ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 1 Jim Baun, BS, RDMS, RVT, FSDMS San Francisco, CA Diagnostic ultrasound provides a non-invasive method of imaging intracranial structures in the neonate. Because the equipment is transportable to the intensive care nursery and because the ultrasound examination does not involve the use of ionizing radiation, the procedure can be performed without risk to the infant. Additionally, the accuracy of sonography is equal to or greater than that of CT, 1 and therefore, should be the initial examination in infants with suspected intracranial abnormalities. When ultrasound examination produces normal findings, CT may be indicated to search for subdural or subarachnoid hematomas. 2 INTRACRANIAL HEMORRHAGE Intracranial hemorrhage (ICH) is a major source of neonatal morbidity and mortality especially in pre term (24-32 wk) infants. It has been reported at autopsy in 50 to 70% of these babies and is more likely to occur in low birth weight (<1500 g) neonates who require ventilatory support. 3 4 The cause of ICH is as yet undetermined but is believed to be related to the immaturity of vascular walls in metabolically active areas of the newborn brain. One of the most developmentally active areas in the fetal brain is the germinal matrix from which most of the developing brains cells are derived. Occupying the majority of the periventricular area early in gestation, germinal matrix regresses and converts into normal cerebral parenchyma as gestation continues. By 24 weeks, the germinal matrix is anatomically indistinct and is confined to the area below the lateral ventricles near the head, and occasionally, the body of the caudate nucleus. (Figs.1a-c) As a source of new brain cells, the germinal matrix requires a continuous supply of oxygenated blood and is one of the most richly perfused areas of the fetal brain. Anoxic events or periods of increased carbon dioxide buildup produce changes in intracranial blood pressure. A normal physiologic response to anoxia is vasodilatation, a process that increased oxygenation to metabolically active tissue by increasing blood volume. The immature blood vessels in the germinal matrix are believed to have limited Neonatal Intracranial Hemorrhage ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 2 vasodilatory capabilities that result in increased intravascular pressure. This increase in pressure can easily rupture the thin-walled vessels. 6 7 Small bleeds remain confined to the germinal matrix region and are termed "subependymal hemorrhages (SEH)." They most commonly occur over the body of the caudate nucleus in infants up to 28 gestational weeks. The bleed is found over the head of the caudate nucleus in infants 29 weeks and older. 8 When the blood remains confined to the region of the germinal matrix, it is classified as grade I, based on a well-established grading system. Sonographically, intracranial hemorrhage appears as a highly echogenic focus, or foci, within the ventricular system. Echogenicity of hemorrhage is greater than that of the medium-level echogenicity of the adjacent caudate nucleus. Small subependymal bleeds may be masked by the highly echogenic choroid plexus; however, position within the ventricular system and associated deformity of the normal choroid configuration can increase sonographic sensitivity. (Figs. 2a-c) As blood continues to build up beneath the thin walled ventricular lining, it may rupture into the ventricle. These bleeds are classified as grade II as long as there is no concomitant dilatation of the ventricle itself. Highly echogenic material may be seen filling the lumen of the lateral and occasionally, the third ventricles. In clinical practice, however, this is rarely encountered since concomitant ventriculomegaly is virtually always present. (Figs. 3a-c) Grade III ICH consists of extravasation of blood into the ventricle, similar to grade II but with associated dilatation of the ventricles. Clot occludes the outflow tract, and CSF builds up proximal to the site and ventriculomegaly results. The consistency and echogenicity of intraventricular hemorrhage changes over time. Early in the event, the blood may be isoechoic with the surrounding cerebrospinal fluid (CSF) and cannot be readily detected with ultrasound. As the blood solidifies into a clot, the echogenicity increases and for a period appears brightly echogenic. Over 1 to 2 weeks, the clot begins to liquefy centrally producing a mixed sonographic appearance that is typically a centralized cystic area surrounded by solid clot. (Figs. 4a-d) Finally, the most serious and complex type of ICH is grade IV, which is the presence of dilated, blood-filled ventricles with concurrent intraparenchymal hemorrhage. 9 Initially, the blood appears as highly echogenic, ill-defined areas adjacent to the ventricles. As the clot matures, central lysis occurs, and cavitation results producing sonographic appearances as previously described. (Figs. 5a- c)The final stage of hemorrhagic resolution is the presence of porencephaly, or the complete cystic degeneration of the clot. (Figs. 6a-c) PERIVENTRICULAR LEUKOMALACIA Periventricular leukomalacia (PVL) refers to cerebral infarctions that occur near the lateral ventricles. Literally translated, it means softening of the white matter that surrounds the ventricles. It results from ischemia or failure of perfusion of cerebral parenchyma, and as in ICH, is related to the rupture of immature blood vessels in the presence of increased intracranial blood pressure. It occurs in a watershed area of the brain surrounding the lateral ventricles where end branches of the cerebral arteries can be found. The hemorrhage into the ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 3 periventricular areas can be microscopic, petechial, or linear streaks that extend into the white matter. 