Functional Network Development in Sagittal Craniosynostosis Treated With Whole Vault Cranioplasty.

INTRODUCTION: In this study, the authors seek to clarify the neurological changes before and after whole vault cranioplasty (WVC) in patients born with sagittal craniosynostosis. METHODS: A case control study design was performed that included thirty functional MRI scans, from 25 individual patients. Functional MRI and diffusion tension imaging data were analyzed with BioImageSuite (Yale University, USA). 9 functional brain networks were analyzed, with appropriate correlated functional regions of the brain and utilized for analysis. RESULTS: Comparing functional MRI the infants after WVC versus infants before WVC group, the after WVC group demonstrated an increased connectivity in the left frontoparietal, secondary (V2), and third (V3) visual networks (P < 0.001). The right frontoparietal (RFPN) had decreased connectivity (P < 0.001). There is also a decrease and increase in anisotropy in the cingulum and precuneus despite surgery, respectively (P < 0.05). Adolescents treated with WVC compared to controls, demonstrated an increased connectivity in the salience and decreased connectivity in the RFPN relative to adolescent controls. CONCLUSIONS: Patients born with sagittal craniosynostosis have different connections in infancy in most of the defined cerebral networks compared to controls. After surgery, there are specific connectivity changes that occur in the RFPN, left frontoparietal, V2, and V3 networks, which are areas associated with executive function and emotional control. Changes identified in white matter tract microstructure connections could be influential in changes in functional connectivity. Although, as a child with sagittal craniosynostosis develops, much of the abnormal network connections, seen in infancy preoperatively, corrects to some degree after surgery. However, some aberrancies in the salience and RFPN networks remain potentially affecting executive functioning.

Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

INTRODUCTION: Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS: Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS: Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. CONCLUSION: Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.

Understanding the Learning Disabilities Linked to Sagittal Craniosynostosis.

OBJECTIVE: The purpose of this study is to investigate further findings that corroborate similarities between corrected sagittal craniosynostosis and attention deficit hyperactivity disorder (ADHD). The aim is to further characterize the neurocognitive deficits seen in adolescents with corrected craniosynostosis by comparing it to established learning deficits such as ADHD. METHODS: A total of 30 functional magnetic resonance imaging (fMRI) of 10 sagittal nonsyndromic craniosynostosis (sNSC), 10 ADHD-combined, and 10 control adolescents were studied. The fMRI scans were analyzed utilizing Statistical Parametric Mapping (University College London, UK) and analyzed with BioImageSuite (Yale University, New Haven, CT). RESULTS: The ADHD has lower connectivity to Brodmann area (BA) 11 (Montreal Neurological Institution [MNI]: -12,26,-21), BA20 (MNI: 62,-24,-25), and BA21 (MNI: 62,-32,-23) compared to sNSC and controls (P < 0.001). The sNSC has a unique visuospatial defect, compared to ADHD, created by decreased connectivity to BA31 (MNI: -3,-68,37), BA7 (MNI: -4,-68,41), BA19 (MNI: 0,-83,31), visual association cortex (MNI: -4,-78,22), and primary visual cortex (MNI: 7,-74,21) (P < 0.001). CONCLUSION: Patients born with sNSC have different neural connections than children born with ADHD. Patients born with sNSC have decreased connections in areas of visual processing and increased connections in areas of attention and auditory processing than patients with ADHD. Therefore, children with sagittal craniosynsotosis may have learning difficulties that, similar, yet different from ADHD.

De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus.

Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10-7), SMARCC1 (p = 8.15 × 10-10), and PTCH1 (p = 1.06 × 10-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10-4). Together, these probands account for ∼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.

Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles.

Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically in infancy to prevent adverse neurologic outcomes. To identify mutations contributing to common non-syndromic midline (sagittal and metopic) craniosynostosis, we performed exome sequencing of 132 parent-offspring trios and 59 additional probands. Thirteen probands (7%) had damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP - induced osteoblast differentiation (p<10-20). SMAD6 mutations nonetheless showed striking incomplete penetrance (<60%). Genotypes of a common variant near BMP2 that is strongly associated with midline craniosynostosis explained nearly all the phenotypic variation in these kindreds, with highly significant evidence of genetic interaction between these loci via both association and analysis of linkage. This epistatic interaction of rare and common variants defines the most frequent cause of midline craniosynostosis and has implications for the genetic basis of other diseases.

Normalization of brain morphology after surgery in sagittal craniosynostosis.

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.

The effects of a state concussion law on the frequency of sport-related concussions as seen in two emergency departments.

