Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis

We assessed axonal loss in the normal appearing white matter of the corpus callosum in postmortem brains of patients with multiple sclerosis, using qu antitative measures of both axonal density and white matter atrophy. The ca lculated total number of axons was reduced significantly (mean +/- SD, 5.4 x 10(7) +/- 3.1 x 10(7) compared with normal controls (11.6 x 107 +/- 2.2 X 107, p 0.001) with a reduction both in axonal density (median, 34%; range, 16-56%; p = 0.004) and area (mean +/- SD: multiple sclerosis, 584 +/- 170 mm(2); controls, 871 +/- 163 mm(2); p = 0.004). These results confirm subst antial axonal loss in the normal appearing white matter and demonstrate tha t measures of both axonal density and white matter volume are necessary to appreciate the full extent of axonal loss.