The prevalence of incidental findings on pelvis MRI of 8-13-year-old children.

BACKGROUND: The prevalence and clinical relevance of incidental findings (IF(s)) on imaging assessing the pelvis in children has not been well documented. METHODS: Three-thousand two-hundred thirty-one children (mean age 10.2 (range 8.6-12.9) years) were evaluated with MRI of the hips, pelvis, and lumbar spine, as part of a prospective population-based pediatric cohort study. Scans were reviewed by trained medical staff for abnormalities. IFs were categorized by clinical relevance and need for further clinical evaluation. RESULTS: 8.3% (n = 267) of children featured at least one IF. One or more musculoskeletal IFs were found in 7.9% (n = 254) of children, however, only 0.8% (n = 2) of musculoskeletal IFs required clinical evaluation. Most frequent abnormalities were simple bone cysts 6.0% (n = 195), chondroid lesions 0.6% (n = 20), and perineural cysts 0.5% (n = 15). Intra-abdominal IFs were detected in 0.5% (n = 17) of children, with over half (n = 9) of these requiring evaluation. The three most common intra-abdominal IFs were a duplex collecting system 0.09% (n = 3), significant ascites 0.06% (n = 2), and hydroureteronephrosis 0.06% (n = 2). CONCLUSIONS: IFs on MRI of the lower abdominal and hip region are relatively common in children aged 8-13 years, most of these can be confidently categorized as clinically irrelevant without the need for additional clinical or radiologic follow up. IMPACT: Our research contributes greatly to the knowledge of the prevalence of (asymptomatic) pathology in children. We evaluated MR images of 3231 children, covering hip joints, pelvic skeleton, lower and mid-abdomen, and lumbar and lower thoracic spine as part of a population study. One or more musculoskeletal incidental finding were found in 7.9% of children. Most of these can be confidently categorized as clinically irrelevant without the need for additional follow up. However 0.8% of musculoskeletal findings required further evaluation. Intra-abdominal incidental findings were detected in 0.5% of children, with over half of the abdominal and urogenital findings requiring further evaluation.

Transcutaneous carbon dioxide monitoring during therapeutic hypothermia for neonatal encephalopathy.

BACKGROUND: In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCO2) monitoring during TH. METHODS: In this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCO2) values and tcPCO2 measurements during TH was determined. TcPCO2 levels during the first 24 h of hypothermia were tested for an association with ischemic brain injury on magnetic resonance imaging (MRI). RESULTS: Thirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCO2 and PaCO2 levels was 3.9 (-12.4-20.2) mm Hg. No relation was found between the body temperature and tcPCO2 levels. TcPCO2 levels differed significantly between patients with considerable and minimal damage on MRI; after 6 h (P = 0.02) and 9 h (P = 0.04). CONCLUSIONS: Although tcPCO2 provided a limited estimation of PaCO2, it can be used for trend monitoring during TH. TcPCO2 levels after birth could provide an early indicator of ischemic brain injury. This relation should be investigated in large prospective studies, in which adjustments for confounders can be made. IMPACT: Transcutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring. Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI. The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders. Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

Is the brain involved in patients with late-onset Pompe disease?

Our objective was to investigate brain structure, cerebral vasculature, and cognitive function in a cohort of patients with late-onset Pompe disease, with particular reference to the differences from those with the classic infantile phenotype, where extensive white-matter abnormalities (WMA) and impaired cognition on long-term enzyme treatment are reported in a subset of patients. Brain imaging (T1, T2, T2 fluid-attenuated inversion recovery, susceptibility-weighted images, and magnetic resonance angiography-time of flight) was combined with extensive cognitive testing of general intelligence (Wechsler IQ Test, Montreal Cognitive Assessment [MoCA]) and specific neuropsychological domains (verbal fluency, cognitive flexibility, attention, memory, and visuospatial abilities). We included 19 patients with late-onset Pompe disease (age range 11-56 years). Two patients showed mild punctate WMA within normal range for age, with a Fazekas score (FS) of 1 to 2. Magnetic resonance angiography revealed a slight vertebrobasilar dolichoectasia in two patients yet did not show any aneurysms or vascular dissections. Most patients had age-adjusted scores within the normal range for the Wechsler index scores (verbal comprehension, perceptual reasoning, working memory, and processing speed) and combined total intelligence (IQ) score (median 101, interquartile range 91-111; one patient had a below-average score for total IQ) as well as for the specific domains verbal fluency, attention, and memory. A subset of patients performed suboptimally on the Rey Complex Figure Test (9/14 patients) or cube-copying/clock-drawing test of the MoCA (8/10 patients). We therefore concluded that our study showed no brain abnormalities, other than minor microvascular lesions considered within normal range for age, nor general cognitive impairment in late-onset Pompe patients. These findings are in sharp contrast with the widespread WMA and cognitive problems found in some classic infantile patients.

MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance.

To date, mutations in 15 actin- or microtubule-associated genes have been associated with the cortical malformation lissencephaly and variable brainstem hypoplasia. During a multicenter review, we recognized a rare lissencephaly variant with a complex brainstem malformation in three unrelated children. We searched our large brain-malformation databases and found another five children with this malformation (as well as one with a less severe variant), analyzed available whole-exome or -genome sequencing data, and tested ciliogenesis in two affected individuals. The brain malformation comprised posterior predominant lissencephaly and midline crossing defects consisting of absent anterior commissure and a striking W-shaped brainstem malformation caused by small or absent pontine crossing fibers. We discovered heterozygous de novo missense variants or an in-frame deletion involving highly conserved zinc-binding residues within the GAR domain of MACF1 in the first eight subjects. We studied cilium formation and found a higher proportion of mutant cells with short cilia than of control cells with short cilia. A ninth child had similar lissencephaly but only subtle brainstem dysplasia associated with a heterozygous de novo missense variant in the spectrin repeat domain of MACF1. Thus, we report variants of the microtubule-binding GAR domain of MACF1 as the cause of a distinctive and most likely pathognomonic brain malformation. A gain-of-function or dominant-negative mechanism appears likely given that many heterozygous mutations leading to protein truncation are included in the ExAC Browser. However, three de novo variants in MACF1 have been observed in large schizophrenia cohorts.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Silent cerebral infarcts in patients with sickle cell disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Silent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences. METHODS: The databases of Embase, MEDLINE ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Trials via Wiley and Google Scholar were searched from inception to June 1, 2019. RESULTS: The search yielded 651 results of which 69 studies met the eligibility criteria. The prevalence of SCIs in patients with SCD ranges from 5.6 to 80.6% with most studies reported in the 20 to 50% range. The pooled prevalence of SCIs in HbSS and HbSß0 SCD patients is 29.5%. SCIs occur more often in patients with the HbSS and HbSß0 genotype in comparison with other SCD genotypes, as SCIs are found in 9.2% of HbSC and HbSß+ patients. Control subjects showed a mean pooled prevalence of SCIs of 9.8%. Data from included studies showed a statistically significant association between increasing mean age of the study population and mean SCI prevalence. Thirty-three studies examined the risk factors for SCIs. The majority of the risk factors show no clear association with prevalence, since more or less equal numbers of studies give evidence for and against the causal association. CONCLUSIONS: This systematic review and meta-analysis shows SCIs are common in patients with SCD. No clear risk factors for their development were identified. Larger, prospective and controlled clinical, neuropsychological and neuroimaging studies are needed to understand how SCD and SCIs affect cognition.

Cervical ribs and other abnormalities of the vertebral pattern in children with esophageal atresia and anorectal malformations.

BACKGROUND: In mammals the vertebral column has a constant pattern, particularly in the cervical region, which is likely the result of stabilizing selection. The prevalence of cervical ribs and extended vertebral pattern abnormalities is increased in deceased fetuses and neonates and associated with structural and chromosomal anomalies. The hypothesized close interaction between vertebral patterning and organogenesis in early embryogenesis could be studied in children with esophageal atresia and anorectal malformations by evaluating the radiographs of the vertebral column and the type and number of associated anomalies METHODS: The vertebral pattern of 367 children diagnosed with an esophageal atresia (n = 135), anorectal malformation (n = 215), or both (n = 17) was assessed on radiographs. RESULTS: The vertebral pattern was abnormal in 170/202 (84.2%) children in whom this could be assessed, and cervical ribs were present in 147/335 (43.9%). Extended vertebral pattern abnormalities became more frequent with an increasing number of associated structural abnormalities. Cervical ribs were particularly common in children with chromosomal and genetic abnormalities (18/20, 90.0%). CONCLUSIONS: Cervical ribs are frequent and abnormal vertebral patterns are more extended in the presence of associated anomalies. These findings support the hypothesized selection against vertebral patterning variations and emphasize the relevance of assessment of the vertebral pattern.

