ALCOHOLISM, Issue 6 2008
Gordon J. Harris
Background:, Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods:, Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results:, Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions:, The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism. [source]

Demyelination Induces the Decline of the Myelinated Fiber Length in Aged Rat White Matter

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2009
Chen Li
Abstract To determine the exact reason for the age-related decline of the myelinated fiber length in white matter, we performed this study. In middle-aged rats, there was age-related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle-aged rat white matter might make the age-related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable. However, in old-aged female rats, the unmyelinated fibers with large and small diameters significantly degenerated together and that the unmyelinated fibers formed from the demyelination of the myelinated fibers could not replenish the age-related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the significant decline of the myelinated fiber length in aged white matter. Anat Rec, 292:528,535, 2009. © 2009 Wiley-Liss, Inc. [source]

Molecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic Insult

BRAIN PATHOLOGY, Issue 4 2003
Ursula Graumann
Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source]

Abnormal Endothelial Tight Junctions in Active Lesions and Normal-appearing White Matter in Multiple Sclerosis

BRAIN PATHOLOGY, Issue 2 2002
Jonnie Plumb
Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10,50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (<2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. [source]

Imaging patterns of brain injury in term-birth asphyxia

ACTA PAEDIATRICA, Issue 3 2009
Renate Swarte
Abstract Aim: To develop an extended asphyxia-score based on cerebral ultrasound (US) and MRI in order to gain further insight into the pathophysiology of asphyxia. Patients and Methods: First week cerebral US and MRI of 80 asphyxiated term infants were scored according to a new scoring system based on separate grading of injury to deep grey matter and to (sub)cortical/white matter. Our findings were compared with published scoring systems. Results: Six patterns of brain injury were derived: deep grey matter injury with either limited or extensive cortical involvement, damage to deep grey matter with watershed injury, isolated watershed injury, isolated white matter injury (leukomalacia) and isolated cortical necrosis. The mortality rate was considerable in patterns with extensive cortical injury. Conclusion: Six patterns of brain injury, following term-birth asphyxia were found using a new imaging score. [source]

Illustrative White Matter Fiber Bundles

COMPUTER GRAPHICS FORUM, Issue 3 2010
Ron Otten
Abstract Diffusion Tensor Imaging (DTI) has made feasible the visualization of the fibrous structure of the brain white matter. In the last decades, several fiber-tracking methods have been developed to reconstruct the fiber tracts from DTI data. Usually these fiber tracts are shown individually based on some selection criteria like region of interest. However, if the white matter as a whole is being visualized clutter is generated by directly rendering the individual fiber tracts. Often users are actually interested in fiber bundles, anatomically meaningful entities that abstract from the fibers they contain. Several clustering techniques have been developed that try to group the fiber tracts in fiber bundles. However, even if clustering succeeds, the complex nature of white matter still makes it difficult to investigate. In this paper, we propose the use of illustration techniques to ease the exploration of white matter clusters. We create a technique to visualize an individual cluster as a whole. The amount of fibers visualized for the cluster is reduced to just a few hint lines, and silhouette and contours are used to improve the definition of the cluster borders. Multiple clusters can be easily visualized by a combination of the single cluster visualizations. Focus+context concepts are used to extend the multiple-cluster renderings. Exploded views ease the exploration of the focus cluster while keeping the context clusters in an abstract form. Real-time results are achieved by the GPU implementation of the presented techniques. [source]

MRI atlas of human white matter

CONCEPTS IN MAGNETIC RESONANCE, Issue 2 2006
Philip R. Szeszko
No abstract is available for this article. [source]

MRI atlas of human white matter

CONCEPTS IN MAGNETIC RESONANCE, Issue 2 2006
Chan Ling Ling M.D.
No abstract is available for this article. [source]

