Finger tapping test catches early, subtle nerve damage in hATTR-PN
New tool may help in detecting, quantifying motor problems, researchers say
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A computerized test that measures how quickly and accurately people perform finger tapping and hand movement tasks was able to detect subtle motor problems in people with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) earlier than some standard clinical assessments.
That’s according to a study in Italy that evaluated hand motor performance in more than 100 hATTR-PN patients using the Hand Test System (HTS), which uses a glove with five sensors. The HTS was tested across disease stages and examined potential associations with standard measures.
“HTS parameters, particularly those derived from Finger Tapping and Complete Sequence tasks, revealed functional alterations that were not consistently captured by conventional tests,” the researchers wrote.
While standard measures remain necessary for clinical testing, this study supports the use of finger tapping and other tests as a “complementary tool,” the team noted.
“Approaches such as the HTS are not intended to replace conventional tools,” the researchers wrote. “In clinical practice, HTS may represent a practical and reproducible tool to complement standard evaluations, particularly in quantifying motor impairment and supporting disease staging.”
The study, “A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis,” was published in the Journal of the Peripheral Nervous System.
In hATTR-PN, also known as familial amyloid polyneuropathy (FAP), mutations in the TTR gene cause the TTR protein to form toxic clumps that tend to build up in nerves outside the brain and spinal cord. Gradual damage to multiple nerves, known as polyneuropathy, causes neurological symptoms.
Treatment for hATTR-PN most effective when started early
While detecting this type of damage early can be difficult, available disease-modifying treatments “are most effective when initiated early, making timely recognition of clinical signs and symptoms essential,” the researchers wrote.
Now, a research team from across Italy tested whether the HTS could detect not only subtle motor problems across all stages of disease, including the earliest ones, but also monitor their progression over time.
The study involved 113 participants: 74 adults identified as carriers of a disease-causing TTR mutation and 39 healthy adults who served as controls. Men comprised two-thirds of the carrier group and slightly less than half of the control group. The mean age was 64.8 years for carriers and 63 years for healthy controls.
All of the participants were right-handed.
The patients were further divided into three groups based on disease severity according to the Coutinho staging system. A total of 16 carriers had no clinical signs or symptoms of hATTR-PN and were dubbed the FAP0 group. However, five of them showed mild signs of carpal tunnel syndrome, which occurs when a nerve passing through the wrist becomes compressed, causing weakness, numbness, or tingling in the hand and fingers. This condition is often linked to hATTR-PN.
Among the remaining carriers, 40 — dubbed the FAP1 group — had mild sensory symptoms, such as numbness or tingling, and/or mild motor symptoms in the lower limbs. The other 18 carriers had more advanced symptoms, including difficulty walking and the need for assistance; this group was called FAP2. The FAP2 stage patients were the oldest, with a mean age of 72. This was followed by the FAP1 group, with an average age of 66, and the FAP0 group, with a mean age of 50.
Most patients (76%) were receiving disease-modifying treatments designed to slow disease progression. These medications were Onpattro (patisiran), tafamidis meglumine (approved in Europe for hATTR-PN under the brand name Vyndaqel), Amvuttra (vutrisiran), and Tegsedi (inotersen; now discontinued). Those without treatment were mainly symptom-free carriers in the FAP0 stage.
Worse results for patients with more severe disease
The HTS measured three parameters: Touch Duration (TD), or the time a finger remains in contact with the screen or sensor; Inter-Tapping Interval (ITI), the time between consecutive taps; and Movement Rate (MR), which reflects the speed of movement. Longer TD and ITI indicate slower performance, while higher MR indicates faster and better motor function.
In a finger tapping task, the FAP2 group performed significantly worse than all other groups, with longer touch and transition times and slower movement rates, the data showed. FAP1 patients also showed slower movement rates than those in the FAP0 stage and healthy adults.
When asked to complete a sequence of finger movements, FAP2 patients also performed significantly worse across all three parameters. While some HTS parameters distinguished FAP1 patients from healthy controls, FAP0 carriers generally performed similarly to healthy adults, suggesting that subtle hand motor problems become detectable during the early symptomatic stage.
Participants also completed other tests, including the 9-Hole Peg Test (9HPT), which measures hand dexterity. Grip and pinch strength tests were used, as was the Thumb Opposition Test (TOT), which measures thumb movement and coordination. Each of the partipants was also asked to complete a questionnaire about disability and quality of life.
In the 9HPT, only FAP2 patients showed significant impairment, suggesting that the HTS may be more sensitive than the 9HPT for detecting early motor problems. Grip and pinch strength tests showed a gradual motor function decline as the disease progressed, with the ability to pinch using the thumb, index finger, and middle finger declining in more advanced stages.
In the TOT, FAP2 patients showed the worst performance, while FAP1 patients performed worse than FAP0 carriers and healthy adults, according to the researchers.
Patients with more advanced disease also reported greater disability in arm, shoulder, and hand function, as well as poorer quality of life. They also had higher Neuropathy Impairment Scores, indicating more severe nerve damage, the researchers found.
Finally, in the HTS test, longer touch and transition times were linked to more severe nerve damage, greater disability, and worse quality of life. Faster movement rates were linked to stronger grip and pinch strength and better overall function.
Altogether, these relationships suggest that the HTS provides a reliable measure and could serve “as a complementary tool for assessing hand motor function across different [hATTR-PN] disease stages,” the researchers wrote.
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