10 Gross hemorrhage into the white matter is associated with a high degree of mortality. (Figs. 7a-b) Porencephaly, as described earlier, is also associated with a significant morbidity and mortality. 10 Over 1 to 2 weeks, the intraparenchymal hematoma organizes and retracts from the surrounding cerebral parenchyma. After 1 to 3 months, the clot is usually resorbed. PVL itself is not lethal but neurologic sequelae, including spastic quadriparesis and mental retardation, may occur in babies who survive. 11 Sonographically, the area of PVL may appear highly echogenic especially if hemorrhagic necrosis has occurred. Some authors have used the term "periventricular intra parenchymal echodensities (IPE) 11 to describe areas that surround the ventricles and are of increased echogenicity. Some have attempted to predict neurologic outcome based on IPE findings. These areas can be focal, diffuse, or scattered throughout the cerebral parenchyma. They may be uni- or bilateral and almost always occur on the same side as IVH. CLINICAL CONSIDERATIONS Neither ICH nor PVL is associated with birth trauma; rather, each is associated with medical conditions that affect the neonate after delivery. Difficult deliveries that require the use of forceps may cause tearing of the vein of Galen or one of the meningeal vascular branches with subsequent subarachnoid or subdural hemorrhages. The mortality rate in these traumatic rupture cases is high and usually occurs in term infants. Because of the superficial location of these bleeds and the low survival rate, sonography does not play a role in their diagnosis. 12 Physiologic hemorrhages are associated with perinatal medical conditions such as prematurity, meconium aspiration, sepsis, primary persistent fetal circulation, congenital heart disease, or diaphragmatic hernia. Any of these conditions is associated with an increase in the incidence of ICH or PVL because of the anoxia that accompanies these types of pathology. Bleeds generally occur during the second or third post-natal day, with the average being 38 hours after birth). 3 The timing of the bleed is important because if the sonogram is routinely performed shortly after birth, chances are that the event will be missed and the sonogram will need to be repeated at additional cost to the patient. The most frequent indications for requesting a neonatal cranial sonogram are clinical observations of events that have a high association with ICH. These include seizures; fall in hematocrit of greater than 10%, and apnea. Less commonly associated clinical conditions, yet valid indications for neonatal neurosonography include bradycardia, clinical deterioration, hypoxia, metabolic acidosis, seizure and, disseminated intravascular coagulopathy (DIC). 13 PROGNOSIS Prognosis varies considerably with the extent of the intracranial lesion. Usually, with grade I and II bleeds no neurologic sequelae occur, and the infants go on to live a developmentally and neurologically normal life. Grades III and IV, however, are associated with subsequent development of hydrocephalus and carry a less optimistic neurologic prognosis. It appears that the most important ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 4 factor is the presence or absence of intraparenchymal hemorrhage. Sequelae include spastic hemiplegia, quadriplegia, and cortical blindness. 4 11 The prognosis in cases of periventricular leukomalacia also varies considerably. The degree of morbidity has recently been correlated with the presence or absence of IPE detected with sonography. With extensive IPE, virtually all infants have neurologic and/or cognitive disorders develop and 79% of infants die. With localized IPE, however, the mortality rate drops to 38%. Major motor deficits are found in 79% of these infants but 43% have almost normal cognitive abilities. 14 A more recent report indicates that the presence of hyperechoic diffuse periventricular areas cannot be correlated with neurologic outcome. Approximately 50% of these infants have significant neurologic abnormalities develop, the other half develop normally. The presence of cystic degeneration in areas of PVL, however, virtually ensures significant sequelae. ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 5 REFERENCES 1. Grant EG, Borts FT, Schellinger D, al. Real-time ultrasonography of neonatal intraventricular hemorrhage and comparison with computed sonography. Radiology1981; 139:687-691. 2. Mack LA, Wright K, Hirsch JH, et al. Intracranial hemorrhage in premature infants: Accuracy of sonographic evaluation. AJR 1981; 137:245-250. 3. Leech RW, Kohnen P. Subependymal and intraventricular hemorrhages in the newborn. Am J Pathol 1974; 77:465-475. 4. Lee BC, Grassi AE, Schechner A, et al. Neonatal intraventricular hemorrhage: A serial computed tomography study. J Comput Assist Tomogr 1979; 3:483-490. 5. Rumack CM, Johnson ML. Perinatal and Infant Brain Imaging. Chicago: Year Book Medical Publishers, Inc., 1984; 45. 