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Objective:To evaluate the tolerability and efficacy of risperidone in childhood autistic disorder.Methods:A multicenter, open-label, dose-titration study involving seven autistic children (mean age 7.6 years) receiving risperidone for 4 weeks.Results:Mean dose was 0.01 mg/kg/day on day 1, 0.019 mg/kg/day on day 7 (range 0.01–0.041 mg/kg/day) and 0.035 mg/kg/day on day 28 (range 0.014–0.064 mg/kg/day). Over the 4-week period, the Ritvo–Freeman Real Life Rating Scale total score measuring autistic behavior was significantly decreased (P = 0.019), as was the affectual reactions subscale (P = 0.029). Aberrant Behavior Checklist total score was significantly improved (P < 0.001), as were all subscales except inappropriate speech. Visual Analog Scale for individual target symptoms was significantly decreased (P = 0.001), and Clinical Global Impression severity of illness score was significantly improved (P = 0.006). The incidence of adverse effects was low, and no extrapyramidal symptoms were observed. No significant changes or clinically relevant abnormalities occurred in laboratory tests, vital signs or electrocardiograms. Plasma concentrations of the drug were similar to those in adult patients.Conclusions:These favorable results suggest that larger controlled trials of risperidone should be performed in autistic or mentally retarded patients with behavioral disturbances.

Alternating hemiplegia of childhood (AHC) is a rare disorder with diagnosis based on clinical criteria, as no laboratory, neuroradiological or genetic markers are currently available. The pathogenic mechanisms are still an enigma. Some hypotheses have been proposed such as hemiplegic migraine variant, epileptic mechanism, channelopathy and mitochondrial disorder, but none of these has been confirmed. Our aim was to analyze the results of metabolic studies performed on a series of 157 European patients who fulfilled diagnostic criteria for AHC. We tried to find a common metabolic abnormality, related with AHC. We did not find significant abnormalities in basic metabolic screening, at different ages. Neurotransmitters in cerebrospinal fluid (n = 26) were normal in all of the patients. Mitochondrial respiratory chain enzyme activities were analyzed in 19 muscle biopsies; in 4 cases, different MRC enzyme deficiencies were demonstrated, ranging from mild-unspecific deficiencies to more profound and probably primary defects. Although we did not find specific metabolic markers in our series, some metabolic disorders such as pyruvate dehydrogenase deficiency, MELAS, cerebral glucose transporter defect and neurotransmitter deficiency can exhibit symptoms similar to those of AHC and need to be ruled out before a diagnosis of AHC can be established. Further studies including high-throughput diagnostic technologies seem necessary to elucidate the etiology of this severe and enigmatic disorder.

The supine posture of 15 low-risk preterm infants was studied to establish whether they have a preferred posture and, if so, whether it changes with age. No over-all preferred posture was found. Almost always one posture was adopted most frequently, but often a great variety of other postures were adopted almost as frequently. There was no correlation between postmenstrual age and preferred posture, the number of different postures, or the duration of longest uninterrupted posture.

SUMMARY Cerebral artery Doppler ultrasonography was used to study the cerebral blood-flow velocity and cerebral oxygen transport of infants requiring a blood transfusion to correct anaemia. Mean flow velocity, pulsatility index and haemoglobin concentration were determined before and after transfusion. 11 stable preterm infants demonstrated an inverse relationship between haemoglobin concentration (or estimated arterial oxygen content) and mean flow velocity, indicating the presence of a homeostatic mechanism keeping brain oxygen transport within certain limits. Three infants with severe post-asphyxial encepalopathy had relatively high mean flow velocities and low pulsatility indices both before and after transfusion. There were no circulatory adjustments in response to an increase in haemoglobin concentration. Thus severe asphyxia at birth disrupted the homeostatic mechanism responsible for keeping brain oxygen transport constant. These findings stress the importance of close monitoring of arterial oxygen content, particularly for infants with severe post-asphyxial encephalopathy. RESUME Deficience de la regulation du transport de l'oxygene cerebral apres asphyxie neo-natale grave Les ultrasons Doppler de l'artere carotidienne ont ete utilises pour etudier la vitesse de circulation sanguine cerebrale et le transport cerebral d'oxygene chez des nourrissons dont l'etat avait exige une transfusion sanguine pour corriger l'anemie. La vitesse circulatoire moyenne, l'index de pulsatilite et la concentration en hemoglobine ont ete determines avant et apres transfusion. Chez 11 prematures en bon etat, il y avail une relation inverse entre la concentration en hemoglobine (ou une estimation du taux d'oxygene arteriel) et la vitesse circulatoire moyenne, indiquant l'existence d'un mecanisme homeostatique maintenant le transport d'oxygene cerebral dans certaines limites. Chez trois nourrissons avec encephalopathie post asphyxique grave, on notait des vitesses circulatoires moyennes relativement elevees et des indices de pulsatilite bas, avant et apres transfusion. 11 n'y avait pas d'adjustements circulatoires en reponse a une elevation de la concentration en hemoglobine. Ainsi l'asphyxie grave a la naissance rompt le mecanisme homeostatique qui maintient constant le transport cerebral d'oxygene. Ces donnees soulignent l'importance d'un controle precis du taux d'oxygene arteriel, particulierement pour les nourrissons avec encephalopathie post-asphyxique grave. ZUSAMMENFASSUNG Regulationsstorungen des cerebralen Sauerstofftransports nach schwerer Geburtsasphyxie Die cerebrale arterielle Doppler Sonographie wurde benutzt, um bei Kindern, die wegen einer Anamie eine Bluttransfusion brauchten, die cerebrale Blutdurchfluzgeschwindigkeit und den cerebralen Sauerstofftransport zu messen. Vor und nach der Transfusion wurden die mittlere Durchfluzgeschwindigkeit, der Pulsatilitatsindex und die Hamoglobinkonzentration bestimmt. 11 Fruhgeborene zeigten eine umgekehrte Beziehung zwischen Hamoglobinkonzentration (oder geschatztem arteriellem Sauerstoffgehalt) und mittlerer Durchfluzgeschwindigkeit, was auf das Vorliegen homoostatischer Mechanismen hinweist, die den cerebralen Sauerstofftransport in bestimmten Grenzen halten. Drei Kinder mit schwerer postasphyktischer Enzepahlopathie hatten relativ hohe mittlere Durchfluzgeschwindigkeiten und niedrige Pulsatilitatsindices sowohl vor, als auch nach der Transfusion. Die Zirkulation anderte sich durch eine Erhohung der Hamoglobinkonzentration nicht. Somit wurde durch eine schwere Geburtsasphyxie der homoostatische Mechanismus, der den Sauerstoffgehalt des Gehirns konstant halten soll, unterbrochen. Diese Befunde unterstreichen die Notwendigkeit einer luckenlosen Uberwachung des arteriellen Sauerstoffgehaltes, besonders bei Kindern mit schwerer post-asphyktischer Encephalopathie. RESUMEN Regulation defectuosa del transporte de oxigeno cerebral despues de una grave asfixia en el parto Se uso la ultrasonografia Doppler cerebral para estudiar la velocidad de flujo cerebral y el transporte de oxigieno en el cerebro, en ninos que necesitaron transfusion sanguinea para corregir una anemia. La velocidad media del flujo, el indice de pulsabilidad y la concentracion de hemoglobina se determinaron antes y despues de la transfusion. 11 lactantes pretermino estables mostraron una relacion inversa entre la concentracion de hemoglobina (o el contenido estimado de oxigeno arterial) y la velocidad media de flujo, indicando la presencia de un mecanismo homeostatico que mantiene el transporte de oxigeno en el cerebro dentro de cierto limites. Tres lactantes con una grave encefalopatia postasfictica tenian una velocidad media de flujo alta y un indice bajo de pulsatilidad antes y despues de la transfusion. No hubo ningun ajuste circulatorio como respuesta a una aumento en la concentracion de hemoglobina. Por lo tanto una asfixia grave al nacer alteraba el mecanismo homeostatico responsable de mantener constante el transporte de oxigeno cerebral. Estos hallazgos dan importancia a la monitorizacion cuidadosa del contenido de oxigeno arterial, especialmente en lactantes con una grave encefalopatia postasfictica.

