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From gene to geometry: the molecular morphogenesis of the fourth ventricle angle and its role in predicting brainstem
Omar Alomari1, Rana Al Juhmani2, Beyzanur Güney3
1Hamidiye International School of Medicine, University of Health Sciences, 3400, Istanbul, 34668, Turkey. dromari2001@gmail.com.
Background And Aim:
Chiari malformation type 1 (CM-1) is traditionally defined by tonsillar herniation, yet clinical symptoms often correlate poorly with simple linear measurements. Emerging research suggests that the geometry of the fourth ventricle may reflect deeper developmental anomalies. This study aimed to evaluate the association between fourth ventricular roof angle (FVRA) geometry and brainstem dysfunction and to determine its utility as a prognostic marker for symptomatic presentation and surgical outcomes.
Methods:
Following PRISMA guidelines and PROSPERO registration (CRD420261301268), a systematic search of Medline, Scopus, Web of Science, and Embase was conducted through January 2026. Studies reporting FVRA and BSD outcomes (apnea, dysphagia, cranial nerve deficits) were included. Statistical analysis was performed using the meta package in R (Version 4.1.0). A random-effects model was employed to calculate pooled Odds Ratios (OR) and 95% confidence intervals (CI), with heterogeneity assessed via I2 and chi-squared tests. Quality was appraised using the NIH Quality Assessment Tool.
Results:
Three high-quality observational cohorts (N = 556 patients) were included. Quantitative synthesis revealed that an FVRA > 65° is a significant radiographic correlate of BSD, demonstrating a nearly threefold increase in symptomatic risk (pooled OR 2.79; 95% CI 1.44-5.41). In the obtuse angle group (> 65°), 29.9% of patients exhibited BSD, compared to 12.5% in the group with angles ≤ 65°. Significant heterogeneity was observed (I2 = 67.7%). Despite the strong univariate association, multivariate data from the included studies indicated that FVRA utility is confounded by tonsillar position and does not reliably predict postoperative surgical outcomes.
Conclusion:
Abnormal fourth ventricular geometry is a statistically significant indicator of the "symptomatic Chiari phenotype," supporting a developmental model of CM-I involving intrinsic neural tube failures. While the FVRA offers high inter-rater reliability, its current clinical role is as a supplemental screening tool within comprehensive assessment algorithms rather than a standalone surgical trigger.
