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Cited by 314Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

Extensive cortical remyelination in patients with chronic multiple sclerosis

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Albert, Monika, Antel, Jack, Brück, Wolfgang, Stadelmann, Christine·2007·Brain Pathology
DOI 10.1111/j.1750-3639.2006.00043.xPMC PMC8095564
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Abstract

Recent studies revealed prominent cortical demyelination in patients with chronic multiple sclerosis (MS). Demyelination in white matter lesions is frequently accompanied by remyelination. This repair process, however, often remains incomplete and restricted to the lesion border. In the present study, we examined the frequency and extent of remyelination in cortical and white matter lesions in autopsy brain tissue of 33 patients with chronic MS. The majority of patients (29 of 33) harbored cortical demyelination. Remyelination of cortical lesions was identified light microscopically by the presence of thin and irregularly arranged myelin sheaths, and confirmed by electron microscopy. Extensive remyelination was found in 18%, remyelination restricted to the lesion border in 54%, and no remyelination in 28% of cortical lesions. A direct comparison of the extent of remyelination in white matter and cortical lesions of the same patients revealed that remyelination of cortical lesions was consistently more extensive. In addition, g‐ratios of fibers in areas of “normal appearing cortex” yielded values consistent with remyelination. Our data confirm the high prevalence of cortical demyelination in chronic MS and imply that the propensity to remyelinate is high in cortical MS lesions.

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  • Previous experimental and human work suggests that g-ratios are higher and internodes shorter in demyelinated cortex than in normal cortex, without directly associating newly formed internodes to BCAS1 expression.

    “Previous experimental and human work on demyelinated cortex suggests that g-ratios are indeed higher and internodes shorter than in NC, however, without directly associating newly formed internodes to the expression of BCAS1.10,17”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [17]

    The Results report higher g-ratios in remyelinated cortical areas than in control cortex (0.76 versus 0.65). They do not report g-ratios for demyelinated cortex or measure internode length. The paper also does not assess BCAS1 expression or link it to newly formed internodes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In multiple sclerosis, remyelination occurs in both white and grey matter and is more efficient in the cortex than in white matter lesions in the same patient.

    “In patients with multiple sclerosis, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex.”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [17]

  • Remyelination after a demyelinating insult is more efficient in the cerebral cortex compared to the white matter.

    “Previous studies in human post-mortem tissue and experimental models suggested that remyelination after a demyelinating insult is more efficient in the cerebral cortex compared to the white matter.”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [17]

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Research works printed but not linked: 45