BACKGROUND: Connecticut (CT) passed its original sport-related concussion (SRC) law (PA 10-62) in 2010. The law requires that a health-care professional evaluate high school athletes with concussion symptoms. The purpose of this study was to evaluate two level 1 Trauma Center Emergency Department (ED) records for SRC before and after the Connecticut Public Act (CT PA) 10-62 to determine if the law had an effect on the presentation to the ED of SRCs. METHODS: A retrospective analysis of two level 1 Trauma Center Emergency Departments database was performed. Monthly data on SRCs treated in the study EDs from July 2003 through June 2012 were collected and analyzed using the autoregressive integrated moving average model. The number of SRCs in the youth (under age 14 years), high school (age 14 to 18 years), and adult (age >18 years) populations prior to CT PA 10-62 was compared to the number of SRCs post implementation of CT PA 10-62 for each academic school year, fall sports season, and summertime. RESULTS: Monthly SRCs in high school students treated in the study EDs increased from 2.5 cases to 5.9 cases between pre and post implementation of CT PA 10-62 (p < 0.001). Statistical modeling revealed that implementation of CT PA 10-62 was associated with significantly increased SRCs treated in the study EDs and that the increase was limited to the high school students in the fall season and during the school year. CONCLUSIONS: There has been a marked increase in the frequency of SRCs treated in the emergency departments in the high school population in Connecticut after the implementation of the sport-related concussion law. The results suggest that the sport-related concussion law in Connecticut is effective in improving the evaluation and detection of SRCs in high school students.

The impact of age at surgery on long-term neuropsychological outcomes in sagittal craniosynostosis.

BACKGROUND: The relationship between surgical age and long-term neuropsychological outcomes in sagittal-suture craniosynostosis remains equivocal. Whole-vault cranioplasty and strip craniectomy are performed at various times in individuals with sagittal-suture craniosynostosis. This study used comprehensive neurological testing to examine the relationship between age at time of surgery and long-term neuropsychological function. METHODS: Seventy sagittal-suture craniosynostosis patients who had previously undergone either whole-vault cranioplasty or strip craniectomy were examined divided into three groups: treatment before 6 months (n = 41), between 6 and 12 months (n = 21), and after 12 months (n = 8). To examine long-term cognitive functioning, participants between the ages of 5 and 25 years underwent neurodevelopmental tests to evaluate intelligence, achievement, and learning disabilities. RESULTS: Compared with those treated between 6 and 12 months and after 12 months, patients who underwent surgery before 6 months demonstrated higher full-scale IQ (p < 0.01) and verbal IQ (p < 0.01). Patients who received surgery before 6 months also demonstrated superior abilities in word reading (p < 0.01), reading comprehension (p < 0.01), spelling (p < 0.01), and numerical operations (p < 0.05) relative to those who had surgery between 6 and 12 months old. A statistically significant higher percentage of patients treated after 6 months had one or more reading-related learning disabilities as compared with those undergoing earlier surgery. CONCLUSIONS: This study suggests that surgery before 6 months old results in improved long-term neurological outcomes. Future studies should examine how the technique of surgery impacts these neuropsychological measures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Intracranial infantile hemangiopericytoma.

Intracranial infantile hemangiopericytomas (HPCs) are exceedingly rare lesions. Only 11 cases have been previously reported in the literature. As such, little is known about the etiology, long-term prognosis, and optimal treatment paradigm. Clinically, they are consistently less aggressive than those in adults. The authors present the case of a 2-month-old boy with an intracranial HPC, review the available literature, discuss the evolving concepts of what defines an HPC, and offer a potential explanation to how HPC histology might relate to the clinical behavior of these lesions.

Thoracic epidural teratoma: case report and review of the literature.

PURPOSE: Spinal teratomas comprise a rare subset of spinal cord tumors, and here, we describe an even rarer childhood thoracic extradural-intracanalicular teratoma. The clinical presentation, management, and pathophysiology of these tumors are reviewed to promote recognition and guide treatment of these lesions. METHODS: We report the case of a 21-month-old boy who presented with marked spasticity, as well as failure to ambulate and meet motor milestones. Additionally, we provide a literature review of spinal teratomas, including their clinical presentation, work-up, pathophysiology, and underlying genetics. RESULTS: An MRI of the spine revealed a large dorsal epidural tumor extending from T3 to T10 with heterogeneous contrast enhancement and severe spinal cord compression. The tumor was resected revealing a cystic mass with tissue resembling hair, muscle, as well as cartilage; pathology confirmed the diagnosis of teratoma. Gross total resection was achieved, and the child eventually gained ambulatory function. CONCLUSIONS: Given that spinal teratomas are rare entities that can present with significant neurologic compromise, they must remain on clinicians' differentials. Unfortunately, the exact origin of these tumors remains inconclusive and requires further investigation.

