R.A. Mullaart

Familial lissencephaly with extreme neopallial hypoplasia.

Two siblings, male and female, with identical lethal brain malformation are described. Their anomaly is characterized by very low brain weight, lissencephaly, wide ventricles and thin neopallium (colpocephaly) varying in thickness between 0.2 and 3 mm. The neocortex is four layered as in classic lissencephaly. Brainstem and cerebellar anomalies are more extensive than in cases hitherto described in detail. No extracranial malformation is found. The parental karyotypes are normal. The relationship to previously reported familial cases of lissencephaly and several inherited syndromes featuring lissencephaly is discussed. The present family may represent a severe expression of previously described autosomal recessive lissencephaly without extracranial anomaly or may represent a new genetic lissencephaly syndrome.

p.[G576S; E689K]: pathogenic combination or polymorphism in Pompe disease?

We discuss four cases of acid α-glucosidase deficiency (EC, 3.2.1.3/20) without evident symptoms of Pompe disease (OMIM No 232300) in individuals of Asian descent. In three cases, the deficiency was associated with homozygosity for the sequence variant c.[1726G>A; 2065G>A] in the acid α-glucosidase gene (GAA) translating into p.[G576S; E689K]. One of these cases was a patient with profound muscular atrophy, another had cardio-myopathy and the third had no symptoms. The fourth case, the mother of a child with Pompe disease, was compound heterozygote for the GAA sequence variants c.[1726G>A; 2065G>A]/c.2338G>A (p.W746X) and had no symptoms either. Further investigations revealed that c.[1726A; 2065A] is a common GAA allele in the Japanese and Chinese populations. Our limited study predicts that approximately 4% of individuals in these populations are homozygote c.[1726A; 2065A]. The height of this figure in contrast to the rarity of Pompe disease in Asian populations and the clinical history of the cases described in this paper virtually exclude that homozygosity for c.[1726A; 2065A] causes Pompe disease. As c.[1726A; 2065A] homozygotes have been observed with similarly low acid α-glucosidase activity as some patients with Pompe disease, we caution they may present as false positives in newborn screening programs especially in Asian populations.

Cerebral blood flow velocity and pulsation in neonatal respiratory distress syndrome and periventricular hemorrhage

The present study addressed the hypotheses that cerebral ischemia and/or excessive cerebral blood pulsation contribute to periventricular hemorrhage in preterm newborns with respiratory distress and that the pulse width is a valuable tool to estimate the contribution of cerebral blood pulsation. These hypotheses were tested by following preterm newborns at risk for respiratory distress and periventricular hemorrhage. We monitored for cerebral blood flow velocity (CBFV), cerebral pulse width, and cerebral pulsatility index; for patent ductus arteriosus, capillary Pco2, heart rate (HR) and behavior; and for the occurrence of respiratory distress and periventricular hemorrhage (PVH). The data obtained were analyzed with linear regression with the mode of respiration (spontaneous or supported) and postnatal age as additional covariates. We observed that (a) respiratory distress, either uncomplicated or complicated by PVH, correlates with a low CBFV and a high cerebral pulsatility index; (b) PVH also correlates with a high cerebral pulse width; (c) the increased pulse width precedes the onset of the hemorrhage; and (d) these CBF alterations can be partly attributed to ductal shunting and are ameliorated by mechanical ventilation.

Ultrasound detection of congenital Arteriovenous aneurysm of the great cerebral vein of Galen

Using combined echoencephalography and Doppler flow determination the diagnosis Arteriovenous aneurysm of the great cerebral vein of Galen could be made in two infants. Without vascular surgery one patient died, the other recovered completely. CT scanning confirmed the diagnosis. Invasive methods such as cerebral angiography were avoided.Case histories, neuropathological findings, ultrasound method and results are presented. Pathogenesis, clinical signs, treatment and prognosis are discussed. With the ultrasound method presented, the nature and location of the vascular anomaly were demonstrable, thus additional higher risk diagnostic methods could be avoided or planned more purposefully.

