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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.

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.

Brain injury in term neonatal hypoxic-ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE.A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures.Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P ≤ 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P ≤ 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns.In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.

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.

For asphyxiated term infants, prediction of neurological outcome based on clinical criteria alone is not always reliable. We have used changes in tissue density on CT scan (known to represent hypoxic-ischaemic injury) as an adjunct to clinical examination to assess the severity of cerebral injury. The study population comprised 56 term newborns with hypoxic-ischaemic encephalopathy. Scans were performed with a General Electric 8800 scanner and classified as Normal, Patchy, Diffuse or Global according to the extent of areas of decreased density (DD). These were correlated with neurological outcome (i.e. Normal, Minor handicap, Major handicap, Indefinite or Death). Death or major handicap occurred in only two of 14 infants in the combined Normal or Patchy DD groups but in 26 of 29 in the combined Diffuse or Global groups. This correlation was highly significant (p less than 0.0005). 13 classified as Indefinite were normal at age three to 10 months but were excluded from analysis because of the short follow-up. The data demonstrate that CT scanning is a valuable adjunct to neurological examination for assessment of cerebral injury in the asphyxiated term infant.

SUMMARY The pathophysiology of pseudotumor cerebri is unclear, but may relate to an abnormality in water transport in the brain. The authors performed MR imaging in seven children with pseudotumor cerebri; the signal intensity in the white matter was normal in all patients. These data suggest that periventricular brain water content is not increased markedly in children with pseudotumor cerebri. The authors speculate that this may relate to the establishment of an equilibrium between increased resistance to cerebrospinal fluid outflow and increased brain stiffness, occurring as a consequence of increased cerebral blood-volume and/or interstitial pressure. RESUME Imagerie par resonance magnetique dans la pseudotumeur cerebrale La physiopathologie de la pseudotumeur cerebrale n'est pas claire mais pourrait etre reliee a une anomalie due au transport hydrique dans le cerveau. Les auteurs ont pratique des IRM chez sept enfants avec pseudotumeur cerebrale; l'intensite du signal dans la substance blanche etait normale chez tous les patients. Les donnees suggerent que ce contenu hydrique cerebral peri-ventriculaire n'est pas accru de facon marquee chez les enfants porteurs de pseudotumeur cerebrale. Les auteurs se demandent si cela ne pourrait s'expliquer par un equilibre entre une resistance accrue a la circulation du liquide cephalo-rachidien et un accroissement de la raideur cerebrale, apparaissant comme une consequence de l'accroissement du volume sanguin cerebral et/ou de la pression interstitielle. ZUSAMMENFASSUNG Magnet-Resonanz-Tomographie beim Peudolumor cerebri Die Pathophysiologic des Pseudotumor cerebri ist unklar, hangt aber vielleicht mit einer Unregelmasigkeit des Wassertransports im Gehirn zusammen. Die Autoren haben bei sieben Kindern mit Pseudotumor cerebri Kernspintomogramme gemacht; bei alien Patienten war die Intensitat in der weisen Substanz normal. Diese Daten lassen vermuten, das der periventrikulare Wassergehalt bei Kindern mit Pseudotumor cerebri nicht stark erhoht ist. Die Autoren sind der Meinung, das dies mit der Herstellung eines Gleichgewichtes zwischen erhohtem Widerstand gegen Liquorausflus und erhohter Hirnverhartung zusammenhangt, was als Folge eines erhohten cerebralen Blutvolumens und/oder Interstitiellen Druckes auftritt. RESUMEN Imagen por Resonancia Magnetica en el pseudotumor cerebral La fisiopatologia del pseudotumor cerebral no esta clara, pero puede relacionarse con una anomalia en el transporte del agua en el cerebro. Los autores practicaron RM en siete ninos con pseudotumor cerebral; en todos los pacientes la densidad de la substantia blanca era normal. Estos hallazgos sugieren que el contenido de agua periventricular no esta muy aumentado en ninos con pseudotumor cerebral. Los autores especulan que puede estar en relacion con el establecimiento de un equilibrio entre un aumento de la resistencia del curso del LCR y un aumento de la rigidez cerebral, como consecuencia de un aumento del volumen de sangre cerebral y/o de la presion intersticial.

Germinal matrix/intraventricular hemorrhage is a common type of cerebral injury in premature newborns. Based on the improved understanding of underlying pathogenetic mechanisms, numerous interventional strategies for prevention have been proposed. This article summarizes and evaluates the efficacy and safety of major interventions that are currently under consideration for the prevention of germinal matrix/intraventricular hemorrhage.

Enhanced survival of very premature infants may be regarded as the most striking demonstration of the major improvements in perinatal medicine during the last two decades. This article discusses recent perinatal interventions in the context of the pathogenesis and known risk factors for intraventricular hemorrhage (IVH). In addition, controversies related to the evolution and management of posthemorragic hyrdocephalus (PHH) are examined, and current concepts concerning potential brain injury to PHH are reviewed.

