pneuRIPTM: A Novel Respiratory Inductance Plethysmography Monitor.

Objective pulmonary function (PF) evaluation is essential for the diagnosis, monitoring, and management of many pediatric respiratory diseases as seen in the emergency room, intensive care, and outpatient settings. In this paper, the development and testing of a new noninvasive PF instrument, pneuRIPTM, which utilizes respiratory inductance plethysmography (RIP) are discussed. The pneuRIPTM hardware includes a small circuit board that connects to the RIP bands and measures and wirelessly transmits the band inductance data to any designated wirelessly connected tablet. The software provides indices of respiratory work presented instantaneously in a user-friendly graphical user interface on the tablet. The system was tested with ten normal children and compared with an existing system, Respitrace (Sensormedics, Yorba Linda, CA), under normal and loaded breathing conditions. Under normal breathing, the percentage differences between the two systems were 2.9% for labored breathing index (LBI), 31.8% for phase angle (Φ), 4.8% for percentage rib cage (RC%), and 26.7% for respiratory rate (BPM). Under loaded breathing, the percentage differences between the two systems were 1.6% for LBI, 4.1% for Φ, 8.5% for RC%, and 52.7% for BPM. For LBI, Φ, and RC%, the two systems were in general agreement. For BPM the pneuRIPTM is shown to be more accurate than the respitrace when compared to manually counting the breaths: 13.2% versus 36.4% accuracy for normal breathing and 16.9% versus 60.7% accuracy for breathing under load, respectively.

Assessing 'second-look' tumour resectability in childhood posterior fossa ependymoma-a centralised review panel and staging tool for future studies.

PURPOSE: To improve uniformity in radiological review/reporting and discussion of surgical resection status in the forthcoming SIOP Ependymoma II trial, a central review of imaging and resection status will be carried out prior to treatment stratification. We present a review of surgical decision-making from the UKCCSG/SIOP Ependymoma trial for very young children (<3 years) (Lancet Oncol 8:696-705, 2007) and propose a primary surgical staging system for residual disease that could be used for Ependymoma II. METHODS: Imaging of 89 patients enrolled in the UKCCSG infant Ependymoma trial was independently reviewed by 3 experienced paediatric neuro-oncology surgeons. Pre- and post-op MRI imaging was available for 28 posterior fossa cases with incomplete resection. Location of residual disease, decision to offer 'second-look' surgery (prior to adjuvant therapy), perceived chance of complete resection, and risk to cranial nerves was assessed. Recommendation for second-look surgery was compared with actual second-look surgery. RESULTS: In the actual study period, 13 patients (46 %) had further surgery at some point. The independent panel, after blinded review of the imaging, would have offered 19 patients overall (68 %) in this same cohort up-front early second-look surgery prior to definitive adjuvant therapy. We devised a 5-point staging system to introduce consistency in staging residual disease and resectability, and this is presented. CONCLUSIONS: Based on scans alone, a surgical panel would have offered second-look surgery to 68 % of patients with residual ependymoma. The potential benefits and drawbacks of a surgical review panel and classification system will be discussed in the context of the forthcoming Ependymoma II trial.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

BACKGROUND AND PURPOSE: Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. METHODS: A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. RESULTS: Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. CONCLUSIONS: These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

A population-based study of newly diagnosed epilepsy in infants.

PURPOSE: Most published data on infants presenting with epilepsy originate from hospital/specialist clinic settings and may therefore not be representative of the general population. We carried out a population-based study to estimate the incidence of epilepsy onset in infants, to characterize the range of phenotypes and associated structural brain abnormalities, and to determine whether specific epilepsy diagnoses could be established at onset. METHODS: Children between 1 and 24 months of age with new-onset epilepsy were ascertained over 13 months from the residents in 15 boroughs of North London. Classification based on clinical information, electroencephalography (EEG), and neuroimaging data was undertaken independently by two pediatric neurologists. Neuroimages were reviewed by two neuroradiologists blinded to clinical details. KEY FINDINGS: A total of 57 children were enrolled giving an ascertainment-adjusted incidence of 70.1 (95% CI [56.3, 88.5])/100,000 children ≤ 2 years of age/year (ascertainment 76%). The incidence was highest among Asian children. An electroclinical syndrome was identified in 24 (42%) cases of which 21 were epileptic encephalopathies. Magnetic resonance (MR) images of 51 cases (89% of the total cohort) were reviewed. These demonstrated positive findings in 37 (72%) of 51 cases, of which 26 (51%) of 51 were etiologically relevant, and included developmental malformations in 11 (21%) of 51. SIGNIFICANCE: In a population setting infantile onset epilepsy presents mostly with complex phenotypes commonly associated with structural brain abnormalities. Routine MR imaging at presentation is therefore justified. However, identification of specific electroclinical syndromes remains difficult at onset.

Investigation of childhood central nervous system vasculitis: magnetic resonance angiography versus catheter cerebral angiography.