Magnetic resonance imaging at term and neuromotor outcome in preterm infants

ACTA PAEDIATRICA, Issue 3 2000
AM Valkama
In order to evaluate the value of neonatal brain magnetic resonance imaging (MRI) for predicting neuromotor outcome in very low birthweight (VLBW) preterm infants, 51 such infants with gestational age <34 wk underwent brain MRI at term age. Myelination, parenchymal lesions (haemorrhage, leukomalacia, infarction, reduction of white matter), parenchymal lesions without subependymal haemorrhage, ventricular/brain ratios and widths of the extracerebral spaces were assessed. The MRI findings were compared with cranial ultrasound (US) performed at term. Infants' neuromotor development was followed up until 18 mo corrected age. Parenchymal lesions seen in MRI at term predicted cerebral palsy (CP) with 100% sensitivity and 79% specificity, the corresponding figures for US being 67% and 85%, respectively. Parenchymal lesions in MRI, excluding subependymal haemorrhages, predicted CP with a sensitivity of 82% and a specificity of 97%, the corresponding figures for US being 58% and 100%, respectively. Delayed myelination, ventricular/brain ratios and widths of the extracerebral spaces failed to predict CP. Term age is a good time for neuroradiological examinations in prematurely born high-risk infants. Parenchymal lesions seen in MRI are reliable predictors for CP. [source]

Vanishing white matter disease: A review with focus on its genetics

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2006
Jan C. Pronk
Abstract Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts of cerebral white matter vanish and are replaced by fluid. Autopsy confirms white matter rarefaction and cystic degeneration. The process of localization and identification of the first two genes related to VWM, EIF2B5 and EIF2B2, was facilitated by two founder effects in the Dutch population. EIF2B5 and EIF2B2 encode the , and , subunits of translation initiation factor eIF2B. Soon it was shown that mutations in all five eIF2B subunit genes can cause VWM. EIF2B is essential for the initiation of translation of RNA into protein and is involved in regulation of the process, especially under stress conditions, which may explain the sensitivity to stress conditions observed in VWM patients. The pathophysiology of the disease is still poorly understood. MRDD Research Reviews 2006;12:123,128. © 2006 Wiley-Liss, Inc. [source]

Cognitive visual dysfunctions in preterm children with periventricular leukomalacia

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2009
ELISA FAZZI MD PHD
Aim, Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method, We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6,15y; mean gestational age 30wks, range 28,36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full-scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions. Results, Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual,spatial skills, and visual memory, and sparing of visual associative abilities, non-verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions. Interpretation, We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed. [source]

Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2008
David E Traul MD PhD
We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity. [source]

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2002
Elizabeth R Sowell PhD
The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents. [source]

Changes within maturing neurons limit axonal regeneration in the developing spinal cord

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2006
Murray Blackmore
Abstract Embryonic birds and mammals display a remarkable ability to regenerate axons after spinal injury, but then lose this ability during a discrete developmental transition. To explain this transition, previous research has emphasized the emergence of myelin and other inhibitory factors in the environment of the spinal cord. However, research in other CNS tracts suggests an important role for neuron-intrinsic limitations to axon regeneration. Here we re-examine this issue quantitatively in the hindbrain-spinal projection of the embryonic chick. Using heterochronic cocultures we show that maturation of the spinal cord environment causes a 55% reduction in axon regeneration, while maturation of hindbrain neurons causes a 90% reduction. We further show that young neurons transplanted in vivo into older spinal cord can regenerate axons into myelinated white matter, while older axons regenerate poorly and have reduced growth cone motility on a variety of growth-permissive ligands in vitro, including laminin, L1, and N-cadherin. Finally, we use video analysis of living growth cones to directly document an age-dependent decline in the motility of brainstem axons. These data show that developmental changes in both the spinal cord environment and in brainstem neurons can reduce regeneration, but that the effect of the environment is only partial, while changes in neurons by themselves cause a nearly complete reduction in regeneration. We conclude that maturational events within neurons are a primary cause for the failure of axon regeneration in the spinal cord. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]

Spontaneous kicking in full-term and preterm infants with and without white matter disorder

