title: Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T(1)-weighted, FLAIR and T2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin A1c (HbA1c) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease.
authors.affiliation: Department of Neurology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guichard
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Frederique
authors.initials: F
authors.lastname: Buffon
authors.forename: Rodica
authors.initials: R
authors.lastname: Cumurcuic
authors.forename: Carole
authors.initials: C
authors.lastname: Boutron
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Markus
authors.initials: M
authors.lastname: Holtmannspötter
authors.forename: Chahin
authors.initials: C
authors.lastname: Pachai
authors.forename: Marie-Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000098:blood supply / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000473:pathology; D020520:Brain Infarction / Q000097:blood / Q000150:complications / Q000503:physiopathology; D001933:Brain Stem / Q000098:blood supply / Q000473:pathology; D046589:CADASIL / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D015331:Cohort Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013788:Thalamus / Q000098:blood supply / Q000473:pathology
chemical_list: D006442:Glycated Hemoglobin