Background: Serum S100 protein has been known to reflect the severity of brain damage. The purpose of this study was to compare the degree of brain damage based on the serum S100 protein level between aneurysm clipping and coiling groups and to evaluate the prognostic value of S100 protein in patients with subarachnoid hemorrhage (SAH). Methods: Serum S100 protein was measured by Elecsys S100 immunoassay at admission, and at 6 and 24 h, and days 3 and 5 postoperatively for 100 consecutive SAH patients (clipping group: 56, coiling group: 44) and for 74 healthy controls. Hunt-Hess grade (HHG), Fisher grade (FG), the presence of intraventricular (IVH) or intracerebral hemorrhage (ICH), and outcome at discharge were evaluated. The time course of serum S100 was compared between the groups. The prognostic value of S100 protein was evaluated by logistic regression analysis. Results: The median S100 level in SAH patients on admission was significantly higher than in healthy controls (0.081 vs. 0.05 µg/l, p < 0.0001) and it was also higher as HHG and FG increased (p < 0.0001). Logistic regression analysis revealed that only the S100 value at admission was an independent prognostic factor for poor outcomes after adjusting for age, sex, HHG, presence of IVH or ICH, and treatment modality (OR: 100.5, 95% CI: 1.65–6,053.61). The baseline S100 value of 0.168 predicted poor outcomes with a sensitivity of 75% and a specificity of 83%. The time course of the median S100 level peaked at 6 h and then decreased serially in both clipping and coiling groups. However, the degree of S100 elevation was marked in the clipping group, especially at 6 h postoperatively (0.177 vs. 0.116 µg/l, p = 0.022), suggesting more severe brain damage in the clipping group. In the coiling group, the S100 value was significantly higher in patients who showed high signal intensity lesions in diffusion-weighted images, suggesting ischemic brain damage. Furthermore, even in patients who were categorized as good clinical grade at admission and as good outcome at discharge, the median S100 values at 6 and 24 h postoperatively were significantly higher in the clipping group than in the coiling group (p < 0.05). Conclusion: The initial S100 protein value is an independent prognostic factor for poor outcomes in SAH patients. Based on the S100 protein level, aneurysm clipping seems to provoke more brain damage than aneurysm coiling. Endovascular coiling should be considered the first therapeutic option for aneurysmal SAH patients.

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