The effects of whole-vault cranioplasty versus strip craniectomy on long-term neuropsychological outcomes in sagittal craniosynostosis.

BACKGROUND: The optimal type of surgical management for isolated sagittal synostosis remains a source of significant debate. There is a paucity of data regarding possible differences in long-term neuropsychological outcomes following treatment with whole-vault cranioplasty or endoscopic strip craniectomy. This study provides the first comparative analysis examining the effects of the two techniques related to long-term intellectual functioning. METHODS: A total of 70 patients were enrolled in this multicenter study, 29 of whom had previously undergone endoscopic strip craniectomy and 41 of whom had previously undergone whole-vault cranioplasty. All patients completed a battery of neurodevelopmental tests (Beery-Buktenica Developmental Test of Visual-Motor Integration, Wechsler Abbreviated Scale of Intelligence, and Wechsler Fundamentals) to evaluate various domains of neuropsychological function. RESULTS: In a group comparison of those treated before 6 months of age, whole-vault patients obtained higher scores relative to endoscopic strip craniectomy patients on visuomotor integration, full-scale intelligence quotient, verbal intelligence quotient, word reading, and reading comprehension (p < 0.05 for all). When compared against strip craniectomy performed before 3 months of age, the whole-vault group still showed significantly higher scores in verbal intelligence quotient, reading comprehension, and word reading (p < 0.05 for all). CONCLUSIONS: The type of surgical intervention for isolated sagittal synostosis impacts long-term neuropsychological outcomes. Patients undergoing early whole-vault cranioplasty attained higher intelligence quotient and achievement scores relative to those undergoing strip craniectomy. Surgical management with whole-vault cranioplasty performed before 6 months of age provides the most favorable long-term intellectual outcomes in patients with isolated sagittal synostosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Back to the basics: identifying positive youth development as the theoretical framework for a youth drug prevention program in rural Saskatchewan, Canada amidst a program evaluation.

BACKGROUND: Despite endorsement by the Saskatchewan government to apply empirically-based approaches to youth drug prevention services in the province, programs are sometimes delivered prior to the establishment of evidence-informed goals and objectives. This paper shares the 'preptory' outcomes of our team's program evaluation of the Prince Albert Parkland Health Region Mental Health and Addiction Services' Outreach Worker Service (OWS) in eight rural, community schools three years following its implementation. Before our independent evaluation team could assess whether expectations of the OWS were being met, we had to assist with establishing its overarching program goals and objectives and 'at-risk' student population, alongside its alliance with an empirically-informed theoretical framework. METHODS: A mixed-methods approach was applied, beginning with in-depth focus groups with the OWS staff to identify the program's goals and objectives and targeted student population. These were supplemented with OWS and school administrator interviews and focus groups with school staff. Alignment with a theoretical focus was determined though a review of the OWS's work to date and explored in focus groups between our evaluation team and the OWS staff and validated with the school staff and OWS and school administration. RESULTS: With improved understanding of the OWS's goals and objectives, our evaluation team and the OWS staff aligned the program with the Positive Youth Development theoretical evidence-base, emphasizing the program's universality, systems focus, strength base, and promotion of assets. Together we also gained clarity about the OWS's definition of and engagement with its 'at-risk' student population. CONCLUSIONS: It is important to draw on expert knowledge to develop youth drug prevention programming, but attention must also be paid to aligning professional health care services with a theoretically informed evidence-base for evaluation purposes. If time does not permit for the establishment of evidence-informed goals and objectives at the start-up of a program, obtaining insight and expertise from program personnel and school staff and administrators can bring the program to a point where this can still be achieved and theoretical linkages made after a program has been implemented. This is a necessary foundation for measuring an intervention's success.

Decompressive hemicraniectomy for ischemic stroke in the pediatric population.

Adult patients with space-occupying hemispheric infarctions have a poor prognosis, with an associated fatality rate of 80%. Decompressive hemicraniectomy (DH) has been studied as a treatment option for patients with malignant cerebral infarction refractory to maximal medical therapy, with reasonable outcomes demonstrated in the adult population if the patient is decompressed within 48 h. However, there are no randomized controlled trials in the pediatric literature to make the same claims. In this study, we evaluated the current literature in regards to DH following malignant stroke in the pediatric population. We found that excellent recovery, with an acceptable quality of life, is possible, particularly in the pediatric patient. Our cohort suggests that pediatric intervention beyond the 48-h time interval may still lead to positive outcomes, unlike adult patients. Regardless, randomized controlled trials are needed to determine optimal timing of intervention following symptom onset, as well as to identify predictors for positive outcome in the pediatric population.

