Lilly Dubowitz

The spectrum of leukomalacia using cranial ultrasound

The spectrum of leukomalacia using cranial ultrasound is discussed. Transient densities not evolving into cystic lesions may represent a mild degree of leukomalacia when persisting for at least a week. A unilateral parenchymal density may be due to bleeding into an ischaemic area, but can also be due to a venous infarction. Cystic leukomalacia can be confidently diagnosed using appropriate equipment and performing sequential scans. A distinction should be made between cysts in the periventricular white matter and cysts in the deep white matter, as the latter carries a higher risk for cerebral visual impairment. Careful ophthalmological examination of these infants will enable us to identify infants with cerebral visual impairment during the first few months of life, allowing the use of special programs aimed at promoting visual development.

Origin and timing of brain lesions in term infants with neonatal encephalopathy

BACKGROUND The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults. METHODS We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2). FINDINGS Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury. INTERPRETATION Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.

Abnormal Magnetic Resonance Signal in the Internal Capsule Predicts Poor Neurodevelopmental Outcome in Infants With Hypoxic-Ischemic Encephalopathy

Objective. The aim of this study was to establish whether abnormal signal intensity in the posterior limb of the internal capsule (PLIC) on magnetic resonance imaging is an accurate predictor of neurodevelopmental outcome at 1 year of age in infants with hypoxic-ischemic encephalopathy (HIE). Methods. We have examined 73 term neonates with HIE between 1 and 17 days after birth with cranial magnetic resonance imaging and related the magnetic resonance imaging findings to neurodevelopmental outcome at 1 year of age. Results. All infants with an abnormal signal intensity in the PLIC developed neurodevelopmental impairment although in 4 infants with very early scans the abnormal signal was not apparent until up to 4 days after birth. A normal signal intensity was associated with a normal outcome in all but 4 cases; 3 of these infants had minor impairments and all had persistent imaging changes within the white matter. The 4th infant with a normal signal intensity on day 2 died before a further image could be obtained. The absence of normal signal predicted abnormal outcome in term infants with HIE with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87. The test correctly predicted outcome in 93% of infants with grade II HIE, according to the Sarnat system. Applying a Bayesian approach, the predictive probability of the test (the probability that the test would predict an outcome correctly) was distributed with a mean of 0.94 and 95% confidence limits of 0.89 to 1.0. Conclusion. Abnormal signal intensity in the PLIC is an accurate predictor of neurodevelopmental outcome in term infants suffering HIE.

Early prognostic indicators of outcome in infants with neonatal cerebral infarction : A clinical, electroencephalogram, and magnetic resonance imaging study

Objective. The aim of this study was to identify prognostic factors in newborns with cerebral infarction. Design. Antenatal and perinatal factors and early clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings were compared with neurodevelopmental outcome in 24 children with evidence of cerebral infarction on neonatal MRI. Results. Out of 24 infants, 19 had an infarction in the territory of a major cerebral vessel and 5 in the borderzone between cerebral arteries. Neuromotor outcome was normal in 17 and abnormal in 7 infants. Of these 7 infants, 5 infants showed a definite hemiplegia, whereas the other 2 showed some asymmetry of tone or function but no definite hemiplegia. None of the adverse antenatal or perinatal factors was significantly associated with abnormal outcome. Neonatal clinical examination was also not always predictive of the outcome. The extent of the lesion on MRI was a better predictor. In particular, it was the concomitant involvement of hemisphere, internal capsule and basal ganglia that was always associated with an abnormal outcome whereas the involvement of only one or two of the three tended to be associated with a normal outcome. EEG was also very helpful. Abnormal background activity either unilateral or bilateral was found in 6 infants and 5 out of 6 developed hemiplegia. In contrast, the presence of seizure activity in presence of a normal background was not related to abnormal outcome. Conclusions. Early MRI and EEG can help to identify the infants with cerebral infarction who are likely to develop hemiplegia.

Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome.

Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss.

Optimality score for the neurologic examination of the infant at 12 and 18 months of age

The aim of this study was to develop and validate a simple, quantifiable, neurologic examination for infants between 2 and 24 months of age. The assessment consists of 37 items, divided into 3 sections. The first section includes 26 items assessing cranial nerve function, posture, movements, tone, and reflexes; the second section of 8 items documents the development of motor function, and the third section of 3 items evaluates the state of behavior. We applied this assessment to a cohort of ninety-two 12-month-old infants and forty-three 18-month-old infants, with no known perinatal risk factors. The proforma presented has been designed according to the frequency distribution of the neurologic findings in this cohort. Each item is scored individually, and a global score is the sum of all individual scores. The quantitative score enhances the value of this examination, both in clinical practice and in research settings.

