Deep immunophenotyping in aneurysmal subarachnoid hemorrhage: a prospective and controlled clinical study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular condition with significant morbidity and mortality. While inflammation plays a critical role in post-hemorrhagic complications, the specific polarization dynamics of monocyte and T cell subpopulations in this context remain poorly understood. This study aims to investigate these immune cell shifts and their correlation with major complications such as angiographic cerebral vasospasm and delayed cerebral ischemia (DCI). METHODS: We conducted a prospective, controlled observational single-center cohort study in a neurovascular university center of maximum care in Germany. A total of 75 patients with aSAH and 20 healthy controls were included. Blood samples were collected on days 1, 4, 7, and 11 post-bleeding. Flow cytometry was used to analyze monocyte (M1, intermediate, M2) and T cell (Th1, Th2, Th17, Treg) polarization patterns. Primary outcomes included the incidence of angiographic cerebral vasospasm, clinical DCI and/or cerebral infarction due to DCI, and clinical outcome assessed at 6 months via the modified Rankin Scale (mRS). RESULTS: Compared to healthy controls, patients with aSAH exhibited a significant decrease in anti-inflammatory alternatively activated monocytes (6.3% vs. 3.0%; p = 0.04) within 24 h post-bleeding, an increase in pro-inflammatory Th17 T cells (36.3% vs. 6.2%; p < 0.001) and decrease in anti-inflammatory Th2 cells (45.5% vs. 75.2%; p < 0.001). A loss of anti-inflammatory alternatively activated monocytes was observed prior to the onset of angiographic cerebral vasospasm (3.8% vs. 2.7%; p = 0.031) and DCI (4.2% vs. 2.9%; p = 0.006). No significant correlation was found between immune cell subpopulations and long-term clinical outcomes. CONCLUSIONS: This study demonstrates a shift toward pro-inflammatory immune cell subpopulations following aSAH, with significant losses of alternatively activated monocytes preceding major complications such as vasospasm and DCI. These findings suggest that immune subpopulation profiling may hold potential as a diagnostic and therapeutic tool in the context of aSAH-related complications. Future studies should aim to clarify whether the observed peripheral immune changes reflect analogous intracerebral immune mechanisms and whether modulating these pathways can improve clinical outcomes.