Intracranial hypertension and cortical thickness in syndromic craniosynostosis.

AIM: To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis. METHOD: ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes. RESULTS: In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo-34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682). INTERPRETATION: Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies. WHAT THIS PAPER ADDS: Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.

Hipertensión intracraneal y grosor cortical en craneosinostosis sindrómica OBJETIVO: Evaluar el impacto de los factores de riesgo de hipertensión intracraneal (HIC) en el grosor de la corteza cerebral en la craneosinostosis sindrómica. MÉTODO: La neuroimagen, y, los factores de riesgo para HIC que incluyeron papiledema, hidrocefalia, apnea obstructiva del sueño (SAOS), posición de la tonsila cerebelosa, edad de desviación de la curva de circunferencia occipitofrontal (CFO) y el sexo, se recogieron de los registros de pacientes con craneosinostosis sindrómica (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzensis). Las imágenes de resonancia magnética fueron analizadas y exportadas para análisis estadístico. Se desarrolló un modelo mixto lineal para determinar las correlaciones con los cambios en el espesor de la corteza cerebral. RESULTADOS: En total se evaluaron 171 exploraciones de 107 pacientes (83 varones, 88 mujeres [incluyendo escaneos repetidos], edad media 8 años 10 meses, rango 1 año 1 mes - 34 años, DE 5 años 9 meses). El espesor medio cortical en esta cohorte fue de 2,78 mm (DS 0,17). Los hallazgos anteriores de papiledema (p=0,036) y de hidrocefalia (p=0,007) se asociaron de forma independiente con el adelgazamiento cortical. El grosor cortical no varió significativamente por sexo (p=0,534), síndrome (p=0,896), SAOS (p=0,464), CFO (p=0,375), o posición tonsilar (p=0,682). INTERPRETACIÓN: La detección de papiledema o hidrocefalia en la craneosinostosis sindrómica, se asocia con cambios significativos en el grosor cortical. Esto apoya la necesidad de estrategias de tratamiento preventivo en lugar de tratamientos reactivos.

Hipertensão intracrianiana e espessura cortical na craniossinostose sindrômica OBJETIVO: Avaliar o impacto de fatores de risco para hipertensão intracraniana (HIC) na espessura cortical em craniossinostose sindrômica. MÉTODO: Fatores de risco para HIC incluindo papiloedema, hidrocefalia, apnéia obstrutiva do sono (AOS), posição das tonsilas do cerebelo, idade de deflexão da curva da circunferência occipitofrontal (COF), e sexo foram coletados dos registros de pacientes com craniossinostose sindrômica (síndromes de Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen) e imagens. As imagens de ressonância magnética foram analisadas e exportadas para análise estatística. Um modelo linear misto foi desenvolvido para determinar correlações com mudanças na espessura do córtex cerebral. RESULTADOS: No total, 171 imagens de 107 pacientes (83 do sexo masculino, 88 do sexo feminino [incluindo varreduras repetidas], média de idade 8a 10m, variação 1a 1m-34a, DP 5a 9m) foram avaliados. A espessura cortical média nesta coorte foi 2,78mm (DP 0,17). Achados prévios de papiloedema (p=0,036) e de hidrocefalia (p=0,007) foram independentemente associados com a redução cortical. A espessura cortical não variou significativamente com o sexo (p=0,534), síndrome (p=0,896), AOS (p=0,464), COF (p=0,375), ou posição tonsilar (p=0,682). INTERPRETAÇÃO: A detecção do papiloedema ou hidrocefalia na craniossinostose sindrômica se associa com mudanças significativas na espessura cortical, sustentando a necessidade de estratégias de tratamento preventivas e não reativas.

A Systematic Review of Neuromonitoring Modalities in Children Beyond Neonatal Period After Cardiac Arrest.

