T2-FLAIR Mismatch: An Imaging Biomarker for Children's MYB/MYBL1-Altered Diffuse Astrocytoma or Angiocentric Glioma.

BACKGROUND AND PURPOSE: T2-FLAIR mismatch is a highly specific imaging biomarker of IDH-mutant diffuse astrocytoma in adults. It has however also been described in MYB/MYBL1-altered low grade tumors. Our aim was to assess the diagnostic power of the T2-FLAIR mismatch in IDH-mutant astrocytoma and MYB/MYBL1-altered low-grade tumors in children and correlate this mismatch with histology. MATERIALS AND METHODS: We evaluated MR imaging examinations of all pediatric patients, performed at the Princess Máxima Center for Pediatric Oncology and the University Medical Center Utrecht between January 2012 and January 2023, with the histomolecular diagnosis of IDH-mutant astrocytoma, diffuse astrocytoma MYB/MYBL1-altered, or angiocentric glioma, and the presence of T2-FLAIR mismatch was assessed. Histologically, the presence of microcysts in the tumor (a phenomenon suggested to be correlated with T2-FLAIR mismatch in IDH-mutant astrocytomas in adults) was evaluated. RESULTS: Nineteen pediatric patients were diagnosed with either IDH-mutant astrocytoma (n = 8) or MYB/MYBL1-altered tumor (n = 11: diffuse astrocytoma, MYB- or MYBL1-altered n = 8; or angiocentric glioma n = 3). T2-FLAIR mismatch was present in 11 patients, 3 (38%) in the IDH-mutant group and 8 (73%) in the MYB/MYBL1 group. No correlation was found between T2-FLAIR mismatch and the presence of microcysts or an enlarged intercellular space in either IDH-mutant astrocytoma (P = .38 and P = .56, respectively) or MYB/MYBL1-altered tumors (P = .36 and P = .90, respectively). CONCLUSIONS: In our pediatric population, T2-FLAIR mismatch was more often found in MYB/MYBL1-altered tumors than in IDH-mutant astrocytomas. In contrast to what has been reported for IDH-mutant astrocytomas in adults, no correlation was found with microcystic changes in the tumor tissue. This finding challenges the hypothesis that such microcystic changes and/or enlarged intercellular spaces in the tissue of these tumors are an important part of explaining the occurrence of the T2-FLAIR mismatch.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

BACKGROUND AND PURPOSE: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book Pediatric Neuroimaging from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation. MATERIALS AND METHODS: This is a multicenter, international, retrospective study. We assessed the patients' medical records, prenatal ultrasounds, MR images, genetic findings, and postmortem results. We reviewed the medical literature for all studies depicting medullary malformations and evaluated cases in which a dorsal medullary protuberance was described. RESULTS: We collected 13 patients: 3 fetuses and 10 children. The medullary caps had multiple characteristics. Associated brain findings were a rotated position of the medulla, a small and flat pons, cerebellar anomalies, a molar tooth sign, and agenesis of the corpus callosum. Systemic findings included the following: polydactyly, hallux valgus, large ears, and coarse facies. Postmortem analysis in 3 patients revealed that the cap contained either neurons or white matter tracts. We found 8 publications describing a dorsal medullary protuberance in 27 patients. The syndromic diagnosis was Joubert-Boltshauser syndrome in 11 and fibrodysplasia ossificans progressiva in 14 patients. CONCLUSIONS: This is the first study to describe a series of 13 patients with medullary tegmental cap dysplasia. The cap has different shapes: distinct in Joubert-Boltshauser syndrome and fibrodysplasia ossificans progressive. Due to the variations in the clinical, imaging, and postmortem findings, we conclude that there are multiple etiologies and pathophysiology. We suggest that in some patients, the pathophysiology might be abnormal axonal guidance.

Introduction of ultra-high-field MR brain imaging in infants: vital parameters, temperature and comfort.

Background: Brain MRI in infants at ultra-high-field scanners might improve diagnostic quality, but safety should be evaluated first. In our previous study, we reported simulated specific absorption rates and acoustic noise data at 7 Tesla. Methods: In this study, we included twenty infants between term-equivalent age and three months of age. The infants were scanned on a 7 Tesla MRI directly after their clinically indicated 3 Tesla brain MRI scan. Vital parameters, temperature, and comfort were monitored throughout the process. Brain temperature was estimated during the MRI scans using proton MR spectroscopy. Results: We found no significant differences in vital parameters, temperature, and comfort during and after 7 Tesla MRI scans, compared to 3 Tesla MRI scans. Conclusions: These data confirm our hypothesis that scanning infants at 7 Tesla MRI appears to be safe and we identified no additional risks from scanning at 3 Tesla MRI.

