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60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

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Higher levels of acute axonal injury in the spinal normal-appearing white matter in multiple sclerosis than neuromyelitis optica

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  • corresponding author presenting/speaker Christiane Wegner - Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • Agnes Swiniarski - Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • Martina Ott - Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • Christine Stadelmann - Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • Wolfgang Brück - Institute of Neuropathology, University Medical Center Goettingen, Goettingen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP22

doi: 10.3205/15dgnn46, urn:nbn:de:0183-15dgnn469

Published: August 25, 2015

© 2015 Wegner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) display inflammatory demyelinating lesions in the spinal cord, brain and optic nerve. In contrast to relative clinical stability between relapses in NMO, MS patients typically accumulate disability independently of relapses during the progressive phase. Pathological changes in the normal-appearing white matter (NAWM) are thought to contribute to the clinical progression of the disease.

Question: The aim of this study was to investigate inflammatory and axonal changes in NAWM in MS and NMO cases.

Patients and methods: We studied cerebral and spinal NAWM in postmortem samples from 24 patients with progressive MS, 5 patients with long-standing NMO and 13 control subjects without neurological disease. LFB/PAS staining and aquaporin-4 (AQP-4) immunostaining were used to identify NAWM. Immunohistochemistry was performed to quantify T cells, microglial cells and acutely damaged axons immunopositive for amyloid precursor protein (APP). Axonal densities were assessed on Bielschowsky silver-stained sections.

Results: NAWM was characterized by regular myelin staining and AQP-4 immunoreactivity. NAWM of MS and NMO cases showed a similar increase of parenchymal T cells in comparison to controls. In addition both diseases displayed higher densities of microglial cells in spinal NAWM than control subjects. However, a higher frequency of microglial nodules was only observed in the normal-appearing spinal cord of MS cases. In spinal NAWM, both diseases displayed a similar substantial reductionin axonal densities of approximately 40% in comparison to control subjects. To test for acute axonal damage, we quantified APP-positive axons. Only MS patients showed a significant four-fold increase of APP-positive axons in spinal NAWM in comparison to NMO and control cases.

Conclusions: Both diseases show inflammation and substantial axonal loss in spinal NAWM. However, only MS cases displayed increased acute axonal injury in the normal-appearing spinal cord. Thus, the MS-related finding of ongoing axonal damage in NAWM is likely to play a role in the insidious increase in disability in progressive MS.