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Neonatal Porencephaly in Very Low Birth Weight Infants: Ultrasound Timing of Asphyxial Injury and Neurodevelopmental Outcome at Two Years of Age

Posted on: Thursday, 26 January 2006, 09:00 CST

By Tonni, G; Ferrari, B; Defelice, C; Centini, G

Abstract

Objective. To investigate and diagnose the timing of asphyxial injury leading to cerebral cavitation with subsequent developing of neonatal porencephaly in the preterm VLBW infant. All newborns underwent careful neurodevelopmental outcome at 2 years of corrected age.

Methods. 250 consecutive VLBW infants (mean gestational age of 28 weeks and mean birthweight of 1150 g) have been study by means of weekly neonatal transfontanellae ultrasonography. Periventricular white matter necrosis was diagnosed when echolucencies were visible after day 3 from birth.

Results. Twelve cases of neonatal porencephaly were diagnosed by ultrasound. The timing of asphyxial insult leading to cerebral cavitation seems to have occurred in 33% of neonates during the antepartum period, in 42% during the peripartum period (antepartum + neonatal period) and 25% in the remaining neonatal period. Periventricular-intraventricular hemorrhage (PVH-IVH) was found in all cases and in 50% a severe IVH (grade III-IV) was diagnosed within 7 days neonatal period. Nine infants had evidence of cerebral palsy at 2 years neurological outcome.

Conclusions. The ultrasound criteria of cerebral cavitation have been priorly selected in order to assure that the damage may have occurred before delivery. A comprehensive prenatal study of fetal brain, integrating ultrasound with high-velocity MRI, is also advocate. This will lead to a more detailed understanding of the underlying cerebral condition that is of critical importance for the clinician in planning the time and mode of delivery and have great deal with further medico-legal consideration.

Keywords: VLBW, porencepholy, ultrasound timing of cavitation, neurological outcome

Introduction

Congenital brain lesions include two types of porencephaly: genetic porencephaly, resulting from maldevelopment during early neuronal migration and encephaloclastic porencephaly that is a late prenatal or perinatal vascular lesion (hypoxicischemic encephalopathy) due to arterial ischemic stroke or venous thrombosis. Periventricular leukomalacia (PVL) is the hallmark of porencephaly, its anatomical distribution coinciding with the junctional zone between the ventriculopetal and ventriculofugal components of arterial circulation within the cerebral hemispheres [1,2].

Hypoxia lasting 1-3 hours may cause brain damage and deficits in surviving infants, especially those with severe acidemia (pH < 7.0) and systemic hypotension [3]. Porencephaly has been described in cases of focal or multifocal cerebrovascular insufficiency, systemic vascular insufficiency, periintraventricular hemorrhage, placental bleeding, maternal toxemia, prenatal and postnatal encephalitis and meningitis, and drug abuse [4-6].

Herein we describe and analyze 12 cases of neonatal porencephaly in which an ultrasound based method was used to determine the probable timing of asphyxiai damage and for which neurological outcome at two years of age was ascertained.

Material and methods

This prospective study covers a ten-year period (1990-2000) and analyzes the data of 250 consecutive deliveries of infants weighing less than 2000g (VLBW) recorded in the permanent computerized perinatal hospital records. Twelve consecutive cases of neonatal porencephaly were identified and the following maternal and neonatal characteristics were analyzed: gestational age, antenatal maternal and fetal complications, antepartum and/or intrapartum cardiotocography, amniotic fluid, mode of delivery, birth weight, 1- , 5- and 10-minute Apgar score and neonatal acid-base assessment. Blood samples for evaluation of neonatal acid-base assessment were obtained before the first breath from a double clamped segment of the umbilical cord artery using a 2.5-mL pre-heparinized syringe (Terumo) and analyzed with an AVL 940 microprocessor (Schaffhausen, Switzerland) in the delivery room.

Acidemia was defined as blood pH <7.15, metabolic acidosis as buffer base (BB) <34Meq/L and respiratory acidosis as blood pCO^sub 2^ < 65 mmHg.

Deliveries were supervised by a neonatologist. Newboms received immediate care and were subsequently transferred to the neonatal intensive care unit (NICU).

Serial neonatal cranial ultrasonography was performed using a 5MHz transducer placed on the anterior fontanellae to obtain a series of sagittal and coronal images. Evidence of periventricularintraventricular hemorrhage (PVH-IVH) was graded according to the criteria of Papile: grade 1 hemorrhage refers to hemorrhage confined to the germinal matrix layer area; grade 2, intraventricular hemorrhage with normal ventricle size; grade 3, intraventricular hemorrhage with ventricular dilation; grade 4, extension of intraventricular hemorrhage to parenchyma. Grades 3 and 4 were regarded as severe hemorrhage.

