Clinical phenotypes associated with cerebral small vessel disease: an overview of systematic reviews

Kancheva, A. K. , Wardlaw, J. M., Lyall, D. M. and Quinn, T. J. (2024) Clinical phenotypes associated with cerebral small vessel disease: an overview of systematic reviews. Neurology, 102(8), (doi: 10.1212/WNL.0000000000209267) (PMID:38552192)

Abstract

Background and Objectives: Cerebral small vessel disease (cSVD) causes lacunar and hemorrhagic stroke and is an important contributor to vascular cognitive impairment. Other potential physical and psychological consequences of cSVD have been described across various body systems. Descriptions of cSVD are available in journals specific to those individual body systems, but a comprehensive assessment of clinical manifestations across this disparate literature is lacking. We conducted an overview of systematic reviews describing clinical cSVD phenotypes. Methods: We searched multidisciplinary databases from inception to December 2023. We included reviews describing concurrent clinical phenotypes in individuals with neuroimaging evidence of cSVD, defined using the STandards for ReportIng Vascular changes on nEuroimaging criteria. We broadly classified phenotypes into cognitive, mood and neuropsychiatric, respiratory, cardiovascular, renal-urinary, peripheral nervous system, locomotor, and gastrointestinal. We included both studies assessing multiple cSVD features and studies examining individual cSVD markers. We extracted risk factor–adjusted effect estimates, where possible, and assessed methodologic quality using the Assessment of Multiple Systematic Reviews-2 tool. Results: After screening 6,156 publications, we included 24 systematic reviews reporting on 685 original studies and 1,135,943 participants. Cognitive and neuropsychiatric phenotypes were examined most often, particularly in relation to white matter hyperintensities (range of risk ratios [RRs] for cognitive phenotypes 1.21–1.49, range of 95% CI 1.01–1.84; for neuropsychiatric, RR 1.02–5.71, 95% CI 0.96–19.69). Two reviews focused solely on perivascular spaces. No reviews assessed lacunes or small subcortical infarcts separately from other cSVD features. Reviews on peripheral nervous system, urinary, or gastrointestinal phenotypes were lacking. Fourteen reviews had high methodologic quality, 5 had moderate quality, and 5 had low quality. Heterogeneity in cSVD definitions and phenotypic assessments was substantial. Discussion: Neuroimaging markers of cSVD are associated with various clinical manifestations, suggesting a multisystem phenotype. However, features classically associated with cSVD, for example, gait, had limited supporting evidence, and for many body systems, there were no available reviews. Similarly, while white matter hyperintensities were relatively well studied, there were limited data on phenotypes associated with other cSVD features. Future studies should characterize the full clinical spectrum of cSVD and explore clinical associations beyond neurocognitive and neuropsychiatric presentations.

• Item Type: Articles
• Additional Information: Angelina K. Kancheva MSc is funded by MRC DTP in Precision Medicine (grant number: MR/W006804/1). Prof. Terence J Quinn is funded by Scottish Funding Council Brain Health Advanced Research Challenge and the David Cargill Trust. Prof. Joanna Wardlaw is funded by the UK Dementia Research Institute, which is funded by the Medical Research Council, Alzheimer’s Research UK and Alzheimer’s Society.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Quinn, Professor Terry and Kancheva, Angelina Kirilova and Lyall, Dr Donald

Creator Roles

Kancheva, A. K.: Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft
Lyall, D.: Writing – review and editing
Quinn, T.: Conceptualization, Methodology, Writing – review and editing, Supervision

• Authors: Kancheva, A. K., Wardlaw, J. M., Lyall, D. M., and Quinn, T. J.
• 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 > Public Health
• Journal Name: Neurology
• Publisher: American Academy of Neurology
• ISSN: 0028-3878
• ISSN (Online): 1526-632X
• Published Online: 29 March 2024
• Copyright Holders: Copyright © 2024 American Academy of Neurology
• First Published: First published in Neurology 102(8)
• Publisher Policy: Reproduced in accordance with the publisher copyright policy