The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Abnormal blood–brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI
Open accessAbstract
OBJECTIVES: To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics. METHODS: Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls. RESULTS: Permeability measured as K(trans) was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment. CONCLUSIONS: Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.
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“More recently, an increase in BBB permeability has been shown in MS patients by DCE-MRI in the cortex and adjacent white matter (392), corpus callosum and internal capsule (121-123, 421, 574), as well as thalamic gray matter (123).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [123]
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Cites
Schumacher, G. A., Beebe, G., Kibler, R. F., Kurland, L. T., Kurtzke, J. F., McDowell, F., Nagler, B., Sibley, W. A., Tourtellotte, W. W., & Willmon, T. L. (1965) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1965.tb20235.x · Cited by 1,438 · cited 1×
“Relapsewasdefined as new or worsening symptoms that lasted 24 h and occurred in the absence of fever or infection (Schumacher et al., 1965).”
BackgroundProgressive multiple sclerosis: pathology and pathogenesis
Lassmann, H., van Horssen, J., & Mahad, D. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.168 · Cited by 1,033 · cited 5×
“…did not include secondary progressive MS patients, where the relationship between inflammation and damage to the BBB is less obvious than in RRMS (Lassmann et al., 2012), secondly, our cohorts were all evaluated for treatment intensification, thus presumably having a high relative disease…”
BackgroundInfluentialBlood-brain barrier disruption in multiple sclerosis
Minagar, A., & Alexander, J. S. (2003) · Multiple Sclerosis · doi:10.1191/1352458503ms965oa · Cited by 685 · cited 2×
“However, the MS disease process itself seems capable of modifying the permeability of the BBB (Larochelle et al., 2011; Minagar and Alexander, 2003) but we observed no correlation between permeability and age, EDSS or years sinceMS onset indicating that BBB abnormalities do not seem toworsen with disease progression.”
BackgroundKERMODE, A. G., THOMPSON, A. J., TOFTS, P., MACMANUS, D. G., KENDALL, B. E., KINGSLEY, D. P. E., MOSELEY, I. F., RUDGE, P., & MCDONALD, W. I. (1990) · Brain · doi:10.1093/brain/113.5.1477 · Cited by 578 · cited 1×
“All rights reser inactive MS lesions as well as normal appearing white matter (NAWM) (Kirk et al., 2003; McQuaid et al., 2009; Plumb et al., 2002; Vos et al., 2005), and serial MRI studies have indicated that structural changes (Filippi et al., 1998; Werring, 2000) and BBB dysfunction (Goodkin et…”
BackgroundHow do immune cells overcome the blood-brain barrier in multiple sclerosis?
Larochelle, C., Alvarez, J. I., & Prat, A. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.04.066 · Cited by 405 · cited 3×
“On the other hand, activated leukocytes themselves are capable of altering BBB permeability through expression and secretion of inflammatory cytokines (Larochelle et al., 2011).”
BackgroundFilippi, M., Rocca, M. A., Martino, G., Horsfield, M. A., & Comi, G. (1998) · Annals of Neurology · doi:10.1002/ana.410430616 · Cited by 395 · cited 2×
“…white matter (NAWM) (Kirk et al., 2003; McQuaid et al., 2009; Plumb et al., 2002; Vos et al., 2005), and serial MRI studies have indicated that structural changes (Filippi et al., 1998; Werring, 2000) and BBB dysfunction (Goodkin et al., 1998) may precedemyelin damage and leukocyte infiltration.”
BackgroundKirk, J., Plumb, J., Mirakhur, M., & McQuaid, S. (2003) · The Journal of Pathology · doi:10.1002/path.1434 · Cited by 375 · cited 2×
“All rights reser inactive MS lesions as well as normal appearing white matter (NAWM) (Kirk et al., 2003; McQuaid et al., 2009; Plumb et al., 2002; Vos et al., 2005), and serial MRI studies have indicated that structural changes (Filippi et al., 1998; Werring, 2000) and BBB dysfunction (Goodkin et…”
BackgroundHarris, J. O., Frank, J., Patronas, N., Mcfarlin, D. E., & McFarland, H. (1991) · Annals of Neurology · doi:10.1002/ana.410290515 · Cited by 334
Werring, D. J. (2000) · Brain · doi:10.1093/brain/123.8.1667 · Cited by 323 · cited 3×
“…white matter (NAWM) (Kirk et al., 2003; McQuaid et al., 2009; Plumb et al., 2002; Vos et al., 2005), and serial MRI studies have indicated that structural changes (Filippi et al., 1998; Werring, 2000) and BBB dysfunction (Goodkin et al., 1998) may precedemyelin damage and leukocyte infiltration.”
BackgroundEpstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain.
Willis, S., Stadelmann, C., Rodig, S., Caron, T. J., Gattenloehner, S., Mallozzi, S. S., Roughan, J. E., Almendinger, S. E., Blewett, M. M., Brück, W., et al. (2009) · Brain : a journal of neurology · doi:10.1093/brain/awp200 · Cited by 304 · cited 1×
“Only a minority of cells need be infected and express viral genes, which would serve to explain the inconsistent detection of EBV in MS brains (Willis et al., 2009) and CSF (Mancuso et al., 2010).”
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Metadata
- Authors
- Cramer, S. P., Simonsen, H., Frederiksen, J. L., Rostrup, E., & Larsson, H. B. W.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Cramer, S.P.
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 4
- Pages
- 182-189
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC3872721
- OpenAlex
- W2039561850
- Cited by
- 232
- References
- 37
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 16 · 2023: 20 · 2022: 24 · 2021: 16 · 2020: 14 · 2019: 20 · 2018: 26 · 2017: 13 · 2016: 16 · 2015: 21 · 2014: 9
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- BIBSYS Brage (BIBSYS (Norway)) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-sa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Biogen
- Scleroseforeningen (14588)
- Multiple Sclerosis Society (14588)
- Region Hovedstaden
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- multiple sclerosis, blood-brain barrier permeability, normal-appearing white matter, periventricular white matter, dynamic contrast-enhanced MRI, MS relapse, immunomodulatory therapy, MS lesions, blood-brain barrier disruption
- MeSH terms
- Adult, Blood-Brain Barrier, Capillary Permeability, Contrast Media, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Severity of Illness Index, Imaging, Three-Dimensional, Perfusion Imaging, White Matter
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