Delivery of Inhaled Nitric Oxide During MRI to Ventilated Neonates and Infants.

BACKGROUND: Many pediatric and neonatal ICU patients receive nitric oxide (NO), with some also requiring magnetic resonance imaging (MRI) scans. MRI-compatible NO delivery devices are not always available. We describe and bench test a method of delivering NO during MRI using standard equipment in which a NO delivery device was positioned in the MRI control room with the NO blender component connected to oxygen and set to 80 ppm and delivering flow via 12 m of tubing to a MRI-compatible ventilator, set up inside the MRI scanner magnet room. METHODS: For our bench test, the ventilator was set up normally and connected to an infant test lung to simulate several patients of differing weight (ie, 4 kg, 10 kg, 20 kg). The NO blender delivered flows of 2-10 L/min to the ventilator to achieve a range of NO and oxygen concentrations monitored via extended tubing. The measured values were compared to calculated values. RESULTS: A range of NO concentrations (12-41 ppm) and FIO2 values (0.67-0.97) were achieved during the bench testing. The additional flow increased delivered peak inspiratory pressure and PEEP by 1-5 cm H2O. Calculated values were within acceptable ranges and were used to create a lookup table. CONCLUSIONS: In clinical use, this system can safely generate a range of NO flows of 15-42 ppm with an accompanying FIO2 range of 0.34-0.98.

Huntington's disease patients display progressive deficits in hippocampal-dependent cognition during a task of spatial memory.

BACKGROUND: Cognitive disturbances occur early in Huntington's disease (HD) and place a significant burden on the lives of patients and family members. Whilst these impairments are typically attributed to deterioration of the frontal-striatal pathways, accumulating evidence suggests that hippocampal dysfunction may also contribute to such impairments. Here, we employ a novel spatial memory task that has previously been shown to elicit impairments in individuals with focal hippocampal lesions, as a means to further investigate the role of hippocampal dysfunction in HD. METHOD: Sixty-four individuals participated in the study, including 32 healthy controls, 11 patients with diagnosed HD and 16 premanifest HD gene carriers. We also included an additional control group of 5 individuals with focal unilateral basal ganglia lesions. Participants undertook a task that measured perception and short-term spatial memory using computer-generated visual scenes. RESULTS: HD patients experienced significant impairments in spatial perception and memory, which strongly correlated with disease burden score (DBS). Premanifest gene carriers performed at a similar level to healthy controls throughout all aspects of the task indicating that the effects seen in the HD patients represent a deterioration in function. Interestingly, basal ganglia lesion patients were not impaired in any aspects of the task. CONCLUSION: There is evidence of significant deficits in hippocampal-dependent spatial cognition in HD that cannot be explained as a function of degeneration to the basal ganglia. The impairments were greatest in individuals with higher DBSs, suggesting that deficits relate to the disease process in HD.

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.

Cognitive follow up of a small cohort of Huntington's disease patients over a 5 year period.

A small group of patients with manifest Huntington's disease (HD) were followed longitudinally to assess cognitive decline in relation to time from disease diagnosis. This article looks at performance on a range of computerised and pencil and paper cognitive tasks in patients 5 years post diagnosis, who were assessed annually for a 5 year follow up period. The almost universal cognitive decline reported in other longitudinal studies of HD was not replicated in this study. It was proposed that longitudinal follow up in HD is complicated by the varying degree to which different tasks are able to withstand repeated administration; a finding which would have significant implications on study design in future trials of cognitive enhansing interventions.

Reduced sensitivity to minimum-jerk biological motion in autism spectrum conditions.

We compared psychophysical thresholds for biological and non-biological motion detection in adults with autism spectrum conditions (ASCs) and controls. Participants watched animations of a biological stimulus (a moving hand) or a non-biological stimulus (a falling tennis ball). The velocity profile of the movement was varied between 100% natural motion (minimum-jerk (MJ) for the hand; gravitational (G) for the ball) and 100% constant velocity (CV). Participants were asked to judge which animation was 'less natural' in a two-interval forced-choice paradigm and thresholds were estimated adaptively. There was a significant interaction between group and condition. Thresholds in the MJ condition were lower than in the G condition for the NC group whereas there was no difference between the thresholds in the two conditions for the ASC group. Thus, unlike the controls, the ASC group did not show an increased sensitivity for perturbation to biological over non-biological velocity profiles.