Pathogenic variants in GCSH encoding the moonlighting H-protein cause combined nonketotic hyperglycinemia and lipoate deficiency.

Maintaining protein lipoylation is vital for cell metabolism. The H-protein encoded by GCSH has a dual role in protein lipoylation required for bioenergetic enzymes including pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase, and in the one-carbon metabolism through its involvement in glycine cleavage enzyme system, intersecting two vital roles for cell survival. Here, we report six patients with biallelic pathogenic variants in GCSH and a broad clinical spectrum ranging from neonatal fatal glycine encephalopathy to an attenuated phenotype of developmental delay, behavioral problems, limited epilepsy and variable movement problems. The mutational spectrum includes one insertion c.293-2_293-1insT, one deletion c.122_(228 + 1_229-1) del, one duplication of exons 4 and 5, one nonsense variant p.Gln76*and four missense p.His57Arg, p.Pro115Leu and p.Thr148Pro and the previously described p.Met1?. Via functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies, we demonstrate for the first time that most variants identified in our cohort produced a hypomorphic effect on both mitochondrial activities, protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affect primarily one function only. The clinical features of the patients reflect the impact of the GCSH changes on any of the two functions analyzed. Our analysis illustrates the complex interplay of functional and clinical impact when pathogenic variants affect a multifunctional protein involved in two metabolic pathways and emphasizes the value of the functional assays to select the treatment and investigate new personalized options.

Prevalence of cerebral sinovenous thrombosis in abusive head trauma.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) has been proposed in legal settings to be an atraumatic mimic of abusive head trauma (AHT). OBJECTIVE: The objective of this study was to determine the prevalence of CSVT and subdural hemorrhage (SDH) in a large AHT population. MATERIALS AND METHODS: This retrospective cohort study measured the prevalence of CSVT and SDH on magnetic resonance venograms in 243 patients diagnosed with AHT at a single center. We also reported additional intra- and extracranial injuries, head injury severity and length of hospital stay. RESULTS: Among 243 patients diagnosed with AHT, 7% (16/243) had CSVT. SDH was present in 94% (15/16) of the CSVT cases. Cytotoxic edema and subarachnoid hemorrhage were in 88% (14/16) and 69% (11/16) of the CSVT cases, respectively. Extracranial signs of abuse were also in 100% (16/16) of the patients with CSVT. Critical to maximal head injury severity (abbreviated injury scale >=5) was in 75% (12/16) of the CSVT population vs. 33% (82/243) in the total AHT population. Length of hospital and pediatric intensive care unit stay was greater in those with CSVT (10 vs. 21.9 and 3.5 vs. 7.3 days). CONCLUSION: These findings suggest that CSVT is uncommon in AHT and is associated with additional traumatic injuries and greater injury severity.

Utility of Early Magnetic Resonance Imaging to Enhance Outcome Prediction in Critically Ill Children with Severe Traumatic Brain Injury.

BACKGROUND: Many children with severe traumatic brain injury (TBI) receive magnetic resonance imaging (MRI) during hospitalization. There are insufficient data on how different patterns of injury on early MRI inform outcomes. METHODS: Children (3-17 years) admitted in 2010-2021 for severe TBI (Glasgow Coma Scale [GCS] score < 9) were identified using our site's trauma registry. We used multivariable modeling to determine whether the hemorrhagic diffuse axonal injury (DAI) grade and the number of regions with restricted diffusion (subcortical white matter, corpus callosum, deep gray matter, and brainstem) on MRI obtained within 7 days of injury were independently associated with time to follow commands and with Functional Independence Measure for Children (WeeFIM) scores at the time of discharge from inpatient rehabilitation. We controlled for the clinical variables age, preadmission cardiopulmonary resuscitation, pupil reactivity, motor GCS score, and fever (> 38 °C) in the first 12 h. RESULTS: Of 260 patients, 136 (52%) underwent MRI within 7 days of injury at a median of 3 days (interquartile range [IQR] 2-4). Patients with early MRI were a median age of 11 years (IQR 7-14), 8 (6%) patients received cardiopulmonary resuscitation, 19 (14%) patients had bilateral unreactive pupils, the median motor GCS score was 1 (IQR 1-4), and 82 (60%) patients had fever. Grade 3 DAI was present in 46 (34%) patients, and restricted diffusion was noted in the corpus callosum in 75 (55%) patients, deep gray matter in 29 (21%) patients, subcortical white matter in 23 (17%) patients, and the brainstem in 20 (15%) patients. After controlling for clinical variables, an increased number of regions with restricted diffusion, but not hemorrhagic DAI grade, was independently associated with longer time to follow commands (hazard ratio 0.68, 95% confidence interval 0.53-0.89) and worse WeeFIM scores (estimate ß - 4.67, 95% confidence interval - 8.33 to - 1.01). CONCLUSIONS: Regional restricted diffusion on early MRI is independently associated with short-term outcomes in children with severe TBI. Multicenter cohort studies are needed to validate these findings and elucidate the association of early MRI features with long-term outcomes in children with severe TBI.

