Timing of cranioplasty after decompressive craniectomy and neurological recovery: A systematic review and meta-analysis

Decompressive craniectomy (DC) creates a large skull defect that may alter cerebral physiology and impair neurological recovery. Cranioplasty (CP) may reverse these effects and enhance functional and cognitive outcomes; however, the optimal timing remains uncertain. Prior systematic reviews have been limited in scope and have not fully examined cognitive outcomes, ultra-early CP (< 45 days), or traumatic brain injury (TBI)-specific effects. We conducted an updated. Systematic review and meta-analysis following PRISMA 2020 guidelines, prospectively registered in PROSPERO (CRD420251130762). MEDLINE, Embase, and LILACS were searched. Eligible studies included adults undergoing CP after DC with extractable timing comparisons (early ≤ 90 days vs. late > 90 days). Functional and cognitive outcomes were assessed using validated instruments. Two reviewers independently performed study selection, data extraction, and quality assessment (Newcastle-Ottawa Scale). Statistical analyses were conducted in R (metafor). Twenty-one studies (1682 patients; 691 early, 991 late) were included. CP, regardless of timing, was associated with significant neurological improvement. In post-CP analyses, early CP demonstrated significantly better outcomes across several functional scales, including BI, FIM, and KPS, and across pooled functional scores (SMD = 0.52 [0.21-0.83], I² = 87.2%). Cognitive recovery assessed by MMSE also favored early CP (SMD = 0.57 [0.34-0.79], I² = 0%). In TBI-only analyses, the effect remained significant (SMD = 0.74 [0.32-1.15], I² = 88.5%). Ultra-early CP showed a favorable but non-significant trend. Heterogeneity was substantial across analyses. Cranioplasty after DC is associated with significant functional and cognitive improvement. Early cranioplasty (≤ 3 months) is associated with better neurological outcomes than delayed reconstruction, with consistent effects across functional scales and in TBI populations. While these findings are biologically plausible, causality remains uncertain as evidence remains largely observational and with substantial heterogeneity. Well-designed multicenter randomized trials are needed to define optimal timing and strengthen clinical guidance.