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Research paper
Differential corticospinal tract degeneration in homozygous ‘D90A’ SOD-1 ALS and sporadic ALS
  1. C R V Blain1,2,
  2. S Brunton3,4,
  3. V C Williams2,
  4. A Leemans5,
  5. M R Turner6,
  6. P M Andersen7,
  7. M Catani3,
  8. B R Stanton2,
  9. J Ganesalingham2,
  10. D K Jones8,
  11. S C R Williams3,4,
  12. P N Leigh1,2,4,
  13. A Simmons2,3,4
  1. 1Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK
  2. 2MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK
  3. 3Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK
  4. 4NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, UK
  5. 5Image Sciences Institute, University Medical Center Utrecht, Heidelberglaan, Utrecht, The Netherlands
  6. 6Department of Clinical Neurology, John Radcliffe Hospital, Oxford University, Oxford, UK
  7. 7Department of Neurology, Umeå University Hospital, Umeå, Sweden
  8. 8CUBRIC Centre, Cardiff University, Cardiff, UK
  1. Correspondence to Dr Andrew Simmons, Department of Neuroimaging, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK; andy.simmons{at}kcl.ac.uk

Abstract

Background The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis.

Method 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using ‘upper motor neuron burden,’ El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length.

Results Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls.

Conclusions Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.

  • Amyotrophic lateral sclerosis
  • diffusion tensor tractography
  • corticospinal tract
  • fractional anisotropy
  • mean diffusivityALSimage analysisMRI

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/jnnp.2010.236018

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    Footnotes

    • See Editorial commentary, p 827

    • Linked article 241521.

    • CRVB and KB are joint first authors.

    • Funding This study was supported by funding from the Motor Neuron Disease Association and the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London. Part of this work was funded through a personal Fellowship from the Wellcome Trust awarded to MRT in 2001. MRT is currently supported by the Medical Research Council/Motor Neurone Disease Association UK Lady Edith Wolfson Clinician Scientist Fellowship. PMA was supported by the Swedish Brain Power Consortium, the Swedish Brain Research Foundation, the Hållstens Research Foundation and the Swedish association for the neurologically disabled.

    • Competing interests None.

    • Ethics approval Ethics approval was provided by the Institute of Psychiatry, King's College London ethics board.

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

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