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J Neurosurg Pediatr. 2016 Apr;17(4):460-8. doi: 10.3171/2015.7.PEDS15221. Epub 2015 Dec 18.

Normalization of brain morphology after surgery in sagittal craniosynostosis.

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Section of Plastic and Reconstructive Surgery.
Department of Neurosurgery, University of California, Los Angeles, California; and.
Department of Diagnostic Radiology, and.
Center for Translational Developmental Neuroscience, Child Study Center, and.
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut;
Department of Biomedical Engineering, Yale University, New Haven, Connecticut.


OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty performed at an early age offers substantial brain normalization by adolescence, but also that some effects of vault constriction may still persist after treatment. Specifically, few areas of expansion in frontoparietal and temporooccipital regions may persist. Overall, data from this small cohort support the primary goal of surgery in allowing for more normalized brain growth. Larger samples, and correlating degree of normalization with cognitive performance in NSC, are warranted.


DBM = deformation-based morphometry; DTI = diffusion tensor imaging; NSC = nonsyndromic craniosynostosis; WISC-III = Wechsler Intelligence Scale for Children, Third Edition; craniofacial; deformation-based morphometry; fMRI = functional MRI; magnetic resonance imaging; sNSC = sagittal NSC; sagittal craniosynostosis; voxel-based morphometry

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