Recent epidemiologic data demonstrate that prenatal factors play a major role in the genesis of brain injury in childhood, e.g., cerebral palsy and mental retardation. Nevertheless, there is extensive experimental, clinical, and neuroimaging data that show that acute, intrapartum hypoxic-ischemic insult is an important factor in the genesis of irreversible brain injury, especially in term newborns. The precise timing of onset of hypoxic-ischemic cerebral injury in premature newborns may be more difficult to establish, and postnatal complications (e.g., intraventricular hemorrhage, posthemorrhagic hydrocephalus) undoubtedly play a major role. When the potential deleterious consequences of severe, intrapartum asphyxia are minimized, there is a risk that important opportunities for prevention of newborn cerebral injury may be missed. In this context, new techniques may permit rapid, in vivo delineation of the critical processes involved in newborn hypoxic-ischemic brain injury that are key factors for the development of effective preventive and interventional strategies. MRDD Research Reviews 3:22–27, 1997. © 1997 Wiley-Liss, Inc.

The development of microcephaly after significant hypoxic-ischemic cerebral injury in the full-term newborn has major prognostic significance. However, the onset of microcephaly in this context may be delayed more than 12 months. Objectives. To determine whether serial head circumference measurements and decreased rate of head growth in asphyxiated full-term newborns during the first few months of life may predict the development of eventual microcephaly. Methodology. Serial head circumference measurements at 4, 8, and 18 months of age were obtained in 54 full-term newborns who had acute, hypoxic-ischemic encephalopathy. The rate of head growth was determined on the basis of changes in head circumference ratios which are calculated as follows: actual head circumference/mean head circumference for age x 100%. Head circumference ratios were correlated with severity of newborn encephalopathy and outcome at 18 months. Results. A decrease in head circumference ratios of >3.1% between birth and 4 months of age was highly predictive of the eventual development of microcephaly before 18 months (sensitivity 90%, specificity 85%). Conclusions. These data demonstrate that serial head circumference measurements during the first 4 months of life and calculation of decreased rate of head growth in full-term newborns with hypoxic-ischemic encephalopathy may predict microcephaly before its actual occurrence.

OBJECTIVE. Our goal was to compare the patterns of brain injury detected by computed tomography, conventional MRI (T1- and T2-weighted sequences), and diffusion-weighted MRI in a cohort of term newborns with neonatal encephalopathy studied uniformly with all 3 modalities on the third day of life.METHODS. Term newborns (≥36 weeks' gestation) admitted to our center with neonatal encephalopathy were scanned with computed tomography, MRI, and diffusion-weighted MRI at 72 (±12) hours of life (n = 48). Each modality was scored independently of the other with previously validated scoring systems. The predominant pattern of brain injury was classified as: normal, watershed, basal nuclei, total (maximal basal nuclei and watershed), and focal-multifocal (presence of strokes and/or white matter injury alone).RESULTS. The agreement for the predominant pattern of injury was excellent between MRI and diffusion-weighted MRI (77% agreement). The agreement for the pattern of injury was also good for computed tomography and diffusion-weighted MRI (67% agreement). The extent of cortical injury and focal-multifocal lesions, such as strokes and white matter injury, were less apparent on computed tomography than diffusion-weighted MRI. In 19 newborns with a repeat MRI in the second week of life, the predominant pattern seen on the day 3 diffusion-weighted MRI was confirmed.CONCLUSIONS. Diffusion-weighted MRI is the most sensitive technique with which to assess brain injury on day 3 of life in term newborns with neonatal encephalopathy, particularly for cortical injury and focal-multifocal lesions such as stroke and white matter injury. All 3 modalities identify the most serious patterns of brain injury similarly.

White matter injury (WMI) is the characteristic pattern of brain injury detected on magnetic resonance imaging in the premature newborn. Focal noncystic WMI is increasingly recognized in populations of term newborns. The aim of this study was to describe the occurrence of focal noncystic WMI in a cohort of 48 term newborns with encephalopathy studied with magnetic resonance imaging at 72 +/- 12 h of life, and to identify clinical risk factors for this pattern of injury. Eleven newborns (23%; 95% CI 11-35) were found to have WMI (four minimal, three moderate, and four severe). In 10 of the 11 newborns, the WMI was associated with restricted diffusion on apparent diffusion coefficient maps. An increasing severity of WMI was associated with lower gestational age at birth (p = 0.05), but not lower birth weight. Newborns with WMI had milder encephalopathy and fewer clinical seizures relative to other newborns in the cohort. Other brain injuries were seen in three of the 11 newborns: basal nuclei predominant pattern of injury in one and cortical strokes in two. These findings suggest that WMI in the term newborn is acquired near birth and that the state of brain maturation is an important determinant of this pattern of brain injury.

Intraventricular hemorrhage is an uncommon problem in the full-term newborn. In a review of 19 full-term infants with intraventricular hemorrhage diagnosed on computed tomography prior to 1 month of age, thalamic hemorrhage associated with the intraventricular hemorrhage was documented in 12 infants. Thus, thalamic hemorrhage appears to be the most common source of intraventricular hemorrhage in this age group, particularly in infants who had uneventful birth histories and in whom clinical abnormalities (signs of increased intracranial pressure, seizures, altered level of consciousness) developed after the first week of life. The majority of these infants had predisposing factors for cerebral venous infarction such as sepsis, cyanotic congenital heart disease, and coagulopathy. The clinical appearance and outcome for infants with thalamic hemorrhage/intraventricular ular hemorrhage were similar to those in infants with intraventricular hemorrhage originating from other sites, except for an increased incidence of cerebral palsy in infants with thalamic hemorrhage/intraventricular hemorrhage. Definitive diagnosis was made on the basis of characteristic radiologic abnormalities.

