Annette Kingma

MAGNETIC-RESONANCE-IMAGING OF THE BRAIN AND NEUROPSYCHOLOGICAL EVALUATION IN CHILDREN TREATED FOR ACUTE LYMPHOBLASTIC-LEUKEMIA AT A YOUNG AGE

PURPOSE To evaluate the adverse late effects of ALL treatment on cognitive functions and brain morphology; to integrate the results of a neuropsychological and neuroradiological study. PATIENTS AND METHODS Cranial magnetic resonance imaging (MRI) and neuropsychological assessments (NA) were performed in 35 children treated for acute lymphoblastic leukemia (ALL) with cranial irradiation (CI) and intrathecal and intravenous methotrexate. Patients were under the age of 7 years (MD: 3.5 years) at diagnosis; median follow-up at MRI and NA was 8 years since diagnosis. RESULTS MRIs were classified as definitely abnormal in 51% and as probably abnormal in another 17% of the patients. White matter damage was most frequently seen. MRI abnormalities were not related to CI dose or age at diagnosis. Patients showed significantly lower scores, compared to the norm group on measures of intelligence, verbal auditory memory, visual motor integration, and fine motor functioning. Lower scores significantly correlated with higher CI dose (25-32 Gy compared to 18-20 Gy) and younger age at diagnosis (< 4.0 years compared to > or = 4.0 years). Forty percent of the patients had to be referred to schools for learning disabled. CONCLUSIONS ALL treatment, including CI and MTX, at a young age is associated with persistent cognitive impairment and MRI abnormalities. However, no correlation was found between MRI results and neuropsychological or academic performance.

Academic career after treatment for acute lymphoblastic leukaemia

AIM To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. PATIENTS Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluation was 20 years; median follow up since diagnosis was 15 years at the time of the study. METHODS Patients and their 134 siblings completed a questionnaire on school career. The percentage of referrals to special primary schools for learning disabled, and the final level of secondary education in patients and siblings were compared, using a six point classification. Within the patient group, the effect of possible risk factors (age at diagnosis, irradiation dose, and gender) was investigated. RESULTS Significantly more patients than siblings were placed in special educational programmes. A significant difference was found for level of secondary education. No effect of gender or irradiation dose was found, but younger age at diagnosis was significantly related to both referrals and school levels. CONCLUSION Treatment for childhood ALL with cranial irradiation and chemotherapy at a young age is clearly associated with poorer academic career.

No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only : A prospective longitudinal study

Purpose To study, using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only. Patients and Methods Twenty consecutive patients underwent three evaluations, including 12 psychometric measures beside IQ. The authors applied strict methodology and a prospective-longitudinal design that started at diagnosis and extended to a median follow-up of 7 years. This report focuses on the outcome of the last evaluation. Test results were compared with healthy controls and to patients with ALL treated on a previous chemotherapy-only protocol. School achievement was evaluated in patients and their siblings. Results At the last evaluation, significantly lower test scores in patients compared with controls were found for only 2 of 14 cognitive measures (1 intelligence and 1 attention measure). No great differences were seen between school achievement of patients and siblings. Compared with the previous chemotherapy protocol, a better outcome was seen in the current study group on two measures (one memory and one attention measure). Conclusions Children surviving ALL have no major cognitive impairment after chemotherapy, including intrathecal and high-dose intravenous methotrexate. The slightly better outcome in the current group may indicate possible adverse effects of more dexamethasone treatment in the previous group.

Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Gross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We conclude that 2 years after cessation of treatment motor problems in ALL survivors were still present. Dysfunctions were mainly pronounced in handwriting and fine motor skills.

Oral administration of deuterium-labelled polyamines to sucking rat pups : luminal uptake, metabolic fate and effects on gastrointestinal maturation

Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuterium-labelled putrescine (Pu-d4; 3 mumol), spermidine (Sd-d4; 5 mumol), spermine (Sp-d4; 3 mumol), or physiological saline twice daily on postnatal days 7-10 or 12-15. They were killed on days 10 and 15. We determined activities of ileal lactase (EC 3.2.1.23), maltase (EC 3.2.1.20), sucrase (EC 3.2.1.48) and diamine oxidase (EC 1.4.3.6) and established villus and crypt lengths. Polyamines and their labelling percentages in organs were determined by GC and mass fragmentography. Treatments did not affect growth rate, but caused lower weights of liver, kidneys and heart. Maltase activity increased, lactase decreased, whereas sucrase and diamine oxidase did not change. Villus and crypt lengths increased. Organ polyamine pools were labelled to different extents. Irrespective of the orally administered polyamine, all organs contained Pu-d4, SD-d4 and Sp-d4. Administered Pu-d4 and Sd-d4 were recovered mainly as Sd-d4, whereas Sp-d4 was recovered as Sp-d4 and Sd-d4. Total polyamines in a caecum, colon and erythrocytes increased, but increases were only to a minor extent with regard to labelled polyamines. Our data confirm precocious gut maturation by exogenous polyamines. Putrescine appears to be limiting factor. The exogenous polyamines were distributed among all investigated organs. They are not only used for the synthesis of higher polyamines, but also retroconverted to their precursors. Changes in erythrocyte polyamine contents suggest precocious stimulation of erythropoiesis.

