The distribution of cerebral lesions induced by acute total asphyxia rarely reproduces the distribution of lesions found in infants who have survived partial but prolonged asphyxia. When prolonged partial asphyxia is induced experimentally, primates develop high carbon dioxide partial pressure (pCO₂) levels and mixed metabolic and respiratory acidosis (78,84). These are usually accompanied by marked brain swelling, which compresses the small blood vessels of the cerebral parenchyma. The resultant increase in vascular resistance superimposed on the systemic alterations leads to various focal cerebral circulatory lesions whose location is governed in part by vascular patterns and in part by the gestational age of the fetus at the time of the asphyxial insult (85,86). Selective necrosis of neurons may be followed by mineralization of those cells.

The neonatal cerebral cortex is vulnerable to laminar necrosis after a severe ischemic insult. This selective neuronal necrosis involves some layers more than others. In preterm and term infants, layers 3 and 5, which contain pyramidal cells, are most vulnerable, but in later infancy and childhood, layer 4 is most severely affected. This layer contains granule cells that are sensory, rather than motor, in function. Layer 4 is largest in the striate (occipital) cortex, where it is the principal visual receptive zone. Laminar necrosis is extensive degeneration of neurons in the affected layers, with relatively better preservation in other layers, though pyknosis and karyorrhexis indicating dying neurons are seen in neurons in all layers. These changes may be expressed in infants who survive as cortical blindness and spastic diplegia, though damage in other parts of the brain, such as the lateral geniculate body and periventricular leukomalacia also contribute to the clinical deficits. Laminar necrosis may be identified in MRI, particularly in fluid-attenuated inversion recovery (FLAIR) sequences, as a bright line of increased signal within the cortex and parallel to the surface of the brain (Fig. 6.5).

One lesion that occurs with particular frequency in the premature infant is periventricular leukomalacia (PVL) (Figs. 6.6 and 6.7). First delineated by Banker and Larroche (87), this condition consists of a bilateral, fairly symmetric necrosis having a periventricular distribution. The two most common sites are at the level of the occipital radiation and in the white matter around the foramen of Monro (88,89). In addition, there can be diffuse cerebral white matter necrosis that usually spares the gyral cores (90). Preterm infants of 22 to 30 weeks’ gestation tend to experience more widespread and confluent periventricular necrosis, whereas older premature infants exhibit more-focal necrosis (91).

The evolution of PVL has been studied by neuropathologic and neuroimaging methods. Within 6 to 12 hours of the suspected insult, coagulation necrosis occurs in the affected areas, accompanied by proliferation of astrocytes and microglia, loss of ependyma, and, in some cases, subcortical degeneration. Focal axonal disruption and death of oligodendroglia are some of the earliest signs of injury, with the developing oligodendroglia being especially vulnerable (4).

The pathogenesis of PVL is uncertain and is most likely to be multifactorial. Five major factors are believed to be operative.

From a clinical point of view, spastic diplegia is the most common and most consistent sequela of PVL. It is nearly always bilateral, although often asymmetric in severity. Because of the propensity of the periventricular necrotizing lesions to appear earliest and most prominently around the occipital horns of the lateral ventricles, optic radiation fibers may be involved and sometimes also result in cortical visual impairment.