SUMMARY Both the age of the infant and the birthweight in relation to age are relevant factors in studying prenatal and neonatal physiology and in evaluating immediate and future clinical risks to the fetus and the newborn. Since the true age of the infant (the time-span from conception) is not available, the first day of the last menstrual period is commonly used as the time reference. In many cases, however, there is doubt as to the accuracy of this reference day, necessitating other criteria to indicate the duration of fetal development or of the postmenstrual age of the newborn. The authors discuss the use of pre- and postnatal evaluations of the developmental changes in various organ systems-by physical measurement, observation, physiological registrations and biochemical analysis - for the estimation of the postmenstrual age. They use the following criteria: Does the observable phenomenon change suddenly from absent to present at a particular postmenstrual age? Does the phenomenon remain unaltered in sick children? Is the method relatively easy and reliable? Is the technique without risk for the fetus, the mother and the newborn? At present, a combination of parameters, serially measured, on the developing nervous system and the developmental changes of the skin seem to be most helpful in pre- and postnatal life, and the authors report that the optimal accuracy obtainable so far still has a range of plus or minus 2–3 weeks. The reasons for this wide range are discussed. RESUME Estimation de & lcar;âge post-menstruel: vue d'ensemble L'âge de l'enfant et le poids de naissance en fonction de l'âge sont tout deux des facteurs importants dans l'etude de la physiologie prenatale et neo-natale, dans l'evaluation clinique des risques immediats et futurs du foetus et du nouveau-ne. Puisque l'âge vrai de l'enfant (duree depuis la conception) ne peut etre connu, le premier jour des dernieres regies est pris generalement comme reference. Dans de nombreux cas cependant, on peut douter de la precision de cette reference et d'autres criteres sont neces-saires pour indiquer la duree du developpement foetal ou l'âge post-menstruel du nouveau-ne. Les auteurs discutent l'emploi de mesures pre et post-natales de modifications liees au developpement au niveau de certains organes pour la determination de l'âge post-menstruel (par mesure physique, observations, enregistrement physiologique et analyse biochimique). lis utilisent les criteres suivants: Le phenomene observe“passe-t-il de l'absence a la presence brusquement a un âge post-menstruel particulier? Ce phenomene persiste-t-il chez les enfants malades? La methode est-elle suffisamment facile et fidele? La technique est-elle sans risque pour le foetus, la mere et le nouveau-ne? A l'heure actuelle, une combinaison de parametres, determines sur des series, au niveau du developpement du systeme nerveux et des modifications progressives de la peau semble etre la plus utile durant la vie pre ou post-natale; les auteurs precisent que la precision optimale atteinte jusqu'a ce jour est de plus ou moins deux ou trois semaines. lis discutent les raisons de cette large erreur. ZUSAMMENFASSUNG Die Schatzung des postmenstruellen Alters: Eine umfassende Synopse Sowohl das Gewicht eines Sauglings als auch das Verhaltnis zwischen Geburtsgewicht und Alter sind wichtige Faktoren beim Studium der pranatalen und neonatalen Physiologie und bei der Bestimmung des unmittelbaren und zukunftigen Risikos des Foetus und des Neugeborenen. Da das wahre Alter des Kindes (die Zeit von der Konzeption an) nicht zu erfahren ist, wird im allgemeinen der erste Tag der letzten Menstruationsperiode als Orientierungspunkt gewahlt. In vielen Fallen mus man jedoch Zweifel haben an der Genauigkeit dieser Angabe, woraus sich die Notwendigkeit ableitet, andere Kriterien fur die Dauer der foetalen Entwicklung oder des postmenstruellen Alters des Neugeborenen zu finden. Die Autoren diskutieren die Verwendung pra- und postnataler Ermittlungen der durch die Entwicklung bedingten Veranderungen in verschiedenen Organsystemen–durch physikalische Messung, Beobachtung, physiologische Bestimmungen und biochemische Analysen–fur die Bestimmung des postmenstruellen Alters. Sie benutzen die folgenden Kriterien: Wechselt das zu beobachtende Phanomen plotzlich von nicht vorhanden zu vorhanden bei einem bestimmten postmenstruellen Alter? Bleibt dieses Phanomen bei kranken Kindern unverandert? Ist die Methode verhaltnimasig einfach und verlaslich? Ist die Technik fur den Foetus, die Mutter und das Neugeborene ohne Risiko? Zur Zeit scheint eine Kombination von regelmasig gemessenen Parametern uber die Entwicklung des Nervensystems und die Veranderungen der Haut im pra- und postnatalen Leben besonders hilfreich zu sein, und die Autoren berichten, das die bisher erreichte Genauigkeit immer noch eine Spanne von plus minus zwei bis drei Wochen betragt. Die Grunde fur diese weite Spanne werden diskutiert.

