Eye and Orbital Anatomy in Metopic Synostosis

Background: Metopic synostosis patients have a high prevalence of orthoptic anomalies, including hyperopia, astigmatism, and amblyopia. We hypothesized altered orbital anatomy contributes to suboptimal visual outcomes by adversely affecting eye anatomy and growth from early life onward. Therefore, we aimed to investigate eye and orbital anatomy in metopic synostosis. Methods: We conducted a retrospective study in nonsyndromic metopic synostosis patients (n = 134, median age 0.43 years [IQR 0.45]) with nonsyndromic sagittal synostosis patients (n = 134, median age 0.27 years [IQR 0.23]) as controls. Primary analyses focused on eye dimensions (axial length, width, and globe height) and orbital dimensions, correcting for sex and age. Measurements were obtained from preoperative computed tomography scans. Results: Axial length and width in metopic synostosis patients did not differ from sagittal synostosis patients, but globe height was significantly smaller (P = 0.0002). Lateral wall interorbital length, lateral orbital wall length, anterior medial interorbital length, and maximal medial interorbital length were significantly smaller, and anterior vertical orbital height and maximal vertical orbital height were significantly larger (P &lt; 0.001). The central orbital axis and interorbital angle were significantly narrower, and medial-to-lateral orbital wall angle was wider (P &lt; 0.001). Conclusions: Metopic synostosis patients have more shallow, wider, and higher orbits. Eye dimensions are similar in sagittal synostosis patients, although globe height was smaller. Altered orbital and eye dimensions in metopic synostosis probably have a causal relation with an unknown order of development. How these dimensions relate to future orthoptic anomalies (eg, refractive error) needs further investigation.</p

Pre-Operative Ocular Findings and Long-Term Follow-Up in a Large Cohort of Non-Syndromic Unicoronal Craniosynostosis

(1) Background: Non-syndromic unicoronal craniosynostosis (UCS) is associated with a high prevalence of ocular anomalies. Currently, the etiology of this association remains obscure, however, it is presumed to be primarily attributed to their orbital malformations and/or secondary to craniofacial surgery. We assessed pre-operative ophthalmological examinations of non-syndromic UCS patients and compared them with their postoperative outcomes and long-term follow-up.(2) Methods: A retrospective case series was conducted on medical records of patients with non-syndromic UCS at Sophia Children’s Hospital, Rotterdam. Ophthalmologic examinations were collected at different time periods: T1 (first visit), T2 (&lt;1 year after cranioplasty), and T3 (long-term follow-up at last visit). The McNemar’s test was used for statistical analysis. (3) Results: A total of 101 patients were included, for whom examinations were available at T1 and T3. Patients had a mean age of 2.8 years (±2.7) and 9.5 (±4.9) at T1 and T3, respectively. At T1, 52 patients (51.5%) were diagnosed with strabismus, and 61 patients (60.4%) at T3. Vertical strabismus increased significantly from 23 patients (22.8%) at T1 to 36 patients (35.6%) at T3 (p = 0.011). Followed by astigmatism, which increased significantly from 38 (37.6%) at T1 to 59 (58.4%) patients at T3 (p = 0.001). T1 was available in 20 patients prior to fronto-orbital advancement (FOA), therefore, a sub-analysis was conducted on these patients, which was followed shortly after FOA at T2. Prior to FOA, strabismus was present in 11 patients (55.0%) and in 12 patients (60.0%) at T2. After FOA, strabismus worsened in two patients. (4) Conclusions: This study showed the high prevalence of ocular anomalies in patients with non-syndromic UCS before and after cranioplasty and at long-term follow-up. The findings of this study show that ophthalmic and orthoptic examinations are an important part of the optimal treatment of patients with non-syndromic UCS.</p

Cerebral cortex maldevelopment in syndromic craniosynostosis

AIM: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. METHOD: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo–24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log‐transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. RESULTS: Mean ICV was greater in patients with FGFR (1519cm(3), SD 269cm(3), p=0.016) than in patients with TWIST1 (1304cm(3), SD 145cm(3)) or controls (1405cm(3), SD 158cm(3)). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61–0.76) in patients with FGFR compared to 0.81 (95% CI 0.50–1.12) in patients with TWIST1 and 0.77 (95% CI 0.61–0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42–0.59) and occipital (0.67, 95% CI 0.54–0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. INTERPRETATION: Despite adequate ICV in FGFR‐mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR

