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Objective To investigate how functional integrity of ascending sensory pathways measured by visual and somatosensory evoked potentials (VEP & SEP) is associated with abnormal glycemia and brain injury in newborns treated with hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods Fifty-four neonates ≥ 36 weeks gestational age with HIE underwent glucose testing, VEPs, SEPs, and magnetic resonance imaging (MRI) the first week of life. Minimum and maximum glucose values recorded prior to evoked potential (EP) testing were compared with VEP and SEP measures using generalized estimating equations. Relationships between VEP and SEP measures and brain injury on MRI were assessed. Results Maximum glucose is associated with decreased P200 amplitude, and increased odds that N300 peak will be delayed/absent. Minimum glucose is associated with decreased P22 amplitude. Presence of P200 and N300 peaks is associated with decreased odds of brain injury in the visual processing pathway, with delayed/absent N300 peak associated with increased odds of brain injury in posterior white matter. Conclusions Deviations from normoglycemia are associated with abnormal EPs, and abnormal VEPs are associated with brain injury on MRI in cooled neonates with HIE. Significance Glucose is a modifiable risk factor associated with atypical brain function in neonates with HIE despite hypothermia treatment.

Objective To investigate the relationship between cerebellar hemorrhage in preterm infants seen on magnetic resonance imaging (MRI), but not on ultrasonography, and neurodevelopmental outcome. Study design Images from a cohort study of MRI in preterm newborns were reviewed for cerebellar hemorrhage. The children were assessed at a mean age of 4.8 years with neurologic examination and developmental testing using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Results Cerebellar hemorrhage was detected on both ultrasonography and MRI in 3 of the 131 preterm newborns evaluated, whereas smaller hemorrhages were seen only on MRI in 10 newborns (total incidence, 10%). Adjusting for gestational age at birth, intraventricular hemorrhage, and white matter injury, cerebellar hemorrhage detectable solely by MRI was associated with a 5-fold increased odds of abnormal neurologic examination compared with newborns without cerebellar hemorrhage (outcome data in 74%). No association with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition score was found. Conclusions Cerebellar hemorrhage is not uncommon in preterm newborns. Although associated with neurologic abnormalities, hemorrhage seen only on MRI is associated with much more optimistic outcomes than that visible on ultrasonography.

Since the original description of hypsarrhythmia by visual inspection as a “chaotic” and disorganized pattern in 1954, we have continued this clinical practice of EEG interpretation with solely visual inspection until the present day. The description of hypsarrhythmia as “chaotic” [Gibbs EL, Fleming MM, Gibbs FA. Pediatrics 1954;13(1):66–73], was challenged by van Putten and Stam 17 years ago [IEEE Eng Med Biol Mag. 2001;20(5):72–9]. We are now conducting the first prospective study in newborn babies with risk factors for infantile spasms. Our rational is that 40 out of the 200 known risk factors can be detected during the neonatal period. After consent, we conduct the longitudinal EEG protocol every 2 months until 1 year of age. Phase synchrony and variability analyses are performed to detect the earliest EEG changes before hypsarrhythmia onset. The EEG analyses from the dynamics perspective opens a new examination of hypsarrhythmia and electrodecremental events (EDEs) in infantile spasms, beyond the sole visual inspection of the EEG. We will present cases to illustrate the value of the phase synchronization index and the temporal variability of the index. Preliminary data suggest that both abnormal EEG patterns, hypsarrhythmia and EDEs are associated with high phase synchronization. These preliminary findings question the prevailing notion that hysparrhythmia is a disorganized pattern and may account for the observed developmental stagnation in these children. The visual inspection of hypsarrhythmia does not appear sufficient to appreciate the highly synchronized EEG pattern in patients with infantile spasms.

Objective To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). Study design A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. Results A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume ( P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume ( P = .30). Greater morphine exposure also predicted poorer motor ( P P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. Conclusions Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.