Fusion of Lateral Calvarial Sutures on Volume-Rendered Computed Tomography Reconstructions in Patients With Known Craniosynostosis.

INTRODUCTION: After treating a child with familial sagittal craniosynostosis, clinocephaly, and bilateral parietomastoid/posterior squamosal suture fusion, the authors wondered if major-suture synostosis and clinocephaly were associated with abnormal fusion of minor lateral calvarial sutures. METHODS: The authors reviewed all preoperative volume-rendered head computed tomography reconstructions performed for craniosynostosis at their institution from 2010 through 2014 and determined whether the sphenoparietal, squamosal, and parietomastoid sutures were open, partially fused, or fused. The authors determined whether any sutures were abnormally fused based upon a previous study from their center, in which abnormal fusion was defined as either 1 of 3 abnormal fusion patterns or abnormally-early fusion. The authors then determined the rate of abnormal fusion of these sutures and whether abnormal fusion was associated with (1) major-suture craniosynostosis, (2) type of craniosynostosis (sutures involved; single-suture versus multisuture; syndromic versus nonsyndromic), and (3) clinocephaly. RESULTS: In 97 included children, minor lateral sutures were abnormally fused in 8, or 8.2%, which was significantly higher than in children without craniosynostosis from our earlier study. Abnormal minor lateral suture fusion was not associated with the type of single-suture synostosis or with multisuture synostosis but was associated with syndromic synostosis. Four of 8 children with abnormal minor lateral suture fusion had multisuture synostosis and 6 had syndromic synostosis. Lateral sutures were abnormally fused in 1 of 4 subjects with clinocephaly, which was not significant. CONCLUSION: Abnormal minor lateral calvarial suture fusion is significantly associated with major-suture craniosynostosis, especially syndromic synostosis.

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic.

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Subpial Hemorrhage of the Neonate.

Background and Purpose- Subpial hemorrhage of the neonate is a rare stroke subtype reported in few case series. Birth trauma and coagulopathy are commonly proposed etiologies. We evaluated our subpial hemorrhage of the neonate patient cohort to expand current understanding Methods- Cases of subpial hemorrhage of the neonate were identified by keyword searches of the institutional database. The medical records and magnetic resonance imagings were reviewed. Results- Seventeen cases were identified. Assisted delivery occurred in 12% of cases, and acute coagulation abnormalities occurred in 77%. Subpial hemorrhage of the neonate was located in the temporal lobe in 82%, with cytotoxic edema and medullary vein congestion and thrombosis subjacent to the hemorrhages in 100% and 76% of cases, respectively. Neurological disability was present in 44% of survivors. Three patients had chronic coagulation abnormalities. Conclusions- In our cohort, clinical findings supporting a potential relationship with birth trauma were infrequent. The imaging findings suggest a nonarterial, deep venous pattern of hemorrhagic ischemia.

Imaging of fetal ventriculomegaly.

Fetal ventriculomegaly is the most common central nervous system abnormality detected by prenatal imaging. It has a high association with other anomalies. Etiologies and prognoses for fetal ventriculomegaly range from normal outcomes to significant neurodevelopmental sequelae. In this paper, we review the development, terminology, pathogenesis, imaging and prognosis of fetal ventriculomegaly.

Brain imaging in classic nonketotic hyperglycinemia: Quantitative analysis and relation to phenotype.

Patients with severe nonketotic hyperglycinemia (NKH) have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain magnetic resonance imaging (MRI) between phenotypes have not been reported. In a retrospective cross-sectional study, we reviewed 38 MRI studies from 24 molecularly proven NKH patients, and 2 transient NKH patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. All patients age <3 months had restricted diffusion in the posterior limb of the internal capsule, anterior brainstem, posterior tegmental tracts, and cerebellum, not present in transient NKH. In older infants, the pattern evolved and included generalized diffusion restriction in the supratentorial white matter, which quantitatively peaked between 3 and 12 months. No patient had absent corpus callosum or gyral malformation. The corpus callosum was relatively short in severe compared to attenuated phenotypes, and thin in severe cases only. The corpus callosum growth rate differed by severity; age-matched Z-scores of thickness worsened in severe cases only. Cerebral volume was decreased in the hippocampus, globus pallidus, cerebral cortex, thalamus, and cerebellum. Severe patients had greatest glycine/creatine ratios. In this study, no brain malformations were identified. The growth failure of the corpus callosum is worse in severe NKH, whereas the diffusion restriction pattern, reflecting microspongiosis, does not discriminate by phenotypic severity. NKH is therefore a disorder of brain growth best recognized in the corpus callosum, whereas spongiosis is not prognostic.

