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Introduction: Venous leg ulceration (VLU), the most common type of chronic ulcer, can be difficult to heal and is a major cause of morbidity and reduced quality of life. Although compression bandaging is the principal treatment, it is time-consuming and bandage application requires specific training. There is evidence that intervention on superficial venous incompetence can help ulcer healing and recurrence, but this is not accessible to all patients. Hence, new treatments are required to address these chronic wounds. One possible adjuvant treatment for VLU is human decellularised dermis (DCD), a type of skin graft derived from skin from deceased tissue donors. Although DCD has the potential to promote ulcer healing, there is a paucity of data for its use in patients with VLU., Methods and Analysis: This is a multicentre, parallel group, pragmatic randomised controlled trial. One hundred and ninety-six patients with VLU will be randomly assigned to receive either the DCD allograft in addition to standard care or standard care alone. The primary outcome is the proportion of participants with a healed index ulcer at 12 weeks post-randomisation in each treatment arm. Secondary outcomes include the time to index ulcer healing and the proportion of participants with a healed index ulcer at 12 months. Changes in quality of life scores and cost-effectiveness will also be assessed. All analyses will be carried out on an intention-to-treat (ITT) basis. A mixed-effects, logistic regression on the outcome of the proportion of those with the index ulcer healed at 12 weeks will be performed. Secondary outcomes will be assessed using various statistical models appropriate to the distribution and nature of these outcomes., Ethics and Dissemination: Ethical approval was granted by the Bloomsbury Research Ethics Committee (19/LO/1271). Findings will be published in a peer-reviewed journal and presented at national and international conferences., Trial Registration Number: ISRCTN21541209., Competing Interests: Competing interests: AC and RL are affiliated to NHSBT, which provided the DCD allografts free of charge. The current version of the protocol is V.9.0. The study commenced recruitment in October 2019. Imperial College London is the main sponsor for this study. Delegated responsibilities are assigned to the NHS trusts taking part in this study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Altered hippocampal morphology and reduced volumes have been found in children born preterm compared to full-term. Stress inhibits neurogenesis in the hippocampus, and neonatal stress/noxious stimulation in rodent pups are associated with long-term alterations in hippocampal volumes. We have previously shown reduced cortical thickness and cerebellar volumes in relation to more exposure to pain-related stress of neonatal invasive procedures in children born very preterm. We have reported targeted gene-by-pain environment interactions that contribute to long-term brain development and outcomes in this population. We now aim to determine whether exposure to pain-related stress (adjusted for clinical factors and genotype) differentially impacts regional structures within the limbic system and thalamus, and investigate relationships with outcomes in very preterm children. Our study included 57 children born very preterm (<32 weeks GA) followed longitudinally from birth who underwent 3-D T1 MRI neuroimaging at ∼8 years. Hippocampal subfields and white matter tracts, thalamus and amygdala were automatically segmented using the MAGeT Brain algorithm. The relationship between those subcortical brain volumes (adjusted for total brain volume) and neonatal invasive procedures, gestational age (GA), illness severity, postnatal infection, days of mechanical ventilation, number of surgeries, morphine exposure, and genotype ( COMT, SLC6A4 , and BDNF ) was examined using constrained principal component analysis. We found that neonatal clinical factors and genotypes accounted for 46% of the overall variance in volumes of hippocampal subregions, tracts, basal ganglia, thalamus and amygdala. After controlling for clinical risk factors and total brain volume, greater neonatal invasive procedures was associated with lower volumes in the amygdala and thalamus ( p = 0.0001) and an interaction with COMT genotype predicted smaller hippocampal subregional volume ( p = 0.0001). More surgeries, days of ventilation, and lower GA were also related to smaller volumes in various subcortical regions ( p < 0.002). These reduced volumes were in turn differentially related to poorer cognitive, visual-motor and behavioral outcomes. Our findings highlight the complexity that interplays when examining how exposure to early-life stress may impact brain development both at the structural and functional level, and provide new insight on possible novel avenues of research to discover brain-protective treatments to improve the care of children born preterm.

