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Open AccessJournal ArticleDOI

Inflammatory Cortical Demyelination in Early Multiple Sclerosis

TLDR
In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation.
Abstract
Background Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease. Methods We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, ...

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How neuroinflammation contributes to neurodegeneration.

TL;DR: Observations indicate that therapies targeting glial cells might provide benefit for those afflicted by neurodegenerative disorders, because the environment is affected during disease in a cascade of processes collectively termed neuroinflammation.
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Pathological mechanisms in progressive multiple sclerosis

TL;DR: It is proposed that the inflammatory demyelinating disease process in early multiple sclerosis triggers a cascade of events that lead to neurodegeneration and are amplified by pathogenic mechanisms related to brain ageing and accumulated disease burden.
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Astrocyte barriers to neurotoxic inflammation

TL;DR: Evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders is discussed.
Journal ArticleDOI

Progressive multiple sclerosis: pathology and pathogenesis

TL;DR: Oxidative stress seems to be mainly driven by inflammation and oxidative burst in microglia; however, its effects might be amplified in patients with progressive MS by age-dependent iron accumulation in the brain and by mitochondrial gene deletions, triggered by the chronic inflammatory process.
References
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Journal ArticleDOI

Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination.

TL;DR: At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
Journal ArticleDOI

Revised diagnostic criteria for neuromyelitis optica

TL;DR: Revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity.
Journal ArticleDOI

Cortical demyelination and diffuse white matter injury in multiple sclerosis

TL;DR: Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
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