Ann L. McCarthy

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome

OBJECTIVE Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. METHODS Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. RESULTS A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). CONCLUSIONS A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury.

Prevalence of and risk factors for acute occlusive arterial injury following pediatric cardiac catheterization: A large single‐center cohort study

To describe the prevalence of and identify risk factors for acute occlusive arterial injury (AOAI) in a large volume pediatric cardiac catheterization laboratory.

Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox—Gastaut Syndrome

OBJECTIVE To evaluate the effectiveness of rufinamide (RFM) in patients with Lennox-Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes using time to treatment failure (retention rate) as the outcome measure. METHODS In this retrospective cohort study, characteristics and outcomes of all patients receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM failure, defined as discontinuation of RFM or initiation of an additional antiepileptic therapy. The secondary outcome measure was discontinuation of RFM. Kaplan-Meier method survival curves were generated for time to RFM failure, for all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The impact of age, seizure type, fast or slow drug titration, and concomitant therapy with valproate on retention rate were evaluated using Cox regression models. RESULTS One hundred thirty-three patients were included, 39 (30%) of whom had LGS. For all patients, the probability of remaining on RFM without additional therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31-0.83), with a median time to failure of 18 months in LGS compared to 6 months in all others (p=0.006). CONCLUSIONS In a broad population of children with refractory epilepsy, around half will continue taking the medication for at least a year without additional therapy. Patients with LGS are two times more likely to continue RFM without additional therapy compared to those without LGS.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS.

Scoring system for periventricular leukomalacia in infants with congenital heart disease.

Background:Currently two magnetic resonance imaging (MRI) methods have been used to assess periventricular leukomalacia (PVL) severity in infants with congenital heart disease: manual volumetric lesion segmentation and an observational categorical scale. Volumetric classification is labor intensive and the categorical scale is quick but unreliable. We propose the quartered point system (QPS) as a novel, intuitive, time-efficient metric with high interrater agreement.Methods:QPS is an observational scale that asks the rater to score MRIs on the basis of lesion size, number, and distribution. Pre- and postoperative brain MRIs were obtained on term congenital heart disease infants. Three independent observers scored PVL severity using all three methods: volumetric segmentation, categorical scale, and QPS.Results:One-hundred and thirty-five MRIs were obtained from 72 infants; PVL was seen in 48 MRIs. Volumetric measurements among the three raters were highly concordant (ρc = 0.94–0.96). Categorical scale severity scores were in poor agreement between observers (κ = 0.17) and fair agreement with volumetrically determined severity (κ = 0.26). QPS scores were in very good agreement between observers (κ = 0.82) and with volumetric severity (κ = 0.81).Conclusion:QPS minimizes training and sophisticated radiologic analysis and increases interrater reliability. QPS offers greater sensitivity to stratify PVL severity and has the potential to more accurately correlate with neurodevelopmental outcomes.

Pre-Operative Cerebral Hemodynamics in Infants with Critical Congenital Heart Disease

We quantified pre-operative cerebral hemodynamics with non-invasive optical spectroscopies in infants with congenital heart disease. We find that cerebral hemodynamics change from birth until surgery and depend on the type of heart defect.

Optical Monitoring of Blood Flow during Extra-Corporeal Membrane Oxygenation Therapy

Extra-corporal membrane oxygenation stabilizes patients at eminent risk of heart/lung failure. We apply diffuse optical and correlation spectroscopies to measure cerebral hemodynamics during ECMO. Initial results suggest impaired autoregulation.