Pathological findings in two patients with Moebius syndrome and lethal fetal akinesia sequence are described. In both patients a congenital brain stem malformation with neuronal loss in the cranial nerve nuclei and tegmental microcalcifications was observed. In one patient, the association with splenogonadal fusion was observed, whilst in the second patient, the association with tetraperomelia was present. As the association of peromelia and splenogonadal fusion is a well-known association, the different combination of splenogonadal fusion, peromelia and Moebius syndrome due to congenital brain stem anomalies with necrosis might be the result of a disruptive phenomenon during a prolonged vulnerable critical period in the 5th and 6th week of embryonic life. The finding of olivary dysplasia in one case, reminiscent of olivary dysplasia in Zellweger syndrome and in Miller Dieker syndrome, might suggest a primary malformation underlying Moebius syndrome due to brain stem defects.

To compare the functional maturation of the human visual system between intra- and extrauterine course flash visual evoked potentials (VEPs) in preterm infants (gestational age 24 to 36 weeks). Previously established normal values, with special reference to the two components of the N1 wave, were employed (Tsuneishi 1995). A cross-sectional analysis of 124 infants at 36 weeks postmenstrual age (PMA), showed that there are no differences in the absolute values of VEP peak latencies depending on the postnatal age (PNA). Conversely, the N1 wave form changes with increasing PNA from a wave in which the early peak (N1a) has a higher amplitude than the late peak (N1b) into the reverse situation with a higher amplitude of the N1b as compared to N1a. This observation may correlate with the maturation of the neuronal networks in the visual cortex. In a longitudinal analysis of 50 infants followed for more than 5 sessions of weekly recordings, we found that the individual rapid decrease in the N1a latency, which may reflect the initiation of myelination in the optic radiation, most frequently occurs at around 37 weeks PMA, regardless of PNA. Preterm extrauterine visual experience has little effect on the myelination process in the visual pathway, but has a marked effect on the developmental changes in VEP wave form which reflect the developmental changes of the neuronal networks in the visual cortex.

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE). Methods: Six newborn piglets were measured at 33, 35, and 37°C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (SaO2) and PaCO2 were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (CaO2 and CvO2) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (SaO2 – TOI)/SaO2. The correlation was calculated with an ANCOVA test. Results: There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between PaCO2 and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and PaCO2 (R = 0.24, p = 0.03). Conclusion: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.

Aim: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. Methods: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were PaO2, PaCO2, pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. Results: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, PaO2, PaCO2, and haemoglobin concentration. Conclusion: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time.

Several studies support the idea that the use of pacifiers can reduce the risk of Sudden Infant Death Syndrome. To investigate the effect of non-nutritive sucking (NNS), we measured heart rate, abdominal respiration, EMG and arterial oxygen saturation of 20 neonates. Also, in 10 of these neonates, changes in cerebral hemoglobin concentrations were acquired by means of near-infrared spectroscopy. Using a parametric technique to model the heart rate as a sum of exponentially damped sinusoids, two main frequency components were found in the heart rate during NNS: a frequency of approximately 0.08 Hz due to the alternation of sucking bursts and pauses, and a frequency of approximately 0.8 Hz that reflects the influence of the respiration. Our analysis shows that it is the alternation of bursts and pauses itself that causes the increased heart rate variability, and that this is not due to increased effort. This suggests that the neuronal mechanism regulating NNS also stimulates the heart rate. From our measurements, no effect of NNS on cerebral or peripheral oxygenation could be found. Furthermore, we show that our model-based signal processing technique is well suited for the analysis of non-stationary biomedical signals.

Peri- en intraventriculaire bloeding is de meest frequente vorm van neonatale intracraniele bloeding en treedt karakteristiek op bij prematuren. Ongeveer 35% van de kinderen die een intraventriculaire bloeding doormaken, ontwikkelt posthemorragische hydrocephalus. We bestudeerden vroege externe drainage ter controle van de hydrocephalus. Volgens sommige onderzoekers heeft deze methode een onaanvaardbaar hoog infectierisico en hogere morbiditeit en mortaliteit dan andere behandelingen. Uit ons onderzoek blijkt echter dat externe ventrikeldrainage een veilige en effectieve methode is, die onder strikte hygienische voorzorgen gedurende lange tijd kan worden toegepast zonder een duidelijk verhoogd infectierisico.

