ReviewActa neuropathologica2025
A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.
Review in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment.Cell reports. Medicine · 2026Trial
- MRI-Based Quantitative Assessment of Normal-Appearing White and Gray Matter Demyelination in Multiple Sclerosis, Parkinson's Disease, Long COVID, and Normal Aging.Biomedicines · 2026Article
- Lesion-specific circular RNA and mRNA signatures in secondary progressive multiple sclerosis.Molecular brain · 2026Article
- Regional IVIM-DWI Abnormalities in Normal-Appearing White Matter and Lesion Tissue in Relapsing-Remitting Multiple Sclerosis.Journal of clinical medicine · 2026Article
- Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.Journal of neuropathology and experimental neurology · 2026Article
- From Phenotypes to Spectrum: Rethinking RRMS, SPMS and PPMS in the Era of PIRA-A Framework Integrating PIRA, Smouldering-Associated Worsening, and Neurologic Reserve to Facilitate Earlier Recognition of Progression.Neurology international · 2026Review
- Smoldering neuroinflammation in progressive multiple sclerosis: mechanisms, imaging biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Enhanced therapeutic potential of paeoniflorin and vitamin B12 in intracerebropeduncle ethidium bromide-induced multiple sclerosis-like pathology.Frontiers in pharmacology · 2026Article
- NOR1 loss relates to inflammation and biological ageing in multiple sclerosis motor cortex.Brain communications · 2026Article
- Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and Ageing-Related Pathway Dysregulation.Journal of extracellular vesicles · 2025Article
- IVIM-DWI-Based Radiomics for Lesion Phenotyping and Clinical Status Prediction in Relapsing-Remitting Multiple Sclerosis.Journal of clinical medicine · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Multiple sclerosis is a chronic neuro-inflammatory and neurodegenerative disease, traditionally characterized by the presence of focal demyelinating lesions in the CNS. However, accumulating evidence suggests that multiple sclerosis pathophysiology extends beyond such classical lesions, affecting also 'normal' appearing tissue in both white and gray matter, referred to as 'normal-appearing white matter' and 'normal-appearing gray matter', respectively. Here, we provide a comprehensive overview of the widespread biochemical, cellular, and microstructural alterations occurring in these 'normal-appearing' CNS regions. Additionally, we discuss the evidence derived from human post-mortem studies that support that normal-appearing white and gray matter could be the drivers of smoldering-associated pathological worsening once repair mechanisms are exhausted. Comprehensive understanding of multiple sclerosis pathology beyond classical lesions not only provides a more complete picture of disease progression, but also provides further insights into potential novel therapeutic avenues in order to slow or halt disability accumulation.
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Registered trials
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