Age-associated hippocampal volume changes in childhood arterial ischemic stroke.

PURPOSE: Recent evidence suggests that recovery from secondary neurodegeneration following arterial ischemic stroke (AIS) may be related to age at injury and site of occlusion. We conducted a study of hippocampal volume (HCV) in a cohort of pediatric patients with middle cerebral artery (MCA) territory AIS to determine whether HCV would be preserved in younger children as compared to older children. METHODS: This single-center, HIPAA-compliant retrospective study was approved by the institutional review board. The medical records of 149 children treated for AIS between 2000 and 2016 were reviewed for inclusion criteria: unilateral MCA territory AIS and availability of high-resolution T1-weighted MR imaging at both acute and chronic time periods. Manual segmentation was utilized to measure stroke-side HCV, contralateral HCV, hemispheric volumes, and stroke volume on each scan. To correct for variable brain size, HCV measurements were ratio normalized. Patients were divided into two age-at-stroke groups: younger (30 days-9 years old) and older (> 9-18 years old). Analysis was performed using Fisher's test or Student's t test. RESULTS: The MR imaging of 19 children (9 younger, 10 older) was analyzed. At follow-up, the average stroke-side HCV increased by 10.9% in the younger group and decreased by 6.3% in the older group (P = 0.010); this between-group difference remained significant even when ratio normalized (P = 0.003). The total brain volume-adjusted acute stroke size between groups was not statistically different (P = 0.649). CONCLUSIONS: In children with AIS, younger age is associated with the relative preservation of HCV, which could reflect differences in age-related plasticity.

Performance of a Deep-Learning Neural Network Model in Assessing Skeletal Maturity on Pediatric Hand Radiographs.

Purpose To compare the performance of a deep-learning bone age assessment model based on hand radiographs with that of expert radiologists and that of existing automated models. Materials and Methods The institutional review board approved the study. A total of 14 036 clinical hand radiographs and corresponding reports were obtained from two children's hospitals to train and validate the model. For the first test set, composed of 200 examinations, the mean of bone age estimates from the clinical report and three additional human reviewers was used as the reference standard. Overall model performance was assessed by comparing the root mean square (RMS) and mean absolute difference (MAD) between the model estimates and the reference standard bone ages. Ninety-five percent limits of agreement were calculated in a pairwise fashion for all reviewers and the model. The RMS of a second test set composed of 913 examinations from the publicly available Digital Hand Atlas was compared with published reports of an existing automated model. Results The mean difference between bone age estimates of the model and of the reviewers was 0 years, with a mean RMS and MAD of 0.63 and 0.50 years, respectively. The estimates of the model, the clinical report, and the three reviewers were within the 95% limits of agreement. RMS for the Digital Hand Atlas data set was 0.73 years, compared with 0.61 years of a previously reported model. Conclusion A deep-learning convolutional neural network model can estimate skeletal maturity with accuracy similar to that of an expert radiologist and to that of existing automated models. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on January 19, 2018.

Predicting Progression of Intracranial Arteriopathies in Childhood Stroke With Vessel Wall Imaging.

BACKGROUND AND PURPOSE: Childhood arterial ischemic stroke is frequently associated with an intracranial arteriopathy that often progresses in the first 3 to 6 months post stroke. We hypothesized that children with enhancing arteriopathies on vessel wall imaging (VWI) would have a higher risk of arteriopathy progression than those without enhancement. METHODS: Our institutional radiographic database was searched for cases of childhood stroke with VWI. Inclusion criteria consisted of age ranging from 1 month through 20 years, diagnosis of arterial ischemic stroke, available VWI, and follow-up magnetic resonance angiogram. Imaging was reviewed to systematically describe VWI findings, categorize arteriopathies, steroid therapy, and identify progressive arteriopathies using CACADE definitions. RESULTS: Sixteen cases of childhood stroke at Children's Hospital Colorado between January 1, 2010 and July 1, 2016 were reviewed. Strong vessel wall enhancement at presentation was associated with progressive arteriopathy in 83% of cases (10/12), when compared with 0% (0/4) without strong enhancement (P=0.008). CONCLUSIONS: Our case series demonstrates the potential benefit of VWI in children with stroke because it may identify patients who will have progressive arterial disease.

