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Brain Abnormalities (brain + abnormality)
Kinds of Brain Abnormalities Selected AbstractsMagnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7ALCOHOLISM, Issue 1 2010Elizabeth A. Godin Background:, This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:, C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 ,m isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:, Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:, Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8ALCOHOLISM, Issue 6 2009Scott E. Parnell Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source] Brain abnormalities in antisocial individuals: implications for the lawBEHAVIORAL SCIENCES & THE LAW, Issue 1 2008Yaling Yang B.S. With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala,hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. Copyright © 2008 John Wiley & Sons, Ltd. [source] Brain magnetic resonance imaging abnormalities in neuromyelitis opticaACTA NEUROLOGICA SCANDINAVICA, Issue 4 2008Y. Li Objective,,, Brain abnormalities in neuromyelitis optica (NMO) attracted much attention. Our study was to identify the brain magnetic resonance imaging (MRI) abnormalities in Chinese NMO patients. Methods,,, Patients who fulfilled the latest diagnostic criteria of NMO proposed by Wingerchuk et al. [Neurology 66 (2006) 1485] and whose brain MRI did not meet the multiple sclerosis (MS) criteria of McDonald et al. [Ann Neurol 50 (2001) 121] were selected to perform MRI scanning of the brain, spinal cord and optic nerves. Results,,, Twenty-eight of 33 patients (84.8%) had abnormal MRI findings. Twenty-two patients (66.7%) presented with well-defined brain parenchymal lesions and the other six patients (18.2%) with macroscopic symmetrical diffuse hyperintensities in deep white matter. Fifteen of 22 patients had more than one lesion (,2 lesions) and the other seven patients had single lesion. In the supratentorium, most lesions were punctate or small round dot and non-specific in juxtacortical, subcortical and deep white matter regions, a few were patchy atypical confluent lesions. Brainstem was easily involved (14/33, 42.4%) especially in medulla (7/33, 21.2%). Conclusions,,, This study demonstrates the characteristics of brain MRI abnormalities in Chinese NMO patients, which are helpful to the revision of diagnostic criteria for NMO. [source] Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI studyACTA PAEDIATRICA, Issue 7 2007Sandra Horsch Abstract Aims: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors. Methods: All infants with gestational age <27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age. Images were analysed using a previously established scoring system for grey and white matter abnormalities. Results: No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities. Conclusion: The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing. [source] The use of neuroimaging in the diagnosis of mitochondrial diseaseDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010Seth D. Friedman Abstract Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:129,135. [source] Autism spectrum disorder and underlying brain mechanism in the oculoauriculovertebral spectrumDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2007Maria Johansson MD As part of a multidisciplinary study, the rate of autism spectrum disorder (ASD), learning disability (LD), and brain abnormalities was examined in 20 participants (12 males, 8 females; age range 8mo-17y, mean age 8y 1mo) diagnosed as falling within the oculoauriculovertebral spectrum (OAV). A neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Two individuals met diagnostic criteria for autism, one for autistic-like condition, and five for autistic traits. Four patients had mild LD, three severe LD, two profound LD, and two borderline intellectual functioning. Neuroimaging indicated cerebral abnormalities in more than half of the patients. Abnormalities of white/grey matter were found in more than half of examined individuals; enlargement of ventricles in more than a third. Results indicate that at least a subgroup of ASD may be associated with errors in early embryonic brain development. Awareness of the coexistence of OAV/ASD is important in habilitation care of individuals with OAV. [source] Modulation of spatial attention in a child with developmental unilateral neglectDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2003Veronika B Dobler MD Attentional neglect of left space is one of the most striking acquired neurological disorders of adulthood. Recent evidence indicates a link between left spatial neglect and general right-hemisphere impairments in sustained attention and alertness. Poor sustained attention and alertness is also a central feature of other disorders, particularly childhood attention-deficit-hyperactivity disorder (ADHD). Here we present the case of a 7-year-old male showing that frank neglect can be present in children with sustained attention problems without a clear aetiological event, or obvious structural brain abnormalities as