Multiple sclerosis: pathogenesisTuesday, June 23, 2009, 15:00 - 15:15Wallerian degeneration contributes to axonal damage in plaques and periplaque white matter in patients with multiple sclerosisT. Dziedzic, I. Metz, F. König, S. Müller, W. Brück (Krakow, PL; Gottingen, DE)
Objectives: Axonal damage is a morphological substrate of permanent clinical disability in patients with multiple sclerosis. Axonal injury takes place in plaques, but it could also affect white matter. Axonal transaction within the plaques could result in Wallerian degeneration in periplaque white matter (PPWM). The aim of our study was to assess the extent of axonal damage and contribution of Wallerian degeneration to injury of PPMW in patients with multiple sclerosis.
Methods: Axonal density was quantified in 44 plaques and 40 areas of PPWM obtained during biopsy from patients with early stage of multiple sclerosis and compared to 4 patients with epilepsy. To assess axonal injury we used the antibodies against phosphorylated neurofilaments (anti-SMI-31), unphosphorylated neurofilaments (anti-SMI-32), and amyloid precursor protein (anti-APP). Wallerian degeneration was visualised using the antibody against neuropeptydy-Y1 receptor (NPY-R).
Results: The number of SMI-32-positive axons was significantly higher in both PPWM and plaques compared to control white matter. The total number of axons (Bielschowsky staining) as well as SMI-31-positive and APP-positive axons did not differ significantly between PPWM and control white matter. The number of NPY-R-positive axons was significantly higher in PPWM (median: 335/mm²) and plaques (median: 200/mm²) than in control white matter (median: 7/mm²).
Conclusions: The results of our study suggest that axonal injury defined as dephoshorylation of neurofilaments has place in PPWM in early phase of multiple sclerosis and that Wallerian degeneration contributes to axonal damage in plaques and PPWM.
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