Fig. 7.

Hypothetical model explaining myelinated axon pathology in normal appearing white matter (NAWM) based on the observed ultrastructural abnormalities in myelinated axons. We argue that a loss of small calibre myelinated axons in NAWM of persons with progressive MS results in a lower myelinated axon density. To compensate for the loss of myelinated axons, remaining axons swell (pink arrow) to increase their size to cover a similar axon area. The swelled axons adjust their myelin thickness (green), explaining the unaltered g-ratio, to preserve axonal shape and limit further swelling