Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2
3206delC fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors.
COL4A2; collagen-IV; porencephaly; small-vessel disease
This paper is concerned with the prediction of the occurrence of Periventricular Leukomalacia (PVL) that occurs in neonates after heart surgery. The data which is collected over a period of 12 hours after the cardiac surgery contains vital measurements as well as blood gas measurements with different resolutions. The decision tree classification technique has been selected as a tool for prediction of the PVL because of its capacity for discovering rules and novel associations in the data. Vital data measured using near-inferred spectroscopy (NIRS) at the sampling rate of 0.25 Hz and blood gas measurement up to 12 times with irregular time intervals for 35 patients collected from Children's Hospital of Philadelphia (CHOP) are used for this study. Vital data contain heart rate (HR), mean arterial pressure (MAP), right atrium pressure (RAP), blood hemoglobin (Hb), hemoglobin oxygen content (HbO2), oxygen saturation (SpO2) and relative cerebral blood flow (rCBF). Features derived from the data include statistical moments (mean, variance, skewness and kurtosis), trend and min and max of the vital data and rate of change, time weighted mean and a custom defined out of range index (ORI) for the blood gas data. A decision tree is developed for the vital data in order to identify the most important vital measurements. In addition, a decision tree is developed for blood gas data to find important factors for the prediction of PVL occurrence. Results show that in blood gas data, maximum rate of change in the concentration of bicarbonate ions in blood (HCO3) and minimum rate of change in the partial pressure of dissolved CO2 in the blood (PaCO2) are the most important factors for prediction of the PVL. Among vital features the kurtosis of HR and Hb are the most important parameters.
Previous studies of pediatric intracerebral hemorrhage have investigated isolated intraparenchymal hemorrhage. We investigated whether detailed assessment of intraventricular hemorrhage enhanced outcome prediction after intracerebral hemorrhage. We prospectively enrolled 46 children, full-term to 17 years, median age 2.7 years with spontaneous intraparenchymal hemorrhage and/or intraventricular hemorrhage. Outcome was assessed with the King’s Outcome Scale for Childhood Head Injury. Twenty-six (57%) had intraparenchymal hemorrhage, 10 (22%) had pure intraventricular hemorrhage, and 10 (22%) had both. There were 2 deaths, both with intraparenchymal hemorrhage + intraventricular hemorrhage volume ≥4% of total brain volume. Presence of intraventricular hemorrhage was not associated with poor outcome, but hydrocephalus showed a trend (p=0.09) toward poor outcome. In receiver operating characteristic curve analysis, combined intraparenchymal hemorrhage + intraventricular hemorrhage volume also showed a trend toward better outcome prediction than intraparenchymal hemorrhage volume alone. Although not an independent outcome predictor, future studies should assess intraventricular hemorrhage qualitatively and quantitatively.
intracerebral hemorrhage; pediatric hemorrhage; intraparenchymal hemorrhage; intraventricular hemorrhage
Advances in medical and surgical care of the high-risk neonate have led to increased survival. A significant number of these neonates suffer from neurodevelopmental delays and failure in school. The focus of clinical research has shifted to understanding events contributing to neurological morbidity in these patients. Assessing changes in cerebral oxygenation and regulation of cerebral blood flow (CBF) is important in evaluating the status of the central nervous system. Traditional CBF imaging methods fail for both ethical and logistical reasons. Optical near infrared spectroscopy (NIRS) is increasingly being used for bedside monitoring of cerebral oxygenation and blood volume in both very low birth weight infants and neonates with congenital heart disease. Although trends in CBF may be inferred from changes in cerebral oxygenation and/or blood volume, NIRS does not allow a direct measure of CBF in these populations. Two relatively new modalities, arterial spin-labeled perfusion magnetic resonance imaging and optical diffuse correlation spectroscopy, provide direct, noninvasive measures of cerebral perfusion suitable for the high-risk neonates. Herein we discuss the instrumentation, applications, and limitations of these noninvasive imaging techniques for measuring and/or monitoring CBF.
infant cerebral blood flow; CBF; arterial spin labeled perfusion; MRI; PVL; optical spectroscopy
To define incidence of seizures as a presenting symptom of acute arterial ischemic stroke (AIS) in children and to determine whether younger age, infarct location, or AIS etiology were risk factors for seizure at AIS presentation.
