Uricolytic enzymes in liver of the Dipnoan Protopterus aethiopicus.

The enzymes uricase, allantoinase, and allantoicase have been measured in liver preparations of the African lungfish Protopterus aethiopicus. The levels for these enzymes in lungfish liver suggest that the amount of urea formed in vivo in Protopterus via a uricolytic pathway may be greater than that derived via the Ornithine-urea cycle. The operation of a "purine cycle" in lungfish liver is proposed.

Fetal nutrition and peripheral nerve conduction velocity.

Fetal nutrition as assessed by skin-fold thickness was correlated with nerve conduction in 27 babies of 39 to 41 weeks' gestation. There was correlation between skin-fold thickness and conduction velocity, suggesting that fetal nutrition may alter peripheral nerve function by influencing myelination.

Vagal nerve stimulation in epileptic encephalopathies.

OBJECTIVE: To study the effect of vagal nerve stimulation (VNS) in children with epileptic encephalopathies. METHODS AND MATERIALS: All children receiving VNS during a 2-year period at our center were studied prospectively for changes in seizure frequency, electroencephalogram (EEG), adaptive behavior, quality of life, and where appropriate, verbal/nonverbal performance. Assessments were made before and for at least 1 year after implant. RESULTS: Sixteen children were studied. One device was removed because of infection. Of the remaining 15 children, 4 had a >50% reduction and 2 had a >50% increase in seizure frequency at 1 year after implant. Median reduction in seizure frequency was 17%. There was no trend toward improvement of the EEG or adaptive behavior. Quality of life was unchanged in most areas, except in perceived treatment side effects and general behavior that were improved. In 6 children undergoing further assessment, there was a significant improvement in verbal performance; this did not correlate with reduction in seizure frequency. CONCLUSION: VNS did not significantly improve seizure frequency, severity, adaptive behavior, or the EEG during the first year of treatment for the group as a whole, although 4 children (27%) had a worthwhile reduction in seizure frequency. There were significant improvements in perceived treatment side effects and general behavior.

Visual and semiquantitative analysis of cortical FDG-PET scans in childhood epileptic encephalopathies.

UNLABELLED: The optimal method for analyzing PET scans in children being considered for epilepsy surgery is unresolved: Fully quantified methods are invasive, and the required controls are generally unavailable. We sought to compare visual inspection with semiquantitative analysis for the detection of cortical metabolic defects. METHODS: Thirty-two children with cryptogenic epileptic encephalopathies were studied prospectively with 18F-fluorodeoxyglucose (FDG) PET. Visual inspection was performed on separate occasions by independent observers. Four-millimeter circular regions of interest were used to sample radiotracer uptake in selected cortical regions. Asymmetry between homologous regions were calculated to detect focal abnormalities. Bilateral and diffuse abnormalities were assessed by comparing the ratio of cortical-to-cerebellar uptake in patients with historical age-matched controls. The sensitivity and specificity of visual inspection was compared with that of semiquantitative analysis for the detection of focal, bilateral and diffuse cortical metabolic abnormalities. RESULTS: Visual inspection revealed full inter-rater agreement for the presence of major focal abnormalities. The sensitivity and specificity for visual inspection compared to semiquantitative analysis were 77% and 92%, respectively, with semiquantitative analysis often revealing abnormalities to be more extensive than had been suspected visually. Compared with semiquantitative analysis, visual inspection had a low sensitivity but high specificity for the detection of bilateral and diffuse hypometabolism. CONCLUSION: Semiquantitative analysis gives clinically useful information additional to that obtained from visual inspection.

Control of adrenocorticotrophin secretion by catecholamines in the pregnant and foetal sheep.