Four newborns presented with isolated radial nerve palsy during the first 2 days of life. In three, there was a history of failure of progression of labor, which may have resulted in prolonged radial nerve compression. Furthermore, three infants had fat necrosis of the upper arm above the elbow, suggestive of compression of the radial nerve in the region of the spiral groove. Significant recovery of function was evident within 1 month in all four infants. The authors review published reports about the rare condition of isolated radial nerve palsy in the newborn.

Perinatal hypoxic-ischemic cerebral injury is a significant cause of neurological morbidity and mortality in childhood. It is often difficult to determine the precise timing of such injury. Data from epidemiological and neuropathological studies have identified several maternal and fetal risk factors that seem to be associated with suspected prenatal brain injury. Hypoxic-ischemic cerebral injury that originates earlier in gestation may result in few, if any, clinical abnormalities during the newborn perlod. Clinical abnormalities may also be difficult to recognize in the premature newborn, and greater reliance must be placed on other adjunctive investigations, eg, neuroimaging. In contrast, term infants who sustain acute, intrapartum hypoxic-ischemic insult of sufficient magnitude to result in long-term sequelae invariably show recognizable encephalopathy during the newborn period. A combination of clinical data and adjunctive investigations during the neonatal period is a powerful predictive tool for long-term outcome.

Review of 17 newborns with muscle disease demonstrated that clinical features associated with survival beyond 1 year of age included gestational age of at least 35 weeks and requirement of mechanical ventilation for less than 21 days. In contrast, poor outcome was associated with Apgar scores below 5 at 5 min, pulmonary complications, arthrogryposis, or other congenital anomalies. The incidence of decreased fetal movements, polyhydramnios, hypotonia, and assisted delivery was not statistically different between infants who died early and those who survived beyond 1 year of age. Clinical features of newborns with muscle disease may be useful for prediction of outcome, especially when muscle biopsy abnormalities are nonspecific.

Acute perinatal hypoxic-ischemic cerebral injury in the term newborn is a major cause of long-term neurologic abnormalities in childhood. Earlier diagnosis and more precise localization of hypoxic-ischemic cerebral injury has been made possible by optimal timing and the use of new imaging modalities (e.g., magnetic resonance imaging, spectroscopy, computed tomography, cerebral perfusion techniques). Recent concepts on pathogenesis of such injury involves metabolic factors, regional distribution of excitatory (glutamate) synapses, and factors related to active myelination in specific areas at the time of insult. Consideration of these aspects of pathogenesis permit a rational approach to the management of this major neurologic problem in the newborn.

• Recent data suggest that early loss of brain tissue water content, ie, decreased extravascular cerebral tissue pressure, may play a role in the pathogenesis of germinal matrix/intraventricular hemorrhage in the premature newborn. This study examines the relationship between the concentration of serum sodium and germinal matrix/intraventricular hemorrhage in 299 premature infants with birth weights of less than 1500 g during the first 4 days of life. Intraventricular hemorrhage developed in 34 (32%) of the 106 infants with maximum serum sodium levels of 145 mmol/L or less and in 54 (28%) of 193 infants whose highest serum sodium levels were greater than 145 mmol/L (χ 2 =0.37). These data suggest that concentrations of serum sodium greater than 145 mmol/L are not associated with an increased risk of germinal matrix/intraventricular hemorrhage in the premature newborn. Consequently, more liberal administration of fluids to maintain extravascular cerebral tissue pressure is unlikely to reduce the incidence of germinal matrix hemorrhage/intraventricular hemorrhage. ( AJDC . 1990;144:1019-1021)

In Reply.— Rooman et al report on an infant who developed thalamic hemorrhage associated with a urinary tract infection caused by Escherichia coli. They speculate that E coli endotoxin may enhance clotting potential via the extrinsic cascade and decrease endothelial thrombomodulin expression, thus shifting the hemostatic balance and increasing the risk of cerebral venous infarction. In our article,1 we suggest that the most probable mechanism causing thalamic/intraventricular hemorrhage in the full-term newborn is thrombosis of the deep cerebral veins resulting in infarction and secondary hemorrhage in the thalamic region.

Periventricular leukomalacia (PVL) occurs commonly in premature infants. The white matter injury is considered to be principally a consequence of ischemic insult to vascular watershed zones with high intrinsic vulnerability. However, other factors, eg., bacterial endotoxins, have also been implicated. In premature newborns with PVL, we observed a high incidence (50%) of presumed antenatal infection compared with controls, based on clinical data. In this study, we describe placental abnormalities associated with cystic PVL and assess their clinical relevance in its pathogenesis.

Purpose: To determine if data transmission errors are related to electromagnetic interference (EMI).

