T2-relaxometry in a large cohort of hereditary transthyretin amyloidosis with polyneuropathy.

BACKGROUND

Previously, T2-relaxation time (T2) and proton spin density (ρ) detected nerve injury in a small group of ATTRv amyloidosis. Here, we aim to quantify peripheral nerve impairment in a large cohort of symptomatic and asymptomatic ATTRv amyloidosis and correlate T2-relaxometry markers with clinical parameters and nerve conduction studies (NCS).

METHODS

Eighty participants with pathologic variants of the gene () and 40 controls prospectively underwent magnetic resonance neurography. T2-relaxometry was performed, allowing to calculate tibial ρ, T2 and cross-sectional-area (CSA). Detailed clinical examinations and NCS of tibial and peroneal nerves were performed.

RESULTS

Forty participants were classified as asymptomatic -carriers, 40 as symptomatic patients with polyneuropathy. ρ, T2 and CSA were significantly higher in symptomatic ATTRv amyloidosis (484.2 ± 14.8 a.u.; 70.6 ± 1.8 ms; 25.7 ± 0.9 mm) versus carriers (413.1 ± 9.4 a.u.,  < 0.0001; 62.3 ± 1.3 ms,  = 0.0002; 19.0 ± 0.8 mm,  < 0.0001) and versus controls (362.6 ± 7.5 a.u.,  < 0.0001; 59.5 ± 1.0 ms,  < 0.0001; 15.4 ± 0.5 mm,  < 0.0001). Only ρ and CSA differentiated carriers from controls. ρ and CSA correlated with NCS in -carriers, while T2 correlated with NCS in symptomatic ATTRv amyloidosis. Both ρ and T2 correlated with clinical score.

CONCLUSION

ρ and CSA can detect early nerve injury and correlate with electrophysiology in asymptomatic -carriers. T2 increases only in symptomatic ATTRv amyloidosis in whom it correlates with clinical scores and electrophysiology. Our results suggest that T2-relaxometry can provide biomarkers for disease- and therapy-monitoring in the future.