155 Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved Neonatal Periventricular Leukomalacia: Real-Time Sonographic Correlation Peter P. Chow1’2 Gerard Horgan1’3 Kenneth J. W. Taylor1 J. Diagnosis The utility of real-time malacia (PVL) has been nosed by serial real-time sonography computed findings tomographic described with CT in the diagnosis of neonatal periventncular leukoSix cases are reported of PVL diagThe sonographic findings were correlated with the only recently. scanning. and the clinical history. In five of six infants in whom was performed, characteristic muftiseptated periventricular cavitations develo_ 2-3 weeks after birth or later. A transition from normal to increased periventricular echogenicity was often observed before the development of the periventricular cavftations in nonhemorrhagic PVL The parenchymal abnormality demonstrated by sonography correlated well with an abnormal neurologic outcome. It is suggested that serial real-time scanning be performed in neonates whose history suggests the possibility of scanning hypoxic-ischemic disturbed brain injury. Nonspecific status, abnormal muscle mental predictors of PVL include seizures, apnea, tone, and leg weakness. Periventricular leukomalacia (PVL) results from an ischemic insult to the neonatal brain with involvement of the periventricular white matter adjacent to the external angles of the lateral ventricles [1 -5]. It is commonly found at autopsy in the brains of neonates. However, it is rarely diagnosed in living infants. Although real-time sonography has been used widely to diagnose intracranial hemorrhage and other abnormalities of the brains in neonates, the sonographic features of PVL are not well known [6-9]. We report six cases of neonatal PVL diagnosed primarily by real-time sonography. The early sonographic findings and the evolution of PVL on serial sonograrns are emphasized. Computed tomographic (CT) scans were obtamed to confirm the nature and extent of the parenchymal lesions. Subjects and Methods Cranial sonograms transducer This article issue of AJNR appears in the May/June 1985 and the July 1985 issue of AJR. neurologic School Representative Science Center, State Brook, Stony 3 of Medicine, Present Health address: Meath Hospital, AJR 145:155-160, Dublin, Department Ireland. July 1985 0361 -803X/85/1 451-0155 0 American Roentgen Ray Society with a real-time Multiple sector scanner coronal Cranial examination or persistent seizure (ATL 300). A 5 MHz and parasagittal obtained through the anterior fontanelle. At least four examinations one of our patients (case 6). The indication for serial sonography Received April 2. 1984; accepted after revision August 28, 1984. 1 Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 0651 0. Address reprint requests to K. J. w. Taylor. 2 Present address: Department of Radiology, University of New York at Stony Brook, NY 11784. were obtained with a 90#{176} field of view was used. images were were performed in all but was usually an abnormal activity. CT scans were obtained on a GE 8800 or 9800 scanner. The patients were scanned at 5 mm intervals with 5-mm-thick slices. A summary of patients and clinical data is shown in table 1 . The sonographic findings are shown in table 2. Representative cases are illustrated. and CT Case Reports Case 1 of Radiology, A twin girl was born at 28 weeks gestation with a birth weight of 1025 g. The pregnancy was complicated by premature rupture of membranes (PROM) 6 weeks before delivery. A cesarean section was performed. The Apgar scores were 6 at both 1 and 5 mm. The infant received assisted ventilation for 3Y2 weeks because of hyaline membrane disease and CHOW 156 TABLE 1 : Summary of Clinical Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved Case No. (ge station [weeksj, birthwe.ght [gramsj) Findings in Infants History 1 (28, 1025) PROM, CS 6, 6 2 (28, 1200) None 3 (32, 1290) 4 (32, 1580) AL. with Periventricular AJR:145, July 1985 Leukomalacia Neur ologic Findings Apgar Scores at 1 , 5 mm Maternal ET cardiac Status Respiratory Status CSF Examination Neonatal Peflod POStneCnat Peflod RDS, apnea Normal Seizure Lost to F/U 8, 3 Pencardial effusion PDA, CHF BPD I Pressure Seizure PROM 7, Bradycardia BPD, apnea Normal Breech, head dystocia 3, 5 PDA RDS, apnea Hemorrhagic Seizure, hypertonia Seizure, hyperreflexia, Spastic diplegia at 6 mo; delayed development at 13 mc Scissoring of legs at 2 mc Lost to F/U - hypertonia in legs 5 (28, 1000) AP, CS 1, 4 PDA BPD Not performed Hyperrefiexia, Spastic diplegia at 8 hypertonia mo in legs 6 (38, 3500) AP, CS 2, 3 Hypotension Normal None Seizure, Lost to F/U hyperreflexia, hypertonia in legs Note.