P. Eken

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.

Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic–ischaemic encephalopathy

AIM To assess the prognostic value of amplitude integrated EEG (aEEG) 3 and 6 hours after birth. METHODS Seventy three term, asphyxiated infants were studied (from two different centres), using the Cerebral Function Monitor (CFM Lectromed). The different aEEG tracings were compared using pattern recognition (flat tracing mainly isoelectric (FT); continuous extremely low voltage (CLV); burst–suppression (BS); discontinuous normal voltage (DNV); continuous normal voltage (CNV)) with subsequent outcome. RESULTS Sixty eight infants were followed up for more than 12 months (range 12 months to 6 years).Twenty one out of 68 infants (31%) showed a change in pattern from 3 to 6 hours, but this was only significant in five cases (24%). In three this changed from BS to CNV with a normal outcome. One infant showed a change in pattern from CNV to FT and had a major handicap at follow up. Another infant showed a change in pattern from DNV to BS, and developed a major handicap at follow up. The other 16 infants did not have any significant changes in pattern: 11 infants had CLV, BS, or FT at 3 and 6 hours and died (n = 9) in the neonatal period or developed a major handicap (n = 2). Five infants had a CNV or DNV pattern at 3 and 6 hours, with a normal outcome. The sensitivity and specificity of BS, together with FT and CLV, for poor outcome at 3 hours was 0.85 and 0.77, respectively; at 6 hours 0.91 and 0.86, respectively. The positive predictive value (PPV) was 78% and the negative predictive value (NPV) 84% 3 hours after birth. At 6 hours the PPV was 86% and the NPV was 91%. CONCLUSION aEEG could be very useful for selecting those infants who might benefit from intervention after birth asphyxia.

Predictive value of early neuroimaging, pulsed Doppler and neurophysiology in full term infants with hypoxic-ischaemic encephalopathy.

To evaluate their prognostic value, five different non-invasive techniques were used on 34 full term infants with hypoxic-ischaemic encephalopathy (HIE) within six hours of delivery. Cranial ultrasonography, the resistance index (RI) of the middle cerebral artery obtained with Doppler ultrasonography, somatosensory evoked potentials (SEPs), visual evoked potentials (VEPs) and the cerebral function monitor (CFM) were used. According to the criteria of Sarnat, 11 infants developed mild, seven moderate, and 16 severe encephalopathy. The CFM had the highest positive (PPV 84.2%) and negative predictive value (NPV 91.7%). All but one of the infants with a continuous pattern had a good outcome. The CFM of 11 cases with a suppression-burst pattern changed to a continuous pattern over 24 to 48 hours in four infants, and was associated with a normal outcome in three. All five cases with an isoelectric CFM died. The SEPs also provided useful information (PPV 81.8%; NPV 91.7%). VEPs were often delayed during the first hours or life and did not carry a poor prognosis in five of 14 cases (PPV 77.3%). Both ultrasonography and Doppler RI were of little value, as they were almost always normal at this early stage. In 34 full term infants with HIE, studied within 6 hours of life, the CFM and SEPs provided the most useful information about the expected course of encephalopathy and subsequent neurodevelopmental outcome.

HAEMORRHAGIC-ISCHAEMIC LESIONS OF THE NEONATAL BRAIN: CORRELATION BETWEEN CEREBRAL VISUAL IMPAIRMENT, NEURODEVELOP-MENTAL OUTCOME AND MRI IN INFANCY

The relationship between the degree of cerebral visual impairment, established using the acuity card procedure, and the extent of neurological sequelae was assessed in 65 at‐risk neonates in a prospective follow‐up study. MRI and CT scans were performed in all infants with severe neurological sequelae. 11 of 12 children with an acuity at or below the 10th centile at 18 months developed cerebral palsy: the underlying condition was extensive cystic leukomalacia in all. An acuity above the 10th centile was no guarantee of normal development, as 10 out of 52 such infants developed cerebral palsy. MRI and CT scans showed that periventricular high signal intensity in the occipital area was a non‐specific finding with regard to visual function. Extensive periventricular white matter loss and involvement of the striate/parastriate cortex was found in the most severely visually impaired infants.

Antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants: prevalence and associated obstetric variables

AIM To assess the prevalence of an antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants; to identify possibly related obstetric risk factors. METHODS A prospective cohort study was made of 1332 infants born at less than 34 completed weeks, using cranial ultrasound, for the presence of antenatal brain lesions (group A) involving the periventricular white matter (PVWM) or central grey matter. Entry criteria were presence of (i) cysts in the PVWM < 7 days; (ii) increased PVWM echogenicity < 6 hours, confirmed to be white matter necrosis at post mortem examination; (iii) a unilateral porencephalic cyst < 3 days; (iv) an intraventricular haemorrhage with unilateral parenchymal involvement < 6 hours; and (v) symmetrical areas of increased echogenicity in the thalami, confirmed to be areas of calcification on post mortem examination. Group B consisted of infants with a normal early neonatal ultrasound scan with subsequent development of the lesions mentioned above. RESULTS Twenty four cases met the entry criteria for group A: 17 died and five of the seven survivors developed cerebral palsy at follow up. Of the whole cohort, 156 (11.7%) infants died and in 63 (40.3%) of these a large ultrasound lesion was present. In 17 (26.9%) cases this lesion was considered to be of antenatal onset. Sixty eight of the 1176 (5.8%) survivors developed cerebral palsy and this was attributed to antenatal onset in five (7.3%). A comparison of the obstetric risk factors between the infants in group A and B, who either died or developed cerebral palsy, showed a significant difference in gestational age between the two groups (30.9vs 28.9 weeks; p<0.001). Prolonged rupture of membranes was significantly more common in group B (p=0.03), while an ominous cardiotachogram was significantly more common in group A (p=0.01), and this remained significant following logistic regression analysis. CONCLUSIONS Although these data suggest that most preterm infants did not develop their brain lesions in utero, an antenatal onset was not uncommon, especially in those with PVWM lesions, who did not survive the neonatal period.

Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis

Rademaker KJ, Groenendaal F, Jansen GH, Eken P, de Vries LS. Unilateral haemorrhagic parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Pædiatr 1994;83:602–8. Stockholm. ISSN 0803–5253

RELATION BETWEEN NEONATAL CRANIAL ULTRASOUND ABNORMALITIES AND CEREBRAL VISUAL IMPAIRMENT IN INFANCY

A prospective follow‐up study was conducted of a cohort of 65 at‐risk neonates to assess the predictive value of neonatal cranial ultrasound abnormalities for cerebral visual impairment in infancy. Visual function was assessed using the acuity card procedure and behavioural visual responses were tested. Normal visual function was found in controls as well as in infants with small haemorrhages or mild leukomalacia. Infants with large haemorrhages performed poorly at 40 weeks postmenstrual age, but recovered to within the normal range in the first half year. In contrast, of the infants with extensive cystic leukomalacia, four of nine preterm infants and three of four term infants were severely visually impaired at 18 months. In the more mature infants, the cystic lesions extended deeper into the subcortical white matter, and this appeared to be associated with a worse visual outcome. Cystic leukomalacia proved to be highly predictive of cerebral visual impairment in infancy.

Prognostic value of early somatosensory evoked potentials for adverse outcome in full-term infants with birth asphyxia

SEPs were examined during the first weeks of life in 34 infants with mild to severe birth asphyxia, in an attempt to provide a more accurate prediction of neurodevelopmental outcome. Normal, delayed and absent responses were compared with the infants acute clinical condition, imaging findings using different imaging techniques and neurodevelopmental outcome. All infants with normal SEPs were normal at follow-up. All but two of the infants with a delayed or absent response died or suffered from severe neurological sequelae. A delayed or absent N1 latency carried a risk for death or severe handicap of 71 and 100%, respectively, compared with 25 and 89% for moderate or severe encephalopathy on neurological assessment, and 29 and 85% for moderate or severe changes seen using different imaging techniques. SEPs may provide useful additional information when assessing the infant with birth asphyxia.

Relation between visual perceptual impairment and neonatal ultrasound diagnosis of haemorrhagic-ischaemic brain lesions in 5-year-old children

Visual‐perceptual abilities were assessed in 5‐year‐old children with the following neonatal neurological conditions: born preterm with normal ultrasound scan (NL, n=17); born preterm with ultrasound diagnosis of intraventricular haemorrhage (IVH, n=17); born preterm with ultrasound diagnosis of periventricular leukomalacia (PVL, n=12); born term with hypoxic‐ischaemic encephalopathy (HIE, n=11). Visual‐perceptual ability was evaluated with the L94: eight visual‐perceptual tasks designed to evaluate different aspects of visual perception at the preschool level in children with multiple disabilities. Impairment was established in comparison to the performance age obtained on non‐verbal intelligence subtests, instead of chronological age. Frequency of L94 impairment was highest in children with PVL, while children with IVH did not differ from the NL control group. Impairment rates were increased also in children with transient periventricular echodensities, and in children with HIE. Impairments were only moderately related to the delay of visual acuity maturation in infancy.