A number of adverse perinatal events correlate with the development of PVL. Most important, PVL tends to occur
in the larger premature infant, with the highest incidence by both neuropathologic and ultrasound criteria being between 27 and 30 weeks’ gestational age (109,110) (Table 6.1). In the more recent French series of Baud and coworkers, published in 1999, the highest incidence (12.9%) was, however, seen in infants whose gestational age was 24 to 26 weeks (111). Other notable risk factors include prenatal factors such as premature, prolonged, or both premature and prolonged rupture of membranes, chorioamnionitis, and intrauterine infections (109,110,112). Several perinatal and postnatal factors also appear to be of importance. These are listed in Table 6.2 (4,113,114). In many instances, however, infants in whom PVL evolved had a relatively benign postnatal course (110). Although systemic hypotension has been suggested as an important pathogenetic factor, several studies failed to show an association between hypotension and PVL (115,116). In part, this lack of documentation reflects the lack of direct and continuous blood pressure recordings, or it might indicate that PVL results from a discrepancy between the metabolic requirements of periventricular white matter and its perfusion (117). We also stress that in infants of less than 31 weeks’ gestation, relatively small reductions in systemic blood pressure (less than 30 mm Hg) for 1 hour or longer suffice to induce cerebral infarcts (118). This is particularly true in those in whom autoregulation is defective or has been disrupted by asphyxia. As a rule, the less mature the periventricular vasculature, the less significant are the clinical complications that accompany the evolution of PVL.

Several observational studies have reported that both maternal preeclampsia and the prenatal administration of magnesium resulted in a lower incidence of spastic diplegia, and by inference of PVL, in very low birth weight infants (119,120,121). These observations could not be confirmed in a controlled, retrospective study (122), and randomized clinical trials will be necessary to determine the effectiveness of magnesium. In addition, there are large and still unexplained differences among centers in the outcomes of extremely low birth weight infants, which also will require controlled clinical trials (123).

Newer imaging techniques such as ultrasonography and magnetic resonance imaging (MRI) permit the following of the evolution of PVL. In the series of infants autopsied by Iida and colleagues (90), the prenatal onset of PVL was observed in 20% of stillborn infants and in 16.4% of infants who died by 3 days of age. These findings have been confirmed by ultrasound studies showing the presence of cystic PVL as early as the third day of life (90,124). The evolution of PVL can be followed by ultrasonography. During the first week of life, transient hyperechoic periventricular areas are frequent and probably represent a persistent germinal matrix (125). Persistent echogenic foci are pathologic, however. They too are seen during the first week of postnatal life. Within 1 to 3 weeks they are replaced with echolucent, cystic foci (cystic leukomalacia) (see Fig. 6.7C and D). As the intracystic fluid becomes resorbed, these cysts disappear and are replaced by gliosis (126). PVL can be accompanied by cystic lesions in the subcortical white matter and by delayed myelination (127). In some instances, gliosis becomes interspersed with areas of microcalcification (128). Calcification is more likely when lesions are not extensive. Premature infants with PVL have a marked reduction in cerebral cortical gray matter volume at term as compared to premature infants without PVL. This may reflect destruction of corticopedal, corticofugal, and associative fibers with secondary impairment of neuronal differentiation (129).

Periventricular echodensities can reflect several neuropathologic entities aside from PVL. They also are observed in hemorrhagic infarctions such as are seen in association with IVH and in ischemic edema (130). PVL becomes hemorrhagic in up to 25% of infants (131), mostly a consequence of a hemorrhage into the ischemic area, the outcome of subsequent reperfusion (4).

The most common site of brain damage in the term newborn is the cortex. Experimental studies have confirmed that the parasagittal cortex is the earliest and most severely damaged on prolonged asphyxia, with the amount of damage increasing geometrically with increasing duration of asphyxia (132). The lesions characteristically involve the territory supplied by the most peripheral branches of the three large cerebral arteries (Fig. 6.8) (133). Infarctions in this area are secondary to arterial or venous stasis and thromboses. One common pattern for the distribution of lesions, termed arterial “border zone” or “watershed lesions,” usually results from a sudden decrease in systolic blood pressure and cerebral perfusion. Watershed is a term first used in the early nineteenth century in England to describe the strip of land between two more or less parallel rivers or streams. This strip was protected from damming of one stream because it had an alternative water supply from the other, but it also was the most vulnerable and the first land to become parched during periods of general drought because it received the last water from both streams. Extrapolated to the cerebrovascular circulation, a watershed thus is the territory between two major arterial supplies, protected from occlusion of one of the arteries but vulnerable to an even transient period of systemic hypotension or hypoperfusion. The best-known watershed zones in the brain are between the anterior and middle cerebral artery circulations and between the middle and posterior cerebral circulations. Watershed zone infarcts are not infrequent in the neonate in these same regions that are affected in adults (Fig. 6.9), and usually denote a previous episode of systemic hypotension associated with fetal distress during late gestation or just prior to birth. Watershed zone infarcts in the full-term neonatal cerebrum are usually ischemic infarcts, but in about 30% of cases they are hemorrhagic. In preterm infants, hemorrhagic watershed infarcts are more frequent than ischemic infarcts.

