Normal muscle strength test results may hide LEMS, delay diagnosis
Patients reported weakness, exhibited abnormalities in nerve function
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Despite substantial self-reported muscle weakness and detectable abnormalities in nerve function tests, people with Lambert-Eaton myasthenic syndrome (LEMS) often show normal results on standard muscle strength tests, a new study highlights.
Notably, normal muscle strength was significantly associated with a longer interval between symptom onset and diagnosis. In addition, people with LEMS experienced longer and more complex diagnostic odysseys than people with myasthenia gravis (MG), a more common autoimmune disorder that also affects the nerve-muscle communication.
These findings highlight that “diagnostic delay in LEMS was associated with the absence of objective muscle weakness on MMT [manual muscle testing],” researchers wrote. “Key diagnostic features of LEMS included subjective muscle fatigue, reduced or absent tendon reflexes, and [impaired nerve function], despite normal MMT findings.”
The study, “Diagnosis of Lambert-Eaton myasthenic syndrome: Muscle fatigue with normal manual muscle testing, areflexia, and electrodiagnostic findings,” was published in the Journal of Neuroimmunology.
Obtaining accurate LEMS diagnosis can be a long process
LEMS is a rare autoimmune disorder in which the immune system attacks nerves that control muscles, interfering with nerve-muscle communication and causing such symptoms as muscle weakness and fatigue. Most cases of LEMS are associated with an underlying cancer.
There isn’t any one test that can diagnose LEMS. The disease is diagnosed based on careful evaluation of a patient’s symptoms, along with medical tests like nerve conduction studies, which measure the electrical activity of nerves.
Because LEMS is rare and its symptoms overlap with those of other diseases, including MG, obtaining an accurate diagnosis can be a long, complex process. It may be months or even years after the onset of symptoms that patients finally receive answers and start appropriate treatment.
More than half of patients had normal strength test results
In this study, a team of scientists set out to identify factors associated with longer diagnostic delays among people with LEMS. They retrospectively analyzed data from 12 people who were diagnosed with LEMS at a Japanese hospital between 2003 and 2024.
Half of these patients had an underlying cancer. All but three patients (75%) tested positive for self-reactive antibodies against P/Q-type voltage-gated calcium channels, the most common type of LEMS-causing antibodies.
All participants reported disease-typical symptoms including fatigue or a general feeling of being unwell, as well as limb weakness, which was mainly described as difficulty generating strength.
Also, virtually all patients showed abnormalities on nerve function tests and had absent or reduced tendon reflexes. However, more than half (58.3%) had normal results in MMT, a standard assessment of muscle strength in the hands.
MMT scores showed no clear association with nerve function test results, as most patients with normal MMT scores showed altered results on nerve conduction tests.
“Patients with LEMS often exhibited normal or only mildly reduced muscle strength despite impaired activities of daily living” and impaired nerve function on nerve conduction studies, the researchers wrote.
To evaluate diagnostic delays in LEMS, the team compared diagnostic process data from LEMS patients with those of 20 MG patients diagnosed at the same hospital. They found that the median number of medical referrals prior to diagnosis was significantly higher in the LEMS group (four) than in the MG group (three).
Clinicians should be aware that MMT can be normal or show only mild impairment in some patients with LEMS, despite prominent subjective muscle weakness.
The median time from symptom onset to LEMS diagnosis was 7.5 months, with no notable differences between patients with or without cancer. This interval was significantly longer than the median 1.5 months it took MG patients to be diagnosed from symptom onset. Treatment was also initiated significantly later relative to symptom onset in the LEMS group (8.5 months vs. two months).
Statistical analyses to identify potential predictors of delayed diagnosis showed a significant association between more normal-appearing MMT results and a longer diagnostic delay. Reduced nerve function was also significantly associated with longer intervals from symptom onset to diagnosis.
The findings highlight that “diagnostic and treatment intervals for patients with LEMS were longer than in those with MG and were correlated with MMT sum scores,” the team wrote.
While this type of analysis isn’t able to detect cause-and-effect relationships, the observed association between normal MMT and longer diagnostic delays “may be explained by the hypothesis that preserved muscle strength masked the severity of LEMS, leading to delayed diagnosis,” the researchers wrote.
“Clinicians should be aware that MMT can be normal or show only mild impairment in some patients with LEMS, despite prominent subjective muscle weakness,” the team concluded.
