Miriam Martinez-Biarge

Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy

Central grey matter damage following perinatal hypoxia-ischaemia frequently leads to death or motor abnormality often with deficits in other developmental domains. Predicting these different outcomes is difficult yet very important for early management, planning and providing for needs on discharge and later and not least for parents to know how their children will be affected. The best single predictor of the pattern of outcomes for an individual infant is an early MRI scan. We present a guide for predicting outcome at 2 years in different developmental domains based on the severity of injury seen in the basal ganglia and thalami (BGT) on neonatal MRI.

White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome.

OBJECTIVE To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami. STUDY DESIGN From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years. RESULTS The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ρ = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth. CONCLUSION Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.

Antepartum and Intrapartum Factors Preceding Neonatal Hypoxic-Ischemic Encephalopathy

OBJECTIVE: To determine whether antepartum factors alone, intrapartum factors alone, or both in combination, are associated with term neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: A total of 405 infants ≥35 weeks’ gestation with early encephalopathy, born between 1992 and 2007, were compared with 239 neurologically normal infants born between 1996 and 1997. All cases met criteria for perinatal asphyxia, had neuroimaging findings consistent with acute hypoxia-ischemia, and had no evidence for a non–hypoxic-ischemic cause of their encephalopathy. RESULTS: Both antepartum and intrapartum factors were associated with the development of HIE on univariate analysis. Case infants were more often delivered by emergency cesarean delivery (CD; 50% vs 11%, P < .001) and none was delivered by elective CD (vs 10% of controls). On logistic regression analysis only 1 antepartum factor (gestation ≥41 weeks) and 7 intrapartum factors (prolonged membrane rupture, abnormal cardiotocography, thick meconium, sentinel event, shoulder dystocia, tight nuchal cord, failed vacuum) remained independently associated with HIE (area under the curve 0.88; confidence interval 0.85–0.91; P < .001). Overall, 6.7% of cases and 43.5% of controls had only antepartum factors; 20% of cases and 5.8% of controls had only intrapartum factors; 69.5% of cases and 31% of controls had antepartum and intrapartum factors; and 3.7% of cases and 19.7% of controls had no identifiable risk factors (P < .001). CONCLUSIONS: Our results do not support the hypothesis that HIE is attributable to antepartum factors alone, but they strongly point to the intrapartum period as the necessary factor in the development of this condition.

General movements in full-term infants with perinatal asphyxia are related to Basal Ganglia and thalamic lesions.

OBJECTIVE To correlate the site and severity of brain lesions seen on magnetic resonance imaging (MRI) with the quality of general movements in term infants with hypoxic-ischemic encephalopathy (HIE) and compare the prognostic value of general movements and MRI for motor outcome. STUDY DESIGN Early brain MRI scans in 34 term infants with HIE not treated with hypothermia were reviewed and scored for site of injury and lesion pattern by an experienced neuroradiologist. General movement quality and trajectories at 1 and 3 postnatal months were evaluated. Motor outcome was assessed at 24 months. RESULTS MRI scores for the basal ganglia and thalami, posterior limb of the internal capsule, white matter, and cortex and lesion patterns were correlated with 1-month and 3-month general movements and general movement trajectories; central gray matter scores were correlated most strongly with cramped-synchronized general movements and abnormal motor outcome. MRI scores were 100% sensitive and 72.2% specific for motor outcome, and cramped-synchronized general movements were 100% specific and 68.7% sensitive for motor outcome. CONCLUSIONS In term infants with HIE, the site and severity of brain lesions seen on early MRI are highly correlated with general movements. Central gray matter damage leads to cramped-synchronized general movements and poor motor outcome. Early MRI scans and general movements are complementary tools for predicting motor outcome.

Feeding and communication impairments in infants with central grey matter lesions following perinatal hypoxic–ischaemic injury

BACKGROUND Basal ganglia and thalamic (BGT) injury is common after acute perinatal hypoxia-ischaemia. Cerebral palsy is the most obvious consequence of BGT injury affecting 70-75% of survivors and is predictable from neonatal magnetic resonance imaging (MRI). However there is no equivalent predictive data for other specific outcomes. Feeding and communication impairments are also common in children following hypoxic-ischaemic encephalopathy (HIE) and BGT injury. AIMS To describe, in infants with HIE and BGT injury, the prevalence of feeding and communication impairments; and to evaluate the accuracy of early MRI for predicting these outcomes. METHODS 175 term infants with HIE and BGT injury were studied. Brain lesions were classified by site and severity from the MRI scans. Motor, feeding and communication impairments were documented at 2 years. RESULTS Feeding and communication impairments occurred in 65% and 82% of 126 survivors respectively and related strongly to the severity of motor impairment. Forty-one children had a gastrostomy or long-term nasogastric tube. Injury severity in all brain regions was significantly associated with feeding and communication impairment on univariate analysis. On logistic regression analysis BGT (OR 10.9) and mesencephalic lesions (OR 3.7) were independently associated with feeding impairment; BGT (OR 10.5) and pontine lesions (OR 3.8) were associated with gastrostomy; the severity of BGT lesions (OR 20.1) was related to the severity of communication impairment. CONCLUSIONS Feeding and communication impairment are very common in children with BGT and brainstem injury of neonatal origin and can be well predicted from early MRI scans.