indicated by a normal MRI. Experimental amelioration of the neglect through left-hand movement and externally alerting stimulation by uninformative sounds further suggest close similarities to the adult disorder. We suggest that such distortions of spatial attention may be more common in childhood than previously thought. [source] High-resolution mapping of the Gli3 deletion in the mouse extra-toesH mutantGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 3 2007Matthieu Genestine Abstract Extra-toes is a semidominant mutation that affects the Gli3 gene and provokes limb and brain abnormalities. Among the different alleles of this mutation, XtH is due to a deletion that has not yet been fully characterized. Using a PCR-based strategy, we undertook a high-resolution mapping of this deletion and confirmed that XtH is a null allele of Gli3. We further designed a PCR test to identify unequivocally heterozygous and homozygous embryos from their wild-type littermates. Despite the length of the XtH deletion, available data on the mouse genome indicate that no genes other than Gli3 are deleted in XtH mutants. Thus, the XtH mutation can be used as a model for studying the effects that absence of Gli3 function has during development. genesis 45:107,112, 2007. © 2007 Wiley-Liss, Inc. [source] Anterior cingulate dysfunction in geriatric depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2008George S. Alexopoulos Abstract Background Although several brain abnormalities have been identified in geriatric depression, their relationship to the pathophysiological mechanisms leading to the development and perpetuation of this syndrome remain unclear. Methods This paper reviews findings on the anterior cingulate cortex (ACC) function and on the relationship of ACC abnormalities to the clinical presentation and the course of geriatric depression in order to elucidate the pathophysiological role of ACC in this disorder. Results The ACC is responsible for conflict detection and emotional evaluation of error and is connected to brain structures that regulate mood, emotional valence of thought and autonomic and visceral responses, which are functions disturbed in depression. Geriatric depression often is accompanied by abnormalities in some executive functions and has a clinical presentation consistent with ACC abnormalities. Indices of ACC dysfunction are associated with adverse outcomes of geriatric depression. Conclusions Converging findings suggest that at least some ACC functions are abnormal in depression and these abnormalities are pathophysiologically meaningful. Indices of ACC dysfunction may be used to identify subgroups of depressed elderly patients with distinct illness course and treatment needs and serve as the theoretical background for novel treatment development. Copyright © 2007 John Wiley & Sons, Ltd. [source] Lactate Detection by MRS in Mitochondrial Encephalopathy: Optimization of Technical ParametersJOURNAL OF NEUROIMAGING, Issue 1 2008Antônio José da Rocha MD ABSTRACT Mitochondriopathies are a heterogeneous group of diseases with variable phenotypic presentation, which can range from subclinical to lethal forms. They are related either to DNA mutations or nuclear-encoded mitochondrial genes that affect the integrity and function of these organelles, compromising adenosine triphosphate (ATP) synthesis. Magnetic resonance (MR) is the most important imaging technique to detect structural and metabolic brain abnormalities in mitochondriopathies, although in some cases these studies may present normal results, or the identified brain abnormalities may be nonspecific. Magnetic resonance spectroscopy (MRS) enables the detection of high cerebral lactate levels, even when the brain has normal appearance by conventional MR scans. MRS is a useful tool for the diagnosis of mitochondriopathies, but must be correlated with clinical, neurophysiological, biochemical, histological, and molecular data to corroborate the diagnosis. Our aim is to clarify the most relevant issues related to the use of MRS in order to optimize its technical parameters, improving its use in the diagnosis of mitochondriopathies, which is often a challenge. [source] Late human cytomegalovirus (HCMV) proteins inhibit differentiation of human neural precursor cells into astrocytesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2007Jenny Odeberg Abstract Human cytomegalovirus (HCMV) is the most common cause of congenital infections in developed countries, with an incidence varying between 0.5,2.2%. Such infection may be the consequence of either a primary infection or reactivation of a latent infection in the mother and the outcome may vary from asymptomatic to severe brain disorders. Moreover, infants that are asymptomatic at the time of birth may still develop neurologic sequelae at a later age. Our hypothesis is that infection of stem cells of the central nervous system by HCMV alters the proliferation, differentiation or migration of these cells, and thereby gives rise to the brain abnormalities observed. We show that infection of human neural precursor cells (NPCs) with the laboratory