Imaging Characteristics of CNS Neuroblastoma-FOXR2: A Retrospective and Multi-Institutional Description of 25 Cases.

BACKGROUND AND PURPOSE: The 5th edition of the World Health Organization Classification of CNS tumors defines the CNS neuroblastoma FOXR2 in the group of embryonal tumors. Published clinical outcomes tend to suggest a favorable outcome after resection, craniospinal irradiation, and chemotherapy. This multicenter study aimed to describe imaging features of CNS neuroblastoma-FOXR2, which have been poorly characterized thus far. MATERIALS AND METHODS: On the basis of a previously published cohort of tumors molecularly classified as CNS neuroblastoma-FOXR2, patients with available imaging data were identified. The imaging features on preoperative MR imaging and CT data were recorded by 8 experienced pediatric neuroradiologists in consensus review meetings. RESULTS: Twenty-five patients were evaluated (13 girls; median age, 4.5 years). The tumors were often large (mean, 115 [ SD, 83] mL), showed no (24%) or limited (60%) perilesional edema, demonstrated heterogeneous enhancement, were often calcified and/or hemorrhagic (52%), were always T2WI-hyperintense to GM, and commonly had cystic and/or necrotic components (96%). The mean ADC values were low (687.8 [SD 136.3] × 10-6 mm2/s). The tumors were always supratentorial. Metastases were infrequent (20%) and, when present, were of nodular appearance and leptomeningeal. CONCLUSIONS: In our cohort, CNS neuroblastoma FOXR2 tumors showed imaging features suggesting high-grade malignancy and, at the same time, showed characteristics of less aggressive behavior. There are important differential diagnoses, but the results of this study may assist in considering this diagnosis preoperatively.

Resting energy expenditure in children at risk of hypothalamic dysfunction.

Objective: Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage. Patients and methods: A retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage. Results: In total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE. Conclusion: REE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.

A diffusion tensor imaging analysis of white matter microstructures in non-operated craniosynostosis patients.

PURPOSE: In 7 to 15-year-old operated syndromic craniosynostosis patients, we have shown the presence of microstructural anomalies in brain white matter by using DTI. To learn more about the cause of these anomalies, the aim of the study is to determine diffusivity values in white matter tracts in non-operated syndromic craniosynostosis patients aged 0-2 years compared to healthy controls. METHODS: DTI datasets of 51 non-operated patients with syndromic craniosynostosis with a median [IQR] age of 0.40 [0.25] years were compared with 17 control subjects with a median of 1.20 [0.85] years. Major white matter tract pathways were reconstructed with ExploreDTI from MRI brain datasets acquired on a 1.5 T MRI system. Eigenvalues of these tract data were examined, with subsequent assessment of the affected tracts. Having syndromic craniosynostosis (versus control), gender, age, frontal occipital horn ratio (FOHR), and tract volume were treated as independent variables. RESULTS: ʎ2 and ʎ3 of the tracts genu of the corpus callosum and the hippocampal segment of the cingulum bundle show a ƞ2 > 0.14 in the comparison of patients vs controls, which indicates a large effect on radial diffusivity. Subsequent linear regressions on radial diffusivity of these tracts show that age and FOHR are significantly associated interacting factors on radial diffusivity (p < 0.025). CONCLUSION: Syndromic craniosynostosis shows not to be a significant factor influencing the major white matter tracts. Enlargement of the ventricles show to be a significant factor on radial diffusivity in the tracts corpus callosum genu and the hippocampal segment of the cingulate bundle. CLINICAL TRIAL REGISTRATION: MEC-2014-461.

The Mammillary Bodies: A Review of Causes of Injury in Infants and Children.

Despite their small size, the mammillary bodies play an important role in supporting recollective memory. However, they have typically been overlooked when assessing neurologic conditions that present with memory impairment. While there is increasing evidence of mammillary body involvement in a wide range of neurologic disorders in adults, very little attention has been given to infants and children. Literature searches of PubMed and EMBASE were performed to identify articles that describe mammillary body pathology on brain MR imaging in children. Mammillary body pathology is present in the pediatric population in several conditions, indicated by signal change and/or atrophy on MR imaging. The main causes of mammillary body pathology are thiamine deficiency, hypoxia-ischemia, direct damage due to masses or hydrocephalus, or deafferentation resulting from pathology within the wider Papez circuit. Optimizing scanning protocols and assessing mammillary body status as a standard procedure are critical, given their role in memory processes.

