Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: progression of MR abnormalities in prospective 7-year follow-up study.
OBJECTIVE
To prospectively investigate the patterns and rates of progression of magnetic resonance (MR) imaging abnormalities in a well-documented cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) cohort 7 years after baseline and to identify the prognostic factors that determine the rates and patterns of this progression.


METHODS
The local ethics committee approved the study, and informed consent was obtained from all participants. From 12 unrelated families, 25 patients who were NOTCH3 mutation carriers and 13 who were non-mutation carriers were examined clinically and with standardized MR imaging at baseline and after 7 years. The progression of white matter hyperintensities (WMHs), lacunar infarcts, microbleeding, and brain volume loss was measured semiquantitatively. Correlation testing and group comparison testing were performed to identify the risk factors associated with increased progression of CADASIL-related MR abnormalities.


RESULTS
Compared with the non-mutation carriers, the mutation carriers showed significant increases in numbers of lacunar infarct (P < .01), WMH (P < .01), and microbleed (P < .05) lesions but no increased loss of brain volume. The distributions of new WMHs and new lacunar infarcts at follow-up were similar to the distributions of these abnormalities at baseline. High WMH (P < .05), lacunar infarct (P < .01), and microbleed (P < .01) lesion loads at baseline--but not cardiovascular risk factors--were associated with faster progression of these abnormalities.


CONCLUSIONS
Patients with CADASIL who have a high MR abnormality lesion load at baseline are at risk for faster progression of MR abnormalities.
Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. m.k.liem@lumc.nl
Michael K
MK
Liem
Saskia A J
SA
Lesnik Oberstein
Joost
J
Haan
Inge L
IL
van der Neut
Rivka
R
van den Boom
Michel D
MD
Ferrari
Mark A
MA
van Buchem
Jeroen
J
van der Grond
D000328:Adult; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000473:pathology; D046589:CADASIL / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009929:Organ Size; D011446:Prospective Studies; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics
C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch