Acute Diffusion-Weighted Imaging Signaling Severe Periventricular Leukomalacia in Preterm Infants: Case Report and Review of Literature.

Introduction: Periventricular leukomalacia occurs in up to 25% of very preterm infants resulting in adverse neurodevelopmental outcomes. In its acute phase, periventricular leukomalacia is clinically silent. Although ultrasonography is widely available, its sensitivity in the early detection of periventricular leukomalacia is low. Case Report and Published Literature: We identified a preterm infant with early diffusion-weighted imaging changes that later evolved to periventricular leukomalacia. Thirty-two cases of abnormal diffusion-weighted imaging reliably heralding severe periventricular leukomalacia in the preterm infant have been published in the literature. Notable features include the following: (1) infants were more mature preterm infants (29-36 weeks' gestation); (2) findings were often serendipitous with benign clinical courses; (3) diffusion-weighted imaging changes only were evident in the first weeks of life with later evolution to more classical abnormalities on conventional magnetic resonance imaging (MRI) or ultrasonography. Conclusion: Diffusion-weighted imaging in the first week of life may be a reliable early marker of severe periventricular leukomalacia injury in more mature preterm infants.

Amplitude-Integrated Electroencephalography Evolution and Magnetic Resonance Imaging Injury in Mild and Moderate to Severe Neonatal Encephalopathy.

OBJECTIVE: This study aimed to describe the evolution of amplitude-integrated electroencephalography (aEEG) in neonatal encephalopathy (NE) during therapeutic hypothermia (TH) and evaluate the association between aEEG parameters and magnetic resonance imaging (MRI) injury. STUDY DESIGN: aEEG data of infants who underwent TH were reviewed for background, sleep wake cycling (SWC), and seizures. Conventional electroencephalography (cEEG) background was assessed from the reports. Discordance of background on aEEG and cEEG was defined if there was a difference in the severity of the background. MRI injury (total score ≥ 5) was assessed by using the Weeke scoring system. RESULTS: A total of 46 infants were included; 23 (50%) with mild NE and 23 (50%) with moderate to severe NE. Comparing mild NE with moderate to severe NE, the initial aEEG background differed with more mild being continuous (70 vs. 52%), with fewer being discontinuous (0 vs. 22%) and flat tracing (0 vs. 4%), whereas burst suppression (4 vs. 4%) and low voltage (26 vs. 18%) did not differ. There was a notably common discordance between the background assessment on cEEG with aEEG in 82% with continuous and 40% low voltage aEEG background. MRI abnormalities were identified in four infants with mild NE and seven infants with moderate to severe NE. MRI injury was associated with aEEG seizures in infants with moderate to severe NE. CONCLUSION: aEEG seizures are useful to predict MRI injury in moderate to severe NE infants. There is a large discrepancy between aEEG, cEEG, and MRI in neonates treated by TH. KEY POINTS: · MRI injury was identified in 29% of moderate NE infants and in 50% of severe NE infants.. · aEEG seizures were associated with MRI injury in the moderate to severe NE infants.. · MRI injury was identified in 16% infants with mild NE.. · Mild NE infants with normal aEEG were unlikely to have MRI injury.. · There was a large discrepancy between aEEG, cEEG, and MRI in infants treated by TH..

Association of early cerebral oxygen saturation and brain injury in extremely preterm infants.

OBJECTIVE: To assess the association between cerebral saturation (crSO2) using Near-Infrared Spectroscopy (NIRS) and brain injury in extremely preterm infants. STUDY DESIGN: This retrospective study includes 62 infants (<28 weeks gestation) who underwent continuous NIRS monitoring in the first 5 days after birth. Median crSO2 were compared in 12 h increments between infants with and without germinal matrix/intraventricular hemorrhage (GM/IVH). crSO2 was also compared by IVH severity, onset, and by grade of injury on term equivalent MRI. RESULTS: After 48 h of life (HOL), infants with GM/IVH had significantly lower crSO2 than those without GM/IVH in analysis adjusted for potential confounding e.g., at 49-60 HOL (69.5 (66.2, 72.8) vs. 74.7 (71.8, 77.6), p = 0.023). There were no significant differences in crSO2 by IVH subcategory or injury severity on MRI. CONCLUSION: Clinical use of NIRS has the potential to identify crSO2 patterns associated with development of GM/IVH.

