The relation between inflammation and neurodegeneration in multiple sclerosis brains

By J. Frischer, S. Bramow, A. Dal-Bianco, C. Lucchinetti, H. Rauschka, M. Schmidbauer, H. Laursen, P. Sørensen, Hans Lassmann. Brain : a journal of neurology, 2009

1,435 citations recorded by the source corpus.

Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological disease or brain lesions. We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone. In older patients (median 76 years) with long-disease duration (median 372 months), inflammatory infiltrates declined to levels similar to those found in age-matched controls and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimer's or vascular disease. Our study suggests a close association between inflammation and neurodegeneration in all lesions and disease stages of multiple sclerosis. It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.

Subfields: Neurology, Pathology and Forensic Medicine, Rheumatology

View Paper: https://www.semanticscholar.org/paper/e634418a98c9f0c0f850cf97b1c73edf25e27d4c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Neurology

1. Hans Lassmann
2. G. Giovannoni
3. Ruth Dobson

In Pathology and Forensic Medicine

1. Hans Lassmann
2. G. Giovannoni
3. F. Aloisi
4. Ruth Dobson
5. R. Ransohoff

In Rheumatology

1. Hans Lassmann

Citations in the corpus

• Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. (2011, background): “…white matter and substantial cortical grey matter pathology (Peterson et al., 2001; Bo et al., 2003b; Kutzelnigg et al., 2005; Zeis et al., 2008; Frischer et al., 2009; Howell et al., 2010; Magliozzi et al., 2010), the latter being suggested as an important determinant of neurological…”
• Multiple Sclerosis Pathology. (2018, background): “myelinating lesions, but is also seen in inactive or remyelinated plaques as well as in the normalappearing white matter (Frischer et al. 2009).”
• Multiple sclerosis – a review (2018, background): “The composition of the inflammatory infiltrate in relapsing-remitting and progressive MS is similar, although the proportion of B-cells and plasma cells is higher in progressive MS[44].”
• Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis (2019, background): “It was not confirmed in a more recent study (47).”
• Oxidative damage in multiple sclerosis lesions (2011, methodology): “Demyelination and axonal injury occurs on a background of chronic inflammation in the relapsing as well as in the progressive stage of the disease (Frischer et al., 2009) and close contacts between activated micro- glia or macrophages and degenerating axons, myelin sheaths and oligodendrocytes have…”