139 COMPARISON OF FOREARM OXYGENATION DURING ISCHAEMIA BY NEAR INFRARED SPECTROSCOPY AND PO 2 HISTOGRAPHY

Aminophylline is commonly used for treatment of apnea and to permit weaning from ventilation in preterm newborns. Previous reports have indicated that it may cause cerebral vasoconstriction and reduction in cerebral blood flow (CBF) and cerebral blood volume (CBV). It is not known whether such reduction in CBF/CBV results in significant reduction in cerebral oxygenation. The purpose of this study was to evaluate the effect of aminophylline therapy on CBV and cerebral oxygenation using near infrared spectroscopy (NIRS Hamamatsu 500), Aminophyllinc (6.5 mg/kg) was given intravenously prior to weaning from the ventilator to 19 stable preterm infants (mean g.a.: 32 wks) with hyaline membrane disease. CBV, Hb diff (HbO2-Hb), deoxyhemoglobin (Hb) and cytochrome oxidase (CtO2) were measured using NIRS before and after aminophylline infusion. Continuous recordings of mean arterial pressure (MAP), tcpCO2 and tcpO2 were correlated with NIRS data. There was a marked fall in CBV after aminophylline infusion in 15 newborns with no significant reduction in tcpCO2. Despite reduction in CBV, cerebral oxygenation (HbD, CtO2) improved in stable preterm newborns.

Magnetic resonance imaging is presently the best modality for evaluating gray/white matter anatomy. However, this modality is expensive and not yet readily available in all countries. Most neuronal migration abnormalities can be accurately diagnosed by computed tomography (CT) provided excellent scanning technique is used. Abnormalities of neuronal migration were identified with CT brain scans in 68 children and were categorized as focal heterotopias (11 patients), multifocal heterotopias (19 patients) of diffuse migration disorders (38 patients). The principal indications for imaging were correlated to the radiological features. Neuropathological confirmation of the migration abnormality was obtained in 8 patients. An increased awareness by both clinicians and radiologists together with optimal CT technique are essential for the accurate diagnosis of migration disorders in children.

Visual defects are often poorly recognized in children with multiple neurologic problems due to perinatal hypoxic-ischemic encephalopathy. We report the clinical, radiologic, and electrodiagnostic characteristics of 20 children with cortical visual impairment secondary to birth asphyxia. Clinical diagnosis often was delayed. Ten patients recovered vision during the first two years of life. Four infants had coexisting damage to the pregeniculate visual pathway. Useful investigations included cranial computed tomography and visual evoked potential mapping. Electroencephalographic abnormalities were nonspecific. The classical definition of cortical blindness must be modified for children.

Ischemic brain injury in the newborn is a common cause of subsequent neurologic deficits seen in older children. Clearly, determination of severity and location of such injury is important for management and prognosis. Although ultrasound scanning of the brain has been used extensively in the premature infant for diagnosis of hemorrhagic lesions, its use in the term infant for recognition of isehemic cerebral lesions has not been reported. Four cases are described in which focal echodense areas were identified on ultrasound scan of the brain. These echodense areas on ultrasound corresponded to the appearance on computed tomographic (CT) scan of areas of decreased density which are known to represent ischemic cerebral injury. In three of the four cases there were focal neurologic findings and/or focal abnormalities on EEG. In two cases, real-time ultrasound scanning demonstrated changes in arterial pulsations in cerebral vessels in the area of the lesions. Thus in both, there was diminution in pulsations within the echodense areas and in one case, an increase in pulsations was observed at the periphery of the echodense lesion. Our data demonstrate the value of ultrasound scanning for assessment of the extent and location of focal cerebral ischemic lesions in the newborn. Such assessment permite assessment of prognosis.

The role of brain swelling following acute hypoxic-ischemic insult in the genesis of brain injury in the term newborn is controversial. Recent experimental animal studies suggest that it may result from prior irreversible cerebral necrosis and therefore represents a consequence as opposed to a cause of major brain injury. In this study, 32 asphyxiated term newborns were studied during the first week of life with serial intracranial pressure measurements. A total of 26 infants had scans during the first five days of life. Seven patients had two CT scans within this period. These investigations were correlated with outcome at 18 months of age. Seven infants had increased intracranial pressure (> 10 mm Hg) that reached a maximum between 36 and 72 hours of age. Cerebral perfusion pressures remained normal, which makes ongoing ischemic injury unlikely as a cause. The seven patients with increased intracranial pressure had decreased attenuation on CT that was generalized in six infants and patchy in one infant. Of the infants with increased intracranial pressure and severe CT abnormalities, three died and four had severe neurologic sequelae. In seven infants, a second CT scan at three to four days of life demonstrated progression of the decrease in tissue attenuation. Most of the infants with normal intracranial pressure (23/25) had no or had only minor neurologic abnormalities at follow-up. These data suggest that brain swelling is relatively uncommon in the asphyxiated term newborn. The temporal profile of increased intracranial pressure and CT abnormalities, with maximum abnormalities at 36 to 72 hours of age, is most consistent with cerebral necrosis as a cause that, in turn, implies a poor prognosis.