Another watershed zone occurs in the tegmentum of the brainstem. A series of 25 to 30 paired triads of vessels arise from the basilar artery; this series extends from the upper midbrain to the lower medulla oblongata. The three vessels of the triad on each side of the brainstem are (a) the paramedian penetrating artery, which extends dorsally next to the midline from the basilar artery to the floor of the fourth ventricle; (b) the short branches of the circumferential artery, which travels from the basilar artery around the outside of the brainstem to penetrate and supply the ventrolateral brainstem; and (c) the long branches of the circumferential artery, which encircles the brainstem and then penetrates dorsolaterally. The tegmentum of the pons and medulla is a watershed zone between the territories of the paramedian penetrating and the long circumferential arteries (Fig. 6.10) (133a).

Damage is maximal in the posterior parietal-occipital region, becoming less marked in the more anterior portions of the cortex. The lesions in the affected area can be located in the cortex or in the white matter. When gray matter is affected, damage usually involves the portions around the depth of the sulci. In part, this distribution can reflect the effect of cerebral edema on the drainage of the cortical veins, and, in part, it can be the consequence of the impoverished vascular supply of this area in the healthy human newborn. Bilateral parasagittal infarction also may result from sagittal sinus thrombosis, an event usually associated with infections (sepsis and meningitis) or with dehydration in young infants.

Lesions involving damage to the deeper portions of gray matter have been termed ulegyria (mantle sclerosis, lobar sclerosis, nodular cortical sclerosis) (3). A common abnormality, ulegyria accounts for approximately one-third of clinical defects caused by circulatory disorders during the neonatal period (133). Its characteristic feature is the localized destruction of the lower parts of the wall of the convolution, with relative sparing of the crown. This produces
a “mushroom” gyrus (Fig. 6.11). The margins of affected gray matter often contain abnormally dense aggregates of myelinated fibers, whereas adjacent white matter shows a considerable amount of myelin loss and compensatory gliosis (134). Later, coarse bundles of abnormally oriented, heavily myelinated fibers traverse the gliotic tissue, and the myelin sheaths enclose astrocytic processes as well as axons, similar to status marmoratus of the basal ganglia (135). Laminar necrosis of layer 3 often accompanies ulegyria.

Ulegyria can be extensive or so restricted that the gross appearance of the brain is normal. It most commonly occurs in major arterial watershed border zones, in a parasagittal distribution in the venous drainage territory of the superior sagittal sinus, or within the territory of a major cerebral artery with partial occlusion (136). The perisulcal topography of the necrosis is related to reduced perfusion as a consequence of impaired sulcal venous drainage resulting from the compression of the stems of veins that ascend between gyri that have become edematous from previous hypoxic episodes (137). When ulegyria is widespread, an associated cystic defect in the subcortical white matter (porencephalic cyst) and dilatation of the lateral ventricles often occur. The meninges overlying the affected area are thickened and the small arteries occasionally can show calcifications in the elastica. Less often, ulegyria involves the cerebellum.

Marin-Padilla studied the postinjury gray matter alterations in ulegyria and found that the surviving cortex acquires a cortical dysplasia that affects the structural and functional differentiation of neurons, glial elements, and synaptic organization. Marin-Padilla proposed that the consequences of the acquired cortical dysplasia represent the main pathogenetic mechanism for epilepsy and other neurologic sequelae to perinatal brain damage (138).

