In the wall lies the truth: a systematic review of diagnostic markers in intracranial aneurysms.

Abstract

Despite recent advances in molecular biology and genetics, the development of intracranial aneurysms (IA) is still poorly understood.Elucidation of the processes occurring in the IA wall is essential for a better understanding of IA pathophysiology. We sought to analyze the current evidence from histological, molecular and genetic studies of IA. We systematically searched PubMed, Scopus, Web of Science and Cochrane Library for articles published before Mar 1, 2019 reporting on different diagnostic markers in human IA specimens. Expression of the markers in IA wall (vs. healthy arterial wall) and association with the rupture status were analyzed. The quality of the included studies and the level of the evidence for the markers were incorporated into the final data assessment. We included 123 studies reporting on analyses of 3476 IA (median 19 IA/study) published between 1966 and 2018. Based on microscopic, biochemical, genetic and biomechanical analyses, data on 358 diagnostic targets in the IA wall were collected. We developed a scale to distribute the diagnostic markers according to their specificity for IA or healthy arterial wall, as well as for ruptured or unruptured IA. We identified different functional pathways, which might reflect the intrinsic and extrinsic processes underlying IA pathophysiology. Multiple histological and molecular markers and the related functional pathways contributing to the development of IA might present promising targets for future therapeutic interventions. Because ofsmall numbers of IA samples in each study, 89% of the analyzed diagnostic markers presented with the lowest level of evidence. This underlines the need for the initiation of a multi-centric prospective histological IA register for pooled data analysis.