(Stroke. 1999;30:2637.)
© 1999 American Heart Association, Inc.
Original Contributions |
Clinical Severity in CADASIL Related to Ultrastructural Damage in White Matter
In Vivo Study With Diffusion Tensor MRI
From the Department of Neurology, CHU Lariboisière, Université Paris VII (H.C., K.V., M.-G.B.); Service Hospitalier Frédéric Joliot, DRM, CEA, Orsay (H.C., C.P., C.A.C., F.P., J.F.M., M.P.C., D.L.B.); and INSERM U334, SHFJ, CEA, Orsay, France (S.P., A.J.).
Correspondence to Dr H. Chabriat, Service de Neurologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France. E-mail chabriat{at}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 mm2/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.
Key Words: dementia • diffusion • leukoencephalopathy • magnetic resonance imaging • white matter
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