Patients who developed delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage showed an early intrathecal shift in the balance between NK cells and Tregs, reflected by a higher CSF NK/Treg ratio around day 3, suggesting a compartment-specific immune alteration associated with DCI.
DCI occurred in nearly half of the study patients at a median of 8.5 days after hemorrhage.
On day 3, the CSF NK/Treg ratio was markedly higher in patients who later developed DCI compared to those who did not.
The immune imbalance reflected by the NK/Treg ratio was more pronounced in CSF than in peripheral blood, suggesting a compartment-specific alteration.
Lower modified Fisher grades were associated with increased NK/Treg ratios in CSF at early time points, suggesting the elevation was not merely a reflection of subarachnoid blood burden.
The study identified CSF-based immune profiling including the NK/Treg ratio as a promising exploratory approach for DCI risk stratification.
This research suggests that in patients who have suffered a brain bleed from a ruptured aneurysm (subarachnoid hemorrhage), an early imbalance in certain immune cells within the fluid surrounding the brain and spinal cord (cerebrospinal fluid, or CSF) may be linked to a serious complication called delayed cerebral ischemia (DCI) — a secondary reduction in blood flow to the brain that can occur days after the initial bleed. Specifically, the study found that around day 3 after hemorrhage, patients who later developed DCI had much higher ratios of natural killer (NK) cells to regulatory T cells (Tregs) in their CSF compared to patients who did not develop DCI. This immune imbalance was far more apparent in the CSF than in the blood, suggesting the process is happening specifically within the brain environment rather than throughout the whole body. The study also found that this elevated immune ratio was not simply explained by how much blood was present in the brain (as measured by imaging scores), which hints that it reflects a genuine immune response rather than just a mechanical consequence of the bleed. These findings suggest that monitoring immune cell profiles in CSF could potentially help identify patients at higher risk for DCI soon after their hemorrhage, before symptoms develop. However, this was a small pilot study of only 21 patients at a single center, and the results showed high variability, meaning the findings are preliminary and not yet statistically definitive. The authors emphasize that larger, multi-center studies are needed before this approach could be considered for clinical use. Nonetheless, this research opens a potentially important window into understanding how the brain's immune response after a hemorrhage might contribute to secondary brain injury.
Pfnür A, Bohnacker A, Dörfer L, Ziebart A, Halbgebauer R, Huber-Lang M, et al.. (2026). Natural killer cells and regulatory T cells in aneurysmal subarachnoid hemorrhage in peripheral blood and cerebrospinal fluid - a pilot study.. Fluids and barriers of the CNS. https://doi.org/10.1186/s12987-026-00824-3