The effect of adrenaline on the maternal and foetal plasma ACTH concentration of twelve pregnant sheep with chronically implanted vascular catheters has been studied. Adrenaline infused into the jugular vein of the ewe or foetus produced carotid arterial adrenaline concentrations of 1-9 ng/ml. The foetal plasma ACTH was 253 +/- 73 pg/ml and it showed a fivefold increase during adrenaline infusion; the ACTH concentration achieved was proportional to the plasma adrenaline. In the ewe plasma ACTH was 99 +/- 23 pg/ml. During adrenaline infusion to the ewe this rose by an amount dependent on the adrenaline concentration achieved and there was also a rise in foetal plasma ACTH but no consistent change in foetal plasma adrenaline. There was no reproducible change in plasma corticosteroid concentration during adrenaline infusion into the foetus but a rise in maternal plasma corticosteroid concentration during infusion into the ewes. Because the adrenaline concentrations achieved during the infusions were within the physiological range, the results indicate that circulating catecholamines may directly or indirectly influence the concentration of ACTH in the circulation. Also, physiological rises in plasma catecholamines in pregnant animals may stimulate the release of ACTH from the foetal pituitary.

Plasma amino acids in childhood epileptic encephalopathies.

Abnormalities in plasma amino acid levels have been noted in patients with various epilepsies, and sometimes also in their first degree relatives. We sought to study plasma amino acid levels in children with epileptic encephalopathies and their parents, relating findings to the pattern of cortical glucose metabolism as determined by 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty-eight children with cryptogenic epileptic encephalopathies were studied prospectively. Cortical glucose metabolism was evaluated by FDG PET with combined visual and semiquantitative analysis used to detect focal cortical defects. The plasma concentration of 21 amino acids in the children and their parents was measured by ion exchange chromatography and compared with control values using non-parametric statistical methods. Multivariate analysis was used to assess antiepileptic drug effects. Children were classified as: Lennox-Gastaut syndrome following infantile spasms (six patients); de-novo Lennox-Gastaut syndrome (eight); severe myoclonic epilepsy in infancy (eight) and myoclonic-astatic epilepsy (two). Four patients remained unclassified. Fourteen patients had focal/multifocal abnormalities on PET scans. The plasma level of aspartate was significantly lower in both the children with epileptic encephalopathies and in their parents (P < 0.005). The lowered aspartate levels could not be accounted for by the antiepileptic drug medication taken by the children. Further analysis showed the lowered aspartate levels to be confined to children and their parents who lacked focal PET abnormalities. These findings suggest a possible genetic abnormality in the aspartate neurotransmitter systems in the pathogenesis of seizures in the childhood epileptic encephalopathies.

Positron emission tomography in imaging spinal cord tumors.

The ability of positron emission tomography (PET) to detect spinal cord tumors was studied prospectively in 14 patients presenting over a 5-year period. Abnormal uptake by [18F]-fluorodeoxyglucose (FDG) or 11C-methionine was detected in all except one. These data were assessed in relation to magnetic resonance imaging (MRI) findings with regard to tumor type and extent preoperatively, findings at operation, and subsequent clinical course. The group consisted of six astrocytomas, five ependymomas, one mixed ependymoma and astrocytoma, one schwannoma, and one ganglioglioma, all confirmed histologically. This is the largest study comparing spinal PET to MRI. Accurate preoperative correlation between PET and MRI was found in all eight patients scanned at first presentation. The PET uptake was in keeping with the low-grade histology of the tumors. Postoperatively, PET and MRI findings were in agreement in nine patients. In eight of these the findings were in keeping with the subsequent clinical course. In three patients, however, the PET findings were at variance with the clinical course and MRI findings. In one, persistent FDG uptake after radiotherapy was seen where there was subsequent tumor resolution. In two patients with low-grade astrocytomas, scanned with FDG and 11C-methionine, respectively, tracer was not taken up by residual tumor. In this small group of patients, PET did not provide additional useful information. This could be because all tumors studied were low grade and the limited spatial resolution of PET does not lend itself to imaging small spinal cord tumors. The prospective study of larger numbers of patients with a wider range of tumor types is required, but this might be difficult to achieve given the rarity of spinal cord tumors.

Late fetal pontine destruction.

A child with an absent pons is described who died 8 weeks after birth. At postmortem examination, the defect was consistent with a vascular event in the last trimester.

Lower limb extensor moments in children with spastic diplegic cerebral palsy.