AIM: We compared the clinical utility of magnetic resonance angiography (MRA) to catheter cerebral angiography (CA) in the investigation of children with suspected central nervous system (CNS) vasculitis. METHOD: Single-centre retrospective review of children with a suspected diagnosis of CNS vasculitis studied with both MRA and CA. MRA and CA-detected abnormalities (location, multiplicity, and morphology) were compared; sensitivity and specificity were calculated on a per lesion and per patient basis for MRA, with CA as the reference standard. RESULTS: Findings in fourteen patients (median age at presentation of 5 y 10 mo [range 1 y 5 mo-14 y 5 mo]; eight males, six females) relating to sixteen paired studies of MRA and CA were reviewed. CA-detected lesions were commonly bilateral (13/16 studies, p<0.05), and likely to be proximally distributed (15/16 studies, p<0.05).The sensitivity and specificity of MRA for CA lesion detection was 63% (95% confidence interval [CI] 48-78) and 89% (95% CI 81-93), respectively with moderate agreement between the two modalities (kappa=0.51, 95% CI 0.37-0.66). The majority of the false negative observations involved the posterior circulation (9/14). The overall sensitivity for MRA diagnosis of vasculitis per patient was 94% (95% CI 67-99). INTERPRETATION: MRA failed to identify all lesions detected on CA, particularly those in the posterior circulation. MRA is a reasonable initial modality in the investigation of suspected CNS vasculitis but in cases of abnormal parenchymal MRI and normal MRA, CA should be considered.

Congenital perisylvian dysfunction - is it a spectrum?

AIM: This study examines the overlap between children with bulbar cerebral palsy (Worster-Drought syndrome [WDS]) and perisylvian polymicrogyria. METHOD: A total of 121 children (81 males, 40 females; mean age 5y 5mo, SD 3y 6mo; age range 1mo-15y 4mo) were studied using retrospective clinical data and magnetic resonance imaging. In all, 70 children had WDS with normal perisylvian imaging, 31 had congenital bilateral perisylvian polymicrogyria (CBPP), and 20 had congenital unilateral perisylvian polymicrogyria (CUPP). RESULTS: All groups shared aetiological markers (male sex, congenital contractures, low familial incidence, excess antenatal events). There was a common phenotype of pseudobulbar palsy with mild limb pyramidal signs in all children with WDS, 90% of those with CBPP, and one-third of those with CUPP, often also associated with learning disability*, epilepsy, and behavioural difficulties. A further 15% of children with CUPP acquired this phenotype through an epileptic encephalopathy. Pseudobulbar palsy rather than polymicrogyria was more predictive of additional impairments other than epilepsy. INTERPRETATION: We propose that congenital perisylvian dysfunction is a spectrum encompassing the WDS phenotype and perisylvian polymicrogyria imaging abnormalities. As with other prenatal brain abnormalities, there is not necessarily concordance between imaging and clinical findings, although the phenotype is often more severe to manifest imaging abnormality. Clinical phenotype is the best indicator of prognosis. Epileptic encephalopathy can cause an acquired form of perisylvian dysfunction where there is.

Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study.

BACKGROUND: Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the child's developing nervous system at a crucial time-with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma. METHODS: Between December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child's treatment centre) showed progressive disease. FINDINGS: 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32-53). With a median follow-up of 6 years (range 1.5-11.3), overall survival for the non-metastatic patients at 3 years was 79.3% (95% CI 68.5-86.8) and at 5 years 63.4% (51.2-73.4). The corresponding values for event-free survival were 47.6% (36.2-58.1) and 41.8% (30.7-52.6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1.6 years (range 0.1-10.2 years). The median age at irradiation of the whole group was 3.6 years (range 1.5-11.9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46.6-91.2), compared with 52% (33.3-68.1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy. INTERPRETATION: This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma.

Magnetic resonance imaging protocols for paediatric neuroradiology.

Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist's review of each patient's images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios.

Post-varicella intracranial haemorrhage in a child.

We report a case of a 7-month-old male with primary intracranial haemorrhage 2 months after infection with varicella zoster virus (VZV). His initial clinical course was complicated by seizures and right hemiparesis; when last seen at 22 months the only positive finding was of left hand preference. Although the literature has recently established the association of arterial ischaemic stroke and VZV infection, primary intracranial haemorrhage has been reported only in one case. The child reported here had anterior interhemispheric haemorrhage due to a focal arteritis of the left anterior cerebral artery. The vascular abnormality was transient and had radiological features compatible with either a focal arteritis or vasospasm as a direct result of blood surrounding the vessels. We postulate that direct invasion of VZV caused extensive inflammation of the vessel wall and aggressive tissue penetration resulting in necrotizing angiitis and intracranial haemorrhage. We suggest that VZV infection should be considered a potential risk factor for intracranial haemorrhage in children.