Table I. Maternal complications, mode of delivery and fetal characteristics.

Intraparenchymal extension of intraventricular hemorrhage was diagnosed when intraventricular clots continued with echogenic areas in the paraventricular white matter. Antenatal white matter necrosis was diagnosed when echolucent areas corresponding to cysts were observed in the white matter adjacent the lateral ventricles by day three after birth. The diagnosis of respiratory distress syndrome (RDS) was made on the basis of oxygen therapy requirements and radiographie findings. Severe newborn hypoxic-ischemic encephalopathy was denned by the presence of generalized tonicclonic seizures and/or recurrent apnea (respiratory pause >30 seconds). Bradycardia was defined as neonatal heart rate < 110 beats/minute. Necrotizing enterocolitis was diagnosed on the evidence of intestinal distension, gastric residua, hematest-positive stools and pneumatosis intestinalis, radiologically denned by the presense of air in the bowel wall in plain antero-posterior and lateral Xrays of the abdomen.

All newborns underwent neurological follow-up at two years of age at the Centre for Neurological Diseases of Parma University.

Results

Newborns with encephaloclastic porencephaly had a mean gestational age of 28 weeks (2SD = 2.1, range 26-33 weeks) and a mean birth weight of 1150 g (2SD = 750, range 640-1950g), with a male:female ratio of 2. All mothers but one underwent planned or emergency cesarean section, performed in five patients due to preeclampsia (42%), in three due to eclampsia (25%), and in the other three due to abruptio placentae (25%) (Table I).

Analysis of acid-base assessment at birth documented neonatal acidemia and neonatal metabolic acidosis in 50% of cases and a mixed pattern (metabolic plus respiratory) in 66%.

Hypoxic-ischemic encephalopathy was observed in 83% of the neonates while bradycardia was observed in 50%, RDS in 42% and IVH in 33% of cases (Table II).

Analysis of serial neonatal ultrasonography revealed that all infants had periventricular leukomalacia and grade 3-4 intraventricular hemorrhage was observed in five cases in the first seven days of postnatal life (Table III).

The hypoxic-ischemic brain injury presumably occurred in the antepartum period in 33% (cases 3, 7, 8 and 9), 42% in the peripartum period (cases 2, 5, 6 and 11) and in the other 25% in the neonatal period. The timing of the insult responsible for cavitation may have been 2-4 weeks before the neonatal ultrasound diagnosis and specifically a mean time period of 9 days in the antepartum, 15 days in the peripartum and 31 days in the neonatal period, respectively.

Table II. Neonatal complications and therapy.

Table III. Weekly neonatal transfontanellae ultrasound.

Neonatal ultrasound findings

Abnormal echo lesions in the periventricular white matter of the cerebral hemispheres were discovered in the first seven days of the neonatal period in eight neonates (66%). Infants who had early characteristic echo-dense lesions in the periventricular white matter developed echo-free areas (periventricular cysts) in sites corresponding to the original echo-dense lesions. Ultrasound showed that the mean timing of this process was 14 days after birth (range 6-40 days). Because the ischemic event is often more widespread than the focal infarction that develops in porencephaly, the hemisphere affected by the lesion tends to be smaller than the contracterai one, often associated with dilation of the ipsilateral ventricle (Figures 1 and 2).

Comment

Porencephaly is an hypoxic-ischemic injury resulting from vascular occlusive disease and brain necrosis caused by hypoxia, systemic vascular occlusion, placental bleeding, maternal toxemia, cystic periventricular leukomalacia, grades 3 to 4 intracranial hemorrhage and cerebral atrophy, chronic lung disease, steroids for chronic lung disease, necrotizing enterocolitis, male gender, viruses, endotoxins, trauma and drug abuse [1-7]. Neuropathological studies have demonstrated that in preterm infants, asphyxiai injury leads to neuronal necrosis in the basal ganglia, thalamus and brain stem with limited evidence of necrosis in the cortex of the cerebral hemispheres and cerebellum [8]. Porencephalic cysts may occur singly or multiply. The cysts are sometimes observed as multicystic encephalomalacia or as hydranencephaly, replacing much of the hemisphere. There is evidence that 5% to 10% of asphyxiai injury in each reproductive time period is initially sublethal, contrib\uting to deficits in surviving infants [8,9].

Figure 1.

Figure 2.

Table IV. Timing of asphyxiai damage assessed by US criteria of cavitation.

Table V. Neurodevelopmental outcome at two years of age.

Previous neuropathological and echoencephalographic studies found that a period of 2-6 weeks ensues between the acute stage of white matter necrosis and development of cystic lesions [3,5,10].