Blood gas measures as predictors for neonatal encephalopathy severity.

OBJECTIVE: To correlate arterial umbilical cord gas (aUCG) and infant blood gas with severity of neurological injury. STUDY DESIGN: Retrospective single-site study of infants evaluated for therapeutic hypothermia. Clinical neurological examination and a validated MRI scoring system were used to assess injury severity. RESULTS: Sixty-eight infants were included. aUCG base deficit (BD) and lactate correlated with infant blood gas counterparts (r = 0.43 and r = 0.56, respectively). aUCG and infant pH did not correlate. Infant blood gas lactate (RADJ2 = 0.40), infant BD (RADJ2 = 0.26), infant pH (RADJ2 = 0.17), aUCG base deficit (RADJ2 = 0.08), and aUCG lactate (RADJ2 = 0.11) were associated with clinical neurological examination severity. aUCG and infant blood gas measures were not correlated with MRI score. CONCLUSION: Metabolic measures from initial infant blood gases were most associated with the clinical neurological examination severity and can be used to evaluate hypoxic-ischemic cerebral injury risk.

Association between cerebral oxygen saturation and brain injury in neonates receiving therapeutic hypothermia for neonatal encephalopathy.

OBJECTIVE: To assess the association of cerebral oxygen saturation (CrSO2) collected by near infrared spectroscopy (NIRS) during therapeutic hypothermia (TH) and rewarming with evidence of brain injury on post-rewarming MRI. STUDY DESIGN: This retrospective cohort study included 49 infants, who received TH for mild to severe neonatal encephalopathy. Of those, 26 presented with brain injury assessed by a novel MRI grading system, whereas 23 had normal MRI scans. RESULTS: CrSO2 increased significantly from the first to the second day of TH in infants with brain injury, whereas it remained stable in patients with normal MRI. Increasing mean CrSO2 values during rewarming was associated with brain injury (aOR 1.14; 95% CI 1.00-1.28), specifically with gray matter (GM) injury (aOR 1.23; 95% CI 1.02-1.49). The area under the ROC curve showed an excellent discrimination for GM involvement. CONCLUSION: Clinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

Encephalopathy in neonates with subgaleal hemorrhage is a key predictor of outcome.

BACKGROUND: Subgaleal hemorrhage (SGH) is reported to be associated with severe hemodynamic instability, coagulopathy, and even mortality. The importance of the presence or absence of neonatal encephalopathy in predicting SGH outcomes has not been explored. The aim of this study was to determine the relationship of clinical encephalopathy to short-term outcomes in neonates with SGH. METHODS: Neonates ≥35 weeks gestation, diagnosed radiologically with SGH between 2010 and 2017, were included. Cases were divided into encephalopathic and non-encephalopathic. Demographic, clinical, and outcome data were compared between groups. RESULTS: Of 54,048 live births, 56 had SGH, of them 13 (23%) had encephalopathy. When compared to the non-encephalopathic neonates, encephalopathic neonates had lower Apgar scores, lower hemoglobin, lower platelet count, longer neonatal intensive care unit stay, two (15%) deaths, and four (31%) required blood transfusion. No non-encephalopathic infant with SGH died or required blood transfusion. Notably, on magnetic resonance imaging (MRI), a majority of subgaleal collections had either no or minimal blood products. CONCLUSIONS: In the absence of encephalopathy, SGH is not associated with adverse short-term outcome. Neurological assessment is likely to identify infants at higher risk for adverse outcome. The absence of MRI signal consistent with blood in subgaleal collection warrants further research.

Dysmaturation of Premature Brain: Importance, Cellular Mechanisms, and Potential Interventions.

