Investigating the origin and evolution of cerebral small vessel disease: The RUN DMC – InTENse study

Annemieke ter Telgte, Kim Wiegertjes, Anil M. Tuladhar, Marlies P. Noz, José P. Marques, Benno Gesierich, Mathias Huebner, Henk Jan M.M. Mutsaerts, Suzette E. Elias-Smale, Marie José Beelen, Stefan Ropele, Roy P.C. Kessels, Niels P. Riksen, Catharina J.M. Klijn, David G. Norris, Marco Duering, Frank Erik de Leeuw

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Background: Neuroimaging in older adults commonly reveals signs of cerebral small vessel disease (SVD). SVD is believed to be caused by chronic hypoperfusion based on animal models and longitudinal studies with inter-scan intervals of years. Recent imaging evidence, however, suggests a role for acute ischaemia, as indicated by incidental diffusion-weighted imaging lesions (DWI+ lesions), in the origin of SVD. Furthermore, it becomes increasingly recognised that focal SVD lesions likely affect the structure and function of brain areas remote from the original SVD lesion. However, the temporal dynamics of these events are largely unknown. Aims: (1) To investigate the monthly incidence of DWI+ lesions in subjects with SVD; (2) to assess to which extent these lesions explain progression of SVD imaging markers; (3) to investigate their effects on cortical thickness, structural and functional connectivity and cognitive and motor performance; and (4) to investigate the potential role of the innate immune system in the pathophysiology of SVD. Design/methods: The RUN DMC – InTENse study is a longitudinal observational study among 54 non-demented RUN DMC survivors with mild to severe SVD and no other presumed cause of ischaemia. We performed MRI assessments monthly during 10 consecutive months (totalling up to 10 scans per subject), complemented with clinical, motor and cognitive examinations. Discussion: Our study will provide a better understanding of the role of DWI+ lesions in the pathophysiology of SVD and will further unravel the structural and functional consequences and clinical importance of these lesions, with an unprecedented temporal resolution. Understanding the role of acute, potentially ischaemic, processes in SVD may provide new strategies for therapies.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalEuropean Stroke Journal
Issue number4
Publication statusPublished - 1 Dec 2018


  • DWI+ lesions
  • Serial imaging
  • acute incidental infarcts
  • cognition
  • ischaemia
  • motor performance
  • remote effects
  • silent stroke

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