Developmental transition in pathophysiological mechanisms of pediatric idiopathic intracranial hypertension and growth plate disorders: A multi-level structural equational modeling systematic review and meta-analysis.

INTRODUCTION

Pediatric idiopathic intracranial hypertension (IIH) and growth plate disorders (GPD) show parallel epidemiological trends and carry possible pathophysiological links, especially regarding obesity and hormonal dysregulation. This study investigated their indirect relationship through structural equation modeling (SEM) to identify age-dependent mechanisms and guide precision treatment strategies.

METHODS

Following PRISMA 2020 guidelines, we searched literature databases from inception to May 15, 2025, identifying studies reporting pediatric IIH and/or GPD parameters. SEM analysis was performed with age-stratified models to evaluate the mediating effects of obesity and hormonal factors between prepubertal (<10-12 years) and postpubertal (>10-12 years) cohorts.

RESULTS

We included 22 eligible studies with total of 2293 individuals. SEM revealed peculiar age-dependent mechanisms. In prepubertal children, venous pressure (β = 0.68, P-value<0.001) and vitamin D/hormonal pathways (β = 0.56, P-value<0.001) dominated, with obesity showing minimal effect (β = 0.28, P-value = 0.001). In a controverse manner, in postpubertal patients, the obesity pathway predominated (β = 0.76, P-value<0.001) with reduced venous (β = 0.29, P-value = 0.003) and hormonal (β = 0.16, P-value = 0.038) contributions. Mechanism-specific therapeutic efficacy showed parallel patterns: acetazolamide/surgical interventions were superior for venous-dominant cases (g = 1.86/1.74), while weight management demonstrated greatest efficacy for obesity-dominant phenotypes (g = 1.75). Vitamin D supplementation showed significant benefit only in hormonal-dominant cases (g = 1.64).

CONCLUSIONS

Pediatric IIH demonstrates fundamental mechanistic heterogeneity across development. A puberty-associated shift from venous/hormonal to obesity-dominant mechanisms explains the changing demographics and provides a framework for precision treatment. Targeted therapeutic approaches based on dominant mechanisms showed 63% improved outcomes compared to standard of care of IIH.