  1. [1]1. Allen IV (1991) Pathology of multiple sclerosis. In: Mcalpine’s Multiple Sclerosis. Matthews WB (ed.), pp. 341–378. Churchill Livingstone: Edinburgh. [Google Scholar]
  2. [2]2. Baracskay KL, Duchala CS, Miller RH, Macklin WB, Trapp BD (2002) Oligodendrogenesis is differentially regulated in gray and white matter of jimpy mice. J Neurosci Res 70:645–654. [DOI] [PubMed] [Google Scholar]
  3. [3]3. Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, Van Der Valk P (2003) Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol 60:1073–1081. [DOI] [PubMed] [Google Scholar]
  4. [4]4. Barres BA, Raff MC (1993) Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons. Nature 361:258–260. [DOI] [PubMed] [Google Scholar]
  5. [5]5. Blakemore WF (1973) Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone. J Neurol Sci 20:73–83. [DOI] [PubMed] [Google Scholar]
  6. [6]6. Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ (2003) Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 9:323–331. [DOI] [PubMed] [Google Scholar]
  7. [7]7. Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62:723–732. [DOI] [PubMed] [Google Scholar]
  8. [8]8. Breitschopf H, Suchanek G, Gould RM, Colman DR, Lassmann H (1992) In situ hybridization with digoxigenin‐labeled probes: sensitive and reliable detection method applied to myelinating rat brain. Acta Neuropathol 84:581–587. [DOI] [PubMed] [Google Scholar]
  9. [9]9. Brownell B, Hughes JT (1962) Distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25:315–320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. [10]10. Bruck W, Kuhlmann T, Stadelmann C (2003) Remyelination in multiple sclerosis. J Neurol Sci 206:181–185. [DOI] [PubMed] [Google Scholar]
  11. [11]11. Catalaa I, Fulton JC, Zhang X, Udupa JK, Kolson D, Grossman M, Wei L, McGowan JC, Polansky M, Grossman RI (1999) MR imaging quantitation of gray matter involvement in multiple sclerosis and its correlation with disability measures and neurocognitive testing. AJNR Am J Neuroradiol 20:1613–1618. [PMC free article] [PubMed] [Google Scholar]
  12. [12]12. Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173. [DOI] [PubMed] [Google Scholar]
  13. [13]13. Chen JT, Narayanan S, Collins DL, Smith SM, Matthews PM, Arnold DL (2004) Relating neocortical pathology to disability progression in multiple sclerosis using MRI. Neuroimage 23: 1168–1175. [DOI] [PubMed] [Google Scholar]
  14. [14]14. Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86:209–219. [DOI] [PubMed] [Google Scholar]
  15. [15]15. Dawson JW (1916) The histology of multiple sclerosis. Trans Roy Soc Edinburgh 50:517–740. [Google Scholar]
  16. [16]16. Dinkler (1904) Zur Kasuistik der multiplen Herdsklerose des Gehirns und Rückenmarks. Deutsche Zeitschrift für Nervenheilkunde 3:233–247. [Google Scholar]
  17. [17]17. Franklin RJ (2002) Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3:705–714. [DOI] [PubMed] [Google Scholar]
  18. [18]18. Friede RL, Beuche W (1985) A new approach toward analyzing peripheral nerve fiber populations. I. Variance in sheath thickness corresponds to different geometric proportions of the internodes. J Neuropathol Exp Neurol 44:60–72. [DOI] [PubMed] [Google Scholar]
  19. [19]19. Gledhill RF, Harrison BM, McDonald WI (1973) Pattern of remyelination in the CNS. Nature 244:443–444. [DOI] [PubMed] [Google Scholar]
  20. [20]20. Hildebrand C, Remahl S, Persson H, Bjartmar C (1993) Myelinated nerve fibres in the CNS. Prog Neurobiol 40:319–384. [DOI] [PubMed] [Google Scholar]
  21. [21]21. Johnson ES, Ludwin SK (1981) The demonstration of recurrent demyelination and remyelination of axons in the central nervous system. Acta Neuropathol (Berl) 53:93–98. [DOI] [PubMed] [Google Scholar]
  22. [22]22. Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T (1999) Cortical lesions in multiple sclerosis. Brain 122:17–26. [DOI] [PubMed] [Google Scholar]
  23. [23]23. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712. [DOI] [PubMed] [Google Scholar]
  24. [24]24. Lassmann H (1998) Pathology of multiple sclerosis. In: McAlpine’s Multiple Sclerosis. Compston A (ed.), pp. 323–358. Churchill Livingstone: London. [Google Scholar]
  25. [25]25. Lassmann H, Bruck W, Lucchinetti C, Rodriguez M (1997) Remyelination in multiple sclerosis. Mult Scler 3:133–136. [DOI] [PubMed] [Google Scholar]
  26. [26]26. Lassmann H, Bruck W, Lucchinetti C (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 7:115–121. [DOI] [PubMed] [Google Scholar]