Intracranial compartment volume changes in sagittal craniosynostosis patients: influence of comprehensive cranioplasty.

BACKGROUND: A retrospective analysis of intracranial compartment volume changes in children with sagittal craniosynostosis was performed to clarify the therapeutic objectives of corrective surgery. METHODS: Chart and computed tomographic review of 53 consecutive children with previously unoperated sagittal synostosis was performed, and preoperative and postoperative computed tomographic scans were examined and compared with 143 age- and gender-matched controls. RESULTS: Preoperative mean intracranial compartment volume and mean brain tissue volume of each subgroup were age dependent. Brain volume was less in unoperated male sagittal synostosis patients (<6 months old) compared with controls (672.63 ml versus 716.14 ml). Brain tissue volume was approximately the same as controls for the 7- to 12-month and 12- to 30-month age groups. Long-term brain volume, however, again became less than controls with longer periods without treatment (31 to 60 months, 1050.6 versus 1291.51 ml, respectively). Intracranial compartment volume was less in unoperated male sagittal synostosis patients (<6 months old) compared with controls (706.6 ml versus 757.76 ml). Preoperative mean intracranial compartment volume, however, was greater than in controls in the 7- to 12-month (979.78 versus 970.34 ml) and 13- to 30-month age groups (1108.23 versus 1177.52 ml). Long term (31 to 60 months), however, intracranial compartment volume was less in untreated sagittal synostosis patients (1206.3 ml versus 1311.37 ml). Comparing day-1 postoperative sagittal synostosis patient data to age- and gender-matched controls to 1 year postoperatively, the operated patients develop an equivalent increase in skull growth compared with normals. CONCLUSIONS: Intracranial compartment volume is increased preoperatively in untreated sagittal synostosis patients older than 6 months. Intracranial compartment volume enlargement is largely attributable to an increase in brain volume. Comprehensive cranioplasty before 12 months of age increases intracranial compartment volume over normal growth.

Primary myxopapillary ependymoma of the medulla: case report.

OBJECTIVE: Myxopapillary ependymoma is a subclassification of ependymoma that is thought to be nearly exclusive to the conus medullaris or filum terminale. Primary intracerebral or brainstem myxopapillary ependymomas are rare. CLINICAL PRESENTATION: An 8-year-old child presented with a 5-month history of nausea and vomiting and a 1-week history of headache. Magnetic resonance imaging revealed a nodular mass in the medulla with an associated cyst extending into the fourth ventricle. INTERVENTION: A suboccipital craniotomy was performed, and a gross total resection of the lesion and cyst was achieved. Histological examination confirmed the diagnosis of myxopapillary ependymoma. A discussion of other reported cases of extraspinal myxopapillary ependymomas is presented. CONCLUSION: This is the first report of a case of myxopapillary ependymoma, confirmed by histology, in the medulla. Although rare, myxopapillary ependymomas outside of the filum terminale do exist.

Primary, non-exophytic, optic nerve germ cell tumors.

Tumors of the optic chiasm are relatively uncommon and usually associated with phakomatoses such as neurofibromatosis. Even more rare is the presentation of a primary, non-exophytic, isolated optic chiasm germ cell tumor (GCT). These tumors have imaging characteristics nearly indistinguishable from optic chiasmatic gliomas (OCGs). Herein we describe two cases of young men who presented with similar findings of progressive, painless visual loss and hypothalamic-pituitary-adrenal axis dysfunction including diabetes insipidus. Brain imaging was non-diagnostic and suggestive of an OCG. Pathology demonstrated GCTs in each case highlighting the importance of biopsy confirmation of the diagnosis. Both patients underwent a pterional craniotomy and sub-frontal approach to the optic chiasm. The chiasm was diffusely enlarged and discolored in each case without evidence of sellar, suprasellar or perichiasmatic pathology. Pathology demonstrated a malignant mixed GCT in the first patient and a germinoma in the second. This case series highlights the importance of tissue biopsy for patients with progressive symptoms from optic chiasm tumors. Furthermore, this is the first report of a primary, non-exophytic malignant mixed GCT. As the treatment regimens differ widely between optic chiasm GCTs and chiasm gliomas, tissue diagnosis is important.

Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence.

OBJECTIVE: Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain. METHODS: We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study. RESULTS: Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter. CONCLUSIONS: Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects.