ABBREVIATIONS FMRIBOxford RESULTS Whole-brain analysis indicated that cerebellar grey matter was significantly reduced in the patients with OMS, particularly in the vermis and flocculonodular lobe. A region-ofinterest analysis indicated significantly lower cerebellar grey matter volume, particularly in patients with the greatest OMS scores. Diffusion-weighted images did not show effects at a whole brain level, but all major cerebellar tracts showed increased mean diffusivity when analysis was restricted to the cerebellum. Cortical thickness was reduced across the motor and visual areas in the OMS group, indicating involvement beyond the cerebellum.INTERPRETATION Across individuals with OMS, there is considerable cerebellar atrophy, particularly in the vermis and flocculonodular lobes with atrophy severity associated with persistent symptomatology. Differences in cerebral cortical thickness indicate disease effects beyond the cerebellum.
Background: The neonatal period carries the highest risk of bacterial meningitis (~1 in 5000 births), bearing high mortality (~10%) and morbidity (20-50%) rates. Lumbar puncture (LP) remains essential to the diagnosis of meningitis. Though LP is a common procedure in neonates, success rates are lower (50-60%) than in other patient populations. None of the currently-practised neonatal LP techniques are supported by evidence from adequatelypowered, randomised controlled trials (RCTs). NeoCLEAR aims to compare two modifications to the traditional technique which are free, accessible, and commonly practised: sitting (as opposed to lying) position, and 'early' (as opposed to 'late') stylet removal.Methods/design: Written parental informed consent permitting, infants in neonatal/maternity wards, of 27 + 0 to 44 + 0 weeks corrected gestational age and weighing ≥1000 g, who require an LP, will be randomly allocated to sitting or lying position, and to early or late stylet removal. The co-primary objectives are to compare success rates (the proportion of infants with cerebrospinal fluid red cell count < 10,000/mm 3 on first LP procedure) in 1020 infants between the two positions, and between the two methods of stylet removal. Secondary outcomes relate to LP procedures, complications, diagnoses of meningitis, duration of antibiotics and hospital stay. A modified intention-to-treat analysis will be conducted.(Continued on next page)
ICAIndependent component analysis OMS Opsoclonus-myoclonus syndrome AIM Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS.METHOD Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (wholebrain echo-planar images; 2mm isotropic voxels; multiband factor 92) for a cross-sectional study. A seed-based analysis identified brain regions in which signal changes over time correlated with the cerebellum. Model-free analysis was used to determine brain networks showing altered connectivity. RESULTSIn patients with OMS, the motor cortex showed significantly reduced connectivity, and the occipito-parietal region significantly increased connectivity with the cerebellum relative to the comparison group. A model-free analysis also showed extensive connectivity within a visual network, including the cerebellum and basal ganglia, not present in the comparison group. No other networks showed any differences between groups.INTERPRETATION Patients with OMS showed reduced connectivity between the cerebellum and motor cortex, but increased connectivity with occipito-parietal regions. This pattern of change supports widespread brain involvement in OMS.Paediatric opsoclonus-myoclonus syndrome (OMS) is an extremely rare condition, affecting approximately one in 5 million total population per year in the UK. 1 While the name describes the rapid, involuntary eye movements (opsoclonus) and myoclonic jerks, affected children may also exhibit ataxia, sleep disturbance, irritability, and behavioural problems. The average IQ in a group of 105 patients with OMS was 81 (standard deviation [SD] 18), 2 although only around 15 of these parents reported formal IQ testing. In this large study, the most significant deficits reported by parents were ataxia, expressive language impairment, behavioural problems, and tremulousness.Despite a growing number of research studies investigating treatment options in OMS (reviewed in Pike 3 and Gorman 4 ), there remain very few studies of the neural effects of the disorder. Because the cerebellum is known to have connections throughout the cerebral cortex, it is possible that the gamut of symptoms could result from a primary disruption in the cerebellum. A recent study from our group 5 has shown that, in addition to damage to the cerebellum, there are changes in cortical thickness across motor and visual areas. Such structural changes may reflect alterations in the pattern of connectivity between the cerebellum and cerebral cortex.To determine whether the structural changes are accompanied by differences in functional correlations between brain areas, we analysed resting-state functiona...
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