Brain, Vol. 123, No. 2, 308-317,
February 2000
© 2000 Oxford University Press
Axonal changes in chronic demyelinated cervical spinal cord plaques
1 Department of Neurology, `Jahn Ferenc' Teaching Hospital, 2 Department of Comparative Physiology, Eötvös Loránd University of Sciences, 3 National Institute of Psychiatry and Neurology and 4 Laboratory of Neuromorphology, Semmelweis University Medical School, Budapest, Hungary
Correspondence to:
Sámuel Komoly, Department of Neurology, `Jahn Ferenc' Teaching Hospital, Köves u. 2–4, Budapest, H-1203, Hungary E-mail: Komoly{at}mail.matav.hu
Imaging and pathomorphological studies in multiple sclerosis suggest that axonal injury and axonal loss are playing a crucial role in those with persistent disability and long-standing disease. Although the existence of axonal injury in multiple sclerosis is proven, especially in the zone of active inflammation, the effect of chronic inflammation on the axons remains elusive. The aim of this study was to perform a quantitative morphometrical analysis, estimating axonal loss and evaluating axonal degenerative changes in cervical spinal cord samples of patients suffering from secondary progressive multiple sclerosis. Completely demyelinated plaques, normal appearing white matter (NAWM) and control material from anatomically identical regions of the cord have been compared. Neurofilament immunostaining was used for identification of the axons. We observed a significant reduction of axonal density (number of axons/mm2) in multiple sclerosis, both in the plaque and in the NAWM compared with the control cases. Axons under ~3.3 µm diameter seemed to be more affected. The intensity of the immunostaining was significantly reduced in the plaque compared with either NAWM or control. Our results on the cervical cord combined with other observations support the concept of slow axonal degeneration rather than acute damage as a cause of chronic disability in multiple sclerosis.
axonal loss; multiple sclerosis; spinal cord; neurofilament 200 kDa immunostaining
APP = amyloid precursor protein; Cr = creatine; EDSS = Expanded Disability Status Scale; LC = lateral column; MRS = magnetic resonance spectroscopy; NAA = N-acetyl aspartate; NAWM = normal appearing white matter; NF-H = neurofilament heavy chain; PC = posterior column; RR = relapsing–remitting; SMI-32 = antibody raised against neurofilament protein epitopes known to be expressed in axonal damage; SP = secondary progressive
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