Neonatal brain injury may impact brain development and lead to lifelong functional impairments. Hypoxic-ischemic encephalopathy (HIE) and congenital heart disease (CHD) are two common causes of ...neonatal brain injury differing in timing and mechanism. Maturation of whole-brain neural networks can be quantified during development using diffusion magnetic resonance imaging (dMRI) in combination with graph theory metrics. DMRI of 35 subjects with CHD and 62 subjects with HIE were compared to understand differences in the effects of HIE and CHD on the development of network topological parameters and functional outcomes. CHD newborns had worse 12-18 month language (P<0.01) and 30 month cognitive (P<0.01), language (P = 0.05), motor outcomes (P = 0.01). Global efficiency, a metric of brain integration, was lower in CHD (P = 0.03) than in HIE, but transitivity, modularity and small-worldness were similar. After controlling for clinical factors known to affect neurodevelopmental outcomes, we observed that global efficiency was highly associated with 30 month motor outcomes (P = 0.02) in both groups. To explore neural correlates of adverse language outcomes in CHD, we used hypothesis-based and data-driven approaches to identify pathways with altered structural connectivity. We found that connectivity strength in the superior longitudinal fasciculus (SLF) tract 2 was inversely associated with expressive language. After false discovery rate correction, a whole connectome edge analysis identified 18 pathways that were hypoconnected in the CHD cohort as compared to HIE. In sum, our study shows that neonatal structural connectivity predicts early motor development after HIE or in subjects with CHD, and regional SLF connectivity is associated with language outcomes. Further research is needed to determine if and how brain networks change over time and whether those changes represent recovery or ongoing dysfunction. This knowledge will directly inform strategies to optimize neurologic functional outcomes after neonatal brain injury.
COL4A1/A2 variants affecting the alpha 1 and 2 chains of type IV collagen are increasingly recognized as a cause of fetal and neonatal intracranial hemorrhage, porencephaly, and schizencephaly. Fetal ...magnetic resonance imaging (MRI) findings in COL4A1/A2-related disorders are not well characterized.
This is a retrospective case series of fetal MRI findings in eight patients with intraparenchymal hemorrhage (IPH) and COL4A1/A2 variants, five of whom have postnatal imaging and clinical follow-up.
IPH was multifocal and bilateral in four of eight patients. IPH involved the frontal lobes in all cases and basal ganglia in six of eight. The median maximum diameter of IPH was 16 mm (range 6 to 65 mm). All patients had ventriculomegaly, and four of eight had intraventricular hemorrhage. Prenatal IPH size correlated clinically with motor outcomes, and none had clinically symptomatic recurrent hemorrhage.
COL4A1/A2 variants can present with a spectrum of IPH prenatally, including small and/or unifocal IPH, as well as multifocal and bilateral IPH, involving the frontal lobes and basal ganglia. Given the wide spectrum of IPH severity seen on fetal brain MRI, genetic testing for COL4A1/A2 variants should be considered in all cases of fetal IPH.
Objective To determine the association of antenatal magnesium sulfate with cerebellar hemorrhage in a prospective cohort of premature newborns evaluated by magnetic resonance imaging (MRI). Study ...design Cross-sectional analysis of baseline characteristics from a prospective cohort of preterm newborns (<33 weeks gestation) evaluated with 3T-MRI shortly after birth. Exclusion criteria were clinical evidence of a congenital syndrome, congenital infection, or clinical status too unstable for transport to MRI. Antenatal magnesium sulfate exposure was abstracted from the medical records and the indication was classified as obstetric or neuroprotection. Two pediatric neuroradiologists, blinded to the clinical history, scored axial T2-weighted and iron susceptibility MRI sequences for cerebellar hemorrhage. The association of antenatal magnesium sulfate with cerebellar hemorrhage was evaluated using multivariable logistic regression, adjusting for postmenstrual age at MRI and known predictors of cerebellar hemorrhage. Results Cerebellar hemorrhage was present in 27 of 73 newborns (37%) imaged at a mean ± SD postmenstrual age of 32.4 ± 2 weeks. Antenatal magnesium sulfate exposure was associated with a significantly reduced risk of cerebellar hemorrhage. Adjusting for postmenstrual age at MRI, and predictors of cerebellar hemorrhage, antenatal magnesium sulfate was independently associated in our cohort with decreased cerebellar hemorrhage (OR, 0.18; 95% CI, 0.049-0.65; P = .009). Conclusion Antenatal magnesium sulfate exposure is independently associated with a decreased risk of MRI-detected cerebellar hemorrhage in premature newborns, which could explain some of the reported neuroprotective effects of magnesium sulfate.