An ultrasonic technique based on measurement of the Doppler frequency shift produced by the movement of red blood cells in an insonated vessel has been useful for measurement of cerebral blood flow velocity in the newborn. When the transducer is applied to the anterior fontanel, flow velocity in each anterior cerebral artery can be determined noninvasively. Reliable application ofthe technique requires utilization of both the audible and visible signals produced by the instrument. Experience and awareness of the anatomy are also important in interpretation. Serial measurements of cerebral blood flow velocity have provided useful information concerning changes in the cerebral circulation under important neonatal circumstances. Examples of the latter include PDA, pneumothorax, hydrocephalus, and hyperviscosity. Most of the changes in the cerebral circulation appear to reflect directly systemic hemodynamic changes. This relation between cerebral and systemic hemodynamic events is compatible with other observations, indicating that in the human newborn—particularly the infant most at risk for hypoxic-ischemic and/or hemorrhagic brain injury—the cerebral circulation is pressure passive. Indeed, the changes in the cerebral circulation observed so far with the Doppler technique may have important implications for the genesis of neonatal ischemic and hemorrhagic brain injury.

The relationship of pneumothorax to the occurrence of intraventricular hemorrhage (IVH) has been studied in the premature newborn. The major objective of the study was to determine whether the systemic hemodynamic changes that occur with pneumothorax are reflected in the cerebral circulation and whether these changes play a role in pathogenesis of IVH. Blood flow velocity was measured in the anterior cerebral arteries by a transcutaneous Doppler technique in nine infants who developed pneumothorax in the first 3 days of life. At the time of pneumothorax there was a marked increase in flow velocity, especially during diastole, and, with resolution of pneumothorax, flow velocity returned to normal levels over the ensuing hours. The changes in flow velocity correlated closely with systemic hemodynamic changes that occurred with pneumothorax, ie, an increase in mean systemic blood pressure, especially diastolic pressure. IVH, documented by serial ultrasound scans, was observed shortly after pneumothorax in the nine infants. The data thus demonstrate a marked increase in flow velocity in the cerebral circulation at the time of pneumothorax. This increase is of importance in the genesis of IVH as is suggested further by the occurrence of IVH soon after the cerebral hemodynamic changes.

The entity of normal pressure hydrocephalus (NPH) following intraventricular hemorrhage in the newborn has been characterized. Of 87 infants with intraventricular hemorrhage, 20 had early and rapidly progressive hydrocephalus with intracranial hypertension and/or death. In 47 cases there was no increase in ventricular size and in 20 cases there was progressive increase in ventricular size with normal intracranial pressure, ie, NPH. Of these infants with NPH, nine had spontaneous arrest with or without resolution of ventriculomegaly, beginning within 31 days of onset. In 11 cases, after a stable period of NPH lasting 12 to 84 days, there was progressive increase in ventricular size accompanied ultimately by raised intracranial pressure. A relationship between the degree of ventriculomegaly and severity of intraventricular hemorrhage was demonstrated. The data thus define a state of NPH after intraventricular hemorrhage and indicate that approximately half of such cases will not develop progressive hydrocephalus with increased intracranial pressure. If arrest or onset of resolution of ventriculomegaly is not apparent within approximately one month, continued progression and necessity for intervention are to be expected. Serial measurements of intracranial pressure and ventricular size in newborns with posthemorrhagic ventricular dilation allow the diagnosis of NPH and permit early recognition of rapidly progressive ventricular dilation with intracranial hypertension which may follow a stable period of NPH. Such early recognition of this potentially harmful state allows prompt ventricular drainage, thereby preventing brain compression.

The effect of ventriculomegaly with or without elevated intracranial pressure (ICP) on pulsatile flow in the anterior cerebral artery has been studied by a noninvasive Doppler technique in 11 infants with hydrocephalus. The cause of hydrocephalus was intraventricular hemorrhage in nine infants, Arnold-Chiari malformation in one, and bacterial meningitis in one. The pulsatility index (PI) (inversely related to pulsatile flow) was calculated from the systolic and diastolic amplitudes of flow in the anterior cerebral artery. All 11 patients with elevated PI had marked ventriculomegaly, and all but two had raised ICP. Four patients with massive ventriculomegaly and elevated ICP had maximal PI (ie, 1.00). The finding of elevated PI with ventriculomegaly and normal ICP, observed in two patients, suggested that ventriculomegaly is a more critical factor than ICP in the pathogenesis of the impaired flow. Treatment of ventriculomegaly in seven patients resulted in a decrease in PI. Of the four untreated patients, three died and one was not available for further study. Compromised flow in the anterior cerebral artery may be a sensitive barometer of impending ischemic injury with evolving ventriculomegaly, particularly following intraventricular hemorrhage. The PI may be a valuable parameter for the study of the mechanism of brain injury and for determination of optimal timing of corrective intervention.

This article reviews the significance of hypoxic-ischemic encephalopathy and the associated patterns of cerebral injury in the context of the most probable timing of the insult and prognosis. The evolution of the clinical features of significant hypoxic-ischemic encephalopathy, and the diagnostic value of imaging and electrophysiologic and metabolic studies are discussed. Current approaches to management are outlined.

Aicardi's syndrome occurs in females and is associated with profound mental retardation, agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms. We report a distinctive combination of abnormalities which was observed on real-time cranial ultrasound scans of two infants with Aicardi's syndrome. These abnormalities include bilateral prominent cysts in the choroid plexus in conjunction with agenesis of the corpus callosum. Recognition of these radiologic findings may suggest the diagnosis of Aicardi's syndrome in early infancy even prior to the onset of seizures or visualization of chorioretinal lacunae. (J Child Neurol 1989;4:307-310).

