Absence of urinary opioid peptides in children with autism.

OBJECTIVE: It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present in the urine of children with autism or of control children. DESIGN: Case-control study SETTING: Cases were recruited from two tertiary referral centres specialising in autistic spectrum disorders, while controls were recruited from mainstream primary and secondary schools in the same geographical area. PARTICIPANTS: 65 boys with autism, mean age 7.4 years (range 5-11) and 158 control boys, mean age 7.8 years (range 4.2-11). INVESTIGATIONS: Urine samples were examined by high pressure liquid chromatography (HPLC) and matrix assisted laser desorbtion ionisation-time of flight mass spectrometry (MALDI-TOF MS) for the presence of a number of putative opioid peptides. OUTCOMES: There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found, MALDI-TOF established that these peaks did not, in fact, represent opioid peptides. CONCLUSIONS: Given the lack of evidence for any opioid peptiduria in children with autism, opioid peptides can neither serve as a biomedical marker for autism nor be employed to predict or monitor response to a casein- and gluten-free diet.

Evolution of a form of pure alexia without agraphia in a child sustaining occipital lobe infarction at 2 1/2 years.

The progress of cognitive visual dysfunction over an 8-year period of a child who sustained bilateral occipital-lobe infarctions at the age of 2 1/2 years is described. She survived with normal intelligence and went on to attend mainstream school. She manifested many features of cognitive visual impairment and, in particular, developed a form of pure alexia without agraphia. She achieved some letter-by-letter reading but no sight vocabulary development, including to her own name. She learned to write imaginatively employing phonetically true spelling but cannot read what she has written. Her progress and the difficulties encountered during the management of her condition are discussed in this first case report of the evolution of pure alexia without agraphia in childhood. The features of this syndrome in the developing child who has never developed the capacity to read are contrasted with that seen in affected adults.

Avoidable late diagnosis of significant sensorineural hearing loss: implications for practice.

The records for all children from a five-year birth cohort in the geographically defined area of Lothian who were referred by their health visitor to a centralized second tier audiology service after they failed their 7-9 month infant distraction hearing screen were reviewed. The sensitivities, specificities, positive predictive values and yield of this screen for the detection of significant sensorineural hearing loss > or =40 dBA requiring aiding and for a conductive loss persisting beyond one month over 30 dBA were determined. In addition, the records were studied for the same five-year birth cohort for children presenting to the centralized multidisciplinary third tier clinic with a significant sensorineural hearing loss requiring aiding, and the reasons for late diagnosis were determined. If high risk neonatal screening had been available for this population then potentially 67.5% (27 out of 40) of cases could have been identified by an appropriate age. Elimination of health visitor distraction screen false negatives for cases with loses over 60 dBA would potentially increase the case identification by the appropriate age to 45% (1 8 out of 40). Thus, there is greater scope for improving our present results with the introduction of high risk neonatal screening than by improvements in the health visitor screen.

Screening and assessment of childhood deafness: experience from a centralized multi-disciplinary service.

A paediatric hearing assessment unit was set up in Lothian in 1978 to provide a clear referral pathway for children with suspected sensorineural hearing impairment and particularly for those children detected by the health visitor screening test. Over a 6-year-period the incidence of bilateral sensorineural deafness was 1.3/1000 suggesting that all children in the region were being seen. The mean age of diagnosis fell significantly over this period. Children in high risk groups, through adverse perinatal events or a positive family history, were not detected any earlier than other children. They were therefore not contributing to this improved earlier age of diagnosis. These findings support the continuation of health visitor screening but changes in practice are needed to encourage earlier diagnosis in high-risk groups.

Childhood dysgraphia. Part 2. A study of hand function.

Sixty-six children were studied who had presented to the paediatric neurology service over a 2-year period, because they were failing to make the expected progress in mainstream school. Their parents were interviewed with a structured questionnaire and the children had a full neurodevelopmental examination which included a detailed assessment of hand function. Thirty-nine per cent of the children had a specific dysgraphia and there was a male predominance. The different populations of affected children had distinguishing characteristics. A family history of written language skill difficulties was elicited for most of the children with a developmental spelling dysgraphia, but it was uncommon in the children with an acquired spelling dysgraphia or motor dysgraphia. Slow speech development occurred frequently in developmental and acquired spelling dysgraphic children. Mixed handedness was significantly commoner in dysgraphic children who had acquired problems (P less than 0.05), whereas handedness in the developmental groups was within the expected normal distribution. Aspects of hand function such as power of hand grip did not distinguish the dysgraphic children. However, children with a spelling or motor dysgraphia had speeds of motor performance on successive finger movements and rapid hand pats outwith the normal range. These simple tests are a useful way of examining pertinent handskill difficulties in dysgraphic children.

