Cognitive function in children with brain tumors in the first year after diagnosis compared to healthy matched controls.

BACKGROUND: Improved survival of children with brain tumors (BTs) has increased focus on ameliorating morbidity. To reduce the risk of progressive cognitive decline, remedial strategies need to be instituted early, based upon accurate appraisal of need, yet few studies have investigated cognition in BT children early post-diagnosis. The study aims were to investigate cognition in children with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy children, exploring the impact of disease and treatment variables. METHODS: Forty-eight children aged 2-16 years with primary BTs, referred to a Regional Neurosurgical Unit over the 2-year study period were eligible for enrollment. The "best friends" model was used to recruit matched controls. Cognition was assessed using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test of Everyday Attention for Children, and Wechsler Quicktest. RESULTS: Patients with BTs had significantly reduced performance compared to controls early post-diagnosis in tests of Performance IQ, processing speed, verbal and visual memory, and selective attention. Improved performance over 12 months was seen in patients with BTs although also, for some measures, in controls. Significant deficits in cognitive performance were seen one year post-diagnosis for Verbal IQ; processing speed, visual and verbal immediate memory, and selective attention. Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and chemotherapy were associated with poorer functioning. CONCLUSION: Early cognitive impairment is present in BT children, sometimes prior to radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high tumor grade and infratentorial site. Future studies should investigate the role of early rehabilitation in improving cognition.

A detailed prospective longitudinal assessment of health status in children with brain tumors in the first year after diagnosis.

PURPOSE: To compare health status (HS) in children with brain tumors at 1 (t1), 6 (t6), and 12 (t12) months after diagnosis with "normal" controls. To assess the relationship between parent-report and self-report HS for patients at t12. METHODS: HS was assessed using the Health Utilities Index Mark III parent-report at all time points and self-report at t12. Twenty-nine patients and 32 controls were included in analysis of parent-report, and 21 patients and 22 controls in self-report HS at t12. Nonparametric analyses were used. RESULTS: Patients scored significantly lower than controls for global overall HS at all time points for parent-report and at t12 for self-report (Pmax=0.009). For parent-report, patients scored significantly lower than controls in the attributes of emotion, cognition, and pain at t1 and t6, in ambulation at t1 and in dexterity at t6. At t12, the difference was statistically significant for parent-report cognition only (all P<0.01). No attributes reached significance for self-report at t12. For patients, correlations between parent-report and self-report were good (rs>0.73) for all Health Utilities Index Mark 3 scores with the exception of emotion and pain. CONCLUSION: HS is significantly compromised in children with brain tumors over the first year after diagnosis, but improves with time. Parent-report and self-report differ, and both should be considered in assessing outcomes or defining interventions.

Child-related determinants of health-related quality of life in children with brain tumours 1 year after diagnosis.

OBJECTIVES: Infratentorial tumour site and health-related quality of life (HRQL) 1 month after diagnosis have been shown to predict HRQL 1 year after diagnosis in children with brain tumours. This study aimed to identify additional early child-related determinants of parent- and child-report HRQL. METHODS: Longitudinal prospective study. Semi-structured interviews took place approximately 1 and 12 months after diagnosis. HRQL was measured using the self- and parent-report Pediatric Quality of Life Scales (PedsQL 4.0) Total Scale Score and Health Utilities Index Mark 3 (HUI3) multi-attribute utility function. Child variables included performance and verbal IQ, general memory, selective attention executive function, behaviour problems, adaptive behaviour, symptoms of depression and anxiety and event related anxiety. Univariate analyses were used to identify potential early predictors of HRQL. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. Multivariate analysis showed infratentorial tumour site remained an important determinant of HRQL 1 year after diagnosis. Infratentorial tumour site and selective attention at 1 month generally best predicted poor self- and parent-report HRQL at 12 months. Adaptive behaviour and performance IQ may be important. CONCLUSION: Selective attention and infratentorial tumour site are most important in predicting both parent- and self-report HRQL at 1 year after diagnosis. Larger prospective studies are needed to confirm these findings. Cognitive remediation or/and pharmacological intervention, particularly aimed at children with infratentorial tumours may improve attention and subsequently HRQL and both merit further investigation.

Family, demographic and illness-related determinants of HRQL in children with brain tumours in the first year after diagnosis.

AIMS: To evaluate the relationship between parent- and child-report Health-Related Quality of Life (HRQL) and demographic, tumour and family variables in children with a brain tumour in the first year after diagnosis and to identify determinants of HRQL at 12 months. PROCEDURE: Longitudinal prospective study: Semi-structured interviews took place approximately 1, 6 and 12 months after diagnosis. HRQL was measured using the self- and parent-report PedsQL 4.0 Total Scale Score. Tumour and treatment variables considered included tumour site and grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family variables included measures of family function, family support and family stress, the primary carer's coping strategies and symptoms of depression and anxiety. Univariate analyses were used at all three time points, and to identify potential early predictors of HRQL at 1 year. Regression analysis was then used to identify the most important determinants of HRQL at 1 year. RESULTS: Thirty-five patients completed the 12-month interviews. There were consistent significant negative correlations between concurrent family impact of illness and parent and self-report HRQL, and positive correlations between concurrent family support and parent-report HRQL. Treatment with radio- or chemotherapy correlated with child-report HRQL only at some time points. Multivariate analysis showed infratentorial tumour site, and poor HRQL at 1 month best predicted poor self- and parent-report HRQL at 12 months. CONCLUSION: Children with infratentorial tumours and poor HRQL early after diagnosis tend to have poor HRQL at 1 year. While family factors are important modulators of concurrent HRQL, they do not appear important in predicting HRQL.