strain Towne or the clinical isolate TB40 of HCMV suppresses the differentiation of these cells into astrocytes even at an multiplicity of infection (MOI) as low as 0.1 (by 33% and 67%, respectively). This inhibition required active viral replication and the expression of late HCMV proteins. Infection as late as 24 hr after the onset of differentiation, but not after 72 hr, also prevented the maturation of infected cultures. Furthermore, in cultures infected with TB40 (at an MOI of 1), approximately 54% of the cells were apoptotic and cell proliferation was significantly attenuated. Clearly, HCMV can reduce the capacity of NPCs to differentiate into astrocytes and this effect may provide part of the explanation for the abnormalities in brain development associated with congenital HCMV infection. © 2006 Wiley-Liss, Inc. [source] BOLD Response During Spatial Working Memory in Youth With Heavy Prenatal Alcohol ExposureALCOHOLISM, Issue 12 2009Andrea D. Spadoni Background:, Prenatal alcohol exposure has been consistently linked to neurocognitive deficits and structural brain abnormalities in affected individuals. Structural brain abnormalities observed in regions supporting spatial working memory (SWM) may contribute to observed deficits in visuospatial functioning in youth with fetal alcohol spectrum disorders (FASDs). Methods:, We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level dependent (BOLD) response in alcohol-exposed individuals during a SWM task. There were 22 young subjects (aged 10,18 years) with documented histories of heavy prenatal alcohol exposure (ALC, n = 10), and age- and sex-matched controls (CON, n = 12). Subjects performed a SWM task during fMRI that alternated between 2-back location matching (SWM) and simple attention (vigilance) conditions. Results:, Groups did not differ on task accuracy or reaction time to the SWM condition, although CON subjects had faster reaction times during the vigilance condition (617 millisecond vs. 684 millisecond, p = 0.03). Both groups showed similar overall patterns of activation to the SWM condition in expected regions encompassing bilateral dorsolateral prefrontal lobes and parietal areas. However, ALC subjects showed greater BOLD response to the demands of the SWM relative to the vigilance condition in frontal, insular, superior, and middle temporal, occipital, and subcortical regions. CON youth evidenced less increased brain activation to the SWM relative to the vigilance task in these areas (p < 0.05, clusters > 1,664 ,l). These differences remained significant after including Full Scale IQ as a covariate. Similar qualitative results were obtained after subjects taking stimulant medication were excluded from the analysis. Conclusions:, In the context of equivalent performance to a SWM task, the current results suggest that widespread increases in BOLD response in youth with FASDs could either indicate decreased efficiency of relevant brain networks, or serve as a compensatory mechanism for deficiency at neural and/or cognitive levels. In context of existing fMRI evidence of heightened prefrontal activation in response to verbal working memory and inhibition demands, the present findings may indicate that frontal structures are taxed to a greater degree during cognitive demands in individuals with FASDs. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8ALCOHOLISM, Issue 6 2009Scott E. Parnell Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source] Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complexNEUROPATHOLOGY, Issue 6 2008Karin Boer Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder caused by mutations in either the TSC1 or TSC2 genes and characterized by developmental brain abnormalities. In the present study we discuss the neuropathological findings of a 32-year-old patient with a germ-line mutation in the TSC2 gene. Post mortem MRI combined with histology and immunocytochemical analysis was applied to demonstrate widespread anatomical abnormalities of gray and white matter structure. TSC brain lesions were analyzed for loss of heterozygosity (LOH) on chromosome 16p13. The neuropathological supratentorial abnormalities were represented by multiple subependymal nodules (SENs) and cortical tubers. In addition to cerebral cortical lesions, cerebellar lesions and hippocampal sclerosis were also observed. LOH was not found in the cortical tubers and SENs of this patient. Immunocytochemical analysis of the TSC brain lesions confirmed the cell-specific activation of the mTOR pathway in cortical tubers, SENs and cerebellum, as well as differential cellular localization of hamartin and tuberin, the TSC1 and TSC2 gene products. Examination of the pathological brain regions revealed activated microglial cells and disruption of blood-brain barrier permeability. Predominant intralesional cell-specific distribution was also detected for the multidrug transporter protein P-gp, possibly explaining the mechanisms underlying the pharmacoresistance to antiepileptic drugs. Autopsy findings confirm the complexity of the brain abnormalities encountered in TSC patients and proved