Non-atherosclerotic vasculopathies in stroke: a pathobiology-based framework

Background Non-atherosclerotic vasculopathies (NAV) are important causes of stroke, particularly in younger adults, but remain difficult to classify due to overlapping mechanisms and imaging features. Objectives This study aimed to propose a three-compartment framework that organises NAV according to the dominant biological process underlying the observed vascular phenotype: structural arterial abnormalities, functional dysregulation of vascular tone or autoregulation, and immune- or infection-mediated vascular injury. Methods We conducted a clinically oriented narrative review of PubMed and Embase, focusing on publications from 2015 onwards and prioritising guidelines, systematic reviews, major observational studies, and randomised trials where available. For this review, NAV were defined as selected cerebrovascular disorders in which a non-atherosclerotic abnormality of arterial structure, vascular tone or autoregulation, or immune- or infection-mediated vascular injury is central to the neurological phenotype. Results NAV can be conceptualised into structural, functional, and inflammatory compartments. Structural disorders involve arterial wall pathologies, functional disorders reflect dysregulation of vascular tone, and inflammatory disorders involve immune-mediated vascular injury. Imaging, particularly vessel wall magnetic resonance imaging, provides supportive differentiation, although interpretation requires clinical correlation. The framework is intended to complement, rather than replace, aetiological and imaging-based classifications by linking vascular phenotypes to mechanism-directed diagnostic testing and initial management. Conclusion A dominant-mechanism framework may help clinicians structure the evaluation of NAV and align diagnostic work-up and early management with the most likely underlying biology.