New Nerve Imaging Tool May Aid Early FAP Diagnosis, Study Suggests

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by Vanessa Pataia |

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Magnetization transfer ratio (MTR), an MRI scanning tool based on nerve imaging, may help diagnose familial amyloid polyneuropathy (FAP) in its early stages, a study suggests.

With delays in diagnosis that often range from 1-5 years, such a determination could possibly lead to earlier treatment for patients with the hard-to-diagnose genetic disease.

The study, “Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis,” was published in the journal Annals of Clinical and Translational Neurology.

FAP, also known as hereditary transthyretin (ATTRv) amyloidosis, is associated with general degeneration of peripheral nerves — or polyneuropathy — due to mutations in the TTR gene.

Early diagnosis and treatment of FAP may be important to prevent irreversible nerve and organ damage. However, in its early stages, the disease affects mainly small nerve fibers. That may complicate detection of FAP onset via traditional methods, such as electroneurography. Often called a nerve conduction study, electroneurography refers to the technique used to test and quantify motor and sensory nerve impulses.

After nerve damage has progressed beyond a certain point, treatment benefits may not be measurable.

Using MTR may address such limitations in both symptomatic and asymptomatic FAP cases. The tool is based on the combination of magnetic resonance neurography, which allows the direct visualization of peripheral nerve lesions, with magnetization transfer contrast imaging — an approach that provides superior imaging compared with conventional MRI.

Here, researchers at the Heidelberg University Hospital, in Germany, used MTR to measure sciatic nerve lesions in people with symptomatic and asymptomatic FAP with polyneuropathy.

The study included 25 patients with symptomatic FAP (mean age 58.8 years), 30 asymptomatic carriers of the mutant TTR gene (mean age 43.3), and 20 age- and sex-matched healthy people (controls).

The results showed that MTR of the sciatic nerve reliably differentiated people with symptomatic FAP from asymptomatic carriers and the controls. That suggests that “critical peripheral nerve damage precedes the symptomatic stage of the disease,” the researchers wrote.  

Specifically, MTR was lower in symptomatic patients (26.4) than in both carriers (32.6) and the healthy controls (39.4).

Lower MTR was associated with greater clinical severity of FAP, as measured by higher scores in the Neuropathy Impairment Score-Lower Limbs (NIS-LL).

Changes in nerve conduction velocities in the legs of symptomatic patients also were linked to MTR.

“MTR reflects the extent of motor and sensory axonal [nerve fiber] degeneration,” the scientists wrote. “This is clinically relevant because MTR is still measurable and hence applicable for disease monitoring at more advanced PNP [polyneuropathy] stages.”

In asymptomatic carriers, MTR also correlated with a parameter called sensory nerve action potential in the calf. That suggests the technique’s potential to detect presymptomatic stages of the disease, the scientists said.

Measurement of the cross‐sectional area (CSA, a measure for nerve caliber) of the sciatic nerve also was able to differentiate people with symptomatic FAP from asymptomatic carriers, and from the healthy controls. The patients with symptomatic disease had higher CSA (34.3 mm3) than participants in the other two groups. Those with asymptomatic FAP also had greater CSA than the controls (26 vs. 20.4 mm3).

CSA values were linked to changes in nerve conduction parameters in symptomatic FAP patients. However, CSA was not associated with NIS‐LL, the results showed.

“Our data favor MTR to be a more promising imaging marker than CSA,” the team wrote.

Overall, “MTR differentiates between symptomatic ATTRv‐PNP and asymptomatic mutTTR [mutant TTR]‐carriers with high sensitivity while correlating well with electrophysiologic examination results, and the NIS‐LL,” the scientists wrote.