Brain imaging factors associated with progression of subcortical hyperintensities in CADASIL over two year follow up

Moreton, F. C., Cullen, B. , Dickie, D. A. , Lopez Gonzalez, R., Santosh, C., Delles, C. and Muir, K. W. (2021) Brain imaging factors associated with progression of subcortical hyperintensities in CADASIL over two year follow up. European Journal of Neurology, 28(1), pp. 220-228. (doi: 10.1111/ene.14534) (PMID:32931073)

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Background: Mutations in the NOTCH3 gene cause CADASIL, a cerebral small vessel disease manifesting with stroke, migraine and dementia in adults. The disease displays significant phenotypic variability which is incompletely explained. Early abnormalities in vascular function have been shown in animal models. We postulated that studying changes in vascular function may offer insights into disease progression. Methods: Twenty two subjects with CADASIL (50% female, 50 (±11) years) from 19 pedigrees were included in a longitudinal multimodality study using brain MRI, clinical measures, neuropsychology, and measures of peripheral vascular function. MRI studies included measurement of structural brain changes, cerebral blood flow (CBF) and cerebrovascular reactivity by arterial spin labelling and a CO2 respiratory challenge. Results: Over two years, new stroke or TIA occurred in 5 (23%) subjects and new significant disability in 1 (5%). There were significant increases in number of lacunes, subcortical hyperintensity volume and microbleeds, and a decrease in brain volume. CBF declined by 3.2 (±4.5) ml/100g/min over two years. CBF and carotid‐femoral pulse wave velocity at baseline predicted change in subcortical hyperintensity volume at follow up. Carotid‐intima‐media thickness and age predicted brain atrophy. Baseline CBF was lower in subjects who showed a decline in attention and working memory. Conclusion: CBF predicts radiological progression of hyperintensities and thus is a potential biomarker of disease progression in CADASIL. Over two years, there were changes in several relevant imaging biomarkers (CBF, brain volume, lacunes, microbleeds, and hyperintensity volume). Future studies in CADASIL should consider assessment of CBF as prognostic factor.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cullen, Dr Breda and Delles, Professor Christian and Dickie, Dr David Alexander and Moreton, Dr Fiona and Muir, Professor Keith and Santosh, Dr Celestine
Authors: Moreton, F. C., Cullen, B., Dickie, D. A., Lopez Gonzalez, R., Santosh, C., Delles, C., and Muir, K. W.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:European Journal of Neurology
ISSN (Online):1468-1331
Published Online:15 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in European Journal of Neurology 28(1):220-228
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190564Cerebral and peripheral perfusion and reactivity in CADASIL: a longitudinal pilot studyKeith MuirChief Scientist Office (CSO)ETM/244NP - Stroke & Brain Imaging