Acute disseminated encephalomyelitis: a review of 18 cases in childhood.

OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) is a treatable inflammatory demyelinating disorder seen more commonly in children than in adults. It typically presents to general paediatricians, often, like encephalitis, with non-specific cerebrospinal fluid findings. The brain computerized tomography scan is usually normal, so is falsely reassuring and delays the diagnosis, which might result in considerable morbidity. The present study was initiated to report on the various modes of presentation and raise the awareness of the diagnosis of ADEM among general paediatricians. METHODS: A retrospective review of the case notes of 18 children with a diagnosis of ADEM established in a tertiary referral centre from 1995 to 2000 was undertaken with particular reference to clinical features, investigations and treatment. RESULTS: The most common presenting features were ataxia (10 cases), followed by headache (eight cases) and weakness (five cases). Magnetic resonance imaging (MRI) of the brain was needed to confirm the diagnosis in all 18 children. Treatment usually included a course of intravenous methylprednisolone followed by a tapering dose of oral prednisolone over several weeks. Although the outcome for most of the children was generally good, two relapsed after cessation of steroids and five children had ongoing disabilities. CONCLUSIONS: The investigation of choice for establishing the diagnosis of ADEM was MRI of the brain. Other investigations were seldom helpful in reaching the diagnosis. Early diagnosis and prompt treatment of ADEM will probably reduce morbidity.

Analysis of ploidy and proliferative activity in childhood non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).

We have performed DNA analysis by means of fluorescence-activated cell cytometry on paraffin-embedded tissue from the diagnostic biopsy specimens in 40 cases of non-Hodgkin's lymphoma (NHL) and 25 of Hodgkin's disease (HD) and from 50 normal tonsils as controls. For HD cases, aneuploidy was found in 7 of 25 (28%), a higher proportion than in two previous studies of mainly adult patients. Diploid tumors showed S-phase fractions (SPFs) similar to those of controls. In the NHL cases aneuploidy was found in 12 of 40 (30%) with no significant association with site, stage, histopathology, immunophenotype, or prognosis. SPFs were highest in abdominal and chest primary sites but were not related to stage. Burkitt's lymphomas had the highest SPFs relative to lymphoblastic (P < .01) and centroblastic lymphomas (P < .05). Significantly higher SPFs were found in B cell than in T cell tumors (P < .001). There was considerable heterogeneity for SPFs within each NHL subgroup. Survival was worse at 5 years for those with high SPFs compared with those with normal SPFs (P = .04). These results suggest that tumor DNA analysis may be useful in the evaluation of children with NHL. Larger studies are needed to define its role as an independent prognostic variable.

Immunophenotypic analysis of childhood Burkitt's lymphoma in the West Midlands 1957-1986.

AIMS: To analyse the immunophenotype of a large number of non-endemic Burkitt's lymphomas to determine whether a B cell phenotype is consistently recognisable using formalin fixed, paraffin wax embedded archival material and a standard panel of commercially available antibodies. METHODS: Archival material was obtained from 30 cases of childhood Burkitt's lymphoma registered with the West Midlands Regional Children's Tumour Research Group. These were analysed by a standard avidin biotin complex immunoperoxidase method using antibodies to CD45, CD43, CD30, CD20, CD15, and immunoglobulin heavy and light chains. RESULTS: There was a high incidence of the CD45RB and CD20 immunophenotypes, with a clearly recognisable B cell lineage even in archival material. IgM was identifiable in 13 of the 23 (56.5%) cases tested. Only three of 17 (18%) cases expressed CD30. Positive membrane staining with CD45RO was observed in two (6.7%) cases. CONCLUSIONS: A B cell lineage can be identified in Burkitt's lymphoma in formalin fixed, paraffin wax embedded material, even in archival tissue. There was a low incidence of membrane staining with CD45RO which is a potential source of diagnostic confusion.

Hodgkin's disease in children in the West Midlands, 1957-1986: a large population-based study.

