Leonard J. Graziani

Neurosonographic features of periventricular echodensities associated with cerebral palsy in preterm infants.

We studied the value of neonatal neurosonograms in preterm infants for predicting the development of cerebral palsy (CP). All infants born at less than 33 weeks of gestation who were admitted to the intensive care nursery of Thomas Jefferson University Hospital from 1982 to 1986 were serially studied with cranial ultrasound methods that reliably detect neonatal periventricular echodensities (PVE) and cysts that are 2 mm in diameter or larger. PVE were graded as mild or as moderate to severe, and cyst size was classified by widest diameter as either large (greater than or equal to 3 mm) or small (less than 3 mm). All 127 surviving infants with PVE or cyst formation or both were followed until spastic forms of CP could be diagnosed or excluded during late infancy. All 26 of the infants in whom spastic CP developed had moderate or severe PVE in the area superior and lateral to the caudothalamic notch as noted on the parasagittal images of the neonatal neurosonograms. All these infants also developed cysts in the periventricular region within the area of the previously noted PVE. Mild or moderate to severe PVE were not associated with the development of spastic CP in 101 infants. Cysts developed in the area of PVE in the neurosonographic studies of 42 of these 101 infants. Mild PVE without cysts and moderate to severe PVE without cysts had negative predictive values for CP of 69% and 76%, respectively. By contrast, the presence of moderate to severe PVEs with large cyst formation had positive and negative predictive values of 90% and 93%, respectively, and was the most sensitive and specific neurosonographic finding for predicting CP, with an efficiency of 92%. The presence or absence of intracranial hemorrhage did not increase the efficiency of the ultrasound test results.

The spinal evoked response in infants and children

Summated responses to peroneal nerve stimulation were recorded from surface electrodes placed over the spine of 60 infants and children. These potentials generally were greater in amplitude in infants than in older children. Over the cauda equina and rostral cord, initially positive triphasic potentials were recorded. Over the caudal cord, complex potentials were recorded in children less than three years of age. The conduction velocity of the response from midlumbar to lower cervical recording sites was less in infants than in older children and progressively increased with age, reaching adult values after the fourth year.

Clinical Antecedents of Neurologic and Audiologic Abnormalities in Survivors of Neonatal Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near-term neonates, although cerebral palsy, mental retardation, and sensorineural hearing loss are observed in 10 to 20% of survivors. The objective of the present study was to identify potential risk factors that may explain the neurologic and audiologic sequelae noted in 19% of 181 survivors of neonatal extracorporeal membrane oxygenation from our hospital. Our results suggest the following findings in survivors of severe cardiorespiratory failure treated with neonatal extracorporeal membrane oxygenation: (1) hypotension or the need for cardiopulmonary resuscitation before extracorporeal membrane oxygenation significantly increases the risk of spastic cerebral palsy, (2) profound hypocarbia before extracorporeal membrane oxygenation is associated with a significantly increased risk of hearing loss, (3) mental retardation in the absence of spastic cerebral palsy is unexplained except when due to abnormal fetal brain development, and (4) hypoxemia in the absence of hypotension does not increase the risk of neurologic or audiologic sequelae. (J Child Neurol 1997;12:415-422).

Utility of serial EEGs in neonates during extracorporeal membrane oxygenation

We found electroencephalographic (EEG) studies to be useful for monitoring cerebral function, for confirming seizure activity, and for limited prediction of short-term outcome in 145 neonates who required extra-corporeal membrane oxygenation (ECMO) of reversible respiratory failure. The EEG tracings were classified as normal or as mildly, moderately, or markedly abnormal; abnormal recordings were further classified as focal, diffuse, or predominantly lateralized. A significant decrease in frequency and degree of EEG abnormalities was observed in recordings obtained after ECMO compared to those obtained prior to (P = .001) or during ECMO (P = .001). There was no significant increase in marked EEG abnormalities when recordings obtained before and during ECMO were compared (P = 0.41). Of 11 infants with electrographic seizures during ECMO, 7 (64%) either died during their nursery courses or were developmentally handicapped at age 1 year which is a significantly greater adverse outcome than that observed in infants without EEG seizure activity (P less than .003). No consistently lateralized EEG abnormalities were observed during or after ECMO when compared to tracings obtained before cannulation of the right common carotid artery. There was no acute change in EEG rhythm or amplitude over the right cerebral hemisphere during right common carotid artery cannulation. Our observations support the value of serial EEG in the assessment of cerebral function in critically ill infants undergoing ECMO. They further suggest that, in this patient population, cannulation of the right common carotid artery is a safe procedure that does not result in lateralized abnormalities of cerebral electrical activity.

