Meige syndrome (MS), initially reported by the French neurologist Henri Meige in 1910, is an infrequent and debilitating neurological condition characterized by involuntary contractions of the eyelids and facial muscles (1), which ultimately leads to significant functional impairment and psychosocial distress for affected individuals. Generally, the condition is more prevalent among individuals aged 40 to 70, with a higher incidence in women than in men (2). Currently, the etiology and pathogenesis of MS remain unknown. It has been suggested that a disruption in the balance of neurotransmitters in the brain, particularly dopamine and acetylcholine, may be involved (3). This neurochemical imbalance has been associated with multiple factors, such as specific medications, psychological stress, dental interventions, and trauma (4). Diagnosis of MS currently depends largely on patients’ clinical symptoms, and there is no definitive diagnostic test available. Consequently, there is a pressing need to identify reliable biomarkers for MS diagnosis.

Impairment of the basal ganglia and related neural pathways plays a key role in the development of MS (5). Research indicates that MS may be linked to an imbalance between acetylcholine and dopamine, while other studies suggest that changes in neuronal plasticity and decreased cortical inhibition could contribute to the condition (3, 6). A variety of neurological disorders have been linked to neuronal cell death due to oxidative stress (7, 8). Many studies have demonstrated that oxidative stress is a key factor in the progression of various neurological disorders, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Huntington’s disease (HD), ischemic stroke, and multiple sclerosis (9). The central nervous system (CNS) exhibits heightened sensitivity to oxidative stress, a result of its high metabolic rate, rich presence of substances susceptible to oxidation, and constrained antioxidant capabilities (10). Reactive nitrogen species (RNS) and reactive oxygen species (ROS) reactive can lead to oxidative stress, which inflicts damage on cellular constituents such as lipids, proteins, and DNA, ultimately resulting in cellular impairment and apoptosis (11). Oxidative stress can also modify the activity of ion channels, which are essential for preserving neuronal excitability and signal transmission (12). Oxidative stress-induced alterations in ion channel regulation can exacerbate the progression of neurological diseases (13).

In recent years, biomarkers such as albumin, gamma-glutamyl transferase (GGT), total bilirubin (TBIL), uric acid (UA), and the urea nitrogen-to-creatinine ratio have emerged as significant indicators of oxidative stress in the context of neurological diseases (14–16). Although these markers have been extensively studied in various contexts, their potential as predictors for MS has not been fully explored. The present study innovatively investigates the relationship between these oxidative stress markers and MS, revealing their potential as novel predictive indicators for MS. To the best of our knowledge, this is the first study to explore the association between these oxidative stress markers in blood and MS, with the largest sample size of MS cases reported to date. Given the lack of definitive diagnostic tests for MS and the critical importance of early diagnostic for improved patient outcomes, our nomogram-a powerful predictive tool-provides a quantitative and reliable method for clinicians to assess MS risk based on these oxidative stress markers. This innovation facilitates early intervention and personalized management strategies.

Studies have suggested that oxidative stress plays a significant role in the pathological mechanisms of various neurological disorders (9). Given its high metabolic activity and oxygen demand, the brain is particularly susceptible to oxidative stress. Excessive ROS, including superoxide, hydrogen peroxide, and hydroxyl radicals, can damage vital biomolecules such as proteins, lipids, and DNA (16). This damage initiates a cascade that can result in cellular dysfunction and, ultimately, neurodegeneration. However, current evidence does not link peripheral blood oxidative stress markers to MS. Thus, investigating the relationship between these markers and MS is crucial.

In this study, compared with HCs, the serum levels of antioxidants, such as GGT, TBIL, albumin, and UA were significantly reduced in patients with MS, while the pro-oxidant the urea nitrogen-to-creatinine ratio was markedly increased. This finding lends credence to the hypothesis that oxidative damage could be a significant factor in the development of MS. Multivariate logistic regression analysis identified GGT, TBIL, albumin, and urea nitrogen-to-creatinine ratio as independent risk predictors for MS. These biomarkers are readily accessible and have potential for broad clinical application. We integrated these variables into a nomogram to develop a predictive model. The model demonstrated strong discriminative ability, with ROC curve areas of 0.930 (95% CI: 0.913–0.948) for the training set and 0.914 (95% CI: 0.885–0.942) for the validation set. Calibration curves and DCA indicated that the model has good consistency and clinical utility.

Serum albumin, the most abundant protein in circulation, has antioxidant properties that significantly mitigate reoxygenation injury (17–19). albumin’s antioxidant properties are due to its molecular structure. The reduced Cys34 residue, the largest pool of thiols in circulation, enables albumin to scavenge nitric oxide (NO), ROS, other reactive nitrogen species, and prostaglandins via this cysteine residue (20–22). Albumin exhibits neuroprotective effects, partly due to its modulation of intracellular signaling in neuronal and glial cells and its antioxidant capabilities (23). In recent years, an increasing amount of evidence has indicated that albumin plays a crucial role in neurological diseases. Some studies have linked lower serum albumin levels to a higher risk of cognitive impairment and dementia (24). Furthermore, research has shown that serum albumin levels are notably reduced in patients with PD and are considered independent risk factors for the condition (25). Similarly, we observed that MS patients had significantly lower albumin levels in their peripheral blood compared to HCs. This reduction in albumin implies a weakened antioxidant capacity, which may exacerbate oxidative stress, induce neural tissue damage, and impede neural recovery, thereby potentially promoting MS development. The potential link between albumin levels and MS risk underscores the importance of further investigating albumin as a biomarker for MS diagnosis and risk assessment.

