Whole body MRI in type I Gaucher patients: evaluation of skeletal involvement.

BACKGROUND: Bone disease is a serious complication of type 1 Gaucher disease, which if untreated can result in pain, disability and reduced quality of life. MRI is the method of choice for assessing and monitoring bone involvement in Gaucher patients. MRI bone evaluation has been predominantly carried out on the lumbar spine and/or lower extremities using quantitative or semi-quantitative methods. We describe evaluation of skeletal involvement in Gaucher patients using whole body MRI scanning. METHODS: Whole body MRI was performed in 39 adult type I Gaucher patients using a 1.5 T superconducting magnet with total imaging matrix technology. A standard MRI protocol was performed in all patients using coronal T1-, T2-weighted (thighs) and STIR-sequences of the whole body, sagittal T1-, T2- (lumbar spine) and STIR-sequences of the entire axial skeleton. Bone marrow involvement was analysed using the Düsseldorf Gaucher score (DGS), bone marrow burden score (BMB), and vertebra-disc-ratio (VDR). Pelvis, humerus, legs and spine were also analysed using the pattern of marrow involvement described by homogeneous type A or non-homogeneous type B morphology. Avascular necrosis (AVN) of the humeral head was determined. RESULTS: Whole body MRI was well tolerated and of diagnostic value in all patients. Thirty one out of 39 patients (79%) showed bone involvement. In fifteen of these 31 patients (48%) humeral bone involvement was observed. The morphological appearance of bone involvement (type A or B) was consistent across the humerus, legs and pelvis. The infiltration pattern was also similar across cervical, thoracic and lumbar vertebral bodies. Humeral bone involvement was present in 89% of patients with type B morphology compared with 32% of patients with type A morphology (p<0.005). Humeral involvement was detected more frequently in patients with severe bone involvement as determined by higher DGS and BMB scores, than in patients with lower DGS and BMB scores (p<0.0001 and p=0.0016). AVN of the humeral head was detected in 6 patients (19%). CONCLUSIONS: In this group of patients, severe bone involvement in the lumbar spine and lower extremities and type B morphology was also associated with humeral involvement. The morphological infiltration pattern was consistent in the entire skeleton indicating the systemic character of bone disease. Whole body MRI presents a feasible means of assessing the entire skeletal system and could be a valuable diagnostic and monitoring tool in the management of patients with type 1 Gaucher disease.

Metastatic spinal cord compression: a review of practice and care.

AIM AND OBJECTIVES: The aim of this review was to address: (1) How is spinal stability assessed? (2) What is the role of bracing/should braces be used? (3) When is it safe to mobilise the patient? (4) What position should the patient be nursed in? BACKGROUND: Controversy surrounds the care for patients with metastatic spinal cord compression (MSCC). There is some evidence to indicate that care for patients with MSCC is based on individual clinician preference rather than evidence-based guidelines which has been shown to cause delays and discrepancies in patient treatment. DESIGN: A structured literature review to synthesise the available evidence about the management of MSCC. METHODS: The following databases were searched: Medline, EMBASE, Cochrane Systematic Reviews Database, SIGN (Scottish Intercollegiate Guidelines Network), NICE (National Institute for Clinical Excellence), AMED (Allied and Complementary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health Literature) and BNI (British Nursing Index). Publications were selected from the past 10 years. The search yielded a total of 1057 hits, 755 abstracts were screened, and 73 articles were retrieved and examined. Thirty-five articles were included. RESULTS: The findings identified a gap and evidence relating to spinal stability, bracing, patient mobilisation, and positioning is limited and may be inconclusive. It is important for patients with a poor prognosis that their preferences and quality of life are considered. CONCLUSION: Currently, the evidence base to underpin care is limited, and further research in this area is necessary for patients and healthcare professionals alike. RELEVANCE TO CLINICAL PRACTICE: Patients who suffer from MSCC suffer numerous physical, psychological and social issues. Because of lack of consensus, the current guidelines to inform clinical decision-making of professional staff are of limited benefit.