In this retrospective study, we quantified the mean extensor moment at the ankle, knee and hip over the stance period in a group of independently ambulant children with spastic diplegia (n = 90; 167 limbs) and in a group of normally-developing (ND) children (n = 22; 22 limbs). The mean knee extensor moment and the mean support moment demonstrated greater variance in children with diplegia than in normally-developing children (P < 0.0001 and P < 0.001). This was explained by a strong relationship between the mean knee extensor moment and minimum knee flexion in stance (r2 = 0.615; P < 0.0001) in the affected group with a positive mean knee extensor moment for all those children who walked in greater than 20 degrees of knee flexion. We also found a linear relationship between the support moment and knee flexion (r2 = 0.805; P < 0.0001). Our data supported the biomechanical analysis of Hof [Gait Posture, 12 (2000) 196] who suggested that his modified support moment should be a linear function with eccentricity at the knee. Extensor moments at the ankle (r2 = 0.001376; P = 0.641) and hip (r2 = 0.0860; P = 0.000168) bore weak relationships with increasing knee flexion even though there was a strong positive relationship between minimum knee flexion and minimum hip flexion (r2 = 0.316; P < 0.0001). We conclude that children with spastic diplegic cerebral palsy (SDCP) who walk with a crouch gait rely on their knee extensors to prevent collapse of the lower limbs. Intervention directed at redistributing extensor moments between the joints of the lower limbs may slow the increase in knee flexion and prolong reasonable walking function in this group.

Accurate measurement of muscle belly length in the motion analysis laboratory: potential for the assessment of contracture.

Two-dimensional ultrasound imaging was combined with motion analysis technology to measure distances between remote anatomical landmarks. The length of the belly of the medial gastrocnemius muscle in five normal adults (nine limbs) was estimated using this technique. Our results in vivo were similar to the reported data for the lengths of muscles in cadavers, and were consistent with the expected relationship between muscle belly length and ankle joint angle. Experiments in vitro demonstrated that the accuracy of the device was better than 2 mm over 20 cm. Measurements on the same subject on different occasions showed that the results were repeatable in vivo. Rendering of the reconstructed volume of a foam phantom gave results comparable to photographic images. This validated technique could be used to measure muscle lengths in children with spastic cerebral palsy and indicate which muscles had fixed shortening, and to what extent.

Conductive education at the Petö Institute, Budapest.

Conductive education, which was developed at the Petö Institute in Budapest, has been publicised incorrectly as a method of treatment for children with cerebral palsy. From the results of information given and our own observations during a week's visit to the institute we conclude that a minority of carefully selected children with cerebral palsy and spina bifida, who have a relatively good prognosis, are educated at the institute; the education is carried out with appropriate medical, surgical, and orthotic intervention; and the children probably function better as a result of the intensive programme than do similar children in Britain in areas where therapy is scarce. They seem to achieve, however, what we would expect similar children in Britain to do when facilities are adequate. Though our findings do not therefore justify using public funds to refer children to the institute, some (self selected) families benefit from a visit, particularly from the positive attitudes of the staff. The role of the conductor and the integration of programmes into a classroom setting have much to recommend them, and conductive education, if successfully transferred to Britain, might be beneficial to a wider range of children than in Hungary.

Effect of lamotrigine on cognition in children with epilepsy.

BACKGROUND: Lamotrigine does not affect cognition in healthy adult volunteers or adult patients with epilepsy, but its effect on cognition in children is uncertain. OBJECTIVE: To compare the effect of lamotrigine and placebo on cognition in children with well-controlled or mild epilepsy. METHOD: In a double-blind, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment phase was 9 weeks, the crossover period 5 weeks. A neuropsychological test battery was performed during EEG monitoring at baseline and at the end of placebo and drug phases. The paired Student' t test was used for statistical analysis for neuropsychological data (two tailed) with a p value of 0.01 considered significant. Carryover and period effect were analyzed with generalized linear modeling (SPSS 10). RESULTS: Forty-eight children completed the study. Seizure frequency was similar during both treatment phases. No significant difference was found in continuous performance, binary choice reaction time, verbal and nonverbal recognition, computerized visual searching task, verbal and spatial delayed recognition, and verbal and nonverbal working memory between placebo and lamotrigine treatment phase. There was no significant carryover and period effect when corrected for randomization. CONCLUSION: Lamotrigine exhibits no clinically significant cognitive effects in adjunctive therapy for children with epilepsy.

