Thalamic microstructural alterations secondary to white-matter damage in CADASIL: evidence from diffusion tensor imaging study
Background and Purpose: Variable microstructural changes have been reported within the white-matter in CADASIL. Lacunar infarcts are frequently observed in the subcortical grey matter. However, whether microstructural tissular alterations are also present within the non-infarcted putamen (NIP) or thalamus (NIT), remains unknown. Methods: We used diffusion tensor imaging, a MRI method highly sensitive to the cerebral microstructure, in 20 CADASIL patients and 12 age-matched controls. Both Trace(D) and anisotropy (volume-ratio index) of diffusion were measured within the NIP and NIT. In addition, diffusion parameters and the load of small infarcts were calculated within the white-matter of the centrum semi-ovale. A one way ANOVA was performed to compare the diffusion parameters between patients and controls. Thereafter, correlations between the significant results in our patients and the diffusion parameters in the white-matter or the MMSE scores were tested. Results: A significant increase in Trace(D) and decrease in anisotropy were observed in both the NIP and NIT in our patients. Conversely to the results in the NIP, only significant in the presence of associated putaminal infarcts, the diffusion changes in the NIT were significant both in the presence and absence of associated thalamic infarcts. The asymmetry indices of Trace(D) in the NIT and in the white-matter were strongly correlated. The diffusion increase in the NIT was also positively correlated both to Trace(D) and to the load of small deep infarcts within the centrum semi-ovale. Elsewhere, the diffusion increase in the NIT, but not in the NIP, was negatively correlated to the MMSE score in our patients. Conclusions: These results suggest that microstructural alterations are present in both the NIP and NIT in CADASIL. In the NIT, microstructural alterations appear secondary to remote lesions of thalamo-cortical pathways. Diffusion measured in the NIT mirror both the degree of white-matter tissular damage and the clinical severity in CADASIL. This study highlights the importance of secondary neurodegeneration in a typical model of “pure vascular dementia”.