Local White Matter Research Articles

Altered Microstructure of White Matter Except the Corpus Callosum Is Independent of Prematurity

Background: Diffusion tensor imaging (DTI) reflects the maturation of the brain microstructure. Although preterm infants are at significant risk for altered brain microstructure, it remains unclear whether this is affected by prematurity itself or other clinical factors. Objectives: To investigate DTI parameters in preterm infants at a term-equivalent age (TEA) compared with healthy term infants and to assess the associations between DTI parameters and clinical factors that may affect brain development. Methods: We studied 34 preterm infants without apparent brain lesions and 12 healthy term infants using tract-based spatial statistics. Region-of-interest analysis was performed in the posterior and anterior limbs of the internal capsule (PLIC and ALIC), corpus callosum (CC), optic radiation, and cerebral peduncle. Results: Preterm infants had significantly decreased fractional anisotropy (FA) in nearly the entire white matter (WM) compared with term infants (p < 0.01). Multiple regression analysis showed that FA in the PLIC, ALIC, optic radiation, and cerebral peduncle were positively associated with postmenstrual age (PMA) at imaging and that the apparent diffusion coefficient was negatively associated with PMA. Only FA in the CC was positively correlated with gestational age. Chronic lung disease (CLD) and postnatal infection were associated with decreased FA in the CC and PLIC, respectively. Conclusions: Preterm infants at TEA showed an altered microstructure of the WM compared with healthy term infants. The altered microstructure of the measured WM except the CC was independent of the degree of prematurity. Chronic lung disease and postnatal infection are related to localized WM alterations.

Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT

White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

Topology-Based Nonlocal Fuzzy Segmentation of Brain MR Image With Inhomogeneous and Partial Volume Intensity

The aim was to automatically segment brain magnetic resonance (MR) image with inhomogeneous and partial volume (PV) intensity for brain and neurophysiology analysis. Rather than assuming the presence of a single bias field over the image data, we first apply a local model to MR image analysis. With the brain topology knowledge, several specific local regions are selected, and typical brain tissues are then extracted for the prior estimation of fuzzy clustering center and member function. A new nonlocal fuzzy labeling scheme is applied to global optimization segmentation based on the block comparison and distance weight, which is robust to noise and inhomogeneous intensity. The nonlocal labeling provides optimized fuzzy member value and local intensity estimation of brain tissues such as cerebrospinal fluid (CSF), white matter (WM), and gray matter (GM). In addition to inhomogeneous intensity, PV may lead to error segmentation. To correct error segmentation because of PV, this article also provides two correction schemes. The first one is to extract CSF in deep sulci, which captures more CSF candidate by intensity comparison and topology shape comparison. The local pure CSF, WM, and GM is then estimated to correct the interfaces of CSF/GM and WM/GM. The segmentation experiments are performed on both brainweb-simulated images and Internet brain segmentation repository database (IBSR) real images. The experimental results demonstrate the robust and efficient performance of our approach. Our approach can be applied to automatic segmentation of the brain MR image.

Neuropathologic measurements in focal cortical dysplasias: validation of the ILAE 2011 classification system and diagnostic implications for MRI

Focal cortical dysplasias (FCD) which represent a composite group of cortical malformations are increasingly recognized as morphological substrate for severe therapy-refractory epilepsy in children and young adults. However, presurgical evaluation remains challenging as not all FCD variants can be reliably detected by high-resolution magnetic resonance imaging (MRI). Here, we studied a cohort of 52 epilepsy patients with neuropathological evidence for FCD using the 2011 classification of the International League against Epilepsy (ILAE) and systematically analysed those histopathologic features applicable also for MRI diagnostics. Histopathologic parameters included quantitative measurements of cellular profiles, cortical thickness, heterotopic neurons in white matter, and myelination that were compared between FCD subtypes and age-/localization-matched controls (n = 36) using multivariate analysis. Dysmorphic neurons in both FCD Type II variants showed significantly increased diameter of their cell bodies and nuclei. Cortical thickness was also increased with a distinct loss of myelin content specifying FCD Type IIb from IIa. The data further suggested that myelination deficits in FCD Type IIb result from compromised oligodendroglial lineage differentiation and we concluded that the "transmantle sign" is a unique finding in FCD Type IIb. In contrast, FCD Type Ia was characterized by a smaller cortical ribbon and higher neuronal densities, but these parameters failed to reach statistical significance (considering age- and location-dependent variability in controls). All FCD variants showed abnormal grey-white matter boundaries with increased numbers of heterotopic neurons. Similar results were obtained also at deep white matter location. Thus, many FCD variants may indeed escape visual MRI inspection, but suspicious areas with increased or decreased cortical thickness as well as grey-white matter blurring may be uncovered using post-processing protocols of neuroimaging data. The systematic analysis of well-specified histopathological features could be helpful to improve sensitivity and specificity in MRI detection during pre-surgical work-up of patients with drug-resistant focal epilepsies.