OBJECTIVES: Postresuscitation care in children focuses on preventing secondary neurologic injury and attempts to provide (precise) prognostication for both caregivers and the medical team. This systematic review provides an overview of neuromonitoring modalities and their potential role in neuroprognostication in postcardiac arrest children. DATA RESOURCES: Databases EMBASE, Web of Science, Cochrane, MEDLINE Ovid, Google Scholar, and PsycINFO Ovid were searched in February 2019. STUDY SELECTION: Enrollment of children after in- and out-of-hospital cardiac arrest between 1 month and 18 years and presence of a neuromonitoring method obtained within the first 2 weeks post cardiac arrest. Two reviewers independently selected appropriate studies based on the citations. DATA EXTRACTION: Data collected included study characteristics and methodologic quality, populations enrolled, neuromonitoring modalities, outcome, and limitations. Evidence tables per neuromonitoring method were constructed using a standardized data extraction form. Each included study was graded according to the Oxford Evidence-Based Medicine scoring system. DATA SYNTHESIS: Of 1,195 citations, 27 studies met the inclusion criteria. There were 16 retrospective studies, nine observational prospective studies, one observational exploratory study, and one pilot randomized controlled trial. Neuromonitoring methods included neurologic examination, routine electroencephalography and continuous electroencephalography, transcranial Doppler, MRI, head CT, plasma biomarkers, somatosensory evoked potentials, and brainstem auditory evoked potential. All evidence was graded 2B-2C. CONCLUSIONS: The appropriate application and precise interpretation of available modalities still need to be determined in relation to the individual patient. International collaboration in standardized data collection during the (acute) clinical course together with detailed long-term outcome measurements (including functional outcome, neuropsychologic assessment, and health-related quality of life) are the first steps toward more precise, patient-specific neuroprognostication after pediatric cardiac arrest.

Posterior Distraction Using Springs in Syndromic and Multisuture Craniosynostosis: Improving the Technique.

INTRODUCTION: Posterior distraction is the preferred surgical treatment for particularly Apert and Crouzon syndrome in most craniofacial centers, using either external distractors or springs. The authors prefer the use of springs and have adapted their technique to further improve outcomes. METHODS: All patients who were treated with the adapted technique for occipital expansion using springs were included. The most significant adaption that the authors introduced in 2017 is using a bony hinge at the top of the vault instead of at the caudal edge of the occiput. RESULTS: A total of 8 posterior expansions with springs were performed. No complications occurred and the springs were also successfully applied in cases with extremely thin bone. If indicated, a simultaneous foramen magnum decompression was performed and this was easier to combine with a hinge at the top of the vault. CONCLUSIONS: Posterior distraction with springs is a safe and effective procedure and allows a simultaneous foramen magnum decompression. Planning the hinge at the vault allows intracranial volume gain at the site of the posterior skull base.

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.

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.

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.

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 (<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.

Diffusion tensor imaging of the brain in Pompe disease.

Enzyme replacement therapy has drastically changed prospects of patients with Pompe disease, a progressive metabolic myopathy. As classic infantile patients survive due to treatment, they exhibit progressive white matter abnormalities, while brain involvement in late-onset patients is not fully elucidated. To study the underlying microstructure of white matter, we acquired structural (T1, T2, FLAIR) and diffusion tensor imaging (DTI) of the brain in 12 classic infantile patients (age 5-20 years) and 18 late-onset Pompe patients (age 11-56 years). Structural images were scored according to a rating scale for classic infantile patients. Fractional anisotropy (FA) and mean diffusivity (MD) from classic infantile patients were compared to a reference population, using a Wilcoxon signed-rank, one sample test. Effect sizes (Hedges' G) were used to compare DTI metrics across different tracts. For late-onset patients, results were compared to (reported) tractography data on normal aging. In classic infantile patients, we found a significant lower FA and higher MD (p < 0.01) compared to the reference population. Large-association fibers were most severely affected. Classic infantile patients with advanced white matter abnormalities on structural MRI showed the largest deviations from the reference population. FA and MD were similar for younger and older late-onset patients in large WM-association fibers. We conclude that, while no deviations from typical neurodevelopment were found in late-onset patients, classic infantile Pompe patients showed quantifiable, substantially altered white matter microstructure, which corresponded with disease stage on structural MRI. DTI holds promise to monitor therapy response in future therapies targeting the brain.

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.

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.

A Diffusion Tensor Imaging Analysis of Frontal Lobe White Matter Microstructure in Trigonocephaly Patients.