Pediatric Brain: Repeated Exposure to Linear Gadolinium-based Contrast Material Is Associated with Increased Signal Intensity at Unenhanced T1-weighted MR Imaging.

Purpose To determine whether repeated exposure of the pediatric brain to a linear gadolinium-based contrast agent (GBCA) is associated with an increase in signal intensity (SI) relative to that in GBCA-naive control subjects at unenhanced T1-weighted magnetic resonance (MR) imaging. Materials and Methods This single-center, retrospective study was approved by the institutional review board and compliant with HIPAA. The authors evaluated 46 pediatric patients who had undergone at least three GBCA-enhanced MR examinations (30 patients for two-group analysis and 16 for pre- and post-GBCA exposure comparisons) and 57 age-matched GBCA-naive control subjects. The SI in the globus pallidus, thalamus, dentate nucleus, and pons was measured at unenhanced T1-weighted MR imaging. Globus pallidus-thalamus and dentate nucleus-pons SI ratios were calculated and compared between groups and relative to total cumulative gadolinium dose, age, sex, and number of and mean time between GBCA-enhanced examinations. Analysis included the Wilcoxon signed rank test, Wilcoxon rank sum test, and Spearman correlation coefficient. Results Patients who underwent multiple GBCA-enhanced examinations had increased SI ratios within the dentate nucleus (mean SI ratio ± standard error of the mean for two-group comparison: 1.007 ± 0.0058 for GBCA-naive group and 1.046 ± 0.0060 for GBCA-exposed group [P < .001]; mean SI ratio for pre- and post-GBCA comparison: 0.995 ± 0.0062 for pre-GBCA group and 1.035 ± 0.0063 for post-GBCA group [P < .001]) but not the globus pallidus (mean SI ratio for two-group comparison: 1.131 ± 0.0070 for GBCA-naive group and 1.014 ± 0.0091 for GBCA-exposed group [P = .21]; mean SI ratio for pre- and post-GBCA comparison: 1.068 ± 0.0094 for pre-GBCA group and 1.093 ± 0.0134 for post-GBCA group [P = .12]). There was a significant correlation between dentate nucleus SI and total cumulative gadolinium dose (r = 0.4; 95% confidence interval [CI]: 0.03, 0.67; P = .03), but not between dentate nucleus SI and patient age (r = 0.23; 95% CI: -0.15, 0.56; P = .22), sex (mean SI ratio: 1.046 ± 0.0072 for boys and 1.045 ± 0.0110 for girls; P = .88), number of contrast-enhanced examinations (r = 0.13; 95% CI: -0.25, 0.48; P = .49), or time between contrast-enhanced examinations (r = -0.06; 95% CI: -0.42, 0.32; P = .75). Conclusion SI in the pediatric brain increases on unenhanced T1-weighted MR images with repeated exposure to a linear GBCA. © RSNA, 2016.

Pediatric Cortical Vein Thrombosis: Frequency and Association With Venous Infarction.

BACKGROUND AND PURPOSE: Cortical vein thrombosis (CVT) is an uncommon site of involvement in cerebral sinovenous thrombosis. Few reports have described pediatric CVT, and none has differentiated its unique attributes. This study assessed the clinical features and radiographic outcome of a cohort of children with cerebral sinovenous thrombosis, comparing those with CVT to those without CVT. METHODS: Children diagnosed with cerebral sinovenous thrombosis were retrospectively reviewed and separated into 2 groups based on the presence or absence of cortical vein involvement. RESULTS: Fifty patients met inclusion criteria, including 12 with CVT. The CVT group was more likely to present with seizure (P=0.0271), altered mental status (P=0.0271), and a family history of clotting disorder (P=0.0477). Acute imaging of the CVT group more commonly demonstrated concurrent superior sagittal sinus thrombosis (P=0.0024), parenchymal hemorrhage (P=0.0141), and restricted diffusion (P<0.0001). At follow-up, the CVT group more commonly showed headache, seizure, and focal neurological deficit (P=0.0449), and venous infarction (P=0.0007). CONCLUSIONS: In our cohort, CVT was significantly associated with seizures at presentation, hemorrhage and restricted diffusion on acute imaging, as well as neurological disability and venous infarction at follow-up. Involvement of cortical veins in cerebral sinovenous thrombosis is associated with an increased risk of infarction and adverse outcome in children.

Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke.

BACKGROUND: Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. OBJECTIVE: Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). MATERIALS AND METHODS: We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. RESULTS: Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm(3) vs. 36,995 mm(3); P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 × 10(-6) mm(2)/s vs. 611 × 10(-6) mm(2)/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. CONCLUSION: Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis.