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 6 2010
Linda Fetters
Abstract Early damage to white matter of the brain may have developmental consequences for prematurely born infants including the coordination of leg movements. Our perspective is that white matter damage initiates an ontogenetic course that may lead to movement dysfunction leading to disability. In this study, spontaneous kicking in the human infant is a "window" for evaluating the potential consequences of perinatal brain damage for sensori-motor coordination. We compare the intra-limb coordination patterns of 5-month-old premature infants with white matter damage (PTWMD) to a group of prematurely born infants without WMD (PT) and a group of full-term (FT) infants. The PT group demonstrates advanced kicking patterns in comparison to both the PTWMD and FT groups. The PTWMD group has less mature patterns than the FT group on some, but not all measures. The movement challenge for PTWMD infants may be in the transition from spontaneous kicking to movements with the legs that require decoupling of intralimb joints. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 524,536, 2010. [source]

Cross-sectional analysis of the association between age and corpus callosum size in chimpanzees (Pan troglodytes)

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2010
William D. Hopkins
Abstract The CC is the major white matter tract connecting the cerebral hemispheres and provides for interhemispheric integration of sensory, motor and higher-order cognitive information. The midsagittal area of the CC has been frequently used as a marker of brain development in humans. We report the first investigation into the development of the corpus callosum and its regional subdivisions in chimpanzees (Pan troglodytes). Magnetic resonance images were collected from 104 chimpanzees (female n,=,63, male n,=,41) ranging in age from 6 years (pre-pubescent period) to 54 years (old age). Sustained linear growth was observed in the area of the CC subdivision of the genu; areas of the posterior midbody and anterior midbody displayed nonlinear growth during development. After adjusting for total brain size, we observed linear growth trajectories of the total CC and CC subdivisions of the genu, posterior midbody, isthmus and splenium, and nonlinear growth trajectories of the rostral body and anterior midbody. These developmental patterns are similar to the development of the CC in humans. As the growth curves of the CC mirrors growth seen in the percentage of white matter in humans, our results suggest chimpanzees show continued white matter development in regions related to cognitive development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:133,141, 2010 [source]

Application of the equivalent multipole moment method with polar translations to forward calculation of neuromagnetic fields

ELECTRONICS & COMMUNICATIONS IN JAPAN, Issue 4 2008
Shoji Hamada
Abstract This paper describes an application of the equivalent multipole moment method (EMMM) with polar translations to calculation of magnetic fields induced by a current dipole placed in a human head model. Although the EMMM is a conventional Laplacian field solver based on spherical harmonic functions, the polar translations enable it to treat eccentric and exclusive spheres in arbitrary arrangements. The head model is composed of seven spheres corresponding to skin, two eyeballs, skull, cerebral spinal fluid, gray matter, and white matter. The validity of the calculated magnetic fields and the magnetic flux linkages with a loop coil located near the model is successfully confirmed by the reciprocity theorem derived by Eaton. © 2008 Wiley Periodicals, Inc. Electron Comm Jpn, 91(4): 34,44, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10079 [source]

Widespread axonal damage in the brain of drug abusers as evidenced by accumulation of ,-amyloid precursor protein (,-APP): an immunohistochemical investigation

ADDICTION, Issue 9 2006
Andreas Büttner
ABSTRACT Background In drug abusers, white matter changes have been described by neuroimaging analyses in different brain regions. A specific pattern of involvement or a predominance of a specific brain region could not be drawn. Aims To examine alterations of the white matter as a possible morphological substrate of the neuroimaging findings. Methods Brain specimens of 30 polydrug abusers and 20 controls were obtained at autopsy. The white matter from 11 different brain regions was analysed by means of immunohistochemistry for ,-amyloid precursor protein (,-APP), a marker of axonal damage. Findings In the white matter of polydrug abusers, ,-APP-immunopositive accumulations were increased significantly compared to controls. They were more prominent in the brains of younger drug abusers than in those of the elderly. With the exception of five cases (four polydrug abusers and one control case), there were no significant white matter changes seen on myelin-stained sections, but there was a concomitant microglial activation. Conclusions Our results show a significant axonal damage in the brains of polydrug abusers, which might represent the morphological substrate of a chronic-progressive drug-induced toxic-metabolic process. It is yet to be established if the observed changes are responsible for the alterations seen in different neuroimaging analyses and which drugs of abuse might be of major pathogenetic significance. [source]