In this case report a patient with bilateral optic nerve hypoplasia, schizencephaly and a pigmented skin lesion is described. The diagnosis of de Morsier syndrome or septo-optic dysplasia is put forward on the basis of the diagnosis of optic nerve hypoplasia. The differential diagnosis with Jadassohn's naevus phakomatosis is discussed. The importance of direct ophthalmoscopy of optic nerve abnormalities is stressed, as well as of magnetic resonance imaging, which has become a guideline in the classification of this syndrome.

We retrospectively reviewed 32 patients operated on for lipoma of the conus and lipomyeloschisis, the two main anatomical subtypes of congenital lumbosacral lipomas associated with tethered cord syndrome. Surgery was proposed to patients when they were symptomatic, and in most cases for progressive symptoms. The evolution of the different symptoms was studied separately. In most patients, symptoms improved or stabilized after surgery; in some, however, postoperative worsening, at least of some of the symptoms, was seen. This postoperative worsening became apparent either early or late after the operation, and was not associated with surgical trauma or postoperative complications. We suggest it was caused mainly by the natural course of the disease (especially in the case of the orthopedic deformities), and in some cases by retethering. Our series is not large enough to detect statistical significance for the different symptoms or for the anatomical subgroups. Importantly, according to our analysis by the different symptoms, the operation did not seem to protect the patients from later development of new deficits. This can be interpreted as an argument against prophylactic surgery in asymptomatic patients.

We describe the first observation of a child with a posterior fossa subdural effusion with secondary hydrocephalus and tonsillar herniation. We diagnosed this entity in a 14-month-old girl with no history of trauma or coagulation disorder. The patient presented in our emergency department with opisthotonus and raised intracranial pressure resulting from supratentorial hydrocephalus. An emergency ventriculo-peritoneal shunt was placed, which resolved the symptoms only temporarily. Eventually external drainage of the subdural fluid was performed. The collection gradually disappeared, and both the external subdural shunt and the ventriculo-peritoneal shunt were removed. The patient made a complete neurological recovery. We review the physiopathology and treatment of subdural effusions in general, and propose some guidelines for the management of symptomatic effusions occurring in the posterior fossa in particular.

To improve patient compliance with and acceptance of intravesical oxybutynin therapy for neurogenic bladder dysfunction we developed a stable oxybutynin solution that eliminates the complicated crushing procedure.From January 1995 to January 1997 we prospectively evaluated 15 children with a mean age of 6.1 years with persistent detrusor hyperactivity or significant side effects on oral oxybutynin therapy who received intravesically 0.2 mg./kg. (maximum 5 mg.) of a stable oxybutynin solution (5 mg./5 ml., pH 5.85) twice daily.The oxybutynin solution remained stable up to 24 months. In 13 of the 15 children therapeutic compliance was excellent. Detrusor hyperactivity decreased and systemic side effects were absent or minimal. After 4 and 24 months mean cystometric bladder capacity plus or minus standard error of mean increased from 114+/-15.2 to 161+/-26.6 and 214+/-21.7 ml. (p0.01), mean ratio of cystometric-to-expected bladder capacity increased from 0.88+/-0.12 to 1.18+/-0.14 and 1.24+/-0.16 (p0.01), and end filling bladder pressure decreased from 57.0+/-7.1 to 25.6+/-4.4 and 30.8+/-4.4 cm. water (p0.01), respectively.Intravesical instillation of a specially prepared oxybutynin solution is safe and reliable in children with persistent detrusor hyperactivity or side effects on oral oxybutynin therapy. Eliminating the complex crushing preparation of the solution by the child or parent has made this therapy easy to use and acceptable in the long term.

To assess the progress in myelination in the developing human brain, a prospective longitudinal study of flash visual evoked potentials (VEPs) was performed in 22 healthy preterm infants with the same gestational age at birth (between 30 weeks 0 day and 31 weeks 0 day). The individual curves of the changes in the N1a peak latency (the early peak of the N1 wave) decrease not linearly but in a stepwise pattern in the preterm period. Twenty-one infants out of the 22 have one or more `acceleration week(s)' in which the latency decreases at a rate of more than 6 ms per week. These stepwise decreases in the latency may reflect a synchronized progress in myelination in several parts of the visual pathway. A detailed analysis of the `acceleration weeks' in relation to postmenstrual age (PMA) indicates that they most prominently occur at 37 weeks PMA. At 37 weeks an initiation of myelination in the optic radiation has been demonstrated in post-mortem studies. We propose that a longitudinal follow-up study of VEPs can be accepted as a functional in vivo evaluation of myelination in the developing human brain.

To treat progressive posthemorrhagic hydrocephalus we used early external ventricular drainage (EVD) in 14 premature infants. We think it is important that the catheters in these critically ill infants be inserted in the neonatal intensive care unit, allowing us to keep the infants in an extremely stable environment. Only after prolonged external ventricular drainage (on average 38.4 days) is a ventriculoperitoneal shunt considered, preferably when the child has reached a body weight of 2000 g. There were no infections or other severe drainage-related problems. We report mean daily EVD volumes (which are related to body weight) and EVD duration. The 14 patients included 9 who required permanent shunting. Comparing the mortality, morbidity and follow-up data to at least 3 months of age in this group with similar data for an earlier cohort treated with lumbar punctures and late permanent shunting, we demonstrate the safety of the policy we have recently adopted.

