Cholinesterase Inhibitors Alone Can Ease LEMS Symptoms, Per Report
The findings suggest that these medications may be particularly useful for managing LEMS in countries where Firdapse (amifampridine) — the only therapy approved in the U.S. to date for treating LEMS symptoms — is not available, according to the researchers.
The two patients described in this case report “responded dramatically to cholinesterase inhibitors,” the researchers noted.
The case study, “Two Lambert-Eaton Myasthenic Syndrome Patients with Ameliorated Activities of Daily Living Due to Cholinesterase Inhibitors,” was published in the journal Internal Medicine.
LEMS is a rare autoimmune disease caused by self-reactive antibodies that mistakenly attack the neuromuscular junction — the region where nerve and muscle cells come into contact and communicate.
Cholinesterase inhibitors are a class of medicines that work by blocking the activity of an enzyme that breaks down acetylcholine — the chemical messenger nerve cells use to signal muscles to contract — thereby increasing its availability at the neuromuscular junction. While cholinesterase inhibitors are not specifically approved for LEMS, they are sometimes used off-label to manage its symptoms.
In Europe and the U.S., Firdapse is typically the first-line treatment for LEMS. However, this medication is not available in other regions, including in countries such as Japan.
A team of researchers in Japan now described the cases of two patients with LEMS whose symptoms were successfully managed with cholinesterase inhibitors.
The first patient was a 76-year-old man with small-cell lung cancer who began experiencing double vision, light-headedness, and lower limb muscle weakness. Laboratory tests revealed the man was positive for VGCC antibodies, which typically cause LEMS, leading physicians to diagnose him with the autoimmune disorder.
The man was then started on treatment with a cholinesterase inhibitor called pyridostigmine. This led to a marked improvement in his condition. For example, his score on the modified Rankin scale (mRS), which assesses the degree of disability in patients with neurological disability, decreased from 4 to 3, indicating a substantial reduction in disability.
Nevertheless, the patient died from cancer 10 months after starting treatment.
The second patient, a 68-year-old man, began feeling unusually tired when climbing stairs and had the sensation that his eyelids were drooping. He later experienced staggering and fatigue while walking, leading him to seek medical care.
As with the first patient, laboratory tests for VGCC antibodies came back positive, leading to a diagnosis of LEMS.
The patient was initially given pyridostigmine, but this resulted in side effects, such as nausea and abdominal pain, prompting a switch to another cholinesterase inhibitor called distigmine bromide. He tolerated this medication well, and his condition markedly improved, with his mRS score decreasing from 2 to 0 after four years.
“Cholinesterase inhibitors alone may be effective in a small portion of LEMS patients,” the researchers wrote. They noted that cholinesterase inhibitors are likely to be most beneficial in people with relatively mild LEMS, such as the two patients described in their study.
The team said that they hope these cases will help to “facilitate the treatment of LEMS in countries without the clinical application” of Firdapse.