Neuroradiologic Findings in Focal Cortical Dysplasia: Histologic Correlation with Surgically Resected Specimens

EPILEPSIA, Issue 2001
Kazumi Matsuda
Summary: ,Purpose: We investigated the neuroradiologic characteristics of focal findings of surgically resected specimens obtained from 47 patients with focal cortical dysplasia (FCD). Methods: Forty cases were detected by magnetic resonance imaging (MRI), and two cases were detected only by single-photon emission computed tomography (SPECT), but five cases could not be detected before operation. Results: MRI revealed abnormal gyri and sulci in 34 patients (pachygyric in 18, polymicrogyric in 10, both in six), and blurring of the gray matter,white matter junction in 29 (72%) patients. Signal abnormalities were found in 36 (90%) patients, in the gray matter in 32, with white matter in 30, and at the gray matter,white matter junction in 13. Moreover, peculiar patterns of abnormal signals in the white matter were recognized, including remarkably abnormal subcortical signals of T2 hyperintensity and T1 hypointensity adjacent to the dysplastic cortex in 15 cases, high radiated T2 signals extending from the ependymal surface of the lateral ventricle to the overlying cortex in 11 cases, and widespread abnormal signals in the white matter with gray matter involvement in four cases. Histologically, these abnormal signals corresponded to various degrees of dyslamination and morphologic abnormalities of neurons and glial cells in the gray matter, and to dysmyelination, ectopic clustering of dysplastic neurons, glial proliferation, and necrotic change in the white matter. Regional cerebral blood flow SPECT showed interictal hypoperfusion in 29 (62%) of the 47 patients, interictal hyperperfusion in two, and ictal hyperperfusion in 28 of the 34 patients associated with FCD. [123I]iomazenil SPECT demonstrating the distribution of central benzodiazepine receptors showed low accumulations localized spatially corresponding to the epileptogenic foci associated with FCD in seven of eight patients. Conclusions: These results demonstrate that neuroimaging reflects various structural and functional changes closely related to epileptogenesis in FCD. [source]

