The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes.

In autoimmune Type 1 diabetes (T1D), immune cells progressively infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, it is unclear how this process, called 'insulitis', develops and progresses within this organ. Here, using highly multiplexed CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples from pre-T1D, T1D, and non-T1D donors, we examine pseudotemporal-spatial patterns of insulitis and exocrine inflammation within large pancreatic tissue sections. We identify four sub-states of insulitis characterized by CD8 + T cells at different stages of activation. We further find that exocrine compartments of pancreatic lobules affected by insulitis have distinct cellularity, suggesting that extra-islet factors may make particular lobules permissive to disease. Finally, we identify "staging areas" - immature tertiary lymphoid structures away from islets where CD8 + T cells appear to assemble before they navigate to islets. Together, these data implicate the extra-islet pancreas in autoimmune insulitis, greatly expanding the boundaries of T1D pathogenesis.

An unusual presentation of paediatric Listeria meningitis with selective spinal grey matter involvement and acute demyelinating polyneuropathy.

BACKGROUND: Paediatric Listeria meningitis is rare, especially in immuno-competent children, but associated with significant mortality and morbidity and frequent complications. METHODS: We report an unusual case of Listeria meningitis in a previously healthy 35 month-old girl with selective spinal grey matter involvement and demyelination in neurophysiological studies. Despite adequate antibiotic treatment, the case was initially complicated by ventriculitis, hydrocephalus and tonsillar herniation through the foramen magnum, requiring external ventricular drainage and subsequent ventriculoperitoneal shunt insertion. Paucity of movements, hypotonia, areflexia and bladder dysfunction then became evident. RESULTS: Electromyogram and nerve conduction studies showed acute inflammatory demyelinating polyneuropathy and the patient received intravenous immunoglobulin followed by corticosteroids. MRI scans with contrast revealed extensive whole cord selective grey matter signal changes. She required extensive neurorehabilitation, making gradual (but incomplete) recovery. CONCLUSION: Spinal cord involvement is rare in neuro-listeriosis and there no previous paediatric reports of Listeria-related myelitis or demyelinating polyneuropathy. The mechanism behind these presentations is unclear but an auto-immune response to the infection might be considered.

Management and outcome of vein of Galen malformation.

OBJECTIVE: To describe our experience of treating children with vein of Galen aneurysmal malformation (VGM) in a single UK centre between 2003 and 2008. METHOD: Retrospective review of case notes and neuroimaging. RESULTS: 33 children were seen (26 neonates, seven infants), of whom 28 underwent endovascular treatment. Four were not offered treatment as they had evidence of severe diffuse brain injury at presentation; treatment was deferred in another who subsequently died. Seven children died (two of whom had endovascular treatment). Of the survivors (all treated), 13 (39%) are neurodevelopmentally intact, seven (21%) have mild neurodevelopmental impairment and the remaining six (18%) have significant neurological impairment. The authors were not able to identify clinical or radiological parameters which strongly predicted outcome. Of note, two children with initially low Bicêtre scores were neurologically intact after successful embolisation. CONCLUSION: The outlook for children with VGM is significantly better since the advent of endovascular treatment. Decisions about the appropriateness and timing of treatment should be taken by an experienced multidisciplinary team.

Two unusual clinical and radiological presentations of biotinidase deficiency.

Biotinidase deficiency is due to a defect in recycling of biotin and is a treatable autosomal recessive inherited disorder. We describe two cases with unusual presenting symptoms and rarely described MRI findings. We propose that the diagnosis of biotinidase deficiency should be considered when there are symmetrical MRI changes in the medial thalamus, dorsal brainstem, medulla and spinal cord as in our two cases. As long as there isn't newborn screening for biotinidase deficiency in the UK; increased awareness of this disorder and recognition of biotinidase deficiency as a cause of bilateral symmetrical MRI patterns similar to our patients, would facilitate early diagnosis and prevent many of the devastating neurological sequelae associated with missing the condition.

Serum amino acids and genesis of protein energy malnutrition.

Twenty four patients of classical marasmus and kwashiorkor along with equal number of healthy controls were selected for the study. Their serum amino acid patterns analysis revealed a mean ratio of glutamate to alanine in fasting samples of normal individuals to be 0.33, while it as 9.3 in kwashiorkor and 1.6 in marasmus. This differences in controls, kwashiorkor and marasmus was statistically significant. This observation may explain evolution of marasmus and kwashiorkor in children with similar diets. On the basis of the present observation it is postulated that in kwashiorkor, the conversion of pyruvate to alanine in presence of glutamate, an aminogroup donor does not proceed normally, resulting in accumulation of glutamate and low alanine. Thus the development of marasmus and kwashiorkor may not be related to dietary inadequacy alone but also to the transaminase function. This could be genetic in origin.

Prevalence of skin and other cancers in patients with psoriasis.