Children aged 2 months to 18 years presenting with AIS from January 2005 to December 2008 were identified from a single center prospective pediatric stroke registry. Clinical data were abstracted, and a neuroradiologist reviewed imaging studies.
Among 60 children who met inclusion criteria, seizures occurred at stroke presentation in 13 (22%). Median age was significantly younger in children who presented with seizures than in those who did not (1.1 versus 10 years, p=0.0009). Seizures were accompanied by hemiparesis in all patients. Three of four children with clinically overt seizures at presentation also had non-convulsive seizures on continuous EEG monitoring.
About one-fifth of children with acute AIS present with seizures. Seizures were always accompanied by focal neurologic deficits. Younger age was a risk factor for seizures at presentation. Seizure at presentation was not associated with infarct location or etiology. Non-convulsive seizures may occur during the acute period.
EEG; non-convulsive seizures; hemiparesis
Background and Purpose: Larger infarct volume as a percent of supratentorial brain volume (SBV) predicts poor outcome and hemorrhagic transformation in childhood arterial ischemic stroke (AIS). In perinatal AIS, higher scores on a modified pediatric version of the Alberta Stroke Program Early CT Score using acute MRI (modASPECTS) predict later seizure occurrence. The objectives were to establish the relationship of modASPECTS to infarct volume in perinatal and childhood AIS and to establish the interrater reliability of the score. Methods: We performed a cross sectional study of 31 neonates and 40 children identified from a tertiary care center stroke registry with supratentorial AIS and acute MRI with diffusion weighted imaging (DWI) and T2 axial sequences. Infarct volume was expressed as a percent of SBV using computer-assisted manual segmentation tracings. ModASPECTS was performed on DWI by three independent raters. The modASPECTS were compared among raters and to infarct volume as a percent of SBV. Results: ModASPECTS correlated well with infarct volume. Spearman rank correlation coefficients (ρ) for the perinatal and childhood groups were 0.76, p < 0.001 and 0.69, p < 0.001, respectively. Excluding one perinatal and two childhood subjects with multifocal punctate ischemia without large or medium sized vessel stroke, ρ for the perinatal and childhood groups were 0.87, p < 0.001 and 0.80, p < 0.001, respectively. The intraclass correlation coefficients for the three raters for the neonates and children were 0.93 [95% confidence interval (CI) 0.89–0.97, p < 0.001] and 0.94 (95% CI 0.91–0.97, p < 0.001), respectively. Conclusion: The modified pediatric ASPECTS on acute MRI can be used to estimate infarct volume as a percent of SBV with a high degree of validity and interrater reliability.
modified pediatric ASPECTS; arterial ischemic stroke; MRI; infarct volume; childhood; perinatal
Although acute seizures are common among neonates with arterial ischemic stroke (AIS), the incidence of subsequent seizures is unknown. The goals of this study were to determine the incidence of seizures following hospital discharge after perinatal acute AIS, and to assess lesion characteristics associated with later seizure occurrence.
Neonates with confirmed acute AIS on MRI were identified through a prospective stroke registry. Clinic visits and telephone follow-up identified occurrence of seizures after hospital discharge. MRI scans were graded for size and characteristics of infarct, and associations with seizures after stroke were analyzed.
At a mean (SD) follow-up of 31.3 (16.1) months, 11 of 46 (23.9%) patients with perinatal AIS had at least 1 seizure. Five patients had a single episode of seizure, and 6 developed epilepsy. The Kaplan-Meier probability of remaining seizure-free at 3 years was 73%. Stroke size on MRI was significantly associated with development of later seizures, with an incidence rate of later seizures 6.2 times higher among those with larger stroke size.