Background: Chronic kidney disease (CKD) is a risk factor for vascular disease and stroke. The spectrum of brain injury and microstructural white matter abnormalities in children with CKD is largely unknown., Methods: Cross sectional study at two North American pediatric hospitals. A cohort of 49 children, 29 with CKD, including renal transplant (mean age 14.4 ± 2.9 years; range 9-18), and 20 healthy controls (mean age 13.7 ± 3.1 years; range 9-18) had their conventional brain magnetic resonance images (MRIs) reviewed by one neuroradiologist to determine the prevalence of brain injury. Fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) were generated to compare white matter microstructure in CKD compared to controls, using tract-based spatial statistics (TBSS)., Results: Focal and multifocal white matter injury was seen on brain MRI in 6 children with CKD (21%). Relative to controls, CKD subjects showed reduced white matter fractional anisotropy and increased mean diffusivity and radial diffusivity in the anterior limb of the internal capsule, suggestive of abnormal myelination., Conclusion: Cerebral white matter abnormalities, including white matter injury, are under-recognized in pediatric CKD patients. Brain imaging studies through progression of CKD are needed to determine the timing of white matter injury and any potentially modifiable risk factors.

Background: Brain injury (BI) is reported in 60% of newborns with critical congenital heart disease as white matter injury (WMI) or stroke. Neurodevelopmental (ND) impairments are reported in these patients. The relationship between neonatal BI and ND outcome has not been established., Objectives: This study sought to determine the association between peri-operative BI and ND outcomes in infants with single ventricle physiology (SVP) and d-transposition of the great arteries (d-TGA)., Methods: Term newborns with d-TGA and SVP had pre-operative and post-operative brain magnetic resonance imaging and ND outcomes assessed at 12 and 30 months with the Bayley Scales of Infant Development-II. BI was categorized by the brain injury severity score and WMI was quantified by volumetric analysis., Results: A total of 104 infants had follow-up at 12 months and 70 had follow-up at 30 months. At 12 months, only clinical variables were associated with ND outcome. At 30 months, subjects with moderate-to-severe WMI had significantly lower Psychomotor Development Index (PDI) scores (13 points lower) as compared with those with none or minimal WMI for d-TGA and SVP (p = 0.03 and p = 0.05, respectively) after adjusting for various factors. Quantitative WMI volume was likewise associated. Stroke was not associated with outcome. The Bland-Altman limits of agreement for PDI scores at 12 and 30 months were wide (-40.3 to 31.2) across the range of mean PDI values., Conclusions: Increasing burden of WMI is associated with worse motor outcomes at 30 months for infants with critical congenital heart disease, whereas no adverse association was seen between small strokes and outcome. These results support the utility of neonatal brain magnetic resonance imaging in this population to aid in predicting later outcomes and the importance of ND follow-up beyond 1 year of age., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Preterm birth is associated with brain injury and altered cognitive development. However, the consequences of extrauterine development are not clearly distinguished from perinatal brain injury. Therefore, we characterized cortical growth patterns from 30 to 46 postmenstrual weeks (PMW) in 27 preterm neonates (25-32 PMW at birth) without detectable brain injury on magnetic resonance imaging. We introduce surface-based morphometric descriptors that quantify radial (thickness) and tangential (area) change rates. Within a tensor-based morphometry framework, we use a temporally weighted formulation of regression to simultaneously model local age-related changes in cortical gray matter (GM) and underlying white matter (WM) mapped onto the cortical surface. The spatiotemporal pattern of GM and WM development corresponded to the expected gyrification time course of primary sulcal deepening and branching. In primary gyri, surface area and thickness rates were below average along sulcal pits and above average on gyral banks and crests in both GM and WM. Above average surface area rates in GM corresponded to emergence of secondary and tertiary folds. These findings map the development of neonatal cortical morphometry in the context of extrauterine brain development using a novel approach. Future studies may compare this developmental trajectory to preterm populations with brain injury. Hum Brain Mapp 38:4322-4336, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m 2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome. Results Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome. Conclusion Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.

Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Thalamic gliomas are rare. The natural history is unpredictable, and the optimal management of these tumors in children is poorly defined. The aim was to identify outcomes, prognostic factors, and response to various modalities of treatment in a relatively large population of pediatric thalamic tumors from many centers within a fairly homogeneous health care system., Methods: We performed a Canadian multicenter retrospective review of pediatric thalamic tumors presenting during the MRI era (1989-2012). Radiology and pathology were reviewed by central independent reviewers. Paraffin shavings for RNA extraction were taken and tested for fusion events involving KIAA1549:BRAF. Tumors were classified as unilateral or bithalamic based on their origin on imaging. Univariate and multivariate analyses on factors influencing survival were performed., Results: Seventy-two thalamic tumors were identified from 11 institutions. Females represented 53% of the study population, and the mean age at presentation was 8.9 years. Sixty-two tumors were unilateral and 10 bithalamic. Unilateral tumors had a greater propensity to grow inferiorly towards the brainstem. These tumors were predominantly low grade in comparison to bithalamic tumors which were high-grade astrocytomas. The 5-year overall survival was 61 ± 13% for unithalamic tumors compared to 37 ± 32% for bithalamic tumors (p = 0.097). Multivariate analysis indicated tumor grade as the only significant prognostic factor for unithalamic tumors. Six unilateral tumors, all low grade, were BRAF fusion positive., Conclusion: Unilateral and bilateral thalamic tumors behave differently. Surgical resection is an appropriate treatment option in unilateral tumors, most of which are low grade, but outcome is not related to extent of resection (EOR). Bilateral thalamic tumors have a poorer prognosis, but the occasional patient does remarkably well. The efficacy of chemotherapy and radiotherapy has not been clearly demonstrated. Novel therapeutic approaches are required to improve the prognosis for malignant unilateral thalamic tumors and bilateral thalamic tumors.

Objective: To examine whether specific neonatal factors differentially influence cerebellar subregional volumes and to investigate relationships between subregional volumes and outcomes in very preterm children at 7 years of age., Study Design: Fifty-six children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-dimensional T(1)-weighted neuroimaging at median age 7.6 years. Children with severe brain injury were excluded. Cerebellar subregions were automatically segmented using the multiple automatically generated templates algorithm. The relation between cerebellum subregional volumes (adjusted for total brain volume and sex) and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and visual-motor integration functions in relation to cerebellar volumes were also investigated., Results: Higher neonatal procedural pain and infection, as well as other clinical factors, were differentially associated with reduced cerebellar volumes in specific subregions. After adjusting for clinical risk factors, neonatal procedural pain was distinctively associated with smaller volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller cerebellar subregional volumes were related to poorer cognition and motor/visual integration., Conclusions: In very preterm children, exposure to painful procedures, as well as additional neonatal risk factors such as infection, were associated with reduced cerebellar volumes in specific subregions and poorer outcomes at school age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Altered brain development is evident in children born very preterm (24-32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age., Methods: 42 right-handed children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling., Results: After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes., Conclusions: In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.

Background: Term newborns with congenital heart disease (CHD) show delayed brain development as early as the third trimester, especially in single-ventricle physiology (SVP). Mechanisms causing delayed brain development in CHD are uncertain but may include impaired fetal brain blood flow. Our objective was to determine if cardiac anatomy associated with obstruction to antegrade flow in the ascending aorta is predictive of delayed brain development as measured by diffusion tensor imaging and magnetic resonance spectroscopic (MRS) imaging., Methods: Echocardiograms from 36 term newborns with SVP were reviewed for the presence of aortic atresia and the diameter of the ascending aorta. Quantitative magnetic resonance imaging parameters measuring brain microstructural (fractional anisotropy (FA) and average diffusivity (Dav)) or metabolic development (N-acetylaspartate (NAA) and lactate/choline (Lac/Cho)) were recorded., Results: Increasing NAA/Cho and white matter (WM) FA, and decreasing Dav and Lac/Cho characterize normal brain development. Consistent with the hypothesis that delayed brain development is related to impaired brain perfusion, smaller ascending aortic diameter and aortic atresia were associated with higher Dav and lower WM FA. Echocardiogram variables were not associated with brain metabolic measures., Conclusions: These observations support the hypothesis that obstruction to fetal cerebral blood flow impairs brain microstructural development.