Abnormalities within the basal ganglia are seen in the majority of patients subjected to perinatal asphyxia [84% in the series of Christensen and Melchior (139)]. One common lesion seen in this area has been termed status marmoratus. This picture was described first by Anton (140) in 1893 and later by the Vogt and Vogt (141). Fundamentally, the pathologic picture is one of glial scarring corresponding to the areas of tissue destruction. It is characterized by a gross shrinkage of the striatum, particularly the globus pallidus, associated with defects in myelination. Although in some cases myelinated nerve fibers, probably of astrocytic origin (135), are found in coarse networks resembling the veining of marble (hence the name of the condition, status marmoratus) (Fig. 6.12), in other cases the principal pattern is one of a symmetric demyelination (status dysmyelinatus) (142). Hypermyelination and demyelination probably represent different responses to the same insult. Hypermyelination probably results from oligodendrocytes becoming activated to produce excessive myelin, and, lacking enough axons to ensheath, they envelop astrocytic processes. The number of nerve cells in the affected areas is usually conspicuously reduced, with the smaller neurons in the putamen and caudate nucleus appearing more vulnerable. Cystic changes within the basal ganglia were stressed by Denny-Brown but are rarely extensive (143). Although the abnormalities within the basal ganglia are often the most striking, a variety of associated cortical lesions can be detected in most instances.

It has been our experience, as well as that of others, that this condition is the result of an acute, severe hypoxic insult (144). As a rule, the asphyxia is not as prolonged as that which results in multicystic encephalomalacia, a condition in which there is also extensive damage to the cerebral cortex and white matter. The reason for the selective vulnerability of the basal ganglia to asphyxia is alluded to in another section of this chapter.

Given that these regions have a higher baseline oxygen consumption than other regions of the brain, as has been evidenced by positron emission tomography (PET) (145), other factors also must be operative to account for the particular vulnerability of the putamen and anterior thalamus (146). The most recent thinking is that the topography of neuronal death points to a primary role of glutamate excitotoxicity in basal ganglia neuronal damage, with the type of cell death induced by asphyxia (necrosis or apoptosis) being determined by neuronal maturity and the severity and duration of asphyxia (147). Also playing a role is the density of excitatory receptors, the differential expression of ionotropic and metabotropic glutamate receptors, their differential sensitivities, and the expression of the various receptor subtypes (76,147). Variations in the subunit composition of the receptor and changes in the expression of glutamate receptors with maturation may also influence the sensitivity of neurons to perinatal asphyxia (147a). Because astrocytes and oligodendroglia also express glutamate receptors, these cells may participate in basal ganglia injury (147). The striatal gamma-aminobutyric acid (GABA)-ergic, medium-sized inhibitory neurons also are sensitive to asphyxia, whereas the striatal cholinergic interneurons are resistant to asphyxia (76). Basal ganglionic neurons expressing nitric oxide synthase participate in oxidative stress and excitotoxicity, which often lead to the death of neighboring cells (147b,148).

In infants who suffer basal ganglia necrosis secondary to asphyxia, neuronal immunoreactivity to the various glutamate receptors was consistently decreased, with the areas of decreased immune reactivity corresponding to the damaged regions (149). Neonatal asphyxia triggers a cascade of gene expressins for tyrosine hydroxylase and D₁ and D₂ dopamine receptors in experimental animals, but the importance of this finding is unclear (150).

The spinal cord is also vulnerable to hypoxic-ischemic injuries, and damage to anterior horn cells results from hypoperfusion of the watershed area between the vascular distribution of the anterior spinal and the dorsal spinal arteries (172). The resultant hypotonia is generally attributed to cerebral injury, but electromyography (EMG) can demonstrate a lower motor neuron injury.