Seizures occurred in <25% of patients during initial follow-up after perinatal AIS. Of those with seizures, nearly half had a single episode of seizure and not early epilepsy. Larger stroke size was associated with higher risk of seizure. These data suggest that prolonged treatment with anticonvulsant agents may not be indicated for seizure prophylaxis after perinatal AIS. These findings may help guide clinicians in counseling families and could form the basis for much-needed future research in this area.
neonates; stroke; seizure; MRI; risk factors
Background and Purpose
To describe the occurrence of hemorrhagic transformation (HT) among children with arterial ischemic stroke (AIS) within 30 days after symptom onset and to describe clinical factors associated with HT.
Sixty-three children age 1 month to 18 years with AIS between January 2005 and November 2008 were identified from a single center prospective pediatric stroke registry. All neuroimaging studies within 30 days of stroke were reviewed by a study neuroradiologist. Hemorrhage was classified according to the European Cooperative Acute Stroke Study-1 definitions. Association of HT with clinical factors, systemic anticoagulation, stroke volume, and outcome was analyzed.
HT occurred in 19 of 63 children (30%; 95%CI 19–43%), only 2 (3%) of whom were symptomatic. Hemorrhage classification was HI1 in 14, HI2 in 2, PH1 in 2, and PH2 in 1. HT was less common in children with vasculopathy (RR 0.27; 95%CI 0.07–1.06; p=0.04) than in those with other stroke mechanisms. HT was not significantly associated with anticoagulation versus antiplatelet therapy (RR 0.6; 95%CI 0.2–1.5; p=0.26) but was associated with larger infarct volumes (p=0.0084). In multivariable analysis, worse PSOM scores were associated with infarct volume ≥5% of total supratentorial brain volume (OR 4.0; 95%CI 1.1–15; p=0.04), and a trend existed toward association of worse PSOM scores with HT (OR 4.0; 95%CI 0.9–18; p=0.07).
HT occurred in 30% of children with AIS within 30 days. Most hemorrhages were petechial and asymptomatic. Infarct volume was associated with HT and worse outcome.
hemorrhagic transformation; arterial ischemic stroke; anticoagulation; pediatric
This paper presents a novel statistical framework for human cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding by a single number, the proposed descriptor unifies multiple characteristics of surface geometry in a high-dimensional space (hundreds/thousands of dimensions). In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. This paper presents new mathematical insights into the relationship of cortical complexity with intra-cranial volume (ICV). It shows that conventional complexity descriptors implicitly handle ICV Differences in Different ways, thereby lending Different meanings to “complexity”. The paper proposes a new application of a non-parametric permutation-based approach for rigorous statistical hypothesis testing with multivariate cortical descriptors. The paper presents two cross-sectional studies applying the proposed framework to study folding Differences between genders and in neonates with complex congenital heart disease. Both studies lead to novel interesting results.
cerebral cortical folding; statistical shape analysis; gender differences; neonatal development
We developed the Recurrence and Recovery Questionnaire (RRQ) by converting the Pediatric Stroke Outcome Measure (PSOM) to a questionnaire for telephone interview and sought to validate the RRQ in a large cohort.
We analyzed parents' RRQ responses and same-day PSOM assessments for 232 children who had arterial ischemic stroke, cerebral sinovenous thrombosis, or presumed perinatal ischemic stroke. We assessed the agreement and consistency of the PSOM and RRQ, and we identified conditions that contributed to differences between the 2 measures. We tested selected factors as predictors of differences between the total PSOM and total RRQ (tPSOM and tRRQ) scores.
Median PSOM score was 1.5 and median RRQ score was 1.5. There was good agreement between tPSOM and tRRQ, and RRQ was a reliable estimator of PSOM at the total and component level. Preexisting neurologic deficits or chronic illnesses increased the difference between the tPSOM and tRRQ; the chronic illness effect was confirmed with univariate analysis.
The RRQ can characterize poststroke function when a child cannot return for examination. While the RRQ is not identical to the PSOM, the 2 measures likely assess closely related aspects of recovery. The RRQ is particularly useful when assessing outcomes of large cohorts, and will be useful in performing long-term follow-up studies of pediatric stroke.
