PEDIATRIC NEUROLOGY
0031-3955/92 $0.00
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PERINATAL CEREBROVASCULAR DISEASE IN THE NEONATE Parenchymal Ischemic Lesions in Term and Preterm Infants Walter C. Allan, MD, and James J. Riviello, Jr, MD
One can argue that most serious injuries to the brains of neonates are a result of cerebrovascular disease. The types of cerebrovascular disease, whether prenatal, perinatal, or postnatal, are similar to those found in older children and adults and can be divided into ischemic and hemorrhagic insults (Table 1). The major differences between the older groups and neonates have to do with the unique features of the cerebrovasculature of the preterm infant and the likely insults suffered during the three phases of fetal and neonatal life that produce cerebrovascular disease. Confusion arises during any discussion of neonatal cerebrovascular brain injuries because of these unique features and the tendency to approach the topic from various viewpoints. Thus, one could classify these injuries on the basis of the neonatal abnormality, the presumed pathophysiologic abnormality, the clinical presentation, or the types of cerebral palsy they produce. All of these factors are interrelated and need to be touched on in any discussion of this topic. This article focuses on the clinical factors apparent in the acute and subacute situation that help establish the diagnosis and prognosis in perinatal cerebrovascular disease. We place special emphasis on ischemic injury. Recent interest in the pathophysiologic aspects of ischemic brain injury has led to new possibilities for treatment in adult cerebrovascular disease that are being proposed for "neonatal asphyxia." These treatments center around the role excitatory amino acids (mainly glutamate) play in brain injury.29, 54, 55 The potential exists, as demonstrated in tissue culture and animal experiments, for receptor blocking agents to modify the extent of damage following ischemic From the University of Vermont School of Medicine; and Division of Pediatric Neurology, Department of Pediatrics, Maine Medical Center, Portland, Maine
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39· NUMBER 4· AUGUST 1992
621
622
ALLAN & RIVIELLO,
JR
Table 1. CLASSIFICATION OF CEREBROVASCULAR DISEASE: OCCURRENCE AND ETIOLOGY Type of Disease Hemorrhage Subarachnoid hemorrhage Intracerebral hemorrhage Ischemia Cerebral hypoperfusion (systemic disease) Embolism (any source) Large artery occlusion (thromboembolism) Small artery thrombosis
Children and/or Adults AVM, aneurysms
Term
Preterm
Fetal
Spontaneous Spontaneous Spontaneous
Hypertension, bleeding Bleeding disorders disorders
IVH and IPH IVH and IPH
Parasag ittal/diffuse infarctions
Parasagittal/ PVLldiffuse infarcts diffuse infarctions
PVLldiffuse infarcts
Multifocal infarcts
Multifocal infarcts Vascular territory infarct
Multifocal infarcts Vascular territory infarct
Single vascular territory infarct
Small subcortical infarcts
Thalamic/ basal ganglia infarct
Multifocal infarcts Vascular territory infarct
?
?
Abbreviations: AVM = arteriovenous malformation; IPH = intraparenchymal hemorrhage; IVH = intraventricular hemorrhage; PVL = periventricular leukomalacia; ? = rare or not known to occur.
insults. The condition commonly termed "neonatal asphyxia" should represent one form of acute (i.e., perinatal) ischemic cerebrovascular disease in neonates. The timely recognition of such lesions has taken on a new importance in the light of these proposed new treatments. We review perinatal onset cerebrovascular disease because it represents the setting in which intervention is being discussed. The "handicapologist's" definition of the perinatal period, i.e., from the onset of labor to 7 days of age, is used for the same reason. Ischemic injury in this setting is divided into those lesions found in term and preterm infants. Table 2 lists the typical clinical manifestations, neonatal abnormalities, and likely form of cerebral palsy produced for each type of perinatal cerebrovascular disease. We present a case in each category with clinical, electroencephalogram (EEG), and imaging findings that allow recognition of the likely abnormality. A discussion follows of the clinical manifestations for that subtype of cerebrovascular disease and its presumed pathophysiologic characteristics. A discussion of the likely type of cerebral palsy that results from such an injury ends each section. We conclude with a general discussion of how little we know of the cause and effect relations that produce cerebral palsy following perinatal cerebrovascular disease. Arguments are advanced that, so far, our approach to intervention has not met with success. Although serial observations in the neonatal period are the best predictors of significant perinatal injury, they require days to weeks to become predictive and cannot be used for planning an intervention. New ideas in this regard have come from study of the neonate's cerebrovasculature itself and may be a useful marker for intervention.