The impact of PET scanning on management of paediatric oncology patients.

PURPOSE: Limited information is available on the use of positron emission tomography (PET) in paediatric oncology. The aim of this study was to review the impact of PET on the management of paediatric patients scanned over a 10-year period. METHODS: One hundred and sixty-five consecutive oncology patients aged 11 months to 17 years were included. Two hundred and thirty-seven scans were performed. Diagnoses included lymphoma (60 patients), central nervous system (CNS) tumour (59), sarcoma (19), plexiform neurofibroma with suspected malignant change (13) and other tumours (14). A questionnaire was sent to the referring clinician to determine whether the PET scan had altered management and whether overall the PET scan was thought to be helpful. RESULTS: One hundred and eighty-nine (80%) questionnaires for 126 patients were returned (63 relating to lymphoma, 62 to CNS tumours, 30 to sarcoma, 16 to plexiform neurofibroma and 18 to other tumours). PET changed disease management in 46 (24%) cases and was helpful in 141 (75%) cases. PET findings were verified by histology, clinical follow-up or other investigations in 141 cases (75%). The returned questionnaires indicated that PET had led to a management change in 20 (32%) lymphoma cases, nine (15%) CNS tumours, four (13%) sarcomas, nine (56%) plexiform neurofibromas and four (22%) cases of other tumours. PET was thought to be helpful in 47 (75%) lymphoma cases, 48 (77%) CNS tumours, 24 (80%) sarcomas, 11 (69%) neurofibromas and 11 (61%) cases of other tumours. PET findings were verified in 44 (70%) lymphoma cases, 53 (85%) CNS tumours, 21 (70%) sarcomas, 12 (75%) neurofibromas and 11 (61%) other tumour cases. CONCLUSION: PET imaging of children with cancer is accurate and practical. PET alters management and is deemed helpful (with or without management change) in a significant number of patients, and the results are comparable with the figures published for the adult oncology population.

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections.

BACKGROUND: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. OBJECTIVE: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. METHODS: CSF from patients with was tested for human herpesviruses types 1-6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. RESULTS: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3-14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. CONCLUSIONS: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Familial schizencephaly.

Familial cases of schizencephaly hitherto have been associated with readily diagnosable metabolic conditions or malformation syndromes. Where such associations are absent, it is usually considered to be a sporadic event without a genetic contribution. Described here are a brother and sister with identical bilateral symmetrical schizencephaly. Genetic counselling must therefore allow for the possibility of an autosomal recessive form of this condition.

Tetraethyl lead poisoning from gasoline sniffing.

In two cases of organic lead poisoning due to habitual gasoline sniffing, one patient had temporary hypomania and recovered with treatment, while the other patient (who died) had signs of severe CNS and peripheral nervous system, muscle, hepatic, and renal damage. In addition he had features of long-term inorganic lead poisoning. This and the response of both cases to chelating agents suggest that organic lead is degraded in vivo to inorganic lead.

White matter attenuation and megalencephaly.

The computed tomogram of a 6 month old girl with familial megalencephaly showed widespread attenuation throughout the white matter. She continued to be developmentally and neurologically normal. Her scan at age 3 years was normal apart from the megalencephaly. A tentative explanation for this unusual series of events is offered.

Arthrogryposis multiplex congenita; feeding, language and other health problems.

A survey of the health problems of 87 individuals with arthrogryposis multiplex congenita revealed a high proportion (51) with major feeding difficulties in infancy. This was generally related to structural abnormalities of the jaw and tongue. Children thus involved were more prone to recurrent chest infections, constipation, and poor growth and weight gain. In addition, there was a strong association between initial feeding difficulties and subsequent language problems. Early identification of a sub-group of children with arthrogryposis multiplex congenita is therefore possible who may require continuing therapy from a number of disciplines.

Ventilator dependency in the United Kingdom.

There are 24 children who are currently long term ventilator dependent in the UK. Nine of these are cared for entirely at home. An additional 11 children have been long term ventilator dependent since March 1983. The prevalence of these children appears to be increasing. The financial and manpower resources needed for these children whether at home or in hospital is considerable. There are reasons to suppose that the apparent increase in prevalence will continue.