Patient-reported Data Reliable, Dutch Analysis Finds

Steve Bryson PhD avatar

by Steve Bryson PhD |

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European LEMS registry

Almost all people with Lambert-Eaton myasthenic syndrome (LEMS) have generalized symptoms at disease onset, according to an analysis of data from a Dutch patient registry.

That finding, and others, were similar between patient-completed questionnaires and medical records, which supported the reliability of patient-reported data, the researchers noted. 

Registry data analyses were reported in the study, “Accuracy of patient-reported data for an online patient registry of autoimmune Myasthenia Gravis and Lambert-Eaton myasthenic syndrome,” published in the journal Neuromuscular Disorders

LEMS is an autoimmune disorder in which the body’s immune system wrongly launches an attack against components of the neuromuscular junction (NMJ) — the place where nerve endings meet the muscles they control. 

About 90% of people with LEMS have antibodies that target a protein called voltage-gated calcium channel (VGCC), which is located at the NMJ and is critical for proper nerve-muscle communication. These antibodies block the transmission of these messages, weakening muscles over time and causing the typical symptoms of the disease

National and international patient registries and databases are essential for collecting large amounts of data about the natural course of this rare disease. The data provide details not only about disease characteristics, but also medications, co-existing conditions (comorbidities), and family history. 

This information improves understanding of the disease by both physicians and patients, and supports the identification of novel therapeutic targets. 

Recently, the Dutch registry for NMJ disorders was established to collect medical information from both treating physicians and patients. The database since has been renamed to the Dutch-Belgian registry to include patients from Belgium. It contains data on LEMS and other NMJ diseases, including myasthenia gravis and congenital myasthenic syndromes. 

Participants registered voluntarily and completed a baseline questionnaire online. A request to the treating physician then is made for the inclusion of extensive available medical information, including medical history, antibody status, and electromyography results. Of note, electromyography is a test that evaluates the overall health of muscles and the nerves that control them by measuring muscles’ electrical activity. 

Participants receive an invitation for a follow-up questionnaire every year to assess the disease course and newly diagnosed conditions.  

This study described information collected from LEMS patients from the Netherlands, with a particular emphasis on the quality of patient-reported data. The analysis was conducted by researchers from Leiden University Medical Center, also located in the Netherlands. 

An epidemiological study estimated the prevalence of LEMS in the Netherlands was about 2.5 cases per million people. Based on these estimates, about 87% of all Dutch LEMS patients are included in the registry, totaling 38 patients. Of these, 36 (95%) completed the baseline questionnaire, and 26 (68%) completed the follow-up questionnaire.

Documented antibody status was available for 87% of LEMS patients. From these, 82% had VGCC antibodies and the remaining 18% were antibody-negative. In the baseline questionnaire, 53% of patients reported VGCC antibodies, 11% said they were negative, while 36% did not know. 

“A large number of patients was unable to report their own antibody status, suggesting a need for patient education,” the team wrote. 

Female LEMS patients tended to be younger at disease onset. In addition, the time from disease onset to diagnosis was longer in female patients compared to males. Still, these differences were not statistically significant, “possibly due to the low number of patients,” the investigators wrote. 

In contrast, the age at diagnosis was significantly lower for female LEMS patients compared to males.

Symptom data

Regarding signs and symptoms, one patient had only eye-related problems during the first six months of the disease, while all others (97%) had generalized symptoms. 

Autonomic symptoms, including constipation, dry mouth and eyes, and erectile dysfunction, were reported frequently by LEMS patients. Of note, these symptoms arise from problems in the autonomic nervous system, which is responsible for controlling non-conscious bodily functions.

A total of 85% reported at least one autonomic symptom in the first six months following disease onset, while 88% when the disease was at its worst. All participants reported symptoms in the three months prior to the baseline questionnaire, with only one reporting autonomic symptoms without muscle weakness.

In the one-year follow-up questionnaire, more than 80% reported generalized symptoms. Notably, five (19%) patients reported no symptoms, and of these, one did not use any medications. All others resorted to symptomatic medicines. The most limiting symptoms were leg weakness (63%), followed by fatigue (20%), and incontinence (5.7%). 

Based on medical files, which were available for nine (24%) LEMS patients, all started experiencing generalized symptoms, which was “similar to what the patients reported in the questionnaires.”

All LEMS patients received amifampridine, also known as 3,4-diaminopyridine or 3,4-DAP (sold as Firdapse and Ruzurgi in the U.S.), to treat their condition.

A total of 6.5% of LEMS patients were treated with intravenous immunoglobulins, and 71% received a combination of amifampridine and pyridostigmine. Immunomodulating therapies like corticosteroids and azathioprine were used by 49% of LEMS patients. 

The most commonly reported comorbidities among LEMS patients included high blood pressure (31%) and heart disease (25%). Type 2 diabetes was reported by 2.8% of LEMS patients. A concurrent autoimmune disorder was seen in 38% of the patients, the most prevalent being thyroid disease (14%), which was “comparable to the physician-reported prevalence.”

According to medical files, three LEMS patients had lung cancer. 

At least one hospitalization occurred in 22% of LEMS patients. Intensive care unit (ICU) admissions were reported by 18% of the patients. Among those admitted to the ICU, 33% required ventilation.

“Registries are a valuable collection of information, especially in rare diseases,” the investigators wrote. “Patient- and physician-reported data provide complementary information” and their combination “enables validation and confirms the reliability of patient-reported data.”