Ultrasonographic assessment of congestion of the choroid plexus in relation to carbon dioxide pressure

Routine cerebral ultrasound examinations of the neonatal brain often show the choroid plexus to be enlarged, without revealing any other structural pathology. This enlargement might be due to congestion of the choroid plexus as a result of increased cerebral blood flow, due to increased partial pressure of carbon dioxide, amongst other factors. In this exploratory study, 76 cerebral ultrasound examinations, performed on 42 newborn infants within the first 10 days after birth, were analysed retrospectively. The ultrasonograms were classified into three diagnostic groups: normal, congestion of the choroid plexus and haemorrhage. The relationship between the diagnostic groups and the estimated mean arterial partial pressure of carbon dioxide (P(a)CO(2)) was investigated. In the first three postnatal days, the estimated mean P(a)CO(2) in the normal group was significantly lower than in the congestion group (P<0.001). No significant differences were found between the P(a)CO(2) in the congestion and the haemorrhage groups. The findings might support a relation between a high P(a)CO(2) and congestion of the choroid plexus in the first three postnatal days and might be a sign of increased risk for a periventricular haemorrhage.

Influence of end expiratory pressure on cerebral blood flow in preterm infants

The effect of interruption of positive and expiratory pressure (PEEP) on cerebral blood flow velocity (CBFV) and CBF fluctuation (CBFF) in the internal carotid arteries and on heart rate, restlessness and wakefulness has been studied in 17 mechanically ventilated neonates with RDS. A decrease in CBFV was found, but no significant change in CBFF. Multiple regression analysis showed that the decrease in CBFV is less pronounced if the PEEP interruption is accompanied by restlessness. It further appeared that the decrease in CBFV is more pronounced if CBFV is high, the ductus arteriosus is patent, or RDS follows a complicated course. These findings indicate that PEEP supports CBF, probably by a decrease in ductal stealing from the brain. Therewith PEEP protects against cerebral hypoperfusion which is one of the major risks in RDS and immaturity. Furthermore, our findings suggest that the decrease in CBF during PEEP interruption is moderated by restlessness and accentuated by brain damage.

Contribution of the Corticospinal Tract to Motor Impairment in Spina Bifida

We aimed to disentangle the proportional contributions of upper and lower motor neuron dysfunction to motor impairment in children with spina bifida. We enrolled 42 children (mean age, 11.2 years; standard deviation, 2.8 years) with spina bifida and 36 control children (mean age, 11.4 years; standard deviation, 2.6 years). Motor impairment was graded to severity scales in children with spina bifida. We recorded motor evoked potentials after transcranial and lumbosacral magnetic stimulation and compound muscle action potentials after electric nerve stimulation. Regarding lower motor neuron function, severely impaired children with spina bifida demonstrated smaller compound muscle action potential areas and lumbosacral motor evoked potential areas than control children; mildly impaired children hardly differed from control children. Compound muscle action potential latencies and lumbosacral motor evoked potential latencies did not differ between children with spina bifida and control children. Regarding upper motor neuron function, children with spina bifida demonstrated smaller transcranial motor evoked potential areas and longer central motor conduction times than control children. The smallest motor evoked potential areas and longest central motor conduction times were observed in severely impaired children. In children with spina bifida, the contribution of upper motor neuron dysfunction to motor impairment is more considerable than expected from clinical neurologic examination.

Determinants of the cerebral blood flow velocity in healthy preterm newborns

Abstract Objective: This study was meant to obtain insight in the inter- and intra-individual range of neonatal cerebral blood flow velocity and the factors which determine this range. Methods: The blood flow velocity in the internal carotid artery was followed during 5 days in fourteen healthy, appropriate for date preterm newborns, using Doppler ultrasound. Results: It was found that cerebral blood flow velocity varies more between than within the infants, and that this is partially attributable to an inverse relation between cerebral blood flow velocity and weight-for-gestational-age, and a positive relation between cerebral blood flow velocity and postnatal age. The relation with postnatal age could be explained in part by closure of the ductus arteriosus. The effects of weight-for-gestational-age and patent ductus arteriosus were greater for end-diastolic than for peak-systolic velocity. Postnatal age showed an opposite effect. Conclusion: Thus, weight-for-gestational-age, postnatal age and patent ductus arteriosus contribute to the inter-and intra-individual variation of cerebral blood flow velocity.