Brain and heart development occurs simultaneously in the fetus with congenital heart disease. Early morphogenetic programs in each organ share common genetic pathways. Brain development occurs across a more protracted time-course with striking brain growth and activity-dependent formation and refinement of connections in the third trimester. This development is associated with increased metabolic activity and the brain is dependent upon the heart for oxygen and nutrient delivery. Congenital heart disease leads to derangements of fetal blood flow that result in impaired brain growth and development that can be measured with advanced magnetic resonance imaging. Delayed development results in a unique vulnerability to cerebral white matter injury in newborns with congenital heart disease. Delayed brain development and acquired white matter injury may underlay mild but pervasive neurodevelopmental impairment commonly observed in children following neonatal congenital heart surgery.
Congenital heart defects; Brain development; White matter injury; Periventricular leukomalacia; Infant heart surgery; Fetal circulation
To our knowledge, the recommendation to measure cerebrospinal opening pressure in the extended, rather than flexed lateral recumbent position to avoid false elevation of the opening pressure has not been formally evaluated in children. 53 children from a single center prospective study had their opening pressure measured in both the flexed and extended lateral recumbent positions prior to removing any cerebrospinal fluid (mean age 11.7 years; 60% male). The difference between the mean opening pressure in flexed (25.1±9.2 cm H2O) and extended (24.4±8.4 cm H2O) positions reached statistical significance (mean difference = 0.6±2.2 cm H2O; Z = 2.021, p< 0.03). 92.4% of opening pressure measures had less than a 5cm H2O difference between positions. Lumbar puncture performed in the extended, rather than flexed lateral recumbent position results in a statistically significant decrease in cerebrospinal fluid opening pressure, although the magnitude of the difference is small and of doubtful clinical significance.
Background and Purpose
To describe features of children with intracerebral hemorrhage (ICH) and to determine predictors of short-term outcome in a single-center prospective cohort study.
Single-center prospective consecutive cohort study of spontaneous ICH in children age 1-18 years from January 2006 to June 2008. Exclusion criteria were inciting trauma; intracranial tumor; isolated epidural, subdural, intraventricular, or subarachnoid hemorrhage; hemorrhagic transformation of ischemic stroke; and cerebral sinovenous thrombosis. Hospitalization records were abstracted. Follow-up assessments included outcome scores using the Pediatric Stroke Outcome Measure (PSOM) and King's Outcome Scale for Childhood Head Injury (KOSCHI). ICH volumes and total brain volumes (TBV) were measured by manual tracing.
Twenty-two patients, median age of 10.3 years (range 4.2-16.6 years), had presenting symptoms of headache in 77%, focal deficits 50%, altered mental status 50%, and seizures 41%. Vascular malformations caused hemorrhage in 91%. Surgical treatment (hematoma evacuation, lesion embolization or excision) was performed during acute hospitalization in 50%. One patient died acutely. At median follow-up of 3.5 months (range 0.3-7.5 months), 71% of survivors had neurological deficits; 55% had clinically significant disability. Outcome based on PSOM and KOSCHI scores was worse in patients with ICH volume >2% of TBV (p=0.023) and altered mental status at presentation (p = 0.005).
Spontaneous childhood ICH was due mostly to vascular malformations. Acute surgical intervention was commonly performed. Although death was rare, 71% of survivors had persisting neurological deficits. Larger ICH volume and altered mental status predicted clinically significant disability.
intracerebral hemorrhage; outcome; childhood; vascular malformation
Sodium bicarbonate (NaHCO3) is a common treatment for metabolic acidemia, however little definitive information exists regarding its treatment efficacy and cerebral hemodynamic effects. This pilot observational study quantifies relative changes in cerebral blood flow (rCBF) and oxy and deoxy-hemoglobin concentrations (ΔHbO2 and ΔHb) due to bolus administration of NaHCO3 in patients with mild base deficits.