-CSF = cerebrospinal fluid; PROM = premature rupture of membrane; cs = cesarean congestive heart failure; BPD = bronchopulmonary dysplasia; mo = months; AP arteriosus; CHF TABLE 2: Sonographic = and CT Findings in Infants Early Sonography Case No. (Total No. of Sonograms) RDS = respiratory distress syndrome; abruption of acenta. section; = with Periventricular F/ti = FDA follow-up; = patent ductus Leukomalacia (<2 weeks) Late Sc:hy ventnculomegaly f cr . Fndngs SEH/IVH cavifations) 1 (1 0) N-+I (1 1d) . . . 2 (14) . . . 3 (4) Grade I 20d - Periventricular and subcortical lu- and subcortical lu- and lu- N 40d + cency Periventricular cency N-+I (8d) 13d + Periventricular subcortical cency 4 (14) 5 (8) 6 (1) Note.-SEH Grade II . . . . . . = subependymal hemorrhage ; IVH = intraventricular I (2d) N-l (9d) I (8d) hemorrhage; 17d 38d Not performed N = normal; apneic episodes. Myoclonic seizures were noted soon Several spinal taps showed no evidence of infection. A cranial sonogram on the second day of life was normal (figs. 1A and 1B). A sonogram on the 1 ith day of life showed increased echogen- I = increased; + Periventricular - Penventricular - Periventricular hemorrhage lucency lucency d = days. occasional after birth. tively. The infant’s distress syndrome, icity failure and was treated initially with indomethacin and subsequently by surgical ligation at 3 weeks of age. Several cranial sonograms were normal in the first month of life. A of the (figs. 1 C and 1 D). Multiseptated the periventricular echogenic areas by 3 weeks of age (figs. 1E and 1F). A cranial CT scan on the same cavitations periventricular areas had within developed day demonstrated prominent bilateral irregular hypodense lesions in the periventricular white matter extending toward the cortex, consistent with PVL (fig. 1 G). sia. A patent sonogram hospital course pneumothoraces, ductus 6 weeks artenosus after birth, was complicated by respiratory and bronchopulmonary dyspla- (PDA) however, resulted revealed in congestive heart ventriculomegaly and bilateral, markedly increased echogenicuty of the periventricular region with multiseptated cavitations (figs. 2A and 2B). CT on the same day demonstrated penventncular and subcortical lucencies and widening of the interhemispheric fissure, consistent with PVL (fig. 2C). Case 2 A ventriculoperitoneal shunt was placed because of progressive was evident at the 6 month neurologic follow-up. At 13 months of age, the patient had delayed developmental age equivalent to 5#{190} months. hydrocephalus. A 1200 9 boy was born at 28 weeks gestation by spontaneous vaginal delivery. Apgar scores were 8 and 3 at 1 and 5 mm, respec- Spastic diplegia NEONATAL Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved AJR:145, July 1985 PERIVENTRICULAR LEUKOMALACIA 157 I .‘4 . - -.‘- .-t.,, Fig. 1 -Case 1 . Nonhemorrhagic PVL. Coronal (A) and left parasagittal (B) sonograms on day 2. Normal penventricular echoes. Coronal (C) and left parasagittal (D) sonograms on day 1 1 . Bilateral increased periventiicular echoes extend from mid ventricle to occipital horn. Coronal (E) and ieft parasagittal (F) sonograms on day 21 . Multiple cysts (arrows) developed in previously echogenic areas. G, Unenhanced CT scan on day 21 . Bilateral penventricular hypodense areas extend toward cortex (arrowheads). Clearly defined cysts could not be seen. to have alternating states of alertness and occasional seizurelike activity with scissoring of his legs and increased muscle tone. Case 3 noted A 1 290 g boy was born at 31 -32 weeks gestation by vaginal delivery. PROM occurred at 32 hr before delivery. The Apgar score was 7 at 1 mm. The infant had respiratory distress syndrome followed by bronchopulmonary dysplasia. Occasional episodes of apnea and was negative. A sonogram bradycardia and increased were noted during the hospitalization. The infant was ‘ wo electroencephalograms hemorrhage. were normal. Cerebrospinal fluid culture at 2 days of age showed a left germinal matrix 8 days after birth revealed ventriculomegaly penventricular echogenicity. Cranial CT at this time A sonogram Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved 158 CHOW Fig. 2.