DeLuca GC et al. (2006) The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129: 1507–1516

Multiple sclerosis (MS) has long been considered a demyelinating disease, with the accumulation of plaque in the brain and spinal cord appearing to parallel disease progression. More recently, axonal loss has also been recognized as a feature of the disease, but the relationships between axonal loss, plaque formation and demyelination are unclear.

In a postmortem study of 55 patients with MS (mean age 57.5 years), DeLuca et al. investigated the nature of axonal loss in relation to plaque formation. They carried out histological staining for axons and myelin in sections of the cerebrum, brainstem and spinal cord, and obtained measures of relative plaque load in the corticospinal and sensory tracts.

There was a significant decrease in axonal density at all levels of the corticospinal tract in patients with MS compared with controls. Axonal loss was symmetric, with small axons being preferentially lost, and there was no evidence that plaque load correlated with axonal density or total number of axons. Similar patterns of axonal loss were found in the upper region of the sensory tract, and although plaque load seemed to correlate with total axon number in the upper cervical cord, this correlation disappeared after adjustment for age, sex and disease duration.

The authors conclude that the lack of evidence for a correlation between plaque load and axonal loss in the spinal cord indicates that demyelination might not be the primary cause of axonal loss in this region. They suggest that parallel mechanisms of axonal loss might operate, which could explain the clinical variability seen in patients with MS.