Dissociation in response to methylphenidate on response variability in a group of medication naïve children with ADHD.

Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to dopamine signaling is suggested in ADHD that may be ameliorated by methylphenidate (MPH). This study investigated the effects of MPH administration on the variability in RT and error performance on a sustained attention task of a group of 31 medication naïve children with ADHD, compared with 22 non-ADHD, non-medicated, control children. All children performed the fixed-sequence sustained attention to response task (SART) at two time-points: at baseline and after six weeks. The children with ADHD were tested when medication naive at baseline and after six weeks of treatment with MPH and whilst on medication. The medication naïve children with ADHD performed the SART with greater errors of commission and omission when compared with the control group. They demonstrated greater standard deviation of RT and fast moment-to-moment variability. They did not differ significantly from the control group in terms of slow variability in RT. MPH administration resulted in reduced and normalised levels of commission errors and fast, moment-to-moment variability in RT. MPH did not affect the rate of omission errors, standard deviation of RT or slow frequency variability in RT. MPH administration may have a specific effect on those performance components that reflect sustained attention and top-down control rather than arousal.

Response variability in attention deficit hyperactivity disorder: evidence for neuropsychological heterogeneity.

Response time (RT) variability is a common finding in ADHD research. RT variability may reflect frontal cortex function and may be related to deficits in sustained attention. The existence of a sustained attention deficit in ADHD has been debated, largely because of inconsistent evidence of time-on-task effects. A fixed-sequence Sustained Attention to Response Task (SART) was given to 29 control, 39 unimpaired and 24 impaired-ADHD children (impairment defined by the number of commission errors). The response time data were analysed using the Fast Fourier Transform, to define the fast-frequency and slow-frequency contributions to overall response variability. The impaired-ADHD group progressively slowed in RT over the course of the 5.5min task, as reflected in this group's greater slow-frequency variability. The fast-frequency trial-to-trial variability was also significantly greater, but did not differentially worsen over the course of the task. The higher error rates of the impaired-ADHD group did not become differentially greater over the length of the task. The progressive slowing in mean RT over the course of the task may relate to a deficit in arousal in the impaired-ADHD group. The consistently poor performance in fast-frequency variability and error rates may be due to difficulties in sustained attention that fluctuate on a trial-to-trial basis.

Predicting language change between 3 and 5 years and its implications for early identification.

BACKGROUND AND OBJECTIVE: Early language delays across the preschool period have important implications for children, parents, and services raising the significance of early identification. Screening tests are an appealing solution but have proved problematic. A combined risk model would seem promising but has yet to be tested. The goal of this study was to examine the factors that predict language change in a nationally representative sample of children between 3 and 5 years when most children are identified as being in need of services. METHODS: By using data from children (n = 13,016) in the Millennium Cohort Study (a national UK birth cohort), linear regression was used to predict 5-year performance from 3-year test performance data coupled with sociodemographic and within-child factors and indicators of parental concern. Patterns of change were identified and logistic regression was used to predict the difference between children for whom profiles change and those for whom they do not. RESULTS: The final model (predicting 32% of the variance) included maternal education, pattern construction, behavior, language concerns, and 3-year vocabulary. Four change patterns were identified: one consistently low (n = 201), one consistently high (n = 12,066), a group that is resilient (n = 572), and one with a declining profile (n = 177). The models accurately predicted 71% of the declining group and 99% of the resilient group. Maternal education (odds ratio: 0.49) and behavior (odds ratio: 0.9) were significant predictors for the former and maternal education (odds ratio: 0.6) and pattern construction (odds ratio: 1.03) the latter. CONCLUSIONS: Early identification of delayed language remains problematic but, once identified, there are key indicators that predict which children are likely to be more or less at risk across time. The implications are discussed in terms of policy and practice.

Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.