Homogeneity of active demyelinating lesions in established multiple sclerosis
Article first published online: 29 JAN 2008
Copyright © 2008 American Neurological Association
Annals of Neurology
Volume 63, Issue 1, pages 16–25, January 2008
How to Cite
Breij, E. C. W., Brink, B. P., Veerhuis, R., van den Berg, C., Vloet, R., Yan, R., Dijkstra, C. D., van der Valk, P. and Bö, L. (2008), Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann Neurol., 63: 16–25. doi: 10.1002/ana.21311
- Issue published online: 29 JAN 2008
- Article first published online: 29 JAN 2008
- Manuscript Accepted: 26 OCT 2007
- Manuscript Revised: 16 OCT 2007
- Manuscript Received: 14 JUL 2007
- Dutch Multiple Sclerosis Foundation “Stichting MS Research”. Grant Numbers: 99-395 MS, 02-499 MS, 02-498 MS
Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS.
All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging–guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions.
Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found.
The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fcγ receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS. Ann Neurol 2008;63:16–25