PERINATAL CEREBROVASCULAR DISEASE IN THE NEONATE
623
Table 2. MAJOR PARENCHYMAL CEREBROVASCULAR LESIONS IN THE PERINATAL PERIOD
Gestation Term
Preterm
Cerebral Vascular Disease Type
Clinical Signs
Cerebral Full neonatal hypoperfusion encephalopathy-abnormal (infant A) EEG/US scan/CT scan at 1-2 days Focal signs and Large artery seizures (no thrombosis coma)-focal (infant B) EEGfUS scan Intracerebral Nonspecific signshemorrhage US scan confirmation at (infant C) 1-3 days (IVHf IPH) Cerebral Nonspecific signshypoperfusion US scan (infant D) confirmation at 1-3 weeks
Abnormality
Cerebral Palsy Type
Widespread cortical/ Spastic quadriparesis subcortical infarcts in parasagittal region and white matter Wedge-shaped Spastic hemiparesis infarction confined to a single vascular territory Hemorrhagic infarction Spastic diplegia in the periventricular white matter contiguous to IVH Ischemic infarction of Spastic diplegia the periventricular white matter + /cystic change (PVL)
Abbreviations: CT = computed tomography; EEG = electroencephalogram; IPH = intraparenchymal hemorrhage; IVH = intraventricular hemorrhage; PVL = periventricular leukomalacia; US = ultrasound.
CEREBRAL HYPOPERFUSION IN THE FULL-TERM INFANT
Case Report Infant A, a 2.95-kg girl, was born at 41 weeks to a primigravida 34-year-old woman who presented in active labor. Over a 25-minute period, a drop in fetal heart rate from 150 to 70 occurred. It did not respond to positioning and maternal oxygen. An emergency caesarean section was arranged. The child was delivered in 30 minutes but just before surgery the heart rate had dropped to 40. At birth no respirations or heart rate was noted. Resuscitation with ventilation, chest compression, and epinephrine was begun. Apgar scores were 0/0/1 at 1, 5, and 10 minutes. The heart rate was obtainable but was less than 100 at 10 minutes. Further epinephrine was given at 12 minutes of age and the heart rate increased. Spontaneous respirations were noted at 20 minutes of age. With controlled assisted ventilation, arterial blood gas at 30 minutes of age, before transfer to the neonatal intensive care center, showed a pH of 6.65, Pco2 of 14, HC0 3 of 2, and a Po, of 142. Blood pressure was supported by pressors for 3 days. Disseminated intravascular coagulation developed by the second day. Cardiac evaluation suggested ischemic myocardial injury, and the child was oliguric for the first 3 days.
Neurologic Course Seizures began at 4 hours of age and did not respond to 30 mg/kg of phenobarbital or 20 mg/kg of phenytoin. A neurologic examination performed at 18 hours of age showed a comatose child who responded to any tactile stimulus with extensor posturing that could not be differentiated from spontaneous tonic seizures. Pupils were small and reactive; oculocephalic maneuver produced conjugate eye movements; corneal and gag reflexes were intact but sluggish. Suck and root reflexes were absent. Results of the
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ALLAN & RIVIELLO,
JR
motor exam were difficult to evaluate because of the elicited extensor posturing. Seizures came under control by day 4; the infant was feeding by nipple by day 11; discharge was possible by day 16, with the infant having periods of wakefulness sufficient to feed and gain weight.
Studies Cranial ultrasound scan at 18 hours showed "bright brain" consistent with cerebral edema or diffuse infarctions (Fig. lA). Repeat ultrasound scans at 2, 4, and 15 days showed apparent resolution of cerebral edema without definite central nervous system injury. A radionuclide brain scan using technetium-99 labeled albumin was normal at 6 days. At 13 weeks, however, the cranial ultrasound scan showed cystic change in the para sagittal white matter with diffuse ventriculomegaly (Fig. IB). An EEG at 20 hours showed a nearly isoelectric pattern with little spontaneous activity. By day 4 a burst-suppression pattern was seen, and at 1 week, the burstsuppression pattern was interrupted by electrographic seizures without clinical correlate emanating from the right temporal leads. At 13 weeks, a modified hypsarrhythmic pattern was seen.
