Muscle ultrasound may help monitor FAP severity

Small Malaysian study suggests the tool discovers biomarkers for diagnosis

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Muscle ultrasound

The parameters of muscle ultrasound, which uses sound waves to make pictures of muscles, are significantly different among people with familial amyloid polyneuropathy (FAP), those not yet showing overt disease symptoms, and healthy people.

That’s according to a small study in Malaysia that suggests this noninvasive imaging scan may be “a sensitive and reliable biomarker of disease severity in [FAP],” the researchers wrote.

The study, “Quantitative muscle ultrasound as a disease biomarker in hereditary transthyretin amyloidosis with polyneuropathy,” was published in the journal Neurological Sciences.

FAP, also called hereditary transthyretin amyloidosis with polyneuropathy or hATTRv-PN, is caused by mutations in the TTR gene. The mutations ultimately result in the formation of abnormal protein clumps that build up mostly in the nerves outside the brain and spinal cord.

These clumps lead to a loss of sensation and muscle weakness in the body’s extremities, which may not manifest until late adulthood. As such, reaching an early diagnosis can be challenging. However, the earlier the diagnosis is made, the sooner treatment can begin and the better the chances of a positive response.

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“The development of biomarkers sensitive to early manifestation of the disease as well as in monitoring disease progression and response to therapy is vital,” the researchers wrote.

Ultrasonography is a noninvasive and nonpainful imaging technique that uses ultrasound to capture live images from inside the body.

“Previous nerve ultrasound studies have shown nerves were enlarged in ATTRv-PN patients,” the researchers wrote, adding that “the role of quantitative muscle ultrasound in ATTRv-PN has not been evaluated.”

Muscle ultrasound can detect changes in muscle thickness and echo intensity (a measure of muscle quality), which can result from damage to, and subsequent loss of, the nerves controlling those muscles.

The study and its data

Now, a team of researchers in Malaysia have evaluated how well quantitative muscle ultrasound may help doctors monitor disease severity in adults carrying FAP-causing TTR mutations.

The study included 20 such carriers, nine of whom (seven men and two women; mean age 66.2) were experiencing FAP symptoms for a median of seven years. All but one of these patients were receiving treatment for FAP, most commonly Amvuttra (vutrisiran).

The remaining 11 adults (five men and six women; mean age 54.4) either had not yet developed FAP symptoms or had isolated carpal tunnel syndrome symptoms, which classified them as presymptomatic. Carpal tunnel syndrome, a condition that affects nerves in the wrist, often precedes a FAP diagnosis.

A total of 25 age- and sex-matched healthy adults were also included as controls.

All participants underwent quantitative muscle ultrasound on six muscles in the upper and lower limbs to calculate muscle thickness and muscle quality (as echo intensity).

Muscle thickness of the first dorsal interosseous, a muscle in the back of the hand, was significantly lower in symptomatic than presymptomatic patients (98.3 vs. 198.3 square millimeters) and healthy controls (184.4 square millimeters).

The other five muscles evaluated were also thinner in symptomatic patients relative to the other two groups, but these differences failed to reach statistical significance.

In the first dorsal interosseous, echo intensity — which has scores ranging from zero (excellent muscle quality) to 255 (poor muscle quality) — was significantly higher in symptomatic patients (48.2) relative to presymptomatic patients (33).

In the biceps, echo intensity was also significantly higher in symptomatic than in presymptomatic patients (76.4 vs. 59.2). In both muscles, echo intensity was significantly higher, indicating poor muscle quality, in symptomatic patients versus healthy adults.

No significant group differences were detected for muscles in the lower limbs.

Both the muscle thickness and echo intensity of the first dorsal interosseous, as well as the echo intensity of the biceps, showed significant associations with several validated clinical measures of disease severity and quality of life. For example, the thinner the first dorsal interosseous, the more severe the disability and the worse the quality of life.

A higher echo intensity in either the first dorsal interosseous or biceps was linked to worse disability and poorer ability of patients to take care of themselves without support. In the biceps, a higher echo intensity was linked to worse quality of life.

“Our study supports the potential role of quantitative muscle ultrasound as an imaging biomarker in symptomatic ATTRv-PN,” the researchers concluded. “In particular, we have demonstrated for the first time that muscle ultrasound is a sensitive biomarker in detecting disease severity in ATTRv-PN.”

Larger studies, following patients over time, are needed to determine the potential use of quantitative muscle ultrasound to determine disease progression and treatment response, researchers said.