Cavernous Sinus Thrombosis in Children: Imaging Characteristics and Clinical Outcomes.

BACKGROUND AND PURPOSE: Cavernous sinus thrombosis (CST) is a rare life-threatening cerebrovascular disease known to cause carotid artery narrowing (CAN) and arterial ischemic stroke. The imaging features of CST and related complications have been reported in adults, but rarely in children. METHODS: We performed a retrospective review of children with imaging confirmed CST from 2003 to 2014, describing presenting symptoms, imaging findings, and treatment. RESULTS: Ten patients with CST were identified. All had CAN and 6 of 10 developed infarcts. Of 8 patients treated with anticoagulation therapy, 3 developed new infarcts. None required discontinuation of anticoagulation therapy because of bleeding. Visual impairment secondary to infectious neuritis was common. Imaging characteristics include cavernous sinus expansion, filling defects, restricted diffusion, arterial wall enhancement, empyema, superior ophthalmic vein enlargement and thrombosis, orbital cellulitis, and pituitary inflammation. CAN resolved in 60% of cases. Outcomes were mostly good, with a modified Rankin Scale score of ≤1 for 7 of 10 patients at discharge and 1 death. CONCLUSIONS: CAN and infarcts were common in this modest cohort of children with CST. Despite the high incidence of CAN and infarction, outcomes were often favorable. Although this is the largest cohort of childhood CST reported to date, large multicenter cohorts are needed to confirm our findings and determine the preferred therapeutic strategies for childhood CST.

Upward Translation of Cerebellar Tonsils following Surgical Expansion of Supratentorial Cranial Vault: A Unified Biomechanical Explanation of Chiari Type I.

Cerebellar tonsils moved significantly upward in 3 patients with Chiari type I who underwent supratentorial cranial vault expansion to alleviate intracranial pressure related to multisutural craniosynostosis. The Chiari type I deformities in these patients were the biomechanical consequence of posterior fossa-cerebellar disproportion caused by supratentorial craniocerebral disproportion secondary to multisutural craniosynostosis. The authors postulate that all cases of Chiari type I deformity share the sine qua non feature of posterior fossa-cerebellar disproportion.

Fractionated stereotactic radiosurgery for recurrent ependymoma in children.

Outcomes for children with relapsed ependymoma are poor. Re-irradiation is a potentially viable salvage option in these patients. Data were reviewed for 12 patients (median age 5.6 years) with relapsed ependymoma who received fractionated stereotactic radiosurgery (fSRS) following maximal surgical resection from 1995 to 2012. Four patients experienced a second recurrence, including 2 in-field and 2 distant failures. Median time to second recurrence (32 months) was significantly longer than time to first recurrence (24 months) (p = 0.008). Three-year local control was 89 %, and median event free survival from fSRS was 3.4 years. Radiation necrosis was observed in 6 patients, 3 who were symptomatic. In conclusion, fSRS offers durable response with a tolerable toxicity profile in children with recurrent EPN.

Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke.

OBJECTIVE: To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN: Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS: Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION: Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

Distinctive pattern of restricted diffusion in a neonate with molybdenum cofactor deficiency.

We present a neonate with molybdenum cofactor deficiency imaged at presentation during the first month of life and at 5 months with diffusion-weighted brain MRI. While the imaging features of this disease have previously been reported, this case highlights a distinctive initial pattern of widespread restricted diffusion involving cortex at the depths of sulci. Other case series have published diffusion-weighted images (DWI) with this pattern but never specifically commented on this finding. This distinct DWI pattern also accounts for the configuration of ulegyria frequently described on later imaging. Early recognition of this unique initial DWI pattern could avoid misdiagnosis and better direct counseling and management.

Megacystis Associated With an Underlying ACTA2 Variant and Diagnosis of Multisystemic Smooth Muscle Dysfunction Syndrome: A Case Report.

Fetal megacystis, or an enlarged fetal bladder, is most often attributed to embryological defects, occurring early in gestation. Recent investigations have demonstrated that the underlying etiology of megacystis may be more myriad than originally thought. We present the third reported patient with megacystis due to an ACTA2 Arg179 substitution variant causing Multisystemic Smooth Muscle Dysfunction Syndrome. We also provide a description of pediatric evaluation and follow up. The growing number of cases in which this ACTA2 variant has been identified in fetal megacystis suggests that molecular sequencing is an appropriate consideration, particularly prenatally, when other features of Multisystemic Smooth Muscle Dysfunction Syndrome cannot be detected.