Cerebral Small Vessel Disease – ESOC 2017 Session Highlights

The small vessel disease (SVD) session covered a broad spectrum, from animal models over disease mechanisms, neuroimaging to treatment. The session was enriched by questions from the audience using the “ask the expert” function within the ESOC smartphone app.

Eric Jouvent summarized imaging findings in SVD and addressed questions that frequently come up in clinical routine, such as differential diagnosis. He emphasized the importance to integrate information from different MRI contrasts. While very small acute lesions can be difficult to detect, follow-up imaging might provide additional information.

Joanna Wardlaw and Marco Duering discussed the role of blood-brain-barrier (BBB) dysfunction in SVD. Human studies in vivo (in particular dynamic contrast enhanced MRI) and post-mortem histopathological analyses suggest increased BBB leakage with aging and in association with SVD. However, some studies are conflicting. Animal models also support a role of BBB failure in SVD: CADASIL transgenic mice show a reduced pericyte coverage and extravasation of plasma proteins. BBB leakage has also been found in Foxf2-knockout mice and FOXF2 has recently been linked to SVD in a genome-wide association study.

Andrew Lawrence focused on network dysfunction in SVD. Structural networks are based on MRI tractography and can be characterized by measures from graph theory, such as global efficiency. These network measures are strongly related to cognitive symptoms in SVD, both in cross-sectional and longitudinal studies. Interestingly, the effects of other SVD markers on cognitive symptoms are largely mediated by network measures, suggesting that network dysfunction might be a common pathway for different SVD-related lesions.

Andy Shih provided fascinating insights on cerebral microinfarcts using rodent models. Cortical microinfarcts can be well modelled and investigated, e.g. using in vivo 2-photon microscopy. Interestingly, microinfarcts cause clinical symptoms that extend beyond the infarct core and originate from perilesional tissue. Microinfarcts may even cause effects remote from the lesion site, e.g. in connected regions, and this will be investigated in future studies.

Hugh Markus summarized the treatment of SVD patients. He emphasized that we have limited knowledge from clinical trials and therefore a great demand for new trials. In addition, there is a need for better stroke subtyping in large stroke trials as many classification systems cannot discriminate between SVD-related infarcts and small infarcts of other etiology. Some specific recommendations: Double platelet inhibition should be avoided, also in the acute phase. Recent data from an Austrian registry suggest that thrombolysis is equally beneficial in SVD-related stroke compared with other stroke subtypes. Antihypertensive treatment is very important, also in SVD patients without stroke. But blood pressure lowering might be harmful in late disease stages, as it can augment hypoperfusion. Ultimately, a better understanding of SVD pathomechanisms is needed in order to develop new therapies.