Meige syndrome (MS) is a rare adult-onset cranial dystonia that mainly involves the muscles of the eyelid, mouth, jaw, and neck, which seriously affects the work and life of patients (Liu et al., 2021). MS commonly occurs in individuals aged between 40 and 70 years, with a notable sex predilection showing a 2–3 times higher prevalence in women than in men (Liu et al., 2022). It can be divided into three subtypes based on the craniofacial muscles involved: blepharospasm (BDS), oromandibular dystonia (ODS), and blepharospasm-oromandibular dystonia (B-ODS) (Ma H. et al., 2021). To date, the etiology and pathogenesis of MS have not been fully elucidated, and the diagnosis of MS remains challenging. The diagnosis of MS relies primarily on clinical symptoms and the exclusion of other conditions, with no established objective biomarkers available. Therefore, identifying reliable and readily accessible biomarkers for the diagnosis and risk assessment of MS patients is of great clinical significance.

MS may be linked to basal ganglia damage and nigrostriatal γ-aminobutyric acid neuron dysfunction, leading to dopamine transmitter imbalance, dopaminergic receptor hypersensitivity, and cholinergic imbalance (Tolosa and Lai, 1979). Importantly, secondary MS can occur following cerebrovascular disease, neurodegenerative diseases (e.g., Parkinson’s disease, multiple system atrophy, corticobasal ganglionic degeneration, and Huntington disease); additionally, it is associated with inflammatory mechanisms (Fu et al., 2024; LeDoux, 2009). Recent studies have reported that vascular pathology is associated with neuronal dysfunction; for instance, vascular disease can reduce blood flow and deprive neurons of essential oxygen and nutrients, which may lead to cell death and promote neurodegenerative processes (Han et al., 2020; Stanimirovic and Friedman, 2012; Watanabe et al., 2020). Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The characteristic feature of PD is degeneration of dopamine neurons in the substantia nigra pars compacta (SNc), resulting in striatal dopamine deficiency and consequent basal ganglia dysfunction that accounts for the cardinal motor features (Albin et al., 1989; Crossman, 1987; DeLong, 1990). PD is also linked to abnormal coagulation in its pathophysiology, involving a complex interplay among neurological, vascular, and inflammatory mechanisms (Adams et al., 2019; Wang et al., 2024). Neurons communicate with astrocytes, microglia, and blood vessels, and their crosstalk at each of these interfaces affects how the neurovascular unit responds to neural activity to trigger neurovascular coupling and regulate alterations in cerebral blood flow (Attwell et al., 2010). Decreased cerebral blood flow results in disruption of blood circulation of certain brain regions (neuron, neocortex and hippocampus), leading to undersupply of the tissue, especially of oxygen (hypoxia), which can induce rapid microvascular thrombosis and fibrin deposition within the brain (Adhami et al., 2006; Li et al., 2014; Nortley et al., 2019). As a key component of the neurovascular unit, endothelial cells play critical roles in regulating vasoconstriction and dilation, the material exchange between the central nervous system (CNS) and periphery, anti-coagulation and angiogenesis (Cai et al., 2017). Under conditions of endothelial dysfunction, endothelial cells trigger fibrin formation, as well as platelet adhesion and aggregation (Yau et al., 2015). Moreover, inflammation is recognized as both a trigger and sustainer of coagulation, with extensive interplay between inflammation and coagulation involving tissue factor, thrombin, the protein C pathway, and fibrinolytic regulators (Levi and van der Poll, 2010; Wang et al., 2024). Given that MS and PD may share common pathophysiological mechanisms, we speculate that MS is associated with coagulation abnormalities. Understanding the specific characteristics of these abnormalities is crucial for improving risk stratification and guiding appropriate management strategies.

Traditional blood coagulation indicators, including platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and international normalized ratio (INR), hold a predominant position in clinical practice. In this study, we first investigated the association between coagulation markers and MS risk. In addition, we constructed a novel and applicable scoring system for disease diagnosis by integrating clinically relevant factors.

MS, a rare focal dystonic movement disorder characterized by blepharospasm and oromandibular dystonia, is associated with basal ganglia dysfunction and dopaminergic imbalance, implicating similar neural pathways as PD. Moreover, both diseases are also involved in vascular pathology and inflammation (Fu et al., 2024; Pajares et al., 2020; Park, 2016; Rektor et al., 2009), suggesting that they may share common pathophysiological mechanisms. Studies have shown that PD is also associated with dysfunctional coagulation, yet the role of coagulation abnormalities in MS remains unexplored. This study, for the first time, systematically investigated the association between coagulation profiles and MS through a substantial cohort analysis, revealing significant alterations in coagulation markers among patients with MS. This study also constructed a nomogram for MS risk prediction, showing favorable discrimination ability in both the training and test cohorts, with AUCs of 0.748 and 0.746, respectively. These findings not only expand our understanding of MS pathophysiology but also highlight the potential clinical utility of coagulation indicators in MS diagnosis and classification.

Our study found significant differences in seven coagulation markers (PT%, APTT, Fib, PLT, PCT, PDW and MPV) between MS patients and HC. Specifically, the PT% was significantly lower in the MS cohort than in the HC cohort (P < 0.0001), suggesting alterations in the activity of coagulation factors. APTT was lower in MS patients than in HCs, indicating alterations in the intrinsic coagulation pathway (Adamus-Grabicka et al., 2024; Berntorp and Salvagno, 2008; Chitlur, 2012; Salvagno and Berntorp, 2010). This shortened APTT can be mechanistically attributed to elevated Factor VIII activity secondary to increased von Willebrand factor levels, and both serve as established biomarkers of endothelial dysfunction and inflammation (Lelas et al., 2021; Mina et al., 2010; Radišić Biljak et al., 2024), indicating the vascular and inflammatory pathology in MS. We also found that APTT was significantly elevated in patients with severe blepharospasm, indicating the potential to distinguish between MS patients with different clinical conditions. The Fib level was significantly reduced in the MS cohort (P < 0.0001). Plasma Fib is involved in blood coagulation and is an important determinant of blood viscosity and hence of blood flow (Lip, 1995). A decrease in Fib levels may impair the formation and stability of blood clots, thereby increasing the risk of bleeding (Grottke et al., 2020; Li et al., 2022). In this study, AUC values for Fib and APTT in the ROC analysis highlighted their discriminatory power in distinguishing patients with MS from HCs (APTT: AUC = 0.7761, P < 0.0001; Fib: AUC = 0.6464, P < 0.0001). Furthermore, significant decreases were observed in platelet-related indicators including PLT (P < 0.0001), PCT (P = 0.0005), and PDW (P < 0.0001), while the MPV in the MS cohort was significantly higher than that in the HC cohort (P < 0.0001). In addition, our study showed that PLT and PCT of MS2 patients were higher than MS1 patients. Univariate and multivariate logistic regression analyses revealed that PT%, Fib, PDW and INR were independent risk factors for MS. PCT, PDW and MPV are a group of platelet parameters determined together in automatic complete blood count profiles. A number of molecular structures exposed to the blood stream after the disruption of endothelial cell integrity are recognized by platelets, including von Willebrand factor, collagen, laminin, vitronectin and fibrinogen (Sotnikov et al., 2013). The simultaneous decrease of both PLT and PCT indicates that platelets have been excessively consumed (Zhang et al., 2015). MPV levels increase when PLT decreases and large platelets are thought to be younger and more reactive. High MPV was associated with a variety of cardio- and cerebrovascular disorders and PD, as well as low-grade inflammatory conditions prone to arterial and venous thromboses (Braekkan et al., 2010; Gasparyan et al., 2011; Koçer et al., 2013; Ulasli et al., 2012). The seemingly contradictory coagulation profile observed in MS patients, characterized by shortened APTT alongside reduced Fib and platelet indices, likely reflects a complex dysregulation rather than a simple hyper- or hypocoagulable state. Similar complex coagulation profiles have been reported in other neurodegenerative diseases like PD, where dysfunctional coagulation is associated with involvement of neurological, vascular, and inflammatory mechanisms (Ma S. X. et al., 2021). These findings highlight the complex coagulation dysregulation underlying MS pathophysiology.

It should be noted that multiple physiological factors can influence coagulation parameters. Diet can acutely modify hemostasis: high-fat meals activate factor VII (FVIIc/FVIIa); variability in vitamin-K intake alters vitamin-K-dependent factor activation and INR stability (de Assis et al., 2009). Systemic inflammation via IL-6 up-regulates fibrinogen, and vWF/FVIII behave as positive acute-phase reactants linked to endothelial activation (Mantovani and Garlanda, 2023). Hormonal status also matters: pregnancy increases fibrinogen, FVIII, vWF, and lowers protein-S activity; combined oral contraceptives shift the profile toward hypercoagulability (Yoon, 2019). In addition, recent strenuous exercise transiently raises FVIII, vWF, thrombin-antithrombin complexes, and D-dimer with a concurrent rise in fibrinolysis, whereas habitual training tends to lower fibrinogen/PAI-1 and enhance resting tPA activity (Prisco et al., 1998).

Despite these promising findings, several limitations should be acknowledged. First, the single-center retrospective design introduced a potential selection bias and limited the generalizability of the conclusions. Validation through multicenter prospective cohorts with diverse populations is required to confirm these observations. Second, our retrospective approach could not control for these potential confounders, including preadmission pharmacotherapy, dietary habits, inflammatory status, and hormonal variations, which may have introduced unmeasured confounding and biased our effect estimates. Finally, the diagnostic complexity of MS poses inherent challenges in establishing reliable pre-disease baselines. Our analyses were restricted to post-diagnosis clinical parameters, potentially obscuring the critical temporal relationships between biomarker fluctuations and early pathological processes.

In conclusion, our study provides evidence of significant differences in coagulation markers between patients with MS and HCs, highlighting the potential role of coagulation abnormalities in MS pathophysiology. The constructed nomogram is a quick and effective screening tool for assessing the risk of MS, thereby contributing to the diagnosis and management of MS. However, future studies should aim to validate these findings and explore their underlying mechanisms.