Department of Neurosurgery, University Hospital of Essen, Essen, Germany.
Clinic for Neuropathology, University Hospital of Essen, Essen, Germany.
Brain Pathol. 2020 May;30(3):437-445. doi: 10.1111/bpa.12828. Epub 2020 Feb 27.
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 of small 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.
尽管分子生物学和遗传学取得了最近的进展，但颅内动脉瘤（IA）的发生机制仍知之甚少。阐明 IA 壁中发生的过程对于更好地理解 IA 的病理生理学至关重要。我们试图分析 IA 的组织学、分子和遗传学研究的现有证据。
我们系统地检索了 PubMed、Scopus、Web of Science 和 Cochrane Library，以查找 2019 年 3 月 1 日前发表的报告人类 IA 标本中不同诊断标志物的文章。分析了标志物在 IA 壁（与健康动脉壁相比）中的表达及其与破裂状态的关系。将纳入研究的质量和标志物的证据水平纳入最终数据评估。
我们纳入了 123 项研究，这些研究报告了 1966 年至 2018 年间分析的 3476 个 IA（中位数每个研究 19 个 IA）。基于显微镜、生化、遗传和生物力学分析，收集了 IA 壁中 358 个诊断靶标的数据。我们开发了一个量表，根据其对 IA 或健康动脉壁、破裂或未破裂 IA 的特异性来分配诊断标志物。我们确定了不同的功能途径，这些途径可能反映了 IA 病理生理学的内在和外在过程。
多种组织学和分子标志物及其相关的功能途径可能为未来的治疗干预提供有希望的靶点。由于每个研究中的 IA 样本数量较少，分析的诊断标志物中有 89%的证据水平最低。这强调了需要启动一个多中心前瞻性的组织学 IA 登记处，以进行汇总数据分析。
