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Neurodegeneration
Research paper
Imaging the pathoanatomy of amyotrophic lateral sclerosis in vivo: targeting a propagation-based biological marker
  1. Jan Kassubek1,
  2. Hans-Peter Müller1,
  3. Kelly Del Tredici2,
  4. Dorothée Lulé1,
  5. Martin Gorges1,
  6. Heiko Braak2,
  7. Albert C Ludolph1
  1. 1 Department of Neurology, University of Ulm, Ulm, Germany
  2. 2 Clinical Neuroanatomy, Department of Neurology, University of Ulm, Ulm, Germany
  1. Correspondence to Professor Jan Kassubek, Department of Neurology, University of Ulm, Ulm 89081, Germany; jan.kassubek{at}uni-ulm.de

Abstract

Objective Neuropathological studies in amyotrophic lateral sclerosis (ALS) have shown a dissemination in a regional sequence in four anatomically defined patterns. The aim of this retrospective study was to see whether longitudinal diffusion tensor imaging (DTI) data support the pathological findings.

Methods The application of DTI analysis to fibre structures that are prone to be involved at each neuropathological pattern of ALS was performed in a monocentre sample of 67 patients with ALS and 31 controls that obtained at least one follow-up scan after a median of 6 months.

Results At the group level, longitudinal ALS data showed significant differences for the stage-related tract systems. At the individual level, 27% of the longitudinally scanned patients with ALS showed an increase in ALS stage, while the remaining were stable or were at the highest ALS stage. Longitudinal fractional anisotropy changes in the respective tract systems correlated significantly with the slope of the revised ALS functional rating scale.

Interpretation The DTI-based protocol was able to image the disease patterns of ALS in vivo cross-sectionally and longitudinally, in support of DTI as a technical marker to image ALS stages.

  • amyotrophic lateral sclerosis
  • diffusion tensor imaging
  • biomarkers

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jnnp-2017-316365

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    Footnotes

    • JK and H-PM are shared first authorship.

    • Contributors JK and H-PM: study concept and design, data analysis and interpretation of data, study supervision, drafting of manuscript. KDT: interpretation of data, critical revision of manuscript for intellectual content. DL: data collection, interpretation of data, critical revision of manuscript for intellectual content. MG: data collection, interpretation of data, critical revision of manuscript for intellectual content. HB: interpretation of data, critical revision of manuscript for intellectual content. ACL: study supervision, interpretation of data, critical revision of manuscript for intellectual content. All authors report no disclosures.

    • Funding This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG Grant Number LU 336/15-1) and the German Network for Motor Neuron Diseases (BMBF01GM1103A).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval All participating patients and controls provided written informed consent for the study according to institutional guidelines. The study was approved by the Ethical Committee of the University of Ulm (reference #19/12).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional unpublished data from the study are available.