A comparison of a similarity-based and a feature-based 2-D-3-D registration method for neurointerventional use.

Two-dimensional (2-D)-to-three-dimensional (3-D) registration can improve visualization which may aid minimally invasive neurointerventions. Using clinical and phantom studies, two state-of-the-art approaches to rigid registration are compared quantitatively: an intensity-based algorithm using the gradient difference similarity measure; and an iterative closest point (ICP)-based algorithm. The gradient difference approach was found to be more accurate, with an average registration accuracy of 1.7 mm for clinical data, compared to the ICP-based algorithm with an average accuracy of 2.8 mm. In phantom studies, the ICP-based algorithm proved more reliable, but with more complicated clinical data, the gradient difference algorithm was more robust. Average computation time for the ICP-based algorithm was 20 s per registration, compared with 14 min and 50 s for the gradient difference algorithm.

Effect of one-rescuer compression/ventilation ratios on cardiopulmonary resuscitation in infant, pediatric, and adult manikins.

OBJECTIVE: Optimal chest compression to ventilation ratio (C:V) for one-rescuer cardiopulmonary resuscitation (CPR) is not known, with current American Heart Association recommendations 3:1 for newborns, 5:1 for children, and 15:2 for adults. C:V ratios influence effectiveness of CPR, but memorizing different ratios is educationally cumbersome. We hypothesized that a 10:2 ratio might provide adequate universal application for all age arrest victims. DESIGN: Clinical study. SETTING: Tertiary care children's hospital. SUBJECTS: Thirty-five health care providers. INTERVENTIONS: Thirty-five health care providers performed 5-min epochs of one-rescuer CPR at C:V ratios of 3:1, 5:1, 10:2, and 15:2 in random order on infant, pediatric, and adult manikins. Compressions were paced at 100/min by metronome. The number of effective compressions and ventilations delivered per minute was recorded by a trained basic life support instructor. Subjective assessments of fatigue (self-report) and exertion (change in rescuer pulse rate compared with baseline) were assessed. Analysis was by repeated measures analysis of variance and paired Student's t-test. MEASUREMENTS AND MAIN RESULTS: Effective infant compressions per minute did not differ by C:V ratio, but ventilations per minute were greater at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05). Effective pediatric compressions per minute were less at 3:1 vs. 5:1, 10:2, and 15:2 (p < .05) and not different between 5:1, 10:2, and 15:2 ratios. Effective pediatric ventilations per minute were greater at 3:1 than all other ratios and both 5:1 and 10:2 were >15:2 (p < .05). Effective adult compressions per minute were progressively greater with 3:1 vs. 5:1 vs. 10:2 vs. 15:2 (p < .05). Self-efficacy was assessed, and rescuers always subjectively rated 10:2 and 15:2 ratios as easier than 5:1 or 3:1 ratios for all manikins. Rescuer pulse change (exertion) was greater after pediatric and adult vs. infant CPR (p < .05), with no significant difference by C:V ratio. CONCLUSIONS: C:V ratio and manikin size have a significant influence on the number of effective compressions and ventilations delivered during ideal, metronome-paced, one-rescuer CPR. Low ratios of 3:1, 5:1, and 10:2 favor ventilation, and high ratios of 15:2 favor compression, especially in adult manikins. Rescuers subjectively preferred C:V ratios of 10:2 and 15:2 over 3:1 or 5:1. Infant CPR caused less exertion and subjective fatigue than pediatric or adult CPR technique, without significant difference by C:V ratio. We speculate that a universal 10:2 C:V ratio for one-rescuer layperson CPR is physiologically reasonable but warrants further study with particular attention to educational value and technique retention.

Intensity-based 2-D-3-D registration of cerebral angiograms.

We propose a new method for aligning three-dimensional (3-D) magnetic resonance angiography (MRA) with 2-D X-ray digital subtraction angiograms (DSA). Our method is developed from our algorithm to register computed tomography volumes to X-ray images based on intensity matching of digitally reconstructed radiographs (DRRs). To make the DSA and DRR more similar, we transform the MRA images to images of the vasculature and set to zero the contralateral side of the MRA to that imaged with DSA. We initialize the search for a match on a user defined circular region of interest. We have tested six similarity measures using both unsegmented MRA and three segmentation variants of the MRA. Registrations were carried out on images of a physical neuro-vascular phantom and images obtained during four neuro-vascular interventions. The most accurate and robust registrations were obtained using the pattern intensity, gradient difference, and gradient correlation similarity measures, when used in conjunction with the most sophisticated MRA segmentations. Using these measures, 95% of the phantom start positions and 82% of the clinical start positions were successfully registered. The lowest root mean square reprojection errors were 1.3 mm (standard deviation 0.6) for the phantom and 1.5 mm (standard deviation 0.9) for the clinical data sets. Finally, we present a novel method for the comparison of similarity measure performance using a technique borrowed from receiver operator characteristic analysis.