Article Text

Research paper
Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron
  1. Lukas Haider1,
  2. Constantina Simeonidou2,
  3. Günther Steinberger1,
  4. Simon Hametner1,
  5. Nikolaos Grigoriadis3,
  6. Georgia Deretzi3,
  7. Gabor G Kovacs4,
  8. Alexandra Kutzelnigg1,5,
  9. Hans Lassmann1,
  10. Josa M Frischer1,6
  1. 1Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria
  2. 2Department of Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  3. 3Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
  4. 4Institute of Neurology, Medical University of Vienna, Vienna, Austria
  5. 5Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
  6. 6Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Dr Josa M Frischer, Department of Neurosurgery, Medical University of Vienna, Waehringerguertel 18-20, A-1090 Vienna, Austria; josa.frischer{at}meduniwien.ac.at

Abstract

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.

  • Multiple Sclerosis
  • Neuroimmunology
  • Iron Deposition

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) 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/3.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

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.

Linked Articles