Cortical Dysplasias and Epilepsy: Multi-Institutional Survey in Japan

EPILEPSIA, Issue 2000
Morimi Shimada
Purpose: Cortical dysplasia (CD) is a major brain malformation causing intractable epilcpsy. Neurosurgery now succcssfully controls some intractable epilepsies associated with CD. In this study, thc incidence 11 epilepsy and thc frequency of seizurcs were analyzed in different types 01 CD. Methods: This study, supported by a rcse;lrch grant from the Ministry of Health and Wellare of Japan, is part of a research project on the clinical presentation and pathogcnesis of brain dysgenesis. Questionnaires regarding the type of CD, family and pact historics, clinical signs and symptoms and their severity were distributed to I200 institutions comprising child neurologists or pediatricians. CDs werc classified into following 6 types; lissencephaly (agyria-pachygyria spcctrum), cobblestone lissencephaly, polymicrogyria including schizencephaly and hilateral perisylvian syndrome, diffuse heterotopia, focal heterotopia, and hemiinegalencephaly. All patients who had been diagnoscd as CD either by MRI, CT, autopsy or histological cxamination at or after surgical treatment wcre included. Diagnosis of CD by CT or MRI was mainly made by a radiologist, child neurologist, or pediatrician. Double classification was corrected. Epilepsy was classified according to criteria of the ILEA. Seizure frcquencies wcre recorded. Results: A total or 676 cases from 328 institutions was availablc, and distributed as follows: 277 of lissencephaly, I48 of cobblestone lissencephaly (10 cases of Walkcr-Warburg syndrome and 138 Fukuyaina type congcnital muscular dystrophy), I30 of polymicrogyria, 40 of diffuse heterotopia (24 subcortical band hetcrotopia and I6 perivcntricular nodular hcterotopia), 37 of focal heterotopia, and 44 of hemimegalencephaly. In 130 cases of polymicrogyria, 13 cases of bilatcral perisylvian syndrome, and 38 cases of schizencephaly were includcd. Of 667 cases available for study, 500 (75.0%) had epilepsy in which generalized epilepsy including West and Lcnnox syndromes comprised 54.1 % and localization-related epilepsies comprised 46.7%. Thc frequency of seizures could be ascertained in 455 cases, of which 36.0% had daily seizures, and I I .4%) had more than onc seizure per week. The incidencc of epilepsy in cach type of CD was as follows: 86% inlissencephaly, 50% in cobblestone lissencephaly (patients with WalkcrWarburg syndrome had epilepsy in 90%, whercas those with Fukuyama type congenital muscular dystrophy had epilepsy in 46.7%), 71.3% in polymicrogyria, 77.5% in diffusc hetcrotopia (9 1.7% in subcortical band heterotopia and 56.2% in periventricular nodular heterotopia), 74.3% in focal heterotopia, and 93.2% in hemimegalcncephaly. Conclusion: As recent investigations have reported, this study confirmed the high incidence of intractable cpilepsy in CDs. Epilepsy was more prevalcnt in cases with subcortical heterotopia than i n cascs with periventricular nodular helcrotopia. Thc incidcnce or epilepsy was also higher in the focal hcterotopias located subcortically than those dccper in white matter or in the periventricular region. Thcse differences in incidence of epilepsy depending on the location of hcterotopia may give somc clues to the nature of epileptogenesis in CD. [source]

IMAGING STUDY: Prefrontal cortex morphometry in abstinent adolescent marijuana users: subtle gender effects

ADDICTION BIOLOGY, Issue 4 2009
Krista Lisdahl Medina
ABSTRACT Adult human studies suggest frontal dysfunction associated with chronic marijuana (MJ) use, but due to continued neuromaturation, adult studies may not generalize to adolescents. This study characterized prefrontal cortex (PFC) morphometry in chronic MJ-using adolescents following 1 month of monitored abstinence. Data were collected from MJ users (n = 16) and controls (n = 16) aged 16,18. Extensive exclusionary criteria included co-morbid psychiatric and neurologic disorders. Substance use and anatomical measures were collected after 28 days of monitored abstinence. PFC volumes were ascertained from manual tracing by reliable raters on high-resolution magnetic resonance images. After controlling for lifetime alcohol use, gender and intracranial volume, MJ users did not differ from controls in PFC volume. However, marginal group-by-gender interactions were observed (P < 0.09): female MJ users demonstrated comparatively larger PFC volumes while male MJ users had smaller volumes compared with same-gender controls. Further, group status and total PFC volume interacted in predicting executive functioning (P < 0.05). Among MJ users, smaller PFC total volume was associated with better executive functioning while the opposite pattern was seen among the controls. These preliminary results indicate that gender may moderate the relationship between MJ use and PFC morphometry. Given the relationship between larger PFC total volumes and poorer executive functioning among MJ users, female MJ users may be at increased risk for neurocognitive consequences. Future research will measure PFC gray and white matter separately and follow boys and girls over adolescence to examine the influence of MJ use on neurodevelopment. [source]

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009
M. L. F. Balthazar
Background:, Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. Methods:, We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. Results:, Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. Discussion:, We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD. [source]

Age-related white matter lesions are associated with reduction of the apparent diffusion coefficient in the cerebellum

EUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2007
P. Bugalho
Cerebellar apparent diffusion coefficient (ADC) was found to be increased after acute cerebral hemispheric stroke. There are no data on cerebellar ADC changes in patients with chronic, age-related white matter lesions (ARWML). We aimed to determine longitudinal ADC variations on cerebral hemispheric and cerebellar white matter regions of patients with ARWML in order to study relations between ADC changes in both regions. ADC was measured serially (1-year interval) on lesioned periventricular frontal white matter, frontal and parietoccipital normal appearing white matter and middle cerebellar peduncles, on 19 aged patients with ARWML, which also underwent gait assessment. We compared regional ADC at 0 and 1 year and calculated variation percentages for each region. Correlation analysis was made between ADC variation in cerebellar regions and in contralateral hemispheric regions and between cerebellar ADC at 1 year and walking speed. After 1 year, ADC was higher on lesioned periventricular frontal white matter and lower on cerebellar regions. ADC variations on these regions were negatively correlated. Cerebellar ADC measured after 1 year was positively correlated with walking speed. This suggests a link between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles. Chronic ischemia in frontal white matter could have interrupted frontal-cerebellar circuits, producing hypometabolism in cerebellar regions (and worse performance on motor tasks), decreased perfusion and hence ADC reduction. [source]

Neurologic manifestations of ulcerative colitis

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007
R. Scheid
Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome. [source]

Cerebral blood flow in patients with diffuse axonal injury , examination of the easy Z -score imaging system utility

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007
T. Okamoto
To evaluate the utility of easy Z -score imaging system (eZIS) in 27 diffuse axonal injury (DAI) cases. Twenty-seven DAI patients were examined with an magnetic resonance imaging (MRI) T2* sequence and with eZIS (seven women, 20 men; age range, 19,35 years; median age: 26.6 years). In this investigation, we excluded patients who exhibited complications such as acute subdural hematoma, acute epidural hematoma, intracerebral hematoma, or brain contusion. We examined the neuropsychological tests and correlated with findings from MRI/eZIS. Furthermore, we evaluated the degree of ventricular enlargement in the bifrontal cerebroventricular index (CVI). Patients were divided into two groups: the enlargement group (bifrontal CVI > 35%, 12 patients) and the non-enlargement group (bifrontal CVI < 35%, 15 patients). All of the patients showed cognitive deficits as observed from the neuropsycological test results. Fifteen out of 27 patients by MRI T1/T2 weighted images and fluid attenuated inversion recovery (FLAIR), 22 out of 27 patients by MRI T2* weighted images and 24 out of 27 patients by eZIS showed abnormal findings. In MRI T2* weighted imaging, the white matter from the frontal lobe, corpus callosum, and brainstem showed abnormal findings. With eZIS, 22 patients (81.5%) showed blood flow degradation in the frontal lobe, and 12 patients (44.4%) in cingulate gyrus. In the enlargement group, Functional Independence Measure, Mini-Mental State Examination, Verbal IQ (VIQ)/Full Scale IQ (FIQ), Trail Making Test-B (TMT-B), and Non-paired of Miyake Paired Test were significantly lower. Amongst 12 patients without ventricular enlargement who had no abnormal findings in MRI T1/T2 weighted images and FLAIR, abnormal findings were detectable in seven patients with MRI T2* weighted imaging and to 10 patients with eZIS. Results of the MRI examination alone cannot fully explain DAI frontal lobe dysfunction. However, addition of the eZIS-assisted analysis derived from the single photon emission computed tomography (SPECT) data enabled us to understand regions where blood flow was decreased, i.e., where neuronal functions conceivably might be reduced. [source]

PET visualization of microglia in multiple sclerosis patients using [11C]PK11195

EUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2003
J. C. Debruyne
Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up-regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno-pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium-lesions was significantly increased compared with normal white matter. Uptake in T2-lesions was generally decreased, suggesting a PBR down-regulation. However, uptake values increased whenever a clinical or MR-relapse was present, suggestive for a dynamic process with a transient PBR up-regulation. During disease progression, an increase of normal-appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS. [source]

