Metabolomic Profiling of Three Body Fluids Differentiates UWS and MCS in Disorders of Consciousness

ABSTRACT Disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are complex brain dysfunctions with various causes. Misdiagnosis is common when relying solely on neurological exams, highlighting the need for accurate differentiation to guide clinical rehabilitation. This study explores metabolomic differences between UWS and MCS across cerebrospinal fluid (CSF), serum, and urine samples to identify biomarkers and metabolic pathways. Fifty‐one subjects were categorized into UWS ( n = 35) and MCS ( n = 16) based on coma recovery scale‐revised (CRS‐R) scores. Ultraperformance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was used to analyze samples, and statistical methods identified 14, 24, and 22 differential metabolites in CSF, serum, and urine, respectively. CSF metabolites were linked to necrosis, apoptosis, and neuroprotection; serum metabolites to lipid metabolism and immune response; and urine metabolites to cell signaling and neural function. Metabolomic panels showed AUC values of 0.85 (95% CI: 0.73–0.96) for CSF (95% CI: 0.86–1.00), 0.94 for serum, and 0.93 (95% CI: 0.79–1.00) for urine in distinguishing UWS from MCS. This profiling offers valuable insights into DOC pathophysiology and aids in accurate differentiation of these states.