Bilirubin, a potent endogenous antioxidant, is found in biological fluids throughout the body and ranks among the strongest natural antioxidants (25). TBIL is the breakdown product of aging red blood cells (26), exhibits potent antioxidant capabilities, enabling it to neutralize harmful oxidative stress byproducts, shield the body’s organs from injury (27), and has direct antioxidant properties in the brain (28). Under normal conditions, the human body possesses an antioxidant defense mechanism that maintains a dynamic equilibrium between oxidizing agents and antioxidants, thereby preventing harm to the body. However, a disruption in this balance can result in heightened oxidative processes, which can lead to tissue damage (29). Our research indicated that compared to the HCs, the TBIL levels in MS are reduced, aligning with prior studies (15). This reduction may be associated with increased oxidative stress and tissue damage in MS. Additionally, elevated TBIL levels have been reported in patients with Parkinson’s disease (PD), potentially due to dopaminergic substitution therapy (30). Two plausible explanations for the altered TBIL levels in neurological disorders are: First, bilirubin exhibits cytoprotective effects against injury caused by oxidative stress. Second, bilirubin has anti-inflammatory properties. The latter has been particularly evident in brain tissue, as demonstrated in models of experimental autoimmune encephalomyelitis, where bilirubin exhibits potent anti-inflammatory activity (31). Therefore, the deficiency of TBIL in MS patients could exacerbate oxidative stress and inflammation, contributing to disease progression. Further investigation into the relationship between TBIL and MS may provide valuable insights into the pathogenesis of MS and identify TBIL as a potential biomarker or therapeutic target for the disease.

GGT primarily facilitates the “glutathione cycle,” which operates at the plasma membrane and is crucial for maintaining cysteine homeostasis, thereby preserving intracellular glutathione levels and the cell’s redox balance (32). Recent studies indicate that GGT contributes significantly to antioxidant defense and the metabolism of xenobiotics (33). As a key antioxidant, GGT serves as an indicator of oxidative stress, with numerous studies linking its activity to the development of a range of diseases, including cardiovascular disease, cancer, lung inflammation, and neurological disorders (14). In our study, MS patients exhibited lower GGT levels compared to HCs, implying that reduced GGT might be a risk factor for MS. However, this finding differs from the results observed in other neurological disorders. Previous studies have shown that higher GGT levels have been correlated with dementia risk (34). The observed discrepancy may be attributed to the dual nature of GGT, which can promote pro-oxidant activity through the degradation of glutathione in the extracellular space under specific conditions (14). In MS, the reduced GGT levels could indicate a diminished antioxidant capacity, potentially exacerbating oxidative stress and contributing to disease progression.

UREA and CREA are end products of nitrogen-containing compounds in the human body and serve as accessible biomarkers for renal function in clinical settings (35). The urea nitrogen-to-creatinine ratio, a laboratory biomarker, has traditionally been used to assess dehydration (36). Recently, it has also been identified as an independent prognostic factor for adverse outcomes in patients with various conditions, such as stroke (16) and heart failure (37). Other research has determined that a reduced level of the urea nitrogen-to-creatinine ratio could potentially elevate the risk of ischemic stroke (38). However, there is inconsistency in the effects of urea nitrogen-to-creatinine ratio on various diseases, and the role of the urea nitrogen-to-creatinine ratio in MS patients remained uncertain. In MS, the role of the urea nitrogen-to-creatinine ratio was previously unexplored. Our study revealed significantly higher serum the urea nitrogen-to-creatinine ratio levels in MS patients compared to HCs, suggesting its potential as a biomarker for MS susceptibility. Previous studies suggested that urea nitrogen-to-creatinine ratio levels correlate with oxidative stress (39), abnormal inflammation (40), and endothelial dysfunction (41) in patients, which could be potential mechanisms underlying the association between elevated the urea nitrogen-to-creatinine ratio and MS risk. Given the established links between the urea nitrogen-to-creatinine ratio and various adverse outcomes, as well as its association with oxidative stress and inflammation, our findings highlight the potential importance of the urea nitrogen-to-creatinine ratio as a biomarker for MS risk.

This study was the first to build an MS prediction model based on oxidative stress markers. The independent predictors included in our model are easily accessible, thereby enhancing the ease of using the model. However, given that this study is a retrospective, single-center analysis, it also has certain limitations. The single-center origin of the data limits the generalizability of the study results, and the lack of external validation further underscores the need for future studies to employ multicenter data for further verification. Moreover, due to its retrospective nature and the fact that the normal controls were individuals undergoing health check-ups, we were unable to accurately obtain data regarding several potential confounding factors, such as medication history prior to admission and dietary habits.

Our study successfully developed a nomogram incorporating GGT, TBIL, albumin, and the urea nitrogen-to-creatinine ratio to predict the risk of MS. This model offers a clinically valuable tool for risk assessment, demonstrating robust performance with high AUCs in both training and validation cohorts. The calibration curves and the DCA results demonstrate that the model exhibits strong concordance and possesses significant clinical application value, ultimately highlighting its potential utility in MS predict.