Serial lumbar punctures for the management of neonatal posthemorrhagic hydrocephalus without intracranial hypertension were evaluated in 16 infants. Cranial ultrasonography to evaluate ventricular size and the Ladd monitor at the anterior fontanel to measure intracranial pressure were utilized immediately before and after lumbar puncture. In 12 patients, a decrease in ventricular size and in anterior fontanel pressure could be effected with each lumbar puncture. In these infants, cessation of progression of the hydrocephalus and intermittent decreases in ventricular size were accomplished. In four patients, lumbar punctures were not successful in decreasing ventricular size or lowering intracranial pressure. Two criteria could be defined to determine whether lumbar puncture could provide at least temporary benefit for the treatment of posthemorrhagic hydrocephalus. The first of these is to establish the presence of communication between lateral ventricles and lumbar subarachnoid space by effecting a decrease in ventricular size and a decrease in intracranial pressure by removal of CSF. The second criterion is to ascertain a critical volume of CSF (usually relatively large) that must be removed in order to effect the above changes. Cranial ultrasonography and measurement of intracranial pressure by application of the Ladd monitor to the anterior fontanel are extremely valuable in the evaluation of lumbar punctures in the management of posthemorrhagic hydrocephalus.

9. Deonna T, Payot M, Probst A, and Prod'ham LS: Neonatal intracranial hemorrhage in premature infants, Pediatrics 56:1056, 1975. 10. Farwell JR, and Scott DT: Intracranial hemorrhage in premature infants: Population characteristics, CSF findings and factors related to outcome, Ann Neurol 4:186, 1978. I1. Fujimura M, Salisbury DM, Robinson RO, Howat P, Emerson PM, Keeling J, and Tizard JPM: Clinical events relating to intraventricular haemorrhage in the newborn, Arch Dis Child 54:409, 1979. i2. Volpe JJ: Intracranial haemorrhage in the newborn: Current understanding and dilemmas, Neurology 29:632, 1979. 13. Lazarra A, Ahmann PA, Dykes FD, Brann D, and Schwartz JF: Clinical predictability of intraventricular hemorrhage in preterm infants, Pediatrics 65:30, 1980. 14. Tsiantos A, Victorin L, Relier JP, Dyer N, Sundell J, Brill AB, and Stahlman M: Intracranial hemorrhage in the prematurely born infant. Timing of clots and evaluation of clinical signs and symptoms, J PEDIATR 85:854, 1974. 15. Krishnamoorthy KS, Fernandez RA, Momose KJ, DeLong GR, Moylan F, Todres ID, and Shannon DC: Evaluation of neonatal intracranial hemorrhage by computerized tomography, Pediatrics 59:165, 1977. 16. Saint-Anne Dargassies S: Neurological development in full-term and premature neonates, Amsterdam, 1977, Elsevier/North Holland/Excerpta Medica. 17. Prechtl H: The neurological examination of the full-term newborn infant, in Clinics in developmental medicine, No. 63, London, 1977, SIMP/Heinemann. 18. Prechtl H, and Beintema D: The neurological examination of the full-term newborn infant, in Clinics in developmental medicine, No. 12, London, 1964, SIMP/Heinemann. 19. Brazelton TB: Neonatal behaviour assessment scale, in Clinics in developmental medicine, No. 50, London, 1973, SIMP/Heinemann.

This article describes four techniques for the noninvasive measurement of intracranial pressure in the newborn, and discusses common pitfalls in their use, and various pathologic states (for example, intraventricular hemorrhage, perinatal asphyxia, posthemorrhagic hydrocephalus, and bacterial meningitis) in which measurements of ICP have been demonstrated to be or are likely to be of value.

The pathogenesis of the intracranial complications of hypernatremia has been the subject of considerable research.1-5 The purpose of this communication is to report unusual appearances on computed tomographic (CT) scan of the brain in an infant who developed hypernatremia as a result of salt poisoning. CASE REPORT The patient, a 6-month-old male infant, was admitted for investigation of seizures. He had been admitted to another hospital on the evening of Jan 25, 1983, because of several episodes in which he rolled his eyes and had generalized stiffening and back arching. Diazepam had been given intramuscularly, and the infant was then given intravenous (IV) fluids (50 mmol of sodium chloride and 33.3 g of dextrose per liter).

Ventricular dilation is common following intraventricular hemorrhage. Neuropathologic studies have demonstrated that chronic posthemorrhagic hydrocephalus most commonly is a result of an obliterative arachnoiditis in the posterior fossa or is due to obstruction of flow of CSF within the ventricular system. Recent use of ultrasound scanning has demonstrated the occurrence of ventricular dilation within days of intraventricular hemorrhage (prior to the expected time of development of arachnoiditis). In the case described, serial realtime ultrasound scans demonstrated small mobile particles within dilated ventricles seven days following intraventicular hemorrhage. There was no obstruction of CSF flow within the ventricular system. Thus, in this case, ventricular dilation may have been secondary to plugging of arachnoid villi by the small particulate matter and, as a consequence, decrease in CSF reabsorption.

