Volume 10 Supplement 1

First European Congress on Hereditary ATTR amyloidosis

Open Access

Quantitative MR-neurographic parameters can determine and specify nerve injury in amyloid related polyneuropathy

  • Jennifer Kollmer1,
  • Ernst Hund2,
  • Stefan Schönland3,
  • Ute Hegenbart3,
  • Christoph Kimmich3,
  • Arnt Kristen4,
  • Martin Bendszus1 and
  • Mirko Pham1
Orphanet Journal of Rare Diseases201510(Suppl 1):O14

https://doi.org/10.1186/1750-1172-10-S1-O14

Published: 2 November 2015

Background

Hereditary transthyretin-familial-amyloid-polyneuropathy (TTR-FAP) usually manifests with a rapidly progressive, distally-symmetric polyneuropathy [Plante-Bordeneuve, V. and G. Said, Lancet Neurol, 2011; Hund et al, Neurology 2001]. Recently, we were able to show that nerve-injury in TTR-FAP is detectable in-vivo by applying high-resolution MR-Neurography [Kollmer et al, Brain 2015]. The aim of the current study is to further quantify nerve-lesions at thigh-level where nerve-injury has been shown to be strongest, and to determine the ability of two quantitative parameters to clearly differentiate between symptomatic TTR-FAP, asymptomatic gene-carriers and healthy volunteers.

Methods

20 patients with confirmed mutations in the TTR-gene (13 with symptomatic TTR-FAP, 7 asymptomatic gene-carriers), and 40 age/gender-matched healthy volunteers were prospectively included and classified according to neurological and electrophysiological findings. MR-Neurography with high structural resolution was performed on a 3T-MR-scanner (Magnetom/TIM-TRIO/Siemens):1) T2-TSE-fs (TR/TE 5970/55ms, voxel-size 0.4x0.3x3.5mm3); 2) Dual-echo-TSE-fs (TR 5210ms, TE1/TE2 12/73ms, voxel-size 0.4x0.3x3.5 mm3).

Manual voxel-vise segmentation of the sciatic/tibial/common-peroneal nerve with subsequent fully-automatic classification as nerve-lesion-voxels was performed on each axial imaging slice (280/subject). The apparent-T2-relaxation-time (T2app) and proton-spin-density as distinct and quantifiable parameters that measure microstructural nerve-tissue-composition in-vivo [Heiland et al, Neurosci Lett. 2002] were then calculated for all nerve-lesion-voxels.

Results

One-way-ANOVA and post-hoc comparisons showed that proton-spin-density was highest in symptomatic TTR-FAP (549.97±35.78), decreased significantly in asymptomatic gene-carriers (406.09±28.22; p=0.002), and further decreased significantly in controls (286.56±10.04; p<0.0001 vs. symptomatic TTR-FAP and vs. asymptomatic gene-carriers (p=0.004).

Post-hoc comparisons showed that T2app was significantly increased only in symptomatic TTR-FAP (103.92ms±6.4) vs. asymptomatic gene-carriers (79.14ms±1.8; p=0.012) and vs. controls (84.08ms±2.54; p=0.003), but not between asymptomatic gene-carriers and controls (p=0.783).

Conclusion

For the first time, we were able to prove that alterations of the evaluated quantitative markers were highly specific: Asymptomatic carrier-status and symptomatic disease were both closely associated with a strong increase of proton-spin-density, while a significant increase of the T2-relaxation-time was found only in symptomatic TTR-FAP, but not in asymptomatic carriers. These findings suggest that proton-spin-density is more sensitive for the detection of early or even subclinical nerve-lesions, while T2app may serve to specifically differentiate increasing disease severity in already symptomatic TTR-FAP.

Authors’ Affiliations

(1)
University of Heidelberg, Department of Neuroradiology
(2)
University of Heidelberg, Department of Neurology
(3)
University of Heidelberg, Medical Department V (Amyloidosis Center)
(4)
University of Heidelberg, Medical Department III (Amyloidosis Center)

Copyright

© Kollmer et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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