Pattern of Brain Injury Predicts Long-Term Epilepsy Following Neonatal Encephalopathy.

OBJECTIVE: To determine if patterns of hypoxic-ischemic brain injury on magnetic resonance imaging (MRI) in term newborns predict subsequent childhood epilepsy. METHODS: This retrospective cohort study includes term newborns with encephalopathy (n = 181) born between 2004-2012 and admitted to British Columbia Children's Hospital. MRI was performed between 3 and 5 days of age. The predominant patterns of hypoxic-ischemic injury were classified as Normal, Watershed, Basal Nuclei, Total, and Focal-Multifocal. Lesions in hippocampus, motor and occipital cortex were noted. RESULTS: Of 181 newborns, 166 (92%) survived the neonatal period, and 132 (80%) had follow-up with a median duration of 61 months (IQR: 28-95). Twenty-three children (17%) developed epilepsy. A higher proportion with Watershed, Basal Nuclei, or Total patterns developed epilepsy (P < .001). Injury to motor cortex, hippocampus, and occipital lobe (P < .01) were independent risk factors for epilepsy. In the adjusting logistic model, Watershed (odds ratio = 16.0, 95% CI [1.3, 197.2], P = .03) and Basal Nuclei injury (odds ratio = 19.4, 95% CI [1.9, 196.3], P = .01) remained independent risk factors. Therapeutic hypothermia did not alter these associations. Severity of brain injury and recurrent neonatal seizures are other clinical risk factors. SIGNIFICANCE: In term newborns with hypoxic-ischemic encephalopathy, the predominant pattern of Watershed and Basal Nuclei injury are valuable predictors for development of epilepsy in later childhood.

Reliability of Early Magnetic Resonance Imaging (MRI) and Necessity of Repeating MRI in Noncooled and Cooled Infants With Neonatal Encephalopathy.

In cooled newborns with encephalopathy, although late magnetic resonance imaging (MRI) scan (10-14 days of age) is reliable in predicting long-term outcome, it is unknown whether early scan (3-6 days of life) is. We compared the predominant pattern and extent of lesion between early and late MRI in 89 term neonates with neonatal encephalopathy. Forty-three neonates (48%) were cooled. The predominant pattern of lesions and the extent of lesion in the watershed region agreed near perfectly in noncooled (kappa = 0.94; k = 0.88) and cooled (k = 0.89; k = 0.87) infants respectively. There was perfect agreement in the extent of lesion in the basal nuclei in noncooled infants (k = 0.83) and excellent agreement in cooled infants (k = 0.67). Changes in extent of lesions on late MRI occurred in 19 of 89 infants, with higher risk in infants with hypoglycemia and moderate-severe lesions in basal nuclei. In most term neonates with neonatal encephalopathy, early MRI (relative to late scan) robustly predicts the predominant pattern and extent of injury.

Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities.

We describe a family with QARS deficiency due to compound heterozygous QARS mutations, including c.1387G > A (p.R463*) in the catalytic core domain and c.2226C > G (p.Q742H) in the anticodon domain, both previously unreported and predicted damaging. The phenotype of the male index further confirms this specific aminoacyl-transfer RNA (tRNA) synthetase disorder as a novel genetic cause of progressive microcephaly with diffuse cerebral atrophy, severely deficient myelination, intractable seizures, and developmental arrest. However, in contrast to the two hitherto published families, the cerebellum and its myelination are not affected. An awareness that QARS mutations may cause isolated supratentorial changes is crucial for properly directing genetic analysis.

The role of hypoxia-ischemia in term newborns with arterial stroke.

