Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis
Abstract Objective To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular cha...
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Series: | Annals of Clinical and Translational Neurology |
Online Access: | https://doi.org/10.1002/acn3.51049 |
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doaj-9e22a57b5bc84ab196b434c089e25a392021-05-02T21:17:23ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-05-017579980710.1002/acn3.51049Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosisJennifer Kollmer0Ute Hegenbart1Christoph Kimmich2Ernst Hund3Jan C. Purrucker4John M. Hayes5Stephen I. Lentz6Georges Sam7Johann M. E. Jende8Stefan O. Schönland9Martin Bendszus10Sabine Heiland11Markus Weiler12Department of Neuroradiology Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyDepartment of Neurology University of Michigan Ann Arbor MIDepartment of Internal Medicine Division of Metabolism Endocrinology & Diabetes University of Michigan Ann Arbor MIDepartment of Neurology Heidelberg University Hospital Heidelberg GermanyDepartment of Neuroradiology Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyDepartment of Neuroradiology Heidelberg University Hospital Heidelberg GermanyDepartment of Neuroradiology Heidelberg University Hospital Heidelberg GermanyAmyloidosis Center Heidelberg Heidelberg University Hospital Heidelberg GermanyAbstract Objective To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes. Methods Twenty‐five patients with symptomatic ATTRv‐PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mutTTR), and 20 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three‐dimensional gradient echo sequences with and without an off‐resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off‐resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off‐resonance saturation pulse. Subsequently, the MTR and cross‐sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv‐PNP patients and mutTTR‐carriers. Results Sciatic nerve MTR and CSA reliably differentiated between ATTRv‐PNP, mutTTR‐carriers, and controls. MTR was lower in ATTRv‐PNP (26.4 ± 0.7; P < 0.0001) and in mutTTR‐carriers (32.6 ± 0.8; P = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv‐PNP versus mutTTR‐carriers (P = 0.0009). MTR correlated negatively with the NIS‐LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv‐PNP (34.3 ± 1.7 mm3) versus mutTTR‐carriers (26.0 ± 1.1 mm3; P = 0.0005) and versus controls (20.4 ± 1.2 mm3; P < 0.0001). CSA was also higher in mutTTR‐carriers versus controls. Interpretation MTR is a novel imaging marker that can quantify macromolecular changes in ATTRv‐PNP and differentiate between symptomatic ATTRv‐PNP and asymptomatic mutTTR‐carriers and correlates with electrophysiology.https://doi.org/10.1002/acn3.51049 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jennifer Kollmer Ute Hegenbart Christoph Kimmich Ernst Hund Jan C. Purrucker John M. Hayes Stephen I. Lentz Georges Sam Johann M. E. Jende Stefan O. Schönland Martin Bendszus Sabine Heiland Markus Weiler |
spellingShingle |
Jennifer Kollmer Ute Hegenbart Christoph Kimmich Ernst Hund Jan C. Purrucker John M. Hayes Stephen I. Lentz Georges Sam Johann M. E. Jende Stefan O. Schönland Martin Bendszus Sabine Heiland Markus Weiler Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis Annals of Clinical and Translational Neurology |
author_facet |
Jennifer Kollmer Ute Hegenbart Christoph Kimmich Ernst Hund Jan C. Purrucker John M. Hayes Stephen I. Lentz Georges Sam Johann M. E. Jende Stefan O. Schönland Martin Bendszus Sabine Heiland Markus Weiler |
author_sort |
Jennifer Kollmer |
title |
Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
title_short |
Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
title_full |
Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
title_fullStr |
Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
title_full_unstemmed |
Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
title_sort |
magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2020-05-01 |
description |
Abstract Objective To quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes. Methods Twenty‐five patients with symptomatic ATTRv‐PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mutTTR), and 20 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three‐dimensional gradient echo sequences with and without an off‐resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off‐resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off‐resonance saturation pulse. Subsequently, the MTR and cross‐sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv‐PNP patients and mutTTR‐carriers. Results Sciatic nerve MTR and CSA reliably differentiated between ATTRv‐PNP, mutTTR‐carriers, and controls. MTR was lower in ATTRv‐PNP (26.4 ± 0.7; P < 0.0001) and in mutTTR‐carriers (32.6 ± 0.8; P = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv‐PNP versus mutTTR‐carriers (P = 0.0009). MTR correlated negatively with the NIS‐LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv‐PNP (34.3 ± 1.7 mm3) versus mutTTR‐carriers (26.0 ± 1.1 mm3; P = 0.0005) and versus controls (20.4 ± 1.2 mm3; P < 0.0001). CSA was also higher in mutTTR‐carriers versus controls. Interpretation MTR is a novel imaging marker that can quantify macromolecular changes in ATTRv‐PNP and differentiate between symptomatic ATTRv‐PNP and asymptomatic mutTTR‐carriers and correlates with electrophysiology. |
url |
https://doi.org/10.1002/acn3.51049 |
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