The Evolution and Recurrence of Chronic Subdural Hematoma was Associated with Different Distribution of Macrophage M1/M2 Polarization.

Abstract

The pathogenesis of chronic subdural hematoma (CSDH) has traditionally been associated with inflammation, but the efficacy of anti-inflammatory drug therapy is limited. Recent literatures suggest that immune dysregulation rather than sole inflammation, plays a vital role in the development of CSDH. In this study, the dynamics of macrophage polarization were explored to elucidate changes in immune status during CSDH evolution. Nakaguchi computerized tomography (CT) classification method was employed to categorize CSDH into four types, including homogeneous, laminar, separated and trabecular subtypes. Samples from the hematoma cavity were collected. The percentages of M1 and M2 macrophages and the M1/M2 proportion were determined by flow cytometry. The M1-related inflammatory (IL-1β, IL-6, IL-12, and TNF-α) and M2-related anti-inflammatory factors (IL-4, IL-10, IL-13, and TGF-β) were measured by ELISA. The relationship among CT subtypes, macrophage polarization and recurrence were evaluated by univariate and multivariate logistic regression analyses. A nomogram was established to score significant factors, and the bootstrap method was used for internal validation to calculate the concordance index (C-index) and generating calibration plots. A total of 127 patients with CSDH were included, among which 28 cases (22.04%) experienced recurrence within three months post-surgery. Significant differences were found in the percentages of M1 and M2 macrophages, the M1/M2 ratio, and related cytokines among different subtypes in CT classifications (P < 0.001). As CSDH evolved according to different CT subtypes, M1 macrophages gradually decreased, while M2 macrophages significantly increased, accompanied by a downregulation of the M1/M2 ratio. The similar changes were found in M1-related inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) and M2-related anti-inflammatory cytokines. Additionally, compared to the non-recurrence group, the recurrence group had higher percentages of M1 and M1/M2 ratio, but lower percentages of M2 (P < 0.05). LASSO regression analysis identified the dichotomized Nakaguchi CT classification, degree of brain atrophy, postoperative drainage volume, and hematoma volume were independent risk factors of recurrence (P < 0.05). Based on this, the established nomogram prediction model showed an AUC of 0.898, indicating good predictive efficacy and accuracy. The study demonstrated that the immune status within the hematoma cavity shifts from an inflammatory to an anti-inflammatory state during CSDH progression. Furthermore, it was found that altered immune balance gives rise to CSDH evolution and recurrence following surgery instead of inflammation itself.