Quantification of muscle involvement in familial amyloid polyneuropathy using MRI.

Background And Purpose: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare genetic disease with autosomal-dominant inheritance. In this study, we aimed to quantify fatty infiltration (fat fraction [FF]) and magnetization transfer ratio (MTR) in individual muscles of patients with symptomatic and asymptomatic TTR-FAP using magnetic resonance imaging. Secondarily, we aimed to assess correlations with clinical and electrophysiological variables.

Methods: A total of 39 patients with a confirmed mutation in the TTR gene (25 symptomatic and 14 asymptomatic) and 14 healthy volunteers were included. A total of 16 muscles were manually delineated in the nondominant lower limb from T1-weighted anatomical images. The corresponding masks were propagated on the MTR and FF maps. Detailed neurological and electrophysiological examinations were conducted in each group.

Results: The MTR was decreased (42.6 AU; p = 0.001) and FF was elevated (14%; p = 0.003) in the lower limbs of the symptomatic group, with preferential posterior and lateral involvement. In the asymptomatic group, elevated FF was quantified in the gastrocnemius lateralis muscle (11%; p = 0.021). FF was significantly correlated with disease duration (r = 0.49, p = 0.015), neuropathy impairment score for the lower limb (r = 0.42, p = 0.041), Overall Neuropathy Limitations Scale score (r = 0.49, p = 0.013), polyneuropathy disability score (r = 0.57, p = 0.03) and the sum of compound muscle action potential (r = 0.52, p = 0.009). MTR was strongly correlated to FF (r = 0.78, p < 0.0001), and a few muscles with an FF within the normal range had a reduced MTR.

Conclusion: These observations suggest that FF and MTR could be interesting biomarkers in TTR-FAP. In asymptomatic patients, FF in the gastrocnemius lateralis muscle could be a good indicator of the transition from an asymptomatic to a symptomatic form of the disease. MTR could be an early biomarker of muscle alterations.