The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain
Open accessAbstract
Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. Multiple sclerosis is characterized by widespread primary demyelination and progressive degeneration, driven by heterogeneous mechanisms. Haider et al. provide a topographic map of the frequency with which different brain regions are affected by these processes, and show that demyelination and neurodegeneration involve inflammatory as well as vascular changes.
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In multiple sclerosis, gray matter lesions are present throughout the entire cortex, but particularly frequently in cingulate and insular cortex.
“Most convincingly, neuropathological work focusing on cortex showed that in multiple sclerosis gray matter lesions are present throughout the entire cortex, but particularly frequently in cingulate and insular cortex (Haider et al., 2016).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Haider et al., 2016
In MS, lesions frequently affect insular cortex.
“For example, in MS, lesions frequently affect insular cortex (Haider et al., 2016);”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Haider et al., 2016
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- Authors
- Haider, L., Zrzavy, T., Hametner, S., Höftberger, R., Bagnato, F., Grabner, G., Trattnig, S., Pfeifenbring, S., Brück, W., & Lassmann, H.
- Affiliations
- Medical University of Vienna (AT)
- Vanderbilt University (US)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Zrzavy, Tobias
- Lassmann, Hans
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-08
- Volume
- 139
- Issue
- 3
- Pages
- 807-815
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC4766379
- OpenAlex
- W2273220492
- Cited by
- 400
- References
- 42
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 42 · 2023: 37 · 2022: 42 · 2021: 53 · 2020: 49 · 2019: 44 · 2018: 38 · 2017: 28 · 2016: 14
- FWCI
- 37.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brain (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- GRO (submittedVersion)
- Funders
- Parkinson's UK (G0909, J-1402)
- Multiple Sclerosis Society (207495)
- Austrian Science Fund (I2114)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- multiple sclerosis, demyelination, neurodegeneration, cerebral cortex, white matter lesions, Sulcis, cerebrospinal fluid flow, drainage area, axonal loss, brain atrophy
- MeSH terms
- Brain, Brain Mapping, Cerebral Cortex, Demyelinating Diseases, Humans, Multiple Sclerosis, Nerve Degeneration, Cohort Studies, White Matter
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