The Influence of Nonaerated Paranasal Sinuses on DTI Parameters of the Brain in 6- to 9-Year-Old Children

BACKGROUND AND PURPOSE: DTI is prone to susceptibility artifacts. Air in the paranasal sinuses can cause field inhomogeneity, thus affecting measurements. Children often have mucus in their sinuses or no pneumatization of them. This study investigated the influence of lack of air in the paranasal sinuses on measurements of WM diffusion characteristics. MATERIALS AND METHODS: The study was embedded in the Generation R Study, a prospective population-based birth cohort in Rotterdam (the Netherlands). Brain MR imaging studies (1070 children, 6-9 years of age) were evaluated for mucosal thickening of the paranasal sinuses. Nonaeration of the paranasal sinuses (modified Lund-Mackay score) was compared with that in a randomly selected control group. The relationship between nonaerated paranasal sinuses and fractional anisotropy and mean diffusivity in the DTI fiber tracts was evaluated using ANCOVA and independent t tests. RESULTS: The prevalence of mucosal thickening was 10.2% (109/1070). The mean modified Lund-Mackay score was 6.87 (SD, 3.76). In 52.3% (57/109), ≥ 1 paranasal sinus was not pneumatized. The results are reported in effect sizes (Cohen's d). Lower mean fractional anisotropy values were found in the uncinate fasciculus (right uncinate fasciculus/right frontal sinus, d = -0.60), superior longitudinal fasciculus (right superior longitudinal fasciculus/right ethmoid sinus, d = -0.56; right superior longitudinal fasciculus/right sphenoid sinus, d = -2.09), and cingulate bundle (right cingulum bundle/right sphenoid sinus, d = -1.28; left cingulum bundle/left sphenoid sinus, d = -1.49). Higher mean diffusivity values were found in the forceps major/right and left sphenoid sinuses, d = 0.78. CONCLUSIONS: Nonaeration of the paranasal sinuses is a common incidental finding on pediatric MR imaging brain scans. The amount of air in the paranasal sinuses can influence fractional anisotropy and, to a lesser degree, mean diffusivity values of WM tracts and should be considered in DTI studies in pediatric populations.</p

Early MRI diagnosis of Sturge Weber Syndrome type 1 in infants

Background: Patients with Sturge-Weber syndrome type 1 (SWS1) have a port-wine birthmark (PWB) as cutaneous hallmark. Up to 35% of neonates with a high risk PWB develop SWS1. Clinical manifestations are severe and often progressive. Especially early onset seizures are associated with worse neurocognitive outcome. Identification of pre-symptomatic SWS1 patients is hampered because brain MRI in the first months of life does not always show the for SWS1 characteristic leptomeningeal capillary malformation (LMC). Objectives: Identification of sensitive and specific MRI predictors for early SWS1 diagnosis. Methods: In this retrospective single centre study, we included 24 SWS1 patients and 20 controls. We studied specificity and sensitivity for SWS1 diagnosis of LMC and indirect MRI signs such as choroid plexus (CP) size and thickness, abnormal white matter signal, lobar cerebral atrophy, ischemia and cortical calcifications. Results: In SWS1 patients CP thickness and CP thickness ratio on non-contrast brain MRI was significantly increased. The optimal cut-off value of 5.6 mm on the affected side corresponded with a sensitivity of 91.7% and a specificity of 100% for confirmation of SWS1 diagnosis. In 21% of children aged ≤3 months with a later confirmed SWS1 diagnosis, LMC on initial MRI could not be discerned but CP thickness ≥5.6 mm on the affected side confirmed SWS1 diagnosis. Conclusions: In this study, CP size ratio and thickness were found to be sensitive and specific signs additional to earlier described criteria to support SWS1 diagnosis in neonates and infants which need to be confirmed in other series

