Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury.
Background: The clinical utility of risk scores predicting shunt dependency after aneurysmal subarachnoid hemorrhage (aSAH) remains limited due to scarce validation data. This multicenter pooled analysis aimed to assess the predictive accuracy of existing post-aSAH shunt risk scores. Methods: Consecutive aSAH cases treated at two German university hospitals from January 2010 to July 2023 were pooled into a validation cohort. Total scores for the CHESS, CHESS-Huckman, and SDASH risk models were calculated, and their diagnostic performance was compared using receiver operating characteristic (ROC) curve analysis. Results: A total of 813 patients were included, of whom 215 (26.4%) required ventriculoperitoneal shunt placement within a median time of 29 days post-aSAH. All three risk scores were significantly associated with shunt dependency. ROC analysis showed that the CHESS-Huckman score had the highest predictive accuracy (AUC: 0.792, 95% CI: 0.761–0.824), followed by the SDASH (AUC: 0.782, 95% CI: 0.750–0.814) and CHESS (AUC: 0.780, 95% CI: 0.748–0.812) scores. Pairwise comparisons of AUCs were not statistically significant. All three scores showed good overall calibration, with CHESS–Huckman performing best, as confirmed by calibration intercepts and slopes, Brier scores, and decile-based analysis. Higher CHESS–Huckman scores correlated with earlier shunt placement, whereas delayed shunting (>30 days after aSAH) was most common in patients with moderate CHESS–Huckman scores (7–8 points), occurring in 47.4% of cases compared to 41.4% and 33.3% in patients scoring 0–6 and 9–10 points, respectively. Conclusions: This multicenter analysis validated existing risk scores for predicting shunt dependency after aSAH, with the CHESS–Huckman score demonstrating the nominally highest diagnostic accuracy. Integrating these risk scores into clinical practice could enhance early identification of patients requiring shunting, potentially reducing external ventricular drain weaning time, shortening hospital stays, and lowering the risk of cerebrospinal fluid infections.