Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex
Neuropathology and Applied Neurobiology
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Indices of brain volume (grey matter, white matter, lesions) are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology, and demyelination. Methods: Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (x60) following stereological principles. Grey and white matter demyelination was outlined on myelin basic protein immuno-stained sections, and expressed as percentages of cortex and white matter, respectively. Results: In MS, the mean number of neurons was 14.9 ± 1.9 billion versus 24.4 ± 2.4 billion in controls (p < 0.011), a 39% difference. The density of neurons was smaller by 28% (p < 0.001), and cortical volume by 26% (p= 0.1). Strong association was detected between number of neurons and cortical volume (p < 0.0001). Demyelination affected 40 ± 13 % of the MS neocortex and 9 ± 12% of the white matter, however neither correlated with neuronal loss. Only weak association was detected between number of neurons and white matter volume. Conclusion: Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS.
AuthorsSCHMIERER, K; Carassiti, D; Petrova, N; Pakkenberg, B; Scaravilli, F; Schmierer, K
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