Won So Young, Kim Museong, Jeong Han-Gil, Yang Bosco Seong Kyu, Choi Huimahn Alex, Kang Dong-Wan, Kim Yong Soo, Kim Young Deok, Lee Si Un, Ban Seung Pil, Bang Jae Seung, Han Moon-Ku, Kwon O-Ki, Oh Chang Wan
Division of Neurocritical Care, Department of Neurosurgery and Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea.
Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Neurol. 2024 Nov 5;15:1491189. doi: 10.3389/fneur.2024.1491189. eCollection 2024.
The immune response following aneurysmal subarachnoid hemorrhage (aSAH) can exacerbate secondary brain injury and impact clinical outcomes. As the immune response after aSAH is a dynamic process, we aim to track and characterize immune cell trajectories over time to identify patterns associated with various clinical outcomes.
In this retrospective single-center study of patients with aSAH, we analyzed immune cell count trajectories, including neutrophil, monocyte, and lymphocyte counts, collected from day 1 to day 14. These trajectories were classified into four distinct clusters utilizing the k-means longitudinal clustering method. A comprehensive multivariable analysis was performed to explore the associations of these immune cell clusters with various clinical outcomes. These outcomes included a Modified Rankin Scale score (mRS) of 3 to 6, indicative of poor functional outcomes, along with complications including shunt dependency, vasospasm, and secondary cerebral infarction.
In this study, 304 patients with aSAH were analyzed. The trajectories of immune cell counts, including neutrophils, monocytes, and lymphocytes, were successfully categorized into four distinct clusters for each immune cell type. Within neutrophil clusters, both persistent neutrophilia and progressive neutrophilia were associated with poor functional outcomes, shunt dependency, and vasospasm, with resolving neutrophilia showing a lesser degree of these associations. Within monocyte clusters, early monocytosis was associated with vasospasm, whereas delayed monocytosis was associated with shunt dependency. Within lymphocyte clusters, both early transient lymphopenia and early prolonged lymphopenia were associated with poor functional outcomes.
Our study demonstrates that distinct immune cell trajectories post-aSAH, identified through unsupervised clustering, are significantly associated with specific clinical outcomes. Understanding these dynamic immune responses may provide key insights with potential for future therapeutic strategies.
动脉瘤性蛛网膜下腔出血（aSAH）后的免疫反应可加重继发性脑损伤并影响临床结局。由于aSAH后的免疫反应是一个动态过程，我们旨在追踪并描述免疫细胞随时间的轨迹，以确定与各种临床结局相关的模式。
在这项针对aSAH患者的回顾性单中心研究中，我们分析了从第1天到第14天收集的免疫细胞计数轨迹，包括中性粒细胞、单核细胞和淋巴细胞计数。利用k均值纵向聚类方法将这些轨迹分为四个不同的簇。进行了全面的多变量分析，以探讨这些免疫细胞簇与各种临床结局之间的关联。这些结局包括改良Rankin量表评分（mRS）为3至6分，表明功能结局较差，以及包括分流依赖、血管痉挛和继发性脑梗死在内的并发症。
在本研究中，对304例aSAH患者进行了分析。每种免疫细胞类型的免疫细胞计数轨迹，包括中性粒细胞、单核细胞和淋巴细胞，均成功分为四个不同的簇。在中性粒细胞簇中，持续性中性粒细胞增多和进行性中性粒细胞增多均与功能结局差、分流依赖和血管痉挛相关，而中性粒细胞增多缓解则显示这些关联程度较低。在单核细胞簇中，早期单核细胞增多与血管痉挛相关，而延迟单核细胞增多与分流依赖相关。在淋巴细胞簇中，早期短暂淋巴细胞减少和早期持续性淋巴细胞减少均与功能结局差相关。
我们的研究表明，通过无监督聚类确定的aSAH后不同的免疫细胞轨迹与特定的临床结局显著相关。了解这些动态免疫反应可能为未来的治疗策略提供关键见解。