Objective: An ultrasound screening program for abdominal aortic aneurysms (AAAs) in men began in Gloucestershire in 1990 and has been running for 20 years. This report examines the workload and results., Methods: We reviewed the screening database for attendance and outcome records from AAA surgery in Gloucestershire and postmortem and death certificate results looking for men who died from ruptured AAAs in the screening cohort. The setting was an AAA screening program in the county of Gloucestershire, UK. Men aged 65 were invited by year of birth to attend for an ultrasound screening for AAAs. Men with an aorta <2.6 cm were reassured and discharged; men with an aorta between 2.6 cm and 5.4 cm were offered follow-up surveillance; men with an aorta >5.4 cm were considered for intervention. We analyzed attendance rates, screening and surveillance outcomes, and intervention rates and outcomes over the 20 years of the study., Results: Some 61,982 men were invited, and 52,690 attended for screening (85% attendance). At first scan, 50,130 men (95.14%) had an aortic diameter <2.6 cm in diameter and were reassured and discharged; 148 men (0.28%) had an AAA >5.4 cm in diameter and were referred for possible treatment; 2412 (4.57%) had an aortic diameter between 2.6 and 5.4 cm and entered a program of ultrasound surveillance. The overall mean aortic diameter on initial scan fell from 2.1 cm to 1.7 cm during the study (reduction 0.015 cm/y, 95% confidence interval [CI], 0.0144-0.0156 cm/y; P < .0001). Some 631 patients with AAAs had intervention treatment with a perioperative mortality rate of 3.9%; during the same interval, 372 AAAs detected incidentally were treated, with a mortality rate of 6.7%. The number of ruptured AAAs treated annually in Gloucestershire fell during the study (χ(2) for trend = 18.31, df = 1; P < .0001)., Conclusions: Screening reduced the number of ruptured AAAs in Gloucestershire during the 20 years of the program. There has been a significant reduction of men with an abnormal aorta, as the mean aortic diameter of the 65-year-old male has reduced over 20 years., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Childhood cerebral X-linked adrenoleukodystrophy (ALD) remains one of the most devastating neurological diseases of childhood. Cardinal features are inflammatory cerebral demyelination that coincides with an advancing zone of gadolinium enhancement on brain MRI. Therapeutic options, including the role of antiinflammatory therapy, are limited and poorly understood. We report the failure of repeated cyclophosphamide pulse therapy to halt the clinical progression or alter the gadolinium accumulation in two cases of childhood cerebral ALD., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Serotonin has an important role in vascular resistance and blood pressure control, and a functional serotonin transporter polymorphism has been associated with migraine. Disturbances in serotonin metabolism have been associated with autism, depression, and myoclonus related conditions, but serotonin has far more functions in the body. Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura in which attacks are associated with hemiparesis., Cases: We present two siblings with hemiplegic migraine, depression, progressive spastic paraparesis, myelopathy, and spinal cord atrophy. One of the sisters presented with prolonged coma after a migraine episode. Both sisters were found to have low cerebrospinal fluid serotonin metabolite (5-hydroxyindoleacetic acid), low platelet serotonin levels, and diminished serotonin transport capacity. Their clinical symptoms improved on 5-hydroxytryptophan replacement therapy. Mutational analysis of the CACNA1A and ATP1A2 genes was negative., Conclusion: This is the first time that systemic serotonin deficiency has been described in familial hemiplegic migraine. We hypothesize that the deficiency of serotonin transport may be part of a complex cellular membrane trafficking dysfunction involving not only the serotonin transporter but also other transporters and ion channels.

More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.

The role of generalized hypoxia-ischemia in the genesis of perinatal focal arterial stroke remains puzzling. Animal studies have demonstrated that hypoxia-ischemia may alter blood flow through the ductus venosus, thereby increasing the risk for placental emboli entering the cerebral circulation. A retrospective review was performed of clinical records of all term newborns admitted to a tertiary perinatal center between January 1995 and May 2007 with acute arterial stroke on neuroimaging during the first week of life. Newborns were classified into 2 groups on the basis of neuroimaging abnormalities: stroke alone, or stroke and nonfocal hypoxic-ischemic brain injury. A total of 62 newborns had focal or multifocal stroke, 36 with stroke alone and 26 with stroke with nonfocal hypoxia-ischemia. Multiple risk factors for hypoxia-ischemia occurred in most newborns in both groups. These data indicate that hypoxia-ischemia may play a role in the genesis of stroke in the term newborn with or without evidence of nonfocal hypoxic-ischemic brain injury on neuroimaging., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: We present an extremely rare case of severe intracranial hypertension secondary to sigmoid sinus compression by a group A streptococcal epidural abscess., Method: Case report and review of the world literature., Results: A five-year-old boy was treated for acute otitis media and group A streptococcal bacteraemia, but subsequently developed severe intracranial hypertension. Computed tomography revealed that, although the sigmoid sinuses were not thrombosed, the patient had a dominant right sigmoid sinus that was almost completely compressed by a small epidural abscess. After surgical decompression of the epidural abscess, with aggressive debridement of the granulation tissue from the sigmoid sinus wall, the patient awoke from general anaesthesia with complete resolution of his symptoms and signs of intracranial hypertension. He suffered no sequelae over the subsequent six months' follow up., Conclusion: This is the first reported case of intracranial hypertension due to an epidural abscess causing sigmoid sinus compression without thrombosis. This case illustrates the fact that, even in the absence of thrombosis of the sigmoid sinus, a small epidural abscess may require urgent surgical treatment.

