[Cerebral Small Vessel Disease: Advances in Understanding its Pathophysiology]. / Zerebrale Mikroangiopathie: Fortschritte im Verständnis der Pathophysiologie.

ABSTRACT

Sporadic cerebral small vessel disease determines age- and vascular-risk-factor-related processes of the small brain vasculature. The underlying pathology develops in a stage-dependent manner - probably over decades - often already starting in midlife. Endothelial and pericyte activation precedes blood-brain barrier leaks, extracellular matrix remodeling and neuroinflammation, which ultimately result in bleeds, synaptic and neural dysfunction. Hemodynamic compromise of the small vessel walls promotes perivascular drainage failure and accumulation of neurotoxic waste products in the brain. Clinical diagnosis is mainly based on magnetic resonance imaging according to the Standards for Reporting Vascular Changes on Neuroimaging 2. Cerebral amyloid angiopathy is particularly stratified according to the Boston v2.0 criteria. Small vessel disease of the brain could be clinically silent, or manifested through a heterogeneous spectrum of diseases, where cognitive decline and stroke-related symptoms are the most common ones. Prevention and therapy are centered around vascular risk factor control, physically and cognitively enriched life style and, presumably, maintenance of a good sleep quality, which promotes sufficient perivascular drainage. Prevention of ischemic stroke through anticoagulation that carries at the same time an increased risk for large brain hemorrhages - particularly in the presence of disseminated cortical superficial siderosis - remains one of the main challenges. The cerebral small vessel disease field is rapidly evolving, focusing on the establishment of early disease stage imaging and biofluid biomarkers of neurovascular unit remodeling and the compromise of perivascular drainage. New prevention and therapy strategies will correspondingly center around the dedicated targeting of, e. g., cellular small vessel wall and perivascular tissue structures. Growing knowledge about brain microvasculature bridging neuroimmunological, neurovascular and neurodegenerative fields might lead to a rethink about apparently separate disease entities and the development of overarching concepts for a common line of prevention and treatment for several diseases.