Hemorrhage into areas of periventricular leukomalacia may occur and range in size from microscopic to massive. Hitherto, the definitive diagnosis has been made only at autopsy. A case is described in which the diagnosis of hemorrhagic periventricular leukomalacia was made antemortem by real-time ultrasound scanning and confirmed at autopsy. Periventricular/intraventricular hemorrhage, a more common hemorrhagic lesion, may extend into periventricular white matter in a location ventral and medial to hemorrhagic periventricular leukomalacia. Real-time ultrasound scanning is a safe and reliable means of defining the topography of these two hemorrhagic lesions and, thereby, of suggesting the correct diagnosis.

The significance of thin ribs among 26 newborns diagnosed as having neuromuscular disease is discussed. 19 had a chest X-ray. Thin ribs were observed in three of seven with congenital myotonic dystrophy, in two of four with myotubular myopathy and in one of five with spinal muscular atrophy. The ribs were normal in one case of nemaline myopathy and two cases of non-specific myopathy. Polyhydramnios was recorded in four of the six cases with thin ribs. Ventilatory support frequently was required for these infants. The observation of thin ribs on X-ray is highly suggestive of neonatal neuromuscular disease, and is neither specific for nor invariable in congenital myotonic dystrophy.

an intraperitoneal air-fluid level on a true horizontal beam roentgenogram; if present, laparotomy is indicated. If a neonate has both a posterior pneumomedias t inum and a large pneumoperi toneum, or a peak inspiratory pressure of at least 30 cm H~O with evidence of extraalveolar air a n d a large pneumoperi toneum, the infant can be safely observed. If a ventilated neonate with a pneumoperi toneum has no extra-alveolar air dissection and a peak inspiratory pressure o f less than 28 cm H20, laparotomy should be undertaken. Although each of our 12 cases could be retrospectively differentiated, some may occur in which a clear differentiation cannot be made because of inconsistency of the above findings. In such a situation, additional information is needed. Paracentesis with an intravascular catheter is advocated as the next diagnostic maneuver to allow a prompt decision regarding operation. Looking for a leak on serial decubitus films performed with water, soluble contrast using Portable equipment in the nurserY , or waiting for the development of an intraperitoneal airfluid level on serial decubitus films wastes time for an infant who may have peritonitis; these findings are helpful only if they are positive. Paracentesis allows prompt assessment of a continuous air leak, measurement of the oxygen concentration in the peritoneal gas, and the sampling of any intra-abdominal fluid present. Bubbling from the drainage tubing with ventilator cycling confirms the respiratory origin of the pneumoperi toneum. 6 A high oxygen concentration in the peritoneal gas favors a respiratory origin of the pneumoperi toneum. 7 Obtaining more than one-half a cubic centimeter of green or turbid brown fluid on aspiration favors a diagnosis of intestinal perforationY

Marked changes in blood flow velocity in the anterior cerebral arteries, measured by a Doppler technique, have been related to PDA in premature infants. Thus, 55 premature infants of birth weight less than 2,000 gm were studied. Ten developed PDA between days three and ten of life. A sharp decrease in diastolic flow velocity and an increase in pulse amplitude in the ACA was observed with the occurrence of PDA. Return of these values to normal occurred promptly following closure of the lesion. These changes in flow velocity and pulse amplitude in the ACA appear to be determined principally by changes in systemic diastolic pressure which accompany PDA. There was no consistent relationship between the changes in flow velocity and arterial PCO2 values. These data suggest that PDA may be involved in the genesis of ischemic and hemorrhagic cerebral injury in the premature newborn infant. Thus, the decrease in flow velocity appears to represent a "steal" of blood from the cerebral arteries, analogous to other documented steal phenomena observed in older patients. Major fluctuations of blood flow velocity in the ACA, with opening and closure of the PDA, and the increase in amplitude of each pulse with PDA may, in the presence of disturbed autoregulation, cause rupture of the capillaries of the germinal matrix and thus, IVH.

Periventricular leukomalacia is an ischemic lesion in periventricular white matter of premature infants. Hemorrhage into the ischemic area occurs in up to 25% of cases. We report two cases in which the diagnosis of periventricular leukomalacia was made during life with real-time ultrasound scanning. In one case, serial scans demonstrated the evolution of echodense regions, observed in the first 3 days of life, to cystic echolucent areas at 4 weeks. In the second case, periventricular echodense areas did not precede the occurrence of cystic echolucent lesions. This may reflect a more chronic ischemic cerebral insult (consistent with recurrent apnea and bradycardia) rather than a presumed acute episode of cerebral ischemia (with or without secondary hemorrhage) sustained by the first case. Real-time ultrasound scanning is a simple, non-invasive technique with which to document the evolution of periventricular leukomalacia, and thus to define the clinical neurological correlates in the neonatal period.

This article reviews recent advances in the antepartum and intrapartum assessment of the fetus and their relationship to brain injury in the newborn. The antepartum assessment involves observation of fetal body and eye movements, the nonstress and contraction stress tests, measurement of amniotic fluid volume, the fetal biophysical score and measurement of fetoplacental blood physiology. There is evidence to suggest that seizures may either be epileptic in origin or initiated and mediated by nonepileptic mechanisms. Therapeutic decisions may be based on bedside assessment of the pathophysiology of observed seizures. Although EEG/video monitoring plays a role in the management of neonatal seizures, clinical evaluation of the seizures may provide initial data critical to decisions concerning immediate management.

