Department of Neonatology

Germinal matrix-intraventricular haemorrhage and subsequent post-haemorrhagic ventricular dilatation (PHVD) are frequently encountered complications in preterm neonates. As progressive dilatation of the lateral ventricles may be associated with elevated intracranial pressure, ultrasound measurements of ventricular size play a major role in the evaluation of neonates at risk of ventricular dilatation as well as in assessing the effect of intervention for PHVD. A systematic search was carried out in Medline and Embase to identify neonatal and foetal ultrasound studies on lateral ventricular size. This review presents an overview of the available data concerning neonatal reference values for lateral ventricular size, the influence of gender, ventricular asymmetry and the effect of the mode of delivery on the phenomenon of ventricular reopening following birth.

excitatory amino acids and Na þ ,K þ -ATPase activity during resuscitation of severely hypoxic newborn piglets. Acta Paediatr 1998; 87: 889-95. Stockholm. ISSN 0803-5253 We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O 2 supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n ¼ 8), 21% O 2 (n ¼ 8), and 100% O 2 groups (n ¼ 8). The hypoxaemic group was mechanically ventilated with 12-18% O 2 adjusted to achieve a cerebral venous O 2 saturation of 17-23% (baseline; 45 Ϯ 1%, mean Ϯ SEM). During the 2 h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p ¼ 0:044 and p ¼ 0:055, respectively) than during resuscitation with 21% O 2 or 100% O 2 , suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na þ ,K þ -ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups ( p ¼ 0:30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O 2 or 100% O 2 . Resuscitation with 21% O 2 was as efficient as resuscitation with 100% O 2 in this newborn piglet hypoxia model. ٖ Asphyxia, hypoxanthine, in vivo microdialysis, oxygen, reoxygenation BA Feet,

van Leuven K, Groenendaal F, Toet MC, Schobben AFAM, Bos SAJ, de Vries LS, Rademaker CMA. Midazolam and amplitude-integrated EEG in asphyxiated full-term neonates. Acta Paediatr 2004; 93: 1221-1227 Aim: In the present, prospective study, the relation between the levels of midazolam, its two active metabolites-1-hydroxy-midazolam (OH-midazolam) and 1-hydroxy-midazolam-glucuronide (glumidazolam)-and the aEEG were examined. Patients and methods: Fifteen full-term neonates with seizures due to hypoxic-ischaemic encephalopathy admitted to our NICU were included. Midazolam (loading dose 0.05 mg/kg in 10 min, maintenance dose 0.15 mg/kg/h) was used as an add-on anti-convulsant after phenobarbital and lidocaine because of continuing seizures. Amplitude-integrated EEG background pattern was scored at the start of midazolam and at the time of blood sampling as continuous normal voltage (CNV), discontinuous normal voltage (DNV), burst suppression (BS), continuous low voltage (CLV) or flat trace (FT). Serum levels of midazolam, OH-midazolam and glu-midazolam were measured at least 8 h after the start with HPLC. Results: In 11/15 patients, seizures were abolished with the addition of midazolam. In the remaining patients, seizure frequency was reduced in one and unchanged in three. Amplitude-integrated EEG background pattern at the start of midazolam was CNV in two, DNV in six, BS in five and CLV in two. Moderate, temporary suppression of the aEEG background pattern lasting less than 2 h was seen in four neonates. Amplitude-integrated EEG at midazolam sampling was CNV in two, DNV in seven, CLV in two and FT in four. Serum levels of midazolam ranged from 0.10 to 1.76 mg/l, OH-midazolam from 0.05 to 0.28 mg/l and glu-midazolam from 0.85 to 4.36 mg/l.