The carbohydrate-deficient glycoconjugate [CDG] syndromes are a family of genetic diseases characterized by a deficiency of the carbohydrate moiety of glycoconjugates. They were first reported in 1980.1 As of June 1997 some 250 patients worldwide (published and unpublished) were known to the authors. Four types have been individualized on the basis of the isoelectrofocusing pattern of serum sialotransferrins, z-6 Only in two has the basic defect been identified: type I is, in the great majority of the patients, due to a deficiency of phosphomannomutase (PMM) (type IA), the second step of the mannose pathway and is thus a pre-endoplasmic reticulum disorder, 7,s while type U is caused by a deficiency in Golgi localized N-acetylglucosaminyltransferase II (GnT-II) 4 (Fig. 1). Most patients belong to

As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of > 400 micromol/l (23.4 mg/dl) were enrolled and screened with a neonatal neurological examination (NNE). The cause of jaundice was low birth weight in 22 (44%), ABO incompatability in 8 (16%), sepsis in 8 (16%) and congenital syphilis (6%) in 3 infants. In 9 infants a cause could not be determined. At 4 months, 2 infants had died and 3 were lost to follow up, leaving 45 infants for the infant motor screen (IMS) at 4 months of age. Mean TSB in the neonatal period was 485 micromol/l (28.2 mg/dl), and 7 infants received an exchange transfusion. Mean TSB of the infants with an exchange transfusion was 637 micromol/l (37.2 mg/dl) (range 429-865 micromol/l (25-50.3 mg/dl)) and of the infants without transfusion 459 micromol/l (26.8 mg/dl) (range 400 740 micromol/l (23.4-43 mg/dl)) (P < 0.0001). The TSB was not associated with birth weight, gestational age, gender or head circumference of the baby. On the IMS, 6 of 45 (13.3%) infants scored abnormal, 6 (13.3%) suspect and 33 (73%) scored normal. Three of the six (50%) remaining infants who received an exchange transfusion scored abnormal on the IMS while only 3 of the 39 (8%) infants without exchange transfusion were abnormal. CONCLUSION: More than 25% of infants with a TSB of > 400 micromol/l (23.4 mg/dl) scored abnormal or suspect at 4 months of age and half of these infants already showed irreversible neurological symptoms. All infants who scored abnormal or suspect on the IMS with bilirubin levels between 400 and 500 micromol/l (23.4 and 29.2 mg/dl) had haemolytic disease or were premature

textabstractBackground: Evidence is accumulating that a dietary supply of long-chain polyunsaturated fatty acids (LC-PUFAs) enhances the development of attention and efficient information processing in infants. However, it is uncertain whether LC-PUFAs in infancy influence cognitive development in later childhood. Objective: The objective was to determine the effects of dietary LC-PUFAs in infancy on measures of cognitive function at age 6 y. Design: Infants were randomly assigned to receive formula containing either docosahexaenoic acid and arachidonic acid or no LCPUFAs for a period of 4 mo. A reference breastfed group was also included. In a follow-up conducted at age 6 y, children received assessments of intelligence quotient (IQ), attention control (Day- Night Test), and speed of processing on the Matching Familiar Figures Test (MFFT). Results: At follow-up there were 71 children in the LC-PUFA group, 76 in the control group, and 88 in the breastfed group. The formula groups did not differ on measures of Full-Scale IQ (LCPUFA mean = 98.0; control mean = 100.9) or attention control (LCPUFA mean = 12.7; control mean = 12.8). MFFT error scores were the same for both formula groups, but when making correct responses, the LC-PUFA group was significantly faster (mean = 6.2 s) than the control group [mean = 7.8 s; F(1, 131) = 6.09, P = 0.015]. Conclusions: IQ scores of children who were fed a formula containing either LC-PUFAs or no LC-PUFAs did not differ at age 6 y. However, children who received LC-PUFAs were faster at processing information compared with children who received unsupplemented formula. Variation in the dietary supply of LC-PUFAs in the first months of life may have long-term consequences for the development of some cognitive functions in later childhood.

Cerebellar mutism has been reported after surgery for posterior fossa tumors in children and, rarely, in adults. The pathogenesis of this syndrome remains unclear, and controversy exists regarding whether it is a purely psychogenic disorder or an organic syndrome. The anatomical substrate for the mutism also remains unknown. We encountered five cases of postoperative transient cerebellar mutism in a consecutive series of 63 children with posterior fossa tumors. These cases were analyzed and compared with the patients without mutism to find predictive factors for the occurrence of mutism, with the hope of elucidating further the pathophysiological mechanism. The most significant finding was the presence in all cases of a period of cerebellar dysarthria after resolution of the muteness. We, therefore, believe that cerebellar mutism is an extreme form of dysarthria, rather than a real cognitive deficit or a psychological disturbance.

We report the cranial CT and MRI findings in three children with Lyme disease (neuroborreliosis). The neuroimaging findings in children have been rarely reported. We found cranial MRI far superior to cranial CT. Ring-enhancing lesions have been described in acute disseminating encephalomyelitis and multiple sclerosis but not in neuroborreliosis. Although other infectious and inflammatory diseases cannot be excluded, Lyme disease should be included in the differential diagnosis and put forward as being the most likely diagnosis in the appropriate clinical setting. Gadopentetate dimeglumine is helpful in assessing the response to antibiotic treatment.

Fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder, is characterized by symmetrical congenital skeletal abnormalities and progressive heterotopic ossification of the connective tissues. At present, more than 300 years after the first report by Patin in 1648 in which he described the woman who "turned to wood", its pathogenesis remains largely unknown and its therapy is limited to symptom-modifying trials. However, significant progress has been recently made and new data on the molecular organization and regulation of normal and disordered bone induction are likely to lead to a more specific therapy. FOP is believed to be a genetic disorder characterized by a disturbed expression of the endochondral osteogenesis programme, and the remarkable "clues from the fly" reported by Kaplan et al. [8] in 1990 suggest a gain-of-function mutation in the genetic regulation of bone morphogenetic proteins.