Objectives To determine the rate of magnetic resonance imaging (MRI)-detected noncystic white matter injury (WMI) in a prospective cohort of premature newborns, and to evaluate its associations with ...changes in clinical predictors of WMI over the study period. Study design A prospective cohort of premature newborns (<33 weeks gestational age) was studied with MRI within 4 weeks of birth and near term-equivalent age. A pediatric neuroradiologist scored the severity of WMI on T1 -weighted MRI according to published criteria. WMI was classified as none/mild or moderate/severe. Subjects with severe cystic WMI, periventricular hemorrhagic infarction, or motion artifact on MRI were excluded. Changes in clinical characteristics and predictors of WMI over the study period (1998-2011) were evaluated. Predictors of moderate/severe WMI, including birth year, were evaluated using multivariate logistic regression. Results Among 267 newborns, 45 (17%) had moderate/severe WMI. The rate of moderate/severe WMI decreased over the study period ( P = .002, χ2 test for trends). On multivariate logistic regression, the odds of moderate/severe WMI decreased by 11% for each birth year of the cohort (OR, 0.89; 95% CI, 0.81-0.98; P = .02). Prolonged exposure to indomethacin also was independently associated with reduced odds of moderate/severe WMI. Conclusion The decreasing burden of MRI-detected moderate/severe noncystic WMI in our cohort of premature newborns is independent over time of changes in the known clinical predictors of WMI. Prolonged exposure to indomethacin is associated with reduced WMI.
Objective
Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients.
Methods
Blood was obtained before and after ...serial monthly natalizumab infusions to track functional expression of VLA‐4 and migratory capacity of immune cells. The impact of infusion on activation thresholds of immune cells was evaluated.
Results
Preinfusion VLA‐4 expression differed across immune cell subsets. Natalizumab significantly, albeit partially, diminished VLA‐4 expression on circulating immune cells. Cell subsets were differentially affected. Treatment significantly decreased migratory capacity of immune cells, correlating well with changes in VLA‐4 expression. Effects of a single dose were not saturating and did not persist through the monthly dose interval. Infusion effect varied across patients but was remarkably stable in individual patients, over multiple infusions. Treatment significantly modulated proliferative responses of immune cells.
Interpretation
To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations. Ann Neurol 2006;59:748–754
Abstract Background To evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy. Methods ...A nested case-control study of infantile spasms in children with term neonatal hypoxic-ischemic encephalopathy was performed. All patients had T1 /T2 -weighted magnetic resonance imaging with diffusion-weighted imaging performed on the third day of life. Using a validated scoring system, the magnetic resonance imaging was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1 /T2 -weighted magnetic resonance imaging and diffusion-weighted imaging blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. Results Eight patients who developed infantile spasms were identified among a cohort of 176 term newborns with hypoxic-ischemic encephalopathy (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal hypoxic-ischemic encephalopathy was significantly associated with basal ganglia/thalamus and total brain injury ( P = 0.001), extent of cortical injury greater than 50% (odds ratio = 11.7, 95% confidence interval = 1.1-158.5, P = 0.01), injury to the midbrain (odds ratio = 13, 95% confidence interval = 1.3-172, P = 0.007) and hypothalamic abnormalities ( P = 0.01). Conclusions The development of infantile spasms after hypoxic-ischemic encephalopathy is associated with injury to the basal ganglia and thalami on neonatal magnetic resonance imaging, particularly when extensive cortical injury and/or injury to the midbrain is present.
Prematurity and congenital heart disease (CHD) are individually associated with increased risk of brain injury and adverse neurodevelopmental outcomes. Delayed brain development in newborns with CHD ...has been documented to begin in utero and predisposes newborns with CHD to brain injury. Little is known about the combined risks when prematurity and CHD co-occur. The purpose of this review is to highlight the unique vulnerability of preterm newborns with CHD to brain dysmaturation and brain injury, and the urgent need for prospective research.
PDF