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated cholinecontaining compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated cholinecontaining compounds and myo-inositol) in both gray and white matter. q

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated cholinecontaining compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated cholinecontaining compounds and myo-inositol) in both gray and white matter. q

The purpose of this study was to test the hypothesis that a high lactate signal and a low N-acetylaspartatelcholine ratio in neonates with postasphyxial encephalopathy indicated a high chance of an adverse outcome in vivo when proton magnetic resonance spectroscopy was used. Twenty-one full-term asphyxiated neonates were examined at a mean postnatal age of 7.1 d. Five patients died, and five survivors had handicaps. Eleven of the 16 survivors (seven without handicaps and four with handicaps) had a second examination at 3 mo of age. After magnetic resonance imaging, spectra were obtained at 1.5 tesla. A 20-mm-thick slice was selected through the basal ganglia. After optimizing the B-O field, we used a double spin-echo pulse sequence (90-180-180") with a time to repeat of 2000 ms and a time to echo of 272 ms. Twodimensional spectroscopic imaging was performed by 32 x 32 phase encoding steps in two directions in a 225-mm field of view, resulting in 1-mL volumes, followed by computerized processing. Neuromotor development was examined at 6 wk, 3 mo, and every 3 mo thereafter. Lactate resonances were seen only in the five patients with grade 3 postasphyxial encephalopathy. Lactate was distributed diffusely (n = 4), or localized in areas of infarction (n = 1). N-acetyl-aspartatelcholine ratios were significantly lower in the patients with an adverse outcome than in the survivors without handicaps, both neonatally ( p < 0.005, Wilcoxon's rank sum test) and at 3 mo ( p < 0.05). In conclusion, the presence of cerebral lactate and a low Nacetyl-aspartatelcholine ratio demonstrated in vivo using proton magnetic resonance spectroscopy in full-term neonates with postasphyxial encephalopathy indicate a poor outcome. (Pediatr Res 35: 148-151, 1994)

Purpose: Diffusion-weighted imaging (DWI) has become a standard method for early evaluation of stroke in adults, but its value in neonates is less well established. In this study neonatal DWI was compared with histopathology in those patients who died, or with sequelae seen on a second MR in the surviving neonates. Patients and Methods: DWI was performed in 2 groups. Group 1: seven neonates who died and had a post-mortem examination (perinatal asphyxia [n = 5], symptomatic hypoglycemia [n = 1], periventricular leukomalacia [n = 1]). Group 2: six surviving neonates with a second MR examination at three months of age (perinatal asphyxia [n = 2], neonatal stroke [n = 3], meningo-encephalitis [n = 1]). Results: In group 1 neonatal DWI showed more extensive involvement than conventional MRI in 6 out of 7 patients. These changes were less extensive, however, than seen post-mortem by histopathology in 5 out of 7. In group 2 neonatal DWI showed more extensive involvement than conventional MRI in 2 out of 6; 4 out of 6, however, showed less extensive cystic evolution on follow-up MRI at 3 months than expected from neonatal imaging. Conclusion: There was a good relation between hyperintense areas on DWI and areas of cytotoxic edema and neuronal damage on histopathology. In the survivors a second MRI showed cystic evolution in all, but the volume of the cysts was smaller than expected on the basis of the neonatal DWI findings.

Background and Purpose-NF-B is a transcription factor that regulates inflammatory and apoptotic pathways. We described previously that intraperitoneal administration of the NF-B inhibitor TAT-NBD at 0 and 3 hours after neonatal hypoxia-ischemia (HI) markedly reduced brain damage. We hypothesize that timing and duration of NF-B inhibition will be a major factor in determining outcome. Methods-HI was induced in P7 rats by unilateral carotid artery occlusion and hypoxia. In vivo TAT-NBD effects were determined on cerebral damage, NF-B activity, cytokine expression, and pro-and antiapoptotic molecules. In vitro effects of TAT-NBD were determined using primary neurons and cell lines. Results-HI induced 2 peaks of cerebral NF-B activity at 3 to 6 and 24 hours after HI. Neuroprotective 0/3-hour TAT-NBD treatment only inhibited early NF-B activity. However, inhibition of both early and late NF-B-activity by 0/6/12-hour TAT-NBD or only late NF-B activity by 18/21-hour TAT-NBD aggravated damage. 0/6/12-hour TAT-NBD did not prevent HI-induced upregulation of cytokines at 24 hours after HI. Protective 0/3-hour TAT-NBD treatment prevented nuclear accumulation of p53 at 24 hours after HI. Nuclear p53 was not reduced after 0/6/12-hour TAT-NBD. Prolonged TAT-NBD increased the proapoptotic factor PUMA and reduced the antiapoptotic factors Bcl-2 and Bcl-xL. Also in neuronal cultures prolonged TAT-NBD exposure overruled protective short-term TAT-NBD treatment. Conclusions-Early NF-B activation contributes to neonatal HI brain damage. Late NF-B provides endogenous neuroprotection and upregulates antiapoptotic molecules. Inhibition of early NF-B activity is neuroprotective only when late NF-B activity is maintained. Moreover, cerebral cytokine production can occur independently of NF-B.

