The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis
Abstract
Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.
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Citations
Cites
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Axonal transection in the lesions of multiple sclerosis
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Axonal damage in acute multiple sclerosis lesions
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“…axonal density in the NAWM (Trapp et al., 1998; van Waesberghe et al., 1999; Evangelou et al., 2000) and the presence of cortical lesions associated with apoptotic loss of neurons, and axonal and dendritic transections (Peterson et al., 2001) in patients with long-standing multiple sclerosis.”
BackgroundInfluentialA longitudinal study of abnormalities on MRI and disability from multiple sclerosis
Brex, P. A., Ciccarelli, O., O'Riordan, J. I., Sailer, M., Thompson, A. J., & Miller, D. H. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011341 · Cited by 861
Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS
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Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies
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Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions
Davie, C. A., Hawkins, C. P., Barker, G. J., Brennan, A., Tofts, P. S., Miller, D. H., & McDonald, W. I. (1994) · Brain · doi:10.1093/brain/117.1.49 · Cited by 534
Evidence of Axonal Damage in the Early Stages of Multiple Sclerosis and Its Relevance to Disability
De Stefano, N., Narayanan, S., Francis, G. S., Arnaoutelis, R., Tartaglia, M. C., Antel, J. P., Matthews, P. M., & Arnold, D. L. (2001) · Archives of Neurology · doi:10.1001/archneur.58.1.65 · Cited by 505
Cited by
Cortical demyelination and diffuse white matter injury in multiple sclerosis
Kutzelnigg, A., Lucchinetti, C. F., Stadelmann, C., Brück, W., Rauschka, H., Bergmann, M., Schmidbauer, M., Parisi, J. E., & Lassmann, H. (2005) · Brain · doi:10.1093/brain/awh641 · Cited by 1,836
Fatigue in neurological disorders
Chaudhuri, A., & Behan, P. O. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15794-2 · Cited by 1,297
Fisniku, L. K., Brex, P. A., Altmann, D. R., Miszkiel, K. A., Benton, C. E., Lanyon, R., Thompson, A. J., & Miller, D. H. (2008) · Brain · doi:10.1093/brain/awm329 · Cited by 897
Kappos, L., Freedman, M. S., Polman, C. H., Edan, G., Hartung, H.-P., Miller, D. H., Montalbán, X., Barkhof, F., Radü, E.-W., Metzig, C., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70237-6 · Cited by 369
Detecting axon damage in spinal cord from a mouse model of multiple sclerosis
Kim, J. H., Budde, M. D., Liang, H.-F., Klein, R. S., Russell, J. H., Cross, A. H., & Song, S.-K. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.09.009 · Cited by 235
Metadata
- Authors
- Filippi, M.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 126
- Issue
- 2
- Pages
- 433-437
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2105551371
- Cited by
- 371
- References
- 34
- FWCI
- 23.69
- Type
- journal article
- Language
- en
- Open access
- closed
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