Microcephaly with Simplified Gyral Pattern in Children: Quantitative Morphometric Assessment on Brain MRI and Correlation with Clinical Outcome.

BACKGROUND AND PURPOSE: Microcephaly with simplified gyral pattern (SGP) represents an often subtle subtype of malformation of cortical development that is commonly accompanied by epilepsy and neurodevelopmental delay. However, whether gyral simplification scales to reduced brain volume and whether MRI features predict clinical outcome still remain unclear. The aims of this study are therefore to apply a quantitative morphometric approach to distinguish a simplified gyral pattern from microcephaly-related effects and to correlate quantitative MRI-derived features with clinical outcome.

MATERIALS AND METHODS: From a single-center cohort of 34 patients with microcephaly and visually confirmed SGP (shallow sulci, normal cortical thickness), 18 subjects (mean age 7.1 ± 6.5 years) who fulfilled the eligibility criteria were retrospectively included for final analysis. Twenty-six age- and sex-matched healthy controls were included. GM/WM volumes (GMVs/WMVs) and surface-based measures were derived using FreeSurfer. Scaling corrections based on log-log robust regression and cortical folding analyses were subsequently analyzed. Principal component analyses clustered along morphometric phenotypes. ANCOVA, Kendall τ correlations, and logistic regression were applied to evaluate group differences and clinical outcome predictors.

RESULTS: Compared with healthy controls, patients showed significantly reduced WMV, cortical surface area, local gyrification index (LGI) (all Q < 0.003), and mildly increased cortical thickness. Allometric modeling indicated that, although WMV and LGI scaled proportionally to total brain volume, cortical surface area was disproportionately reduced, suggesting deviation beyond microcephalic scaling. Spectral folding analysis showed loss of specifically macroscale (primary) folding power. Morphometric clustering separated 4 subtypes differing in cortical thickness and area, of which the cluster with the lowest surface area and LGI exhibited universal developmental delay and included both early deaths. Across the cohort, neurodevelopmental delay correlated negatively with surface area. Logistic regression suggested lower surface area, WMV, and LGI as predictors of adverse clinical outcome (Q < 0.02).

CONCLUSIONS: The presence of SGP may reflect additional disturbance of primary sulcation and tangential cortical expansion beyond scaling to microcephaly alone. Our results suggest reduced cortical surface area as a key morphometric marker and a strong MRI feature predictive of neurodevelopmental delay, underscoring the clinical value of quantitative morphometry for stratifying disease severity in microcephaly with an SGP.