SUMMARY An infant with hydrocephalus which had been diagnosed at birth died at one month of age. Subsequent neuropathological studies demonstrated old germinal matrix haemorrhage and complete occlusion of the aqueduct of Sylvius by fibroglial tissue, both of which appeared to be older than four weeks, indicating that they had occurred in utero. These observations are consistent with the occurrence of intra-uterine intraventricular haemorrhage secondary to haemorrhage of the subependymal germinal matrix, leading to occlusion of the aqueduct of Sylvius and hydrocephalus prior to birth. RESUME Hydrocephalie congenitale secondaire a une hemorragie intraventriculaire. intra-uterine de la couche germinative Un nourrisson, chez qui le diagnostic d'hydrocephalie avait ete posea la naissance mourut a l'age d'un mois. Les etudes neuro-pathologiques ulterieures revelerent une ancienne hemorragie de la couche germinative avec occlusion complete de l'aqueduc de Sylvius par du tissu fibroglial, ces lesions paraissant avoir plus de quatre semaines, ce qui indiquait qu'elles etaient survenues in utero. Ces observations sont en accord avec la survenue d'hemorragies intraventriculaires intra-uterines secondaires a une hemorragie de la couche germinative sous-ependymaire, conduisant a une occlusion de l'aqueduc de Sylvius et une hydrocephalie avant la naissance. ZUSAMMENFASSUNG Congenitafer Hydrocephalus als Folge para- und intraventrikufarer Bfurung in Urero Ein Kind, das mit Hydrocephalus geboren wurde, starb im Alter von vier Wochen. Die durchgefohrten neuropathologischen Studien zeigten eine alte Blutung im Bereich der Matrix germinativum und einen vollstandigen Verschluβ des Aquaeductus Sylvii durch fibroses Gliagewebe. Beides schien alter als vier Wochen zu sein, was bedeutet, daβ es in Utero entstanden sein mug. Diese Beobachtungen sprechen fur das Auftreten einer intra-uterinen intraventrikularen Blutung aus der subependymalen Matrix germinativum, wodurch der Aquaeductus Sylvii verschlossen wird und sich vor der Geburt ein Hydrocephalus ausbildet. RESUMEN Hidrocefalia congenita secundaria a una hemorragia intra-uterina en la marriz germinal/intraventricular Un lactante con hidrocefalia que habia sido diagnosticado al nacer murio al mes de edad. Los estudios neuropatologicos subsiguientes demostraron una antigua hemorragia de la matriz germinal y una oclusion completa del acueducto de Silvio por un tejido fibroglial, ambos de mh de cuatro semanas antiguedad, lo que indicaba que habian tenido lugar in utero. Estas observaciones son coherentes con la aparicion de hemorragia intraventricular inrauterina secundaria a una hemorragia subependimaria de la matriz germinal, que da lugar a la oclusion del acueducto de Silvio y a una hidrocefalia anterior al nacimiento.

Hemorrhage into periventricular white matter may be due to intraparenchymal extension of intraventricular hemorrhage (IVH) or to secondary hemorrhage into areas of infarction, i.e. HPVL. Because IVH and HPVL occur principally in the premature infant, they may coexist. Distinction is important because IVH with intraparenchymal extension may not be followed by major parenchymal injury whereas prominent HPVL is indicative of severe brain infarction. Using US, we have made the antemortem diagnosis of HPVL, (confirmed at autopsy), in a premature infant with prior severe hypotension. The infant sustained several postnatal hypoxic-ischemic episodes followed by restoration of circulation. US at age 31 days was compatible with hemorrhage in the periventricular regions dorsal and lateral to the germinal matrix. There was no evidence of IVH. Death occurred on day 34 and autopsy examination revealed massive hemorrhagic infarction in the periventricular regions and no evidence of IVH. The use of the noninvasive technique of US permitted antemortem diagnosis of HPVL and differentiation from IVH with intraparenchymal extension. HPVL has been hitherto diagnosed only at autopsy. Although HPVL may be less common than IVH, its recognition during life is important, because in infants who survive, awareness of site and extent of cerebral injury provides valuable prognostic information.

• The role of thrombocytopenia as a risk factor for intraventricular hemorrhage in infants of very low birth weight is unclear. This study investigates the relationship between the lowest platelet count and the occurrence of intraventricular hemorrhage in 302 consecutively admitted infants with birth weights under 1500 g. Intraventricular hemorrhage, which occurred in 90 infants (29.8%), was correlated with the lowest platelet count obtained during the first 4 days of life. In 27 infants with intraventricular hemorrhage, the lowest platelet count was less than 100×10 9 /L. Statistical analysis of the data demonstrated that reduced platelet count was not associated significantly with intraventricular hemorrhage. Similarly, the severity of intraventricular hemorrhage did not correlate with the lowest platelet count. These data suggest that a reduced platelet count does not play a major role in the pathogenesis of intraventricular hemorrhage in infants of very low birth weight. ( AJDC 1988;142:1222-1224)