did not ease throughout this period, as assessed with the modified Rankin Scale (mRS).

The remaining six people were followed for more than two years (up to a maximum of 14 years), and showed long-lasting neurological improvements, as evident by a post-treatment decrease of one to two points in their mRS score. These improvements were mostly in the lower limbs.

All had difficulties with walking at disease onset, three patients showing ocular (eye) muscle weakness, and three also experienced bulbar symptoms (which may include problems with chewing, swallowing, and breathing).

Three patients developed urinary problems, another three had constipation, and two patients had dry mouth and changes in perspiration.

People with LEMS and SCLC had no signs of degeneration in cerebellum region of the brain, the center for motor coordination.

Levels of autoantibodies against voltage-gated calcium channels were elevated in these six people, in agreement with a LEMS diagnosis.

Three of five patients with a score of three or four in the Delta-P score — a clinical tool that predicts the risk of cancer in LEMS patients — had SCLC. This zero to six scale assigns a greater cancer likelihood to higher values. The two others with higher DELTA-P scores were still being regularly screened for cancer at the last reported examination.

The two LEMS patients with Delta-P scores of one or two remained cancer-free in repeated screenings over two years.

Cholinesterase inhibitors, prescribed off-label to treat LEMS, were given to five patients, but led to either no responses or only partial responses in neurological symptoms.

All four patients without SCLC were given oral prednisolone, and three also underwent plasmapheresis (a process used to “clean” the blood of harmful antibodies by removing the plasma, its liquid portion) early in their disease.

Oral prednisolone was maintained through the last examination to ensure an easing in neurological symptoms.

Treatment with the immunosuppressant azathioprine was given to three patients to lower their prednisolone dose, but was discontinued because of liver irregularities.

All patients with SCLC underwent the same chemotherapy regimen (cisplatin and etoposide) with or without immunotherapy.

These two people were found to be cancer free after the first chemotherapy series, but one experienced a cancer relapse with a mild worsening in gait and fatigue. This was resolved after additional cancer treatment.

These findings suggest that “in Japanese LEMS patients, the long-term neurological outcome is generally favourable,” the researchers wrote.

“Our results also suggest that even in LEMS with SCLC patients, successful treatment for their cancer could result in sustained improvement in neurological symptoms,” they added.