Neurodevelopmental outcome in children with congenital heart disease

Children with congenital heart disease (CHD) have multiple factors contributing toward their risk of later neurodevelopmental difficulties. With earlier diagnosis and improved survival rates, the management of CHD now includes the recognition of neurodevelopmental risks and optimisation of neurodevelopmental outcomes is emphasised. Neuroimaging studies have shown early differences in brain development for children with CHD, who then are vulnerable to additional brain injury in the perinatal period. For some children, complications and co-morbidities may further increase the risk of brain injury. Synthesis of multiple factors is necessary to estimate neurodevelopmental prognosis for an individual child. Long-term neurodevelopmental follow-up of children with CHD is warranted for early identification of and intervention for difficulties.

MRI Based Preterm White Matter Injury Classification: The Importance of Sequential Imaging in Determining Severity of Injury

Background The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings. Methods Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI. Results 138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2–6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami. Conclusion In infants with extensive WM cysts at 2–6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI.

A Prognostic Neonatal Neuroimaging Scale for Symptomatic Congenital Cytomegalovirus Infection

Background: Congenital cytomegalovirus (cCMV) can cause brain inflammation/destruction and teratogenic effects. The only validated neuroimaging prognostic categorization for symptomatic cCMV available is based on destructive lesions seen on computed tomography (CT). Objective: The aim of this study was to establish the predictive ability of a comprehensive neonatal neuroimaging scale in symptomatic cCMV. Methods: Twenty-six infants were studied by neonatal cranial ultrasound scans (US; n = 25), CT (n = 11) and magnetic resonance imaging (MRI; n = 9). A previously validated neuroimaging scale comprising calcifications, ventriculomegaly and atrophy was compared to a newly proposed system adding cerebral dysgenesis and white matter disease. The findings were graded from 0 to 3. Neurodevelopmental assessment included motor and cognitive functions, epilepsy, vision, hearing and behavioral disorders. Results: Both scales showed a significant association with outcome (p < 0.005). Our scale was more accurate in predicting death or moderate-severe disability (area under the curve for scores ≥2, 0.88 ± 0.06 vs. 0.80 ± 0.08). All 5 infants with normal neuroimaging survived with intact neurological function. While our scale was highly associated with outcome in patients studied by MRI, it was unable to predict unfavorable outcomes in 2 patients with mildly abnormal US and/or CT. Conclusions: A comprehensive scale based on US and MRI predicts neurodevelopment in symptomatic cCMV. Significant destructive lesions are associated with a poor prognosis. While a strictly normal cranial US predicts a favorable outcome, in case of subtle US abnormalities, MRI is crucial for prognostication.

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy had favourable outcomes at a referral hospital in a middle-income country.

This South African study documented the survival and neurodevelopmental outcomes of infants with hypoxic‐ischaemic encephalopathy (HIE) after introducing cooling to a neonatal intensive care unit and identified early markers for neurodevelopmental outcome.

Neurodevelopment After Perinatal Arterial Ischemic Stroke

With this study, we distinguish different neurodevelopmental outcome domains in perinatal stroke subtypes and specify several risk factors for these outcomes. BACKGROUND AND OBJECTIVES: Perinatal arterial ischemic stroke (PAIS) leads to cerebral palsy in ∼30% of affected children and has other neurologic sequelae. Authors of most outcome studies focus on middle cerebral artery (MCA) stroke without differentiating between site and extent of affected tissue. Our aim with this study was to report outcomes after different PAIS subtypes. METHODS: Between 1990 and 2015, 188 term infants from 2 centers (London [n = 79] and Utrecht [n = 109]) had PAIS on their neonatal MRI. Scans were reevaluated to classify stroke territory and determine specific tissue involvement. At 18 to 93 (median 41.7) months, adverse neurodevelopmental outcomes were recorded as 1 or more of cerebral palsy, cognitive deficit, language delay, epilepsy, behavioral problems, or visual field defect. RESULTS: The MCA territory was most often involved (90%), with posterior or anterior cerebral artery territory strokes occurring in 9% and 1%, respectively. Three infants died, and 24 had scans unavailable for reevaluation or were lost to follow-up. Of 161 infants seen, 54% had an adverse outcome. Outcomes were the same between centers. Main branch MCA stroke resulted in 100% adverse outcome, whereas other stroke subtypes had adverse outcomes in only 29% to 57%. The most important outcome predictors were involvement of the corticospinal tracts and basal ganglia. CONCLUSIONS: Although neurodevelopmental outcome was adverse in at least 1 domain with main branch MCA stroke, in other PAIS subtypes outcome was favorable in 43% to 71% of children. Site and tissue involvement is most important in determining the outcome in PAIS.