Feasibility of neuropsychological assessment in leukaemia patients shortly after diagnosis: directions for future prospective research

Aims: To study neuropsychological functioning of newly diagnosed children with acute lymphoblastic leukaemia (ALL) within two weeks after diagnosis in order to determine the feasibility of a sibling controlled prospective study design. Methods: Fifty consecutive patients (median age at testing 6.6 years, range 4–12) were included in a prospective, longitudinal, nationwide study. Treatment would include intrathecal and systemic chemotherapy according to the DCLSG ALL-9 protocol. Children were evaluated with an extensive neuropsychological battery including measures of intelligence, memory, attention, language, visual-constructive function, and fine-motor abilities within two weeks after start of the chemotherapy. The control group consisted of 29 healthy siblings (median age at testing 8.2 years, range 4–12), who were tested <4 weeks after the patients’ assessment. Results: Mean scores on Wechsler Intelligence Scales did not differ significantly between patients and siblings; mean IQ scores for both the patients and the controls were high average. To examine specific neuropsychological functions, norm scores based on the exact age were acquired by fitting procedures, but no significant differences were found. Conclusions: Neuropsychological assessment of patients during early hospitalisation is feasible. The results indicate no adverse effect of illness and psychological factors on IQ and neuropsychological functioning of patients with recently diagnosed ALL. The prospective design of this study of cognitive late effects of chemotherapy will allow discrimination between adverse sequelae of disease and treatment.

CEREBROVASCULAR COMPLICATIONS OF L-ASPARAGINASE THERAPY IN CHILDREN WITH LEUKEMIA - APHASIA AND OTHER NEUROPSYCHOLOGICAL DEFICITS

Children with acute lymphoblastic leukemia (ALL), treated with L-asparaginase are at risk for cerebral thrombosis or hemorrhage because of coagulation protein deficiencies. The results and the importance of serial neuropsychological examinations after such complications in three children with ALL are presented. All patients showed marked aphasia and other cognitive deficits. Recovery was complete in two of three children.

Social Competence in Children with Brain Disorders: A Meta-analytic Review

Social competence, i.e. appropriate or effective social functioning, is an important determinant of quality of life. Social competence consists of social skills, social performance and social adjustment. The current paper reviews social skills, in particular emotion recognition performance and its relationship with social adjustment in children with brain disorders. In this review, normal development and the neuro-anatomical correlates of emotion recognition in both healthy children and adults and in various groups of children with brain disorders, will be discussed. A systematic literature search conducted on PubMed, yielded nine papers. Emotion recognition tasks were categorized on the basis of task design and emotional categories to ensure optimal comparison across studies before an explorative meta-analysis was conducted. This meta-analytic review suggests that children with brain disorders show impaired emotion recognition, with the recognition of sad and fearful expressions being most impaired. Performance did not seem to be related to derivative measures of social adjustment. Despite the limited number of studies on a variety of brain disorders and control groups, outcomes were quite consistent across analyses and corresponded largely with the existing literature on development of emotion recognition in typically developing children. More longitudinal prospective studies on emotion recognition are needed to gain insight into recovery and subsequent development of children with distinct brain disorders. This will aid development, selection and implementation of interventions for improvement of social competence and quality of life in children with a brain disorder.

336 Neuropsychological functioning in children with cystic fibrosis: First results of a prospective comparative study

Objectives: The aim of this study was understand the treatment itinerary of Brazilian scholar children with Cystic Fibrosis from their perspective and was supported for the medical anthropology framework. Methods: Data was collected through 15 months following with 7 scholar children, both sex, with CF and their families, with the ethnographic method. Data were analyzed with the hermeneutic framework. Conclusion: CF is part of the life experience of the children and so, it’s an important issue of their existence. It has an important role in the decisions of plenty issues like the period of school, the kind of sport that the kid will do and the daily life routine. Most of children did not know clearly what the disease is and nether their treatment and medications names and functions and reported never have been included in his health treatment discussion, what can lead to poor adherence and high dependence to do the daily treatment. Children also have their own explanatory model for the disease and it is different from those of family and CF team, what can lead to truncated communication, understanding and evaluating of the treatment process. Nurses must understand the children perspective about the disease and how their understanding influences their evaluation about the treatment and defines the search for cure. With this we will be able to plan a health care treatment based on the family, children and CF team expectations, with an unified goal that priories the quality of life instead of the disease control.

Multidisciplinary Approach to the Treatment of Supratentorial Tumors in Children

Brain tumors can only be treated by the combined efforts of neurosurgeons, radiotherapists, and medical oncologists. This holds especially true in children, where close cooperation with other specialists in mandatory, i.e., the child neurologist for timely diagnosis and follow-up, the neuropsychologist for assessment of treatment effects, and so on. Since standard treatment — surgery and radiotherapy — is not sufficient in a lot of cases, while on the other hand the results of chemotherapy in brain tumors are far from satisfactory, multimodality treatment protocols become more and more necessary for adequate management of brain tumors.