useful in clarifying certain aspects of the pathogenesis, epileptogenesis and pharmacoresistance of TSC lesions. [source] Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucencyPRENATAL DIAGNOSIS, Issue 5 2001P. Schwärzler Abstract A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero. Copyright © 2001 John Wiley & Sons, Ltd. [source] Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive,compulsive disorder: A voxel-based morphometric studyPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2010Ryohei Matsumoto MD Aims:, Previous morphometric studies using magnetic resonance imaging (MRI) have revealed structural brain abnormalities in obsessive,compulsive disorder (OCD). The aim of the present study was to investigate the alterations in brain structure of patients with OCD using a voxel-based morphometry (VBM) method. Methods:, Sixteen patients with OCD free of comorbid major depression, and 32 sex- and age-matched healthy subjects underwent MRI using a 1.5-T MR scanner. OCD severity was assessed with the Yale,Brown Obsessive,Compulsive Scale (mean ± SD: 22 ± 7.6; range: 7,32). MR images were spatially normalized and segmented using the VBM5 package (http://dbm.neuro.uni-jena.de/vbm/). Statistical analysis was performed using statistical parametric mapping software. Results:, Significant reductions in regional gray matter volume were detected in the left caudal anterior cingulate cortex and right dorsal posterior cingulate cortex in the patients with OCD as compared to healthy controls (uncorrected, P < 0.001). No significant differences in white matter volumes were observed in any brain regions of the patients. No significant correlation between Yale,Brown Obsessive,Compulsive Scale score and regional gray matter or white matter volume was observed. Conclusions:, Regional gray matter alteration in the dorsal cingulate cortex, which is suggested to play a role in non-emotional cognitive processes, may be related to the pathophysiology in OCD. [source] Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorderTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 12 2007Sarah Brieber Background:, Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap between ADHD and autism at the behavioural, neurocognitive, and brain levels are needed. Methods:, We examined regional grey matter differences and similarities in children and adolescents with ASD and ADHD in comparison to healthy controls using structural magnetic resonance imaging (MRI) and voxel-based morphometry. Results:, With regard to clinical criteria, the clinical groups did not differ with respect to ADHD symptoms; however, only patients with ASD showed deficits in social communication and interaction, according to parental rating. Structural abnormalities across both clinical groups compared to controls became evident as grey matter reductions in the left medial temporal lobe and as higher grey matter volumes in the left inferior parietal cortex. In addition, autism-specific brain abnormalities were found as increased grey matter volume in the right supramarginal gyrus. Conclusions:, While the shared structural deviations in the medial temporal lobe might be attributed to an unspecific delay in brain development and might be associated with memory deficits, the structural abnormalities in the inferior parietal lobe may correspond to attentional deficits observed in both ASD and ADHD. By contrast, the autism-specific grey matter abnormalities near the right temporo-parietal junction may be associated with impaired ,theory of mind' abilities. These findings shed some light on both similarities and differences in the neurocognitive profiles of ADHD and ASD patients. [source] R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007Anton Reiner Abstract The R6/2 mouse possesses mutant exon 1 of human Hdh, and R6/2 mice with 150 CAG repeats show neurological abnormalities by 10 weeks and die by 15 weeks. Few brain abnormalities, however, are evident at death, other than widespread ubiquitinated neuronal intranuclear inclusions (NIIs). We constructed R6/2t+/t, , wildtype (WT) chimeric mice to prolong survival of R6/2 cells and determine if neuronal death and/or neuronal injury become evident with longer survival. ROSA26 mice (which bear a lacZ transgene) were used as WT to distinguish between R6/2 and WT neurons. Chimeric mice consisting partly of R6/2 cells lived longer than pure R6/2 mice (up to 10 months), with the survival proportional to the R6/2 contribution. Genotypically R6/2 cells formed NIIs in the chimeras, and these NIIs grew only slightly larger than in 12-week pure R6/2 mice, even after 10 months. Additionally, neuropil aggregates formed near R6/2 neurons in chimeric mice older than 15 weeks. Thus, R6/2 neurons could survive well beyond 15 weeks in chimeras. Moreover, little neuronal degeneration was evident in either cortex or striatum by routine histological stains. Nonetheless, striatal shrinkage and ventricular enlargement occurred, and striatal projection neuron markers characteristically reduced in Huntington's disease were diminished. Consistent with such abnormalities, cortex and striatum in chimeras showed increased astrocytic glial fibrillary acidic protein. These results suggest that while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein. J. Comp. Neurol. 