The atonic stomach: a dangerous condition prior to scoliosis surgery.

A dilated atonic stomach as part of neuromuscular or syndromic disorders can have devastating results after scoliosis surgery. Patients can be asymptomatic preoperatively and non-clinical signs can be easily overlooked. Awareness of the condition, however, can prevent severe complications such as aspiration.

Neurological deficits are present in syndromic craniosynostosis patients with and without tonsillar herniation.

BACKGROUND: Children with syndromic craniosynostosis (sCS) have a higher incidence of cerebellar tonsillar herniation (TH) than the general population. In the general population, TH ≥ 5 mm below the foramen magnum is associated with typical neurological deficits but, in sCS, we do not know whether this degree of TH is required before such deficits occur. OBJECTIVE: This prospective cohort study aimed to determine the association between findings on neurological assessment and cerebellar tonsillar position. METHODS: Magnetic resonance imaging (MRI) was used to determine TH ≥ 5 mm and the presence of syringomyelia. In regard to the outcome of neurological deficits, these were categorized according to: A, cerebellar function; B, cranial nerve abnormalities; and C, sensory or motor dysfunction. RESULTS: Twenty of 63 patients with sCS (32% [95% confidence interval 21-45%]) had TH ≥ 5 mm and/or syringomyelia. There was no significant difference in proportion between individual forms of sCS: 16/34 Crouzon, 2/11 Muenke, 2/12 Apert, and 0/7 Saethre-Chotzen patients. Neurological deficits were prevalent (73% [95% confidence interval 60-83%]), and as frequent in patients with TH ≥ 5 mm and/or syringomyelia as those without. Surgery occurred in 3 patients overall, and only in Crouzon patients. CONCLUSION: Determining the effect of TH ≥ 5 mm on neurologic functioning in sCS patients is used to better determine when surgical intervention is warranted. However, we have found that neurological deficits are prevalent in sCS patients, irrespective of cerebellar tonsillar position, suggesting that such findings are developmental and, in part, syndrome-specific central nervous system features.

A New Ultrasound Marker for Bedside Monitoring of Preterm Brain Growth.

BACKGROUND AND PURPOSE: Preterm neonates are at risk for neurodevelopmental impairment, but reliable, bedside-available markers to monitor preterm brain growth during hospital stay are still lacking. The aim of this study was to assess the feasibility of corpus callosum-fastigium length as a new cranial sonography marker for monitoring of preterm brain growth. MATERIALS AND METHODS: In this longitudinal prospective cohort study, cranial ultrasound was planned on the day of birth, days 1, 2, 3, and 7 of life; and then weekly until discharge in preterm infants born before 29 weeks of gestational age. Reproducibility and associations between clinical variables and corpus callosum-fastigium growth trajectories were studied. RESULTS: A series of 1-8 cranial ultrasounds was performed in 140 infants (median gestational age at birth, 27(+2) weeks (interquartile range, 26(+1) to 28(+1); 57.9% male infants). Corpus callosum-fastigium measurements showed good-to-excellent agreement for inter- and intraobserver reproducibility (intraclass correlation coefficient >0.89). Growth charts for preterm infants between 24 and 32 weeks of gestation were developed. Male sex and birth weight SD score were positively associated with corpus callosum-fastigium growth rate. CONCLUSIONS: Corpus callosum-fastigium length measurement is a new reproducible marker applicable for bedside monitoring of preterm brain growth during neonatal intensive care stay.

Abnormal transcranial Doppler cerebral blood flow velocity and blood pressure profiles in children with syndromic craniosynostosis and papilledema.

OBJECTIVE: Children with syndromic craniosynostosis are at risk of intracranial hypertension. This study aims to examine patient profiles of transcranial Doppler (TCD) cerebral blood flow velocity (CBFv) and systemic blood pressure (BP) in subjects with and without papilledema at the time of surgery, and subsequent effect of cranial vault expansion. METHODS: Prospective study of patients treated at a national referral center. Patients underwent TCD of the middle cerebral artery 1 day before and 3 weeks after surgery. Measurements included mean CBFv, peak systolic velocity, and end diastolic velocity; age-corrected resistive index (RI) was calculated. Systemic BP was recorded. Papilledema was used to indicate intracranial hypertension. RESULTS: Twelve patients (mean age 3.1 years, range 0.4-9.5) underwent TCD; 6 subjects had papilledema. Pre-operatively, patients with papilledema, in comparison to those without, had higher TCD values, RI, and BP (all p = 0.04); post-operatively, the distinction regarding BP remained (p = 0.04). There is a significant effect of time following vault surgery with a decrease in RI (p < 0.01). CONCLUSION: Patients with syndromic craniosynostosis who have papilledema have a different TCD profile with raised BP. Vault surgery results in increased CBFv and decrease in RI, however the associated systemic BP response to intracranial hypertension remained at short-term follow-up.

