T2-highlighted U-fibres and rapid parenchymal volume loss in AESD: An under-recognised subtype of paediatric acute encephalopathy syndromes.

Acute Encephalopathy with Reduced Subcortical Diffusion or AED is a unique subtype of acute paediatric encephalopathy which presents with altered mental status, prolonged seizures and developing characteristic radiological signal changes within the subcortical white matter. Reports of such cases have mainly been from Japan (Takanashi, 2009) and this radiological finding has been recognised as a novel feature of AED. We present three paediatric cases from a tertiary paediatric neurosciences centre in Manchester (Royal Manchester Children's hospital) with characteristic subcortical signal change, and furthermore, follow up imaging which in all 3 patients demonstrated a varying degree of cerebral atrophy. We recommend that children presenting with prolonged seizures should be considered for MR imaging ideally after 48hours if clinically stable, and early MR imaging follow-up (at 2-3 months) be performed routinely in patients with AED to assess for presence and degree of parenchymal volume loss for prognostication and to start neuroprotective therapy.

U-shape short-range extrinsic connectivity organisation around the human central sulcus.

The central sulcus is probably one of the most studied folds in the human brain, owing to its clear relationship with primary sensory-motor functional areas. However, due to the difficulty of estimating the trajectories of the U-shape fibres from diffusion MRI, the short structural connectivity of this sulcus remains relatively unknown. In this context, we studied the spatial organization of these U-shape fibres along the central sulcus. Based on high quality diffusion MRI data of 100 right-handed subjects and state-of-the-art pre-processing pipeline, we first define a connectivity space that provides a comprehensive and continuous description of the short-range anatomical connectivity around the central sulcus at both the individual and group levels. We then infer the presence of five major U-shape fibre bundles at the group level in both hemispheres by applying unsupervised clustering in the connectivity space. We propose a quantitative investigation of their position and number of streamlines as a function of hemisphere, sex and functional scores such as handedness and manual dexterity. Main findings of this study are twofold: a description of U-shape short-range connectivity along the central sulcus at group level and the evidence of a significant relationship between the position of three hand related U-shape fibre bundles and the handedness score of subjects.

Dysmature superficial white matter microstructure in developmental focal epilepsy.

Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.