505:603,629, 2007. © 2007 Wiley-Liss, Inc. [source] Lacunar stroke is associated with diffuse blood,brain barrier dysfunction,ANNALS OF NEUROLOGY, Issue 2 2009FMedSci, Joanna M. Wardlaw MD Objective Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood,brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. Methods We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. Results We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference. Interpretation Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke. Ann Neurol 2009;65:194,202 [source] Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complexANNALS OF NEUROLOGY, Issue 4 2008Ling-Hui Zeng MD Objective Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in preventing or treating epilepsy in patients with TSC. Mice with conditional inactivation of the Tsc1 gene primarily in glia (Tsc1GFAPCKO mice) develop glial proliferation, progressive epilepsy, and premature death. Here, we tested whether rapamycin could prevent or reverse epilepsy, as well as other cellular and molecular brain abnormalities in Tsc1GFAPCKO mice. Methods Tsc1GFAPCKO mice and littermate control animals were treated with rapamycin or vehicle starting at postnatal day 14 (early treatment) or 6 weeks of age (late treatment), corresponding to times before and after onset of neurological abnormalities in Tsc1GFAPCKO mice. Mice were monitored for seizures by serial video-electroencephalogram and for long-term survival. Brains were examined histologically for astrogliosis and neuronal organization. Expression of phospho-S6 and other molecular markers correlating with epileptogenesis was measured by Western blotting. Results Early treatment with rapamycin prevented the development of epilepsy and premature death observed in vehicle-treated Tsc1GFAPCKO mice. Late treatment with rapamycin suppressed seizures and prolonged survival in Tsc1GFAPCKO mice that had already developed epilepsy. Correspondingly, rapamycin inhibited the abnormal activation of the mammalian target of rapamycin pathway, astrogliosis, and neuronal disorganization, and increased brain size in Tsc1GFAPCKO mice. Interpretation Rapamycin has strong efficacy for preventing seizures and prolonging survival in Tsc1GFAPCKO mice. Ann Neurol 2008 [source] Gray matter, white matter, brain, and intracranial volumes in first-episode bipolar disorder: a meta-analysis of magnetic resonance imaging studiesBIPOLAR DISORDERS, Issue 8 2009Antonio Vita Objectives:, To perform a comprehensive quantitative analysis of the existing magnetic resonance imaging (MRI) studies of the brain conducted on patients with first-episode bipolar disorder (BD). Methods:, A systematic search was performed of MRI studies that reported quantitative measurements of brain volumes of first-episode bipolar patients and healthy controls. Four meta-analyses were performed for four cerebral regions. Results:, Significant overall effect sizes were demonstrated, with a reduction detected in patients with BD for total intracranial and white matter volumes, but not for gray matter and whole brain volumes. Conclusions:, The available MRI literature indicates that specific structural brain abnormalities are already present in first-episode bipolar patients. These do not overlap with those emerging from previous meta-analyses performed in patients with chronic BD. These findings support the hypothesis of different patterns of changes in brain morphology over the time course of bipolar disorder. [source] Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder?BIPOLAR DISORDERS, Issue 2 2002Stephen M Strakowski The authors reviewed magnetic resonance imaging volumetric imaging results in major mood disorders, particularly comparing similarities and differences from studies of bipolar disorder and unipolar major depression. Abnormalities of cerebral brain regions appear inconsistently in mood disorders and, when present, typically consist of decreased frontal or prefrontal cortical volumes in both unipolar depression and bipolar disorder. In contrast, subcortical and medial temporal abnormalities are more commonly observed and are different between these two major classes of affective illness. Specifically, whereas structural enlargement of the basal ganglia and amygdala have been observed in bipolar disorder, in unipolar depression, these structures appear to be smaller in patients than healthy subjects. These findings suggest that affective illnesses may share in common an underdeveloped or atrophied prefrontal region, leading to loss of cortical modulation of limbic emotional networks. The effect of this loss results in unipolar depression or cycling (mania with depression) depending on the abnormalities of the subcortical structures involved. The cerebellum may also play a role in the presentation of mood disorders. This hypothesis remains speculative as much more research is needed to specifically examine