title: Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.
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.
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Haider
authors.affiliation: Department of Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Constantina
authors.initials: C
authors.lastname: Simeonidou
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Steinberger
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Hametner
authors.affiliation: Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.affiliation: Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Deretzi
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kutzelnigg
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Vienna, Austria Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Josa M
authors.initials: JM
authors.lastname: Frischer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000473:pathology; D003711:Demyelinating Diseases / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007031:Hypothalamus / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D007501:Iron / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology
chemical_list: D007501:Iron
keywords: Iron Deposition; Multiple Sclerosis; Neuroimmunology