-Case 2. Nonhemorrhagic PVL. Coronal (A) and right parasagittal (B) sonograms at 40 days of age. Multiple bilateral periventncular cysts in region of tngone of lateral ventricle (arrows). Mild ventnculomegaly. C, Unen- ET AL. AJR:145, July 1985 hanced CT scan at 40 days of age. Marked bilateral periventncular hypodense areas with subcortical extension (arrows). Widening of interhemispheric fissure indicated cerebral atrophy. Fig. 3.-Case 3. Nonhemorrhagic PVL. Initial sonograms showed left germinal matrix hemorrhage at 2 days and ventriculomegaly and increased penventricular echogenicity at 8 days. Coronal (A) and left parasagittal (B) sonograms on day 1 3. Small cysts (arrowheads) had developed within periventncular echogenic areas. Lateral borders of echogenic areas were irregular but well defined. revealed marked periventricular hypodense days of age showed early cavitations tricular areas (figs. 3A and 3B). areas. A sonogram within the echogenic at 13 periven- showed confluence of the small cysts and communication cysts with the ventricles and subcortical (figs. 4F and 4G). CT showed of these penventricular lucencies but did not reveal definite cysts. Discussion Case 4 tricular hemorrhage on CT (fig. 4D). Multiseptated cavitations were shown by’ sonography to have ‘developed within the periventricular PVL is a common variety of neonatal hypoxic-ischemic encephalopathy [10]. The reported incidence of PVL varies with the selection of case material. The overall autopsy mcidance of PVL approximates 20% [1-6]. PVL is observed particularly often in premature infants with postnatal survival of more than 6 days [4]. A significant history of cardiorespiratory disturbances in the neonatal period is especially cornmon among these patients. There are no early neurologic findings specific for PVL. Seizure, apneic spells, disturbance in mental status, abnormal muscle tone, and leg weakness may be found [1 0]. PVL is not a lethal lesion, but may lead to degeneration of the echogenic corticospinal A 1580 g boy was born at about 32 weeks gestation vaginal delivery. The infant had asphyxia of 3 and 5 at 1 and 5 mm, respectively. by breech at birth with Apgar scores Due to hyaline membrane disease and episodes of apnea, assisted ventilation was required for 5 weeks. A PDA was treated with indomethacin. Myoclonic seizure was noted 2 days after birth. Neurologic examination revealed symmetric, brisk deep tendon reflexes, creased passive tone in the legs. decreased active tone, and in- A sonogram on the second day of life revealed bilateral subependymal and intraventricular hemorrhage (figs. 4A-4C). There were also bilateral intense areas periventricular echoes that corresponded on the 1 7th day (fig. 4E). Subsequent to periven- sonograms tract, particularly to the legs. The major long- Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved AJR:145, Fig. NEONATAL July 1985 4.-Case 4. Hemorrhagic PVL. PERIVENTRICULAR LEUKOMALACIA 159 A-C, at 2 days of age. A, Anterior coronal sonogram. Bilateral germinal matrix hemorrhage. Posterior coronal (B) and right parasagittal (C) Sonograms sonograms. Bilateral intense penventricular echoes were diff,cult to distinguish from choroid plexus. D, Unenhanced CT scan at age 5 days. Bilateral germinal matnx/intraventncular hemorrhage and penventricular hemorrhage. E, Right parasagittal sonogram on day 17. Multipie cysts within periventricular echogenic areas. Ventnculomegaly. F, Unenhanced CT scan on day 29. No definite cysts discernible within periventricular hypodense areas. Coronal (G) and left parasagittal (H) sonograms on day 29. Penventricular cysts enlarged and cornmunicated with ventricles. term sequela of PVL is spastic diplegia. Severe lesions may affect the arms as well as visual and intellectual functions. Most authors now believe PVL to be the result of a localized infarctive process in watershed areas between the ventriculopetal and ventriculofugal branches of deep penetrating arteries [2-4]. The two most common sites for PVL are the occipital radiation at the trigone of the lateral ventricles and the white matter around the foramen of Monro. PVL has not been