According to the ultrasound criteria assessed by Bejar et al. [9] and Volpe [11], the most likely timing of cerebral cavitation in our series has occurred in the antenatal period in 33% (cases 3, 7, 8 and 9), in the peripartum in 42% (cases 2, 5, 6, 11 and 12) and in the neonatal period in 25% (cases 1, 4 and 10) (Table IV). Our study also indicates that the sequence of events leading to cystic degeneration may have occurred in the vast majority of cases (75%) in the antepartum period, at least 1 or 2 weeks before delivery (Table IV).

Data regarding the neurodevelopmental outcome at two years of age (Table V) furthermore revealed that the three different types of cerebral palsy (tetraplegia, diplegia and hemiplegia) were evenly encountered in 25% of all cases, with tetraplegia associated with the most severe grade of fetal hypoxia.

The evidence that cerebral damage causing porencephaly has probably had its origin well before the onset of labor will have a great impact on medicolegal considerations and in turn emphasizes the important role of an antepartum and peripartum detection of the brain anatomy of preterm infants [6,1O]. In our study, postnatally- acquired white matter necrosis was diagnosed when echolucencies were discovered by day three after birth and this criterion was selected to indicate that damage to the cerebral white matter might have occurred before delivery [9,11]. This is a conservative diagnosis because cystic lesions in the white matter appear two or more weeks after the acute stage [9,11].

Abnormal antepartum color-Doppler sonography, initial ultrasound signs of brain deterioration and antenatal and/or postnatal cerebral magnetic resonance imaging (MRI) could help perinatologists plan the timing of delivery, when clinically possible.

References

1. Scher MS, Belfar H, Martin J, Painter MJ. Destructive brain lesions of presumed fetal onset: Antepartum causes of cerebral palsy. Pediatrics 1991;88:898-906.

2. Cross JH, Harrison CJ, Preston PR, Rushton DI, Newell SJ, Morgan ME, Durbin GM. Postnatal encephaloclastic porencephaly - a new lesion? Arch Dis Child 1992;67:307-311.

3. Low JA. Relationship of fetal asphyxia to neuropathology and deficits in children. Clin Invest Med 1993;16:133-140.

4. Dominguez R, Aguirre VC, Slopis JM, Bohan TP. Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs. Am J Dis Child 1991;145: 688-695.

5. Bejar RF, Vaucher YE, Benirschke K, Berry CC. Postnatal white matter necrosis in preterm infants. J Perinatol 1992;12:3-8.

6. Stanava KN, Hartmann S, Uhlemann M, Diete H, Reschke E, Koepe E, Sadenwasser W, Kultz T. Neonatal ultrasonographic cerebral findings: Association with risk factor for cerebral palsy. Z Geburtshilfe Neonatol 2002;206:142-150.

7. Vohr BR, Wright LL, Dusick AM, MeIe L, Verier J, Steichen JJ, Simon NO, Wilson DC, Broyles S, Bauer CR, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the Neonatal Institute of Child Health and Human Development Neonatal Research Network, 1993-1994. Pediatrics 2000;105:1216-1226.

8. Low JA, Robertson DM, Simpson LL. Temporal evaluation of neuropathologic conditions caused by perinatal asphyxia. Am J Obstet Gynecol 1989;160:608-614.

9. Bejar R, Woznik P, Allard M, Benirscke K, et al. Antenatal origin of neurologic damage in newborn infants. Am J Obstet Gynecol 1988;159:357-363.

10. Rusthon DI, Preston PR, Durbin GM. Structure and evolution of echo-dense lesions in the neonatal brain. Arch Disease Child 1985;60:799-808.

11. Volpe JJ- Hypoxic-ischemic encephalopathy: Clinical aspects. In: Neurology of the newborns. 4th ed. Philadelphia: WB Saunders; 2001.

G. TONNI1, B. FERRARI2, C. DEFELICE3, & G. CENTINI4

1 Department of Obstetrics Gynaecology, AUSL Reggio Emilia, Regio Emilia, Italy, 2 Department of Obstetrics & Gynaecology, University of Parma, Parma, Italy, 3 Department of Paediatrics & Neonatology, Policlinic Hospital "Le Scotte", University of Siena, Siena, Italy, and 4 Department of Obstetrics and Gynaecology, Policlinic Hospital "Le Scone", University of Siena, Siena, Italy

Correspondence: Dr Gabriele Tonni, MD PhD, Research Doctorate in Obstetrics & Gynaecology, Department of Obstetrics & Gynaecology, AUSL Reggio Emilia, Guastalla Civil Hospital, Via Donatori di Sangue, 1, Guastalla Reggio Emilia, Italy. Tel: +39 0522 837231. E- mail: tonni.gabriele@ausl.re.it

Copyright CRC Press Dec 2005

Source: Journal of Maternal - Fetal & Neonatal Medicine

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