BACKGROUND: Children with trigonocephaly are at risk for neurodevelopmental disorders. The aim of this study is to investigate white matter properties of the frontal lobes in young, unoperated patients with metopic synostosis as compared to healthy controls using diffusion tension imaging (DTI). METHODS: Preoperative DTI data sets of 46 patients with trigonocephaly with a median age of 0.49 (interquartile range: 0.38) years were compared with 21 controls with a median age of 1.44 (0.98) years. White matter metrics of the tracts in the frontal lobe were calculated using FMRIB Software Library (FSL). The mean value of tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were estimated for each subject and compared to healthy controls. By linear regression, FA and MD values per tract were assessed by trigonocephaly, sex, and age. RESULTS: The mean FA and MD values in the frontal lobe tracts of untreated trigonocephaly patients, younger than 3 years, were not significantly different in comparison to controls, where age showed to be a significant associated factor. CONCLUSIONS: Microstructural parameters of white matter tracts of the frontal lobe of patients with trigonocephaly are comparable to those of controls aged 0-3 years.

Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study.

BACKGROUND: Craniofacial surgery is the standard treatment for children with moderate to severe trigonocephaly. The added value of surgery to release restriction of the frontal lobes is unproven, however. In this study, the authors aim to address the hypothesis that the frontal lobe perfusion is not restricted in trigonocephaly patients by investigating cerebral blood flow. METHODS: Between 2018 and 2020, trigonocephaly patients for whom a surgical correction was considered underwent magnetic resonance imaging brain studies with arterial spin labeling to measure cerebral perfusion. The mean value of cerebral blood flow in the frontal lobe was calculated for each subject and compared to that of healthy controls. RESULTS: Magnetic resonance imaging scans of 36 trigonocephaly patients (median age, 0.5 years; interquartile range, 0.3; 11 female patients) were included and compared to those of 16 controls (median age, 0.83 years; interquartile range, 0.56; 10 female patients). The mean cerebral blood flow values in the frontal lobe of the trigonocephaly patients (73.0 ml/100 g/min; SE, 2.97 ml/100 g/min) were not significantly different in comparison to control values (70.5 ml/100 g/min; SE, 4.45 ml/100 g/min; p = 0.65). The superior, middle, and inferior gyri of the frontal lobe showed no significant differences either. CONCLUSIONS: The authors' findings suggest that the frontal lobes of trigonocephaly patients aged less than 18 months have a normal cerebral blood flow before surgery. In addition to the very low prevalence of papilledema or impaired skull growth previously reported, this finding further supports the authors' hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure or restricted perfusion for patients younger than 18 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Does the association between abnormal anatomy of the skull base and cerebellar tonsillar position also exist in syndromic craniosynostosis?

PURPOSE: Cerebellar tonsillar herniation (TH) occurs frequently in syndromic craniosynostosis; however, the exact pathogenesis is unknown. This study evaluates the association between skull base deformities and TH in syndromic craniosynostosis. METHODS: Retrospective study MRI study comparing syndromic craniosynostosis to controls. Measured parameters included clivus length, skull base angle, Boogard's angle, foramen magnum area, and cerebellar tonsillar position (TP). The association between skull base parameters and TP was evaluated with linear mixed models, correcting for age and risk factors for TH in craniosynostosis (hydrocephalus, intracranial hypertension, craniocerebral disproportion, and lambdoid synostosis). RESULTS: Two hundred and eighty-two scans in 145 patients were included, and 146 scans in 146 controls. The clivus was smaller at birth, and its growth was retarded in all syndromes. The skull base angle was smaller at birth in Apert and Crouzon syndromes, and the evolution through time was normal. Boogard's angle was smaller at birth in Apert syndrome, and its evolution was disturbed in Apert and Saethre-Chotzen syndromes. The foramen magnum was smaller at birth in Crouzon and Saethre-Chotzen syndromes, and its growth was disturbed in Apert, Crouzon, and Saethre-Chotzen syndromes. TP was higher at birth in Apert syndrome, but lowered faster. In Crouzon syndrome, TP was lower at birth and throughout life. A smaller clivus and larger foramen magnum were associated with a lower TP in controls (p<0.001, p=0.007), and in Crouzon syndrome, this applied to only foramen magnum size (p=0.004). CONCLUSION: The skull base and its growth are significantly different in syndromic craniosynostosis compared to controls. However, only foramen magnum area is associated with TP in Crouzon syndrome.