Effort testing in contemporary UK neuropsychological practice.

A survey of members of the British Psychological Society Division of Neuropsychology (N = 588) was conducted via email to ascertain current practice with respect to the use of symptom validity testing (SVT) in clinical and legal neuropsychological assessments. Replies were received from 130 practicing neuropsychologists. Results showed that 59% frequently use SVT in legal assessments, but a minority (15%) employ them in clinical assessments. Practice in the UK is only moderately different to that in North America with respect to frequency of use of SVT, although methods employed showed greater diversity. Favored tests, respondents' justifications for use of SVT and rationales for not using SVT are reported.

The King's Outcome Scale for Childhood Head Injury and injury severity and outcome measures in children with traumatic brain injury.

The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The male:female ratio was 1.8:1. The mean age was 11 years 10 months (SD 3.6, range 5-16y). Discharge KOSCHI categories were good (n=34), moderate (n=39), severe (n=6), and unclassifiable (n=2). KOSCHI category correlated strongly with admission Glasgow Coma Score, length of hospital stay, and post-traumatic amnesia. It also correlated significantly with Verbal IQ and Performance IQ (Wechsler); measures of attention; health status (Health Utilities Index [HUI]); health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]); depressive symptoms (Birleson Depression Scale) assessed within 3 months postTBI; and with Verbal IQ, selective attention (map mission), and HUI and PedsQL domains assessed at least 6 months post-TBI discharge. KOSCHI did not correlate with behaviour or executive function. We conclude that the KOSCHI scored at hospital discharge correlates with severity of injury and some cognitive, health status, and HRQL outcomes early after TBI. It is not helpful at predicting later difficulties, or behavioural and emotional problems.

Health related quality of life in the first year after diagnosis in children with brain tumours compared with matched healthy controls; a prospective longitudinal study.

This paper compares parent- and self-report health-related quality of life (HRQL) in children aged 2-16 years with brain tumours, one, six and twelve months after diagnosis with matched normal controls. HRQL was assessed using the PedsQL generic core scales. 37 tumour patients and 42 controls were included in analysis of parent-report, and 27 patients and 31 controls in self-report HRQL. Parent-report scores were significantly lower in patients than controls for all PedsQL scores at all time points (max p=0.002). Differences in self-report PedsQL between patients and controls were variable. The relationship between self- and parent-report in patients and controls was inconsistent; varied over time; and did not consistently correlate with parental depressive symptoms, suggesting parents and their children do not regard HRQL in a similar way. Prospective, longitudinal assessment of HRQL is important, but should be supplemented with other outcome measures such as health status and behaviour in this population.

Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.

Unilateral subthalamotomy in the treatment of Parkinson's disease.

Hyperactivity in the subthalamic nucleus (STN) is seen in animal models of Parkinson's disease, and lesioning of the STN dramatically relieves the animal's parkinsonism. Deep brain stimulation (DBS) of the STN is an effective treatment for patients with advanced Parkinson's disease. We have studied the effects of a unilateral lesion placed in the STN in predominantly hemi-parkinsonian patients. Twenty-one patients with advanced idiopathic Parkinson's disease were studied. Seventeen had asymmetrical tremor-dominant Parkinson's disease and four had bilateral disease. All patients underwent radiofrequency lesioning of the dorsolateral part of the STN under stereotactic guidance. The four patients with bilateral disease had, in addition, an electrode implanted contralaterally in the STN. Twenty-one patients have been followed for a minimum of 12 months. Clinical evaluation included the use of the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgery. Post-operative high-resolution MRI was performed in each patient to confirm lesion location, and this was correlated with clinical outcome. There was improvement in contralateral tremor, rigidity and bradykinesia in all patients followed for 6, 12 and 24 months, with the effect on tremor being greatest. L-dopa equivalent daily intake was approximately halved, and this resulted in a significant reduction in dyskinesia. Psychometric test scores were mostly unchanged or improved. All lesions were successfully located in the dorsolateral STN. Nineteen of the 21 lesions extended beyond the STN to involve pallidofugal fibres (H2 field of Forel) and the zona incerta (ZI). Lesion-induced dyskinesias were not a management problem except in one patient, whose lesion was confined to the STN. This patient was successfully treated with deep brain stimulator placement in the region of H2/ZI. Unilateral STN lesions can be made safely and are an effective alternative to thalamotomy, pallidotomy and unilateral STN DBS for the treatment of asymmetrical tremor-dominant advanced Parkinson's disease. Com bined lesioning of the dorsolateral STN and H2/ZI is particularly effective.