Clinical severity in CADASIL related to ultrastructural damage in white matter - In vivo study with diffusion tensor MRI

Background and Purpose-CADASIL is a newly recognized cause of subcortical i schemic strokes that progressively leads to dementia associated with pseudo bulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected su bjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly u nderstood, Methods-To address this issue, we used diffusion tensor imaging (DTI), a ne w MRI technique highly sensitive to white-matter microstructural changes, i n 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified o n T2-weighted images (T2WI) and outside these lesions on 4 slices at the le vel of centrum semiovale. Results-We found a 60% increase of water mean diffusivity and a parallel lo ss of diffusion anisotropy in hyperintensities identified on T2WI, The same pattern of diffusion changes, but of lesser intensity, was found in the no rmal-appearing white matter on T2WI, Mean diffusivity in regions with incre ased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13t0.11 1 0(-3) mm(2)/s, P<0.01), Furthermore, diffusion measured within T2 hyperinte nsities correlated with both the Mini-Mental State Examination and Rankin s cale scores. In patients with a severe clinical status, the increase of wat er diffusion in these regions exceeded 70% in comparison with values obtain ed in the normal white matter in control subjects. Conclusions-These results indicate that DTI is able to detect important ult rastructural changes in regions with increased signal on T2WI and within th e normal-appearing white matter in CADASIL, The diffusion changes might be related to both neuronal loss and demyelination, The degree of the underlyi ng ultrastructural alterations is related to the severity of the clinical s tatus with a possible threshold level of white-matter damage above which se vere neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.