Alena Svátková

Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood‐brain barrier (BBB) which limits treatment effects of intravenously applied α‐L‐iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre‐ and post‐treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient.

Unique white matter microstructural patterns in ADHD presentations—a diffusion tensor imaging study

Attention‐deficit/hyperactivity disorder predominantly inattentive (ADHD‐PI) and combined (ADHD‐C) presentations are likely distinct disorders that differ neuroanatomically, neurochemically, and neuropsychologically. However, to date, little is known about specific white matter (WM) regions differentiating ADHD presentations. This study examined differences in WM microstructure using diffusion tensor imaging (DTI) data from 20 ADHD‐PI, 18 ADHD‐C, and 27 typically developed children. Voxel‐wise analysis of DTI measurements in major fiber bundles was carried out using tract‐based spatial statistics (TBSS). Clusters showing diffusivity abnormalities were used as regions of interest for regression analysis between fractional anisotropy (FA) and neuropsychological outcomes. Compared to neurotypicals, ADHD‐PI children showed higher FA in the anterior thalamic radiations (ATR), bilateral inferior longitudinal fasciculus (ILF), and in the left corticospinal tract (CST). In contrast, the ADHD‐C group exhibited higher FA in the bilateral cingulum bundle (CB). In the ADHD‐PI group, differences in FA in the left ILF and ATR were accompanied by axial diffusivity (AD) abnormalities. In addition, the ADHD‐PI group exhibited atypical mean diffusivity in the forceps minor (FMi) and left ATR and AD differences in right CB compared to healthy subjects. Direct comparison between ADHD presentations demonstrated radial diffusivity differences in FMi. WM clusters with FA irregularities in ADHD were associated with neurobehavioral performance across groups. In conclusion, differences in WM microstructure in ADHD presentations strengthen the theory that ADHD‐PI and ADHD‐C are two distinct disorders. Regions with WM irregularity seen in both ADHD presentations might serve as predictors of executive and behavioral functioning across groups. Hum Brain Mapp 37:3323–3336, 2016.

White matter alterations in Parkinson’s disease with normal cognition precede grey matter atrophy

Introduction While progressive MRI brain changes characterize advanced Parkinson’s disease (PD), little has been discovered about structural alterations in the earliest phase of the disease, i.e. in patients with motor symptoms and with normal cognition. Our study aimed to detect grey matter (GM) and white matter (WM) changes in PD patients without cognitive impairment. Methods Twenty PD patients and twenty-one healthy controls (HC) were tested for attention, executive function, working memory, and visuospatial and language domains. High-resolution T1-weighted and 60 directional diffusion-weighted 3T MRI images were acquired. The cortical, deep GM and WM volumes and density, as well as the diffusion properties of WM, were calculated. Analyses were repeated on data flipped to the side of the disease origin. Results PD patients did not show any significant differences from HC in cognitive functioning or in brain volumes. Decreased GM intensity was found in the left superior parietal lobe in the right (p<0.02) and left (p<0.01) flipped data. The analysis of original, un-flipped data demonstrated elevated axial diffusivity (p<0.01) in the superior and anterior corona radiata, internal capsule, and external capsule in the left hemisphere of PD relative to HC, while higher mean and radial diffusivity were discovered in the right (p<0.02 and p<0.03, respectively) and left (p<0.02 and p<0.02, respectively) in the fronto-temporal WM utilizing flipped data. Conclusions PD patients without cognitive impairment and GM atrophy demonstrated widespread alterations of WM microstructure. Thus, WM impairment in PD might be a sensitive sign preceding the neuronal loss in associated GM regions.

Fast In Vivo High-Resolution Diffusion MRI of the Human Cervical Spinal Cord Microstructure

Diffusion Magnetic Resonance Imaging (dMRI) is a widely-utilized method for assessment of microstructural properties in the central nervous system i.e., the brain and spinal cord (SC). In the SC, almost all previous human studies utilized Diffusion Tensor Imaging (DTI), which cannot accurately model areas where white matter (WM) pathways cross or diverge. While High Angular Diffusion Resolution Imaging (HARDI) can overcome some of these limitations, longer acquisition times critically limit its applicability to clinical human studies. In addition, previous human HARDI studies have used limited spatial resolution, with typically a few slices and voxel size ~1 × 1 × 5 mm3 being acquired in tens of minutes. Thus, we have optimized a novel fast HARDI protocol that allows collecting dMRI data at high angular and spatial resolutions in clinically-feasible time. Our data was acquired, using a 3T Siemens Prisma scanner, in less than 9 min. It has a total of 75 diffusion-weighted volumes and high spatial resolution of 0.67 × 0.67 × 3 mm3 (after interpolation in Fourier space) covering the cervical segments C4–C6. Our preliminary results demonstrate applicability of our technique in healthy individuals with good correspondence between low fractional anisotropy (FA) gray matter areas from the dMRI scans, and the same regions delineated on T2-weighted MR images with spatial resolution of 0.35 × 0.35 × 2.5 mm3. Our data also allows the detection of crossing fibers that were previously shown in vivo only in animal studies.

Corrigendum: Multi-modal brain MRI in subjects with PD and iRBD [Front. Neurosci, 11, (2017) (709)] DOI: 10.3389/fnins.2017.00709

[This corrects the article on p. 709 in vol. 11, PMID: 29311789.].

White matter measures correlate with essential tremor severity-A pilot diffusion tensor imaging study

An evolving pathophysiological concept of essential tremor (ET) points to diffuse brain network involvement, which emphasizes the need to investigate white matter (WM) changes associated with motor symptoms of ET.

EPA-1717 – Effects of exercise therapy on white matter integrity in patients with schizophrenia and healthy controls- a longitudinal DTI study

Introduction In the recent years, interest of researchers has been focused on exercise as a possible way to efficiently influence brain functions and plasticity. Several studies concluded that exercise can change brain morphology by affecting synapses, neurogenesis and angiogenesis and improve efficiency in working memory and executive performance. In schizophrenia, white matter integrity is compromised and to what extent exercise affects white matter integrity is unclear. Aims To investigate the effect of 6 months exercise therapy on white matter integrity in healthy controls and patients with schizophrenia. Methods A total of 33 patients with schizophrenia and 48 healthy controls, matched for demographic characteristics, were randomized into exercise or occupational therapy/life-as-usual. 3T-DTI data were acquired twice. After susceptibility-artifacts and ECC correction, TBSS was used for registration to standard space and computation of the FA-skeleton. The JHU-ICBM-tract atlas was used to define regions of interest (ROI) for the various fiber tracts. Mean FA values for the FA-skeleton within the separate tract ROIs were calculated. GLM-repeated measures design was done with time as within-subject factor, group and therapy as between-factors, and compliance as covariate. Results Significant increases in FA were found for time by randomization in the left corticospinal tract (LCST) (F=4,15, p=0,045), left superior longitudinal fascicle (LSLF)(F=5,092, p=0,027) and forceps major (F=5,687, p=0,02). Conclusions Exercise positively affects FA of tracts involved in primary motor functions (LCST), regulation of motor behavior, spatial attention, oculomotor functions and transfer of somatosensory information (LSLF) as well as interhemispheric connections (Forceps major) in both groups.