Researchers find way to make diagnosis of ALS more accurate
Combining 2 blood biomarkers also helps predict how fast disease will progress
Combining two blood biomarkers may make the diagnosis of amyotrophic lateral sclerosis (ALS) more accurate and help predict how fast the disease will progress, according to a new German study.
The two markers are soluble neurofilament light chain, called sNfL — a known marker of nerve damage — and cardiac troponin T, or cTnT, which is an established biomarker of heart muscle damage.
“Our results demonstrate that combining sNfL and cTnT improves diagnostic accuracy in ALS and also provides valuable insights into disease progression,” Patrick Weydt, MD, study lead author and head of the ALS and Other Motor Neuron Disease Clinic at University Hospital Bonn in Germany, said in a university press release, which noted that making an ALS diagnosis “remains challenging, particularly when distinguishing it from clinically similar neurodegenerative disorders.”
The study, “Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis,” was published in the journal Annals of Neurology.
Diagnosing ALS is often difficult for clinicians because its symptoms can resemble those of other diseases. To address this, researchers have been searching for blood biomarkers that could make the diagnosis of ALS more accurate.
Elevated levels of sNfL — a protein that’s released from damaged nerve cells into the blood or other fluids in the body — are an established biomarker of ALS. However, it’s not specific to ALS, as increased levels of this biomarker are also observed in other neurodegenerative diseases.
Taking the study of blood biomarkers in ALS one step further
Here, the researchers took the known data one step further and studied sNfL in combination with cTnT, a heart protein that’s been shown to increase as ALS progresses.
“In everyday clinical practice, it is crucial to reliably differentiate ALS from other neurological diseases at an early stage,” said Torsten Grehl, MD, one of the study’s researchers from Alfried Krupp Hospital Essen.
According to Grehl, “the combination of sNfL and cTnT offers a real diagnostic advantage — using established, routine laboratory methods.”
For this study, the scientists used blood samples from 293 adults with ALS, 85 with other neurodegenerative diseases, and 29 healthy people. The ALS patients had been living with the disease for a median of 18 months, or approximately 1.5 years, and were significantly older than those with other neurodegenerative diseases.
Samples from a second group of 501 adults with ALS, who were younger than those in the first group, were used to validate the results.
The data showed that adults with ALS had higher sNfL levels than people with other neurodegenerative diseases and healthy adults. The median cTnT levels of the ALS patients were also higher than those in the other groups.
The combination of sNfL and cTnT offers a real diagnostic advantage — using established, routine laboratory methods.
Statistical analyses indicated that levels of sNfL could distinguish ALS from healthy adults with 94% accuracy. However, it was less effective when comparing ALS to other neurodegenerative diseases, with an accuracy of 82%.
When the researchers added cTnT to the analysis, accuracy improved. While the accuracy of cTnT alone reached 77%, the two biomarkers combined could distinguish people with ALS from those with other neurodegenerative conditions with accuracy of 90%.
This means that using both biomarkers together may make the test more reliable, the researchers noted. Further, data from the second group of patients confirmed these results, suggesting they are reproducible.
Team made adjustments to improve accuracy in an ALS diagnosis
To make cTnT more useful for diagnosing ALS, the researchers adjusted the cut-off level used to test for heart disease from 14 to 8.35 ng/L. This level was also used to compare patients with normal or elevated levels of both biomarkers.
The data showed that so-called biomarker-positive patients — those who had elevated levels of both sNfL and cTnT — had been living with the disease for less time than those who were biomarker-negative. The disease progressed faster for the biomarker-positive patients.
“Although sNfL alone performs well in distinguishing ALS from healthy controls, repurposing cTnT for ALS provides additional value in discriminating ALS from disease controls,” the researchers wrote.
Overall, according to the team, “the combination of sNfL and cTnT improves diagnostic accuracy and may help identify prognostically distinct ALS subgroups.”
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