Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL.

BACKGROUND AND PURPOSE: Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL. METHODS: Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested. RESULTS: BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (P<0.0001), Mini-Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (P<0.0001), volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages. CONCLUSIONS: In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.

Electrocardiogram in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy patients without any clinical evidence of coronary artery disease: a case-control study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic arteriopathy caused by highly stereotyped mutations in NOTCH3. The clinical expression of CADASIL is confined to the central nervous system with characteristic recurrent subcortical infarcts and vascular dementia. However, cases have been reported with associated circulatory small vessel abnormalities in the retina or the myocardium and with myocardial infarction. Classical cardiovascular risk factors may influence such circulatory abnormalities. Thus, we conducted a case control study to determine the frequency of electrical abnormalities on a 12-lead resting ECG in CADASIL patients without classical atherosclerotic risk factors. METHODS: Twenty-three CADASIL patients (mean age+/-SD; 55.1+/-11 years) free of any classical cardiovascular risk factors except for hypercholesterolemia were recruited from 1 neurology department and compared with 23 sex- and age-matched healthy controls (mean age+/-SD; 54.7+/-9.5 years). A resting supine 12-lead ECG was recorded at inclusion and analyzed later by 2 reviewers. Signs of myocardial infarction or ischemia, conduction, and rhythm disturbances were looked for. RESULTS: We found no ECG sign evoking myocardial infarction or myocardial ischemia. CADASIL patients had, compared with healthy controls, a significantly higher heart rate and a significantly lower Sokolow index, but these values remained in the normal ranges. CONCLUSIONS: In this case-control study, we found no ECG evidence for myocardial infarction or ischemia, conduction disturbances, or arrhythmias in CADASIL patients compared with healthy controls.