Automated measurement of local white matter lesion volume

It has been hypothesized that white matter lesions at different locations may have different etiology and clinical consequences. Several approaches for the quantification of local white matter lesion load have been proposed in the literature, most of which rely on a distinction between lesions in a periventricular region close to the ventricles and a subcortical zone further away. In this work we present a novel automated method for local white matter lesion volume quantification in magnetic resonance images. The method segments and measures the white matter lesion volume in 43 regions defined by orientation and distance to the ventricles, which allows a more spatially detailed study of lesion load. The potential of the method was demonstrated by analyzing the effect of blood pressure on the regional white matter lesion volume in 490 elderly subjects taken from a longitudinal population study. The method was also compared to two commonly used techniques to assess the periventricular and subcortical lesion load. The main finding was that high blood pressure was primarily associated with lesion load in the vascular watershed area that forms the border between the periventricular and subcortical regions. It explains the associations found for both the periventricular and subcortical load computed for the same data, and that were reported in the literature. But the proposed method can localize the region of association with greater precision than techniques that distinguish between periventricular and subcortical lesions only.

Microstructure of a three-way anatomical network predicts individual differences in response inhibition: A tractography study

Response inhibition is thought to depend critically on the inferior frontal gyrus, pars opercularis (IFGoper), presupplementary motor area (preSMA) and basal ganglia, including the subthalamic nucleus (STN), but the differential contribution of structural connections within this network to response inhibition remains unclear. Using diffusion tensor imaging and probabilistic fiber tractography, we investigated the relative associations between local white matter microstructure and stop-signal response inhibition in fronto-basal ganglia tracts delineated by probabilistic tractography. In a tract-of-interest approach, we identify significant associations with fractional anisotropy (FA) in fibers connecting the right STN region to both preSMA/SMA and IFGoper and in bilateral tracts connecting preSMA/SMA to IFGoper and the striatum. In addition, significant associations with radial diffusivity (RD) were found in fibers connecting the right preSMA/SMA to striatum and in bilateral tracts between IFGoper and STN region. In our whole-brain analysis, additional significant clusters were identified in the corpus callosum, optic radiation, inferior fronto-occipital tract and white matter of the precentral gyrus. To investigate the relative importance of regional white matter characteristics to response inhibition performance, we performed a step-wise multiple regression analysis that yielded FA in tracts connecting preSMA/SMA to the STN region and striatum, respectively, and RD in fibers connecting IFGoper to the STN region as best predictors of response inhibition performance (42% explained variance). These findings point to a specific contribution of white matter pathways connecting distinct basal ganglia structures with both medial frontal and ventrolateral prefrontal regions to response inhibition.

A framework for voxel-based morphometric analysis of the optic radiation using diffusion tensor imaging in glaucoma