To establish normal values for flash visual evoked potentials (VEPs) in the preterm period, we analyzed 356 records from 63 neurologically normal infants (26-35 weeks gestation) followed longitudinally. Using both sleep and drowsy state recording within the same session and a mean of 5.7 weekly recording sessions per infant, we hypothesized that the prominent negative wave (N1) consisted of 2 negative components, N1a (early) and N1b (late). This hypothesis could explain the previously reported variability in VEP indices. With a precise definition of the N1a peak, we were able to establish reference ranges for N1a peak latencies at various postmenstrual ages (PMA) which, unlike those previously reported, are narrow enough to be clinically useful. From a cross-sectional analysis we found that the N1a peak latency decreased with maturation at about 4.6 msec/week between 30 and 40 weeks PMA (P < 0.001). We also analyzed the N1 wave form and demonstrated its developmental maturation during this period. There were significant decreases in the amplitudes of both the N1a and N1b peaks with maturation (P < 0.001), but the decrease of the N1a amplitude was steeper than that of N1b. The N1 wave form changed from a wave in which the early peak (N1a) was higher than the late peak (N1b) into the reverse with N1b higher than N1a. This wave change may be related to developmental processes in the visual system. Longitudinal follow-up revealed that extra-uterine life may accelerate the maturation of the N1 wave form but has no effect on the decrease of the absolute values of peak latencies.

In preterm neonates, the risk for intracerebral haemorrhage is linked to immaturity of cerebral autoregulation. The preterm's 2-5/min cyclic variation pattern of cerebral blood flow velocity is thought to reflect the degree of immaturity of autoregulation--a speculation to be tested. In a cross-sectional study 15 infants (gestational age 26-40 weeks, postconceptional age (PCA) 26-42 weeks, age 1-99 days were investigated. We performed a 10 min pulsed Doppler tracing on an internal carotid artery by means of a computer controlled 5 MHz Duplex device. Systolic velocity (Vs) was recorded pulse by pulse. After appropriate data transformation, in all infants the Fast Fourier Transform of the time course of Vs revealed the presence of a 2-5/min cyclic variation pattern (one sample z-test, P0.0001). There was no significant correlation between proportionate spectral power of the 2-5/min frequency band and either PCA (r = 0.23, P = 0.42) or age (r = 0.41, P = 0.13). Between 26 and 42 weeks PCA, the cycling phenomenon is constant thus not reflecting cerebral maturation, and its presence does not mean immaturity of cerebral autoregulation.

In recent years increased attention has been devoted to evoked potentials (EP) in newborns. This paper reviews the literature and data from our research group in an attempt to assess the diagnostic and prognostic value of evoked responses in the first weeks of life and their use in different age-specific clinical conditions. The results show that EP are a very sensitive measure of the integrity of the sensory pathways. They make it possible to follow normal physiological maturation and the abnormalities of development resulting from neurological lesions. Repeated measurements of visual evoked potentials and somatosensorial evoked potential are prognostically useful in term infants, but seem much more limited in preterm newborns in predicting neurodevelopmental outcome.

The alterations in cerebral hemodynamics during and following 39 episodes with bradycardia of different severity have been studied by analysis of Doppler flow velocity waveforms amongst 16 stable preterm infants (range of conceptional age at the time of study 33-39 weeks; weight 1730-2820 g). Each episode with bradycardia has been classified as mild on seven occasions (heart rate between 100-120 beats/min), moderate on 15 occasions (80-100), or severe on 17 occasions (heart rate below 80) Depending on the severity of the bradycardia, the time-averaged mean flow velocity (V) could decrease by 80% below the preexistent baseline value and the end-diastolic velocity (D) dropped towards the zero line, whereas peak systolic velocities did not change The magnitude of the percentage decrease of V correlated positively with the severity of bradycardia, indicating a progressive decline of cerebral blood flow (CBF). Following bradycardia, V could increase up to 75% above the preexistent baseline value. Simultaneously, an increase of mean arterial blood pressure and D could be documented. Peak systolic velocities remained unaltered. The magnitude of the percentage increase of V following bradycardia depended both on the severity of bradycardia as well as on the drop in transcutaneous oxygen during the preceding bradycardia. Interpretation of these findings suggested that the transient cerebral hyperperfusion following bradycardia compensates for the hypoxic-ischemic episode, sustained during the preceding epoch of apnea and bradycardia.

The cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) reflect the cerebral oxygenation. We studied the effect of glycaemia on the TOI and FTOE, as measured by near-infrared-spectroscopy (NIRS). We continuously measured TOI, glycaemia, mean arterial blood pressure (MABP), saturation (SaO(2)) and transcutaneous carbon dioxide pressure (tPCO(2)) for at least 4 h during the first week of life in neonates with gestational age (GA)32 weeks and weight1500 g. FTOE was calculated. 24 measurements in 11 neonates were analyzed. We found a significant negative correlation (r = -0.077; p = 0.0344) between glycaemia and TOI, also after correction for MABP, SaO(2) and tPCO(2) (r = -0.118; p = 0.002) and a significant positive correlation between glycaemia and FTOE (r = 0.147; p0.000) which remained significant after correction for MABP and tPCO(2) (r = 0.116; p = 0.001). Our results indicate that in neonates during the first days of life glycaemia - even within the normal ranges and after correction for MABP, SaO(2) and tPCO(2) - influences the cerebral oxygenation.

