He Qiheng, Huo Ran, Sun Yingfan, Zheng Zhiyao, Xu Hongyuan, Zhao Shaozhi, Ni Yang, Yu Qifeng, Jiao Yuming, Zhang Wenqian, Zhao Jizong, Cao Yong
Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing China.
Basic and Translational Medicine Center China National Clinical Research Center for Neurological Diseases Beijing China.
MedComm (2020). 2024 Dec 8;5(12):e70027. doi: 10.1002/mco2.70027. eCollection 2024 Dec.
Cerebral vascular malformations (CVMs), particularly cerebral cavernous malformations and cerebral arteriovenous malformations, pose significant neurological challenges due to their complex etiologies and clinical implications. Traditionally viewed as congenital conditions with structural abnormalities, CVMs have been treated primarily through resection, embolization, and stereotactic radiosurgery. While these approaches offer some efficacy, they often pose risks to neurological integrity due to their invasive nature. Advances in next-generation sequencing, particularly high-depth whole-exome sequencing and bioinformatics, have facilitated the identification of gene variants from neurosurgically resected CVMs samples. These advancements have deepened our understanding of CVM pathogenesis. Somatic mutations in key mechanistic pathways have been identified as causative factors, leading to a paradigm shift in CVM treatment. Additionally, recent progress in noninvasive and minimally invasive techniques, including gene imaging genomics, liquid biopsy, or endovascular biopsies (endovascular sampling of blood vessel lumens), has enabled the identification of gene variants associated with CVMs. These methods, in conjunction with clinical data, offer potential for early detection, dynamic monitoring, and targeted therapies that could be used as monotherapy or adjuncts to surgery. This review highlights advancements in CVM pathogenesis and precision therapies, outlining the future potential of precision medicine in CVM management.
脑血管畸形(CVMs),尤其是脑海绵状畸形和脑动静脉畸形,由于其复杂的病因和临床影响,带来了重大的神经学挑战。传统上,CVMs被视为具有结构异常的先天性疾病,主要通过切除、栓塞和立体定向放射外科进行治疗。虽然这些方法有一定疗效,但由于其侵入性,往往对神经完整性构成风险。新一代测序技术的进步,特别是高深度全外显子测序和生物信息学,有助于从神经外科切除的CVMs样本中识别基因变异。这些进展加深了我们对CVM发病机制的理解。关键机制途径中的体细胞突变已被确定为致病因素,导致CVM治疗发生范式转变。此外,非侵入性和微创技术的最新进展,包括基因成像基因组学、液体活检或血管内活检(血管腔的血管内采样),使得识别与CVMs相关的基因变异成为可能。这些方法与临床数据相结合,为早期检测、动态监测和靶向治疗提供了潜力,这些治疗可作为单一疗法或手术辅助手段。本综述强调了CVM发病机制和精准治疗方面的进展,概述了精准医学在CVM管理中的未来潜力。