Developmental sequence of periventricular leukomalacia. Correlation of ultrasound, clinical, and nuclear magnetic resonance functions.

The evolution of severe periventricular leukomalacia was followed by ultrasonography in three newborn infants, and the subsequent myelination of the brain was assessed by nuclear magnetic resonance imaging. Four stages of periventricular leukomalacia could be identified by ultrasonography; (1) initial congestion, followed by (2) relative normalisation, (3) development of cysts, and (4) resolution of cysts but development of ventricular enlargement. All infants exhibited abnormal neurological signs from 36 weeks conceptual age and had unequivocal signs of cerebral palsy by 6 to 9 months of age. One infant became cortically blind but the other two seemed to have normal vision. Nuclear magnetic resonance imaging showed some abnormality of the ventricular system and delayed myelination in all three infants. The delay was most noticeable in the opticothalamic region, which was also the site of the most extensive lesions observed on ultrasonography. Progress in myelination was observed in the infants where a repeat scan was performed.

Minor neurological signs and perceptual-motor difficulties in prematurely born children

AIM To examine the spectrum of neurological dysfunction and perceptual-motor difficulties at school age in a cohort of prematurely born children, and the relation of these measures to neonatal brain lesions, intelligence quotient, and behavioural adjustment. METHOD One hundred and eighty three children were tested at the age of 6 years using Touwen’s Examination of the Child with Minor Neurological Dysfunction, the Movement Assessment Battery for Children (Movement ABC), the Developmental Test of Visual-Motor Integration (VMI), British Ability Scales, and Rutter Scales. RESULTS Twenty six children had definite cerebral palsy and one was blind. Of the remaining 156, the proportions falling below the 15th centile point were 31% on Touwen’s Examination, 44% on the Movement ABC, and 17% on the VMI. Forty two passed all three tests. No child with a normal ultrasound scan developed cerebral palsy, whereas nearly all those with major lesions did. Minor lesions, however, were not generally predictive of later outcome. Correlations between the tests were generally low. CONCLUSIONS These findings stress the need to assess neurological and perceptual motor functioning separately at school age and to monitor relationships with other aspects of development.

Patterns Of Visual Impairment Associated With Lesions Of The Preterm Infant Bran

The visual function of 42 children with hacmorrhagic and/or ischaemic cerebral lesions acquired before a gestational age of 35 weeks was examined and related to cranial ultrasound in the neonatal period and to MR1 and neurodevelopmental status at follow‐up. All 37 children with abnormal ultrasound scans and one of the five with normal ultrasound scans showed impairment of one or more aspects of visual function. While impaired acuity was more frequent among infants with MRI evidence of visual pathway damage, this was not an invariable finding. Normal or near‐normal visual acuity did not preclude the presence of other functional visual deficits. The authors conclude that preterm cerebral insults may produce a variety of visual difficulties, the pattern and severity of which cannot be predicted on imaging. Each child therefore requires individual assessment of multiple aspects of visual function.

An optimality score for the neurologic examination of the term newborn

We describe the application of a revised version of the Dubowitz neurologic examination of the newborn in 224 low-risk, term newborn infants. The method has been updated by eliminating less useful items and including new items evaluating general movements and patterns of distribution of tone. An optimality score is included to make the evaluation more quantitative and for comparison with sequential examinations with neurophysiologic and imaging findings. The score is based on the distribution of the scores for each item in the population of low-risk term infants. We defined not only the most common pattern for each item but also the variability of the findings by using 10th and 5th centiles. Because most of the items assessing tone and the Moro reflex varied with gestational age between 37 and 42 weeks, the changes were incorporated in the scoring system. The total optimality score was the sum of the optimality scores of individual items. Although the association of 4 or more deviant scores was found in less than 10% of our infants, deviant results on 1 or 2 single items could be observed in a third of this normal population, suggesting that isolated deviant signs have little diagnostic value. In contrast, an abnormal distribution of tone patterns, which we have commonly observed in infants with brain lesions, was not found in this cohort.