Simple diagnostic test may detect hATTR-PN early, study finds
Accessible test could be useful in areas lacking specialized resources
Written by |
An easily accessible diagnostic test called pain-related evoked potentials with concentric electrodes (PrEP-CE) may help detect the onset of hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), according to a small study in Brazil.
Changes in PrEP-CE measures were able to discriminate between people with manifest hATTR-PN and those carrying disease-causing mutations but not yet showing symptoms, data showed.
“PrEP- CE can be obtained using standard electrodiagnostic equipment requiring minimal adjustments and accessories,” and “may represent an important test for regions (such as Brazil), where [hATTR-PN] is [more common], but the availability of other specific small fiber tests … is limited,” the researchers wrote.
The study, “Pain-Related Evoked Potentials in Hereditary Transthyretin Amyloidosis With Polyneuropathy,” was published in Muscle & Nerve.
hATTR-PN, also referred to as ATTRv-PN, is caused by mutations in the TTR gene that lead to production of an abnormal protein that forms clumps in the body’s tissues. These aggregates mainly accumulate in the nerves outside the brain and spinal cord, ultimately resulting in nerve damage. The disease usually first affects small nerve fibers, such as those that detect sensation and pain, which is why abnormal sensations are a common symptom of ATTRv-PN.
Test focuses on the first nerves affected
PrEP-CE is a noninvasive test that uses an electrode placed on the skin to detect the electrical activity of small nerve fibers. Because these are often the first nerves affected by ATTRv-PN, this test could help detect early disease activity.
“Despite that, it has not yet been explored in ATTRv-PN,” the researchers wrote.
The team of scientists in Brazil conducted a preliminary study to explore the potential utility of PrEP-CE as a tool for monitoring hATTR-PN. The study looked at 17 people with manifest hATTR-PN, 12 people who carried a TTR mutation but had not yet developed symptoms (pre-hATTR-PN), and 13 healthy people to serve as controls.
They tested each participant on both hands and feet, with the procedure lasting 10-20 minutes.
“All subjects were able to complete the procedure, with no major report of pain or discomfort, indicating that it was a fast and well-tolerated procedure,” the team wrote.
Results showed that absent PrEP-CE responses were significantly more frequent among people with manifest hATTR-PN. In these patients, PrEP-CE of both the hands and feet demonstrated abnormally long latencies and reduced amplitudes relative to healthy controls. This meant that small nerve fibers were firing more slowly and weakly than in people without a disease-causing mutation.
PrEP-CE responses were significantly associated with measures of disease severity, meaning patients with more abnormal PrEP-CE results tended to report more severe disease.
In people who carried the mutation but did not yet have symptoms, abnormalities relative to healthy controls were detected in PrEP-CE amplitudes and certain measures of latency in the feet, but not the hands. These data suggest that PrEP-CE of the lower limbs might be particularly valuable for detecting early signs of the disease, the researchers said.
“We found that both latencies and amplitudes could differentiate patients with hereditary transthyretin amyloidosis with polyneuropathy and carriers of TTR mutations from healthy controls,” the scientists wrote. “This finding underscores the potential value of this technique for early recognition of disease onset and supports its clinical applicability.”
They stressed that the study was small and more work is needed to validate the tool’s clinical utility.
“There is a need for additional studies with a [follow-up] design, larger sample sizes, and more comprehensive [clinical] characterization to validate and expand the clinical use of PrEP-CE in the context of ATTRv-PN,” the team wrote.