Cerebrospinal fluid nucleotide metabolites following short febrile convulsions.

Cerebrospinal fluid (CSF) markers of cerebral energy depletion were measured in 32 infants and children following short (less than 10 minutes) febrile convulsions, and in 19 controls. Specific and sensitive indices of high-energy phosphate compound depletion (hypoxanthine, xanthine and uridine) showed no marked changes. Values for patients and febrile controls were significantly higher than for afebrile controls, which is consistent with increased cerebral metabolism in febrile patients. There were no differences in pH, lactate or creatine kinase levels in the CSF of patients and controls. The results suggest that short febrile convulsions are benign and that in the absence of risk factors for the subsequent development of epilepsy, prophylactic anticonvulsant treatment is not indicated.

Childhood dysgraphia. Part 1. An illustrated clinical classification.

In this paper we propose a clinical neurological classification of childhood dysgraphia (medical model). The subject is introduced by briefly considering the childhood learning disorders as a whole, and subsequently dysgraphia will be considered in particular with description and illustration of the different types. In our second paper we report a detailed neuropsychological study which we made of 66 children with dysgraphia. In view of the differing definitions used between professionals, this first paper is an attempt to define the terms used in our classification so that subsequent statistical analysis of individual factors in aetiology and neurology can be interpreted.

Cranial computerized tomography and cerebrospinal fluid procoagulant activity in childhood acute lymphoblastic leukemia.

Thirty-three children with acute lymphoblastic leukemia (ALL) were studied using serial cranial computerized tomography (CCT) and cerebrospinal fluid procoagulant activity (PCA) for 5 years from the time of diagnosis. PCA was also studied in control children without neurological disease and in those with a variety of neurological disorders. Temporary elevation in the CSF PCA was observed during the phase of prophylactic central nervous system treatment in ALL and there was a late rise at 2-3 years off treatment. PCA also rose in the CSF following CNS disturbance in neurologically abnormal children, which suggests that the elevation observed in ALL is not specific to myelin disturbance.

Computerized psychometry screening in long-term survivors of childhood acute lymphoblastic leukemia.

This study assessed the diagnostic utility of a computerized psychometry battery of tests: the Bexley-Maudsley Automated Psychological Screening Test and Category Sorting Test in the screening for deficits in cognitive function in a population of children who had been treated for acute lymphoblastic leukemia. Central nervous system therapy with radiotherapy and intrathecal chemotherapy has been incriminated as a cause of psychological morbidity in survivors. Twenty-nine children who were surviving in their first hematological remission, following cessation of their treatment for acute lymphoblastic leukemia, were studied. No child had evidence of central nervous system leukemic involvement, and they were all attending normal schools. Their performances were compared with 29 control children matched by age, sex, and social class. The children treated for leukemia showed a reduced ability to sustain attention (p less than 0.025), a reduction in verbal recognition short term memory (p less than 0.02), and difficulties in abstract problem solving (p less than 0.01). These results confirm the presence of neurophysical morbidity in children treated for acute lymphoblastic leukemia. It is suggested that this computerized psychometry test battery is a useful method for examining children at risk of neurological impairment and identifies specific deficits that require further evaluation and remedial help.

Specific enlargement of the fourth ventricle after ventriculo-peritoneal shunt for post-haemorrhagic hydrocephalus.

Disproportionate enlargement or isolation of the fourth ventricle are rare complications of ventriculo-peritoneal shunt for post-haemorrhagic hydrocephalus. Obvious features such as ataxia may indicate raised intracranial pressure in the posterior fossa. The child may, however, present with less specific signs of vomiting, anorexia, and lethargy and these symptoms may be misinterpreted as secondary to dilation of the lateral ventricular system due to malfunction of the ventriculo-peritoneal shunt. Two children with disproportionate enlargement of the fourth ventricle and two children with isolation of the fourth ventricle are described to illustrate the wide variations in clinical presentation. These rare complications can be diagnosed by real time ultrasound examination of the brain or computed tomography of the head. They should be considered in the differential diagnosis of a child who deteriorates after lateral ventriculo-peritoneal shunting for post-haemorrhagic hydrocephalus, and dealt with specifically to avoid the risk of upward herniation of the enlarged fourth ventricle.

