Amifampridine eases symptoms in LEMS case linked to prostate cancer

Report details rare case of disease tied to this cancer type in man, 69

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A man in his 60s who developed Lambert-Eaton myasthenic syndrome (LEMS) secondary to prostate cancer saw his neurological symptoms ease after receiving treatment with amifampridine — the active ingredient in the approved LEMS therapy Firdapse.

That’s according to a report detailing the man’s case, unusual, per the researchers, as “the association between LEMS and prostate adenocarcinoma [cancer that forms in the glandular tissue] is very rare.” Indeed, the team noted that the “first description [of such a case] was made … in 1995.”

“In current neurological practice, we must extend the clinical reasoning to … LEMS when we have in front of us an oncological patient with clinical signs in favor of a neuromuscular junction disorder,” the researchers wrote.

The study, “Acute onset of Lambert Eaton myasthenic syndrome in prostate adenocarcinoma: a case report,” was published in the journal Medicine and Pharmacy Reports.

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LEMS most commonly linked to lung, not prostate cancer

LEMS is an autoimmune disease that affects the neuromuscular junction, which is the site where nerves and muscles communicate. It’s caused by the immune system mistakenly attacking voltage-gated calcium channels (VGCCs) found in nerve cells. These protein channels are required for nerve cells to be able to send out signals to muscle cells instructing them to contract.

When VGCCs are damaged or destroyed, nerve cells are unable to send out those signals effectively, causing patients to develop the typical LEMS symptoms of muscle weakness and fatigue.

In about half of cases, the disease is associated with an underlying cancer. Most commonly, it’s linked to small cell lung cancer (SCLC), though other cancer types have been reported to be associated with LEMS. It is thought that the antibodies the immune system makes to fight off cancer cells wrongly target VGCCs on nerve cells, leading to the onset of LEMS.

In this report, a team of researchers in Romania described the case of a patient in whom LEMS developed in association with prostate adenocarcinoma, a type of prostate cancer.

The 69-year-old man was referred to the emergency room after experiencing proximal muscle weakness, that is, weakness in the muscles closer to the center of the body, with acute onset in the lower limbs. His symptoms worsened in the next days, to the point that four days after being admitted, he could no longer climb stairs. On the fifth day, he also started having difficulty walking with a cane.

His medical history included having an enlarged prostate and cardiovascular risk factors. He also was a former heavy smoker: He had smoked four packs per day for 30 years, but had since remained abstinent for about 20 years.

At physical examination, the patient was pale and was found to have lost 10 kg (22 pounds) in three months. He had no respiratory complaints, but had severe mouth dryness.

Initial tests to assess his muscles’ electrical responses to nerve signals and the speed at which nerve cells send out signals came back abnormal.

However, that diagnosis was overlooked, and the patient was referred to a center for neurological diseases as his muscle weakness progressed to the arms.

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Amifampridine, active ingredient in Fridapse, eased man’s symptoms

One month after his symptoms began, a neurological reexamination revealed slight eyelid droopiness, known as ptosis, generalized muscle weakness, and lack of tendon reflexes in both legs. Blood work revealed he had mild anemia and elevated levels of two tumor markers. He also had high levels of anti-VGCC antibodies, consistent with the diagnosis of LEMS.

Further imaging tests and tissue microscopic analysis revealed the presence of prostate adenocarcinoma, the most common type of prostate cancer.

Our patient confirms that [a] LEMS … diagnosis confirmation can easily escape … the first evaluation.

He was started on hormone therapies to treat his prostate cancer.

However, treatment with azathioprine, an immunosuppressant therapy, and pyridostigmine, used off-label to treat muscle weakness in LEMS, did not improve his condition.

He then started taking 3,4-diaminopyridine (amifampridine), which is the active ingredient in Firdapse. The use of amifampridine was found to ease his neurological symptoms.

The patient eventually died 16 months after his initial symptoms due to prostate cancer progression and bone cancer spread.

“Our patient confirms that [a] LEMS … diagnosis confirmation can easily escape … the first evaluation,” the researchers wrote, noting that this man’s case “has several particularities.”

As particular challenges in this case, the team highlighted the occurrence of neurological manifestations before the cancer diagnosis, as well as the very rare association between LEMS and prostate adenocarcinoma.