Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study
Creators: name: Vegezzi Elisa
name: Andrea, Cortese
name: Niels, Bergsland
name: Roberta, Mussinelli
name: Matteo, Paoletti
name: Francesca, Solazzo
name: Currò Riccardo
name: Ascagni Lucia
name: Callegari Ilaria
name: Quartesan Ilaria
name: Alessandro, Lozza
name: Deligianni Xeni
name: Francesco, Santini
name: Enrico, Marchioni
name: Cosentino Giuseppe
name: Alfonsi Enrico
name: Cristina, Tassorelli
name: Stefano, Bastianello
name: Giampaolo, Merlini
name: Giovanni, Palladini
name: Laura, Obici
name: Anna, Pichiecchio
Publisher: name: Zenodo
Year: 2022
Subjects: polyneuropathy
ATTR
magnetic resonance imaging (MRI)
outcome measure
biomarker

description: <strong>Background</strong>. 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 (title of the article: <em>Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study</em>) was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. <strong>Methods</strong>. 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. <strong>Results</strong>- 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. <strong>Conclusions. </strong>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.
description: Funding: Ricerca Corrente 2017-2019/2020 Ministry of Health (Italy); Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia 1751723); Medical Research Council (MR/T001712/1); Fondazione CARIPLO (2019-1836); Inherited Neuropathy Consortium (INC); Fondazione CARIPLO "Harnessing the plasma cell secretory capacity against systemic light chain amyloidosis" (2018-0257); Italian Medicines Agency grant AIFA-2016-02364602 "A phase III randomized study of doxycycline and tauroursodeoxycholic acid (Doxy-TUDCA) plus standard supportive therapy versus standard supportive therapy alone in cardiac amyloidosis caused by transthyretin"; European Academy of Neurology (EAN) Research Fellowship 2021