The role of generalized hypoxia-ischemia in the genesis of perinatal focal arterial stroke remains puzzling. Animal studies have demonstrated that hypoxia-ischemia may alter blood flow through the ductus venosus, thereby increasing the risk for placental emboli entering the cerebral circulation. A retrospective review was performed of clinical records of all term newborns admitted to a tertiary perinatal center between January 1995 and May 2007 with acute arterial stroke on neuroimaging during the first week of life. Newborns were classified into 2 groups on the basis of neuroimaging abnormalities: stroke alone, or stroke and nonfocal hypoxic-ischemic brain injury. A total of 62 newborns had focal or multifocal stroke, 36 with stroke alone and 26 with stroke with nonfocal hypoxia-ischemia. Multiple risk factors for hypoxia-ischemia occurred in most newborns in both groups. These data indicate that hypoxia-ischemia may play a role in the genesis of stroke in the term newborn with or without evidence of nonfocal hypoxic-ischemic brain injury on neuroimaging.

Cerebellar vermian atrophy after neonatal hypoxic-ischemic encephalopathy.

BACKGROUND AND PURPOSE: Although pathologic evidence of cerebellar injury due to birth asphyxia is well described, neuroimaging evidence is sparse. The primary purpose of this retrospective study was to evaluate the early and late imaging findings in the cerebellum of patients who had neonatal hypoxic-ischemic encephalopathy with thalamic edema shown by neonatal CT. The secondary aims were to validate thalamic edema shown by neonatal CT as a marker of thalamic injury and to assess the late cerebral cortical abnormalities associated with neonatal thalamic edema. METHODS: Fifty-five neonates with thalamic edema shown by CT performed when patients were 3 days old were identified from a cohort of full-term neonates with hypoxic-ischemic encephalopathy. Twenty-six of the 55 underwent follow-up neuroimaging. All sonograms, CT scans, and MR images of the brains of the 55 neonates were retrospectively reviewed by two pediatric neuroradiologists. The examinations were reviewed for evidence of hemorrhage, edema, atrophy, and CT attenuation or MR signal intensity abnormalities in the cerebellum, basal ganglia, and cerebral cortex. The neonatal autopsy findings in four cases were reviewed separately by a pediatric neuropathologist. RESULTS: Of the 55 neonates with thalamic edema shown by neonatal CT, 28 (51%) had thalamic edema with diffuse cerebral cortical edema, and 27 (49%) had thalamic edema without diffuse cortical edema. The cerebellar vermes appeared normal on all neonatal sonograms, CT scans, and MR images. However, atrophy of the cerebellar vermis was found in 12 (46%) of 26 patients by use of follow-up studies (95% CI, 27-65%). One of the 12 patients also had cerebellar hemispheric atrophy. Cerebellar vermian atrophy was shown at follow-up in eight (67%) of 12 patients who had neonatal thalamic edema with cortical sparing, compared with four (29%) of 14 patients who had thalamic edema with diffuse cortical edema. The difference did not reach statistical significance. The thalami appeared abnormal on follow-up neuroimages in 25 of 26 cases. Different patterns of cortical atrophy were observed on the images of patients who had thalamic edema with cortical sparing compared with those obtained in patients who had thalamic edema with cortical involvement. CONCLUSION: Cerebellar vermian atrophy is a frequent finding on follow-up images of patients in whom neonatal CT showed hypoxic-ischemic encephalopathy with abnormal thalami.

Germinal matrix-intraventricular hemorrhage in the premature newborn: management and outcome.

Germinal matrix-intraventricular hemorrhage (GMH-IVH) in the premature newborn results from rupture of fragile capillaries in the germinal matrix. Its pathogenesis is multifactorial and relates principally to a pressure-passive cerebral circulation, fluctuations in cerebral blood flow, and derangements of coagulation and fragility of the germinal matrix microvasculature. Several interventions have beneficial effects for prevention of GMH-IVH. Outcome after GMH-IVH relates largely to the severity of hemorrhage, the extent of hemorrhagic and ischemic parenchymal involvement, and complications (e.g., posthemorrhagic hydrocephalus). Even in the absence of neuroimaging abnormalities, VLBW infants have a high incidence of academic and behavioral problems which persist into adolescence and early adulthood.