Eye and Orbital Anatomy in Metopic Synostosis

Background:. Metopic synostosis patients have a high prevalence of orthoptic anomalies, including hyperopia, astigmatism, and amblyopia. We hypothesized altered orbital anatomy contributes to suboptimal visual outcomes by adversely affecting eye anatomy and growth from early life onward. Therefore, we aimed to investigate eye and orbital anatomy in metopic synostosis. Methods:. We conducted a retrospective study in nonsyndromic metopic synostosis patients (n = 134, median age 0.43 years [IQR 0.45]) with nonsyndromic sagittal synostosis patients (n = 134, median age 0.27 years [IQR 0.23]) as controls. Primary analyses focused on eye dimensions (axial length, width, and globe height) and orbital dimensions, correcting for sex and age. Measurements were obtained from preoperative computed tomography scans. Results:. Axial length and width in metopic synostosis patients did not differ from sagittal synostosis patients, but globe height was significantly smaller (P = 0.0002). Lateral wall interorbital length, lateral orbital wall length, anterior medial interorbital length, and maximal medial interorbital length were significantly smaller, and anterior vertical orbital height and maximal vertical orbital height were significantly larger (P < 0.001). The central orbital axis and interorbital angle were significantly narrower, and medial-to-lateral orbital wall angle was wider (P < 0.001). Conclusions:. Metopic synostosis patients have more shallow, wider, and higher orbits. Eye dimensions are similar in sagittal synostosis patients, although globe height was smaller. Altered orbital and eye dimensions in metopic synostosis probably have a causal relation with an unknown order of development. How these dimensions relate to future orthoptic anomalies (eg, refractive error) needs further investigation

Added value of arterial spin labeling magnetic resonance imaging in pediatric neuroradiology : pitfalls and applications

Arterial spin labeling is a noninvasive, non-gadolinium-dependent magnetic resonance imaging (MRI) technique to assess cerebral blood flow. It provides insight into both tissue metabolic activity and vascular supply. Because of its non-sensitivity toward blood–brain barrier leakage, arterial spin labeling is also more accurate in cerebral blood flow quantification than gadolinium-dependent methods. The aim of this pictorial essay is to promote the application of arterial spin labeling in pediatric neuroradiology. The authors provide information on artifacts and pitfalls as well as numerous fields of application based on pediatric cases

A novel family illustrating the mild phenotypic spectrum of TUBB2B variants

TUBB2B codes for one of the isotypes of β-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies. We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. First, at 21 [Formula presented] weeks of gestation ultrasonography revealed a fetus with a relatively small head, enlarged lateral ventricles, borderline hypoplastic cerebellum and a thin corpus callosum. The couple opted for pregnancy termination. Exome sequencing on fetal material afterwards identified a heterozygous maternally inherited variant in TUBB2B (NM_178012.4 (TUBB2B):c.530A > T, p.(Asp177Val)), not present in GnomAD and predicted as damaging. The healthy mother had only a language delay in childhood. This inherited TUBB2B variant prompted re-evaluation of the older son of the couple, who presented with a mild delay in motor skills and speech. His MRI revealed mildly enlarged lateral ventricles, a thin corpus callosum, mild cortical dysgyria, and dysmorphic vermis and basal ganglia, a pattern typical of tubulinopathies. This son finally showed the same TUBB2B variant, supporting pathogenicity of the TUBB2B variant. These observations illustrate the wide phenotypic heterogeneity of tubulinopathies, including reduced penetrance and mild expressivity, that require careful evaluation in pre- and postnatal counseling

Can neuroimaging measures differentiate the disease course of anorexia nervosa? A systematic review

Anorexia nervosa (AN) entails many uncertainties regarding the clinical outcome, due to large heterogeneity in the disease course. AN is associated with global decrease in brain volumes and altered brain functioning during acute illness. However, it is unclear whether structural and functional brain alterations can predict clinical outcome. We aimed to systematically review the predictive value of volumetric and functional brain outcome measures of structural and functional brain magnetic resonance imaging (MRI) on the disease course of AN. Four databases (Embase, Medline, Psycinfo, and Cochrane Central Register) were systematically searched. A total of 15 studies (structural MRI: n = 6, functional MRI: n = 9) were reviewed. In total 464 unique AN patients, and 328 controls were included. Follow-up time ranged between 1 and 43 months. Structural neuroimaging studies showed that lower brain volumes of the cerebellum, subcortical grey matter, and cortical white matter at admission predicted a worse clinical outcome. A smaller increase of the anterior cingulate cortex volume in the early phase of the disease predicted a worse clinical outcome. Lower overall gyrification, and a higher clustering coefficient predicted a worse clinical outcome. Functional MRI studies showed that frontal, parietal and temporal activity during task-based algorithms predicted follow-up body mass index, although results were bidirectional possibly due to the large heterogeneity in methodological approaches. Neuroimaging measures may predict the clinical outcome of AN. However, there is a lack of replication studies. Future studies are needed to validate the prognostic utility of neuroimaging measures in AN patients, and should harmonize demographic, clinical and neuroimaging features in order to enhance comparability