The prevalence of skin and internal malignancies was estimated from the general practitioners' notes of 2247 patients with psoriasis and 4494 age- and sex-matched controls. The prevalence of skin cancer in the psoriatics was 155% that of controls, but this was not significant at the 5% level. Subgroup analysis showed an increase in skin cancers in women (P < 0.05). There was no difference in the age of onset of skin cancers between psoriatics and controls and there was no evidence of a cumulative therapeutic risk. There was no difference in the prevalence of non-skin cancers between psoriatics and controls.

Development and evaluation of a diagnostic algorithm for depression in childhood.

This paper describes the development and validation of a brief questionnaire intended for the rapid assessment of depression in childhood. It is primarily a clinical interview but there is an associated algorithm for the diagnosis of a syndrome of depression. It can equally be used for the clinical diagnosis of a depressive disorder. The current battery includes features representative both of "depressive cognitions" and "endogenous depression". However, it is less effective in the identification of a syndrome of endogenous depression than depressive cognitions.

AIDS: education and adults with a mental handicap.

At present, there is a lot of concern about the acquired immune deficiency syndrome (AIDS). Efforts are being made to educate the public about AIDS, so that individuals can take precautions against acquiring or transmitting the disease. Many people with a mental handicap may not benefit from the current education campaign because of limitations in their general understanding and poor or non-existent reading skills. Two cases are presented to illustrate the difficulties encountered in educating people with a mental handicap about AIDS.

Diagnosing childhood depression who should be interviewed--parent or child? The Newcastle Child Depression Project.

The extent of the similarities and discrepancies in the reporting of depressive symptomatology by children and their mothers was examined. Child-parent agreement was not always impressive, particularly for more subjective symptoms. It is suggested that direct psychiatric assessment of children provides a more accurate picture of their mental state regardless of presenting disorder, but particularly where depression is suspected.

Reliability and validity of two self-rating scales in the assessment of childhood depression.

A comparison was made of the reliability and validity of two self-rating scales, the Children's Depression Inventory (CDI) and Depression Self-Rating Scale (DSRS), in the diagnosis of depression in 93 children (aged 8-16 years) attending a university child psychiatry department. The two scales were of comparable merit but had only moderate discrimination between depressed and non-depressed children, with each scale having a misclassification rate of 25%. Better agreement was obtained in more verbally intelligent children, irrespective of age. Girls scored higher on the instruments than boys. No significant relationship was found between teacher assessment of classroom behaviour and the two self-rating depression instruments.

The context of childhood depression. The Newcastle Childhood Depression Project.

This paper examines the family background, premorbid personality traits and adverse life events preceding childhood depression. The non-depressed group proved more likely to have experienced pre-school bereavement and familial disturbance, and to come from the more deprived background; there was also an excess of premorbid anxiety and hysterical personality traits in this group. School phobia and premorbid obsessional traits were associated with the depressed group. Although there was an association between depression and the total number of adverse life events, this was more substantial when the perceived impact of the events was taken into account. Of the individual classes of life event, only illness and a change in social relationships were associated specifically with depression.

The dexamethasone suppression test in children: lack of an association with diagnosis.

The dexamethasone suppression test was carried out on 44 children to assess agreement with diagnosis of depression. No significant association was found between suppression of plasma cortisol and depression diagnosed clinically or by cluster analysis.

The Newcastle Child Depression Project. Diagnosis and classification of depression.

A total of 275 successive referrals to a university child psychiatry unit out-patient department were examined using the Child Depression Inventory. Of these, 95 children were examined further by a structured clinical interview, and the relationship between different instruments for the assessment of depression in childhood was investigated. Just over one-third of the children (35%) had significant depression, and it was found that depression may be missed unless children with other psychiatric diagnoses are examined closely. Multivariate analyses of the clinical data provided factorial validation of diagnoses when employing different clinical diagnostic schemas.

Nocturnal faecal soiling and anal masturbation.

Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied. The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted. We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised.

Classification and diagnosis of depression in school phobia.

Fifty-one school phobic children, aged nine to fourteen years, were assessed for psychiatric diagnosis; this revealed the presence of two clinically meaningful sub-groups--depressed and residual school phobic. A wide range of symptoms were studied to identify those which might prove useful in diagnosing adult-type depression in childhood and early adolescence, both in terms of frequency of symptoms in the depressed group and the extent of the distinction between the two groups. Eleven such key symptoms were identified and based on these, a formula for diagnosing adult-type depression was evolved. The validity of several different ways of classifying the above cases were explored; these covered: kind of disorder; type of onset; adolescence versus pre-adolescence; and sex of the child. However, on only one dichotomy--depression versus absence of depression--were there many significant discriminants. Affective symptomatology of more recent onset was contrasted with pre-morbid personality traits, usually associated with school phobia. There was no evidence to support the concept of 'masked depression' in childhood.