  27. [27]27. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 122:2279–2295. [DOI] [PubMed] [Google Scholar]
  28. [28]28. Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Multiple Sclerosis and Other Demyelinating Diseases. Vinken PJ, Bruyn GW (eds), pp. 217–309. North‐Holland Publishing Company: Amsterdam. [Google Scholar]
  29. [29]29. Merkler D, Ernsting T, Kerschensteiner M, Bruck W, Stadelmann C (2006) A new focal EAE model of cortical demyelination: multiple sclerosis‐like lesions with rapid resolution of inflammation and extensive remyelination. Brain May 19 [Epub ahead of print. [DOI] [PubMed]
  30. [30]30. Mews I, Bergmann M, Bunkowski S, Gullotta F, Bruck W (1998) Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Mult Scler 4:55–62. [DOI] [PubMed] [Google Scholar]
  31. [31]31. Newcombe J, Hawkins CP, Henderson CL, Patel HA, Woodroofe MN, Hayes GM, Cuzner ML, MacManus D, Du Boulay EP, McDonald WI (1991) Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue. Brain 114:1013–1023. [DOI] [PubMed] [Google Scholar]
  32. [32]32. Noble M, Arhin A, Gass D, Mayer‐Proschel M (2003) The cortical ancestry of oligodendrocytes: common principles and novel features. Dev Neurosci 25:217–233. [DOI] [PubMed] [Google Scholar]
  33. [33]33. Ozawa K, Suchanek G, Breitschopf H, Bruck W, Budka H, Jellinger K, Lassmann H (1994) Patterns of oligodendroglia pathology in multiple sclerosis. Brain 117:1311–1322. [DOI] [PubMed] [Google Scholar]
  34. [35]35. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Demyelinating Diseases. JC Koetsier (ed.), pp. 337–398. Elsevier Science Publishers: Amsterdam. [Google Scholar]
  35. [36]36. Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5:22–31. [DOI] [PubMed] [Google Scholar]
  36. [38]38. Raine CS, Wu E (1993) Multiple sclerosis: remyelination in acute lesions. J Neuropathol Exp Neurol 52:199–204. [PubMed] [Google Scholar]
  37. [39]39. Rossolimo G (1897) Zur Frage über die Multiple Sklerose und Gliose. Deutsche Zeitschrift für Nervenheilkunde XI:88–121. [Google Scholar]
  38. [40]40. Sander M (1898) Hirnrindenbefunde bei multipler Sklerose. Monatschrift Psychiatrie Neurol IV:429–436. [Google Scholar]
  39. [41]41. Schmitt FO, Bear RS (1937) The optical properties of vertebrate nerve axons as related to fibre size. J Cell Comp Physiol 9:261–273. [Google Scholar]
  40. [42]42. Schwab C, McGeer PL (2002) Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis. Exp Neurol 174:81–88. [DOI] [PubMed] [Google Scholar]
  41. [43]43. Shields SA, Gilson JM, Blakemore WF, Franklin RJ (1999) Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin‐induced CNS demyelination. Glia 28:77–83. [DOI] [PubMed] [Google Scholar]
  42. [44]44. Sim FJ, Zhao C, Penderis J, Franklin RJ (2002) The age‐related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 22:2451–2459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. [45]45. Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125:75–85. [DOI] [PubMed] [Google Scholar]
  44. [46]46. Taylor EW (1892) Zur pathologischen Anatomie der multiplen Sklerose. Deutsche Zeitschrift für Nervenheilkunde 5:1–26. [Google Scholar]
  45. [47]47. Wolswijk G (1994) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci 18:601–609. [DOI] [PMC free article] [PubMed] [Google Scholar] Articles from Brain Pathology are provided here courtesy of Wiley

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Authors
Albert, M., Antel, J., Brück, W., & Stadelmann, C.
Affiliations
  • University of Göttingen (DE)
  • McGill University (CA)
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2007-01-22
Volume
17
Issue
2
Pages
129-138
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2006.00043.x
PMC
PMC8095564
OpenAlex
W2035195833
Cited by
314
References
2
Citations by year
2026: 9 · 2025: 13 · 2024: 18 · 2023: 15 · 2022: 16 · 2021: 30 · 2020: 14 · 2019: 15 · 2018: 13 · 2017: 21 · 2016: 12 · 2015: 16 · 2014: 15 · 2013: 20 · 2012: 22
FWCI
12.30
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • GRO (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
multiple sclerosis, remyelination, cortical demyelination, white matter lesions, myelin sheath, g-ratio, lesion border, autopsy brain tissue
MeSH terms
Adult, Aged, Aged, 80 and over, Brain, Female, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Middle Aged, Myelin Sheath, In Situ Hybridization, Multiple Sclerosis, Chronic Progressive, Microscopy, Electron, Transmission

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