Article Text

Download PDFPDF

222 Investigating directionality of neurodegeneration in vivo in ALS using multimodal MRI
  1. Charmaine L Toh1,
  2. Andrew Keslake1,
  3. Joseph Harding2,
  4. Kathleen Baster3,
  5. Nigel Hoggard2,
  6. Julia Bigley2,
  7. Christopher J McDermott1,4,
  8. Pamela J Shaw1,4,
  9. Iain D Wilkinson2,
  10. Thomas M Jenkins1,4
  1. 1Sheffield Institute for Translational Neuroscience, University of Sheffield
  2. 2Academic Unit of Radiology, University of Sheffield
  3. 3Statistical Services Unit, University of Sheffield
  4. 4Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust

Abstract

Background The anatomical location of the earliest damage in amyotrophic lateral sclerosis (ALS) is still debated. Two main competing hypotheses have been proposed: the dying-forward hypothesis states the damage occurs in the precentral gyrus (PCG) and spreads caudally, which is in contrast with the dying-back hypothesis. This study aims to address this question of directionality of neurodegeneration in vivo using a multimodal neuroimaging approach to derive measures of damage of the motor pathway and analyse them in a common domain.

Methods MRI was performed on 78 ALS patients and 13 controls. PCG thickness was derived from using FreeSurfer, corticospinal tract (CST) fractional anisotropy (FA) from diffusion tensor imaging using FSL, and axial C3 cord area estimates using Philips online software. Comparisons between patients and controls were reported using unpaired t-tests. Parameter estimates were converted to z-scores, referenced to control data, plotted from PCG through CST to cord and directionality of damage assessed by fitting a mixed-effects linear regression model.

Results Z-scores were not significantly different between PCG and FA (0.24,[95%CI -0.13,0.61], p=0.208) but were significantly lower in FA compared to cross-sectional cord area (-0.85,[95%CI -1.25,-0.46] p<0.001).

Discussion This novel multimodal imaging approach supports a dying-forward neurodegenerative process in ALS.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.