The aim of this study was to investigate whether neurological symptoms related to a specific axonal fiber tract in brain white matter were associated with a higher degree of tissue damage in that region, in patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis. To this end, a magnetic resonance imaging (MRI) method to segment and evaluate the fiber bundle of interest was implemented, taking care to circumvent the problems caused by pathology. Diffusion tensor (DT) MRI tractography was used to construct, from healthy volunteer data, a probability map for the pyramidal tract (PYT), and this map was applied to patients to calculate DT-derived metrics inside the PYT. In CIS patients with clinical symptoms related to motor function, the DT-derived mean diffusivity and the lesion volume in the PYT were found to be increased, while the fractional anisotropy was no different, when compared to those patients without motor symptoms. These results may be explained by several microstructural changes in the damaged tissue, such as changes in the permeability of axonal cell membranes, decreases of axonal density and edema. The approach taken to analyze a specific fiber tract was possible because the axons in the tract have a high orientational coherence, allowing tissue structure changes to be isolated from the tissue architecture. Its extension to other white matter fiber bundles is therefore limited to bundles with high orientational coherence.