Zerebrale Mikroangiopathie: Fortschritte im Verständnis der Pathophysiologie

Zusammenfassung

Die sporadische zerebrale Mikroangiopathie umfasst altersabhängige Veränderungen der kleinen Hirngefäße, die durch das Vorliegen vaskulärer Risikofaktoren beschleunigt werden. Die mikrovaskulären Wandveränderungen entwickeln sich eher langsam, mit möglichem Beginn bereits in der mittleren Lebensphase – über Dekaden – und zeigen einen stadienhaften Verlauf. Dieser wird durch eine Aktivierung von Zellen der neurovaskulären Einheit, wie Endothel und Perizyten, induziert und setzt sich dann über eine Blut-Hirn-Schranken-Störung, den Umbau der extrazellulären Matrix und Neuroinflammation zu den Spätstadien aus Blutungen, synaptischer und neuronaler Dysfunktion fort. Begleitend kommt es bereits früh zu Störungen der perivaskulären Drainage von neurotoxischen Substanzen und deren Akkumulation im Hirngewebe. Die Diagnose der Mikroangiopathie erfolgt allgemein im Wesentlichen anhand der “Standards for Reporting Vascular Changes on Neuroimaging 2” in der Magnetresonanztomographie, und die der zerebralen Amyloidangiopathie im Speziellen anhand der neuen Boston-Version-2.0 Kriterien. Klinisch kann die Mikroangiopathie asymptomatisch verlaufen oder sich in einem sehr heterogenen phänotypischen Spektrum manifestieren. Kognitive Defizite und Schlaganfallsymptome sind hier, je nach Kohorte, sicher die häufigsten Präsentationen. In der Therapie und Beratung betroffener Patienten steht die Kontrolle vaskulärer Risikofaktoren sowie die Empfehlung körperlicher und kognitiver Aktivität zusammen mit einer guten Schlafhygiene, die die perivaskuläre Drainage fördert, im Vordergrund. Herausfordernd bleiben individuelle Konstellationen der Ischämieprävention durch Antikoagulantien bei gleichzeitig hohem Hirnblutungsrisiko, v. a. bei Vorliegen einer kortikalen superfizialen Siderose. Die sehr dynamischen wissenschaftlichen und translationalen Entwicklungen im Feld der zerebralen Mikroangiopathie zielen auf die Etablierung von Bildgebungs- und anderen Biomarkern, z. B. in Blut und Liquor, ab, die bereits die frühen Krankheitsstadien erfassen, bevor es zur Hirnparenchymschädigung und klinischen Symptomen kommt. Entsprechend fokussiert werden sich neue Therapieansätze auch dezidiert auf die Stabilisierung der neurovaskulären Einheit und eine Verbesserung der Drainagefunktion konzentrieren. Die Mikrovaskulatur und deren Veränderungen spielen auch für das Verständnis anderer neurologischer Erkrankungen aus dem Feld der primären Neuroimmunologie und Neurodegeneration eine zentrale Rolle. Einige, bisher als separate, neurologische Entitäten betrachtete Erkrankungen könnten zukünftig folglich zunehmend als Spektrum ähnlicher pathophysiologischer Prozesse verstanden werden. Das legt perspektivisch den Grundstein für die Entwicklung und Anwendung überlappender Therapiekonzepte.

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.

Schlüsselwörter

zerebrale Mikroangiopathie - STRIVE-2 - zerebrale Amyloidangiopathie - Perizyten - Drainage

Keywords

cerebral small vessel disease - STRIVE-2 - cerebral amyloid angiopathy - pericytes - drainage

Publication History

Received: 04 July 2023

Accepted: 06 October 2023

Article published online:
11 December 2023

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