An infarct, the consequence of a focal or generalized disorder of cerebral circulation that occurs during the antenatal or early postnatal period and acts in isolation, is a relatively rare cause of brain damage. In the series of autopsies studied by Barmada and colleagues, arterial infarcts were seen in 5.4%, and infarcts of venous origin were found in 2.4% (173). Almost 90% are unilateral, and in 83% the infarct is in the distribution of the middle cerebral artery (4). It is presumed to be the result of embolization arising from placental infarcts or of thrombosis caused by vascular maldevelopment, sepsis, or, as in the case of a twin to a macerated fetus, the exchange of thromboplastic material from the dead infant (3). In the series of Fujimoto and colleagues, 22% followed perinatal asphyxia; their onset was in the first 3 days of life (174). Infarcts can be asymptomatic or present with convulsions. Of 90 term infants presenting with seizures solely within 72 hours of birth, Cowan et al. found that 35 (39%) had focal cerebral infarction in arterial or parasagital distribution (30). Such infarctions are generally thought to be unrelated to intrapartum difficulties or the presence of neonatal encephalopathy, although the incidence of antenatal and intrapartum problems is higher in this group of infants than in a control population (175). Sreenan and coworkers had a different experience (176). In their series neonatal encephalopathy was encountered in 56% of infants who developed cerebral infarctions, and various adverse perinatal events occurred in about 75%. The presence of an inherited thrombophilic abnormality increased the risk of focal infarction. In the same population Mercuri and coworkers found that 30% of infants with focal infarction had a thrombophilic abnormality, usually heterozygosity for factor V Leiden or a high factor VIII concentration (177). In the series of Golumb and coworkers (178), 70% of infants with ischemic stroke who did not suffer from neonatal encephalopathy had anticardiolipin antibodies. Golumb reviewed the various prothrombotic disorders that contribute to the development of neonatal thrombotic infarcts (179).

Focal infarctions are less common in the premature than the term infant, and compared with the term infant the premature infant has a better prognosis with regard to neurologic residua (180).

With increased use of neuroimaging studies, dural sinus thrombosis can be demonstrated as a consequence of severe perinatal asphyxia (181). The condition is also seen in a variety of other conditions that predispose the infant to a hypercoagulable state (182,183).

A porencephalic cyst is a large intraparenchymal cyst that always communicates with the ventricular system. Loculated cysts entirely within the subcortical white matter are not porencephalic and are pseudocysts rather than true cysts because they lack an epithelial lining. Porencephalic cysts are partly, though usually sparsely, covered by ependyma. Porencephaly results from infarction in the territory of a major artery, usually the middle cerebral artery, although at times it may be a sequel to a grade 4 intraventricular hemorrhage (IVH) that extends the ventricle lumen into the empty parenchymal space left by the reabsorption of the hematoma. It is not a watershed infarct.

Porencephalic cysts often appear to communicate also with the overlying subarachnoid space, and such a communication may be reported by radiologists, but careful neuropathologic examination demonstrates that a thin pial membrane and sometimes arachnoidal tissue separate the porencephalic and subarachnoid compartments. (Fig. 6.13). The pia derives its vascular supply from meningeal rather than cerebral vessels. This membrane is too thin to resolve by CT or MRI, but is important during life in terms of fluid shifts and CSF flow.

The cerebral cortex immediately surrounding a porencephalic cyst often appears to be polymicrogyric. This is secondary to ischemia and atrophy of immature gyri and should not be misconstrued as a primary dysgenesis. These small gyri are gliotic and have extensive neuronal loss.

