Frontiers in neurology · 2026
Serial serum calcium dynamics predict delayed hydrocephalus after spontaneous subarachnoid hemorrhage: development and validation of a clinical nomogram in an observational cohort.
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Wu Di, Zhai Xingye, Zhang Xinyue, Han Xu, Hao Lingyu, Wang Cong, Wang Sihan, Wang Zhen, Wang Zengguang, Wang Yi
Аннотация
BACKGROUND: Delayed hydrocephalus, a severe complication following spontaneous subarachnoid hemorrhage (SAH), lacks reliable early biomarkers. Calcium dysregulation has emerged as a potential mediator of secondary brain injury, but the predictive value of serum calcium dynamics for delayed hydrocephalus remains unexplored.
METHODS: In this observational cohort study, we analyzed serial serum calcium measurements (admission, 72 h, and 7 days post-ictus) in SAH patients monitored for 90 days to identify delayed hydrocephalus, defined by radiological ventricular enlargement and clinical neurological deterioration requiring cerebrospinal fluid diversion. Predictive accuracy was evaluated using ROC analysis, and a clinical decision pathway integrating calcium thresholds with neurological assessments was proposed. An admission-variable nomogram was developed using LASSO and logistic regression modeling for early risk stratification. The model was externally validated in a cohort from two hospitals.
RESULTS: Among 302 patients analyzed, delayed hydrocephalus occurred in 24.2%. Serum calcium levels declined over the first week after SAH and were consistently lower at all measured time points among patients who developed delayed hydrocephalus (p < 0.001). Serum calcium at 72 h showed the highest predictive accuracy (AUC = 0.854), superior to conventional severity scales, with a cutoff ≤7.65 mg/dL (sensitivity 85.6%, specificity 80.3%). The admission-based nomogram incorporating admission serum calcium, hypertension, Hunt-Hess grade, smoking history, dyslipidemia, alcohol use and diabetes demonstrated excellent performance with an AUC > 0.93 in internal validation and an AUC of 0.898 in external validation.
CONCLUSION: Dynamic serum calcium levels, particularly hypocalcemia at 72 h, were strongly associated with delayed hydrocephalus after spontaneous SAH and showed good discriminatory performance. An admission-based nomogram provides early individualized risk stratification. These accessible tools could support clinical decision-making, but the proposed calcium cutoff may vary across laboratory assays and therefore warrants multicenter and cross-platform validation (with local calibration where appropriate) and further mechanistic studies.
METHODS: In this observational cohort study, we analyzed serial serum calcium measurements (admission, 72 h, and 7 days post-ictus) in SAH patients monitored for 90 days to identify delayed hydrocephalus, defined by radiological ventricular enlargement and clinical neurological deterioration requiring cerebrospinal fluid diversion. Predictive accuracy was evaluated using ROC analysis, and a clinical decision pathway integrating calcium thresholds with neurological assessments was proposed. An admission-variable nomogram was developed using LASSO and logistic regression modeling for early risk stratification. The model was externally validated in a cohort from two hospitals.
RESULTS: Among 302 patients analyzed, delayed hydrocephalus occurred in 24.2%. Serum calcium levels declined over the first week after SAH and were consistently lower at all measured time points among patients who developed delayed hydrocephalus (p < 0.001). Serum calcium at 72 h showed the highest predictive accuracy (AUC = 0.854), superior to conventional severity scales, with a cutoff ≤7.65 mg/dL (sensitivity 85.6%, specificity 80.3%). The admission-based nomogram incorporating admission serum calcium, hypertension, Hunt-Hess grade, smoking history, dyslipidemia, alcohol use and diabetes demonstrated excellent performance with an AUC > 0.93 in internal validation and an AUC of 0.898 in external validation.
CONCLUSION: Dynamic serum calcium levels, particularly hypocalcemia at 72 h, were strongly associated with delayed hydrocephalus after spontaneous SAH and showed good discriminatory performance. An admission-based nomogram provides early individualized risk stratification. These accessible tools could support clinical decision-making, but the proposed calcium cutoff may vary across laboratory assays and therefore warrants multicenter and cross-platform validation (with local calibration where appropriate) and further mechanistic studies.