Glaucoma is an optic neuropathy affecting the entire visual system. The understanding of the glaucoma mechanism and causes remains unresolved. Diffusion tensor imaging (DTI) has been used to analyze the optic nerve and optic radiation showing global fiber abnormalities associated with glaucoma. Nevertheless, the complex structure of the optic radiation and the limitations of DTI make the localization of the glaucoma effect a difficult task. The aim of this work is to establish a framework for the determination of the local changes of the optic radiation due to glaucoma using DTI. The proposed system utilizes a semiautomated algorithm to produce an efficient identification of the optic radiation. Segmented optic radiations are transformed to a unified space using shape-based nonrigid registration. Using the deformation fields that resulted from the registration, the maps of the diffusion tensor-derived parameters are transformed to the unified space. This allows for statistical voxel-wise analysis to produce significant abnormality maps. The proposed system is applied to a group of 13 glaucoma patients and a normal control group of 10 subjects. The groups are age matched to eliminate the age effect on the analysis. Diffusion-related parameters (axial, radial and mean diffusivities) and an anisotropy index (fractional anisotropy) are studied. The anisotropy analysis indicates that the majority of the significant voxels show decreased fractional anisotropy in the glaucoma patients compared with the control group. In addition, the significant regions are mainly distributed in the middle (in reference to anterior–posterior orientation) of the optic radiation. Glaucoma subjects have increased radial diffusivity and mean diffusivity significant voxels with a main concentration in the proximal part of the right optic radiation. The proposed analysis provides a framework to capture the significant local changes of the optic radiation due to glaucoma. The preliminary analysis suggests that the glaucomatous optic radiation may suffer from localized white matter degeneration. The framework facilitates further studies and understanding of the pathophysiology of glaucoma.

Atrophy, hypometabolism and white matter abnormalities in semantic dementia tell a coherent story

Semantic dementia, in which there is progressive deterioration of semantic knowledge, is associated with focal, typically asymmetric, temporal lobe degeneration. The ventrorostral temporal lobe is most severely affected and there is concordance between atrophy and reduced metabolic activity. In this study, we confirmed the veracity of this claim using ¹⁸F-fluorodeoxyglucose positron emission tomography and anatomical magnetic resonance images. The principal aim, however, was to understand the impact on neuronal projections from the ventrorostral temporal cortex lesion by studying the full extent of white matter changes, with no a priori assumptions about the nature or spatial location of the tracts involved. Using an unbiased voxel-wise approach known as tract-based spatial statistics, we compared results of whole-brain diffusion tensor imaging--absolute metrics of axial, radial and mean diffusion as well as fractional anisotropy--from 10 patients with mild/moderate semantic dementia and 21 matched controls. Distributions of increased absolute diffusivity and reduced fractional anisotropy for patients with semantic dementia were spatially concordant with each other. Abnormalities in all metrics were highly statistically significant in ventrorostral temporal white matter, more extreme on the left side, thus closely matching results from structural and functional imaging of grey matter. The most sensitive marker of change was radial diffusion. Local white matter tract abnormalities extended rostrally towards the frontal lobe and dorsocaudally towards the superior temporal and supramarginal gyri. To examine more remote changes, we performed a skeletonized probabilistic tractography analysis--'seeding' the rostral temporal voxels identified as abnormal in the patient group--in a healthy control group. Three major neural pathways were found to emanate from this 'seed region': uncinate, arcuate and inferior longitudinal fasciculi. At a less conservative threshold, tensor abnormalities in the semantic dementia group mapped onto the tractographies for the uncinate and arcuate bundles well beyond the rostral temporal lobe; this was not the case for the inferior longitudinal bundle, where abnormalities in semantic dementia did not extend caudal to the atrophic/hypometabolic zone. The results offer direct evidence for how the ventrorostral temporal lesion, proposed to be responsible for deteriorating semantic knowledge in semantic dementia and separate from 'classic' language areas, is associated with degeneration of efferent white matter projections to such language areas.

Neuroanatomical correlates of intellectual ability across the life span

Attempts to correlate measures of intellectual ability with localized anatomical imaging features of the brain have yielded variable findings distributed across frontal, parietal, and temporal lobes. To better define the gray and white matter correlates of intellectual ability and the effects of sex and age, we analyzed the brains of 105 healthy individuals, ages 7–57 years, who had a Full Scale Intelligence Quotient (FSIQ) of 70 or higher. We examined associations of FSIQ with cortical thickness and with white matter volume throughout the cerebrum. Thinning of left ventromedial and right dorsolateral prefrontal cortices correlated significantly with FSIQ. Sex modified correlations of cortical thickness with FSIQ in the left inferior frontal, left cingulate, and right dorsomedial prefrontal cortices. Correlations of local white matter volumes with FSIQ varied by age, with adults showing inverse correlations of white matter volume with FSIQ in a large territory of right frontal white matter likely corresponding to fiber tracts of the superior corona radiata and superior longitudinal fasciculus. These findings corroborate the role of frontal and parietal association cortices and long association white matter fibers in higher intelligence and suggest ways in which the neuroanatomical correlates of higher intelligence may vary by sex and age.

