Background: The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of Multiple Sclerosis (CIS) is unclear and whole brain or whole normalized grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability.
Methods: We have used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyze regional atrophy and perform voxel-wise correlations between volume and clinical metrics in forty-one untreated CIS patients at presentation compared to forty-nine healthy controls.
Results: Our results confirmed that there was no significant difference in whole normalized grey matter volume between CIS and controls while VBM showed significant areas of bilateral thalamic, hypothalamic, putamen, and caudate atrophy. Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores, and MSFC, and the MSFC was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of Multiple Sclerosis.
Conclusions: Atrophy is present in CIS patients at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.
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