Weak electrical signals may offer an early ALS diagnosis
FFPS are generated by nerve stimulation and recorded away from their source
Far-field potentials (FFPs), weak electrical signals triggered by nerve stimulation that can be recorded noninvasively on the skin, may serve as reliable clinical biomarkers to support early diagnosis and disease monitoring in people with amyotrophic lateral sclerosis (ALS), a study suggests.
The strength of these signals, or FFP amplitude, was significantly lower in people with ALS than in those with other conditions with similar symptoms, allowing researchers to distinguish between the groups as accurately as other common diagnostic tests. FFP amplitude also correlated with certain clinical measures, suggesting it may reflect both the severity and progression of the disease.
“Incorporating [FFP recordings] into clinical diagnostics and clinical trials could substantially enhance early diagnosis and disease monitoring, and could serve as a robust surrogate outcome marker for ALS progression, improving both patient care and trial efficiency,” the researchers wrote. The study, “Clinical Utility of Far- Field Potentials in Amyotrophic Lateral Sclerosis,” was published in Muscle & Nerve.
Diagnosing ALS can be difficult, especially in its early stages or when its symptoms don’t follow the typical pattern. Doing so usually involves detecting signs of ongoing nerve damage while also ruling out conditions with similar symptoms, which can delay a diagnosis.
“Consequently, reliable and sensitive biomarkers are essential for early detection and for monitoring disease progression,” the researchers wrote.
To help identify nerve damage, clinicians often use nerve tests that measure how well electrical signals travel from nerves to muscles. A common one records a muscle’s electrical response after nerve stimulation, with the strength of the response giving clues about damage to the nerve cells responsible for muscle movement, called motor neurons. While helpful, the test often may not fully reflect the extent of damage and can be influenced by technical factors, such as where the electrodes are placed.
Measuring nerve activity with FFPs
To improve accuracy, researchers have developed more refined ways to measure nerve activity. One involves FFPs which have shown promise as more reliable markers for identifying motor neuron damage in ALS. Because the diagnostic value of FFPs in ALS is still not fully clear, an international team of researchers sought to determine how well they could detect signs of motor neuron damage in ALS over standard diagnostic tests.
The researchers recruited 106 participants with suspected ALS from two ALS clinics affiliated with the University of Sydney between February 2024 and 2025. Of them, 64 people were diagnosed with ALS and 42 had ALS-like conditions. Most participants with ALS began developing symptoms in their arms or legs and showed signs of moderate muscle weakness along with motor neuron dysfunction.
To measure FFPs, the researchers delivered a small electrical stimulus to the ulnar nerve at the wrist and placed electrodes on the skin over the wrist and a finger.
As seen with other nerve tests, FFP amplitude was significantly lower in those with ALS (5.07 millivolts, or mV) than those with ALS-mimicking conditions (8.25 mV), 42 of which were represented, including myasthenia gravis, multifocal motor neuropathy, and cramp fasciculation syndrome.
FFP amplitude was positively linked with several clinical measures, including muscle strength in the hands and arms and fine motor skills, “suggesting that FFP amplitude may reflect motor function and disease severity in ALS,” the researchers wrote. It also showed a negative association with the rate of fine motor decline, which “suggests that lower FFP amplitudes may be associated with a faster rate of disease progression in fine motor function,” they wrote.
FFP amplitude was able to reliably distinguish ALS from similar conditions, with a diagnostic performance comparable to that of standard ALS biomarkers.
When the cutoff value, the threshold used to decide whether someone likely has ALS, was set to 6.15 mV, the test correctly identified ALS in about 72% of cases and correctly ruled it out in 85% of non-ALS cases. Importantly, FFPs’ ability to detect ALS remained “consistent across various ALS [clinical presentations], regardless of disease onset, duration, or functional impairment, reinforcing its robustness as a potential diagnostic biomarker for ALS,” wrote the the researchers, who called FFP amplitude a “valuable diagnostic and prognostic biomarker for ALS.”
“The simplicity, reliability, and reproducibility of FFP recordings make them an attractive, easily implementable biomarker for routine clinical use,” they wrote.
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