The latency of the visual evoked potential as an index of myelin disturbance in children treated for acute lymphoblastic leukemia.

The phase of central nervous system prophylaxis using cranial irradiation and intrathecal chemotherapy during the treatment of childhood leukemia, may disturb myelination. It has been suggested that this disturbance may be permanent in some children. In this study we report the visual evoked potentials from flash and pattern stimuli in 29 children who were in long-term hematological remission following treatment for acute lymphoblastic leukemia, and who were attending normal schools. We compared these to 29 control children who were matched for age, sex and social class. No difference was detected in the latencies of the response, and we conclude that we could demonstrate no permanent disturbance of myelination by this technique in these long-term survivors.

Sedimentation cytomorphology of the CSF in ventriculitis.

The cytological technique of cytocentrifugation and millipore filter collection of cells allows accurate identification of cells in the CSF. This study reports the changing CSF cell-populations during 26 episodes of ventriculitis in children with shunts to control hjydrocephalus. There was a significant discordance between lymphocytes and macrophages in the CSF. Neurosurgery led to a 20 per cent increase in neutrophils on the first postoperative day, with a progressive decline to a mean of 10 cells on the fourth postoperative day. There was a small decrease in lymphocytes on the first postoperative day, followed by an increase on the second day. Macrophages were reduced by 12 per cent on the first postoperative day and then steadily increased from the second to the fourth day. A mean number of two peaks (of all cells) occurred during the treatment for ventriculitis: there was a greater number of of neutrophils in the first peak, with less lymphocytes and macrophages than in the second peak. This study supports the advantages of this technique in the diagnosis and management of ventriculitis.

Bleeding disorders and non-accidental injury.

Fifty children with suspected non-accidental injury, most of whom had bruising, were investigated to exclude a bleeding disorder. The following investigations were undertaken in each child: full blood count; platelet count, size, and shape; prothrombin time; partial thromboplastin time including mix with normal plasma; fibrinogen; and a bleeding time. The results of these initial investigations were abnormal in eight children (16%). One child had a severe coagulopathy secondary to spontaneously acquired inhibitory activity to coagulation factors which led to spontaneous bruising and noticeable signs of injury after a minor accident. The remaining children had several features supporting a diagnosis of non-accidental injury. Two had associated bleeding disorders in the form of von Willebrand's disease and a platelet aggregation abnormality and a baby had an acquired platelet disorder secondary to salicylates, provoking severe haemorrhage from a minor injury. The remaining four children initially had an abnormal laboratory finding--a prolonged partial thromboplastin time--which resulted in lengthy discussions during subsequent legal proceedings. Evidence of a bleeding disorder is not uncommon in non-accidental injury and the two conditions are not mutually exclusive.

Persisting vitamin D deficiency in the Asian adolescent.

A study of 221 children admitted to hospital in the course of a year allowed establishment of a reference range for plasma 25-hydroxyvitamin D. None of these children had evidence of biochemical rickets. Most Asian children, however, were vitamin D deficient in comparison, and this deficiency was most noticeable in girls aged 13 to 15 years: biochemical rickets occurred in six per cent of these adolescent Asians. If vitamin D requirements are not met during the physiological growth spurt, permanent pelvic deformity may result. Vitamin D deficiency persisting into pregnancy will adversely affect the infant, producing an increased risk of hypocalcaemic fits, dental enamel hypoplasia, infantile rickets, and reduced postnatal growth. Our data support the need for vitamin D supplementation, and we suggest that annual oral vitamin D supplements in the autumn would alleviate the problem.

Deletion of the long arm of chromosome 11 [46,XX,del(11)(q24.1--qter)].

A child who presented at three months of age with pyloric stenosis and pancytopenia was found to have a partial deletion of the long arm of chromosome 11, del(11)(q24.1----qter). Only two previous cases have been described with an apparently identical chromosomal deletion, and both exhibit similar phenotypic features. Other patients with larger deletions of the distal region of the long arm of chromosome 11 show many features in common with these three cases. It is suggested that the region of the long arm of chromosome 11 from band q24.1 to qter may contain the genetic material responsible for the expression of the 11q - phenotype.