Differences in tears can distinguish bulbar-onset ALS vs. spinal-onset
Tear metabolites may be 'innovative method' to differentiate ALS onset
Differences in tear metabolites — the products of metabolism that are found in human tears — in people with amyotrophic lateral sclerosis (ALS) were able to distinguish bulbar-onset disease, in which symptoms initially affect the face and throat, from spinal-onset ALS, where the first symptoms usually are weakness in the hands or feet, a new study found.
According to the scientists, these differences could be a biomarker for differentiating between these two types of symptom onset in ALS.
However, despite these findings, the overall tear metabolite composition of people with ALS was not able to distinguish patients from healthy individuals, and it also did not correlate with disease severity or progression.
Still, “basal tear [metabolites] could represent an innovative method to better characterize ALS [variability],” the researchers concluded.
Their study, “Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study,” was published in the journal The Ocular Surface.
Symptoms in bulbar-onset ALS typically affect speech, swallowing
ALS is caused by the progressive degeneration of nerve cells in the spinal cord and brain, leading to its hallmark symptom of muscle weakness.
The majority of patients first notice this weakness in the muscles of the hands and feet, and are classified as spinal-onset ALS. Bulbar-onset disease manifests in the other third, with these patients first experiencing weakness around the throat and mouth that present as problems with speech and swallowing.
Because ALS is highly heterogeneous — meaning its symptom severity and progression can vary widely from person to person — most patients experience significant delays in diagnosis following the onset of disease symptoms. This “underscores the critical need for the development of accessible diagnostic biomarkers,” the researchers wrote.
Research suggests that the composition of tears may represent an informative biomarker for other neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease.
But to date, “no study has investigated the metabolomics signature of tears of patients with ALS,” the team wrote.
The body’s lacrimal glands can produce three types of tears. Basal tears provide nutrients to the eye surface, maintain a wet and smooth surface, and remove debris from that surface. Reflex tears, meanwhile, are released in response to irritants, and emotional tears are those secreted during emotional distress.
According to the team, measuring levels of metabolites, or metabolomics, within tears could represent a potential noninvasive, rapid, and painless examination method to accelerate the diagnosis of ALS.
To that end, researchers in Tours, France, collected basal tears from 25 ALS patients and 30 age- and gender-matched controls — people without ALS visiting the ophthalmology department or relatives from people with ALS. Among the patients, 21 were diagnosed with sporadic ALS, indicating no family history of the disease, and four with familial ALS.
Overall, about 101 metabolites were detected using a technique called ultra-high performance liquid chromatography coupled with mass spectrometry. However, metabolite tear composition did not significantly differ between the ALS patients and controls.
Tear metabolites did not correlate with ALS severity
Still, the researchers detected six metabolites whose levels were significantly different in people with bulbar-onset ALS compared with those with spinal-onset disease. Of them, five were lower in people with bulbar-onset disease, and one was higher. After an adjusted analysis, the difference between the two groups remained highly significant.
“The close anatomical relationship between the eye and brain in bulbar forms presents a compelling hypothesis for these differences,” the researchers wrote.
No correlation was found between tear metabolomics and ALS severity, as assessed by the Revised ALS Functional Rating Scale (ALSFRS-R) and lung function. Nor were any correlations found with disease progression or duration.
The close anatomical relationship between the eye and brain in bulbar forms presents a compelling hypothesis for these differences.
“Basal tear metabolomics does not represent a diagnostic tool discriminating patients with ALS and controls and does not correlate with disease severity or evolution,” the researchers wrote. However, “basal tear [metabolites] discriminate patients with bulbar and spinal forms of ALS.”
These results provide “a proof of concept” for basal tears as a potential biomarker for characterizing ALS, the team noted.
“Continued investigation, particularly with expanded [groups], is essential to validate and extend these initial findings,” they concluded.
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