Follow-up At 6 wee\
0031-3955/92 $0.00
+ .20
PERINATAL CEREBROVASCULAR DISEASE IN THE NEONATE Parenchymal Ischemic Lesions in Term and Preterm Infants Walter C. Allan, MD, and James J. Riviello, Jr, MD
One can argue that most serious injuries to the brains of neonates are a result of cerebrovascular disease. The types of cerebrovascular disease, whether prenatal, perinatal, or postnatal, are similar to those found in older children and adults and can be divided into ischemic and hemorrhagic insults (Table 1). The major differences between the older groups and neonates have to do with the unique features of the cerebrovasculature of the preterm infant and the likely insults suffered during the three phases of fetal and neonatal life that produce cerebrovascular disease. Confusion arises during any discussion of neonatal cerebrovascular brain injuries because of these unique features and the tendency to approach the topic from various viewpoints. Thus, one could classify these injuries on the basis of the neonatal abnormality, the presumed pathophysiologic abnormality, the clinical presentation, or the types of cerebral palsy they produce. All of these factors are interrelated and need to be touched on in any discussion of this topic. This article focuses on the clinical factors apparent in the acute and subacute situation that help establish the diagnosis and prognosis in perinatal cerebrovascular disease. We place special emphasis on ischemic injury. Recent interest in the pathophysiologic aspects of ischemic brain injury has led to new possibilities for treatment in adult cerebrovascular disease that are being proposed for "neonatal asphyxia." These treatments center around the role excitatory amino acids (mainly glutamate) play in brain injury.29, 54, 55 The potential exists, as demonstrated in tissue culture and animal experiments, for receptor blocking agents to modify the extent of damage following ischemic From the University of Vermont School of Medicine; and Division of Pediatric Neurology, Department of Pediatrics, Maine Medical Center, Portland, Maine
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39· NUMBER 4· AUGUST 1992
621
622
ALLAN & RIVIELLO,
JR
Table 1. CLASSIFICATION OF CEREBROVASCULAR DISEASE: OCCURRENCE AND ETIOLOGY Type of Disease Hemorrhage Subarachnoid hemorrhage Intracerebral hemorrhage Ischemia Cerebral hypoperfusion (systemic disease) Embolism (any source) Large artery occlusion (thromboembolism) Small artery thrombosis
Children and/or Adults AVM, aneurysms
Term
Preterm
Fetal
Spontaneous Spontaneous Spontaneous
Hypertension, bleeding Bleeding disorders disorders
IVH and IPH IVH and IPH
Parasag ittal/diffuse infarctions
Parasagittal/ PVLldiffuse infarcts diffuse infarctions
PVLldiffuse infarcts
Multifocal infarcts
Multifocal infarcts Vascular territory infarct
Multifocal infarcts Vascular territory infarct
Single vascular territory infarct
Small subcortical infarcts
Thalamic/ basal ganglia infarct
Multifocal infarcts Vascular territory infarct
?
?
Abbreviations: AVM = arteriovenous malformation; IPH = intraparenchymal hemorrhage; IVH = intraventricular hemorrhage; PVL = periventricular leukomalacia; ? = rare or not known to occur.
insults. The condition commonly termed "neonatal asphyxia" should represent one form of acute (i.e., perinatal) ischemic cerebrovascular disease in neonates. The timely recognition of such lesions has taken on a new importance in the light of these proposed new treatments. We review perinatal onset cerebrovascular disease because it represents the setting in which intervention is being discussed. The "handicapologist's" definition of the perinatal period, i.e., from the onset of labor to 7 days of age, is used for the same reason. Ischemic injury in this setting is divided into those lesions found in term and preterm infants. Table 2 lists the typical clinical manifestations, neonatal abnormalities, and likely form of cerebral palsy produced for each type of perinatal cerebrovascular disease. We present a case in each category with clinical, electroencephalogram (EEG), and imaging findings that allow recognition of the likely abnormality. A discussion follows of the clinical manifestations for that subtype of cerebrovascular disease and its presumed pathophysiologic characteristics. A discussion of the likely type of cerebral palsy that results from such an injury ends each section. We conclude with a general discussion of how little we know of the cause and effect relations that produce cerebral palsy following perinatal cerebrovascular disease. Arguments are advanced that, so far, our approach to intervention has not met with success. Although serial observations in the neonatal period are the best predictors of significant perinatal injury, they require days to weeks to become predictive and cannot be used for planning an intervention. New ideas in this regard have come from study of the neonate's cerebrovasculature itself and may be a useful marker for intervention.
