TY - JOUR
T1 - Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy
T2 - a cross-sectional study
AU - Vegezzi, Elisa
AU - Cortese, Andrea
AU - Bergsland, Niels
AU - Mussinelli, Roberta
AU - Paoletti, Matteo
AU - Solazzo, Francesca
AU - Currò, Riccardo
AU - Ascagni, Lucia
AU - Callegari, Ilaria
AU - Quartesan, Ilaria
AU - Lozza, Alessandro
AU - Deligianni, Xeni
AU - Santini, Francesco
AU - Marchioni, Enrico
AU - Cosentino, Giuseppe
AU - Alfonsi, Enrico
AU - Tassorelli, Cristina
AU - Bastianello, Stefano
AU - Merlini, Giampaolo
AU - Palladini, Giovanni
AU - Obici, Laura
AU - Pichiecchio, Anna
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1
Y1 - 2023/1
N2 - Background: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. Methods: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. Results: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. Conclusions: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.
AB - Background: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. Methods: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. Results: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. Conclusions: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.
KW - ATTR
KW - Biomarker
KW - Magnetic resonance imaging (MRI)
KW - Outcome measure
KW - Polyneuropathy
UR - https://www.scopus.com/pages/publications/85137442056
U2 - 10.1007/s00415-022-11336-z
DO - 10.1007/s00415-022-11336-z
M3 - Article
C2 - 36064814
AN - SCOPUS:85137442056
SN - 0340-5354
VL - 270
SP - 328
EP - 339
JO - Journal of Neurology
JF - Journal of Neurology
IS - 1
ER -