Loss of corticospinal tract integrity in early MS disease stages

Abstract

Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages.

Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study.

Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified.

Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy.

Figure 1. CST pathways affected or not affected by focal white matter lesions.

Pyramidal tracts (CST) in a 35-year-old male patient with clinically isolated syndrome (CIS) diagnosed two months ago (EDSS = 1) are shown. In the right hemisphere, CST is affected by a white matter lesion (the T2-intense lesion is shown in red, the T1-intense overlapping lesion is demonstrated in white). CST proportions passing the lesion are demonstrated in blue (affected CST, aCST). Within the left hemisphere CST (in blue) is not affected by any white matter lesions (not affected CST, naCST).

Figure 2. Comparison of corticospinal tract diffusion values between controls, patients and the patients' subgroups.

Means (horizontal bars) and standard deviations (whiskers) are given. CIS = clinically isolated syndrome; HCs = healthy controls; FA = fractional anisotropy; MD = mean diffusivity; RRMS = relapsing-remitting multiple sclerosis. MD is given in mm²/s * 10⁻³. *P < 0.005; **P < 0.001.

Figure 3. Comparison of diffusion values between corticospinal tracts (CST) of controls and CSTs of the patients not affected (naCST) or affected (aCST) by white matter lesions.

Means (horizontal bars) and standard deviations (whiskers) are given. HCs = healthy controls; FA = fractional anisotropy; MD = mean diffusivity. MD is given in mm²/s * 10^–3. *P < 0.005; **P < 0.001.