6. Hambleton G, Wigglesworth JS. Origin of intraventricular hemorrhage in the preterm infant. Arch Dis Child 1976; 51:651-659. 7. Cavazzutti M, Duffy TE. Regulation of local cerebral blood flow in normal and hypoxic newborn dogs. Ann Neurol 1982; 1l:247-254. 8. Leech RW, Kohnen P. Subependymal and intraventricular hemorrhages in the newborn. Am J Path 1974; 77:465-475. 9. Papile L, Burstein J, Burstein R, et al. Incidence and of evolution of subependymal and intraventricular hemorrhage: A study of infants with a birth weight of less than 1500 grams. J Peds1978; 92:529-534. 10. Armstrong 0, Norman MG. Peri ventricular leukomalacia in neonates: Complications and sequelae. Arch Dis Gild 1974; 49:367-375. 11. Krishnamoorthy KS, Shannon DC, DeLong GR, et al. Neurological sequelae in the survivors of neonatal intraventricular hemorrhage. Pediatrics 1979; 64:233-237. 12. Haller ES, Nesbitt RE, Anderson GW. Clinical and pathologic concepts of gross intracranial hemorrhage in perinatal mortality. Obstet Gynecol Surv 1956; 11:179- 204. 13. Tsiantos A, Victorin L, Relier Jr, et al. Intracranial hemorrhage in the prematurely born infant. J Ped 1974; 85:854-859. Guzzetta F, Shackelford GO, Volpe S, et al. Periventricular intraparenchymal echodensities in the premature newborn: Critical determinant of neurologic outcome. Pediatrics1986; 78:995- 1006. ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 6 Table of Images: Figure 1a: anatomical coronal schematic demonstrating approximate location of the germinal matrix Figure 1b: sagittal sonogram through the lateral ventricle demonstrating the area of the germinal matrix (yellow stars) beneath the head of the caudate nucleus (CN). Figure 1c: coronal sonogram demonstrating the area of the germinal matrix (yellow stars) and associated normal intracranial anatomy. 1) cerebral cortex, 2) caudate nucleus, 3) corpus callosum, 5) third ventricle, 7) lateral ventricle - body, 11) pons, 10) lateral ventricle - occipital horn. Figure 2a: schematic representation of a localized subependymal bleed confined to the germinal matrix (grade I) beneath the head of the caudate nucleus (red area). Figure 2b: coronal sonogram demonstrating small bilateral subependymal bleeds (grade I) and a 30-week neonate (yellow arrow) Figure 2c: sagittal sonogram demonstrating a small irregularly contoured echogenic focus at the caduo-thalmic notch. (Grade I) Figure 3a: gross pathology of a confined intraventricular bleed in an autopsy specimen. (Grade II) Figure 3b: coronal sonogram demonstrating complex echogenic filling of the body of the right lateral ventricle and a 27-week neonate. Note the presence of the cavum septum pellucidum between the bodies of the two lateral ventricles (yellow star) (Grade II) Figure 3c: sagittal sonogram through the lateral ventricle demonstrating increased echogenicity filling the ventricular cavity. There is no concomitant ventriculomegaly. (Grade II) Figure 4a: coronal section through a cadaver brain demonstrating a large thrombus filling the right lateral and third ventricles. There is mild ventriculomegaly in the left lateral ventricle. (Grade III) Figure 4b: sagittal sonogram in a 32-week neonate demonstrating a large organized thrombus within the head and body of the lateral ventricle. There is concomitant ventriculomegaly (yellow stars). (Grade III) Figure 4c: coronal sonogram in the same neonate demonstrating a smaller well-organized thrombus confined within the right lateral ventricle. A much larger thrombus is seen surrounding the more echogenic choroid plexus and the left lateral ventricle. Figure 4d: two examples grade III hemorrhage. Extensive organized intraventricular thrombus with associated ventriculomegaly in the image on the left. Image on the right demonstrates an enlarged lateral ventricle filled with thrombus. Figure 5a: coronal sections through a cadaver brain demonstrating the presence of thrombus within both lateral and third ventricles. There is extension the hemorrhagic process into the parenchyma of the left cerebral hemisphere. (Grade IV). ProSono copyright 2009 Journal of Diagnostic Medical Sonography 7:121-131, May/June 1991. 7 Figure 5b: coronal sonogram through the posterior portion of the cerebral hemisphere's demonstrating areas of irregularly marginated echogenic material surrounding the bodies of both lateral ventricles. (Grade IV) Figure 5c: sagittal sonogram demonstrating gross distortion of the morphology of the lateral ventricle with organized thrombus within (yellow stars) with extension of thrombus into the cerebral parenchyma. (Grade IV) Figure 6a: coronal sonogram demonstrating cystic degeneration of an intraparenchymal hemorrhage. (Porencephaly) Figure 6b: sagittal sonogram in the same patient. (Porencephaly) Figure 6d; small cystic area in body of lateral ventricle representing liquefaction of a small subependymal bleed. Figure 6c: gross pathology cadaver section (coronal) demonstrating cystic degeneration in the cerebral parenchyma. Old, organized thrombus is seen in the porencephalic lesion and in the dilated ventricular system (yellow star) Figure 7a: schematic representation of periventricular infarction and hemorrhagic necrosis. Figure 7b” sagittal sonogram through a thrombus-filled lateral ventricle (yellow star) and demonstrating hemorrhage in the periventricular cerebral parenchyma resulting in periventricular leukomalacia.