Magnetic resonance in studies of glaucoma

SummaryGlaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated.

Appreciating symptoms and deficits in schizophrenia: Right posterior insula and poor insight

Poor insight is one of the most prominent clinical features of psychosis. Loss of insight in schizophrenia is characterised by abnormalities in awareness and attribution of the origin of pathological mental phenomena. Converging lines of investigations suggest that in healthy individuals, right posterior insula plays an important role in awareness and self-attribution of mental phenomena, contributing to the emergence of a sense of self (Craig, 2002; Farrer et al., 2003). In addition, neuroimaging studies investigating brain morphometry in schizophrenia have consistently reported deficits in the structure of insula (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we investigated the relationship between the morphometry of posterior insula and degree of insight in a sample of 57 patients in a stable phase of illness using high resolution Magnetic Resonance Imaging. We measured the cortical surface area and local white matter volume of posterior insula. A significant inverse relationship was found between right posterior insular structure and degree of insight in schizophrenia. No such relationship was noted for left posterior insula. Our results highlight the importance of a predominantly right-sided network that includes posterior insula as the neural basis of insight. Abnormalities in interoceptive awareness and self-appraisal of emotional states may contribute to the loss of insight seen in schizophrenia.

Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs.

Diffusion tensor imaging of focal cortical dysplasia: a preliminary study

Objective To evaluate the subcortical white matter changes adjacent to focal cortical dysplasia(FCD) by applying diffusion tensor imaging (DTI) and to investigate its potential value in the diagnosis of FCD.Methods The clinical information, MRI images and DTI data of 12 patients with FCD were retrospectively evaluated.The DTI images were postprocessed.The mean diffusivity(MD), fractional anisotrophy (FA) and color-encoded tensor images were acquired.Ellipsoid ROIs were set in the subcortical white matter under FCD lesions and corresponding areas on the contralateral side.The MD value and FA value were measured in each ROI.The paired t test was employed to compare the MD and FA values between the areas ipsilateral and contralateral to the lesion.In diffusion tensor tractography (DTT), the same ROI as DTI measurement was set using T_2 WI images as reference.One ROI served as seed point, all the white matter fiber tracts crossing the ROI were acquired.Results Focal cortical thickening and blurring of the gray-white matter junction were found in all cases of FCD on conventional MRI images.Seven patients demonstrated hyperintensity on T_2 WI images and hypointensity on T_1 WI images in the subcortical white matter adjacent to FCD.Two patients demonstrated focal subcortical white matter atrophy.No abnormal findings were detected in the subcortical white matter in 3 patients.Quantitative analysis of DTI data showed significant fractional anisotrophy (FA) decrease (ipsilateral side to FCD 0.31±0.05, contralateral side 0.42 ±0.08,t=- 3.995, P<0.01), and mean diffusivity (MD) increase in comparison to thecontralateral region [ipsilateral side to FCD (1.02 ±0.16) × 10~(-3) mm~2/s, contralateral side (0.86±0.13) ×10~(-3) mm~2/s,t=2.655,P<0.05].On diffusion tensor tractography (DTT), 10 patients showed definite reduction in the volume of subcortical white matter bundles and the connections between the subcortex and deep white matter were sparse.Two patients showed probable reduction compared with the contralateral normal side.Conclusions FCD not only has cortical abnormalities but also affects local white matter development.DTI is an important supplement to conventional MRI. Key words: Cerebral cortex; Nervous system abnormalities; Diffusion magnetic resonance imaging

Local white matter geometry from diffusion tensor gradients

We introduce a mathematical framework for computing geometrical properties of white matter fibers directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fiber dispersion and (2) fiber curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia.

