The relation between inflammation and neurodegeneration in multiple sclerosis brains

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

Imaging cortical multiple sclerosis lesions with ultra-high field MRI

BACKGROUND: Cortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7 T and above provides technological advances suited to optimize the detection of cortical lesions in MS. PURPOSE: To provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS. METHODS: A systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3 T and 7 T MRI and between 7 T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology. RESULTS: 7 T MRI detected on average 52 ± 26% (mean ± 95% confidence interval) more cortical lesions than the best performing image contrast at 3 T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17 ± 6 per patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Yet, there was no difference in lesion type ratio between these MS subtypes. Furthermore, superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33 ± 6% and 71 ± 10%, respectively, with the highest sensitivity towards type I and type IV lesions. CONCLUSION: UHF MRI improves cortical lesion detection in MS considerably compared to 3 T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7 T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed