The Evolving Landscape of Cerebral Venous Sinus Thrombosis: Emerging Risk Factors and Treatments

Cerebral venous sinus thrombosis (CVST) is a rare yet serious condition, representing an uncommon manifestation of venous thromboembolism (VTE) [1]. Unlike deep vein thrombosis (DVT) or pulmonary embolism (PE), CVST disproportionately affects younger individuals, particularly women, highlighting distinct pathophysiological mechanisms [2].

While traditional risk factors such as hormonal influences and inherited thrombophilias have long been recognized, emerging contributors, including obesity [3], polycystic ovary syndrome (PCOS) [4], and COVID-19-related conditions [5], are reshaping our understanding of this disorder. Additionally, advances in treatment options, such as direct oral anticoagulants (DOACs) [6] and endovascular therapies [7], are transforming management strategies.

A recent review explored contemporary risk factors and etiologies for CVST, while discussing evidence for the use of direct oral anticoagulants (DOACs) in its treatment [8].

Epidemiology and Risk Factors

The incidence of CVST is estimated at 1.3 to 2.6 cases per 100,000, with a higher prevalence among women aged 18 to 44 years [1,4]. This gender disparity is largely attributed to hormonal factors, including oral contraceptives (COCs), pregnancy, and the postpartum period. Notably, newer risk factors such as obesity and PCOS are gaining prominence. Obesity, a global health epidemic, has been associated with a 2.63-fold increased risk of CVST, potentially linked to the procoagulant effects of adipokines and increased intra-abdominal pressure [9, 10].

PCOS, a prevalent endocrine disorder affecting up to 20% of women globally, further amplifies CVST risk through metabolic changes and prothrombotic states [4]. Has been reported a 1.5 to 2-fold increased risk of venous thromboembolism in women with PCOS, independent of obesity or COC use [11]. These findings underscore the need for heightened vigilance in managing high-risk individuals [4,11].

The COVID-19 pandemic has also introduced unique challenges. Both the infection and vaccine-induced immune thrombotic thrombocytopenia (VITT) have been implicated in CVST cases. VITT, characterized by thrombocytopenia and anti-PF4 antibodies, exhibits a predilection for unusual thrombotic sites, including cerebral venous sinuses, with a high mortality rate exceeding 40% in severe cases [12]. Furthermore, emerging data suggest that even “VITT-like” disorders, which occur without recent vaccination, may contribute to CVST risk [13].

Advances in Diagnosis and Treatment

The clinical presentation of CVST often includes severe headache, seizures, and focal neurological deficits. Imaging plays a pivotal role, with magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) being the gold standards. In resource-limited settings, computed tomography venography (CTV) serves as a viable alternative. Laboratory investigations, including D-dimer levels and coagulation profiles, are essential for risk stratification [14].

Anticoagulation remains the cornerstone of CVST management. Historically, vitamin K antagonists (VKAs) were the standard, but DOACs are now emerging as a safe and effective alternative. Recent studies have demonstrated comparable efficacy between DOACs and VKAs, with fewer bleeding complications and greater convenience due to oral administration [15, 16]. The ongoing DOAC-CVT trial aims to provide further clarity on their role in CVST treatment [17].

For patients with VITT, immediate discontinuation of heparin products and initiation of non-heparin anticoagulants, such as fondaparinux or argatroban, is critical. High-dose intravenous immunoglobulin (IVIg) and plasma exchange have shown promise in mitigating severe cases, emphasizing the importance of early and accurate diagnosis [12, 13].

In refractory cases or those with severe intracranial hypertension, endovascular therapies such as mechanical thrombectomy or catheter-directed thrombolysis may be considered. Although these approaches are associated with higher procedural risks, they offer life-saving potential in select scenarios. Decompressive craniectomy remains an option for patients with impending herniation [18, 19]. Additionally, recent recommendations highlight the importance of managing raised intracranial pressure early to prevent fatal outcomes [14].

Emerging Challenges and Future Directions

Despite these advancements, several challenges persist. The heterogeneity of CVST’s clinical presentation and underlying risk factors necessitates a multidisciplinary approach involving neurologists, hematologists, and interventional radiologists [4, 5]. Furthermore, the lack of robust randomized controlled trials limits definitive conclusions on the superiority of specific treatment modalities, particularly for DOACs in diverse patient populations [15, 17].

The integration of personalized medicine, leveraging genetic and biomarker-based risk stratification, holds promise for optimizing CVST management [1, 2]. For example, identifying patients with high-risk thrombophilias or comorbid conditions such as obesity and PCOS can guide tailored interventions [3, 4]. Similarly, advancements in artificial intelligence may enhance diagnostic accuracy, enabling earlier detection and intervention [14, 19].

Ongoing research into the pathophysiological mechanisms of novel risk factors will further refine prevention and treatment strategies. For instance, understanding how adipokines influence coagulation pathways in obesity or delineating the hemostatic changes associated with PCOS could inform targeted therapies [9, 11]. Moreover, the role of systemic inflammation in COVID-19-related CVST highlights the need for anti-inflammatory approaches alongside traditional anticoagulation [12, 13].

Conclusion

CVST represents a distinct and evolving entity within the spectrum of venous thromboembolism. The recognition of emerging risk factors, coupled with advancements in diagnostic and therapeutic modalities, underscores the progress made in understanding and managing this condition. However, continued research and collaboration are essential to address remaining knowledge gaps and improve outcomes for affected individuals. As our understanding of CVST deepens, integrating multidisciplinary expertise and leveraging novel technologies will be critical to advancing care and reducing morbidity and mortality.

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