IRCCS Mondino Foundation
Published August 29, 2022 | Version v1
Other Restricted

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study

Authors/Creators

  • 1. IRCCS Mondino Foundation, Pavia; University of Pavia (Italy)
  • 2. UCL Queen Square Institute of Neurology; National Hospital Neurology Neurosurgery, London (UK); University of Pavia (Italy)
  • 3. University at Buffalo, NY (USA); IRCCS Fondazione Don Gnocchi (Italy)
  • 4. IRCCS Policlinico S. Matteo, Pavia; University of Pavia (Italy)
  • 5. IRCCS Mondino Foundation, Pavia (Italy)
  • 6. University of Pavia (Italy)
  • 7. University of Pavia (Italy); UCL Queen Square Institute of Neurology; National Hospital Neurology Neurosurgery, London (UK)
  • 8. Meyer Children's University Hospital, Florence (Italy)
  • 9. University Hospital Basel (Switzerland)
  • 10. IRCCS Policlinico S. Matteo; University of Pavia (Italy)
  • 11. IRCCS Mondino Foundation, Pavia, (Italy)

Description

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 (title of the article: Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional 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.

Notes

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

Files

Restricted

The record is publicly accessible, but files are restricted. <a href="https://zenodo.org/account/settings/login?next=https://zenodo.org/records/7030896">Log in</a> to check if you have access.

Request access

If you would like to request access to these files, please fill out the form below.

You need to satisfy these conditions in order for this request to be accepted:

This data set of raw data is accessible under request by writing to the Scientific Direction of the IRCCS Mondino Foundation (dirsci@mondino.it) specifying:

  1. own affiliation;
  2. how one intends to use data.

You are currently not logged in. Do you have an account? Log in here

Additional details

Related works

Is published in
Journal article: 10.1007/s00415-022-11336-z (DOI)