ArticleAnnals of neurology2026
Endogenous Repair in Vanishing White Matter.
Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
objectiveVanishing white matter is a leukodystrophy with remarkable regional variation in disease severity. The cerebral and cerebellar white matter chronically degenerates, while stress-induced episodes of rapid neurological deterioration coincide with the appearance of acute focal lesions in the deep gray structures and brainstem. With clinical recovery, these acute lesions spontaneously improve or completely resolve on magnetic resonance imaging, suggesting endogenous repair. Repair is not observed in cerebral and cerebellar white matter. Here, we investigated whether differences in cellular pathology might explain the regional variation in repair potential.
methodsWe assessed the pathology of astrocytes, microglia, oligodendrocytes, myelin and axons in postmortem human brain tissue of vanishing white matter patients, who died either during or long after episodes of clinical decline, and of controls. We compared the most severely affected frontal white matter with the least affected pons white matter.
resultsIn the frontal white matter, astrocytes, microglia and oligodendrocytes were abnormal with evident failure of their mature functions, whereas in the pons white matter, their morphology was relatively preserved with evidence of better preserved functions, suggesting that differences in neuropathology underlie the divergent regional potential for intrinsic repair.
interpretationLoss of glial cell functions in the cerebral white matter relates to irreversible degeneration, whereas preserved glial functions and valid inflammatory response in the pons coincide with spontaneous repair in vanishing white matter. Unraveling the cellular behavior underlying the potential for repair in the pons could pave the way to novel treatment strategies for this still incurable disease. ANN NEUROL 2026;99:737-747.
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