attributed to generalized hypoxia because these lesions are pathologically characteristic of infarction and because areas characteristically damaged by hypoxia (cerebellar cortax and hippocampus) are normal [2, 3]. The evolution of PVL was postulated by DeReuck et al. [2] in an autopsy series of 1 3 cases. The earliest stage is char- Downloaded from www.ajronline.org by 187.95.190.228 on 11/13/15 from IP address 187.95.190.228. Copyright ARRS. For personal use only; all rights reserved 160 CHOW ET AL. AJR:145, July 1985 acterized by foci of coagulation necrosis. Later, there is proliferation of astrocytes and macrophages, followed by phagocytosis of the necrotic tissue, with resulting periventricular cavities of varying size surrounded by gliosis. If the ependyma is destroyed, the cavities may then communicate with the ventricular system. Secondary hemorrhage, ranging from microscopic to massive, may occur within these periventricular infarcts, and this feature was demonstrated in 25% of cases studied at postmortem examination by Armstrong and Norman [3]. Thinning of the white matter can lead to van- [1 0]. In neonates at risk for the development of PVL, the periventnicular echogenicity should be evaluated carefully. Appreciation of the abnormal, increased echogenicity equal to or greater than that of the choroid plexus and in the characteristic anatomic location should raise suspicion of PVL. The predictable evolution of the sonographic appearances on sequential scans will establish the diagnosis of this distinct entity. triculomegaly REFERENCES in larger infarcts. The progression of the sonographic findings of PVL in our study correlates well with the pathologic evolution. The initial sonogram shortly after birth is often normal. Increased penventricular echogenicity may be demonstrated in the first 2 weeks of life, representing ischemia or hemorrhage [8, 1 11. CT at this stage demonstrates periventnicular lucency unless secondary hemorrhage has occurred. It is not until about 23 weeks after birth and sometimes later that the characteristic periventnicular multiseptated cysts develop and then the diagnosis of PVL becomes certain. Therefore, in neonates with a history of asphyxia and a normal sonogram shortly after birth, follow-up sonograms should be obtained, perhaps on a weekly basis. Our study demonstrated the value of sonography in the diagnosis of neonatal PVL. The location and extent of the parenchymal lesions can be assessed accurately by sonography. Although it is unable to distinguish hemorrhagic from nonhemorrhagic infarction, sonography demonstrates penventricular cystic changes not well seen on CT. The fact that neither CT nor sonography detects PVL as often as in autopsy series suggests that both have limited sensitivity. Magnetic resonance imaging may prove to be superior [1 2, 13]. Subependymal/intraventricular hemorrhage, a more cornmon hemorrhagic lesion of premature infants, may extend into the peniventnicular white matter and mimic hemorrhagic PVL. The characteristic position for PVL, dorsal and lateral to the germinal matrix layer, helps differentiate these entities. Similarly, focal and multifocal ischemic brain necrosis is associated with cavity formation, tending to follow the distribution of the major cerebral vessels. Multiple cystic encephalomalacia results from a variety of insults [1 4, 15], producing cysts of relatively large size and not necessarily located in the periventnicular white matter. Recognition of PVL is of considerable clinical significance as it implies significant brain damage and a less favorable neurologic developmental outcome. Prompt diagnosis with real-time sonography may affect family counseling and further management. Vigorous supportive care, particularly maintenance of ventilation and perfusion, and control of seizure can be instituted to prevent accentuation of the existing injury 1 . Banker BQ, Larroche Arch Neurol 2. DeReuck JC. Periventricular leukomalacia of infancy. 1962;7:386-410 J, Chattha AS, Richardson of periventricular 1972;27:229-236 EP. Pathogenesis leukomalacia evolution in infancy. Arch and Neurol 3. Armstrong D, Norman MG. Periventricular leucomalacia in neonates: complications and sequelae. Arch Dis Child 1974;49:367375 4. Shuman RM, Selednik U. 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