Corpus callosum atrophy correlates with gray matter atrophy in patients with MS
Diagnosis, monitoring and biomarkers:
The corpus callosum represents a white matter (WM) region of distinct interest because of the predilection for MS pathology. In this study, the authors describe a new method to assess callosal atrophy from 3T MRI and characterize its relationship to global cerebral atrophy.
Thirty eight relapsing-remitting (RR) MS subjects and 21 age-matched healthy controls (HC) were enroled. At the time of enrolment, MS subjects were on treatment with glatirimer acetetate (n = 16), interferon beta (n = 16) or no disease-modifying therapy (n = 6). All subjects underwent the 25 foot timed walk test, the Expanded Disability Status Scale (EDSS) examination and whole brain MR imaging at 3T. Axial FLAIR and Coronal 3-D modified driven equilibrium Fourier transform (MDEFT) were acquired. All image analysis was performed in a blinded manner, without knowledge of group assignment or clinical information. Corpus Callosum Area (CCA) determination was obtained from MDEFT images using Jim software. Whole brain FLAIR lesion volume (FLV) was obtained by a semi-automated edge-finding method based on local thresholding as previously described.
CCA was lower in MS subjects versus HC (20.1% mean decrease; P < .001). The effect size for CCA (d = .62) was greater than any of the global atrophy measures. Thus, the corpus callosum showed selective disproportionate atrophy vs. global cerebral measures in patients with RRMS. CCA did not correlate with BPF, GMF, or WMF in control subjects.
CCA correlated with BPF (r = .55; P < .001) and GMF (r = .45; P = .005), but not WMF (r = .18; P = .29) in MS subjects. An inverse correlation with FLV (r = −.40; P = .01) was detected for CCA, indicating a relationship between WM lesions and corpus callosum degeneration.
There was a trend for correlation of CCA with EDSS score. Of the volumetric atrophy measures, only BPF correlated with EDSS. CCA did not correlate with disease duration (r = .05; P = .43) or 25-foot timed walk (r = −.19; P = .23) in MS subjects. Only BPF correlated with 25-foot timed walk. Although only a single slice is used, the uniformity of the corpus callosum implies that a midsagittal slice should be representative. This led to a highly reliable estimation of corpus callosum volume.
This study was limited by its cross-sectional design. A logical extension of this study would include longitudinal study of change in CCA in conjunction with measuring changes in other atrophy outcomes in relationship to disability. Future studies may also investigate the relationship between CCA and regional (deep and cortical) GMV. Addition of cognitive testing would further strengthen the significance of these results.
: Klawiter EC, Ceccarelli A.
: J Neuroimaging. 2014 May 9. doi: 10.1111/jon.12124. [Epub ahead of print]
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