Porencephaly is usually limited to one hemisphere, and the clinical correlates are spastic hemiplegia, hemisensory deficits, and often hemianopia. Porencephalic cysts following grade 4 IVH are visualized in survivors 10 days to 8 weeks after the event (184). Although it is not a
progressive lesion and does not obstruct the flow of CSF in the chronic phase, the porencephalic cyst occasionally enlarges and causes symptoms of intracranial hypertension. The reason for this phenomenon is the pulsation of the choroid plexus, which may induce a “waterhammer effect” because the force of the pulsations is transmitted to a larger surface area and the resistance to stretch is therefore less. The choroid plexus does not derive its blood supply from the middle cerebral artery; hence it usually survives the infarct. In some cases, a ventriculoperitoneal shunt may be required to prevent further enlargement of the porencephalic cyst, encroachment on functional brain, and midline shift.

Rarely, porencephaly is transmitted as an autosomal dominant disorder with incomplete penetrance. The presentation is with variable degrees of hemiparesis, seizures, and mental retardation (185). A thrombotic event during late pregnancy is believed to be responsible. The gene has been mapped to chromosome 13qter (186).

Whereas mechanical trauma can be responsible for a subdural hemorrhage and, less commonly, a primary subarachnoid hemorrhage, it plays a relatively unimportant role in the evolution of periventricular-intraventricular hemorrhage (IVH), the most common form of neonatal intracranial hemorrhage (Table 6.4) (4,187,188). The various grades of hemorrhage are defined in Table 6.5 and depicted in Figs. 6.14, 6.15, and 6.16.

The site of the bleeding that results in an IVH is determined by the maturity of the infant. In the premature
infant, bleeding originates in the capillaries of the subependymal germinal matrix, usually over the body of the caudate nucleus (188). With increasing maturation the germinal matrix involutes, so that in the term infant the choroid plexus becomes the principal site of the hemorrhage (114,188). Although Hayden and coworkers encountered IVH in 4.6% of term neonates (189), its incidence increases markedly with decreasing maturity, so that when ultrasonography is performed on infants with birth weights less than 1,500 g, a hemorrhage can be documented in as many as 50%. A high-grade hemorrhage is more common in this group than in infants with birth weights greater than 1,500 g (190,191,192). At times, even premature infants of advanced gestational age may have extensive hemorrhages that can destroy the thalamus or basal ganglia (Figs. 6.3 and 6.15).

The pathogenesis of IVH is not completely understood. The predisposition of the premature infant to IVH is in part due to the presence of a highly vascularized subependymal germinal matrix, to which a major portion of the blood supply of the immature cerebrum is directed. Furthermore, the capillaries of the premature infant have less basement membrane than those of the mature brain, and there is a paucity of tight junctions that is compounded by incomplete coverage of blood vessels by astrocytic end feet leading to fragility of the blood vessels. Finally, abnormalities in the autoregulation of arterioles in premature and distressed term infants impair the infants’ response to hypoxia and hypercarbia and thus permit transmission of arterial pressure fluctuations to the fragile periventricular capillary bed.

Prenatal as well as perinatal and postnatal factors have been implicated in the evolution of IVH. Lack of adequate matching for gestational age and birth weight have, however, confounded many results (193). As a rule, IVH that develops in the first 12 hours of life is associated with variables relating to labor and delivery, whereas IVH that starts
later is associated with postpartum variables. Premature rupture of membranes and maternal chorioamnionitis increase the risk for the condition, suggesting that cytokines play a role in its evolution (192,194,195).

In most infants, acute fluctuations in cerebral blood flow and an impaired cerebral vascular autoregulation are more important than prenatal factors in the evolution of an IVH. Clinical studies have shown that infants with intact cerebrovascular autoregulation are at low risk for IVH. In contrast, a variety of adverse factors that disrupt autoregulation are associated with a high risk of IVH. These include low Apgar scores, respiratory distress, artificial ventilation, the presence of a patent ductus arteriosus, and the various complications of perinatal and postnatal asphyxia (192,194,196). An elevation of venous pressure also has been implicated. Such an elevation can occur in the course of labor and delivery, or it can accompany positive-pressure ventilation, pneumothorax, hypoxic-ischemic myocardial failure, or hyperosmolality induced by administration of excess sodium bicarbonate (4).