Diffusion Tensor Imaging and Fiber Tractography in Children with Craniosynostosis Syndromes.

BACKGROUND AND PURPOSE: Patients with craniosynostosis syndromes caused by mutations in FGFR-2, FGFR-3, and TWIST1 genes are characterized by having prematurely fused skull sutures and skull base synchondroses, which result in a skull deformity and are accompanied by brain anomalies, including altered white matter microarchitecture. In this study, the reliability and reproducibility of DTI fiber tractography was investigated in these patients. The outcomes were compared with those of controls. MATERIALS AND METHODS: DTI datasets were acquired with a 1.5T MR imaging system with 25 diffusion gradient orientations (voxel size = 1.8 × 1.8 × 3.0 mm(3), b-value = 1000 s/mm(2)). White matter tracts studied included the following: corpus callosum, cingulate gyrus, fornix, corticospinal tracts, and medial cerebellar peduncle. Tract pathways were reconstructed with ExploreDTI in 58 surgically treated patients with craniosynostosis syndromes and 7 controls (age range, 6-18 years). RESULTS: Because of the brain deformity and abnormal ventricular shape and size, DTI fiber tractography was challenging to perform in patients with craniosynostosis syndromes. To provide reliable tracts, we adapted standard tracking protocols. Fractional anisotropy was equal to that in controls (0.44 versus 0.45 ± 0.02, P = .536), whereas mean, axial, and radial diffusivity parameters of the mean white matter were increased in patients with craniosynostosis syndromes (P < .001). No craniosynostosis syndrome-specific difference in DTI properties was seen for any of the fiber tracts studied in this work. CONCLUSIONS: Performing DTI fiber tractography in patients with craniosynostosis syndromes was difficult due to partial volume effects caused by an anisotropic voxel size and deformed brain structures. Although these patients have a normal fiber organization, increased diffusivity parameters suggest abnormal microstructural tissue properties of the investigated white matter tracts.

Atypical presentation of a newborn with Apert syndrome.

INTRODUCTION: Apert syndrome is a rare syndrome characterized by a consistent phenotype including bilateral coronal suture synostosis with an enlarged anterior fontanel, midface hypoplasia, and complex symmetric syndactyly of hands and feet. CASE REPORT: We present a boy with Apert syndrome caused by the pathogenic c.755C > G p.Ser252Trp mutation in the FGFR2 gene with atypical characteristics, including premature fusion of the metopic suture with a small anterior fontanel, hypotelorism, and a massive posterior fontanel. Directly after birth, he showed papilledema, epilepsy, and central apneas. CONCLUSION: We present a newborn with Apert syndrome with atypical craniofacial presentation.

Developmental venous anomaly in the newborn brain.

INTRODUCTION: Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. METHODS: Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. RESULTS: DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. CONCLUSIONS: This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age.

Choice of diffusion tensor estimation approach affects fiber tractography of the fornix in preterm brain.

BACKGROUND AND PURPOSE: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results. MATERIALS AND METHODS: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method. RESULTS: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data. CONCLUSIONS: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome.

Optimal timing of cerebral MRI in preterm infants to predict long-term neurodevelopmental outcome: a systematic review.

SUMMARY: Advances in neonatal neuroimaging have improved detection of preterm brain injury responsible for abnormal neuromotor and cognitive development. Increasingly sophisticated MR imaging setups allow scanning during early preterm life. In this review, we investigated how brain MR imaging in preterm infants should be timed to best predict long-term outcome. Given the strong evidence that structural brain abnormalities are related to long-term neurodevelopment, MR imaging should preferably be performed at term-equivalent age. Early MR imaging is promising because it can guide early intervention studies and is indispensable in research on preterm brain injury.

Acquisition guidelines and quality assessment tools for analyzing neonatal diffusion tensor MRI data.

Diffusion tensor imaging is a valuable measure in clinical settings to assess diagnosis and prognosis of neonatal brain development. However, obtaining reliable images is not straightforward because of the tissue characteristics of the neonatal brain and the high likelihood of motion artifacts. In this review, we present guidelines on how to acquire DTI data of the neonatal brain and recommend high-quality data acquisition and processing as an essential means to obtain accurate and robust parametric maps. Sudden head movements are problematic for DTI in neonates, and these may lead to incorrect values. We describe strategies to minimize the corrupting effects both in terms of acquisition (eg, more gradient directions) and postprocessing (eg, tensor estimation methods). In addition, tools are described that can help assess whether a dataset is of sufficient quality for further assessment.

