Daniel J. Licht

Brain maturation is delayed in infants with complex congenital heart defects.

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Pediatric Perfusion Imaging Using Pulsed Arterial Spin Labeling

To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T.

Preoperative Brain Injury in Transposition of the Great Arteries Is Associated With Oxygenation and Time to Surgery, Not Balloon Atrial Septostomy

Background— 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. Conclusions— 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.

Reference Range for Cerebrospinal Fluid Opening Pressure in Children

To the Editor: A reference range for cerebrospinal fluid (CSF) opening pressure in children undergoing diagnostic lumbar puncture has not been established.1 The influence of age, body-mass index (B...

Mimics of Childhood Stroke: Characteristics of a Prospective Cohort

BACKGROUND. Little is known about the clinical features and spectrum of diagnoses in children with “stroke mimics,” those with acute neurologic deficits but without cerebrovascular diseases. OBJECTIVES. Our goal was to describe patients with stroke mimics and to determine if clinical features predict benign diagnoses. METHODS. Our stroke consult team registered a prospective consecutive cohort of 143 patients with acute presentations suspicious for cerebrovascular disease from November 2003 to November 2004. Cases in which stroke was ruled out (stroke mimics) were reviewed for clinical features and diagnostic test results and were classified “benign” if there was no structural brain lesion and there was an expectation of complete recovery. RESULTS. Of the 143 cases evaluated for suspected stroke, 30 (21%) had stroke mimics. Presenting signs included seizure (n = 11), headache (n = 9), mental status change (n = 6), focal weakness (n = 14), and focal sensory change (n = 7). Eleven patients had “benign” diagnoses (3 migraine, 3 psychogenic diagnoses, 3 musculoskeletal abnormalities, 1 delirium, and 1 episodic vital sign changes). Nineteen patients had “not-benign” diagnoses (3 reversible posterior leukoencephalopathy syndrome, 3 neonatal seizures, 2 vascular anomalies, 2 inflammatory disease, 2 intracranial infection, 2 epilepsy, 2 metabolic stroke, 1 tumor, 1 drug toxicity, and 1 idiopathic intracranial hypertension). Except for the presence of seizures, there were no significant differences in presentation or risk factors between benign and not-benign cases. CONCLUSIONS. Many disorders mimic childhood stroke. History and clinical presentation often do not distinguish the one third of patients with benign disorders from the two thirds with more serious problems, necessitating timely comprehensive investigations, especially brain MRI.

Cerebral hemodynamics in preterm infants during positional intervention measured with diffuse correlation spectroscopy and transcranial Doppler ultrasound

Four very low birth weight, very premature infants were monitored during a 12 degrees 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 (p(A) =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 degrees ) in these patients.

Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects

We employ a hybrid diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) monitor for neonates with congenital heart disease (n=33). The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow (rCBF(DCS)); and oxygen metabolism (rCMRO(2)). Concurrent measurements with arterial spin-labeled magnetic resonance imaging (rCBF(ASL-MRI), n=12) cross-validate rCBF(DCS) against rCBF(ASL-MRI), showing good agreement (R=0.7, p=0.01). The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population.

Predictors of Outcome in Childhood Intracerebral Hemorrhage A Prospective Consecutive Cohort Study

Background and Purpose— The purposes of this study were to describe features of children with intracerebral hemorrhage (ICH) and to determine predictors of short-term outcome in a single-center prospective cohort study. Methods— A single-center prospective consecutive cohort study was conducted of spontaneous ICH in children aged 1 to 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 and Kings Outcome Scale for Childhood Head Injury. ICH volumes and total brain volumes were measured by manual tracing. Results— Twenty-two patients, median age 10.3 years (range, 4.2 to 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 a median follow-up of 3.5 months (range, 0.3 to 7.5 months), 71% of survivors had neurological deficits; 55% had clinically significant disability. Outcome based on Pediatric Stroke Outcome Measure and Kings Outcome Scale for Childhood Head Injury scores was worse in patients with ICH volume >2% of total brain volume (P=0.023) and altered mental status at presentation (P=0.005). Conclusions— 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.

Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics.

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO2) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (SvO2) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO2 in physiologic units. In addition, microvascular tissue oxygenation (StO2) and indices of microvascular CBF (BFI) and CMRO2 (CMRO2i) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O2/minute per 100 g, respectively. These CBF and CMRO2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global SvO2, CBF, and CMRO2 with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R2=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

The Cerebral Vasculopathy of PHACES Syndrome

Background and Purpose— PHACES syndrome is a neurocutaneous disorder of unknown etiology. We studied the spectrum of associated congenital and progressive cerebral vascular anomalies. Methods— The medical records of 7 patients with PHACES syndrome were reviewed and combined with an additional 108 PHACES cases identified from the literature. We reviewed the clinical characteristics, calculated the relative frequencies of each type of vascular anomaly, and assessed site of vessel involvement relative to hemangioma location. Results— Among a total of 115 PHACES cases, 89 (77.4%) had congenital and/or progressive cerebral vascular anomalies. The most commonly detected congenital arterial anomalies included dysplasia, aberrant origin or course, hypoplasia, and absence or agenesis. Arterial occlusions and stenoses were detected in 24 (20.9%) and 21 (18.3%) cases, respectively. Twenty (17.4%) had persistent embryonic arteries; 15 (13%) had saccular aneurysms. There appears to be a close relation between the regional distributions of cervicofacial hemangiomas and the locations of intracranial and extracranial vascular (and cardiac) anomalies. Conclusion— The vasculopathy of PHACES chiefly comprises a spectrum of congenital and progressive large artery lesions. Based on known embryology and the relative frequencies of specific congenital vascular anomalies, we can predict that the initial cerebral vascular changes occur early in embryogenesis, by the fifth gestational week or earlier. There appears to be both a temporal and a regional link between the arterial anomalies of PHACES and the cutaneous infantile hemangioma.