Prematurity, especially preterm birth (less than 32 weeks' gestation), is common and associated with high rates of both survival and neurodevelopmental disability, especially apparent in cognitive spheres. The neuropathological substrate of this disability is now recognized to be related to a variety of dysmaturational disturbances of the brain. These disturbances follow initial brain injury, particularly cerebral white matter injury, and involve many of the extraordinary array of developmental events active in cerebral white and gray matter structures during the premature period. This review delineates these developmental events and the dysmaturational disturbances that occur in premature infants. The cellular mechanisms involved in the genesis of the dysmaturation are emphasized, with particular focus on the preoligodendrocyte. A central role for the diffusely distributed activated microglia and reactive astrocytes in the dysmaturation is now apparent. As these dysmaturational cellular mechanisms appear to occur over a relatively long time window, interventions to prevent or ameliorate the dysmaturation, that is, neurorestorative interventions, seem possible. Such interventions include pharmacologic agents, especially erythropoietin, and particular attention has also been paid to such nutritional factors as quality and source of milk, breastfeeding, polyunsaturated fatty acids, iron, and zinc. Recent studies also suggest a potent role for interventions directed at various experiential factors in the neonatal period and infancy, i.e., provision of optimal auditory and visual exposures, minimization of pain and stress, and a variety of other means of environmental behavioral enrichment, in enhancing brain development.

Differences in subependymal vein anatomy may predispose preterm infants to GMH-IVH.

BACKGROUND AND PURPOSE: The anatomy of the deep venous system plays an important role in the pathogenesis of brain lesions in the preterm brain as shown by different histological studies. The aims of this study were to compare the subependymal vein anatomy of preterm neonates with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH), as evaluated by susceptibility-weighted imaging (SWI) venography, with a group of age-matched controls with normal brain MRI, and to explore the relationship between the anatomical features of subependymal veins and clinical risk factors for GMH-IVH. METHODS: SWI venographies of 48 neonates with GMH-IVH and 130 neonates with normal brain MRI were retrospectively evaluated. Subependymal vein anatomy was classified into six different patterns: type 1 represented the classic pattern and types 2-6 were considered anatomic variants. A quantitative analysis of the venous curvature index was performed. Variables were analysed by using Mann-Whitney U and χ2 tests, and a multiple logistic regression analysis was performed to evaluate the association between anatomical features, clinical factors and GMH-IVH. RESULTS: A significant difference was noticed among the six anatomical patterns according to the presence of GMH-IVH (χ2=14.242, p=0.014). Anatomic variants were observed with higher frequency in neonates with GMH-IVH than in controls (62.2% and 49.6%, respectively). Neonates with GMH-IVH presented a narrower curvature of the terminal portion of subependymal veins (p<0.05). These anatomical features were significantly associated with GMH-IVH (p<0.05). CONCLUSION: Preterm neonates with GMH-IVH show higher variability of subependymal veins anatomy confirming a potential role as predisposing factor for GMH-IVH.

A Century of Germinal Matrix Intraventricular Hemorrhage in Autopsied Premature Infants: A Historical Account.

The care of premature infants in the 20th century is remarkable for technical advances that have dramatically improved survival, but little is known about temporal changes in the neuropathology of the premature infant over this time frame. We hypothesize that the autopsy rate of germinal matrix hemorrhage changed in the 20th century relative to combined influences of clinical interventions that were both harmful and helpful. We examined germinal matrix hemorrhage with intraventricular hemorrhage (GMH-IVH) in 345 premature infants (gestational age 25-36 weeks) autopsied at Boston Children's Hospital from 1914 to 2015. There was a median of 19 cases/decade (range 7-68). Over the course of the study median gestational age decreased from 33 to 27 gestational weeks (P<0.001), and median postnatal survival increased from 2 to 26 days (P=0.02). The incidence of GMH-IVH increased from 4.7% before 1960 to 50.0% from 1975 to 1980, and then decreased to 12.5% after 2005 (P<0.001). The incidence of GMH-IVH increased >3-fold around the time of the introduction of positive pressure ventilation into premature intensive care in the mid-1960s. The increased incidence of GMH-IVH in the 1970s-1980s likely reflects respiratory and hemodynamic imbalances complicating mechanical ventilation. We speculate that the subsequent decreased incidence of GMH-IVH likely reflects stabilization of respiratory function with improvements in ventilators and in ventilator management beginning in the 1970s and the use of surfactant and antenatal steroids in the 1980s.