Cranial ultrasound and clinical studies in preterm infants.

Serial ultrasound imaging of the brain was used to determine the ventricular index (VI), and the ratio (VR) of the VI to the cranial hemidiameter during the nursery course and first year post-term in preterm infants of less than 33 weeks gestation. Twenty-nine of the infant survivors with no intracranial hemorrhage or major medical complication during their nursery course composed group 1. Twenty-two survivors with intracranial hemorrhage unassociated with early ventricular dilation composed group 2. Group 3 was comprised of 10 other survivors who had neonatal intraventricular hemorrhage with early ventriculomegaly; all 10 infants had at least one major medical complication during their neonatal course. In groups 1 and 2 the VR decreased and the VI increased significantly with age post-conception. Infants in group 3, compared with those in groups 1 or 2, had decreased occipitofrontal growth during the early postnatal period and increased VR and VI during the neonatal period and first year post-term. These results suggest that the ventriculomegaly associated with neonatal intracranial hemorrhage cannot be explained by posthemorrhagic hydrocephalus alone and may also be related to cerebral atrophy or decreased brain growth or both. Neurodevelopmental assessments at 20 to 30 months of age disclosed significantly lower Bayley Motor Development scores in group 3 compared with groups 1 or 2. Four infants in group 3, but none in groups 1 or 2, had cerebral palsy. The neurodevelopmental deficits in group 3 infants may reflect the complex pathogenesis of the ventriculomegaly as well as the effects of the intraventricular hemorrhage and posthemorrhagic hydrocephalus.

Right common carotid artery reconstruction after extracorporeal membrane oxygenation : vascular imaging, cerebral circulation, electroencephalographic, and neurodevelopmental correlates to recovery

OBJECTIVE Right common carotid artery (RCCA) ligation after extracorporeal membrane oxygenation by venoarterial bypass may contribute to lateralized cerebral injury. Reconstruction of this artery after extracorporeal membrane oxygenation has proved feasible but has not been evaluated for neurologic outcome in any substantial series of infants. METHODS We evaluated RCCA reconstruction in 47 infants treated with ECMO and compared their cerebrovascular and neuroanatomic imaging findings, electroencephalograms, and developmental outcomes with those of 93 infants who had no reconstruction. SUMMARY RESULTS: Color Doppler blood flow imaging revealed that carotid artery patency was usually obtained after RCCA reconstruction. Right internal carotid and bilateral anterior and middle cerebral arterial blood flow velocities were generally higher, and were more symmetrically distributed in infants with reconstructed RCCA. Electroencephalography did not disclose an increased risk of deterioration or marked abnormalities in infants after reconstruction, nor were neuroimaging findings consistent with an increased number of either focal or generalized abnormalities. Neurodevelopmental follow-up revealed no differences in the incidence of delays between those with a reconstructed RCCA and those with a ligated RCCA during the first year of life. CONCLUSIONS Reconstruction of the RCCA after extracorporeal membrane oxygenation may facilitate normal distribution of cerebral blood flow through the circle of Willis, and may augment both left and right middle cerebral artery blood flow immediately after decannulation. The long-term consequences of either ligation or reconstruction of the RCCA will require careful scrutiny, however, before either course is recommended routinely.

Sensitivity and specificity of the neonatal brain-stem auditory evoked potential for hearing and language deficits in survivors of extracorporeal membrane oxygenation.