Determination of the optimal length of insertion of central venous catheters in pediatric patients by endovascular ECG.

BACKGROUND: In children the position of the tip of central venous catheters (CVC) is most often examined by chest radiography. Endovascular electrocardiography (ECG), using the CVC as an electrode, permits the correct placement of a CVC without the need for a chest X-ray. The use of a commercialised endovascular ECG-system (Alphacard®) for CVC-placement was evaluated in pediatric patients. METHODS: ECG-guidance was prospectively applied in 50 children (0-17 years, stratified into 5 age related subgroups). Positioning of the CVC was performed under ECG-guidance and subsequently assessed by chest X-ray. The frequency of correct ECG-guided CVC-placement in one single attempt, duration until confirmation by ECG and X-ray, and body weight-related depth of CVC-insertion were assessed. RESULTS: In 44 patients ECG-guidance resulted in a correct placement of the CVC-tip. Duration (median and [IQR] in sec.) to confirmation of correct placement was shorter with the ECG method (78[49-136]) than with X-ray (720[249-1095]) (P<0.0001). In five patients the ECG method failed because the CVC chosen was too short or the anesthetist did not trust the ECG-method. In one patient an unknown anatomical anomaly was present. Depth of insertion of the CVC was positively correlated with body weight (r2 0.68, P<0.0001). Stratification for age had no impact on duration until confirmation of CVC-position. No complications occurred during CVC-placement. CONCLUSION: ECG guidance of CVC-placement in children is a reliable technique, preventing children and health care providers from unnecessary X-ray exposure. Depending on local infrastructure and protocols it can furthermore shorten the procedure of CVC placement.

Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy.

OBJECTIVE: Classic infantile Pompe disease affects many tissues, including the brain. Untreated infants die within their first year. Although enzyme-replacement therapy (ERT) significantly increases survival, its potential limitation is that the drug cannot cross the blood-brain barrier. We therefore investigated long-term cognitive development in patients treated with ERT. METHODS: We prospectively assessed cognitive functioning in 10 children with classic infantile Pompe disease who had been treated with ERT since 1999. Brain imaging was performed in 6 children. RESULTS: During the first 4 years of life, developmental scores in 10 children ranged from above-average development to severe developmental delay; they were influenced by the type of intelligence test used, severity of motor problems, speech/language difficulties, and age at start of therapy. Five of the children were also tested from 5 years onward. Among them were 2 tetraplegic children whose earlier scores had indicated severe developmental delay. These scores now ranged between normal and mild developmental delay and indicated that at young age poor motor functioning may interfere with proper assessment of cognition. We found delayed processing speed in 2 children. Brain imaging revealed periventricular white matter abnormalities in 4 children. CONCLUSIONS: Cognitive development at school age ranged between normal and mildly delayed in our long-term survivors with classic infantile Pompe disease treated with ERT. The oldest was 12 years. We found that cognition is easily underestimated in children younger than 5 years with poor motor functioning.

Brain and ventricular volume in patients with syndromic and complex craniosynostosis.

PURPOSE: Brain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have normal brain volumes. The purpose of this study was to evaluate brain and ventricular volume measurements in patients with syndromic and complex craniosynostosis. This knowledge will improve our understanding of brain development and the origin of raised intracranial pressure in syndromic craniosynostosis. METHODS: Brain and ventricular volumes were calculated from MRI scans of patients with craniosynostosis, 0.3 to 18.3 years of age. Brain volume was compared to age matched controls from the literature. All patient charts were reviewed to look for possible predictors of brain and ventricular volume. RESULTS: Total brain volume in syndromic craniosynostosis equals that of normal controls, in the age range of 1 to 12 years. Brain growth occurred particularly in the first 5 years of age, after which it stabilized. Within the studied population, ventricular volume was significantly larger in Apert syndrome compared to all other syndromes and in patients with a Chiari I malformation. CONCLUSIONS: Patients with syndromic craniosynostosis have a normal total brain volume compared to normal controls. Increased ventricular volume is associated with Apert syndrome and Chiari I malformations, which is most commonly found in Crouzon syndrome. We advice screening of all patients with Apert and Crouzon syndrome for the development of enlarged ventricle volume and the presence of a Chiari I malformation.