Infants and children with hypoplastic left heart syndrome (HLHS) were recruited prior to cardiac surgery. NaHCO3 was given as needed for treatment of base deficit. Diffuse optical spectroscopies were employed for 15 minutes post-injection to non-invasively monitor ΔHb, ΔHbO2 and rCBF relative to baseline prior to NaHCO3 administration.
Twenty-two anesthetized and mechanically ventilated HLHS patients (1 day to 4 years old) received a median (interquartile range) dose of 1.1 (0.8, 1.8) mEq/kg NaHCO3 administered intravenously over 10–20 seconds to treat a base deficit of −4 (−6, −3) mEq/l. NaHCO3 caused significant dose-dependent increases in rCBF, however population averaged ΔHb or Δ4HbO2 compared to controls were not significant.
Dose-dependent increases in cerebral blood flow (CBF) caused by bolus NaHCO3 are an important consideration in vulnerable populations wherein risk of rapid CBF fluctuations does not outweigh the benefit of treating a base deficit.
Intravenous (IV) levetiracetam (LEV) is approved for use in patients older than 16 years and may be useful in critically ill children, although there is little data available regarding pharmacokinetics. We aim to investigate the safety, an appropriate dosing, and efficacy of IV LEV in critically ill children.
We describe a cohort of critically ill children who received IV LEV for status epilepticus, including refractory or nonconvulsive status, or acute repetitive seizures.
There were no acute adverse effects noted. Children had temporary cessation of ongoing refractory status epilepticus, termination of ongoing nonconvulsive status epilepticus, cessation of acute repetitive seizures, or reduction in epileptiform discharges with clinical correlate.
IV LEV was effective in terminating status epilepticus or acute repetitive seizures and well tolerated in critically ill children. Further study is needed to elucidate the role of IV LEV in critically ill children.
levetiracetam; status epilepticus; seizure; pediatric
A complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval.
The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrine systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to the neurological system. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases.
Although neurological injury and adverse neurodevelopmental outcome can follow procedures for congenital cardiac defects, much of the variability in neurological outcome is now recognized to be more related to patient specific factors rather than procedural factors. Additionally, the recognition of pre and postoperative neurological morbidity requires procedures and imaging modalities that can be resource-intensive to acquire and analyze, and little is known or described about variations in “sampling rate” from centre to centre.
The purpose of this effort is to propose an initial set of consensus definitions for neurological complications following congenital cardiac surgery and intervention. Given the dramatic advances in understanding achieved to date, and those yet to occur, this effort is explicitly recognized as only the initial first step of a process that must remain iterative. This list is a component of a systems-based compendium of complications that may help standardize terminology and possibly enhance the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease may be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.
Congenital heart disease; quality improvement; patient safety; outcomes; registry; operative morbidity; paediatric; surgery; congenital abnormalities; cardiac surgical procedures; postoperative stroke
Periventricular leukomalacia (PVL) is part of a spectrum of cerebral white matter injury which is associated with adverse neurodevelopmental outcome in preterm infants. While PVL is common in neonates with cardiac disease, both before and after surgery, it is less common in older infants with cardiac disease. Pre-, intra-, and postoperative risk factors for the occurrence of PVL are poorly understood. The main objective of the present work is to identify potential hemodynamic risk factors for PVL occurrence in neonates with complex heart disease using logistic regression analysis and decision tree algorithms.
The postoperative hemodynamic and arterial blood gas data (monitoring variables) collected in the cardiac intensive care unit of Children's Hospital of Philadelphia were used for predicting the occurrence of PVL. Three categories of datasets for 103 infants and neonates were used-—(1) original data without any preprocessing, (2) partial data keeping the admission, the maximum and the minimum values of the monitoring variables, and (3) extracted dataset of statistical features. The datasets were used as inputs for forward stepwise logistic regression to select the most significant variables as predictors. The selected features were then used as inputs to the decision tree induction algorithm for generating easily interpretable rules for prediction of PVL.
