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Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor
H Chabriat1, S Pappata, C Poupon
1Department of Neurology, CHU Lariboisière, Université Paris VII, France. chabriat@ccr.jussieu.fr
Background And Purpose:
CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood.
Methods:
To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale.
Results:
We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects.
Conclusions:
These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.
Insights
Diffusion tensor imaging (DTI) reveals significant white matter changes in Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). These microstructural alterations correlate with disease severity, suggesting DTI
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic disorder causing progressive subcortical ischemic strokes, dementia, and motor disability.
- The clinical presentation and disease progression in CADASIL are highly variable.
- The role of MRI-detected white matter abnormalities in the clinical severity of CADASIL is not well understood.
Purpose of the Study:
- To investigate the relationship between white matter microstructural changes and clinical severity in CADASIL using diffusion tensor imaging (DTI).
- To assess the sensitivity of DTI in detecting ultrastructural alterations in both lesional and non-lesional white matter in CADASIL patients.
Main Methods:
- Diffusion tensor imaging (DTI) was performed on 16 symptomatic CADASIL patients and 10 age-matched controls.
- Mean diffusivity and diffusion anisotropy were measured within T2-weighted image (T2WI) hyperintensities and normal-appearing white matter.
- Measurements were taken on four slices at the centrum semiovale level.
Main Results:
- DTI revealed a 60% increase in mean diffusivity and reduced anisotropy within T2WI hyperintensities in CADASIL patients compared to controls.
- Similar, though less pronounced, diffusion changes were observed in normal-appearing white matter.
- Increased diffusivity in T2WI lesions correlated with Mini-Mental State Examination and Rankin scale scores, with higher diffusivity in severely affected patients.
Conclusions:
- DTI effectively detects significant ultrastructural changes in both lesional and normal-appearing white matter in CADASIL.
- These diffusion changes, potentially reflecting neuronal loss and demyelination, correlate with clinical disability severity.
- DTI shows promise as a tool for monitoring disease progression in CADASIL.