Age-related microstructural changes in subcortical white matter during postadolescent periods in men revealed by diffusion-weighted MR imaging

Continuous maturation of cerebral white matter (WM) in the postadolescent period is not fully understood. To elucidate the time course and location of possible postadolescent maturational changes in cerebral WM, we studied 60 healthy male subjects who were in their second to seventh decade using diffusion-weighted imaging. Mean diffusivity (MD) in subcortical WM was measured in 78 cortical regions in each subject's brain using an automated method. Regression analysis was used to model the age-related change in MD by either a linear or a quadratic function in each region. Age-related changes in subcortical MD were best modeled by either a linear function or a quadratic function in 27 regions including language-related regions, visual or multimodal areas in the bilateral occipital and temporal lobes, limbic areas including the bilateral parahippocampal gyri, and the bilateral postcentral and left precentral gyri. In these regions, the MD rapidly decreased until middle age and thereafter reached a plateau. Our results revealed microstructural changes in local subcortical WM and suggests a continuing maturational process in postoadolescent periods.

Malformations of cortical development and epilepsies: neuropathological findings with emphasis on focal cortical dysplasia

Structural brain abnormalities can be increasingly recognized in patients suffering from intractable focal epilepsies using high-resolution imaging techniques. Epilepsy surgery has become a successful treatment option for many of these patients. A broad spectrum of malformations of cortical development (MCD) can be histopathologically identified in resective surgical brain samples. Here, we discuss neuropathological findings and available classification systems in children and adult patients. Particular emphasis will be paid to the classification system for focal cortical dysplasias (FCD), which can be histopathologically distinguished as type I and II. Also mild forms of cortical malformations (mMCD) may be present, including heterotopic neurons in white matter location. However, different cohorts of epilepsy patients may present with similar histopathological findings and clinico-pathological correlations are not always comparable with respect to outcome prediction. We will, therefore, discuss also the difficulties to classify some FCD variants. Notwithstanding, the underlying pathomechanisms in all FCD entities need to be specified. A comprehensive approach taking all currently available data into consideration will be mandatory to further develop our current understanding of FCDs, and to continuously improve our concept for a reliable classification system.

Mapping the regional influence of genetics on brain structure variability — A Tensor-Based Morphometry study

Genetic and environmental factors influence brain structure and function profoundly. The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins' 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject's anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions that have a more protracted maturational time-course.

A framework for quantitative and visual analysis of white matter integrity using Diffusion Tensor Imaging

A new quantitative and visual analysis technique is developed to study the white matter integrity along fibre bundles using Diffusion Tensor Imaging (DTI) tractography. Our approach takes advantages of DTI tractography and geodesic path mapping, which establishes group-wise correspondences to allow direct cross-subject evaluation of diffusion properties. The 3D volumetric fibre bundle is approximated by streamlines reconstructed using DTI. We present the fibre bundle mask strategy to measure thin fibre bundles in group analysis. A novel isonode visualisation method is developed to facilitate the visual inspection of local white matter alterations within a neural pathway.

Opticospinal multiple sclerosis in Iran

Clinical course, magnetic resonance imaging (MRI) findings and cerebrospinal fluid data (CSF) on 20 patients among 520 with clinically definite multiple sclerosis (MS) according to the criteria of Poser et al., with opticospinal clinical presentation above 5 years and mean disease duration of 8 ± 4.4 years were reviewed. The prevalence rate was 3.8%. The clinical course was relapsing-remitting (RR) for all patients. The mean age of onset was 24 ± 8.2 years. The gender ratio was 2.3:1 female:male. First clinical presentation was spinal signs in 12 (60%), optic neuritis in 7 (35%) and simultaneous involvement of both eyes in 1 (5%) patient. No transverse myelitis (TM), sustained severe optic neuritis (SSON) or minor brain stem signs were recorded. No conversion to conventional MS (CMS) or secondary progressive MS (SPMS) was identified during the study period and no case had positive family history for the disease. The yearly number of attacks was 0.66 ± 0.84, with mean Kurtzke expanded disability status scale (EDSS) of 2.5 ± 1.2. All patients had 1 to 5 hemispheral T2 lesions in brain MRI, non-fulfilled Barkhof criteria for brain lesions. All had preventricular and 14 (70%) had juxtacortical lesions. None had gadolinium T1 enhanced lesions. No involvement of the brainstem or cerebellar structures was detected. Fifteen had 1 cervical lesion, five had 2 and four had 1 concomitant thoracic cord signal, all extending below three vertebral segments in sagittal planes with peripheral white matter location on the axial planes. Spinal fluid contained normal cell and protein with negative oligoclonal bands (OB).

Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.