PERINATAL CEREBROVASCULAR DISEASE IN THE NEONATE
623
Table 2. MAJOR PARENCHYMAL CEREBROVASCULAR LESIONS IN THE PERINATAL PERIOD
Gestation Term
Preterm
Cerebral Vascular Disease Type
Clinical Signs
Cerebral Full neonatal hypoperfusion encephalopathy-abnormal (infant A) EEG/US scan/CT scan at 1-2 days Focal signs and Large artery seizures (no thrombosis coma)-focal (infant B) EEGfUS scan Intracerebral Nonspecific signshemorrhage US scan confirmation at (infant C) 1-3 days (IVHf IPH) Cerebral Nonspecific signshypoperfusion US scan (infant D) confirmation at 1-3 weeks
Abnormality
Cerebral Palsy Type
Widespread cortical/ Spastic quadriparesis subcortical infarcts in parasagittal region and white matter Wedge-shaped Spastic hemiparesis infarction confined to a single vascular territory Hemorrhagic infarction Spastic diplegia in the periventricular white matter contiguous to IVH Ischemic infarction of Spastic diplegia the periventricular white matter + /cystic change (PVL)
Abbreviations: CT = computed tomography; EEG = electroencephalogram; IPH = intraparenchymal hemorrhage; IVH = intraventricular hemorrhage; PVL = periventricular leukomalacia; US = ultrasound.
CEREBRAL HYPOPERFUSION IN THE FULL-TERM INFANT
Case Report Infant A, a 2.95-kg girl, was born at 41 weeks to a primigravida 34-year-old woman who presented in active labor. Over a 25-minute period, a drop in fetal heart rate from 150 to 70 occurred. It did not respond to positioning and maternal oxygen. An emergency caesarean section was arranged. The child was delivered in 30 minutes but just before surgery the heart rate had dropped to 40. At birth no respirations or heart rate was noted. Resuscitation with ventilation, chest compression, and epinephrine was begun. Apgar scores were 0/0/1 at 1, 5, and 10 minutes. The heart rate was obtainable but was less than 100 at 10 minutes. Further epinephrine was given at 12 minutes of age and the heart rate increased. Spontaneous respirations were noted at 20 minutes of age. With controlled assisted ventilation, arterial blood gas at 30 minutes of age, before transfer to the neonatal intensive care center, showed a pH of 6.65, Pco2 of 14, HC0 3 of 2, and a Po, of 142. Blood pressure was supported by pressors for 3 days. Disseminated intravascular coagulation developed by the second day. Cardiac evaluation suggested ischemic myocardial injury, and the child was oliguric for the first 3 days.
Neurologic Course Seizures began at 4 hours of age and did not respond to 30 mg/kg of phenobarbital or 20 mg/kg of phenytoin. A neurologic examination performed at 18 hours of age showed a comatose child who responded to any tactile stimulus with extensor posturing that could not be differentiated from spontaneous tonic seizures. Pupils were small and reactive; oculocephalic maneuver produced conjugate eye movements; corneal and gag reflexes were intact but sluggish. Suck and root reflexes were absent. Results of the
624
ALLAN & RIVIELLO,
JR
motor exam were difficult to evaluate because of the elicited extensor posturing. Seizures came under control by day 4; the infant was feeding by nipple by day 11; discharge was possible by day 16, with the infant having periods of wakefulness sufficient to feed and gain weight.
Studies Cranial ultrasound scan at 18 hours showed "bright brain" consistent with cerebral edema or diffuse infarctions (Fig. lA). Repeat ultrasound scans at 2, 4, and 15 days showed apparent resolution of cerebral edema without definite central nervous system injury. A radionuclide brain scan using technetium-99 labeled albumin was normal at 6 days. At 13 weeks, however, the cranial ultrasound scan showed cystic change in the para sagittal white matter with diffuse ventriculomegaly (Fig. IB). An EEG at 20 hours showed a nearly isoelectric pattern with little spontaneous activity. By day 4 a burst-suppression pattern was seen, and at 1 week, the burstsuppression pattern was interrupted by electrographic seizures without clinical correlate emanating from the right temporal leads. At 13 weeks, a modified hypsarrhythmic pattern was seen.
Follow-up At 6 wee\