One hundred and twenty six preterm infants, with a gestational age of 34 weeks or less, were studied to compare the predictive value of somatosensory evoked potentials (SEPs) with that of cranial ultrasound. A normal N1 latency was no guarantee of a normal outcome, nor did a persistently delayed N1 latency always correlate with a poor outcome. As a predictor of cerebral palsy, SEPs had a sensitivity of 44% and a specificity of 92%. The presence of a large haemorrhage (grade IIb/III) or cystic leukomalacia on cranial ultrasound predicted cerebral palsy with a sensitivity of 73.6% and a specificity of 83.1%. These results demonstrate that the role of SEPs recorded after median nerve stimulation is limited in preterm infants.

Prior to and 24 h following blood transfusion serial determinations of both cerebral artery flow velocity waveforms and mean arterial blood pressure have been used to reconstruct the autoregulatory curve and its upper blood pressure limit among five stable preterm infants. Prior to transfusion the autoregulatory range of cerebral blood flow (CBF) was narrow due to a relatively low-set upper blood pressure limit. At 24 h after transfusion each individual has been re-examined. Following correction of anemia both a significant reduction of CBF velocities as well as a concomitant rise of the Pulsatility Index (PI) occurred over the entire range of blood pressures indicating a reduction of CBF after transfusion. In addition a right-sided shift of the upper limit towards higher mean blood pressures occurred after transfusion and resulted in an extension of the autoregulatory plateau of CBF. These favourable effects of blood transfusion ameliorating autoregulation of brain blood flow particularly at higher blood pressures might well bear important therapeutic perspectives in our effort to prevent intracranial haemorrhage among sick preterm infants.

One full-term and three premature newborns with a unilateral thalamic haemorrhage are reported. The lesion was diagnosed using cranial ultrasonography and confirmed in three using magnetic resonance imaging. Severe perinatal asphyxia occurred in all infants. The neonatal clinical history, subsequent neuro-developmental outcome and neuroimaging findings are discussed. As the prognosis appears to be much better than for infants with bilateral thalamic densities, it is important that this type of lesion is recognised as a separate entity.

Three different neuro-imaging studies were performed in 3 infants with hemorrhagic shock and encephalopathy syndrome (HSE). Areas of cerebral infarction were noted on CT. Single photon emission computed tomography (SPECT) showed decreased perfusion in these areas in one infant. Magnetic resonance imaging (MRI) also identified the areas of infarction, noted on CT, but provided additional information showing non-haem iron deposition in the thalami and basal ganglia.

Spontaneous motor behaviour was longitudinally studied in 7 low-risk pre-term infants. The object of this study was to determine whether or not certain recognizable behavioural states exist between 32 and 36 weeks postmenstrual age (PMA), in order to have a well defined recognizable pattern of behaviour during which the pre-term infant can be clinically examined. The criteria used to define a behavioural state were: eyes open/closed; crying presentjabsent; gross body movements present/absent; and respiration regular/irregular. A total of 35 videotapes were made (total time, 99 hours and 25 minutes). For analyzing the data, one second and three-minute windows were used. Our data provide convincing evidence that spontaneous behaviour of pre-term infants of 32–36 weeks of PMA can be classified into behavioural states. The variables gross body movements and respiration, are not independent ones. The observed states can be used as a defined clinical condition during which the pre-term infants can be clinically examined Key words: Behavioural state, pre-term infants.

The cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) reflect the cerebral oxygenation. We studied the effect of glycaemia on the TOI and FTOE, as measured by near-infrared-spectroscopy (NIRS). We continuously measured TOI, glycaemia, mean arterial blood pressure (MABP), saturation (SaO2) and transcutaneous carbon dioxide pressure (tPCO2) for at least 4 h during the first week of life in neonates with gestational age (GA) < 32 weeks and weight < 1500 g. FTOE was calculated. 24 measurements in 11 neonates were analyzed. We found a significant negative correlation (r = −0.077; p = 0.0344) between glycaemia and TOI, also after correction for MABP, SaO2 and tPCO2 (r = −0.118; p = 0.002) and a significant positive correlation between glycaemia and FTOE (r = 0.147; p < 0.000) which remained significant after correction for MABP and tPCO2 (r = 0.116; p = 0.001). Our results indicate that in neonates during the first days of life glycaemia – even within the normal ranges and after correction for MABP, SaO2 and tPCO2 – influences the cerebral oxygenation.

SEPs were examined during the first weeks of life in 34 infants with mild to severe birth asphyxia, in an attempt to provide a more accurate prediction of neurodevelopmental outcome. Normal, delayed and absent responses were compared with the infant's acute clinical condition, imaging findings using different imaging techniques and neurodevelopmental outcome. All infants with normal SEPs were normal at follow-up. All but two of the infants with a delayed or absent response died or suffered from severe neurological sequelae. A delayed or absent N1 latency carried a risk for death or severe handicap of 71 and 100%, respectively, compared with 25 and 89% for moderate or severe encephalopathy on neurological assessment, and 29 and 85% for moderate or severe changes seen using different imaging techniques. SEPs may provide useful additional information when assessing the infant with birth asphyxia.

The value of magnetic resonance imaging (MRI) in lumbosacral spinal dysraphism is reviewed. Althoigh some technical problems still remain to be overcome, it is obvious tha MRI is the examination of choice for the preoperative assessment of these congenital disesses.

The effect of hydrocephalus on somatosensory evoked potentials was studied in nine infants. An increase in N1 latency was found in five infants studied longitudinally during a period of progressive ventricular dilatation. A marked decrease in N1 latency was noted in 7 infants, within one week following shunt insertion and in two infants who showed spontaneous arrest of ventricular growth. A correlation was found between cerebrospinal fluid pressure and the delay in N1 latency, but the number of infants studied is still small. SEPs appear to be a useful additional test when assessing infants with progressive ventricular dilatation. Once a baseline value for N1 has been obtained following shunt insertion, SEPs may subsequently be useful when assessing a child with possible shunt dysfunction.