One hundred forty-one children were diagnosed with Hodgkin's disease between 1957 and 1986 in the West Midlands Health Authority Region (1991 population, 1.1 million children). Eighty-seven were boys and 54 were girls, representing a significant male:female ratio of 1.5:1 (P < 0.01). The average age-standardized incidence rate was 3.6 per million per year with a significant increase in the older age group (> or = 10 years) in the second half of the period (P = 0.02). The mixed cellularity subtype was more common in those younger than 10 years, with nodular sclerosing disease being seen more in those < or = 10 years. Overall survival at 5 years was 76% (65% at 10 years) with a significant difference (P < 0.001) in survival between the first and last decades. There was six second malignancies, five of which could have been treatment related. A positive history of cancer in close relatives was found in 11 patients, and higher social class was found in more older than younger children. These findings support the hypothesis that Hodgkin's disease may have a viral etiology and may be linked with socioeconomic conditions.

Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells.

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.

Changes in the postenteropathic form of the hemolytic uremic syndrome in children.

An analysis was made of clinical and laboratory findings in children with the diarrheal form of the hemolytic uremic syndrome (HUS) treated at The Children's Hospital, Birmingham between 1970 und 1987. From 1982 the rate of referral increased, the prodromal illness more often consisted of bloody diarrhea, and the mean age at presentation doubled from 2 to 4 years. For patients with a good outcome there was an excess of males in the period 1970-81, and females in the period 1982-87. Moreover, in the years 1982-87 the disorder was distinguished from that of the earlier time by a positive correlation between adverse outcome and both neutrophil leukocytosis and a higher hemoglobin concentration at presentation. Prognostic scores obtained by logistic regression analysis were specific for each period. From July 1983 stool samples were analyzed for verocytotoxin-producing Escherichia coli (VTEC) and neutralizable verotoxin. Positive results were obtained in 39% of cases. The nature of HUS has changed and the new form of the disorder is associated with VTEC infection.

The clinical significance of the glomerular location of segmental lesions in focal segmental glomerulosclerosis.

Serial sections of renal biopsies obtained from 44 nephrotic children with focal segmental glomerulosclerosis (FSGS) were reviewed in order to determine the glomerular location of segmental lesions and relate the findings to the outcome of illness. There were 23 boys and 21 girls aged 0.9-14.2 years at onset. FSGS was classified as "hilar" in biopsies containing at least one lesion contiguous with or involving the hilum, regardless of the location of other lesions, and as "peripheral" in the absence of hilar lesions. Of the 44 initial biopsies, 33 were designated hilar and 6 peripheral; the remaining 5 were unclassifiable as it was not possible to determine the location of 1-3 lesions in each biopsy. Twenty-eight of the 33 hilar biopsies also contained peripheral lesions, including paratubular (glomerular "tip") lesions in 15 instances. Paratubular lesions as the predominant abnormality were observed in only four biopsies. Repeat biopsies showed that transition occurred from one type to another, and only 4 biopsies remained with a final designation of peripheral FSGS. After a follow-up period of 1.6-24.9 years (mean 9.3), there was no significant difference in outcome between hilar and peripheral FSGS, whether diagnosed on the initial or repeat biopsy. The division into separate categories is not clearcut, and the use of this as a prognostic aid does not justify the additional cost of preparing and examining numerous serial sections.

Gangliorhabdomyosarcoma: a histopathological and immunohistochemical study of three cases.

A histopathological and immunoperoxidase study on three cases of genitourinary gangliorhabdomyosarcoma using a spectrum of conventional staining methods and antibodies against myoglobin, neuron-specific enolase and S-100 protein is presented. The results of the study have shown that differentiated myoblasts, ganglion cells and Schwann cells reacted positively with the particular antisera, but the majority of undifferentiated cells were negative. From the immunopathology results it was not possible to determine whether the undifferentiated cells were precursors of neural cells or myoblasts; the histological appearance resembled that of mesenchymal cells commonly seen in rhabdomyosarcomas. Theories concerning the origin of these tumours from neural crest ectomesenchyme or from neural crest and somitic mesenchyme are considered. Further study is needed to establish their histogenesis.