Infantile-onset Krabbe disease results from a deficiency of the lysosomal enzyme galactocerebrosidase and leads to death from profound central and peripheral demyelination. Neonatal hematopoietic cell transplantation may result in near-normal cognitive development and partial rescue of gross motor development. The long-term course of the disorder for treated patients seems to involve slowly progressive neurological impairment. We describe the detailed 3-year outcomes of this experimental procedure using umbilical cord blood in a prenatally-diagnosed newborn with Krabbe disease. Substantial perivascular calcifications and atrophy of the white matter developed in the first year post-transplantation. Despite persistent neuroradiological and electrophysiological evidence of leukodystrophy, at age 3 years she has had only mildly impaired non-motor development and moderately impaired motor skills. The cause of these severe white matter changes may have been due to ongoing Krabbe disease or to effects of the chemotherapy regimen or to an interaction of these factors. Extended long-term follow-up of children neonatally transplanted for Krabbe disease is needed before the full utility and limitations of neonatal transplantation can be determined., (Georg Thieme Verlag KG Stuttgart New York.)

Objective: To report a case series in which basal ganglia calcifications without mass effect proved to be germ cell tumors., Design: Case series., Setting: Tertiary care hospital., Patients: Four patients., Interventions: Computed tomography, magnetic resonance imaging, positron emission tomography, biopsy, chemotherapy, and radiation therapy., Main Outcome Measures: Recognition of clinical syndrome and radiological features., Results: All patients had progressive hemiparesis, and 1 patient also had frontal lobe dementia. Imaging demonstrated progressive asymmetric signal abnormality with basal ganglia calcification and associated brainstem atrophy. Fludeoxyglucose F 18-positron emission tomography showed hypometabolism in contrast to malignant glioma., Conclusion: Germ cell tumor should be considered in patients with an indolently progressive neurological course, particularly if basal ganglia calcification is present with or without enhancement, asymmetric brain atrophy, or a mass.

Objective: Our objective was to identify clinical predictors of progressive white matter injury., Methods: We evaluated 133 infants of <34 weeks of gestation at birth from 2 university hospitals. Infants underwent MRI twice, initially when in stable condition for transport and again at term-equivalent age or before transfer or discharge. Two neuroradiologists who were blinded to the clinical course graded MRI white matter injury severity by using a validated scale. Potential risk factors were extracted from medical charts., Results: Twelve neonates (9.0%) had progressive white matter injury. In the unadjusted analysis of 10 newborns without Candida meningoencephalitis, recurrent culture-positive postnatal infection and chronic lung disease were associated with progressive white matter injury. Exposure to multiple episodes of culture-positive infection significantly increased the risk of progressive white matter injury. Of the 11 neonates with >1 infection, 36.4% (4 infants) had progressive injury, compared with 5.0% (6 infants) of those with

Purpose: Magnetic resonance imaging has been used to detect occult neuropathy in patients with nonneurogenic lower urinary tract dysfunction. There is substantial controversy surrounding the role of this test for lower urinary tract dysfunction. We identified factors associated with positive magnetic resonance imaging to improve patient selection., Materials and Methods: A case-control study was done in all pediatric patients referred to our radiology department for spinal magnetic resonance imaging primarily because of lower urinary tract symptoms between 1995 and 2004. Patients with known neurological disorders or anomalies associated with neurogenic bladder (overt spinal dysraphism, imperforate anus, etc) were excluded. A total of 80 patients with a median age of 6.5 years (range 4 to 17) were identified, of whom 47 (59%) were female. Bivariate analysis was used to evaluate the association of certain variables with positive magnetic resonance imaging findings, including patient age, gender, type of urinary symptoms, fecal soiling, abnormal neuro-orthopedic examination, lumbar cutaneous findings, resistance to medical management and urodynamic findings., Results: Magnetic resonance imaging revealed spinal abnormalities in 6 cases (7.5%), including intradural arachnoid cyst in 1, sacral dysgenesis in 3, syrinx/hydromyelia in 1 and tethered cord in 1. An abnormal lumbar cutaneous finding was the only variable associated with positive magnetic resonance imaging (Fisher's exact test p = 0.002)., Conclusions: Spinal magnetic resonance imaging has a low impact in the management of lower urinary tract dysfunction. With proper patient selection the pretest probability of positive magnetic resonance imaging may be increased and, therefore, many unnecessary studies may be avoided. Abnormal cutaneous findings are associated with abnormal magnetic resonance imaging.