The importance of pneumothorax caused by positive-pressure ventilation in producing IVH was stressed by McCord and coworkers, who were able to reduce the incidence of respiratory distress syndrome and with it the incidence of IVH by treatment with surfactant (197). In addition to surfactant, maternal tocolysis using ritrodrine, early low-dose indomethacin, and antenatal steroid treatment also reduce the incidence of IVH in very low birth weight premature infants (193,198,199,200). Neonatal risk factors that predispose to the evolution of IVH include clotting disorders, reduced hemoglobin, hypercarbia, and hypoglycemia (4).

In the premature infant, the hemorrhage does not occur at the time of delivery but tends to commence later, most commonly 24 to 48 hours after a major asphyxial insult, whether at the time of birth or subsequently (192,201). In the experience of Ment and associates, 74% of hemorrhages were detected by ultrasonography within 30 hours after birth (202) (Fig. 6.16). In the series of Trounce and colleagues, 15% of infants developed an IVH after 2 weeks
of age (191). In some infants bleeding can be a slow process rather than a sudden event (203). The extent of the hemorrhage can range from a slight oozing to a massive intraventricular bleed with an associated asymmetric periventricular hemorrhagic infarction and an extension of the blood into the subarachnoid space of the posterior fossa (see Figs. 6.14 and 6.15) (204).

Blood usually clears rapidly from the intraventricular and subarachnoid spaces. In fact, hemosiderin deposition, a reliable and permanent neuropathologic marker of old hemorrhage in the adult brain, is found rarely in children’s brains after an IVH. Despite the resolution of the fresh blood, brain injury is a relatively common result of IVH. Several mechanisms are believed to play a role (4).

Progressive ventricular dilatation is a common sequel to IVH (Fig. 6.18). Evolving 1 to 3 weeks after the hemorrhage, it is caused by a fibrotic reaction that obliterates the subarachnoid spaces and induces ventricular dilatation with or without increased intracranial pressure (normal-pressure hydrocephalus) (4). The factors responsible for normal-pressure hydrocephalus in the neonate are poorly understood.

When an IVH occurs in term infants, it generally emanates from the choroid plexus, less frequently from the subependymal germinal matrix. The major causes are trauma and perinatal asphyxia (4). In the experience of Volpe, approximately one-half of term newborns with IVH experienced difficult deliveries. The experience of Palmer and Donn is similar (214). In approximately 25% of cases, the IVH is of unknown etiology. One cause that probably accounts for a large number of these cases is a cryptic hemangioma of the choroid plexus, well demonstrated at autopsy (215,216). The lesions range in size from thin-walled cavernous angiomas to fully formed arteriovenous malformations. They are sometimes difficult to show by imaging, in part because the hemorrhage may destroy the original vascular malformation or obscure its remains (216). Unruptured angiomas of the choroid villi are not uncommon as incidental findings at autopsy and must be distinguished from simple vascular congestion. It is a relatively common complication of Sturge-Weber syndrome (see Chapter 12). One of us (H.S.) has found them to be more frequent in patients with cerebral malformations or chromosomal abnormalities.

Term infants with IVH tend to become symptomatic at a later age, often not until the fourth week of life. Irritability, changes in alertness, and seizures are common presenting symptoms. In the series of Palmer and Donn, seizures were the first symptom in 69% of cases; 23% of infants presented with apnea (214).

Extension of intracranial hemorrhage to the spinal canal is more frequent than is recognized. Both epidural and subdural bleeding have been encountered, the former being far more common. Epidural bleeding is associated not only with intracranial hemorrhage owing to asphyxia, but also with traumatic birth injuries (217,218). Although these hemorrhages either are asymptomatic or induce deficits that are obscured by the more obvious symptoms of an intracranial hemorrhage, diagnosis by MRI of the spinal cord is now possible.