Immunometabolic Profiling of Chronic Subdural Hematoma through Untargeted Mass Spectrometry Analysis: Preliminary Findings of a Novel Approach

Abstract

Objective: Metabolomics has growing importance in the research of inflammatory processes. Chronic subdural hematoma (cSDH) is considered to be, at least in part, of inflammatory nature, but no metabolic analyses yet exist. Therefore, a mass spectrometry untargeted metabolic analysis was performed on hematoma samples from patients with cSDH. Methods: A prospective analytical cross-sectional study on the efficacy of subperiosteal drains in cSDH was performed. Newly diagnosed patients had the option of granting permission for the collection of a hematoma sample upon its removal. The samples were analyzed using liquid chromatography–mass spectrometry to obtain different types of metabolites from diverse biochemical classes. The statistical analysis included data cleaning, imputation, and log transformation, followed by PCA, PLS-DA, HCA, and ANOVA. The postoperative course of the disease was followed for 3 months. The metabolite concentrations in the hematoma fluid were compared based on whether a recurrence of the disease was recorded within this time frame. Results: Fifty-nine samples from patients who were operated on because of a cSDH were gathered. Among those, 8 samples were eliminated because of missing metabolites, and only 51 samples were analyzed further. Additionally, 39 samples were from patients who showed no recurrence over the course of a 3-month follow-up, and 12 samples were from a group with later recurrence. We recorded a noticeable drop (35%) in the concentration of acylcarnitines in the ”recurrence group“, where 10 of the 22 tested metabolites showed a significant reduction (p < 0.05). Furthermore, a noticeable reduction in different Acyl-CoA-dehydrogenases was detected (VLCAD-deficiency p < 0.05, MCAD-deficiency p = 0.07). No further changes were detected between both populations. Conclusions: The current study presents a new approach to the research of cSDH. The measurements presented us with new data, which, to date, are without any reference values. Therefore, it is difficult to interpret the information, and our conclusions should be considered to be only speculative. The results do, however, point in the direction of impaired fatty acid oxidation for cases with later recurrence. As fatty acid oxidation plays an important role in inflammatory energy metabolism, the results suggest that inflammatory processes could be aggravated in cases with recurrence. Because our findings are neither proven through further analyses nor offer an obvious therapy option, their implications would not change everyday practice in the management of cSDH. They do, however, present a further possibility of research that might, in the future, be relevant to the therapy.