OBJECTIVE We determined the sensitivity and specificity of neonatal brain-stem auditory evoked potentials (BAEP) as markers for subsequent hearing impairment and for developmental problems found later in infancy and childhood. METHODS BAEP studies were performed before discharge in infants treated with extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were analyzed: elevated threshold and delayed central auditory conduction. Behavioral audiometry was repeated during periodic follow-up until reliable responses were obtained for all frequencies, and standardized developmental testing was also conducted. The sensitivity and specificity of an elevated threshold on the neonatal BAEP for detecting subsequent hearing loss, and the relationship of any neonatal BAEP abnormality to language or developmental disorders in infancy, were calculated. RESULTS Test results for 46 ECMO-treated infants (57.5%) were normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings. Most significantly, 7 (58%) of the 12 children with subsequent sensorineural hearing loss had left the hospital after showing normal results on threshold tests. There was no significant difference in the frequency of hearing loss between subjects with abnormal (5/21, or 24%) and those with normal BAEP thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity of neonatal BAEP testing for predicting subsequent hearing loss was only 42%. Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In contrast, on language development testing, 19 children demonstrated receptive language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test results, or both (p = 0.04). CONCLUSIONS Neonatal BAEP threshold recordings were of limited value for predicting subsequent hearing loss common in ECMO-treated survivors. However, an abnormal neonatal BAEP significantly increased the probability of finding a receptive language delay during early childhood, even in those with subsequently normal audiometry findings. Because neonatal ECMO is associated with a high risk of hearing and receptive language disorders, parents should be counseled that audiologic and developmental follow-up evaluations in surviving children are essential regardless of the results of neonatal BAEP testing.

Predictive value of neonatal electroencephalograms before and during extracorporeal membrane oxygenation

We studied the prognostic significance of electroencephalograms recorded serially at 2- to 4-day intervals during the acute neonatal course of 119 near-term infants with severe respiratory failure treated by venoarterial extracorporeal membrane oxygenation (ECMO). A poor prognosis was defined as early death (n = 27), an abnormally low developmental assessment score (n = 14), or cerebral palsy (n = 14) at 12 to 45 months of age. The only electroencephalographic abnormalities that were significantly related to a poor prognosis were burst suppression (B-S) and electrographic seizure (ES). The 30 infants with two or more recordings of B-S or ES, when compared with the 58 neonates without such electroencephalographic abnormalities, had an odds ratio for a poor prognosis of 6.6 (95% confidence limits, 2.2 to 20.2). The 31 infants with a single ES or B-S recording did not have a significantly increased risk for a poor prognosis. Cardiopulmonary resuscitation immediately before ECMO (n = 8) and the lowest systolic blood pressure before or during ECMO were significantly related to the occurrence of ES or B-S recordings. There was no significant predilection of ES for either cerebral hemisphere. We conclude that in near-term neonates with respiratory failure, serial electroencephalographic recordings are of predictive value, and may facilitate clinical care including the decision to initiate or to continue ECMO.

When Combined, Early Bedside Head Ultrasound and Electroencephalography Predict Abnormal Computerized Tomography or Magnetic Resonance Brain Images Obtained After Extracorporeal Membrane Oxygenation Treatment

Definitive neuroimaging of the brain using computerized tomography (CT) or magnetic resonance imaging (MRI) in extracorporeal membrane oxygenation (ECMO)–treated infants must be delayed until after this therapy is completed. Bedside head ultrasound (HUS) and electroencephalography (EEG) studies during ECMO, if highly correlated with later definitive neuroimaging, might be used to affect the acute clinical care and early parental counseling of infants with severe cardiorespiratory failure. One hundred and sixty ECMO-treated patients had both bedside EEG and HUS studies performed during ECMO, as well as a later CT or MRI study prior to hospital discharge. There was a significant difference in CT or MRI findings among patients having normal studies on both the HUS and EEG, compared to those having an abnormality on either the HUS or the EEG, and compared to those having abnormalities on both studies. In ECMO-treated infants, the combination of a normal bedside HUS and an EEG without marked abnormalities is highly predictive of normal post-ECMO CT and MRI neuroimaging studies.

MATERNALLY-ADMINISTERED MAGNESIUM SULFATE (MgSO 4 ) PROTECTS AGAINST EARLY BRAIN INJURY AND LONG-TERM ADVERSE NEURODEVELOPMENTAL OUTCOMES IN PRETERM INFANTS: A PROSPECTIVE STUDY. 1502

MATERNALLY-ADMINISTERED MAGNESIUM SULFATE (MgSO 4 ) PROTECTS AGAINST EARLY BRAIN INJURY AND LONG-TERM ADVERSE NEURODEVELOPMENTAL OUTCOMES IN PRETERM INFANTS: A PROSPECTIVE STUDY. 1502