Objective: Hypodensities on computed tomographic (CT) brain scans are thought to take at least 6 hours to become apparent after blunt head trauma. This finding, in conjunction with the later evolution of the hypodensities, is used in timing the injury in children with suspected non-accidental brain injury, in whom the history may be inaccurate. The purpose of this study is to report the occurrence of diffuse cerebral parenchymal hypodensities on CT scans performed within 5 hours of a well-defined accidental head injury., Methods: A retrospective review was performed of five patients admitted to British Columbia Children's Hospital who had accidental head injury and who were identified as having diffuse cerebral hemispheric hypodensities on early CT scans., Results: We present five patients (age range, 4 mo-14 yr) with well-documented accidental head injuries who demonstrated obvious and extensive CT brain scan cerebral hemispheric hypodensity from 60 minutes to 4.5 hours after trauma. All five patients presented with severe head injuries and immediate, unremitting coma, and all five progressed rapidly to brain death within 48 hours., Conclusion: It is unusual, but possible, to develop CT hypodensities as early as 1 hour after accidental head injury. In our small series of cerebral hemispheric hypodensity occurring less than 5 hours after trauma, all five patients had a uniformly fatal outcome. These observations may be important medicolegally in the assessment of the timing of head injury when the history of the trauma is not clear, as in children with suspected non-accidentally inflicted injury. It is inappropriate to generalize these findings to patients who are not unconscious immediately after a head injury, who regain consciousness after an injury before deteriorating, or who do not progress rapidly to brain death.

We report a newborn with progressive leukoencephalopathy and lactic acidaemia, diagnosed with isolated sulfite oxidase deficiency. We show that low plasma total homocysteine (PTHcy) is a valuable early indicator of sulfite oxidase dysfunction, providing a crucial first-line screen, whereas plasma cystine is not always informative in the first few days of life.

Case Report: The authors report a child in whom residual cerebellar astrocytoma after surgical resection was documented on serial computed tomography scans to undergo gradual complete regression spontaneously over a period of 11 years. In this case, the time course of regression has been well documented., Conclusion: The time course of regression may provide clues as to the underlying cause of this phenomenon.

Objective: A comparison between the literature and our management of pediatric patients presenting with otogenic lateral sinus thrombosis., Design: A retrospective case series of five pediatric patients., Setting: Four patients were treated at BC Children's Hospital, whereas the fifth patient was treated in New Westminster, BC. All were treated between 1994 and 2001., Methods: A retrospective chart review was conducted with a literature review for otogenic lateral sinus thrombosis., Main Outcome Measures: Treatment success was based on resolution of acute infection and neurologic symptoms., Results: Five patients, four males and one female, aged 2 to 14 years were reviewed. Three patients were treated successfully without mastoidectomy. One patient received a mastoidectomy that yielded no pus or granulation tissue within the mastoid cavity. One patient required a mastoidectomy after failure to respond to bilateral myringotomy and tympanostomy tube insertion. Although no pus was seen in the mastoid cavity, perisinus pus was found after unroofing the sigmoid sinus plate; free flow of blood was obtained on needle aspiration of the sinus, and the sinus was not surgically opened., Conclusion: The current literature states that the management of otogenic lateral sinus thrombosis includes high-dose intravenous antibiotics with a mastoidectomy and possible opening of the sinus. In our retrospective case series, three of five patients recovered completely without mastoidectomy, and a fourth had a mastoidectomy deemed to have been unnecessary. We conclude that intravenous antibiotics and insertion of a tympanostomy tube are sufficient treatment for selected cases of otogenic lateral sinus thrombosis. Mastoidectomy with possible opening of the sinus should be reserved for patients refractory to the above conservative treatment.