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated cholinecontaining compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated cholinecontaining compounds and myo-inositol) in both gray and white matter. q

Objective: To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs. Methods: Clinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported. Results: Nine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow-up of one infant was only 9 months. Interpretation: HPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion-weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real-time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures.

Background. Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides realtime neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years.

To evaluate their prognostic value, five different non-invasive techniques were used on 34 full term infants with hypoxicischaemic encephalopathy (HIE) within six hours of delivery. Cranial ultrasonography, the resistance index (RI) of the middle cerebral artery obtained with Doppler ultrasonography, somatosensory evoked potentials (SEPs), visual evoked potentials (VEPs) and the cerebral function monitor (CFM) were used. According to the criteria of Sarnat, 11 infants developed mild, seven moderate, and 16 severe encephalopathy. The CFM had the highest positive (PPV 84.2%) and negative predictive value (NPV 9177%). All but one of the infants with a continuous pattern had a good outcome. The CFM of 11 cases with a suppression-burst pattern changed to a continuous pattern over 24 to 48 hours in four infants, and was associated with a normal outcome in three. AU five cases with an isoelectric CFM died. The SEPs also provided useful information (PPV 81.8%; NPV 91.7%). VEPs were often delayed during the first hours or life and did not carry a poor prognosis in five of 14 cases (PPV 77.3%). Both ultrasonography and Doppler RI were oflittle value, as they were almost always normal at this early stage.

Aim-To assess the prognostic value of amplitude integrated EEG (aEEG) 3 and 6 hours after birth. Methods-Seventy three term, asphyxiated infants were studied (from two diVerent centres), using the Cerebral Function Monitor (CFM Lectromed). The diVerent aEEG tracings were compared using pattern recognition (flat tracing mainly isoelectric (FT); continuous extremely low voltage (CLV); burstsuppression (BS); discontinuous normal voltage (DNV); continuous normal voltage (CNV)) with subsequent outcome. Results-Sixty eight infants were followed up for more than 12 months (range 12 months to 6 years).Twenty one out of 68 infants (31%) showed a change in pattern from 3 to 6 hours, but this was only significant in five cases (24%). In three this changed from BS to CNV with a normal outcome. One infant showed a change in pattern from CNV to FT and had a major handicap at follow up. Another infant showed a change in pattern from DNV to BS, and developed a major handicap at follow up. The other 16 infants did not have any significant changes in pattern: 11 infants had CLV, BS, or FT at 3 and 6 hours and died (n = 9) in the neonatal period or developed a major handicap (n = 2). Five infants had a CNV or DNV pattern at 3 and 6 hours, with a normal outcome. The sensitivity and specificity of BS, together with FT and CLV, for poor outcome at 3 hours was 0.85 and 0.77, respectively; at 6 hours 0.91 and 0.86, respectively. The positive predictive value (PPV) was 78% and the negative predictive value (NPV) 84% 3 hours after birth. At 6 hours the PPV was 86% and the NPV was 91%. Conclusion-aEEG could be very useful for selecting those infants who might benefit from intervention after birth asphyxia.