Three sets of data were analyzed in SPSS for identifying statistically significant predictors (p < 0.05) of PVL through stepwise logistic regression and their correlations. The classification success of the Case 3 dataset of extracted statistical features was best with sensitivity (SN), specificity (SP) and accuracy (AC) of 87, 88 and 87%, respectively. The identified features, when used with decision tree algorithms, gave SN, SP and AC of 90, 97 and 94% in training and 73, 58 and 65% in test. The identified variables in Case 3 dataset mainly included blood pressure, both systolic and diastolic, partial pressures pO2 and pCO2, and their statistical features like average, variance, skewness (a measure of asymmetry) and kurtosis (a measure of abrupt changes). Rules for prediction of PVL were generated automatically through the decision tree algorithms.
The proposed approach combines the advantages of statistical approach (regression analysis) and data mining techniques (decision tree) for generation of easily interpretable rules for PVL prediction. The present work extends an earlier research [Galli KK, Zimmerman RA, Jarvik GP, Wernovsky G, Kuijpers M, Clancy RR, et al. Periventricular leukomalacia is common after cardiac surgery. J Thorac Cardiovasc Surg 2004;127:692–704] in the form of expanding the feature set, identifying additional prognostic factors (namely pCO2) emphasizing the temporal variations in addition to upper or lower values, and generating decision rules. The Case 3 dataset was further investigated in Part II for feature selection through computational intelligence.
Congenital heart disease; Data mining; Decision tree algorithms; Logistic regression; Prognostics; Periventricular leukomalacia
Preoperative brain injury is an increasingly recognized phenomenon in neonates with complex congenital heart disease. Recently, reports have been published that associate preoperative brain injury in neonates with transposition of the great arteries with the performance of balloon atrial septostomy (BAS), a procedure that improves systemic oxygenation preoperatively. It is unclear whether BAS is the cause of brain injury or is a confounder, because neonates who require BAS are typically more hypoxemic. We sought to determine the relationship between preoperative brain injury in neonates with transposition of the great arteries and the performance of BAS. We hypothesized that brain injury results from hypoxic injury, not from the BAS itself.
Methods and Results
Infants with transposition of the great arteries (n=26) were retrospectively included from a larger cohort of infants with congenital heart disease who underwent preoperative brain MRI as part of 2 separate prospective studies. Data collected included all preoperative pulse oximetry recordings, all values from preoperative arterial blood gas measurements, and BAS procedure data. MRI scans were performed on the day of surgery, before the surgical repair. Of the 26 neonates, 14 underwent BAS. No stroke was seen in the entire cohort, whereas 10 (38%) of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. Periventricular leukomalacia was not associated with BAS; however, neonates with periventricular leukomalacia had lower preoperative oxygenation (P=0.026) and a longer time to surgery (P=0.028) than those without periventricular leukomalacia.
Preoperative brain injury in neonates with transposition of the great arteries is associated with hypoxemia and longer time to surgery. We found no association between BAS and brain injury.
heart defects, congenital; oxygen; brain; catheterization; magnetic resonance imaging
To investigate the feasibility and utility of arterial spin labeling (ASL) perfusion MRI in characterizing alterations of cerebral blood flow (CBF) in pediatric patients with arterial ischemic stroke (AIS).
Materials and Methods
Ten children with AIS were studied within 4–125 hours following symptom onset, using a pulsed ASL (PASL) protocol attached to clinically indicated MR examinations. The inter-hemisphere perfusion deficit (IHPD) was measured in predetermined vascular territories and infarct regions of restricted diffusion, which were compared with the degree of arterial stenosis and volumes of ischemic infarcts.
Interpretable CBF maps were obtained in all 10 patients, showing simple lesion in 9 patients (5 hypoperfusion, 2 hyperperfusion, and 2 normal perfusion) and complex lesions in one patient. Both acute and follow-up infarct volumes were significantly larger in cases with hypoperfusion than in either hyper-or normal perfusion cases. The IHPD was found to correlate with the degree of stenosis, diffusion lesion and follow-up T2 infarct volumes. Mismatch between perfusion and diffusion lesions was observed. Brain regions presenting delayed arterial transit effects were tentatively associated with positive outcome.
This study demonstrates the clinical utility of ASL in the neuroimaging diagnosis of pediatric AIS.
Ischemic stroke; Magnetic resonance imaging; Perfusion; Pediatrics
Four very low birth weight, very premature infants were monitored during a 12° postural elevation using diffuse correlation spectroscopy (DCS) to measure microvascular cerebral blood flow (CBF) and transcranial Doppler ultrasound (TCD) to measure macrovascular blood flow velocity in the middle cerebral artery. DCS data correlated significantly with peak systolic, end diastolic, and mean velocities measured by TCD (pA =0.036, 0.036, 0.047). Moreover, population averaged TCD and DCS data yielded no significant hemodynamic response to this postural change (p>0.05). We thus demonstrate feasibility of DCS in this population, we show correlation between absolute measures of blood flow from DCS and blood flow velocity from TCD, and we do not detect significant changes in CBF associated with a small postural change (12°) in these patients.
The objective of Part II is to analyze the dataset of extracted hemodynamic features (Case 3 of Part I) through computational intelligence (CI) techniques for identification of potential prognostic factors for periventricular leukomalacia (PVL) occurrence in neonates with congenital heart disease.
The extracted features (Case 3 dataset of Part I) were used as inputs to CI based classifiers, namely, multi-layer perceptron (MLP) and probabilistic neural network (PNN) in combination with genetic algorithms (GA) for selection of the most suitable features predicting the occurrence of PVL. The selected features were next used as inputs to a decision tree (DT) algorithm for generating easily interpretable rules of PVL prediction.
Prediction performance for two CI based classifiers, MLP and PNN coupled with GA are presented for different number of selected features. The best prediction performances were achieved with 6 and 7 selected features. The prediction success was 100% in training and the best ranges of sensitivity (SN), specificity (SP) and accuracy (AC) in test were 60-73%, 74-84% and 71-74%, respectively. The identified features when used with the DTalgorithm gave best SN, SP and AC in the ranges of 87-90% in training and 80-87%, 74-79% and 79-82% in test. Among the variables selected in CI, systolic and diastolic blood pressures, and pCO2 figured prominently similar to Part I. Decision tree based rules for prediction of PVL occurrence were obtained using the CI selected features.
The proposed approach combines the generalization capability of CI based feature selection approach and generation of easily interpretable classification rules of the decision tree. The combination of CI techniques with DT gave substantially better test prediction performance than using CI and DT separately.
Congenital heart disease; Computational intelligence; Data mining; Decision tree; Genetic algorithms; Neural networks; Periventricular leukomalacia
Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. This study tests the hypothesis that congenital heart defects delay in utero structural brain development.
Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue.
The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 ± 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 ± 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development.
Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.
Background and Purpose
The Pediatric National Institutes of Health Stroke Scale (PedNIHSS), an adaptation of the adult NIH Stroke Scale, is a quantitative measure of stroke severity shown to be reliable when scored prospectively. The ability to calculate the PedNIHSS score retrospectively would be invaluable in the conduct of observational pediatric stroke studies. The study objective was to assess the concurrent validity and reliability of estimating the PedNIHSS score retrospectively from medical records.
Neurological examinations from medical records of 75 children enrolled in a prospective PedNIHSS validation study were photocopied. Four neurologists of varying training levels blinded to the prospective PedNIHSS scores reviewed the records and retrospectively assigned PedNIHSS scores. Retrospective scores were compared among raters and to the prospective scores.
Total retrospective PedNIHSS scores correlated highly with total prospective scores (R2=0.76). Interrater reliability for the total scores was “excellent” (intraclass correlation coefficient of 0.95, 95% confidence interval 0.94–0.97). Interrater reliability for individual test items was “substantial” or “excellent” for 14 of 15 items.
The PedNIHSS score can be scored retrospectively from medical records with a high degree of concurrent validity and reliability. This tool can be used to improve the quality of retrospective pediatric stroke studies.
arterial ischemic stroke; pediatric; NIH stroke scale