External hydrocephalus was diagnosed using computed tomography in seven children presenting with macrocephaly. The value of different imaging techniques in distinguishing between subdural effusions and external hydrocephalus was investigated. High resolution ultrasonography combined with magnetic resonance imaging appeared to provide enough information to make a distinction between these two conditions. Radionuclide cisternography was still required to assess the flow pattern of the cerebrospinal fluid (CSF) which was important when placement of a lumboperitoneal shunt was considered.

To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE).Six newborn piglets were measured at 33, 35, and 37 degrees C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (S(a)O(2)) and P(a)CO(2) were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (C(a)O(2) and C(v)O(2)) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (S(a)O(2) - TOI)/S(a)O(2). The correlation was calculated with an ANCOVA test.There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between P(a)CO(2) and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and P(a)CO(2) (R = 0.24, p = 0.03).The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.

BACKGROUND: T-helper type 2 (Th2) cells play an important role in the pathogenesis of allergic diseases. Recent studies have demonstrated that allergen-specific T cells can also be found in the blood of healthy individuals. Both IL-10 and IFN-gamma might modulate the induction and maintenance of allergen-specific tolerance. AIM: To study the phenotype and functional characteristics of allergen-specific T cells in healthy non-atopic children. METHODS: Peripheral blood mononuclear cells (PBMC) from 13 symptomatic house dust mite (HDM)-allergic children and from nine matched healthy control children were stimulated with recombinant (r)Der p 2, a major allergen from HDMs. RESULTS: Stimulation with rDer p 2 resulted in Th2 cytokine production in cultures of PBMC from allergic but not from healthy children. In contrast, IL-10 and IFN-gamma were induced in PBMC cultures from both healthy and HDM-allergic children. Intracellular staining revealed that IL-10 and IFN-gamma are largely produced by the same T cells. Stimulation of T cells from healthy children with rDer p 2 also induced expression of inducible costimulator (ICOS) on a small T cell subset. CONCLUSION: Allergen-specific memory T cells from healthy non-atopic children produce IL-10 and IFN-gamma (but not Th2 cytokines) and express ICOS upon stimulation. These cells might be responsible for a normal immune balance after allergen encounter in non-atopics.

Contains fulltext : 49888.pdf (Publisher’s version ) (Closed access) BACKGROUND: Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by l-dopa responsive, diurnally fluctuating dystonia and parkinsonian symptoms. OBJECTIVE: To delineate the neurological and psychiatric phenotype in all affected individuals of three extended families. METHODS: GTP cyclohydrolase deficiency was documented by biochemical analyses, enzymatic measurements in fibroblasts, and molecular investigations. All affected individuals were examined neurologically, and psychiatric data were systematically reviewed. RESULTS: Eighteen affected patients from three families with proven GTP cyclohydrolase deficiency were identified. Eight patients presenting at less than 20 years of age had typical motor symptoms of dystonia with diurnal variation. Five family members had late-presenting mild dopa-responsive symptoms of rigidity, frequent falls, and tendonitis. Among mutation carriers older than 20 years of age, major depressive disorder, often recurrent, and obsessive-compulsive disorder were strikingly more frequent than observed in the general population. Patients responded well to medication increasing serotonergic neurotransmission and to l-dopa substitution. Sleep disorders including difficulty in sleep onset and maintenance, excessive sleepiness, and frequent disturbing nightmares were present in 55% of patients. CONCLUSION: Physicians should be aware of this expanded phenotype in affected members of families with GTP cyclohydrolase deficiency.

A study by Tsuji et al. (2000) suggests that, under certain circumstances, concordant changes in cerebral intravascular oxygenation and mean arterial blood pressure reflect impaired cerebrovascular autoregulation. In this paper, we propose a new measure to quantify this concordance, derived from the common subspace of these signals. The method is compared to correlation and coherence analysis with respect to our application, but it is also suited to other biomedical signals. Furthermore, this model-based approach is not restricted to applications involving only two signals.

textabstractObjectives: To document pain expression characteristics in former preterm infants in the first year of life in whom systematic evaluation and treatment of pain was provided. Methods: Data on the Modified Behavioral Pain Scale (MBPS), Visual Analogue Scale (VAS, crying time and heart rate were collected during immunization. The effect of clinical characteristics {postconception and gestational age [PCA], surgery, ventilation, fentanyl, length of stay (LOS)} on bio-behavioral parameters was evaluated. Results: 121 procedures were recorded in 49 infants. GA was 28 (25-32) weeks. PCA was 60 (34-90) weeks. Median MBPS was 8 (2-10), median crying time 44 (0-112) s. Median pre-procedural heart rate was 144 (103-201) and increased to 184 (147-220) afterwards, resulting in a relative increase of 29 (5-99)%. Median VAS score was 7 (1-10). Significant correlations of PCA with pre-procedural heart rate (r=-0.36) and with relative increase in heart rate (r=0.33) were identified. A correlation of LOS on crying time (r=0.37) was observed. Conclusions: Correlations of PCA with pre-procedural and relative increase in heart rate reflect the maturational decrease in heart rate. LOS had an effect on pain expression, potentially reflecting the impact of cumulative 'minor' procedural pain. Copyright

Eleven institutionalized children (7 girls, 4 boys) with refractory epilepsy received fenfluramine as add-on therapy. Besides therapy resistance, the patients manifested self-induction of seizures. Eight patients were photosensitive and/or pattern sensitive. All antiepileptic drugs of doubtful efficacy were withdrawn. During withdrawal, patients did neither improve nor show an increase in seizure frequency. Fenfluramine was then added and administered once to three times daily at dosages between 0.5 and 1 mg/kg.day. Side effects were mild and transient. Of the 11 patients, 7 became seizure-free and in 4 patients a more than 75% decrease of all seizures was obtained.