Linking structural, metabolic and functional changes in multiple sclerosis

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2001
Massimo Filippi
In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has markedly improved our ability to detect the macroscopic abnormalities of the brain and spinal cord. New quantitative magnetic resonance (MR) approaches with increased sensitivity to subtle normal-appearing white matter (NAWM) and grey matter changes and increased specificity to the heterogeneous pathological substrates of MS may give information complementary to conventional MRI. Magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to provide important information on the structural changes occurring within and outside T2-visible lesions. Magnetic resonance spectroscopy (MRS) adds information on the biochemical nature of such changes. Functional MRI might quantify the efficiency of brain plasticity in response to MS injury and improve our understanding of the link between structural damage and clinical manifestations. The present review summarizes how the application of these MR techniques to the study of MS is dramatically changing our understanding of how MS causes irreversible neurological deficits. [source]

Extracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identities

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2010
Chiara Rolando
Abstract Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host-specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region-specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar-specific regulatory genes. In addition, their major structural features, the expression profiles of type-specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear-cut cerebellar identities. [source]

Overexpression of GAP-43 modifies the distribution of the receptors for myelin-associated growth-inhibitory proteins in injured Purkinje axons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2009
Simona Foscarin
Abstract Neurons with enhanced intrinsic growth capabilities can elongate their axons into non-permissive territories, but the mechanisms that enable the outgrowing processes to overcome environmental inhibition are largely unknown. To address this issue, we examined adult mouse Purkinje cells that overexpress the axonal growth-associated protein GAP-43. After injury, these neurons exhibit sprouting along the intracortical neuritic course and at the severed stump in the white matter. To determine whether GAP-43-overexpressing Purkinje cells are responsive to extrinsic inhibitory cues, we investigated the content and subcellular localization of major receptors for myelin-associated inhibitory proteins, PlexinB1 and the Nogo receptor (NgR) with the related co-receptors LINGO-1 and p75. Expression of these molecules, estimated by measuring perikaryal immunostaining intensity and Western blot, was not different in wild-type or transgenic mice, and it was not overtly modified after axotomy. Following injury, however, the content of PlexinB1 was significantly reduced in GAP-43-overexpressing neurites. Furthermore, in the same axons the distribution of both PlexinB1 and NgR was altered, being inverse to that of GAP-43. Labelling for the two receptors was conspicuously reduced on the axonal surface and it was almost undetectable in the outgrowing sprouts, which showed strong GAP-43 immunoreactivity. These observations indicate that although GAP-43 overexpression does not modify the expression of receptors for myelin-associated inhibitory factors, it interferes with their subcellular localization and exposure on the neuritic membrane. Therefore, GAP-43 promotes axon growth by multiple synergistic mechanisms that potentiate the intrinsic motility of the elongating processes, while reducing their sensitivity to environmental inhibition. [source]

Glial cell loss, proliferation and replacement in the contused murine spinal cord

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007
Judith M. Lytle
Abstract Studies in the rat have shown that contusive spinal cord injury (SCI) results in devastating pathology, including significant loss of mature oligodendrocytes and astrocytes even in spared white matter. Subsequently, there is increased proliferation of endogenous NG2+ cells, postulated to contribute to replacement of mature glia chronically, which is important for functional recovery. Studies of mechanisms that stimulate endogenous progenitor cells would be facilitated by using mouse models with naturally occurring and genetically engineered mutations. To determine whether the murine response is similar to that in the rat, we performed contusive SCI on adult female C57Bl/6 mice at the T8,9 level. Animals received bromodeoxyuridine injections in the first week following injury and were killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia and the temporal,spatial response of NG2+ cells after SCI in the (C57Bl/6) mouse was very similar to that in the (Sprague,Dawley) rat. By 24 h after SCI nearly half of the macroglia in spared ventral white matter had been lost. Cell proliferation was increased at 1,7 DPI, peaking at 3,4 DPI. Dividing cells included NG2+ cells and Cd11b+ macrophages and microglia. Furthermore, cells dividing in the first week expressed markers of mature glia at 28 DPI. The similarities in endogenous progenitor cell response to SCI in the mouse and rat suggest that this is a fundamental injury response, and that transgenic mouse models may be used to further probe how this cellular response to SCI might be enhanced to improve recovery after SCI. [source]