Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation.

BACKGROUND: We report striking and unanticipated improvements in maladaptive behaviours in Prader-Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild-moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. METHODS: Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. RESULTS: Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. CONCLUSIONS: We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.

School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants.

BACKGROUND: Hospitalisation due to respiratory syncytial virus (RSV) infection in the first 2 years after birth has been associated with increased healthcare utilisation and associated costs up to 5 years of age in children born prematurely at less than 32 weeks of gestation who developed bronchopulmonary dysplasia (BPD). A study was undertaken to determine whether hospitalisation due to RSV infection in the first 2 years was associated with increased morbidity and lung function abnormalities in such children at school age, and if any effects were influenced by age. METHODS: Healthcare utilisation and cost of care in years 5-7 were reviewed in 147 children and changes in healthcare utilisation between 0 and 8 years were assessed also using results from two previous studies. At age 8-10 years, 77 children had their lung function assessed and bronchial hyper-responsiveness determined. RESULTS: Children hospitalised with RSV infection (n = 25) in the first 2 years had a greater cost of care related to outpatient attendance than those with a non-respiratory or no admission (n = 72) when aged 5-7 years (p = 0.008). At 8-10 years of age, children hospitalised with RSV infection (n = 14) had lower forced expiratory volume in 0.75 s (FEV(0.75)) (p = 0.015), FEV(0.75)/forced vital capacity (p = 0.027) and flows at 50% (p = 0.034) and 75% (p = 0.006) of vital capacity than children hospitalised for non-RSV causes (n = 63). Healthcare utilisation decreased with increasing age regardless of RSV hospitalisation status. CONCLUSIONS: In prematurely born children who had BPD, hospitalisation due to RSV infection in the first 2 years is associated with reduced airway calibre at school age.

Peak expiratory flow in Afro-Caribbean children with and without sickle cell anaemia.

AIMS: To create a reference range of peak expiratory flow (PEF) results of Afro-Caribbean children and determine whether interpretation of PEF results in children with sickle cell anaemia (SCA) differed according to whether comparison was made of results obtained from children of similar age or height. METHODS: A prospective observational study was carried out in two specialist sickle cell disease clinics. Seventy-eight nonasthmatic African and Caribbean (AC) controls (age range 2.6-17.8 years), and 99 nonasthmatic SCA children (age range 3.4-17.3 years) were recruited. PEF was measured using a dry rolling sealed spirometer before and after bronchodilator therapy. RESULTS: PEF results in the AC controls correlated with height (r = 0.88, p< 0.0001). Comparison of similarly aged children demonstrated that pre- (p = 0.02) and post- (p = 0.04) bronchodilator PEF results were lower in the SCA children, but comparison of children of similar height revealed no statistically significant differences in PEF results between children with SCA and controls. The SCA children tended to be shorter than the controls. CONCLUSION: The results suggest PEF measurements are not a useful method of monitoring the respiratory status of children with sickle cell disease.

Computed tomography and pulmonary function abnormalities in sickle cell disease.

The aim of this study was to determine whether patients with sickle cell disease (SCD) in steady state had pulmonary abnormalities seen on high-resolution computed tomography (HRCT) and whether any abnormalities correlated with contemporaneously diagnosed lung function abnormalities. A subsidiary question was whether the results of a noninvasive measure of haemolysis (end-tidal carbon monoxide (ETCO) levels) correlated with pulmonary function abnormalities. Thirty three patients with SCD, median (range) age 36 yrs (17-67 yrs) were examined. The degree of lobar volume loss and ground-glass opacification and prominence of central vessels on HRCT were quantitatively assessed. Pulmonary function was assessed by measurements of lung volumes, spirometry, gas transfer and oxygen saturation. ETCO levels were measured using an end-tidal CO monitor. Forced expiratory volume in one second (FEV1), forced vital capacity and total lung capacity significantly correlated with HRCT findings, particularly lobar volume loss. ETCO levels significantly negatively correlated with FEV1, vital capacity measured using a plethysmograph, specific airway conductance and arterial oxygen saturation measured by pulse oxymetry. In conclusion, the present results suggest that high-resolution computed tomography noninvasive assessment of haemolysis might be useful to identify sickle cell disease patients with respiratory function impairment.

Pulmonary function abnormalities in children with sickle cell disease.

BACKGROUND: Adults with sickle cell disease (SCD) have restrictive lung function abnormalities which are thought to result from repeated lung damage caused by episodes of pulmonary vaso-occlusion; such episodes start in childhood. A study was therefore undertaken to determine whether children with SCD have restrictive lung function abnormalities and whether the severity of such abnormalities increases with age. METHODS: Sixty four children with SCD aged 5-16 years and 64 ethnic matched controls were recruited. Weight and sitting and standing height were measured, and lung function was assessed by measurement of lung volumes and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) before and after bronchodilator. RESULTS: Compared with the control subjects, the children with SCD had lower mean (SD) sitting height (69 (6.3) cm v 73 (7.7) cm; p=0.004), sitting:standing height ratio (0.50 (0.02) v 0.51 (0.01); p<0.0001), weight (33 (10.9) kg v 41 (14.9) kg; p=0.001), functional residual capacity measured by a helium gas dilution technique (1.2 (0.3) l v 1.3 (0.4) l; p=0.04), FEV1 (1.5 (0.5) l v 1.9 (0.7) l; p=0.0008), FVC (1.7 (0.6) l v 2.1 (0.8) l; p=0.001), and PEF (3.9 (1.3) l/s v 4.8 (1.5) l/s; p=0.0004). The effect of age on lung function differed significantly between the children with SCD and the controls for total lung capacity and vital capacity measured by plethysmography and functional residual capacity measured by helium gas dilution. CONCLUSION: Lung function differs significantly in children with SCD compared with ethnic matched controls of a similar age. Our results suggest that restrictive abnormalities may become more prominent with increasing age.

The importance of using ethnically appropriate reference ranges for growth assessment in sickle cell disease.

Height and weight were measured and body mass index (BMI) calculated in 56 sickle cell disease (SCD), 57 Caucasian (CC), and 63 African/Caribbean (AC) 3-9 year old children. The SCD children were taller, but had similar weight and BMI to the CC controls. The SCD group had lower weight and BMI than the AC controls. The AC controls were of greater height, weight, and BMI than CC controls. These data highlight the importance of using ethnically appropriate reference ranges.