Hyperhomocysteinemia as a risk factor for cerebral venous thrombosis: a systematic review and meta-analysis of the...

Cerebral venous thrombosis (CVT) is relatively rare but has severe thrombotic manifestations with a high mortality rate, the potential to cause disability, and the propensity to recur. There are limited data on the role of hyperhomocysteinemia as a risk factor for CVT. In this context, no large-scale meta-analysis has been conducted. Our meta-analysis aims to assess hyperhomocysteinemia as a risk factor for CVT using the data from case-control studies.

We conducted a meta-analysis to investigate hyperhomocysteinemia as a risk factor among patients with CVT. A literature search was conducted using PubMed, Embase, Google Scholar, and Scopus databases until August 2025. A meta-analysis was performed using high-quality case-control studies that compared the homocysteine levels in patients with CVT and healthy controls. At least two authors extracted summary data. Between studies, heterogeneity was assessed using the I ² statistic. For each exposure-outcome pair, a random or fixed effect meta-analysis was conducted based on the degree of heterogeneity to pool the odds ratio (OR), prevalence of hyperhomocysteinemia, and the mean difference (MD) in homocysteine level with a 95% confidence interval (CI) from the individual studies using RevMan version 5.4.

This meta-analysis included six eligible studies. These studies involved 1355 participants (455 CVT cases and 900 controls). There were 123 men in the CVT group and 295 men in the control group. There was a statistically significant increased risk of CVT among patients with hyperhomocysteine levels (OR = 4.17, CI = 2.34-7.43, P-value < 0.00001, I ² = 70%). Furthermore, the homocysteine level was significantly higher in the CVT patients compared with the healthy controls (MD = 7.00, 95% CI = 3.21-10.79, I ² = 88%, P-value = 0.0003). The prevalence of hyperhomocysteine levels among CVT patients was higher compared with healthy controls (37%, 95% CI = 29-46%, I ² = 66%) versus (15%, 95% CI = 9-23%, I ² = 90.4%).

In conclusion, this meta-analysis demonstrates a strong association between CVT and hyperhomocysteinemia, with a notably high prevalence among CVT patients. While these findings suggest that hyperhomocysteinemia may be a potential risk factor for CVT, current evidence is limited. Larger-scale studies are needed to further clarify this association and inform future clinical recommendations.