how morphometric brain abnormalities translate into the neurophysiologic deficits that produce mood disorders. [source] The neuropsychology and neuroanatomy of bipolar affective disorder: a critical reviewBIPOLAR DISORDERS, Issue 3 2001Carrie E Bearden Objectives: To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions. Methods: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review. Results: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple-episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions (,signal hyperintensities') in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness. Conclusions: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first-episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease-specific impairments and genetic markers of neurocognitive function in bipolar disorder. [source] Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation period,BIRTH DEFECTS RESEARCH, Issue 7 2007Daisuke Higashiyama Abstract BACKGROUND: Prenatal exposure to ethanol induces holoprosencephalic malformations in both humans and laboratory animals. However, its teratogenic window for inducing holoprosencephaly is narrow, and the teratogenic mechanism is not well understood. In the present study, we examined the morphological changes in the craniofacial structures of mouse embryos/fetuses at intervals following ethanol treatment and evaluated gene expression patterns in the embryos. METHODS: Pregnant C57BL/6J mice were given two doses of ethanol (30 mg/kg in total) on the morning (7:00 and 11:00 AM) of day 7. The fetuses were observed at E10.5 and E15.5 grossly and/or histologically. The expression of Shh and Nkx2.1 gene transcripts was examined at E8.5 by in situ hybridization. RESULTS: Gross and histological abnormalities of the brain and face were found in ethanol-exposed fetuses, and their midline structures were most frequently affected. The midline commissural fibers were often lacking in ethanol-exposed fetuses, even in those cases without external gross malformations. In situ hybridization revealed down-regulation of Shh and Nkx2.1 genes in ethanol-exposed embryos. CONCLUSIONS: The results indicate that ethanol may perturb the expression of some developmental genes at a critical stage of embryonic development and induce holoprosencephaly and other midline craniofacial malformations, including histological brain abnormalities. Birth Defects Research (Part A), 2007. © 2007 Wiley-Liss, Inc. [source] When to image neurologically normal children with headaches: development of a decision ruleACTA PAEDIATRICA, Issue 6 2010MAS Ahmed Abstract Aims:, The aim of this study was to develop and refine a decision rule on when to undertake brain imaging (BI) in neurologically normal children with headaches. Methods:, From the literature and a questionnaire study, a list of red flags (RFs) was drawn-up. During the prospective 4-year period, consecutive children with headache were classified according to RFs and the headache diagnosis. Result:, Three of 709 (0.4%) neurologically normal children had significant brain abnormalities. BI was carried out in 389 of 498 (78%) children with RFs. Significant abnormalities were found in three of 389 children (0.8%), all had unclassified headache (UH). BI was not arranged for the 211 children with no RFs. None of these developed RFs or abnormal signs on follow-up for a mean of 13 months. Conclusion:, In addition to BI for those with neurological signs, we think BI should be considered for neurologically normal patients with UH and RFs. This would have saved imaging children needlessly: only 101 of 709 (14%) would have had scans arranged, instead of 389 of 709. [source] Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI studyACTA PAEDIATRICA, Issue 7 2007Sandra Horsch Abstract Aims: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors. Methods: All infants with gestational age <27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age. Images were analysed using a previously established scoring system for grey and white matter abnormalities. Results: No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities. Conclusion: The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing. [source] Partial cerebellar hypoplasia in a patient with Prader-Willi syndromeACTA PAEDIATRICA, Issue 7 2006Luigi Titomanlio Abstract We report a 3-y-old male infant with Prader-Willi syndrome (PWS) caused by a de novo interstitial deletion of 15q11-q13. Additional features included a right cerebellar hemisphere hypoplasia. The extent of deletion was determined by FISH analysis using an SNRPN PW/AS probe that maps in the PWS/AS critical region (CR) and with specific 15q BACs. We unravelled an interstitial 15q11.2-q13.1 deletion spanning about 3 Mb. Conclusion: To date only a few other PWS patients,including autopsy cases,with CNS structural anomalies have been described. Our case report adds knowledge to the issue of brain involvement in Prader-Willi syndrome. Further MRI studies of PWS patients will be helpful to clarify a correlation between PWS and brain abnormalities. [source] | ||||||||||||||||||||||||||||