ArticleAnnals of clinical and translational neurology2024
Micro-diffusely abnormal white matter: An early multiple sclerosis lesion phase with intensified myelin blistering.
Article in Annals of clinical and translational neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Experimental induction of myelin damage in post-mortem human brain slice cultures.Acta neuropathologica communications · 2026Article
- Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.Journal of neuropathology and experimental neurology · 2026Article
- Myelin sheaths in the central nervous system can withstand damage and dynamically remodel.Science (New York, N.Y.) · 2026Article
- Label-free tracking of subcortical white matter degradationBiomedical optics express · 2026Article
- Multiple sclerosis and autoimmunity: a reappraisal of the evidence.Frontiers in immunology · 2026Review
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- Recent developments in multiple sclerosis neuropathology.Current opinion in neurology · 2025Review
- Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis.Nature reviews. Neurology · 2025Review
- Dynamic imaging of myelin pathology in physiologically preserved human brain tissue using third harmonic generation microscopy.PloS one · 2025Article
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Differential Analysis of Venous Sinus Diameters: Unveiling Vascular Alterations in Patients with Multiple Sclerosis.Diagnostics (Basel, Switzerland) · 2024Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveMultiple sclerosis (MS) is a chronic central nervous system disease whose white matter lesion origin remains debated. Recently, we reported subtle changes in the MS normal appearing white matter (NAWM), presenting with an increase in myelin blisters and myelin protein citrullination, which may recapitulate some of the prodromal degenerative processes involved in MS pathogenesis. Here, to clarify the relevance of these changes for subsequent MS myelin degeneration we explored their prevalence in WM regions characterized by subtly reduced myelination (dubbed as micro-diffusely abnormal white matter, mDAWM).
methodsWe used an in-depth (immuno)histochemistry approach in 27 MS donors with histological presence of mDAWM and 5 controls. An antibody panel against degenerative markers was combined and the presence of myelin/axonal aberrations was analyzed and compared with the NAWM from the same cases/slices/regions.
resultsmDAWM-defined areas exhibit ill-defined borders, no signs of Wallerian degeneration, and they associate with visible veins. Remarkably, such areas present with augmented myelin blister frequency, enhanced prevalence of polar myelin phospholipids, citrullination, and degradation of myelin basic protein (MBP) when compared with the NAWM. Furthermore, enhanced reactivity of microglia/macrophages against citrullinated MBP was also observed in this tissue.
interpretationWe report a new histologically defined early phase in MS lesion formation, namely mDAWM, which lacks signs of Wallerian pathology. These results support the prelesional nature of the mDAWM. We conceptualize that evolution to pathologically evident lesions comprises the previously documented imbalance of axo-myelinic units (myelin blistering) leading to their degeneration and immune system activation by released myelin components.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.